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WO2025151806A1 - P75 neurotrophin receptor (p75ntr)-binding proteins and p75ntr-mediated delivery to the nervous system - Google Patents

P75 neurotrophin receptor (p75ntr)-binding proteins and p75ntr-mediated delivery to the nervous system

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Publication number
WO2025151806A1
WO2025151806A1 PCT/US2025/011219 US2025011219W WO2025151806A1 WO 2025151806 A1 WO2025151806 A1 WO 2025151806A1 US 2025011219 W US2025011219 W US 2025011219W WO 2025151806 A1 WO2025151806 A1 WO 2025151806A1
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WIPO (PCT)
Prior art keywords
seq
variant
amino acid
acid sequence
set forth
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PCT/US2025/011219
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French (fr)
Inventor
Adina BUXBAUM
Chitra Suri
Celestine THOMAS
Deanna LIN
Yonaton RAY
Raghavendar Reddy SANGANNA GARI
Ashique Rafique
Nicole ALESSANDRI-HABER
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Regeneron Pharmaceuticals Inc
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Regeneron Pharmaceuticals Inc
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Publication of WO2025151806A1 publication Critical patent/WO2025151806A1/en
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
    • C07K16/2878—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the NGF-receptor/TNF-receptor superfamily, e.g. CD27, CD30, CD40, CD95
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
    • A61K47/68—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
    • A61K47/6801—Drug-antibody or immunoglobulin conjugates defined by the pharmacologically or therapeutically active agent
    • A61K47/6803—Drugs conjugated to an antibody or immunoglobulin, e.g. cisplatin-antibody conjugates
    • A61K47/6807—Drugs conjugated to an antibody or immunoglobulin, e.g. cisplatin-antibody conjugates the drug or compound being a sugar, nucleoside, nucleotide, nucleic acid, e.g. RNA antisense
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
    • A61K47/68—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
    • A61K47/6835—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment the modifying agent being an antibody or an immunoglobulin bearing at least one antigen-binding site
    • A61K47/6849—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment the modifying agent being an antibody or an immunoglobulin bearing at least one antigen-binding site the antibody targeting a receptor, a cell surface antigen or a cell surface determinant
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K39/395—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
    • A61K39/39533—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals
    • A61K39/39541—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals against normal tissues, cells
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/30—Immunoglobulins specific features characterized by aspects of specificity or valency
    • C07K2317/33—Crossreactivity, e.g. for species or epitope, or lack of said crossreactivity
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
    • C07K2317/76—Antagonist effect on antigen, e.g. neutralization or inhibition of binding
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/90—Immunoglobulins specific features characterized by (pharmaco)kinetic aspects or by stability of the immunoglobulin
    • C07K2317/92—Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value

Definitions

  • the present invention relates to p75 neurotrophin receptor (p75 NTR ) antigen-binding proteins and protein-drug conjugates including a p75 NTR antigen-binding protein conjugated to a molecular cargo, as well as method of treating diseases with such antigen-binding proteins and protein-drug conjugates.
  • p75 NTR neurotrophin receptor
  • BACKGROUND OF THE INVENTION [0004] The development of drug delivery approaches to improve safety and efficacy of nervous system therapeutics is an increasingly critical and evolving field.
  • BBB blood–brain barrier
  • PNS peripheral nervous system
  • PK/PD pharmacokinetic/pharmacodynamic
  • Effective delivery of therapeutics to the nervous system may provide potential treatment opportunities for chronic pain and itch indications and otherwise uncurable Attorney Docket No.250298.000780 diseases such as spinal cord degeneration, amyotrophic lateral sclerosis (ALS), and neurodegenerative diseases such as Alzheimer’s disease (AD).
  • ALS amyotrophic lateral sclerosis
  • AD Alzheimer’s disease
  • SUMMARY OF THE INVENTION As mentioned in the background section above, there is an unmet need in the art to develop effective means to deliver therapeutics to the nervous system, such as to the peripheral nervous system (PNS), of a subject. This application provides compositions and methods to address this and other related needs.
  • PNS peripheral nervous system
  • an antigen-binding protein that binds to p75 neurotrophin receptor (p75 NTR ), wherein the antigen-binding protein exhibits less than 50% inhibition of an activity of the extracellular domain of human p75 NTR , wherein the activity of the extracellular domain of p75 NTR is the blocking of human nerve growth factor (NGF)-dependent activation of human tropomyosin receptor kinase A (TrkA) signaling, as measured in a cell-based assay.
  • NGF nerve growth factor
  • TrkA human tropomyosin receptor kinase A
  • the cell-based assay comprises the steps of: a) incubating a soluble extracellular domain of human p75 NTR with mature human NGF in the presence of the antigen-binding protein, optionally the extracellular domain of human p75 NTR is fused to an Fc domain of IgG, b) incubating the mixture of step (a) with a population of recombinant mammalian cells which stably expresses TrkA and a serum response element fused to a luciferase reporter.
  • step (b) measuring luciferase activity in Relative Luminescence Units (RLU) from the mixture of step (b), and d) calculating % inhibition using the formula R LU 0 X antige ⁇ RLU 10 n ⁇ binding protein soluble p75 wherein, RLU soluble p75 same conditions with an antigen-binding protein which does not bind to p75 NTR , and RLU NGF is the RLU value from cells treated with only the human mature NGF in the absence of the soluble extracellular domain of p75 NTR .
  • the antigen-binding protein comprises: (1) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 531, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 533, or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 535, or a variant thereof; and/or a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 539, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 541, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 543, or a variant thereof; (2) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 551, or a variant thereof, a HCDR2 comprising
  • an antigen-binding protein that binds to p75 neurotrophin receptor (p75 NTR ), comprising: (i) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 2, 22, 42, 58, 78, 98, 116, 136, 155, 173, 189, 207, 227, 245, 261, 279, 297, 315, 331, 349, 369, 387, 401, 417, 427, 437, 445, 455, 465, 475, 484, 493, 503, 513, 519, 529, 549, 569, 589 or 609, or a variant thereof; and/or (ii) a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 10, 30, 50, 66, 86,
  • the antigen-binding protein comprises: (1) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 2, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 10, or a variant thereof; (2) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 22, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 30, or a variant thereof; (3) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 42, or a variant thereof;
  • the antigen-binding protein comprises: (1) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 189, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 197, or a variant thereof; (2) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 227, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 235, or a variant thereof; (3) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 189, or
  • the antigen-binding protein comprises: (1) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 22, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 30, or a variant thereof; (2) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 78, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 86, or a variant thereof; (3) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 86, or a variant thereof;
  • the antigen-binding protein comprises: (1) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 4, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 6, or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 8, or a variant thereof; and a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 12, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 14, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 16, or a variant thereof; (2) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 24, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 26 or
  • the antigen-binding protein comprises: (1) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 4, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 6 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 8, or a variant thereof; and/or a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 12, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 14, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 16, or a variant thereof; (2) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 24, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO:
  • the antigen-binding protein comprises: (1) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 191, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 193 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 195, or a variant thereof; and/or a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 199, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 14, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 201, or a variant thereof; (2) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 229, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID
  • the antigen-binding protein comprises: (1) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 24, or a variant thereof, a HCDR2 comprising the amino acid sequence set Attorney Docket No.250298.000780 forth in SEQ ID NO: 26 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 28, or a variant thereof; and/or a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 32, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 34, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 36, or a variant thereof; (2) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 80, or a variant thereof, a HCVR
  • the antigen-binding protein comprises: (1) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 2, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 10, or a variant thereof; (2) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 22, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 30, or a variant thereof; (3) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 42, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 50, or a variant thereof; (4) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 58, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 66, or a variant thereof; (5) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 2,
  • the antigen-binding protein comprises: (1) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 2, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 10, or a variant thereof; (2) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 22, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 30, or a variant thereof; (3) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 42, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 50, or a variant thereof; (4) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 58, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 66, or a variant thereof; (5) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 2,
  • the antigen-binding protein comprises: (1) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 189, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 197, or a variant thereof; (2) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 227, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 235, or a variant thereof; Attorney Docket No.250298.000780 (3) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 261, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 269, or a variant thereof; (4) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 331, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 339,
  • the antigen-binding protein comprises: (1) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 18, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 20, or a variant thereof; (2) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 38, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 40, or a variant thereof; (3) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 54, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 56, or a variant thereof; (4) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 74, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 76, or a variant thereof; (5) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO:
  • the antigen-binding protein comprises: (1) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 18, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 20, or a variant thereof; Attorney Docket No.250298.000780 (2) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 38, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 40, or a variant thereof; (3) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 54, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 56, or a variant thereof; (4) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 74, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 76, or a variant thereof; (5) a heavy chain that comprises:
  • the antigen-binding protein comprises: (1) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 203, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 205, or a variant thereof; (2) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 241, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 243, or a variant thereof; (3) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 275, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 277, or a variant thereof; (4) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 345, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 347, or a variant thereof; (5) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 3
  • the antigen-binding protein comprises: (1) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 38, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 40, or a variant thereof; (2) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 94, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 96, or a variant thereof; (3) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 151, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 153, or a variant thereof; (4) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 275, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 277, or a variant thereof; (5) a heavy chain that comprises the amino acid sequence set forth
  • the antigen binding protein blocks the binding of a human neurotrophin receptor mouse Fc dimer (human p75-mFc) to human neurotrophin 3 (hNT-3) by at least about 50%. [0031] In some embodiments, the antigen binding protein blocks the binding of a human neurotrophin receptor mouse Fc dimer (human p75-mFc) to human neurotrophin 3 (hNT-3) by less than about 50%.
  • Attorney Docket No.250298.000780 [0032]
  • an antigen-binding protein that binds to the same epitope on p75 NTR as an antibody comprising an HCVR/LCVR amino acid sequence pair as set forth in Table 1-1.
  • an antigen-binding protein that competes for binding to p75 NTR with an antibody comprising an HCVR/LCVR amino acid sequence pair as set forth in Table 1-1.
  • the antigen-binding protein comprises an antibody or antigen- binding fragment thereof.
  • the antigen-binding protein is selected from a humanized antibody or antigen binding fragment thereof, human antibody or antigen binding fragment thereof, murine antibody or antigen binding fragment thereof, chimeric antibody or antigen binding fragment thereof, monovalent Fab', divalent Fab2, F(ab)'3 fragments, single-chain fragment variable (scFv), bis-scFv, (scFv)2, diabody, minibody, nanobody, triabody, tetrabody, disulfide stabilized Fv protein (dsFv), single-domain antibody (sdAb), Ig NAR, single heavy chain antibody, bispecific antibody or biding fragment thereof, bi-specific T-cell engager (BiTE), trispecific antibody, or chemically modified derivatives thereof.
  • a humanized antibody or antigen binding fragment thereof human antibody or antigen binding fragment thereof, murine antibody or antigen binding fragment thereof, chimeric antibody or antigen binding fragment thereof, monovalent Fab', divalent Fab2, F(ab)'3 fragments, single-chain fragment
  • the antigen-binding protein comprises a fragment antigen-binding region (Fab).
  • the antigen-binding protein comprises a single chain fragment variable (scFv).
  • the scFv comprises variable regions arranged in the following orientation from N-terminus to C-terminus: HCVR-LCVR.
  • the scFv comprises variable regions arranged in the following orientation from N-terminus to C-terminus: LCVR-HCVR.
  • the variable regions in the scFv are connected by a linker.
  • the linker is a peptide linker.
  • the peptide linker is -(GGGGS) n - (SEQ ID NO: 668), wherein n is any integral selected from 1-10.
  • the antigen-binding protein binds to human p75 NTR .
  • the antigen-binding protein binds to human p75 NTR with a KD of about 1X10 -9 M or a stronger affinity.
  • provided herein is an isolated polynucleotide encoding the antigen- binding protein as described herein.
  • a vector comprising the isolated polynucleotide as described herein.
  • a host cell comprising the antigen-binding protein as described herein, the isolated polynucleotide as described herein or the vector as described herein.
  • the host cell is a Chinese hamster ovary (CHO) cell.
  • a protein-drug conjugate comprising an antigen- binding protein that binds to p75 neurotrophin receptor (p75 NTR ) and is conjugated to a molecular cargo.
  • Fig.6 shows that anti-p75 NTR antibody internalizes in all lumbar DRGs 3 days following subcutaneous injection. Fluorescent anti-p75 NTR is detected in all lumbar DRGs 3 days post subcutaneous injection of 0.5 mg/kg fluorescently tagged antibody. A647 fluorescent image of lumbar DRGs overlayed onto transmitted light image of DRG is shown. [00141] Figs. 7A-7B show that anti-p75 NTR antibody internalizes in DRG neurons 3 days following subcutaneous injection.20X confocal single slice images with 1.5x zoom allow visualization of intracellular distribution of fluorescently tagged anti-p75 NTR REGN14187 in DRG neurons. Punctate, intracellular anti-p75 NTR antibody is detected in neurons.
  • FIG. 12D 10X confocal images of sagittal brain sections show anti- p75 NTR antibody observed in choroid plexus (arrows) 5 days following subcutaneous injection, with little or no detection in other regions of the brain.
  • Figs.12A-12D show that low levels of anti-p75 NTR antibodies are detected in the brain following ICV injection.
  • Fluorescent, 5x confocal images of sagittal brain sections demonstrate low accumulation of anti-p75 NTR specific labeling in ventral and cortical regions (Fig. 12D).
  • Both anti-Fel D1 (Fig. 12B) and anti-p75 NTR antibodies (Fig. 12D) show accumulation in the ventricle, the site of injection.
  • Figs.13A-13D show that Alexa-conjugated anti-p75 (Alexa-anti-p75) antibody is detected in sensory neurons in trigeminal ganglia that are ipsilateral (Fig.13B), but not contralateral (Fig.13D), to the injection site at sensory neuron terminals in the whisker pad, indicative of retrograde transport of the fluorescently conjugated antibodies along sensory neuron axons from the axon terminals to the sensory neuron cell body.
  • Confocal images of DAPI staining of ipsilateral (Fig.13A) and contralateral (Fig.13C) trigeminal ganglia are also included.
  • conjugates described herein can be useful for delivery of a molecular cargo described herein to cells such as dermal fibers, celiac ganglion cells, Müller glia, Leydig cells, ionocytes, dendritic cells, Schwann cells, salivary gland cells, retinal bipolar neurons, basal respiratory cells, basal squamous epithelial cells, and the like.
  • a polynucleotide includes DNA and RNA.
  • the present disclosure includes any polynucleotide described herein which is operably linked to a promoter or other expression control sequence.
  • the term “p75 NTR ” or “p75NTR” refers to p75 neurotrophin receptor.
  • the p75 neurotrophin receptor (p75 NTR ) belongs to the tumor necrosis factor receptor superfamily (TNFRSF).
  • a human p75 NTR protein described herein may be encoded by the nucleotide sequence of: ATGGGGGCAGGTGCCACCGGCCGCGCCATGGACGGGCCGCGCCTGCTGCTGTTGCT GCTTCTGGGGGTGTCCCTTGGAGGTGCCAAGGAGGCATGCCCCACAGGCCTGTACAC ACACAGCGGTGAGTGCTGCAAAGCCTGCAACCTGGGCGAGGGTGTGGCCCAGCCTT GTGGAGCCAACCAGACCGTGTGTGAGCCCTGCCTGGACAGCGTGACGTTCTCCGACG TGGTGAGCGCGACCGAGCCGTGCAAGCCGTGCACCGAGTGCGTGGGGCTCCAGAGC ATGTCGGCCGTGCGTGGAGGCCGACGACGCCGTGTGCCGCTGCGCCTACGGCTA CTACCAGGATGACGACTGGGCGCTGCGAGGCGTGCCGCGTGTGCGAGGCGGGCT CGGGCT CGGGCCTCGTGTTCCTGCCAGGACAAGCAGAACACCGTGTGCGAGG
  • Non-limiting examples of cell types to which a p75 NTR binding protein-drug conjugate described herein can deliver a conjugated molecular cargo include neurons, Müller glial cells, Leydig cells, ionocytes, dorsal root ganglion (DRG) cells, trigeminal ganglion cells, sympathetic ganglion cells, dermal fiber cells, retinal cells, myenteric plexus cells, celiac ganglion cells, dendritic cells, Schwann cells, salivary gland cells, retinal bipolar neurons, basal respiratory cells, basal squamous epithelial cells, and oligodendrocytes.
  • DDG dorsal root ganglion
  • each antibody heavy chain (HC) comprises a heavy chain variable region (“HCVR” or “VH”) (e.g., SEQ ID NO: 2, 22, 42, 58, 78, 98, 116, 136, 155, 173, 189, 207, 227, 245, 261, 279, 297, 315, 331, 349, 369, 387, 401, 417, 427, 437, 445, 455, 465, 475, 484, 493, 503, 513, 519, 529, 549, 569, 589, 609 or a variant thereof) and a heavy chain constant region; and each antibody light chain (LC) comprises a light chain variable region (“LCVR or “V L ”) (e.g., SEQ ID NO: 10, 30, 50, 66, 86, 106, 124, 144, 162, 179, 197, 215, 235, 251, 269, 287, 304, 323, 339, 357, 377, 391, 409, 537
  • an antigen-binding fragment of an antibody described herein may comprise a homo-dimer or hetero-dimer (or other multimer) of any of the variable and constant domain configurations listed above in non-covalent association with one another and/or with one or more monomeric V H or V L domain (e.g., by disulfide bond(s)).
  • the present disclosure includes an antigen-binding fragment of an antigen-binding protein such as an antibody set forth herein, for example, REGN14148; REGN14149; REGN14150; REGN14151; REGN14152; REGN14153; REGN14154; REGN14155; REGN14156; REGN14157; REGN14158; REGN14159; REGN14160; REGN14161; REGN14162; REGN14163; REGN14164; REGN14165; REGN14175; Attorney Docket No.250298.000780 REGN14176; REGN14177; REGN14178; REGN14179; REGN14180; REGN14181; REGN14182; REGN14183; REGN14184; REGN14185; REGN14186; REGN14187; REGN14188; REGN14189; REGN14190; REGN14191; REGN19513; REGN19514; REGN19515; REGN19516; or REGN19517.
  • an antibody set forth herein for example
  • an antigen-binding protein e.g., an antibody or antigen- binding fragment thereof
  • an antigen-binding protein specifically binds to an antigen
  • specific binding is measured in a surface plasmon resonance assay, e.g., at 25°C or 37°C.
  • An antigen-binding protein (e.g., an antibody or antigen-binding fragment thereof) that specifically binds an antigen from one species may or may not have cross-reactivity to other antigens, such as an orthologous antigen from another species.
  • the present disclosure includes antigen-binding proteins that specifically bind to p75 NTR protein (e.g., human p75 NTR protein, mouse p75 NTR protein, and/or cynomolgus monkey p75 NTR protein).
  • Anti-p75 NTR refers to an antigen-binding protein (or other molecule), for example an antibody or antigen-binding fragment thereof, that binds specifically to p75 NTR .
  • isolated antigen-binding proteins e.g., antibodies or antigen-binding fragments thereof
  • polypeptides polynucleotides and vectors
  • Such biological molecules include nucleic acids, proteins, other antibodies or antigen-binding fragments, lipids, carbohydrates, or other material such as cellular debris and growth medium.
  • An isolated antigen-binding protein may further be at least partially free of expression system components such as biological molecules from a host cell or of the growth medium thereof.
  • isolated is not intended to refer to a complete absence of such biological molecules (e.g., minor or insignificant amounts of impurity may remain) or to an absence of water, buffers, or salts or to components of a pharmaceutical formulation that includes the antigen-binding proteins (e.g., antibodies or antigen-binding fragments).
  • antigen-binding proteins e.g., antibodies or antigen-binding fragments
  • antigen-binding proteins e.g., antibodies or antigen-binding fragments, that bind to the same epitope as an antigen-binding protein described herein (e.g., REGN14148; REGN14149; REGN14150; REGN14151; REGN14152; REGN14153; REGN14154; REGN14155; REGN14156; REGN14157; REGN14158; REGN14159; REGN14160; REGN14161; REGN14162; REGN14163; REGN14164; REGN14165; REGN14175; REGN14176; REGN14177; REGN14178; REGN14179; REGN14180; REGN14181; REGN14182; REGN14183; REGN14184; REGN14185; REGN14186; REGN14187; REGN14188; REGN14189; REGN14190; REGN14191; REGN19513; REGN19514; REGN19515; REGN19516; or REGN
  • An antigen is a molecule, such as a peptide (e.g., p75 NTR or a fragment thereof (an antigenic fragment)), to which, for example, an antibody or antigen-binding fragment thereof binds.
  • a peptide e.g., p75 NTR or a fragment thereof (an antigenic fragment)
  • an antibody or antigen-binding fragment thereof binds.
  • the specific region on an antigen that an antibody recognizes and binds to is called the epitope.
  • Antigen-binding proteins e.g., antibodies described herein that specifically bind to such antigens are part of the present disclosure.
  • epitope refers to an antigenic determinant (e.g., on p75 NTR ) that interacts with a specific antigen-binding site of an antigen-binding protein, e.g., a variable region of an antibody, known as a paratope.
  • a single antigen may have more than one epitope.
  • different antibodies may bind to different areas on an antigen and may have different biological effects.
  • epitopes may also refer to a site on an antigen to which B and/or T cells respond and/or to a region of an antigen that is bound by an antibody. Epitopes may be defined as structural or functional.
  • Epitopes are generally a subset of the structural epitopes and have those residues that directly contribute to the affinity Attorney Docket No.250298.000780 of the interaction.
  • Epitopes may be linear or conformational, that is, composed of non-linear amino acids.
  • epitopes may include determinants that are chemically active surface groupings of molecules such as amino acids, sugar side chains, phosphoryl groups, or sulfonyl groups, and, in certain embodiments, may have specific three-dimensional structural characteristics, and/or specific charge characteristics.
  • Epitopes to which antigen- binding proteins described herein bind may be included in fragments of p75 NTR , for example the extracellular domain thereof.
  • Antigen-binding proteins e.g., antibodies
  • Antigen-binding proteins e.g., antibodies
  • Methods for determining the epitope of an antigen-binding protein, e.g., antibody or fragment or polypeptide include alanine scanning mutational analysis, peptide blot analysis (Reineke (2004) Methods Mol. Biol. 248: 443-63), peptide cleavage analysis, crystallographic studies and NMR analysis.
  • methods such as epitope excision, epitope extraction and chemical modification of antigens can be employed (Tomer (2000) Prot. Sci.9: 487-496).
  • Another method that can be used to identify the amino acids within a polypeptide with which an antigen-binding protein (e.g., antibody or fragment or polypeptide) interacts is hydrogen/deuterium exchange detected by mass spectrometry. See, e.g., Ehring (1999) Analytical Biochemistry 267: 252-259; Engen and Smith (2001) Anal. Chem.73: 256A- 265A.
  • an antibody or antigen-binding fragment described herein retains at least 20%, 50%, 70%, 80%, 90%, 95% or 100% or more of the p75 NTR binding affinity as the parental antibody. It is also intended that an antibody or antigen-binding fragment described herein may include conservative or non-conservative amino acid substitutions (referred to as "conservative variants" or “function conserved variants” of the antibody) that do not substantially alter its biologic activity.
  • An p75 NTR binding protein described herein may be a monoclonal antibody or an antigen-binding fragment of a monoclonal antibody which optionally may be conjugated to a molecular cargo.
  • an p75 NTR binding protein e.g., antibody or antigen-binding fragment (which optionally may be conjugated to a molecular cargo) comprises a heavy chain constant domain, e.g., of the type IgA (e.g., IgA1 or IgA2), IgD, IgE, IgG (e.g., IgG1, IgG2, IgG3 and IgG4) or IgM.
  • an antigen-binding protein e.g., antibody or antigen-binding fragment, comprises a light chain constant domain, e.g., of the type kappa or lambda.
  • antigen-binding proteins comprising the variable domains set forth herein (e.g., REGN14148; REGN14149; REGN14150; REGN14151; REGN14152; REGN14153; REGN14154; REGN14155; REGN14156; REGN14157; REGN14158; REGN14159; REGN14160; REGN14161; REGN14162; REGN14163; REGN14164; REGN14165; REGN14175; REGN14176; REGN14177; REGN14178; REGN14179; REGN14180; REGN14181; REGN14182; REGN14183; REGN14184; REGN14185; REGN14186; REGN14187; REGN14188; REGN14189; REGN14190; REGN14191; REGN19513; REGN19514; REGN19515; REGN19516; or REGN19517), which are linked to a heavy and/or light chain constant domain, e.g., as set forth herein.
  • the present disclosure includes human p75 NTR binding proteins which optionally may be conjugated to a molecular cargo.
  • human antigen-binding protein such as an antibody or antigen-binding fragment, as used herein, includes antibodies and fragments having human amino acid sequence; for example, variable and constant regions derived from human germline immunoglobulin sequences whether in a human cell or grafted into a non-human cell, e.g., a mouse cell. See e.g., U.S. Patent Nos. 8,502,018; 6,596,541 or 5,789,215.
  • the anti-p75 NTR human mAbs described herein may include amino acid residues not encoded by human germline immunoglobulin sequences (e.g., mutations introduced by random or site-specific mutagenesis in vitro or by somatic mutation in vivo), for example in the CDRs and in particular CDR3.
  • human antibody as used Attorney Docket No.250298.000780 herein, is not intended to include mAbs in which CDR sequences derived from the germline of another mammalian species (e.g., mouse) have been grafted onto human FR sequences.
  • the term includes antibodies recombinantly produced in a non-human mammal or in cells of a non-human mammal.
  • the present disclosure includes anti-p75 NTR chimeric antigen-binding proteins, e.g., antibodies and antigen-binding fragments thereof (which optionally may be conjugated to a molecular cargo), and methods of use thereof.
  • a "chimeric antibody” is an antibody having the variable domain from a first antibody and the constant domain from a second antibody, where the first and second antibodies are from different species.
  • the present disclosure includes chimeric antibodies comprising the variable domains which are set forth herein (e.g., from REGN14148; REGN14149; REGN14150; REGN14151; REGN14152; REGN14153; REGN14154; REGN14155; REGN14156; REGN14157; REGN14158; REGN14159; REGN14160; REGN14161; REGN14162; REGN14163; REGN14164; REGN14165; REGN14175; REGN14176; REGN14177; REGN14178; REGN14179; REGN14180; REGN14181; REGN14182; REGN14183; REGN14184; REGN14185; REGN14186; REGN14187; REGN14188; REGN14189; REGN14190; REGN14191; REGN19513; REGN19514; REGN19515; REGN19516; or REGN19517) and a non-human constant domain.
  • Non- limiting, exemplary configurations of variable and constant domains that may be found within an antigen-binding fragment of an antibody described herein include: (i) VH -CH1; (ii) VH - CH2; (iii) VH -CH3; (iv) VH-CH1-CH2; (v) VH -CH1-CH2-CH3; (vi) VH -CH2-CH3; (vii) VH -CL; (viii) VL -CH1; (ix) VL -CH2; (x) VL -CH3; (xi) VL -CH1-CH2; (xii) VL-CH1-CH2-CH3; (xiii) VL - CH2-CH3; and (xiv) V L -CL.
  • a "variant" of a polypeptide such as an immunoglobulin chain (e.g., an REGN14148; REGN14149; REGN14150; REGN14151; REGN14152; REGN14153; REGN14154; REGN14155; REGN14156; REGN14157; REGN14158; REGN14159; REGN14160; REGN14161; REGN14162; REGN14163; REGN14164; REGN14165; REGN14175; REGN14176; REGN14177; REGN14178; REGN14179; REGN14180; REGN14181; REGN14182; REGN14183; REGN14184; REGN14185; REGN14186; REGN14187; REGN14188; REGN14189; REGN14190; REGN14191; REGN19513; REGN19514; REGN19515; REGN19516; or REGN19517 VH, VL, HC or LC or CDR thereof comprising the amino acid sequence specifically set forth
  • a variant of a polypeptide may include a polypeptide such as an immunoglobulin chain (e.g., an REGN14148; REGN14149; REGN14150; REGN14151; REGN14152; REGN14153; REGN14154; REGN14155; REGN14156; REGN14157; REGN14158; REGN14159; REGN14160; REGN14161; REGN14162; REGN14163; REGN14164; REGN14165; REGN14175; REGN14176; REGN14177; REGN14178; REGN14179; REGN14180; REGN14181; REGN14182; REGN14183; REGN14184; REGN14185; REGN14186; REGN14187; REGN14188; REGN14189; REGN14190; REGN14191; REGN19513; REGN19514; REGN19515; REGN19516; or REGN19517 VH, VL, HC or LC or CDR thereof) which
  • Those of skill in this art recognize that, in general, single amino acid substitutions in non-essential regions of a polypeptide do not substantially alter biological activity (see, e.g., Watson et al.
  • Examples of groups of amino acids that have side chains with similar chemical properties include 1) aliphatic side chains: glycine, alanine, valine, leucine and isoleucine; 2) aliphatic-hydroxyl side chains: serine and threonine; 3) amide-containing side chains: asparagine and glutamine; 4) aromatic side chains: phenylalanine, tyrosine, and tryptophan; 5) basic side chains: lysine, arginine, and histidine; 6) acidic side chains: aspartate and glutamate, and 7) sulfur-containing side chains: cysteine and methionine.
  • a conservative replacement is any change having a positive value in the PAM250 log-likelihood matrix disclosed in Gonnet et al. (1992) Science 256: 1443-45.
  • Antibodies and antigen-binding fragments described herein comprise immunoglobulin chains including the amino acid sequences specifically set forth herein (and variants thereof) as well as cellular and in
  • the present disclosure includes antibodies and antigen-binding fragments thereof that specifically bind to p75 NTR comprising heavy and/or light chain amino acid sequences set forth herein as well as antibodies and fragments wherein one or more asparagine, serine and/or threonine residues is glycosylated, one or more asparagine residues is deamidated, one or more residues (e.g., Met, Trp and/or His) is oxidized, the N-terminal glutamine is pyroglutamate (pyroE) and/or the C-terminal lysine or other amino acid is missing.
  • one or more asparagine, serine and/or threonine residues is glycosylated
  • one or more asparagine residues is deamidated
  • one or more residues e.g., Met, Trp and/or His
  • the N-terminal glutamine is pyroglutamate (pyroE) and/or the C-terminal lysine or other amino acid
  • the nucleotide sequences encoding the amino acid sequences of domains or chains in p75 NTR binding proteins or protein-drug conjugates of the present disclosure are also summarized within Table 1-2.
  • the present disclosure includes any antibody or antigen-binding fragment thereof that includes an HCVR and LCVR having a sequence as set forth below or an HCVR and LCVR having the HCDRs and LCDRs thereof, respectively.
  • the antigen-binding protein comprises: (1) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 2, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 10, or a variant thereof; (2) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 22, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 30, or a variant thereof; (3) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 42, or a variant thereof;
  • the antigen-binding protein comprises: (1) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 2, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 10, or a variant thereof; (2) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 22, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 30, or a variant thereof; (3) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 42, or a variant thereof;
  • the antigen-binding protein comprises: (1) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 189, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 197, or a variant thereof; (2) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 227, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 235, or a variant thereof; (3) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 189, or
  • the antigen-binding protein comprises: (1) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 22, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 30, or a variant thereof; (2) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 78, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 86, or a variant thereof; (3) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 86, or a variant thereof;
  • the antigen-binding protein comprises: (1) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 529, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 537, or a variant thereof; (2) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 549, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 557, or a variant thereof; (3) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 529, or
  • the antigen-binding protein comprises: (1) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 4, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 6, or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 8, or a variant thereof; and a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 12, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 14, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 16, or a variant thereof; (2) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 24, or a Attorney Docket No.250298.000780 variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID
  • the antigen-binding protein comprises: (1) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 4, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 6 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 8, or a variant thereof; and/or a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 12, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 14, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 16, or a variant thereof; (2) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 24, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO:
  • the antigen-binding protein comprises: (1) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 2, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 10, or a variant thereof; (2) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 22, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 30, or a variant thereof; (3) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 42, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 50, or a variant thereof; (4) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 58, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 66, or a variant thereof; (5) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 2,
  • the antigen-binding protein comprises: (1) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 189, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 197, or a variant thereof; (2) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 227, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 235, or a variant thereof; (3) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 261, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 269, or a variant thereof; (4) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 331, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 339, or a variant thereof; (5) a HCVR that comprises the amino acid sequence set
  • the antigen-binding protein comprises: (1) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 18, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 20, or a variant thereof; (2) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 38, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 40, or a variant thereof; (3) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 54, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 56, or a variant thereof; (4) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 74, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 76, or a variant thereof; (5) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO:
  • the antigen-binding protein comprises: (1) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 18, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 20, or a variant thereof; (2) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 38, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 40, or a variant thereof; (3) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 54, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 56, or a variant thereof; (4) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 74, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 76, or a variant thereof; (5) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 18, or a variant thereof, and
  • the antigen-binding protein comprises: (1) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 38, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 40, or a variant thereof; (2) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 94, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 96, or a variant thereof; (3) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 151, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 153, or a variant thereof; (4) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 275, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 277, or a variant thereof;
  • the antigen-binding protein comprises: (1) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 545, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 547, or a variant thereof; (2) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 565, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 567, or a variant thereof; (3) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 585, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 587, or a variant thereof; (4) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 605, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 607, or a variant thereof; and/or (5) a heavy chain that comprises the
  • an antigen-binding protein described herein can block the binding of, e.g., a human neurotrophin receptor mouse Fc dimer (human p75-mFc) to human neurotrophin 3 (hNT-3) by at least about 5%, at least about 10%, at least about 15%, at least about 20%, at least about 25%, at least about 30%, at least about 35%, at least about 40%, at least about 45%, at least about 50%, at least about 60%, at least about Attorney Docket No.250298.000780 65%, at least about 70%, at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 95%, or 100%.
  • a human neurotrophin receptor mouse Fc dimer human p75-mFc
  • hNT-3 human neurotrophin 3
  • the antigen-binding protein competes for binding to Attorney Docket No.250298.000780 p75 NTR with an antibody comprising an HCVR/LCVR amino acid sequence pair as set forth in Table 1-1.
  • the present disclosure provides anti-p75 NTR protein-drug conjugates comprising an antibody or antigen-binding fragment thereof that specifically binds to p75 NTR or an antigenic fragment thereof comprising: a heavy chain variable region (HCVR) that comprises the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NOs: 2, 22, 42, 58, 78, 98, 116, 136, 155, 173, 189, 207, 227, 245, 261, 279, 297, 315, 331, 349, 369, 387, 401, 417, 427, 437, 445, 455, 465, 475, 484, 493, 503, 513, 519, 529, 5
  • HCVR heavy chain
  • the present disclosure also provides anti-p75 NTR protein-drug conjugates comprising an isolated antibody or antigen-binding fragment thereof that specifically binds to p75 NTR or an antigenic fragment thereof comprising: (1) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 189, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 197, or a variant thereof; (2) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises Attorney Docket No.250298.000780 the amino acid sequence set forth in SEQ ID NO: 227, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO:
  • the present disclosure also provides anti-p75 NTR protein-drug conjugates comprising an isolated antibody or antigen-binding fragment thereof that specifically binds to p75 NTR or an antigenic fragment thereof comprising: (1) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 529, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 537, or a variant thereof; (2) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 549, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 557, or a variant thereof; (3) a HCVR
  • the present disclosure also provides anti-p75 NTR protein-drug conjugates comprising an isolated antibody or antigen-binding fragment thereof that specifically binds to Attorney Docket No.250298.000780 p75 NTR or an antigenic fragment thereof comprising: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 191, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 193 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 195, or a variant thereof; and/or a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 199, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 14, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 201, or a variant thereof; (2) a HCVR that comprises:
  • the present disclosure also provides anti-p75 NTR protein-drug conjugates comprising an isolated antibody or antigen-binding fragment thereof that specifically binds to p75 NTR or an antigenic fragment thereof comprising: (1) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 38, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 40, or a variant thereof; (2) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 94, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 96, or a variant thereof; (3) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 151, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 153, or a variant thereof; (4) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 275, or a variant thereof, and a light chain
  • the method comprises piercing the body of the subject with a needle of a syringe and injecting the protein-drug conjugate into the body of the subject, e.g., into the brain or spinal cord of the subject.
  • the protein-drug conjugate may be introduced into the subject via intrathecal, intracisternal (e.g., cisterna magna), intracerebroventricular, or intraparenchymal injection into the central nervous system.
  • the method for delivering a molecular cargo to a tissue or cell type expressing p75 NTR in the body of a subject described herein comprises administering to the subject a protein-drug conjugate described herein, or the pharmaceutical composition described herein.
  • the protein-drug conjugate is introduced into the body of the subject via intramuscular, subcutaneous, or intravenous administration. In some embodiments, the protein-drug conjugate is administered into the body of the subject via subcutaneous, intrathecal, intracisternal, intracerebroventricular, or intraparenchymal administration. In some embodiments, the protein-drug conjugate is administered into the body of the subject via intravitreal administration into the eye. In some embodiments, the protein-drug conjugate is administered into the body of the subject via subcutaneous administration. In some embodiments, the protein-drug conjugate is administered into the body of the subject via intracerebroventricular administration.
  • a molecular cargo described herein is delivered, e.g., to the central nervous system of a subject including, e.g., to brain and/or the spinal cord tissues of the central nervous system which express p75 NTR , and the protein-drug conjugate described herein or the pharmaceutical composition described herein, is administered to the subject via intracerebroventricular administration.
  • the present disclosure further provides a cell line useful for screening the p75 NTR binding proteins or anti-p75 NTR protein-drug conjugates described herein.
  • the cell lines described herein express p75NTR on the cell surface, and optionally further comprise an exogenous nucleic acid to express one or more reporter proteins.
  • the anti-p75 NTR antibody or an antigen-binding fragment thereof described herein can be delivered to a target tissue (e.g., brain or spinal cord, peripheral nervous system, autonomic nervous system, enteric nervous system, and/or eye) or a target cell (e.g., a sensory neuron (such as, but not limited to, a dorsal root ganglion cell or a trigeminal ganglion cell) a sympathetic neuron, a parasympathetic neuron, and/or an enteric neuron) by receptor-mediated retrograde delivery.
  • a target tissue e.g., brain or spinal cord, peripheral nervous system, autonomic nervous system, enteric nervous system, and/or eye
  • a target cell e.g., a sensory neuron (such as, but not limited to, a dorsal root ganglion cell or a trigeminal ganglion cell) a sympathetic neuron, a parasympathetic neuron, and/or an enteric neuron) by receptor-mediated
  • Sugar moieties of a nucleic acid can be ribose, deoxyribose, or similar compounds with optional substitutions, e.g., methoxy or 2’ halide substitutions.
  • polynucleotides up to about 30 nucleotides in length can be referred to herein as an “oligonucleotide”.
  • Oligonucleotides may be of a variety of different lengths, e.g., depending on the form. In some embodiments, an oligonucleotide is 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, or more nucleotides in length.
  • the oligonucleotide is 8 to 30 nucleotides in length, 10 to 15 nucleotides in length, 10 to 20 nucleotides in length, 15 to 25 nucleotides in length, 21 to 23 nucleotides in lengths.
  • the molecular cargo comprises a polypeptide molecule.
  • polypeptide and “protein” used interchangeably herein encompass native or artificial proteins, protein fragments and polypeptide analogs of a protein sequence.
  • a polypeptide or protein may be monomeric or polymeric.
  • the molecular cargo described herein may comprise a carrier, such as a liposome or lipid nanoparticle (LNP).
  • a lipid particle e.g., a liposome or lipid nanoparticle disclosed herein, may include a lipid formulation that can be used to deliver a therapeutic nucleic acid (e.g., gRNA) to a target site of interest (e.g., cell, tissue, organ, and the like).
  • a therapeutic nucleic acid e.g., gRNA
  • a target site of interest e.g., cell, tissue, organ, and the like.
  • carriers may be used, e.g., as a means for delivery of a polynucleotide disclosed herein and/or a protein disclosed herein.
  • a carrier e.g., liposome or LNP
  • a nucleic acid e.g., DNA or RNA
  • protein e.g., RNA-guided DNA binding agent
  • a carrier e.g., liposome or LNP
  • the molecular cargo comprises a small molecule.
  • a small molecule (SM) can enter cells easily because it has a low molecular weight (typically, up to about 1 kDa).
  • proteins including, e.g., voltage-gated sodium channel Nav1.7, voltage-gated sodium channel Nav1.8, voltage-gated sodium channel Nav1.9, voltage-gated sodium channel Nav1.6, tropomyosin receptor kinase A (TrkA), tropomyosin receptor kinase C (TrkC), acid-sensing ion channel subunit 1 (ASIC1), acid-sensing ion channel subunit 1 (ASIC3), transient receptor potential vanilloid 1 (TRPV1), transient receptor potential vanilloid 1 (TRPV4), transient receptor potential cation channel, subfamily A, member 1 (TRPA1), transient receptor potential cation Attorney Docket No.250298.000780 channel subfamily C, member 6 (TRPC6), transient receptor potential cation channel subfamily M, member 8 (TRPM8), fatty acid amide hydrolase (FAAH), piezo type mechanosensitive i
  • TrkA tropomyosin receptor
  • polynucleotide molecules that are useful as molecular cargoes in the protein-drug conjugates of the present disclosure include, but are not limited to, interfering nucleic acids (e.g., shRNAs, siRNAs, microRNAs, antisense oligonucleotides), gapmers, mixmers, ribozymes, phosphorodiamidite morpholinos, peptide nucleic acids, aptamers, and guide nucleic acids (e.g., Cas9 guide RNAs), mRNAs, etc.
  • interfering nucleic acids e.g., shRNAs, siRNAs, microRNAs, antisense oligonucleotides
  • gapmers e.g., mixmers, ribozymes, phosphorodiamidite morpholinos
  • peptide nucleic acids e.g., aptamers
  • guide nucleic acids e.g., Cas9 guide RNAs
  • a polynucleotide may comprise one or more modified nucleotides. In various embodiments, a polynucleotide may comprise one or more modified inter-nucleotide linkage. Polynucleotides may be single-stranded or double-stranded. In some embodiments, the polynucleotide molecule targets a gene or gene product associated with pain, itch (also known as pruritis), and/or a neurological disease or disorder.
  • Non-limiting examples of gene or gene products associated with pain, itch, and/or a neurological disease or disorder include Attorney Docket No.250298.000780 voltage-gated sodium channel Nav1.7, voltage-gated sodium channel Nav1.8, voltage-gated sodium channel Nav1.9, voltage-gated sodium channel Nav1.6, tropomyosin receptor kinase A (TrkA), tropomyosin receptor kinase C (TrkC), acid-sensing ion channel subunit 1 (ASIC1), acid-sensing ion channel subunit 1 (ASIC3), transient receptor potential vanilloid 1 (TRPV1), transient receptor potential vanilloid 1 (TRPV4), transient receptor potential cation channel, subfamily A, member 1 (TRPA1), transient receptor potential cation channel subfamily C, member 6 (TRPC6), transient receptor potential cation channel subfamily M, member 8 (TRPM8), fatty acid amide hydrolase (FAAH), piezo type me
  • the gene or gene product associated with a neurological disease or disorder is Sodium Voltage-Gated Channel Alpha Subunit 9 (SCN9A).
  • the polynucleotide molecule targets a gene or gene product associated pain, e.g., pain targets which may be expressed in DG and/or TG, such as, but not limited to Nav1.7, Nav1.8, Nav1.9, TRPV1, TRPV4, TRPA1, TRPC6, TRPM8, PIEZO1, PIEZO2, CALCA, HCN, TrkA, TrkC, ASIC1, ASIC3, and P2X3.
  • the molecular cargo comprises at least one polynucleotide molecule.
  • the molecular cargo comprises at least 2, at least 3, at least 4, at least 5, or at least 10 polynucleotide molecules.
  • the polynucleotide molecule is DNA.
  • the polynucleotide molecule is RNA.
  • a polynucleotide described herein e.g., interfering nucleic acid or guide RNA
  • a region of complementarity of a polynucleotide to a target nucleic acid may be 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, Attorney Docket No.250298.000780 43, 44, 45, 46, 47, 48, 49, or 50 nucleotides in length.
  • the region of complementarity may be complementary with at least 10 consecutive nucleotides of a target nucleic acid.
  • a polynucleotide may contain 1, 2, 3, 4 or 5 base mismatches compared to the portion of the consecutive nucleotides of target nucleic acid. In some embodiments the polynucleotide may have up to 3 mismatches over 15 bases, or up to 4 mismatches over 10 bases. In some embodiments, the polynucleotide is complementary (e.g., at least 80%, at least 85% at least 90%, at least 95%, or 100%) to a target sequence of any one of the polynucleotides of the present disclosure. In various embodiments, such target sequence may be 100% complementary to the polynucleotide described herein.
  • any one or more of the thymine bases (T's) in any one of the polynucleotides described herein may be uracil bases (U's), and/or any one or more of the U's may be T's.
  • a target sequence described herein may comprise a sequence of nucleic acid in a target gene that has complementarity to the guide sequence of the gRNA. The interaction of the target sequence and the guide sequence directs an RNA-guided DNA- binding agent (e.g., Cas protein) to bind, and potentially nick or cleave (depending on the activity of the agent), within the target sequence.
  • an RNA-guided DNA- binding agent e.g., Cas protein
  • polynucleotides described herein may be modified, e.g., comprise a modified nucleotide, a modified internucleoside linkage, and/or a modified sugar moiety, or combinations thereof.
  • polynucleotides can possess one or more of the following properties: have improved cell uptake compared to unmodified polynucleotides; are not toxic to cells or mammals are not immune stimulatory; avoid pattern recognition receptors do not mediate alternative splicing; are nuclease resistant; have improved endosomal exit internally in a cell; or minimizes TLR stimulation. Any of the various modified chemistries or formats of polynucleotides disclosed herein may be combined with together.
  • nucleotide modification(s) may be used that render a polynucleotide into which the modification(s) are incorporated more resistant to nuclease digestion than the native oligoribonucleotide or oligodeoxynucleotide molecules; such modified polynucleotides survive intact for a longer time than unmodified polynucleotides.
  • the polynucleotide may be of 8 to 15 nucleotides in length in which 2 to 4, 2 to 5, 2 to 6, 2 to 7, 2 to 8, 2 to 9, 2 to 10, 2 to 11, 2 to 12, 2 to 13, 2 to 14 nucleotides of the polynucleotide are modified nucleotides.
  • the polynucleotides can have every nucleotide except 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15 nucleotides modified.
  • the polynucleotide disclosed herein may comprise at least one nucleoside, e.g., modified at the 2' position of the sugar.
  • all of the nucleosides in the polynucleotide are 2’-modified nucleosides.
  • a polynucleotide comprises at least one 2'-modified nucleoside.
  • the polynucleotide disclosed herein may one or more non-bicyclic 2’-modified nucleosides, e.g., 2’-O-dimethylaminoethyloxyethyl (2’-O- DMAEOE)2’-O-methyl (2’-O-Me), 2’-O-dimethylaminoethyl (2’-O-DMAOE), 2’-O- methoxyethyl (2’-MOE), 2’-deoxy, 2’-O-N-methylacetamido (2’-O-NMA) modified nucleoside, 2’-fluoro (2’-F), 2’-O-aminopropyl (2’-O
  • the polynucleotide of the present disclosure may comprise one or more 2’-4’ bicyclic nucleosides in which the ribose ring may comprise a bridge moiety, e.g., connecting two atoms in the ring (e.g., connecting the 2’-O atom to the 4’-C atom via an ethylene (ENA) bridge, a methylene (LNA) bridge, or a (S)-constrained ethyl (cEt) bridge).
  • ENA ethylene
  • LNA methylene
  • cEt a (S)-constrained ethyl
  • Non-limiting examples of LNAs are disclosed in PCT Patent Application Publication No. WO2008/043753, the contents of which are incorporated herein by reference in its entirety.
  • Non-limiting examples of cEt are disclosed Attorney Docket No.250298.000780 in in U.S.
  • Patent Nos 7,569,686, 7,101,993, and 7,399,845 each of which is herein incorporated by reference in its entirety.
  • the polynucleotide described herein may comprise a modified nucleoside disclosed in, for example, US Patent Nos. 8,022,193; 7,569,686; 7,399,845; 7,741,457; 7,335,765; 7,816,333; 8,957,201; 7,314,923, the entire contents of each of which are incorporated herein by reference for all purposes.
  • the polynucleotide may have a plurality of modified nucleosides that result in a total increase in Tm of the polynucleotide in a range of 2 °C, 3 °C, 4 °C, 5 °C, 6 °C, 7 °C, 8 °C, 9 °C, 10 °C, 15 °C, 20 °C, 25 °C, 30 °C, 35 °C, 40 °C, 45 °C, 50 °C, 55 °C, 60 °C or more as compared to a polynucleotide which does not have the modified nucleoside.
  • the oligonucleotide may comprise alternating 2’-4’ bicyclic nucleosides and 2’-MOE, 2’-fluoro, or 2’-O-Me modified nucleosides.
  • the oligonucleotide may comprise alternating non-bicyclic 2’-modified nucleosides (e.g., 2’-MOE, 2’-fluoro, or 2’-O-Me) and 2’- 4’ bicyclic nucleosides (e.g., LNA, ENA, cEt).
  • Non-limiting examples of phosphorus-containing linkages include aminoalkylphosphotriesters phosphorothioates, chiral phosphorothioates, phosphotriesters, phosphorodithioates, methyl and other alkyl phosphonates comprising 3’alkylene phosphonates and chiral phosphonates, phosphinates, phosphoramidates comprising 3’- amino phosphoramidate and aminoalkylphosphoramidates, thionoalkylphosphonates, thionophosphoramidates, thionoalkylphosphotriesters, and boranophosphates having normal 3’-5’ linkages, 2’-5’ linked analogs of these, and those having inverted polarity wherein the adjacent pairs of nucleoside units are linked 3’-5’ to 5’-3’ or 2’-5’ to 5’-2’; see U.S.
  • a polynucleotide of the present disclosure may have heteroatom backbones, e.g., or peptide nucleic acid (PNA) backbones (wherein the phosphodiester backbone of the oligonucleotide is replaced with a polyamide backbone, the nucleotides being bound directly or indirectly to the aza nitrogen atoms of the polyamide backbone, see Nielsen et al., Science 1991, 254, 1497), morpholino backbones (see Summerton and Weller, U.S. Patent No.5,034,506); amide backbones (see De Mesmaeker et al. Ace. Chem.
  • PNA peptide nucleic acid
  • Nitrogenous bases can be conventional bases (A, G, C, T, U), analogs thereof (e.g., modified uridines such as 5-methoxyuridine, pseudouridine, or N1 - Attorney Docket No.250298.000780 methylpseudouridine, or others); inosine; derivatives of purines or pyrimidines (e.g., N4- methyl deoxyguanosine, deaza- or aza-purines, deaza- or aza-pyrimidines, pyrimidine bases with substituent groups at the 5 or 6 position (e.g., 5-methylcytosine), purine bases with a substituent at the 2, 6, or 8 positions, 2- amino-6-methylaminopurine, 6-O -methylguanine, 4- thio-pyrimidines, 4-amino-pyrimidines, 4- dimethylhydrazine-
  • modified uridines such as 5-methoxyuridine, pseudouridine, or N1 - Attorney Docket No.
  • Nucleic acids can include one or more “abasic” residues where the backbone includes no nitrogenous base for position(s) of the polymer (U.S. Patent No.5,585,481).
  • a nucleic acid can comprise only conventional RNA or DNA sugars, bases and linkages, or can include both conventional components and substitutions (e.g., conventional nucleosides with 2’ methoxy substituents, or polymers containing both conventional nucleotides and one or more nucleotide analogs).
  • Nucleic acid includes “locked nucleic acid” (LNA), an analogue containing one or more LNA nucleotide monomers with a bicyclic furanose unit locked in an RNA mimicking sugar conformation, which enhance hybridization affinity toward complementary RNA and DNA sequences (Vester and Wengel, 2004, Biochemistry 43(42): 13233-41).
  • LNA locked nucleic acid
  • RNA and DNA have different sugar moieties and can differ by the presence of uracil or analogs thereof in RNA and thymine or analogs thereof in DNA.
  • a conjugated molecular cargo may comprise a polynucleotide molecule(s) which is capable of modifying expression of one more genes (e.g., inhibiting gene expression and/or translation, modulating RNA splicing or inducing exon skipping) in a target cell.
  • the polynucleotide molecule may be an interfering nucleic acid molecule, e.g., an siRNA, an shRNA, a miRNA, or an antisense oligonucleotide (ASO), that targets, e.g., an RNA (e.g., an mRNA).
  • the interfering nucleic acid molecule may modify expression of one more genes associated with a neurological disease and/or disorder.
  • the interfering nucleic acid molecule may inhibit the expression of one or more genes encoding a receptor or ion channel that plays a role in pain processing such as, but not limited to, Nav1.7, Nav1.8, Nav1.9, TRPV1, TRPV4, TRPA1, TRPC6, TRPM8, PIEZO1, PIEZO2, CALCA, HCN, TRKA, TRKC, ASIC1, ASIC3, and P2X3.
  • the interfering nucleic acid molecule is an anti-p75 NTR -Nav1.7 siRNA.
  • interfering nucleic acid molecules that selectively target and inhibit the activity or expression of a product (e.g., an mRNA product) of a targeted gene are used in compositions and methods described herein.
  • An interfering nucleic acid molecule may inhibit the expression or activity of a product (e.g., an mRNA product) of at least one targeted gene by at least 5%, at least 10%, at least 15%, at least 20%, at least 25%, at least 30%, at least 35%, at least 40%, at least 45%, at least 50%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100%.
  • An agent disclosed herein may comprise a nucleobase sequence that is at least at least 80%, at least 85%, at least 90%, at least 95%, or 100% complementarity to a product (e.g., an mRNA product) of at least targeted gene.
  • a product e.g., an mRNA product
  • complementarity of nucleic acids can mean that a nucleotide sequence in one strand of nucleic acid, due to orientation of its nucleobase groups, forms hydrogen bonds with another sequence on an opposing nucleic acid strand.
  • the complementary bases in DNA are typically A with T and C with G. In RNA, they are typically C with G and U with A. Complementarity can be perfect or substantial/sufficient.
  • Tm includes the temperature at which a population of hybridization complexes formed between two nucleic acid strands are 50% denatured (i.e., a population of double- stranded nucleic acid molecules becomes half dissociated into single strands). At a temperature below the Tm, formation of a hybridization complex is favored, whereas at a temperature above the Tm, melting or separation of the strands in the hybridization complex is favored.
  • both the sense strand and the antisense strand of an siRNA molecule are 21 nucleotides in length.
  • siRNA molecules that comprise a nucleotide sequence complementary to all or a portion of the target sequence, i.e., an antisense sequence may be designed and prepared using suitable methods (see, Attorney Docket No.250298.000780 e.g., U.S. Patent Publication Nos. 2004/0077574 and 2008/0081791 and PCT Publication No. WO 2004/016735).
  • the siRNA molecule may be single-stranded (i.e.
  • an siRNA molecule described herein may comprises 3' overhangs of about 1 to about 3 nucleotides on both ends of the molecule. In some embodiments, the siRNA molecule comprises 3’ overhangs of about 1 to about 3 nucleotides on both the sense strand and the antisense strand. In some embodiments, the siRNA molecule comprises 3’ overhangs of about 1 to about 3 nucleotides on the antisense strand. In some embodiments, the siRNA molecule may comprise 3’ overhangs of about 1 to about 3 nucleotides on the sense strand.
  • the siRNA molecule comprises one or more modified nucleotides (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15 or more). In some embodiments, all of the nucleotides of the sense strand and/or the antisense strand of the siRNA molecule are modified. In certain embodiments, the siRNA molecule can comprise one or more modified nucleotides and/or one or more modified internucleotide linkages. In some embodiments, the siRNA molecule may comprise modified internucleotide linkages at the first and second internucleoside linkages at the 5′ end of the siRNA molecule sense strand.
  • modified nucleotides e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15 or more. In some embodiments, all of the nucleotides of the sense strand and/or the antisense strand of the siRNA molecule are modified. In certain embodiments, the siRNA molecule can comprise one or more modified nucleotides and/or one or
  • the siRNA molecule may comprise modified internucleotide linkages at the first and second internucleoside linkages at the 5′ and 3′ ends of the siRNA molecule antisense strand. In some embodiments, the siRNA molecule may comprise modified internucleotide linkages at the first and second internucleoside linkages at the 5′ end of the siRNA molecule sense strand and at the first and second internucleoside linkages at the 5′ and 3′ ends of the siRNA molecule antisense strand. [00344] In some embodiments, the modified nucleotide may comprise a modified sugar moiety (e.g., a 2' modified nucleotide).
  • a modified sugar moiety e.g., a 2' modified nucleotide
  • the siRNA molecule can comprise one or more 2’ modified nucleotides, e.g., a 2'-deoxy, 2'-fluoro (2’-F), 2'-O-methyl (2’-O-Me), 2'-O-methoxyethyl (2'-MOE), 2'-O-aminopropyl (2'-O-AP), 2'-O- dimethylaminoethyl (2'-O-DMAOE), 2'-O-dimethylaminopropyl (2'-O-DMAP), 2'-O- Attorney Docket No.250298.000780 dimethylaminoethyloxyethyl (2'-O-DMAEOE), or 2'-O-N-methylacetamido (2'-O-NMA).
  • 2’ modified nucleotides e.g., a 2'-deoxy, 2'-fluoro (2’-F), 2'-O-methyl (2’-O-Me), 2'-O
  • each nucleotide of the siRNA molecule can a modified nucleotide (e.g., a 2'-modified nucleotide).
  • the siRNA molecule may comprise one or more phosphorodiamidate morpholinos.
  • each nucleotide of the siRNA molecule consists of a phosphorodiamidate morpholino.
  • the siRNA molecule may comprise a phosphorothioate or other modified internucleotide linkage.
  • the siRNA molecule may comprise, e.g., a phosphorothioate internucleoside linkage(s).
  • the siRNA molecule may comprise a phosphorothioate internucleoside linkage(s) between two or more nucleotides. In some embodiments, the siRNA molecule may comprise a phosphorothioate internucleoside linkage(s) between all nucleotides. In some embodiments, the siRNA molecule may comprise modified internucleotide linkages at the first, second, and/or third internucleoside linkage at the 5' or 3' end of the siRNA molecule. In some embodiments, the siRNA molecule may comprise modified internucleotide linkages at the first and second internucleoside linkages at the 5′ and/or 3′ end of the siRNA molecule.
  • the siRNA molecule may comprise modified internucleotide linkages at the first and second internucleoside linkages at the 5′ end of the siRNA molecule sense strand. In some embodiments, the siRNA molecule may comprise modified internucleotide linkages at the first and second internucleoside linkages at the 5′ and 3′ ends of the siRNA molecule antisense strand. In some embodiments, the siRNA molecule may comprise modified internucleotide linkages at the first and second internucleoside linkages at the 5′ end of the siRNA molecule sense strand and at the first and second internucleoside linkages at the 5′ and 3′ ends of the siRNA molecule antisense strand.
  • the siRNA molecule may comprise modified internucleotide linkages at the first internucleoside linkage at the 5′ and 3′ ends of the siRNA molecule sense strand, at the first, second, and third internucleoside linkages at the 5′ end of the siRNA molecule antisense strand, and at the first internucleoside linkage at the 3′ end of the siRNA molecule antisense strand.
  • the modified internucleotide linkages may comprise phosphorus-containing linkages.
  • phosphorus-containing linkages which may be used in the practice of the present disclosure include, without limitation, chiral phosphorothioates, phosphorothioates, phosphorodithioates, aminoalkylphosphotriesters, phosphotriesters, methyl and other alkyl phosphonates comprising 3'alkylene phosphonates and chiral phosphonates, phosphoramidates comprising 3'-amino phosphoramidate and Attorney Docket No.250298.000780 aminoalkylphosphoramidates, phosphinates, thionoalkylphosphonates, thionophosphoramidates, thionoalkylphosphotriesters, and boranophosphates having normal 3'-5' linkages, 2'-5' linked analogs of these, and those having inverted polarity wherein the adjacent pairs of nucleoside units are linked 3'-5' to 5'-3' or 2'-5' to 5'-2'; see US Patent Nos.
  • the antisense strand may comprise one or more modified nucleotides (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15 or more).
  • the antisense strand may comprise one or more modified nucleotides and/or one or more modified internucleotide linkage(s).
  • the modified nucleotide may comprise a modified sugar moiety (e.g., a 2' modified nucleotide).
  • the antisense strand comprises one or more 2' modified nucleotides, e.g., a 2'-deoxy, 2'-fluoro (2’-F), 2'-O-methyl (2’-O-Me), 2'-O-methoxyethyl (2'-MOE), 2'-O- aminopropyl (2'-O-AP), 2'-O- dimethylaminoethyl (2'-O-DMAOE), 2'-O-dimethylaminopropyl (2'-O-DMAP), 2'-O- dimethylaminoethyloxyethyl (2'-O-DMAEOE), or 2'-O-N-methylacetamido (2'-O-NMA).
  • each nucleotide of the antisense strand can be a modified nucleotide (e.g., a 2'-modified nucleotide).
  • the antisense strand may comprise one or more phosphorodiamidate morpholinos.
  • the antisense strand consists of a phosphorodiamidate morpholino oligomer (PMO).
  • PMO phosphorodiamidate morpholino oligomer
  • antisense strand contains a phosphorothioate or other modified internucleotide linkage.
  • the antisense strand may comprise phosphorothioate internucleoside linkage(s).
  • the antisense strand may comprise phosphorothioate internucleoside linkage(s) between two or more nucleotides. In some embodiments, the antisense strand may comprise phosphorothioate internucleoside linkage(s) between all nucleotides. In some embodiments, the antisense strand may comprise modified internucleotide linkages at the first, second, and/or third nucleotide at the 5' or 3' end of the antisense strand.
  • the antisense strand may comprise Attorney Docket No.250298.000780 modified internucleotide linkages at the first and second nucleotide positions (e.g., between the first and second and between the second and third nucleotides) at the 5′ and 3′ ends of the antisense strand.
  • the modified internucleotide linkages may comprise phosphorus-containing linkages of the antisense strand.
  • phosphorus- containing linkages which may be used in the practice of the present disclosure include, without limitation, chiral phosphorothioates, phosphorothioates, phosphorodithioates, aminoalkylphosphotriesters, phosphotriesters, methyl and other alkyl phosphonates comprising 3' alkylene phosphonates and chiral phosphonates, phosphoramidates comprising 3'-amino phosphoramidate and aminoalkylphosphoramidates, phosphinates, thionoalkylphosphonates, thionophosphoramidates, thionoalkylphosphotriesters, and boranophosphates having normal 3'-5' linkages, 2'-5' linked analogs of these, and those having inverted polarity wherein the adjacent pairs of nucleoside units are linked 3'-5' to 5'-3' or 2'-5' to 5'-2'; see US Patent Nos.5,625,050; 3,687,808; 4,
  • the sense strand comprises one or more modified nucleotides (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 11, 12, 13, 14, 15 or more).
  • the antisense strand may comprise one or more modified nucleotides and/or one or more modified internucleotide linkage(s).
  • the modified nucleotide may comprise a modified sugar moiety (e.g., a 2' modified nucleotide).
  • the sense strand of the siRNA molecule may be fully substituted with morpholino, 2'-MOE and/ or 2'-O-Me residues, and may not be recognized by RISC, e.g., as disclosed in Kole et al., (2012) Nature reviews. Drug Discovery 11(2): 125- 140, incorporated herein by reference in its entirety.
  • the sense strand of the siRNA molecule may comprise a 5'-morpholino modification.
  • the 5'-morpholino modification may reduce RISC loading of the sense strand and/or improves RNAi activity and/or antisense strand selection, e.g., as disclosed in Kumar et al., (2019) Chem Commun (Camb) 55(35):5139-5142, incorporated herein by reference in its entirety.
  • the sense strand of the siRNA molecule may be modified, for example, with a synthetic RNA-like high affinity nucleotide analogue called Locked Nucleic Acid (LNA) that may reduce RISC loading of the sense strand and promote antisense strand incorporation into RISC, e.g., as disclosed in Elman et al., (2005) Nucleic Acids Res. 33(1): 439-447, incorporated herein by reference in its entirety.
  • LNA Locked Nucleic Acid
  • the sense strand of Attorney Docket No.250298.000780 the siRNA molecule may comprise a 5' unlocked nucleic acid (UNA) modification.
  • At least one (e.g., at least 2, at least 3, at least 4, at least 5, at least 6, at least 5, at least 8, at least 9, at least 10 or more) siRNA molecule may be conjugated, for example, covalently to an p75 NTR binding protein described herein.
  • the p75 NTR binding protein may be conjugated to the 5’ end of the sense strand of the siRNA molecule.
  • the p75 NTR binding protein may be conjugated to the 3’ end of the sense strand of the siRNA molecule.
  • the p75 NTR binding protein may be conjugated internally to the sense strand of the siRNA molecule.
  • Single stranded regions of an siRNA molecule may be modified or include nucleoside surrogates, e.g., the unpaired region or regions of a hairpin structure, e.g., a region which links two complementary regions, can have modifications or nucleoside surrogates. Modification to stabilize one or more 3'- or 5 '-termini of an siRNA molecule, e.g., against exonucleases, or to favor the antisense siRNA agent to enter into RISC are also useful.
  • Modifications can include C3 (or C6, C7, C12) amino linkers, thiol linkers, carboxyl linkers, non-nucleotidic spacers (e.g., C3-C12 (e.g., C3, C6, C9, C12), abasic, tri ethylene glycol, hexaethylene glycol), biotin or fluorescein reagents that come as phosphoramidites and that have another DMT-protected hydroxyl group, allowing multiple couplings during RNA synthesis.
  • the sense strand is 23 nucleotides in length and the antisense strand is 21 nucleotides in length.
  • the antisense strand contain two or three phosphorothioate internucleotide linkages at the 5′-terminus and 1 phosphorothioate internucleotide linkage at the 3′-terminus.
  • the siRNA molecule may be linked to a targeting moiety at the 5′ or 3′ end of the sense strand.
  • the sense strand is 21 nucleotides in length and the antisense strand is 23 nucleotides in length, wherein the antisense strand contains a 2 nucleobase 3′ overhang.
  • the antisense strand of the siRNA molecule contains 1-3 phosphorothioate linkages at the 3′ and 5′ ends and the sense strand of the siRNA molecule contains 1-2 phosphorothioate linkages at the 3′ end. In some embodiments, the antisense strand of the siRNA molecule contains 2-3 phosphorothioate linkages at the 5′ end and 2 phosphorothioate linkages at the 3′, and the sense strand of the siRNA molecule contains 2 phosphorothioate linkages at the 5′ end.
  • the siRNA molecule may be linked to a targeting moiety at the 5′ or 3′ end of the sense strand.
  • the siRNA molecules described herein may be conjugated to a moiety that directs delivery to the CNS, e.g., a lipophilic ligand, optionally a C16 ligand, as described in WO2021119226A1, which is incorporated herein by reference in its entirety.
  • a moiety that directs delivery to the CNS e.g., a lipophilic ligand, optionally a C16 ligand, as described in WO2021119226A1, which is incorporated herein by reference in its entirety.
  • the lipophilic moiety is a lipid, cholesterol, retinoic acid, cholic acid, adamantane acetic acid, 1-pyrene butyric acid, dihydrotestosterone, l,3-bis- O(hexadecyl)glycerol, geranyloxyhexyanol, hexadecylglycerol, bomeol, menthol, 1,3- propanediol, heptadecyl group, palmitic acid, myristic acid, O3-(oleoyl)lithocholic acid, O3- (oleoyl)cholenic acid, dimethoxytrityl, or phenoxazine.
  • the lipophilic moiety contains a saturated or unsaturated C4-C30 hydrocarbon chain, and an optional functional group selected from the group consisting of hydroxyl, amine, carboxylic acid, sulfonate, phosphate, thiol, azide, and alkyne.
  • the lipophilic moiety contains a saturated or unsaturated C6-C18 hydrocarbon chain.
  • the lipophilic moiety contains a saturated or unsaturated C16 hydrocarbon chain.
  • the saturated or unsaturated C16 hydrocarbon chain is conjugated to position 6, from the 5 ’-end of the strand.
  • the lipophilic moiety is conjugated via a carrier that replaces one or more nucleotide(s) in the internal position(s) or the double stranded region.
  • the carrier is a cyclic group selected from the group consisting of pyrrolidinyl, pyrazolinyl, pyrazolidinyl, imidazolinyl, imidazolidinyl, piperidinyl, piperazinyl, [l,3]dioxolanyl, oxazolidinyl, isoxazolidinyl, morpholinyl, thiazolidinyl, isothiazolidinyl, quinoxalinyl, pyridazinonyl, tetrahydrofuranyl, and decalinyl; or is an acyclic moiety based on a serinol backbone or a diethanolamine backbone.
  • the lipophilic moiety is conjugated to the double-stranded siRNA agent via a linker containing an ether, thioether, urea, carbonate, amine, amide, maleimide-thioether, disulfide, phosphodiester, sulfonamide linkage, a product of a click reaction, or carbamate.
  • the lipophilic moiety is conjugated to a nucleobase, sugar moiety, or intemucleosidic linkage.
  • the lipophilic moiety or targeting ligand is conjugated via a bio-cleavable linker selected from the group consisting of DNA, RNA, disulfide, amide, functionalized monosaccharides or oligosaccharides of galactosamine, glucosamine, glucose, galactose, mannose, and combinations thereof.
  • a bio-cleavable linker selected from the group consisting of DNA, RNA, disulfide, amide, functionalized monosaccharides or oligosaccharides of galactosamine, glucosamine, glucose, galactose, mannose, and combinations thereof.
  • the 3 ’ end of the sense strand is protected via an end cap which is a cyclic group having an amine, said cyclic group being selected from the group consisting of pyrrolidinyl, pyrazolinyl, pyrazolidinyl, imidazolinyl, imidazolidinyl, piperidinyl, piperazinyl, [l,3]dioxolanyl, oxazolidinyl, isoxazolidinyl, morpholinyl, thiazolidinyl, isothiazolidinyl, quinoxalinyl, pyridazinonyl, tetrahydrofuranyl, and decalinyl.
  • an end cap which is a cyclic group having an amine, said cyclic group being selected from the group consisting of pyrrolidinyl, pyrazolinyl, pyrazolidinyl, imidazolinyl, imidazolidinyl,
  • the interfering nucleic acid molecule is a short hairpin RNA (shRNA).
  • shRNA short hairpin RNA
  • a “small hairpin RNA ” or “short hairpin RNA” or “shRNA” described herein may include a short RNA sequence that makes a tight hairpin turn that can be used to silence gene expression via RNA interference.
  • the shRNAs provided herein may be chemically synthesized or transcribed from a transcriptional cassette in a DNA plasmid. The shRNA hairpin structure may be cleaved by the cellular machinery into siRNA, which is then bound to the RNA-induced silencing complex (RISC).
  • RISC RNA-induced silencing complex
  • Non-limiting examples of shRNAs include a double-stranded polynucleotide molecule assembled from a single-stranded molecule, where the sense and antisense regions are linked by a nucleic acid-based or non-nucleic acid-based linker; and a double- stranded polynucleotide molecule with a hairpin secondary structure having self- complementary sense and antisense regions.
  • the sense and antisense strands of the shRNA are linked by a loop structure comprising from about 1 to Attorney Docket No.250298.000780 about 25 nucleotides, from about 2 to about 20 nucleotides, from about 4 to about 15 nucleotides, from about 5 to about 12 nucleotides, or 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, or more nucleotides.
  • Additional embodiments related to the shRNAs, as well as methods of designing and synthesizing such shRNAs, are described in U.S. Patent Publication No. 2011/0071208, the disclosure of which is herein incorporated by reference in its entirety for all purposes.
  • the interfering nucleic acid molecule is a micro RNA (miRNA).
  • miRNAs represent a large group of small RNAs produced naturally in organisms, some of which regulate the expression of target genes. miRNAs are short hairpin RNAs about 18 to about 25 nucleotides in length that function in RNA silencing and post-translational regulation of gene expression. Typically, miRNAs are generated from large RNA precursors (termed pri-miRNAs) that are processed in the nucleus into approximately 70 nucleotide pre- miRNAs, which fold into imperfect stem-loop structures.
  • miRNAs typically undergo an additional processing step within the cytoplasm where mature miRNAs of 18-25 nucleotides in length are excised from one side of the pre-miRNA hairpin by an rNase III enzyme, Dicer. miRNAs are not translated into proteins, but instead bind to specific messenger RNAs, thereby blocking translation. In some embodiments, miRNAs base-pair imprecisely with their targets to inhibit translation. [00372] miRNAs as described herein can include pri-miRNA, pre-miRNA, mature miRNA or fragments of variants thereof that retain the biological activity of mature miRNA. In some embodiments, the size range of the miRNA can be from 21 nucleotides to 170 nucleotides.
  • certain oligonucleotides may have about or at least about 70% sequence complementarity, e.g, 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence complementarity, between the oligonucleotide and the target sequence.
  • Oligonucleotide backbones that are less susceptible to cleavage by nucleases are discussed herein.
  • an interfering nucleic acid molecule described herein is a gapmer.
  • each nucleoside in the gap region Y is a 2'- Attorney Docket No.250298.000780 deoxyribonucleoside, and neither the 5' wing region X or the 3' wing region Z comprises any 2'-deoxyribonucleosides.
  • the gap region of the gapmer polynucleotide may contain modified nucleotides known to be acceptable for efficient rNase H action in addition to DNA nucleotides, such as C4'-substituted nucleotides, acyclic nucleotides, and arabino- configured nucleotides.
  • the gap region comprises one or more unmodified internucleosides.
  • each internucleotide linkage in the 5′ or 3′ wing region comprises a phosphorothioate linkage. In some embodiments, each internucleotide linkage in the gapmer comprises a phosphorothioate linkage.
  • the Y region may comprise a contiguous stretch of nucleotides, e.g., a region of 5 or more DNA nucleotides, which can be capable of recruiting an rNase including but not limited to rNase H.
  • the gapmer may bind to a target nucleic acid such that an rNase is recruited to cleave the target nucleic acid.
  • the Y region may be flanked both 5' and 3' by regions X and Z comprising high-affinity modified nucleosides, e.g., 1-10 high-affinity modified nucleosides.
  • high affinity modified nucleosides include, without limitation, 2'-4' bicyclic nucleosides (e.g., LNA, cEt, ENA) and 2'-modified nucleosides (e.g., 2'-MOE, 2'O-Me, 2'-F).
  • the flanking sequences X and Z may be of 1-30 nucleotides, 1-20 nucleotides, 1-10 nucleotides, or 1-5 nucleotides in length.
  • flanking sequences X and Z may be of similar length or of dissimilar lengths. In some embodiments, the flanking sequences X and Z are each 5 nucleotides in length. In some embodiments, the flanking sequences X and Z are each 3 nucleotides in length. In some embodiments, the gap-segment Y may be a nucleotide sequence of 5-30 nucleotides, 5-20 nucleotides, or 5-10 nucleotides in length. In some embodiments, the gap segment is 10 nucleotides in length. Attorney Docket No.250298.000780 [00379] A gapmer may be produced using suitable methods. Preparation of gapmers is described in, for example, U.S. Pat.
  • a gapmer may be 10-50, 10-45, 10-40, 10-35, 10-30, 10-25, 10-20, 10-15, 15-40, 15-35, 15- 30, 15-25, 15-20, 20-40, 20-35, 20-30, 20-25, 25-40, 25-35, 25-30, 30-40, 30-35, or 35-40 nucleosides in length.
  • a gapmer is 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, or 40 nucleosides in length.
  • a gapmer is about 16 to about 20 nucleosides in length.
  • a gapmer is 16 nucleotides in length.
  • a gapmer is 20 nucleotides in length.
  • the 5' wing region and the 3' wing region of a gapmer are independently 1-20 nucleosides (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 nucleosides) long.
  • the 5' wing region and the 3' wing region of the gapmer may be independently 1- 20, 1-15, 1-10, 1-7, 1-5, 1-3, 1-2, 2-5, 2-7, 3-5, 3-7, 5- 20, 5-15, 5-10, 10-20, 10-15, or 15-20 nucleosides long.
  • the sulfurization of the internucleotide bond reduces the action of endo-and exonucleases including 5’ to 3’ and 3’ to 5’ DNA POL 1 exonuclease, nucleases SI and PI, rNases, serum nucleases and snake venom phosphodiesterase.
  • Interfering nucleic acid molecules can be prepared, for example, by chemical synthesis, in vitro transcription, or digestion of long dsRNA by rNase III or Dicer. These can be introduced into cells by transfection, electroporation, or other methods known in the art. See Hannon, GJ, 2002, Nature 418: 244- 251; Bernstein E et al., 2002, RNA 7: 1509-1521; Hutvagner G et al., Curr. Opin. Genetics & Development 12: 225-232; Brummelkamp, 2002, Science 296: 550-553; Lee NS, et al.2002. Nature Biotechnol.20:500-505; Miyagishi M, and Taira K.
  • a conjugated molecular cargo comprises a guide RNA or a DNA encoding a guide RNA.
  • a “guide RNA” or “gRNA” is an RNA molecule that binds to a Cas protein (e.g., Cas9 protein) and targets the Cas protein to a specific location within a target DNA.
  • Guide RNAs can comprise two segments: a “DNA-targeting segment” (also Attorney Docket No.250298.000780 called “guide sequence”) and a “protein-binding segment.” “Segment” includes a section or region of a molecule, such as a contiguous stretch of nucleotides in an RNA.
  • gRNAs such as those for Cas9
  • an “activator-RNA” e.g., tracrRNA
  • a “targeter-RNA” e.g., CRISPR RNA or crRNA
  • a gRNA is a S. aureus Cas9 gRNA or an equivalent thereof.
  • An exemplary two-molecule gRNA comprises a crRNA-like (“CRISPR RNA” or “targeter-RNA” or “crRNA” or “crRNA repeat”) molecule and a corresponding tracrRNA-like (“trans-activating CRISPR RNA” or “activator-RNA” or “tracrRNA”) molecule.
  • a corresponding tracrRNA comprises a stretch of nucleotides that forms the other half of the dsRNA duplex of the protein-binding segment of the gRNA.
  • a stretch of nucleotides of a crRNA are complementary to and hybridize with a stretch of nucleotides of a tracrRNA to form the dsRNA duplex of the protein-binding domain of the gRNA. As such, each crRNA can be said to have a corresponding tracrRNA.
  • Examples of Attorney Docket No.250298.000780 tracrRNA sequences comprise, consist essentially of, or consist of any one of AGCAUAGCAAGUUAAAAUAAGGCUAGUCCGUUAUCAACUUGAAAAAGUGGCACCGAG UCGGUGCUUU (SEQ ID NO: 627), AAACAGCAUAGCAAGUUAAAAUAAGGCUAGUCCGUUAUCAACUUGAAAAAGUGGCAC CGAGUCGGUGCUUUU (SEQ ID NO: 628), or GUUGGAACCAUUCAAAACAGCAUAGCAAGUUAAAAUAAGGCUAGUCCGUUAUCAACU UGAAAAAGUGGCACCGAGUCGGUGC (SEQ ID NO: 629).
  • the crRNA and the corresponding tracrRNA hybridize to form a gRNA.
  • the crRNA can be the gRNA.
  • the crRNA additionally provides the single-stranded DNA-targeting segment that hybridizes to the complementary strand of a target DNA. If used for modification within a cell, the exact sequence of a given crRNA or tracrRNA molecule can be designed to be specific to the species in which the RNA molecules will be used. See, e.g., Mali et al. (2013) Science 339(6121):823-826; Jinek et al.
  • the DNA-targeting segment (crRNA) of a given gRNA comprises a nucleotide sequence that is complementary to a sequence on the complementary strand of the target DNA, as described in more detail below.
  • the DNA-targeting segment of a gRNA interacts with the target DNA in a sequence-specific manner via hybridization (i.e., base pairing).
  • the nucleotide sequence of the DNA-targeting segment may vary and determines the location within the target DNA with which the gRNA and the target DNA will interact.
  • the DNA-targeting segment of a subject gRNA can be modified to hybridize to any desired sequence within a target DNA.
  • Naturally occurring crRNAs differ depending on the CRISPR/Cas system and organism but often contain a targeting segment of between 21 to 72 nucleotides length, flanked by two direct repeats (DR) of a length of between 21 to 46 nucleotides (see, e.g., WO 2014/131833, herein incorporated by reference in its entirety for all purposes).
  • DR direct repeats
  • the DRs are 36 nucleotides long and the targeting segment is 30 nucleotides long.
  • the 3’ located DR is complementary to and hybridizes with the corresponding tracrRNA, which in turn binds to the Cas protein.
  • the DNA- targeting segment and the corresponding guide RNA target sequence can contain one or more mismatches.
  • the DNA-targeting segment of the guide RNA and the corresponding guide RNA target sequence can contain 1-4, 1-3, 1-2, 1, 2, 3, or 4 mismatches (e.g., where the total length of the guide RNA target sequence is at least 17, at least 18, at least 19, or at least 20 or more nucleotides).
  • the DNA-targeting segment of the guide RNA and the corresponding guide RNA target sequence can contain 1-4, 1-3, 1-2, 1, 2, 3, or 4 mismatches where the total length of the guide RNA target sequence 20 nucleotides.
  • the DNA-targeting segment In some guide RNAs, at least 17 nucleotides within the DNA-targeting segment are complementary to the complementary strand of the target DNA.
  • the DNA-targeting segment can be 20 nucleotides in length and can comprise 1, 2, or 3 mismatches with the complementary strand of the target DNA.
  • the mismatches are not adjacent to the region of the complementary strand corresponding to the protospacer adjacent motif (PAM) sequence (i.e., the reverse complement of the PAM sequence) (e.g., the mismatches are in the 5’ end of the DNA- targeting segment of the guide RNA, or the mismatches are at least 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, or 19 base pairs away from the region of the complementary strand corresponding to the PAM sequence).
  • PAM protospacer adjacent motif
  • the protein-binding segment of a gRNA can comprise two stretches of nucleotides that are complementary to one another.
  • the sugar modification can comprise a sugar group which may also contain one or more carbons that possess the opposite stereochemical configuration than that of the corresponding carbon in ribose.
  • a modified nucleic acid can include nucleotides containing e.g., arabinose, as the sugar.
  • the modified nucleic acids can also include abasic sugars. These abasic sugars can also be further modified at one or more of the constituent sugar atoms.
  • the modified nucleic acids can also include one or more sugars that are in the L form (e.g. L- nucleosides).
  • the nucleobase can include, for example, naturally-occurring and synthetic derivatives of a base.
  • each of the crRNA and the tracrRNA can contain modifications. Such modifications may be at one or both ends of the crRNA and/or tracrRNA.
  • one or more residues at one or both ends of the sgRNA may be chemically modified, and/or internal nucleosides may be modified, and/or the entire sgRNA may be chemically modified.
  • Some gRNAs comprise a 5’ end modification.
  • Some gRNAs comprise a 3’ end modification.
  • any of the guide RNAs described herein can comprise at least one modification.
  • the at least one modification comprises a 2’-O-methyl (2’- O-Me) modified nucleotide, a phosphorothioate (PS) bond between nucleotides, a 2’-fluoro (2’-F) modified nucleotide, or a combination thereof.
  • the guide RNA comprises a modification at one or more of the first five nucleotides at the 5’ end of the guide RNA
  • the guide RNA comprises a modification at one or more of the last five nucleotides of the 3’ end of the guide RNA, or a combination thereof.
  • the guide RNA can comprise phosphorothioate bonds between the first four nucleotides of the guide RNA, phosphorothioate bonds between the last four nucleotides of the guide RNA, or a combination thereof.
  • the guide RNA can comprise 2’-O-Me modified nucleotides at the first three nucleotides at the 5’ end of the guide RNA, can Attorney Docket No.250298.000780 comprise 2’-O-Me modified nucleotides at the last three nucleotides at the 3’ end of the guide RNA, or a combination thereof.
  • a modified gRNA can comprise the following sequence: mN*mN*mN*NNNNNNNNNNNNNNNNNGUUUUAGAmGmCmUmAmGmAmAmAmUmAm GmCAAGUUAAAAUAAGGCUAGUCCGUUAUCAmAmCmUmUmGmAmAmAmAmAmGmU mGmGmAmGmUmCmGmGmUmGmCmU*mU*mU*mU*mU (SEQ ID NO: 637), where “N” may be any natural or non-natural nucleotide.
  • the totality of N residues can comprise a DNA-targeting segment as described herein.
  • mA nucleotide
  • mC nucleotide
  • mU nucleotide
  • mG denotes a nucleotide (A, C, U, and G, respectively) that has been modified with 2’-O-Me.
  • the symbol “*” depicts a phosphorothioate modification.
  • A, C, G, U, and N independently denote a ribose sugar, i.e., 2’-OH.
  • A, C, G, U, and N denote a ribose sugar, i.e., 2’-OH.
  • a phosphorothioate linkage or bond refers to a bond where a sulfur is substituted for one nonbridging phosphate oxygen in a phosphodiester linkage, for example in the bonds between nucleotides bases.
  • the modified oligonucleotides may also be referred to as S-oligos.
  • the terms A*, C*, U*, or G* denote a nucleotide that is linked to the next (e.g., 3’) nucleotide with a phosphorothioate bond.
  • mA* denote a nucleotide (A, C, U, and G, respectively) that has been substituted with 2’-O-Me and that is linked to the next (e.g., 3’) nucleotide with a phosphorothioate bond.
  • Another chemical modification that has been shown to influence nucleotide sugar rings is halogen substitution.
  • 2’-fluoro (2’-F) substitution on nucleotide sugar rings can increase oligonucleotide binding affinity and nuclease stability.
  • Abasic nucleotides refer to those which lack nitrogenous bases.
  • Inverted bases refer to those with linkages that are inverted from the normal 5’ to 3' linkage (i.e., either a 5’ to 5’ linkage or a 3’ to 3’ linkage).
  • An abasic nucleotide can be attached with an inverted linkage.
  • an abasic nucleotide may be attached to the terminal 5’ nucleotide via a 5’ to 5’ linkage, or an abasic nucleotide may be attached to the terminal 3’ nucleotide via a 3’ to 3’ linkage.
  • An inverted abasic nucleotide at either the terminal 5’ or 3’ nucleotide may also be called an inverted abasic end cap.
  • one or more of the first three, four, or five nucleotides at the 5’ terminus, and one or more of the last three, four, or five nucleotides at the 3’ terminus are Attorney Docket No.250298.000780 modified.
  • the modification can be, for example, a 2’-O-Me, 2’-F, inverted abasic nucleotide, phosphorothioate bond, or other nucleotide modification well known to increase stability and/or performance.
  • the first four nucleotides at the 5’ terminus, and the last four nucleotides at the 3’ terminus can be linked with phosphorothioate bonds.
  • the first three nucleotides at the 5’ terminus, and the last three nucleotides at the 3’ terminus can comprise a 2’-O-methyl (2’-O-Me) modified nucleotide.
  • the first three nucleotides at the 5’ terminus, and the last three nucleotides at the 3’ terminus comprise a 2’-fluoro (2’-F) modified nucleotide.
  • the first three nucleotides at the 5’ terminus, and the last three nucleotides at the 3’ terminus comprise an inverted abasic nucleotide.
  • Guide RNAs can be provided in any form.
  • the gRNA can be conjugated to the p75 NTR binding protein disclosed herein, such as an scFv or an antibody or an antigen-binding fragment thereof, in the form of RNA, either as two molecules (separate crRNA and tracrRNA) or as one molecule (sgRNA), and optionally in the form of a complex with a Cas protein.
  • the gRNA can be conjugated to the p75 NTR binding protein disclosed herein, such as an scFv or an antibody or an antigen-binding fragment thereof, in the form of DNA encoding the gRNA.
  • 1, 2, 3, 4, 5 or more guide RNAs are conjugated to the p75 NTR binding protein disclosed herein, such as an scFv or an antibody or an antigen-binding fragment thereof.
  • the gRNA either in the form of RNA or DNA, may be incorporated into a carrier (e.g., liposomes or LNPs) which is conjugated to the p75 NTR binding protein disclosed herein, such as an scFv or an antibody or an antigen-binding fragment thereof.
  • the carrier can further comprise a Cas protein, such as a Cas9 protein, or a nucleic acid (e.g., mRNA) encoding a Cas protein.
  • the DNA encoding the gRNA can be in a vector comprising a heterologous nucleic acid, such as a nucleic acid encoding a Cas protein.
  • a heterologous nucleic acid such as a nucleic acid encoding a Cas protein.
  • it can be in a vector or a plasmid that is separate from the vector comprising the nucleic acid encoding the Cas protein.
  • Non-limiting examples of such carriers include poly(lactic acid) (PLA) microspheres, poly(D,L-lactic-coglycolic-acid) (PLGA) microspheres, liposomes, micelles, inverse micelles, lipid cochleates, and lipid microtubules.
  • Such compositions can further comprise a Cas protein, such as a Cas9 protein, or a nucleic acid encoding a Cas protein.
  • Target DNAs for guide RNAs include nucleic acid sequences present in a DNA to which a DNA-targeting segment of a gRNA will bind, provided sufficient conditions for binding exist. Suitable DNA/RNA binding conditions include physiological conditions normally present in a cell.
  • the target DNA includes both the sequence on the complementary strand to which the guide RNA hybridizes and the corresponding sequence on the non-complementary strand (e.g., adjacent to the protospacer adjacent motif (PAM)).
  • the term “guide RNA target sequence” as used herein refers specifically to the sequence on the non-complementary strand corresponding to (i.e., the reverse complement of) the sequence to which the guide RNA hybridizes on the complementary strand. That is, the guide RNA target sequence refers to the sequence on the non-complementary strand adjacent to the PAM (e.g., upstream or 5’ of the PAM in the case of Cas9).
  • the guide RNA target sequence can be a sequence coding a gene product (e.g., a protein) or a non-coding sequence (e.g., a regulatory sequence) or can include both.
  • the target sequence (e.g., guide RNA target sequence) for the DNA-binding protein can be anywhere within a targeted gene that is suitable for altering expression of the targeted gene.
  • the target sequence can be within a regulatory element, such as an enhancer or promoter, or can be in proximity to a regulatory element.
  • the target sequence can be within about 10, 20, 30, 40, 50, 100, 200, 300, 400, 500, or 1,000 nucleotides of the start codon.
  • the cleavage site of Cas proteins can be about 1 to about 10 or about 2 to about 5 base pairs (e.g, 3 base pairs) upstream or downstream of the PAM sequence (e.g., within the guide RNA target sequence).
  • the PAM sequence i.e., on the non-complementary strand
  • the PAM sequence can be 5’-NiGG-3’, where Ni is any DNA nucleotide, and where the PAM is immediately 3’ of the guide RNA target sequence on the non-complementary strand of the target DNA.
  • the PAM can have the sequence 5’-TBN-3’, wherein B is G, T, or C.
  • An example of a guide RNA target sequence is a 20-nucleotide DNA sequence immediately preceding an NGG motif recognized by an SpCas9 protein. The guanine at the 5’ end can facilitate transcription by RNA polymerase in cells.
  • Other examples of guide RNA target sequences plus PAMs can include two guanine nucleotides at the 5’ end to facilitate efficient transcription by T7 polymerase in vitro. See, e.g., WO 2014/065596, herein incorporated by reference in its entirety for all purposes.
  • RNA target sequences plus PAMs can have between 4-22 nucleotides in length, including the 5’ G or GG and the 3’ GG or NGG. Yet other guide RNA target sequences plus PAMs can have between 14 and 20 nucleotides in length. [00446] Formation of a CRISPR complex hybridized to a target DNA can result in cleavage of one or both strands of the target DNA within or near the region corresponding to the guide RNA target sequence (i.e., the guide RNA target sequence on the non- complementary strand of the target DNA and the reverse complement on the complementary strand to which the guide RNA hybridizes).
  • Staggered ends can be produced, for example, by using two Cas proteins, each of which produces a single-strand break at a different cleavage site on a different strand, thereby producing a double-strand break.
  • a first nickase can create a single-strand break on the first strand of double-stranded DNA (dsDNA)
  • a second nickase can create a single-strand break on the second strand of dsDNA such that overhanging sequences are Attorney Docket No.250298.000780 created.
  • a molecular cargo e.g., a polynucleotide molecule described herein may comprise a ribozyme (ribonucleic acid enzyme).
  • a ribozyme is a molecule, commonly an RNA molecule, that is capable of performing specific biochemical reactions, akin to the action of protein enzymes.
  • Ribozymes comprise molecules possessing catalytic activities such as, but not limited to, the capacity to cleave at specific phosphodiester linkages in RNA molecules to which they have hybridized, e.g., RNA-containing substrates, IncRNAs, mRNAs, and ribozymes. [00448] Ribozymes may take on one of several physical structures, one such structure is termed "hammerhead".
  • a hammerhead ribozyme can comprise, e.g., a catalytic core comprising nine conserved bases, two regions complementary to the target RNA flanking regions the catalytic core, and a double-stranded stem and loop structure (stem-loop II).
  • the flanking regions may permit the binding of the ribozyme to the target RNA, in particular, by forming double-stranded stems I and III.
  • Cleavage may occur in trans (cleavage of an RNA substrate other than that containing the ribozyme) or in cis (cleavage of the same RNA molecule that contains the hammerhead motif) adjacent to a specific ribonucleotide triplet by a transesterification reaction from a 3', 5'- phosphate diester to a 2', 3'-cyclic phosphate diester.
  • this catalytic activity may require the presence of specific, highly conserved sequences in the catalytic region of the ribozyme.
  • Modifications in ribozyme structure can include the replacement or substitution of non-core portions of the molecule with non-nucleotidic molecules.
  • Ma et al. (Biochem. (1993) 32:1751-1758; Nucleic Acids Res. (1993) 21:2585- 2589) replaced the six-nucleotide loop of the TAR ribozyme hairpin with non-nucleotidic, ethylene glycol-related linkers.
  • Thomson et al. (Nucleic Acids Res. (1993) 21:5600-5603) replaced loop II with linear, non-nucleotidic linkers of 13, 17, and 19 atoms in length.
  • Benseler et al. J. Am. Chem. Soc.
  • Ribozyme polynucleotides may be generated using any of various suitable methods known in the art (see, e.g., U.S. Pat. Nos 5,436,143 and 5,650,502; and PCT Publications Nos.
  • the ribozyme polynucleotide described herein can incorporate nucleotide analogs, e.g., to increase the resistance of the oligonucleotide to degradation by nucleases in a cell.
  • the ribozyme may be synthesized in any known manner, e.g., by use of a commercially available synthesizer produced, e.g., by Applied Biosystems, Inc. or Milligen.
  • ribozyme RNA sequences maybe synthesized conventionally, for example, by using RNA polymerases such as T7 or SP6.
  • the ribozyme may also be produced in recombinant vectors by suitable means.
  • internucleotidic phosphorus atoms of the polynucleotide molecules disclosed herein may be chiral, and the properties of the polynucleotides by adjusted based on the configuration of the chiral phosphorus atoms.
  • phosphorothioate-containing oligonucleotides may comprise nucleoside units that can be joined together by either substantially all Rp or substantially all Sp phosphorothioate inter-sugar linkages.
  • such phosphorothioate oligonucleotides comprising substantially chirally pure inter-sugar linkages may be produced via chemical synthesis or enzymatic approaches, as disclosed, e.g., in U.S. Patent No.5,587,261, the contents of which are incorporated herein by reference in their entirety.
  • chirally controlled polynucleotide molecules described may provide selective cleavage patterns of a target nucleic acid.
  • Morpholino-based oligomeric compounds are also described in, e.g., U.S. Patent No. 5,034,506, and Genesis, volume 30, issue 3, 2001; Heasman, J., Dev. Biol., 2002, 243, 209- 214; Dwaine A. Braasch and David R. Corey, Biochemistry, 2002, 41(14), 4503-4510); Nasevicius et al., Nat. Genet., 2000, 26, 216-220; Lacerra et al., Proc. Natl.
  • a polynucleotide molecule described herein may comprise an aptamer.
  • An aptamer may comprise any nucleic acid which specifically binds specifically to a target, e.g., protein, a small molecule, nucleic acid in a cell.
  • the aptamer is a DNA aptamer or an RNA aptamer.
  • a nucleic acid aptamer may comprise a single-stranded RNA (ssDNA or ssRNA) or DNA.
  • a single-stranded nucleic acid aptamer may form loop(s) and/or helice(s) structures.
  • the nucleic acid that forms the nucleic acid aptamer may comprise naturally occurring nucleotides, modified nucleotides with hydrocarbon or PEG linkers inserted between one or more nucleotides, modified nucleotides, naturally occurring nucleotides with hydrocarbon linkers (e.g., an alkylene) or a polyether linker (e.g., a PEG linker) inserted between one or more nucleotides, or a combination of thereof.
  • hydrocarbon linkers e.g., an alkylene
  • a polyether linker e.g., a PEG linker
  • mixmers can be polynucleotides that comprise both naturally and non-naturally occurring nucleosides or comprise two different types of non- naturally occurring nucleosides commonly in an alternating pattern.
  • Mixmers may have higher binding affinity than unmodified polynucleotides and may be used, in particular, to specifically bind a target molecule, e.g., to block a binding site on the target molecule.
  • mixmers may not recruit an rNase to a Attorney Docket No.250298.000780 target molecule and hence do not promote cleavage of the target molecule.
  • a mixmer disclosed herein may comprise a repeating pattern of naturally occurring nucleosides and nucleoside analogues, or, e.g., one type of nucleoside analogue and a second type of nucleoside analogue.
  • a mixmer need not comprise a repeating pattern and may instead comprise any arrangement of modified naturally occurring nucleosides and nucleosides or any arrangement of one type of modified nucleoside and a second type of modified nucleoside.
  • a mixmer may not comprise a region of more than 6. more than 5, more than 4, more than 3, or more than 2 consecutive naturally occurring nucleosides (e.g., DNA nucleosides).
  • the mixmer may comprise at least a region comprising at least two consecutive modified nucleosides, for example, at least two consecutive LNAs.
  • the mixmer may comprise at least a region consisting of at least three consecutive modified nucleoside units, e.g., at least three consecutive LNAs.
  • the mixmer may not comprise a region of more than 8, more than 7, more than 6, more than 5, more than 4, more than 3, or more than 2 consecutive nucleoside analogues, e.g., LNAs.
  • LNA units may be replaced with other nucleoside analogues including, but not limited to, those referred to herein.
  • mixmers may be designed to comprise a mixture of affinity enhancing modified nucleosides, such as, without limitation, in LNA nucleosides and 2'-O-Me nucleosides.
  • a mixmer may comprise modified internucleoside linkages (e.g., phosphorothioate internucleoside linkages or other linkages) between at least two, at least three, at least four, at least five, at least six or more nucleosides. [00459] In some embodiments, a mixmer may comprise one or more morpholino nucleosides.
  • a mixmer may comprise morpholino nucleosides mixed Attorney Docket No.250298.000780 (e.g., in an alternating manner) with one or more other nucleosides (e.g., DNA, RNA nucleosides) or modified nucleosides (e.g., 2'-O-Me nucleosides, LNA).
  • mixmers may be useful for splice correcting or exon skipping, for example, as described in Chen S. et al., Molecules 2016, 21, 1582, Touznik A., et al., Scientific Reports, volume 7, Article number: 3672 (2017), the contents of each which are incorporated herein by reference.
  • a mixmer may be produced using any suitable method. Preparation of mixmers is described in, for example, U.S. Patent No. 7687617, and U.S. Patent Application Publication Nos. US2012/0322851, US2009/0209748, US2009/0298916, US2006/0128646, and US2011/0077288. Additional examples of multimers are described, for example, in US Patent No.5,693,773, US Patent Application Publication Nos.2015/0247141; 2015/0315588; US 2011/0158937; the contents of each of which are incorporated herein by reference in their entireties.
  • polynucleotide molecules comprising molecular cargos disclosed herein may comprise multimers (e.g., concatemers) of two or more polynucleotide molecules connected, e.g., by a linker. Polynucleotides in a multimer may be the same or different (e.g., targeting different sites on the same gene different genes or products thereof). [00463] In some embodiments, multimers may comprise two or more polynucleotide molecules linked together by a cleavable linker. In some embodiments, multimers may comprise two or more polynucleotide molecules linked together, e.g., by a non-cleavable linker.
  • a multimer may comprise 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20 or more polynucleotide molecules linked together. In some embodiments, a multimer may comprises 2 to 5, 2 to 10, 4 to 20 or 5 to 30 polynucleotide molecules linked together. [00464] In some embodiments, a multimer may comprises two or more polynucleotide molecules linked in a linear arrangement, e.g., end-to-end. In some embodiments, a multimer may comprises two or more polynucleotide molecules linked end-to-end via a polynucleotide- based linker (e.g., an abasic linker, a poly-dT linker).
  • a polynucleotide- based linker e.g., an abasic linker, a poly-dT linker
  • a multimer comprises a 3’ end of one polynucleotide linked to a 3’ end of another polynucleotide. In some embodiments, a multimer may comprise a 5’ end of one polynucleotide linked to a 3’ end of another polynucleotide. In some embodiments, a multimer comprises a 5’ end of one polynucleotide linked to a 5’ end of another polynucleotide . In some embodiments, multimers Attorney Docket No.250298.000780 may comprise a branched structure comprising multiple polynucleotides linked together by a branching linker.
  • a polynucleotide molecule of the present disclosure can target splicing.
  • the polynucleotide can targets splicing by inducing exon skipping and restoring the reading frame within a gene.
  • the oligonucleotide may induce skipping of an exon encoding a frameshift mutation and/or an exon that encodes a premature stop codon.
  • a polynucleotide may induce exon skipping by, e.g., blocking spliceosome recognition of a splice site.
  • a polynucleotide molecule disclosed herein may induce inclusion of an exon by targeting a splice site inhibitory sequence.
  • the oligonucleotide promotes inclusion of a particular exon.
  • exon skipping results in a truncated but functional protein compared to the reference protein.
  • the polynucleotide molecule described herein may be a messenger RNA (mRNA). mRNAs comprise an open reading frame that can be translated into a polypeptide (i.e., can serve as a substrate for translation by a ribosome and amino- acylated tRNAs).
  • mRNA can comprise a phosphate-sugar backbone including ribose residues or analogs thereof, e.g., 2’-methoxy ribose residues.
  • the sugars of an mRNA phosphate-sugar backbone consist essentially of ribose residues, 2’- methoxy ribose residues, or a combination thereof.
  • Bases of an mRNA can be modified bases such as pseudouridine, N-1-methyl-pseudouridine, or other naturally occurring or non- naturally occurring bases.
  • Polypeptide Molecules [00467]
  • the molecular cargo described herein comprises a polypeptide molecule.
  • conjugates may also be referred to as “fusion proteins”.
  • fused polypeptides refers to polypeptides joined directly or indirectly (e.g., via a linker or other polypeptide).
  • the fusion protein is encoded by a single nucleic acid that encodes the p75 NTR binding protein with the polypeptide molecule.
  • the polypeptide molecule is an enzyme, a neuroprotective molecule, or an antigen-binding protein that binds to a target other than p75 NTR .
  • the polypeptide molecule is associated with pain, itch, and/or a neurological disease and/or disorder Attorney Docket No.250298.000780 described herein.
  • the polypeptide molecule is a neurotrophic factor, an antibody or antibody fragment, an antibody receptor fusion protein, or a suppressor of cytokine signaling.
  • the anti-p75 NTR fusion proteins may be useful, for example, for delivery of the fused polypeptide molecule to various tissues (e.g., nervous tissue) and/or cells in the body, including brain cells, spinal cord cells, peripheral nervous system cells e.g., sensory neurons (such as, but not limited to, dorsal root ganglion cells or trigeminal ganglion cells) and/or eye cells (e.g., retinal cells).
  • tissues e.g., nervous tissue
  • peripheral nervous system cells e.g., sensory neurons (such as, but not limited to, dorsal root ganglion cells or trigeminal ganglion cells) and/or eye cells (e.g., retinal cells).
  • Non-limiting examples of polypeptide molecules that can be fused with an p75 NTR binding protein described herein can include, e.g., enzymes, neuroprotective proteins and molecules, or other antigen-binding proteins (e.g., antibodies and antigen-binding fragments thereof).
  • Enzymes can include, without limitation, a hydrolase, including esterases, glycosylases, hydrolases that act on ether bonds, peptidases, linear amidases, diphosphatases, ketone hydrolases, halogenases, phosphoamidases, sulfohydrolases, sulfinases, desulfinases, and the like.
  • the enzyme is a glycosylase, including glycosidases and N-glycosylases.
  • the enzyme is a glycosidase, including alpha-amylase, beta-amylase, glucan 1,4-alpha-glucosidase, cellulose, endo-1,3(4)-beta-glucanase, inulinase, endo-1,4-beta-xylanase, endo-1,4-b- xylanase, dextranase, chitinase, polygalacturonidase, lysozyme, exo-alpha-sialidase, alpha- glucosidase, beta-glucosidase, alpha-galactosidase, beta-galactosidase, alpha- mannosidase, beta-mannosidase, beta-fructofuranosidase, alpha,alpha-trehalose, beta- glucuronidase, xylan endo-1,3-beta-xylosidase, x
  • the present disclosure includes anti-p75 NTR fusion proteins, e.g., wherein the antigen-binding protein of the fusion is an antibody or antigen- binding fragment thereof set forth herein, and wherein the molecular cargo is a therapeutic agent useful for treating or preventing pain, itch, e.g., a chronic itch, and/or a neurological disease or disorder.
  • the neurological disease or disorder is a neurodegenerative disease or disorder, a neurodevelopmental disease or disorder, a chronic neuropathic pain, a chronic ataxia, a physical injury, a neuropsychiatric disease or disorder, or a neurological cancer.
  • the neurodegenerative disease or disorder is Alzheimer’s disease (AD), Parkinson’s disease (PD), amyotrophic lateral sclerosis (ALS) or multiple sclerosis (MS).
  • the physical injury is traumatic brain injury, Attorney Docket No.250298.000780 spinal cord injury, stroke, or brain edema.
  • the neurological cancer is a brain cancer or a peripheral nerve cancer.
  • the pain is peripheral chronic pain, a chronic neuropathic pain, somatic pain, chronic post-operative pain, chronic itch, small fiber peripheral neuropathy, chemotherapy-induced neuropathy, painful diabetic-induced neuropathy, post-herpetic neuralgia, osteoarthritis, back pain, joint pain, trigeminal neuralgia, trigeminal pain, temporo-mandibular pain, migraine, dysautonomia, myofascial pain syndrome, or myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS).
  • the chronic neuropathic pain is trigeminal pain or trigeminal neuralgia.
  • Example methods for preparing a fusion protein comprising an antigen-binding protein are described in, e.g., US Patent No. 11,208,458, US Patent Publication No. US 2019/0112588, and Baik et al., Mol Ther. 2021 Dec 1;29(12):3512-3524; the contents of all of which are incorporated herein by reference in their entireties.
  • the p75 NTR binding proteins may also be fused to other polypeptide molecules such as, but are not limited to, an epitope (e.g., FLAG) or a tag sequence (e.g., His 6 (SEQ ID NO: 619), and the like) to allow for the detection and/or isolation of the anti-p75 NTR antigen binding protein; a ligand or a portion thereof which binds to a transmembrane receptor protein; an enzyme or portion thereof which is catalytically active; a polypeptide or peptide which promotes oligomerization, such as a leucine zipper domain; a polypeptide or peptide which increases stability, such as an immunoglobulin constant region (e.g., an Fc domain); a half- life extending polypeptide (e.g., albumin or albumin-binding peptides/proteins); a functional or non-functional antibody, or a heavy or light chain thereof; and a polypeptide which has an activity, such
  • the polypeptide molecule can be a gene editing nuclease, such as Cas protein, ZFN, TALEN. Gene editing nucleases are described in further details below.
  • anti-p75 NTR fusion proteins can be made by fusing the heterologous polypeptide molecule at either the N-terminus or at the C-terminus of the anti- p75 NTR antigen binding protein (e.g., the heavy chain and/or light chain).
  • Heterologous sequences can be fused either directly to the anti-p75 NTR antigen binding protein, either chemically or by recombinant expression from a single polynucleotide or they may be joined via a linker or adapter molecule.
  • a peptidyl linker or adapter molecule can be one or more Attorney Docket No.250298.000780 amino acid residues (or -mers), e.g., 1, 2, 3, 4, 5, 6, 7, 8, or 9 residues (or -mers), preferably from 10 to 50 amino acid residues (or -mers), e.g., 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 25, 30, 35, 40, 45, or 50 residues (or -mers), and more preferably from 15 to 35 amino acid residues (or -mers).
  • a linker or adapter molecule can also be designed with a cleavage site for a protease to allow for the separation of the fused moieties.
  • a linker can be employed.
  • the linker can be made up of amino acids linked together by peptide bonds, i.e., a peptidyl linker.
  • the linker is made up of from 1 to 20 or more amino acids linked by peptide bonds, wherein the amino acids are selected from the 20 naturally occurring amino acids.
  • the amino acids are selected from the amino acids glycine, serine, and glutamate.
  • suitable linkers include, for example, GSGEGEGSEGSG (SEQ ID NO: 642); GGSEGEGSEGGS (SEQ ID NO: 643); GGGGS (SEQ ID NO: 644), GGGS (SEQ ID NO: 645), and (GGGGS)n (SEQ ID NO: 668); wherein n is 1-10.
  • GSGEGEGSEGSG SEQ ID NO: 642
  • GGSEGEGSEGGS SEQ ID NO: 643
  • GGGGS SEQ ID NO: 644
  • GGGS SEQ ID NO: 645
  • GGGGS n
  • a conjugated molecular cargo described herein comprises a carrier, for example, a lipid-based carrier, such as a lipid nanoparticle (LNP), a liposome, a lipidoid, or a lipoplex, a polymeric nanoparticle, an inorganic nanoparticle, a peptide carrier, a nanoparticle mimic, or a nanotube.
  • a conjugated molecular cargo described herein comprises a liposome or LNP. Liposomes and LNPs are vesicles including one or more lipid bilayers.
  • a liposome or LNP includes two or more concentric bilayers separated by aqueous compartments.
  • Lipid bilayers can be functionalized and/or crosslinked to one another.
  • Lipid bilayers can include one or more proteins, polysaccharides or other molecules.
  • Lipid formulations can protect biological molecules from degradation while improving their cellular uptake.
  • Liposomes or LNPs are particles comprising a plurality of lipid molecules physically associated with each other by intermolecular forces. These include microspheres (including unilamellar and multilamellar vesicles, e.g., liposomes), a dispersed phase in an emulsion, micelles, or an internal phase in a suspension.
  • Such liposomes or LNPs can be used to encapsulate one or more nucleic acids or proteins for delivery.
  • Formulations which contain cationic lipids are useful for delivering polyanions such as nucleic Attorney Docket No.250298.000780 acids.
  • Other lipids that can be included are neutral lipids (i.e., uncharged or zwitterionic lipids), anionic lipids, helper lipids that enhance transfection, and stealth lipids that increase the length of time for which nanoparticles can exist in vivo.
  • An exemplary lipid nanoparticle can comprise a cationic lipid and one or more other components.
  • the other component can comprise a helper lipid such as cholesterol.
  • the other components can comprise a helper lipid such as cholesterol and a neutral lipid such as distearoylphosphatidylcholine (DSPC).
  • DSPC distearoylphosphatidylcholine
  • the other components can comprise a helper lipid such as cholesterol, an optional neutral lipid such as DSPC, and a stealth lipid such as S010, S024, S027, S031, or S033.
  • a helper lipid such as cholesterol
  • an optional neutral lipid such as DSPC
  • a stealth lipid such as S010, S024, S027, S031, or S033.
  • Liposomes are amphiphilic lipids which can form bilayers in an aqueous environment to encapsulate an aqueous core.
  • the polypeptide e.g., Cas protein
  • polynucleotide e.g., guide RNA
  • These lipids can have an anionic, cationic or zwitterionic hydrophilic head group.
  • Liposomes can be formed from a single lipid or from a mixture of lipids.
  • a mixture may comprise (1) a mixture of anionic lipids; (2) a mixture of cationic lipids; (3) a mixture of zwitterionic lipids; (4) a mixture of anionic lipids and cationic lipids; (5) a mixture of anionic lipids and zwitterionic lipids; (6) a mixture of zwitterionic lipids and cationic lipids; or (7) a mixture of anionic lipids, cationic lipids and zwitterionic lipids.
  • a mixture may comprise both saturated and unsaturated lipids.
  • Exemplary phospholipids include, but are not limited to, phosphatidylethanolamines, phosphatidylcholines, phosphatidylserines, and phosphatidylglycerols.
  • Cationic lipids include, but are not limited to, 1,2-distearyloxy-N,N-dimethyl-3-aminopropane (DSDMA), dioleoyl trimethylammonium propane (DOTAP), 1,2-dioleyloxy-N,Ndimethyl-3-aminopropane (DODMA), 1,2-dilinoleyloxy-N,N-dimethyl-3-aminopropane (DLinDMA), 1,2-dilinolenyloxy- N,N-dimethyl-3-aminopropane (DLenDMA).
  • DSDMA 1,2-distearyloxy-N,N-dimethyl-3-aminopropane
  • DOTAP dioleoyl trimethylammonium
  • Zwitterionic lipids include, but are not limited to, acyl zwitterionic lipids and ether zwitterionic lipids. Examples of useful zwitterionic lipids include dodecylphosphocholine, DPPC, and DOPC.
  • the liposomes or LNPs may contain one or more or all of the following: (i) a lipid for encapsulation and for endosomal escape; (ii) a neutral lipid for stabilization; (iii) a helper lipid for stabilization; and (iv) a stealth lipid. See, e.g., Finn et al. (2016) Cell Rep.
  • the liposomes or LNPs comprise cationic lipids.
  • the liposomes or LNPs comprise (9Z,12Z)-3-((4,4-bis(octyloxy)butanoyl)oxy)-2- ((((3- (diethylamino)propoxy)carbonyl)oxy)methyl)propyl octadeca-9,12-dienoate, also called 3-((4,4-bis(octyloxy)butanoyl)oxy)-2-(((3-(diethylamino)propoxy)carbonyl)oxy)methyl)propyl (9Z,12Z)-octadeca-9,12-dienoate) or another ionizable lipid.
  • the LNPs comprise molar ratios of a cationic lipid amine to RNA phosphate (N:P) of about 4.5, about 5.0, about 5.5, about 6.0, or about 6.5.
  • N:P RNA phosphate
  • the terms cationic and ionizable in the context of LNP lipids are interchangeable (e.g., wherein ionizable lipids are cationic depending on the pH).
  • the lipid for encapsulation and endosomal escape can be a cationic lipid.
  • the lipid can also be a biodegradable lipid, such as a biodegradable ionizable lipid.
  • a suitable lipid is Lipid A or LP01, which is (9Z,12Z)-3-((4,4-bis(octyloxy)butanoyl)oxy)-2- ((((3-(diethylamino)propoxy)carbonyl)oxy)methyl)propyl octadeca-9,12-dienoate, also called 3-((4,4-bis(octyloxy)butanoyl)oxy)-2-(((3-(diethylamino)propoxy)carbonyl)oxy)methyl)propyl (9Z,12Z)-octadeca-9,12-dienoate.
  • Lipid C is 2-((4-(((3- (dimethylamino)propoxy)carbonyl)oxy)hexadecanoyl)oxy)propane-1,3-diyl(9Z,9'Z,12Z,12'Z)- bis(octadeca-9,12-dienoate).
  • Lipid D is 3-(((3- (dimethylamino)propoxy)carbonyl)oxy)-13-(octanoyloxy)tridecyl 3-octylundecanoate.
  • the cationic lipids comprise C18 alkyl chains, ether linkages between the head group and alkyl chains, and 0 to 3 double bonds.
  • Such lipids include, e.g., DSDMA, DLinDMA, DLenDMA, and DODMA.
  • the cationic lipids may comprise ether linkages and pH titratable head groups.
  • Such lipids include, e.g., DODMA. Additional cationic lipids are described in U.S. Patent Nos.
  • the cationic lipids may comprise a protonatable tertiary amine head group.
  • Such lipids are referred to herein as ionizable lipids.
  • Ionizable lipids refer to lipid species comprising an ionizable amine head group and typically comprising a pKa of less than about 7.
  • ionizable amine head group In environments with an acidic pH, the ionizable amine head group is protonated such that the ionizable lipid preferentially interacts with negatively charged molecules (e.g., nucleic acids such as the recombinant polynucleotides described herein) thus facilitating liposome or LNP assembly and encapsulation. Therefore, in some embodiments, ionizable lipids can increase the loading of nucleic acids into liposomes or LNPs. In environments where the pH is greater than about 7 (e.g., physiologic pH of 7.4), the ionizable lipid comprises a neutral charge.
  • the pH is greater than about 7 (e.g., physiologic pH of 7.4)
  • the ionizable lipid comprises a neutral charge.
  • the liposomes or LNPs may comprise one or more non- cationic helper lipids.
  • helper lipids include (1,2-dilauroyl-sn-glycero-3- phosphoethanolamine) (DLPE), 1,2-diphytanoyl-sn-glycero-3-phosphoethanolamine (D iPPE), 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC), 1,2-dipalmitoyl-sn-glycero-3- phosphocholine (DPPC), 1,2-dioleyl-sn-glycero-3-phosphoethanolamine (DOPE), 1,2- dipalmitoyl-sn-glycero-3-phosphoethanolamine (DPPE), 1,2-dimyristoyl-sn-glycero-3- phosphoethanolamine (DMPE), (1,2-dioleoyl-sn-glycero-3-phospho-(1′-rac-glycerol) Attorney Docket No.250298.000780 (DOPG), 1,2-distearoyl-sn-glycero
  • biodegradable lipids suitable for use in the liposomes or LNPs described herein are biodegradable in vivo.
  • biodegradable lipids include, but are not limited to, (9Z,12Z)-3-((4,4-bis(octyloxy)butanoyl)oxy)-2-((((3-20 (diethylamino)propoxy)carbonyl)oxy)methyl)propyl octadeca-9,12-dienoate, also called 3- ((4,4-bis(octyloxy)butanoyl)oxy)-2-(((3- (diethylamino)propoxy)carbonyl)oxy)methyl)propyl(9Z,12Z)-octadeca-9,12-dienoate) or another ionizable lipid.
  • cationic and ionizable in the context of liposome or LNP lipids is interchangeable, e.g., wherein ionizable lipids are cationic depending on the pH.
  • Such lipids may be ionizable depending upon the pH of the medium they are in. For example, in a slightly acidic medium, the lipids may be protonated and thus bear a positive charge. Conversely, in a slightly basic medium, such as, for example, blood where pH is approximately 7.35, the lipids may not be protonated and thus bear no charge.
  • neutral phospholipids suitable for use in the present disclosure include, but are not limited to, 5-heptadecylbenzene-1,3-diol (resorcinol), dipalmitoylphosphatidylcholine (DPPC), distearoylphosphatidylcholine or 1,2-distearoyl-sn- glycero-3-phosphocholine (DSPC), phosphocholine (DOPC), dimyristoylphosphatidylcholine (DMPC), phosphatidylcholine (PLPC), 1,2-diarachidonoyl-sn-glycero-3-phosphocholine (DAPC), phosphatidylethanolamine (PE), egg phosphatidylcholine (EPC), dilauryloylphosphatidylcholine (DLPC), dimyristoylphosphatidylcholine (DMPC), 1-myristoyl- 2-palmitoyl phosphatidylcholine (MPPC), 1-palmitoyl
  • the neutral phospholipid may be selected from the group consisting of distearoylphosphatidylcholine (DSPC) and dimyristoyl phosphatidyl ethanolamine (DMPE).
  • Helper lipids include lipids that enhance transfection. The mechanism by which the helper lipid enhances transfection can include enhancing particle stability. In certain cases, the helper lipid can enhance membrane fusogenicity. Helper lipids include steroids, sterols, and alkyl resorcinols. Examples of suitable helper lipids suitable include cholesterol, 5-heptadecylresorcinol, and cholesterol hemisuccinate. In one example, the helper lipid may be cholesterol or cholesterol hemisuccinate.
  • Stealth lipids include lipids that alter the length of time the nanoparticles can exist in vivo. Stealth lipids may assist in the formulation process by, for example, reducing particle aggregation and controlling particle size. Stealth lipids may modulate pharmacokinetic properties of the liposomes or LNPs. Suitable stealth lipids include lipids having a hydrophilic head group linked to a lipid moiety.
  • the hydrophilic head group of stealth lipid can comprise, for example, a polymer moiety selected from polymers based on PEG (sometimes referred to as poly(ethylene oxide)), poly(oxazoline), poly(vinyl alcohol), poly(glycerol), poly(N- vinylpyrrolidone), polyaminoacids, and poly N-(2-hydroxypropyl)methacrylamide.
  • PEG means any polyethylene glycol or other polyalkylene ether polymer.
  • the PEG is a PEG-2K, also termed PEG 2000, which has an average molecular weight of about 2,000 daltons.
  • the lipid moiety of the stealth lipid may be derived, for example, from diacylglycerol or diacylglycamide, including those comprising a dialkylglycerol or dialkylglycamide group having alkyl chain length independently comprising from about C4 to about C40 saturated or unsaturated carbon atoms, wherein the chain may comprise one or more functional groups such as, for example, an amide or ester.
  • the dialkylglycerol or dialkylglycamide group can further comprise one or more substituted alkyl groups.
  • the guide RNA and the Cas protein are each introduced in the form of RNA via LNP-mediated delivery in the same LNP.
  • one or more of the RNAs can be modified.
  • guide RNAs can be modified to comprise one or more stabilizing end modifications at the 5’ end and/or the 3’ end.
  • Such modifications can include, for example, one or more phosphorothioate linkages at the 5’ end and/or the 3’ end and/or one or more 2’- Attorney Docket No.250298.000780 O-methyl modifications at the 5’ end and/or the 3’ end.
  • Cas mRNA modifications can include substitution with pseudouridine (e.g., fully substituted with pseudouridine), 5’ caps, and polyadenylation. Other modifications are also contemplated as disclosed elsewhere herein. Delivery through such methods can result in transient Cas expression and/or transient presence of the guide RNA, and the biodegradable lipids improve clearance, improve tolerability, and decrease immunogenicity.
  • the cargo can include a guide RNA or a nucleic acid encoding a guide RNA.
  • the cargo can include an mRNA encoding a Cas nuclease, such as Cas9, and a guide RNA or a nucleic acid encoding a guide RNA.
  • the cargo can include a nucleic acid construct encoding a polypeptide of interest (e.g., multidomain therapeutic protein) as described elsewhere herein.
  • the cargo can include an mRNA encoding a Cas nuclease, such as Cas9, a guide RNA or a nucleic acid encoding a guide RNA, and a nucleic acid construct encoding a polypeptide of interest (e.g., multidomain therapeutic protein).
  • the lipid component comprises an amine lipid such as a biodegradable, ionizable lipid. In some instances, the lipid component comprises biodegradable, ionizable lipid, cholesterol, DSPC, and PEG-DMG.
  • Cas9 mRNA and gRNA can be delivered to cells and animals utilizing lipid formulations comprising ionizable lipid ((9Z,12Z)-3-((4,4-bis(octyloxy)butanoyl)oxy)-2-((((3- (diethylamino)propoxy)carbonyl)oxy)methyl)propyl octadeca-9,12-dienoate, also called 3- ((4,4-bis(octyloxy)butanoyl)oxy)-2-(((3-(diethylamino)propoxy)carbonyl)oxy)methyl)propyl (9Z, 12Z)-octadeca-9,12-dienoate), cholesterol, DSPC, and PEG2k-DMG.
  • lipid formulations comprising ionizable lipid ((9Z,12Z)-3-((4,4-bis(octyloxy)butanoyl)oxy)-2-(((3
  • the cargo can comprise Cas mRNA (e.g., Cas9 mRNA) and gRNA.
  • the Cas mRNA and gRNAs can be in different ratios.
  • the LNP formulation can include a ratio of Cas mRNA to gRNA nucleic acid ranging from about 25:1 to about 1:25.
  • the liposome or LNP formulation can include a ratio of Cas mRNA to gRNA nucleic acid of from about 2:1 to about 1:2.
  • the ratio of Cas mRNA to gRNA can be about 2:1.
  • a specific example of a suitable LNP has a nitrogen-to-phosphate (N/P) ratio of about 4.5 and contains biodegradable cationic lipid, cholesterol, DSPC, and PEG2k-DMG in an about 45:44:9:2 molar ratio (about 45:about 44:about 9:about 2).
  • N/P nitrogen-to-phosphate
  • the biodegradable cationic lipid can be (9Z,12Z)-3-((4,4-bis(octyloxy)butanoyl)oxy)-2-((((3- (diethylamino)propoxy)carbonyl)oxy)methyl)propyl octadeca-9,12-dienoate, also called 3- ((4,4-bis(octyloxy)butanoyl)oxy)-2-(((3-(diethylamino)propoxy)carbonyl)oxy)methyl)propyl (9Z,12Z)-octadeca-9,12-dienoate. See, e.g., Finn et al. (2016) Cell Rep.
  • the biodegradable cationic lipid can be Lipid A ((9Z,12Z)-3-((4,4-bis(octyloxy)butanoyl)oxy)-2- ((((3-(diethylamino)propoxy)carbonyl)oxy)methyl)propyl octadeca-9,12-dienoate, also called 3-((4,4-bis(octyloxy)butanoyl)oxy)-2-(((3-(diethylamino)propoxy)carbonyl)oxy)methyl)propyl (9Z,12Z)-octadeca-9,12-dienoate).
  • the Cas9 mRNA can be in an about 1:2 ratio (about 1:about 2) by weight to the guide RNA.
  • the Cas9 mRNA can be in an about 1:1 ratio (about 1:about 1)by weight to the guide RNA.
  • the Cas9 mRNA can be in an about 2:1 (about 2:about 1) ratio by weight to the guide RNA.
  • modified Cas protein is the modified eSpCas9 variant (K848A/K1003A/R1060A) designed to reduce off-target effects. See, e.g., Slaymaker et al. (2016) Science 351(6268):84-88, herein incorporated by reference in its entirety for all purposes.
  • Other SpCas9 variants include K855A and K810A/K1003A/R1060A.
  • Cas proteins can also comprise at least two nuclease domains, such as dNase domains.
  • a wild type Cas9 protein generally comprises a RuvC-like nuclease domain and an HNH-like nuclease domain.
  • the RuvC and HNH domains can each cut a different strand of double-stranded DNA to make a double-stranded break in the DNA. See, e.g., Jinek et al. (2012) Science 337(6096):816-821, herein incorporated by reference in its entirety for all purposes.
  • One or more or all of the nuclease domains can be deleted or mutated so that they are no longer functional or have reduced nuclease activity.
  • the resulting Cas9 protein can be referred to as a nickase and can generate a single-strand break within a double-stranded target DNA but not a double-strand break (i.e., it can cleave the complementary strand or the non-complementary strand, but not both).
  • the resulting Cas protein (e.g., Cas9) will have a reduced ability to cleave both strands of a double-stranded DNA (e.g., a nuclease-null or nuclease-inactive Cas protein, or a catalytically dead Cas protein (dCas)). If none of the nuclease domains is deleted or mutated in a Cas9 protein, the Cas9 protein will retain double-strand-break-inducing activity.
  • a double-stranded DNA e.g., a nuclease-null or nuclease-inactive Cas protein, or a catalytically dead Cas protein (dCas)
  • An example of a mutation that converts Cas9 into a nickase is a D10A (aspartate to alanine at position 10 of Cas9) mutation in the RuvC domain of Cas9 from S. pyogenes.
  • H939A histidine to alanine at amino acid position 839
  • H840A histidine to alanine at amino acid position 840
  • N863A asparagine to alanine at amino acid position N863 in the HNH Attorney Docket No.250298.000780 domain of Cas9 from S. pyogenes can convert the Cas9 into a nickase.
  • mutations that convert Cas9 into a nickase include the corresponding mutations to Cas9 from S. thermophilus. See, e.g., Sapranauskas et al. (2011) Nucleic Acids Res.39(21):9275-9282 and WO 2013/141680, each of which is herein incorporated by reference in its entirety for all purposes.
  • Such mutations can be generated using methods such as site-directed mutagenesis, PCR-mediated mutagenesis, or total gene synthesis. Examples of other mutations creating nickases can be found, for example, in WO 2013/176772 and WO 2013/142578, each of which is herein incorporated by reference in its entirety for all purposes.
  • the resulting Cas protein (e.g., Cas9) will have a reduced ability to cleave both strands of a double-stranded DNA (e.g., a nuclease-null or nuclease-inactive Cas protein).
  • a double-stranded DNA e.g., a nuclease-null or nuclease-inactive Cas protein.
  • One specific example is a D10A/H840A S. pyogenes Cas9 double mutant or a corresponding double mutant in a Cas9 from another species when optimally aligned with S. pyogenes Cas9.
  • Another specific example is a D10A/N863A S. pyogenes Cas9 double mutant or a corresponding double mutant in a Cas9 from another species when optimally aligned with S. pyogenes Cas9.
  • Examples of inactivating mutations in the catalytic domains of xCas9 are the same as those described above for SpCas9.
  • Examples of inactivating mutations in the catalytic domains of Staphylococcus aureus Cas9 proteins are also known.
  • the Staphylococcus aureus Cas9 enzyme may comprise a substitution at position N580 (e.g., N580A substitution) or a substitution at position D10 (e.g., D10A substitution) to generate a Cas nickase.
  • N580A substitution e.g., N580A substitution
  • D10A substitution e.g., D10A substitution
  • Examples of inactivating mutations in the catalytic domains of Nme2Cas9 are also known (e.g., D16A or H588A).
  • Cas proteins can also be operably linked to heterologous polypeptides as fusion proteins.
  • a Cas nuclease can be fused to a cleavage domain, an epigenetic modification domain, a transcriptional activation domain, or a transcriptional repressor domain. See WO 2014/089290, herein incorporated by reference in its entirety for all purposes.
  • transcriptional activation domains include a herpes simplex virus VP 16 activation domain, VP64 (which is a tetrameric derivative of VP 16), a NFKB p65 activation domain, p53 activation domains 1 and 2, a CREB (cAMP response element binding protein) activation domain, an E2A activation domain, and an NFAT (nuclear factor of activated T-cells) activation domain.
  • a transcriptional activation system comprising a dCas9-VP64 fusion protein paired with MS2-p65-HSFl.
  • Such subcellular localization signals can be located at the N- terminus, the C-terminus, or anywhere within the Cas protein.
  • An NLS can comprise a stretch of basic amino acids, and can be a monopartite sequence or a bipartite sequence.
  • a Cas protein can comprise two or more NLSs, including an NLS (e.g., an alpha-importin NLS or a monopartite NLS) at the N-terminus and an NLS (e.g., an SV40 NLS or a bipartite NLS) at the C-terminus.
  • a Cas protein can also comprise two or more NLSs at the N-terminus and/or two or more NLSs at the C-terminus.
  • the Cas protein can be fused to two SV40 NLS sequences linked at the carboxy terminus.
  • the Cas protein may be fused with two NLSs, one linked at the N-terminus and one at the C-terminus.
  • the Cas protein may be fused with 3 NLSs or with no NLS.
  • the NLS may be a Attorney Docket No.250298.000780 monopartite sequence, such as, e.g., the SV40 NLS, PKKKRKV (SEQ ID NO: 646) or PKKKRRV (SEQ ID NO: 647).
  • the NLS may be a bipartite sequence, such as the NLS of nucleoplasmin, KRPAATKKAGQAKKKK (SEQ ID NO: 648).
  • a single PKKKRKV (SEQ ID NO: 646) NLS may be linked at the C-terminus of the Cas protein.
  • One or more linkers are optionally included at the fusion site.
  • Cas proteins can also be operably linked to a cell-penetrating domain or protein transduction domain.
  • the cell-penetrating domain can be derived from the HIV- 1 TAT protein, the TLM cell-penetrating motif from human hepatitis B virus, MPG, Pep-1, VP22, a cell penetrating peptide from Herpes simplex virus, or a polyarginine peptide sequence. See, e.g., WO 2014/089290 and WO 2013/176772, each of which is herein incorporated by reference in its entirety for all purposes.
  • the cell-penetrating domain can be located at the N-terminus, the C-terminus, or anywhere within the Cas protein.
  • Cas proteins can also be operably linked to a heterologous polypeptide for ease of tracking or purification, such as a fluorescent protein, a purification tag, or an epitope tag.
  • fluorescent proteins include green fluorescent proteins (e.g., GFP, GFP-2, tagGFP, turboGFP, eGFP, Emerald, Azami Green, Monomeric Azami Green, CopGFP, AceGFP, ZsGreenl), yellow fluorescent proteins (e.g., YFP, eYFP, Citrine, Venus, yPet, PhiYFP, ZsYellowl), blue fluorescent proteins (e.g., eBFP, eBFP2, Azurite, mKalamal, GFPuv, Sapphire, T-sapphire), cyan fluorescent proteins (e.g., eCFP, Cerulean, CyPet, AmCyanl, Midoriishi-Cyan), red fluorescent proteins (e.g., mKate, mKate2, m
  • Noncovalent strategies for synthesizing protein-nucleic acid conjugates include biotin-streptavidin and nickel-histidine methods.
  • Covalent protein-nucleic acid conjugates can be synthesized by connecting appropriately functionalized nucleic acids and proteins using a wide variety of chemistries.
  • the labeled nucleic acid is tethered to the C-terminus or the N-terminus of the Cas protein.
  • the Cas protein can be tethered to the 5’ end, the 3’ end, or to an internal region within the labeled nucleic acid. That is, the labeled nucleic acid can be tethered in any orientation and polarity.
  • the Cas protein can be tethered to the 5’ end or the 3’ end of the labeled nucleic acid.
  • Cas proteins can be provided in any form.
  • a Cas protein can be provided in the form of a protein, such as a Cas protein complexed with a gRNA.
  • the nucleic acid encoding the Cas nuclease is codon-optimized for expression in a mammalian cell. In some embodiments, the nucleic acid encoding the Cas nuclease is codon-optimized for expression in a human cell. Codon usage tables are readily available, Attorney Docket No.250298.000780 for example, at the “Codon Usage Database.” These tables can be adapted in a number of ways. See Nakamura et al. (2000) Nucleic Acids Research 28:292, herein incorporated by reference in its entirety for all purposes. Computer algorithms for codon optimization of a particular sequence for expression in a particular host are also available (see, e.g., Gene Forge).
  • Promoters that can be used in an expression construct include promoters active, for example, in one or more of a eukaryotic cell, a human cell, a non-human cell, a mammalian cell, a non-human mammalian cell, a rodent cell, a mouse cell, a rat cell, a pluripotent cell, an embryonic stem (ES) cell, an adult stem cell, a developmentally restricted progenitor cell, an induced pluripotent stem (iPS) cell, or a one-cell stage embryo.
  • Such promoters can be, for example, conditional promoters, inducible promoters, constitutive promoters, or tissue- specific promoters.
  • Cas mRNA fully substituted with pseudouridine can be used (i.e., all standard uracil residues are replaced with pseudouridine, a uridine isomer in which the uracil is attached with a carbon-carbon bond rather than nitrogen-carbon).
  • Cas mRNAs can be modified by depletion of uridine using synonymous codons.
  • capped and polyadenylated Cas mRNA fully substituted with pseudouridine can be used.
  • Attorney Docket No.250298.000780 [00565]
  • Cas mRNAs can comprise a modified uridine at least at one, a plurality of, or all uridine positions.
  • the modified uridine is a combination of 5-iodouridine and 5-methoxyuridine.
  • Cas mRNAs disclosed herein can also comprise a 5’ cap, such as a Cap0, Cap1, or Cap2.
  • a 5’ cap is generally a 7-methylguanine ribonucleotide (which may be further modified, e.g., with respect to ARCA) linked through a 5’-triphosphate to the 5’ position of the first nucleotide of the 5’-to-3’ chain of the mRNA (i.e., the first cap-proximal nucleotide).
  • Cap1 or Cap2 Most endogenous higher eukaryotic mRNAs, including mammalian mRNAs such as human mRNAs, comprise Cap1 or Cap2.
  • Cap0 and other cap structures differing from Cap1 and Cap2 may be immunogenic in mammals, such as humans, due to recognition as non-self by components of the innate immune system such as IFIT-1 and IFIT-5, which can result in elevated cytokine levels including type I interferon.
  • Vaccinia capping enzyme is commercially available (New England Biolabs Cat. No. M2080S) and has RNA triphosphatase and guanylyltransferase activities, provided by its D1 subunit, and guanine methyltransferase, provided by its D12 subunit.
  • a construct comprising a transgene may be heterologous with respect to its insertion site, for example, insertion of a heterologous transgene into a “safe harbor” locus.
  • a construct comprising a transgene may be non-heterologous with respect to its insertion site, for example, insertion of a wild-type transgene into its endogenous locus.
  • safe harbor loci can be targeted with high efficiency, and safe harbor loci can be disrupted with no overt phenotype.
  • safe harbor loci include ALB, CCR5, HPRT, AAVS1 (PPP1 R12C), Rosa (e.g., Rosa26), AngptiS, ApoC3, ASGR2, FIX (F9), G6PC, Gys2, HGD, Lp(a), Pcsk9, SERPINA1, TF, and TTR. See, e.g., US Patent Nos. 7,888,121; 7,972,854; 7,914,796; 7,951,925; 8,110,379; 8,409,861; 8,586,526; and US Patent Publication Nos.
  • target genomic loci include an ALB locus, a EESYR locus, a SARS locus, position 188,083,272 of human chromosome 1 or its non-human mammalian orthologue, position 3,046,320 of human chromosome 10 or its non-human mammalian orthologue, position 67, 328,980 of human chromosome 17 or its non-human mammalian orthologue, an adeno-associated virus site 1 (AAVS1) on chromosome, a naturally occurring site of integration of AAV virus on human chromosome 19 or its non-human mammalian orthologue, a chemokine receptor 5 (CCR5) gene, a chemokine receptor gene encoding an HIV-1 coreceptor, or a mouse Rosa26 locus or its non-murine mammalian orthologue.
  • ALB locus an ALB locus
  • EESYR locus a SARS locus
  • SARS locus position 188,083,272 of human chromosome
  • the heterologous gene may be inserted into a safe harbor locus and use the safe harbor locus’s endogenous signal sequence.
  • the heterologous gene may comprise its own signal sequence, may be inserted into the safe harbor locus, and may further use the safe harbor locus’s endogenous signal sequence.
  • the gene may comprise its own signal sequence and an internal ribosomal entry site (IRES), may be inserted into the safe harbor locus, and may further use the safe harbor locus’s endogenous signal sequence.
  • IRS internal ribosomal entry site
  • nuclease agents can be used, one targeting a nuclease target sequence including or proximate to the start codon, and one targeting a nuclease target sequence including or proximate to the stop codon, wherein cleavage by the nuclease agents can result in deletion of the coding region between the two nuclease target sequences.
  • nuclease agents can be used, with one or more (e.g., two) targeting nuclease target sequences including or proximate to the start codon, and one or more (e.g., two) targeting nuclease target sequences including or proximate to the stop codon, wherein cleavage by the nuclease agents can result in deletion of the coding region between the nuclease target sequences including or proximate to the start codon and the nuclease target sequence including or proximate to the stop codon.
  • CRISPR/Cas systems used in the compositions and methods disclosed herein can be non-naturally occurring.
  • the Cas protein (e.g., Cas9) may be complexed with a gRNA to form a ribonucleoprotein complex (RNP).
  • a molecular cargo (e.g., liposome or LNP) of the present disclosure comprises a ribonucleoprotein complex (RNP) comprising a Cas protein (e.g., Cas9) and a gRNA.
  • a molecular cargo (e.g., liposomes and LNPs) described herein may comprise one or more components from gene editing systems other than a CRISPR/Cas system.
  • the target sequence can be endogenous (or native) to the cell or the target sequence can be exogenous to the cell.
  • a target sequence that is exogenous to the cell is not naturally occurring in the genome of the cell.
  • the target sequence can also exogenous to the polynucleotides of interest that one desires to be positioned at the target locus. In some cases, the target sequence is present only once in the genome of the host cell. [00581] Active variants and fragments of the exemplified target sequences are also provided.
  • nuclease molecular cargo that can be employed in the various methods and compositions disclosed herein is a Transcription Activator-Like Effector Attorney Docket No.250298.000780 Nuclease (TALEN).
  • TAL effector nucleases are a class of sequence-specific nucleases that can be used to make double-strand breaks at specific target sequences in the genome of a prokaryotic or eukaryotic organism.
  • TAL effector nucleases are created by fusing a native or engineered transcription activator-like (TAL) effector, or functional part thereof, to the catalytic domain of an endonuclease such as Fokl.
  • the unique, modular TAL effector DNA binding domain allows for the design of proteins with potentially any given DNA recognition specificity.
  • the DNA binding domains of the TAL effector nucleases can be engineered to recognize specific DNA target sites and thus, used to make double-strand breaks at desired target sequences. See WO 2010/079430; Morbitzer et al. (2010) Proc. Natl. Acad. Sci. U.S.A. 107(50:21617- 21622; Scholze & Boch (2010) Virulence 1:428-432; Christian et al. (2010) Genetics 186:757-761; Li et al. (2011) Nucleic Acids Res. 39(l):359-372; and Miller et al.
  • TALENs can be used to edit genomes by inducing double-strand breaks (DSB), which cells respond to with repair mechanisms.
  • DSB double-strand breaks
  • Examples of suitable TAL nucleases, and methods for preparing suitable TAL nucleases, are disclosed, e.g., in US 2011/0239315 Al, US 2011/0269234 A1, US 2011/0145940 A1, US 2003/0232410 A1, US 2005/0208489 A1, US 2005/0026157 A1, US 2005/0064474 A1, US 2006/0188987 A1, and US 2006/0063231 A1, each of which is herein incorporated by reference in its entirety for all purposes.
  • TALENs Transcription Activator-Like Effector Nucleases
  • TALEs Transcription activator- like effectors
  • TALEN is also used to refer to one or both members of a pair of TALENs that are engineered to work together to Attorney Docket No.250298.000780 cleave DNA at the same site.
  • TALENs that work together may be referred to as a left-TALEN and a right-TALEN, which references the handedness of DNA. See U.S. Patent Nos. 8,586,363; 8,450,471; 8,440,431; 8,440,432; and 8,697,853, all of which are incorporated by reference herein in their entirety.
  • Another example of a DNA-binding protein is a zinc finger protein.
  • Such zinc finger proteins can be linked or fused to, for example, an epigenetic modification domain, a transcriptional activation domain, or a transcriptional repressor domain. Examples of such domains are described with respect to Cas proteins, below, and can also be found, for example, in WO 2011/145121, herein incorporated by reference in its entirety for all purposes.
  • another example of a nuclease molecular cargo that can be employed in the various methods and compositions disclosed herein is a zinc-finger nuclease (ZFN).
  • ZFN zinc-finger nuclease
  • each monomer of the ZFN comprises three or more zinc finger-based DNA binding domains, wherein each zinc finger-based DNA binding domain binds to a 3 bp subsite.
  • the ZFN is a chimeric protein comprising a zinc finger-based DNA binding domain operably linked to an independent nuclease such as a Fokl endonuclease.
  • the nuclease molecular cargo can comprise a first ZFN and a second ZFN, wherein each of the first ZFN and the second ZFN is operably linked to a Fokl nuclease subunit, wherein the first and the second ZFN recognize two contiguous target DNA sequences in each strand of the target DNA sequence separated by about 5-7 bp spacer, and wherein the Fokl nuclease subunits dimerize to create an active nuclease that makes a double strand break.
  • a molecular cargo described herein e.g., a polynucleotide molecule described herein, or a liposome or LNP
  • an p75 NTR binding protein for delivery to a site of interest (e.g., brain or spinal cord).
  • the p75 NTR binding protein is conjugated to at least one molecular cargo (e.g., polynucleotide molecule, polypeptide molecule, or liposome or LNP).
  • an p75 NTR binding protein is conjugated to the 5' terminus of a polynucleotide molecule, the 3' terminus of a polynucleotide molecule, an internal site on a polynucleotide molecule, or in any combinations thereof.
  • an p75 NTR binding protein is conjugated to the N terminus of a polypeptide molecule, the C terminus of a polypeptide molecule, an internal site on a polypeptide molecule, or in any combinations thereof.
  • the p75 NTR binding protein is conjugated to at least one molecular cargo (e.g., at least one polynucleotide molecule, polypeptide molecule and/ or liposome or LNP).
  • the p75 NTR binding protein is conjugated to at least 2, 3, 4, 5, 6, 7, 8, 10, 12, 16, 20, 24, 30 or more molecular cargoes described herein (e.g., at least 2, 3, 4, 5, 6, 7, 8, 10, 12, 16, 20, 24, 30 or more polynucleotide molecules, polypeptide molecules, and/or liposomes or LNPs).
  • the p75 NTR binding protein is conjugated to a molecular cargo (e.g., polynucleotide molecule, polypeptide molecule, or liposome or LNP) in a site- specific manner.
  • a molecular cargo e.g., polynucleotide molecule, polypeptide molecule, or liposome or LNP
  • a lysine residue e.g., polynucleotide molecule, polypeptide molecule, or liposome or LNP
  • a lysine residue e.g., polynucleotide molecule, polypeptide molecule, or liposome or LNP
  • a lysine residue e.g., polynucleotide molecule, polypeptide molecule, or liposome or LNP
  • one or more molecular cargoes is conjugated to an FGFR3 binding protein .
  • about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 20, 24, 30, 36 or more molecular cargoes are conjugated to one p75 NTR binding protein.
  • 1 molecular cargo is conjugated to one p75 NTR binding protein.
  • 2 molecular cargoes are conjugated to one p75 NTR binding protein .
  • the one or Attorney Docket No.250298.000780 more molecular cargoes are the same. In other cases, the one or more molecular cargoes are different. [00599] In some embodiments, the number of molecular cargoes conjugated to an p75 NTR binding protein forms a ratio. In some embodiments, the ratio is referred to as a DAR (drug-to-antibody) ratio, in which the drug as referred to herein is a molecular cargo described herein (e.g., polynucleotide molecule, polypeptide molecule, or liposome or LNP).
  • DAR drug-to-antibody ratio
  • the DAR ratio of the molecular cargo to p75 NTR binding protein is about 11 or greater. In some embodiments, the DAR ratio of the molecular cargo to p75 NTR binding protein is about 12 or greater. In some embodiments, the DAR ratio of the molecular cargo to p75 NTR binding protein is about 16 or greater. In some embodiments, the DAR ratio of the molecular cargo to p75 NTR binding protein is about 20 or greater. In some embodiments, the DAR ratio of the molecular cargo to p75 NTR binding protein is about 24 or greater.
  • the DAR ratio of the molecular cargo to p75 NTR binding protein is about 11. In some embodiments, the DAR ratio of the molecular cargo to p75 NTR binding protein is about 12. In some embodiments, the DAR ratio of the molecular cargo to p75 NTR binding protein is about 13. In some embodiments, the DAR ratio of the molecular cargo to p75 NTR binding protein is about 14. In some embodiments, the DAR ratio of the molecular cargo to p75 NTR binding protein is about 15. In some embodiments, the DAR ratio of the molecular cargo to p75 NTR binding protein is about 16.
  • a molecular cargo described herein e.g., a polynucleotide molecule or polypeptide molecule described herein, or a Attorney Docket No.250298.000780 liposome or LNP
  • a molecular cargo described herein is conjugated to an p75 NTR binding protein directly.
  • a molecular cargo described herein e.g., a polynucleotide molecule or polypeptide molecule described herein, or a liposome or LNP
  • the conjugation is as described in: Dawson, et al. "Synthesis of proteins by native chemical ligation,” Science 1994, 266, 776- 779; Dawson, et al. "Modulation of Reactivity in Native Chemical Ligation through the Use of Thiol Additives," J. Am. Chem. Soc.1997, 119, 4325-4329;
  • Hackeng, et al. Protein synthesis by native chemical ligation: Expanded scope by using straightforward methodology.
  • Wu, et al. Building complex glycopeptides: Development of a cysteine-free native chemical ligation protocol," Angew. Chem.
  • the conjugation is as described in U.S. Patent No. 8,936,910.
  • the molecular cargo described herein e.g., a polynucleotide molecule or polypeptide molecule, described herein, or a liposome or LNP
  • the molecular cargo described herein is conjugated to the p75 NTR binding protein either site-specifically or non-specifically via native ligation chemistry.
  • the molecular cargo described herein e.g., a polynucleotide molecule or polypeptide molecule described herein, or a liposome or LNP
  • the unnatural amino acid comprises p-acetylphenylalanine (pAcPhe).
  • the keto group of pAcPhe is selectively coupled to an alkoxy-amine derivatived conjugating moiety to form an oxime bond.
  • the molecular cargo described herein e.g., a polynucleotide molecule or polypeptide molecule described herein, or a liposome or LNP
  • the molecular cargo described herein is conjugated to the p75 NTR binding protein by a site-directed method utilizing an enzyme- catalyzed process.
  • the site-directed method utilizes SMARTagTM technology (Catalent, Inc.).
  • the SMARTagTM technology comprises generation of a formylglycine (fGly) residue from cysteine by formylglycine-generating enzyme (FGE) through an oxidation process under the presence of an aldehyde tag and the subsequent conjugation of fGly to an alkylhydraine-functionalized molecular cargo described herein (e.g., a polynucleotide molecule or polypeptide molecule described herein, or a liposome or LNP) via hydrazino-Pictet-Spengler (HIPS) ligation.
  • FGE formylglycine residue from cysteine by formylglycine-generating enzyme
  • HIPS hydrazino-Pictet-Spengler
  • the enzyme-catalyzed process comprises transglutaminase, e.g., microbial transglutaminase (mTG).
  • the molecular cargo described herein (e.g., a polynucleotide molecule or polypeptide molecule described herein, or a liposome or LNP) is conjugated to the p75 NTR binding protein utilizing a microbial transglutaminase-catalyzed process.
  • mTG catalyzes the formation of a covalent bond between the amide side chain of a glutamine within the recognition sequence and a primary amine of a functionalized molecular cargo described herein (e.g., a polynucleotide molecule or polypeptide molecule described herein, or a liposome or LNP).
  • mTG is produced from Streptomyces mobarensis. (see Strop et al., "Location matters: site of conjugation modulates stability and pharmacokinetics of antibody drug conjugates," Chemistry and Biology 20(2) 161-167 (2013)). Attorney Docket No.250298.000780 [00610]
  • a sequence of amino acids comprising an acceptor glutamine residue are incorporated into (e.g., appended to) a polypeptide sequence, under suitable conditions, for recognition by a TG. This sequence leads to cross-linking by the TG through a reaction between an amino acid side chain within the sequence of amino acids and a reaction partner.
  • the recognition tag may be a peptide sequence that is not naturally present in the polypeptide comprising the TG recognition tag.
  • the TG recognition tag comprises at least one Gln.
  • the tGase recognition tag comprises an amino acid sequence XXQX, wherein X is any amino acid (e.g., conventional amino acid Leu, Ala, Gly, Ser, Val, Phe, Tyr, His, Arg, Asn, Glu, Asp, Cys, Gln, Ile, Met, Pro, Thr, Lys, or Trp or nonconventional amino acid).
  • the acyl donor glutamine-containing tag comprises an amino acid sequence selected from the group consisting of LLQGG (SEQ ID NO: 650), LLQG (SEQ ID NO: 651), LSLSQG (SEQ ID NO: 652), gGGLLQGG (SEQ ID NO: 653), gLLQG (SEQ ID NO: 654), LLQ, gSPLAQSHGG (SEQ ID NO: 655), gLLQGGG (SEQ ID NO: 656), gLLQGG (SEQ ID NO: 657), gLLQ (SEQ ID NO: 658), LLQLLQGA (SEQ ID NO: 659), LLQGA (SEQ ID NO: 660), LLQYQGA (SEQ ID NO: 661), LLQGSG (SEQ ID NO: 624), LLQYQG (SEQ ID NO: 662), LLQLLQG (SEQ ID NO: 663), SLLQG (SEQ ID NO: 650),
  • the acyl donor glutamine-containing tag is present at the N-terminus of the antigen-binding protein. In some embodiments, the acyl donor glutamine-containing tag is present at the C-terminus of the antigen-binding protein. In some embodiments, the acyl donor glutamine-containing tag is present both at the N-terminus and the C-terminus of the antigen-binding protein. In some embodiments, the antigen-binding protein and the molecular cargo described herein are conjugated via a linker.
  • the molecular cargo described herein (e.g., a polynucleotide molecule or polypeptide molecule described herein, or a liposome or LNP) is conjugated to the p75NTR binding protein by a method as described in PCT Publication No. W02014/140317, which utilizes a sequence-specific transpeptidase.
  • the molecular cargo described herein (e.g., a polynucleotide molecule or polypeptide molecule described herein, or a liposome or LNP) is conjugated to the p75 NTR binding protein by a method as described in U.S.
  • the molecular cargo described herein e.g., a polynucleotide molecule or polypeptide molecule described herein, or a liposome or LNP
  • the molecular cargo described herein is Attorney Docket No.250298.000780 conjugated to the p75 NTR binding protein utilizing Azide-Alkyne Cycloaddition (CuAAC) click chemistry.
  • Azides and alkynes can undergo catalyst free [3+2] cycloaddition by a using the reaction of activated alkynes with azides.
  • a tetrazine (Tzn)-activated p75 NTR binding protein may be cross-linked to a trans-cyclooctene (TCO)-activated molecular cargo described herein (e.g., a polynucleotide molecule or polypeptide molecule described herein, or a liposome or LNP).
  • TCO trans-cyclooctene
  • a TCO-activated p75 NTR binding protein may be crosslinked to a Tzn- activated molecular cargo described herein (e.g., a polynucleotide molecule or polypeptide molecule described herein, or a liposome or LNP).
  • Linkers e.g., Linkers [00614]
  • Complexes described herein generally comprise a linker that connects a binding agent to a molecular cargo (e.g., a polynucleotide molecule, polypeptide molecule, a liposome or an LNP).
  • a linker comprises at least one covalent bond.
  • a linker may be a single bond, e.g., a disulfide bond or disulfide bridge, that connects a binding agent to a polynucleotide molecule, polypeptide molecule, or a liposome or LNP.
  • a linker may connect a binding agent to a polynucleotide molecule, polypeptide molecule, or a liposome or LNP through multiple covalent bonds.
  • a linker is generally stable in vitro and in vivo, and may be stable in certain cellular environments.
  • linker does not negatively impact the functional properties of either the binding agent or the polynucleotide molecule, polypeptide molecule, or a liposome or LNP.
  • Examples and methods of synthesis of linkers are known in the art (see, e.g. Kline, T. Attorney Docket No.250298.000780 et al. "Methods to Make Homogenous Antibody Drug Conjugates.” Pharmaceutical Research, 2015, 32:11, 3480-3493; Jain, N. et al. "Current ADC Linker Chemistry” Pharm Res. 2015, 32:11, 3526-3540; McCombs, J. R. and Owen, S.
  • a precursor to a linker typically will contain two different reactive species that allow for attachment to both the binding agent and a polynucleotide molecule, polypeptide molecule, or a liposome or LNP.
  • the two different reactive species may be a nucleophile and/or an electrophile.
  • a linker is connected to a binding agent via conjugation to a lysine residue or a cysteine residue of the binding agent.
  • a linker is connected to a cysteine residue of a muscle-targeting agent via a maleimide-containing linker, wherein optionally the maleimide-containing linker comprises a maleimidocaproyl or maleimidomethyl cyclohexane- 1 -carboxylate group.
  • a linker is connected to a cysteine residue of a muscle-targeting agent or thiol functionalized molecular cargo via a 3-arylpropionitrile functional group.
  • a cleavable linker may be a protease-sensitive linker, a pH-sensitive linker, or a glutathione-sensitive linker. These linkers are generally cleavable only intracellularly and are preferably stable in extracellular environments.
  • Protease-sensitive linkers are cleavable by protease enzymatic activity. These linkers typically comprise peptide sequences and may be 2-10 amino acids, about 2-5 amino acids, about 5-10 amino acids, about 10 amino acids, about 5 amino acids, about 3 amino acids, or about 2 amino acids in length. In some embodiments, a peptide sequence may comprise naturally-occurring amino acids, e.g.
  • Photocleavable linkers can also be used with the present disclosure. Photocleavable linkers are cleaved upon exposure to light (see, e.g., Goldmacher et al., Bioconj. Chem. 3:104-107, 1992), thereby releasing the targeted agent upon exposure to light. (Hazum et al., Proc. Eur. Pept. Symp., 16 th , Brunfeldt, K (Ed), pp. 105 110, 1981; nitrobenzyl group as a photocleavable protective group for cysteine; Yen et al., Makromol.
  • a polynucleotide of the present disclosure is fused to a secretion signal sequence.
  • Polypeptides encoded by such polynucleotides are also within the scope of the present disclosure.
  • a polynucleotide described herein can be DNA or RNA.
  • Nucleotide sequences of HCVRs and LCVRs of anti-p75 NTR protein-drug conjugates set forth herein are summarized below in Table 1-2.
  • Polynucleotides encoding an anti-p75 NTR protein-drug conjugates, or polypeptide portion(s) thereof, that include one or more of the HCVRs and/or LCVRs set forth in Table 1-2 form part of the present disclosure.
  • a nucleic acid molecule as described herein comprises a nucleic acid sequence encoding any of the HCVR amino acid sequences listed in Table 1- 2; in certain embodiments the nucleic acid molecule comprises a polynucleotide sequence selected from any of the HCVR nucleic acid sequences listed in Table 1-2, or a substantially similar sequence thereof having at least 90%, at least 95%, at least 98% or at least 99% sequence identity thereto.
  • the nucleic acid molecule comprises a polynucleotide sequence selected from any of the LCVR nucleic acid sequences listed in Table 1-2, or a substantially similar sequence thereof having at least 90%, at least 95%, at least 98% or at least 99% sequence identity thereto.
  • the nucleic acid molecule comprises a polynucleotide sequence selected from any of the HCDR1 nucleic acid sequences listed in Table 1-2, or a substantially similar sequence thereof having at least 90%, at least 95%, at least 98% or at least 99% sequence identity thereto.
  • the nucleic acid molecule comprises a polynucleotide sequence selected from any of the HCDR2 nucleic acid sequences listed in Table 1-2, or a substantially similar sequence thereof having at least 90%, at least 95%, at least 98% or at least 99% sequence identity thereto.
  • the nucleic acid molecule comprises a polynucleotide sequence selected from any of the HCDR3 nucleic acid sequences listed in Table 1-2, or a substantially similar sequence thereof having at least 90%, at least 95%, at least 98% or at least 99% sequence identity thereto.
  • the nucleic acid molecule comprises a polynucleotide sequence selected from any of the LCDR1 nucleic acid sequences listed in Table 1-2, or a Attorney Docket No.250298.000780 substantially similar sequence thereof having at least 90%, at least 95%, at least 98% or at least 99% sequence identity thereto.
  • the nucleic acid molecule comprises a polynucleotide sequence selected from any of the LCDR2 nucleic acid sequences listed in Table 1-2, or a substantially similar sequence thereof having at least 90%, at least 95%, at least 98% or at least 99% sequence identity thereto.
  • the nucleic acid molecule comprises a polynucleotide sequence selected from any of the LCDR3 nucleic acid sequences listed in Table 1-2, or a substantially similar sequence thereof having at least 90%, at least 95%, at least 98% or at least 99% sequence identity thereto.
  • a "promoter” or “promoter sequence” is a DNA regulatory region capable of binding an RNA polymerase in a cell (e.g., directly or through other promoter- bound proteins or substances) and initiating transcription of a coding sequence.
  • a promoter may be operably linked to other expression control sequences, including enhancer and repressor sequences and/or with a polynucleotide of the disclosure.
  • a polynucleotide encoding a polypeptide is "operably linked" to a promoter or other expression control sequence when, in a cell or other expression system, the sequence directs RNA polymerase mediated transcription of the coding sequence into RNA, preferably mRNA, which then may be RNA spliced (if it contains introns) and, optionally, translated into a protein encoded by the coding sequence.
  • the present disclosure includes a polynucleotide comprising the following polynucleotide pairs encoding a VH and VL: SEQ ID NO: 1 and SEQ ID NO: 9; SEQ ID NO: 2 and SEQ ID NO: 29; SEQ ID NO: 41 and SEQ ID NO: 49; SEQ ID NO: 57 and SEQ ID NO: 65; SEQ ID NO: 77 and SEQ ID NO: 85; SEQ ID NO: 97 and SEQ ID NO: 105; SEQ ID NO: 115 and SEQ ID NO: 123; SEQ ID NO: 135 and SEQ ID NO: 143; SEQ ID NO: 154 and SEQ ID NO: 161; SEQ ID NO: 172 and SEQ ID NO: 178; SEQ ID NO: 188 and SEQ ID NO: 196; SEQ ID NO: 206 and SEQ ID NO: 214; SEQ ID NO: 226 and SEQ ID NO: 234; SEQ
  • the present disclosure includes a polynucleotide comprising the following polynucleotide sets which encode a HCDR1, HCDR2, HCDR3, LCDR1, LCDR2 and LCDR3: SEQ ID NOs: 3, 5, 7, 11, 13 and 15; SEQ ID NOs: 23, 25, 27, 31, 33 and 35; SEQ ID NOs: 43, 45, 47, 11, 13 and 51; SEQ ID NOs: 59, 61, 63, 67, 69 and 71; SEQ ID NOs: 79, 81, 83, 87, 89 and 91; SEQ ID NOs: 99, 101, 103, 107, 33 and 109; SEQ ID NOs: 117, 119, 121, 125, 127 and 129; SEQ ID NOs: 137, 139, 141, 145, 147 and 148; SEQ ID NOs: 156, 157, 159, 163, 165 and 166; SEQ ID NOs: 156, 174,
  • the present disclosure includes a polynucleotide comprising the following polynucleotide pairs encoding a HC and LC: SEQ ID NO: 17 and SEQ ID NO: 19; SEQ ID NO: 37 and SEQ ID NO: 39; SEQ ID NO: 53 and SEQ ID NO: 55; SEQ ID NO: 73 and SEQ ID NO: 75; SEQ ID NO: 93 and SEQ ID NO: 95; SEQ ID NO: 111 and SEQ ID NO: 113; SEQ ID NO: 131 and SEQ ID NO: 133; SEQ ID NO: 150 and SEQ ID NO: 152; SEQ ID NO: 168 and SEQ ID NO: 170; SEQ ID NO: 184 and SEQ ID NO: 186; SEQ ID NO: 202 and SEQ ID NO: 204; SEQ ID NO: 222 and SEQ ID NO: 224; SEQ ID NO: 240 and SEQ ID NO: 242; SEQ ID NO: 256 and SEQ ID NO: 258
  • a "variant" of a polynucleotide refers to a polynucleotide comprising a nucleotide sequence that is at least about 70-99.9% (e.g., 70, 72, 74, 75, 76, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 99.5, 99.9%) identical to a referenced nucleotide sequence that is set forth herein; when the comparison is performed by a BLAST algorithm wherein the parameters of the algorithm are selected to give the largest match between the respective sequences over the entire length of the respective reference sequences (e.g., expect threshold: 10; word size: 28; max matches in a query range: 0; match/mismatch scores: 1, -2; gap costs: linear).
  • a variant of a nucleotide Attorney Docket No.250298.000780 sequence specifically set forth herein comprises one or more (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 or 12) point mutations, insertions (e.g., in frame insertions) or deletions (e.g., in frame deletions) of one or more nucleotides.
  • Such mutations may, in an embodiment, be missense or nonsense mutations.
  • such a variant polynucleotide encodes an immunoglobulin polypeptide chain which can be incorporated into an p75 NTR binding protein, i.e., such that the protein retains specific binding to p75 NTR .
  • Eukaryotic and prokaryotic host cells may be used as hosts for expression of an p75 NTR binding protein (e.g., antibody or antigen-binding fragment thereof).
  • p75 NTR binding protein e.g., antibody or antigen-binding fragment thereof.
  • host cells are well known in the art and many are available from the American Type Culture Collection (ATCC). These host cells include, inter alia, Chinese hamster ovary (CHO) cells, NSO, SP2 cells, HeLa cells, baby hamster kidney (BHK) cells, monkey kidney cells (COS), human hepatocellular carcinoma cells (e.g., Hep G2), A549 cells, 3T3 cells, HEK-293 cells and a number of other cell lines.
  • CHO Chinese hamster ovary
  • SP2 cells HeLa cells
  • BHK baby hamster kidney
  • COS monkey kidney cells
  • human hepatocellular carcinoma cells e.g., Hep G2
  • A549 cells 3T3 cells
  • Mammalian host cells include human, mouse, rat, dog, monkey, pig, goat, bovine, horse and hamster cells.
  • Other cell lines that may be used are insect cell lines (e.g., Spodoptera frugiperda or Trichoplusia ni), amphibian cells, bacterial cells, plant cells and fungal cells.
  • Fungal cells include yeast and filamentous fungus cells including, for example, Pichia, Pichia pastoris, Pichia finlandica, Pichia trehalophila, Pichia koclamae, Pichia membranaefaciens, Pichia minuta (Ogataea minuta, Pichia lindneri), Pichia opuntiae, Pichia thermotolerans, Pichia salictaria, Pichia guercuum, Pichia pijperi, Pichia stiptis, Pichia methanolica, Pichia sp., Saccharomyces cerevisiae, Saccharomyces sp., Hansenula polymorpha, Kluyveromyces sp., Kluyveromyces lactis, Candida albicans, Aspergillus nidulans, Aspergillus niger, Aspergillus oryzae, Trichoderma reesei, Chry
  • the present disclosure includes an isolated host cell (e.g., a CHO cell or any type of host cell set forth above) comprising an antigen-binding protein, a VH, VL, HC, LC or CDRs thereof (or variant thereof), such as REGN14148; REGN14149; REGN14150; REGN14151; REGN14152; REGN14153; REGN14154; REGN14155; REGN14156; REGN14157; REGN14158; REGN14159; REGN14160; REGN14161; REGN14162; REGN14163; REGN14164; REGN14165; REGN14175; REGN14176; REGN14177; REGN14178; REGN14179; REGN14180; REGN14181; REGN14182; REGN14183; REGN14184; REGN14185; REGN14186; REGN14187; REGN14188; REGN14189; REGN14190; REGN14191; REGN19513; REGN19514; REGN19515;
  • a host cell includes two separate polynucleotides, one encoding a V H and the other encoding a V L ; or one encoding a HC and the other encoding a LC.
  • the present disclosure also includes a cell which is expressing p75 NTR or an antigenic fragment or fusion thereof (e.g., His6 (SEQ ID NO: 619), Fc (e.g., mouse Fc (mFc)), myc, or mycmycHis6 (mmh) (“His6” disclosed as SEQ ID NO: 619)) which is bound by an antigen-binding protein of the present disclosure (e.g., an antibody or antigen-binding fragment thereof), for example, REGN14148; REGN14149; REGN14150; REGN14151; REGN14152; REGN14153; REGN14154; REGN14155; REGN14156; REGN14157; REGN14158; REGN14159; REGN14160;
  • the present disclosure also provides a complex comprising an p75 NTR binding protein, e.g., antibody or antigen-binding fragment thereof, as discussed herein complexed with p75 NTR polypeptide or an antigenic fragment thereof or fusion thereof and/or with a secondary antibody or antigen- binding fragment thereof (e.g., detectably labeled secondary antibody) that binds specifically to the anti-p75 NTR antibody or fragment.
  • the complex is in vitro (e.g., is immobilized to a solid substrate) or is in the body of a subject.
  • a myc tag has the amino acid sequence EQKLISEEDLGG (SEQ ID NO: 618), a His6 (SEQ ID NO: 619) or hexahis (SEQ ID NO: 619) or hexahistidine (SEQ ID NO: 619) tag has the amino acid sequence HHHHHH (SEQ ID NO: 619), an mmh tag has the amino acid sequence EQKLISEEDLGGEQKLISEEDLHHHHHH (SEQ ID NO: 620) and a mouse Fc tag has the amino acid sequence EPRGPTIKPCPPCKCPAPNLLGGPSVFIFPPKIKDVLMISLSPIVTCVVVDVSEDDPDVQISWFVNNVEVHTAQTQT HREDYNSTLRVVSALPIQHQDWMSGKEFKCKVNNKDLPAPIERTISKPKGSVRAPQVYVLPPPEEEMTKKQVTLTCM VTDFMPEDIYVEWTNNGKTELNYKNTEPV
  • the present disclosure also provides a complex comprising an anti- p75 NTR protein-drug conjugate, as discussed herein complexed with a p75 NTR polypeptide or Attorney Docket No.250298.000780 an antigenic fragment thereof or fusion thereof and/or with a secondary antibody or antigen- binding fragment thereof (e.g., detectably labeled secondary antibody) that binds specifically to the anti-p75 NTR protein-drug conjugate.
  • the complex is in vitro (e.g., is immobilized to a solid substrate) or is in the body of a subject.
  • Recombinant p75 NTR binding proteins e.g., antibodies and antigen-binding fragments, or anti-p75 NTR fusion proteins disclosed herein may also be produced in an E. coli/T7 expression system.
  • polynucleotides encoding the anti-p75 NTR antibody immunoglobulin molecules described herein e.g., HC, LC, VH and/or VL or CDRs thereof of (REGN14148; REGN14149; REGN14150; REGN14151; REGN14152; REGN14153; REGN14154; REGN14155; REGN14156; REGN14157; REGN14158; REGN14159; REGN14160; REGN14161; REGN14162; REGN14163; REGN14164; REGN14165; REGN14175; REGN14176; REGN14177; REGN14178; REGN14179; REGN14180; REGN14181; REGN14182; REGN14183; REGN
  • the present disclosure includes methods for expressing an antibody or antigen-binding fragment thereof or immunoglobulin chain thereof in a host cell (e.g., bacterial host cell such as E. coli such as BL21 or BL21DE3) comprising T7 RNA polymerase in the cell which also includes a polynucleotide encoding an immunoglobulin chain (e.g., including the nucleotide sequence in any one or more of SEQ ID NOs: 1, 3, 5, 7, 9, 11, 13, 15, 17 or 19; or a variant thereof) that is operably linked to a T7 promoter.
  • a bacterial host cell such as an E.
  • coli includes a polynucleotide encoding the T7 RNA polymerase gene operably linked to a lac promoter and expression of the polymerase and the chain is induced by incubation of the host cell with IPTG (isopropyl-beta-D-thiogalactopyranoside).
  • IPTG isopropyl-beta-D-thiogalactopyranoside.
  • Transformation can be by any known method for introducing polynucleotides into a host cell.
  • Methods for introduction of heterologous polynucleotides into mammalian Attorney Docket No.250298.000780 cells are well known in the art and include dextran-mediated transfection, calcium phosphate precipitation, polybrene-mediated transfection, protoplast fusion, electroporation, encapsulation of the polynucleotide(s) in liposomes, biolistic injection and direct microinjection of the DNA into nuclei.
  • nucleic acid molecules may be introduced into mammalian cells by viral vectors.
  • the present disclosure includes recombinant methods for making an anti-p75 NTR antigen- binding protein, such as an antibody or antigen-binding fragment thereof of the present disclosure, or an immunoglobulin chain thereof, comprising (i) introducing, into a host cell, one or more polynucleotides (e.g., including the nucleotide sequence in any one or more of SEQ ID NOs: 1, 9, 17 and/or 19; or a variant thereof) encoding light and/or heavy immunoglobulin chains of the antigen-binding protein, e.g., REGN14148; REGN14149; REGN14150; REGN14151; REGN14152; REGN14153; REGN14154; REGN14155; REGN14156; REGN14157; REGN14158; REGN14
  • an antigen-binding protein e.g., antibody or antigen-binding fragment
  • an immunoglobulin chain e.g., an antibody that comprises two heavy immunoglobulin chains and two light immunoglobulin chains
  • co-expression of the chains in a single host cell leads to association of the chains, e.g., in the cell or on the cell surface or outside the cell if such chains are secreted, so as to form the antigen-binding protein (e.g., antibody or antigen-binding fragment).
  • the methods of the present disclosure include those wherein only a heavy immunoglobulin chain or only a light immunoglobulin chain or both (e.g., any of those discussed herein including mature fragments and/or variable domains thereof) are expressed in a cell.
  • Such single chains are useful, for example, as intermediates in the expression of an antibody or antigen-binding fragment that includes such Attorney Docket No.250298.000780 a chain.
  • the present disclosure also includes p75 NTR binding proteins, such as antibodies and antigen-binding fragments thereof which are the product of the production methods set forth herein, and, optionally, the purification methods set forth herein.
  • a method for making an anti-p75 NTR antigen-binding protein includes a method of purifying the antigen-binding protein, e.g., by column chromatography, precipitation and/or filtration. As discussed, the product of such a method also forms part of the present disclosure.
  • the present disclosure provides methods for making protein-drug conjugates described herein, the methods comprising (a) contacting the antigen- binding protein, with a molecular cargo described herein, under conditions favorable for conjugation of the antigen-binding protein to the molecular cargo; and (b) optionally, isolating the protein-drug conjugate produced in step (a).
  • the present disclosure provides methods for making protein-drug conjugates described herein, the method comprising (a) culturing a host cell described herein comprising a polynucleotide encoding the protein-drug conjugate described herein under conditions that allow expression of the protein-drug conjugate; and (b) optionally, isolating the protein-drug conjugate produced in step (a).
  • mouse constant regions are replaced with a desired human constant region, for example wild-type or modified IgG1 or IgG4, to generate a fully human anti-p75 NTR antibody.
  • a desired human constant region for example wild-type or modified IgG1 or IgG4
  • high affinity antigen- binding and target specificity characteristics reside in the variable region.
  • fully human anti-p75 NTR antibodies are isolated directly from antigen-positive B cells. See, for example, US Patent No.6,596,541, Regeneron Pharmaceuticals, VELOCIMMUNE®.
  • the present disclosure provides anti-p75 NTR antigen-binding proteins or antigen-binding fragments thereof, and protein-drug conjugates which can be used, for example, for delivering a molecular cargo to the body of a subject (e.g., the nervous system including the peripheral nervous system, autonomic nervous system, enteric nervous system, brain and the spinal cord, or eye, and, in particular, sensory neurons (such as, but not limited to, dorsal root ganglion cells or trigeminal ganglion cells) residing therein), for treating or preventing a disease or disorder (e.g., neurological disease or disorder), in the body of the subject.
  • a subject e.g., the nervous system including the peripheral nervous system, autonomic nervous system, enteric nervous system, brain and the spinal cord, or eye, and, in particular, sensory neurons (such as, but not limited to, dorsal root ganglion cells or trigeminal ganglion cells) residing therein
  • a disease or disorder e.g., neurological disease
  • the administering of the protein-drug conjugates and/or antigen-binding proteins or antigen-binding fragments thereof to the subject described herein does not modulate (i.e., increase or decrease) the expression and/or activity of p75 NTR , e.g., in regions or subregions of the nervous system that express p75 NTR .
  • the disease or disorder being treated herein can present dysfunctional pathways in regions or subregions of the nervous system that express p75 NTR .
  • the disclosure provides a pharmaceutical composition
  • a pharmaceutical composition comprising an antigen-binding protein or antigen-binding fragment thereof (e.g., an anti- p75 NTR or antigen-binding fragment thereof described herein) and/or a protein-drug conjugate described herein together with a pharmaceutically acceptable carrier and/or excipient.
  • pharmaceutically acceptable refers to molecular entities and other ingredients of such compositions that are physiologically tolerable and do not typically produce untoward reactions when administered to a mammal (e.g., a human).
  • pharmaceutically acceptable means approved by a regulatory agency of the Federal or a state government or listed in the U.S.
  • Suitable acids for preparing acid salts include both organic acids, e.g., acetic acid, benzoic acid, citric acid, propionic acid, glycolic acid, trifluoroacetic acid, pyruvic acid, oxalic acid, malic acid, malonic acid, maleic acid, succinic acid, fumaric acid, tartaric acid, cinnamic acid, mandelic acid, methanesulfonic acid, ethanesulfonic acid, p-toluenesulfonic acid, salicylic acid, and the like, as well as inorganic acids, e.g., hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid Attorney Docket No.250298.000780 phosphoric acid and the like.
  • organic acids e.g., acetic acid, benzoic acid, citric acid, propionic acid, glycolic acid, trifluoroacetic acid, pyruvic acid, oxalic acid,
  • preparation of basic salts of acid moieties which may be present on a protein-drug conjugates are prepared using a pharmaceutically acceptable base such as sodium hydroxide, potassium hydroxide, ammonium hydroxide, calcium hydroxide, trimethylamine or the like.
  • the protein-drug conjugates described herein may be present in a solution at a concentration of about 1 ⁇ g/mL to 50 mg/mL, for example, about 0.1 mg/mL to 10 mg/mL, about 0.2 mg/mL to 5 mg/mL, about 0.5 mg/mL to 8 mg/mL, about 0.8 mg/mL to 12 mg/mL, about 1 mg/mL to 15 mg/mL, about 2 mg/mL to 20 mg/mL, or about 5 mg/mL to 25 mg/mL, or about 0.1 mg/mL, 0.2 mg/mL, 0.3 mg/mL, 0.4 mg/mL, 0.5 mg/mL, 0.6 mg/mL, 0.7 mg/mL, 0.8 mg/mL, 0.9 mg/mL, 1 mg/mL, 1.25 mg/mL, 1.5 mg/mL, 1.75 mg/mL, 2 mg/mL, 2.25 mg/mL, 2.5 mg/mL
  • the antigen-binding proteins or antigen-binding fragments thereof described herein may be present in a solution at a concentration of about 1 ⁇ g/mL to 50 mg/mL, for example, about 0.1 mg/mL to 10 mg/mL, about 0.2 mg/mL to 5 mg/mL, about 0.5 mg/mL to 8 mg/mL, about 0.8 mg/mL to 12 mg/mL, about 1 mg/mL to 15 mg/mL, about 2 mg/mL to 20 mg/mL, or about 5 mg/mL to 25 mg/mL, or about 0.1 mg/mL, 0.2 mg/mL, 0.3 mg/mL, 0.4 mg/mL, 0.5 mg/mL, 0.6 mg/mL, 0.7 mg/mL, 0.8 mg/mL, 0.9 mg/mL, 1 mg/mL, 1.25 mg/mL, 1.5 mg/mL, 1.75 mg/mL, 2 mg/mL, 2.25 mg
  • compositions based on the antigen-binding proteins or antigen-binding fragments thereof and/or protein-drug conjugates disclosed herein can be formulated in any conventional manner using one or more physiologically acceptable carriers and/or excipients.
  • the antigen-binding proteins or antigen-binding fragments thereof and/or protein-drug conjugates may be formulated for administration by, for example, injection, inhalation, or insulation (either through the mouth or the nose) or by parenteral administration, or by administration directly to an organ or tissue.
  • the present disclosure provides methods for delivering a molecular cargo to a tissue or cell type expressing p75 NTR in the body of a subject comprising administering to the subject the protein- drug conjugate of the present disclosure or the pharmaceutical compositions of the present disclosure.
  • the tissue is brain, spinal cord, peripheral nervous system, autonomic nervous system, enteric nervous system, and/or eye.
  • the cell type is a sensory neuron.
  • the cell type is a dorsal root ganglion cell or a trigeminal ganglion cell.
  • the pharmaceutical compositions can be formulated for a variety of modes of administration, including systemic, topical, or localized administration.
  • localized injection is used, including intrathecal, intracisternal (e.g., cisterna magna), intracerebroventricular, intraparenchymal injection.
  • the pharmaceutical compositions can be formulated in liquid solutions, preferably in physiologically compatible buffers, such as Hank’s solution or Ringer’s solution.
  • the pharmaceutical compositions may be formulated in solid form and redissolved or suspended immediately prior to use. Lyophilized forms of the pharmaceutical composition are also suitable.
  • the pharmaceutical compositions of the present disclosure may be lyophilized.
  • the obtained lyophilizate can be reconstituted into a hydrous composition by adding a hydrous solvent.
  • the hydrous composition may be able to be directly administered parenterally (e.g., via intrathecal, intracisternal (e.g., cisterna magna), intracerebroventricular, or intraparenchymal injection) to a patient. Therefore, a further embodiment of the present disclosure is a hydrous pharmaceutical composition, obtainable via reconstitution of the lyophilizate with a hydrous solvent.
  • the pharmaceutical composition disclosed herein may comprise a lyophilized formulation.
  • the lyophilization formulation may comprise antigen-binding proteins (e.g., antibodies or antigen-binding fragments thereof) and/or protein-drug conjugates of the disclosure, mannitol, and/or TWEEN 80®.
  • the lyophilization formulation may comprise antigen-binding proteins (e.g., antibodies or antigen-binding fragments thereof) and/or protein-drug conjugates disclosed herein, mannitol and poloxamer 188.
  • the pharmaceutical composition may comprise a lyophilization formulation comprising a reconstituted-liquid composition.
  • the composition can be easily provided to a patient in need of treatment via any appropriate delivery route disclosed herein, e.g., parenteral (including intrathecal, intracisternal (e.g., cisterna magna), intracerebroventricular, or intraparenchymal injections), enteral (including oral or rectal), inhalation, or intranasal routes.
  • parenteral including intrathecal, intracisternal (e.g., cisterna magna), intracerebroventricular, or intraparenchymal injections), enteral (including oral or rectal), inhalation, or intranasal routes.
  • the pH-value of the resulting solution may be between pH 2.7 and pH 9.
  • the pharmaceutical compositions of the present disclosure may be desiccated, e.g., freeze-dried, or a pharmaceutical formulation thereof that includes a pharmaceutically acceptable carrier but substantially lacks water.
  • the pharmaceutical compositions may take the form of, for example, tablets or capsules prepared by conventional means with pharmaceutically acceptable excipients such as binding agents (e.g. pregelatinized maize starch, polyvinylpyrrolidone or hydroxypropyl methylcellulose); fillers (e.g. lactose, microcrystalline cellulose or calcium hydrogen phosphate); lubricants (e.g. magnesium stearate, talc or silica); disintegrants (e.g. potato starch or sodium starch glycolate); or wetting agents (e.g. sodium Attorney Docket No.250298.000780 lauryl sulfate).
  • binding agents e.g. pregelatinized maize starch, polyvinylpyrrolidone or hydroxypropyl methylcellulose
  • fillers e.g. lactose, microcrystalline cellulose or calcium hydrogen phosphate
  • lubricants e.g. magnesium stearate, talc or silica
  • disintegrants e.g
  • Liquid preparations for oral administration may take the form of, for example, solutions, syrups or suspensions, or they may be presented as a dry product for constitution with water or other suitable vehicle before use.
  • Such liquid preparations may be prepared by conventional means with pharmaceutically acceptable additives such as suspending agents (e.g. sorbitol syrup, cellulose derivatives or hydrogenated edible fats); emulsifying agents (e.g. lecithin or acacia); non-aqueous vehicles (e.g. ationd oil, oily esters, ethyl alcohol or fractionated vegetable oils); and preservatives (e.g. methyl or propyl-p-hydroxybenzoates or sorbic acid).
  • suspending agents e.g. sorbitol syrup, cellulose derivatives or hydrogenated edible fats
  • emulsifying agents e.g. lecithin or acacia
  • non-aqueous vehicles e.g. ationd oil, oily esters, ethyl alcohol or
  • the preparations can also contain buffer salts, flavoring, coloring and sweetening agents as appropriate.
  • the pharmaceutical compositions can be formulated for parenteral administration by injection, e.g. by bolus injection or continuous infusion. Formulations for injection can be presented in a unit dosage form, e.g. in ampoules or in multi-dose containers, with an optionally added preservative.
  • the pharmaceutical compositions can further be formulated as suspensions, solutions or emulsions in oily or aqueous vehicles, and may contain other agents including suspending, stabilizing and/or dispersing agents.
  • the pharmaceutical compositions can also be formulated as a depot preparation. These long-acting formulations can be administered by implantation (e.g.
  • the compounds may be formulated with suitable polymeric or hydrophobic materials (e.g. as an emulsion in an acceptable oil) or ion exchange resins, or as sparingly soluble derivatives, for example, as a sparingly soluble salt.
  • suitable delivery systems include microspheres, which offer the possibility of local noninvasive delivery of drugs over an extended period of time. This technology can include microspheres having a precapillary size, which can be injected via a coronary catheter into any selected part of an organ without causing inflammation or ischemia. The administered therapeutic is then slowly released from the microspheres and absorbed by the surrounding cells present in the selected tissue.
  • Systemic administration can also be by transmucosal or transdermal means.
  • penetrants appropriate to the barrier to be permeated are used in the formulation.
  • penetrants are generally known in the art, and include, for example, for transmucosal administration, bile salts, and fusidic acid derivatives.
  • detergents may be used to facilitate permeation.
  • Transmucosal administration can occur using nasal sprays or suppositories.
  • the vector particles Attorney Docket No.250298.000780 described herein can be formulated into ointments, salves, gels, or creams as generally known in the art.
  • a wash solution can also be used locally to treat an injury or inflammation in order to accelerate healing.
  • Pharmaceutical forms suitable for injectable use can include sterile aqueous solutions or dispersions; formulations including sesame oil, peanut oil or aqueous propylene glycol; and sterile powders for the extemporaneous preparation of sterile injectable solutions or dispersions. In all cases, the form must be sterile and must be fluid. It must be stable under the conditions of manufacture and certain storage parameters (e.g. refrigeration and freezing) and must be preserved against the contaminating action of microorganisms, such as bacteria and fungi.
  • An antigen-binding protein e.g., an antibody or antigen-binding fragment thereof
  • a protein-drug conjugate described herein can be formulated into a composition in a neutral or salt form.
  • Pharmaceutically acceptable salts include the acid addition salts (formed with the free amino groups of the protein) and which are formed with inorganic acids such as, for example, hydrochloric or phosphoric acids, or such organic acids as acetic, oxalic, tartaric, mandelic, and the like.
  • the prevention of the action of microorganisms can be brought about by various antibacterial and antifungal agents known in the art. In many cases, it will be preferable to include isotonic agents, for example, sugars or sodium chloride. Prolonged absorption of the injectable compositions can be brought about by the use in the compositions of agents delaying absorption, for example, aluminum monostearate and gelatin. [00704] Sterile injectable solutions can be prepared by incorporating the active compounds or constructs in the required amount in the appropriate solvent with various of the other ingredients enumerated above, as required, followed by filtered sterilization.
  • solutions can be administered in a manner compatible with the dosage formulation and in such amount as is therapeutically effective.
  • the formulations are easily administered in a variety of dosage forms, such as the type of injectable solutions described above, but slow-release capsules or microparticles and microspheres and the like can also be employed.
  • the solution should be suitably buffered if necessary and the liquid diluent first rendered isotonic with sufficient saline or glucose.
  • sterile aqueous media that can be employed will be known to those of skill in the art in light of the present disclosure.
  • one dosage could be dissolved in 1 ml of isotonic NaCl solution and either added to 1000 ml of hypodermoclysis fluid or injected at the proposed site of infusion.
  • the person responsible for administration will, in any event, determine the appropriate dose for the individual subject.
  • a subject may be administered the antigen-binding proteins (e.g., antibodies or antigen-binding fragments thereof) and/or protein-drug conjugates described herein on a daily or weekly basis for a time period or on a monthly, bi-yearly or yearly basis.
  • nasal solutions can be aqueous solutions designed to be administered to the nasal passages in drops or sprays. Nasal solutions can be prepared so that they are similar in many respects to nasal secretions.
  • the aqueous nasal solutions usually are isotonic and slightly buffered to maintain a pH of 5.5 to 7.5.
  • antimicrobial preservatives similar to those used in ophthalmic preparations, and appropriate drug stabilizers, if required, may be included in the formulation.
  • Various commercial nasal preparations are known and can include, for example, antibiotics and antihistamines and are used for asthma prophylaxis.
  • Oral formulations can include excipients as, for example, pharmaceutical grades of mannitol, lactose, starch, magnesium stearate, sodium saccharine, cellulose, magnesium carbonate and the like. These compositions take the form of solutions, suspensions, tablets, pills, capsules, sustained release formulations or powders.
  • the tablets, troches, pills, capsules and the like may also contain the following: a binder, as gum tragacanth, acacia, cornstarch, or gelatin; excipients, such as dicalcium phosphate; a disintegrating agent, such as corn starch, potato starch, alginic acid and the like; a lubricant, such as magnesium stearate; and a sweetening agent, such as sucrose, lactose or saccharin may be added or a flavoring agent, such as peppermint, oil of wintergreen, or cherry flavoring.
  • a binder as gum tragacanth, acacia, cornstarch, or gelatin
  • excipients such as dicalcium phosphate
  • a disintegrating agent such as corn starch, potato starch, alginic acid and the like
  • a lubricant such as magnesium stearate
  • a sweetening agent such as sucrose, lactose or saccharin may be added or a flavor
  • p75 NTR binding proteins e.g., the anti-p75 NTR antibodies or antigen-binding fragments thereof described herein
  • the anti-p75 NTR protein-drug conjugates or composition thereof can vary.
  • Routes of administration include parenteral, non-parenteral, oral, rectal, transmucosal, intestinal, parenteral; intramuscular, subcutaneous, intradermal, intramedullary, intrathecal, intracisternal (e.g., cisterna magna), intracerebroventricular, direct intraventricular, intravenous, intraperitoneal, intranasal, intraocular, inhalation, insufflation, topical, cutaneous, intraocular, intravitreal, transdermal or intra-arterial.
  • intramuscular subcutaneous, intradermal, intramedullary
  • intrathecal intracisternal (e.g., cisterna magna)
  • intracerebroventricular direct intraventricular, intravenous, intraperitoneal, intranasal, intraocular, inhalation, insufflation, topical, cutaneous, intraocular, intravitreal, transdermal or intra-arterial.
  • compositions as disclosed herein can also include adjuvants such as aluminum salts and other mineral adjuvants, tensoactive agents, bacterial derivatives, vehicles and cytokines. Adjuvants can also have antagonizing immunomodulating properties. Compositions and methods as disclosed herein can also include adjuvant therapy. [00715]
  • the pharmaceutical compositions of the disclosure may be administered directly into the patient, into the affected organ or systemically, or applied ex vivo to cells derived from the patient or a human cell line which are subsequently administered to the patient, or used in vitro to select a subpopulation of cells derived from the patient, which are then re-administered to the patient.
  • the present disclosure provides a vessel (e.g., a plastic or glass vial, e.g., with a cap or a chromatography column, hollow bore needle or a syringe cylinder) comprising any of the p75 NTR binding proteins or antigen-binding fragments thereof and/or the anti-p75 NTR protein-drug conjugates, or a pharmaceutical formulation comprising a pharmaceutically acceptable carrier thereof.
  • a vessel e.g., a plastic or glass vial, e.g., with a cap or a chromatography column, hollow bore needle or a syringe cylinder
  • a pharmaceutical formulation comprising a pharmaceutically acceptable carrier thereof.
  • p75 NTR binding proteins described herein e.g., anti- p75 NTR antibodies or antigen-binding fragments thereof described herein
  • anti-p75 NTR protein-drug conjugates described herein are used for treating or preventing pain.
  • Non- limiting examples of pain include, but are not limited to, peripheral chronic pain (e.g., by delivering Nav1.7 siRNA or another siRNA targeting any other various gene or gene products associated with pain, e.g., chronic pain such as peripheral chronic pain, contemplated herein), somatic pain, small fiber peripheral neuropathy, chemotherapy-induced neuropathy, painful diabetic-induced neuropathy, chronic itch, trigeminal neuralgia, post-herpetic neuralgia, temporo-mandibular pain, migraine, dysautonomia, Sickle cell disease, joint pain, back pain, myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), myofascial pain syndrome, herpes zoster, or pelvic pain.
  • peripheral chronic pain e.g., by delivering Nav1.7 siRNA or another siRNA targeting any other various gene or gene products associated with pain, e.g., chronic pain such as peripheral chronic pain, contemplated herein
  • somatic pain small fiber peripheral neuropathy
  • p75 NTR binding proteins described herein e.g., anti- p75 NTR antibodies or antigen-binding fragments thereof described herein
  • anti-p75 NTR protein-drug conjugates described herein are used for treating or preventing itch (e.g., chronic itch).
  • p75 NTR binding proteins described herein e.g., anti- p75 NTR antibodies or antigen-binding fragments thereof described herein
  • anti-p75 NTR protein-drug conjugates described herein are used for treating or preventing a neurological disease or disorder.
  • Non-limiting examples of neurological diseases or disorders include, but are not limited to, lysosomal storage diseases, amyloidosis, neuropathy, neurodegenerative diseases, leukodystrophy, neuropsychiatric diseases, traumatic brain injury, neurodevelopmental diseases, and neuromuscular diseases, seizure, behavioral disorders, ocular diseases or disorders, viral or microbial infections, inflammation, ischemia, and cancer.
  • neurological disorders include, but are not limited to, neurodegenerative diseases (e.g., Parkinson's disease, striatonigral degeneration, Shy-Draeger syndrome, tauopathies (e.g., Alzheimer disease), motor neuron disease, and nervous system heterodegenerative disorders (e.g., Alexander's disease, Cockayne syndrome, Canavan disease, hepatolenticular degeneration, hereditary sensory ataxia, dementia (e.g., spinocerebellar ataxia), cancer (e.g., central nervous system (CNS) cancers, including brain metastases resulting from cancer elsewhere in the body).
  • neurodegenerative diseases e.g., Parkinson's disease, striatonigral degeneration, Shy-Draeger syndrome, tauopathies (e.g., Alzheimer disease), motor neuron disease, and nervous system heterodegenerative disorders (e.g., Alexander's disease, Cockayne syndrome, Canavan disease, hepatolenticular degeneration, hereditary sensory ataxia, dementia (e.
  • the p75 NTR binding proteins described herein e.g., anti- p75 NTR antibodies or antigen-binding fragments thereof described herein
  • the p75 NTR protein-drug conjugates described herein are used for treating or preventing, for example, without limitation, chronic pain (e.g., peripheral chronic pain), somatic pain, chronic itch, migraine, trigeminal neuralgia, post-herpetic neuralgia, joint pain, back pain, Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, myofascial pain syndrome, herpes zoster, and/or pelvic pain.
  • chronic pain e.g., peripheral chronic pain
  • somatic pain e.g., chronic itch
  • migraine trigeminal neuralgia
  • post-herpetic neuralgia joint pain
  • back pain Alzheimer's disease
  • Parkinson's disease amyotrophic lateral sclerosis
  • myofascial pain syndrome herpes zoster
  • p75 NTR binding proteins described herein e.g., anti- p75 NTR antibodies or antigen-binding fragments thereof described herein
  • anti-p75 NTR protein-drug conjugates described herein are used for treating or preventing glioblastoma multiforme (GBM).
  • GBM glioblastoma multiforme
  • GBM is a rapidly-growing type of tumor typically of the brain or spinal cord. It is the most common type of primary malignant brain tumor in adults. Only 25% of glioblastoma patients survive more than one year and 5% of patients survive more than five years.
  • Symptoms of can depend on the brain region where the Attorney Docket No.250298.000780 glioblastoma is located.
  • the tumor can grow in areas of the brain that lead to difficulties in forming words or in moving limbs. Expanding tumors can increase pressure within the skull, leading to headaches. Other symptoms include impaired vision, nausea and vomiting, loss of appetite; mood swings; loss of balance, problems with memory or concentration, problems speaking and/or seizures.
  • the term “subject” refers to a mammal (e.g., rat, mouse, cat, dog, cow, sheep, horse, goat, rabbit), preferably a human, for example, in need of prevention and/or treatment of a disease or disorder described herein.
  • the present disclosure includes combinations including a p75 NTR binding protein described herein (e.g., an anti-p75 NTR antibody or antigen-binding fragment thereof described herein) and/or an anti-p75 NTR protein-drug conjugate described herein, in association with one or more further therapeutic agents or treatments.
  • a further therapeutic agent that is administered to a subject in association with a p75 NTR binding protein described herein e.g., an anti-p75 NTR antibody or antigen-binding fragment thereof described herein
  • an anti-p75 NTR protein-drug conjugate is administered to the subject in accordance with the Physicians' Desk Reference 2003 (Thomson Healthcare; 57th edition (Nov.1, 2002)).
  • the p75 NTR binding protein and/or anti-p75 NTR protein-drug conjugate and the further therapeutic agent can be in a single composition or in separate compositions.
  • Methods for treating or preventing a disease or disorder in a subject in need of said treatment or prevention by administering a p75 NTR binding protein (e.g., an anti-p75 NTR antibody or antigen-binding fragment thereof described herein) and/or an anti-p75 NTR protein- drug conjugate, in association with a further therapeutic agent are part of the present disclosure.
  • Compositions comprising the p75 NTR binding protein and/or the anti-p75 NTR protein-drug conjugate in association with one or more further therapeutic agents also form part of the present disclosure.
  • association with indicates that components, an p75 NTR binding protein, e.g., antibody or antigen-binding fragment thereof of the present disclosure, along with another agent such as methotrexate, can be formulated into a single composition, e.g., for simultaneous delivery, or formulated separately into two or more compositions (e.g., a kit including each component).
  • Components administered in association with each another can be administered to a subject at a different time than when the other component is administered; for example, each administration may be given non-simultaneously (e.g., separately or sequentially) at intervals over a given period of time.
  • a p75 NTR binding protein e.g., an anti-p75 NTR antibody or antigen-binding fragment thereof described herein
  • an anti-p75 NTR protein-drug conjugate may be administered in association with a further therapeutic agent such as an anesthetic or analgesic for the treatment of chronic and somatic pain.
  • Suitable anesthetics include, but are not limited to, local anesthetics, general anesthetics, inhaled agents, intravenous agents, and muscle relaxants.
  • local anesthetics include, but are not limited to, articaine, benzocaine, bupivacaine, cinchocaine/dibucaine, chloroprocaine, cocaine, cyclomethycaine, dimethocaine/loracaine, etidocaine, eugenol, lidocaine/lignocaine, mepivacaine, menthol, piperocaine, propoxycaine, procaine/novocaine, proparacaine, tetracaine/amethocaine, levobupivacaine, prilocaine, ropivacaine, trimecaine, saxitoxin, tetrodotoxin, and combinations and derivations thereof.
  • Examples of general anesthetics include, but are not limited to, amobarbital, atracurium, alcuronium, alfentanil, butorphanol, cisatracurium, diamorphine, decamethonium, desflurane, diazepam, doxacurium, etomidate, enflurane, halothane, isoflurane, methoxyflurane, meperidine, methadone, morphine, nalbuphine, nitrous oxide, sevoflurane, methohexital, thiamylal, thiopental, lorazepam, midazolam, ketamine, propofol, fentanyl, remifentanil, sufentanil, buprenorphine, hydromorphone, levorphanol, oxycodone, oxymorphone, pentazocine, succinylcholine, mivacurium, rapacuronium,
  • anesthesia includes, including, but not limited to, anesthesia that is administered orally, by dermal contact, subcutaneously, intravenously, by epidural means, spinally, and by inhalation.
  • analgesics include, but are not limited to, opioids, such as codeine, dexamethasone, morphine, fentanyl, hydromorphone, hydrocodone, tramadol, oxycodone, ondansetron, methadone, alfentanil, remifentanil, and derivations thereof, and non-opioid analgesics, including acetaminophen, nonsteroidal anti-inflammatory drugs (NSAIDs), dexmedetomidine, clonidine, capsaicin, anti-convulsants such as gabapentin and pregabalin, steroids such as Dexamethasone, prednisone, prednisolone, and combinations and derivations thereof.
  • opioids such as codeine, dexamethas
  • a p75 NTR binding protein e.g., an anti-p75 NTR antibody or antigen-binding fragment thereof described herein
  • an anti-p75 NTR protein-drug conjugate may be administered in association with a further therapeutic agent such as a pain reliever (e.g., aspirin or ibuprofen, acetaminophen), triptan (e.g., sumatriptan (Imitrex, Tosymra) and rizatriptan (Maxalt, Maxalt-MLT)), dihydroergotamine (Migranal, Trudhesa), Lasmiditan (Reyvow), oral calcitonin gene-related peptides antagonists (e.g, ubrogepant (Ubrelvy) and rimegepant (Nurtec ODT)), intranasal zavegepant (Zavzpret
  • a pain reliever e.g., aspirin or ibuprofen
  • a p75 NTR binding protein e.g., an anti-p75 NTR antibody or antigen-binding fragment thereof described herein
  • an anticonvulsant e.g., carbamazepine (Tegretol, Carbatrol, others), oxcarbazepine (Trileptal, Oxtellar XR), lamotrigine (Lamictal), valproate and phenytoin (Dilantin, Phenytek, Cerebyx), clonazepam (Klonopin), topiramate (Qsymia, Topamax, others), pregabalin (Lyrica) and gabapentin (Neurontin, Gralise, Horizant)), a muscle relaxant (e.g., baclofen (Gablofen, Lioresal, Ozobax)),
  • baclofen e.g., baclofen (Gablofen, Lioresal, Ozobax)
  • a p75 NTR binding protein e.g., an anti-p75 NTR antibody or antigen-binding fragment thereof described herein
  • an anti-p75 NTR protein-drug conjugate may be administered in association with a further therapeutic agent such as Aducanumab (AduhelmTM), Donepezil (Aricept®), Galantamine (Razadyne®), Lecanemab, Memantine (Namenda®), Rivastigmine (Exelon®), Donepezil and memantine (Namzaric®), Orexin receptor antagonist (Belsomra®), or Suvorexant (Belsomra®) for the treatment of Alzheimer’s disease.
  • Aducanumab AduhelmTM
  • Donepezil Aricept®
  • Galantamine Radyne®
  • Lecanemab Memantine (Namenda®), Rivastigmine (Exelon®), Donepezil and memantine
  • Orexin receptor antagonist Be
  • a p75 NTR binding protein e.g., an anti-p75 NTR antibody or antigen-binding fragment thereof described herein
  • an anti-p75 NTR protein-drug conjugate may be administered in association with a further therapeutic agent such as Carbidopa-levodopa (Sinemet), Carbidopa-levodopa (controlled release) (Sinemet CR), Carbidopa-levodopa (orally disintegrating tablet) (Parcopa), Carbidopa-levodopa (extended release capsules) (Rytary), Carbidopa-levodopa-entacapone (enteral suspension) (Duopa), Levodopa Inhalation powder (Inbrija), Entacapone (Comtan), Tolcapone (Tasmar), Opicapone (Ongentys), Carbidopa/Levodopa Entacapone (Stalevo
  • a p75 NTR binding protein e.g., an anti-p75 NTR antibody or antigen-binding fragment thereof described herein
  • an anti-p75 NTR protein-drug conjugate may be administered in association with a further therapeutic agent such as Methylprednisolone, Tirilazad mesylate, Lyrica (pregabalin), Riluzole, GM1 ganglioside, Gacyclidine, or naloxone for the treatment of Spinal cord injury.
  • a further therapeutic agent such as Methylprednisolone, Tirilazad mesylate, Lyrica (pregabalin), Riluzole, GM1 ganglioside, Gacyclidine, or naloxone for the treatment of Spinal cord injury.
  • a p75 NTR binding protein e.g., an anti-p75 NTR antibody or antigen-binding fragment thereof described herein
  • an anti-p75 NTR protein-drug conjugate may be administered in association with a further therapeutic agent such as Dexamethasone, Mannitol, Dexamethasone Intensol, Osmitrol, De-Sone LA, Dxevo, HiDex, or Zcort for the treatment of brain edema.
  • a further therapeutic agent such as Dexamethasone, Mannitol, Dexamethasone Intensol, Osmitrol, De-Sone LA, Dxevo, HiDex, or Zcort for the treatment of brain edema.
  • an effective or therapeutically effective amount of p75 NTR binding protein for treating or preventing a disease or condition described herein refers to the amount of the antigen-binding protein sufficient to alleviate one or more signs and/or symptoms of the disease or condition in the treated subject, whether by inducing the regression or elimination of such signs and/or symptoms or by inhibiting the progression of such signs and/or symptoms.
  • an effective or therapeutically effective amount of p75 NTR binding protein is about 2-30 mg/kg. This dose may be administered, for example, about once a month. The dose amount may vary depending upon the age and the size of a subject to be administered, target disease, conditions, route of administration, and the like.
  • the initial dose may be followed by administration of a second or a plurality of subsequent doses of antigen- Attorney Docket No.250298.000780 binding protein in an amount that can be approximately the same or less or more than that of the initial dose, wherein the subsequent doses are separated by days or weeks or months.
  • a symptom is a manifestation of disease apparent to the patient himself, while a sign is a manifestation of disease that the physician perceives. Reduction, fully or in part, of a sign or symptom may be referred to as alleviation of the sign or symptom.
  • an effective or therapeutically effective dose of p75 NTR binding protein and/or anti-p75 NTR protein-drug conjugate is about 1 mg/kg and 50 mg/kg body weight.
  • the dose amount may vary depending upon the age and the size of a subject to be administered, target disease, conditions, route of administration, and the like.
  • the initial dose may be followed by administration of a second or a plurality of subsequent doses of antigen-binding protein in an amount that can be approximately the same or less or more than that of the initial dose, wherein the subsequent doses are separated by days or weeks.
  • the recombinant human hp75-mFc protein (REGN6869) (SEQ ID NO: 675) used in the experiments comprises a portion of the human p75 NTR extracellular domain (amino acids K29-N250) (REGN6869) (SEQ ID NO: 676), fused to the Fc portion of the mouse IgG2a at the C-terminus of human p75 NTR (REGN6869) (SEQ ID NO: 621).
  • the human NTF-3 UniProt Attorney Docket No.250298.000780 accession number P20783.1 expressed with amino acids W139-T257 (K196R) (SEQ ID NO: 679) was commercially obtained from R&D Systems.
  • hNT-3 was passively absorbed at a concentration of 2 ⁇ g/mL in PBS on a 96-well microtiter plate overnight at 4°C. Nonspecific binding sites were subsequently blocked using a 0.5% (w/v) solution of BSA in PBS for 1 hour at room temperature.
  • a fixed amount of 1 nM human p75 NTR -mFc was bound for one hour with anti- hp75 monoclonal antibody supernatants or sample media at a dilution of 1:5 or 0.5 ⁇ g/ml of the control anti-human/canine NGFR-mIgG1 monoclonal antibody in assay buffer.
  • the fixed concentration of human p75 NTR -mFc was selected to be near the concentration that generated 50% of the maximal binding (EC 50 value) to plate-adhered hNT-3 protein. After the incubation, the antibody-protein complexes were transferred to the microtiter plate coated with hNT-3. After one hour incubation at room temperature, the wells were washed, and hNT-3 bound human p75-mFc was detected with a horseradish peroxidase-conjugated goat anti-mouse IgG Fc ⁇ fragment specific polyclonal antibody.
  • anti-human p75 monoclonal antibody supernatants to bind human p75 neurotrophin receptor (hp75) (NCBI accession number NP_002498.1) (SEQ ID NO: 669), or Macaca fascicularis p75 neurotrophin receptor (mfp75) (NCBI accession number XP_005583674.1) (SEQ ID NO: 671), or mouse neurotrophin receptor (mp75) (GenBank accession number AAH38365) (SEQ ID NO: 673) expressing cells was determined using an electrochemiluminescence based assay.
  • NIH3T3 cells were engineered to express hp75, or mfp75, or mp75 by transfecting the cells with hygromycin resistant pLVxEF1a.hNGFR expression plasmid encoding hp75 (amino acids M1-V399, NCBI accession number NP_002498.1) (SEQ ID NO: 669), or pLVx.mfNGFR expression plasmid encoding mfp75 (M1-V427, NCBI accession number XP_005583674.1) (SEQ ID NO: 671), or pLVxEF1a.mNGFR expression plasmid encoding mp75 (amino acids M1-V427, GenBank accession number AAH38365 (SEQ ID NO: 673).
  • NIH3T3/SRELuc The p75 negative NIH3T3/SRELuc (NIH3T3/SRELuc) cells showed no detectable expression of p75 by fluorescence activated cell sorting (FACS) with a commercial p75 antibody and were included in the experiments as a background binding control.
  • FACS fluorescence activated cell sorting
  • the cell pellets were washed once with 1xPBS with Ca 2+ /Mg 2+ and counted with a Cellometer TM Auto T4 cell counter (Nexcelom Bioscience, Lawrence, MA). Approximately 2.0x10 4 NIH3T3/hp75, NIH3T3/mfp75, NIH3T3/mp75 or NIH3T3/SRELuc cells per well were seeded separately onto 96-well carbon electrode plates (Meso Scale Discovery, Rockville, MD) and incubated for 1 hour at 37 ° C to allow the cells to Attorney Docket No.250298.000780 adhere.
  • Nonspecific binding sites were blocked by incubating with 2% BSA (w/v) in 1xPBS with Ca 2+ /Mg 2+ for 1 hour at room temperature.
  • BSA w/v
  • 1xPBS Ca 2+ /Mg 2+
  • anti-p75 monoclonal antibody supernatants at a dilution of 1:10, 0.5 ⁇ g/ml of the control antibody in assay buffer and buffer with no antibody were added followed by 1 hour incubation at room temperature. Plates were then washed to remove unbound antibodies using an AquaMax2000 plate washer with a cell washing head (MDS Analytical Technologies, Sunnyvale, CA).
  • the plate-bound anti-p75-hIgG samples were detected with SULFO-TAG TM -conjugated goat polyclonal anti-human IgG antibody specific for heavy and light chains (Jackson Immunoresearch Labs, West Grove, PA) and the plate-bound anti-p75-mIgG (ME20.4 purified anti-hp75) was detected with SULFO-TAG TM -conjugated goat polyclonal anti-mouse IgG antibody specific for Fc ⁇ fragment (Jackson Immunoresearch Labs, West Grove, PA) for 1 hour at room temperature.
  • All tested anti-p75 monoclonal antibodies displayed binding signals greater than 3000 RLU on NIH3T3/hp75 cells with ratios of binding on NIH3T3/hp75 to NIH3T3/SREluc cells greater than 14 suggesting these antibodies are capable of specific binding to human p75.
  • all anti-p75 antibodies displayed binding signals Attorney Docket No.250298.000780 greater than 4000 RLU and ratio of binding on NIH3T3/mfp75 to NIH3T3/SRELuc cells greater than 11 and were characterized as mfp75 binders.
  • the Biacore CM5 sensor surface was first derivatized by amine coupling with a monoclonal mouse anti-human Fc antibody (REGN2567) to capture anti- p75 NTR monoclonal antibodies.
  • a monoclonal mouse anti-human Fc antibody REGN2567
  • Different concentrations of p75 NTR reagents human p75 NTR extracellular domain expressed with a C-terminal myc-myc-hexahistidine tag (“hexahistidine” disclosed as SEQ ID NO: 619) (hP75 NTR -MMH; REGN6870), monkey p75 NTR extracellular domain expressed with a C-terminal myc-myc-hexahistidine tag (“hexahistidine” disclosed as SEQ ID NO: 619) (mfP75 NTR -MMH; REGN6942), mouse p75 NTR extracellular domain expressed with a C-terminal myc-myc-hexahistidine tag (“hexahistidine
  • the dissociation of different p75 NTR reagents bound to anti-p75 NTR monoclonal antibodies was monitored for 10 minutes in HBS-EP running buffer. At the end of each cycle, the anti-p75 NTR monoclonal antibodies capture surface was regenerated using a 12 second injection of 20 mM H 3 PO 4 .
  • the association rate (ka) and dissociation rate (kd) were determined by fitting the real-time binding sensorgrams to a 1:1 binding model with mass transport limitation using Scrubber 2.0c curve-fitting software.
  • the equilibrium and kinetic binding parameters for anti-p75 NTR monoclonal antibodies binding to hp75 NTR -MMH, mfp75 NTR -MMH, hP75 NTR -mFc, mp75 NTR -MMH, and mp75 NTR -mFc at 25°C are shown in Table 4-3 through Table 4-7, respectively.
  • Attorney Docket No.250298.000780 [00759]
  • Binding competition between different anti-p75 monoclonal antibodies (mAbs) was determined using a real time, label-free bio-layer interferometry (BLI) assay on the Octet HTX biosensor platform (Pall ForteBio Corp.). The entire experiment was performed at 25°C in 10 mM HEPES buffer containing 150 mM NaCl, 3 mM EDTA, 1 mg/mL BSA, 0.02% NaN3, and 0.05% v/v Surfactant Tween-20 at pH7.4 (HBS-EP) with the plate shaking at a speed of 1000 rpm.
  • HBS-EP pH7.4
  • hexahistidine disclosed as SEQ ID NO: 619
  • hp75 NTR -MMH recombinant human p75 NTR extracellular domain expressed with a C-terminal myc-myc-hexahistidine (“hexahistidine” disclosed as SEQ ID NO: 619) (hp75 NTR -MMH) (REGN6870) was first captured onto anti-Penta-His antibody coated Octet biosensor tips (Fortebio Inc, # 18-5122) by submerging the biosensor tips in wells containing 45 ⁇ g/mL solution of the hp75 NTR -MMH for 120 seconds.
  • the antigen captured biosensor tips were then saturated with a first anti-p75 NTR monoclonal antibody (subsequently referred to as mAb-1) by dipping into wells containing 50 ⁇ g/mL solution of mAb-1 for 4 minutes.
  • the biosensor tips were then subsequently dipped into wells containing 50 ⁇ g/mL solution of a second anti-p75 NTR monoclonal antibody (subsequently referred to as mAb-2) for 3 minutes.
  • the biosensor tips were washed in HBS-EBT buffer in between every Attorney Docket No.250298.000780 step of the experiment. The real-time binding response was monitored and the binding response at the end of every step was recorded.
  • the Biacore CM5 sensor surface was first derivatized by amine coupling with a monoclonal mouse anti-human Fc antibody (REGN2567) followed by a step to capture anti-p75 NTR monoclonal antibodies in CHO conditioned media.
  • Human p75 NTR extracellular domain expressed with a C-terminal myc-myc-hexahistidine tag (“hexahistidine” disclosed as SEQ ID NO: 619) (hp75 NTR -mmh; REGN6870) at concentrations of 100 nM in HBS-EP running buffer were injected at a flow rate of 50 ⁇ L/min for 1.5 minutes.
  • the dissociation of p75 NTR bound to anti-p75 NTR monoclonal antibodies was monitored for 2 minutes in HBS-EP running buffer. At the end of each cycle, the anti-p75 NTR monoclonal antibodies capture surface was regenerated using a 12-second injection of 20mM H 3 PO 4 .
  • the association rate (ka) and dissociation rate (kd) were determined by fitting the real-time binding sensorgrams to a 1:1 binding model with mass transport limitation using Scrubber 2.0c software.
  • the equilibrium binding constant and the kinetic binding constants are summarized in Table 6-3 for human p75 NTR .
  • Table 6-2 Equilibrium and kinetic binding parameters for the interaction of p75 NTR - mmh with anti-p75 NTR monoclonal antibodies at 25°C.
  • mAb Clone IDs REGN # Clone ID Ab
  • PID REGN14160 927-1-61C4 PN62906
  • Attorney Docket No.250298.000780 REGN14183 927-8-69A2 PN63034 REGN14184 927-8-69H2 PN63037 abe - .
  • eagens used Reagent Source Identification 0
  • TNFR tumor necrosis factor receptor
  • C2.3T3/SRE-luc/hTrkA cl.C2 cells were further engineered to stably express full-length human p75 NTR NCBI accession number NP_002498.1 (amino acids 1-427 of UniProt accession number P08138) (SEQ ID NO: 669) and the resulting cell line was named 3T3/SRE-luc/hTrkA cl.C2/hp75 NTR .
  • Cell based assay testing regulation of NGF-dependent TrkA signaling by the extracellular domain of p75 NTR in the presence of various anti-p75 NTR antibodies.
  • 3T3/SRE-luc/hTrkA cl.C2 cells were plated at 20,000 cells per well in assay media (Opti-MEM media containing 0.1% fetal bovine serum and 1X Penicillin-Streptomycin- Glutamine) and incubated overnight at 37°C in 5% CO2.
  • assay media Opti-MEM media containing 0.1% fetal bovine serum and 1X Penicillin-Streptomycin- Glutamine
  • NGF human nerve growth factor
  • hNGF ⁇ human nerve growth factor
  • REGN205 200 pM mature human nerve growth factor (NGF) ⁇ (hNGF ⁇ ) (amino acids 122-241 of UniProt accession number P01138) (SEQ ID NO: 677), referred to hereafter as NGF or REGN205, before adding to cells.
  • NGF nerve growth factor
  • REGN1666 200 pM of NGF with 100 nM of irrelevant Fc fusion protein, REGN1666 (SEQ ID NO: 678), was added to the cells.
  • RLU Relative Luminescence Units
  • RLU soluble p75 refers to the RLU value from cells treated with 100nM irrelevant antibody, 5 nM p75 NTR -mFc and 200pM NGF and is defined as 0% inhibition.
  • RLUUNGF refers to the RLU value from cells treated with 100 nM REGN1666 and 200 pM NGF and is defined as 100% inhibition.
  • 3T3/SRE-luc/hTrkA cl.C2 and 3T3/SRE-luc/hTrkA cl.C2/hp75 NTR cells were plated at 20,000 cells per well in assay media and incubated overnight at 37 ⁇ C in 5% CO 2. The following day, supernatants containing the antibodies of the invention (subclass hIgG1) or control antibody, 40 nM REGN2390, were preincubated with 3T3/SRE-luc/hTrkA cl.C2 or 3T3/SRE-luc cl.C2/hp75 NTR cells for 30 minutes at 37 ⁇ C in 5%CO2 before the addition of 200 pM NGF (REGN205).
  • Results were analyzed using the following equations to calculate inhibition by anti- p75 NTR antibodies:
  • R LU % Activation [ ⁇ ] 100 X ⁇ ⁇ RLUNGF min RLUNGF max ⁇ RLUNGF min Attorney Docket No.250298.000780 % Activation [200pM NGF]p75&Trk ⁇ % Activation [mAb] %
  • Inhibition 100 X A p75&TrkA % Activation [200pM NGF] p75&TrkA ⁇ % Activation [mAb] TrkA [00773]
  • “RLU ⁇ ” refers to RLU values for conditions containing 200 pM NGF alone, or antibody with 200 pM NGF (mAb).
  • RLU NGF min and “RLU NGF max ” refer to the minimum and maximum RLU values from cells alone without NGF and with 50 nM NGF, respectively.
  • p75&TrkA” and “TrkA” refer to cells co-expressing two receptors or TrkA alone.
  • 40 antibodies of the invention were each incubated with the soluble, extracellular domain of p75 NTR , p75 NTR -mFc, to examine effects on NGF dependent activation of TrkA signaling in 3T3/SRE-luc/hTrkA cl.C2 cells; blocking of p75 NTR inhibition of TrkA signaling ranged from 2.76% to 112.50%.
  • Reagents used Reagent Source Identification 9 Attorney Docket No.250298.000780 Control antibody #1 Regeneron REGN1945, lot REGN1945-L54 was performed to assess internalization of 6 anti-p75 NTR antibodies in 3T3/p75 NTR /SRE-luc cl.4B5 cells that stably express full-length human p75 NTR NCBI accession number NP_002498.1 (amino acids 1-427 of UniProt accession number P08138) (SEQ ID NO: 427) and the SRE- luc reporter gene.
  • antibodies of the invention or an hIgG4 subclass control antibody were serially diluted (1:3) from 5 nM to 0.762 pM (with an additional well without test molecule) and then added to the cells along with 20 nM of anti-human Fc-cleavable linker-duocarmycin conjugated (Moradec, cat#AH-202DD-20) secondary Fab.
  • duocarmycin free drug REGN, lot#M0111-140610-2
  • anti-p75 NTR antibodies of the invention showed maximum internalization and killing of 3T3/p75 NTR/ SRE-luc cl.4B5 cells with duocarmycin conjugated secondary Fab ranging from 41% to 60% with IC 50 values ranging from 21 pM to 63 pM.
  • Control antibody showed no internalization or killing of 3T3/p75 NTR /SRE-luc cl.4B5 cells.
  • Duocarmycin free drug showed 100% killing of both 3T3/p75 NTR /SRE-luc cl.4B5 and 3T3 parental cells with IC50 values of 71 pM and 49 pM, respectively.

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Abstract

The present invention provides anti-p75 neurotrophin receptor (p75NTR) antigen-binding proteins and protein-drug conjugates including an anti-p75NTR antigen-binding protein conjugated to a molecular cargo, as well as methods of treating diseases with such antigen-binding proteins and protein-drug conjugates.

Description

Attorney Docket No.250298.000780 P75 NEUROTROPHIN RECEPTOR (P75NTR)-BINDING PROTEINS AND P75NTR- MEDIATED DELIVERY TO THE NERVOUS SYSTEM CROSS-REFERENCE TO RELATED APPLICATION [0001] This patent application claims the benefit of U.S. Provisional Application No. 63/619,934, filed January 11, 2024, and U.S. Provisional Application No. 63/672,471, filed July 17, 2024, the disclosure of each of which is incorporated by reference herein in its entirety for all purposes. SEQUENCE LISTING [0002] The instant application contains a Sequence Listing which has been submitted electronically in XML file format and is hereby incorporated by reference in its entirety. Said XML copy, created on January 6, 2025, is named 250298_000780_SL.xml and is 741,077 bytes in size. FIELD OF THE INVENTION [0003] The present invention relates to p75 neurotrophin receptor (p75NTR) antigen-binding proteins and protein-drug conjugates including a p75NTR antigen-binding protein conjugated to a molecular cargo, as well as method of treating diseases with such antigen-binding proteins and protein-drug conjugates. BACKGROUND OF THE INVENTION [0004] The development of drug delivery approaches to improve safety and efficacy of nervous system therapeutics is an increasingly critical and evolving field. Overcoming the blood–brain barrier (BBB) has been a challenge for the delivery of therapeutics to the brain. While the peripheral nervous system (PNS) does not have a BBB, it has been very challenging to appropriately deliver therapeutics to cells of interest in the PNS. Safe and efficacious nervous system therapeutics also require appropriate pharmacokinetic/pharmacodynamic (PK/PD) properties of the therapeutic in the nervous tissue of interest and limited potential effects on other regions of the nervous system. Moreover, the options for achieving retrograde targeting for therapeutic delivery are limited. [0005] Effective delivery of therapeutics to the nervous system may provide potential treatment opportunities for chronic pain and itch indications and otherwise uncurable Attorney Docket No.250298.000780 diseases such as spinal cord degeneration, amyotrophic lateral sclerosis (ALS), and neurodegenerative diseases such as Alzheimer’s disease (AD). SUMMARY OF THE INVENTION [0006] As mentioned in the background section above, there is an unmet need in the art to develop effective means to deliver therapeutics to the nervous system, such as to the peripheral nervous system (PNS), of a subject. This application provides compositions and methods to address this and other related needs. [0007] In one aspect, provided herein is an antigen-binding protein that binds to p75 neurotrophin receptor (p75NTR), wherein the antigen-binding protein exhibits less than 50% inhibition of an activity of the extracellular domain of human p75NTR, wherein the activity of the extracellular domain of p75NTR is the blocking of human nerve growth factor (NGF)- dependent activation of human tropomyosin receptor kinase A (TrkA) signaling, as measured in a cell-based assay. [0008] In some embodiments, the cell-based assay comprises the steps of: a) incubating a soluble extracellular domain of human p75NTR with mature human NGF in the presence of the antigen-binding protein, optionally the extracellular domain of human p75NTR is fused to an Fc domain of IgG, b) incubating the mixture of step (a) with a population of recombinant mammalian cells which stably expresses TrkA and a serum response element fused to a luciferase reporter. c) measuring luciferase activity in Relative Luminescence Units (RLU) from the mixture of step (b), and d) calculating % inhibition using the formula RLU 0 X antige − RLU 10 n−binding protein soluble p75 wherein, RLUsoluble p75 same conditions with an antigen-binding protein which does not bind to p75NTR , and RLUNGF is the RLU value from cells treated with only the human mature NGF in the absence of the soluble extracellular domain of p75NTR . [0009] In some embodiments, the antigen-binding protein comprises: (1) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 529, or a variant thereof; and a LCVR Attorney Docket No.250298.000780 comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 537, or a variant thereof; (2) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 549, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 557, or a variant thereof; (3) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 569, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 577, or a variant thereof; (4) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 589, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 597, or a variant thereof; and/or (5) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 609, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 597, or a variant thereof. [0010] In some embodiments, the antigen-binding protein comprises: (1) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 531, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 533, or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 535, or a variant thereof; and/or a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 539, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 541, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 543, or a variant thereof; (2) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 551, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 553, or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 555, or a variant thereof; and/or a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 559, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth Attorney Docket No.250298.000780 in SEQ ID NO: 561, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 563, or a variant thereof; (3) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 571, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 573, or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 575, or a variant thereof; and/or a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 579, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 581, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 583, or a variant thereof; (4) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 591, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 593, or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 595, or a variant thereof; and/or a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 599, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 601, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 603, or a variant thereof; and/or (5) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 611, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 613 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 615, or a variant thereof; and/or a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 599, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 601, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 603, or a variant thereof. [0011] In some embodiments, the antigen-binding protein comprises: (1) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 529, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 537, or a variant thereof; (2) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 549, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 557, or a variant thereof; Attorney Docket No.250298.000780 (3) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 569, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 577, or a variant thereof; (4) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 589, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 597, or a variant thereof; and/or (5) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 609, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 597, or a variant thereof. [0012] In some embodiments, the antigen-binding protein comprises: (1) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 545, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 547, or a variant thereof; (2) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 565, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 567, or a variant thereof; (3) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 585, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 587, or a variant thereof; (4) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 605, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 607, or a variant thereof; and/or (5) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 617, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 607, or a variant thereof. [0013] In one aspect, provided herein is an antigen-binding protein that binds to p75 neurotrophin receptor (p75NTR), comprising: (i) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 2, 22, 42, 58, 78, 98, 116, 136, 155, 173, 189, 207, 227, 245, 261, 279, 297, 315, 331, 349, 369, 387, 401, 417, 427, 437, 445, 455, 465, 475, 484, 493, 503, 513, 519, 529, 549, 569, 589 or 609, or a variant thereof; and/or (ii) a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 10, 30, 50, 66, 86, 106, 124, 144, 162, 179, Attorney Docket No.250298.000780 197, 215, 235, 251, 269, 287, 304, 323, 339, 357, 377, 391, 409, 537, 557, 577, or 597, or a variant thereof. [0014] In some embodiments, the antigen-binding protein comprises: (1) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 2, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 10, or a variant thereof; (2) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 22, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 30, or a variant thereof; (3) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 42, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 50, or a variant thereof; (4) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 58, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 66, or a variant thereof; (5) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 78, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 86, or a variant thereof; (6) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 98, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 106, or a variant thereof; (7) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 116, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 124, or a variant thereof; (8) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 136, or a variant thereof; and a LCVR Attorney Docket No.250298.000780 comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 144, or a variant thereof; (9) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 155, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 162, or a variant thereof; (10) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 173, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 179, or a variant thereof; (11) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 189, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 197, or a variant thereof; (12) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 207, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 215, or a variant thereof; (13) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 227, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 235, or a variant thereof; (14) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 245, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 251, or a variant thereof; (15) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 261, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 269, or a variant thereof; (16) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 279, or a variant thereof; and a LCVR Attorney Docket No.250298.000780 comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 287, or a variant thereof; (17) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 297, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 304, or a variant thereof; (18) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 315, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 323, or a variant thereof; (19) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 331, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 339, or a variant thereof; (20) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 349, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 357, or a variant thereof; (21) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 369, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 377, or a variant thereof; (22) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 387, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 391, or a variant thereof; (23) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 401, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof; (24) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 417, or a variant thereof; and a LCVR Attorney Docket No.250298.000780 comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof; (25) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 427, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof; (26) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 437, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof; (27) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 445, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof; (28) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 455, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof; (29) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 465, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof; (30) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 475, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof; (31) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 484, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof; (32) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 493, or a variant thereof; and a LCVR Attorney Docket No.250298.000780 comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof; (33) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 503, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof; (34) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 513, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof; (35) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 519, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof; (36) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 529, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 537, or a variant thereof; (37) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 549, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 557, or a variant thereof; (38) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 569, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 577, or a variant thereof; (39) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 589, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 597, or a variant thereof; and/or (40) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 609, or a variant thereof; and a LCVR Attorney Docket No.250298.000780 comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 597, or a variant thereof. [0015] In some embodiments, the antigen-binding protein comprises: (1) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 2, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 10, or a variant thereof; (2) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 22, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 30, or a variant thereof; (3) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 42, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 50, or a variant thereof; (4) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 58, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 66, or a variant thereof; (5) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 78, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 86, or a variant thereof; (6) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 98, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 106, or a variant thereof; (7) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 116, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 124, or a variant thereof; (8) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 136, or a variant thereof; and a LCVR Attorney Docket No.250298.000780 comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 144, or a variant thereof; (9) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 155, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 162, or a variant thereof; (10) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 173, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 179, or a variant thereof; (11) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 207, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 215, or a variant thereof; (12) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 245, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 251, or a variant thereof; (13) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 279, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 287, or a variant thereof; (14) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 297, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 304, or a variant thereof; (15) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 315, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 323, or a variant thereof; (16) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 349, or a variant thereof; and a LCVR Attorney Docket No.250298.000780 comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 357, or a variant thereof; (17) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 387, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 391, or a variant thereof; (18) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 417, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof; (19) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 427, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof; (20) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 437, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof; (21) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 445, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof; (22) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 455, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof; (23) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 465, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof; (24) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 475, or a variant thereof; and a LCVR Attorney Docket No.250298.000780 comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof; (25) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 493, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof; (26) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 503, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof; (27) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 513, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof; and/or (28) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 519, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof. [0016] In some embodiments, the antigen-binding protein comprises: (1) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 189, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 197, or a variant thereof; (2) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 227, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 235, or a variant thereof; (3) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 261, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 269, or a variant thereof; (4) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 331, or a variant thereof; and a LCVR Attorney Docket No.250298.000780 comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 339, or a variant thereof; (5) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 369, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 377, or a variant thereof; (6) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 401, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof; and/or (7) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 484, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof. [0017] In some embodiments, the antigen-binding protein comprises: (1) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 22, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 30, or a variant thereof; (2) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 78, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 86, or a variant thereof; (3) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 136, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 144, or a variant thereof; (4) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 261, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 269, or a variant thereof; (5) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 369, or a variant thereof; and a LCVR Attorney Docket No.250298.000780 comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 377, or a variant thereof; and/or (6) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 484, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof. [0018] In some embodiments, the antigen-binding protein comprises: (1) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 4, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 6, or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 8, or a variant thereof; and a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 12, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 14, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 16, or a variant thereof; (2) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 24, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 26 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 28, or a variant thereof; and a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 32, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 34, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 36, or a variant thereof; (3) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 44, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 46 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 48, or a variant thereof; and a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 12, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 14, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 52, or a variant thereof; (4) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 60, or a variant thereof, a HCDR2 comprising the amino acid sequence set Attorney Docket No.250298.000780 forth in SEQ ID NO: 62 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 64, or a variant thereof; and a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 68, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 70, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 72, or a variant thereof; (5) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 80, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 82, or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 84, or a variant thereof; and a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 88, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 90, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 92, or a variant thereof; (6) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 100, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 102 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 104, or a variant thereof; and a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 108, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 34, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 110, or a variant thereof; (7) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 118, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 120, or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 122, or a variant thereof; and a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 126, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 128, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 130, or a variant thereof; (8) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 138, or a variant thereof, a HCDR2 comprising the amino acid sequence set Attorney Docket No.250298.000780 forth in SEQ ID NO: 140, or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 142, or a variant thereof; and a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 146, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 90, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 149, or a variant thereof; (9) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 100, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 158 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 160, or a variant thereof; and a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 164, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 90, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 167, or a variant thereof; (10) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 100, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 175 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 177, or a variant thereof; and a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 181, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 70, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 183, or a variant thereof; (11) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 191, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 193 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 195, or a variant thereof; and a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 199, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 14, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 201, or a variant thereof; (12) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 209, or a variant thereof, a HCDR2 comprising the amino acid sequence set Attorney Docket No.250298.000780 forth in SEQ ID NO: 211 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 213, or a variant thereof; and a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 217, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 219, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 221, or a variant thereof; (13) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 229, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 231 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 233, or a variant thereof; and a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 237, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 14, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 239, or a variant thereof; (14) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 100, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 247 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 249, or a variant thereof; and a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 253, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 70, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 255, or a variant thereof; (15) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 263, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 265 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 267, or a variant thereof; and a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 271, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 90, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 273, or a variant thereof; (16) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 281, or a variant thereof, a HCDR2 comprising the amino acid sequence set Attorney Docket No.250298.000780 forth in SEQ ID NO: 283 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 285, or a variant thereof; and a LCVR that comprises: an LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 289, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 14, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 291, or a variant thereof; (17) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 299, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 193 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 302, or a variant thereof; and a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 237, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 307, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 309, or a variant thereof; (18) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 317, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 319 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 321, or a variant thereof; and a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 12, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 14, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 325, or a variant thereof; (19) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 333, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 335 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 337, or a variant thereof; and a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 237, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 341, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 343, or a variant thereof; (20) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 351, or a variant thereof, a HCDR2 comprising the amino acid sequence set Attorney Docket No.250298.000780 forth in SEQ ID NO: 353 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 355, or a variant thereof; and a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 359, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 361, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 363, or a variant thereof; (21) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 371, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 373 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 375, or a variant thereof; and a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 379, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 90, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 381, or a variant thereof; (22) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 138, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 319 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 389, or a variant thereof; and a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 393, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 361, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 395, or a variant thereof; (23) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 403, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 405 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 407, or a variant thereof; and a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 237, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 14, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 411, or a variant thereof; (24) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 419, or a variant thereof, a HCDR2 comprising the amino acid sequence set Attorney Docket No.250298.000780 forth in SEQ ID NO: 421 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 423, or a variant thereof; and a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 237, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 14, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 411, or a variant thereof; (25) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 429, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 431 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 433, or a variant thereof; and a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 237, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 14, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 411, or a variant thereof; (26) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 191, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 335 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 441, or a variant thereof; and a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 237, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 14, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 411, or a variant thereof; (27) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 447, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 449 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 451, or a variant thereof; and a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 237, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 14, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 411, or a variant thereof; (28) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 457, or a variant thereof, a HCDR2 comprising the amino acid sequence set Attorney Docket No.250298.000780 forth in SEQ ID NO: 459 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 461, or a variant thereof; and a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 237, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 14, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 411, or a variant thereof; (29) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 467, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 469 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 471, or a variant thereof; and a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 237, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 14, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 411, or a variant thereof; (30) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 477, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 158 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 480, or a variant thereof; and a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 237, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 14, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 411, or a variant thereof; (31) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 486, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 283 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 489, or a variant thereof; and a LCVR that comprises: LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 237, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 14, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 411, or a variant thereof; (32) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 495, or a variant thereof, a HCDR2 comprising the amino acid sequence set Attorney Docket No.250298.000780 forth in SEQ ID NO: 497 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 499, or a variant thereof; and a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 237, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 14, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 411, or a variant thereof; (33) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 505, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 507 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 509, or a variant thereof; and a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 237, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 14, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 411, or a variant thereof; (34) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 138, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 319 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 515, or a variant thereof; and a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 237, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 14, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 411, or a variant thereof; (35) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 521, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 523 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 525, or a variant thereof; and a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 237, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 14, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 411, or a variant thereof; (36) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 531, or a variant thereof, a HCDR2 comprising the amino acid sequence set Attorney Docket No.250298.000780 forth in SEQ ID NO: 533 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 535, or a variant thereof; and a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 539, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 541, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 543, or a variant thereof; (37) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 551, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 553 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 555, or a variant thereof; and a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 559, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 561, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 563, or a variant thereof; (38) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 571, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 573 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 575, or a variant thereof; and a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 579, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 581, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 583, or a variant thereof; (39) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 591, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 593 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 595, or a variant thereof; and a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 599, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 601, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 603, or a variant thereof; (40) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 611, or a variant thereof, a HCDR2 comprising the amino acid sequence set Attorney Docket No.250298.000780 forth in SEQ ID NO: 613 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 615, or a variant thereof; and/or a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 599, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 601, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 603, or a variant thereof. [0019] In some embodiments, the antigen-binding protein comprises: (1) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 4, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 6 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 8, or a variant thereof; and/or a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 12, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 14, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 16, or a variant thereof; (2) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 24, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 26 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 28, or a variant thereof; and/or a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 32, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 34, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 36, or a variant thereof; (3) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 44, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 46 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 48, or a variant thereof; and/or a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 12, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 14, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 52, or a variant thereof; (4) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 60, or a variant thereof, a HCDR2 comprising the amino acid sequence set Attorney Docket No.250298.000780 forth in SEQ ID NO: 62 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 64, or a variant thereof; and/or a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 68, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 70, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 72, or a variant thereof; (5) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 80, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 82 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 84, or a variant thereof; and/or a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 88, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 90, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 92, or a variant thereof; (6) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 100, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 102 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 104, or a variant thereof; and/or a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 108, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 34, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 110, or a variant thereof; (7) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 118, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 120 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 122, or a variant thereof; and/or a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 126, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 128, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 130, or a variant thereof; (8) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 138, or a variant thereof, a HCDR2 comprising the amino acid sequence set Attorney Docket No.250298.000780 forth in SEQ ID NO: 140 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 142, or a variant thereof; and/or a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 146, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 90, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 149, or a variant thereof; (9) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 100, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 158 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 160, or a variant thereof; and/or a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 164, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 90, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 167, or a variant thereof; (10) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 100, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 175 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 177, or a variant thereof; and/or a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 181, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 70, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 183, or a variant thereof; (11) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 209, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 211 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 213, or a variant thereof; and/or a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 217, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 219, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 221, or a variant thereof; (12) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 100, or a variant thereof, a HCDR2 comprising the amino acid sequence set Attorney Docket No.250298.000780 forth in SEQ ID NO: 247 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 249, or a variant thereof; and/or a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 253, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 70, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 255, or a variant thereof; (13) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 281, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 283 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 285, or a variant thereof; and/or a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 289, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 14, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 291, or a variant thereof; (14) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 299, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 193 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 302, or a variant thereof; and/or a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 237, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 307, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 309, or a variant thereof; (15) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 317, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 319 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 321, or a variant thereof; and/or a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 12, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 14, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 325, or a variant thereof; (16) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 351, or a variant thereof, a HCDR2 comprising the amino acid sequence set Attorney Docket No.250298.000780 forth in SEQ ID NO: 353 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 355, or a variant thereof; and/or a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 359, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 361, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 363, or a variant thereof; (17) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 138, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 319 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 389, or a variant thereof; and/or a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 393, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 361, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 395, or a variant thereof; (18) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 419, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 421 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 423, or a variant thereof; and/or a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 237, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 14, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 411, or a variant thereof; (19) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 429, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 431 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 433, or a variant thereof; and/or a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 237, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 14, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 411, or a variant thereof; (20) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 191, or a variant thereof, a HCDR2 comprising the amino acid sequence set Attorney Docket No.250298.000780 forth in SEQ ID NO: 335 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 441, or a variant thereof; and/or a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 237, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 14, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 411, or a variant thereof; (21) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 447, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 449 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 451, or a variant thereof; and/or a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 237, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 14, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 411, or a variant thereof; (22) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 457, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 459 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 461, or a variant thereof; and/or a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 237, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 14, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 411, or a variant thereof; (23) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 467, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 469 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 471, or a variant thereof; and/or a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 237, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 14, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 411, or a variant thereof; (24) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 477, or a variant thereof, a HCDR2 comprising the amino acid sequence set Attorney Docket No.250298.000780 forth in SEQ ID NO: 158 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 480, or a variant thereof; and/or a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 237, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 14, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 411, or a variant thereof; (25) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 495, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 497 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 499, or a variant thereof; and/or a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 237, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 14, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 411, or a variant thereof; (26) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 505, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 507 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 509, or a variant thereof; and/or a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 237, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 14, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 411, or a variant thereof; (27) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 138, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 319 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 515, or a variant thereof; and/or a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 237, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 14, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 411, or a variant thereof; and/or (28) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 521, or a variant thereof, a HCDR2 comprising the amino acid sequence set Attorney Docket No.250298.000780 forth in SEQ ID NO: 523 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 525, or a variant thereof; and/or a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 237, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 14, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 411, or a variant thereof. [0020] In some embodiments, the antigen-binding protein comprises: (1) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 191, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 193 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 195, or a variant thereof; and/or a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 199, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 14, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 201, or a variant thereof; (2) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 229, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 231 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 233, or a variant thereof; and/or a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 237, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 14, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 239, or a variant thereof; (3) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 263, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 265 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 267, or a variant thereof; and/or a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 271, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 90, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 273, or a variant thereof; (4) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 333, or a variant thereof, a HCDR2 comprising the amino acid sequence set Attorney Docket No.250298.000780 forth in SEQ ID NO: 335 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 337, or a variant thereof; and/or a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 237, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 341, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 343, or a variant thereof; (5) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 371, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 373 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 375, or a variant thereof; and/or a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 379, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 90, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 381, or a variant thereof; (6) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 403, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 405 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 407, or a variant thereof; and/or a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 237, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 14, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 411, or a variant thereof; and/or (7) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 486, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 283 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 489, or a variant thereof; and/or a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 237, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 14, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 411, or a variant thereof. [0021] In some embodiments, the antigen-binding protein comprises: (1) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 24, or a variant thereof, a HCDR2 comprising the amino acid sequence set Attorney Docket No.250298.000780 forth in SEQ ID NO: 26 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 28, or a variant thereof; and/or a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 32, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 34, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 36, or a variant thereof; (2) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 80, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 82 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 84, or a variant thereof; and/or a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 88, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 90, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 92, or a variant thereof; (3) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 138, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 140 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 142, or a variant thereof; and/or a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 146, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 90, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 149, or a variant thereof; (4) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 263, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 265 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 267, or a variant thereof; and/or a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 271, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 90, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 273, or a variant thereof; (5) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 371, or a variant thereof, a HCDR2 comprising the amino acid sequence set Attorney Docket No.250298.000780 forth in SEQ ID NO: 373 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 375, or a variant thereof; and/or a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 379, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 90, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 381, or a variant thereof; and/or (6) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 486, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 283 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 489, or a variant thereof; and/or a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 237, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 14, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 411, or a variant thereof. [0022] In some embodiments, the antigen-binding protein comprises: (1) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 2, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 10, or a variant thereof; (2) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 22, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 30, or a variant thereof; (3) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 42, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 50, or a variant thereof; (4) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 58, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 66, or a variant thereof; (5) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 78, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 86, or a variant thereof; (6) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 98, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 106, or a variant thereof; Attorney Docket No.250298.000780 (7) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 116, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 124, or a variant thereof; (8) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 136, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 144, or a variant thereof; (9) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 155, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 162, or a variant thereof; (10) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 173, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 179, or a variant thereof; (11) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 189, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 197, or a variant thereof; (12) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 207, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 215, or a variant thereof; (13) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 227, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 235, or a variant thereof; (14) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 245, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 251, or a variant thereof; (15) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 261, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 269, or a variant thereof; (16) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 279, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 287, or a variant thereof; (17) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 297, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 304, or a variant thereof; Attorney Docket No.250298.000780 (18) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 315, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 323, or a variant thereof; (19) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 331, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 339, or a variant thereof; (20) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 349, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 357, or a variant thereof; (21) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 369, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 377, or a variant thereof; (22) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 387, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 391, or a variant thereof; (23) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 401, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof; (24) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 417, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof; (25) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 427, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof; (26) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 437, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof; (27) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 445, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof; (28) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 455, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof; Attorney Docket No.250298.000780 (29) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 465, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof; (30) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 475, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof; (31) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 484, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof; (32) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 493, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof; (33) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 503, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof; (34) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 513, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof; (35) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 519, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof; (36) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 529, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 537, or a variant thereof; (37) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 549, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 557, or a variant thereof; (38) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 569, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 577, or a variant thereof; (39) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 589, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 597, or a variant thereof; and/or Attorney Docket No.250298.000780 (40) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 609, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 597, or a variant thereof. [0023] In some embodiments, the antigen-binding protein comprises: (1) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 2, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 10, or a variant thereof; (2) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 22, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 30, or a variant thereof; (3) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 42, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 50, or a variant thereof; (4) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 58, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 66, or a variant thereof; (5) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 78, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 86, or a variant thereof; (6) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 98, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 106, or a variant thereof; (7) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 116, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 124, or a variant thereof; (8) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 136, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 144, or a variant thereof; (9) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 155, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 162, or a variant thereof; Attorney Docket No.250298.000780 (10) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 173, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 179, or a variant thereof; (11) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 207, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 215, or a variant thereof; (12) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 245, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 251, or a variant thereof; (13) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 279, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 287, or a variant thereof; (14) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 297, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 304, or a variant thereof; (15) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 315, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 323, or a variant thereof; (16) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 349, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 357, or a variant thereof; (17) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 387, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 391, or a variant thereof; (18) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 417, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof; (19) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 427, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof; (20) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 437, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof; Attorney Docket No.250298.000780 (21) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 445, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof; (22) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 455, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof; (23) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 465, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof; (24) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 475, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof; (25) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 493, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof; (26) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 503, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof; (27) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 513, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof; and/or 28) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 519, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof. [0024] In some embodiments, the antigen-binding protein comprises: (1) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 189, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 197, or a variant thereof; (2) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 227, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 235, or a variant thereof; Attorney Docket No.250298.000780 (3) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 261, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 269, or a variant thereof; (4) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 331, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 339, or a variant thereof; (5) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 369, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 377, or a variant thereof; (6) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 401, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof; and/or (7) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 484, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof. [0025] In some embodiments, the antigen-binding protein comprises: (1) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 22, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 30, or a variant thereof; (2) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 78, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 86, or a variant thereof; (3) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 136, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 144, or a variant thereof; (4) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 261, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 269, or a variant thereof; (5) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 369, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 377, or a variant thereof; and/or Attorney Docket No.250298.000780 (6) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 484, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof. [0026] In some embodiments, the antigen-binding protein comprises: (1) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 18, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 20, or a variant thereof; (2) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 38, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 40, or a variant thereof; (3) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 54, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 56, or a variant thereof; (4) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 74, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 76, or a variant thereof; (5) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 94, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 96, or a variant thereof; (6) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 112, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 114, or a variant thereof; (7) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 132, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 134, or a variant thereof; (8) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 151, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 153, or a variant thereof; (9) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 169, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 171, or a variant thereof; Attorney Docket No.250298.000780 (10) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 185, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 187, or a variant thereof; (11) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 203, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 205, or a variant thereof; (12) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 223, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 225, or a variant thereof; (13) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 241, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 243, or a variant thereof; (14) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 257, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 259, or a variant thereof; (15) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 275, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 277, or a variant thereof; (16) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 293, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 295, or a variant thereof; (17) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 311, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 313, or a variant thereof; (18) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 327, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 329, or a variant thereof; (19) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 345, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 347, or a variant thereof; (20) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 365, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 367, or a variant thereof; Attorney Docket No.250298.000780 (21) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 383, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 385, or a variant thereof; (22) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 397, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 399, or a variant thereof; (23) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 413, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 415, or a variant thereof; (24) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 425, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 415, or a variant thereof; (25) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 435, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 415, or a variant thereof; (26) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 443, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 415, or a variant thereof; (27) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 453, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 415, or a variant thereof; (28) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 463, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 415, or a variant thereof; (29) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 473, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 415, or a variant thereof; (30) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 482, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 415, or a variant thereof; (31) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 491, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 415, or a variant thereof; Attorney Docket No.250298.000780 (32) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 501, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 415, or a variant thereof; (33) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 511, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 415, or a variant thereof; (34) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 517, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 415, or a variant thereof; (35) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 527, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 415, or a variant thereof; (36) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 545, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 547, or a variant thereof; (37) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 565, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 567, or a variant thereof; (38) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 585, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 587, or a variant thereof; (39) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 605, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 607, or a variant thereof; and/or (40) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 617, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 607, or a variant thereof. [0027] In some embodiments, the antigen-binding protein comprises: (1) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 18, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 20, or a variant thereof; Attorney Docket No.250298.000780 (2) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 38, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 40, or a variant thereof; (3) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 54, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 56, or a variant thereof; (4) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 74, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 76, or a variant thereof; (5) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 94, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 96, or a variant thereof; (6) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 112, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 114, or a variant thereof; (7) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 132, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 134, or a variant thereof; (8) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 151, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 153, or a variant thereof; (9) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 169, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 171, or a variant thereof; (10) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 185, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 187, or a variant thereof; (11) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 223, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 225, or a variant thereof; (12) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 257, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 259, or a variant thereof; Attorney Docket No.250298.000780 (13) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 293, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 295, or a variant thereof; (14) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 311, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 313, or a variant thereof; (15) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 327, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 329, or a variant thereof; (16) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 365, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 367, or a variant thereof; (17) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 397, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 399, or a variant thereof; (18) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 425, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 415, or a variant thereof; (19) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 435, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 415, or a variant thereof; (20) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 443, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 415, or a variant thereof; (21) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 453, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 415, or a variant thereof; (22) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 463, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 415, or a variant thereof; (23) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 473, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 415, or a variant thereof; Attorney Docket No.250298.000780 (24) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 482, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 415, or a variant thereof; (25) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 501, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 415, or a variant thereof; (26) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 511, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 415, or a variant thereof; (27) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 517, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 415, or a variant thereof; and/or (28) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 527, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 415, or a variant thereof. [0028] In some embodiments, the antigen-binding protein comprises: (1) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 203, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 205, or a variant thereof; (2) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 241, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 243, or a variant thereof; (3) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 275, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 277, or a variant thereof; (4) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 345, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 347, or a variant thereof; (5) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 383, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 385, or a variant thereof; Attorney Docket No.250298.000780 (6) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 413, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 415, or a variant thereof; and/or (7) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 491, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 415, or a variant thereof. [0029] In some embodiments, the antigen-binding protein comprises: (1) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 38, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 40, or a variant thereof; (2) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 94, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 96, or a variant thereof; (3) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 151, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 153, or a variant thereof; (4) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 275, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 277, or a variant thereof; (5) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 383, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 385, or a variant thereof; and/or (6) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 491, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 415, or a variant thereof. [0030] In some embodiments, the antigen binding protein blocks the binding of a human neurotrophin receptor mouse Fc dimer (human p75-mFc) to human neurotrophin 3 (hNT-3) by at least about 50%. [0031] In some embodiments, the antigen binding protein blocks the binding of a human neurotrophin receptor mouse Fc dimer (human p75-mFc) to human neurotrophin 3 (hNT-3) by less than about 50%. Attorney Docket No.250298.000780 [0032] In another aspect, provided herein is an antigen-binding protein that binds to the same epitope on p75NTR as an antibody comprising an HCVR/LCVR amino acid sequence pair as set forth in Table 1-1. [0033] In a further aspect, provided herein is an antigen-binding protein that competes for binding to p75NTR with an antibody comprising an HCVR/LCVR amino acid sequence pair as set forth in Table 1-1. [0034] In some embodiments, the antigen-binding protein comprises an antibody or antigen- binding fragment thereof. [0035] In some embodiments, the antigen-binding protein is selected from a humanized antibody or antigen binding fragment thereof, human antibody or antigen binding fragment thereof, murine antibody or antigen binding fragment thereof, chimeric antibody or antigen binding fragment thereof, monovalent Fab', divalent Fab2, F(ab)'3 fragments, single-chain fragment variable (scFv), bis-scFv, (scFv)2, diabody, minibody, nanobody, triabody, tetrabody, disulfide stabilized Fv protein (dsFv), single-domain antibody (sdAb), Ig NAR, single heavy chain antibody, bispecific antibody or biding fragment thereof, bi-specific T-cell engager (BiTE), trispecific antibody, or chemically modified derivatives thereof. [0036] In one embodiment, the antigen-binding protein comprises a fragment antigen-binding region (Fab). [0037] In one embodiment, the antigen-binding protein comprises a single chain fragment variable (scFv). [0038] In one embodiment, the scFv comprises variable regions arranged in the following orientation from N-terminus to C-terminus: HCVR-LCVR. [0039] In one embodiment, the scFv comprises variable regions arranged in the following orientation from N-terminus to C-terminus: LCVR-HCVR. [0040] In some embodiments, the variable regions in the scFv are connected by a linker. [0041] In one embodiment, the linker is a peptide linker. [0042] In one embodiment, the peptide linker is -(GGGGS) n - (SEQ ID NO: 668), wherein n is any integral selected from 1-10. [0043] In some embodiments, the antigen-binding protein binds to human p75NTR. [0044] In one embodiment, the antigen-binding protein binds to human p75NTR with a KD of about 1X10-9 M or a stronger affinity. [0045] In another aspect, provided herein is an isolated polynucleotide encoding the antigen- binding protein as described herein. Attorney Docket No.250298.000780 [0046] In a further aspect, provided herein is a vector comprising the isolated polynucleotide as described herein. [0047] In a further aspect, provided herein is a host cell comprising the antigen-binding protein as described herein, the isolated polynucleotide as described herein or the vector as described herein. [0048] In one embodiment, the host cell is a Chinese hamster ovary (CHO) cell. [0049] In another aspect, provided herein is a protein-drug conjugate comprising an antigen- binding protein that binds to p75 neurotrophin receptor (p75NTR) and is conjugated to a molecular cargo. [0050] In some embodiments, the antigen-binding protein of the protein-drug conjugate comprises the antigen-binding protein as described herein. [0051] In one embodiment, the antigen-binding protein and the molecular cargo are conjugated via a linker. [0052] In some embodiments, the molecular cargo comprises a polynucleotide molecule, a polypeptide molecule, a carrier, or a small molecule. [0053] In one embodiment, the molecular cargo comprises a polynucleotide molecule. [0054] In some embodiments, the polynucleotide molecule is an interfering nucleic acid molecule, a guide RNA, a ribozyme, an aptamer, a mixmer, a multimer, or an mRNA. [0055] In one embodiment, the interfering nucleic acid molecule is an siRNA, an shRNA, a miRNA, an antisense oligonucleotide, or a gapmer. [0056] In some embodiments, the interfering nucleic acid molecule is an siRNA. [0057] In one embodiment, the siRNA comprises a sense strand of 21 nucleotides in length. [0058] In one embodiment, the siRNA comprises an antisense strand of 23 nucleotides in length. [0059] In some embodiments, the siRNA comprises two phosphorothioate linkages at the first and second internucleoside linkages at the 5’ end of the sense strand. [0060] In some embodiments, the siRNA comprises two phosphorothioate linkages at the first and second internucleoside linkages at the 3’ and/or 5’ ends of the antisense strand. [0061] In one embodiment, the interfering nucleic acid molecule is an antisense oligonucleotide. [0062] In one embodiment, the polynucleotide molecule is a guide RNA. [0063] In some embodiments, the polynucleotide molecule targets a gene or gene product associated with pain, itch, or a neurological disease or disorder. Attorney Docket No.250298.000780 [0064] In some embodiments, the gene or gene product associated with pain, itch, or a neurological disease or disorder is voltage-gated sodium channel Nav1.7, voltage-gated sodium channel Nav1.8, voltage-gated sodium channel Nav1.9, voltage-gated sodium channel Nav1.6, tropomyosin receptor kinase A (TrkA), tropomyosin receptor kinase C (TRKC), acid-sensing ion channel subunit 1 (ASIC1), acid-sensing ion channel subunit 3 (ASIC3), transient receptor potential vanilloid 1 (TRPV1), transient receptor potential vanilloid 4 (TRPV4), transient receptor potential cation channel, subfamily A, member 1 (TRPA1), transient receptor potential cation channel subfamily M, member 8 (TRPM8), fatty acid amide hydrolase (FAAH), piezo type mechanosensitive ion channel component 1 (PIEZO1), piezo type mechanosensitive ion channel component 2 (PIEZO2), enkephalin, RET proto- oncogene (RET), interleukin 4 receptor (IL4R), interleukin 13 receptor (IL13R), interleukin 31 receptor (IL31R), interleukin 6 receptor alpha (IL6Ra), glycoprotein 130 (gp130), FXYD domain containing ion transport regulator 2 (FXYD2), P2X purinoceptor 3 (P2X3), calcitonin gene-related peptide (CGRP), pituitary adenylate cyclase-activating polypeptide (PACAP), or interleukin 6 (IL6). [0065] In some embodiments, the polynucleotide molecule comprises one or more modified nucleotides. [0066] In some embodiments, the molecular cargo comprises a polypeptide molecule. [0067] In some embodiments, the polypeptide molecule is an enzyme, a neuroprotective molecule, or an antigen-binding protein that binds to a target other than p75NTR. [0068] In some embodiments, the polypeptide molecule is associated with pain, itch, or a neurological disease or disorder. [0069] In some embodiments, the polypeptide molecule is a neurotrophic factor, an antibody or antibody fragment, an antibody receptor fusion protein, or a suppressor of cytokine signaling. [0070] In some embodiments, the protein-drug conjugate is for use in treating or preventing pain, itch, or a neurological disease or disorder. [0071] In some embodiments, the pain is peripheral chronic pain, a chronic neuropathic pain, somatic pain, chronic post-operative pain, small fiber peripheral neuropathy, chemotherapy- induced neuropathy, painful diabetic-induced neuropathy, post-herpetic neuralgia, osteoarthritis, back pain, joint pain, trigeminal neuralgia, trigeminal pain, temporo-mandibular pain, migraine, dysautonomia, or myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Attorney Docket No.250298.000780 [0072] In one embodiment, the chronic neuropathic pain is trigeminal pain or trigeminal neuralgia. [0073] In one embodiment, the itch is chronic itch. [0074] In some embodiments, the neurological disease or disorder is a neurodegenerative disease or disorder, a neurodevelopmental disease or disorder, a physical injury, a neuropsychiatric disease or disorder, or a neurological cancer. [0075] In one embodiment, the neurodegenerative disease or disorder is Alzheimer’s disease (AD), Parkinson’s disease (PD), amyotrophic lateral sclerosis (ALS), or multiple sclerosis (MS). [0076] In one embodiment, the physical injury is traumatic brain injury, spinal cord injury, stroke, or brain edema. [0077] In one embodiment, the neurological cancer is a brain cancer or a peripheral nerve cancer. [0078] In one embodiment, the pain, itch, or neurological disease or disorder is associated with a sensory neuron, a dorsal root ganglion cell or a trigeminal ganglion cell, or a population thereof. [0079] In some embodiments, the molecular cargo comprises a carrier. [0080] In some embodiments, the carrier is a lipid-based carrier. [0081] In some embodiments, the lipid-based carrier is a lipid nanoparticle (LNP), a liposome, a lipidoid, or a lipoplex. [0082] In one embodiment, the lipid-based carrier is a LNP. [0083] In some embodiments, the LNP further comprises a polynucleotide molecule and/or a polypeptide molecule. [0084] In some embodiments, the LNP comprises one or more components of a gene editing system. [0085] In some embodiments, the LNP comprises: (a) a Cas nuclease, or a nucleic acid encoding the Cas nuclease, and/or (b) a guide RNA, or one or more DNAs encoding the guide RNA. [0086] In one embodiment, the Cas nuclease is a Cas9 protein. [0087] In some embodiments, the Cas9 protein is derived from a Streptococcus pyogenes Cas9 protein, a Staphylococcus aureus Cas9 protein, a Campylobacter jejuni Cas9 protein, a Streptococcus thermophilus Cas9 protein, or a Neisseria meningitidis Cas9 protein. Attorney Docket No.250298.000780 [0088] In some embodiments, the nucleic acid encoding the Cas nuclease is codon-optimized for expression in a mammalian cell. [0089] In one embodiment, the nucleic acid encoding the Cas nuclease is codon-optimized for expression in a human cell. [0090] In one embodiment, the nucleic acid encoding the Cas nuclease is an mRNA. [0091] In one embodiment, the guide RNA is a single guide RNA (sgRNA). [0092] In some embodiments, the LNP comprises a zinc finger nuclease (ZFN), or a transcription activator-like effector nuclease (TALEN). [0093] In some embodiments, the LNP comprises a cationic lipid, a neutral lipid, a helper lipid, a stealth lipid, or any combination thereof. [0094] In one embodiment, the neutral lipid is distearoylphosphatidylcholine (DSPC). [0095] In one embodiment, the helper lipid is cholesterol. [0096] In one embodiment, the stealth lipid is PEG2k-DMG. [0097] In another aspect, provided herein is a pharmaceutical composition comprising the antigen-binding protein as described herein, the isolated polynucleotide as described herein, the vector as described herein, or the protein-drug conjugate as described herein and a pharmaceutically acceptable carrier. [0098] In a further aspect, provided herein is a composition or kit comprising the antigen- binding protein as described herein, the isolated polynucleotide as described herein, the vector as described herein, or the protein-drug conjugate as described herein or pharmaceutical composition as described herein and a further therapeutic agent. [0099] In another aspect, provided herein is a complex comprising the antigen-binding protein as described herein or the protein-drug conjugate as described herein bound to a human p75 neurotrophin receptor (p75NTR) polypeptide. [00100] In a further aspect, provided herein is a method for making the antigen-binding protein as described herein, comprising culturing a host cell comprising a polynucleotide that encodes the antigen-binding protein in a culture medium under conditions favorable to expression of the antigen-binding protein. [00101] In some embodiments, the method for making the antigen-binding protein as described herein comprises the steps: (a) introducing said polynucleotide into a host cell; (b) culturing the host cell under conditions favorable to expression of the antigen- binding protein; Attorney Docket No.250298.000780 (c) optionally, isolating the antigen-binding protein from the culture medium and/or host cell; and (d) optionally, conjugating the antigen-binding protein to a molecular cargo. [00102] In another aspect, provided herein is an antigen-binding protein which is produced by or obtainable by the method as described herein. [00103] In a further aspect, provided herein is a method for making a protein-drug conjugate as described herein comprising: (a) contacting the antigen-binding protein, with the molecular cargo under the conditions favorable for conjugation of the antigen-binding protein to the molecular cargo; and (b) optionally, isolating the protein-drug conjugate produced in step (a). [00104] In another aspect, provided herein is a method for making a protein-drug conjugate as described herein, wherein the molecular cargo comprises a polypeptide molecule, comprising: (a) culturing a host cell comprising a polynucleotide encoding the protein-drug conjugate under conditions that allow expression of the protein-drug conjugate; and (b) optionally, isolating the protein-drug conjugate produced in step (a). [00105] In a further aspect, provided herein is a protein-drug conjugate which is produced by or obtainable by the method as described herein. [00106] In another aspect, provided herein is a vessel or injection device comprising the antigen-binding protein as described herein, the isolated polynucleotide as described herein, the vector as described herein, or the protein-drug conjugate as described herein. [00107] In a further aspect, provided herein is a method for administering the antigen- binding protein as described herein, the isolated polynucleotide as described herein, the vector as described herein, or the protein-drug conjugate as described herein to a subject comprising introducing the antigen-binding protein, the polynucleotide, the vector, or the protein-drug conjugate into the body of the subject. [00108] In some embodiments, the antigen-binding protein, the polynucleotide, the vector, or the protein-drug conjugate is introduced into the body of the subject via subcutaneous, intramuscular, or intravenous administration. [00109] In some embodiments, the antigen-binding protein, the polynucleotide, the vector, or the protein-drug conjugate is administered into the body of the subject via intrathecal, intracisternal, intracerebroventricular, or intraparenchymal administration. Attorney Docket No.250298.000780 [00110] In one embodiment, the antigen-binding protein, the polynucleotide, the vector, or the protein-drug conjugate is administered into the body of the subject via intravitreal administration into the eye. [00111] In another aspect, provided herein is a method for delivering a molecular cargo to a tissue or cell type expressing p75NTR in the body of a subject comprising administering to the subject the protein-drug conjugate as described herein, or the pharmaceutical composition as described herein. [00112] In some embodiments, the tissue is brain, spinal cord, peripheral nervous system, autonomic nervous system, enteric nervous system, or eye. [00113] In one embodiment, the tissue is brain or spinal cord. [00114] In one embodiment, the cell type is a sensory neuron. [00115] In one embodiment, the cell type is a dorsal root ganglion cell or a trigeminal ganglion cell. [00116] In some embodiments, the protein-drug conjugate is introduced into the body of the subject via subcutaneous, intramuscular, or intravenous administration. [00117] In some embodiments, the protein-drug conjugate is administered into the body of the subject via subcutaneous, intrathecal, intracisternal, intracerebroventricular, or intraparenchymal administration. [00118] In one embodiment, the protein-drug conjugate is administered into the body of the subject via intravitreal administration into the eye. [00119] In one embodiment, the protein-drug conjugate is administered into the body of the subject via subcutaneous administration. [00120] In one embodiment, the protein-drug conjugate is administered into the body of the subject via intracerebroventricular administration. [00121] In a further aspect, provided herein is a method for treating or preventing pain, itch, or a neurological disease or disorder in a subject in need thereof comprising administering to the subject an effective amount of the antigen-binding protein as described herein, the isolated polynucleotide as described herein, the vector as described herein, or the protein-drug conjugate as described herein, or the pharmaceutical composition as described herein. [00122] In some embodiments, the antigen-binding protein, the polynucleotide, the vector, or the protein-drug conjugate is administered via subcutaneous, intramuscular, or intravenous administration. Attorney Docket No.250298.000780 [00123] In some embodiments, the antigen-binding protein, the polynucleotide, the vector, or the protein-drug conjugate is administered into the body of the subject via intrathecal, intracisternal, intracerebroventricular, or intraparenchymal administration. [00124] In one embodiment, the antigen-binding protein, the polynucleotide, the vector, or the protein-drug conjugate is administered into the body of the subject via intravitreal administration into the eye. [00125] In some embodiments, the pain is peripheral chronic pain, a chronic neuropathic pain, somatic pain, chronic post-operative pain, small fiber peripheral neuropathy, chemotherapy-induced neuropathy, painful diabetic-induced neuropathy, post- herpetic neuralgia, osteoarthritis, back pain, joint pain, trigeminal neuralgia, trigeminal pain, temporo-mandibular pain, migraine, dysautonomia, or myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). [00126] In one embodiment, the chronic neuropathic pain is trigeminal pain or trigeminal neuralgia. [00127] In one embodiment, the itch is chronic itch. [00128] In some embodiments, the neurological disease or disorder is a neurodegenerative disease, a neurodevelopmental disease, a chronic neuropathic pain, a physical injury, a neuropsychiatric disease, or a neurological cancer. [00129] In one embodiment, the neurodegenerative disease or disorder is Alzheimer’s disease (AD), Parkinson’s disease (PD), amyotrophic lateral sclerosis (ALS), or multiple sclerosis (MS). [00130] In one embodiment, the physical injury is traumatic brain injury, spinal cord injury, stroke, or brain edema. [00131] In one embodiment, the neurological cancer is a brain cancer or a peripheral nerve cancer. [00132] In some embodiments, the pain, itch, or a neurological disease or disorder is associated with a sensory neuron, a dorsal root ganglion cell, a trigeminal ganglion cell, or a population thereof. [00133] In some embodiments, the method as described herein further comprises administering an additional treatment to the subject. [00134] In some embodiments, the additional treatment comprises administering a nonsteroidal anti-inflammatory drug (NSAID), acetaminophen, a local anesthetic, capsaicin, a Cox-2 inhibitor, an antidepressant, an anti-seizure medication, an anti-epileptic medication, Attorney Docket No.250298.000780 an opioid, a steroid, an anticonvulsant, a muscle relaxant, a triptan, dihydroergotamine, Lasmiditan, a calcitonin gene-related peptides antagonist, an anti-nausea drug, a beta blocker, a calcium channel blocker, a serotonin and norepinephrine reuptake inhibitor (SNRI), onabotulinumtoxinA, or a benzodiazepine, or a combination thereof BRIEF DESCRIPTION OF THE FIGURES [00135] Fig. 1 shows that anti-p75NTR antibody is internalized in ex vivo dorsal root ganglion (DRG) tissue. Live, time-lapse confocal imaging of DRGs grown ex vivo. Alexa 647 conjugated antibodies were applied at t=0, maximum projections of 3 confocal optical slices 10 µm apart are shown. Axons are labeled within 5 minutes of addition of fluorescently conjugated anti-p75NTR antibody to the culture media. Internalization into neuronal cell bodies is seen 1-4 hours post antibody addition. [00136] Figs. 2A-2B show that anti-p75NTR antibody is internalized in ex vivo DRG tissue. Live, time-lapse confocal imaging of DRGs grown ex vivo. Alexa 647 conjugated antibodies were applied at t=0, maximum projections of 3 confocal optical slices 10 µm apart are shown. Axons are labeled within 5 minutes of addition of fluorescently conjugated anti- p75NTR antibody to the culture media. Internalization into neuronal cell bodies is seen 1-4 hours post antibody addition. [00137] Figs. 3A-3F show that anti-p75NTR antibody internalizes in DRGs following intraplantar injection. Maximum projection of confocal Z stack images of whole DRGs harvested 5 days post injection of fluorescently conjugated antibody into the hind foot pad. Lumbar DRG ipsilateral to intraplantar injection of anti-Fel D1 (Fig. 3A), or anti-p75NTR REGN14155 (Fig.3B), or anti-p75NTR REGN14187 (Fig.3C). Lumbar DRG contralateral to intraplantar injection of anti-Fel D1 (Fig.3D), or anti-p75NTR REGN14155 (Fig.3E), or anti- p75NTR REGN14187. CT-B labels DRG neurons on the ipsilateral side of injection (Figs.3A- 3C), but not the contralateral side (Figs.3D-3F). Anti-p75NTR antibody shows uptake in DRGs on both sides. CT-B, Cholera Toxin subunit B - Alexa 488 (Fig.3F). [00138] Figs.4A-4C show that anti-p75NTR antibody internalizes in trigeminal ganglion (TG) following intraplantar injection. Maximum projection of confocal Z stack images of whole trigeminal ganglia harvested 5 days post injection of fluorescently conjugated antibody into the hind foot pad. Transmitted light and fluorescent image of trigeminal ganglion from: Attorney Docket No.250298.000780 intraplantar injection of anti-Fel D1 (Fig.4A); intraplantar injection of anti-p75NTR REGN14155 (Fig.4B); intraplantar injection of anti-p75NTR REGN14187 (Fig.4C). [00139] Figs. 5A-5F show that anti-p75NTR antibody internalizes in DRGs and TG following intramuscular injection. Maximum projection of confocal Z stack images of whole DRGs harvested 5 days post injection of fluorescently conjugated antibody into the gastrocnemius muscle. Lumbar DRG ipsilateral to intramuscular injection of anti-Fel D1 (Fig. 5A). Lumbar DRG ipsilateral to intramuscular injection of anti-p75NTR REGN14187 (Fig.5B). Lumbar DRG contralateral to intramuscular injection of anti-Fel D1 (Fig.5C). Lumbar DRG contralateral to intramuscular injection of anti-p75NTR REGN14187 (Fig. 5D). Trigeminal ganglia from mouse injected with anti-Fel D1 in gastrocnemius muscle (Fig.5E). Trigeminal ganglia from mouse injected with anti-p75NTR REGN14187 in gastrocnemius muscle (Fig. 5F). CT-B labels DRG neurons on the ipsilateral side of injection (Figs.5A-5B), but not the contralateral side (Figs.5C-5D) or TG (Figs.5E-5F). Anti-p75NTR shows uptake in DRGs on both sides and uptake in trigeminal ganglion. CT-B, Cholera Toxin subunit B - Alexa 488. [00140] Fig.6 shows that anti-p75NTR antibody internalizes in all lumbar DRGs 3 days following subcutaneous injection. Fluorescent anti-p75NTR is detected in all lumbar DRGs 3 days post subcutaneous injection of 0.5 mg/kg fluorescently tagged antibody. A647 fluorescent image of lumbar DRGs overlayed onto transmitted light image of DRG is shown. [00141] Figs. 7A-7B show that anti-p75NTR antibody internalizes in DRG neurons 3 days following subcutaneous injection.20X confocal single slice images with 1.5x zoom allow visualization of intracellular distribution of fluorescently tagged anti-p75NTR REGN14187 in DRG neurons. Punctate, intracellular anti-p75NTR antibody is detected in neurons. [00142] Figs.8A-8C show that anti-p75NTR antibody internalizes in DRG neurons that express the marker of peripheral neurons, peripherin. Widefield, fluorescent images of DRG sections from mice that were injected with subcutaneously anti-p75NTR REGN14187, then stained with anti-peripherin to identify neurons. [00143] Figs.9A-9N shows that anti-p75NTR antibody internalizes in DRGs, TG, colon, eye and sympathetic ganglia 5 days following subcutaneous injection. Fluorescent anti- p75NTR antibody is detected in TG (Fig.9B), cervical DRG (Fig.9D), thoracic DRG (Fig.9E) and lumbar DRGs (Fig.9F) 5 days post subcutaneous injection of 0.7 mg/kg fluorescently tagged antibody. A647 fluorescent image of TG and DRGs overlayed onto transmitted light image of DRG is shown in Figs.9A-9F. Fluorescent anti-p75NTR antibody is detected in colon (Fig. 9H). Higher magnification image of colon tissue shows that fluorescent anti-p75NTR Attorney Docket No.250298.000780 antibody internalizes in cells in the myenteric plexus (Fig. 9I). Fluorescent anti-p75NTR antibody is detected in the eye (Fig.9K). A647 fluorescent confocal image of colon or eye tissue is shown in Figs.9G-9K. Fluorescent anti-p75NTR antibody is detected in sympathetic ganglia (Fig.9M). A647 fluorescent widefield image of ventral side of the thoracic spinal cord and is shown in Figs.9L-9M. In all tissue, subcutaneous injection of fluorescent anti-Fel D1 does not show fluorescent signal (Figs.9A, 9C, 9G, 9J, and 9L). Co-labeling with neuron and glial markers in DRG confirmed that anti-p75NTR antibodies internalized in DRG neurons and not surrounding satellite glia (Fig.9N). [00144] Figs.10A-10F show that that anti-p75NTR antibody has undetectable presence in cerebellum (Fig.10A), hippocampus (Fig.10B), liver (Fig.10C) and spinal cord (Fig.10F) following subcutaneous injection. Low detection of anti-p75NTR antibody is detected in choroid plexus (Fig.10B), kidney (Fig.10C) and heart (Fig.10E) following subcutaneous injection. Confocal images of DAPI and A647 channels are shown. [00145] Figs. 11A-11D show that anti-p75NTR antibody is detected in choroid plexus following subcutaneous injection. 10X confocal images of sagittal brain sections show anti- p75NTR antibody observed in choroid plexus (arrows) 5 days following subcutaneous injection, with little or no detection in other regions of the brain. [00146] Figs.12A-12D show that low levels of anti-p75NTR antibodies are detected in the brain following ICV injection. Fluorescent, 5x confocal images of sagittal brain sections demonstrate low accumulation of anti-p75NTR specific labeling in ventral and cortical regions (Fig. 12D). Both anti-Fel D1 (Fig. 12B) and anti-p75NTR antibodies (Fig. 12D) show accumulation in the ventricle, the site of injection. [00147] Figs.13A-13D show that Alexa-conjugated anti-p75 (Alexa-anti-p75) antibody is detected in sensory neurons in trigeminal ganglia that are ipsilateral (Fig.13B), but not contralateral (Fig.13D), to the injection site at sensory neuron terminals in the whisker pad, indicative of retrograde transport of the fluorescently conjugated antibodies along sensory neuron axons from the axon terminals to the sensory neuron cell body. Confocal images of DAPI staining of ipsilateral (Fig.13A) and contralateral (Fig.13C) trigeminal ganglia are also included. [00148] Fig.14 shows that intravenous delivery of anti-p75NTR antibody-Nav1.7 siRNA conjugates improves Scn9a transcript reduction in trigeminal ganglia compared to isotype conjugated controls. Humanized Nav1.7 mice were injected twice intravenously (I.V.) with 50mg/kg of anti-p75NTR antibody-Nav1.7 siRNA conjugate or isotype antibody conjugated Attorney Docket No.250298.000780 control. Trigeminal ganglia were collected 14 days following the first I.V. dose for quantitative PCR analysis. A reduction of approximately 30% of Nav1.7 mRNA transcript is observed with anti-p75NTR antibody conjugation compared to isotype conjugated controls. n=3 mice per group. [00149] Figs.15A-15H show that internalization of fluorescent REGN anti-p75NTR into neurons was observed following intravenous injection of REGN19516 in the trigeminal ganglia (Fig.15D) and DRG (Fig.15H). Intravenous injection of fluorescent isotype control antibody, REGN1945, did not demonstrate labeling in TG or DRGs (Figs.15B, 15F). DETAILED DESCRIPTION OF THE INVENTION [00150] The present disclosure provides antigen-binding proteins that specifically bind to p75 neurotrophin receptor (p75NTR), or an antigenic fragment thereof. The present disclosure further provides protein-drug conjugates comprising an antigen-binding protein that specifically binds to p75NTR, or an antigenic fragment thereof, and that is conjugated to a molecular cargo. Such conjugates are useful, for example, for delivery of the molecular cargo to various tissues, e.g., peripheral nervous system, autonomic nervous system (such as sympathetic/parasympathetic nervous system, e.g., sympathetic and/or parasympathetic ganglia), enteric nervous system (such as myenteric plexus), central nervous system (CNS) and eye tissues, and/or cells, e.g., sensory neurons (such as, but not limited to, dorsal root ganglion (DRG) cells and/or trigeminal ganglion (TG) cells), sympathetic neurons, parasympathetic neurons and enteric neurons, in the body. In some embodiments, conjugates described herein can be useful for delivery of a molecular cargo described herein to cells such as dermal fibers, celiac ganglion cells, Müller glia, Leydig cells, ionocytes, dendritic cells, Schwann cells, salivary gland cells, retinal bipolar neurons, basal respiratory cells, basal squamous epithelial cells, and the like. The conjugates described herein have an ability to efficiently deliver molecular cargoes to the nervous system including the peripheral nervous system, brain and the spinal cord and, in particular, DRG cells (e.g., neurons) and TG cells (e.g., neurons) therein and thus, can be used for treatment of pain (e.g., chronic pain including peripheral chronic pain), itch (e.g., chronic itch) and neurological diseases and disorders such as neurodegenerative, neurodevelopmental and neuropsychiatric disorders. In some embodiments, the conjugates described herein have an ability to efficiently deliver molecular cargoes to peptidergic and non-peptidergic sensory neurons (peripherin) in DRG. Attorney Docket No.250298.000780 In some embodiments, anti-p75NTR can be taken up in a high percentage of DRG and/or TG cells (e.g., neurons) efficiently, with little uptake in peripheral tissues and brain. [00151] In accordance with the present disclosure there may be employed conventional molecular biology, microbiology, and recombinant DNA techniques within the skill of the art. Such techniques are explained fully in the literature. See, e.g., Sambrook, Fritsch & Maniatis, Molecular Cloning: A Laboratory Manual, Second Edition (1989) Cold Spring Harbor Laboratory Press, Cold Spring Harbor, N.Y. (herein "Sambrook, et al., 1989"); DNA Cloning: A Practical Approach, Volumes I and II (D. N. Glover ed. 1985); Oligonucleotide Synthesis (M. J. Gait ed.1984); Nucleic Acid Hybridization (B. D. Hames & S. J. Higgins eds. (1985)); Transcription And Translation (B. D. Hames & S. J. Higgins, eds. (1984)); Animal Cell Culture (R. I. Freshney, ed. (1986)); Immobilized Cells And Enzymes (IRL Press, (1986)); B. Perbal, A Practical Guide To Molecular Cloning (1984); F. M. Ausubel, et al. (eds.), Current Protocols in Molecular Biology, John Wiley & Sons, Inc. (1994). [00152] A polynucleotide includes DNA and RNA. The present disclosure includes any polynucleotide described herein which is operably linked to a promoter or other expression control sequence. [00153] The term “p75NTR” or “p75NTR” refers to p75 neurotrophin receptor. The p75 neurotrophin receptor (p75NTR) belongs to the tumor necrosis factor receptor superfamily (TNFRSF). p75NTR receptors expressed at axon terminals at the periphery are known to transport retrogradely to the soma, delivering survival, apoptosis and differentiation signals to the cell body. Rabies virus binds p75NTR receptors and hijacks retrograde transport machinery to infect neurons. In the presence of TrkA, p75NTR potentiates NGF signaling and increases survival and differentiation. In the absence of TrkA, NGF binding to p75NTR promotes apoptosis. p75NTR expression is increased in a number of pathological conditions such as Alzheimer’s disease (AD), Amyotrophic Lateral Sclerosis (ALS), and ischemia. In the peripheral nervous system (PNS), p75NTR can be found, e.g., in sympathetic and sensory neurons (Qin et al., Journal of Neuroscience Research, 98(10), 1987-1998 (2000); Yamamoto et al., Neurochem Res 21, 929–938 (1996); each is incorporated herein by reference in its entirety), and in subsets of parasympathetic neurons and some enteric neurons. In non-neuronal tissue, p75NTR can be found in mesenchymal cells within several organs/structures, limb, maxillary pad, tooth, lung, muscle, testis, retina, pituitary, hair follicles, salivary glands, perivascular cells and meninges. Attorney Docket No.250298.000780 [00154] In an embodiment, an exemplary human p75NTR protein (NCBI accession number NP_002498.1) comprises the amino acid sequence: MGAGATGRAMDGPRLLLLLLLGVSLGGAKEACPTGLYTHSGECCKACNLGEGVAQPCGA NQTVCEPCLDSVTFSDVVSATEPCKPCTECVGLQSMSAPCVEADDAVCRCAYGYYQDET TGRCEACRVCEAGSGLVFSCQDKQNTVCEECPDGTYSDEANHVDPCLPCTVCEDTERQL RECTRWADAECEEIPGRWITRSTPPEGSDSTAPSTQEPEAPPEQDLIASTVAGVVTTVMG SSQPVVTRGTTDNLIPVYCSILAAVVVGLVAYIAFKRWNSCKQNKQGANSRPVNQTPPPEG EKLHSDSGISVDSQSLHDQQPHTQTASGQALKGDGGLYSSLPPAKREEVEKLLNGSAGDT WRHLAGELGYQPEHIDSFTHEACPVRALLASWATQDSATLDALLAALRRIQRADLVESLCS ESTATSPV (SEQ ID NO: 669). [00155] In some embodiments, a human p75NTR protein described herein may be encoded by the nucleotide sequence of: ATGGGGGCAGGTGCCACCGGCCGCGCCATGGACGGGCCGCGCCTGCTGCTGTTGCT GCTTCTGGGGGTGTCCCTTGGAGGTGCCAAGGAGGCATGCCCCACAGGCCTGTACAC ACACAGCGGTGAGTGCTGCAAAGCCTGCAACCTGGGCGAGGGTGTGGCCCAGCCTT GTGGAGCCAACCAGACCGTGTGTGAGCCCTGCCTGGACAGCGTGACGTTCTCCGACG TGGTGAGCGCGACCGAGCCGTGCAAGCCGTGCACCGAGTGCGTGGGGCTCCAGAGC ATGTCGGCGCCGTGCGTGGAGGCCGACGACGCCGTGTGCCGCTGCGCCTACGGCTA CTACCAGGATGAGACGACTGGGCGCTGCGAGGCGTGCCGCGTGTGCGAGGCGGGCT CGGGCCTCGTGTTCTCCTGCCAGGACAAGCAGAACACCGTGTGCGAGGAGTGCCCCG ACGGCACGTATTCCGACGAGGCCAACCACGTGGACCCGTGCCTGCCCTGCACCGTGT GCGAGGACACCGAGCGCCAGCTCCGCGAGTGCACACGCTGGGCCGACGCCGAGTGC GAGGAGATCCCTGGCCGTTGGATTACACGGTCCACACCCCCAGAGGGCTCGGACAGC ACAGCCCCCAGCACCCAGGAGCCTGAGGCACCTCCAGAACAAGACCTCATAGCCAGC ACGGTGGCAGGTGTGGTGACCACAGTGATGGGCAGCTCCCAGCCCGTGGTGACCCG AGGCACCACCGACAACCTCATCCCTGTCTATTGCTCCATCCTGGCTGCTGTGGTTGTG GGCCTTGTGGCCTACATAGCCTTCAAGAGGTGGAACAGCTGCAAGCAGAACAAGCAA GGAGCCAACAGCCGGCCAGTGAACCAGACGCCCCCACCAGAGGGAGAAAAACTCCA CAGCGACAGTGGCATCTCCGTGGACAGCCAGAGCCTGCATGACCAGCAGCCCCACAC GCAGACAGCCTCGGGCCAGGCCCTCAAGGGTGACGGAGGCCTCTACAGCAGCCTGC CCCCAGCCAAGCGGGAGGAGGTGGAGAAGCTTCTCAACGGCTCTGCGGGGGACACC TGGCGGCACCTGGCGGGCGAGCTGGGCTACCAGCCCGAGCACATAGACTCCTTTACC CATGAGGCCTGCCCCGTTCGCGCCCTGCTTGCAAGCTGGGCCACCCAGGACAGCGC Attorney Docket No.250298.000780 CACACTGGACGCCCTCCTGGCCGCCCTGCGCCGCATCCAGCGAGCCGACCTCGTGG AGAGTCTGTGCAGTGAGTCCACTGCCACATCCCCGGTG (SEQ ID NO: 670). p75NTR Binding Proteins and Protein-Drug Conjugates [00156] In one aspect, the present disclosure provides antigen-binding proteins that bind specifically to p75NTR. [00157] An antigen-binding protein that specifically binds to p75NTR may bind at about 25°C, to p75NTR or a fusion protein thereof, for example, a tag such as His6 (SEQ ID NO: 619) and/or myc fused to e.g., human p75NTR or monkey p75NTR, e.g., in a surface plasmon resonance assay, with a KD of about 1x10-9 M or a stronger affinity. Such an antigen-binding protein may be referred to as “anti-p75NTR”. [00158] In some embodiments, the antigen-binding protein that specifically binds to p75NTR may comprise an antibody, or an antigen-binding fragment of an antibody, such as a fragment antigen-binding region (Fab) or single chain fragment variable (scFv). [00159] The present disclosure further provides p75NTR binding protein-drug conjugates. A p75NTR binding protein-drug conjugate may comprise an optional signal peptide, connected to an antigen-binding protein (e.g., an antibody or an antigen-binding fragment of an antibody such as a fragment antigen-binding region (Fab) or single chain fragment variable (scFv)) that binds specifically to p75NTR, such as human p75NTR, and that is conjugated (optionally by a linker) to molecular cargo. The p75NTR binding protein-drug conjugates described herein can deliver the conjugated molecular cargo to a desired tissue (e.g., nervous tissue) and/or desired cell type (e.g., sensory neurons (such as, but not limited to, dorsal root ganglion cells and/or trigeminal ganglion cells)) in the body. Non-limiting examples of cell types to which a p75NTR binding protein-drug conjugate described herein can deliver a conjugated molecular cargo include neurons, Müller glial cells, Leydig cells, ionocytes, dorsal root ganglion (DRG) cells, trigeminal ganglion cells, sympathetic ganglion cells, dermal fiber cells, retinal cells, myenteric plexus cells, celiac ganglion cells, dendritic cells, Schwann cells, salivary gland cells, retinal bipolar neurons, basal respiratory cells, basal squamous epithelial cells, and oligodendrocytes. [00160] The term "conjugate" means a body in which two substances are linked covalently, or non-covalently. The term "covalently linked" refers to a characteristic of at least two molecules being linked together by way of one or more covalent bond(s). In various embodiments, two molecules can be covalently linked together by a single bond, e.g., a Attorney Docket No.250298.000780 disulfide bridge or a disulfide bond, that operates as a linker between the molecules. In some embodiments, two or more molecules may be covalently linked together by way of a molecule that operates as a linker that joins the at least two molecules together via multiple covalent bonds. In certain embodiments, a linker can be a cleavable linker or a non-cleavable linker. In the conjugate, the two substances may be linked directly or may be linked via a linker. In the present disclosure, one of the two substances is an antigen-binding protein, e.g., an antibody or antigen-binding fragment thereof, and the other is a drug (e.g., a polynucleotide, a polypeptide, or a liposome or LNP disclosed herein). In the present disclosure, the linker may be a cleavable linker or may be a non-cleavable linker. In some embodiments, two polypeptide molecules that are covalently linked, either directly or indirectly (e.g., by a linker), may be expressed from one single polynucleotide molecule. [00161] As used herein, the term "antibody-drug conjugate" or “ADC” means a conjugate of an antibody or antigen-binding fragment thereof with a drug (e.g., a polynucleotide, a polypeptide, or a liposome or LNP disclosed herein). The affinity to an antigen is imparted to a drug by linking an antibody or antigen-binding fragment thereof with the drug (e.g., a polynucleotide, or a liposome or LNP disclosed herein), thereby increasing the efficiency of delivering the drug to a target site in vivo. “Antibody-drug conjugates” or “ADCs” as used herein also encompass fusion proteins wherein the antibody or antigen- binding fragment thereof is fused with another polypeptide molecule. [00162] The present disclosure includes antibodies and antigen-binding fragments thereof, such as Fabs and scFvs, that bind specifically to p75NTR, such as the human p75NTR. [00163] The term "antibody", as used herein, refers to immunoglobulin molecules comprising four polypeptide chains, two heavy chains (HCs) and two light chains (LCs), inter- connected by disulfide bonds (e.g., IgG). In an embodiment, each antibody heavy chain (HC) comprises a heavy chain variable region (“HCVR” or “VH”) (e.g., SEQ ID NO: 2, 22, 42, 58, 78, 98, 116, 136, 155, 173, 189, 207, 227, 245, 261, 279, 297, 315, 331, 349, 369, 387, 401, 417, 427, 437, 445, 455, 465, 475, 484, 493, 503, 513, 519, 529, 549, 569, 589, 609 or a variant thereof) and a heavy chain constant region; and each antibody light chain (LC) comprises a light chain variable region (“LCVR or “VL”) (e.g., SEQ ID NO: 10, 30, 50, 66, 86, 106, 124, 144, 162, 179, 197, 215, 235, 251, 269, 287, 304, 323, 339, 357, 377, 391, 409, 537, 557, 577, 597 or a variant thereof) and a light chain constant region (CL). The VH and VL regions can be further subdivided into regions of hypervariability, termed complementarity Attorney Docket No.250298.000780 determining regions (CDR), interspersed with regions that are more conserved, termed framework regions (FR). Each VH and VL comprises three CDRs and four FRs. [00164] In an embodiment, the assignment of amino acids to each framework or CDR domain in an immunoglobulin is in accordance with the definitions of Sequences of Proteins of Immunological Interest, Kabat et al.; National Institutes of Health, Bethesda, Md.; 5th ed.; NIH Publ. No.91-3242 (1991); Kabat (1978) Adv. Prot. Chem.32:1-75; Kabat et al., (1977) J. Biol. Chem.252:6609-6616; Chothia, et al., (1987) J Mol. Biol.196:901-917 or Chothia, et al., (1989) Nature 342: 878-883. Thus, the present disclosure includes antibodies and antigen-binding fragments including the CDRs of a VH and the CDRs of a VL, which VH and VL comprise amino acid sequences as set forth herein (see e.g., sequences of Table 1-1, or a variant thereof), wherein the CDRs are as defined according to Kabat and/or Chothia. [00165] An p75NTR binding protein described herein may be an antigen-binding fragment of an antibody which optionally may be conjugated to a molecular cargo. The terms "antigen-binding portion" or "antigen-binding fragment" of an antibody, as used herein, refers to an immunoglobulin molecule that binds antigen but that does not include all of the sequences of a full antibody (preferably, the full antibody is an IgG). Non-limiting examples of antigen-binding fragments include: (i) Fab fragments; (ii) F(ab')2 fragments; (iii) Fd fragments; (iv) Fv fragments; (v) single-chain Fv (scFv) molecules; and (vi) dAb fragments; consisting of the amino acid residues that mimic the hypervariable region of an antibody (e.g., an isolated complementarity determining region (CDR) such as a CDR3 peptide), or a constrained FR3-CDR3-FR4 peptide. Other engineered molecules, such as domain-specific antibodies, single domain antibodies, domain-deleted antibodies, chimeric antibodies, CDR- grafted antibodies, diabodies, triabodies, tetrabodies, minibodies and small modular immunopharmaceuticals (SMIPs), are also encompassed within the expression "antigen- binding fragment," as used herein. [00166] As mentioned, an p75NTR binding protein described herein may be an scFv which optionally may be conjugated to a molecular cargo. An scFv (single chain fragment variable) has variable regions of heavy (VH) and light (VL) domains (in either order), which, preferably, are joined together by a flexible linker (e.g., peptide linker). The length of the flexible linker used to link both of the V regions may be important for yielding the correct folding of the polypeptide chain. Previously, it has been estimated that the peptide linker must span 3.5 nm (35 Å) between the carboxy terminus of the variable domain and the amino terminus of the other domain without affecting the ability of the domains to fold and form an Attorney Docket No.250298.000780 intact antigen-binding site (Huston et al., Protein engineering of single-chain Fv analogs and fusion proteins. Methods in Enzymology. 1991;203:46–88). In an embodiment, the linker comprises an amino acid sequence of such length to separate the variable domains by about 3.5 nm. [00167] In some embodiments, an antigen-binding protein that specifically binds to p75NTR comprises a heavy chain variable region (HCVR or VH) and/or a light chain variable region (LCVR or VL). [00168] In an embodiment, an antigen-binding protein that specifically binds to p75NTR comprises an anti-p75NTR scFv comprising the arrangement of variable regions as follows LCVR-HCVR or HCVR-LCVR, wherein the HCVR and LCVR are optionally connected by a linker. [00169] In some embodiments, a p75NTR binding protein-drug conjugate comprises a heavy chain variable region (HCVR or VH) and/or a light chain variable region (LCVR or VL). [00170] In an embodiment, a p75NTR binding protein-drug conjugate includes an anti- p75NTR scFv comprising the arrangement of variable regions as follows LCVR-HCVR or HCVR-LCVR, wherein the HCVR and LCVR are optionally connected by a linker and the scFv is connected, optionally by a linker, to a molecular cargo (e.g., LCVR-(Gly4Ser)3 (SEQ ID NO: 623)-HCVR-molecular cargo; or LCVR-(Gly4Ser)3 (SEQ ID NO: 623)-HCVR-molecular cargo). [00171] In some embodiments, an p75NTR binding protein described herein comprises a monovalent or “one-armed” antibody. The monovalent or "one-armed" antibodies as used herein refer to immunoglobulin proteins comprising a single variable domain. For example, the one-armed antibody may comprise a single variable domain within a Fab wherein the Fab is linked to at least one Fc fragment. In certain embodiments, the one-armed antibody comprises: (i) a heavy chain comprising a heavy chain constant region and a heavy chain variable region, (ii) a light chain comprising a light chain constant region and a light chain variable region, and (iii) a polypeptide comprising a Fc fragment or a truncated heavy chain. In certain embodiments, the Fc fragment or a truncated heavy chain comprised in the separate polypeptide is a "dummy Fc," which refers to an Fc fragment that is not linked to an antigen binding domain. The one-armed antibodies of the present disclosure may comprise any of the HCVR/LCVR pairs or CDR amino acid sequences as set forth in Table 1-1 herein. One-armed antibodies comprising a full-length heavy chain, a full-length light chain and an additional Fc domain polypeptide can be constructed using standard methodologies (see, Attorney Docket No.250298.000780 e.g., WO2010151792, which is incorporated herein by reference in its entirety), wherein the heavy chain constant region differs from the Fc domain polypeptide by at least two amino acids (e.g., H95R and Y96F according to the IMGT exon numbering system; or H435R and Y436F according to the EU numbering system). Such modifications are useful in purification of the monovalent antibodies (see WO2010151792). [00172] An antigen-binding fragment of an antibody will, in an embodiment, comprise at least one variable domain. The variable domain may be of any size or amino acid composition and will generally comprise at least one CDR, which is adjacent to or in frame with one or more framework sequences. In antigen-binding fragments having a VH domain associated with a VL domain, the VH and VL domains may be situated relative to one another in any suitable arrangement. For example, the variable region may be dimeric and contain VH - VH, VH - VL or VL - VL dimers. Alternatively, the antigen-binding fragment of an antibody may contain a monomeric VH and/or VL domain which are bound non-covalently. [00173] In certain embodiments, an antigen-binding fragment of an antibody may contain at least one variable domain covalently linked to at least one constant domain. Non- limiting, exemplary configurations of variable and constant domains that may be found within an antigen-binding fragment of an antibody described herein include: (i) VH -CH1; (ii) VH - CH2; (iii) VH -CH3; (iv) VH-CH1-CH2; (v) VH -CH1-CH2-CH3; (vi) VH -CH2-CH3; (vii) VH -CL; (viii) VL -CH1; (ix) VL -CH2; (x) VL -CH3; (xi) VL -CH1-CH2; (xii) VL-CH1-CH2-CH3; (xiii) VL - CH2-CH3; and (xiv) VL -CL. In any configuration of variable and constant domains, including any of the exemplary configurations listed above, the variable and constant domains may be either directly linked to one another or may be linked by a full or partial hinge or linker region. A hinge region may consist of at least 2 (e.g., 5, 10, 15, 20, 40, 60 or more) amino acids, which result in a flexible or semi-flexible linkage between adjacent variable and/or constant domains in a single polypeptide molecule. Moreover, an antigen-binding fragment of an antibody described herein may comprise a homo-dimer or hetero-dimer (or other multimer) of any of the variable and constant domain configurations listed above in non-covalent association with one another and/or with one or more monomeric VH or VL domain (e.g., by disulfide bond(s)). The present disclosure includes an antigen-binding fragment of an antigen-binding protein such as an antibody set forth herein, for example, REGN14148; REGN14149; REGN14150; REGN14151; REGN14152; REGN14153; REGN14154; REGN14155; REGN14156; REGN14157; REGN14158; REGN14159; REGN14160; REGN14161; REGN14162; REGN14163; REGN14164; REGN14165; REGN14175; Attorney Docket No.250298.000780 REGN14176; REGN14177; REGN14178; REGN14179; REGN14180; REGN14181; REGN14182; REGN14183; REGN14184; REGN14185; REGN14186; REGN14187; REGN14188; REGN14189; REGN14190; REGN14191; REGN19513; REGN19514; REGN19515; REGN19516; or REGN19517. [00174] Antigen-binding proteins (e.g., antibodies and antigen-binding fragments) may be monospecific or multispecific (e.g., bispecific). Multispecific antigen-binding proteins are discussed further herein. The present disclosure includes monospecific as well as multispecific (e.g., bispecific) antigen-binding fragments comprising one or more variable domains from an antigen-binding protein that is specifically set forth herein (e.g., REGN14148; REGN14149; REGN14150; REGN14151; REGN14152; REGN14153; REGN14154; REGN14155; REGN14156; REGN14157; REGN14158; REGN14159; REGN14160; REGN14161; REGN14162; REGN14163; REGN14164; REGN14165; REGN14175; REGN14176; REGN14177; REGN14178; REGN14179; REGN14180; REGN14181; REGN14182; REGN14183; REGN14184; REGN14185; REGN14186; REGN14187; REGN14188; REGN14189; REGN14190; REGN14191; REGN19513; REGN19514; REGN19515; REGN19516; or REGN19517). [00175] The term “specifically binds” or “binds specifically”, or the like, means that an antigen-binding protein (e.g., an antibody or antigen-binding fragment thereof) forms a complex with an antigen that is relatively stable under physiologic conditions. Specific binding can be characterized by an equilibrium dissociation constant (KD) of about 1x10-6 M or less, e.g., 10-7M, 10-8M, 10-9M, 10-10M, 10-11M, or 10-12M (a smaller KD denotes a tighter binding). Methods for determining whether an antigen-binding protein (e.g., an antibody or antigen- binding fragment thereof) specifically binds to an antigen are known in the art and include, for example, equilibrium dialysis, surface plasmon resonance (e.g., BIACORETM), bio-layer interferometry assay (e.g., Octet® HTX biosensor), solution-affinity ELISA, and the like. In some embodiments, specific binding is measured in a surface plasmon resonance assay, e.g., at 25°C or 37°C. An antigen-binding protein (e.g., an antibody or antigen-binding fragment thereof) that specifically binds an antigen from one species may or may not have cross-reactivity to other antigens, such as an orthologous antigen from another species. The present disclosure includes antigen-binding proteins that specifically bind to p75NTR protein (e.g., human p75NTR protein, mouse p75NTR protein, and/or cynomolgus monkey p75NTR protein). “Anti-p75NTR” refers to an antigen-binding protein (or other molecule), for example an antibody or antigen-binding fragment thereof, that binds specifically to p75NTR. Attorney Docket No.250298.000780 [00176] "Isolated" antigen-binding proteins (e.g., antibodies or antigen-binding fragments thereof), polypeptides, polynucleotides and vectors, are at least partially free of other biological molecules from the cells or cell culture from which they are produced. Such biological molecules include nucleic acids, proteins, other antibodies or antigen-binding fragments, lipids, carbohydrates, or other material such as cellular debris and growth medium. An isolated antigen-binding protein may further be at least partially free of expression system components such as biological molecules from a host cell or of the growth medium thereof. Generally, the term "isolated" is not intended to refer to a complete absence of such biological molecules (e.g., minor or insignificant amounts of impurity may remain) or to an absence of water, buffers, or salts or to components of a pharmaceutical formulation that includes the antigen-binding proteins (e.g., antibodies or antigen-binding fragments). [00177] The present disclosure includes antigen-binding proteins, e.g., antibodies or antigen-binding fragments, that bind to the same epitope as an antigen-binding protein described herein (e.g., REGN14148; REGN14149; REGN14150; REGN14151; REGN14152; REGN14153; REGN14154; REGN14155; REGN14156; REGN14157; REGN14158; REGN14159; REGN14160; REGN14161; REGN14162; REGN14163; REGN14164; REGN14165; REGN14175; REGN14176; REGN14177; REGN14178; REGN14179; REGN14180; REGN14181; REGN14182; REGN14183; REGN14184; REGN14185; REGN14186; REGN14187; REGN14188; REGN14189; REGN14190; REGN14191; REGN19513; REGN19514; REGN19515; REGN19516; or REGN19517). [00178] An antigen is a molecule, such as a peptide (e.g., p75NTR or a fragment thereof (an antigenic fragment)), to which, for example, an antibody or antigen-binding fragment thereof binds. The specific region on an antigen that an antibody recognizes and binds to is called the epitope. Antigen-binding proteins (e.g., antibodies) described herein that specifically bind to such antigens are part of the present disclosure. [00179] The term “epitope” refers to an antigenic determinant (e.g., on p75NTR) that interacts with a specific antigen-binding site of an antigen-binding protein, e.g., a variable region of an antibody, known as a paratope. A single antigen may have more than one epitope. Thus, different antibodies may bind to different areas on an antigen and may have different biological effects. The term “epitope” may also refer to a site on an antigen to which B and/or T cells respond and/or to a region of an antigen that is bound by an antibody. Epitopes may be defined as structural or functional. Functional epitopes are generally a subset of the structural epitopes and have those residues that directly contribute to the affinity Attorney Docket No.250298.000780 of the interaction. Epitopes may be linear or conformational, that is, composed of non-linear amino acids. In certain embodiments, epitopes may include determinants that are chemically active surface groupings of molecules such as amino acids, sugar side chains, phosphoryl groups, or sulfonyl groups, and, in certain embodiments, may have specific three-dimensional structural characteristics, and/or specific charge characteristics. Epitopes to which antigen- binding proteins described herein bind may be included in fragments of p75NTR, for example the extracellular domain thereof. Antigen-binding proteins (e.g., antibodies) described herein that bind to such epitopes are part of the present disclosure. [00180] Methods for determining the epitope of an antigen-binding protein, e.g., antibody or fragment or polypeptide, include alanine scanning mutational analysis, peptide blot analysis (Reineke (2004) Methods Mol. Biol. 248: 443-63), peptide cleavage analysis, crystallographic studies and NMR analysis. In addition, methods such as epitope excision, epitope extraction and chemical modification of antigens can be employed (Tomer (2000) Prot. Sci.9: 487-496). Another method that can be used to identify the amino acids within a polypeptide with which an antigen-binding protein (e.g., antibody or fragment or polypeptide) interacts is hydrogen/deuterium exchange detected by mass spectrometry. See, e.g., Ehring (1999) Analytical Biochemistry 267: 252-259; Engen and Smith (2001) Anal. Chem.73: 256A- 265A. [00181] The present disclosure includes antigen-binding proteins that compete for binding to p75NTR, e.g., an p75NTR epitope as discussed herein, with an antigen-binding protein described herein, e.g., REGN14148; REGN14149; REGN14150; REGN14151; REGN14152; REGN14153; REGN14154; REGN14155; REGN14156; REGN14157; REGN14158; REGN14159; REGN14160; REGN14161; REGN14162; REGN14163; REGN14164; REGN14165; REGN14175; REGN14176; REGN14177; REGN14178; REGN14179; REGN14180; REGN14181; REGN14182; REGN14183; REGN14184; REGN14185; REGN14186; REGN14187; REGN14188; REGN14189; REGN14190; REGN14191; REGN19513; REGN19514; REGN19515; REGN19516; or REGN19517. The term “competes” as used herein, refers to an antigen-binding protein (e.g., antibody or antigen-binding fragment thereof) that binds to an antigen (e.g., p75NTR) and inhibits or blocks the binding of another antigen-binding protein (e.g., antibody or antigen-binding fragment thereof) to the antigen. Unless otherwise stated, the term also includes competition between two antigen-binding proteins e.g., antibodies, in both orientations, i.e., a first antibody that binds antigen and blocks binding by a second antibody and vice versa. Thus, in an Attorney Docket No.250298.000780 embodiment, competition occurs in one such orientation. In certain embodiments, the first antigen-binding protein (e.g., antibody) and second antigen-binding protein (e.g., antibody) may bind to the same epitope. Alternatively, the first and second antigen-binding proteins (e.g., antibodies) may bind to different, but, for example, overlapping or non-overlapping epitopes, wherein binding of one inhibits or blocks the binding of the second antibody, e.g., via steric hindrance. Competition between antigen-binding proteins (e.g., antibodies) may be measured by methods known in the art, for example, by a real-time, label-free bio-layer interferometry assay. Also, binding competition between anti-p75NTR antigen-binding proteins (e.g., monoclonal antibodies (mAbs)) can be determined using a real time, label-free bio-layer interferometry assay on an Octet RED384 biosensor (Pall ForteBio Corp.). [00182] Typically, an antibody or antigen-binding fragment described herein which is modified in some way retains the ability to specifically bind to p75NTR, e.g., retains at least 10% of its p75NTR binding activity (when compared to the parental antibody) when that activity is expressed on a molar basis. Preferably, an antibody or antigen-binding fragment described herein retains at least 20%, 50%, 70%, 80%, 90%, 95% or 100% or more of the p75NTR binding affinity as the parental antibody. It is also intended that an antibody or antigen-binding fragment described herein may include conservative or non-conservative amino acid substitutions (referred to as "conservative variants" or "function conserved variants" of the antibody) that do not substantially alter its biologic activity. [00183] An p75NTR binding protein described herein may be a monoclonal antibody or an antigen-binding fragment of a monoclonal antibody which optionally may be conjugated to a molecular cargo. The present disclosure includes monoclonal p75NTR binding proteins, e.g., antibodies and antigen-binding fragments thereof (e.g., REGN14148; REGN14149; REGN14150; REGN14151; REGN14152; REGN14153; REGN14154; REGN14155; REGN14156; REGN14157; REGN14158; REGN14159; REGN14160; REGN14161; REGN14162; REGN14163; REGN14164; REGN14165; REGN14175; REGN14176; REGN14177; REGN14178; REGN14179; REGN14180; REGN14181; REGN14182; REGN14183; REGN14184; REGN14185; REGN14186; REGN14187; REGN14188; REGN14189; REGN14190; REGN14191; REGN19513; REGN19514; REGN19515; REGN19516; or REGN19517), as well as monoclonal compositions comprising a plurality of isolated monoclonal antigen-binding proteins. The term "monoclonal antibody" or “mAb”, as used herein, refers to a member of a population of substantially homogeneous antibodies, i.e., the antibody molecules comprising the population are identical in amino acid sequence Attorney Docket No.250298.000780 except for possible naturally occurring mutations that may be present in minor amounts. A "plurality" of such monoclonal antibodies and fragments in a composition refers to a concentration of identical (i.e., as discussed above, in amino acid sequence except for possible naturally occurring mutations that may be present in minor amounts) antibodies and fragments which is above that which would normally occur in nature, e.g., in the blood of a host organism such as a mouse or a human. [00184] In an embodiment, an p75NTR binding protein, e.g., antibody or antigen-binding fragment (which optionally may be conjugated to a molecular cargo) comprises a heavy chain constant domain, e.g., of the type IgA (e.g., IgA1 or IgA2), IgD, IgE, IgG (e.g., IgG1, IgG2, IgG3 and IgG4) or IgM. In an embodiment, an antigen-binding protein, e.g., antibody or antigen-binding fragment, comprises a light chain constant domain, e.g., of the type kappa or lambda. In an embodiment, a VH as set forth herein is linked to a human heavy chain constant domain (e.g., IgG) and a VL as set forth herein is linked to a human light chain constant domain (e.g., kappa). The present disclosure includes antigen-binding proteins comprising the variable domains set forth herein (e.g., REGN14148; REGN14149; REGN14150; REGN14151; REGN14152; REGN14153; REGN14154; REGN14155; REGN14156; REGN14157; REGN14158; REGN14159; REGN14160; REGN14161; REGN14162; REGN14163; REGN14164; REGN14165; REGN14175; REGN14176; REGN14177; REGN14178; REGN14179; REGN14180; REGN14181; REGN14182; REGN14183; REGN14184; REGN14185; REGN14186; REGN14187; REGN14188; REGN14189; REGN14190; REGN14191; REGN19513; REGN19514; REGN19515; REGN19516; or REGN19517), which are linked to a heavy and/or light chain constant domain, e.g., as set forth herein. [00185] The present disclosure includes human p75NTR binding proteins which optionally may be conjugated to a molecular cargo. The term "human” antigen-binding protein, such as an antibody or antigen-binding fragment, as used herein, includes antibodies and fragments having human amino acid sequence; for example, variable and constant regions derived from human germline immunoglobulin sequences whether in a human cell or grafted into a non-human cell, e.g., a mouse cell. See e.g., U.S. Patent Nos. 8,502,018; 6,596,541 or 5,789,215. The anti-p75NTR human mAbs described herein may include amino acid residues not encoded by human germline immunoglobulin sequences (e.g., mutations introduced by random or site-specific mutagenesis in vitro or by somatic mutation in vivo), for example in the CDRs and in particular CDR3. However, the term "human antibody", as used Attorney Docket No.250298.000780 herein, is not intended to include mAbs in which CDR sequences derived from the germline of another mammalian species (e.g., mouse) have been grafted onto human FR sequences. The term includes antibodies recombinantly produced in a non-human mammal or in cells of a non-human mammal. The term is not intended to include natural antibodies directly isolated from a human subject. The present disclosure includes human antigen-binding proteins (e.g., antibodies or antigen-binding fragments thereof such as REGN14148; REGN14149; REGN14150; REGN14151; REGN14152; REGN14153; REGN14154; REGN14155; REGN14156; REGN14157; REGN14158; REGN14159; REGN14160; REGN14161; REGN14162; REGN14163; REGN14164; REGN14165; REGN14175; REGN14176; REGN14177; REGN14178; REGN14179; REGN14180; REGN14181; REGN14182; REGN14183; REGN14184; REGN14185; REGN14186; REGN14187; REGN14188; REGN14189; REGN14190; REGN14191; REGN19513; REGN19514; REGN19515; REGN19516; or REGN19517). [00186] The present disclosure includes anti-p75NTR chimeric antigen-binding proteins, e.g., antibodies and antigen-binding fragments thereof (which optionally may be conjugated to a molecular cargo), and methods of use thereof. As used herein, a "chimeric antibody" is an antibody having the variable domain from a first antibody and the constant domain from a second antibody, where the first and second antibodies are from different species. (see e.g., US4816567; and Morrison et al., (1984) Proc. Natl. Acad. Sci. USA 81: 6851-6855). The present disclosure includes chimeric antibodies comprising the variable domains which are set forth herein (e.g., from REGN14148; REGN14149; REGN14150; REGN14151; REGN14152; REGN14153; REGN14154; REGN14155; REGN14156; REGN14157; REGN14158; REGN14159; REGN14160; REGN14161; REGN14162; REGN14163; REGN14164; REGN14165; REGN14175; REGN14176; REGN14177; REGN14178; REGN14179; REGN14180; REGN14181; REGN14182; REGN14183; REGN14184; REGN14185; REGN14186; REGN14187; REGN14188; REGN14189; REGN14190; REGN14191; REGN19513; REGN19514; REGN19515; REGN19516; or REGN19517) and a non-human constant domain. [00187] The term “recombinant” p75NTR binding proteins, such as antibodies or antigen- binding fragments thereof (which optionally may be conjugated to a molecular cargo), refers to such molecules created, expressed, isolated or obtained by technologies or methods known in the art as recombinant DNA technology which include, e.g., DNA splicing and transgenic expression. The term includes antibodies expressed in a non-human mammal Attorney Docket No.250298.000780 (including transgenic non-human mammals, e.g., transgenic mice), or a cell (e.g., CHO cells) such as a cellular expression system or isolated from a recombinant combinatorial human antibody library. The present disclosure includes recombinant antigen-binding proteins, such as antibodies and antigen-binding fragments as set forth herein (e.g., REGN14148; REGN14149; REGN14150; REGN14151; REGN14152; REGN14153; REGN14154; REGN14155; REGN14156; REGN14157; REGN14158; REGN14159; REGN14160; REGN14161; REGN14162; REGN14163; REGN14164; REGN14165; REGN14175; REGN14176; REGN14177; REGN14178; REGN14179; REGN14180; REGN14181; REGN14182; REGN14183; REGN14184; REGN14185; REGN14186; REGN14187; REGN14188; REGN14189; REGN14190; REGN14191; REGN19513; REGN19514; REGN19515; REGN19516; or REGN19517). [00188] An antigen-binding fragment of an antibody will, in an embodiment, comprise less than a full antibody but still binds specifically to antigen, e.g., p75NTR, e.g., including at least one variable domain. The variable domain may be of any size or amino acid composition and will generally comprise at least one (e.g., 3) CDR(s), which is adjacent to or in frame with one or more framework sequences. In antigen-binding fragments having a VH domain associated with a VL domain, the VH and VL domains may be situated relative to one another in any suitable arrangement. For example, the variable region may be dimeric and contain VH - VH, VH - VL or VL - VL dimers. Alternatively, the antigen-binding fragment of an antibody may contain a monomeric VH and/or VL domain which are bound non-covalently. [00189] In certain embodiments, an antigen-binding fragment of an antibody may contain at least one variable domain covalently linked to at least one constant domain. Non- limiting, exemplary configurations of variable and constant domains that may be found within an antigen-binding fragment of an antibody described herein include: (i) VH -CH1; (ii) VH - CH2; (iii) VH -CH3; (iv) VH-CH1-CH2; (v) VH -CH1-CH2-CH3; (vi) VH -CH2-CH3; (vii) VH -CL; (viii) VL -CH1; (ix) VL -CH2; (x) VL -CH3; (xi) VL -CH1-CH2; (xii) VL-CH1-CH2-CH3; (xiii) VL - CH2-CH3; and (xiv) V L -CL. In any configuration of variable and constant domains, including any of the exemplary configurations listed above, the variable and constant domains may be either directly linked to one another or may be linked by a full or partial hinge or linker region. A hinge region may consist of at least 2 (e.g., 5, 10, 15, 20, 40, 60 or more) amino acids, which result in a flexible or semi-flexible linkage between adjacent variable and/or constant domains in a single polypeptide molecule. Moreover, an antigen-binding fragment of an antibody described herein may comprise a homo-dimer or hetero-dimer (or other multimer) Attorney Docket No.250298.000780 of any of the variable and constant domain configurations listed above in non-covalent association with one another and/or with one or more monomeric VH or VL domain (e.g., by disulfide bond(s)). The present disclosure includes an antigen-binding fragment of an antigen-binding protein such as an antibody set forth herein, for example, REGN14148; REGN14149; REGN14150; REGN14151; REGN14152; REGN14153; REGN14154; REGN14155; REGN14156; REGN14157; REGN14158; REGN14159; REGN14160; REGN14161; REGN14162; REGN14163; REGN14164; REGN14165; REGN14175; REGN14176; REGN14177; REGN14178; REGN14179; REGN14180; REGN14181; REGN14182; REGN14183; REGN14184; REGN14185; REGN14186; REGN14187; REGN14188; REGN14189; REGN14190; REGN14191; REGN19513; REGN19514; REGN19515; REGN19516; or REGN19517. [00190] Antigen-binding proteins (e.g., antibodies and antigen-binding fragments) may be monospecific or multi-specific (e.g., bispecific). Multispecific antigen-binding proteins are discussed further herein. The present disclosure includes monospecific as well as multispecific (e.g., bispecific) antigen-binding fragments comprising one or more variable domains from an antigen-binding protein that is specifically set forth herein (e.g., REGN14148; REGN14149; REGN14150; REGN14151; REGN14152; REGN14153; REGN14154; REGN14155; REGN14156; REGN14157; REGN14158; REGN14159; REGN14160; REGN14161; REGN14162; REGN14163; REGN14164; REGN14165; REGN14175; REGN14176; REGN14177; REGN14178; REGN14179; REGN14180; REGN14181; REGN14182; REGN14183; REGN14184; REGN14185; REGN14186; REGN14187; REGN14188; REGN14189; REGN14190; REGN14191; REGN19513; REGN19514; REGN19515; REGN19516; or REGN19517). [00191] A "variant" of a polypeptide, such as an immunoglobulin chain (e.g., an REGN14148; REGN14149; REGN14150; REGN14151; REGN14152; REGN14153; REGN14154; REGN14155; REGN14156; REGN14157; REGN14158; REGN14159; REGN14160; REGN14161; REGN14162; REGN14163; REGN14164; REGN14165; REGN14175; REGN14176; REGN14177; REGN14178; REGN14179; REGN14180; REGN14181; REGN14182; REGN14183; REGN14184; REGN14185; REGN14186; REGN14187; REGN14188; REGN14189; REGN14190; REGN14191; REGN19513; REGN19514; REGN19515; REGN19516; or REGN19517 VH, VL, HC or LC or CDR thereof comprising the amino acid sequence specifically set forth herein), refers to a polypeptide comprising an amino acid sequence that is at least about 70-99.9% (e.g., at least 70, 72, 74, Attorney Docket No.250298.000780 75, 76, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 99.5 or 99.9%) identical or similar to a referenced amino acid sequence that is set forth herein (e.g., any of SEQ ID NOs: 2, 10, 18, 20, 22, 30, 38, 40, 42, 50, 54, 56, 58, 66, 74, 76, 78, 86, 94, 96, 98, 106, 112, 114, 116, 124, 132, 134, 136, 144, 151, 153, 155, 162, 169, 171, 173, 179, 185, 187, 189, 197, 203, 205, 207, 215, 223, 225, 227, 235, 241, 243, 245, 251, 257, 259, 261, 269, 275, 277, 279, 287, 293, 295, 297, 304, 311, 313, 315, 323, 327, 329, 331, 339, 345, 347, 349, 357, 365, 367, 369, 377, 383, 385, 387, 391, 397, 399, 401, 409, 413, 415, 417, 425, 427, 435, 437, 443, 445, 453, 455, 463, 465, 473, 475, 482, 484, 491, 493, 501, 503, 511, 513, 517, 519, 527, 529, 545, 547, 549, 565, 567, 569, 585, 587, 589, 605, 607, 609 or 617); when the comparison is performed by a BLAST algorithm wherein the parameters of the algorithm are selected to give the largest match between the respective sequences over the entire length of the respective reference sequences (e.g., expect threshold: 10; word size: 3; max matches in a query range: 0; BLOSUM 62 matrix; gap costs: existence 11, extension 1; conditional compositional score matrix adjustment) and/or comprising the amino acid sequence but having one or more (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10) mutations (e.g., point mutation, insertion, truncation, and/or deletion). [00192] Moreover, a variant of a polypeptide may include a polypeptide such as an immunoglobulin chain (e.g., an REGN14148; REGN14149; REGN14150; REGN14151; REGN14152; REGN14153; REGN14154; REGN14155; REGN14156; REGN14157; REGN14158; REGN14159; REGN14160; REGN14161; REGN14162; REGN14163; REGN14164; REGN14165; REGN14175; REGN14176; REGN14177; REGN14178; REGN14179; REGN14180; REGN14181; REGN14182; REGN14183; REGN14184; REGN14185; REGN14186; REGN14187; REGN14188; REGN14189; REGN14190; REGN14191; REGN19513; REGN19514; REGN19515; REGN19516; or REGN19517 VH, VL, HC or LC or CDR thereof) which may include the amino acid sequence of the reference polypeptide whose amino acid sequence is specifically set forth herein but for one or more (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10) mutations, e.g., one or more missense mutations (e.g., conservative substitutions), non-sense mutations, deletions, or insertions. See Table 1-1. For example, the present disclosure includes p75NTR binding proteins which include an immunoglobulin light chain (or VL) variant comprising the amino acid sequence set forth in SEQ ID NO: 10 but having one or more of such mutations and/or an immunoglobulin heavy chain (or VH) variant comprising the amino acid sequence set forth in SEQ ID NO: 2 but having one or more of such mutations. In an embodiment, an p75NTR binding protein includes Attorney Docket No.250298.000780 an immunoglobulin light chain variant comprising LCDR1, LCDR2 and LCDR3 wherein one or more (e.g., 1 or 2 or 3) of such CDRs has one or more of such mutations (e.g., conservative substitutions) and/or an immunoglobulin heavy chain variant comprising HCDR1, HCDR2 and HCDR3 wherein one or more (e.g., 1 or 2 or 3) of such CDRs has one or more of such mutations (e.g., conservative substitutions). [00193] The following references relate to BLAST algorithms often used for sequence analysis: BLAST ALGORITHMS: Altschul et al. (2005) FEBS J.272(20): 5101-5109; Altschul, S. F., et al., (1990) J. Mol. Biol. 215:403-410; Gish, W., et al., (1993) Nature Genet.3:266- 272; Madden, T. L., et al., (1996) Meth. Enzymol.266:131-141; Altschul, S. F., et al., (1997) Nucleic Acids Res.25:3389-3402; Zhang, J., et al., (1997) Genome Res.7:649-656; Wootton, J. C., et al., (1993) Comput. Chem.17:149-163; Hancock, J. M. et al., (1994) Comput. Appl. Biosci. 10:67-70; ALIGNMENT SCORING SYSTEMS: Dayhoff, M. O., et al., "A model of evolutionary change in proteins." in Atlas of Protein Sequence and Structure, (1978) vol. 5, suppl. 3. M. O. Dayhoff (ed.), pp. 345-352, Natl. Biomed. Res. Found., Washington, D.C.; Schwartz, R. M., et al., "Matrices for detecting distant relationships." in Atlas of Protein Sequence and Structure, (1978) vol. 5, suppl. 3.'' M. O. Dayhoff (ed.), pp. 353-358, Natl. Biomed. Res. Found., Washington, D.C.; Altschul, S. F., (1991) J. Mol. Biol. 219:555-565; States, D. J., et al., (1991) Methods 3:66-70; Henikoff, S., et al., (1992) Proc. Natl. Acad. Sci. USA 89:10915-10919; Altschul, S. F., et al., (1993) J. Mol. Evol.36:290-300; ALIGNMENT STATISTICS: Karlin, S., et al., (1990) Proc. Natl. Acad. Sci. USA 87:2264-2268; Karlin, S., et al., (1993) Proc. Natl. Acad. Sci. USA 90:5873-5877; Dembo, A., et al., (1994) Ann. Prob. 22:2022-2039; and Altschul, S. F. "Evaluating the statistical significance of multiple distinct local alignments." in Theoretical and Computational Methods in Genome Research (S. Suhai, ed.), (1997) pp.1-14, Plenum, N.Y. [00194] A "conservatively modified variant" or a "conservative substitution", e.g., of an immunoglobulin chain set forth herein, refers to a variant wherein there is one or more substitutions of amino acids in a polypeptide with other amino acids having similar characteristics (e.g., charge, side-chain size, hydrophobicity/hydrophilicity, backbone conformation and rigidity, etc.). Such changes can frequently be made without significantly disrupting the biological activity of the antibody or fragment. Those of skill in this art recognize that, in general, single amino acid substitutions in non-essential regions of a polypeptide do not substantially alter biological activity (see, e.g., Watson et al. (1987) Molecular Biology of the Gene, The Benjamin/Cummings Pub. Co., p.224 (4th Ed.)). In addition, substitutions of Attorney Docket No.250298.000780 structurally or functionally similar amino acids are less likely to significantly disrupt biological activity. The present disclosure includes p75NTR binding proteins comprising such conservatively modified variant immunoglobulin chains. [00195] Examples of groups of amino acids that have side chains with similar chemical properties include 1) aliphatic side chains: glycine, alanine, valine, leucine and isoleucine; 2) aliphatic-hydroxyl side chains: serine and threonine; 3) amide-containing side chains: asparagine and glutamine; 4) aromatic side chains: phenylalanine, tyrosine, and tryptophan; 5) basic side chains: lysine, arginine, and histidine; 6) acidic side chains: aspartate and glutamate, and 7) sulfur-containing side chains: cysteine and methionine. Alternatively, a conservative replacement is any change having a positive value in the PAM250 log-likelihood matrix disclosed in Gonnet et al. (1992) Science 256: 1443-45. [00196] “REGN14148”; “REGN14149”; “REGN14150”; “REGN14151”; “REGN14152”; “REGN14153”; “REGN14154”; “REGN14155”; “REGN14156”; “REGN14157”; “REGN14158”; “REGN14159”; “REGN14160”; “REGN14161”; “REGN14162”; “REGN14163”; “REGN14164”; “REGN14165”; “REGN14175”; “REGN14176”; “REGN14177”; “REGN14178”; “REGN14179”; “REGN14180”; “REGN14181”; “REGN14182”; “REGN14183”; “REGN14184”; “REGN14185”; “REGN14186”; “REGN14187”; “REGN14188”; “REGN14189”; “REGN14190”; “REGN14191”; “REGN19513”; “REGN19514”; “REGN19515”; “REGN19516”; and “REGN19517” unless otherwise stated, refer to p75NTR binding proteins, e.g., antibodies and antigen-binding fragments thereof (including multispecific antigen-binding proteins), comprising an immunoglobulin heavy chain variable region (VH) and an immunoglobulin light chain variable region (VL) comprising the amino acid sequence pair specifically set forth in SEQ ID NOs: 2 &10; 22 & 30; 42 & 50; 58 & 66; 78 & 86; 98 & 106; 116 & 124; 136 & 144; 155 & 162; 173 & 179; 189 & 197; 207 & 215; 227 & 235; 245 & 251; 261 & 269; 279 & 287; 297 & 304; 315 & 323; 331 & 339; 349 & 357; 369 & 377; 387 & 391; 401 & 409; 417 & 409; 427 & 409; 437 & 409; 445 & 409; 455 & 409; 465 & 409; 475 & 409; 484 & 409; 493 & 409; 503 & 409; 513 & 409; 519 & 409; 529 & 537; 549 & 557; 569 & 577; 589 & 597; and 609 & 597 (or a variant of any of said sequences), respectively; or comprising an immunoglobulin heavy chain (HC) and an immunoglobulin light chain (LC) comprising the amino acid sequence pair specifically set forth in SEQ ID NOs: 18 & 20; 38 & 40; 54 & 56; 74 & 76; 94 & 96; 112 & 114; 132 & 134; 151 & 153; 169 & 171; 185 & 187; 203 & 205; 223 & 225; 241 & 243; 257 & 259; 275 & 277; 293 & 295; 311 & 313; 327 & 329; 345 & 347; 365 & 367; 383 & 385; 397 & 399; 413 & 415; Attorney Docket No.250298.000780 425 & 415; 435 & 415; 443 & 415; 453 & 415; 463 & 415; 473 & 415; 482 & 415; 491 & 415; 501 & 415; 511 & 415; 517 & 415; 527 & 415; 545 & 547; 565 & 567; 585 & 587; 605 & 607; and 617 & 607 (or a variant of any of said sequences), respectively; or that comprise a heavy chain or VH that comprises the CDRs thereof (HCDR1 (or a variant thereof), HCDR2 (or a variant thereof) and HCDR3 (or a variant thereof)) and/or a light chain or VL that comprises the CDRs thereof (LCDR1 (or a variant thereof), LCDR2 (or a variant thereof) and LCDR3 (or a variant thereof)). In an embodiment, the VH is linked to an IgG constant heavy chain domain, for example, human IgG constant heavy chain domain (e.g., IgG1 or IgG4 (e.g., comprising the S228P and/or S108P mutation)) and/or the VL is linked to a light chain constant domain, for example a human light chain constant domain (e.g., lambda or kappa constant light chain domain). Polynucleotides encoding one or more of any such immunoglobulin chains (e.g., VH, VL, HC and/or LC) forms part of the present disclosure. [00197] Antibodies and antigen-binding fragments described herein (e.g., REGN14148; REGN14149; REGN14150; REGN14151; REGN14152; REGN14153; REGN14154; REGN14155; REGN14156; REGN14157; REGN14158; REGN14159; REGN14160; REGN14161; REGN14162; REGN14163; REGN14164; REGN14165; REGN14175; REGN14176; REGN14177; REGN14178; REGN14179; REGN14180; REGN14181; REGN14182; REGN14183; REGN14184; REGN14185; REGN14186; REGN14187; REGN14188; REGN14189; REGN14190; REGN14191; REGN19513; REGN19514; REGN19515; REGN19516; or REGN19517) comprise immunoglobulin chains including the amino acid sequences specifically set forth herein (and variants thereof) as well as cellular and in vitro post-translational modifications to the antibody or fragment. For example, the present disclosure includes antibodies and antigen-binding fragments thereof that specifically bind to p75NTR comprising heavy and/or light chain amino acid sequences set forth herein as well as antibodies and fragments wherein one or more asparagine, serine and/or threonine residues is glycosylated, one or more asparagine residues is deamidated, one or more residues (e.g., Met, Trp and/or His) is oxidized, the N-terminal glutamine is pyroglutamate (pyroE) and/or the C-terminal lysine or other amino acid is missing. [00198] The amino acid sequences of domains and chains in p75NTR binding proteins or p75NTR binding protein-drug conjugates of the present disclosure are summarized below in Table 1-1. For example, anti-p75NTR antibodies and antigen-binding fragments thereof (e.g., scFvs and Fabs) comprising the HCVR and LCVR of the molecules in Table 1-1; or Attorney Docket No.250298.000780 comprising the CDRs thereof, or comprising the HC and LC of the molecules in Table 1-1, optionally conjugated to a molecular cargo, form part of the present disclosure. Table 1-1. SEQ ID NOs of Amino Acid Sequences of Domains in Antibodies or Antigen-binding Fragments (e.g., Fabs or scFv Molecules) or Protein-Drug Conjugates of the Present Disclosure. ＃ anti-p75NTR HCVR HCDR1 HCDR2 HCDR3 LCVR LCDR1 LCDR2 LCDR3 HC LC Molecule Attorney Docket No.250298.000780 30 REGN14186 475 477 158 480 409 237 14 411 482 415 31 REGN14187 484 486 283 489 409 237 14 411 491 415 NTR antibodies or antigen-binding fragments (e.g., Fabs or scFv molecules) or protein-drug conjugates described herein are set forth below. The nucleotide sequences encoding the amino acid sequences of domains or chains in p75NTR binding proteins or protein-drug conjugates of the present disclosure are also summarized within Table 1-2. The present disclosure includes any antibody or antigen-binding fragment thereof that includes an HCVR and LCVR having a sequence as set forth below or an HCVR and LCVR having the HCDRs and LCDRs thereof, respectively. REGN14148 HCVR DNA Sequence GAGGTGCAGCTGGTGGAGTCTGGGGGAGGCTTGGTCCAGCCTGGGGGGTCCCTGAG ACTCTCCTGTGCGGCCTCTGGATTCACCTTTAATAACTATTGGATGAGCTGGATCCGC CAGGCTCCAGGGAAGGGGCTGGAGTGGGTGGCCAACATAAAGCCAGATGGAAGTGA GAAATCATATGTGGACTCTGTGAAGGGCCGATTCACCATCTCCAGAGACAACGCCAAG AAATCACTGTTTCTGCAAATGACCAGCCTGAGAGCCGAGGACACGGCTGTTTATTACT GTGCGACGAACTGGGGGTTTGACTGGGGCCAGGGAACCCTGGTCACCGTCTCCTCA (SEQ ID NO: 1) HCVR Amino Acid Sequence EVQLVESGGGLVQPGGSLRLSCAASGFTFNNYWMSWIRQAPGKGLEWVANIKPDGSEKS YVDSVKGRFTISRDNAKKSLFLQMTSLRAEDTAVYYCATNWGFDWGQGTLVTVSS Attorney Docket No.250298.000780 (SEQ ID NO: 2) CDR1 DNA Sequence GGA TTC ACC TTT AAT AAC TAT TGG (SEQ ID NO: 3) CDR1 Amino Acid Sequence G F T F N N Y W (SEQ ID NO: 4) CDR2 DNA Sequence ATA AAG CCA GAT GGA AGT GAG AAA (SEQ ID NO: 5) CDR2 Amino Acid Sequence I K P D G S E K (SEQ ID NO: 6) CDR3 DNA Sequence GCG ACG AAC TGG GGG TTT GAC (SEQ ID NO: 7) CDR3 Amino Acid Sequence A T N W G F D (SEQ ID NO: 8) LCVR DNA Sequence GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTGGGAGACAGAGTCA CCGTCACTTGCCGGGCAAGTCAGGACATTAGAAATGATTTAGGCTGGTTTCAGCAGAA ACCAGGGAAAGCCCCTAAGCGCCTGATCTATGCTGCATCCAGTTTGCAAAGTGGGGTC CCATCAAGGTTCAGCGGCAGTGGATCTGGGACAGACTTCACTCTCACAATCAGCAGCC TGCAGCCTGAAGATTTTGCAACTTATTACTGTCTACAGTATAATAGTTACCCGTGGACG TTCGGCCAAGGGACCAAGGTGGAAATCAAA Attorney Docket No.250298.000780 (SEQ ID NO: 9) LCVR Amino Acid Sequence DIQMTQSPSSLSASVGDRVTVTCRASQDIRNDLGWFQQKPGKAPKRLIYAASSLQSGVPS RFSGSGSGTDFTLTISSLQPEDFATYYCLQYNSYPWTFGQGTKVEIK (SEQ ID NO: 10) CDR1 DNA Sequence CAG GAC ATT AGA AAT GAT (SEQ ID NO: 11) CDR1 Amino Acid Sequence Q D I R N D (SEQ ID NO: 12) CDR2 DNA Sequence GCT GCA TCC (SEQ ID NO: 13) CDR2 Amino Acid Sequence A A S (SEQ ID NO: 14) CDR3 DNA Sequence CTA CAG TAT AAT AGT TAC CCG TGG ACG (SEQ ID NO: 15) CDR3 Amino Acid Sequence L Q Y N S Y P W T (SEQ ID NO: 16) HC DNA Sequence Attorney Docket No.250298.000780 GAGGTGCAGCTGGTGGAGTCTGGGGGAGGCTTGGTCCAGCCTGGGGGGTCCCTGAG ACTCTCCTGTGCGGCCTCTGGATTCACCTTTAATAACTATTGGATGAGCTGGATCCGC CAGGCTCCAGGGAAGGGGCTGGAGTGGGTGGCCAACATAAAGCCAGATGGAAGTGA GAAATCATATGTGGACTCTGTGAAGGGCCGATTCACCATCTCCAGAGACAACGCCAAG AAATCACTGTTTCTGCAAATGACCAGCCTGAGAGCCGAGGACACGGCTGTTTATTACT GTGCGACGAACTGGGGGTTTGACTGGGGCCAGGGAACCCTGGTCACCGTCTCCTCAG CCTCCACCAAGGGCCCATCGGTCTTCCCCCTGGCGCCCTGCTCCAGGAGCACCTCCG AGAGCACAGCCGCCCTGGGCTGCCTGGTCAAGGACTACTTCCCCGAACCGGTGACGG TGTCGTGGAACTCAGGCGCCCTGACCAGCGGCGTGCACACCTTCCCGGCTGTCCTAC AGTCCTCAGGACTCTACTCCCTCAGCAGCGTGGTGACCGTGCCCTCCAGCAGCTTGG GCACGAAGACCTACACCTGCAACGTAGATCACAAGCCCAGCAACACCAAGGTGGACA AGAGAGTTGAGTCCAAATATGGTCCCCCATGCCCACCGTGCCCAGCACCACCTGTGG CAGGACCATCAGTCTTCCTGTTCCCCCCAAAACCCAAGGACACTCTCATGATCTCCCG GACCCCTGAGGTCACGTGCGTGGTGGTGGACGTGAGCCAGGAAGACCCCGAGGTCC AGTTCAACTGGTACGTGGATGGCGTGGAGGTGCATAATGCCAAGACAAAGCCGCGGG AGGAGCAGTTCAACAGCACGTACCGTGTGGTCAGCGTCCTCACCGTCCTGCACCAGG ACTGGCTGAACGGCAAGGAGTACAAGTGCAAGGTCTCCAACAAAGGCCTCCCGTCCT CCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGAGAGCCACAGGTGTACA CCCTGCCCCCATCCCAGGAGGAGATGACCAAGAACCAGGTCAGCCTGACCTGCCTGG TCAAAGGCTTCTACCCCAGCGACATCGCCGTGGAGTGGGAGAGCAATGGGCAGCCGG AGAACAACTACAAGACCACGCCTCCCGTGCTGGACTCCGACGGCTCCTTCTTCCTCTA CAGCAGGCTCACCGTGGACAAGAGCAGGTGGCAGGAGGGGAATGTCTTCTCATGCTC CGTGATGCATGAGGCTCTGCACAACCACTACACACAGAAGTCCCTCTCCCTGTCTCTG GGTAAATGA (SEQ ID NO: 17) HC Amino Acid Sequence EVQLVESGGGLVQPGGSLRLSCAASGFTFNNYWMSWIRQAPGKGLEWVANIKPDGSEKS YVDSVKGRFTISRDNAKKSLFLQMTSLRAEDTAVYYCATNWGFDWGQGTLVTVSSASTKG PSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLS SVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPPVAGPSVFLFPPKP KDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLT VLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTC Attorney Docket No.250298.000780 LVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSV MHEALHNHYTQKSLSLSLGK* (SEQ ID NO: 18) LC DNA Sequence GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTGGGAGACAGAGTCA CCGTCACTTGCCGGGCAAGTCAGGACATTAGAAATGATTTAGGCTGGTTTCAGCAGAA ACCAGGGAAAGCCCCTAAGCGCCTGATCTATGCTGCATCCAGTTTGCAAAGTGGGGTC CCATCAAGGTTCAGCGGCAGTGGATCTGGGACAGACTTCACTCTCACAATCAGCAGCC TGCAGCCTGAAGATTTTGCAACTTATTACTGTCTACAGTATAATAGTTACCCGTGGACG TTCGGCCAAGGGACCAAGGTGGAAATCAAACGAACTGTGGCTGCACCATCTGTCTTCA TCTTCCCGCCATCTGATGAGCAGTTGAAATCTGGAACTGCCTCTGTTGTGTGCCTGCT GAATAACTTCTATCCCAGAGAGGCCAAAGTACAGTGGAAGGTGGATAACGCCCTCCAA TCGGGTAACTCCCAGGAGAGTGTCACAGAGCAGGACAGCAAGGACAGCACCTACAGC CTCAGCAGCACCCTGACGCTGAGCAAAGCAGACTACGAGAAACACAAAGTCTACGCCT GCGAAGTCACCCATCAGGGCCTGAGCTCGCCCGTCACAAAGAGCTTCAACAGGGGAG AGTGTTAG (SEQ ID NO: 19) LC Amino Acid Sequence DIQMTQSPSSLSASVGDRVTVTCRASQDIRNDLGWFQQKPGKAPKRLIYAASSLQSGVPS RFSGSGSGTDFTLTISSLQPEDFATYYCLQYNSYPWTFGQGTKVEIKRTVAAPSVFIFPPSD EQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLS KADYEKHKVYACEVTHQGLSSPVTKSFNRGEC* (SEQ ID NO: 20) REGN14149 HCVR DNA Sequence GAGGTGCAGCTGGTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGAG ACTCTCCTGTGCAGCCTCTGGATTCACCTTTACCACCTATGCCATGAGCTGGGTCCGC CAGGCTCCAGGGAAGGGGCTGGAGTGGGTCTCAGCTATTAGTGCTACTGGTAGTGGC ACATACTATGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCAGAGAGAATTCCAAGA ACACGCTGTATCTGCAAATGAAAAGCCTGAGAGCCGAGGACACGGCCGTATATTACTG Attorney Docket No.250298.000780 TGTGAAAGGTCCGTATAGTAACAGCCGGAACGTGGGCTTCCAGCACTGGGGCCAGGG CACCCTGGTCACCGTCTCCTCA (SEQ ID NO: 21) HCVR Amino Acid Sequence EVQLVESGGGLVQPGGSLRLSCAASGFTFTTYAMSWVRQAPGKGLEWVSAISATGSGTY YADSVKGRFTISRENSKNTLYLQMKSLRAEDTAVYYCVKGPYSNSRNVGFQHWGQGTLV TVSS (SEQ ID NO: 22) CDR1 DNA Sequence GGA TTC ACC TTT ACC ACC TAT GCC (SEQ ID NO: 23) CDR1 Amino Acid Sequence G F T F T T Y A (SEQ ID NO: 24) CDR2 DNA Sequence ATT AGT GCT ACT GGT AGT GGC ACA (SEQ ID NO: 25) CDR2 Amino Acid Sequence I S A T G S G T (SEQ ID NO: 26) CDR3 DNA Sequence GTG AAA GGT CCG TAT AGT AAC AGC CGG AAC GTG GGC TTC CAG CAC (SEQ ID NO: 27) CDR3 Amino Acid Sequence V K G P Y S N S R N V G F Q H (SEQ ID NO: 28) Attorney Docket No.250298.000780 LCVR DNA Sequence GATATTGTGATGACTCAGTCTCCACTCTCCCTGCCCGTCACCCCTGGAGAGCCGGCCT CCATCTCCTGCAGGTCTAGTCAGAGCCTCCTACATAGTAATGGATACAACTATTTGGAT TGGTACCTGCAGAAGCCAGGGCAGTCTCCACAACTCCTGATCTATTTGGGTTCTAATC GGGCCTCCGGGGTCCCTGACAGGTTCAGTGGCAGTGGATCAGGCACAGATTTTACAC TGAAAATCAGCAGAGTGGAGGCTGAGGATGTTGGGGTTTATTTCTGCATGCAACATCT ACAAACTCCCATGTACACTTTTGGCCAGGGGACCAAGCTGGAGATCAAA (SEQ ID NO: 29) LCVR Amino Acid Sequence DIVMTQSPLSLPVTPGEPASISCRSSQSLLHSNGYNYLDWYLQKPGQSPQLLIYLGSNRAS GVPDRFSGSGSGTDFTLKISRVEAEDVGVYFCMQHLQTPMYTFGQGTKLEIK (SEQ ID NO: 30) CDR1 DNA Sequence CAG AGC CTC CTA CAT AGT AAT GGA TAC AAC TAT (SEQ ID NO: 31) CDR1 Amino Acid Sequence Q S L L H S N G Y N Y (SEQ ID NO: 32) CDR2 DNA Sequence TTG GGT TCT (SEQ ID NO: 33) CDR2 Amino Acid Sequence L G S (SEQ ID NO: 34) CDR3 DNA Sequence ATG CAA CAT CTA CAA ACT CCC ATG TAC ACT Attorney Docket No.250298.000780 (SEQ ID NO: 35) CDR3 Amino Acid Sequence M Q H L Q T P M Y T (SEQ ID NO: 36) HC DNA Sequence GAGGTGCAGCTGGTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGAG ACTCTCCTGTGCAGCCTCTGGATTCACCTTTACCACCTATGCCATGAGCTGGGTCCGC CAGGCTCCAGGGAAGGGGCTGGAGTGGGTCTCAGCTATTAGTGCTACTGGTAGTGGC ACATACTATGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCAGAGAGAATTCCAAGA ACACGCTGTATCTGCAAATGAAAAGCCTGAGAGCCGAGGACACGGCCGTATATTACTG TGTGAAAGGTCCGTATAGTAACAGCCGGAACGTGGGCTTCCAGCACTGGGGCCAGGG CACCCTGGTCACCGTCTCCTCAGCCTCCACCAAGGGCCCATCGGTCTTCCCCCTGGC GCCCTGCTCCAGGAGCACCTCCGAGAGCACAGCCGCCCTGGGCTGCCTGGTCAAGG ACTACTTCCCCGAACCGGTGACGGTGTCGTGGAACTCAGGCGCCCTGACCAGCGGCG TGCACACCTTCCCGGCTGTCCTACAGTCCTCAGGACTCTACTCCCTCAGCAGCGTGGT GACCGTGCCCTCCAGCAGCTTGGGCACGAAGACCTACACCTGCAACGTAGATCACAA GCCCAGCAACACCAAGGTGGACAAGAGAGTTGAGTCCAAATATGGTCCCCCATGCCC ACCGTGCCCAGCACCACCTGTGGCAGGACCATCAGTCTTCCTGTTCCCCCCAAAACCC AAGGACACTCTCATGATCTCCCGGACCCCTGAGGTCACGTGCGTGGTGGTGGACGTG AGCCAGGAAGACCCCGAGGTCCAGTTCAACTGGTACGTGGATGGCGTGGAGGTGCAT AATGCCAAGACAAAGCCGCGGGAGGAGCAGTTCAACAGCACGTACCGTGTGGTCAGC GTCCTCACCGTCCTGCACCAGGACTGGCTGAACGGCAAGGAGTACAAGTGCAAGGTC TCCAACAAAGGCCTCCCGTCCTCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGC CCCGAGAGCCACAGGTGTACACCCTGCCCCCATCCCAGGAGGAGATGACCAAGAACC AGGTCAGCCTGACCTGCCTGGTCAAAGGCTTCTACCCCAGCGACATCGCCGTGGAGT GGGAGAGCAATGGGCAGCCGGAGAACAACTACAAGACCACGCCTCCCGTGCTGGACT CCGACGGCTCCTTCTTCCTCTACAGCAGGCTCACCGTGGACAAGAGCAGGTGGCAGG AGGGGAATGTCTTCTCATGCTCCGTGATGCATGAGGCTCTGCACAACCACTACACACA GAAGTCCCTCTCCCTGTCTCTGGGTAAATGA (SEQ ID NO: 37) Attorney Docket No.250298.000780 HC Amino Acid Sequence EVQLVESGGGLVQPGGSLRLSCAASGFTFTTYAMSWVRQAPGKGLEWVSAISATGSGTY YADSVKGRFTISRENSKNTLYLQMKSLRAEDTAVYYCVKGPYSNSRNVGFQHWGQGTLV TVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVL QSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPPVAGP SVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNS TYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMT KNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQE GNVFSCSVMHEALHNHYTQKSLSLSLGK* (SEQ ID NO: 38) LC DNA Sequence GATATTGTGATGACTCAGTCTCCACTCTCCCTGCCCGTCACCCCTGGAGAGCCGGCCT CCATCTCCTGCAGGTCTAGTCAGAGCCTCCTACATAGTAATGGATACAACTATTTGGAT TGGTACCTGCAGAAGCCAGGGCAGTCTCCACAACTCCTGATCTATTTGGGTTCTAATC GGGCCTCCGGGGTCCCTGACAGGTTCAGTGGCAGTGGATCAGGCACAGATTTTACAC TGAAAATCAGCAGAGTGGAGGCTGAGGATGTTGGGGTTTATTTCTGCATGCAACATCT ACAAACTCCCATGTACACTTTTGGCCAGGGGACCAAGCTGGAGATCAAACGAACTGTG GCTGCACCATCTGTCTTCATCTTCCCGCCATCTGATGAGCAGTTGAAATCTGGAACTG CCTCTGTTGTGTGCCTGCTGAATAACTTCTATCCCAGAGAGGCCAAAGTACAGTGGAA GGTGGATAACGCCCTCCAATCGGGTAACTCCCAGGAGAGTGTCACAGAGCAGGACAG CAAGGACAGCACCTACAGCCTCAGCAGCACCCTGACGCTGAGCAAAGCAGACTACGA GAAACACAAAGTCTACGCCTGCGAAGTCACCCATCAGGGCCTGAGCTCGCCCGTCAC AAAGAGCTTCAACAGGGGAGAGTGTTAG (SEQ ID NO: 39) LC Amino Acid Sequence DIVMTQSPLSLPVTPGEPASISCRSSQSLLHSNGYNYLDWYLQKPGQSPQLLIYLGSNRAS GVPDRFSGSGSGTDFTLKISRVEAEDVGVYFCMQHLQTPMYTFGQGTKLEIKRTVAAPSV FIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSL SSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC* (SEQ ID NO: 40) Attorney Docket No.250298.000780 REGN14150 HCVR DNA Sequence CAGGTTCAGCTGGTGCAGTCTGGAGCTGAGGTGAAGAAGCCTGGGGCCTCAGTGAAA GTCTCCTGTAAGGCTTCTGGTTACACCTTTAGTAGCCATGGTATCACCTGGGTGCGAC AGGCCCCTGGACAAGGGCTTGAGTGGATGGGATGGATCAGCGCTTATAATGGTGACA CAAACTATGCACAGAAAGTCCAGGGCAGAGTCACCATGACCACAGACACATCCACGAG TACAGCCTACATGGAACTGAGGAGCCTGAGATCTGACGACACGGCCGTGTTTTACTGT GCGCGATATAGGGGAATAGTAGGTCGTAATTACAACTACTATGGTATGGACGTCTGGG GCCAAGGGACCACGGTCACCGTCTCCTCA (SEQ ID NO: 41) HCVR Amino Acid Sequence QVQLVQSGAEVKKPGASVKVSCKASGYTFSSHGITWVRQAPGQGLEWMGWISAYNGDT NYAQKVQGRVTMTTDTSTSTAYMELRSLRSDDTAVFYCARYRGIVGRNYNYYGMDVWG QGTTVTVSS (SEQ ID NO: 42) CDR1 DNA Sequence GGT TAC ACC TTT AGT AGC CAT GGT (SEQ ID NO: 43) CDR1 Amino Acid Sequence G Y T F S S H G (SEQ ID NO: 44) CDR2 DNA Sequence ATC AGC GCT TAT AAT GGT GAC ACA (SEQ ID NO: 45) CDR2 Amino Acid Sequence I S A Y N G D T (SEQ ID NO: 46) Attorney Docket No.250298.000780 CDR3 DNA Sequence GCG CGA TAT AGG GGA ATA GTA GGT CGT AAT TAC AAC TAC TAT GGT ATG GAC GTC (SEQ ID NO: 47) CDR3 Amino Acid Sequence A R Y R G I V G R N Y N Y Y G M D V (SEQ ID NO: 48) LCVR DNA Sequence GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGAGAGAGTCA CCATCACTTGCCGGGCAAGTCAGGACATTAGAAATGATTTAGGCTGGTATCAGCAGAA ACCAGGGAAAGCCCCTAAGCGCCTGATGTATGCTGCATCCAGTTTGCAAAGTGGGGT CCCATCAAGGTTCAGCGGCAGTGGATCTGGGACAGAATTCACTCTCACAATCAGCACC CTGCAGCCTGAAGATTTTGCAACTTATTACTGTCTACAGCATAATAGTTACCCCCTCAC TTTCGGCGGAGGGACCAAGGTGGAGATCAAA (SEQ ID NO: 49) LCVR Amino Acid Sequence DIQMTQSPSSLSASVGERVTITCRASQDIRNDLGWYQQKPGKAPKRLMYAASSLQSGVPS RFSGSGSGTEFTLTISTLQPEDFATYYCLQHNSYPLTFGGGTKVEIK (SEQ ID NO: 50) CDR1 DNA Sequence CAG GAC ATT AGA AAT GAT (SEQ ID NO: 11) CDR1 Amino Acid Sequence Q D I R N D (SEQ ID NO: 12) CDR2 DNA Sequence Attorney Docket No.250298.000780 GCT GCA TCC (SEQ ID NO: 13) CDR2 Amino Acid Sequence A A S (SEQ ID NO: 14) CDR3 DNA Sequence CTA CAG CAT AAT AGT TAC CCC CTC ACT (SEQ ID NO: 51) CDR3 Amino Acid Sequence L Q H N S Y P L T (SEQ ID NO: 52) HC DNA Sequence CAGGTTCAGCTGGTGCAGTCTGGAGCTGAGGTGAAGAAGCCTGGGGCCTCAGTGAAA GTCTCCTGTAAGGCTTCTGGTTACACCTTTAGTAGCCATGGTATCACCTGGGTGCGAC AGGCCCCTGGACAAGGGCTTGAGTGGATGGGATGGATCAGCGCTTATAATGGTGACA CAAACTATGCACAGAAAGTCCAGGGCAGAGTCACCATGACCACAGACACATCCACGAG TACAGCCTACATGGAACTGAGGAGCCTGAGATCTGACGACACGGCCGTGTTTTACTGT GCGCGATATAGGGGAATAGTAGGTCGTAATTACAACTACTATGGTATGGACGTCTGGG GCCAAGGGACCACGGTCACCGTCTCCTCAGCCTCCACCAAGGGCCCATCGGTCTTCC CCCTGGCGCCCTGCTCCAGGAGCACCTCCGAGAGCACAGCCGCCCTGGGCTGCCTG GTCAAGGACTACTTCCCCGAACCGGTGACGGTGTCGTGGAACTCAGGCGCCCTGACC AGCGGCGTGCACACCTTCCCGGCTGTCCTACAGTCCTCAGGACTCTACTCCCTCAGCA GCGTGGTGACCGTGCCCTCCAGCAGCTTGGGCACGAAGACCTACACCTGCAACGTAG ATCACAAGCCCAGCAACACCAAGGTGGACAAGAGAGTTGAGTCCAAATATGGTCCCCC ATGCCCACCGTGCCCAGCACCACCTGTGGCAGGACCATCAGTCTTCCTGTTCCCCCC AAAACCCAAGGACACTCTCATGATCTCCCGGACCCCTGAGGTCACGTGCGTGGTGGT GGACGTGAGCCAGGAAGACCCCGAGGTCCAGTTCAACTGGTACGTGGATGGCGTGGA GGTGCATAATGCCAAGACAAAGCCGCGGGAGGAGCAGTTCAACAGCACGTACCGTGT GGTCAGCGTCCTCACCGTCCTGCACCAGGACTGGCTGAACGGCAAGGAGTACAAGTG Attorney Docket No.250298.000780 CAAGGTCTCCAACAAAGGCCTCCCGTCCTCCATCGAGAAAACCATCTCCAAAGCCAAA GGGCAGCCCCGAGAGCCACAGGTGTACACCCTGCCCCCATCCCAGGAGGAGATGAC CAAGAACCAGGTCAGCCTGACCTGCCTGGTCAAAGGCTTCTACCCCAGCGACATCGC CGTGGAGTGGGAGAGCAATGGGCAGCCGGAGAACAACTACAAGACCACGCCTCCCGT GCTGGACTCCGACGGCTCCTTCTTCCTCTACAGCAGGCTCACCGTGGACAAGAGCAG GTGGCAGGAGGGGAATGTCTTCTCATGCTCCGTGATGCATGAGGCTCTGCACAACCA CTACACACAGAAGTCCCTCTCCCTGTCTCTGGGTAAATGA (SEQ ID NO: 53) HC Amino Acid Sequence QVQLVQSGAEVKKPGASVKVSCKASGYTFSSHGITWVRQAPGQGLEWMGWISAYNGDT NYAQKVQGRVTMTTDTSTSTAYMELRSLRSDDTAVFYCARYRGIVGRNYNYYGMDVWG QGTTVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVH TFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPA PPVAGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPR EEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPP SQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVD KSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGK* (SEQ ID NO: 54) LC DNA Sequence GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGAGAGAGTCA CCATCACTTGCCGGGCAAGTCAGGACATTAGAAATGATTTAGGCTGGTATCAGCAGAA ACCAGGGAAAGCCCCTAAGCGCCTGATGTATGCTGCATCCAGTTTGCAAAGTGGGGT CCCATCAAGGTTCAGCGGCAGTGGATCTGGGACAGAATTCACTCTCACAATCAGCACC CTGCAGCCTGAAGATTTTGCAACTTATTACTGTCTACAGCATAATAGTTACCCCCTCAC TTTCGGCGGAGGGACCAAGGTGGAGATCAAACGAACTGTGGCTGCACCATCTGTCTT CATCTTCCCGCCATCTGATGAGCAGTTGAAATCTGGAACTGCCTCTGTTGTGTGCCTG CTGAATAACTTCTATCCCAGAGAGGCCAAAGTACAGTGGAAGGTGGATAACGCCCTCC AATCGGGTAACTCCCAGGAGAGTGTCACAGAGCAGGACAGCAAGGACAGCACCTACA GCCTCAGCAGCACCCTGACGCTGAGCAAAGCAGACTACGAGAAACACAAAGTCTACG CCTGCGAAGTCACCCATCAGGGCCTGAGCTCGCCCGTCACAAAGAGCTTCAACAGGG GAGAGTGTTAG Attorney Docket No.250298.000780 (SEQ ID NO: 55) LC Amino Acid Sequence DIQMTQSPSSLSASVGERVTITCRASQDIRNDLGWYQQKPGKAPKRLMYAASSLQSGVPS RFSGSGSGTEFTLTISTLQPEDFATYYCLQHNSYPLTFGGGTKVEIKRTVAAPSVFIFPPSD EQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLS KADYEKHKVYACEVTHQGLSSPVTKSFNRGEC* (SEQ ID NO: 56) REGN14151 HCVR DNA Sequence CAGGTACAGCTGCAGCAGTCAGGTCCAGGACTGGTGAAGCCCTCGCAGACCCTCTCA CTCACCTGTGCCTTCTCCGGGGACAGTGTCTCTAGGAACAGTGCTGCTTGGAACTGGA TCAGGCAGTCCCCATCGAGAGGCCTTGAGTGGCTGGGAAGGACATACTACAGGTCCA AGTGGTATAATGATTATGCAGTATCTGTGAAAAGTCGAATAACCATCAACCCAGACACA GCCAAGAACCAGTTCTCCCTGCAGCTGAAATCTGTGACTCCCGAGGACACGGCTGTGT ATTACTGTGCAAGAGAGGGGCCCTATTTTGACTACTGGGGCCAGGGAACCCTGGTCA CCGTCTCCTCA (SEQ ID NO: 57) HCVR Amino Acid Sequence QVQLQQSGPGLVKPSQTLSLTCAFSGDSVSRNSAAWNWIRQSPSRGLEWLGRTYYRSK WYNDYAVSVKSRITINPDTAKNQFSLQLKSVTPEDTAVYYCAREGPYFDYWGQGTLVTVS S (SEQ ID NO: 58) CDR1 DNA Sequence GGG GAC AGT GTC TCT AGG AAC AGT GCT GCT (SEQ ID NO: 59) CDR1 Amino Acid Sequence G D S V S R N S A A (SEQ ID NO: 60) Attorney Docket No.250298.000780 CDR2 DNA Sequence ACA TAC TAC AGG TCC AAG TGG TAT AAT (SEQ ID NO: 61) CDR2 Amino Acid Sequence T Y Y R S K W Y N (SEQ ID NO: 62) CDR3 DNA Sequence GCA AGA GAG GGG CCC TAT TTT GAC TAC (SEQ ID NO: 63) CDR3 Amino Acid Sequence A R E G P Y F D Y (SEQ ID NO: 64) LCVR DNA Sequence GACATCGTGATGACCCAGTCTCCAGACTCCCTGGCTGTGTCTCTGGGCGAGAGGGCC ACCATCAACTGCAAGTCCAGCCAGAGTGTTTTACACAGCTCCAACAATATGAACTACTT AGCTTGGTACCAGCAGAAACCAGGACAGCCTCCTAAGTTGCTCATTTACTGGGCATCT ACCCGGAAATCCGGGGTCCCTGACCGATTCAGTGGCAGCGGGTCTGGGACAGATTTC ACTCTCACCATCAGCAGCCTTCAGGCTGCTGATGTGGCAGTTTATTACTGTCTGCAATA TTATAATACTCCTCGAACGTTCGGCCAAGGGACCAAGGTGGAAATCAAA (SEQ ID NO: 65) LCVR Amino Acid Sequence DIVMTQSPDSLAVSLGERATINCKSSQSVLHSSNNMNYLAWYQQKPGQPPKLLIYWASTR KSGVPDRFSGSGSGTDFTLTISSLQAADVAVYYCLQYYNTPRTFGQGTKVEIK (SEQ ID NO: 66) CDR1 DNA Sequence CAG AGT GTT TTA CAC AGC TCC AAC AAT ATG AAC TAC Attorney Docket No.250298.000780 (SEQ ID NO: 67) CDR1 Amino Acid Sequence Q S V L H S S N N M N Y (SEQ ID NO: 68) CDR2 DNA Sequence TGG GCA TCT (SEQ ID NO: 69) CDR2 Amino Acid Sequence W A S (SEQ ID NO: 70) CDR3 DNA Sequence CTG CAA TAT TAT AAT ACT CCT CGA ACG (SEQ ID NO: 71) CDR3 Amino Acid Sequence L Q Y Y N T P R T (SEQ ID NO: 72) HC DNA Sequence CAGGTACAGCTGCAGCAGTCAGGTCCAGGACTGGTGAAGCCCTCGCAGACCCTCTCA CTCACCTGTGCCTTCTCCGGGGACAGTGTCTCTAGGAACAGTGCTGCTTGGAACTGGA TCAGGCAGTCCCCATCGAGAGGCCTTGAGTGGCTGGGAAGGACATACTACAGGTCCA AGTGGTATAATGATTATGCAGTATCTGTGAAAAGTCGAATAACCATCAACCCAGACACA GCCAAGAACCAGTTCTCCCTGCAGCTGAAATCTGTGACTCCCGAGGACACGGCTGTGT ATTACTGTGCAAGAGAGGGGCCCTATTTTGACTACTGGGGCCAGGGAACCCTGGTCA CCGTCTCCTCAGCCTCCACCAAGGGCCCATCGGTCTTCCCCCTGGCGCCCTGCTCCA GGAGCACCTCCGAGAGCACAGCCGCCCTGGGCTGCCTGGTCAAGGACTACTTCCCCG AACCGGTGACGGTGTCGTGGAACTCAGGCGCCCTGACCAGCGGCGTGCACACCTTCC CGGCTGTCCTACAGTCCTCAGGACTCTACTCCCTCAGCAGCGTGGTGACCGTGCCCT Attorney Docket No.250298.000780 CCAGCAGCTTGGGCACGAAGACCTACACCTGCAACGTAGATCACAAGCCCAGCAACA CCAAGGTGGACAAGAGAGTTGAGTCCAAATATGGTCCCCCATGCCCACCGTGCCCAG CACCACCTGTGGCAGGACCATCAGTCTTCCTGTTCCCCCCAAAACCCAAGGACACTCT CATGATCTCCCGGACCCCTGAGGTCACGTGCGTGGTGGTGGACGTGAGCCAGGAAGA CCCCGAGGTCCAGTTCAACTGGTACGTGGATGGCGTGGAGGTGCATAATGCCAAGAC AAAGCCGCGGGAGGAGCAGTTCAACAGCACGTACCGTGTGGTCAGCGTCCTCACCGT CCTGCACCAGGACTGGCTGAACGGCAAGGAGTACAAGTGCAAGGTCTCCAACAAAGG CCTCCCGTCCTCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGAGAGCC ACAGGTGTACACCCTGCCCCCATCCCAGGAGGAGATGACCAAGAACCAGGTCAGCCT GACCTGCCTGGTCAAAGGCTTCTACCCCAGCGACATCGCCGTGGAGTGGGAGAGCAA TGGGCAGCCGGAGAACAACTACAAGACCACGCCTCCCGTGCTGGACTCCGACGGCTC CTTCTTCCTCTACAGCAGGCTCACCGTGGACAAGAGCAGGTGGCAGGAGGGGAATGT CTTCTCATGCTCCGTGATGCATGAGGCTCTGCACAACCACTACACACAGAAGTCCCTC TCCCTGTCTCTGGGTAAATGA (SEQ ID NO: 73) HC Amino Acid Sequence QVQLQQSGPGLVKPSQTLSLTCAFSGDSVSRNSAAWNWIRQSPSRGLEWLGRTYYRSK WYNDYAVSVKSRITINPDTAKNQFSLQLKSVTPEDTAVYYCAREGPYFDYWGQGTLVTVS SASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQS SGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPPVAGPSV FLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTY RVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTK NQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEG NVFSCSVMHEALHNHYTQKSLSLSLGK* (SEQ ID NO: 74) LC DNA Sequence GACATCGTGATGACCCAGTCTCCAGACTCCCTGGCTGTGTCTCTGGGCGAGAGGGCC ACCATCAACTGCAAGTCCAGCCAGAGTGTTTTACACAGCTCCAACAATATGAACTACTT AGCTTGGTACCAGCAGAAACCAGGACAGCCTCCTAAGTTGCTCATTTACTGGGCATCT ACCCGGAAATCCGGGGTCCCTGACCGATTCAGTGGCAGCGGGTCTGGGACAGATTTC ACTCTCACCATCAGCAGCCTTCAGGCTGCTGATGTGGCAGTTTATTACTGTCTGCAATA Attorney Docket No.250298.000780 TTATAATACTCCTCGAACGTTCGGCCAAGGGACCAAGGTGGAAATCAAACGAACTGTG GCTGCACCATCTGTCTTCATCTTCCCGCCATCTGATGAGCAGTTGAAATCTGGAACTG CCTCTGTTGTGTGCCTGCTGAATAACTTCTATCCCAGAGAGGCCAAAGTACAGTGGAA GGTGGATAACGCCCTCCAATCGGGTAACTCCCAGGAGAGTGTCACAGAGCAGGACAG CAAGGACAGCACCTACAGCCTCAGCAGCACCCTGACGCTGAGCAAAGCAGACTACGA GAAACACAAAGTCTACGCCTGCGAAGTCACCCATCAGGGCCTGAGCTCGCCCGTCAC AAAGAGCTTCAACAGGGGAGAGTGTTAG (SEQ ID NO: 75) LC Amino Acid Sequence DIVMTQSPDSLAVSLGERATINCKSSQSVLHSSNNMNYLAWYQQKPGQPPKLLIYWASTR KSGVPDRFSGSGSGTDFTLTISSLQAADVAVYYCLQYYNTPRTFGQGTKVEIKRTVAAPSV FIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSL SSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC* (SEQ ID NO: 76) REGN14152 HCVR DNA Sequence GAGGTGCAGCTGGTGGAGTCTGAGGGAGGCTGGGTACAGCCTGGGGGGTCCCTGAG ACTCTCCTGTGCAGCCTCTGGAATCACCTTTAGCATCTATGCCATGGCCTGGGTCCGC CAGGCTCCAGGGAAGGGACTTGAGTGGGTCTCAACTATTAGTGGTAGTGGTGATTCCA CATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCAGAGACAATTCCAAGAA CACGCTGTTTCTGCAAATGAACAGCCTGAGAGCCGTGGACACGGCCATATATTACTGT GCGAAAAGAGGATTTGCAGCTTTTGACTACTGGGGCCAGGGAACCCTGGTCACCGTC TCCTCA (SEQ ID NO: 77) HCVR Amino Acid Sequence EVQLVESEGGWVQPGGSLRLSCAASGITFSIYAMAWVRQAPGKGLEWVSTISGSGDSTY YADSVKGRFTISRDNSKNTLFLQMNSLRAVDTAIYYCAKRGFAAFDYWGQGTLVTVSS (SEQ ID NO: 78) CDR1 DNA Sequence Attorney Docket No.250298.000780 GGA ATC ACC TTT AGC ATC TAT GCC (SEQ ID NO: 79) CDR1 Amino Acid Sequence G I T F S I Y A (SEQ ID NO: 80) CDR2 DNA Sequence ATT AGT GGT AGT GGT GAT TCC ACA (SEQ ID NO: 81) CDR2 Amino Acid Sequence I S G S G D S T (SEQ ID NO: 82) CDR3 DNA Sequence GCG AAA AGA GGA TTT GCA GCT TTT GAC TAC (SEQ ID NO: 83) CDR3 Amino Acid Sequence A K R G F A A F D Y (SEQ ID NO: 84) LCVR DNA Sequence GAAATTGTGTTGACGCAGTCTCCAGGCACCCTGTCTTTGTCTCCAGGGGAAAGAGCCA CCCTCTCCTGTAGGGCCAGTCAGAGTGTTAGCAGCACCTACTTAGCCTGGTACCAGCA GAAACCTGGCCAGTCTCCCAGGCTCCTCATCTATGGTGCATCAAACAGGGCCACTGG CATCCCAGACAGGTTCAGTGGCAGTGGGTCTGGGACAGACTTCACTCTCACCATCAGC AGACTGGAGCCTGAAGATTTTGCAGTGTATTACTGTCAGCAGTATGGTAGCTCACGTC TGCTCAGTTTCGGCGGAGGGACCAAGGTGGAGATCAAA (SEQ ID NO: 85) LCVR Amino Acid Sequence Attorney Docket No.250298.000780 EIVLTQSPGTLSLSPGERATLSCRASQSVSSTYLAWYQQKPGQSPRLLIYGASNRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYCQQYGSSRLLSFGGGTKVEIK (SEQ ID NO: 86) CDR1 DNA Sequence CAG AGT GTT AGC AGC ACC TAC (SEQ ID NO: 87) CDR1 Amino Acid Sequence Q S V S S T Y (SEQ ID NO: 88) CDR2 DNA Sequence GGT GCA TCA (SEQ ID NO: 89) CDR2 Amino Acid Sequence G A S (SEQ ID NO: 90) CDR3 DNA Sequence CAG CAG TAT GGT AGC TCA CGT CTG CTC AGT (SEQ ID NO: 91) CDR3 Amino Acid Sequence Q Q Y G S S R L L S (SEQ ID NO: 92) HC DNA Sequence GAGGTGCAGCTGGTGGAGTCTGAGGGAGGCTGGGTACAGCCTGGGGGGTCCCTGAG ACTCTCCTGTGCAGCCTCTGGAATCACCTTTAGCATCTATGCCATGGCCTGGGTCCGC CAGGCTCCAGGGAAGGGACTTGAGTGGGTCTCAACTATTAGTGGTAGTGGTGATTCCA CATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCAGAGACAATTCCAAGAA Attorney Docket No.250298.000780 CACGCTGTTTCTGCAAATGAACAGCCTGAGAGCCGTGGACACGGCCATATATTACTGT GCGAAAAGAGGATTTGCAGCTTTTGACTACTGGGGCCAGGGAACCCTGGTCACCGTC TCCTCAGCCTCCACCAAGGGCCCATCGGTCTTCCCCCTGGCGCCCTGCTCCAGGAGC ACCTCCGAGAGCACAGCCGCCCTGGGCTGCCTGGTCAAGGACTACTTCCCCGAACCG GTGACGGTGTCGTGGAACTCAGGCGCCCTGACCAGCGGCGTGCACACCTTCCCGGCT GTCCTACAGTCCTCAGGACTCTACTCCCTCAGCAGCGTGGTGACCGTGCCCTCCAGC AGCTTGGGCACGAAGACCTACACCTGCAACGTAGATCACAAGCCCAGCAACACCAAG GTGGACAAGAGAGTTGAGTCCAAATATGGTCCCCCATGCCCACCGTGCCCAGCACCA CCTGTGGCAGGACCATCAGTCTTCCTGTTCCCCCCAAAACCCAAGGACACTCTCATGA TCTCCCGGACCCCTGAGGTCACGTGCGTGGTGGTGGACGTGAGCCAGGAAGACCCC GAGGTCCAGTTCAACTGGTACGTGGATGGCGTGGAGGTGCATAATGCCAAGACAAAG CCGCGGGAGGAGCAGTTCAACAGCACGTACCGTGTGGTCAGCGTCCTCACCGTCCTG CACCAGGACTGGCTGAACGGCAAGGAGTACAAGTGCAAGGTCTCCAACAAAGGCCTC CCGTCCTCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGAGAGCCACAG GTGTACACCCTGCCCCCATCCCAGGAGGAGATGACCAAGAACCAGGTCAGCCTGACC TGCCTGGTCAAAGGCTTCTACCCCAGCGACATCGCCGTGGAGTGGGAGAGCAATGGG CAGCCGGAGAACAACTACAAGACCACGCCTCCCGTGCTGGACTCCGACGGCTCCTTC TTCCTCTACAGCAGGCTCACCGTGGACAAGAGCAGGTGGCAGGAGGGGAATGTCTTC TCATGCTCCGTGATGCATGAGGCTCTGCACAACCACTACACACAGAAGTCCCTCTCCC TGTCTCTGGGTAAATGA (SEQ ID NO: 93) HC Amino Acid Sequence EVQLVESEGGWVQPGGSLRLSCAASGITFSIYAMAWVRQAPGKGLEWVSTISGSGDSTY YADSVKGRFTISRDNSKNTLFLQMNSLRAVDTAIYYCAKRGFAAFDYWGQGTLVTVSSAST KGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLY SLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPPVAGPSVFLFP PKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVS VLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVS LTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFS CSVMHEALHNHYTQKSLSLSLGK* (SEQ ID NO: 94) Attorney Docket No.250298.000780 LC DNA Sequence GAAATTGTGTTGACGCAGTCTCCAGGCACCCTGTCTTTGTCTCCAGGGGAAAGAGCCA CCCTCTCCTGTAGGGCCAGTCAGAGTGTTAGCAGCACCTACTTAGCCTGGTACCAGCA GAAACCTGGCCAGTCTCCCAGGCTCCTCATCTATGGTGCATCAAACAGGGCCACTGG CATCCCAGACAGGTTCAGTGGCAGTGGGTCTGGGACAGACTTCACTCTCACCATCAGC AGACTGGAGCCTGAAGATTTTGCAGTGTATTACTGTCAGCAGTATGGTAGCTCACGTC TGCTCAGTTTCGGCGGAGGGACCAAGGTGGAGATCAAACGAACTGTGGCTGCACCAT CTGTCTTCATCTTCCCGCCATCTGATGAGCAGTTGAAATCTGGAACTGCCTCTGTTGTG TGCCTGCTGAATAACTTCTATCCCAGAGAGGCCAAAGTACAGTGGAAGGTGGATAACG CCCTCCAATCGGGTAACTCCCAGGAGAGTGTCACAGAGCAGGACAGCAAGGACAGCA CCTACAGCCTCAGCAGCACCCTGACGCTGAGCAAAGCAGACTACGAGAAACACAAAG TCTACGCCTGCGAAGTCACCCATCAGGGCCTGAGCTCGCCCGTCACAAAGAGCTTCA ACAGGGGAGAGTGTTAG (SEQ ID NO: 95) LC Amino Acid Sequence EIVLTQSPGTLSLSPGERATLSCRASQSVSSTYLAWYQQKPGQSPRLLIYGASNRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYCQQYGSSRLLSFGGGTKVEIKRTVAAPSVFIFPPS DEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTL SKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC* (SEQ ID NO: 96) REGN14153 HCVR DNA Sequence GAGGTGCAGCTGGTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGAG ACTCTCCTGTGCAGCCTCTGGATTCACCTTTAGTAGTTATGCCATGAACTGGGTCCGC CAGGCTCCAGGGGAGGGCCTGGAGTGGGTCTCAACTTTGACTGGTAGTGGTGGTAGT ACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCAGAGACAATTCCAAGA ACACGCTGTTTCTGCACATGAGCAGCCTGAGAGCCGAGGACACGGCCGTATATTACTG TGCGAAAGGTGGAGTGGGATCTACTAAGGTTGTCTACTACGGTTTGGACGTCTGGGG CCAAGGGACCACGGTCACCGTCTCCTCA (SEQ ID NO: 97) Attorney Docket No.250298.000780 HCVR Amino Acid Sequence EVQLVESGGGLVQPGGSLRLSCAASGFTFSSYAMNWVRQAPGEGLEWVSTLTGSGGST YYADSVKGRFTISRDNSKNTLFLHMSSLRAEDTAVYYCAKGGVGSTKVVYYGLDVWGQG TTVTVSS (SEQ ID NO: 98) CDR1 DNA Sequence GGA TTC ACC TTT AGT AGT TAT GCC (SEQ ID NO: 99) CDR1 Amino Acid Sequence G F T F S S Y A (SEQ ID NO: 100) CDR2 DNA Sequence TTG ACT GGT AGT GGT GGT AGT ACA (SEQ ID NO: 101) CDR2 Amino Acid Sequence L T G S G G S T (SEQ ID NO: 102) CDR3 DNA Sequence GCG AAA GGT GGA GTG GGA TCT ACT AAG GTT GTC TAC TAC GGT TTG GAC GTC (SEQ ID NO: 103) CDR3 Amino Acid Sequence A K G G V G S T K V V Y Y G L D V (SEQ ID NO: 104) LCVR DNA Sequence GATATTGTGATGACTCAGTCTCCACTTTCCCTGCCCGTCATCCCTGGAGAGCCGGCCT CCATCTCCTGCAGGTCTAGTCAGAGCCTCCTGCATCGTAATGGATACAACTTTTTGGAT Attorney Docket No.250298.000780 TGGTACCTGCGGAAGCCAGGGCAGTCTCCACAGCTCCTGATCTATTTGGGTTCTAATC GGGCCTCCGGGGTCCCTGACAGGTTCAGTGGCAGTGGATCAGGCACAGATTTTACAC TGAAAATCAGCAGAGTGGAGGCTGAGGATGTTGGGGTTTATTACTGCATGCAAGCTCT ACAAACTCCGCTCACTTTCGGCGGAGGGACCAAGGTGGAGATCAAA (SEQ ID NO: 105) LCVR Amino Acid Sequence DIVMTQSPLSLPVIPGEPASISCRSSQSLLHRNGYNFLDWYLRKPGQSPQLLIYLGSNRAS GVPDRFSGSGSGTDFTLKISRVEAEDVGVYYCMQALQTPLTFGGGTKVEIK (SEQ ID NO: 106) CDR1 DNA Sequence CAG AGC CTC CTG CAT CGT AAT GGA TAC AAC TTT (SEQ ID NO: 107) CDR1 Amino Acid Sequence Q S L L H R N G Y N F (SEQ ID NO: 108) CDR2 DNA Sequence TTG GGT TCT (SEQ ID NO: 33) CDR2 Amino Acid Sequence L G S (SEQ ID NO: 34) CDR3 DNA Sequence ATG CAA GCT CTA CAA ACT CCG CTC ACT (SEQ ID NO: 109) CDR3 Amino Acid Sequence M Q A L Q T P L T Attorney Docket No.250298.000780 (SEQ ID NO: 110) HC DNA Sequence GAGGTGCAGCTGGTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGAG ACTCTCCTGTGCAGCCTCTGGATTCACCTTTAGTAGTTATGCCATGAACTGGGTCCGC CAGGCTCCAGGGGAGGGCCTGGAGTGGGTCTCAACTTTGACTGGTAGTGGTGGTAGT ACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCAGAGACAATTCCAAGA ACACGCTGTTTCTGCACATGAGCAGCCTGAGAGCCGAGGACACGGCCGTATATTACTG TGCGAAAGGTGGAGTGGGATCTACTAAGGTTGTCTACTACGGTTTGGACGTCTGGGG CCAAGGGACCACGGTCACCGTCTCCTCAGCCTCCACCAAGGGCCCATCGGTCTTCCC CCTGGCGCCCTGCTCCAGGAGCACCTCCGAGAGCACAGCCGCCCTGGGCTGCCTGG TCAAGGACTACTTCCCCGAACCGGTGACGGTGTCGTGGAACTCAGGCGCCCTGACCA GCGGCGTGCACACCTTCCCGGCTGTCCTACAGTCCTCAGGACTCTACTCCCTCAGCA GCGTGGTGACCGTGCCCTCCAGCAGCTTGGGCACGAAGACCTACACCTGCAACGTAG ATCACAAGCCCAGCAACACCAAGGTGGACAAGAGAGTTGAGTCCAAATATGGTCCCCC ATGCCCACCGTGCCCAGCACCACCTGTGGCAGGACCATCAGTCTTCCTGTTCCCCCC AAAACCCAAGGACACTCTCATGATCTCCCGGACCCCTGAGGTCACGTGCGTGGTGGT GGACGTGAGCCAGGAAGACCCCGAGGTCCAGTTCAACTGGTACGTGGATGGCGTGGA GGTGCATAATGCCAAGACAAAGCCGCGGGAGGAGCAGTTCAACAGCACGTACCGTGT GGTCAGCGTCCTCACCGTCCTGCACCAGGACTGGCTGAACGGCAAGGAGTACAAGTG CAAGGTCTCCAACAAAGGCCTCCCGTCCTCCATCGAGAAAACCATCTCCAAAGCCAAA GGGCAGCCCCGAGAGCCACAGGTGTACACCCTGCCCCCATCCCAGGAGGAGATGAC CAAGAACCAGGTCAGCCTGACCTGCCTGGTCAAAGGCTTCTACCCCAGCGACATCGC CGTGGAGTGGGAGAGCAATGGGCAGCCGGAGAACAACTACAAGACCACGCCTCCCGT GCTGGACTCCGACGGCTCCTTCTTCCTCTACAGCAGGCTCACCGTGGACAAGAGCAG GTGGCAGGAGGGGAATGTCTTCTCATGCTCCGTGATGCATGAGGCTCTGCACAACCA CTACACACAGAAGTCCCTCTCCCTGTCTCTGGGTAAATGA (SEQ ID NO: 111) HC Amino Acid Sequence EVQLVESGGGLVQPGGSLRLSCAASGFTFSSYAMNWVRQAPGEGLEWVSTLTGSGGST YYADSVKGRFTISRDNSKNTLFLHMSSLRAEDTAVYYCAKGGVGSTKVVYYGLDVWGQG TTVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFP Attorney Docket No.250298.000780 AVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPPV AGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQ FNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQE EMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSR WQEGNVFSCSVMHEALHNHYTQKSLSLSLGK* (SEQ ID NO: 112) LC DNA Sequence GATATTGTGATGACTCAGTCTCCACTTTCCCTGCCCGTCATCCCTGGAGAGCCGGCCT CCATCTCCTGCAGGTCTAGTCAGAGCCTCCTGCATCGTAATGGATACAACTTTTTGGAT TGGTACCTGCGGAAGCCAGGGCAGTCTCCACAGCTCCTGATCTATTTGGGTTCTAATC GGGCCTCCGGGGTCCCTGACAGGTTCAGTGGCAGTGGATCAGGCACAGATTTTACAC TGAAAATCAGCAGAGTGGAGGCTGAGGATGTTGGGGTTTATTACTGCATGCAAGCTCT ACAAACTCCGCTCACTTTCGGCGGAGGGACCAAGGTGGAGATCAAACGAACTGTGGC TGCACCATCTGTCTTCATCTTCCCGCCATCTGATGAGCAGTTGAAATCTGGAACTGCCT CTGTTGTGTGCCTGCTGAATAACTTCTATCCCAGAGAGGCCAAAGTACAGTGGAAGGT GGATAACGCCCTCCAATCGGGTAACTCCCAGGAGAGTGTCACAGAGCAGGACAGCAA GGACAGCACCTACAGCCTCAGCAGCACCCTGACGCTGAGCAAAGCAGACTACGAGAA ACACAAAGTCTACGCCTGCGAAGTCACCCATCAGGGCCTGAGCTCGCCCGTCACAAA GAGCTTCAACAGGGGAGAGTGTTAG (SEQ ID NO: 113) LC Amino Acid Sequence DIVMTQSPLSLPVIPGEPASISCRSSQSLLHRNGYNFLDWYLRKPGQSPQLLIYLGSNRAS GVPDRFSGSGSGTDFTLKISRVEAEDVGVYYCMQALQTPLTFGGGTKVEIKRTVAAPSVFI FPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLS STLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC* (SEQ ID NO: 114) REGN14154 HCVR DNA Sequence CAGCTGCAGCTGCAGGAGTCGGGCCCAGGACTGGTGAAGCCTTCGGAGACCCTGTC CCTCACTTGCACTGTCTCGGGTGGCTCCAGCAGCAGAAGTAGTTACTACTGGGGCTG Attorney Docket No.250298.000780 GATCCGCCAGCCCCCAGGGAAGGGACTGGAGTGGATTGGGAGTATCTATTATAGTGG GAACACCTACTACAACCCGTCCCTCCAGAGTCGAGTCACCATATCCGTAGACACGTCC AAGAACCAGTTCTCCCTGAAACTGAACTCTGTGACCGCCGCAGACACGGCTGTATTTT ATTGTGCGAGACACAAACCTACTACGTGGGCTTTTGATATCTGGGGCCAAGGGACAAT GGTCACCGTCTCTTCA (SEQ ID NO: 115) HCVR Amino Acid Sequence QLQLQESGPGLVKPSETLSLTCTVSGGSSSRSSYYWGWIRQPPGKGLEWIGSIYYSGNTY YNPSLQSRVTISVDTSKNQFSLKLNSVTAADTAVFYCARHKPTTWAFDIWGQGTMVTVSS (SEQ ID NO: 116) CDR1 DNA Sequence GGT GGC TCC AGC AGC AGA AGT AGT TAC TAC (SEQ ID NO: 117) CDR1 Amino Acid Sequence G G S S S R S S Y Y (SEQ ID NO: 118) CDR2 DNA Sequence ATC TAT TAT AGT GGG AAC ACC (SEQ ID NO: 119) CDR2 Amino Acid Sequence I Y Y S G N T (SEQ ID NO: 120) CDR3 DNA Sequence GCG AGA CAC AAA CCT ACT ACG TGG GCT TTT GAT ATC (SEQ ID NO: 121) CDR3 Amino Acid Sequence Attorney Docket No.250298.000780 A R H K P T T W A F D I (SEQ ID NO: 122) LCVR DNA Sequence GACATCCAGATGACCCAGTCTCCTTCCACCCTGTCTGCATCTGTAGGAGACAGAGTCA CCATCACTTGCCGGGCCAGTCAGAGTATCAGTAGTTGGTTGGCCTGGTATCAGCAGAA ACCAGGGAAAGTCCCAAAGTTGCTGATCTATAAGGCGTCTAATTTAGAAAGTGGGGTC CCCTCAAGGTTCAGCGGCAGTGGATCTGGGACAGAATTCACTCTCACCATCAGCGACC TGCAGCCTGATGATTTTGCAAGTTATTACTGCCAACAGTATAGTACTTATTCTCGGACG TTCGGCCGAGGGACCAAGGTGGAGATCAAA (SEQ ID NO: 123) LCVR Amino Acid Sequence DIQMTQSPSTLSASVGDRVTITCRASQSISSWLAWYQQKPGKVPKLLIYKASNLESGVPSR FSGSGSGTEFTLTISDLQPDDFASYYCQQYSTYSRTFGRGTKVEIK (SEQ ID NO: 124) CDR1 DNA Sequence CAG AGT ATC AGT AGT TGG (SEQ ID NO: 125) CDR1 Amino Acid Sequence Q S I S S W (SEQ ID NO: 126) CDR2 DNA Sequence AAG GCG TCT (SEQ ID NO: 127) CDR2 Amino Acid Sequence K A S (SEQ ID NO: 128) Attorney Docket No.250298.000780 CDR3 DNA Sequence CAA CAG TAT AGT ACT TAT TCT CGG ACG (SEQ ID NO: 129) CDR3 Amino Acid Sequence Q Q Y S T Y S R T (SEQ ID NO: 130) HC DNA Sequence CAGCTGCAGCTGCAGGAGTCGGGCCCAGGACTGGTGAAGCCTTCGGAGACCCTGTC CCTCACTTGCACTGTCTCGGGTGGCTCCAGCAGCAGAAGTAGTTACTACTGGGGCTG GATCCGCCAGCCCCCAGGGAAGGGACTGGAGTGGATTGGGAGTATCTATTATAGTGG GAACACCTACTACAACCCGTCCCTCCAGAGTCGAGTCACCATATCCGTAGACACGTCC AAGAACCAGTTCTCCCTGAAACTGAACTCTGTGACCGCCGCAGACACGGCTGTATTTT ATTGTGCGAGACACAAACCTACTACGTGGGCTTTTGATATCTGGGGCCAAGGGACAAT GGTCACCGTCTCTTCAGCCTCCACCAAGGGCCCATCGGTCTTCCCCCTGGCGCCCTG CTCCAGGAGCACCTCCGAGAGCACAGCCGCCCTGGGCTGCCTGGTCAAGGACTACTT CCCCGAACCGGTGACGGTGTCGTGGAACTCAGGCGCCCTGACCAGCGGCGTGCACA CCTTCCCGGCTGTCCTACAGTCCTCAGGACTCTACTCCCTCAGCAGCGTGGTGACCGT GCCCTCCAGCAGCTTGGGCACGAAGACCTACACCTGCAACGTAGATCACAAGCCCAG CAACACCAAGGTGGACAAGAGAGTTGAGTCCAAATATGGTCCCCCATGCCCACCGTG CCCAGCACCACCTGTGGCAGGACCATCAGTCTTCCTGTTCCCCCCAAAACCCAAGGAC ACTCTCATGATCTCCCGGACCCCTGAGGTCACGTGCGTGGTGGTGGACGTGAGCCAG GAAGACCCCGAGGTCCAGTTCAACTGGTACGTGGATGGCGTGGAGGTGCATAATGCC AAGACAAAGCCGCGGGAGGAGCAGTTCAACAGCACGTACCGTGTGGTCAGCGTCCTC ACCGTCCTGCACCAGGACTGGCTGAACGGCAAGGAGTACAAGTGCAAGGTCTCCAAC AAAGGCCTCCCGTCCTCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGA GAGCCACAGGTGTACACCCTGCCCCCATCCCAGGAGGAGATGACCAAGAACCAGGTC AGCCTGACCTGCCTGGTCAAAGGCTTCTACCCCAGCGACATCGCCGTGGAGTGGGAG AGCAATGGGCAGCCGGAGAACAACTACAAGACCACGCCTCCCGTGCTGGACTCCGAC GGCTCCTTCTTCCTCTACAGCAGGCTCACCGTGGACAAGAGCAGGTGGCAGGAGGGG AATGTCTTCTCATGCTCCGTGATGCATGAGGCTCTGCACAACCACTACACACAGAAGT CCCTCTCCCTGTCTCTGGGTAAATGA Attorney Docket No.250298.000780 (SEQ ID NO: 131) HC Amino Acid Sequence QLQLQESGPGLVKPSETLSLTCTVSGGSSSRSSYYWGWIRQPPGKGLEWIGSIYYSGNTY YNPSLQSRVTISVDTSKNQFSLKLNSVTAADTAVFYCARHKPTTWAFDIWGQGTMVTVSS ASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSS GLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPPVAGPSVF LFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYR VVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKN QVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGN VFSCSVMHEALHNHYTQKSLSLSLGK* (SEQ ID NO: 132) LC DNA Sequence GACATCCAGATGACCCAGTCTCCTTCCACCCTGTCTGCATCTGTAGGAGACAGAGTCA CCATCACTTGCCGGGCCAGTCAGAGTATCAGTAGTTGGTTGGCCTGGTATCAGCAGAA ACCAGGGAAAGTCCCAAAGTTGCTGATCTATAAGGCGTCTAATTTAGAAAGTGGGGTC CCCTCAAGGTTCAGCGGCAGTGGATCTGGGACAGAATTCACTCTCACCATCAGCGACC TGCAGCCTGATGATTTTGCAAGTTATTACTGCCAACAGTATAGTACTTATTCTCGGACG TTCGGCCGAGGGACCAAGGTGGAGATCAAACGAACTGTGGCTGCACCATCTGTCTTC ATCTTCCCGCCATCTGATGAGCAGTTGAAATCTGGAACTGCCTCTGTTGTGTGCCTGC TGAATAACTTCTATCCCAGAGAGGCCAAAGTACAGTGGAAGGTGGATAACGCCCTCCA ATCGGGTAACTCCCAGGAGAGTGTCACAGAGCAGGACAGCAAGGACAGCACCTACAG CCTCAGCAGCACCCTGACGCTGAGCAAAGCAGACTACGAGAAACACAAAGTCTACGC CTGCGAAGTCACCCATCAGGGCCTGAGCTCGCCCGTCACAAAGAGCTTCAACAGGGG AGAGTGTTAG (SEQ ID NO: 133) LC Amino Acid Sequence DIQMTQSPSTLSASVGDRVTITCRASQSISSWLAWYQQKPGKVPKLLIYKASNLESGVPSR FSGSGSGTEFTLTISDLQPDDFASYYCQQYSTYSRTFGRGTKVEIKRTVAAPSVFIFPPSDE QLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSK ADYEKHKVYACEVTHQGLSSPVTKSFNRGEC* Attorney Docket No.250298.000780 (SEQ ID NO: 134) REGN14155 HCVR DNA Sequence CAGGTTCAGCTGGTGCAGTCTGGAGGTGAGGTGAAGAAGCCTGGGGACTCAGTGAAG GTCTCCTGCAAGGCTTCTGGTTACACCTTTACCAGCTATGGTATCAGCTGGGTGCGAC AGGCCCCTGGACAAGGGCTTGAGTGGATGGGATGGATCAGCGTCTACAGTGGTAAAA AAAACTACGCACGGAAGGTCCAGGACAGAGTCACCATGACCACAGACACATCCACGA GCACAGCCTACATGGAGGTGAGGAGCCTGCGATCTGACGACACGGCCATATATTATTG TACAAGAAGGGGAGTGTCTTCGATGGTCGGTGCTTTTGAAATCTGGGGCCAAGGGAC AATGGTCACCGTCTCTTCA (SEQ ID NO: 135) HCVR Amino Acid Sequence QVQLVQSGGEVKKPGDSVKVSCKASGYTFTSYGISWVRQAPGQGLEWMGWISVYSGKK NYARKVQDRVTMTTDTSTSTAYMEVRSLRSDDTAIYYCTRRGVSSMVGAFEIWGQGTMV TVSS (SEQ ID NO: 136) CDR1 DNA Sequence GGT TAC ACC TTT ACC AGC TAT GGT (SEQ ID NO: 137) CDR1 Amino Acid Sequence G Y T F T S Y G (SEQ ID NO: 138) CDR2 DNA Sequence ATC AGC GTC TAC AGT GGT AAA AAA (SEQ ID NO: 139) CDR2 Amino Acid Sequence I S V Y S G K K Attorney Docket No.250298.000780 (SEQ ID NO: 140) CDR3 DNA Sequence ACA AGA AGG GGA GTG TCT TCG ATG GTC GGT GCT TTT GAA ATC (SEQ ID NO: 141) CDR3 Amino Acid Sequence T R R G V S S M V G A F E I (SEQ ID NO: 142) LCVR DNA Sequence GAAATTGTGTTGACGCAGTCTCCAGGCATTCTGTCTTTGTCTCCAGGGGAAAGAGCCA CCCTCTCCTGCAAGGCCAGTCAGAGTGTTAGCAACAGCTACTTAGCCTGGTACCAGCA GAAACCTGGCCAGGCTCCCAGGCTCCTCATCTATGGAGCATCTAGTAGGGCCACTGG CATCCCAGACAGGTTCAGTGGCAGTGGGTCTGGGACAGACTTCACTGTCACCATCAG CAGACTGGAGCCTGAAGATTTTGCAGTCTATTACTGTCAGCAGTATGGTAGCTCACCG CTCACTTTCGGCGGAGGGACCAAGGTGGAGATCAAA (SEQ ID NO: 143) LCVR Amino Acid Sequence EIVLTQSPGILSLSPGERATLSCKASQSVSNSYLAWYQQKPGQAPRLLIYGASSRATGIPDR FSGSGSGTDFTVTISRLEPEDFAVYYCQQYGSSPLTFGGGTKVEIK (SEQ ID NO: 144) CDR1 DNA Sequence CAG AGT GTT AGC AAC AGC TAC (SEQ ID NO: 145) CDR1 Amino Acid Sequence Q S V S N S Y (SEQ ID NO: 146) CDR2 DNA Sequence Attorney Docket No.250298.000780 GGA GCA TCT (SEQ ID NO: 147) CDR2 Amino Acid Sequence G A S (SEQ ID NO: 90) CDR3 DNA Sequence CAG CAG TAT GGT AGC TCA CCG CTC ACT (SEQ ID NO: 148) CDR3 Amino Acid Sequence Q Q Y G S S P L T (SEQ ID NO: 149) HC DNA Sequence CAGGTTCAGCTGGTGCAGTCTGGAGGTGAGGTGAAGAAGCCTGGGGACTCAGTGAAG GTCTCCTGCAAGGCTTCTGGTTACACCTTTACCAGCTATGGTATCAGCTGGGTGCGAC AGGCCCCTGGACAAGGGCTTGAGTGGATGGGATGGATCAGCGTCTACAGTGGTAAAA AAAACTACGCACGGAAGGTCCAGGACAGAGTCACCATGACCACAGACACATCCACGA GCACAGCCTACATGGAGGTGAGGAGCCTGCGATCTGACGACACGGCCATATATTATTG TACAAGAAGGGGAGTGTCTTCGATGGTCGGTGCTTTTGAAATCTGGGGCCAAGGGAC AATGGTCACCGTCTCTTCAGCCTCCACCAAGGGCCCATCGGTCTTCCCCCTGGCGCC CTGCTCCAGGAGCACCTCCGAGAGCACAGCCGCCCTGGGCTGCCTGGTCAAGGACTA CTTCCCCGAACCGGTGACGGTGTCGTGGAACTCAGGCGCCCTGACCAGCGGCGTGC ACACCTTCCCGGCTGTCCTACAGTCCTCAGGACTCTACTCCCTCAGCAGCGTGGTGAC CGTGCCCTCCAGCAGCTTGGGCACGAAGACCTACACCTGCAACGTAGATCACAAGCC CAGCAACACCAAGGTGGACAAGAGAGTTGAGTCCAAATATGGTCCCCCATGCCCACC GTGCCCAGCACCACCTGTGGCAGGACCATCAGTCTTCCTGTTCCCCCCAAAACCCAAG GACACTCTCATGATCTCCCGGACCCCTGAGGTCACGTGCGTGGTGGTGGACGTGAGC CAGGAAGACCCCGAGGTCCAGTTCAACTGGTACGTGGATGGCGTGGAGGTGCATAAT GCCAAGACAAAGCCGCGGGAGGAGCAGTTCAACAGCACGTACCGTGTGGTCAGCGTC CTCACCGTCCTGCACCAGGACTGGCTGAACGGCAAGGAGTACAAGTGCAAGGTCTCC Attorney Docket No.250298.000780 AACAAAGGCCTCCCGTCCTCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCC CGAGAGCCACAGGTGTACACCCTGCCCCCATCCCAGGAGGAGATGACCAAGAACCAG GTCAGCCTGACCTGCCTGGTCAAAGGCTTCTACCCCAGCGACATCGCCGTGGAGTGG GAGAGCAATGGGCAGCCGGAGAACAACTACAAGACCACGCCTCCCGTGCTGGACTCC GACGGCTCCTTCTTCCTCTACAGCAGGCTCACCGTGGACAAGAGCAGGTGGCAGGAG GGGAATGTCTTCTCATGCTCCGTGATGCATGAGGCTCTGCACAACCACTACACACAGA AGTCCCTCTCCCTGTCTCTGGGTAAATGA (SEQ ID NO: 150) HC Amino Acid Sequence QVQLVQSGGEVKKPGDSVKVSCKASGYTFTSYGISWVRQAPGQGLEWMGWISVYSGKK NYARKVQDRVTMTTDTSTSTAYMEVRSLRSDDTAIYYCTRRGVSSMVGAFEIWGQGTMV TVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVL QSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPPVAGP SVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNS TYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMT KNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQE GNVFSCSVMHEALHNHYTQKSLSLSLGK* (SEQ ID NO: 151) LC DNA Sequence GAAATTGTGTTGACGCAGTCTCCAGGCATTCTGTCTTTGTCTCCAGGGGAAAGAGCCA CCCTCTCCTGCAAGGCCAGTCAGAGTGTTAGCAACAGCTACTTAGCCTGGTACCAGCA GAAACCTGGCCAGGCTCCCAGGCTCCTCATCTATGGAGCATCTAGTAGGGCCACTGG CATCCCAGACAGGTTCAGTGGCAGTGGGTCTGGGACAGACTTCACTGTCACCATCAG CAGACTGGAGCCTGAAGATTTTGCAGTCTATTACTGTCAGCAGTATGGTAGCTCACCG CTCACTTTCGGCGGAGGGACCAAGGTGGAGATCAAACGAACTGTGGCTGCACCATCT GTCTTCATCTTCCCGCCATCTGATGAGCAGTTGAAATCTGGAACTGCCTCTGTTGTGTG CCTGCTGAATAACTTCTATCCCAGAGAGGCCAAAGTACAGTGGAAGGTGGATAACGCC CTCCAATCGGGTAACTCCCAGGAGAGTGTCACAGAGCAGGACAGCAAGGACAGCACC TACAGCCTCAGCAGCACCCTGACGCTGAGCAAAGCAGACTACGAGAAACACAAAGTCT ACGCCTGCGAAGTCACCCATCAGGGCCTGAGCTCGCCCGTCACAAAGAGCTTCAACA GGGGAGAGTGTTAG Attorney Docket No.250298.000780 (SEQ ID NO: 152) LC Amino Acid Sequence EIVLTQSPGILSLSPGERATLSCKASQSVSNSYLAWYQQKPGQAPRLLIYGASSRATGIPDR FSGSGSGTDFTVTISRLEPEDFAVYYCQQYGSSPLTFGGGTKVEIKRTVAAPSVFIFPPSDE QLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSK ADYEKHKVYACEVTHQGLSSPVTKSFNRGEC* (SEQ ID NO: 153) REGN14156 HCVR DNA Sequence GAGGTGCAGCTGGTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGAGTCCCTGAG ACTCTCCTGTGCAGCCTCTGGATTCACCTTTAGCAGCTATGCCATGACCTGGGTCCGC CAGGCTCCAGGGAAGGGGCTGGAGTGGGTCTCAACTATTAGTGGTAGTGGTGGTAAC ACATACTACGCAGTCTCCGTGAAGGGCCGGTTCACCATCTCCAGAGACACTTCCAAGA ACACGCTGTATCTGCAAATGAACGGCCTGAGAGCCGAGGACACGGCCGTATATTACTG TGCGACCCTCACCAGTGGCTGGTACCTTTTTGAGTACTGGGGCCAGGGAACCCTGGT CACCGTCTCCTCA (SEQ ID NO: 154) HCVR Amino Acid Sequence EVQLVESGGGLVQPGESLRLSCAASGFTFSSYAMTWVRQAPGKGLEWVSTISGSGGNTY YAVSVKGRFTISRDTSKNTLYLQMNGLRAEDTAVYYCATLTSGWYLFEYWGQGTLVTVSS (SEQ ID NO: 155) CDR1 DNA Sequence GGA TTC ACC TTT AGC AGC TAT GCC (SEQ ID NO: 156) CDR1 Amino Acid Sequence G F T F S S Y A (SEQ ID NO: 100) Attorney Docket No.250298.000780 CDR2 DNA Sequence ATT AGT GGT AGT GGT GGT AAC ACA (SEQ ID NO: 157) CDR2 Amino Acid Sequence I S G S G G N T (SEQ ID NO: 158) CDR3 DNA Sequence GCG ACC CTC ACC AGT GGC TGG TAC CTT TTT GAG TAC (SEQ ID NO: 159) CDR3 Amino Acid Sequence A T L T S G W Y L F E Y (SEQ ID NO: 160) LCVR DNA Sequence GAAATTGTGTTGACGCAGTCTCCAGGCACCCTGTCTTTGGCTCCAGGGGAAAGAGCCA CCCTCTCCTGCAGGGCCAGTCAGAGTGTTAGCAGCAGCTTCTTTGCCTGGTACCAGCA GAAACCTGGCCAGGCTCCCAGGCTCCTCATCTATGGTGCATCCAGCAGGGCCACTGG CATCCCAGACAGGTTCAGTGGCAGTGGGTCTGGGACAGACTTCACTCTCACCATCAGC AGACTGGAGCCTGAAGATTTTGCAGTGTATTACTGTCAGCAGTATGGAAGCTCACCTC CGTGGACGTTCGGCCAAGGGACCAAGGTGGAAATCAAA (SEQ ID NO: 161) LCVR Amino Acid Sequence EIVLTQSPGTLSLAPGERATLSCRASQSVSSSFFAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYCQQYGSSPPWTFGQGTKVEIK (SEQ ID NO: 162) CDR1 DNA Sequence CAG AGT GTT AGC AGC AGC TTC (SEQ ID NO: 163) Attorney Docket No.250298.000780 CDR1 Amino Acid Sequence Q S V S S S F (SEQ ID NO: 164) CDR2 DNA Sequence GGT GCA TCC (SEQ ID NO: 165) CDR2 Amino Acid Sequence G A S (SEQ ID NO: 90) CDR3 DNA Sequence CAG CAG TAT GGA AGC TCA CCT CCG TGG ACG (SEQ ID NO: 166) CDR3 Amino Acid Sequence Q Q Y G S S P P W T (SEQ ID NO: 167) HC DNA Sequence GAGGTGCAGCTGGTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGAGTCCCTGAG ACTCTCCTGTGCAGCCTCTGGATTCACCTTTAGCAGCTATGCCATGACCTGGGTCCGC CAGGCTCCAGGGAAGGGGCTGGAGTGGGTCTCAACTATTAGTGGTAGTGGTGGTAAC ACATACTACGCAGTCTCCGTGAAGGGCCGGTTCACCATCTCCAGAGACACTTCCAAGA ACACGCTGTATCTGCAAATGAACGGCCTGAGAGCCGAGGACACGGCCGTATATTACTG TGCGACCCTCACCAGTGGCTGGTACCTTTTTGAGTACTGGGGCCAGGGAACCCTGGT CACCGTCTCCTCAGCCTCCACCAAGGGCCCATCGGTCTTCCCCCTGGCGCCCTGCTC CAGGAGCACCTCCGAGAGCACAGCCGCCCTGGGCTGCCTGGTCAAGGACTACTTCCC CGAACCGGTGACGGTGTCGTGGAACTCAGGCGCCCTGACCAGCGGCGTGCACACCTT CCCGGCTGTCCTACAGTCCTCAGGACTCTACTCCCTCAGCAGCGTGGTGACCGTGCC CTCCAGCAGCTTGGGCACGAAGACCTACACCTGCAACGTAGATCACAAGCCCAGCAA Attorney Docket No.250298.000780 CACCAAGGTGGACAAGAGAGTTGAGTCCAAATATGGTCCCCCATGCCCACCGTGCCC AGCACCACCTGTGGCAGGACCATCAGTCTTCCTGTTCCCCCCAAAACCCAAGGACACT CTCATGATCTCCCGGACCCCTGAGGTCACGTGCGTGGTGGTGGACGTGAGCCAGGAA GACCCCGAGGTCCAGTTCAACTGGTACGTGGATGGCGTGGAGGTGCATAATGCCAAG ACAAAGCCGCGGGAGGAGCAGTTCAACAGCACGTACCGTGTGGTCAGCGTCCTCACC GTCCTGCACCAGGACTGGCTGAACGGCAAGGAGTACAAGTGCAAGGTCTCCAACAAA GGCCTCCCGTCCTCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGAGAG CCACAGGTGTACACCCTGCCCCCATCCCAGGAGGAGATGACCAAGAACCAGGTCAGC CTGACCTGCCTGGTCAAAGGCTTCTACCCCAGCGACATCGCCGTGGAGTGGGAGAGC AATGGGCAGCCGGAGAACAACTACAAGACCACGCCTCCCGTGCTGGACTCCGACGGC TCCTTCTTCCTCTACAGCAGGCTCACCGTGGACAAGAGCAGGTGGCAGGAGGGGAAT GTCTTCTCATGCTCCGTGATGCATGAGGCTCTGCACAACCACTACACACAGAAGTCCC TCTCCCTGTCTCTGGGTAAATGA (SEQ ID NO: 168) HC Amino Acid Sequence EVQLVESGGGLVQPGESLRLSCAASGFTFSSYAMTWVRQAPGKGLEWVSTISGSGGNTY YAVSVKGRFTISRDTSKNTLYLQMNGLRAEDTAVYYCATLTSGWYLFEYWGQGTLVTVSS ASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSS GLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPPVAGPSVF LFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYR VVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKN QVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGN VFSCSVMHEALHNHYTQKSLSLSLGK* (SEQ ID NO: 169) LC DNA Sequence GAAATTGTGTTGACGCAGTCTCCAGGCACCCTGTCTTTGGCTCCAGGGGAAAGAGCCA CCCTCTCCTGCAGGGCCAGTCAGAGTGTTAGCAGCAGCTTCTTTGCCTGGTACCAGCA GAAACCTGGCCAGGCTCCCAGGCTCCTCATCTATGGTGCATCCAGCAGGGCCACTGG CATCCCAGACAGGTTCAGTGGCAGTGGGTCTGGGACAGACTTCACTCTCACCATCAGC AGACTGGAGCCTGAAGATTTTGCAGTGTATTACTGTCAGCAGTATGGAAGCTCACCTC CGTGGACGTTCGGCCAAGGGACCAAGGTGGAAATCAAACGAACTGTGGCTGCACCAT Attorney Docket No.250298.000780 CTGTCTTCATCTTCCCGCCATCTGATGAGCAGTTGAAATCTGGAACTGCCTCTGTTGTG TGCCTGCTGAATAACTTCTATCCCAGAGAGGCCAAAGTACAGTGGAAGGTGGATAACG CCCTCCAATCGGGTAACTCCCAGGAGAGTGTCACAGAGCAGGACAGCAAGGACAGCA CCTACAGCCTCAGCAGCACCCTGACGCTGAGCAAAGCAGACTACGAGAAACACAAAG TCTACGCCTGCGAAGTCACCCATCAGGGCCTGAGCTCGCCCGTCACAAAGAGCTTCA ACAGGGGAGAGTGTTAG (SEQ ID NO: 170) LC Amino Acid Sequence EIVLTQSPGTLSLAPGERATLSCRASQSVSSSFFAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYCQQYGSSPPWTFGQGTKVEIKRTVAAPSVFIFPP SDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLT LSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC* (SEQ ID NO: 171) REGN14157 HCVR DNA Sequence GAGGTGCAGCTGGTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGAG ACTCTCCTGTGCAGCCTCTGGATTCACCTTTAGCAGCTATGCCATGAGCTGGGTCCGC CAGGCTCCAGGGAAGGGGCTGGAGTGGGTCTCAGCTATTAGTGGTAGTGGTGATAAC ACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCAGAGACAATTCCAAGA ACACGCTGTATCTGCAAATGAACAGCCTGAGAGTCGAGGATACGGCCGTATATTATTG TGCGAAAGAGAAGAGCAGTGGCTGGTACGAATACTGGGGCCAGGGAACCCTGGTCAC CGTCTCCTCA (SEQ ID NO: 172) HCVR Amino Acid Sequence EVQLVESGGGLVQPGGSLRLSCAASGFTFSSYAMSWVRQAPGKGLEWVSAISGSGDNTY YADSVKGRFTISRDNSKNTLYLQMNSLRVEDTAVYYCAKEKSSGWYEYWGQGTLVTVSS (SEQ ID NO: 173) CDR1 DNA Sequence GGA TTC ACC TTT AGC AGC TAT GCC Attorney Docket No.250298.000780 (SEQ ID NO: 156) CDR1 Amino Acid Sequence G F T F S S Y A (SEQ ID NO: 100) CDR2 DNA Sequence ATT AGT GGT AGT GGT GAT AAC ACA (SEQ ID NO: 174) CDR2 Amino Acid Sequence I S G S G D N T (SEQ ID NO: 175) CDR3 DNA Sequence GCG AAA GAG AAG AGC AGT GGC TGG TAC GAA TAC (SEQ ID NO: 176) CDR3 Amino Acid Sequence A K E K S S G W Y E Y (SEQ ID NO: 177) LCVR DNA Sequence GACATCGTGATGACCCAGTCTCCAGACTCCCTGGCTGTGTCTCTGGGCGAGAGGGCC ACCATCAACTGCAAGTCCAGCCAGAGTGTTTTATACAGTTCCAACAATAAGAATTACTT AGCTTGGTACCAGCAGAAACCAGGACAGACTCCTAAACTGCTCATTTACTGGGCATCT ACCCGGGAATCCGGGGTCCCTGACCGATTCAGTGGCAGCGGGTCTGGGACAGATTTC ACTCTCACCATCAGCAGCCTGCAGGCTGAAGATGTGGCAGTTTATTACTGTCAGCAAT ATTATTTTATTCCGTACACTTTTGGCCAGGGGACCAAGCTGGAGATCAAA (SEQ ID NO: 178) LCVR Amino Acid Sequence Attorney Docket No.250298.000780 DIVMTQSPDSLAVSLGERATINCKSSQSVLYSSNNKNYLAWYQQKPGQTPKLLIYWASTRE SGVPDRFSGSGSGTDFTLTISSLQAEDVAVYYCQQYYFIPYTFGQGTKLEIK (SEQ ID NO: 179) CDR1 DNA Sequence CAG AGT GTT TTA TAC AGT TCC AAC AAT AAG AAT TAC (SEQ ID NO: 180) CDR1 Amino Acid Sequence Q S V L Y S S N N K N Y (SEQ ID NO: 181) CDR2 DNA Sequence TGG GCA TCT (SEQ ID NO: 69) CDR2 Amino Acid Sequence W A S (SEQ ID NO: 70) CDR3 DNA Sequence CAG CAA TAT TAT TTT ATT CCG TAC ACT (SEQ ID NO: 182) CDR3 Amino Acid Sequence Q Q Y Y F I P Y T (SEQ ID NO: 183) HC DNA Sequence GAGGTGCAGCTGGTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGAG ACTCTCCTGTGCAGCCTCTGGATTCACCTTTAGCAGCTATGCCATGAGCTGGGTCCGC CAGGCTCCAGGGAAGGGGCTGGAGTGGGTCTCAGCTATTAGTGGTAGTGGTGATAAC ACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCAGAGACAATTCCAAGA ACACGCTGTATCTGCAAATGAACAGCCTGAGAGTCGAGGATACGGCCGTATATTATTG Attorney Docket No.250298.000780 TGCGAAAGAGAAGAGCAGTGGCTGGTACGAATACTGGGGCCAGGGAACCCTGGTCAC CGTCTCCTCAGCCTCCACCAAGGGCCCATCGGTCTTCCCCCTGGCGCCCTGCTCCAG GAGCACCTCCGAGAGCACAGCCGCCCTGGGCTGCCTGGTCAAGGACTACTTCCCCGA ACCGGTGACGGTGTCGTGGAACTCAGGCGCCCTGACCAGCGGCGTGCACACCTTCCC GGCTGTCCTACAGTCCTCAGGACTCTACTCCCTCAGCAGCGTGGTGACCGTGCCCTC CAGCAGCTTGGGCACGAAGACCTACACCTGCAACGTAGATCACAAGCCCAGCAACAC CAAGGTGGACAAGAGAGTTGAGTCCAAATATGGTCCCCCATGCCCACCGTGCCCAGC ACCACCTGTGGCAGGACCATCAGTCTTCCTGTTCCCCCCAAAACCCAAGGACACTCTC ATGATCTCCCGGACCCCTGAGGTCACGTGCGTGGTGGTGGACGTGAGCCAGGAAGAC CCCGAGGTCCAGTTCAACTGGTACGTGGATGGCGTGGAGGTGCATAATGCCAAGACA AAGCCGCGGGAGGAGCAGTTCAACAGCACGTACCGTGTGGTCAGCGTCCTCACCGTC CTGCACCAGGACTGGCTGAACGGCAAGGAGTACAAGTGCAAGGTCTCCAACAAAGGC CTCCCGTCCTCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGAGAGCCA CAGGTGTACACCCTGCCCCCATCCCAGGAGGAGATGACCAAGAACCAGGTCAGCCTG ACCTGCCTGGTCAAAGGCTTCTACCCCAGCGACATCGCCGTGGAGTGGGAGAGCAAT GGGCAGCCGGAGAACAACTACAAGACCACGCCTCCCGTGCTGGACTCCGACGGCTCC TTCTTCCTCTACAGCAGGCTCACCGTGGACAAGAGCAGGTGGCAGGAGGGGAATGTC TTCTCATGCTCCGTGATGCATGAGGCTCTGCACAACCACTACACACAGAAGTCCCTCT CCCTGTCTCTGGGTAAATGA (SEQ ID NO: 184) HC Amino Acid Sequence EVQLVESGGGLVQPGGSLRLSCAASGFTFSSYAMSWVRQAPGKGLEWVSAISGSGDNTY YADSVKGRFTISRDNSKNTLYLQMNSLRVEDTAVYYCAKEKSSGWYEYWGQGTLVTVSS ASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSS GLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPPVAGPSVF LFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYR VVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKN QVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGN VFSCSVMHEALHNHYTQKSLSLSLGK* (SEQ ID NO: 185) LC DNA Sequence Attorney Docket No.250298.000780 GACATCGTGATGACCCAGTCTCCAGACTCCCTGGCTGTGTCTCTGGGCGAGAGGGCC ACCATCAACTGCAAGTCCAGCCAGAGTGTTTTATACAGTTCCAACAATAAGAATTACTT AGCTTGGTACCAGCAGAAACCAGGACAGACTCCTAAACTGCTCATTTACTGGGCATCT ACCCGGGAATCCGGGGTCCCTGACCGATTCAGTGGCAGCGGGTCTGGGACAGATTTC ACTCTCACCATCAGCAGCCTGCAGGCTGAAGATGTGGCAGTTTATTACTGTCAGCAAT ATTATTTTATTCCGTACACTTTTGGCCAGGGGACCAAGCTGGAGATCAAACGAACTGTG GCTGCACCATCTGTCTTCATCTTCCCGCCATCTGATGAGCAGTTGAAATCTGGAACTG CCTCTGTTGTGTGCCTGCTGAATAACTTCTATCCCAGAGAGGCCAAAGTACAGTGGAA GGTGGATAACGCCCTCCAATCGGGTAACTCCCAGGAGAGTGTCACAGAGCAGGACAG CAAGGACAGCACCTACAGCCTCAGCAGCACCCTGACGCTGAGCAAAGCAGACTACGA GAAACACAAAGTCTACGCCTGCGAAGTCACCCATCAGGGCCTGAGCTCGCCCGTCAC AAAGAGCTTCAACAGGGGAGAGTGTTAG (SEQ ID NO: 186) LC Amino Acid Sequence DIVMTQSPDSLAVSLGERATINCKSSQSVLYSSNNKNYLAWYQQKPGQTPKLLIYWASTRE SGVPDRFSGSGSGTDFTLTISSLQAEDVAVYYCQQYYFIPYTFGQGTKLEIKRTVAAPSVFI FPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLS STLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC* (SEQ ID NO: 187) REGN14158 HCVR DNA Sequence CAGGTGCAGCTGGTGGAGTCTGGGGGAGGCGTGGTCCAGCCTGGGAGGTCCCTGAG ACTCTCCTGTGCAGCCTCTGGATTCACCTTCAGTCACTATGGCATGCACTGGGTCCGC CAGGCTCCAGGCAAGGGGCTGGAGTGGATGGCAGTTATATCATATGATGGAAGTAAC AAATATTATGCAGACTCCGTGAAGGGCCGATTCACCATCTCCAGAGACAATTCCAGGA ACACGCTGTATCTGCAAATGAACAGCCTGAGAACTGAGGACACGGCTGTGTTTTATTG TGCGAAAGAGTCGAGTATAACAGCCCGTCCGAGAGACTACAACTACGGTATGGACGTC TGGGGCCAAGGGACCACGGTCACCGTCTCCTCA (SEQ ID NO: 188) HCVR Amino Acid Sequence Attorney Docket No.250298.000780 QVQLVESGGGVVQPGRSLRLSCAASGFTFSHYGMHWVRQAPGKGLEWMAVISYDGSNK YYADSVKGRFTISRDNSRNTLYLQMNSLRTEDTAVFYCAKESSITARPRDYNYGMDVWGQ GTTVTVSS (SEQ ID NO: 189) CDR1 DNA Sequence GGA TTC ACC TTC AGT CAC TAT GGC (SEQ ID NO: 190) CDR1 Amino Acid Sequence G F T F S H Y G (SEQ ID NO: 191) CDR2 DNA Sequence ATA TCA TAT GAT GGA AGT AAC AAA (SEQ ID NO: 192) CDR2 Amino Acid Sequence I S Y D G S N K (SEQ ID NO: 193) CDR3 DNA Sequence GCG AAA GAG TCG AGT ATA ACA GCC CGT CCG AGA GAC TAC AAC TAC GGT ATG GAC GTC (SEQ ID NO: 194) CDR3 Amino Acid Sequence A K E S S I T A R P R D Y N Y G M D V (SEQ ID NO: 195) LCVR DNA Sequence GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACAGAGTCA CCATCACTTGCCGGGCAAGTCAGAGCATTAGCGGCTATTTAAATTGGTTTCAGCAGAA Attorney Docket No.250298.000780 ACCAGGGAAAGCCCCTAAACTCCTAATCTATGCTGCATCCACTTTGCAAACTGGGGTC CCATCAAGGTTCAGCGGCAGTGGATCTGGGACAGATTTCACTCTCATCATCAGCAGTC TGCAGCCTGACGATTTTGCAACTTACCACTGTCAACAGAGTTACACTTCCCCTTTCACT TTCGGCCCTGGGACCAAAGTGGATATCAAA (SEQ ID NO: 196) LCVR Amino Acid Sequence DIQMTQSPSSLSASVGDRVTITCRASQSISGYLNWFQQKPGKAPKLLIYAASTLQTGVPSR FSGSGSGTDFTLIISSLQPDDFATYHCQQSYTSPFTFGPGTKVDIK (SEQ ID NO: 197) CDR1 DNA Sequence CAG AGC ATT AGC GGC TAT (SEQ ID NO: 198) CDR1 Amino Acid Sequence Q S I S G Y (SEQ ID NO: 199) CDR2 DNA Sequence GCT GCA TCC (SEQ ID NO: 13) CDR2 Amino Acid Sequence A A S (SEQ ID NO: 14) CDR3 DNA Sequence CAA CAG AGT TAC ACT TCC CCT TTC ACT (SEQ ID NO: 200) CDR3 Amino Acid Sequence Q Q S Y T S P F T Attorney Docket No.250298.000780 (SEQ ID NO: 201) HC DNA Sequence CAGGTGCAGCTGGTGGAGTCTGGGGGAGGCGTGGTCCAGCCTGGGAGGTCCCTGAG ACTCTCCTGTGCAGCCTCTGGATTCACCTTCAGTCACTATGGCATGCACTGGGTCCGC CAGGCTCCAGGCAAGGGGCTGGAGTGGATGGCAGTTATATCATATGATGGAAGTAAC AAATATTATGCAGACTCCGTGAAGGGCCGATTCACCATCTCCAGAGACAATTCCAGGA ACACGCTGTATCTGCAAATGAACAGCCTGAGAACTGAGGACACGGCTGTGTTTTATTG TGCGAAAGAGTCGAGTATAACAGCCCGTCCGAGAGACTACAACTACGGTATGGACGTC TGGGGCCAAGGGACCACGGTCACCGTCTCCTCAGCCTCCACCAAGGGCCCATCGGTC TTCCCCCTGGCGCCCTGCTCCAGGAGCACCTCCGAGAGCACAGCCGCCCTGGGCTG CCTGGTCAAGGACTACTTCCCCGAACCGGTGACGGTGTCGTGGAACTCAGGCGCCCT GACCAGCGGCGTGCACACCTTCCCGGCTGTCCTACAGTCCTCAGGACTCTACTCCCT CAGCAGCGTGGTGACCGTGCCCTCCAGCAGCTTGGGCACGAAGACCTACACCTGCAA CGTAGATCACAAGCCCAGCAACACCAAGGTGGACAAGAGAGTTGAGTCCAAATATGGT CCCCCATGCCCACCGTGCCCAGCACCACCTGTGGCAGGACCATCAGTCTTCCTGTTC CCCCCAAAACCCAAGGACACTCTCATGATCTCCCGGACCCCTGAGGTCACGTGCGTG GTGGTGGACGTGAGCCAGGAAGACCCCGAGGTCCAGTTCAACTGGTACGTGGATGGC GTGGAGGTGCATAATGCCAAGACAAAGCCGCGGGAGGAGCAGTTCAACAGCACGTAC CGTGTGGTCAGCGTCCTCACCGTCCTGCACCAGGACTGGCTGAACGGCAAGGAGTAC AAGTGCAAGGTCTCCAACAAAGGCCTCCCGTCCTCCATCGAGAAAACCATCTCCAAAG CCAAAGGGCAGCCCCGAGAGCCACAGGTGTACACCCTGCCCCCATCCCAGGAGGAG ATGACCAAGAACCAGGTCAGCCTGACCTGCCTGGTCAAAGGCTTCTACCCCAGCGAC ATCGCCGTGGAGTGGGAGAGCAATGGGCAGCCGGAGAACAACTACAAGACCACGCCT CCCGTGCTGGACTCCGACGGCTCCTTCTTCCTCTACAGCAGGCTCACCGTGGACAAG AGCAGGTGGCAGGAGGGGAATGTCTTCTCATGCTCCGTGATGCATGAGGCTCTGCAC AACCACTACACACAGAAGTCCCTCTCCCTGTCTCTGGGTAAATGA (SEQ ID NO: 202) HC Amino Acid Sequence QVQLVESGGGVVQPGRSLRLSCAASGFTFSHYGMHWVRQAPGKGLEWMAVISYDGSNK YYADSVKGRFTISRDNSRNTLYLQMNSLRTEDTAVFYCAKESSITARPRDYNYGMDVWGQ GTTVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHT Attorney Docket No.250298.000780 FPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAP PVAGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPRE EQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPS QEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDK SRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGK* (SEQ ID NO: 203) LC DNA Sequence GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACAGAGTCA CCATCACTTGCCGGGCAAGTCAGAGCATTAGCGGCTATTTAAATTGGTTTCAGCAGAA ACCAGGGAAAGCCCCTAAACTCCTAATCTATGCTGCATCCACTTTGCAAACTGGGGTC CCATCAAGGTTCAGCGGCAGTGGATCTGGGACAGATTTCACTCTCATCATCAGCAGTC TGCAGCCTGACGATTTTGCAACTTACCACTGTCAACAGAGTTACACTTCCCCTTTCACT TTCGGCCCTGGGACCAAAGTGGATATCAAACGAACTGTGGCTGCACCATCTGTCTTCA TCTTCCCGCCATCTGATGAGCAGTTGAAATCTGGAACTGCCTCTGTTGTGTGCCTGCT GAATAACTTCTATCCCAGAGAGGCCAAAGTACAGTGGAAGGTGGATAACGCCCTCCAA TCGGGTAACTCCCAGGAGAGTGTCACAGAGCAGGACAGCAAGGACAGCACCTACAGC CTCAGCAGCACCCTGACGCTGAGCAAAGCAGACTACGAGAAACACAAAGTCTACGCCT GCGAAGTCACCCATCAGGGCCTGAGCTCGCCCGTCACAAAGAGCTTCAACAGGGGAG AGTGTTAG (SEQ ID NO: 204) LC Amino Acid Sequence DIQMTQSPSSLSASVGDRVTITCRASQSISGYLNWFQQKPGKAPKLLIYAASTLQTGVPSR FSGSGSGTDFTLIISSLQPDDFATYHCQQSYTSPFTFGPGTKVDIKRTVAAPSVFIFPPSDE QLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSK ADYEKHKVYACEVTHQGLSSPVTKSFNRGEC* (SEQ ID NO: 205) REGN14159 HCVR DNA Sequence GAGGTGCAGCTGGTGGAGTCTGGGGGAGGCTTGGCACAGCGGGGGGGGTCCCTGA GACTCTCCTGTGCAGCCTCTGGATTCACCTTTAGCGACTATGCCGTGAGCTGGGTCCG Attorney Docket No.250298.000780 CCAGGCTCCAGGGAAGGGGCTGGAGTGGGTCTCAGGTATTAGCCGTGGTGGTGATTA CACGTACTACGCAGACTCCGTGAAGGGCCGGTTCATCATCTCCAGAGACAATTCCAAG AATATGTTGTATCTGCAAATGAACAGCCTGAGAGCCGAGGACACGGCCGTATATTATT GTGCGAAAAACTGGGGATCACTTGACTACTGGGGCCAGGGAACCCTGGTCACCGTCT CCTCA (SEQ ID NO: 206) HCVR Amino Acid Sequence EVQLVESGGGLAQRGGSLRLSCAASGFTFSDYAVSWVRQAPGKGLEWVSGISRGGDYTY YADSVKGRFIISRDNSKNMLYLQMNSLRAEDTAVYYCAKNWGSLDYWGQGTLVTVSS (SEQ ID NO: 207) CDR1 DNA Sequence GGA TTC ACC TTT AGC GAC TAT GCC (SEQ ID NO: 208) CDR1 Amino Acid Sequence G F T F S D Y A (SEQ ID NO: 209) CDR2 DNA Sequence ATT AGC CGT GGT GGT GAT TAC ACG (SEQ ID NO: 210) CDR2 Amino Acid Sequence I S R G G D Y T (SEQ ID NO: 211) CDR3 DNA Sequence GCG AAA AAC TGG GGA TCA CTT GAC TAC (SEQ ID NO: 212) CDR3 Amino Acid Sequence Attorney Docket No.250298.000780 A K N W G S L D Y (SEQ ID NO: 213) LCVR DNA Sequence GAAATTGTGTTGACACAGTCTCCAGCCACCCTGTCTTTGTCTCCAGGGGAAAGAGCCA CCCTCTCCTGCAGGGCCAGTCAGAGTGTTAGCAGCTACTTAGCCTGGTACCAACAGAA ACCTGGCCAGGCTCCCAGACTCCTCATCTATGATGCATCCAACAGGGTCACTGGCATC CCAGCCAGGTTCAGTGGCAGTGGGTCTGGGACAGACTTCACTCTCACCATCAGCAGC CTAGAGCCTGAAGATTTTGCAGTTTATTACTGTCAGCAGCGTAGCAACTGGCCTCGAA CTTTTGGCCAGGGGACCAAGCTGGAGATCAAA (SEQ ID NO: 214) LCVR Amino Acid Sequence EIVLTQSPATLSLSPGERATLSCRASQSVSSYLAWYQQKPGQAPRLLIYDASNRVTGIPAR FSGSGSGTDFTLTISSLEPEDFAVYYCQQRSNWPRTFGQGTKLEIK (SEQ ID NO: 215) CDR1 DNA Sequence CAG AGT GTT AGC AGC TAC (SEQ ID NO: 216) CDR1 Amino Acid Sequence Q S V S S Y (SEQ ID NO: 217) CDR2 DNA Sequence GAT GCA TCC (SEQ ID NO: 218) CDR2 Amino Acid Sequence D A S (SEQ ID NO: 219) Attorney Docket No.250298.000780 CDR3 DNA Sequence CAG CAG CGT AGC AAC TGG CCT CGA ACT (SEQ ID NO: 220) CDR3 Amino Acid Sequence Q Q R S N W P R T (SEQ ID NO: 221) HC DNA Sequence GAGGTGCAGCTGGTGGAGTCTGGGGGAGGCTTGGCACAGCGGGGGGGGTCCCTGA GACTCTCCTGTGCAGCCTCTGGATTCACCTTTAGCGACTATGCCGTGAGCTGGGTCCG CCAGGCTCCAGGGAAGGGGCTGGAGTGGGTCTCAGGTATTAGCCGTGGTGGTGATTA CACGTACTACGCAGACTCCGTGAAGGGCCGGTTCATCATCTCCAGAGACAATTCCAAG AATATGTTGTATCTGCAAATGAACAGCCTGAGAGCCGAGGACACGGCCGTATATTATT GTGCGAAAAACTGGGGATCACTTGACTACTGGGGCCAGGGAACCCTGGTCACCGTCT CCTCAGCCTCCACCAAGGGCCCATCGGTCTTCCCCCTGGCGCCCTGCTCCAGGAGCA CCTCCGAGAGCACAGCCGCCCTGGGCTGCCTGGTCAAGGACTACTTCCCCGAACCGG TGACGGTGTCGTGGAACTCAGGCGCCCTGACCAGCGGCGTGCACACCTTCCCGGCTG TCCTACAGTCCTCAGGACTCTACTCCCTCAGCAGCGTGGTGACCGTGCCCTCCAGCA GCTTGGGCACGAAGACCTACACCTGCAACGTAGATCACAAGCCCAGCAACACCAAGG TGGACAAGAGAGTTGAGTCCAAATATGGTCCCCCATGCCCACCGTGCCCAGCACCAC CTGTGGCAGGACCATCAGTCTTCCTGTTCCCCCCAAAACCCAAGGACACTCTCATGAT CTCCCGGACCCCTGAGGTCACGTGCGTGGTGGTGGACGTGAGCCAGGAAGACCCCG AGGTCCAGTTCAACTGGTACGTGGATGGCGTGGAGGTGCATAATGCCAAGACAAAGC CGCGGGAGGAGCAGTTCAACAGCACGTACCGTGTGGTCAGCGTCCTCACCGTCCTGC ACCAGGACTGGCTGAACGGCAAGGAGTACAAGTGCAAGGTCTCCAACAAAGGCCTCC CGTCCTCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGAGAGCCACAGG TGTACACCCTGCCCCCATCCCAGGAGGAGATGACCAAGAACCAGGTCAGCCTGACCT GCCTGGTCAAAGGCTTCTACCCCAGCGACATCGCCGTGGAGTGGGAGAGCAATGGGC AGCCGGAGAACAACTACAAGACCACGCCTCCCGTGCTGGACTCCGACGGCTCCTTCT TCCTCTACAGCAGGCTCACCGTGGACAAGAGCAGGTGGCAGGAGGGGAATGTCTTCT CATGCTCCGTGATGCATGAGGCTCTGCACAACCACTACACACAGAAGTCCCTCTCCCT GTCTCTGGGTAAATGA Attorney Docket No.250298.000780 (SEQ ID NO: 222) HC Amino Acid Sequence EVQLVESGGGLAQRGGSLRLSCAASGFTFSDYAVSWVRQAPGKGLEWVSGISRGGDYTY YADSVKGRFIISRDNSKNMLYLQMNSLRAEDTAVYYCAKNWGSLDYWGQGTLVTVSSAST KGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLY SLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPPVAGPSVFLFP PKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVS VLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVS LTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFS CSVMHEALHNHYTQKSLSLSLGK* (SEQ ID NO: 223) LC DNA Sequence GAAATTGTGTTGACACAGTCTCCAGCCACCCTGTCTTTGTCTCCAGGGGAAAGAGCCA CCCTCTCCTGCAGGGCCAGTCAGAGTGTTAGCAGCTACTTAGCCTGGTACCAACAGAA ACCTGGCCAGGCTCCCAGACTCCTCATCTATGATGCATCCAACAGGGTCACTGGCATC CCAGCCAGGTTCAGTGGCAGTGGGTCTGGGACAGACTTCACTCTCACCATCAGCAGC CTAGAGCCTGAAGATTTTGCAGTTTATTACTGTCAGCAGCGTAGCAACTGGCCTCGAA CTTTTGGCCAGGGGACCAAGCTGGAGATCAAACGAACTGTGGCTGCACCATCTGTCTT CATCTTCCCGCCATCTGATGAGCAGTTGAAATCTGGAACTGCCTCTGTTGTGTGCCTG CTGAATAACTTCTATCCCAGAGAGGCCAAAGTACAGTGGAAGGTGGATAACGCCCTCC AATCGGGTAACTCCCAGGAGAGTGTCACAGAGCAGGACAGCAAGGACAGCACCTACA GCCTCAGCAGCACCCTGACGCTGAGCAAAGCAGACTACGAGAAACACAAAGTCTACG CCTGCGAAGTCACCCATCAGGGCCTGAGCTCGCCCGTCACAAAGAGCTTCAACAGGG GAGAGTGTTAG (SEQ ID NO: 224) LC Amino Acid Sequence EIVLTQSPATLSLSPGERATLSCRASQSVSSYLAWYQQKPGQAPRLLIYDASNRVTGIPAR FSGSGSGTDFTLTISSLEPEDFAVYYCQQRSNWPRTFGQGTKLEIKRTVAAPSVFIFPPSD EQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLS KADYEKHKVYACEVTHQGLSSPVTKSFNRGEC* Attorney Docket No.250298.000780 (SEQ ID NO: 225) REGN14160 HCVR DNA Sequence CAGGTGCAGCTGGTGGAGTCTGGGGGAGGCGTGGTCCAGCCTGGGAGGTCCCTGAG ACTCTCCTGTGCAGCCTCTGGATTCACCTTCAGTTACTATGTCATGCACTGGGTCCGC CAGGCTCCAGGCAAGGGGCTGGAATGGGTGACAGTTATATCATATGATGGAACTAAGA AACACTATGCAGACTCCGTGAAGGGCCGATTCACCATCTCCAGAGACAATTCCAAGAA CACCTTGTATCTGCAAATGAACAGCCTGAGAGCTGACGACACGGCTGTGTATTACTGT GCGAAAACGCATAGTACGTCATCCAGGGCCGACTACTTCTACGGTATGGACGTCTGG GGCCAAGGGACCACGGTCACCGTCTCCTCA (SEQ ID NO: 226) HCVR Amino Acid Sequence QVQLVESGGGVVQPGRSLRLSCAASGFTFSYYVMHWVRQAPGKGLEWVTVISYDGTKKH YADSVKGRFTISRDNSKNTLYLQMNSLRADDTAVYYCAKTHSTSSRADYFYGMDVWGQG TTVTVSS (SEQ ID NO: 227) CDR1 DNA Sequence GGA TTC ACC TTC AGT TAC TAT GTC (SEQ ID NO: 228) CDR1 Amino Acid Sequence G F T F S Y Y V (SEQ ID NO: 229) CDR2 DNA Sequence ATA TCA TAT GAT GGA ACT AAG AAA (SEQ ID NO: 230) CDR2 Amino Acid Sequence I S Y D G T K K Attorney Docket No.250298.000780 (SEQ ID NO: 231) CDR3 DNA Sequence GCG AAA ACG CAT AGT ACG TCA TCC AGG GCC GAC TAC TTC TAC GGT ATG GAC GTC (SEQ ID NO: 232) CDR3 Amino Acid Sequence A K T H S T S S R A D Y F Y G M D V (SEQ ID NO: 233) LCVR DNA Sequence GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACAGAGTCA CCATCACTTGCCGGGCAAGTCAGAGCATTAGCAGCTATTTAAATTGGTATCAGCAGAA ACCAGGGAAAGCCCCTCAGTTCCTGATCTATGCTGCATCCAGTTTGCAAAGTGGGGTC CCATCAAGGTTCAGTGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGTC TGCAACCTGAAGATTTTGCAACTTACTACTGTCAACAGAGTTACAGTACCCTCCTCACT TTCGGCGGAGGGACCAAGGTGGAGATCAAA (SEQ ID NO: 234) LCVR Amino Acid Sequence DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPQFLIYAASSLQSGVPSR FSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTLLTFGGGTKVEIK (SEQ ID NO: 235) CDR1 DNA Sequence CAG AGC ATT AGC AGC TAT (SEQ ID NO: 236) CDR1 Amino Acid Sequence Q S I S S Y (SEQ ID NO: 237) Attorney Docket No.250298.000780 CDR2 DNA Sequence GCT GCA TCC (SEQ ID NO: 13) CDR2 Amino Acid Sequence A A S (SEQ ID NO: 14) CDR3 DNA Sequence CAA CAG AGT TAC AGT ACC CTC CTC ACT (SEQ ID NO: 238) CDR3 Amino Acid Sequence Q Q S Y S T L L T (SEQ ID NO: 239) HC DNA Sequence CAGGTGCAGCTGGTGGAGTCTGGGGGAGGCGTGGTCCAGCCTGGGAGGTCCCTGAG ACTCTCCTGTGCAGCCTCTGGATTCACCTTCAGTTACTATGTCATGCACTGGGTCCGC CAGGCTCCAGGCAAGGGGCTGGAATGGGTGACAGTTATATCATATGATGGAACTAAGA AACACTATGCAGACTCCGTGAAGGGCCGATTCACCATCTCCAGAGACAATTCCAAGAA CACCTTGTATCTGCAAATGAACAGCCTGAGAGCTGACGACACGGCTGTGTATTACTGT GCGAAAACGCATAGTACGTCATCCAGGGCCGACTACTTCTACGGTATGGACGTCTGG GGCCAAGGGACCACGGTCACCGTCTCCTCAGCCTCCACCAAGGGCCCATCGGTCTTC CCCCTGGCGCCCTGCTCCAGGAGCACCTCCGAGAGCACAGCCGCCCTGGGCTGCCT GGTCAAGGACTACTTCCCCGAACCGGTGACGGTGTCGTGGAACTCAGGCGCCCTGAC CAGCGGCGTGCACACCTTCCCGGCTGTCCTACAGTCCTCAGGACTCTACTCCCTCAG CAGCGTGGTGACCGTGCCCTCCAGCAGCTTGGGCACGAAGACCTACACCTGCAACGT AGATCACAAGCCCAGCAACACCAAGGTGGACAAGAGAGTTGAGTCCAAATATGGTCCC CCATGCCCACCGTGCCCAGCACCACCTGTGGCAGGACCATCAGTCTTCCTGTTCCCC CCAAAACCCAAGGACACTCTCATGATCTCCCGGACCCCTGAGGTCACGTGCGTGGTG GTGGACGTGAGCCAGGAAGACCCCGAGGTCCAGTTCAACTGGTACGTGGATGGCGTG GAGGTGCATAATGCCAAGACAAAGCCGCGGGAGGAGCAGTTCAACAGCACGTACCGT Attorney Docket No.250298.000780 GTGGTCAGCGTCCTCACCGTCCTGCACCAGGACTGGCTGAACGGCAAGGAGTACAAG TGCAAGGTCTCCAACAAAGGCCTCCCGTCCTCCATCGAGAAAACCATCTCCAAAGCCA AAGGGCAGCCCCGAGAGCCACAGGTGTACACCCTGCCCCCATCCCAGGAGGAGATG ACCAAGAACCAGGTCAGCCTGACCTGCCTGGTCAAAGGCTTCTACCCCAGCGACATC GCCGTGGAGTGGGAGAGCAATGGGCAGCCGGAGAACAACTACAAGACCACGCCTCC CGTGCTGGACTCCGACGGCTCCTTCTTCCTCTACAGCAGGCTCACCGTGGACAAGAG CAGGTGGCAGGAGGGGAATGTCTTCTCATGCTCCGTGATGCATGAGGCTCTGCACAA CCACTACACACAGAAGTCCCTCTCCCTGTCTCTGGGTAAATGA (SEQ ID NO: 240) HC Amino Acid Sequence QVQLVESGGGVVQPGRSLRLSCAASGFTFSYYVMHWVRQAPGKGLEWVTVISYDGTKKH YADSVKGRFTISRDNSKNTLYLQMNSLRADDTAVYYCAKTHSTSSRADYFYGMDVWGQG TTVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFP AVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPPV AGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQ FNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQE EMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSR WQEGNVFSCSVMHEALHNHYTQKSLSLSLGK* (SEQ ID NO: 241) LC DNA Sequence GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACAGAGTCA CCATCACTTGCCGGGCAAGTCAGAGCATTAGCAGCTATTTAAATTGGTATCAGCAGAA ACCAGGGAAAGCCCCTCAGTTCCTGATCTATGCTGCATCCAGTTTGCAAAGTGGGGTC CCATCAAGGTTCAGTGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGTC TGCAACCTGAAGATTTTGCAACTTACTACTGTCAACAGAGTTACAGTACCCTCCTCACT TTCGGCGGAGGGACCAAGGTGGAGATCAAACGAACTGTGGCTGCACCATCTGTCTTC ATCTTCCCGCCATCTGATGAGCAGTTGAAATCTGGAACTGCCTCTGTTGTGTGCCTGC TGAATAACTTCTATCCCAGAGAGGCCAAAGTACAGTGGAAGGTGGATAACGCCCTCCA ATCGGGTAACTCCCAGGAGAGTGTCACAGAGCAGGACAGCAAGGACAGCACCTACAG CCTCAGCAGCACCCTGACGCTGAGCAAAGCAGACTACGAGAAACACAAAGTCTACGC Attorney Docket No.250298.000780 CTGCGAAGTCACCCATCAGGGCCTGAGCTCGCCCGTCACAAAGAGCTTCAACAGGGG AGAGTGTTAG (SEQ ID NO: 242) LC Amino Acid Sequence DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPQFLIYAASSLQSGVPSR FSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTLLTFGGGTKVEIKRTVAAPSVFIFPPSDE QLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSK ADYEKHKVYACEVTHQGLSSPVTKSFNRGEC* (SEQ ID NO: 243) REGN14161 HCVR DNA Sequence GAGGTGCAGCTGGTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGAG ACTCTCCTGTGCAGCCTCTGGATTCACCTTTAGCAGCTATGCCATGACCTGGGTCCGC CAGGCTCCAGGGAAGGGGCTGGAGTGGGTCTCAACTATTAATACTAATGGTGGTAGC ACATTCTTCGCAGACTCCGTGAAGGGCCGTTTCACCATCTCCAGAGACAATTCCAAGA ACACGCTGTATCTGCAAATGAACAGCCTGAGAGCCGAGGACACGGCCATATATTACTG TGCGAAAGAAAAACGGGGCGGTATGGACGTCTGGGGCCAAGGGACCACGGTCACCG TCTCCTCA (SEQ ID NO: 244) HCVR Amino Acid Sequence EVQLVESGGGLVQPGGSLRLSCAASGFTFSSYAMTWVRQAPGKGLEWVSTINTNGGSTF FADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAIYYCAKEKRGGMDVWGQGTTVTVSS (SEQ ID NO: 245) CDR1 DNA Sequence GGA TTC ACC TTT AGC AGC TAT GCC (SEQ ID NO: 156) CDR1 Amino Acid Sequence G F T F S S Y A Attorney Docket No.250298.000780 (SEQ ID NO: 100) CDR2 DNA Sequence ATT AAT ACT AAT GGT GGT AGC ACA (SEQ ID NO: 246) CDR2 Amino Acid Sequence I N T N G G S T (SEQ ID NO: 247) CDR3 DNA Sequence GCG AAA GAA AAA CGG GGC GGT ATG GAC GTC (SEQ ID NO: 248) CDR3 Amino Acid Sequence A K E K R G G M D V (SEQ ID NO: 249) LCVR DNA Sequence GACATCGTGATGACCCAGTCTCCAGACTCCCTGGCTGTGTCTCTGGGCGAGAGGGCC ACCATCAACTGCAAGTCCAGCCAGAGTGTTTTATATGGCTCCAACAAAAAGAACTACTT AGCTTGGTACCAACAGAAACCAGGACAGCCTCCTAAGCTGCTCATTTACTGGGCATCT ACCCGGGAATCCGGGGTCCCTGACCGATTCAGTGGCAGCGGGTCTGGGACAGATTTC ACTCTCACCATCAGTAGCCTGCAGGCTGAAGATGTGGCAGTTTATTACTGTCAGCAATA TTATAGTACTCTCACGTGGACGTTCGGCCAAGGGACCAAGGTGGAAATCAAA (SEQ ID NO: 250) LCVR Amino Acid Sequence DIVMTQSPDSLAVSLGERATINCKSSQSVLYGSNKKNYLAWYQQKPGQPPKLLIYWASTR ESGVPDRFSGSGSGTDFTLTISSLQAEDVAVYYCQQYYSTLTWTFGQGTKVEIK (SEQ ID NO: 251) CDR1 DNA Sequence Attorney Docket No.250298.000780 CAG AGT GTT TTA TAT GGC TCC AAC AAA AAG AAC TAC (SEQ ID NO: 252) CDR1 Amino Acid Sequence Q S V L Y G S N K K N Y (SEQ ID NO: 253) CDR2 DNA Sequence TGG GCA TCT (SEQ ID NO: 69) CDR2 Amino Acid Sequence W A S (SEQ ID NO: 70) CDR3 DNA Sequence CAG CAA TAT TAT AGT ACT CTC ACG TGG ACG (SEQ ID NO: 254) CDR3 Amino Acid Sequence Q Q Y Y S T L T W T (SEQ ID NO: 255) HC DNA Sequence GAGGTGCAGCTGGTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGAG ACTCTCCTGTGCAGCCTCTGGATTCACCTTTAGCAGCTATGCCATGACCTGGGTCCGC CAGGCTCCAGGGAAGGGGCTGGAGTGGGTCTCAACTATTAATACTAATGGTGGTAGC ACATTCTTCGCAGACTCCGTGAAGGGCCGTTTCACCATCTCCAGAGACAATTCCAAGA ACACGCTGTATCTGCAAATGAACAGCCTGAGAGCCGAGGACACGGCCATATATTACTG TGCGAAAGAAAAACGGGGCGGTATGGACGTCTGGGGCCAAGGGACCACGGTCACCG TCTCCTCAGCCTCCACCAAGGGCCCATCGGTCTTCCCCCTGGCGCCCTGCTCCAGGA GCACCTCCGAGAGCACAGCCGCCCTGGGCTGCCTGGTCAAGGACTACTTCCCCGAAC CGGTGACGGTGTCGTGGAACTCAGGCGCCCTGACCAGCGGCGTGCACACCTTCCCG Attorney Docket No.250298.000780 GCTGTCCTACAGTCCTCAGGACTCTACTCCCTCAGCAGCGTGGTGACCGTGCCCTCCA GCAGCTTGGGCACGAAGACCTACACCTGCAACGTAGATCACAAGCCCAGCAACACCA AGGTGGACAAGAGAGTTGAGTCCAAATATGGTCCCCCATGCCCACCGTGCCCAGCAC CACCTGTGGCAGGACCATCAGTCTTCCTGTTCCCCCCAAAACCCAAGGACACTCTCAT GATCTCCCGGACCCCTGAGGTCACGTGCGTGGTGGTGGACGTGAGCCAGGAAGACC CCGAGGTCCAGTTCAACTGGTACGTGGATGGCGTGGAGGTGCATAATGCCAAGACAA AGCCGCGGGAGGAGCAGTTCAACAGCACGTACCGTGTGGTCAGCGTCCTCACCGTCC TGCACCAGGACTGGCTGAACGGCAAGGAGTACAAGTGCAAGGTCTCCAACAAAGGCC TCCCGTCCTCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGAGAGCCAC AGGTGTACACCCTGCCCCCATCCCAGGAGGAGATGACCAAGAACCAGGTCAGCCTGA CCTGCCTGGTCAAAGGCTTCTACCCCAGCGACATCGCCGTGGAGTGGGAGAGCAATG GGCAGCCGGAGAACAACTACAAGACCACGCCTCCCGTGCTGGACTCCGACGGCTCCT TCTTCCTCTACAGCAGGCTCACCGTGGACAAGAGCAGGTGGCAGGAGGGGAATGTCT TCTCATGCTCCGTGATGCATGAGGCTCTGCACAACCACTACACACAGAAGTCCCTCTC CCTGTCTCTGGGTAAATGA (SEQ ID NO: 256) HC Amino Acid Sequence EVQLVESGGGLVQPGGSLRLSCAASGFTFSSYAMTWVRQAPGKGLEWVSTINTNGGSTF FADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAIYYCAKEKRGGMDVWGQGTTVTVSSAS TKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGL YSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPPVAGPSVFLF PPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVV SVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQV SLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVF SCSVMHEALHNHYTQKSLSLSLGK* (SEQ ID NO: 257) LC DNA Sequence GACATCGTGATGACCCAGTCTCCAGACTCCCTGGCTGTGTCTCTGGGCGAGAGGGCC ACCATCAACTGCAAGTCCAGCCAGAGTGTTTTATATGGCTCCAACAAAAAGAACTACTT AGCTTGGTACCAACAGAAACCAGGACAGCCTCCTAAGCTGCTCATTTACTGGGCATCT ACCCGGGAATCCGGGGTCCCTGACCGATTCAGTGGCAGCGGGTCTGGGACAGATTTC Attorney Docket No.250298.000780 ACTCTCACCATCAGTAGCCTGCAGGCTGAAGATGTGGCAGTTTATTACTGTCAGCAATA TTATAGTACTCTCACGTGGACGTTCGGCCAAGGGACCAAGGTGGAAATCAAACGAACT GTGGCTGCACCATCTGTCTTCATCTTCCCGCCATCTGATGAGCAGTTGAAATCTGGAA CTGCCTCTGTTGTGTGCCTGCTGAATAACTTCTATCCCAGAGAGGCCAAAGTACAGTG GAAGGTGGATAACGCCCTCCAATCGGGTAACTCCCAGGAGAGTGTCACAGAGCAGGA CAGCAAGGACAGCACCTACAGCCTCAGCAGCACCCTGACGCTGAGCAAAGCAGACTA CGAGAAACACAAAGTCTACGCCTGCGAAGTCACCCATCAGGGCCTGAGCTCGCCCGT CACAAAGAGCTTCAACAGGGGAGAGTGTTAG (SEQ ID NO: 258) LC Amino Acid Sequence DIVMTQSPDSLAVSLGERATINCKSSQSVLYGSNKKNYLAWYQQKPGQPPKLLIYWASTR ESGVPDRFSGSGSGTDFTLTISSLQAEDVAVYYCQQYYSTLTWTFGQGTKVEIKRTVAAPS VFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYS LSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC* (SEQ ID NO: 259) REGN14162 HCVR DNA Sequence CAGGTGCAGCTGCAGGAGTCGGGCCCAGGACTGGTGAAGCCTTCGGAGACCCTGTC CCTCACCTGCACTGTTTCTGGTGACTCCATCAGTACTTACTACTGGAGCTGGATCCGG CAGCCCCCAGGAAAGGGACTGGAGTGGATTGGGTTTTTCCATTACAGTGGGAGCAGC AAATACAAGCCCTCCCTCAAGAGTCGAGTCACCATATCACTAGACACGTCCAAGAATC AGTTCTCCCTGAACCTGCGGTCTGTGACCGCTGCGGACACGGCCGTGTATTATTGTGC GAGATTAGGCTGGGGATTTGACTACTGGGGCCAGGGAACCCTGGTCACCGTCTCCTC A (SEQ ID NO: 260) HCVR Amino Acid Sequence QVQLQESGPGLVKPSETLSLTCTVSGDSISTYYWSWIRQPPGKGLEWIGFFHYSGSSKYK PSLKSRVTISLDTSKNQFSLNLRSVTAADTAVYYCARLGWGFDYWGQGTLVTVSS (SEQ ID NO: 261) Attorney Docket No.250298.000780 CDR1 DNA Sequence GGT GAC TCC ATC AGT ACT TAC TAC (SEQ ID NO: 262) CDR1 Amino Acid Sequence G D S I S T Y Y (SEQ ID NO: 263) CDR2 DNA Sequence TTC CAT TAC AGT GGG AGC AGC (SEQ ID NO: 264) CDR2 Amino Acid Sequence F H Y S G S S (SEQ ID NO: 265) CDR3 DNA Sequence GCG AGA TTA GGC TGG GGA TTT GAC TAC (SEQ ID NO: 266) CDR3 Amino Acid Sequence A R L G W G F D Y (SEQ ID NO: 267) LCVR DNA Sequence GAAATTGTGTTGACGCAGTCTCCAGGCACCCTGTCTTTGTCTCCAGGGGAAAGAGCCA CCCTCTCCTGCAGGGCCAGTCAGAGTGTTAGCAGCAACTACTTAGCCTGGTACCAGCA GAAACCTGGCCAGGCTCCCAGGCTCCTCATCTATGGTGCATCCAGCAGGGCCACTGG CATCCCAGACAGGTTCAGTGGCAGTGGGTCTGGGACAGACTTCACTCTCACCATCAGC AGACTGGAGCCTGAAGATTTTGCAGTGTATTACTGTCAGCAGTATGGTAGCTCAGCATT CACTTTCGGCCCTGGGACCAAAGTGGATATCAAA (SEQ ID NO: 268) Attorney Docket No.250298.000780 LCVR Amino Acid Sequence EIVLTQSPGTLSLSPGERATLSCRASQSVSSNYLAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYCQQYGSSAFTFGPGTKVDIK (SEQ ID NO: 269) CDR1 DNA Sequence CAG AGT GTT AGC AGC AAC TAC (SEQ ID NO: 270) CDR1 Amino Acid Sequence Q S V S S N Y (SEQ ID NO: 271) CDR2 DNA Sequence GGT GCA TCC (SEQ ID NO: 165) CDR2 Amino Acid Sequence G A S (SEQ ID NO: 90) CDR3 DNA Sequence CAG CAG TAT GGT AGC TCA GCA TTC ACT (SEQ ID NO: 272) CDR3 Amino Acid Sequence Q Q Y G S S A F T (SEQ ID NO: 273) HC DNA Sequence CAGGTGCAGCTGCAGGAGTCGGGCCCAGGACTGGTGAAGCCTTCGGAGACCCTGTC CCTCACCTGCACTGTTTCTGGTGACTCCATCAGTACTTACTACTGGAGCTGGATCCGG CAGCCCCCAGGAAAGGGACTGGAGTGGATTGGGTTTTTCCATTACAGTGGGAGCAGC Attorney Docket No.250298.000780 AAATACAAGCCCTCCCTCAAGAGTCGAGTCACCATATCACTAGACACGTCCAAGAATC AGTTCTCCCTGAACCTGCGGTCTGTGACCGCTGCGGACACGGCCGTGTATTATTGTGC GAGATTAGGCTGGGGATTTGACTACTGGGGCCAGGGAACCCTGGTCACCGTCTCCTC AGCCTCCACCAAGGGCCCATCGGTCTTCCCCCTGGCGCCCTGCTCCAGGAGCACCTC CGAGAGCACAGCCGCCCTGGGCTGCCTGGTCAAGGACTACTTCCCCGAACCGGTGAC GGTGTCGTGGAACTCAGGCGCCCTGACCAGCGGCGTGCACACCTTCCCGGCTGTCCT ACAGTCCTCAGGACTCTACTCCCTCAGCAGCGTGGTGACCGTGCCCTCCAGCAGCTT GGGCACGAAGACCTACACCTGCAACGTAGATCACAAGCCCAGCAACACCAAGGTGGA CAAGAGAGTTGAGTCCAAATATGGTCCCCCATGCCCACCGTGCCCAGCACCACCTGT GGCAGGACCATCAGTCTTCCTGTTCCCCCCAAAACCCAAGGACACTCTCATGATCTCC CGGACCCCTGAGGTCACGTGCGTGGTGGTGGACGTGAGCCAGGAAGACCCCGAGGT CCAGTTCAACTGGTACGTGGATGGCGTGGAGGTGCATAATGCCAAGACAAAGCCGCG GGAGGAGCAGTTCAACAGCACGTACCGTGTGGTCAGCGTCCTCACCGTCCTGCACCA GGACTGGCTGAACGGCAAGGAGTACAAGTGCAAGGTCTCCAACAAAGGCCTCCCGTC CTCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGAGAGCCACAGGTGTA CACCCTGCCCCCATCCCAGGAGGAGATGACCAAGAACCAGGTCAGCCTGACCTGCCT GGTCAAAGGCTTCTACCCCAGCGACATCGCCGTGGAGTGGGAGAGCAATGGGCAGCC GGAGAACAACTACAAGACCACGCCTCCCGTGCTGGACTCCGACGGCTCCTTCTTCCTC TACAGCAGGCTCACCGTGGACAAGAGCAGGTGGCAGGAGGGGAATGTCTTCTCATGC TCCGTGATGCATGAGGCTCTGCACAACCACTACACACAGAAGTCCCTCTCCCTGTCTC TGGGTAAATGA (SEQ ID NO: 274) HC Amino Acid Sequence QVQLQESGPGLVKPSETLSLTCTVSGDSISTYYWSWIRQPPGKGLEWIGFFHYSGSSKYK PSLKSRVTISLDTSKNQFSLNLRSVTAADTAVYYCARLGWGFDYWGQGTLVTVSSASTKG PSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLS SVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPPVAGPSVFLFPPKP KDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLT VLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTC LVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSV MHEALHNHYTQKSLSLSLGK* (SEQ ID NO: 275) Attorney Docket No.250298.000780 LC DNA Sequence GAAATTGTGTTGACGCAGTCTCCAGGCACCCTGTCTTTGTCTCCAGGGGAAAGAGCCA CCCTCTCCTGCAGGGCCAGTCAGAGTGTTAGCAGCAACTACTTAGCCTGGTACCAGCA GAAACCTGGCCAGGCTCCCAGGCTCCTCATCTATGGTGCATCCAGCAGGGCCACTGG CATCCCAGACAGGTTCAGTGGCAGTGGGTCTGGGACAGACTTCACTCTCACCATCAGC AGACTGGAGCCTGAAGATTTTGCAGTGTATTACTGTCAGCAGTATGGTAGCTCAGCATT CACTTTCGGCCCTGGGACCAAAGTGGATATCAAACGAACTGTGGCTGCACCATCTGTC TTCATCTTCCCGCCATCTGATGAGCAGTTGAAATCTGGAACTGCCTCTGTTGTGTGCCT GCTGAATAACTTCTATCCCAGAGAGGCCAAAGTACAGTGGAAGGTGGATAACGCCCTC CAATCGGGTAACTCCCAGGAGAGTGTCACAGAGCAGGACAGCAAGGACAGCACCTAC AGCCTCAGCAGCACCCTGACGCTGAGCAAAGCAGACTACGAGAAACACAAAGTCTAC GCCTGCGAAGTCACCCATCAGGGCCTGAGCTCGCCCGTCACAAAGAGCTTCAACAGG GGAGAGTGTTAG (SEQ ID NO: 276) LC Amino Acid Sequence EIVLTQSPGTLSLSPGERATLSCRASQSVSSNYLAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYCQQYGSSAFTFGPGTKVDIKRTVAAPSVFIFPPSD EQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLS KADYEKHKVYACEVTHQGLSSPVTKSFNRGEC* (SEQ ID NO: 277) REGN14163 HCVR DNA Sequence GAGGTGCAGCTGGTGGAGTCTGGGGGAGGCTTGGTCCAGCCTGGGGGGTCCCTGAG ACTCTCCTGTGCAGCCTCTGGATTCACCTTTAGTAACTATTGGATGAACTGGGTCCGC CAGGCTCCAGGGAAGGGGCTGGAGTGGGTGGCCAACATAAAGCAAGATGGAAGTGA GAAGTACTATGTGGACTCTGTGAAGGGCCGATTCACCATCTCCAGAGACAACGCCAAG AACTCACTGTATCTGCAAATGAACAGCCTGAGAGCCGAGGACACGGCTGTGTATTACT GTGCGAGACGTGGATACACCTATGGCAGCTTTGACTACTGGGGCCAGGGAACCCTGG TCACCGTCTCCTCA (SEQ ID NO: 278) Attorney Docket No.250298.000780 HCVR Amino Acid Sequence EVQLVESGGGLVQPGGSLRLSCAASGFTFSNYWMNWVRQAPGKGLEWVANIKQDGSEK YYVDSVKGRFTISRDNAKNSLYLQMNSLRAEDTAVYYCARRGYTYGSFDYWGQGTLVTV SS (SEQ ID NO: 279) CDR1 DNA Sequence GGA TTC ACC TTT AGT AAC TAT TGG (SEQ ID NO: 280) CDR1 Amino Acid Sequence G F T F S N Y W (SEQ ID NO: 281) CDR2 DNA Sequence ATA AAG CAA GAT GGA AGT GAG AAG (SEQ ID NO: 282) CDR2 Amino Acid Sequence I K Q D G S E K (SEQ ID NO: 283) CDR3 DNA Sequence GCG AGA CGT GGA TAC ACC TAT GGC AGC TTT GAC TAC (SEQ ID NO: 284) CDR3 Amino Acid Sequence A R R G Y T Y G S F D Y (SEQ ID NO: 285) LCVR DNA Sequence Attorney Docket No.250298.000780 GACATCCAGATGACCCAGTCTCCATCTTCCGTGTCTGCATCTGTAGGAGACAGAGTCA CCATCACTTGTCGGGCGCGTCAGGGTTTTAGCATCTGGTTAGCCTGGTATCAGCAGAA ACCAGGGAAAGCCCCTAAGGTCCTGATCTATGCTGCATCCACTTTGCAGAGTGGGGTC CCATCAAGGTTCAGCGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGCC TGCAGCCTGAAGATTTTGCAACTTACTTTTGTCAACAGGCTAACAGTTTCCCTCCCACT TTCGGCGGAGGGACCAAGGTGGAGATCAAA (SEQ ID NO: 286) LCVR Amino Acid Sequence DIQMTQSPSSVSASVGDRVTITCRARQGFSIWLAWYQQKPGKAPKVLIYAASTLQSGVPS RFSGSGSGTDFTLTISSLQPEDFATYFCQQANSFPPTFGGGTKVEIK (SEQ ID NO: 287) CDR1 DNA Sequence CAG GGT TTT AGC ATC TGG (SEQ ID NO: 288) CDR1 Amino Acid Sequence Q G F S I W (SEQ ID NO: 289) CDR2 DNA Sequence GCT GCA TCC (SEQ ID NO: 13) CDR2 Amino Acid Sequence A A S (SEQ ID NO: 14) CDR3 DNA Sequence CAA CAG GCT AAC AGT TTC CCT CCC ACT (SEQ ID NO: 290) Attorney Docket No.250298.000780 CDR3 Amino Acid Sequence Q Q A N S F P P T (SEQ ID NO: 291) HC DNA Sequence GAGGTGCAGCTGGTGGAGTCTGGGGGAGGCTTGGTCCAGCCTGGGGGGTCCCTGAG ACTCTCCTGTGCAGCCTCTGGATTCACCTTTAGTAACTATTGGATGAACTGGGTCCGC CAGGCTCCAGGGAAGGGGCTGGAGTGGGTGGCCAACATAAAGCAAGATGGAAGTGA GAAGTACTATGTGGACTCTGTGAAGGGCCGATTCACCATCTCCAGAGACAACGCCAAG AACTCACTGTATCTGCAAATGAACAGCCTGAGAGCCGAGGACACGGCTGTGTATTACT GTGCGAGACGTGGATACACCTATGGCAGCTTTGACTACTGGGGCCAGGGAACCCTGG TCACCGTCTCCTCAGCCTCCACCAAGGGCCCATCGGTCTTCCCCCTGGCGCCCTGCT CCAGGAGCACCTCCGAGAGCACAGCCGCCCTGGGCTGCCTGGTCAAGGACTACTTCC CCGAACCGGTGACGGTGTCGTGGAACTCAGGCGCCCTGACCAGCGGCGTGCACACC TTCCCGGCTGTCCTACAGTCCTCAGGACTCTACTCCCTCAGCAGCGTGGTGACCGTGC CCTCCAGCAGCTTGGGCACGAAGACCTACACCTGCAACGTAGATCACAAGCCCAGCA ACACCAAGGTGGACAAGAGAGTTGAGTCCAAATATGGTCCCCCATGCCCACCGTGCC CAGCACCACCTGTGGCAGGACCATCAGTCTTCCTGTTCCCCCCAAAACCCAAGGACAC TCTCATGATCTCCCGGACCCCTGAGGTCACGTGCGTGGTGGTGGACGTGAGCCAGGA AGACCCCGAGGTCCAGTTCAACTGGTACGTGGATGGCGTGGAGGTGCATAATGCCAA GACAAAGCCGCGGGAGGAGCAGTTCAACAGCACGTACCGTGTGGTCAGCGTCCTCAC CGTCCTGCACCAGGACTGGCTGAACGGCAAGGAGTACAAGTGCAAGGTCTCCAACAA AGGCCTCCCGTCCTCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGAGA GCCACAGGTGTACACCCTGCCCCCATCCCAGGAGGAGATGACCAAGAACCAGGTCAG CCTGACCTGCCTGGTCAAAGGCTTCTACCCCAGCGACATCGCCGTGGAGTGGGAGAG CAATGGGCAGCCGGAGAACAACTACAAGACCACGCCTCCCGTGCTGGACTCCGACGG CTCCTTCTTCCTCTACAGCAGGCTCACCGTGGACAAGAGCAGGTGGCAGGAGGGGAA TGTCTTCTCATGCTCCGTGATGCATGAGGCTCTGCACAACCACTACACACAGAAGTCC CTCTCCCTGTCTCTGGGTAAATGA (SEQ ID NO: 292) HC Amino Acid Sequence Attorney Docket No.250298.000780 EVQLVESGGGLVQPGGSLRLSCAASGFTFSNYWMNWVRQAPGKGLEWVANIKQDGSEK YYVDSVKGRFTISRDNAKNSLYLQMNSLRAEDTAVYYCARRGYTYGSFDYWGQGTLVTV SSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQ SSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPPVAGPS VFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNST YRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMT KNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQE GNVFSCSVMHEALHNHYTQKSLSLSLGK* (SEQ ID NO: 293) LC DNA Sequence GACATCCAGATGACCCAGTCTCCATCTTCCGTGTCTGCATCTGTAGGAGACAGAGTCA CCATCACTTGTCGGGCGCGTCAGGGTTTTAGCATCTGGTTAGCCTGGTATCAGCAGAA ACCAGGGAAAGCCCCTAAGGTCCTGATCTATGCTGCATCCACTTTGCAGAGTGGGGTC CCATCAAGGTTCAGCGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGCC TGCAGCCTGAAGATTTTGCAACTTACTTTTGTCAACAGGCTAACAGTTTCCCTCCCACT TTCGGCGGAGGGACCAAGGTGGAGATCAAACGAACTGTGGCTGCACCATCTGTCTTC ATCTTCCCGCCATCTGATGAGCAGTTGAAATCTGGAACTGCCTCTGTTGTGTGCCTGC TGAATAACTTCTATCCCAGAGAGGCCAAAGTACAGTGGAAGGTGGATAACGCCCTCCA ATCGGGTAACTCCCAGGAGAGTGTCACAGAGCAGGACAGCAAGGACAGCACCTACAG CCTCAGCAGCACCCTGACGCTGAGCAAAGCAGACTACGAGAAACACAAAGTCTACGC CTGCGAAGTCACCCATCAGGGCCTGAGCTCGCCCGTCACAAAGAGCTTCAACAGGGG AGAGTGTTAG (SEQ ID NO: 294) LC Amino Acid Sequence DIQMTQSPSSVSASVGDRVTITCRARQGFSIWLAWYQQKPGKAPKVLIYAASTLQSGVPS RFSGSGSGTDFTLTISSLQPEDFATYFCQQANSFPPTFGGGTKVEIKRTVAAPSVFIFPPSD EQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLS KADYEKHKVYACEVTHQGLSSPVTKSFNRGEC* (SEQ ID NO: 295) REGN14164 Attorney Docket No.250298.000780 HCVR DNA Sequence CAGGTGCAGCTGGTGGAGTCTGGGGGAGGCGTGGTCCAGCCTGGGAGGTCCCTGAG ACTCTCCTGTGCAGCCTCTGGATTCACCTTCAGTAACTATGGCATGTACTGGGTCCGC CAGGCTCCAGGCAAGGGTCTGGAGTGGGTGTCAATTATATCATATGATGGAAGTAATA AATACTATGCAGACTCCGTGAAGGGCCGATTCACCAGCTCCAGAGACAATTCCAAGAA CACGCTGTATCTTCAAATGAACAGCCTGAGAGGTGAGGACACGGCTGTGTATTACTGT GCGAAAGATAGAGGAGCTGGAACTACAGCCTTCCACTACGGTATGGACGTCTGGGGC CAAGGGACCACGGTCACCGTCTCCTCA (SEQ ID NO: 296) HCVR Amino Acid Sequence QVQLVESGGGVVQPGRSLRLSCAASGFTFSNYGMYWVRQAPGKGLEWVSIISYDGSNKY YADSVKGRFTSSRDNSKNTLYLQMNSLRGEDTAVYYCAKDRGAGTTAFHYGMDVWGQG TTVTVSS (SEQ ID NO: 297) CDR1 DNA Sequence GGA TTC ACC TTC AGT AAC TAT GGC (SEQ ID NO: 298) CDR1 Amino Acid Sequence G F T F S N Y G (SEQ ID NO: 299) CDR2 DNA Sequence ATA TCA TAT GAT GGA AGT AAT AAA (SEQ ID NO: 300) CDR2 Amino Acid Sequence I S Y D G S N K (SEQ ID NO: 193) CDR3 DNA Sequence Attorney Docket No.250298.000780 GCG AAA GAT AGA GGA GCT GGA ACT ACA GCC TTC CAC TAC GGT ATG GAC GTC (SEQ ID NO: 301) CDR3 Amino Acid Sequence A K D R G A G T T A F H Y G M D V (SEQ ID NO: 302) LCVR DNA Sequence GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACAGAGTCA CCATCACTTGCCGGGCAAGTCAGAGCATTAGCAGTTATTTAAATTGGTATCAGCAGAAA CCAGGGAAAGCCCCTAAGGTCCTGATCTATGCTGCATTCAGTTTGCAAAGTGGGGTCC CTTCAAGGTTCAGTGGCAGTGGATCTGGGACAGATTTCACTCTAACTATCAGTAGCCT GCAACCTGAGGATTTCGCAACTTACTATTGTCACCAGACTTATAGTGTTCCTCCGATCA CCTTCGGCCAAGGGACCAAGCTGGAGATCAAA (SEQ ID NO: 303) LCVR Amino Acid Sequence DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKVLIYAAFSLQSGVPSR FSGSGSGTDFTLTISSLQPEDFATYYCHQTYSVPPITFGQGTKLEIK (SEQ ID NO: 304) CDR1 DNA Sequence CAG AGC ATT AGC AGT TAT (SEQ ID NO: 305) CDR1 Amino Acid Sequence Q S I S S Y (SEQ ID NO: 237) CDR2 DNA Sequence GCT GCA TTC (SEQ ID NO: 306) Attorney Docket No.250298.000780 CDR2 Amino Acid Sequence A A F (SEQ ID NO: 307) CDR3 DNA Sequence CAC CAG ACT TAT AGT GTT CCT CCG ATC ACC (SEQ ID NO: 308) CDR3 Amino Acid Sequence H Q T Y S V P P I T (SEQ ID NO: 309) HC DNA Sequence CAGGTGCAGCTGGTGGAGTCTGGGGGAGGCGTGGTCCAGCCTGGGAGGTCCCTGAG ACTCTCCTGTGCAGCCTCTGGATTCACCTTCAGTAACTATGGCATGTACTGGGTCCGC CAGGCTCCAGGCAAGGGTCTGGAGTGGGTGTCAATTATATCATATGATGGAAGTAATA AATACTATGCAGACTCCGTGAAGGGCCGATTCACCAGCTCCAGAGACAATTCCAAGAA CACGCTGTATCTTCAAATGAACAGCCTGAGAGGTGAGGACACGGCTGTGTATTACTGT GCGAAAGATAGAGGAGCTGGAACTACAGCCTTCCACTACGGTATGGACGTCTGGGGC CAAGGGACCACGGTCACCGTCTCCTCAGCCTCCACCAAGGGCCCATCGGTCTTCCCC CTGGCGCCCTGCTCCAGGAGCACCTCCGAGAGCACAGCCGCCCTGGGCTGCCTGGT CAAGGACTACTTCCCCGAACCGGTGACGGTGTCGTGGAACTCAGGCGCCCTGACCAG CGGCGTGCACACCTTCCCGGCTGTCCTACAGTCCTCAGGACTCTACTCCCTCAGCAG CGTGGTGACCGTGCCCTCCAGCAGCTTGGGCACGAAGACCTACACCTGCAACGTAGA TCACAAGCCCAGCAACACCAAGGTGGACAAGAGAGTTGAGTCCAAATATGGTCCCCCA TGCCCACCGTGCCCAGCACCACCTGTGGCAGGACCATCAGTCTTCCTGTTCCCCCCA AAACCCAAGGACACTCTCATGATCTCCCGGACCCCTGAGGTCACGTGCGTGGTGGTG GACGTGAGCCAGGAAGACCCCGAGGTCCAGTTCAACTGGTACGTGGATGGCGTGGAG GTGCATAATGCCAAGACAAAGCCGCGGGAGGAGCAGTTCAACAGCACGTACCGTGTG GTCAGCGTCCTCACCGTCCTGCACCAGGACTGGCTGAACGGCAAGGAGTACAAGTGC AAGGTCTCCAACAAAGGCCTCCCGTCCTCCATCGAGAAAACCATCTCCAAAGCCAAAG GGCAGCCCCGAGAGCCACAGGTGTACACCCTGCCCCCATCCCAGGAGGAGATGACC AAGAACCAGGTCAGCCTGACCTGCCTGGTCAAAGGCTTCTACCCCAGCGACATCGCC Attorney Docket No.250298.000780 GTGGAGTGGGAGAGCAATGGGCAGCCGGAGAACAACTACAAGACCACGCCTCCCGT GCTGGACTCCGACGGCTCCTTCTTCCTCTACAGCAGGCTCACCGTGGACAAGAGCAG GTGGCAGGAGGGGAATGTCTTCTCATGCTCCGTGATGCATGAGGCTCTGCACAACCA CTACACACAGAAGTCCCTCTCCCTGTCTCTGGGTAAATGA (SEQ ID NO: 310) HC Amino Acid Sequence QVQLVESGGGVVQPGRSLRLSCAASGFTFSNYGMYWVRQAPGKGLEWVSIISYDGSNKY YADSVKGRFTSSRDNSKNTLYLQMNSLRGEDTAVYYCAKDRGAGTTAFHYGMDVWGQG TTVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFP AVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPPV AGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQ FNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQE EMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSR WQEGNVFSCSVMHEALHNHYTQKSLSLSLGK* (SEQ ID NO: 311) LC DNA Sequence GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACAGAGTCA CCATCACTTGCCGGGCAAGTCAGAGCATTAGCAGTTATTTAAATTGGTATCAGCAGAAA CCAGGGAAAGCCCCTAAGGTCCTGATCTATGCTGCATTCAGTTTGCAAAGTGGGGTCC CTTCAAGGTTCAGTGGCAGTGGATCTGGGACAGATTTCACTCTAACTATCAGTAGCCT GCAACCTGAGGATTTCGCAACTTACTATTGTCACCAGACTTATAGTGTTCCTCCGATCA CCTTCGGCCAAGGGACCAAGCTGGAGATCAAACGAACTGTGGCTGCACCATCTGTCTT CATCTTCCCGCCATCTGATGAGCAGTTGAAATCTGGAACTGCCTCTGTTGTGTGCCTG CTGAATAACTTCTATCCCAGAGAGGCCAAAGTACAGTGGAAGGTGGATAACGCCCTCC AATCGGGTAACTCCCAGGAGAGTGTCACAGAGCAGGACAGCAAGGACAGCACCTACA GCCTCAGCAGCACCCTGACGCTGAGCAAAGCAGACTACGAGAAACACAAAGTCTACG CCTGCGAAGTCACCCATCAGGGCCTGAGCTCGCCCGTCACAAAGAGCTTCAACAGGG GAGAGTGTTAG (SEQ ID NO: 312) LC Amino Acid Sequence Attorney Docket No.250298.000780 DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKVLIYAAFSLQSGVPSR FSGSGSGTDFTLTISSLQPEDFATYYCHQTYSVPPITFGQGTKLEIKRTVAAPSVFIFPPSDE QLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSK ADYEKHKVYACEVTHQGLSSPVTKSFNRGEC* (SEQ ID NO: 313) REGN14165 HCVR DNA Sequence CAGGTTCAGCTGGTGCAGTCTGGAGGTGAGGTGAAGAAGCCTGGGGCCTCAGTGAAG GTCTCCTGCAAGGCTTCTGGTTACACCTTTACCAACTATGGAATCAGCTGGATACGACA GGCCCCTGGACAAGGGCTTGAGTGGATGGGATGGATCAGCGCTTACAATGGTAACAC AAACTATGCACAGAAGGTCCAGGGCAGAGTCACCATGACCACAGACACATCCACGAC CACAGCCTACATGGAGCTGAGGAGCCTGAGATCTGACGACACGGCCGTATATTTCTGT GCGAGAGATCGGGGACAACTGGATCGAGGAGGAAACTACTACTTCTACATTATGAGCG TCTGGGGCCAAGGGACCACGGTCACCGTCTCCTCA (SEQ ID NO: 314) HCVR Amino Acid Sequence QVQLVQSGGEVKKPGASVKVSCKASGYTFTNYGISWIRQAPGQGLEWMGWISAYNGNTN YAQKVQGRVTMTTDTSTTTAYMELRSLRSDDTAVYFCARDRGQLDRGGNYYFYIMSVWG QGTTVTVSS (SEQ ID NO: 315) CDR1 DNA Sequence GGT TAC ACC TTT ACC AAC TAT GGA (SEQ ID NO: 316) CDR1 Amino Acid Sequence G Y T F T N Y G (SEQ ID NO: 317) CDR2 DNA Sequence ATC AGC GCT TAC AAT GGT AAC ACA Attorney Docket No.250298.000780 (SEQ ID NO: 318) CDR2 Amino Acid Sequence I S A Y N G N T (SEQ ID NO: 319) CDR3 DNA Sequence GCG AGA GAT CGG GGA CAA CTG GAT CGA GGA GGA AAC TAC TAC TTC TAC ATT ATG AGC GTC (SEQ ID NO: 320) CDR3 Amino Acid Sequence A R D R G Q L D R G G N Y Y F Y I M S V (SEQ ID NO: 321) LCVR DNA Sequence GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACAGAGTCA CCATCACTTGCCGGGCAAGTCAGGACATTAGAAATGATTTAGGCTGGTATCAGCAGAA ACCAGGGAAAGCCCCTAAGCGCCTAATCTATGCTGCATCCAATTTGCAAAGTGGGGTC CCATCAAGGTTCAGCGGCAGTGGATCTGGGACAGAATTCACTCTCACAATCAGCAGCC TGCAGCCTGAAGATTTTGCAACTTATTACTGTCTACAGCATAGTAGTTACCCGTGGACG TTCGGCCAAGGGACCAAGGTGGAAATCAAA (SEQ ID NO: 322) LCVR Amino Acid Sequence DIQMTQSPSSLSASVGDRVTITCRASQDIRNDLGWYQQKPGKAPKRLIYAASNLQSGVPS RFSGSGSGTEFTLTISSLQPEDFATYYCLQHSSYPWTFGQGTKVEIK (SEQ ID NO: 323) CDR1 DNA Sequence CAG GAC ATT AGA AAT GAT (SEQ ID NO: 11) Attorney Docket No.250298.000780 CDR1 Amino Acid Sequence Q D I R N D (SEQ ID NO: 12) CDR2 DNA Sequence GCT GCA TCC (SEQ ID NO: 13) CDR2 Amino Acid Sequence A A S (SEQ ID NO: 14) CDR3 DNA Sequence CTA CAG CAT AGT AGT TAC CCG TGG ACG (SEQ ID NO: 324) CDR3 Amino Acid Sequence L Q H S S Y P W T (SEQ ID NO: 325) HC DNA Sequence CAGGTTCAGCTGGTGCAGTCTGGAGGTGAGGTGAAGAAGCCTGGGGCCTCAGTGAAG GTCTCCTGCAAGGCTTCTGGTTACACCTTTACCAACTATGGAATCAGCTGGATACGACA GGCCCCTGGACAAGGGCTTGAGTGGATGGGATGGATCAGCGCTTACAATGGTAACAC AAACTATGCACAGAAGGTCCAGGGCAGAGTCACCATGACCACAGACACATCCACGAC CACAGCCTACATGGAGCTGAGGAGCCTGAGATCTGACGACACGGCCGTATATTTCTGT GCGAGAGATCGGGGACAACTGGATCGAGGAGGAAACTACTACTTCTACATTATGAGCG TCTGGGGCCAAGGGACCACGGTCACCGTCTCCTCAGCCTCCACCAAGGGCCCATCGG TCTTCCCCCTGGCGCCCTGCTCCAGGAGCACCTCCGAGAGCACAGCCGCCCTGGGCT GCCTGGTCAAGGACTACTTCCCCGAACCGGTGACGGTGTCGTGGAACTCAGGCGCCC TGACCAGCGGCGTGCACACCTTCCCGGCTGTCCTACAGTCCTCAGGACTCTACTCCCT CAGCAGCGTGGTGACCGTGCCCTCCAGCAGCTTGGGCACGAAGACCTACACCTGCAA CGTAGATCACAAGCCCAGCAACACCAAGGTGGACAAGAGAGTTGAGTCCAAATATGGT Attorney Docket No.250298.000780 CCCCCATGCCCACCGTGCCCAGCACCACCTGTGGCAGGACCATCAGTCTTCCTGTTC CCCCCAAAACCCAAGGACACTCTCATGATCTCCCGGACCCCTGAGGTCACGTGCGTG GTGGTGGACGTGAGCCAGGAAGACCCCGAGGTCCAGTTCAACTGGTACGTGGATGGC GTGGAGGTGCATAATGCCAAGACAAAGCCGCGGGAGGAGCAGTTCAACAGCACGTAC CGTGTGGTCAGCGTCCTCACCGTCCTGCACCAGGACTGGCTGAACGGCAAGGAGTAC AAGTGCAAGGTCTCCAACAAAGGCCTCCCGTCCTCCATCGAGAAAACCATCTCCAAAG CCAAAGGGCAGCCCCGAGAGCCACAGGTGTACACCCTGCCCCCATCCCAGGAGGAG ATGACCAAGAACCAGGTCAGCCTGACCTGCCTGGTCAAAGGCTTCTACCCCAGCGAC ATCGCCGTGGAGTGGGAGAGCAATGGGCAGCCGGAGAACAACTACAAGACCACGCCT CCCGTGCTGGACTCCGACGGCTCCTTCTTCCTCTACAGCAGGCTCACCGTGGACAAG AGCAGGTGGCAGGAGGGGAATGTCTTCTCATGCTCCGTGATGCATGAGGCTCTGCAC AACCACTACACACAGAAGTCCCTCTCCCTGTCTCTGGGTAAATGA (SEQ ID NO: 326) HC Amino Acid Sequence QVQLVQSGGEVKKPGASVKVSCKASGYTFTNYGISWIRQAPGQGLEWMGWISAYNGNTN YAQKVQGRVTMTTDTSTTTAYMELRSLRSDDTAVYFCARDRGQLDRGGNYYFYIMSVWG QGTTVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVH TFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPA PPVAGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPR EEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPP SQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVD KSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGK* (SEQ ID NO: 327) LC DNA Sequence GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACAGAGTCA CCATCACTTGCCGGGCAAGTCAGGACATTAGAAATGATTTAGGCTGGTATCAGCAGAA ACCAGGGAAAGCCCCTAAGCGCCTAATCTATGCTGCATCCAATTTGCAAAGTGGGGTC CCATCAAGGTTCAGCGGCAGTGGATCTGGGACAGAATTCACTCTCACAATCAGCAGCC TGCAGCCTGAAGATTTTGCAACTTATTACTGTCTACAGCATAGTAGTTACCCGTGGACG TTCGGCCAAGGGACCAAGGTGGAAATCAAACGAACTGTGGCTGCACCATCTGTCTTCA TCTTCCCGCCATCTGATGAGCAGTTGAAATCTGGAACTGCCTCTGTTGTGTGCCTGCT Attorney Docket No.250298.000780 GAATAACTTCTATCCCAGAGAGGCCAAAGTACAGTGGAAGGTGGATAACGCCCTCCAA TCGGGTAACTCCCAGGAGAGTGTCACAGAGCAGGACAGCAAGGACAGCACCTACAGC CTCAGCAGCACCCTGACGCTGAGCAAAGCAGACTACGAGAAACACAAAGTCTACGCCT GCGAAGTCACCCATCAGGGCCTGAGCTCGCCCGTCACAAAGAGCTTCAACAGGGGAG AGTGTTAG (SEQ ID NO: 328) LC Amino Acid Sequence DIQMTQSPSSLSASVGDRVTITCRASQDIRNDLGWYQQKPGKAPKRLIYAASNLQSGVPS RFSGSGSGTEFTLTISSLQPEDFATYYCLQHSSYPWTFGQGTKVEIKRTVAAPSVFIFPPSD EQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLS KADYEKHKVYACEVTHQGLSSPVTKSFNRGEC* (SEQ ID NO: 329) REGN14175 HCVR DNA Sequence CAGGTGCAGCTGGTGGAGTCTGGGGGAGGCGTGGTCCAGCCTGGGAGGTCCCTGAG ACTCTCCTGTGCAGCCTCTGGATTCAGATTCAGTAGTTATGGCATGCACTGGGTCCGC CAGGCTCCAGGCAAGGGGCTGGAGTGGGTGGCAGTCATTTCATATGATGGAAGTGAT AAATATTATGCAGACTCCGTGAAGGGCCGATTCACCATCTCCAGAGACAATTCCAAGA ACACGCTTTATATGCAAATGAACAGACTGAAAAGTGAGGACACGGCTGTTTATTATTGT GCGAAAGAGAGAAGTACAGCAGCTCGTCGGGGGGACTACTACGACTACGGTATGGAC GTCTGGGGCCAAGGGACCACGGTCACCGTCTCCTCA (SEQ ID NO: 330) HCVR Amino Acid Sequence QVQLVESGGGVVQPGRSLRLSCAASGFRFSSYGMHWVRQAPGKGLEWVAVISYDGSDK YYADSVKGRFTISRDNSKNTLYMQMNRLKSEDTAVYYCAKERSTAARRGDYYDYGMDVW GQGTTVTVSS (SEQ ID NO: 331) CDR1 DNA Sequence GGA TTC AGA TTC AGT AGT TAT GGC Attorney Docket No.250298.000780 (SEQ ID NO: 332) CDR1 Amino Acid Sequence G F R F S S Y G (SEQ ID NO: 333) CDR2 DNA Sequence ATT TCA TAT GAT GGA AGT GAT AAA (SEQ ID NO: 334) CDR2 Amino Acid Sequence I S Y D G S D K (SEQ ID NO: 335) CDR3 DNA Sequence GCG AAA GAG AGA AGT ACA GCA GCT CGT CGG GGG GAC TAC TAC GAC TAC GGT ATG GAC GTC (SEQ ID NO: 336) CDR3 Amino Acid Sequence A K E R S T A A R R G D Y Y D Y G M D V (SEQ ID NO: 337) LCVR DNA Sequence GACATCCAGATGACCCAGTCTCCATCCTCCCTGTTTGCATCTGTGGGAGACAGAGTCA CCATCACTTGCCGGGCAAGTCAGAGCATTAGCAGCTATTTAAATTGGTATCACCAGAAA CCAGGGAGAGCCCCTAAACTCCTGATCTTTGCTTCATTCAGTTTGCAAAGTGGGGTCC CGTCAAGGTTCAGTGGCAGTGGATCTGGAACAGATTTCACTCTCACCATCAGCAGTGT GGAACCTGAAGATTTTGCATCTTACTACTGTCAACAGAGTTACAGTACCCCATTCACTT TCGGCCCTGGGACCAAAGTGGATATCAAA (SEQ ID NO: 338) LCVR Amino Acid Sequence Attorney Docket No.250298.000780 DIQMTQSPSSLFASVGDRVTITCRASQSISSYLNWYHQKPGRAPKLLIFASFSLQSGVPSRF SGSGSGTDFTLTISSVEPEDFASYYCQQSYSTPFTFGPGTKVDIK (SEQ ID NO: 339) CDR1 DNA Sequence CAG AGC ATT AGC AGC TAT (SEQ ID NO: 236) CDR1 Amino Acid Sequence Q S I S S Y (SEQ ID NO: 237) CDR2 DNA Sequence GCT TCA TTC (SEQ ID NO: 340) CDR2 Amino Acid Sequence A S F (SEQ ID NO: 341) CDR3 DNA Sequence CAA CAG AGT TAC AGT ACC CCA TTC ACT (SEQ ID NO: 342) CDR3 Amino Acid Sequence Q Q S Y S T P F T (SEQ ID NO: 343) HC DNA Sequence CAGGTGCAGCTGGTGGAGTCTGGGGGAGGCGTGGTCCAGCCTGGGAGGTCCCTGAG ACTCTCCTGTGCAGCCTCTGGATTCAGATTCAGTAGTTATGGCATGCACTGGGTCCGC CAGGCTCCAGGCAAGGGGCTGGAGTGGGTGGCAGTCATTTCATATGATGGAAGTGAT AAATATTATGCAGACTCCGTGAAGGGCCGATTCACCATCTCCAGAGACAATTCCAAGA Attorney Docket No.250298.000780 ACACGCTTTATATGCAAATGAACAGACTGAAAAGTGAGGACACGGCTGTTTATTATTGT GCGAAAGAGAGAAGTACAGCAGCTCGTCGGGGGGACTACTACGACTACGGTATGGAC GTCTGGGGCCAAGGGACCACGGTCACCGTCTCCTCAGCCTCCACCAAGGGCCCATCG GTCTTCCCCCTGGCGCCCTGCTCCAGGAGCACCTCCGAGAGCACAGCCGCCCTGGG CTGCCTGGTCAAGGACTACTTCCCCGAACCGGTGACGGTGTCGTGGAACTCAGGCGC CCTGACCAGCGGCGTGCACACCTTCCCGGCTGTCCTACAGTCCTCAGGACTCTACTC CCTCAGCAGCGTGGTGACCGTGCCCTCCAGCAGCTTGGGCACGAAGACCTACACCTG CAACGTAGATCACAAGCCCAGCAACACCAAGGTGGACAAGAGAGTTGAGTCCAAATAT GGTCCCCCATGCCCACCGTGCCCAGCACCACCTGTGGCAGGACCATCAGTCTTCCTG TTCCCCCCAAAACCCAAGGACACTCTCATGATCTCCCGGACCCCTGAGGTCACGTGCG TGGTGGTGGACGTGAGCCAGGAAGACCCCGAGGTCCAGTTCAACTGGTACGTGGATG GCGTGGAGGTGCATAATGCCAAGACAAAGCCGCGGGAGGAGCAGTTCAACAGCACGT ACCGTGTGGTCAGCGTCCTCACCGTCCTGCACCAGGACTGGCTGAACGGCAAGGAGT ACAAGTGCAAGGTCTCCAACAAAGGCCTCCCGTCCTCCATCGAGAAAACCATCTCCAA AGCCAAAGGGCAGCCCCGAGAGCCACAGGTGTACACCCTGCCCCCATCCCAGGAGG AGATGACCAAGAACCAGGTCAGCCTGACCTGCCTGGTCAAAGGCTTCTACCCCAGCG ACATCGCCGTGGAGTGGGAGAGCAATGGGCAGCCGGAGAACAACTACAAGACCACGC CTCCCGTGCTGGACTCCGACGGCTCCTTCTTCCTCTACAGCAGGCTCACCGTGGACAA GAGCAGGTGGCAGGAGGGGAATGTCTTCTCATGCTCCGTGATGCATGAGGCTCTGCA CAACCACTACACACAGAAGTCCCTCTCCCTGTCTCTGGGTAAATGA (SEQ ID NO: 344) HC Amino Acid Sequence QVQLVESGGGVVQPGRSLRLSCAASGFRFSSYGMHWVRQAPGKGLEWVAVISYDGSDK YYADSVKGRFTISRDNSKNTLYMQMNRLKSEDTAVYYCAKERSTAARRGDYYDYGMDVW GQGTTVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGV HTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCP APPVAGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKP REEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLP PSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTV DKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGK* (SEQ ID NO: 345) Attorney Docket No.250298.000780 LC DNA Sequence GACATCCAGATGACCCAGTCTCCATCCTCCCTGTTTGCATCTGTGGGAGACAGAGTCA CCATCACTTGCCGGGCAAGTCAGAGCATTAGCAGCTATTTAAATTGGTATCACCAGAAA CCAGGGAGAGCCCCTAAACTCCTGATCTTTGCTTCATTCAGTTTGCAAAGTGGGGTCC CGTCAAGGTTCAGTGGCAGTGGATCTGGAACAGATTTCACTCTCACCATCAGCAGTGT GGAACCTGAAGATTTTGCATCTTACTACTGTCAACAGAGTTACAGTACCCCATTCACTT TCGGCCCTGGGACCAAAGTGGATATCAAACGAACTGTGGCTGCACCATCTGTCTTCAT CTTCCCGCCATCTGATGAGCAGTTGAAATCTGGAACTGCCTCTGTTGTGTGCCTGCTG AATAACTTCTATCCCAGAGAGGCCAAAGTACAGTGGAAGGTGGATAACGCCCTCCAAT CGGGTAACTCCCAGGAGAGTGTCACAGAGCAGGACAGCAAGGACAGCACCTACAGCC TCAGCAGCACCCTGACGCTGAGCAAAGCAGACTACGAGAAACACAAAGTCTACGCCT GCGAAGTCACCCATCAGGGCCTGAGCTCGCCCGTCACAAAGAGCTTCAACAGGGGAG AGTGTTAG (SEQ ID NO: 346) LC Amino Acid Sequence DIQMTQSPSSLFASVGDRVTITCRASQSISSYLNWYHQKPGRAPKLLIFASFSLQSGVPSRF SGSGSGTDFTLTISSVEPEDFASYYCQQSYSTPFTFGPGTKVDIKRTVAAPSVFIFPPSDEQ LKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKA DYEKHKVYACEVTHQGLSSPVTKSFNRGEC* (SEQ ID NO: 347) REGN14176 HCVR DNA Sequence CAGGTTCAGCTGGTGCAGTCTGGAACTGAGGTGAAGAAGCCTGGGGCCTCAGTGACG GTCTCCTGCAAGGCTTCTGGTTACACTTTTACCAGCTATAGTGTCAGCTGGGTGCGAC AGGCCCCTGGACAAGGGCTTGAGTGGATGGGATGGATCAACGCTTACAATGGTGACA CAAACTATGCACAGAGGTTCCACGGCAGAGTCACCATGACCACAGACACATCCACGAG CACAGCCTATATGGACTTGAGGAGCCTGAGATCTGACGACACGGCCGTGTATTACTGT GCGAGAGATCGGATAAGTGGAACCTTAGACTACTGGGGCCAGGGAACCCTGGTCACC GTCTCCTCA (SEQ ID NO: 348) Attorney Docket No.250298.000780 HCVR Amino Acid Sequence QVQLVQSGTEVKKPGASVTVSCKASGYTFTSYSVSWVRQAPGQGLEWMGWINAYNGDT NYAQRFHGRVTMTTDTSTSTAYMDLRSLRSDDTAVYYCARDRISGTLDYWGQGTLVTVSS (SEQ ID NO: 349) CDR1 DNA Sequence GGT TAC ACT TTT ACC AGC TAT AGT (SEQ ID NO: 350) CDR1 Amino Acid Sequence G Y T F T S Y S (SEQ ID NO: 351) CDR2 DNA Sequence ATC AAC GCT TAC AAT GGT GAC ACA (SEQ ID NO: 352) CDR2 Amino Acid Sequence I N A Y N G D T (SEQ ID NO: 353) CDR3 DNA Sequence GCG AGA GAT CGG ATA AGT GGA ACC TTA GAC TAC (SEQ ID NO: 354) CDR3 Amino Acid Sequence A R D R I S G T L D Y (SEQ ID NO: 355) LCVR DNA Sequence GATGTTGTGATGACTCAGTCTCCACTCTCCCTGCCCGTCACCCTTGGACAGTCGGCCT CCATCTCCTGCAGGTCTAGTCAAAGCCTCGTATACAGTAATGGAAACACCTACTTGAAT TGGTTTCAGCAGAGGCCAGGCCAATCTCCACGGCGCCTATTTTATAAGGTTTCTAACC Attorney Docket No.250298.000780 GGGACTCTGGGGTCCCAGACAGATTCAGCGGCATTGGGTCAGGCACTGATTTCACAC TGAAAATCAGCAGGGTGGAGGCTGAGGATGTTGGATTTTATTACTGCATGCAAGGTAC ACACTGGCCTCGGACTTTTGGCCAGGGGACCAAGCTGGAGATCAAA (SEQ ID NO: 356) LCVR Amino Acid Sequence DVVMTQSPLSLPVTLGQSASISCRSSQSLVYSNGNTYLNWFQQRPGQSPRRLFYKVSNR DSGVPDRFSGIGSGTDFTLKISRVEAEDVGFYYCMQGTHWPRTFGQGTKLEIK (SEQ ID NO: 357) CDR1 DNA Sequence CAA AGC CTC GTA TAC AGT AAT GGA AAC ACC TAC (SEQ ID NO: 358) CDR1 Amino Acid Sequence Q S L V Y S N G N T Y (SEQ ID NO: 359) CDR2 DNA Sequence AAG GTT TCT (SEQ ID NO: 360) CDR2 Amino Acid Sequence K V S (SEQ ID NO: 361) CDR3 DNA Sequence ATG CAA GGT ACA CAC TGG CCT CGG ACT (SEQ ID NO: 362) CDR3 Amino Acid Sequence M Q G T H W P R T (SEQ ID NO: 363) Attorney Docket No.250298.000780 HC DNA Sequence CAGGTTCAGCTGGTGCAGTCTGGAACTGAGGTGAAGAAGCCTGGGGCCTCAGTGACG GTCTCCTGCAAGGCTTCTGGTTACACTTTTACCAGCTATAGTGTCAGCTGGGTGCGAC AGGCCCCTGGACAAGGGCTTGAGTGGATGGGATGGATCAACGCTTACAATGGTGACA CAAACTATGCACAGAGGTTCCACGGCAGAGTCACCATGACCACAGACACATCCACGAG CACAGCCTATATGGACTTGAGGAGCCTGAGATCTGACGACACGGCCGTGTATTACTGT GCGAGAGATCGGATAAGTGGAACCTTAGACTACTGGGGCCAGGGAACCCTGGTCACC GTCTCCTCAGCCTCCACCAAGGGCCCATCGGTCTTCCCCCTGGCGCCCTGCTCCAGG AGCACCTCCGAGAGCACAGCCGCCCTGGGCTGCCTGGTCAAGGACTACTTCCCCGAA CCGGTGACGGTGTCGTGGAACTCAGGCGCCCTGACCAGCGGCGTGCACACCTTCCC GGCTGTCCTACAGTCCTCAGGACTCTACTCCCTCAGCAGCGTGGTGACCGTGCCCTC CAGCAGCTTGGGCACGAAGACCTACACCTGCAACGTAGATCACAAGCCCAGCAACAC CAAGGTGGACAAGAGAGTTGAGTCCAAATATGGTCCCCCATGCCCACCGTGCCCAGC ACCACCTGTGGCAGGACCATCAGTCTTCCTGTTCCCCCCAAAACCCAAGGACACTCTC ATGATCTCCCGGACCCCTGAGGTCACGTGCGTGGTGGTGGACGTGAGCCAGGAAGAC CCCGAGGTCCAGTTCAACTGGTACGTGGATGGCGTGGAGGTGCATAATGCCAAGACA AAGCCGCGGGAGGAGCAGTTCAACAGCACGTACCGTGTGGTCAGCGTCCTCACCGTC CTGCACCAGGACTGGCTGAACGGCAAGGAGTACAAGTGCAAGGTCTCCAACAAAGGC CTCCCGTCCTCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGAGAGCCA CAGGTGTACACCCTGCCCCCATCCCAGGAGGAGATGACCAAGAACCAGGTCAGCCTG ACCTGCCTGGTCAAAGGCTTCTACCCCAGCGACATCGCCGTGGAGTGGGAGAGCAAT GGGCAGCCGGAGAACAACTACAAGACCACGCCTCCCGTGCTGGACTCCGACGGCTCC TTCTTCCTCTACAGCAGGCTCACCGTGGACAAGAGCAGGTGGCAGGAGGGGAATGTC TTCTCATGCTCCGTGATGCATGAGGCTCTGCACAACCACTACACACAGAAGTCCCTCT CCCTGTCTCTGGGTAAATGA (SEQ ID NO: 364) HC Amino Acid Sequence QVQLVQSGTEVKKPGASVTVSCKASGYTFTSYSVSWVRQAPGQGLEWMGWINAYNGDT NYAQRFHGRVTMTTDTSTSTAYMDLRSLRSDDTAVYYCARDRISGTLDYWGQGTLVTVSS ASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSS GLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPPVAGPSVF Attorney Docket No.250298.000780 LFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYR VVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKN QVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGN VFSCSVMHEALHNHYTQKSLSLSLGK* (SEQ ID NO: 365) LC DNA Sequence GATGTTGTGATGACTCAGTCTCCACTCTCCCTGCCCGTCACCCTTGGACAGTCGGCCT CCATCTCCTGCAGGTCTAGTCAAAGCCTCGTATACAGTAATGGAAACACCTACTTGAAT TGGTTTCAGCAGAGGCCAGGCCAATCTCCACGGCGCCTATTTTATAAGGTTTCTAACC GGGACTCTGGGGTCCCAGACAGATTCAGCGGCATTGGGTCAGGCACTGATTTCACAC TGAAAATCAGCAGGGTGGAGGCTGAGGATGTTGGATTTTATTACTGCATGCAAGGTAC ACACTGGCCTCGGACTTTTGGCCAGGGGACCAAGCTGGAGATCAAACGAACTGTGGC TGCACCATCTGTCTTCATCTTCCCGCCATCTGATGAGCAGTTGAAATCTGGAACTGCCT CTGTTGTGTGCCTGCTGAATAACTTCTATCCCAGAGAGGCCAAAGTACAGTGGAAGGT GGATAACGCCCTCCAATCGGGTAACTCCCAGGAGAGTGTCACAGAGCAGGACAGCAA GGACAGCACCTACAGCCTCAGCAGCACCCTGACGCTGAGCAAAGCAGACTACGAGAA ACACAAAGTCTACGCCTGCGAAGTCACCCATCAGGGCCTGAGCTCGCCCGTCACAAA GAGCTTCAACAGGGGAGAGTGTTAG (SEQ ID NO: 366) LC Amino Acid Sequence DVVMTQSPLSLPVTLGQSASISCRSSQSLVYSNGNTYLNWFQQRPGQSPRRLFYKVSNR DSGVPDRFSGIGSGTDFTLKISRVEAEDVGFYYCMQGTHWPRTFGQGTKLEIKRTVAAPS VFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYS LSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC* (SEQ ID NO: 367) REGN14177 HCVR DNA Sequence CAGGTGCAGCTGGTGGAGTCTGGGGGAGGCTTGGTCAAGCCTGGAGGGTCCCTGAG ACTCTCCTGTGCAGCCTCTGGATTCACCTTCAGCGACTATTACATGAGCTGGATCCGC CAGGCTCCAGGGAAGGGGCTGGAGTGGGTTTCATACATCAGTAAAAGTGGTACTACC Attorney Docket No.250298.000780 AAATACTACGCAGACTCTGTGAAGGGCCGATTCACCATCTCCAGGGACAACGCCAAGA ACTCAGTGTATCTGCAAATGAACAGTTTGAGAGCCGAGGACACGGCCGTCTATTACTG TGAGAAAAGGGGCAGCTTGGGCCAGGGAACCCTGGTCACCGTCTCCTCA (SEQ ID NO: 368) HCVR Amino Acid Sequence QVQLVESGGGLVKPGGSLRLSCAASGFTFSDYYMSWIRQAPGKGLEWVSYISKSGTTKYY ADSVKGRFTISRDNAKNSVYLQMNSLRAEDTAVYYCEKRGSLGQGTLVTVSS (SEQ ID NO: 369) CDR1 DNA Sequence GGA TTC ACC TTC AGC GAC TAT TAC (SEQ ID NO: 370) CDR1 Amino Acid Sequence G F T F S D Y Y (SEQ ID NO: 371) CDR2 DNA Sequence ATC AGT AAA AGT GGT ACT ACC AAA (SEQ ID NO: 372) CDR2 Amino Acid Sequence I S K S G T T K (SEQ ID NO: 373) CDR3 DNA Sequence GAG AAA AGG GGC AGC (SEQ ID NO: 374) CDR3 Amino Acid Sequence E K R G S (SEQ ID NO: 375) Attorney Docket No.250298.000780 LCVR DNA Sequence GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACAGAGTCA CCATCACTTGCCAGGCGAGTCAGGACATTAGCAAGTATTTAAATTGGTATCAGCAGAA GCCAGGGAAAGCCCCTAAGCTCCTGATCTACGGTGCATCCTATTTGGAAACAGGGGTC CCATCAAGGTTCAGTGGAAGTGGATCTGGGACAGATTTTACTTTTACCATCAGCAGCCT GCAGCCTGAAGATATTGCAACATATTTCTGTCAACAATATGATATTGTCCGGTTCACTTT TGGCCAGGGGACCAAGCTGGAGATCAAA (SEQ ID NO: 376) LCVR Amino Acid Sequence DIQMTQSPSSLSASVGDRVTITCQASQDISKYLNWYQQKPGKAPKLLIYGASYLETGVPSR FSGSGSGTDFTFTISSLQPEDIATYFCQQYDIVRFTFGQGTKLEIK (SEQ ID NO: 377) CDR1 DNA Sequence CAG GAC ATT AGC AAG TAT (SEQ ID NO: 378) CDR1 Amino Acid Sequence Q D I S K Y (SEQ ID NO: 379) CDR2 DNA Sequence GGT GCA TCC (SEQ ID NO: 165) CDR2 Amino Acid Sequence G A S (SEQ ID NO: 90) CDR3 DNA Sequence CAA CAA TAT GAT ATT GTC CGG TTC ACT Attorney Docket No.250298.000780 (SEQ ID NO: 380) CDR3 Amino Acid Sequence Q Q Y D I V R F T (SEQ ID NO: 381) HC DNA Sequence CAGGTGCAGCTGGTGGAGTCTGGGGGAGGCTTGGTCAAGCCTGGAGGGTCCCTGAG ACTCTCCTGTGCAGCCTCTGGATTCACCTTCAGCGACTATTACATGAGCTGGATCCGC CAGGCTCCAGGGAAGGGGCTGGAGTGGGTTTCATACATCAGTAAAAGTGGTACTACC AAATACTACGCAGACTCTGTGAAGGGCCGATTCACCATCTCCAGGGACAACGCCAAGA ACTCAGTGTATCTGCAAATGAACAGTTTGAGAGCCGAGGACACGGCCGTCTATTACTG TGAGAAAAGGGGCAGCTTGGGCCAGGGAACCCTGGTCACCGTCTCCTCAGCCTCCAC CAAGGGCCCATCGGTCTTCCCCCTGGCGCCCTGCTCCAGGAGCACCTCCGAGAGCAC AGCCGCCCTGGGCTGCCTGGTCAAGGACTACTTCCCCGAACCGGTGACGGTGTCGTG GAACTCAGGCGCCCTGACCAGCGGCGTGCACACCTTCCCGGCTGTCCTACAGTCCTC AGGACTCTACTCCCTCAGCAGCGTGGTGACCGTGCCCTCCAGCAGCTTGGGCACGAA GACCTACACCTGCAACGTAGATCACAAGCCCAGCAACACCAAGGTGGACAAGAGAGTT GAGTCCAAATATGGTCCCCCATGCCCACCGTGCCCAGCACCACCTGTGGCAGGACCA TCAGTCTTCCTGTTCCCCCCAAAACCCAAGGACACTCTCATGATCTCCCGGACCCCTG AGGTCACGTGCGTGGTGGTGGACGTGAGCCAGGAAGACCCCGAGGTCCAGTTCAACT GGTACGTGGATGGCGTGGAGGTGCATAATGCCAAGACAAAGCCGCGGGAGGAGCAG TTCAACAGCACGTACCGTGTGGTCAGCGTCCTCACCGTCCTGCACCAGGACTGGCTG AACGGCAAGGAGTACAAGTGCAAGGTCTCCAACAAAGGCCTCCCGTCCTCCATCGAG AAAACCATCTCCAAAGCCAAAGGGCAGCCCCGAGAGCCACAGGTGTACACCCTGCCC CCATCCCAGGAGGAGATGACCAAGAACCAGGTCAGCCTGACCTGCCTGGTCAAAGGC TTCTACCCCAGCGACATCGCCGTGGAGTGGGAGAGCAATGGGCAGCCGGAGAACAAC TACAAGACCACGCCTCCCGTGCTGGACTCCGACGGCTCCTTCTTCCTCTACAGCAGGC TCACCGTGGACAAGAGCAGGTGGCAGGAGGGGAATGTCTTCTCATGCTCCGTGATGC ATGAGGCTCTGCACAACCACTACACACAGAAGTCCCTCTCCCTGTCTCTGGGTAAATG A (SEQ ID NO: 382) Attorney Docket No.250298.000780 HC Amino Acid Sequence QVQLVESGGGLVKPGGSLRLSCAASGFTFSDYYMSWIRQAPGKGLEWVSYISKSGTTKYY ADSVKGRFTISRDNAKNSVYLQMNSLRAEDTAVYYCEKRGSLGQGTLVTVSSASTKGPSV FPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVV TVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPPVAGPSVFLFPPKPKDT LMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLH QDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVK GFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMH EALHNHYTQKSLSLSLGK* (SEQ ID NO: 383) LC DNA Sequence GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACAGAGTCA CCATCACTTGCCAGGCGAGTCAGGACATTAGCAAGTATTTAAATTGGTATCAGCAGAA GCCAGGGAAAGCCCCTAAGCTCCTGATCTACGGTGCATCCTATTTGGAAACAGGGGTC CCATCAAGGTTCAGTGGAAGTGGATCTGGGACAGATTTTACTTTTACCATCAGCAGCCT GCAGCCTGAAGATATTGCAACATATTTCTGTCAACAATATGATATTGTCCGGTTCACTTT TGGCCAGGGGACCAAGCTGGAGATCAAACGAACTGTGGCTGCACCATCTGTCTTCATC TTCCCGCCATCTGATGAGCAGTTGAAATCTGGAACTGCCTCTGTTGTGTGCCTGCTGA ATAACTTCTATCCCAGAGAGGCCAAAGTACAGTGGAAGGTGGATAACGCCCTCCAATC GGGTAACTCCCAGGAGAGTGTCACAGAGCAGGACAGCAAGGACAGCACCTACAGCCT CAGCAGCACCCTGACGCTGAGCAAAGCAGACTACGAGAAACACAAAGTCTACGCCTG CGAAGTCACCCATCAGGGCCTGAGCTCGCCCGTCACAAAGAGCTTCAACAGGGGAGA GTGTTAG (SEQ ID NO: 384) LC Amino Acid Sequence DIQMTQSPSSLSASVGDRVTITCQASQDISKYLNWYQQKPGKAPKLLIYGASYLETGVPSR FSGSGSGTDFTFTISSLQPEDIATYFCQQYDIVRFTFGQGTKLEIKRTVAAPSVFIFPPSDEQ LKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKA DYEKHKVYACEVTHQGLSSPVTKSFNRGEC* (SEQ ID NO: 385) Attorney Docket No.250298.000780 REGN14178 HCVR DNA Sequence CAGGTTCAGCTGGTGCAGTCTGGACCTGAGGTGAAGAAGCCTGGGGCCTCAGTGAAG GTCTCCTGCAAGGCTTCTGGTTACACCTTTACCAGCTATGGTTTCAGTTGGGTGCGAC AGGCCCCTGGACAAGGGCTTGAGTGGATGGGATGGATCAGCGCTTACAATGGTAACA CAAACTATGCACAGAAGTTCCAGGACAGAGTCACCATGACCACAGACTCATCCACGAG CACAGCCTACATGGAGCTGAGGAGCCTGAGATCTGACGACACGGCCGTTTATTCCTGT GCGAGAGATCGTGGATTTTGGAGAGCCTATTATGTCTTTGACTACTGGGGCCAGGGAA CCCTGGTCACCGTCTCCTCA (SEQ ID NO: 386) HCVR Amino Acid Sequence QVQLVQSGPEVKKPGASVKVSCKASGYTFTSYGFSWVRQAPGQGLEWMGWISAYNGNT NYAQKFQDRVTMTTDSSTSTAYMELRSLRSDDTAVYSCARDRGFWRAYYVFDYWGQGT LVTVSS (SEQ ID NO: 387) CDR1 DNA Sequence GGT TAC ACC TTT ACC AGC TAT GGT (SEQ ID NO: 137) CDR1 Amino Acid Sequence G Y T F T S Y G (SEQ ID NO: 138) CDR2 DNA Sequence ATC AGC GCT TAC AAT GGT AAC ACA (SEQ ID NO: 318) CDR2 Amino Acid Sequence I S A Y N G N T (SEQ ID NO: 319) Attorney Docket No.250298.000780 CDR3 DNA Sequence GCG AGA GAT CGT GGA TTT TGG AGA GCC TAT TAT GTC TTT GAC TAC (SEQ ID NO: 388) CDR3 Amino Acid Sequence A R D R G F W R A Y Y V F D Y (SEQ ID NO: 389) LCVR DNA Sequence GATGTTGTGATGACTCAGTCTCCACTCTCCCTGCCCGTCACCCTTGGACAGCCGGCCT CCATCTCCTGCAGGTCTAGTCAAAGCCTCGTGTACAGTGATGGAAACAACTACTTGAAT TGGTTTCAGCGGAGGCCAGGCCAATCTCCAAGGCGCCTAATTTATAAGGTTTCTGATC GGGACTCTGGGGTCCCAGACAGATTCAGCGGCAGTGGGTCAGGCACTGATTTCACAC TGAAAATCAGCAGGGTGGAGGCTGAGGATGTTGGGGTTTATTACTGCATGCAATATAC ACACTGGCCGTACACTTTTGGCCAGGGGACCAAGCTGGAGATCAAA (SEQ ID NO: 390) LCVR Amino Acid Sequence DVVMTQSPLSLPVTLGQPASISCRSSQSLVYSDGNNYLNWFQRRPGQSPRRLIYKVSDRD SGVPDRFSGSGSGTDFTLKISRVEAEDVGVYYCMQYTHWPYTFGQGTKLEIK (SEQ ID NO: 391) CDR1 DNA Sequence CAA AGC CTC GTG TAC AGT GAT GGA AAC AAC TAC (SEQ ID NO: 392) CDR1 Amino Acid Sequence Q S L V Y S D G N N Y (SEQ ID NO: 393) CDR2 DNA Sequence AAG GTT TCT (SEQ ID NO: 360) Attorney Docket No.250298.000780 CDR2 Amino Acid Sequence K V S (SEQ ID NO: 361) CDR3 DNA Sequence ATG CAA TAT ACA CAC TGG CCG TAC ACT (SEQ ID NO: 394) CDR3 Amino Acid Sequence M Q Y T H W P Y T (SEQ ID NO: 395) HC DNA Sequence CAGGTTCAGCTGGTGCAGTCTGGACCTGAGGTGAAGAAGCCTGGGGCCTCAGTGAAG GTCTCCTGCAAGGCTTCTGGTTACACCTTTACCAGCTATGGTTTCAGTTGGGTGCGAC AGGCCCCTGGACAAGGGCTTGAGTGGATGGGATGGATCAGCGCTTACAATGGTAACA CAAACTATGCACAGAAGTTCCAGGACAGAGTCACCATGACCACAGACTCATCCACGAG CACAGCCTACATGGAGCTGAGGAGCCTGAGATCTGACGACACGGCCGTTTATTCCTGT GCGAGAGATCGTGGATTTTGGAGAGCCTATTATGTCTTTGACTACTGGGGCCAGGGAA CCCTGGTCACCGTCTCCTCAGCCTCCACCAAGGGCCCATCGGTCTTCCCCCTGGCGC CCTGCTCCAGGAGCACCTCCGAGAGCACAGCCGCCCTGGGCTGCCTGGTCAAGGACT ACTTCCCCGAACCGGTGACGGTGTCGTGGAACTCAGGCGCCCTGACCAGCGGCGTG CACACCTTCCCGGCTGTCCTACAGTCCTCAGGACTCTACTCCCTCAGCAGCGTGGTGA CCGTGCCCTCCAGCAGCTTGGGCACGAAGACCTACACCTGCAACGTAGATCACAAGC CCAGCAACACCAAGGTGGACAAGAGAGTTGAGTCCAAATATGGTCCCCCATGCCCAC CGTGCCCAGCACCACCTGTGGCAGGACCATCAGTCTTCCTGTTCCCCCCAAAACCCAA GGACACTCTCATGATCTCCCGGACCCCTGAGGTCACGTGCGTGGTGGTGGACGTGAG CCAGGAAGACCCCGAGGTCCAGTTCAACTGGTACGTGGATGGCGTGGAGGTGCATAA TGCCAAGACAAAGCCGCGGGAGGAGCAGTTCAACAGCACGTACCGTGTGGTCAGCGT CCTCACCGTCCTGCACCAGGACTGGCTGAACGGCAAGGAGTACAAGTGCAAGGTCTC CAACAAAGGCCTCCCGTCCTCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCC CCGAGAGCCACAGGTGTACACCCTGCCCCCATCCCAGGAGGAGATGACCAAGAACCA Attorney Docket No.250298.000780 GGTCAGCCTGACCTGCCTGGTCAAAGGCTTCTACCCCAGCGACATCGCCGTGGAGTG GGAGAGCAATGGGCAGCCGGAGAACAACTACAAGACCACGCCTCCCGTGCTGGACTC CGACGGCTCCTTCTTCCTCTACAGCAGGCTCACCGTGGACAAGAGCAGGTGGCAGGA GGGGAATGTCTTCTCATGCTCCGTGATGCATGAGGCTCTGCACAACCACTACACACAG AAGTCCCTCTCCCTGTCTCTGGGTAAATGA (SEQ ID NO: 396) HC Amino Acid Sequence QVQLVQSGPEVKKPGASVKVSCKASGYTFTSYGFSWVRQAPGQGLEWMGWISAYNGNT NYAQKFQDRVTMTTDSSTSTAYMELRSLRSDDTAVYSCARDRGFWRAYYVFDYWGQGT LVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPA VLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPPVA GPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQF NSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEE MTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRW QEGNVFSCSVMHEALHNHYTQKSLSLSLGK* (SEQ ID NO: 397) LC DNA Sequence GATGTTGTGATGACTCAGTCTCCACTCTCCCTGCCCGTCACCCTTGGACAGCCGGCCT CCATCTCCTGCAGGTCTAGTCAAAGCCTCGTGTACAGTGATGGAAACAACTACTTGAAT TGGTTTCAGCGGAGGCCAGGCCAATCTCCAAGGCGCCTAATTTATAAGGTTTCTGATC GGGACTCTGGGGTCCCAGACAGATTCAGCGGCAGTGGGTCAGGCACTGATTTCACAC TGAAAATCAGCAGGGTGGAGGCTGAGGATGTTGGGGTTTATTACTGCATGCAATATAC ACACTGGCCGTACACTTTTGGCCAGGGGACCAAGCTGGAGATCAAACGAACTGTGGC TGCACCATCTGTCTTCATCTTCCCGCCATCTGATGAGCAGTTGAAATCTGGAACTGCCT CTGTTGTGTGCCTGCTGAATAACTTCTATCCCAGAGAGGCCAAAGTACAGTGGAAGGT GGATAACGCCCTCCAATCGGGTAACTCCCAGGAGAGTGTCACAGAGCAGGACAGCAA GGACAGCACCTACAGCCTCAGCAGCACCCTGACGCTGAGCAAAGCAGACTACGAGAA ACACAAAGTCTACGCCTGCGAAGTCACCCATCAGGGCCTGAGCTCGCCCGTCACAAA GAGCTTCAACAGGGGAGAGTGTTAG (SEQ ID NO: 398) Attorney Docket No.250298.000780 LC Amino Acid Sequence DVVMTQSPLSLPVTLGQPASISCRSSQSLVYSDGNNYLNWFQRRPGQSPRRLIYKVSDRD SGVPDRFSGSGSGTDFTLKISRVEAEDVGVYYCMQYTHWPYTFGQGTKLEIKRTVAAPSV FIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSL SSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC* (SEQ ID NO: 399) REGN14179 HCVR DNA Sequence GAAGTGCAGCTGGTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGCAGGTCCCTGAG ACTCTCCTGTGCAGCCTCTGGATTCACCTTTGATGCTTATGCCATGCACTGGGTCCGT CAAGTTCCAGGAAAGGGCCTGCAGTGGGTCTCAGGTATTAGTTGGAATAGTGATAATA TAGACTATACGGACTCTGTGAAGGGCCGATTCACCATCTCCAGAGACAACGCCAAGAA CTCCCTGTATCTGCAAATGGACAGTCTGAGAGATGAGGACACGGCCTTGTATTTCTGT GCAAAAGATAGGGTTCGGGGAGTTCGTTACTACTACCACTACGGCATGGACGTCTGG GGCCAAGGGACCACGGTCACCGTCTCCTCA (SEQ ID NO: 400) HCVR Amino Acid Sequence EVQLVESGGGLVQPGRSLRLSCAASGFTFDAYAMHWVRQVPGKGLQWVSGISWNSDNI DYTDSVKGRFTISRDNAKNSLYLQMDSLRDEDTALYFCAKDRVRGVRYYYHYGMDVWGQ GTTVTVSS (SEQ ID NO: 401) CDR1 DNA Sequence GGA TTC ACC TTT GAT GCT TAT GCC (SEQ ID NO: 402) CDR1 Amino Acid Sequence G F T F D A Y A (SEQ ID NO: 403) CDR2 DNA Sequence Attorney Docket No.250298.000780 ATT AGT TGG AAT AGT GAT AAT ATA (SEQ ID NO: 404) CDR2 Amino Acid Sequence I S W N S D N I (SEQ ID NO: 405) CDR3 DNA Sequence GCA AAA GAT AGG GTT CGG GGA GTT CGT TAC TAC TAC CAC TAC GGC ATG GAC GTC (SEQ ID NO: 406) CDR3 Amino Acid Sequence A K D R V R G V R Y Y Y H Y G M D V (SEQ ID NO: 407) LCVR DNA Sequence GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACAGAGTCA CCATCACTTGCCGGGCAAGTCAGAGCATTAGCAGCTATTTAAATTGGTATCAGCAGAA ACCAGGGAAAGCCCCTAAGCTCCTGATCTATGCTGCATCCAGTTTGCAAAGTGGGGTC CCGTCAAGGTTCAGTGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGTC TGCAACCTGAAGATTTTGCAACTTACTACTGTCAACAGAGTTACAGTACCCCTCCGATC ACCTTCGGCCAAGGGACACGACTGGAGATTAAA (SEQ ID NO: 408) LCVR Amino Acid Sequence DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSR FSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPPITFGQGTRLEIK (SEQ ID NO: 409) CDR1 DNA Sequence CAG AGC ATT AGC AGC TAT (SEQ ID NO: 236) Attorney Docket No.250298.000780 CDR1 Amino Acid Sequence Q S I S S Y (SEQ ID NO: 237) CDR2 DNA Sequence GCT GCA TCC (SEQ ID NO: 13) CDR2 Amino Acid Sequence A A S (SEQ ID NO: 14) CDR3 DNA Sequence CAA CAG AGT TAC AGT ACC CCT CCG ATC ACC (SEQ ID NO: 410) CDR3 Amino Acid Sequence Q Q S Y S T P P I T (SEQ ID NO: 411) HC DNA Sequence GAAGTGCAGCTGGTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGCAGGTCCCTGAG ACTCTCCTGTGCAGCCTCTGGATTCACCTTTGATGCTTATGCCATGCACTGGGTCCGT CAAGTTCCAGGAAAGGGCCTGCAGTGGGTCTCAGGTATTAGTTGGAATAGTGATAATA TAGACTATACGGACTCTGTGAAGGGCCGATTCACCATCTCCAGAGACAACGCCAAGAA CTCCCTGTATCTGCAAATGGACAGTCTGAGAGATGAGGACACGGCCTTGTATTTCTGT GCAAAAGATAGGGTTCGGGGAGTTCGTTACTACTACCACTACGGCATGGACGTCTGG GGCCAAGGGACCACGGTCACCGTCTCCTCAGCCTCCACCAAGGGCCCATCGGTCTTC CCCCTGGCGCCCTGCTCCAGGAGCACCTCCGAGAGCACAGCCGCCCTGGGCTGCCT GGTCAAGGACTACTTCCCCGAACCGGTGACGGTGTCGTGGAACTCAGGCGCCCTGAC CAGCGGCGTGCACACCTTCCCGGCTGTCCTACAGTCCTCAGGACTCTACTCCCTCAG CAGCGTGGTGACCGTGCCCTCCAGCAGCTTGGGCACGAAGACCTACACCTGCAACGT Attorney Docket No.250298.000780 AGATCACAAGCCCAGCAACACCAAGGTGGACAAGAGAGTTGAGTCCAAATATGGTCCC CCATGCCCACCGTGCCCAGCACCACCTGTGGCAGGACCATCAGTCTTCCTGTTCCCC CCAAAACCCAAGGACACTCTCATGATCTCCCGGACCCCTGAGGTCACGTGCGTGGTG GTGGACGTGAGCCAGGAAGACCCCGAGGTCCAGTTCAACTGGTACGTGGATGGCGTG GAGGTGCATAATGCCAAGACAAAGCCGCGGGAGGAGCAGTTCAACAGCACGTACCGT GTGGTCAGCGTCCTCACCGTCCTGCACCAGGACTGGCTGAACGGCAAGGAGTACAAG TGCAAGGTCTCCAACAAAGGCCTCCCGTCCTCCATCGAGAAAACCATCTCCAAAGCCA AAGGGCAGCCCCGAGAGCCACAGGTGTACACCCTGCCCCCATCCCAGGAGGAGATG ACCAAGAACCAGGTCAGCCTGACCTGCCTGGTCAAAGGCTTCTACCCCAGCGACATC GCCGTGGAGTGGGAGAGCAATGGGCAGCCGGAGAACAACTACAAGACCACGCCTCC CGTGCTGGACTCCGACGGCTCCTTCTTCCTCTACAGCAGGCTCACCGTGGACAAGAG CAGGTGGCAGGAGGGGAATGTCTTCTCATGCTCCGTGATGCATGAGGCTCTGCACAA CCACTACACACAGAAGTCCCTCTCCCTGTCTCTGGGTAAATGA (SEQ ID NO: 412) HC Amino Acid Sequence EVQLVESGGGLVQPGRSLRLSCAASGFTFDAYAMHWVRQVPGKGLQWVSGISWNSDNI DYTDSVKGRFTISRDNAKNSLYLQMDSLRDEDTALYFCAKDRVRGVRYYYHYGMDVWGQ GTTVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHT FPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAP PVAGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPRE EQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPS QEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDK SRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGK* (SEQ ID NO: 413) LC DNA Sequence GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACAGAGTCA CCATCACTTGCCGGGCAAGTCAGAGCATTAGCAGCTATTTAAATTGGTATCAGCAGAA ACCAGGGAAAGCCCCTAAGCTCCTGATCTATGCTGCATCCAGTTTGCAAAGTGGGGTC CCGTCAAGGTTCAGTGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGTC TGCAACCTGAAGATTTTGCAACTTACTACTGTCAACAGAGTTACAGTACCCCTCCGATC ACCTTCGGCCAAGGGACACGACTGGAGATTAAACGAACTGTGGCTGCACCATCTGTCT Attorney Docket No.250298.000780 TCATCTTCCCGCCATCTGATGAGCAGTTGAAATCTGGAACTGCCTCTGTTGTGTGCCT GCTGAATAACTTCTATCCCAGAGAGGCCAAAGTACAGTGGAAGGTGGATAACGCCCTC CAATCGGGTAACTCCCAGGAGAGTGTCACAGAGCAGGACAGCAAGGACAGCACCTAC AGCCTCAGCAGCACCCTGACGCTGAGCAAAGCAGACTACGAGAAACACAAAGTCTAC GCCTGCGAAGTCACCCATCAGGGCCTGAGCTCGCCCGTCACAAAGAGCTTCAACAGG GGAGAGTGTTAG (SEQ ID NO: 414) LC Amino Acid Sequence DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSR FSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPPITFGQGTRLEIKRTVAAPSVFIFPPSDE QLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSK ADYEKHKVYACEVTHQGLSSPVTKSFNRGEC* (SEQ ID NO: 415) REGN14180 HCVR DNA Sequence GAGGTGCAGCTGGTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGAG ACTCTCCTGTACAGCCTCTGGATTCACCTTTAGCAGCTTTGTCATGAGCTGGGTCCGC CAGGCTCCAGGGAAGGGACTGGAGTGGGTCTCAGCTATTCGGGATACTGGTGATAAC ACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCAGAGACAATTCCAAGA ACACGCTGTATCTGCAAATGAACAGCCTGAGAACCGAGGACACGGCCGTAATTTACTG TGCGAGAGGGGGGAGAACTAGAATTCCGTTTGACTACTGGGGCCAGGGAACCCTGGT CACCGTCTCCTCA (SEQ ID NO: 416) HCVR Amino Acid Sequence EVQLVESGGGLVQPGGSLRLSCTASGFTFSSFVMSWVRQAPGKGLEWVSAIRDTGDNTY YADSVKGRFTISRDNSKNTLYLQMNSLRTEDTAVIYCARGGRTRIPFDYWGQGTLVTVSS (SEQ ID NO: 417) CDR1 DNA Sequence GGA TTC ACC TTT AGC AGC TTT GTC Attorney Docket No.250298.000780 (SEQ ID NO: 418) CDR1 Amino Acid Sequence G F T F S S F V (SEQ ID NO: 419) CDR2 DNA Sequence ATT CGG GAT ACT GGT GAT AAC ACA (SEQ ID NO: 420) CDR2 Amino Acid Sequence I R D T G D N T (SEQ ID NO: 421) CDR3 DNA Sequence GCG AGA GGG GGG AGA ACT AGA ATT CCG TTT GAC TAC (SEQ ID NO: 422) CDR3 Amino Acid Sequence A R G G R T R I P F D Y (SEQ ID NO: 423) LCVR DNA Sequence GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACAGAGTCA CCATCACTTGCCGGGCAAGTCAGAGCATTAGCAGCTATTTAAATTGGTATCAGCAGAA ACCAGGGAAAGCCCCTAAGCTCCTGATCTATGCTGCATCCAGTTTGCAAAGTGGGGTC CCGTCAAGGTTCAGTGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGTC TGCAACCTGAAGATTTTGCAACTTACTACTGTCAACAGAGTTACAGTACCCCTCCGATC ACCTTCGGCCAAGGGACACGACTGGAGATTAAA (SEQ ID NO: 408) LCVR Amino Acid Sequence Attorney Docket No.250298.000780 DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSR FSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPPITFGQGTRLEIK (SEQ ID NO: 409) CDR1 DNA Sequence CAG AGC ATT AGC AGC TAT (SEQ ID NO: 236) CDR1 Amino Acid Sequence Q S I S S Y (SEQ ID NO: 237) CDR2 DNA Sequence GCT GCA TCC (SEQ ID NO: 13) CDR2 Amino Acid Sequence A A S (SEQ ID NO: 14) CDR3 DNA Sequence CAA CAG AGT TAC AGT ACC CCT CCG ATC ACC (SEQ ID NO: 410) CDR3 Amino Acid Sequence Q Q S Y S T P P I T (SEQ ID NO: 411) HC DNA Sequence GAGGTGCAGCTGGTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGAG ACTCTCCTGTACAGCCTCTGGATTCACCTTTAGCAGCTTTGTCATGAGCTGGGTCCGC CAGGCTCCAGGGAAGGGACTGGAGTGGGTCTCAGCTATTCGGGATACTGGTGATAAC ACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCAGAGACAATTCCAAGA Attorney Docket No.250298.000780 ACACGCTGTATCTGCAAATGAACAGCCTGAGAACCGAGGACACGGCCGTAATTTACTG TGCGAGAGGGGGGAGAACTAGAATTCCGTTTGACTACTGGGGCCAGGGAACCCTGGT CACCGTCTCCTCAGCCTCCACCAAGGGCCCATCGGTCTTCCCCCTGGCGCCCTGCTC CAGGAGCACCTCCGAGAGCACAGCCGCCCTGGGCTGCCTGGTCAAGGACTACTTCCC CGAACCGGTGACGGTGTCGTGGAACTCAGGCGCCCTGACCAGCGGCGTGCACACCTT CCCGGCTGTCCTACAGTCCTCAGGACTCTACTCCCTCAGCAGCGTGGTGACCGTGCC CTCCAGCAGCTTGGGCACGAAGACCTACACCTGCAACGTAGATCACAAGCCCAGCAA CACCAAGGTGGACAAGAGAGTTGAGTCCAAATATGGTCCCCCATGCCCACCGTGCCC AGCACCACCTGTGGCAGGACCATCAGTCTTCCTGTTCCCCCCAAAACCCAAGGACACT CTCATGATCTCCCGGACCCCTGAGGTCACGTGCGTGGTGGTGGACGTGAGCCAGGAA GACCCCGAGGTCCAGTTCAACTGGTACGTGGATGGCGTGGAGGTGCATAATGCCAAG ACAAAGCCGCGGGAGGAGCAGTTCAACAGCACGTACCGTGTGGTCAGCGTCCTCACC GTCCTGCACCAGGACTGGCTGAACGGCAAGGAGTACAAGTGCAAGGTCTCCAACAAA GGCCTCCCGTCCTCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGAGAG CCACAGGTGTACACCCTGCCCCCATCCCAGGAGGAGATGACCAAGAACCAGGTCAGC CTGACCTGCCTGGTCAAAGGCTTCTACCCCAGCGACATCGCCGTGGAGTGGGAGAGC AATGGGCAGCCGGAGAACAACTACAAGACCACGCCTCCCGTGCTGGACTCCGACGGC TCCTTCTTCCTCTACAGCAGGCTCACCGTGGACAAGAGCAGGTGGCAGGAGGGGAAT GTCTTCTCATGCTCCGTGATGCATGAGGCTCTGCACAACCACTACACACAGAAGTCCC TCTCCCTGTCTCTGGGTAAATGA (SEQ ID NO: 424) HC Amino Acid Sequence EVQLVESGGGLVQPGGSLRLSCTASGFTFSSFVMSWVRQAPGKGLEWVSAIRDTGDNTY YADSVKGRFTISRDNSKNTLYLQMNSLRTEDTAVIYCARGGRTRIPFDYWGQGTLVTVSSA STKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSG LYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPPVAGPSVFLF PPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVV SVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQV SLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVF SCSVMHEALHNHYTQKSLSLSLGK* (SEQ ID NO: 425) Attorney Docket No.250298.000780 LC DNA Sequence GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACAGAGTCA CCATCACTTGCCGGGCAAGTCAGAGCATTAGCAGCTATTTAAATTGGTATCAGCAGAA ACCAGGGAAAGCCCCTAAGCTCCTGATCTATGCTGCATCCAGTTTGCAAAGTGGGGTC CCGTCAAGGTTCAGTGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGTC TGCAACCTGAAGATTTTGCAACTTACTACTGTCAACAGAGTTACAGTACCCCTCCGATC ACCTTCGGCCAAGGGACACGACTGGAGATTAAACGAACTGTGGCTGCACCATCTGTCT TCATCTTCCCGCCATCTGATGAGCAGTTGAAATCTGGAACTGCCTCTGTTGTGTGCCT GCTGAATAACTTCTATCCCAGAGAGGCCAAAGTACAGTGGAAGGTGGATAACGCCCTC CAATCGGGTAACTCCCAGGAGAGTGTCACAGAGCAGGACAGCAAGGACAGCACCTAC AGCCTCAGCAGCACCCTGACGCTGAGCAAAGCAGACTACGAGAAACACAAAGTCTAC GCCTGCGAAGTCACCCATCAGGGCCTGAGCTCGCCCGTCACAAAGAGCTTCAACAGG GGAGAGTGTTAG (SEQ ID NO: 414) LC Amino Acid Sequence DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSR FSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPPITFGQGTRLEIKRTVAAPSVFIFPPSDE QLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSK ADYEKHKVYACEVTHQGLSSPVTKSFNRGEC* (SEQ ID NO: 415) REGN14181 HCVR DNA Sequence CAGGTGCAGCTGGTGGAGTCTGGGGGAGGCGTGGTCCAGCCTGGGAGGTCCCTGAG ACTCTCCTGTGCAGCCTCTGGATTCATCTTCAGTAACTATGGCATGCACTGGGTCCGC CAGGCTCCAGGCAAGGGGCTGGAGTGGGTGGCAATTATATCTTTTGATGGAAATAATA AATACTATGCAGACTCCGTGAAGCGCCGATTCACCATCTCCAGAGACAATTTCAAGAG CACGCTGTATCTGCAATTGAACAGCCTGACAATTGAGGACACGGCTGTATATTTCTGTG CGAAAGAGTTTAGCAGGCGGAATTTCTTTGACCACTGGGGCCAGGGAACCCTGGTCA CCGTCTCCTCA (SEQ ID NO: 426) Attorney Docket No.250298.000780 HCVR Amino Acid Sequence QVQLVESGGGVVQPGRSLRLSCAASGFIFSNYGMHWVRQAPGKGLEWVAIISFDGNNKY YADSVKRRFTISRDNFKSTLYLQLNSLTIEDTAVYFCAKEFSRRNFFDHWGQGTLVTVSS (SEQ ID NO: 427) CDR1 DNA Sequence GGA TTC ATC TTC AGT AAC TAT GGC (SEQ ID NO: 428) CDR1 Amino Acid Sequence G F I F S N Y G (SEQ ID NO: 429) CDR2 DNA Sequence ATA TCT TTT GAT GGA AAT AAT AAA (SEQ ID NO: 430) CDR2 Amino Acid Sequence I S F D G N N K (SEQ ID NO: 431) CDR3 DNA Sequence GCG AAA GAG TTT AGC AGG CGG AAT TTC TTT GAC CAC (SEQ ID NO: 432) CDR3 Amino Acid Sequence A K E F S R R N F F D H (SEQ ID NO: 433) LCVR DNA Sequence GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACAGAGTCA CCATCACTTGCCGGGCAAGTCAGAGCATTAGCAGCTATTTAAATTGGTATCAGCAGAA ACCAGGGAAAGCCCCTAAGCTCCTGATCTATGCTGCATCCAGTTTGCAAAGTGGGGTC Attorney Docket No.250298.000780 CCGTCAAGGTTCAGTGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGTC TGCAACCTGAAGATTTTGCAACTTACTACTGTCAACAGAGTTACAGTACCCCTCCGATC ACCTTCGGCCAAGGGACACGACTGGAGATTAAA (SEQ ID NO: 408) LCVR Amino Acid Sequence DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSR FSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPPITFGQGTRLEIK (SEQ ID NO: 409) CDR1 DNA Sequence CAG AGC ATT AGC AGC TAT (SEQ ID NO: 236) CDR1 Amino Acid Sequence Q S I S S Y (SEQ ID NO: 237) CDR2 DNA Sequence GCT GCA TCC (SEQ ID NO: 13) CDR2 Amino Acid Sequence A A S (SEQ ID NO: 14) CDR3 DNA Sequence CAA CAG AGT TAC AGT ACC CCT CCG ATC ACC (SEQ ID NO: 410) CDR3 Amino Acid Sequence Q Q S Y S T P P I T (SEQ ID NO: 411) Attorney Docket No.250298.000780 HC DNA Sequence CAGGTGCAGCTGGTGGAGTCTGGGGGAGGCGTGGTCCAGCCTGGGAGGTCCCTGAG ACTCTCCTGTGCAGCCTCTGGATTCATCTTCAGTAACTATGGCATGCACTGGGTCCGC CAGGCTCCAGGCAAGGGGCTGGAGTGGGTGGCAATTATATCTTTTGATGGAAATAATA AATACTATGCAGACTCCGTGAAGCGCCGATTCACCATCTCCAGAGACAATTTCAAGAG CACGCTGTATCTGCAATTGAACAGCCTGACAATTGAGGACACGGCTGTATATTTCTGTG CGAAAGAGTTTAGCAGGCGGAATTTCTTTGACCACTGGGGCCAGGGAACCCTGGTCA CCGTCTCCTCAGCCTCCACCAAGGGCCCATCGGTCTTCCCCCTGGCGCCCTGCTCCA GGAGCACCTCCGAGAGCACAGCCGCCCTGGGCTGCCTGGTCAAGGACTACTTCCCCG AACCGGTGACGGTGTCGTGGAACTCAGGCGCCCTGACCAGCGGCGTGCACACCTTCC CGGCTGTCCTACAGTCCTCAGGACTCTACTCCCTCAGCAGCGTGGTGACCGTGCCCT CCAGCAGCTTGGGCACGAAGACCTACACCTGCAACGTAGATCACAAGCCCAGCAACA CCAAGGTGGACAAGAGAGTTGAGTCCAAATATGGTCCCCCATGCCCACCGTGCCCAG CACCACCTGTGGCAGGACCATCAGTCTTCCTGTTCCCCCCAAAACCCAAGGACACTCT CATGATCTCCCGGACCCCTGAGGTCACGTGCGTGGTGGTGGACGTGAGCCAGGAAGA CCCCGAGGTCCAGTTCAACTGGTACGTGGATGGCGTGGAGGTGCATAATGCCAAGAC AAAGCCGCGGGAGGAGCAGTTCAACAGCACGTACCGTGTGGTCAGCGTCCTCACCGT CCTGCACCAGGACTGGCTGAACGGCAAGGAGTACAAGTGCAAGGTCTCCAACAAAGG CCTCCCGTCCTCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGAGAGCC ACAGGTGTACACCCTGCCCCCATCCCAGGAGGAGATGACCAAGAACCAGGTCAGCCT GACCTGCCTGGTCAAAGGCTTCTACCCCAGCGACATCGCCGTGGAGTGGGAGAGCAA TGGGCAGCCGGAGAACAACTACAAGACCACGCCTCCCGTGCTGGACTCCGACGGCTC CTTCTTCCTCTACAGCAGGCTCACCGTGGACAAGAGCAGGTGGCAGGAGGGGAATGT CTTCTCATGCTCCGTGATGCATGAGGCTCTGCACAACCACTACACACAGAAGTCCCTC TCCCTGTCTCTGGGTAAATGA (SEQ ID NO: 434) HC Amino Acid Sequence QVQLVESGGGVVQPGRSLRLSCAASGFIFSNYGMHWVRQAPGKGLEWVAIISFDGNNKY YADSVKRRFTISRDNFKSTLYLQLNSLTIEDTAVYFCAKEFSRRNFFDHWGQGTLVTVSSA STKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSG LYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPPVAGPSVFLF Attorney Docket No.250298.000780 PPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVV SVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQV SLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVF SCSVMHEALHNHYTQKSLSLSLGK* (SEQ ID NO: 435) LC DNA Sequence GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACAGAGTCA CCATCACTTGCCGGGCAAGTCAGAGCATTAGCAGCTATTTAAATTGGTATCAGCAGAA ACCAGGGAAAGCCCCTAAGCTCCTGATCTATGCTGCATCCAGTTTGCAAAGTGGGGTC CCGTCAAGGTTCAGTGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGTC TGCAACCTGAAGATTTTGCAACTTACTACTGTCAACAGAGTTACAGTACCCCTCCGATC ACCTTCGGCCAAGGGACACGACTGGAGATTAAACGAACTGTGGCTGCACCATCTGTCT TCATCTTCCCGCCATCTGATGAGCAGTTGAAATCTGGAACTGCCTCTGTTGTGTGCCT GCTGAATAACTTCTATCCCAGAGAGGCCAAAGTACAGTGGAAGGTGGATAACGCCCTC CAATCGGGTAACTCCCAGGAGAGTGTCACAGAGCAGGACAGCAAGGACAGCACCTAC AGCCTCAGCAGCACCCTGACGCTGAGCAAAGCAGACTACGAGAAACACAAAGTCTAC GCCTGCGAAGTCACCCATCAGGGCCTGAGCTCGCCCGTCACAAAGAGCTTCAACAGG GGAGAGTGTTAG (SEQ ID NO: 414) LC Amino Acid Sequence DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSR FSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPPITFGQGTRLEIKRTVAAPSVFIFPPSDE QLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSK ADYEKHKVYACEVTHQGLSSPVTKSFNRGEC* (SEQ ID NO: 415) REGN14182 HCVR DNA Sequence CAGGTGCAGCTGGTGGAGTCTGGGGGAGGCGTGGTCCAGCCTGGGAGGTCCCTGAG ACTCTCCTGTGCAGCCTCTGGATTCACCTTCAGTCATTATGGCATGCACTGGGTCCGC CAGGCTCCAGGCAAGGGGCTGGAGTGGATGGCTATCATCTCATATGACGGAAGTGAT Attorney Docket No.250298.000780 AAATACTATGCAGACTCCGTGAAGGGCCGATTCACCATCTCCAGAGACAATTCCGAGA ACACACTATATCTGCAAATGAGCAGCCTGAGAACTGAAGACACGGCTGTGTATTACTG TGCGAAAGCCAGTATAACTGGAACTTACTACTTCTTCTACGGTATGGACGTCTGGGGC CAAGGGACCACGGTCACCGTCTCCTCA (SEQ ID NO: 436) HCVR Amino Acid Sequence QVQLVESGGGVVQPGRSLRLSCAASGFTFSHYGMHWVRQAPGKGLEWMAIISYDGSDK YYADSVKGRFTISRDNSENTLYLQMSSLRTEDTAVYYCAKASITGTYYFFYGMDVWGQGT TVTVSS (SEQ ID NO: 437) CDR1 DNA Sequence GGA TTC ACC TTC AGT CAT TAT GGC (SEQ ID NO: 438) CDR1 Amino Acid Sequence G F T F S H Y G (SEQ ID NO: 191) CDR2 DNA Sequence ATC TCA TAT GAC GGA AGT GAT AAA (SEQ ID NO: 439) CDR2 Amino Acid Sequence I S Y D G S D K (SEQ ID NO: 335) CDR3 DNA Sequence GCG AAA GCC AGT ATA ACT GGA ACT TAC TAC TTC TTC TAC GGT ATG GAC GTC (SEQ ID NO: 440) CDR3 Amino Acid Sequence Attorney Docket No.250298.000780 A K A S I T G T Y Y F F Y G M D V (SEQ ID NO: 441) LCVR DNA Sequence GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACAGAGTCA CCATCACTTGCCGGGCAAGTCAGAGCATTAGCAGCTATTTAAATTGGTATCAGCAGAA ACCAGGGAAAGCCCCTAAGCTCCTGATCTATGCTGCATCCAGTTTGCAAAGTGGGGTC CCGTCAAGGTTCAGTGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGTC TGCAACCTGAAGATTTTGCAACTTACTACTGTCAACAGAGTTACAGTACCCCTCCGATC ACCTTCGGCCAAGGGACACGACTGGAGATTAAA (SEQ ID NO: 408) LCVR Amino Acid Sequence DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSR FSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPPITFGQGTRLEIK (SEQ ID NO: 409) CDR1 DNA Sequence CAG AGC ATT AGC AGC TAT (SEQ ID NO: 236) CDR1 Amino Acid Sequence Q S I S S Y (SEQ ID NO: 237) CDR2 DNA Sequence GCT GCA TCC (SEQ ID NO: 13) CDR2 Amino Acid Sequence A A S (SEQ ID NO: 14) Attorney Docket No.250298.000780 CDR3 DNA Sequence CAA CAG AGT TAC AGT ACC CCT CCG ATC ACC (SEQ ID NO: 410) CDR3 Amino Acid Sequence Q Q S Y S T P P I T (SEQ ID NO: 411) HC DNA Sequence CAGGTGCAGCTGGTGGAGTCTGGGGGAGGCGTGGTCCAGCCTGGGAGGTCCCTGAG ACTCTCCTGTGCAGCCTCTGGATTCACCTTCAGTCATTATGGCATGCACTGGGTCCGC CAGGCTCCAGGCAAGGGGCTGGAGTGGATGGCTATCATCTCATATGACGGAAGTGAT AAATACTATGCAGACTCCGTGAAGGGCCGATTCACCATCTCCAGAGACAATTCCGAGA ACACACTATATCTGCAAATGAGCAGCCTGAGAACTGAAGACACGGCTGTGTATTACTG TGCGAAAGCCAGTATAACTGGAACTTACTACTTCTTCTACGGTATGGACGTCTGGGGC CAAGGGACCACGGTCACCGTCTCCTCAGCCTCCACCAAGGGCCCATCGGTCTTCCCC CTGGCGCCCTGCTCCAGGAGCACCTCCGAGAGCACAGCCGCCCTGGGCTGCCTGGT CAAGGACTACTTCCCCGAACCGGTGACGGTGTCGTGGAACTCAGGCGCCCTGACCAG CGGCGTGCACACCTTCCCGGCTGTCCTACAGTCCTCAGGACTCTACTCCCTCAGCAG CGTGGTGACCGTGCCCTCCAGCAGCTTGGGCACGAAGACCTACACCTGCAACGTAGA TCACAAGCCCAGCAACACCAAGGTGGACAAGAGAGTTGAGTCCAAATATGGTCCCCCA TGCCCACCGTGCCCAGCACCACCTGTGGCAGGACCATCAGTCTTCCTGTTCCCCCCA AAACCCAAGGACACTCTCATGATCTCCCGGACCCCTGAGGTCACGTGCGTGGTGGTG GACGTGAGCCAGGAAGACCCCGAGGTCCAGTTCAACTGGTACGTGGATGGCGTGGAG GTGCATAATGCCAAGACAAAGCCGCGGGAGGAGCAGTTCAACAGCACGTACCGTGTG GTCAGCGTCCTCACCGTCCTGCACCAGGACTGGCTGAACGGCAAGGAGTACAAGTGC AAGGTCTCCAACAAAGGCCTCCCGTCCTCCATCGAGAAAACCATCTCCAAAGCCAAAG GGCAGCCCCGAGAGCCACAGGTGTACACCCTGCCCCCATCCCAGGAGGAGATGACC AAGAACCAGGTCAGCCTGACCTGCCTGGTCAAAGGCTTCTACCCCAGCGACATCGCC GTGGAGTGGGAGAGCAATGGGCAGCCGGAGAACAACTACAAGACCACGCCTCCCGT GCTGGACTCCGACGGCTCCTTCTTCCTCTACAGCAGGCTCACCGTGGACAAGAGCAG GTGGCAGGAGGGGAATGTCTTCTCATGCTCCGTGATGCATGAGGCTCTGCACAACCA CTACACACAGAAGTCCCTCTCCCTGTCTCTGGGTAAATGA Attorney Docket No.250298.000780 (SEQ ID NO: 442) HC Amino Acid Sequence QVQLVESGGGVVQPGRSLRLSCAASGFTFSHYGMHWVRQAPGKGLEWMAIISYDGSDK YYADSVKGRFTISRDNSENTLYLQMSSLRTEDTAVYYCAKASITGTYYFFYGMDVWGQGT TVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPA VLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPPVA GPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQF NSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEE MTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRW QEGNVFSCSVMHEALHNHYTQKSLSLSLGK* (SEQ ID NO: 443) LC DNA Sequence GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACAGAGTCA CCATCACTTGCCGGGCAAGTCAGAGCATTAGCAGCTATTTAAATTGGTATCAGCAGAA ACCAGGGAAAGCCCCTAAGCTCCTGATCTATGCTGCATCCAGTTTGCAAAGTGGGGTC CCGTCAAGGTTCAGTGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGTC TGCAACCTGAAGATTTTGCAACTTACTACTGTCAACAGAGTTACAGTACCCCTCCGATC ACCTTCGGCCAAGGGACACGACTGGAGATTAAACGAACTGTGGCTGCACCATCTGTCT TCATCTTCCCGCCATCTGATGAGCAGTTGAAATCTGGAACTGCCTCTGTTGTGTGCCT GCTGAATAACTTCTATCCCAGAGAGGCCAAAGTACAGTGGAAGGTGGATAACGCCCTC CAATCGGGTAACTCCCAGGAGAGTGTCACAGAGCAGGACAGCAAGGACAGCACCTAC AGCCTCAGCAGCACCCTGACGCTGAGCAAAGCAGACTACGAGAAACACAAAGTCTAC GCCTGCGAAGTCACCCATCAGGGCCTGAGCTCGCCCGTCACAAAGAGCTTCAACAGG GGAGAGTGTTAG (SEQ ID NO: 414) LC Amino Acid Sequence DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSR FSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPPITFGQGTRLEIKRTVAAPSVFIFPPSDE QLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSK ADYEKHKVYACEVTHQGLSSPVTKSFNRGEC* Attorney Docket No.250298.000780 (SEQ ID NO: 415) REGN14183 HCVR DNA Sequence GAGGTGCAGCTGGTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGAG ACTCTCCTGTGCAGTCTCTGGATTCACCTTTAGCAGCTATGTCATGAGCTGGGTCCGC CAGGCTCCAGGGAAGGGGCTGGAGTGGGTCTCAGCTATTAGTGATAGTGGTGGTAAC ACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCAGAGACAATTCCAAGA ACACGCTGTATCTGCAAATGAACAGCCAGAGAGCCGAGGACACGGCCGTGTATTATTG TGCGAAGGGGGGGCGCAGCAGGTTCCCTTTTGACTACTGGGGCCAGGGAACCCTGG TCACCGTCTCCTCA (SEQ ID NO: 444) HCVR Amino Acid Sequence EVQLVESGGGLVQPGGSLRLSCAVSGFTFSSYVMSWVRQAPGKGLEWVSAISDSGGNTY YADSVKGRFTISRDNSKNTLYLQMNSQRAEDTAVYYCAKGGRSRFPFDYWGQGTLVTVS S (SEQ ID NO: 445) CDR1 DNA Sequence GGA TTC ACC TTT AGC AGC TAT GTC (SEQ ID NO: 446) CDR1 Amino Acid Sequence G F T F S S Y V (SEQ ID NO: 447) CDR2 DNA Sequence ATT AGT GAT AGT GGT GGT AAC ACA (SEQ ID NO: 448) CDR2 Amino Acid Sequence I S D S G G N T Attorney Docket No.250298.000780 (SEQ ID NO: 449) CDR3 DNA Sequence GCG AAG GGG GGG CGC AGC AGG TTC CCT TTT GAC TAC (SEQ ID NO: 450) CDR3 Amino Acid Sequence A K G G R S R F P F D Y (SEQ ID NO: 451) LCVR DNA Sequence GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACAGAGTCA CCATCACTTGCCGGGCAAGTCAGAGCATTAGCAGCTATTTAAATTGGTATCAGCAGAA ACCAGGGAAAGCCCCTAAGCTCCTGATCTATGCTGCATCCAGTTTGCAAAGTGGGGTC CCGTCAAGGTTCAGTGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGTC TGCAACCTGAAGATTTTGCAACTTACTACTGTCAACAGAGTTACAGTACCCCTCCGATC ACCTTCGGCCAAGGGACACGACTGGAGATTAAA (SEQ ID NO: 408) LCVR Amino Acid Sequence DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSR FSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPPITFGQGTRLEIK (SEQ ID NO: 409) CDR1 DNA Sequence CAG AGC ATT AGC AGC TAT (SEQ ID NO: 236) CDR1 Amino Acid Sequence Q S I S S Y (SEQ ID NO: 237) CDR2 DNA Sequence Attorney Docket No.250298.000780 GCT GCA TCC (SEQ ID NO: 13) CDR2 Amino Acid Sequence A A S (SEQ ID NO: 14) CDR3 DNA Sequence CAA CAG AGT TAC AGT ACC CCT CCG ATC ACC (SEQ ID NO: 410) CDR3 Amino Acid Sequence Q Q S Y S T P P I T (SEQ ID NO: 411) HC DNA Sequence GAGGTGCAGCTGGTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGAG ACTCTCCTGTGCAGTCTCTGGATTCACCTTTAGCAGCTATGTCATGAGCTGGGTCCGC CAGGCTCCAGGGAAGGGGCTGGAGTGGGTCTCAGCTATTAGTGATAGTGGTGGTAAC ACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCAGAGACAATTCCAAGA ACACGCTGTATCTGCAAATGAACAGCCAGAGAGCCGAGGACACGGCCGTGTATTATTG TGCGAAGGGGGGGCGCAGCAGGTTCCCTTTTGACTACTGGGGCCAGGGAACCCTGG TCACCGTCTCCTCAGCCTCCACCAAGGGCCCATCGGTCTTCCCCCTGGCGCCCTGCT CCAGGAGCACCTCCGAGAGCACAGCCGCCCTGGGCTGCCTGGTCAAGGACTACTTCC CCGAACCGGTGACGGTGTCGTGGAACTCAGGCGCCCTGACCAGCGGCGTGCACACC TTCCCGGCTGTCCTACAGTCCTCAGGACTCTACTCCCTCAGCAGCGTGGTGACCGTGC CCTCCAGCAGCTTGGGCACGAAGACCTACACCTGCAACGTAGATCACAAGCCCAGCA ACACCAAGGTGGACAAGAGAGTTGAGTCCAAATATGGTCCCCCATGCCCACCGTGCC CAGCACCACCTGTGGCAGGACCATCAGTCTTCCTGTTCCCCCCAAAACCCAAGGACAC TCTCATGATCTCCCGGACCCCTGAGGTCACGTGCGTGGTGGTGGACGTGAGCCAGGA AGACCCCGAGGTCCAGTTCAACTGGTACGTGGATGGCGTGGAGGTGCATAATGCCAA GACAAAGCCGCGGGAGGAGCAGTTCAACAGCACGTACCGTGTGGTCAGCGTCCTCAC CGTCCTGCACCAGGACTGGCTGAACGGCAAGGAGTACAAGTGCAAGGTCTCCAACAA Attorney Docket No.250298.000780 AGGCCTCCCGTCCTCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGAGA GCCACAGGTGTACACCCTGCCCCCATCCCAGGAGGAGATGACCAAGAACCAGGTCAG CCTGACCTGCCTGGTCAAAGGCTTCTACCCCAGCGACATCGCCGTGGAGTGGGAGAG CAATGGGCAGCCGGAGAACAACTACAAGACCACGCCTCCCGTGCTGGACTCCGACGG CTCCTTCTTCCTCTACAGCAGGCTCACCGTGGACAAGAGCAGGTGGCAGGAGGGGAA TGTCTTCTCATGCTCCGTGATGCATGAGGCTCTGCACAACCACTACACACAGAAGTCC CTCTCCCTGTCTCTGGGTAAATGA (SEQ ID NO: 452) HC Amino Acid Sequence EVQLVESGGGLVQPGGSLRLSCAVSGFTFSSYVMSWVRQAPGKGLEWVSAISDSGGNTY YADSVKGRFTISRDNSKNTLYLQMNSQRAEDTAVYYCAKGGRSRFPFDYWGQGTLVTVS SASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQS SGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPPVAGPSV FLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTY RVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTK NQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEG NVFSCSVMHEALHNHYTQKSLSLSLGK* (SEQ ID NO: 453) LC DNA Sequence GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACAGAGTCA CCATCACTTGCCGGGCAAGTCAGAGCATTAGCAGCTATTTAAATTGGTATCAGCAGAA ACCAGGGAAAGCCCCTAAGCTCCTGATCTATGCTGCATCCAGTTTGCAAAGTGGGGTC CCGTCAAGGTTCAGTGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGTC TGCAACCTGAAGATTTTGCAACTTACTACTGTCAACAGAGTTACAGTACCCCTCCGATC ACCTTCGGCCAAGGGACACGACTGGAGATTAAACGAACTGTGGCTGCACCATCTGTCT TCATCTTCCCGCCATCTGATGAGCAGTTGAAATCTGGAACTGCCTCTGTTGTGTGCCT GCTGAATAACTTCTATCCCAGAGAGGCCAAAGTACAGTGGAAGGTGGATAACGCCCTC CAATCGGGTAACTCCCAGGAGAGTGTCACAGAGCAGGACAGCAAGGACAGCACCTAC AGCCTCAGCAGCACCCTGACGCTGAGCAAAGCAGACTACGAGAAACACAAAGTCTAC GCCTGCGAAGTCACCCATCAGGGCCTGAGCTCGCCCGTCACAAAGAGCTTCAACAGG GGAGAGTGTTAG Attorney Docket No.250298.000780 (SEQ ID NO: 414) LC Amino Acid Sequence DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSR FSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPPITFGQGTRLEIKRTVAAPSVFIFPPSDE QLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSK ADYEKHKVYACEVTHQGLSSPVTKSFNRGEC* (SEQ ID NO: 415) REGN14184 HCVR DNA Sequence GAGGTGCAGCTGGTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGAG ACTCTCCTGTGCAGCCTCTAAATTCATCTTTAGCAACTATGCCATGACCTGGGTCCGCC AGGCTCCAGGGAAGGGGCTGGAATGGGTCTCAATTATTAGTGGTAGTGGTGGAAATTC ATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCAGAGACAATTCCAAGAAC ACGCTATATCTGCAAATGAACAGCCTGAGAGCCGAGGACACGGCCGTTTATTACTGTG CGAAAGGGGGAACAGCTCGAAGCTGGTTCGACCCCTGGGGCCAGGGAACCCTGGTC ACCGTCTCCTCA (SEQ ID NO: 454) HCVR Amino Acid Sequence EVQLVESGGGLVQPGGSLRLSCAASKFIFSNYAMTWVRQAPGKGLEWVSIISGSGGNSYY ADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAKGGTARSWFDPWGQGTLVTVSS (SEQ ID NO: 455) CDR1 DNA Sequence AAA TTC ATC TTT AGC AAC TAT GCC (SEQ ID NO: 456) CDR1 Amino Acid Sequence K F I F S N Y A (SEQ ID NO: 457) Attorney Docket No.250298.000780 CDR2 DNA Sequence ATT AGT GGT AGT GGT GGA AAT TCA (SEQ ID NO: 458) CDR2 Amino Acid Sequence I S G S G G N S (SEQ ID NO: 459) CDR3 DNA Sequence GCG AAA GGG GGA ACA GCT CGA AGC TGG TTC GAC CCC (SEQ ID NO: 460) CDR3 Amino Acid Sequence A K G G T A R S W F D P (SEQ ID NO: 461) LCVR DNA Sequence GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACAGAGTCA CCATCACTTGCCGGGCAAGTCAGAGCATTAGCAGCTATTTAAATTGGTATCAGCAGAA ACCAGGGAAAGCCCCTAAGCTCCTGATCTATGCTGCATCCAGTTTGCAAAGTGGGGTC CCGTCAAGGTTCAGTGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGTC TGCAACCTGAAGATTTTGCAACTTACTACTGTCAACAGAGTTACAGTACCCCTCCGATC ACCTTCGGCCAAGGGACACGACTGGAGATTAAA (SEQ ID NO: 408) LCVR Amino Acid Sequence DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSR FSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPPITFGQGTRLEIK (SEQ ID NO: 409) CDR1 DNA Sequence CAG AGC ATT AGC AGC TAT (SEQ ID NO: 236) Attorney Docket No.250298.000780 CDR1 Amino Acid Sequence Q S I S S Y (SEQ ID NO: 237) CDR2 DNA Sequence GCT GCA TCC (SEQ ID NO: 13) CDR2 Amino Acid Sequence A A S (SEQ ID NO: 14) CDR3 DNA Sequence CAA CAG AGT TAC AGT ACC CCT CCG ATC ACC (SEQ ID NO: 410) CDR3 Amino Acid Sequence Q Q S Y S T P P I T (SEQ ID NO: 411) HC DNA Sequence GAGGTGCAGCTGGTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGAG ACTCTCCTGTGCAGCCTCTAAATTCATCTTTAGCAACTATGCCATGACCTGGGTCCGCC AGGCTCCAGGGAAGGGGCTGGAATGGGTCTCAATTATTAGTGGTAGTGGTGGAAATTC ATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCAGAGACAATTCCAAGAAC ACGCTATATCTGCAAATGAACAGCCTGAGAGCCGAGGACACGGCCGTTTATTACTGTG CGAAAGGGGGAACAGCTCGAAGCTGGTTCGACCCCTGGGGCCAGGGAACCCTGGTC ACCGTCTCCTCAGCCTCCACCAAGGGCCCATCGGTCTTCCCCCTGGCGCCCTGCTCC AGGAGCACCTCCGAGAGCACAGCCGCCCTGGGCTGCCTGGTCAAGGACTACTTCCCC GAACCGGTGACGGTGTCGTGGAACTCAGGCGCCCTGACCAGCGGCGTGCACACCTTC CCGGCTGTCCTACAGTCCTCAGGACTCTACTCCCTCAGCAGCGTGGTGACCGTGCCC TCCAGCAGCTTGGGCACGAAGACCTACACCTGCAACGTAGATCACAAGCCCAGCAAC Attorney Docket No.250298.000780 ACCAAGGTGGACAAGAGAGTTGAGTCCAAATATGGTCCCCCATGCCCACCGTGCCCA GCACCACCTGTGGCAGGACCATCAGTCTTCCTGTTCCCCCCAAAACCCAAGGACACTC TCATGATCTCCCGGACCCCTGAGGTCACGTGCGTGGTGGTGGACGTGAGCCAGGAAG ACCCCGAGGTCCAGTTCAACTGGTACGTGGATGGCGTGGAGGTGCATAATGCCAAGA CAAAGCCGCGGGAGGAGCAGTTCAACAGCACGTACCGTGTGGTCAGCGTCCTCACCG TCCTGCACCAGGACTGGCTGAACGGCAAGGAGTACAAGTGCAAGGTCTCCAACAAAG GCCTCCCGTCCTCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGAGAGC CACAGGTGTACACCCTGCCCCCATCCCAGGAGGAGATGACCAAGAACCAGGTCAGCC TGACCTGCCTGGTCAAAGGCTTCTACCCCAGCGACATCGCCGTGGAGTGGGAGAGCA ATGGGCAGCCGGAGAACAACTACAAGACCACGCCTCCCGTGCTGGACTCCGACGGCT CCTTCTTCCTCTACAGCAGGCTCACCGTGGACAAGAGCAGGTGGCAGGAGGGGAATG TCTTCTCATGCTCCGTGATGCATGAGGCTCTGCACAACCACTACACACAGAAGTCCCT CTCCCTGTCTCTGGGTAAATGA (SEQ ID NO: 462) HC Amino Acid Sequence EVQLVESGGGLVQPGGSLRLSCAASKFIFSNYAMTWVRQAPGKGLEWVSIISGSGGNSYY ADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAKGGTARSWFDPWGQGTLVTVSS ASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSS GLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPPVAGPSVF LFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYR VVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKN QVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGN VFSCSVMHEALHNHYTQKSLSLSLGK* (SEQ ID NO: 463) LC DNA Sequence GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACAGAGTCA CCATCACTTGCCGGGCAAGTCAGAGCATTAGCAGCTATTTAAATTGGTATCAGCAGAA ACCAGGGAAAGCCCCTAAGCTCCTGATCTATGCTGCATCCAGTTTGCAAAGTGGGGTC CCGTCAAGGTTCAGTGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGTC TGCAACCTGAAGATTTTGCAACTTACTACTGTCAACAGAGTTACAGTACCCCTCCGATC ACCTTCGGCCAAGGGACACGACTGGAGATTAAACGAACTGTGGCTGCACCATCTGTCT Attorney Docket No.250298.000780 TCATCTTCCCGCCATCTGATGAGCAGTTGAAATCTGGAACTGCCTCTGTTGTGTGCCT GCTGAATAACTTCTATCCCAGAGAGGCCAAAGTACAGTGGAAGGTGGATAACGCCCTC CAATCGGGTAACTCCCAGGAGAGTGTCACAGAGCAGGACAGCAAGGACAGCACCTAC AGCCTCAGCAGCACCCTGACGCTGAGCAAAGCAGACTACGAGAAACACAAAGTCTAC GCCTGCGAAGTCACCCATCAGGGCCTGAGCTCGCCCGTCACAAAGAGCTTCAACAGG GGAGAGTGTTAG (SEQ ID NO: 414) LC Amino Acid Sequence DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSR FSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPPITFGQGTRLEIKRTVAAPSVFIFPPSDE QLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSK ADYEKHKVYACEVTHQGLSSPVTKSFNRGEC* (SEQ ID NO: 415) REGN14185 HCVR DNA Sequence GAGGTGCAGCTGGTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGAG ACTCTCCTGTGCAGCCTCTGGATTCACTCTTAGCAGCTATGCCATGAGCTGGGTCCGC CAGGCTCCAGGGAAGGGGCTGGAGTGGGTCTCAGCAATTAGTGATAGTGGTGATAAC AAATACCACGCAGACTCCGTGAAGGGCCGGTTCTCCATCTCCAGAGACAATTCCAAGA ACACGCTGTATCTGCAAATGAACAGCCTGAGAGCCGAGGACGCGGCCGTATATTACTG TGCGAAAGGGGGGAGAACTAGAACTCCTTTTGACTATTGGGGCCAGGGAACCCTGGT CACCGTCTCCTCA (SEQ ID NO: 464) HCVR Amino Acid Sequence EVQLVESGGGLVQPGGSLRLSCAASGFTLSSYAMSWVRQAPGKGLEWVSAISDSGDNKY HADSVKGRFSISRDNSKNTLYLQMNSLRAEDAAVYYCAKGGRTRTPFDYWGQGTLVTVS S (SEQ ID NO: 465) CDR1 DNA Sequence Attorney Docket No.250298.000780 GGA TTC ACT CTT AGC AGC TAT GCC (SEQ ID NO: 466) CDR1 Amino Acid Sequence G F T L S S Y A (SEQ ID NO: 467) CDR2 DNA Sequence ATT AGT GAT AGT GGT GAT AAC AAA (SEQ ID NO: 468) CDR2 Amino Acid Sequence I S D S G D N K (SEQ ID NO: 469) CDR3 DNA Sequence GCG AAA GGG GGG AGA ACT AGA ACT CCT TTT GAC TAT (SEQ ID NO: 470) CDR3 Amino Acid Sequence A K G G R T R T P F D Y (SEQ ID NO: 471) LCVR DNA Sequence GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACAGAGTCA CCATCACTTGCCGGGCAAGTCAGAGCATTAGCAGCTATTTAAATTGGTATCAGCAGAA ACCAGGGAAAGCCCCTAAGCTCCTGATCTATGCTGCATCCAGTTTGCAAAGTGGGGTC CCGTCAAGGTTCAGTGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGTC TGCAACCTGAAGATTTTGCAACTTACTACTGTCAACAGAGTTACAGTACCCCTCCGATC ACCTTCGGCCAAGGGACACGACTGGAGATTAAA (SEQ ID NO: 408) LCVR Amino Acid Sequence Attorney Docket No.250298.000780 DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSR FSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPPITFGQGTRLEIK (SEQ ID NO: 409) CDR1 DNA Sequence CAG AGC ATT AGC AGC TAT (SEQ ID NO: 236) CDR1 Amino Acid Sequence Q S I S S Y (SEQ ID NO: 237) CDR2 DNA Sequence GCT GCA TCC (SEQ ID NO: 13) CDR2 Amino Acid Sequence A A S (SEQ ID NO: 14) CDR3 DNA Sequence CAA CAG AGT TAC AGT ACC CCT CCG ATC ACC (SEQ ID NO: 410) CDR3 Amino Acid Sequence Q Q S Y S T P P I T (SEQ ID NO: 411) HC DNA Sequence GAGGTGCAGCTGGTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGAG ACTCTCCTGTGCAGCCTCTGGATTCACTCTTAGCAGCTATGCCATGAGCTGGGTCCGC CAGGCTCCAGGGAAGGGGCTGGAGTGGGTCTCAGCAATTAGTGATAGTGGTGATAAC AAATACCACGCAGACTCCGTGAAGGGCCGGTTCTCCATCTCCAGAGACAATTCCAAGA Attorney Docket No.250298.000780 ACACGCTGTATCTGCAAATGAACAGCCTGAGAGCCGAGGACGCGGCCGTATATTACTG TGCGAAAGGGGGGAGAACTAGAACTCCTTTTGACTATTGGGGCCAGGGAACCCTGGT CACCGTCTCCTCAGCCTCCACCAAGGGCCCATCGGTCTTCCCCCTGGCGCCCTGCTC CAGGAGCACCTCCGAGAGCACAGCCGCCCTGGGCTGCCTGGTCAAGGACTACTTCCC CGAACCGGTGACGGTGTCGTGGAACTCAGGCGCCCTGACCAGCGGCGTGCACACCTT CCCGGCTGTCCTACAGTCCTCAGGACTCTACTCCCTCAGCAGCGTGGTGACCGTGCC CTCCAGCAGCTTGGGCACGAAGACCTACACCTGCAACGTAGATCACAAGCCCAGCAA CACCAAGGTGGACAAGAGAGTTGAGTCCAAATATGGTCCCCCATGCCCACCGTGCCC AGCACCACCTGTGGCAGGACCATCAGTCTTCCTGTTCCCCCCAAAACCCAAGGACACT CTCATGATCTCCCGGACCCCTGAGGTCACGTGCGTGGTGGTGGACGTGAGCCAGGAA GACCCCGAGGTCCAGTTCAACTGGTACGTGGATGGCGTGGAGGTGCATAATGCCAAG ACAAAGCCGCGGGAGGAGCAGTTCAACAGCACGTACCGTGTGGTCAGCGTCCTCACC GTCCTGCACCAGGACTGGCTGAACGGCAAGGAGTACAAGTGCAAGGTCTCCAACAAA GGCCTCCCGTCCTCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGAGAG CCACAGGTGTACACCCTGCCCCCATCCCAGGAGGAGATGACCAAGAACCAGGTCAGC CTGACCTGCCTGGTCAAAGGCTTCTACCCCAGCGACATCGCCGTGGAGTGGGAGAGC AATGGGCAGCCGGAGAACAACTACAAGACCACGCCTCCCGTGCTGGACTCCGACGGC TCCTTCTTCCTCTACAGCAGGCTCACCGTGGACAAGAGCAGGTGGCAGGAGGGGAAT GTCTTCTCATGCTCCGTGATGCATGAGGCTCTGCACAACCACTACACACAGAAGTCCC TCTCCCTGTCTCTGGGTAAATGA (SEQ ID NO: 472) HC Amino Acid Sequence EVQLVESGGGLVQPGGSLRLSCAASGFTLSSYAMSWVRQAPGKGLEWVSAISDSGDNKY HADSVKGRFSISRDNSKNTLYLQMNSLRAEDAAVYYCAKGGRTRTPFDYWGQGTLVTVS SASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQS SGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPPVAGPSV FLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTY RVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTK NQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEG NVFSCSVMHEALHNHYTQKSLSLSLGK* (SEQ ID NO: 473) Attorney Docket No.250298.000780 LC DNA Sequence GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACAGAGTCA CCATCACTTGCCGGGCAAGTCAGAGCATTAGCAGCTATTTAAATTGGTATCAGCAGAA ACCAGGGAAAGCCCCTAAGCTCCTGATCTATGCTGCATCCAGTTTGCAAAGTGGGGTC CCGTCAAGGTTCAGTGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGTC TGCAACCTGAAGATTTTGCAACTTACTACTGTCAACAGAGTTACAGTACCCCTCCGATC ACCTTCGGCCAAGGGACACGACTGGAGATTAAACGAACTGTGGCTGCACCATCTGTCT TCATCTTCCCGCCATCTGATGAGCAGTTGAAATCTGGAACTGCCTCTGTTGTGTGCCT GCTGAATAACTTCTATCCCAGAGAGGCCAAAGTACAGTGGAAGGTGGATAACGCCCTC CAATCGGGTAACTCCCAGGAGAGTGTCACAGAGCAGGACAGCAAGGACAGCACCTAC AGCCTCAGCAGCACCCTGACGCTGAGCAAAGCAGACTACGAGAAACACAAAGTCTAC GCCTGCGAAGTCACCCATCAGGGCCTGAGCTCGCCCGTCACAAAGAGCTTCAACAGG GGAGAGTGTTAG (SEQ ID NO: 414) LC Amino Acid Sequence DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSR FSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPPITFGQGTRLEIKRTVAAPSVFIFPPSDE QLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSK ADYEKHKVYACEVTHQGLSSPVTKSFNRGEC* (SEQ ID NO: 415) REGN14186 HCVR DNA Sequence GAGGTGCAGCTGGTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGAG ACTCTCCTGTGCAGCCTCTGGATTCACCTTTAGCGCCTATGCCATGACCTGGGTCCGC CAGGCTCCAGGGAAGGGGCTGGAGTGGGTCTCACTTATTAGTGGAAGTGGTGGTAAC ACATACTATGCAGACACCGTGAAGGGCCGGTCCACCATCTCCAGAGACAACTCCAAGA CCACGCTGTATCTGCAAATGAACAGCCTGAGAGCCGAGGACACGGCCGTATATTACTG TGCGAAATGGGGCCTAATGGTGTATGCTATGAGGGCCTTTGACTATTGGGGCCAGGG AACCCTGGTCACCGTCTCCTCA (SEQ ID NO: 474) Attorney Docket No.250298.000780 HCVR Amino Acid Sequence EVQLVESGGGLVQPGGSLRLSCAASGFTFSAYAMTWVRQAPGKGLEWVSLISGSGGNTY YADTVKGRSTISRDNSKTTLYLQMNSLRAEDTAVYYCAKWGLMVYAMRAFDYWGQGTLV TVSS (SEQ ID NO: 475) CDR1 DNA Sequence GGA TTC ACC TTT AGC GCC TAT GCC (SEQ ID NO: 476) CDR1 Amino Acid Sequence G F T F S A Y A (SEQ ID NO: 477) CDR2 DNA Sequence ATT AGT GGA AGT GGT GGT AAC ACA (SEQ ID NO: 478) CDR2 Amino Acid Sequence I S G S G G N T (SEQ ID NO: 158) CDR3 DNA Sequence GCG AAA TGG GGC CTA ATG GTG TAT GCT ATG AGG GCC TTT GAC TAT (SEQ ID NO: 479) CDR3 Amino Acid Sequence A K W G L M V Y A M R A F D Y (SEQ ID NO: 480) LCVR DNA Sequence GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACAGAGTCA CCATCACTTGCCGGGCAAGTCAGAGCATTAGCAGCTATTTAAATTGGTATCAGCAGAA Attorney Docket No.250298.000780 ACCAGGGAAAGCCCCTAAGCTCCTGATCTATGCTGCATCCAGTTTGCAAAGTGGGGTC CCGTCAAGGTTCAGTGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGTC TGCAACCTGAAGATTTTGCAACTTACTACTGTCAACAGAGTTACAGTACCCCTCCGATC ACCTTCGGCCAAGGGACACGACTGGAGATTAAA (SEQ ID NO: 408) LCVR Amino Acid Sequence DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSR FSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPPITFGQGTRLEIK (SEQ ID NO: 409) CDR1 DNA Sequence CAG AGC ATT AGC AGC TAT (SEQ ID NO: 236) CDR1 Amino Acid Sequence Q S I S S Y (SEQ ID NO: 237) CDR2 DNA Sequence GCT GCA TCC (SEQ ID NO: 13) CDR2 Amino Acid Sequence A A S (SEQ ID NO: 14) CDR3 DNA Sequence CAA CAG AGT TAC AGT ACC CCT CCG ATC ACC (SEQ ID NO: 410) CDR3 Amino Acid Sequence Q Q S Y S T P P I T Attorney Docket No.250298.000780 (SEQ ID NO: 411) HC DNA Sequence GAGGTGCAGCTGGTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGAG ACTCTCCTGTGCAGCCTCTGGATTCACCTTTAGCGCCTATGCCATGACCTGGGTCCGC CAGGCTCCAGGGAAGGGGCTGGAGTGGGTCTCACTTATTAGTGGAAGTGGTGGTAAC ACATACTATGCAGACACCGTGAAGGGCCGGTCCACCATCTCCAGAGACAACTCCAAGA CCACGCTGTATCTGCAAATGAACAGCCTGAGAGCCGAGGACACGGCCGTATATTACTG TGCGAAATGGGGCCTAATGGTGTATGCTATGAGGGCCTTTGACTATTGGGGCCAGGG AACCCTGGTCACCGTCTCCTCAGCCTCCACCAAGGGCCCATCGGTCTTCCCCCTGGC GCCCTGCTCCAGGAGCACCTCCGAGAGCACAGCCGCCCTGGGCTGCCTGGTCAAGG ACTACTTCCCCGAACCGGTGACGGTGTCGTGGAACTCAGGCGCCCTGACCAGCGGCG TGCACACCTTCCCGGCTGTCCTACAGTCCTCAGGACTCTACTCCCTCAGCAGCGTGGT GACCGTGCCCTCCAGCAGCTTGGGCACGAAGACCTACACCTGCAACGTAGATCACAA GCCCAGCAACACCAAGGTGGACAAGAGAGTTGAGTCCAAATATGGTCCCCCATGCCC ACCGTGCCCAGCACCACCTGTGGCAGGACCATCAGTCTTCCTGTTCCCCCCAAAACCC AAGGACACTCTCATGATCTCCCGGACCCCTGAGGTCACGTGCGTGGTGGTGGACGTG AGCCAGGAAGACCCCGAGGTCCAGTTCAACTGGTACGTGGATGGCGTGGAGGTGCAT AATGCCAAGACAAAGCCGCGGGAGGAGCAGTTCAACAGCACGTACCGTGTGGTCAGC GTCCTCACCGTCCTGCACCAGGACTGGCTGAACGGCAAGGAGTACAAGTGCAAGGTC TCCAACAAAGGCCTCCCGTCCTCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGC CCCGAGAGCCACAGGTGTACACCCTGCCCCCATCCCAGGAGGAGATGACCAAGAACC AGGTCAGCCTGACCTGCCTGGTCAAAGGCTTCTACCCCAGCGACATCGCCGTGGAGT GGGAGAGCAATGGGCAGCCGGAGAACAACTACAAGACCACGCCTCCCGTGCTGGACT CCGACGGCTCCTTCTTCCTCTACAGCAGGCTCACCGTGGACAAGAGCAGGTGGCAGG AGGGGAATGTCTTCTCATGCTCCGTGATGCATGAGGCTCTGCACAACCACTACACACA GAAGTCCCTCTCCCTGTCTCTGGGTAAATGA (SEQ ID NO: 481) HC Amino Acid Sequence EVQLVESGGGLVQPGGSLRLSCAASGFTFSAYAMTWVRQAPGKGLEWVSLISGSGGNTY YADTVKGRSTISRDNSKTTLYLQMNSLRAEDTAVYYCAKWGLMVYAMRAFDYWGQGTLV TVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVL Attorney Docket No.250298.000780 QSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPPVAGP SVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNS TYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMT KNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQE GNVFSCSVMHEALHNHYTQKSLSLSLGK* (SEQ ID NO: 482) LC DNA Sequence GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACAGAGTCA CCATCACTTGCCGGGCAAGTCAGAGCATTAGCAGCTATTTAAATTGGTATCAGCAGAA ACCAGGGAAAGCCCCTAAGCTCCTGATCTATGCTGCATCCAGTTTGCAAAGTGGGGTC CCGTCAAGGTTCAGTGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGTC TGCAACCTGAAGATTTTGCAACTTACTACTGTCAACAGAGTTACAGTACCCCTCCGATC ACCTTCGGCCAAGGGACACGACTGGAGATTAAACGAACTGTGGCTGCACCATCTGTCT TCATCTTCCCGCCATCTGATGAGCAGTTGAAATCTGGAACTGCCTCTGTTGTGTGCCT GCTGAATAACTTCTATCCCAGAGAGGCCAAAGTACAGTGGAAGGTGGATAACGCCCTC CAATCGGGTAACTCCCAGGAGAGTGTCACAGAGCAGGACAGCAAGGACAGCACCTAC AGCCTCAGCAGCACCCTGACGCTGAGCAAAGCAGACTACGAGAAACACAAAGTCTAC GCCTGCGAAGTCACCCATCAGGGCCTGAGCTCGCCCGTCACAAAGAGCTTCAACAGG GGAGAGTGTTAG (SEQ ID NO: 414) LC Amino Acid Sequence DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSR FSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPPITFGQGTRLEIKRTVAAPSVFIFPPSDE QLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSK ADYEKHKVYACEVTHQGLSSPVTKSFNRGEC* (SEQ ID NO: 415) REGN14187 HCVR DNA Sequence GAGGTGCAGCTGGTGGAGTCTGGGGGAGGCTTGGTCCAGCCGGGGGGGTCCCTGAG ACTCTCCTGTGCAGCCTCTGGATTCACCTTTAGTTACTATTGGATGAACTGGGTCCGCC Attorney Docket No.250298.000780 AGGCTCCAGGGAAGGGGCTGGAGTGGGTGGCCAACATAAAGCAAGATGGAAGTGAG AAATACTATGTGGACTCTGTGAAGGGCCGAGTCACCATCTCCAGAGACAACGCCAAGA ACTCACTGTATCTGCAAATGAACAGCCTGAGAGCCGAGGACACGGGTGTGTATTACTG TGCGACAGATAAGGTTCGCGGGCGATACCACGACCACTACGGTTTGGACGTCTGGGG CCAAGGGACCACGGTCACCGTCTCCTCA (SEQ ID NO: 483) HCVR Amino Acid Sequence EVQLVESGGGLVQPGGSLRLSCAASGFTFSYYWMNWVRQAPGKGLEWVANIKQDGSEK YYVDSVKGRVTISRDNAKNSLYLQMNSLRAEDTGVYYCATDKVRGRYHDHYGLDVWGQG TTVTVSS (SEQ ID NO: 484) CDR1 DNA Sequence GGA TTC ACC TTT AGT TAC TAT TGG (SEQ ID NO: 485) CDR1 Amino Acid Sequence G F T F S Y Y W (SEQ ID NO: 486) CDR2 DNA Sequence ATA AAG CAA GAT GGA AGT GAG AAA (SEQ ID NO: 487) CDR2 Amino Acid Sequence I K Q D G S E K (SEQ ID NO: 283) CDR3 DNA Sequence GCG ACA GAT AAG GTT CGC GGG CGA TAC CAC GAC CAC TAC GGT TTG GAC GTC (SEQ ID NO: 488) Attorney Docket No.250298.000780 CDR3 Amino Acid Sequence A T D K V R G R Y H D H Y G L D V (SEQ ID NO: 489) LCVR DNA Sequence GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACAGAGTCA CCATCACTTGCCGGGCAAGTCAGAGCATTAGCAGCTATTTAAATTGGTATCAGCAGAA ACCAGGGAAAGCCCCTAAGCTCCTGATCTATGCTGCATCCAGTTTGCAAAGTGGGGTC CCGTCAAGGTTCAGTGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGTC TGCAACCTGAAGATTTTGCAACTTACTACTGTCAACAGAGTTACAGTACCCCTCCGATC ACCTTCGGCCAAGGGACACGACTGGAGATTAAA (SEQ ID NO: 408) LCVR Amino Acid Sequence DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSR FSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPPITFGQGTRLEIK (SEQ ID NO: 409) CDR1 DNA Sequence CAG AGC ATT AGC AGC TAT (SEQ ID NO: 236) CDR1 Amino Acid Sequence Q S I S S Y (SEQ ID NO: 237) CDR2 DNA Sequence GCT GCA TCC (SEQ ID NO: 13) CDR2 Amino Acid Sequence A A S (SEQ ID NO: 14) Attorney Docket No.250298.000780 CDR3 DNA Sequence CAA CAG AGT TAC AGT ACC CCT CCG ATC ACC (SEQ ID NO: 410) CDR3 Amino Acid Sequence Q Q S Y S T P P I T (SEQ ID NO: 411) HC DNA Sequence GAGGTGCAGCTGGTGGAGTCTGGGGGAGGCTTGGTCCAGCCGGGGGGGTCCCTGAG ACTCTCCTGTGCAGCCTCTGGATTCACCTTTAGTTACTATTGGATGAACTGGGTCCGCC AGGCTCCAGGGAAGGGGCTGGAGTGGGTGGCCAACATAAAGCAAGATGGAAGTGAG AAATACTATGTGGACTCTGTGAAGGGCCGAGTCACCATCTCCAGAGACAACGCCAAGA ACTCACTGTATCTGCAAATGAACAGCCTGAGAGCCGAGGACACGGGTGTGTATTACTG TGCGACAGATAAGGTTCGCGGGCGATACCACGACCACTACGGTTTGGACGTCTGGGG CCAAGGGACCACGGTCACCGTCTCCTCAGCCTCCACCAAGGGCCCATCGGTCTTCCC CCTGGCGCCCTGCTCCAGGAGCACCTCCGAGAGCACAGCCGCCCTGGGCTGCCTGG TCAAGGACTACTTCCCCGAACCGGTGACGGTGTCGTGGAACTCAGGCGCCCTGACCA GCGGCGTGCACACCTTCCCGGCTGTCCTACAGTCCTCAGGACTCTACTCCCTCAGCA GCGTGGTGACCGTGCCCTCCAGCAGCTTGGGCACGAAGACCTACACCTGCAACGTAG ATCACAAGCCCAGCAACACCAAGGTGGACAAGAGAGTTGAGTCCAAATATGGTCCCCC ATGCCCACCGTGCCCAGCACCACCTGTGGCAGGACCATCAGTCTTCCTGTTCCCCCC AAAACCCAAGGACACTCTCATGATCTCCCGGACCCCTGAGGTCACGTGCGTGGTGGT GGACGTGAGCCAGGAAGACCCCGAGGTCCAGTTCAACTGGTACGTGGATGGCGTGGA GGTGCATAATGCCAAGACAAAGCCGCGGGAGGAGCAGTTCAACAGCACGTACCGTGT GGTCAGCGTCCTCACCGTCCTGCACCAGGACTGGCTGAACGGCAAGGAGTACAAGTG CAAGGTCTCCAACAAAGGCCTCCCGTCCTCCATCGAGAAAACCATCTCCAAAGCCAAA GGGCAGCCCCGAGAGCCACAGGTGTACACCCTGCCCCCATCCCAGGAGGAGATGAC CAAGAACCAGGTCAGCCTGACCTGCCTGGTCAAAGGCTTCTACCCCAGCGACATCGC CGTGGAGTGGGAGAGCAATGGGCAGCCGGAGAACAACTACAAGACCACGCCTCCCGT GCTGGACTCCGACGGCTCCTTCTTCCTCTACAGCAGGCTCACCGTGGACAAGAGCAG Attorney Docket No.250298.000780 GTGGCAGGAGGGGAATGTCTTCTCATGCTCCGTGATGCATGAGGCTCTGCACAACCA CTACACACAGAAGTCCCTCTCCCTGTCTCTGGGTAAATGA (SEQ ID NO: 490) HC Amino Acid Sequence EVQLVESGGGLVQPGGSLRLSCAASGFTFSYYWMNWVRQAPGKGLEWVANIKQDGSEK YYVDSVKGRVTISRDNAKNSLYLQMNSLRAEDTGVYYCATDKVRGRYHDHYGLDVWGQG TTVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFP AVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPPV AGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQ FNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQE EMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSR WQEGNVFSCSVMHEALHNHYTQKSLSLSLGK* (SEQ ID NO: 491) LC DNA Sequence GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACAGAGTCA CCATCACTTGCCGGGCAAGTCAGAGCATTAGCAGCTATTTAAATTGGTATCAGCAGAA ACCAGGGAAAGCCCCTAAGCTCCTGATCTATGCTGCATCCAGTTTGCAAAGTGGGGTC CCGTCAAGGTTCAGTGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGTC TGCAACCTGAAGATTTTGCAACTTACTACTGTCAACAGAGTTACAGTACCCCTCCGATC ACCTTCGGCCAAGGGACACGACTGGAGATTAAACGAACTGTGGCTGCACCATCTGTCT TCATCTTCCCGCCATCTGATGAGCAGTTGAAATCTGGAACTGCCTCTGTTGTGTGCCT GCTGAATAACTTCTATCCCAGAGAGGCCAAAGTACAGTGGAAGGTGGATAACGCCCTC CAATCGGGTAACTCCCAGGAGAGTGTCACAGAGCAGGACAGCAAGGACAGCACCTAC AGCCTCAGCAGCACCCTGACGCTGAGCAAAGCAGACTACGAGAAACACAAAGTCTAC GCCTGCGAAGTCACCCATCAGGGCCTGAGCTCGCCCGTCACAAAGAGCTTCAACAGG GGAGAGTGTTAG (SEQ ID NO: 414) LC Amino Acid Sequence DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSR FSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPPITFGQGTRLEIKRTVAAPSVFIFPPSDE Attorney Docket No.250298.000780 QLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSK ADYEKHKVYACEVTHQGLSSPVTKSFNRGEC* (SEQ ID NO: 415) REGN14188 HCVR DNA Sequence GAGGTGCAGCTGGTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGAG ACTCTCCTGTGCAGCCTCTGGATTCACCTTTACCAACTATGCCATGAGCTGGGTCCGC CAGGCTCCAGGGAAGGGTCTGGAGTGGGTCTCAACTATTAGTGATAGTGGTGGTGGC ACATACTACGCAGACTCCGTGAGGGGCCGGTTCACCATCTCCAGAGACAATTCCAAGA ACACGCTGTATCTGCAAATGAACAGCCTGAGAGCCGAGGACACGGCCATATATTTCTG TGCGAAAGGGACAAGATCTCGTTTCCCCTTGGACTACTGGGGCCAGGGAACCCTGGT CACCGTCTCCTCA (SEQ ID NO: 492) HCVR Amino Acid Sequence EVQLVESGGGLVQPGGSLRLSCAASGFTFTNYAMSWVRQAPGKGLEWVSTISDSGGGTY YADSVRGRFTISRDNSKNTLYLQMNSLRAEDTAIYFCAKGTRSRFPLDYWGQGTLVTVSS (SEQ ID NO: 493) CDR1 DNA Sequence GGA TTC ACC TTT ACC AAC TAT GCC (SEQ ID NO: 494) CDR1 Amino Acid Sequence G F T F T N Y A (SEQ ID NO: 495) CDR2 DNA Sequence ATT AGT GAT AGT GGT GGT GGC ACA (SEQ ID NO: 496) CDR2 Amino Acid Sequence Attorney Docket No.250298.000780 I S D S G G G T (SEQ ID NO: 497) CDR3 DNA Sequence GCG AAA GGG ACA AGA TCT CGT TTC CCC TTG GAC TAC (SEQ ID NO: 498) CDR3 Amino Acid Sequence A K G T R S R F P L D Y (SEQ ID NO: 499) LCVR DNA Sequence GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACAGAGTCA CCATCACTTGCCGGGCAAGTCAGAGCATTAGCAGCTATTTAAATTGGTATCAGCAGAA ACCAGGGAAAGCCCCTAAGCTCCTGATCTATGCTGCATCCAGTTTGCAAAGTGGGGTC CCGTCAAGGTTCAGTGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGTC TGCAACCTGAAGATTTTGCAACTTACTACTGTCAACAGAGTTACAGTACCCCTCCGATC ACCTTCGGCCAAGGGACACGACTGGAGATTAAA (SEQ ID NO: 408) LCVR Amino Acid Sequence DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSR FSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPPITFGQGTRLEIK (SEQ ID NO: 409) CDR1 DNA Sequence CAG AGC ATT AGC AGC TAT (SEQ ID NO: 236) CDR1 Amino Acid Sequence Q S I S S Y (SEQ ID NO: 237) Attorney Docket No.250298.000780 CDR2 DNA Sequence GCT GCA TCC (SEQ ID NO: 13) CDR2 Amino Acid Sequence A A S (SEQ ID NO: 14) CDR3 DNA Sequence CAA CAG AGT TAC AGT ACC CCT CCG ATC ACC (SEQ ID NO: 410) CDR3 Amino Acid Sequence Q Q S Y S T P P I T (SEQ ID NO: 411) HC DNA Sequence GAGGTGCAGCTGGTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGAG ACTCTCCTGTGCAGCCTCTGGATTCACCTTTACCAACTATGCCATGAGCTGGGTCCGC CAGGCTCCAGGGAAGGGTCTGGAGTGGGTCTCAACTATTAGTGATAGTGGTGGTGGC ACATACTACGCAGACTCCGTGAGGGGCCGGTTCACCATCTCCAGAGACAATTCCAAGA ACACGCTGTATCTGCAAATGAACAGCCTGAGAGCCGAGGACACGGCCATATATTTCTG TGCGAAAGGGACAAGATCTCGTTTCCCCTTGGACTACTGGGGCCAGGGAACCCTGGT CACCGTCTCCTCAGCCTCCACCAAGGGCCCATCGGTCTTCCCCCTGGCGCCCTGCTC CAGGAGCACCTCCGAGAGCACAGCCGCCCTGGGCTGCCTGGTCAAGGACTACTTCCC CGAACCGGTGACGGTGTCGTGGAACTCAGGCGCCCTGACCAGCGGCGTGCACACCTT CCCGGCTGTCCTACAGTCCTCAGGACTCTACTCCCTCAGCAGCGTGGTGACCGTGCC CTCCAGCAGCTTGGGCACGAAGACCTACACCTGCAACGTAGATCACAAGCCCAGCAA CACCAAGGTGGACAAGAGAGTTGAGTCCAAATATGGTCCCCCATGCCCACCGTGCCC AGCACCACCTGTGGCAGGACCATCAGTCTTCCTGTTCCCCCCAAAACCCAAGGACACT CTCATGATCTCCCGGACCCCTGAGGTCACGTGCGTGGTGGTGGACGTGAGCCAGGAA GACCCCGAGGTCCAGTTCAACTGGTACGTGGATGGCGTGGAGGTGCATAATGCCAAG ACAAAGCCGCGGGAGGAGCAGTTCAACAGCACGTACCGTGTGGTCAGCGTCCTCACC Attorney Docket No.250298.000780 GTCCTGCACCAGGACTGGCTGAACGGCAAGGAGTACAAGTGCAAGGTCTCCAACAAA GGCCTCCCGTCCTCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGAGAG CCACAGGTGTACACCCTGCCCCCATCCCAGGAGGAGATGACCAAGAACCAGGTCAGC CTGACCTGCCTGGTCAAAGGCTTCTACCCCAGCGACATCGCCGTGGAGTGGGAGAGC AATGGGCAGCCGGAGAACAACTACAAGACCACGCCTCCCGTGCTGGACTCCGACGGC TCCTTCTTCCTCTACAGCAGGCTCACCGTGGACAAGAGCAGGTGGCAGGAGGGGAAT GTCTTCTCATGCTCCGTGATGCATGAGGCTCTGCACAACCACTACACACAGAAGTCCC TCTCCCTGTCTCTGGGTAAATGA (SEQ ID NO: 500) HC Amino Acid Sequence EVQLVESGGGLVQPGGSLRLSCAASGFTFTNYAMSWVRQAPGKGLEWVSTISDSGGGTY YADSVRGRFTISRDNSKNTLYLQMNSLRAEDTAIYFCAKGTRSRFPLDYWGQGTLVTVSS ASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSS GLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPPVAGPSVF LFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYR VVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKN QVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGN VFSCSVMHEALHNHYTQKSLSLSLGK* (SEQ ID NO: 501) LC DNA Sequence GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACAGAGTCA CCATCACTTGCCGGGCAAGTCAGAGCATTAGCAGCTATTTAAATTGGTATCAGCAGAA ACCAGGGAAAGCCCCTAAGCTCCTGATCTATGCTGCATCCAGTTTGCAAAGTGGGGTC CCGTCAAGGTTCAGTGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGTC TGCAACCTGAAGATTTTGCAACTTACTACTGTCAACAGAGTTACAGTACCCCTCCGATC ACCTTCGGCCAAGGGACACGACTGGAGATTAAACGAACTGTGGCTGCACCATCTGTCT TCATCTTCCCGCCATCTGATGAGCAGTTGAAATCTGGAACTGCCTCTGTTGTGTGCCT GCTGAATAACTTCTATCCCAGAGAGGCCAAAGTACAGTGGAAGGTGGATAACGCCCTC CAATCGGGTAACTCCCAGGAGAGTGTCACAGAGCAGGACAGCAAGGACAGCACCTAC AGCCTCAGCAGCACCCTGACGCTGAGCAAAGCAGACTACGAGAAACACAAAGTCTAC Attorney Docket No.250298.000780 GCCTGCGAAGTCACCCATCAGGGCCTGAGCTCGCCCGTCACAAAGAGCTTCAACAGG GGAGAGTGTTAG (SEQ ID NO: 414) LC Amino Acid Sequence DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSR FSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPPITFGQGTRLEIKRTVAAPSVFIFPPSDE QLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSK ADYEKHKVYACEVTHQGLSSPVTKSFNRGEC* (SEQ ID NO: 415) REGN14189 HCVR DNA Sequence GAGGTGCAGCTGGTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGAG CCTCTCCTGTGCAGCCTCTGGATTCACCTTTATCAACTATGCCATGACCTGGGTCCGC CAGGCTCCAGGGAAGGGGCTGGAGTGGGTCTCAATTATAAGTGGTAGTGGTGGTAGA AAGTACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCAGAGACAATTCCAAGA ACACGCTGTCTCTGCAAATGAACAGCCTGAGAGCCGAGGACACGGCCGTATATTACTG TGCGAGATTTCCGGGTTTAGCAGCAGCCGTCTTAGACTACTGGGGCCAGGGAACCCT GGTCACCGTCTCCTCA (SEQ ID NO: 502) HCVR Amino Acid Sequence EVQLVESGGGLVQPGGSLSLSCAASGFTFINYAMTWVRQAPGKGLEWVSIISGSGGRKYY ADSVKGRFTISRDNSKNTLSLQMNSLRAEDTAVYYCARFPGLAAAVLDYWGQGTLVTVSS (SEQ ID NO: 503) CDR1 DNA Sequence GGA TTC ACC TTT ATC AAC TAT GCC (SEQ ID NO: 504) CDR1 Amino Acid Sequence G F T F I N Y A Attorney Docket No.250298.000780 (SEQ ID NO: 505) CDR2 DNA Sequence ATA AGT GGT AGT GGT GGT AGA AAG (SEQ ID NO: 506) CDR2 Amino Acid Sequence I S G S G G R K (SEQ ID NO: 507) CDR3 DNA Sequence GCG AGA TTT CCG GGT TTA GCA GCA GCC GTC TTA GAC TAC (SEQ ID NO: 508) CDR3 Amino Acid Sequence A R F P G L A A A V L D Y (SEQ ID NO: 509) LCVR DNA Sequence GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACAGAGTCA CCATCACTTGCCGGGCAAGTCAGAGCATTAGCAGCTATTTAAATTGGTATCAGCAGAA ACCAGGGAAAGCCCCTAAGCTCCTGATCTATGCTGCATCCAGTTTGCAAAGTGGGGTC CCGTCAAGGTTCAGTGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGTC TGCAACCTGAAGATTTTGCAACTTACTACTGTCAACAGAGTTACAGTACCCCTCCGATC ACCTTCGGCCAAGGGACACGACTGGAGATTAAA (SEQ ID NO: 408) LCVR Amino Acid Sequence DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSR FSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPPITFGQGTRLEIK (SEQ ID NO: 409) CDR1 DNA Sequence Attorney Docket No.250298.000780 CAG AGC ATT AGC AGC TAT (SEQ ID NO: 236) CDR1 Amino Acid Sequence Q S I S S Y (SEQ ID NO: 237) CDR2 DNA Sequence GCT GCA TCC (SEQ ID NO: 13) CDR2 Amino Acid Sequence A A S (SEQ ID NO: 14) CDR3 DNA Sequence CAA CAG AGT TAC AGT ACC CCT CCG ATC ACC (SEQ ID NO: 410) CDR3 Amino Acid Sequence Q Q S Y S T P P I T (SEQ ID NO: 411) HC DNA Sequence GAGGTGCAGCTGGTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGAG CCTCTCCTGTGCAGCCTCTGGATTCACCTTTATCAACTATGCCATGACCTGGGTCCGC CAGGCTCCAGGGAAGGGGCTGGAGTGGGTCTCAATTATAAGTGGTAGTGGTGGTAGA AAGTACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCAGAGACAATTCCAAGA ACACGCTGTCTCTGCAAATGAACAGCCTGAGAGCCGAGGACACGGCCGTATATTACTG TGCGAGATTTCCGGGTTTAGCAGCAGCCGTCTTAGACTACTGGGGCCAGGGAACCCT GGTCACCGTCTCCTCAGCCTCCACCAAGGGCCCATCGGTCTTCCCCCTGGCGCCCTG CTCCAGGAGCACCTCCGAGAGCACAGCCGCCCTGGGCTGCCTGGTCAAGGACTACTT CCCCGAACCGGTGACGGTGTCGTGGAACTCAGGCGCCCTGACCAGCGGCGTGCACA Attorney Docket No.250298.000780 CCTTCCCGGCTGTCCTACAGTCCTCAGGACTCTACTCCCTCAGCAGCGTGGTGACCGT GCCCTCCAGCAGCTTGGGCACGAAGACCTACACCTGCAACGTAGATCACAAGCCCAG CAACACCAAGGTGGACAAGAGAGTTGAGTCCAAATATGGTCCCCCATGCCCACCGTG CCCAGCACCACCTGTGGCAGGACCATCAGTCTTCCTGTTCCCCCCAAAACCCAAGGAC ACTCTCATGATCTCCCGGACCCCTGAGGTCACGTGCGTGGTGGTGGACGTGAGCCAG GAAGACCCCGAGGTCCAGTTCAACTGGTACGTGGATGGCGTGGAGGTGCATAATGCC AAGACAAAGCCGCGGGAGGAGCAGTTCAACAGCACGTACCGTGTGGTCAGCGTCCTC ACCGTCCTGCACCAGGACTGGCTGAACGGCAAGGAGTACAAGTGCAAGGTCTCCAAC AAAGGCCTCCCGTCCTCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGA GAGCCACAGGTGTACACCCTGCCCCCATCCCAGGAGGAGATGACCAAGAACCAGGTC AGCCTGACCTGCCTGGTCAAAGGCTTCTACCCCAGCGACATCGCCGTGGAGTGGGAG AGCAATGGGCAGCCGGAGAACAACTACAAGACCACGCCTCCCGTGCTGGACTCCGAC GGCTCCTTCTTCCTCTACAGCAGGCTCACCGTGGACAAGAGCAGGTGGCAGGAGGGG AATGTCTTCTCATGCTCCGTGATGCATGAGGCTCTGCACAACCACTACACACAGAAGT CCCTCTCCCTGTCTCTGGGTAAATGA (SEQ ID NO: 510) HC Amino Acid Sequence EVQLVESGGGLVQPGGSLSLSCAASGFTFINYAMTWVRQAPGKGLEWVSIISGSGGRKYY ADSVKGRFTISRDNSKNTLSLQMNSLRAEDTAVYYCARFPGLAAAVLDYWGQGTLVTVSS ASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSS GLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPPVAGPSVF LFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYR VVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKN QVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGN VFSCSVMHEALHNHYTQKSLSLSLGK* (SEQ ID NO: 511) LC DNA Sequence GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACAGAGTCA CCATCACTTGCCGGGCAAGTCAGAGCATTAGCAGCTATTTAAATTGGTATCAGCAGAA ACCAGGGAAAGCCCCTAAGCTCCTGATCTATGCTGCATCCAGTTTGCAAAGTGGGGTC CCGTCAAGGTTCAGTGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGTC Attorney Docket No.250298.000780 TGCAACCTGAAGATTTTGCAACTTACTACTGTCAACAGAGTTACAGTACCCCTCCGATC ACCTTCGGCCAAGGGACACGACTGGAGATTAAACGAACTGTGGCTGCACCATCTGTCT TCATCTTCCCGCCATCTGATGAGCAGTTGAAATCTGGAACTGCCTCTGTTGTGTGCCT GCTGAATAACTTCTATCCCAGAGAGGCCAAAGTACAGTGGAAGGTGGATAACGCCCTC CAATCGGGTAACTCCCAGGAGAGTGTCACAGAGCAGGACAGCAAGGACAGCACCTAC AGCCTCAGCAGCACCCTGACGCTGAGCAAAGCAGACTACGAGAAACACAAAGTCTAC GCCTGCGAAGTCACCCATCAGGGCCTGAGCTCGCCCGTCACAAAGAGCTTCAACAGG GGAGAGTGTTAG (SEQ ID NO: 414) LC Amino Acid Sequence DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSR FSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPPITFGQGTRLEIKRTVAAPSVFIFPPSDE QLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSK ADYEKHKVYACEVTHQGLSSPVTKSFNRGEC* (SEQ ID NO: 415) REGN14190 HCVR DNA Sequence CAGGTTCAGCTGGTGCAGTCTGGAGCTGAGGTGAAGAAGCCTGGGGCCTCAGTGAAG GTCTCCTGCAAGGCTTCTGGTTACACCTTTACCAGCTATGGTATCAGCTGGGTGCGAC AGGCCCCTGGACAAGGACTTGAGTGGATGGGATGGATCAGCGCTTACAATGGTAACA CAAAGTATGCACAGAAGTTCCAGGGCAGAGTCACCATGACCAGAGACACATCCACGA GCACAGCCTACATGGAGCTGAGGAGCCTGAGATCTGACGACACGGCCGTTTATTACT GTGCGAGATGGGTCTCTATGTTTCGGGGAGTCCCGGGGGACTCCTGGGGCCAGGGA ACCCTGGTCACCGTCTCCTCA (SEQ ID NO: 512) HCVR Amino Acid Sequence QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYGISWVRQAPGQGLEWMGWISAYNGNT KYAQKFQGRVTMTRDTSTSTAYMELRSLRSDDTAVYYCARWVSMFRGVPGDSWGQGTL VTVSS (SEQ ID NO: 513) Attorney Docket No.250298.000780 CDR1 DNA Sequence GGT TAC ACC TTT ACC AGC TAT GGT (SEQ ID NO: 137) CDR1 Amino Acid Sequence G Y T F T S Y G (SEQ ID NO: 138) CDR2 DNA Sequence ATC AGC GCT TAC AAT GGT AAC ACA (SEQ ID NO: 318) CDR2 Amino Acid Sequence I S A Y N G N T (SEQ ID NO: 319) CDR3 DNA Sequence GCG AGA TGG GTC TCT ATG TTT CGG GGA GTC CCG GGG GAC TCC (SEQ ID NO: 514) CDR3 Amino Acid Sequence A R W V S M F R G V P G D S (SEQ ID NO: 515) LCVR DNA Sequence GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACAGAGTCA CCATCACTTGCCGGGCAAGTCAGAGCATTAGCAGCTATTTAAATTGGTATCAGCAGAA ACCAGGGAAAGCCCCTAAGCTCCTGATCTATGCTGCATCCAGTTTGCAAAGTGGGGTC CCGTCAAGGTTCAGTGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGTC TGCAACCTGAAGATTTTGCAACTTACTACTGTCAACAGAGTTACAGTACCCCTCCGATC ACCTTCGGCCAAGGGACACGACTGGAGATTAAA (SEQ ID NO: 408) Attorney Docket No.250298.000780 LCVR Amino Acid Sequence DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSR FSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPPITFGQGTRLEIK (SEQ ID NO: 409) CDR1 DNA Sequence CAG AGC ATT AGC AGC TAT (SEQ ID NO: 236) CDR1 Amino Acid Sequence Q S I S S Y (SEQ ID NO: 237) CDR2 DNA Sequence GCT GCA TCC (SEQ ID NO: 13) CDR2 Amino Acid Sequence A A S (SEQ ID NO: 14) CDR3 DNA Sequence CAA CAG AGT TAC AGT ACC CCT CCG ATC ACC (SEQ ID NO: 410) CDR3 Amino Acid Sequence Q Q S Y S T P P I T (SEQ ID NO: 411) HC DNA Sequence CAGGTTCAGCTGGTGCAGTCTGGAGCTGAGGTGAAGAAGCCTGGGGCCTCAGTGAAG GTCTCCTGCAAGGCTTCTGGTTACACCTTTACCAGCTATGGTATCAGCTGGGTGCGAC Attorney Docket No.250298.000780 AGGCCCCTGGACAAGGACTTGAGTGGATGGGATGGATCAGCGCTTACAATGGTAACA CAAAGTATGCACAGAAGTTCCAGGGCAGAGTCACCATGACCAGAGACACATCCACGA GCACAGCCTACATGGAGCTGAGGAGCCTGAGATCTGACGACACGGCCGTTTATTACT GTGCGAGATGGGTCTCTATGTTTCGGGGAGTCCCGGGGGACTCCTGGGGCCAGGGA ACCCTGGTCACCGTCTCCTCAGCCTCCACCAAGGGCCCATCGGTCTTCCCCCTGGCG CCCTGCTCCAGGAGCACCTCCGAGAGCACAGCCGCCCTGGGCTGCCTGGTCAAGGA CTACTTCCCCGAACCGGTGACGGTGTCGTGGAACTCAGGCGCCCTGACCAGCGGCGT GCACACCTTCCCGGCTGTCCTACAGTCCTCAGGACTCTACTCCCTCAGCAGCGTGGTG ACCGTGCCCTCCAGCAGCTTGGGCACGAAGACCTACACCTGCAACGTAGATCACAAG CCCAGCAACACCAAGGTGGACAAGAGAGTTGAGTCCAAATATGGTCCCCCATGCCCA CCGTGCCCAGCACCACCTGTGGCAGGACCATCAGTCTTCCTGTTCCCCCCAAAACCCA AGGACACTCTCATGATCTCCCGGACCCCTGAGGTCACGTGCGTGGTGGTGGACGTGA GCCAGGAAGACCCCGAGGTCCAGTTCAACTGGTACGTGGATGGCGTGGAGGTGCATA ATGCCAAGACAAAGCCGCGGGAGGAGCAGTTCAACAGCACGTACCGTGTGGTCAGCG TCCTCACCGTCCTGCACCAGGACTGGCTGAACGGCAAGGAGTACAAGTGCAAGGTCT CCAACAAAGGCCTCCCGTCCTCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGC CCCGAGAGCCACAGGTGTACACCCTGCCCCCATCCCAGGAGGAGATGACCAAGAACC AGGTCAGCCTGACCTGCCTGGTCAAAGGCTTCTACCCCAGCGACATCGCCGTGGAGT GGGAGAGCAATGGGCAGCCGGAGAACAACTACAAGACCACGCCTCCCGTGCTGGACT CCGACGGCTCCTTCTTCCTCTACAGCAGGCTCACCGTGGACAAGAGCAGGTGGCAGG AGGGGAATGTCTTCTCATGCTCCGTGATGCATGAGGCTCTGCACAACCACTACACACA GAAGTCCCTCTCCCTGTCTCTGGGTAAATGA (SEQ ID NO: 516) HC Amino Acid Sequence QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYGISWVRQAPGQGLEWMGWISAYNGNT KYAQKFQGRVTMTRDTSTSTAYMELRSLRSDDTAVYYCARWVSMFRGVPGDSWGQGTL VTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPA VLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPPVA GPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQF NSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEE MTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRW QEGNVFSCSVMHEALHNHYTQKSLSLSLGK* Attorney Docket No.250298.000780 (SEQ ID NO: 517) LC DNA Sequence GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACAGAGTCA CCATCACTTGCCGGGCAAGTCAGAGCATTAGCAGCTATTTAAATTGGTATCAGCAGAA ACCAGGGAAAGCCCCTAAGCTCCTGATCTATGCTGCATCCAGTTTGCAAAGTGGGGTC CCGTCAAGGTTCAGTGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGTC TGCAACCTGAAGATTTTGCAACTTACTACTGTCAACAGAGTTACAGTACCCCTCCGATC ACCTTCGGCCAAGGGACACGACTGGAGATTAAACGAACTGTGGCTGCACCATCTGTCT TCATCTTCCCGCCATCTGATGAGCAGTTGAAATCTGGAACTGCCTCTGTTGTGTGCCT GCTGAATAACTTCTATCCCAGAGAGGCCAAAGTACAGTGGAAGGTGGATAACGCCCTC CAATCGGGTAACTCCCAGGAGAGTGTCACAGAGCAGGACAGCAAGGACAGCACCTAC AGCCTCAGCAGCACCCTGACGCTGAGCAAAGCAGACTACGAGAAACACAAAGTCTAC GCCTGCGAAGTCACCCATCAGGGCCTGAGCTCGCCCGTCACAAAGAGCTTCAACAGG GGAGAGTGTTAG (SEQ ID NO: 414) LC Amino Acid Sequence DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSR FSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPPITFGQGTRLEIKRTVAAPSVFIFPPSDE QLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSK ADYEKHKVYACEVTHQGLSSPVTKSFNRGEC* (SEQ ID NO: 415) REGN14191 HCVR DNA Sequence CAGGTGCAGCTGGTGCAGTCTGGGGCTGAAGTGAAGAAGCCTGGGGCCTCAGTGAA GGTCTCCTGCAAGGCTTCTGGATACACCTTCACCGGCTACTATTTACACTGGCTGCGA CAGGCCCCTGGACAAGGACTTGAGTGGATGGGATGGATCAACCCTAACAGTGGTCGC CCAAACTATGCACAGAAGTTTCAGGGCAGGGTCACCATGACCAGGGACACGTCCATCA GCACGGCCTACATGGAACTGCACAGTCTGAGATCTGACGACACGGCCGTGTATTATTG TGCGAAAGAAACGGGAACTACGAGGGGCTGGTTCGACCCCTGGGGCCAGGGAACCC TGGTCACCGTCTCCTCA Attorney Docket No.250298.000780 (SEQ ID NO: 518) HCVR Amino Acid Sequence QVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYLHWLRQAPGQGLEWMGWINPNSGRP NYAQKFQGRVTMTRDTSISTAYMELHSLRSDDTAVYYCAKETGTTRGWFDPWGQGTLVT VSS (SEQ ID NO: 519) CDR1 DNA Sequence GGA TAC ACC TTC ACC GGC TAC TAT (SEQ ID NO: 520) CDR1 Amino Acid Sequence G Y T F T G Y Y (SEQ ID NO: 521) CDR2 DNA Sequence ATC AAC CCT AAC AGT GGT CGC CCA (SEQ ID NO: 522) CDR2 Amino Acid Sequence I N P N S G R P (SEQ ID NO: 523) CDR3 DNA Sequence GCG AAA GAA ACG GGA ACT ACG AGG GGC TGG TTC GAC CCC (SEQ ID NO: 524) CDR3 Amino Acid Sequence A K E T G T T R G W F D P (SEQ ID NO: 525) LCVR DNA Sequence Attorney Docket No.250298.000780 GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACAGAGTCA CCATCACTTGCCGGGCAAGTCAGAGCATTAGCAGCTATTTAAATTGGTATCAGCAGAA ACCAGGGAAAGCCCCTAAGCTCCTGATCTATGCTGCATCCAGTTTGCAAAGTGGGGTC CCGTCAAGGTTCAGTGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGTC TGCAACCTGAAGATTTTGCAACTTACTACTGTCAACAGAGTTACAGTACCCCTCCGATC ACCTTCGGCCAAGGGACACGACTGGAGATTAAA (SEQ ID NO: 408) LCVR Amino Acid Sequence DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSR FSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPPITFGQGTRLEIK (SEQ ID NO: 409) CDR1 DNA Sequence CAG AGC ATT AGC AGC TAT (SEQ ID NO: 236) CDR1 Amino Acid Sequence Q S I S S Y (SEQ ID NO: 237) CDR2 DNA Sequence GCT GCA TCC (SEQ ID NO: 13) CDR2 Amino Acid Sequence A A S (SEQ ID NO: 14) CDR3 DNA Sequence CAA CAG AGT TAC AGT ACC CCT CCG ATC ACC (SEQ ID NO: 410) Attorney Docket No.250298.000780 CDR3 Amino Acid Sequence Q Q S Y S T P P I T (SEQ ID NO: 411) HC DNA Sequence CAGGTGCAGCTGGTGCAGTCTGGGGCTGAAGTGAAGAAGCCTGGGGCCTCAGTGAA GGTCTCCTGCAAGGCTTCTGGATACACCTTCACCGGCTACTATTTACACTGGCTGCGA CAGGCCCCTGGACAAGGACTTGAGTGGATGGGATGGATCAACCCTAACAGTGGTCGC CCAAACTATGCACAGAAGTTTCAGGGCAGGGTCACCATGACCAGGGACACGTCCATCA GCACGGCCTACATGGAACTGCACAGTCTGAGATCTGACGACACGGCCGTGTATTATTG TGCGAAAGAAACGGGAACTACGAGGGGCTGGTTCGACCCCTGGGGCCAGGGAACCC TGGTCACCGTCTCCTCAGCCTCCACCAAGGGCCCATCGGTCTTCCCCCTGGCGCCCT GCTCCAGGAGCACCTCCGAGAGCACAGCCGCCCTGGGCTGCCTGGTCAAGGACTACT TCCCCGAACCGGTGACGGTGTCGTGGAACTCAGGCGCCCTGACCAGCGGCGTGCAC ACCTTCCCGGCTGTCCTACAGTCCTCAGGACTCTACTCCCTCAGCAGCGTGGTGACCG TGCCCTCCAGCAGCTTGGGCACGAAGACCTACACCTGCAACGTAGATCACAAGCCCA GCAACACCAAGGTGGACAAGAGAGTTGAGTCCAAATATGGTCCCCCATGCCCACCGT GCCCAGCACCACCTGTGGCAGGACCATCAGTCTTCCTGTTCCCCCCAAAACCCAAGG ACACTCTCATGATCTCCCGGACCCCTGAGGTCACGTGCGTGGTGGTGGACGTGAGCC AGGAAGACCCCGAGGTCCAGTTCAACTGGTACGTGGATGGCGTGGAGGTGCATAATG CCAAGACAAAGCCGCGGGAGGAGCAGTTCAACAGCACGTACCGTGTGGTCAGCGTCC TCACCGTCCTGCACCAGGACTGGCTGAACGGCAAGGAGTACAAGTGCAAGGTCTCCA ACAAAGGCCTCCCGTCCTCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCC GAGAGCCACAGGTGTACACCCTGCCCCCATCCCAGGAGGAGATGACCAAGAACCAGG TCAGCCTGACCTGCCTGGTCAAAGGCTTCTACCCCAGCGACATCGCCGTGGAGTGGG AGAGCAATGGGCAGCCGGAGAACAACTACAAGACCACGCCTCCCGTGCTGGACTCCG ACGGCTCCTTCTTCCTCTACAGCAGGCTCACCGTGGACAAGAGCAGGTGGCAGGAGG GGAATGTCTTCTCATGCTCCGTGATGCATGAGGCTCTGCACAACCACTACACACAGAA GTCCCTCTCCCTGTCTCTGGGTAAATGA (SEQ ID NO: 526) HC Amino Acid Sequence Attorney Docket No.250298.000780 QVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYLHWLRQAPGQGLEWMGWINPNSGRP NYAQKFQGRVTMTRDTSISTAYMELHSLRSDDTAVYYCAKETGTTRGWFDPWGQGTLVT VSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVL QSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPPVAGP SVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNS TYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMT KNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQE GNVFSCSVMHEALHNHYTQKSLSLSLGK* (SEQ ID NO: 527) LC DNA Sequence GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACAGAGTCA CCATCACTTGCCGGGCAAGTCAGAGCATTAGCAGCTATTTAAATTGGTATCAGCAGAA ACCAGGGAAAGCCCCTAAGCTCCTGATCTATGCTGCATCCAGTTTGCAAAGTGGGGTC CCGTCAAGGTTCAGTGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGTC TGCAACCTGAAGATTTTGCAACTTACTACTGTCAACAGAGTTACAGTACCCCTCCGATC ACCTTCGGCCAAGGGACACGACTGGAGATTAAACGAACTGTGGCTGCACCATCTGTCT TCATCTTCCCGCCATCTGATGAGCAGTTGAAATCTGGAACTGCCTCTGTTGTGTGCCT GCTGAATAACTTCTATCCCAGAGAGGCCAAAGTACAGTGGAAGGTGGATAACGCCCTC CAATCGGGTAACTCCCAGGAGAGTGTCACAGAGCAGGACAGCAAGGACAGCACCTAC AGCCTCAGCAGCACCCTGACGCTGAGCAAAGCAGACTACGAGAAACACAAAGTCTAC GCCTGCGAAGTCACCCATCAGGGCCTGAGCTCGCCCGTCACAAAGAGCTTCAACAGG GGAGAGTGTTAG (SEQ ID NO: 414) LC Amino Acid Sequence DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSR FSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPPITFGQGTRLEIKRTVAAPSVFIFPPSDE QLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSK ADYEKHKVYACEVTHQGLSSPVTKSFNRGEC* (SEQ ID NO: 415) REGN19513 Attorney Docket No.250298.000780 HCVR DNA Sequence GAGGTGCAGCTGGTGGAGTCTGGGGGAGGCTTGGTGCAGCCTGGGGGGTCCCTGAG GCTCTCCTGTGCAGCCTCTGGATTCACCTTTAACAACTATGCCATGACCTGGGTCCGC CAGGCTCCAGGGAAGGGGCTGGAGTGGGTCTCAGCTGTTACTGGTAGTGGTCGTGAC ACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCGTCTCCAGAGACAATTCCAAGA ACACGCTGTATCTGCAAATGAGCAGCCTGAGAGCCGAGGACACGGCCGTATATTTCTG TGCGAAGAAAGCTGCGGACTACTATTACGGTATGGACGTCTGGGGCCAAGGGACCAC GGTCACCGTCTCCTCA (SEQ ID NO: 528) HCVR Amino Acid Sequence EVQLVESGGGLVQPGGSLRLSCAASGFTFNNYAMTWVRQAPGKGLEWVSAVTGSGRDT YYADSVKGRFTVSRDNSKNTLYLQMSSLRAEDTAVYFCAKKAADYYYGMDVWGQGTTVT VSS (SEQ ID NO: 529) CDR1 DNA Sequence GGA TTC ACC TTT AAC AAC TAT GCC (SEQ ID NO: 530) CDR1 Amino Acid Sequence G F T F N N Y A (SEQ ID NO: 531) CDR2 DNA Sequence GTT ACT GGT AGT GGT CGT GAC ACA (SEQ ID NO: 532) CDR2 Amino Acid Sequence V T G S G R D T (SEQ ID NO: 533) CDR3 DNA Sequence Attorney Docket No.250298.000780 GCG AAG AAA GCT GCG GAC TAC TAT TAC GGT ATG GAC GTC (SEQ ID NO: 534) CDR3 Amino Acid Sequence A K K A A D Y Y Y G M D V (SEQ ID NO: 535) LCVR DNA Sequence GACATCCAGATGACCCAGTCTCCATCTTCCGTGTCTGCATCTGTGGGAGACAGAGTCA CCATCACTTGTCGGGCGAGTCAGGGTATTAGCAGCTGGTCAGCCTGGTATCAGCAGA AACCAGGAAAAGCCCCTAAACTCCTGATCTATACTACATCCAGTTTCCAAAGTGGGGTC CCATCAAGGTTCAGCGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGCC TGCAGCCTGAAGATTTTGCAAGTTACTATTGTCAACAGGCTCACGACTTCTCGCTCACT TTCGGCGGAGGGACCAAGGTGGAGATCAAA (SEQ ID NO: 536) LCVR Amino Acid Sequence DIQMTQSPSSVSASVGDRVTITCRASQGISSWSAWYQQKPGKAPKLLIYTTSSFQSGVPS RFSGSGSGTDFTLTISSLQPEDFASYYCQQAHDFSLTFGGGTKVEIK (SEQ ID NO: 537) CDR1 DNA Sequence CAG GGT ATT AGC AGC TGG (SEQ ID NO: 538) CDR1 Amino Acid Sequence Q G I S S W (SEQ ID NO: 539) CDR2 DNA Sequence ACT ACA TCC (SEQ ID NO: 540) Attorney Docket No.250298.000780 CDR2 Amino Acid Sequence T T S (SEQ ID NO: 541) CDR3 DNA Sequence CAA CAG GCT CAC GAC TTC TCG CTC ACT (SEQ ID NO: 542) CDR3 Amino Acid Sequence Q Q A H D F S L T (SEQ ID NO: 543) HC DNA Sequence GAGGTGCAGCTGGTGGAGTCTGGGGGAGGCTTGGTGCAGCCTGGGGGGTCCCTGAG GCTCTCCTGTGCAGCCTCTGGATTCACCTTTAACAACTATGCCATGACCTGGGTCCGC CAGGCTCCAGGGAAGGGGCTGGAGTGGGTCTCAGCTGTTACTGGTAGTGGTCGTGAC ACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCGTCTCCAGAGACAATTCCAAGA ACACGCTGTATCTGCAAATGAGCAGCCTGAGAGCCGAGGACACGGCCGTATATTTCTG TGCGAAGAAAGCTGCGGACTACTATTACGGTATGGACGTCTGGGGCCAAGGGACCAC GGTCACCGTCTCCTCAGCCTCCACCAAGGGCCCATCGGTCTTCCCCCTGGCGCCCTG CTCCAGGAGCACCTCCGAGAGCACAGCCGCCCTGGGCTGCCTGGTCAAGGACTACTT CCCCGAACCGGTGACGGTGTCGTGGAACTCAGGCGCCCTGACCAGCGGCGTGCACA CCTTCCCGGCTGTCCTACAGTCCTCAGGACTCTACTCCCTCAGCAGCGTGGTGACCGT GCCCTCCAGCAGCTTGGGCACGAAGACCTACACCTGCAACGTAGATCACAAGCCCAG CAACACCAAGGTGGACAAGAGAGTTGAGTCCAAATATGGTCCCCCATGCCCACCCTGC CCAGCACCTGAGTTCCTGGGGGGACCATCAGTCTTCCTGTTCCCCCCAAAACCCAAG GACACTCTCATGATCTCCCGGACCCCTGAGGTCACGTGCGTGGTGGTGGACGTGAGC CAGGAAGACCCCGAGGTCCAGTTCAACTGGTACGTGGATGGCGTGGAGGTGCATAAT GCCAAGACAAAGCCGCGGGAGGAGCAGTTCAACAGCACGTACCGTGTGGTCAGCGTC CTCACCGTCCTGCACCAGGACTGGCTGAACGGCAAGGAGTACAAGTGCAAGGTCTCC AACAAAGGCCTCCCGTCCTCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCC CGAGAGCCACAGGTGTACACCCTGCCCCCATCCCAGGAGGAGATGACCAAGAACCAG GTCAGCCTGACCTGCCTGGTCAAAGGCTTCTACCCCAGCGACATCGCCGTGGAGTGG Attorney Docket No.250298.000780 GAGAGCAATGGGCAGCCGGAGAACAACTACAAGACCACGCCTCCCGTGCTGGACTCC GACGGCTCCTTCTTCCTCTACAGCAGGCTCACCGTGGACAAGAGCAGGTGGCAGGAG GGGAATGTCTTCTCATGCTCCGTGATGCATGAGGCTCTGCACAACCACTACACACAGA AGTCCCTCTCCCTGTCTCTGGGTAAATGA (SEQ ID NO: 544) HC Amino Acid Sequence EVQLVESGGGLVQPGGSLRLSCAASGFTFNNYAMTWVRQAPGKGLEWVSAVTGSGRDT YYADSVKGRFTVSRDNSKNTLYLQMSSLRAEDTAVYFCAKKAADYYYGMDVWGQGTTVT VSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVL QSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPEFLGG PSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFN STYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEE MTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRW QEGNVFSCSVMHEALHNHYTQKSLSLSLGK* (SEQ ID NO: 545) LC DNA Sequence GACATCCAGATGACCCAGTCTCCATCTTCCGTGTCTGCATCTGTGGGAGACAGAGTCA CCATCACTTGTCGGGCGAGTCAGGGTATTAGCAGCTGGTCAGCCTGGTATCAGCAGA AACCAGGAAAAGCCCCTAAACTCCTGATCTATACTACATCCAGTTTCCAAAGTGGGGTC CCATCAAGGTTCAGCGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGCC TGCAGCCTGAAGATTTTGCAAGTTACTATTGTCAACAGGCTCACGACTTCTCGCTCACT TTCGGCGGAGGGACCAAGGTGGAGATCAAACGAACTGTGGCTGCACCATCTGTCTTC ATCTTCCCGCCATCTGATGAGCAGTTGAAATCTGGAACTGCCTCTGTTGTGTGCCTGC TGAATAACTTCTATCCCAGAGAGGCCAAAGTACAGTGGAAGGTGGATAACGCCCTCCA ATCGGGTAACTCCCAGGAGAGTGTCACAGAGCAGGACAGCAAGGACAGCACCTACAG CCTCAGCAGCACCCTGACGCTGAGCAAAGCAGACTACGAGAAACACAAAGTCTACGC CTGCGAAGTCACCCATCAGGGCCTGAGCTCGCCCGTCACAAAGAGCTTCAACAGGGG AGAGTGTTAG (SEQ ID NO: 546) LC Amino Acid Sequence Attorney Docket No.250298.000780 DIQMTQSPSSVSASVGDRVTITCRASQGISSWSAWYQQKPGKAPKLLIYTTSSFQSGVPS RFSGSGSGTDFTLTISSLQPEDFASYYCQQAHDFSLTFGGGTKVEIKRTVAAPSVFIFPPSD EQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLS KADYEKHKVYACEVTHQGLSSPVTKSFNRGEC* (SEQ ID NO: 547) REGN19514 HCVR DNA Sequence GAGGTGCAGCTGGTGGAGTCTGGGGGAGACTTGGTCCAGCCGGGGGGGTCCCTGAG ACTCTCCTGTGTAGCCTCTGGATTCACCTTTAGTAGCTTTTGGATGAGCTGGGTCCGC CAGGCTCCAGGGAAGGGGCTGGAGTGGGTGGCCAACATAAAACAAGATGGAAGTGAG AACTACTATGTGGACTCTGTGAAGGGCCGATTCACCATCTCCAGAGACAACGCCAAGA ACTCACTGTATCTGCAAATGAACAGCCTGAGAGCAGAGGACACGGCTATGTATTACTG TGCGGTAAACTGGGGAAACTACTGGGGCCAGGGAACCCTGGTCACCGTCTCCTCA (SEQ ID NO: 548) HCVR Amino Acid Sequence EVQLVESGGDLVQPGGSLRLSCVASGFTFSSFWMSWVRQAPGKGLEWVANIKQDGSEN YYVDSVKGRFTISRDNAKNSLYLQMNSLRAEDTAMYYCAVNWGNYWGQGTLVTVSS (SEQ ID NO: 549) CDR1 DNA Sequence GGA TTC ACC TTT AGT AGC TTT TGG (SEQ ID NO: 550) CDR1 Amino Acid Sequence G F T F S S F W (SEQ ID NO: 551) CDR2 DNA Sequence ATA AAA CAA GAT GGA AGT GAG AAC (SEQ ID NO: 552) Attorney Docket No.250298.000780 CDR2 Amino Acid Sequence I K Q D G S E N (SEQ ID NO: 553) CDR3 DNA Sequence GCG GTA AAC TGG GGA AAC TAC (SEQ ID NO: 554) CDR3 Amino Acid Sequence A V N W G N Y (SEQ ID NO: 555) LCVR DNA Sequence GACATCGTGATGACCCAGTCTCCAGACTCCCTGGCTGTGTCTCTGGGCGTGCGGGCC ACCATCAACTGCAGGTCCAGCCAGAGTGTTTTATACAGCTCCAACAATAAAAACTACTT AGCTTGGTTCATGCAGAAGCCAGGACAGCCTCCCAAGTTGCTCATTTACTGGGCATCT ACCCGGGACTCCGGGGTCCCTGACCGATTCAGTGGCAGCGGGTCTGGGACAGATTTC ACTCTCACCATCACCAGTCTACAGGCTGAAGATGTGGCAGTTTATTACTGTCAGCAAAA TTATGGTATTCCTTGGACGTTCGGCCAAGGGACCAAGGTGGAAATCAAA (SEQ ID NO: 556) LCVR Amino Acid Sequence DIVMTQSPDSLAVSLGVRATINCRSSQSVLYSSNNKNYLAWFMQKPGQPPKLLIYWASTR DSGVPDRFSGSGSGTDFTLTITSLQAEDVAVYYCQQNYGIPWTFGQGTKVEIK (SEQ ID NO: 557) CDR1 DNA Sequence CAG AGT GTT TTA TAC AGC TCC AAC AAT AAA AAC TAC (SEQ ID NO: 558) CDR1 Amino Acid Sequence Q S V L Y S S N N K N Y (SEQ ID NO: 559) Attorney Docket No.250298.000780 CDR2 DNA Sequence TGG GCA TCT (SEQ ID NO: 560) CDR2 Amino Acid Sequence W A S (SEQ ID NO: 561) CDR3 DNA Sequence CAG CAA AAT TAT GGT ATT CCT TGG ACG (SEQ ID NO: 562) CDR3 Amino Acid Sequence Q Q N Y G I P W T (SEQ ID NO: 563) HC DNA Sequence GAGGTGCAGCTGGTGGAGTCTGGGGGAGACTTGGTCCAGCCGGGGGGGTCCCTGAG ACTCTCCTGTGTAGCCTCTGGATTCACCTTTAGTAGCTTTTGGATGAGCTGGGTCCGC CAGGCTCCAGGGAAGGGGCTGGAGTGGGTGGCCAACATAAAACAAGATGGAAGTGAG AACTACTATGTGGACTCTGTGAAGGGCCGATTCACCATCTCCAGAGACAACGCCAAGA ACTCACTGTATCTGCAAATGAACAGCCTGAGAGCAGAGGACACGGCTATGTATTACTG TGCGGTAAACTGGGGAAACTACTGGGGCCAGGGAACCCTGGTCACCGTCTCCTCAGC CTCCACCAAGGGCCCATCGGTCTTCCCCCTGGCGCCCTGCTCCAGGAGCACCTCCGA GAGCACAGCCGCCCTGGGCTGCCTGGTCAAGGACTACTTCCCCGAACCGGTGACGGT GTCGTGGAACTCAGGCGCCCTGACCAGCGGCGTGCACACCTTCCCGGCTGTCCTACA GTCCTCAGGACTCTACTCCCTCAGCAGCGTGGTGACCGTGCCCTCCAGCAGCTTGGG CACGAAGACCTACACCTGCAACGTAGATCACAAGCCCAGCAACACCAAGGTGGACAA GAGAGTTGAGTCCAAATATGGTCCCCCATGCCCACCCTGCCCAGCACCTGAGTTCCTG GGGGGACCATCAGTCTTCCTGTTCCCCCCAAAACCCAAGGACACTCTCATGATCTCCC GGACCCCTGAGGTCACGTGCGTGGTGGTGGACGTGAGCCAGGAAGACCCCGAGGTC CAGTTCAACTGGTACGTGGATGGCGTGGAGGTGCATAATGCCAAGACAAAGCCGCGG Attorney Docket No.250298.000780 GAGGAGCAGTTCAACAGCACGTACCGTGTGGTCAGCGTCCTCACCGTCCTGCACCAG GACTGGCTGAACGGCAAGGAGTACAAGTGCAAGGTCTCCAACAAAGGCCTCCCGTCC TCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGAGAGCCACAGGTGTAC ACCCTGCCCCCATCCCAGGAGGAGATGACCAAGAACCAGGTCAGCCTGACCTGCCTG GTCAAAGGCTTCTACCCCAGCGACATCGCCGTGGAGTGGGAGAGCAATGGGCAGCCG GAGAACAACTACAAGACCACGCCTCCCGTGCTGGACTCCGACGGCTCCTTCTTCCTCT ACAGCAGGCTCACCGTGGACAAGAGCAGGTGGCAGGAGGGGAATGTCTTCTCATGCT CCGTGATGCATGAGGCTCTGCACAACCACTACACACAGAAGTCCCTCTCCCTGTCTCT GGGTAAATGA (SEQ ID NO: 564) HC Amino Acid Sequence EVQLVESGGDLVQPGGSLRLSCVASGFTFSSFWMSWVRQAPGKGLEWVANIKQDGSEN YYVDSVKGRFTISRDNAKNSLYLQMNSLRAEDTAMYYCAVNWGNYWGQGTLVTVSSAST KGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLY SLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPEFLGGPSVFLF PPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVV SVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQV SLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVF SCSVMHEALHNHYTQKSLSLSLGK* (SEQ ID NO: 565) LC DNA Sequence GACATCGTGATGACCCAGTCTCCAGACTCCCTGGCTGTGTCTCTGGGCGTGCGGGCC ACCATCAACTGCAGGTCCAGCCAGAGTGTTTTATACAGCTCCAACAATAAAAACTACTT AGCTTGGTTCATGCAGAAGCCAGGACAGCCTCCCAAGTTGCTCATTTACTGGGCATCT ACCCGGGACTCCGGGGTCCCTGACCGATTCAGTGGCAGCGGGTCTGGGACAGATTTC ACTCTCACCATCACCAGTCTACAGGCTGAAGATGTGGCAGTTTATTACTGTCAGCAAAA TTATGGTATTCCTTGGACGTTCGGCCAAGGGACCAAGGTGGAAATCAAACGAACTGTG GCTGCACCATCTGTCTTCATCTTCCCGCCATCTGATGAGCAGTTGAAATCTGGAACTG CCTCTGTTGTGTGCCTGCTGAATAACTTCTATCCCAGAGAGGCCAAAGTACAGTGGAA GGTGGATAACGCCCTCCAATCGGGTAACTCCCAGGAGAGTGTCACAGAGCAGGACAG CAAGGACAGCACCTACAGCCTCAGCAGCACCCTGACGCTGAGCAAAGCAGACTACGA Attorney Docket No.250298.000780 GAAACACAAAGTCTACGCCTGCGAAGTCACCCATCAGGGCCTGAGCTCGCCCGTCAC AAAGAGCTTCAACAGGGGAGAGTGTTAG (SEQ ID NO: 566) LC Amino Acid Sequence DIVMTQSPDSLAVSLGVRATINCRSSQSVLYSSNNKNYLAWFMQKPGQPPKLLIYWASTR DSGVPDRFSGSGSGTDFTLTITSLQAEDVAVYYCQQNYGIPWTFGQGTKVEIKRTVAAPSV FIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSL SSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC* (SEQ ID NO: 567) REGN19515 HCVR DNA Sequence CAGGTGCAGCTGGTGCAGTCTGGGGCTGAGGTGAAGAAGCCTGGGTCCTCGGTGAA GGTCTCCTGCAAGTCTTCTGGAGGCACCTTCAGTAGTTATGGTATCAGCTGGGTGCGA CAGGCCCCTGGACAAGGGCTTGAGTGGATGGGAGGGATCATCCCTCTCTTTGGTACA ACAAATTACGCACAGAAGTTCCAGGCCAGAGTCACGATTACCTCGGTCGAATCAACGA CCACAGCCTACATGGAACTGAACAGCCTGAGATCTGAGGACACGGCCGTATATTACTG TGCGAAAGATCGACGTGGATACAGCTCTGTTTCCCTACCTCAGTTCCACTCCTTCGGTT TGGACGTCTGGGGCCAAGGGACCACGGTCACCGTCTCCTCA (SEQ ID NO: 568) HCVR Amino Acid Sequence QVQLVQSGAEVKKPGSSVKVSCKSSGGTFSSYGISWVRQAPGQGLEWMGGIIPLFGTTN YAQKFQARVTITSVESTTTAYMELNSLRSEDTAVYYCAKDRRGYSSVSLPQFHSFGLDVW GQGTTVTVSS (SEQ ID NO: 569) CDR1 DNA Sequence GGA GGC ACC TTC AGT AGT TAT GGT (SEQ ID NO: 570) CDR1 Amino Acid Sequence Attorney Docket No.250298.000780 G G T F S S Y G (SEQ ID NO: 571) CDR2 DNA Sequence ATC ATC CCT CTC TTT GGT ACA ACA (SEQ ID NO: 572) CDR2 Amino Acid Sequence I I P L F G T T (SEQ ID NO: 573) CDR3 DNA Sequence GCGAAAGATCGACGTGGATACAGCTCTGTTTCCCTACCTCAGTTCCACTCCTTCGGTTT GGACGTC (SEQ ID NO: 574) CDR3 Amino Acid Sequence AKDRRGYSSVSLPQFHSFGLDV (SEQ ID NO: 575) LCVR DNA Sequence GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACAGAGTCA CCATCACTTGCCGGGCAAGTCAGAGCATTAGCAGCTATTTAAATTGGTATCAGCAGAA ACCAGGGAAAGCCCCTAAGCTCCTGATCTATGCTGCATCCAGTTTGCAAAGTGGGGTC CCGTCAAGGTTCAGTGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGTC TGCAACCTGAAGATTTTGCAACTTACTACTGTCAACAGAGTTACAGTACCCCTCCGATC ACCTTCGGCCAAGGGACACGACTGGAGATTAAA (SEQ ID NO: 576) LCVR Amino Acid Sequence DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSR FSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPPITFGQGTRLEIK (SEQ ID NO: 577) Attorney Docket No.250298.000780 CDR1 DNA Sequence CAG AGC ATT AGC AGC TAT (SEQ ID NO: 578) CDR1 Amino Acid Sequence Q S I S S Y (SEQ ID NO: 579) CDR2 DNA Sequence GCT GCA TCC (SEQ ID NO: 580) CDR2 Amino Acid Sequence A A S (SEQ ID NO: 581) CDR3 DNA Sequence CAA CAG AGT TAC AGT ACC CCT CCG ATC ACC (SEQ ID NO: 582) CDR3 Amino Acid Sequence Q Q S Y S T P P I T (SEQ ID NO: 583) HC DNA Sequence CAGGTGCAGCTGGTGCAGTCTGGGGCTGAGGTGAAGAAGCCTGGGTCCTCGGTGAA GGTCTCCTGCAAGTCTTCTGGAGGCACCTTCAGTAGTTATGGTATCAGCTGGGTGCGA CAGGCCCCTGGACAAGGGCTTGAGTGGATGGGAGGGATCATCCCTCTCTTTGGTACA ACAAATTACGCACAGAAGTTCCAGGCCAGAGTCACGATTACCTCGGTCGAATCAACGA CCACAGCCTACATGGAACTGAACAGCCTGAGATCTGAGGACACGGCCGTATATTACTG TGCGAAAGATCGACGTGGATACAGCTCTGTTTCCCTACCTCAGTTCCACTCCTTCGGTT TGGACGTCTGGGGCCAAGGGACCACGGTCACCGTCTCCTCAGCCTCCACCAAGGGCC Attorney Docket No.250298.000780 CATCGGTCTTCCCCCTGGCGCCCTGCTCCAGGAGCACCTCCGAGAGCACAGCCGCCC TGGGCTGCCTGGTCAAGGACTACTTCCCCGAACCGGTGACGGTGTCGTGGAACTCAG GCGCCCTGACCAGCGGCGTGCACACCTTCCCGGCTGTCCTACAGTCCTCAGGACTCT ACTCCCTCAGCAGCGTGGTGACCGTGCCCTCCAGCAGCTTGGGCACGAAGACCTACA CCTGCAACGTAGATCACAAGCCCAGCAACACCAAGGTGGACAAGAGAGTTGAGTCCA AATATGGTCCCCCATGCCCACCCTGCCCAGCACCTGAGTTCCTGGGGGGACCATCAG TCTTCCTGTTCCCCCCAAAACCCAAGGACACTCTCATGATCTCCCGGACCCCTGAGGT CACGTGCGTGGTGGTGGACGTGAGCCAGGAAGACCCCGAGGTCCAGTTCAACTGGTA CGTGGATGGCGTGGAGGTGCATAATGCCAAGACAAAGCCGCGGGAGGAGCAGTTCAA CAGCACGTACCGTGTGGTCAGCGTCCTCACCGTCCTGCACCAGGACTGGCTGAACGG CAAGGAGTACAAGTGCAAGGTCTCCAACAAAGGCCTCCCGTCCTCCATCGAGAAAACC ATCTCCAAAGCCAAAGGGCAGCCCCGAGAGCCACAGGTGTACACCCTGCCCCCATCC CAGGAGGAGATGACCAAGAACCAGGTCAGCCTGACCTGCCTGGTCAAAGGCTTCTAC CCCAGCGACATCGCCGTGGAGTGGGAGAGCAATGGGCAGCCGGAGAACAACTACAA GACCACGCCTCCCGTGCTGGACTCCGACGGCTCCTTCTTCCTCTACAGCAGGCTCAC CGTGGACAAGAGCAGGTGGCAGGAGGGGAATGTCTTCTCATGCTCCGTGATGCATGA GGCTCTGCACAACCACTACACACAGAAGTCCCTCTCCCTGTCTCTGGGTAAATGA (SEQ ID NO: 584) HC Amino Acid Sequence QVQLVQSGAEVKKPGSSVKVSCKSSGGTFSSYGISWVRQAPGQGLEWMGGIIPLFGTTN YAQKFQARVTITSVESTTTAYMELNSLRSEDTAVYYCAKDRRGYSSVSLPQFHSFGLDVW GQGTTVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGV HTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCP APEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTK PREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTL PPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLT VDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGK* (SEQ ID NO: 585) LC DNA Sequence GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACAGAGTCA CCATCACTTGCCGGGCAAGTCAGAGCATTAGCAGCTATTTAAATTGGTATCAGCAGAA Attorney Docket No.250298.000780 ACCAGGGAAAGCCCCTAAGCTCCTGATCTATGCTGCATCCAGTTTGCAAAGTGGGGTC CCGTCAAGGTTCAGTGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGTC TGCAACCTGAAGATTTTGCAACTTACTACTGTCAACAGAGTTACAGTACCCCTCCGATC ACCTTCGGCCAAGGGACACGACTGGAGATTAAACGAACTGTGGCTGCACCATCTGTCT TCATCTTCCCGCCATCTGATGAGCAGTTGAAATCTGGAACTGCCTCTGTTGTGTGCCT GCTGAATAACTTCTATCCCAGAGAGGCCAAAGTACAGTGGAAGGTGGATAACGCCCTC CAATCGGGTAACTCCCAGGAGAGTGTCACAGAGCAGGACAGCAAGGACAGCACCTAC AGCCTCAGCAGCACCCTGACGCTGAGCAAAGCAGACTACGAGAAACACAAAGTCTAC GCCTGCGAAGTCACCCATCAGGGCCTGAGCTCGCCCGTCACAAAGAGCTTCAACAGG GGAGAGTGTTAG (SEQ ID NO: 586) LC Amino Acid Sequence DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSR FSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPPITFGQGTRLEIKRTVAAPSVFIFPPSDE QLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSK ADYEKHKVYACEVTHQGLSSPVTKSFNRGEC* (SEQ ID NO: 587) REGN19516 HCVR DNA Sequence CAGGTGCAGCTGGTGGAGTCTGGGGGAGGCGTGGTCCAGCCTGGGAGGTCCCTGAG ACTCTCCTGTGCAGCGTCTGGATTCACCTTCAGCGCCTATGTCATGCACTGGGTCCGC CAGGCTCCAGGCAAGGGGCTGGAGTGGATTACAGTTATTGATTATGATGCAAAGAATA AATACTATGCAGACTCCGTGAGGGGCCGATTCACCGTCTCCAGAGACAATTCCAAGAA CACGCTGTTTCTGCAAATGAACAGCCTGAGAGCCGAGGACACGGCTGTGTATTACTGT GCGAGAAATAGAGGTGGCTACAATTACTTTGACTACTGGGGCCAGGGAACCCTGGTCA CCGTCTCCTCA (SEQ ID NO: 588) HCVR Amino Acid Sequence Attorney Docket No.250298.000780 QVQLVESGGGVVQPGRSLRLSCAASGFTFSAYVMHWVRQAPGKGLEWITVIDYDAKNKY YADSVRGRFTVSRDNSKNTLFLQMNSLRAEDTAVYYCARNRGGYNYFDYWGQGTLVTVS S (SEQ ID NO: 589) CDR1 DNA Sequence GGA TTC ACC TTC AGC GCC TAT GTC (SEQ ID NO: 590) CDR1 Amino Acid Sequence G F T F S A Y V (SEQ ID NO: 591) CDR2 DNA Sequence ATT GAT TAT GAT GCA AAG AAT AAA (SEQ ID NO: 592) CDR2 Amino Acid Sequence I D Y D A K N K (SEQ ID NO: 593) CDR3 DNA Sequence GCG AGA AAT AGA GGT GGC TAC AAT TAC TTT GAC TAC (SEQ ID NO: 594) CDR3 Amino Acid Sequence A R N R G G Y N Y F D Y (SEQ ID NO: 595) LCVR DNA Sequence GAAATAGTTTTGACACAGAGTCCCGGCACACTGTCACTCTCTCCCGGGGAAAGAGCCA CCTTGTCATGTAGAGCAAGTCAGTCAGTCTCTAGCTCTTATCTCGCCTGGTACCAGCA GAAGCCGGGACAGGCCCCTAGACTGCTGATCTACGGGGCAAGTTCCAGGGCCACCG Attorney Docket No.250298.000780 GAATCCCCGACCGGTTCAGTGGAAGCGGAAGCGGAACCGATTTTACTTTGACGATTTC TAGACTGGAGCCAGAGGATTTCGCCGTTTACTATTGTCAACAGTACGGAAGCAGCCCG TGGACGTTTGGCCAGGGCACGAAGGTAGAAATCAAG (SEQ ID NO: 596) LCVR Amino Acid Sequence EIVLTQSPGTLSLSPGERATLSCRASQSVSSSYLAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYCQQYGSSPWTFGQGTKVEIK (SEQ ID NO: 597) CDR1 DNA Sequence CAG TCA GTC TCT AGC TCT TAT (SEQ ID NO: 598) CDR1 Amino Acid Sequence Q S V S S S Y (SEQ ID NO: 599) CDR2 DNA Sequence GGG GCA AGT (SEQ ID NO: 600) CDR2 Amino Acid Sequence G A S (SEQ ID NO: 601) CDR3 DNA Sequence CAA CAG TAC GGA AGC AGC CCG TGG ACG (SEQ ID NO: 602) CDR3 Amino Acid Sequence Q Q Y G S S P W T (SEQ ID NO: 603) Attorney Docket No.250298.000780 HC DNA Sequence CAGGTGCAGCTGGTGGAGTCTGGGGGAGGCGTGGTCCAGCCTGGGAGGTCCCTGAG ACTCTCCTGTGCAGCGTCTGGATTCACCTTCAGCGCCTATGTCATGCACTGGGTCCGC CAGGCTCCAGGCAAGGGGCTGGAGTGGATTACAGTTATTGATTATGATGCAAAGAATA AATACTATGCAGACTCCGTGAGGGGCCGATTCACCGTCTCCAGAGACAATTCCAAGAA CACGCTGTTTCTGCAAATGAACAGCCTGAGAGCCGAGGACACGGCTGTGTATTACTGT GCGAGAAATAGAGGTGGCTACAATTACTTTGACTACTGGGGCCAGGGAACCCTGGTCA CCGTCTCCTCAGCCTCCACCAAGGGCCCATCGGTCTTCCCCCTGGCGCCCTGCTCCA GGAGCACCTCCGAGAGCACAGCCGCCCTGGGCTGCCTGGTCAAGGACTACTTCCCCG AACCGGTGACGGTGTCGTGGAACTCAGGCGCCCTGACCAGCGGCGTGCACACCTTCC CGGCTGTCCTACAGTCCTCAGGACTCTACTCCCTCAGCAGCGTGGTGACCGTGCCCT CCAGCAGCTTGGGCACGAAGACCTACACCTGCAACGTAGATCACAAGCCCAGCAACA CCAAGGTGGACAAGAGAGTTGAGTCCAAATATGGTCCCCCATGCCCACCCTGCCCAG CACCTGAGTTCCTGGGGGGACCATCAGTCTTCCTGTTCCCCCCAAAACCCAAGGACAC TCTCATGATCTCCCGGACCCCTGAGGTCACGTGCGTGGTGGTGGACGTGAGCCAGGA AGACCCCGAGGTCCAGTTCAACTGGTACGTGGATGGCGTGGAGGTGCATAATGCCAA GACAAAGCCGCGGGAGGAGCAGTTCAACAGCACGTACCGTGTGGTCAGCGTCCTCAC CGTCCTGCACCAGGACTGGCTGAACGGCAAGGAGTACAAGTGCAAGGTCTCCAACAA AGGCCTCCCGTCCTCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGAGA GCCACAGGTGTACACCCTGCCCCCATCCCAGGAGGAGATGACCAAGAACCAGGTCAG CCTGACCTGCCTGGTCAAAGGCTTCTACCCCAGCGACATCGCCGTGGAGTGGGAGAG CAATGGGCAGCCGGAGAACAACTACAAGACCACGCCTCCCGTGCTGGACTCCGACGG CTCCTTCTTCCTCTACAGCAGGCTCACCGTGGACAAGAGCAGGTGGCAGGAGGGGAA TGTCTTCTCATGCTCCGTGATGCATGAGGCTCTGCACAACCACTACACACAGAAGTCC CTCTCCCTGTCTCTGGGTAAATGA (SEQ ID NO: 604) HC Amino Acid Sequence QVQLVESGGGVVQPGRSLRLSCAASGFTFSAYVMHWVRQAPGKGLEWITVIDYDAKNKY YADSVRGRFTVSRDNSKNTLFLQMNSLRAEDTAVYYCARNRGGYNYFDYWGQGTLVTVS SASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQS SGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPEFLGGPS Attorney Docket No.250298.000780 VFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNST YRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMT KNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQE GNVFSCSVMHEALHNHYTQKSLSLSLGK* (SEQ ID NO: 605) LC DNA Sequence GAAATAGTTTTGACACAGAGTCCCGGCACACTGTCACTCTCTCCCGGGGAAAGAGCCA CCTTGTCATGTAGAGCAAGTCAGTCAGTCTCTAGCTCTTATCTCGCCTGGTACCAGCA GAAGCCGGGACAGGCCCCTAGACTGCTGATCTACGGGGCAAGTTCCAGGGCCACCG GAATCCCCGACCGGTTCAGTGGAAGCGGAAGCGGAACCGATTTTACTTTGACGATTTC TAGACTGGAGCCAGAGGATTTCGCCGTTTACTATTGTCAACAGTACGGAAGCAGCCCG TGGACGTTTGGCCAGGGCACGAAGGTAGAAATCAAGCGAACTGTGGCTGCACCATCT GTCTTCATCTTCCCGCCATCTGATGAGCAGTTGAAATCTGGAACTGCCTCTGTTGTGTG CCTGCTGAATAACTTCTATCCCAGAGAGGCCAAAGTACAGTGGAAGGTGGATAACGCC CTCCAATCGGGTAACTCCCAGGAGAGTGTCACAGAGCAGGACAGCAAGGACAGCACC TACAGCCTCAGCAGCACCCTGACGCTGAGCAAAGCAGACTACGAGAAACACAAAGTCT ACGCCTGCGAAGTCACCCATCAGGGCCTGAGCTCGCCCGTCACAAAGAGCTTCAACA GGGGAGAGTGTTAG (SEQ ID NO: 606) LC Amino Acid Sequence EIVLTQSPGTLSLSPGERATLSCRASQSVSSSYLAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYCQQYGSSPWTFGQGTKVEIKRTVAAPSVFIFPPS DEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTL SKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC* (SEQ ID NO: 607) REGN19517 HCVR DNA Sequence GAGGTGCAGCTGGTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGAG ACTCTCCTGTGCAGCCTCTGGATTCACCTTTAGCAGTTATGTCATGAGCTGGGTCCGC CAGGCTCCAGGGAAGGGGCTGGAGTGGGTCTCAGATATTAGTGGTCGTGGTGGTAGC Attorney Docket No.250298.000780 ACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATTTCCAGAGACAATTCCAAGA GCACGCTGCATCTGCAAATGAACAGCCTGAGAGCCGAGGACACGGCCGTATATTACT GTGCGAAAGTGGGGCACCTCGTCCGGGATCACTACTACTACTACGGTATGGACGTCT GGGGCCAAGGGACCACGGTCACCGTCTCCTCA (SEQ ID NO: 608) HCVR Amino Acid Sequence EVQLVESGGGLVQPGGSLRLSCAASGFTFSSYVMSWVRQAPGKGLEWVSDISGRGGST YYADSVKGRFTISRDNSKSTLHLQMNSLRAEDTAVYYCAKVGHLVRDHYYYYGMDVWGQ GTTVTVSS (SEQ ID NO: 609) CDR1 DNA Sequence GGA TTC ACC TTT AGC AGT TAT GTC (SEQ ID NO: 610) CDR1 Amino Acid Sequence G F T F S S Y V (SEQ ID NO: 611) CDR2 DNA Sequence ATT AGT GGT CGT GGT GGT AGC ACA (SEQ ID NO: 612) CDR2 Amino Acid Sequence I S G R G G S T (SEQ ID NO: 613) CDR3 DNA Sequence GCG AAA GTG GGG CAC CTC GTC CGG GAT CAC TAC TAC TAC TAC GGT ATG GAC GTC (SEQ ID NO: 614) Attorney Docket No.250298.000780 CDR3 Amino Acid Sequence A K V G H L V R D H Y Y Y Y G M D V (SEQ ID NO: 615) LCVR DNA Sequence GAAATAGTTTTGACACAGAGTCCCGGCACACTGTCACTCTCTCCCGGGGAAAGAGCCA CCTTGTCATGTAGAGCAAGTCAGTCAGTCTCTAGCTCTTATCTCGCCTGGTACCAGCA GAAGCCGGGACAGGCCCCTAGACTGCTGATCTACGGGGCAAGTTCCAGGGCCACCG GAATCCCCGACCGGTTCAGTGGAAGCGGAAGCGGAACCGATTTTACTTTGACGATTTC TAGACTGGAGCCAGAGGATTTCGCCGTTTACTATTGTCAACAGTACGGAAGCAGCCCG TGGACGTTTGGCCAGGGCACGAAGGTAGAAATCAAG (SEQ ID NO: 596) LCVR Amino Acid Sequence EIVLTQSPGTLSLSPGERATLSCRASQSVSSSYLAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYCQQYGSSPWTFGQGTKVEIK (SEQ ID NO: 597) CDR1 DNA Sequence CAG TCA GTC TCT AGC TCT TAT (SEQ ID NO: 598) CDR1 Amino Acid Sequence Q S V S S S Y (SEQ ID NO: 599) CDR2 DNA Sequence GGG GCA AGT (SEQ ID NO: 600) CDR2 Amino Acid Sequence G A S (SEQ ID NO: 601) Attorney Docket No.250298.000780 CDR3 DNA Sequence CAA CAG TAC GGA AGC AGC CCG TGG ACG (SEQ ID NO: 602) CDR3 Amino Acid Sequence Q Q Y G S S P W T (SEQ ID NO: 603) HC DNA Sequence GAGGTGCAGCTGGTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGAG ACTCTCCTGTGCAGCCTCTGGATTCACCTTTAGCAGTTATGTCATGAGCTGGGTCCGC CAGGCTCCAGGGAAGGGGCTGGAGTGGGTCTCAGATATTAGTGGTCGTGGTGGTAGC ACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATTTCCAGAGACAATTCCAAGA GCACGCTGCATCTGCAAATGAACAGCCTGAGAGCCGAGGACACGGCCGTATATTACT GTGCGAAAGTGGGGCACCTCGTCCGGGATCACTACTACTACTACGGTATGGACGTCT GGGGCCAAGGGACCACGGTCACCGTCTCCTCAGCCTCCACCAAGGGCCCATCGGTCT TCCCCCTGGCGCCCTGCTCCAGGAGCACCTCCGAGAGCACAGCCGCCCTGGGCTGC CTGGTCAAGGACTACTTCCCCGAACCGGTGACGGTGTCGTGGAACTCAGGCGCCCTG ACCAGCGGCGTGCACACCTTCCCGGCTGTCCTACAGTCCTCAGGACTCTACTCCCTCA GCAGCGTGGTGACCGTGCCCTCCAGCAGCTTGGGCACGAAGACCTACACCTGCAACG TAGATCACAAGCCCAGCAACACCAAGGTGGACAAGAGAGTTGAGTCCAAATATGGTCC CCCATGCCCACCCTGCCCAGCACCTGAGTTCCTGGGGGGACCATCAGTCTTCCTGTT CCCCCCAAAACCCAAGGACACTCTCATGATCTCCCGGACCCCTGAGGTCACGTGCGT GGTGGTGGACGTGAGCCAGGAAGACCCCGAGGTCCAGTTCAACTGGTACGTGGATGG CGTGGAGGTGCATAATGCCAAGACAAAGCCGCGGGAGGAGCAGTTCAACAGCACGTA CCGTGTGGTCAGCGTCCTCACCGTCCTGCACCAGGACTGGCTGAACGGCAAGGAGTA CAAGTGCAAGGTCTCCAACAAAGGCCTCCCGTCCTCCATCGAGAAAACCATCTCCAAA GCCAAAGGGCAGCCCCGAGAGCCACAGGTGTACACCCTGCCCCCATCCCAGGAGGA GATGACCAAGAACCAGGTCAGCCTGACCTGCCTGGTCAAAGGCTTCTACCCCAGCGA CATCGCCGTGGAGTGGGAGAGCAATGGGCAGCCGGAGAACAACTACAAGACCACGC CTCCCGTGCTGGACTCCGACGGCTCCTTCTTCCTCTACAGCAGGCTCACCGTGGACAA Attorney Docket No.250298.000780 GAGCAGGTGGCAGGAGGGGAATGTCTTCTCATGCTCCGTGATGCATGAGGCTCTGCA CAACCACTACACACAGAAGTCCCTCTCCCTGTCTCTGGGTAAATGA (SEQ ID NO: 616) HC Amino Acid Sequence EVQLVESGGGLVQPGGSLRLSCAASGFTFSSYVMSWVRQAPGKGLEWVSDISGRGGST YYADSVKGRFTISRDNSKSTLHLQMNSLRAEDTAVYYCAKVGHLVRDHYYYYGMDVWGQ GTTVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHT FPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAP EFLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPR EEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPP SQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVD KSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGK* (SEQ ID NO: 617) LC DNA Sequence GAAATAGTTTTGACACAGAGTCCCGGCACACTGTCACTCTCTCCCGGGGAAAGAGCCA CCTTGTCATGTAGAGCAAGTCAGTCAGTCTCTAGCTCTTATCTCGCCTGGTACCAGCA GAAGCCGGGACAGGCCCCTAGACTGCTGATCTACGGGGCAAGTTCCAGGGCCACCG GAATCCCCGACCGGTTCAGTGGAAGCGGAAGCGGAACCGATTTTACTTTGACGATTTC TAGACTGGAGCCAGAGGATTTCGCCGTTTACTATTGTCAACAGTACGGAAGCAGCCCG TGGACGTTTGGCCAGGGCACGAAGGTAGAAATCAAGCGAACTGTGGCTGCACCATCT GTCTTCATCTTCCCGCCATCTGATGAGCAGTTGAAATCTGGAACTGCCTCTGTTGTGTG CCTGCTGAATAACTTCTATCCCAGAGAGGCCAAAGTACAGTGGAAGGTGGATAACGCC CTCCAATCGGGTAACTCCCAGGAGAGTGTCACAGAGCAGGACAGCAAGGACAGCACC TACAGCCTCAGCAGCACCCTGACGCTGAGCAAAGCAGACTACGAGAAACACAAAGTCT ACGCCTGCGAAGTCACCCATCAGGGCCTGAGCTCGCCCGTCACAAAGAGCTTCAACA GGGGAGAGTGTTAG (SEQ ID NO: 606) LC Amino Acid Sequence EIVLTQSPGTLSLSPGERATLSCRASQSVSSSYLAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYCQQYGSSPWTFGQGTKVEIKRTVAAPSVFIFPPS Attorney Docket No.250298.000780 DEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTL SKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC* (SEQ ID NO: 607) [00200] In one aspect, the present disclosure provides an antigen-binding protein that binds specifically to p75 neurotrophin receptor (p75NTR) or an antigenic-fragment thereof or a variant thereof which comprises:(i) a HCVR that comprises the HCDR1, HCDR2 and HCDR3 of a HCVR comprising the amino acid sequence set forth in SEQ ID NO: 2, 22, 42, 58, 78, 98, 116, 136, 155, 173, 189, 207, 227, 245, 261, 279, 297, 315, 331, 349, 369, 387, 401, 417, 427, 437, 445, 455, 465, 475, 484, 493, 503, 513, 519, 529, 549, 569, 589 or 609, or a variant thereof; and/or (ii) a LCVR that comprises the LCDR1, LCDR2 and LCDR3 of a LCVR comprising the amino acid sequence set forth in SEQ ID NO: 10, 30, 50, 66, 86, 106, 124, 144, 162, 179, 197, 215, 235, 251, 269, 287, 304, 323, 339, 357, 377, 391, 409, 537, 557, 577, or 597, or a variant thereof. [00201] In some embodiments, the antigen-binding protein comprises: (1) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 2, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 10, or a variant thereof; (2) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 22, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 30, or a variant thereof; (3) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 42, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 50, or a variant thereof; (4) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 58, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 66, or a variant thereof; (5) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 78, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 86, or a variant thereof; (6) a HCVR comprising the HCDR1, HCDR2 and HCDR3 Attorney Docket No.250298.000780 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 98, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 106, or a variant thereof; (7) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 116, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 124, or a variant thereof; (8) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 136, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 144, or a variant thereof; (9) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 155, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 162, or a variant thereof; (10) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 173, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 179, or a variant thereof; (11) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 189, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 197, or a variant thereof; (12) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 207, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 215, or a variant thereof; (13) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 227, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 235, or a variant thereof; (14) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 245, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 251, or a variant thereof; (15) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 261, or a variant thereof; and a LCVR comprising the Attorney Docket No.250298.000780 LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 269, or a variant thereof; (16) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 279, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 287, or a variant thereof; (17) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 297, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 304, or a variant thereof; (18) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 315, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 323, or a variant thereof; (19) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 331, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 339, or a variant thereof; (20) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 349, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 357, or a variant thereof; (21) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 369, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 377, or a variant thereof; (22) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 387, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 391, or a variant thereof; (23) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 401, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof; (24) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 417, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof; (25) a Attorney Docket No.250298.000780 HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 427, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof; (26) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 437, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof; (27) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 445, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof; (28) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 455, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof; (29) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 465, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof; (30) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 475, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof; (31) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 484, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof; (32) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 493, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof; (33) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 503, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof; (34) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 513, or Attorney Docket No.250298.000780 a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof; (35) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 519, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof; (36) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 529, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 537, or a variant thereof; (37) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 549, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 557, or a variant thereof; (38) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 569, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 577, or a variant thereof; (39) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 589, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 597, or a variant thereof; and/or (40) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 609, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 597, or a variant thereof. [00202] In some embodiments, the antigen-binding protein comprises: (1) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 2, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 10, or a variant thereof; (2) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 22, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 30, or a variant thereof; (3) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 42, or a variant thereof; and a LCVR comprising the Attorney Docket No.250298.000780 LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 50, or a variant thereof; (4) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 58, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 66, or a variant thereof; (5) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 78, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 86, or a variant thereof; (6) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 98, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 106, or a variant thereof; (7) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 116, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 124, or a variant thereof; (8) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 136, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 144, or a variant thereof; (9) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 155, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 162, or a variant thereof; (10) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 173, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 179, or a variant thereof; (11) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 207, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 215, or a variant thereof; (12) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 245, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 251, or a variant thereof; (13) a Attorney Docket No.250298.000780 HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 279, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 287, or a variant thereof; (14) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 297, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 304, or a variant thereof; (15) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 315, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 323, or a variant thereof; (16) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 349, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 357, or a variant thereof; (17) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 387, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 391, or a variant thereof; (18) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 417, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof; (19) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 427, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof; (20) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 437, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof; (21) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 445, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof; (22) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 455, or Attorney Docket No.250298.000780 a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof; (23) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 465, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof; (24) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 475, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof; (25) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 493, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof; (26) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 503, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof; (27) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 513, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof; and/or (28) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 519, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof. [00203] In some embodiments, the antigen-binding protein comprises: (1) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 189, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 197, or a variant thereof; (2) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 227, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 235, or a variant thereof; (3) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 261, or a variant thereof; and a LCVR comprising the Attorney Docket No.250298.000780 LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 269, or a variant thereof; (4) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 331, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 339, or a variant thereof; (5) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 369, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 377, or a variant thereof; (6) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 401, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof; and/or (7) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 484, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof. [00204] In some embodiments, the antigen-binding protein comprises: (1) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 22, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 30, or a variant thereof; (2) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 78, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 86, or a variant thereof; (3) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 136, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 144, or a variant thereof; (4) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 261, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 269, or a variant thereof; (5) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 369, or a variant thereof; and a LCVR comprising the Attorney Docket No.250298.000780 LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 377, or a variant thereof; and/or (6) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 484, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof. [00205] In some embodiments, the antigen-binding protein comprises: (1) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 529, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 537, or a variant thereof; (2) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 549, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 557, or a variant thereof; (3) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 569, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 577, or a variant thereof; (4) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 589, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 597, or a variant thereof; and/or (5) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 609, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 597, or a variant thereof. [00206] In some embodiments, the antigen-binding protein comprises: (1) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 4, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 6, or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 8, or a variant thereof; and a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 12, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 14, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 16, or a variant thereof; (2) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 24, or a Attorney Docket No.250298.000780 variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 26 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 28, or a variant thereof; and a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 32, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 34, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 36, or a variant thereof; (3) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 44, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 46 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 48, or a variant thereof; and a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 12, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 14, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 52, or a variant thereof; (4) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 60, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 62 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 64, or a variant thereof; and a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 68, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 70, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 72, or a variant thereof; (5) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 80, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 82, or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 84, or a variant thereof; and a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 88, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 90, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 92, or a variant thereof; (6) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 100, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 102 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 104, or a variant thereof; and a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 108, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 34, or a variant thereof, and a Attorney Docket No.250298.000780 LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 110, or a variant thereof; (7) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 118, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 120, or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 122, or a variant thereof; and a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 126, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 128, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 130, or a variant thereof; (8) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 138, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 140, or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 142, or a variant thereof; and a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 146, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 90, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 149, or a variant thereof; (9) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 100, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 158 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 160, or a variant thereof; and a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 164, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 90, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 167, or a variant thereof; (10) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 100, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 175 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 177, or a variant thereof; and a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 181, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 70, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 183, or a variant thereof; (11) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 191, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 193 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 195, or a variant thereof; and a LCVR that Attorney Docket No.250298.000780 comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 199, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 14, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 201, or a variant thereof; (12) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 209, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 211 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 213, or a variant thereof; and a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 217, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 219, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 221, or a variant thereof; (13) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 229, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 231 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 233, or a variant thereof; and a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 237, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 14, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 239, or a variant thereof; (14) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 100, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 247 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 249, or a variant thereof; and a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 253, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 70, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 255, or a variant thereof; (15) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 263, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 265 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 267, or a variant thereof; and a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 271, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 90, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 273, or a variant thereof; (16) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 281, or a variant thereof, a HCDR2 comprising Attorney Docket No.250298.000780 the amino acid sequence set forth in SEQ ID NO: 283 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 285, or a variant thereof; and a LCVR that comprises: an LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 289, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 14, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 291, or a variant thereof; (17) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 299, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 193 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 302, or a variant thereof; and a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 237, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 307, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 309, or a variant thereof; (18) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 317, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 319 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 321, or a variant thereof; and a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 12, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 14, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 325, or a variant thereof; (19) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 333, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 335 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 337, or a variant thereof; and a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 237, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 341, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 343, or a variant thereof; (20) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 351, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 353 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 355, or a variant thereof; and a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 359, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 361, or a variant thereof, and a LCDR3 Attorney Docket No.250298.000780 comprising the amino acid sequence set forth in SEQ ID NO: 363, or a variant thereof; (21) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 371, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 373 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 375, or a variant thereof; and a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 379, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 90, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 381, or a variant thereof; (22) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 138, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 319 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 389, or a variant thereof; and a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 393, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 361, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 395, or a variant thereof; (23) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 403, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 405 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 407, or a variant thereof; and a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 237, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 14, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 411, or a variant thereof; (24) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 419, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 421 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 423, or a variant thereof; and a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 237, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 14, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 411, or a variant thereof; (25) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 429, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 431 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 433, or a variant thereof; and a LCVR that Attorney Docket No.250298.000780 comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 237, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 14, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 411, or a variant thereof; (26) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 191, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 335 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 441, or a variant thereof; and a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 237, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 14, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 411, or a variant thereof; (27) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 447, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 449 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 451, or a variant thereof; and a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 237, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 14, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 411, or a variant thereof; (28) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 457, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 459 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 461, or a variant thereof; and a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 237, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 14, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 411, or a variant thereof; (29) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 467, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 469 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 471, or a variant thereof; and a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 237, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 14, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 411, or a variant thereof; (30) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 477, or a variant thereof, a HCDR2 comprising the amino Attorney Docket No.250298.000780 acid sequence set forth in SEQ ID NO: 158 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 480, or a variant thereof; and a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 237, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 14, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 411, or a variant thereof; (31) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 486, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 283 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 489, or a variant thereof; and a LCVR that comprises: LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 237, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 14, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 411, or a variant thereof; (32) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 495, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 497 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 499, or a variant thereof; and a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 237, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 14, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 411, or a variant thereof; (33) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 505, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 507 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 509, or a variant thereof; and a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 237, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 14, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 411, or a variant thereof; (34) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 138, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 319 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 515, or a variant thereof; and a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 237, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 14, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: Attorney Docket No.250298.000780 411, or a variant thereof; (35) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 521, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 523 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 525, or a variant thereof; and a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 237, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 14, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 411, or a variant thereof; (36) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 531, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 533 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 535, or a variant thereof; and a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 539, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 541, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 543, or a variant thereof; (37) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 551, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 553 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 555, or a variant thereof; and a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 559, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 561, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 563, or a variant thereof; (38) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 571, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 573 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 575, or a variant thereof; and a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 579, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 581, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 583, or a variant thereof; (39) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 591, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 593 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 595, or a variant thereof; and a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: Attorney Docket No.250298.000780 599, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 601, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 603, or a variant thereof; (40) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 611, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 613 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 615, or a variant thereof; and/or a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 599, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 601, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 603, or a variant thereof. [00207] In some embodiments, the antigen-binding protein comprises: (1) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 4, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 6 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 8, or a variant thereof; and/or a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 12, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 14, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 16, or a variant thereof; (2) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 24, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 26 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 28, or a variant thereof; and/or a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 32, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 34, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 36, or a variant thereof; (3) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 44, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 46 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 48, or a variant thereof; and/or a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 12, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 14, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 52, or a variant thereof; (4) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 60, or a Attorney Docket No.250298.000780 variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 62 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 64, or a variant thereof; and/or a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 68, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 70, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 72, or a variant thereof; (5) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 80, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 82 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 84, or a variant thereof; and/or a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 88, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 90, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 92, or a variant thereof; (6) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 100, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 102 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 104, or a variant thereof; and/or a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 108, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 34, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 110, or a variant thereof; (7) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 118, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 120 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 122, or a variant thereof; and/or a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 126, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 128, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 130, or a variant thereof; (8) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 138, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 140 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 142, or a variant thereof; and/or a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 146, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 90, or a variant thereof, Attorney Docket No.250298.000780 and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 149, or a variant thereof; (9) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 100, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 158 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 160, or a variant thereof; and/or a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 164, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 90, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 167, or a variant thereof; (10) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 100, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 175 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 177, or a variant thereof; and/or a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 181, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 70, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 183, or a variant thereof; (11) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 209, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 211 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 213, or a variant thereof; and/or a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 217, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 219, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 221, or a variant thereof; (12) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 100, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 247 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 249, or a variant thereof; and/or a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 253, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 70, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 255, or a variant thereof; (13) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 281, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 283 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 285, or a variant Attorney Docket No.250298.000780 thereof; and/or a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 289, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 14, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 291, or a variant thereof; (14) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 299, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 193 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 302, or a variant thereof; and/or a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 237, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 307, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 309, or a variant thereof; (15) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 317, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 319 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 321, or a variant thereof; and/or a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 12, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 14, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 325, or a variant thereof; (16) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 351, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 353 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 355, or a variant thereof; and/or a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 359, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 361, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 363, or a variant thereof; (17) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 138, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 319 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 389, or a variant thereof; and/or a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 393, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 361, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 395, or a variant thereof; (18) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth Attorney Docket No.250298.000780 in SEQ ID NO: 419, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 421 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 423, or a variant thereof; and/or a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 237, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 14, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 411, or a variant thereof; (19) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 429, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 431 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 433, or a variant thereof; and/or a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 237, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 14, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 411, or a variant thereof; (20) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 191, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 335 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 441, or a variant thereof; and/or a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 237, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 14, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 411, or a variant thereof; (21) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 447, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 449 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 451, or a variant thereof; and/or a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 237, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 14, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 411, or a variant thereof; (22) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 457, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 459 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 461, or a variant thereof; and/or a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 237, or a variant thereof, a LCDR2 comprising the amino acid sequence Attorney Docket No.250298.000780 set forth in SEQ ID NO: 14, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 411, or a variant thereof; (23) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 467, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 469 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 471, or a variant thereof; and/or a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 237, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 14, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 411, or a variant thereof; (24) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 477, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 158 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 480, or a variant thereof; and/or a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 237, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 14, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 411, or a variant thereof; (25) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 495, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 497 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 499, or a variant thereof; and/or a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 237, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 14, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 411, or a variant thereof; (26) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 505, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 507 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 509, or a variant thereof; and/or a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 237, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 14, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 411, or a variant thereof; (27) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 138, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 319 or a variant thereof, and a HCDR3 comprising the amino acid Attorney Docket No.250298.000780 sequence set forth in SEQ ID NO: 515, or a variant thereof; and/or a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 237, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 14, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 411, or a variant thereof; and/or (28) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 521, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 523 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 525, or a variant thereof; and/or a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 237, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 14, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 411, or a variant thereof. [00208] In some embodiments, the antigen-binding protein comprises (1) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 191, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 193 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 195, or a variant thereof; and/or a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 199, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 14, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 201, or a variant thereof; (2) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 229, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 231 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 233, or a variant thereof; and/or a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 237, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 14, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 239, or a variant thereof; (3) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 263, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 265 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 267, or a variant thereof; and/or a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 271, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 90, or a variant thereof, Attorney Docket No.250298.000780 and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 273, or a variant thereof; (4) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 333, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 335 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 337, or a variant thereof; and/or a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 237, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 341, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 343, or a variant thereof; (5) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 371, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 373 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 375, or a variant thereof; and/or a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 379, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 90, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 381, or a variant thereof; (6) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 403, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 405 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 407, or a variant thereof; and/or a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 237, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 14, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 411, or a variant thereof; and/or (7) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 486, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 283 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 489, or a variant thereof; and/or a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 237, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 14, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 411, or a variant thereof. [00209] In some embodiments, the antigen-binding protein comprises: (1) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 24, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 26 or Attorney Docket No.250298.000780 a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 28, or a variant thereof; and/or a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 32, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 34, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 36, or a variant thereof; (2) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 80, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 82 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 84, or a variant thereof; and/or a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 88, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 90, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 92, or a variant thereof; (3) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 138, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 140 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 142, or a variant thereof; and/or a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 146, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 90, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 149, or a variant thereof; (4) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 263, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 265 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 267, or a variant thereof; and/or a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 271, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 90, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 273, or a variant thereof; (5) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 371, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 373 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 375, or a variant thereof; and/or a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 379, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 90, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 381, or a variant Attorney Docket No.250298.000780 thereof; and/or (6) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 486, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 283 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 489, or a variant thereof; and/or a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 237, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 14, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 411, or a variant thereof. [00210] In some embodiments, the antigen-binding protein comprises: (1) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 531, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 533, or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 535, or a variant thereof; and/or a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 539, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 541, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 543, or a variant thereof; (2) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 551, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 553, or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 555, or a variant thereof; and/or a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 559, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 561, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 563, or a variant thereof; (3) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 571, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 573, or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 575, or a variant thereof; and/or a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 579, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 581, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 583, or a variant thereof; (4) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 591, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 593, or a variant thereof, and a HCDR3 comprising the amino acid Attorney Docket No.250298.000780 sequence set forth in SEQ ID NO: 595, or a variant thereof; and/or a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 599, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 601, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 603, or a variant thereof; and/or (5) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 611, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 613 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 615, or a variant thereof; and/or a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 599, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 601, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 603, or a variant thereof. [00211] In some embodiments, the antigen-binding protein comprises: (1) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 2, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 10, or a variant thereof; (2) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 22, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 30, or a variant thereof; (3) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 42, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 50, or a variant thereof; (4) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 58, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 66, or a variant thereof; (5) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 78, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 86, or a variant thereof; (6) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 98, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 106, or a variant thereof; (7) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 116, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 124, or a variant thereof; (8) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 136, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 144, or a variant thereof; (9) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 155, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 162, or a variant Attorney Docket No.250298.000780 thereof; (10) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 173, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 179, or a variant thereof; (11) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 189, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 197, or a variant thereof; (12) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 207, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 215, or a variant thereof; (13) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 227, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 235, or a variant thereof; (14) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 245, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 251, or a variant thereof; (15) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 261, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 269, or a variant thereof; (16) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 279, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 287, or a variant thereof; (17) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 297, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 304, or a variant thereof; (18) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 315, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 323, or a variant thereof; (19) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 331, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 339, or a variant thereof; (20) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 349, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 357, or a variant thereof; (21) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 369, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 377, or a variant thereof; (22) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 387, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 391, or a variant thereof; (23) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 401, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof; (24) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 417, Attorney Docket No.250298.000780 or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof; (25) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 427, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof; (26) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 437, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof; (27) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 445, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof; (28) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 455, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof; (29) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 465, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof; (30) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 475, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof; (31) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 484, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof; (32) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 493, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof; (33) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 503, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof; (34) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 513, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof; (35) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 519, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof; (36) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 529, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 537, or a variant thereof; (37) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 549, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 557, or a variant thereof; (38) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 569, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ Attorney Docket No.250298.000780 ID NO: 577, or a variant thereof; (39) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 589, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 597, or a variant thereof; and/or (40) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 609, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 597, or a variant thereof. [00212] In some embodiments, the antigen-binding protein comprises: (1) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 2, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 10, or a variant thereof; (2) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 22, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 30, or a variant thereof; (3) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 42, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 50, or a variant thereof; (4) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 58, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 66, or a variant thereof; (5) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 78, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 86, or a variant thereof; (6) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 98, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 106, or a variant thereof; (7) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 116, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 124, or a variant thereof; (8) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 136, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 144, or a variant thereof; (9) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 155, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 162, or a variant thereof; (10) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 173, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 179, or a variant thereof; (11) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 207, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 215, or a variant thereof; (12) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 245, or a variant thereof; and a LCVR that Attorney Docket No.250298.000780 comprises the amino acid sequence set forth in SEQ ID NO: 251, or a variant thereof; (13) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 279, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 287, or a variant thereof; (14) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 297, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 304, or a variant thereof; (15) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 315, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 323, or a variant thereof; (16) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 349, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 357, or a variant thereof; (17) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 387, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 391, or a variant thereof; (18) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 417, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof; (19) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 427, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof; (20) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 437, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof; (21) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 445, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof; (22) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 455, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof; (23) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 465, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof; (24) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 475, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof; (25) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 493, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof; (26) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 503, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof; (27) a Attorney Docket No.250298.000780 HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 513, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof; and/or 28) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 519, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof. [00213] In some embodiments, the antigen-binding protein comprises: (1) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 189, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 197, or a variant thereof; (2) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 227, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 235, or a variant thereof; (3) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 261, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 269, or a variant thereof; (4) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 331, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 339, or a variant thereof; (5) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 369, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 377, or a variant thereof; (6) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 401, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof; and/or (7) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 484, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof. [00214] In some embodiments, the antigen-binding protein comprises: (1) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 22, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 30, or a variant thereof; (2) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 78, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 86, or a variant thereof; (3) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 136, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 144, or a variant thereof; (4) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 261, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 269, or a variant thereof; (5) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 369, or a variant thereof; and a Attorney Docket No.250298.000780 LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 377, or a variant thereof; and/or (6) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 484, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof. [00215] In some embodiments, the antigen-binding protein comprises: (1) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 529, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 537, or a variant thereof; (2) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 549, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 557, or a variant thereof; (3) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 569, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 577, or a variant thereof; (4) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 589, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 597, or a variant thereof; and/or (5) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 609, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 597, or a variant thereof. [00216] In some embodiments, the antigen-binding protein comprises: (1) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 18, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 20, or a variant thereof; (2) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 38, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 40, or a variant thereof; (3) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 54, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 56, or a variant thereof; (4) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 74, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 76, or a variant thereof; (5) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 94, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 96, or a variant thereof; (6) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 112, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 114, or a variant thereof; (7) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 132, or a variant thereof, Attorney Docket No.250298.000780 and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 134, or a variant thereof; (8) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 151, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 153, or a variant thereof; (9) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 169, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 171, or a variant thereof; (10) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 185, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 187, or a variant thereof; (11) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 203, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 205, or a variant thereof; (12) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 223, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 225, or a variant thereof; (13) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 241, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 243, or a variant thereof; (14) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 257, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 259, or a variant thereof; (15) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 275, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 277, or a variant thereof; (16) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 293, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 295, or a variant thereof; (17) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 311, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 313, or a variant thereof; (18) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 327, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 329, or a variant thereof; (19) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 345, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 347, or a variant thereof; (20) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 365, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 367, or a variant thereof; (21) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 383, or a variant Attorney Docket No.250298.000780 thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 385, or a variant thereof; (22) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 397, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 399, or a variant thereof; (23) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 413, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 415, or a variant thereof; (24) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 425, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 415, or a variant thereof; (25) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 435, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 415, or a variant thereof; (26) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 443, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 415, or a variant thereof; (27) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 453, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 415, or a variant thereof; (28) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 463, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 415, or a variant thereof; (29) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 473, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 415, or a variant thereof; (30) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 482, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 415, or a variant thereof; (31) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 491, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 415, or a variant thereof; (32) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 501, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 415, or a variant thereof; (33) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 511, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 415, or a variant thereof; (34) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 517, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 415, or a variant thereof; (35) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 527, or Attorney Docket No.250298.000780 a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 415, or a variant thereof; (36) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 545, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 547, or a variant thereof; (37) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 565, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 567, or a variant thereof; (38) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 585, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 587, or a variant thereof; (39) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 605, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 607, or a variant thereof; and/or (40) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 617, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 607, or a variant thereof. [00217] In some embodiments, the antigen-binding protein comprises: (1) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 18, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 20, or a variant thereof; (2) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 38, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 40, or a variant thereof; (3) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 54, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 56, or a variant thereof; (4) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 74, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 76, or a variant thereof; (5) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 94, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 96, or a variant thereof; (6) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 112, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 114, or a variant thereof; (7) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 132, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 134, or a variant thereof; (8) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 151, or a variant thereof, and a light chain that comprises the amino acid sequence Attorney Docket No.250298.000780 set forth in SEQ ID NO: 153, or a variant thereof; (9) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 169, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 171, or a variant thereof; (10) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 185, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 187, or a variant thereof; (11) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 223, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 225, or a variant thereof; (12) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 257, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 259, or a variant thereof; (13) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 293, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 295, or a variant thereof; (14) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 311, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 313, or a variant thereof; (15) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 327, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 329, or a variant thereof; (16) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 365, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 367, or a variant thereof; (17) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 397, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 399, or a variant thereof; (18) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 425, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 415, or a variant thereof; (19) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 435, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 415, or a variant thereof; (20) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 443, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 415, or a variant thereof; (21) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 453, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 415, or a variant thereof; (22) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 463, or a variant thereof, and a light chain that comprises the amino acid Attorney Docket No.250298.000780 sequence set forth in SEQ ID NO: 415, or a variant thereof; (23) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 473, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 415, or a variant thereof; (24) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 482, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 415, or a variant thereof; (25) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 501, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 415, or a variant thereof; (26) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 511, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 415, or a variant thereof; (27) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 517, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 415, or a variant thereof; and/or (28) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 527, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 415, or a variant thereof. [00218] In some embodiments, the antigen-binding protein comprises: (1) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 203, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 205, or a variant thereof; (2) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 241, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 243, or a variant thereof; (3) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 275, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 277, or a variant thereof; (4) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 345, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 347, or a variant thereof; (5) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 383, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 385, or a variant thereof; (6) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 413, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 415, or a variant thereof; and/or (7) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 491, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 415, or a variant thereof. Attorney Docket No.250298.000780 [00219] In some embodiments, the antigen-binding protein comprises: (1) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 38, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 40, or a variant thereof; (2) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 94, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 96, or a variant thereof; (3) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 151, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 153, or a variant thereof; (4) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 275, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 277, or a variant thereof; (5) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 383, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 385, or a variant thereof; and/or (6) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 491, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 415, or a variant thereof. [00220] In some embodiments, the antigen-binding protein comprises: (1) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 545, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 547, or a variant thereof; (2) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 565, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 567, or a variant thereof; (3) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 585, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 587, or a variant thereof; (4) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 605, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 607, or a variant thereof; and/or (5) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 617, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 607, or a variant thereof. [00221] In various embodiments, an antigen-binding protein described herein can block the binding of, e.g., a human neurotrophin receptor mouse Fc dimer (human p75-mFc) to human neurotrophin 3 (hNT-3) by at least about 5%, at least about 10%, at least about 15%, at least about 20%, at least about 25%, at least about 30%, at least about 35%, at least about 40%, at least about 45%, at least about 50%, at least about 60%, at least about Attorney Docket No.250298.000780 65%, at least about 70%, at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 95%, or 100%. [00222] In some embodiments, an antigen-binding protein described herein can block the binding of, e.g., a human neurotrophin receptor mouse Fc dimer (human p75-mFc) to human neurotrophin 3 (hNT-3) by from at least about 5% to at least about 10%, from at least about 5% to at least about 15%, from at least about 5% to at least about 20%, from at least about 5% to at least about 25%, from at least about 5% to at least about 30%, from at least about 5% to at least about 35%, from at least about 5% to at least about 40%, from at least about 5% to at least about 45%, from at least about 5% to at least about 50%, from at least about 10% to at least about 15%, from at least about 10% to at least about 20%, from at least about 10% to at least about 25%, from at least about 10% to at least about 30%, from at least about 10% to at least about 35%, from at least about 10% to at least about 40%, from at least about 10% to at least about 45%, from at least about 10% to at least about 50%, from at least about 15% to at least about 20%, from at least about 15% to at least about 25%, from at least about 15% to at least about 30%, from at least about 15% to at least about 35%, from at least about 15% to at least about 40%, from at least about 15% to at least about 45%, from at least about 15% to at least about 50%, from at least about 20% to at least about 25%, from at least about 20% to at least about 30%, from at least about 20% to at least about 35%, from at least about 20% to at least about 40%, from at least about 20% to at least about 45%, from at least about 20% to at least about 50%, from at least about 25% to at least about 30%, from at least about 25% to at least about 35%, from at least about 25% to at least about 40%, from at least about 25% to at least about 45%, from at least about 25% to at least about 50%, from at least about 30% to at least about 35%, from at least about 30% to at least about 40%, from at least about 30% to at least about 45%, from at least about 30% to at least about 50%, from at least about 35% to at least about 40%, from at least about 35% to at least about 45%, from at least about 35% to at least about 50%, from at least about 40% to at least about 45%, from at least about 40% to at least about 50%, from at least about 45% to at least about 50%, or more. [00223] In some embodiments, an antigen-binding protein described herein can block the binding of, e.g., a human neurotrophin receptor mouse Fc dimer (human p75-mFc) to human neurotrophin 3 (hNT-3) by from at least about 50% to at least about 60%, from at least about 50% to at least about 70%, from at least about 50% to at least about 80%, from at least about 50% to at least about 90%, more than 60%, from at least about 60% to at least about 70%, from at least about 60% to at least about 80%, from at least about 60% to at least about Attorney Docket No.250298.000780 90%, more than at least about 70%, from at least about 70% to at least about 80%, from at least about 70% to at least about 90%, more than at least about 80%, from at least about 80% to at least about 90%, more than 90%, from at least about 90% to at least about 95%, from at least about 90% to at least about 98%, more than 95%, from at least about 95% to at least about 98%, more than at least about 98%, or more than at least about 99%. In some embodiments, the expression or activity of a product (e.g., an mRNA product) of at least one targeted gene may be inhibited by at least about 50%, at least about 55%, at least about 60%, at least about 65%, at least about 70%, at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 91%, at least about 92%, at least about 93%, at least about 94%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99% or even 100%. [00224] [In some embodiments an antigen-binding protein described herein can block the binding of, e.g., a human neurotrophin receptor mouse Fc dimer (human p75-mFc) to human neurotrophin 3 (hNT-3) by at least 1%, at least 2%, at least 3%, at least 4%, at least 5%, at least 6%, at least 7%, at least 8%, at least 9%, at least 10%, at least 11%, at least 12%, at least 13%, at least 14%, at least 15%, at least 16%, at least 17%, at least 18%, at least 19%, at least 20%, at least 21%, at least 22%, at least 23%, at least 24%, at least 25%, at least 26%, at least 27%, at least 28%, at least 29%, at least 30%, at least 31%, at least 32%, at least 33%, at least 34%, at least 35%, at least 36%, at least 37%, at least 38%, at least 39%, at least 40%, at least 41%, at least 42%, at least 43%, at least 44%, at least 45%, at least 46%, at least 47%, at least 48%, at least 49%, at least 50%, at least 51%, at least 52%, at least 53%, at least 54%, at least 55%, at least 56%, at least 57%, at least 58%, at least 59%, at least 60%, at least 61%, at least 62%, at least 63%, at least 64%, at least 65%, at least 66%, at least 67%, at least 68%, at least 69%, at least 70%, at least 71%, at least 72%, at least 73%, at least 74%, or at least 75%, or more. [00225] In some embodiments, the antigen-binding protein can block the binding of a human neurotrophin receptor mouse Fc dimer (human p75-mFc) to human neurotrophin 3 (hNT-3) by at least about 50%.In some embodiments, the antigen-binding protein can block the binding of a human neurotrophin receptor mouse Fc dimer (human p75-mFc) to human neurotrophin 3 (hNT-3) by less than about 50%. [00226] In some embodiments, the antigen-binding protein binds to the same epitope on p75NTR as an antibody comprising an HCVR/LCVR amino acid sequence pair as set forth in Table 1-1. In some embodiments, the antigen-binding protein competes for binding to Attorney Docket No.250298.000780 p75NTR with an antibody comprising an HCVR/LCVR amino acid sequence pair as set forth in Table 1-1. [00227] The present disclosure provides anti-p75NTR protein-drug conjugates comprising an antibody or antigen-binding fragment thereof that specifically binds to p75NTR or an antigenic fragment thereof comprising: a heavy chain variable region (HCVR) that comprises the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NOs: 2, 22, 42, 58, 78, 98, 116, 136, 155, 173, 189, 207, 227, 245, 261, 279, 297, 315, 331, 349, 369, 387, 401, 417, 427, 437, 445, 455, 465, 475, 484, 493, 503, 513, 519, 529, 549, 569, 589 or 609 (e.g., fused to an IgG4 Fc having a S108P mutation), and a light chain variable region (LCVR) that comprises the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 10, 30, 50, 66, 86, 106, 124, 144, 162, 179, 197, 215, 235, 251, 269, 287, 304, 323, 339, 357, 377, 391, 409, 537, 557, 577, or 597. [00228] The present disclosure also provides an anti-p75NTR protein-drug conjugate comprising an isolated antibody or antigen-binding fragment thereof that specifically binds to p75NTR or an antigenic fragment thereof comprising: (1) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 2 (or a variant thereof); and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 10 (or a variant thereof); (2) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 22 (or a variant thereof); and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 30 (or a variant thereof); (3) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 42 (or a variant thereof); and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 50 (or a variant thereof); (4) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 58 (or a variant thereof); and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 66 (or a variant thereof); (5) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 78 (or a variant thereof); and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 86 (or a Attorney Docket No.250298.000780 variant thereof); (6) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 98 (or a variant thereof); and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 106 (or a variant thereof); (7) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 116 (or a variant thereof); and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 124 (or a variant thereof); (8) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 136 (or a variant thereof); and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 144 (or a variant thereof); (9) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 155 (or a variant thereof); and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 162 (or a variant thereof); (10) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 173 (or a variant thereof); and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 179 (or a variant thereof); (11) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 189 (or a variant thereof); and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 197 (or a variant thereof); (12) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 207 (or a variant thereof); and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 215 (or a variant thereof); (13) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 227 (or a variant thereof); and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 235 (or a variant thereof); (14) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 245 (or a variant thereof); and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 251 (or a variant thereof); (15) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth Attorney Docket No.250298.000780 in SEQ ID NO: 261 (or a variant thereof); and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 269 (or a variant thereof); (16) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 279 (or a variant thereof); and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 287 (or a variant thereof); (17) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 297 (or a variant thereof); and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 304 (or a variant thereof); (18) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 315 (or a variant thereof); and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 323 (or a variant thereof); (19) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 331 (or a variant thereof); and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 339 (or a variant thereof); (20) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 349 (or a variant thereof); and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 357 (or a variant thereof); (21) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 369 (or a variant thereof); and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 377 (or a variant thereof); (22) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 387 (or a variant thereof); and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 391 (or a variant thereof); (23) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 401 (or a variant thereof); and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409 (or a variant thereof); (24) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 417 (or a variant thereof); and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid Attorney Docket No.250298.000780 sequence set forth in SEQ ID NO: 409 (or a variant thereof); (25) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 427 (or a variant thereof); and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409 (or a variant thereof); (26) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 437 (or a variant thereof); and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409 (or a variant thereof); (27) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 445 (or a variant thereof); and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409 (or a variant thereof); (28) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 455 (or a variant thereof); and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409 (or a variant thereof); (29) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 465 (or a variant thereof); and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409 (or a variant thereof); (30) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 475 (or a variant thereof); and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409 (or a variant thereof); (31) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 484 (or a variant thereof); and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409 (or a variant thereof); (32) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 493 (or a variant thereof); and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409 (or a variant thereof); (33) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 503 (or a variant thereof); and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409 (or a variant thereof); (34) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that Attorney Docket No.250298.000780 comprises the amino acid sequence set forth in SEQ ID NO: 513 (or a variant thereof); and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409 (or a variant thereof); (35) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 519 (or a variant thereof); and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409 (or a variant thereof); (36) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 529 (or a variant thereof); and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 537 (or a variant thereof); (37) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 549 (or a variant thereof); and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 557 (or a variant thereof); (38) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 569 (or a variant thereof); and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 577 (or a variant thereof); (39) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 589 (or a variant thereof); and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 597 (or a variant thereof); and/or (40) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 609 (or a variant thereof); and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 597 (or a variant thereof). [00229] The present disclosure also provides anti-p75NTR protein-drug conjugates comprising an isolated antibody or antigen-binding fragment thereof that specifically binds to p75NTR or an antigenic fragment thereof comprising: (1) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 2, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 10, or a variant thereof; (2) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 22, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid Attorney Docket No.250298.000780 sequence set forth in SEQ ID NO: 30, or a variant thereof; (3) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 42, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 50, or a variant thereof; (4) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 58, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 66, or a variant thereof; (5) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 78, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 86, or a variant thereof; (6) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 98, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 106, or a variant thereof; (7) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 116, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 124, or a variant thereof; (8) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 136, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 144, or a variant thereof; (9) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 155, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 162, or a variant thereof; (10) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 173, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 179, or a variant thereof; (11) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 207, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 215, or a variant thereof; (12) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that Attorney Docket No.250298.000780 comprises the amino acid sequence set forth in SEQ ID NO: 245, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 251, or a variant thereof; (13) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 279, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 287, or a variant thereof; (14) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 297, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 304, or a variant thereof; (15) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 315, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 323, or a variant thereof; (16) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 349, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 357, or a variant thereof; (17) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 387, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 391, or a variant thereof; (18) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 417, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof; (19) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 427, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof; (20) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 437, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof; (21) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 445, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and Attorney Docket No.250298.000780 LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof; (22) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 455, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof; (23) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 465, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof; (24) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 475, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof; (25) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 493, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof; (26) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 503, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof; (27) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 513, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof; and/or (28) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 519, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof. [00230] The present disclosure also provides anti-p75NTR protein-drug conjugates comprising an isolated antibody or antigen-binding fragment thereof that specifically binds to p75NTR or an antigenic fragment thereof comprising: (1) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 189, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 197, or a variant thereof; (2) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises Attorney Docket No.250298.000780 the amino acid sequence set forth in SEQ ID NO: 227, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 235, or a variant thereof; (3) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 261, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 269, or a variant thereof; (4) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 331, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 339, or a variant thereof; (5) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 369, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 377, or a variant thereof; (6) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 401, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof; and/or (7) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 484, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof. [00231] The present disclosure also provides anti-p75NTR protein-drug conjugates comprising an isolated antibody or antigen-binding fragment thereof that specifically binds to p75NTR or an antigenic fragment thereof comprising: (1) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 22, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 30, or a variant thereof; (2) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 78, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 86, or a variant thereof; (3) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 136, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a Attorney Docket No.250298.000780 LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 144, or a variant thereof; (4) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 261, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 269, or a variant thereof; (5) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 369, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 377, or a variant thereof; and/or (6) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 484, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof. [00232] The present disclosure also provides anti-p75NTR protein-drug conjugates comprising an isolated antibody or antigen-binding fragment thereof that specifically binds to p75NTR or an antigenic fragment thereof comprising: (1) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 529, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 537, or a variant thereof; (2) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 549, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 557, or a variant thereof; (3) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 569, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 577, or a variant thereof; (4) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 589, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 597, or a variant thereof; and/or (5) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 609, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 597, or a variant thereof. Attorney Docket No.250298.000780 [00233] The present disclosure also provides anti-p75NTR protein-drug conjugates comprising an isolated antibody or antigen-binding fragment thereof that specifically binds to p75NTR or an antigenic fragment thereof comprising: (1) a HCVR that comprises an HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 4 (or a variant thereof), an HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 6 (or a variant thereof), and an HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 8 (or a variant thereof), and a LCVR that comprises an LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 12 (or a variant thereof), an LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 14 (or a variant thereof), and an LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 16 (or a variant thereof); (2) a HCVR that comprises an HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 24 (or a variant thereof), an HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 26 (or a variant thereof), and an HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 28 (or a variant thereof), and a LCVR that comprises an LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 32 (or a variant thereof), an LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 34 (or a variant thereof), and an LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 36 (or a variant thereof); (3) a HCVR that comprises an HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 44 (or a variant thereof), an HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 46 (or a variant thereof), and an HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 48 (or a variant thereof), and a LCVR that comprises an LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 12 (or a variant thereof), an LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 14 (or a variant thereof), and an LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 52 (or a variant thereof); (4) a HCVR that comprises an HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 60 (or a variant thereof), an HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 62 (or a variant thereof), and an HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 64 (or a variant thereof), and a LCVR that comprises an LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 68 (or a variant thereof), an LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 70 (or a variant thereof), and an LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 72 (or a variant thereof); (5) a HCVR that comprises an HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 80 (or a variant thereof), an HCDR2 comprising the amino acid sequence set Attorney Docket No.250298.000780 forth in SEQ ID NO: 82 (or a variant thereof), and an HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 84 (or a variant thereof), and a LCVR that comprises an LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 88 (or a variant thereof), an LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 90 (or a variant thereof), and an LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 92 (or a variant thereof); (6) a HCVR that comprises an HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 100 (or a variant thereof), an HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 102 (or a variant thereof), and an HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 104 (or a variant thereof), and a LCVR that comprises an LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 108 (or a variant thereof), an LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 34 (or a variant thereof), and an LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 110 (or a variant thereof); (7) a HCVR that comprises an HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 118 (or a variant thereof), an HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 120 (or a variant thereof), and an HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 122 (or a variant thereof), and a LCVR that comprises an LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 126 (or a variant thereof), an LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 128 (or a variant thereof), and an LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 130 (or a variant thereof); (8)a HCVR that comprises an HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 138 (or a variant thereof), an HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 140 (or a variant thereof), and an HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 142 (or a variant thereof), and a LCVR that comprises an LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 146 (or a variant thereof), an LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 90 (or a variant thereof), and an LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 149 (or a variant thereof); (9) a HCVR that comprises an HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 100 (or a variant thereof), an HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 158 (or a variant thereof), and an HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 160 (or a variant thereof), and a LCVR that comprises an LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 164 (or a variant thereof), an LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 90 (or a variant thereof), and an LCDR3 Attorney Docket No.250298.000780 comprising the amino acid sequence set forth in SEQ ID NO: 167 (or a variant thereof); (10) a HCVR that comprises an HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 100 (or a variant thereof), an HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 175 (or a variant thereof), and an HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 177 (or a variant thereof), and a LCVR that comprises an LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 181 (or a variant thereof), an LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 70 (or a variant thereof), and an LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 183 (or a variant thereof); (11) a HCVR that comprises an HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 191 (or a variant thereof), an HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 193 (or a variant thereof), and an HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 195 (or a variant thereof), and a LCVR that comprises an LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 199 (or a variant thereof), an LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 14 (or a variant thereof), and an LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 201 (or a variant thereof); (12) a HCVR that comprises an HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 209 (or a variant thereof), an HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 211 (or a variant thereof), and an HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 213 (or a variant thereof), and a LCVR that comprises an LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 217 (or a variant thereof), an LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 219 (or a variant thereof), and an LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 221 (or a variant thereof); (13) a HCVR that comprises an HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 229 (or a variant thereof), an HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 231 (or a variant thereof), and an HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 233 (or a variant thereof), and a LCVR that comprises an LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 237 (or a variant thereof), an LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 14 (or a variant thereof), and an LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 239 (or a variant thereof); (14) a HCVR that comprises an HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 100 (or a variant thereof), an HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 247 (or a variant thereof), and an HCDR3 comprising the amino acid sequence set forth in Attorney Docket No.250298.000780 SEQ ID NO: 249 (or a variant thereof), and a LCVR that comprises an LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 253 (or a variant thereof), an LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 70 (or a variant thereof), and an LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 255 (or a variant thereof); (15) a HCVR that comprises an HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 263 (or a variant thereof), an HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 265 (or a variant thereof), and an HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 267 (or a variant thereof), and a LCVR that comprises an LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 271 (or a variant thereof), an LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 90 (or a variant thereof), and an LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 273 (or a variant thereof); (16) a HCVR that comprises an HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 281 (or a variant thereof), an HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 283 (or a variant thereof), and an HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 285 (or a variant thereof), and a LCVR that comprises an LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 289 (or a variant thereof), an LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 14 (or a variant thereof), and an LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 291 (or a variant thereof); (17) a HCVR that comprises an HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 299 (or a variant thereof), an HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 193 (or a variant thereof), and an HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 302 (or a variant thereof), and a LCVR that comprises an LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 237 (or a variant thereof), an LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 307 (or a variant thereof), and an LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 309 (or a variant thereof); (18) a HCVR that comprises an HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 317 (or a variant thereof), an HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 319 (or a variant thereof), and an HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 321 (or a variant thereof), and a LCVR that comprises an LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 12 (or a variant thereof), an LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 14 (or a variant thereof), and an LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 325 (or a variant thereof); (19) a HCVR that Attorney Docket No.250298.000780 comprises an HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 333 (or a variant thereof), an HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 335 (or a variant thereof), and an HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 337 (or a variant thereof), and a LCVR that comprises an LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 237 (or a variant thereof), an LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 341 (or a variant thereof), and an LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 343 (or a variant thereof); (20) a HCVR that comprises an HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 351 (or a variant thereof), an HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 353 (or a variant thereof), and an HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 355 (or a variant thereof), and a LCVR that comprises an LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 359 (or a variant thereof), an LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 361 (or a variant thereof), and an LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 363 (or a variant thereof); (21) a HCVR that comprises an HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 371 (or a variant thereof), an HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 373 (or a variant thereof), and an HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 375 (or a variant thereof), and a LCVR that comprises an LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 379 (or a variant thereof), an LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 90 (or a variant thereof), and an LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 381 (or a variant thereof); (22) a HCVR that comprises an HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 138 (or a variant thereof), an HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 319 (or a variant thereof), and an HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 389 (or a variant thereof), and a LCVR that comprises an LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 393 (or a variant thereof), an LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 361 (or a variant thereof), and an LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 395 (or a variant thereof); (23) a HCVR that comprises an HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 403 (or a variant thereof), an HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 405 (or a variant thereof), and an HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 407 (or a variant thereof), and a LCVR that comprises an LCDR1 comprising the amino acid Attorney Docket No.250298.000780 sequence set forth in SEQ ID NO: 237 (or a variant thereof), an LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 14 (or a variant thereof), and an LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 411 (or a variant thereof); (24) a HCVR that comprises an HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 419 (or a variant thereof), an HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 421 (or a variant thereof), and an HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 423 (or a variant thereof), and a LCVR that comprises an LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 237 (or a variant thereof), an LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 14 (or a variant thereof), and an LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 411 (or a variant thereof); (25) a HCVR that comprises an HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 429 (or a variant thereof), an HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 431 (or a variant thereof), and an HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 433 (or a variant thereof), and a LCVR that comprises an LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 237 (or a variant thereof), an LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 14 (or a variant thereof), and an LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 411 (or a variant thereof); (26) a HCVR that comprises an HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 191 (or a variant thereof), an HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 335 (or a variant thereof), and an HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 441 (or a variant thereof), and a LCVR that comprises an LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 237 (or a variant thereof), an LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 14 (or a variant thereof), and an LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 411 (or a variant thereof); (27) a HCVR that comprises an HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 447 (or a variant thereof), an HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 449 (or a variant thereof), and an HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 451 (or a variant thereof), and a LCVR that comprises an LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 237 (or a variant thereof), an LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 14 (or a variant thereof), and an LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 411 (or a variant thereof); (28) a HCVR that comprises an HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 457 (or a variant Attorney Docket No.250298.000780 thereof), an HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 459 (or a variant thereof), and an HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 461 (or a variant thereof), and a LCVR that comprises an LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 237 (or a variant thereof), an LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 14 (or a variant thereof), and an LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 411 (or a variant thereof); (29) a HCVR that comprises an HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 467 (or a variant thereof), an HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 469 (or a variant thereof), and an HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 471 (or a variant thereof), and a LCVR that comprises an LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 237 (or a variant thereof), an LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 14 (or a variant thereof), and an LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 411 (or a variant thereof); (30) a HCVR that comprises an HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 477 (or a variant thereof), an HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 158 (or a variant thereof), and an HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 480 (or a variant thereof), and a LCVR that comprises an LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 237 (or a variant thereof), an LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 14 (or a variant thereof), and an LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 411 (or a variant thereof); (31) a HCVR that comprises an HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 486 (or a variant thereof), an HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 283 (or a variant thereof), and an HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 489 (or a variant thereof), and a LCVR that comprises an LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 237 (or a variant thereof), an LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 14 (or a variant thereof), and an LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 411 (or a variant thereof); (32) a HCVR that comprises an HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 495 (or a variant thereof), an HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 497 (or a variant thereof), and an HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 499 (or a variant thereof), and a LCVR that comprises an LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 237 (or a variant thereof), an LCDR2 comprising the amino acid sequence Attorney Docket No.250298.000780 set forth in SEQ ID NO: 14 (or a variant thereof), and an LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 411 (or a variant thereof); (33) a HCVR that comprises an HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 505 (or a variant thereof), an HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 507 (or a variant thereof), and an HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 509 (or a variant thereof), and a LCVR that comprises an LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 237 (or a variant thereof), an LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 14 (or a variant thereof), and an LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 411 (or a variant thereof); (34) a HCVR that comprises an HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 138 (or a variant thereof), an HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 319 (or a variant thereof), and an HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 515 (or a variant thereof), and a LCVR that comprises an LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 237 (or a variant thereof), an LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 14 (or a variant thereof), and an LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 411 (or a variant thereof); (35) a HCVR that comprises an HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 521 (or a variant thereof), an HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 523 (or a variant thereof), and an HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 525 (or a variant thereof), and a LCVR that comprises an LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 237 (or a variant thereof), an LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 14 (or a variant thereof), and an LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 411 (or a variant thereof); (36) a HCVR that comprises an HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 531 (or a variant thereof), an HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 533(or a variant thereof), and an HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 535 (or a variant thereof), and a LCVR that comprises an LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 539 (or a variant thereof), an LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 541 (or a variant thereof), and an LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 543 (or a variant thereof); (37) a HCVR that comprises an HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 551 (or a variant thereof), an HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 553 (or a variant thereof), and Attorney Docket No.250298.000780 an HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 555 (or a variant thereof), and a LCVR that comprises an LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 559 (or a variant thereof), an LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 561 (or a variant thereof), and an LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 563 (or a variant thereof); (38) a HCVR that comprises an HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 571 (or a variant thereof), an HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 573 (or a variant thereof), and an HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 575 (or a variant thereof), and a LCVR that comprises an LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 579 (or a variant thereof), an LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 581 (or a variant thereof), and an LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 583 (or a variant thereof); (39) a HCVR that comprises an HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 591 (or a variant thereof), an HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 593 (or a variant thereof), and an HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 595 (or a variant thereof), and a LCVR that comprises an LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 599 (or a variant thereof), an LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 601 (or a variant thereof), and an LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 603 (or a variant thereof); and/ or (40) a HCVR that comprises an HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 611 (or a variant thereof), an HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 613 (or a variant thereof), and an HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 615 (or a variant thereof), and a LCVR that comprises an LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 599 (or a variant thereof), an LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 601 (or a variant thereof), and an LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 603 (or a variant thereof). [00234] The present disclosure also provides anti-p75NTR protein-drug conjugates comprising an isolated antibody or antigen-binding fragment thereof that specifically binds to p75NTR or an antigenic fragment thereof comprising: (1) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 4, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 6 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 8, or a variant thereof; Attorney Docket No.250298.000780 and/or a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 12, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 14, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 16, or a variant thereof; (2) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 24, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 26 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 28, or a variant thereof; and/or a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 32, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 34, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 36, or a variant thereof; (3) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 44, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 46 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 48, or a variant thereof; and/or a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 12, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 14, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 52, or a variant thereof; (4) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 60, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 62 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 64, or a variant thereof; and/or a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 68, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 70, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 72, or a variant thereof; (5) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 80, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 82 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 84, or a variant thereof; and/or a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 88, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 90, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 92, or a variant thereof; (6) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 100, or a variant thereof, Attorney Docket No.250298.000780 a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 102 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 104, or a variant thereof; and/or a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 108, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 34, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 110, or a variant thereof; (7) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 118, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 120 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 122, or a variant thereof; and/or a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 126, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 128, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 130, or a variant thereof; (8) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 138, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 140 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 142, or a variant thereof; and/or a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 146, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 90, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 149, or a variant thereof; (9) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 100, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 158 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 160, or a variant thereof; and/or a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 164, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 90, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 167, or a variant thereof; (10) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 100, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 175 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 177, or a variant thereof; and/or a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 181, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 70, or a Attorney Docket No.250298.000780 variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 183, or a variant thereof; (11) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 209, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 211 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 213, or a variant thereof; and/or a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 217, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 219, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 221, or a variant thereof; (12) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 100, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 247 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 249, or a variant thereof; and/or a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 253, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 70, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 255, or a variant thereof; (13) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 281, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 283 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 285, or a variant thereof; and/or a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 289, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 14, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 291, or a variant thereof; (14) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 299, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 193 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 302, or a variant thereof; and/or a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 237, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 307, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 309, or a variant thereof; (15) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 317, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 319 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 321, or Attorney Docket No.250298.000780 a variant thereof; and/or a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 12, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 14, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 325, or a variant thereof; (16) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 351, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 353 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 355, or a variant thereof; and/or a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 359, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 361, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 363, or a variant thereof; (17) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 138, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 319 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 389, or a variant thereof; and/or a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 393, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 361, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 395, or a variant thereof; (18) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 419, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 421 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 423, or a variant thereof; and/or a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 237, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 14, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 411, or a variant thereof; (19) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 429, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 431 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 433, or a variant thereof; and/or a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 237, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 14, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 411, or a variant thereof; (20) a HCVR that comprises: a HCDR1 comprising the amino acid Attorney Docket No.250298.000780 sequence set forth in SEQ ID NO: 191, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 335 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 441, or a variant thereof; and/or a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 237, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 14, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 411, or a variant thereof; (21) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 447, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 449 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 451, or a variant thereof; and/or a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 237, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 14, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 411, or a variant thereof; (22) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 457, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 459 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 461, or a variant thereof; and/or a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 237, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 14, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 411, or a variant thereof; (23) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 467, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 469 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 471, or a variant thereof; and/or a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 237, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 14, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 411, or a variant thereof; (24) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 477, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 158 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 480, or a variant thereof; and/or a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 237, or a variant thereof, a LCDR2 comprising the amino Attorney Docket No.250298.000780 acid sequence set forth in SEQ ID NO: 14, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 411, or a variant thereof; (25) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 495, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 497 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 499, or a variant thereof; and/or a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 237, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 14, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 411, or a variant thereof; (26) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 505, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 507 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 509, or a variant thereof; and/or a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 237, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 14, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 411, or a variant thereof; (27) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 138, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 319 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 515, or a variant thereof; and/or a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 237, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 14, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 411, or a variant thereof; and/or (28) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 521, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 523 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 525, or a variant thereof; and/or a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 237, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 14, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 411, or a variant thereof. [00235] The present disclosure also provides anti-p75NTR protein-drug conjugates comprising an isolated antibody or antigen-binding fragment thereof that specifically binds to Attorney Docket No.250298.000780 p75NTR or an antigenic fragment thereof comprising: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 191, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 193 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 195, or a variant thereof; and/or a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 199, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 14, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 201, or a variant thereof; (2) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 229, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 231 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 233, or a variant thereof; and/or a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 237, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 14, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 239, or a variant thereof; (3) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 263, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 265 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 267, or a variant thereof; and/or a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 271, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 90, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 273, or a variant thereof; (4) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 333, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 335 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 337, or a variant thereof; and/or a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 237, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 341, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 343, or a variant thereof; (5) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 371, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 373 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 375, or a variant thereof; and/or a LCVR that comprises: a LCDR1 comprising the amino acid Attorney Docket No.250298.000780 sequence set forth in SEQ ID NO: 379, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 90, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 381, or a variant thereof; (6) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 403, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 405 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 407, or a variant thereof; and/or a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 237, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 14, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 411, or a variant thereof; and/or (7) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 486, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 283 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 489, or a variant thereof; and/or a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 237, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 14, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 411, or a variant thereof. [00236] The present disclosure also provides anti-p75NTR protein-drug conjugates comprising an isolated antibody or antigen-binding fragment thereof that specifically binds to p75NTR or an antigenic fragment thereof comprising: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 24, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 26 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 28, or a variant thereof; and/or a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 32, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 34, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 36, or a variant thereof; (2) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 80, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 82 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 84, or a variant thereof; and/or a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 88, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 90, or Attorney Docket No.250298.000780 a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 92, or a variant thereof; (3) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 138, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 140 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 142, or a variant thereof; and/or a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 146, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 90, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 149, or a variant thereof; (4) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 263, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 265 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 267, or a variant thereof; and/or a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 271, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 90, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 273, or a variant thereof; (5) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 371, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 373 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 375, or a variant thereof; and/or a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 379, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 90, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 381, or a variant thereof; and/or (6) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 486, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 283 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 489, or a variant thereof; and/or a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 237, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 14, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 411, or a variant thereof. [00237] The present disclosure also provides anti-p75NTR protein-drug conjugates comprising an isolated antibody or antigen-binding fragment thereof that specifically binds to p75NTR or an antigenic fragment thereof comprising: (1) a HCVR that comprises: a HCDR1 Attorney Docket No.250298.000780 comprising the amino acid sequence set forth in SEQ ID NO: 531, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 533, or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 535, or a variant thereof; and/or a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 539, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 541, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 543, or a variant thereof; (2) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 551, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 553, or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 555, or a variant thereof; and/or a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 559, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 561, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 563, or a variant thereof; (3) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 571, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 573, or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 575, or a variant thereof; and/or a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 579, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 581, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 583, or a variant thereof; (4) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 591, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 593, or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 595, or a variant thereof; and/or a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 599, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 601, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 603, or a variant thereof; and/or (5) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 611, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 613 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 615, or a variant thereof; and/or a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 599, or a variant thereof, Attorney Docket No.250298.000780 a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 601, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 603, or a variant thereof. [00238] The present disclosure further provides anti-p75NTR protein-drug conjugates comprising an isolated antibody or antigen-binding fragment thereof that specifically binds to p75NTR or an antigenic fragment thereof comprising a heavy chain variable region (HCVR) that comprises the amino acid sequence set forth in SEQ ID NO: 2, 22, 42, 58, 78, 98, 116, 136, 155, 173, 189, 207, 227, 245, 261, 279, 297, 315, 331, 349, 369, 387, 401, 417, 427, 437, 445, 455, 465, 475, 484, 493, 503, 513, 519, 529, 549, 569, 589 or 609, and a light chain variable (LCVR) region that comprises the amino acid sequence set forth in SEQ ID NO: 10, 30, 50, 66, 86, 106, 124, 144, 162, 179, 197, 215, 235, 251, 269, 287, 304, 323, 339, 357, 377, 391, 409, 537, 557, 577, or 597. [00239] In addition, the present disclosure provides an isolated antibody or antigen- binding fragment thereof that specifically binds to p75NTR or an antigenic fragment thereof comprising: (1) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 2 (or a variant thereof); and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 10 (or a variant thereof); (2) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 22 (or a variant thereof); and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 30 (or a variant thereof); (3) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 42 (or a variant thereof); and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 50 (or a variant thereof); (4) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 58 (or a variant thereof); and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 66 (or a variant thereof); (5) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 78 (or a variant thereof); and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 86 (or a variant thereof); (6) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 98 (or a variant thereof); and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 106 (or a variant thereof); (7) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 116 (or a variant thereof); and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 124 (or a variant thereof); (8) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 136 (or a variant thereof); and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 144 (or a variant thereof); (9) a HCVR that comprises the amino acid sequence set forth in SEQ Attorney Docket No.250298.000780 ID NO: 155 (or a variant thereof); and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 162 (or a variant thereof); (10) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 173 (or a variant thereof); and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 179 (or a variant thereof); (11) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 189 (or a variant thereof); and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 197 (or a variant thereof); (12) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 207 (or a variant thereof); and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 215 (or a variant thereof); (13) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 227 (or a variant thereof); and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 235 (or a variant thereof); (14) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 245 (or a variant thereof); and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 251 (or a variant thereof); (15) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 261 (or a variant thereof); and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 269 (or a variant thereof); (16) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 279 (or a variant thereof); and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 287 (or a variant thereof); (17) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 297 (or a variant thereof); and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 304 (or a variant thereof); (18) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 315 (or a variant thereof); and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 323 (or a variant thereof); (19) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 331 (or a variant thereof); and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 339 (or a variant thereof); (20) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 349 (or a variant thereof); and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 357 (or a variant thereof); (21) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 369 (or a variant thereof); and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 377 (or a variant thereof); (22) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 387 (or a variant thereof); and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 391 (or a variant thereof); (23) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 401 (or a variant thereof); and a LCVR that comprises the amino acid sequence set Attorney Docket No.250298.000780 forth in SEQ ID NO: 409 (or a variant thereof); (24) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 417 (or a variant thereof); and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409 (or a variant thereof); (25) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 427 (or a variant thereof); and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409 (or a variant thereof); (26) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 437 (or a variant thereof); and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409 (or a variant thereof); (27) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 445 (or a variant thereof); and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409 (or a variant thereof); (28) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 455 (or a variant thereof); and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409 (or a variant thereof); (29) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 465 (or a variant thereof); and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409 (or a variant thereof); (30) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 475 (or a variant thereof); and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409 (or a variant thereof); (31) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 484 (or a variant thereof); and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409 (or a variant thereof); (32) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 493 (or a variant thereof); and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409 (or a variant thereof); (33) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 503 (or a variant thereof); and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409 (or a variant thereof); (34) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 513 (or a variant thereof); and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409 (or a variant thereof); (35) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 519 (or a variant thereof); and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409 (or a variant thereof); (36) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 529 (or a variant thereof); and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 537 (or a variant thereof); (37) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 549 (or a variant thereof); and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 557 (or a variant thereof); (38) a HCVR that comprises the amino acid Attorney Docket No.250298.000780 sequence set forth in SEQ ID NO: 569 (or a variant thereof); and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 577 (or a variant thereof); (39) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 589 (or a variant thereof); and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 597 (or a variant thereof); or (40) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 609 (or a variant thereof); and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 597 (or a variant thereof); e.g., wherein the heavy chain variable region is fused to an IgG4 Fc having a S108P mutation. [00240] The present disclosure also provides anti-p75NTR protein-drug conjugates comprising an isolated antibody or antigen-binding fragment thereof that specifically binds to p75NTR or an antigenic fragment thereof comprising: (1) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 2, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 10, or a variant thereof; (2) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 22, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 30, or a variant thereof; (3) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 42, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 50, or a variant thereof; (4) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 58, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 66, or a variant thereof; (5) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 78, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 86, or a variant thereof; (6) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 98, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 106, or a variant thereof; (7) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 116, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 124, or a variant thereof; (8) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 136, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 144, or a variant thereof; (9) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 155, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 162, or a variant thereof; (10) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 173, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 179, or a variant Attorney Docket No.250298.000780 thereof; (11) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 207, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 215, or a variant thereof; (12) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 245, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 251, or a variant thereof; (13) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 279, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 287, or a variant thereof; (14) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 297, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 304, or a variant thereof; (15) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 315, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 323, or a variant thereof; (16) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 349, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 357, or a variant thereof; (17) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 387, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 391, or a variant thereof; (18) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 417, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof; (19) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 427, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof; (20) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 437, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof; (21) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 445, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof; (22) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 455, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof; (23) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 465, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof; (24) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 475, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof; (25) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 493, Attorney Docket No.250298.000780 or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof; (26) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 503, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof; (27) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 513, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof; and/or 28) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 519, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof. [00241] The present disclosure also provides anti-p75NTR protein-drug conjugates comprising an isolated antibody or antigen-binding fragment thereof that specifically binds to p75NTR or an antigenic fragment thereof comprising: (1) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 189, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 197, or a variant thereof; (2) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 227, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 235, or a variant thereof; (3) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 261, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 269, or a variant thereof; (4) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 331, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 339, or a variant thereof; (5) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 369, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 377, or a variant thereof; (6) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 401, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof; and/or (7) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 484, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof. [00242] The present disclosure also provides anti-p75NTR protein-drug conjugates comprising an isolated antibody or antigen-binding fragment thereof that specifically binds to p75NTR or an antigenic fragment thereof comprising: (1) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 22, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 30, or a variant thereof; (2) a HCVR that Attorney Docket No.250298.000780 comprises the amino acid sequence set forth in SEQ ID NO: 78, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 86, or a variant thereof; (3) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 136, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 144, or a variant thereof; (4) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 261, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 269, or a variant thereof; (5) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 369, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 377, or a variant thereof; and/or (6) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 484, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof. [00243] The present disclosure also provides anti-p75NTR protein-drug conjugates comprising an isolated antibody or antigen-binding fragment thereof that specifically binds to p75NTR or an antigenic fragment thereof comprising: (1) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 529, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 537, or a variant thereof; (2) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 549, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 557, or a variant thereof; (3) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 569, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 577, or a variant thereof; (4) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 589, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 597, or a variant thereof; and/or (5) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 609, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 597, or a variant thereof. [00244] The present disclosure provides anti-p75NTR protein-drug conjugates comprising an isolated antibody or antigen-binding fragment thereof that specifically binds to p75NTR or an antigenic fragment thereof comprising a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 18, 38, 54, 74, 94, 112, 132, 151, 169, 185, 203, 223, 241, 257, 275, 293, 311, 327, 345, 365, 383, 397, 413, 425, 435, 443, 453, 463, 473, 482, 491, 501, 511, 517, 527, 545, 565, 585, 605 or 617, and a light chain that comprises the Attorney Docket No.250298.000780 amino acid sequence set forth in SEQ ID NO: 20, 40, 56, 76, 96, 114, 134, 153, 171, 187, 205, 225, 243, 259, 277, 295, 313, 329, 347, 367, 385, 399, 415, 547, 567, 587 or 607. [00245] The present disclosure also provides anti-p75NTR protein-drug conjugates comprising an isolated antibody or antigen-binding fragment thereof that specifically binds to p75NTR or an antigenic fragment thereof comprising:(1) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 18, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 20; (2) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 38, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 40; (3) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 54, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 56; (4) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 74, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 76; (5) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 94, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 96; (6) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 112, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 114; (7) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 132, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 134; (8) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 151, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 153; (9) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 169, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 171; (10) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 185, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 187; (11) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 203, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 205; (12) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 223, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 225; (13) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 241, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 243; (14) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 257, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 259; (15) a heavy chain that comprises the amino acid Attorney Docket No.250298.000780 sequence set forth in SEQ ID NO: 275, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 277; (16) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 293, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 295; (17) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 311, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 313; (18) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 327, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 329; (19) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 345, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 347; (20) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 365, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 367; (21) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 383, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 385; (22) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 397, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 399; (23) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 413, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 415; (24) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 425, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 415; (25) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 435, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 415; (26) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 443, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 415; (27) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 453, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 415; (28) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 463, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 415; (29) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 473, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 415; (30) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 482, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 415; (31) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 491, and a light chain that comprises the amino acid Attorney Docket No.250298.000780 sequence set forth in SEQ ID NO: 415; (32) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 501, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 415; (33) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 511, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 415; (34) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 517, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 415; (35) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 527, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 415; (36) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 545, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 547; (37) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 565, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 567; (38) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 585, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 587; (39) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 605, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 607; and/or (40) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 617, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 607. [00246] The present disclosure also provides anti-p75NTR protein-drug conjugates comprising an isolated antibody or antigen-binding fragment thereof that specifically binds to p75NTR or an antigenic fragment thereof comprising: (1) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 18, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 20, or a variant thereof; (2) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 38, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 40, or a variant thereof; (3) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 54, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 56, or a variant thereof; (4) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 74, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 76, or a variant thereof; (5) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 94, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID Attorney Docket No.250298.000780 NO: 96, or a variant thereof; (6) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 112, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 114, or a variant thereof; (7) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 132, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 134, or a variant thereof; (8) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 151, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 153, or a variant thereof; (9) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 169, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 171, or a variant thereof; (10) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 185, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 187, or a variant thereof; (11) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 223, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 225, or a variant thereof; (12) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 257, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 259, or a variant thereof; (13) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 293, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 295, or a variant thereof; (14) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 311, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 313, or a variant thereof; (15) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 327, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 329, or a variant thereof; (16) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 365, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 367, or a variant thereof; (17) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 397, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 399, or a variant thereof; (18) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 425, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 415, or a variant thereof; (19) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 435, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: Attorney Docket No.250298.000780 415, or a variant thereof; (20) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 443, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 415, or a variant thereof; (21) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 453, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 415, or a variant thereof; (22) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 463, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 415, or a variant thereof; (23) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 473, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 415, or a variant thereof; (24) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 482, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 415, or a variant thereof; (25) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 501, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 415, or a variant thereof; (26) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 511, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 415, or a variant thereof; (27) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 517, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 415, or a variant thereof; and/or (28) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 527, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 415, or a variant thereof. [00247] The present disclosure also provides anti-p75NTR protein-drug conjugates comprising an isolated antibody or antigen-binding fragment thereof that specifically binds to p75NTR or an antigenic fragment thereof comprising: (1) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 203, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 205, or a variant thereof; (2) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 241, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 243, or a variant thereof; (3) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 275, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 277, or a variant thereof; (4) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 345, or a variant thereof, and a light chain Attorney Docket No.250298.000780 that comprises the amino acid sequence set forth in SEQ ID NO: 347, or a variant thereof; (5) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 383, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 385, or a variant thereof; (6) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 413, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 415, or a variant thereof; and/or (7) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 491, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 415, or a variant thereof. [00248] The present disclosure also provides anti-p75NTR protein-drug conjugates comprising an isolated antibody or antigen-binding fragment thereof that specifically binds to p75NTR or an antigenic fragment thereof comprising: (1) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 38, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 40, or a variant thereof; (2) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 94, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 96, or a variant thereof; (3) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 151, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 153, or a variant thereof; (4) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 275, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 277, or a variant thereof; (5) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 383, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 385, or a variant thereof; and/or (6) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 491, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 415, or a variant thereof. [00249] The present disclosure also provides anti-p75NTR protein-drug conjugates comprising an isolated antibody or antigen-binding fragment thereof that specifically binds to p75NTR or an antigenic fragment thereof comprising: (1) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 545, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 547, or a variant thereof; (2) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 565, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: Attorney Docket No.250298.000780 567, or a variant thereof; (3) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 585, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 587, or a variant thereof; (4) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 605, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 607, or a variant thereof; and/or (5) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 617, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 607, or a variant thereof. [00250] In various embodiments, an antigen-binding protein described herein demonstrates less than about 10% to less than about 70% inhibition of an activity of the extracellular domain of human p75NTR, wherein the activity of the extracellular domain of p75NTR is the blocking of human nerve growth factor (NGF)-dependent activation of human tropomyosin receptor kinase A (TrkA) signaling, as measured in a cell-based assay. [00251] In various embodiments, an antigen-binding protein described herein demonstrates antigen-binding protein demonstrates less than about 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, or 68% inhibition of an activity of the extracellular domain of human p75NTR, wherein the activity of the extracellular domain of p75NTR is the blocking of human nerve growth factor (NGF)-dependent activation of human tropomyosin receptor kinase A (TrkA) signaling, as measured in a cell-based assay. [00252] In various embodiments, an antigen-binding protein described herein demonstrates antigen-binding protein demonstrates less than about 50% inhibition of an activity of the extracellular domain of human p75NTR, wherein the activity of the extracellular domain of p75NTR is the blocking of human nerve growth factor (NGF)-dependent activation of human tropomyosin receptor kinase A (TrkA) signaling, as measured in a cell-based assay. [00253] In various embodiments, the cell-based assay described herein comprises the steps of: a) incubating a soluble extracellular domain of human p75NTR with mature human NGF in the presence of the antigen-binding protein, optionally the extracellular domain of human p75NTR is fused to an Fc domain of IgG, b) incubating the mixture of step (a) with a population of recombinant mammalian cells which stably expresses TrkA and a serum response element fused to a luciferase reporter. Attorney Docket No.250298.000780 c) measuring luciferase activity in Relative Luminescence Units (RLU) from the mixture of step (b), and d) calculating % inhibition using the formula RLU 100 X antigen−binding protein − RLUsoluble p75 RLUNGF − RLUsoluble p75 wherein, RLUsoluble p75 same conditions with an antigen-binding , is the RLU value from cells treated with only the human mature NGF in the absence of the soluble extracellular domain of p75NTR . [00254] In some embodiments, the cell-based assay is performed as described, for example, in Example 6 presented herein. [00255] In various embodiments, an antigen-binding protein described herein can block the binding of, e.g., a human neurotrophin receptor mouse Fc dimer (human p75-mFc) to human neurotrophin 3 (hNT-3) by at least about 5%, at least about 10%, at least about 15%, at least about 20%, at least about 25%, at least about 30%, at least about 35%, at least about 40%, at least about 45%, at least about 50%, at least about 60%, at least about 65%, at least about 70%, at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 95%, or 100%. [00256] In some embodiments, an antigen-binding protein described herein can block the binding of, e.g., a human neurotrophin receptor mouse Fc dimer (human p75-mFc) to human neurotrophin 3 (hNT-3) by from at least about 5% to at least about 10%, from at least about 5% to at least about 15%, from at least about 5% to at least about 20%, from at least about 5% to at least about 25%, from at least about 5% to at least about 30%, from at least about 5% to at least about 35%, from at least about 5% to at least about 40%, from at least about 5% to at least about 45%, from at least about 5% to at least about 50%, from at least about 10% to at least about 15%, from at least about 10% to at least about 20%, from at least about 10% to at least about 25%, from at least about 10% to at least about 30%, from at least about 10% to at least about 35%, from at least about 10% to at least about 40%, from at least about 10% to at least about 45%, from at least about 10% to at least about 50%, from at least about 15% to at least about 20%, from at least about 15% to at least about 25%, from at least about 15% to at least about 30%, from at least about 15% to at least about 35%, from at least about 15% to at least about 40%, from at least about 15% to at least about 45%, from at least about 15% to at least about 50%, from at least about 20% to at least about 25%, from at least Attorney Docket No.250298.000780 about 20% to at least about 30%, from at least about 20% to at least about 35%, from at least about 20% to at least about 40%, from at least about 20% to at least about 45%, from at least about 20% to at least about 50%, from at least about 25% to at least about 30%, from at least about 25% to at least about 35%, from at least about 25% to at least about 40%, from at least about 25% to at least about 45%, from at least about 25% to at least about 50%, from at least about 30% to at least about 35%, from at least about 30% to at least about 40%, from at least about 30% to at least about 45%, from at least about 30% to at least about 50%, from at least about 35% to at least about 40%, from at least about 35% to at least about 45%, from at least about 35% to at least about 50%, from at least about 40% to at least about 45%, from at least about 40% to at least about 50%, from at least about 45% to at least about 50%, or more. [00257] In some embodiments, an antigen-binding protein described herein can block the binding of, e.g., a human neurotrophin receptor mouse Fc dimer (human p75-mFc) to human neurotrophin 3 (hNT-3) by from at least about 50% to at least about 60%, from at least about 50% to at least about 70%, from at least about 50% to at least about 80%, from at least about 50% to at least about 90%, more than 60%, from at least about 60% to at least about 70%, from at least about 60% to at least about 80%, from at least about 60% to at least about 90%, more than at least about 70%, from at least about 70% to at least about 80%, from at least about 70% to at least about 90%, more than at least about 80%, from at least about 80% to at least about 90%, more than 90%, from at least about 90% to at least about 95%, from at least about 90% to at least about 98%, more than 95%, from at least about 95% to at least about 98%, more than at least about 98%, or more than at least about 99%. In some embodiments, the expression or activity of a product (e.g., an mRNA product) of at least one targeted gene may be inhibited by at least about 50%, at least about 55%, at least about 60%, at least about 65%, at least about 70%, at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 91%, at least about 92%, at least about 93%, at least about 94%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99% or even 100%. [00258] In some embodiments an antigen-binding protein described herein can block the binding of, e.g., a human neurotrophin receptor mouse Fc dimer (human p75-mFc) to human neurotrophin 3 (hNT-3) by at least 1%, at least 2%, at least 3%, at least 4%, at least 5%, at least 6%, at least 7%, at least 8%, at least 9%, at least 10%, at least 11%, at least 12%, at least 13%, at least 14%, at least 15%, at least 16%, at least 17%, at least 18%, at least 19%, at least 20%, at least 21%, at least 22%, at least 23%, at least 24%, at least 25%, Attorney Docket No.250298.000780 at least 26%, at least 27%, at least 28%, at least 29%, at least 30%, at least 31%, at least 32%, at least 33%, at least 34%, at least 35%, at least 36%, at least 37%, at least 38%, at least 39%, at least 40%, at least 41%, at least 42%, at least 43%, at least 44%, at least 45%, at least 46%, at least 47%, at least 48%, at least 49%, at least 50%, at least 51%, at least 52%, at least 53%, at least 54%, at least 55%, at least 56%, at least 57%, at least 58%, at least 59%, at least 60%, at least 61%, at least 62%, at least 63%, at least 64%, at least 65%, at least 66%, at least 67%, at least 68%, at least 69%, at least 70%, at least 71%, at least 72%, at least 73%, at least 74%, or at least 75%, or more. [00259] In some embodiments, the antigen-binding protein can block the binding of a human neurotrophin receptor mouse Fc dimer (human p75-mFc) to human neurotrophin 3 (hNT-3) by at least about 50%.In some embodiments, the antigen-binding protein can block the binding of a human neurotrophin receptor mouse Fc dimer (human p75-mFc) to human neurotrophin 3 (hNT-3) by less than about 50%. [00260] In some embodiments, the antigen-binding protein binds to the same epitope on p75NTR as an antibody comprising an HCVR/LCVR amino acid sequence pair as set forth in Table 1-1. In some embodiments, the antigen-binding protein competes for binding to p75NTR with an antibody comprising an HCVR/LCVR amino acid sequence pair as set forth in Table 1-1. [00261] As discussed, an anti-p75NTR protein-drug conjugate may comprise an anti- p75NTR scFv comprising an optional signal peptide (e.g., mROR signal sequence), connected to an scFv (e.g., including a VL and a VH optionally connected by a linker), connected to an option linker, connected to a molecular cargo. In various embodiments, the optional signal peptide is, for example, the signal peptide from Mus musculus Ror1 (e.g., comprising or consisting of the amino acids MHRPRRRGTRPPPLALLAALLLAARGADA (SEQ ID NO: 622)). [00262] In some embodiments, an anti-p75NTR scFv described herein, in VL-(Gly4Ser)3 (SEQ ID NO: 623)-VH format, comprises an amino acid sequence as set forth in Table 1-1. In other embodiments, the present disclosure includes scFvs that are in the format VH- (Gly4Ser)3 (SEQ ID NO: 623)-VL. Optionally, an anti-p75NTR scFv of the present disclosure further includes a tag sequence LLQGSG (SEQ ID NO: 624) and/or HHHHHH (SEQ ID NO: 619). The tag sequence LLQGSG (SEQ ID NO: 624) or HHHHHH (SEQ ID NO: 619) may be included at the N-terminus and/or C-terminus of the anti-p75NTR scFv. In one embodiment, an Attorney Docket No.250298.000780 anti-p75NTR scFv of the present invention further includes an N-terminal LLQGSG (SEQ ID NO: 624) and/or a C-terminal HHHHHH (SEQ ID NO: 619). [00263] In some embodiments, the p75NTR binding protein described herein comprises a humanized antibody or antigen binding fragment thereof, human antibody or antigen binding fragment thereof, murine antibody or antigen binding fragment thereof, chimeric antibody or antigen binding fragment thereof, monoclonal antibody or antigen binding fragment thereof (e.g., monovalent Fab', divalent Fab2, F(ab)'3 fragments, single-chain variable fragment (scFv), bis-scFv, (scFv)2, diabody, bivalent antibody, one-armed antibody, minibody, nanobody, triabody, tetrabody, disulfide stabilized Fv protein (dsFv), single-domain antibody (sdAb), Ig NAR, camelid antibody or antigen binding fragment thereof, single heavy chain antibody, bispecific antibody or binding fragment thereof, (e.g., bisscFv, or a bi-specific T-cell engager (BiTE)), trispecific antibody (e.g., F(ab)'3 fragments or a triabody), or a chemically modified derivative thereof. In some embodiments, the p75NTR binding protein described herein comprises a fragment antigen-binding region (Fab). In some embodiments, the anti- p75 antigen-binding protein can be bivalent. In some embodiments, the anti-p75 antigen- binding protein can be monovalent (e.g., one-arm antibody). [00264] The term “humanized antibody”, as used herein, includes antibodies in which CDR sequences derived from the germline of another mammalian species, such as a mouse, have been grafted onto human framework sequences, or otherwise modified to increase their similarity to antibody variants produced naturally in humans. [00265] In some cases, the p75NTR binding protein is an antibody which comprises one or more mutations in a framework region, e.g., in the CH1 domain, CH2 domain, CH3 domain, hinge region, or a combination thereof. In some embodiments, the one or more mutations are to stabilize the antibody and/or to increase half-life. In some embodiments, the one or more mutations are to modulate Fc receptor interactions, to reduce or eliminate Fc effector functions such as FcyR, antibody-dependent cell-mediated cytotoxicity (ADCC), or complement-dependent cytotoxicity (CDC). In additional embodiments, the one or more mutations are to modulate glycosylation. [00266] In some embodiments, one, two or more mutations (e.g., amino acid substitutions) are introduced into the Fc region of an antibody described herein (e.g., in a CH2 domain (residues 231-340 of human IgG1) and/or CH3 domain (residues 341-447 of human IgG1) and/or the hinge region, with numbering according to the Kabat numbering system (e.g., the EU index in Kabat)) to alter one or more functional properties of the antibody, Attorney Docket No.250298.000780 such as serum half-life, complement fixation, Fc receptor binding and/or antigen-dependent cellular cytotoxicity. In some embodiments, one, two or more mutations (e.g., amino acid substitutions) are introduced into the hinge region of the Fc region (CH1 domain) such that the number of cysteine residues in the hinge region are altered (e.g., increased or decreased) as described in, e.g., U.S. Patent No. 5,677,425. The number of cysteine residues in the hinge region of the CH1 domain can be altered to, e.g., facilitate assembly of the light and heavy chains, or to alter (e.g., increase or decrease) the stability of the antibody or to facilitate linker conjugation. [00267] In some embodiments, one, two or more amino acid mutations (i.e., substitutions, insertions or deletions) are introduced into an IgG constant domain, or FcRn- binding fragment thereof (preferably an Fc or hinge-Fc domain fragment) to alter (e.g., decrease or increase) half-life of the antibody in vivo. See, e.g., PCT Publication Nos. WO 02/060919; WO 98/23289; and WO 97/34631; and U.S. Pat. Nos. 5,869,046, 6,121,022, 6,277,375 and 6,165,745 for examples of mutations that will alter (e.g., decrease or increase) the half-life of an antibody in vivo. In some embodiments, the Fc region comprises a mutation at residue position L234, L235, or a combination thereof. In some embodiments, the mutations comprise L234 and L235. In some embodiments, the mutations comprise L234A and L235A. [00268] The anti-p75NTR antibodies and antigen-binding fragments described herein may be modified after translation, e.g., glycosylated. [00269] For example, antibodies and antigen-binding fragments described herein may be glycosylated (e.g., N-glycosylated and/or O-glycosylated) or aglycosylated. Typically, antibodies and antigen-binding fragments are glycosylated at the conserved residue N297 of the IgG Fc domain. Some antibodies and fragments include one or more additional glycosylation sites in a variable region. In an embodiment, the glycosylation site is in the following context: FN297S or YN297S. [00270] In an embodiment, said glycosylation is any one or more of three different N- glycan types: high mannose, complex and/or hybrid that are found on IgGs with their respective linkage. Complex and hybrid types exist with core fucosylation, addition of a fucose residue to the innermost N-acetylglucosamine, and without core fucosylation. [00271] In some cases, the p75NTR binding protein is an aglycosylated antibody, i.e., an antibody that does not comprise a glycosylation sequence that might interfere with a transglutamination reaction, for instance an antibody that does not have a saccharide group Attorney Docket No.250298.000780 at N180 and/or N297 on one or more heavy chains. In particular embodiments, an antibody heavy chain has an N180 mutation. In other words, the antibody is mutated to no longer have an asparagine residue at position 180 according to the EU numbering system as disclosed by Kabat et al. In particular embodiments, an antibody heavy chain has an N180Q mutation. In particular embodiments, an antibody heavy chain has an N297 mutation. In particular embodiments, an antibody heavy chain has an N297Q or an N297D mutation. Antibodies comprising such above-described mutations can be prepared by site-directed mutagenesis to remove or disable a glycosylation sequence or by site-directed mutagenesis to insert a glutamine residue at site apart from any interfering glycosylation site or any other interfering structure. Such antibodies also can be isolated from natural or artificial sources. Aglycosylated antibodies also include antibodies comprising a T299 or S298P or other mutations, or combinations of mutations that result in a lack of glycosylation. [00272] In some cases, the antigen-binding protein is a deglycosylated antibody, i.e., an antibody in which a saccharide group at is removed to facilitate transglutaminase-mediated conjugation. Saccharides include, but are not limited to, N-linked oligosaccharides. In some embodiments, deglycosylation is performed at residue N180. In some embodiments, deglycosylation is performed at residue N297. In some embodiments, removal of saccharide groups is accomplished enzymatically, included but not limited to via PNGase. [00273] In an embodiment, an antibody or fragment described herein is afucosylated. [00274] The antibodies and antigen-binding fragments described herein may also be post-translationally modified in other ways including, for example: Glu or Gln cyclization at N- terminus; Loss of positive N-terminal charge; Lys variants at C-terminus; Deamidation (Asn to Asp); Isomerization (Asp to isoAsp); Deamidation (Gln to Glu); Oxidation (Cys, His, Met, Tyr, Trp); and/or Disulfide bond heterogeneity (Shuffling, thioether and trisulfide formation). [00275] In some embodiments, an antibody disclosed herein comprises Q295 which can be native to the antibody heavy chain sequence. In some embodiments, an antibody heavy chain disclosed herein may comprise Q295. In some embodiments, an antibody heavy chain disclosed herein may comprise Q295 and an amino acid substitution N297D. [00276] According to certain embodiments of the present disclosure, anti-p75NTR antibodies and antigen-binding fragments (e.g., REGN14148; REGN14149; REGN14150; REGN14151; REGN14152; REGN14153; REGN14154; REGN14155; REGN14156; REGN14157; REGN14158; REGN14159; REGN14160; REGN14161; REGN14162; REGN14163; REGN14164; REGN14165; REGN14175; REGN14176; REGN14177; Attorney Docket No.250298.000780 REGN14178; REGN14179; REGN14180; REGN14181; REGN14182; REGN14183; REGN14184; REGN14185; REGN14186; REGN14187; REGN14188; REGN14189; REGN14190; REGN14191; REGN19513; REGN19514; REGN19515; REGN19516; or REGN19517) are provided comprising an Fc domain comprising one or more mutations which enhance or diminish antibody binding to the FcRn receptor, e.g., at acidic pH as compared to neutral pH (e.g., REGN14148; REGN14149; REGN14150; REGN14151; REGN14152; REGN14153; REGN14154; REGN14155; REGN14156; REGN14157; REGN14158; REGN14159; REGN14160; REGN14161; REGN14162; REGN14163; REGN14164; REGN14165; REGN14175; REGN14176; REGN14177; REGN14178; REGN14179; REGN14180; REGN14181; REGN14182; REGN14183; REGN14184; REGN14185; REGN14186; REGN14187; REGN14188; REGN14189; REGN14190; REGN14191; REGN19513; REGN19514; REGN19515; REGN19516; or REGN19517). For example, the present disclosure includes anti-p75NTR antibodies comprising a mutation in the CH2 or a CH3 region of the Fc domain, wherein the mutation(s) increases the affinity of the Fc domain to FcRn in an acidic environment (e.g., in an endosome where pH ranges from about 5.5 to about 6.0). Such mutations may result in an increase in serum half-life of the antibody when administered to an animal. [00277] Non-limiting examples of such Fc modifications include, e.g., a modification at position: • 250 (e.g., E or Q); • 250 and 428 (e.g., L or F); • 252 (e.g., L/Y/F/W or T), • 254 (e.g., S or T), and/or • 256 (e.g., S/R/Q/E/D or T); and/or a modification at position: • 428 and/or 433 (e.g., H/L/R/S/P/Q or K), and/or • 434 (e.g., H/F or Y); and/or a modification at position: • 250 and/or 428; and/or a modification at position: • 307 or 308 (e.g., 308F, V308F), and/or • 434. [00278] In an embodiment, the modification comprises: Attorney Docket No.250298.000780 • a 428L (e.g., M428L) and 434S (e.g., N434S) modification; • a 428L, 259I (e.g., V259I), and 308F (e.g., V308F) modification; • a 433K (e.g., H433K) and a 434 (e.g., 434Y) modification; • a 252, 254, and 256 (e.g., 252Y, 254T, and 256E) modification; • a 250Q and 428L modification (e.g., T250Q and M428L); and/or • a 307 and/or 308 modification (e.g., 308F or 308P). [00279] For example, the present disclosure includes anti-p75NTR antibodies comprising an Fc domain comprising one or more pairs or groups of mutations selected from the group consisting of: • 250Q and 248L (e.g., T250Q and M248L); • 252Y, 254T and 256E (e.g., M252Y, S254T and T256E); • 257I and 311I (e.g., P257I and Q311I); • 257I and 434H (e.g., P257I and N434H); • 376V and 434H (e.g., D376V and N434H); • 307A, 380A and 434A (e.g., T307A, E380A and N434A); • 428L and 434S (e.g., M428L and N434S); and • 433K and 434F (e.g., H433K and N434F). [00280] In yet another embodiment, the modification comprises a 265A (e.g., D265A) and/or a 297A (e.g., N297A) modification. [00281] In an embodiment, the heavy chain constant domain is gamma-4 comprising an S228P and/or S108P mutation. See Angal et al., A single amino acid substitution abolishes the heterogeneity of chimeric mouse/human (IgG4) antibody, Mol Immunol.1993 Jan;30(1):105-108. [00282] All possible combinations of the foregoing Fc domain mutations, and other mutations within the antibody variable domains disclosed herein, are contemplated within the scope of the present disclosure. [00283] The anti-p75NTR antibodies described herein may comprise a modified Fc domain having reduced effector function. As used herein, a "modified Fc domain having reduced effector function" means any Fc portion of an immunoglobulin that has been modified, mutated, truncated, etc., relative to a wild-type, naturally occurring Fc domain such that a molecule comprising the modified Fc exhibits a reduction in the severity or extent of at least one effect selected from the group consisting of cell killing (e.g., ADCC and/or CDC), complement activation, phagocytosis and opsonization, relative to a comparator molecule Attorney Docket No.250298.000780 comprising the wild-type, naturally occurring version of the Fc portion. In certain embodiments, a "modified Fc domain having reduced effector function" is an Fc domain with reduced or attenuated binding to an Fc receptor (e.g., FcγR). [00284] In certain embodiments, the modified Fc domain is a variant IgG1 Fc or a variant IgG4 Fc comprising a substitution in the hinge region. For example, a modified Fc for use in the context of the present disclosure may comprise a variant IgG1 Fc wherein at least one amino acid of the IgG1 Fc hinge region is replaced with the corresponding amino acid from the IgG2 Fc hinge region. Alternatively, a modified Fc for use in the context of the present disclosure may comprise a variant IgG4 Fc wherein at least one amino acid of the IgG4 Fc hinge region is replaced with the corresponding amino acid from the IgG2 Fc hinge region. Non-limiting, exemplary modified Fc regions that can be used in the context of the present disclosure are set forth in US Patent Application Publication No.2014/0243504, the disclosure of which is hereby incorporated by reference in its entirety, as well as any functionally equivalent variants of the modified Fc regions set forth therein. [00285] Also provided herein are antigen-binding proteins (e.g., antibodies or antigen- binding fragments), comprising a HCVR set forth herein and a chimeric heavy chain constant (CH) region, wherein the chimeric CH region comprises segments derived from the CH regions of more than one immunoglobulin isotype. For example, the antibodies of the disclosure may comprise a chimeric CH region comprising part or all of a CH2 domain derived from a human IgG1, human IgG2 or human IgG4 molecule, combined with part or all of a CH3 domain derived from a human IgG1, human IgG2 or human IgG4 molecule. According to certain embodiments, the antibodies provided herein comprise a chimeric CH region having a chimeric hinge region. For example, a chimeric hinge may comprise an “upper hinge” amino acid sequence (amino acid residues from positions 216 to 227 according to EU numbering) derived from a human IgG1, a human IgG2 or a human IgG4 hinge region, combined with a “lower hinge” sequence (amino acid residues from positions 228 to 236 according to EU numbering) derived from a human IgG1, a human IgG2 or a human IgG4 hinge region. According to certain embodiments, the chimeric hinge region comprises amino acid residues derived from a human IgG1 or a human IgG4 upper hinge and amino acid residues derived from a human IgG2 lower hinge. An antibody comprising a chimeric CH region as described herein may, in certain embodiments, exhibit modified Fc effector functions without adversely affecting the therapeutic or pharmacokinetic properties of the antibody. See, e.g., WO2014/022540. Attorney Docket No.250298.000780 [00286] Other modified Fc domains and Fc modifications that can be used in the context of the present disclosure include any of the modifications as set forth in US2014/0171623; US 8,697,396; US2014/0134162; WO2014/043361, the disclosures of which are hereby incorporated by reference in their entireties. Methods of constructing antibodies or other antigen-binding fusion proteins comprising a modified Fc domain as described herein are known in the art. [00287] The present disclosure provides a vessel (e.g., a plastic or glass vial, e.g., with a cap or a chromatography column, hollow bore needle or a syringe cylinder) comprising an antigen-binding protein (e.g., an anti-p75NTR antibody or antigen-binding fragment thereof described herein) and/or anti-p75NTR protein-drug conjugates, e.g., p75NTR binding protein- drug conjugates or anti-p75NTR Fab-drug conjugates described herein. [00288] The present disclosure also provides an injection device comprising an antigen-binding protein (e.g., an anti-p75NTR antibody or antigen-binding fragment thereof described herein) and/or an anti-p75NTR protein-drug conjugate, e.g., anti-p75NTR scFv-drug conjugates or anti-p75NTR Fab-drug conjugates described herein, or a pharmaceutical composition thereof. The injection device may be packaged into a kit. An injection device is a device that introduces a substance into the body of a subject via a parenteral route, e.g., intrathecal, intracisternal (e.g., cisterna magna), intracerebroventricular, intraparenchymal, intraocular, intravitreal, intramuscular, subcutaneous or intravenous. For example, an injection device may be a syringe or an auto-injector (e.g., pre-filled with the pharmaceutical formulation) which, for example, includes a cylinder or barrel for holding fluid to be injected (e.g., comprising the antibody or fragment or a pharmaceutical formulation thereof), a needle for piecing skin, blood vessels or other tissue for injection of the fluid; and a plunger for pushing the fluid out of the cylinder and through the needle bore and into the body of the subject. [00289] The present disclosure provides methods for administering an anti-p75NTR antigen-binding protein, e.g., antibody or antigen-binding fragment thereof (e.g., REGN14148; REGN14149; REGN14150; REGN14151; REGN14152; REGN14153; REGN14154; REGN14155; REGN14156; REGN14157; REGN14158; REGN14159; REGN14160; REGN14161; REGN14162; REGN14163; REGN14164; REGN14165; REGN14175; REGN14176; REGN14177; REGN14178; REGN14179; REGN14180; REGN14181; REGN14182; REGN14183; REGN14184; REGN14185; REGN14186; REGN14187; REGN14188; REGN14189; REGN14190; REGN14191; REGN19513; Attorney Docket No.250298.000780 REGN19514; REGN19515; REGN19516; or REGN19517) to a subject, comprising introducing the protein or a pharmaceutical formulation thereof into the body of the subject. For example, in an embodiment, the method comprises piercing the body of the subject, e.g., with a needle of a syringe, and injecting the antigen-binding protein or a pharmaceutical formulation thereof into the body of the subject, e.g., into the eye, vein, artery, muscular tissue or subcutis of the subject. [00290] The present disclosure further provides methods for delivering a molecular cargo, wherein the molecular cargo is conjugated to, e.g., an antigen-binding protein described herein, e.g., an anti-p75NTR scFv or an anti-p75NTR Fab described herein, to a target tissue (e.g., brain, spinal cord, peripheral nervous system, autonomic nervous system, enteric nervous system and/or eye) or a target cell (e.g., sensory neurons (such as, but not limited to, dorsal root ganglion cells or trigeminal ganglion cells)) in a subject, comprising introducing the protein-drug conjugate into the body of the subject (e.g., a human), for example, parenterally (e.g., via intradermal, subcutaneous, intramuscular, and/or intravenous injection), and/or via intrathecal, intracerebroventricular (ICV), intracisternal (e.g., cisterna magna), and/or intraparenchymal injection. For example, the method comprises piercing the body of the subject with a needle of a syringe and injecting the protein-drug conjugate into the body of the subject, e.g., into the brain or spinal cord of the subject. For example, the protein-drug conjugate may be introduced into the subject via intrathecal, intracisternal (e.g., cisterna magna), intracerebroventricular, or intraparenchymal injection into the central nervous system. [00291] In some embodiments, the method for delivering a molecular cargo to a tissue or cell type expressing p75NTR in the body of a subject described herein comprises administering to the subject a protein-drug conjugate described herein, or the pharmaceutical composition described herein. In some embodiments, the tissue is brain, spinal cord, peripheral nervous system, autonomic nervous system, enteric nervous system, or eye. In some embodiments, the tissue is brain or spinal cord. In some embodiments, the cell type is a neuron such as, but not limited to a sensory neuron. In some embodiments, the cell type is a dorsal root ganglion cell or a trigeminal ganglion cell. In some embodiments, the cell type is a Müller glial cell. In some embodiments, the cell type is a Leydig cell. In some embodiments, the cell type is an ionocyte. In some embodiments, the cell type is a sympathetic ganglion cell. In some embodiments, the cell type is a dermal fiber cell. In some embodiments, the cell type is a retina cell. In some embodiments, the cell type is a myenteric Attorney Docket No.250298.000780 plexus cell. In some embodiments, the cell type is a celiac ganglion cell. In some embodiments, the cell type is a dendritic cell. In some embodiments, the cell type is a Schwann cell. In some embodiments, the cell type is a salivary gland cell. In some embodiments, the cell type is a retinal bipolar neuron. In some embodiments, the cell type is a basal respiratory cell. In some embodiments, the cell type is a basal squamous epithelial cell. In some embodiments, the cell type is an oligodendrocyte. In some embodiments, the protein-drug conjugate is introduced into the body of the subject via intramuscular, subcutaneous, or intravenous administration. In some embodiments, the protein-drug conjugate is administered into the body of the subject via subcutaneous, intrathecal, intracisternal, intracerebroventricular, or intraparenchymal administration. In some embodiments, the protein-drug conjugate is administered into the body of the subject via intravitreal administration into the eye. In some embodiments, the protein-drug conjugate is administered into the body of the subject via subcutaneous administration. In some embodiments, the protein-drug conjugate is administered into the body of the subject via intracerebroventricular administration. [00292] In some embodiments, a molecular cargo described herein is delivered, e.g., to the central nervous system of a subject including, e.g., to the brain and/or the spinal cord tissues of the central nervous system which express p75NTR, and the protein-drug conjugate described herein or the pharmaceutical composition described herein, is administered to the subject via subcutaneous administration. In some embodiments, a molecular cargo described herein is delivered, e.g., to the central nervous system of a subject including, e.g., to brain and/or the spinal cord tissues of the central nervous system which express p75NTR, and the protein-drug conjugate described herein or the pharmaceutical composition described herein, is administered to the subject via intracerebroventricular administration. [00293] The present disclosure further provides a cell line useful for screening the p75NTR binding proteins or anti-p75NTR protein-drug conjugates described herein. The cell lines described herein express p75NTR on the cell surface, and optionally further comprise an exogenous nucleic acid to express one or more reporter proteins. In some embodiments, the cell line is modified from a brain cell line, such as a glioblastoma cell line. In one embodiment, the cell line is modified from the U87 glioblastoma cell line. [00294] In some embodiments, the cell line comprise an exogenous nucleic acid (e.g., mRNA) to express two reporter proteins. Non-limiting examples of reporter proteins that can be used in the present application include fluorescent proteins, such as green fluorescent Attorney Docket No.250298.000780 protein (GFP), red fluorescent protein (RFP), yellow fluorescent protein (YFP), blue fluorescent protein (BFP), or luminescent proteins, such as firefly luciferase, Renilla luciferase, or Nanoluc luciferase. In some embodiments, the cell lines comprise an exogenous nucleic acid to express both GFP and firefly luciferase. The genes encoding the two reporter proteins are optionally separated by a sequence encoding a self-cleaving peptide or an internal ribosomal entry site (IRES). The self-cleaving peptide can be a 2A peptide such as T2A, P2A, E2A, or F2A peptide. [00295] In some embodiments, the cell lines can be used to assess binding and/or internalization properties of the p75NTR binding proteins or anti-p75NTR protein-drug conjugates described herein. The cell lines allow for high throughput screening of p75NTR binding proteins or anti-p75NTR protein-drug conjugates to identify the best candidate for therapeutic delivery, and/or allow for testing of the most efficient siRNA modifications, linker chemistries, as well as LNP chemistries. [00296] In some embodiments, the cell lines can be used to screen for interfering nucleic acids (e.g., siRNAs) or gRNAs to identify genes or factors that could further promote endosomal escape (or alleviate the burden of lack of endosomal escape) of p75NTR protein- drug conjugates to allow the cargo to be better delivered to the target cells. Molecular Cargoes [00297] In some aspects, the present disclosure includes methods and compositions for delivering a conjugated molecular cargo to a cell or tissue. In certain aspects the antigen- binding protein that binds specifically to p75 neurotrophin receptor (p75NTR) disclosed herein, e.g., an antibody or an antigen-binding fragment thereof (e.g., an scFv), may be conjugated (e.g., covalently conjugated) to the molecular cargo. [00298] As used herein, the term “molecular cargo” refers to a molecule that operates to effect a biological outcome. As a non-limiting example, the molecular cargo may operate to modulate the transcription of a DNA sequence, to modulate the expression of a protein, or to modulate the activity of a protein, to delete or disrupt an endogenous gene (or fragment thereof), to achieve an enzymatic activity, to supplement or replace a deficient endogenous protein, to insert an exogenous gene (or fragment thereof), or to replace an endogenous gene (or fragment thereof) with an exogenous gene (or fragment thereof). In various embodiments, the molecular cargo may comprise a polynucleotide. In various embodiments, the molecular Attorney Docket No.250298.000780 cargo may comprise a polypeptide. In various embodiments, the molecular cargo comprises a lipid nanoparticle, liposome, or non-lipid nanoparticle described herein, which optionally comprises one or more polynucleotide and/or a protein molecules. In various embodiments, the molecular cargo may comprise a small molecule. [00299] In some embodiments, the anti-p75NTR antibody or an antigen-binding fragment thereof disclosed herein may be used, for example, to deliver the conjugated molecular cargo to a cell or a tissue that expresses p75NTR (e.g., brain or spinal cord, peripheral nervous system, autonomic nervous system, enteric nervous system, and/or eye) for diagnosing and or treating a disease (e.g., a neurological disease or disorder). In some embodiments, the molecular cargoes conjugated to the anti-p75NTR antibody or antigen-binding fragment thereof may be taken up by, e.g., sensory neurons (such as, but not limited to, dorsal root ganglion cells or trigeminal ganglion cells), via binding to the p75NTR, which may be endocytosed, e.g., via clathrin-mediated endocytosis, or clatherin- and dynamin-independent pathways (Haugsten et al., PLoS One. 2011;6(7):e21708). In some embodiments, the anti-p75NTR antibody or an antigen-binding fragment thereof described herein can exhibit superior activity, e.g., in delivering a molecular cargo into a target tissue (e.g., brain or spinal cord, peripheral nervous system, autonomic nervous system, enteric nervous system, and/or eye) or a target cell (e.g., a sensory neuron (such as, but not limited to, a dorsal root ganglion cell or a trigeminal ganglion cell), a sympathetic neuron, a parasympathetic neuron, and/or an enteric neuron). In some embodiments, the anti-p75NTR antibody or an antigen-binding fragment thereof described herein can be delivered to a target tissue (e.g., brain or spinal cord, peripheral nervous system, autonomic nervous system, enteric nervous system, and/or eye) or a target cell (e.g., a sensory neuron (such as, but not limited to, a dorsal root ganglion cell or a trigeminal ganglion cell) a sympathetic neuron, a parasympathetic neuron, and/or an enteric neuron) by receptor-mediated retrograde delivery. [00300] In some embodiments, the molecular cargo comprises a polynucleotide molecule. The terms “polynucleotide” and “nucleic acid” are used interchangeably herein to refer to a multimeric compound comprising nucleosides or nucleoside analogs which have nitrogenous heterocyclic bases or base analogs linked together along a backbone, including conventional RNA, DNA, mixed RNA-DNA, and polymers that are analogs thereof. A nucleic acid “backbone” can be made up of a variety of linkages, including one or more of sugar- phosphodiester linkages, peptide-nucleic acid bonds (“peptide nucleic acids” or PNA; PCT No. WO 95/32305), phosphorothioate linkages, methylphosphonate linkages, or Attorney Docket No.250298.000780 combinations thereof. Sugar moieties of a nucleic acid can be ribose, deoxyribose, or similar compounds with optional substitutions, e.g., methoxy or 2’ halide substitutions. In some embodiments, polynucleotides up to about 30 nucleotides in length can be referred to herein as an “oligonucleotide”. Oligonucleotides may be of a variety of different lengths, e.g., depending on the form. In some embodiments, an oligonucleotide is 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, or more nucleotides in length. In some embodiments, the oligonucleotide is 8 to 30 nucleotides in length, 10 to 15 nucleotides in length, 10 to 20 nucleotides in length, 15 to 25 nucleotides in length, 21 to 23 nucleotides in lengths. [00301] In some embodiments, the molecular cargo comprises a polypeptide molecule. The terms “polypeptide” and “protein” used interchangeably herein encompass native or artificial proteins, protein fragments and polypeptide analogs of a protein sequence. A polypeptide or protein may be monomeric or polymeric. [00302] In some embodiments, the molecular cargo described herein may comprise a carrier, such as a liposome or lipid nanoparticle (LNP). A lipid particle, e.g., a liposome or lipid nanoparticle disclosed herein, may include a lipid formulation that can be used to deliver a therapeutic nucleic acid (e.g., gRNA) to a target site of interest (e.g., cell, tissue, organ, and the like). Without wishing to be bound by theory, carriers may be used, e.g., as a means for delivery of a polynucleotide disclosed herein and/or a protein disclosed herein. In some embodiments, a carrier (e.g., liposome or LNP) may be useful for the delivery of a nucleic acid (e.g., DNA or RNA), protein (e.g., RNA-guided DNA binding agent), or a combination thereof. By way of a non-limiting example, a carrier (e.g., liposome or LNP) may be used to deliver various components of a gene editing system, for example, a CRISPR/Cas system or additional gene editing systems described herein. [00303] In some embodiments, the molecular cargo comprises a small molecule. A small molecule (SM) can enter cells easily because it has a low molecular weight (typically, up to about 1 kDa). Once inside the cells, it can affect other molecules, such as proteins including, e.g., voltage-gated sodium channel Nav1.7, voltage-gated sodium channel Nav1.8, voltage-gated sodium channel Nav1.9, voltage-gated sodium channel Nav1.6, tropomyosin receptor kinase A (TrkA), tropomyosin receptor kinase C (TrkC), acid-sensing ion channel subunit 1 (ASIC1), acid-sensing ion channel subunit 1 (ASIC3), transient receptor potential vanilloid 1 (TRPV1), transient receptor potential vanilloid 1 (TRPV4), transient receptor potential cation channel, subfamily A, member 1 (TRPA1), transient receptor potential cation Attorney Docket No.250298.000780 channel subfamily C, member 6 (TRPC6), transient receptor potential cation channel subfamily M, member 8 (TRPM8), fatty acid amide hydrolase (FAAH), piezo type mechanosensitive ion channel component 1 (PIEZO1), piezo type mechanosensitive ion channel component 2 (PIEZO2), sodium voltage-gated channel alpha subunit 9 (SCN9A), Enkephalin, RET proto-oncogene (RET), interleukin 4 receptor (IL4R), interleukin 13 receptor (IL13R), interleukin 31 receptor (IL31R), interleukin 6 receptor (e.g., IL6 receptor alpha (IL6Ra) and glycoprotein 130 (gp130)), FXYD domain containing ion transport regulator 2 (FXYD2), calcitonin related polypeptide alpha (CALCA), hyperpolarization-activated, cyclic nucleotide-gated channel (HCN), P2X purinoceptor 3 (P2X3), calcitonin gene-related peptide (CGRP), pituitary adenylate cyclase-activating polypeptide (PACAP), and interleukin 6 (IL6). In various embodiments, the small molecule can affect, e.g., Nav1.7, Nav1.8, Nav1.9, TRPV1, TRPV4, TRPA1, TRPC5, MOR, DOR, PIEZO1, PIEZO2. This is different from many large molecular weight molecules such as antibodies. As an example, a small molecule may be conjugated to an p75NTR binding protein to form an anti-p75NTR:SM conjugate. A SM for delivery by way of anti-p75NTR -mediated delivery may be suitable for targeting pathological consequences of, e.g., a neurodegenerative disease, a neurodevelopmental disease, physical injury, or a disease or disorder of neuropsychiatric origin (e.g., cell death). [00304] Exemplary molecular cargoes are described in further detail herein, however, it should be appreciated that the exemplary molecular cargoes provided herein are not intended to be limiting. Polynucleotide Molecules [00305] Non-limiting examples of polynucleotide molecules that are useful as molecular cargoes in the protein-drug conjugates of the present disclosure include, but are not limited to, interfering nucleic acids (e.g., shRNAs, siRNAs, microRNAs, antisense oligonucleotides), gapmers, mixmers, ribozymes, phosphorodiamidite morpholinos, peptide nucleic acids, aptamers, and guide nucleic acids (e.g., Cas9 guide RNAs), mRNAs, etc. In various embodiments, a polynucleotide may comprise one or more modified nucleotides. In various embodiments, a polynucleotide may comprise one or more modified inter-nucleotide linkage. Polynucleotides may be single-stranded or double-stranded. In some embodiments, the polynucleotide molecule targets a gene or gene product associated with pain, itch (also known as pruritis), and/or a neurological disease or disorder. Non-limiting examples of gene or gene products associated with pain, itch, and/or a neurological disease or disorder include Attorney Docket No.250298.000780 voltage-gated sodium channel Nav1.7, voltage-gated sodium channel Nav1.8, voltage-gated sodium channel Nav1.9, voltage-gated sodium channel Nav1.6, tropomyosin receptor kinase A (TrkA), tropomyosin receptor kinase C (TrkC), acid-sensing ion channel subunit 1 (ASIC1), acid-sensing ion channel subunit 1 (ASIC3), transient receptor potential vanilloid 1 (TRPV1), transient receptor potential vanilloid 1 (TRPV4), transient receptor potential cation channel, subfamily A, member 1 (TRPA1), transient receptor potential cation channel subfamily C, member 6 (TRPC6), transient receptor potential cation channel subfamily M, member 8 (TRPM8), fatty acid amide hydrolase (FAAH), piezo type mechanosensitive ion channel component 1 (PIEZO1), piezo type mechanosensitive ion channel component 2 (PIEZO2), sodium voltage-gated channel alpha subunit 9 (SCN9A), Enkephalin, RET proto-oncogene (RET), interleukin 4 receptor (IL4R), interleukin 13 receptor (IL13R), interleukin 31 receptor (IL31R), interleukin 6 receptor (e.g., IL6 receptor alpha (IL6Ra) and glycoprotein 130 (gp130)), FXYD domain containing ion transport regulator 2 (FXYD2), calcitonin related polypeptide alpha (CALCA), hyperpolarization-activated, cyclic nucleotide-gated channel (HCN), P2X purinoceptor 3 (P2X3), calcitonin gene-related peptide (CGRP), pituitary adenylate cyclase-activating polypeptide (PACAP), and interleukin 6 (IL6). [00306] In some embodiments, the gene or gene product associated with a neurological disease or disorder is Sodium Voltage-Gated Channel Alpha Subunit 9 (SCN9A). In some embodiments, the polynucleotide molecule targets a gene or gene product associated pain, e.g., pain targets which may be expressed in DG and/or TG, such as, but not limited to Nav1.7, Nav1.8, Nav1.9, TRPV1, TRPV4, TRPA1, TRPC6, TRPM8, PIEZO1, PIEZO2, CALCA, HCN, TrkA, TrkC, ASIC1, ASIC3, and P2X3. [00307] In some embodiments, the molecular cargo comprises at least one polynucleotide molecule. In some embodiments, the molecular cargo comprises at least 2, at least 3, at least 4, at least 5, or at least 10 polynucleotide molecules. [00308] In some embodiments, the polynucleotide molecule is DNA. In some embodiments, the polynucleotide molecule is RNA. [00309] In various embodiments, a polynucleotide described herein (e.g., interfering nucleic acid or guide RNA) may comprise a region of complementarity to a target nucleic acid which can be in the range of 8 to 15, 8 to 30, 8 to 40, or 10 to 50, or 5 to 50, or 5 to 40 nucleotides in length. In certain embodiments, a region of complementarity of a polynucleotide to a target nucleic acid may be 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, Attorney Docket No.250298.000780 43, 44, 45, 46, 47, 48, 49, or 50 nucleotides in length. In some embodiments, the region of complementarity may be complementary with at least 10 consecutive nucleotides of a target nucleic acid. In some embodiments, a polynucleotide may contain 1, 2, 3, 4 or 5 base mismatches compared to the portion of the consecutive nucleotides of target nucleic acid. In some embodiments the polynucleotide may have up to 3 mismatches over 15 bases, or up to 4 mismatches over 10 bases. In some embodiments, the polynucleotide is complementary (e.g., at least 80%, at least 85% at least 90%, at least 95%, or 100%) to a target sequence of any one of the polynucleotides of the present disclosure. In various embodiments, such target sequence may be 100% complementary to the polynucleotide described herein. In some embodiments, any one or more of the thymine bases (T's) in any one of the polynucleotides described herein may be uracil bases (U's), and/or any one or more of the U's may be T's. A target sequence described herein may comprise a sequence of nucleic acid in a target gene that has complementarity to the guide sequence of the gRNA. The interaction of the target sequence and the guide sequence directs an RNA-guided DNA- binding agent (e.g., Cas protein) to bind, and potentially nick or cleave (depending on the activity of the agent), within the target sequence. [00310] The polynucleotides described herein may be modified, e.g., comprise a modified nucleotide, a modified internucleoside linkage, and/or a modified sugar moiety, or combinations thereof. In addition, polynucleotides can possess one or more of the following properties: have improved cell uptake compared to unmodified polynucleotides; are not toxic to cells or mammals are not immune stimulatory; avoid pattern recognition receptors do not mediate alternative splicing; are nuclease resistant; have improved endosomal exit internally in a cell; or minimizes TLR stimulation. Any of the various modified chemistries or formats of polynucleotides disclosed herein may be combined with together. As a non-limiting example, one, two, three, four, five, six, seven, eight or more different types of modifications may be included within the same polynucleotide. [00311] In various embodiments, particular nucleotide modification(s) may be used that render a polynucleotide into which the modification(s) are incorporated more resistant to nuclease digestion than the native oligoribonucleotide or oligodeoxynucleotide molecules; such modified polynucleotides survive intact for a longer time than unmodified polynucleotides. Exemplary modified polynucleotides include those comprising modified backbones, for example, modified internucleoside linkages such as, methyl phosphonates, phosphotriesters, phosphorothioates short chain alkyl or cycloalkyl intersugar linkages Attorney Docket No.250298.000780 heterocyclic intersugar linkages or short chain heteroatomic or. As such, polynucleotides described herein may be stabilized against nucleolytic degradation, e.g., via incorporation of a modification, e.g., a nucleotide modification. [00312] In various embodiments, a polynucleotide may be of up to 50 nucleotides in length in which 2 to 10, 2 to 15, 2 to 16, 2 to 17, 2 to 18, 2 to 19, 2 to 20, 2 to 25, 2 to 30, 2 to 40, or 2 to 45, nucleotides of the polynucleotide may be modified nucleotides. The polynucleotide may be of 8 to 30 nucleotides in length in which 2 to 10, 2 to 15, 2 to 16, 2 to 17, 2 to 18, 2 to 19, 2 to 20, 2 to 25, 2 to 30 nucleotides of the polynucleotide can be modified nucleotides. In some embodiments, the polynucleotide may be of 8 to 15 nucleotides in length in which 2 to 4, 2 to 5, 2 to 6, 2 to 7, 2 to 8, 2 to 9, 2 to 10, 2 to 11, 2 to 12, 2 to 13, 2 to 14 nucleotides of the polynucleotide are modified nucleotides. In some embodiments, the polynucleotides can have every nucleotide except 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15 nucleotides modified. [00313] In various embodiments, the polynucleotide disclosed herein may comprise at least one nucleoside, e.g., modified at the 2' position of the sugar. In some embodiments, all of the nucleosides in the polynucleotide are 2’-modified nucleosides. In some embodiments, a polynucleotide comprises at least one 2'-modified nucleoside. [00314] In various embodiments, the polynucleotide disclosed herein may one or more non-bicyclic 2’-modified nucleosides, e.g., 2’-O-dimethylaminoethyloxyethyl (2’-O- DMAEOE)2’-O-methyl (2’-O-Me), 2’-O-dimethylaminoethyl (2’-O-DMAOE), 2’-O- methoxyethyl (2’-MOE), 2’-deoxy, 2’-O-N-methylacetamido (2’-O-NMA) modified nucleoside, 2’-fluoro (2’-F), 2’-O-aminopropyl (2’-O-AP), or 2’-O-dimethylaminopropyl (2’-O-DMAP). [00315] In some embodiments, the polynucleotide of the present disclosure may comprise one or more 2’-4’ bicyclic nucleosides in which the ribose ring may comprise a bridge moiety, e.g., connecting two atoms in the ring (e.g., connecting the 2’-O atom to the 4’-C atom via an ethylene (ENA) bridge, a methylene (LNA) bridge, or a (S)-constrained ethyl (cEt) bridge). Non-limiting examples of ENAs are disclosed in PCT Publication No. WO 2005/042777; Morita et al., Nucleic Acid Res., Suppl 1:241-242, 2001; Koizumi, Curr. Opin. Mol. Ther., 8:144-149, 2006, Surono et al., Hum. Gene Ther., 15:749-757, 2004; and Horie et al., Nucleic Acids Symp. Ser (Oxf), 49:171-172, 2005; the disclosures of which are incorporated herein by reference in their entireties. Non-limiting examples of LNAs are disclosed in PCT Patent Application Publication No. WO2008/043753, the contents of which are incorporated herein by reference in its entirety. Non-limiting examples of cEt are disclosed Attorney Docket No.250298.000780 in in U.S. Patent Nos 7,569,686, 7,101,993, and 7,399,845 each of which is herein incorporated by reference in its entirety. [00316] In various embodiments, the polynucleotide described herein may comprise a modified nucleoside disclosed in, for example, US Patent Nos. 8,022,193; 7,569,686; 7,399,845; 7,741,457; 7,335,765; 7,816,333; 8,957,201; 7,314,923, the entire contents of each of which are incorporated herein by reference for all purposes. [00317] In various embodiments, the polynucleotide comprises at least one modified nucleoside that results in an increase in Tm of the polynucleotide in a range of 1°C to 10°C compared with a polynucleotide that does not have the at least one modified nucleoside . The polynucleotide may have a plurality of modified nucleosides that result in a total increase in Tm of the polynucleotide in a range of 2 °C, 3 °C, 4 °C, 5 °C, 6 °C, 7 °C, 8 °C, 9 °C, 10 °C, 15 °C, 20 °C, 25 °C, 30 °C, 35 °C, 40 °C, 45 °C, 50 °C, 55 °C, 60 °C or more as compared to a polynucleotide which does not have the modified nucleoside. [00318] In some embodiments, the polynucleotide may comprise a mix of nucleosides of different kinds. A polynucleotide may comprise a mix of deoxyribonucleosides or ribonucleosides and 2’-O-Me modified nucleosides. A polynucleotide may comprise a mix of 2’-4’ bicyclic nucleosides and 2’-MOE, 2’-fluoro, or 2’-O-Me modified nucleosides. A polynucleotide may comprise a mix of non-bicyclic 2’-modified nucleosides (e.g., 2’-MOE, 2’- fluoro, or 2’-O-Me) and 2’-4’ bicyclic nucleosides (e.g., LNA, ENA, cEt). A polynucleotide may comprise a mix of 2’-deoxyribonucleosides or ribonucleosides and 2’-fluoro modified nucleosides. A polynucleotide may comprise a mix of 2’-fluoro modified nucleosides and 2’- O-Me modified nucleosides. [00319] In various embodiments, the oligonucleotide may comprise alternating nucleosides of different types. In certain embodiments, the oligonucleotide may comprise alternating deoxyribonucleosides or ribonucleosides and 2’-O-Me modified nucleosides. In certain embodiments, a polynucleotide may comprise alternating 2’-deoxyribonucleosides or ribonucleosides and 2’-fluoro modified nucleosides. In certain embodiments, the oligonucleotide may comprise alternating 2’-fluoro modified nucleosides and 2’-O-Me modified nucleosides. In certain embodiments, the oligonucleotide may comprise alternating 2’-4’ bicyclic nucleosides and 2’-MOE, 2’-fluoro, or 2’-O-Me modified nucleosides. In certain embodiments, the oligonucleotide may comprise alternating non-bicyclic 2’-modified nucleosides (e.g., 2’-MOE, 2’-fluoro, or 2’-O-Me) and 2’- 4’ bicyclic nucleosides (e.g., LNA, ENA, cEt). Attorney Docket No.250298.000780 [00320] In various embodiments, a polynucleotide of the present disclosure may comprise one or more abasic residues, a 5 – vinylphosphonate modification, and/or one or more inverted abasic residues. [00321] In various embodiments, the oligonucleotide may comprise a phosphorothioate or other modified internucleoside linkage. In various embodiments, the oligonucleotide may comprise phosphorothioate internucleoside linkages. In various embodiments, the oligonucleotide comprises phosphorothioate internucleoside linkages between at least two nucleotides. In various embodiments, the oligonucleotide comprises phosphorothioate internucleoside linkages between all nucleotides. By way of a non-limiting example, in certain embodiments, oligonucleotides comprise modified internucleoside linkages at the first, second, and/or (e.g., and) third internucleoside linkage at the 5’ or 3’ end of the nucleotide sequence. [00322] Non-limiting examples of phosphorus-containing linkages include aminoalkylphosphotriesters phosphorothioates, chiral phosphorothioates, phosphotriesters, phosphorodithioates, methyl and other alkyl phosphonates comprising 3’alkylene phosphonates and chiral phosphonates, phosphinates, phosphoramidates comprising 3’- amino phosphoramidate and aminoalkylphosphoramidates, thionoalkylphosphonates, thionophosphoramidates, thionoalkylphosphotriesters, and boranophosphates having normal 3’-5’ linkages, 2’-5’ linked analogs of these, and those having inverted polarity wherein the adjacent pairs of nucleoside units are linked 3’-5’ to 5’-3’ or 2’-5’ to 5’-2’; see U.S. Pat. Nos. 5,625,050; 4,469,863; 4,476,301; 5,023,243; 5,550,111; 5,177,196; 5,587,361; 5,188,897; 5,264,423; 5,276,019; 5,519,126; 5,278,302; 5,286,717; 5,321,131; 5,399,676; 5,405,939; 5,453,496; 5,455, 233; 5,466,677; 5,476,925; 5,536,821; 5,541,306; 5,563, 253; 5,571,799; and 3,687,808. [00323] In various embodiments, a polynucleotide of the present disclosure may have heteroatom backbones, e.g., or peptide nucleic acid (PNA) backbones (wherein the phosphodiester backbone of the oligonucleotide is replaced with a polyamide backbone, the nucleotides being bound directly or indirectly to the aza nitrogen atoms of the polyamide backbone, see Nielsen et al., Science 1991, 254, 1497), morpholino backbones (see Summerton and Weller, U.S. Patent No.5,034,506); amide backbones (see De Mesmaeker et al. Ace. Chem. Res.1995, 28:366-374); or MMI or methylene (methylimino) backbones. [00324] Nitrogenous bases can be conventional bases (A, G, C, T, U), analogs thereof (e.g., modified uridines such as 5-methoxyuridine, pseudouridine, or N1 - Attorney Docket No.250298.000780 methylpseudouridine, or others); inosine; derivatives of purines or pyrimidines (e.g., N4- methyl deoxyguanosine, deaza- or aza-purines, deaza- or aza-pyrimidines, pyrimidine bases with substituent groups at the 5 or 6 position (e.g., 5-methylcytosine), purine bases with a substituent at the 2, 6, or 8 positions, 2- amino-6-methylaminopurine, 6-O -methylguanine, 4- thio-pyrimidines, 4-amino-pyrimidines, 4- dimethylhydrazine-pyrimidines, and 4-O-alkyl- pyrimidines; U.S. Patent No.5,378,825 and PCT Publication No. WO 93/13121). For general discussion see Adams et al, The Biochemistry of the Nucleic Acids 5-36, 11th ed., 1992. Nucleic acids can include one or more “abasic” residues where the backbone includes no nitrogenous base for position(s) of the polymer (U.S. Patent No.5,585,481). A nucleic acid can comprise only conventional RNA or DNA sugars, bases and linkages, or can include both conventional components and substitutions (e.g., conventional nucleosides with 2’ methoxy substituents, or polymers containing both conventional nucleotides and one or more nucleotide analogs). Nucleic acid includes “locked nucleic acid” (LNA), an analogue containing one or more LNA nucleotide monomers with a bicyclic furanose unit locked in an RNA mimicking sugar conformation, which enhance hybridization affinity toward complementary RNA and DNA sequences (Vester and Wengel, 2004, Biochemistry 43(42): 13233-41). RNA and DNA have different sugar moieties and can differ by the presence of uracil or analogs thereof in RNA and thymine or analogs thereof in DNA. Interfering Nucleic Acids [00325] In some embodiments, a conjugated molecular cargo may comprise a polynucleotide molecule(s) which is capable of modifying expression of one more genes (e.g., inhibiting gene expression and/or translation, modulating RNA splicing or inducing exon skipping) in a target cell. In some embodiments, the polynucleotide molecule may be an interfering nucleic acid molecule, e.g., an siRNA, an shRNA, a miRNA, or an antisense oligonucleotide (ASO), that targets, e.g., an RNA (e.g., an mRNA). [00326] In some embodiments, the interfering nucleic acid molecule may modify expression of one more genes e.g., voltage-gated sodium channel Nav1.7, voltage-gated sodium channel Nav1.8, voltage-gated sodium channel Nav1.9, voltage-gated sodium channel Nav1.6, tropomyosin receptor kinase A (TrkA), tropomyosin receptor kinase C (TrkC), acid-sensing ion channel subunit 1 (ASIC1), acid-sensing ion channel subunit 1 (ASIC3), transient receptor potential vanilloid 1 (TRPV1), transient receptor potential vanilloid 1 (TRPV4), transient receptor potential cation channel, subfamily A, member 1 (TRPA1), Attorney Docket No.250298.000780 transient receptor potential cation channel subfamily C, member 6 (TRPC6), transient receptor potential cation channel subfamily M, member 8 (TRPM8), fatty acid amide hydrolase (FAAH), piezo type mechanosensitive ion channel component 1 (PIEZO1), piezo type mechanosensitive ion channel component 2 (PIEZO2), sodium voltage-gated channel alpha subunit 9 (SCN9A), Enkephalin, RET proto-oncogene (RET), interleukin 4 receptor (IL4R), interleukin 13 receptor (IL13R), interleukin 31 receptor (IL31R), interleukin 6 receptor (e.g., IL6 receptor alpha (IL6Ra) and glycoprotein 130 (gp130)), FXYD domain containing ion transport regulator 2 (FXYD2), calcitonin related polypeptide alpha (CALCA), hyperpolarization-activated, cyclic nucleotide-gated channel (HCN), P2X purinoceptor 3 (P2X3), calcitonin gene-related peptide (CGRP), pituitary adenylate cyclase-activating polypeptide (PACAP), or interleukin 6 (IL6). [00327] In some embodiments, the interfering nucleic acid molecule may modify expression of one more genes associated with a neurological disease and/or disorder. In some embodiments, the interfering nucleic acid molecule may inhibit the expression of one or more genes encoding a receptor or ion channel that plays a role in pain processing such as, but not limited to, Nav1.7, Nav1.8, Nav1.9, TRPV1, TRPV4, TRPA1, TRPC6, TRPM8, PIEZO1, PIEZO2, CALCA, HCN, TRKA, TRKC, ASIC1, ASIC3, and P2X3. In some embodiments, the interfering nucleic acid molecule is an anti-p75NTR-Nav1.7 siRNA. [00328] In certain embodiments, interfering nucleic acid molecules that selectively target and inhibit the activity or expression of a product (e.g., an mRNA product) of a targeted gene are used in compositions and methods described herein. An interfering nucleic acid molecule may inhibit the expression or activity of a product (e.g., an mRNA product) of at least one targeted gene by at least 5%, at least 10%, at least 15%, at least 20%, at least 25%, at least 30%, at least 35%, at least 40%, at least 45%, at least 50%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100%. An agent disclosed herein may comprise a nucleobase sequence that is at least at least 80%, at least 85%, at least 90%, at least 95%, or 100% complementarity to a product (e.g., an mRNA product) of at least targeted gene. Without wishing to be bound by theory, “complementarity” of nucleic acids can mean that a nucleotide sequence in one strand of nucleic acid, due to orientation of its nucleobase groups, forms hydrogen bonds with another sequence on an opposing nucleic acid strand. The complementary bases in DNA are typically A with T and C with G. In RNA, they are typically C with G and U with A. Complementarity can be perfect or substantial/sufficient. Perfect complementarity between two nucleic acids Attorney Docket No.250298.000780 means that the two nucleic acids can form a duplex in which every base in the duplex is bonded to a complementary base by Watson-Crick pairing. “Substantial” or “sufficient” complementary means that a sequence in one strand is not completely and/or perfectly complementary to a sequence in an opposing strand, but that sufficient bonding occurs between bases on the two strands to form a stable hybrid complex in set of hybridization conditions (e.g., salt concentration and temperature). Such conditions can be predicted by using the sequences and standard mathematical calculations to predict the Tm (melting temperature) of hybridized strands, or by empirical determination of Tm by using routine methods. Tm includes the temperature at which a population of hybridization complexes formed between two nucleic acid strands are 50% denatured (i.e., a population of double- stranded nucleic acid molecules becomes half dissociated into single strands). At a temperature below the Tm, formation of a hybridization complex is favored, whereas at a temperature above the Tm, melting or separation of the strands in the hybridization complex is favored. Tm may be estimated for a nucleic acid having a known G+C content in an aqueous 1 M NaCl solution by using, e.g., Tm=81.5+0.41(% G+C), although other known Tm computations take into account nucleic acid structural characteristics. [00329] Interfering nucleic acids can include a sequence of cyclic subunits, each bearing a base-pairing moiety, linked by intersubunit linkages that allow the base-pairing moieties to hybridize to a target sequence in a nucleic acid (typically an RNA) by Watson- Crick base pairing, to form a nucleic acid:oligomer heteroduplex within the target sequence. [00330] Typically, at least 17, 18, 19, 20, 21, 22 or 23 nucleotides of the complement of the target mRNA sequence are sufficient to mediate inhibition of a target transcript. Perfect complementarity is not necessary. In some embodiments, the interfering nucleic acid molecule is single-stranded RNA. In some embodiments, the interfering nucleic acid molecule is double-stranded RNA. The double-stranded RNA molecule may have a 1-3 nucleotide 3′ and/or 5′ overhang in either a sense strand and/or an antisense strand. In some embodiments, the double-stranded RNA molecule has a 2 nucleotide 3′ overhang. In some embodiments, the two RNA strands are connected via a hairpin structure, forming a shRNA molecule. shRNA molecules can contain hairpins derived from microRNA molecules. [00331] Interfering nucleic acid molecules described herein can contain RNA bases, non-RNA bases or a mixture of RNA bases and non-RNA bases. For example, interfering nucleic acid molecules described herein can be primarily composed of RNA bases or modified RNA bases, but also contain DNA bases, modified DNA bases, and/or non-naturally occurring Attorney Docket No.250298.000780 nucleotides. The term “ribonucleotide” or “nucleotide” can, in the case of a modified RNA or nucleotide surrogate, also refer to a modified nucleotide, or surrogate replacement moiety at one or more positions. [00332] In some embodiments, the interfering nucleic acid molecule is a small interfering RNAs (siRNA), also known as short interfering RNA or silencing RNA. siRNAs are a class of double-stranded RNA molecules, typically about 20-25 base pairs in length that target nucleic acids (e.g., mRNAs) for degradation via the RNA interference (RNAi) pathway in cells. Such siRNA molecules typically include a region of sufficient homology to the target region, and are of sufficient length in terms of nucleotides, such that the siRNA molecules down-regulate target nucleic acid. It is not necessary that there be perfect complementarity between the siRNA molecule and the target, but the correspondence must be sufficient to enable the siRNA molecule to direct sequence-specific silencing, such as by RNAi cleavage of the target RNA. In some embodiments, the sense strand need only be sufficiently complementary with the antisense strand to maintain the overall double-strand character of the molecule. [00333] Specificity of siRNA molecules may be measured via the binding of the antisense strand of the molecule to its target RNA. Effective siRNA molecules are often fewer than 30 to 35 base pairs in length, e.g., to prevent stimulation of non-specific RNA interference pathways in the cell by way of the interferon response, however longer siRNA may also be effective. In various embodiments, the siRNA molecules are 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, or 30 base pairs in length. In various embodiments, the siRNA molecules are about 35 to about 70 more base pairs in length In some embodiments, the siRNA molecules are more than 70 base pairs in length. In some embodiments, the siRNA molecules are 8 to 40 base pairs in length, 10 to 20 base pairs in length, 10 to 30 base pairs in length, 15 to 20 base pairs in length, 19 to 23 base pairs in length, 21 to 24 base pairs in length. In some embodiments, the sense and antisense strands of the siRNA molecules are each independently about 19 to about 24 nucleotides in length. In some embodiments, the sense strand of an siRNA molecule is 23 nucleotides in length and the antisense strand is 21 nucleotides in length. In some embodiments, both the sense strand and the antisense strand of an siRNA molecule are 21 nucleotides in length. [00334] After selection of an suitable target RNA sequence, siRNA molecules that comprise a nucleotide sequence complementary to all or a portion of the target sequence, i.e., an antisense sequence, may be designed and prepared using suitable methods (see, Attorney Docket No.250298.000780 e.g., U.S. Patent Publication Nos. 2004/0077574 and 2008/0081791 and PCT Publication No. WO 2004/016735). In some embodiments, the siRNA molecule may be single-stranded (i.e. a ssRNA molecule comprising just an antisense strand) or double stranded (i.e. a dsRNA molecule comprising an antisense strand and a complementary sense strand that hybridizes to form the dsRNA). In various embodiments, the siRNA molecules may comprise a duplex, asymmetric duplex, hairpin or asymmetric hairpin secondary structure, comprising self- complementary sense and/or antisense strands. [00335] In various embodiments, the antisense strand of the siRNA molecule is 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, or 30 nucleotides in length. In various embodiment, the antisense strand of the siRNA molecule is about 35 to about 70 nucleotides in length. In various embodiment, the antisense strand of the siRNA molecule is more than 70 nucleotides in length. In some embodiments, the antisense strand is 8 to 40 nucleotides in length, 10 to 20 nucleotides in length, 10 to 30 nucleotides in length, 15 to 20 nucleotides in length, 19 to 23 nucleotides in length, or 21 to 24 nucleotides in length. [00336] In some embodiments, the sense strand of the siRNA molecule is 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, or 30 more nucleotides in length. In various embodiments, the sense strand of the siRNA molecule is about 30 to about 70 nucleotides in length. In various embodiments, the sense strand of the siRNA molecule more than 70 nucleotides in length. In some embodiments, the sense strand is 8 to 40 nucleotides in length, 10 to 20 nucleotides in length, 10 to 30 nucleotides in length, 15 to 20 nucleotides in length, 19 to 23 nucleotides in length, 21 to 24 nucleotides in length. [00337] In various embodiments, siRNA molecules can comprise an antisense strand comprising a region of complementarity to a target region in a target mRNA. In some embodiments, the region of complementarity is at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% complementary to a target region in a target mRNA. In some embodiments, the target region may comprise a region of consecutive nucleotides in the target mRNA. In some embodiments, it may not be requisite for a region of complementarity to be 100% complementary to that of its target to be specifically hybridizable or specific for a target RNA sequence. [00338] In some embodiments, siRNA molecules disclosed herein may comprise an antisense strand that comprises a region of complementarity to a target RNA sequence and Attorney Docket No.250298.000780 the region of complementarity is in the range of 8 to 20, 8 to 35, 8 to 45, or 10 to 50, or 5 to 55, or 5 to 40 nucleotides in length. In some embodiments, a region of complementarity is 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, or 50 nucleotides in length. In some embodiments, the region of complementarity is complementary with at least 5, at least 6, at least 7, at least 8, at least 9, at least 10, at least 11, at least 12, at least 13, at least 14, at least 15, at least 16, at least 17, at least 18, at least 19, at least 20, at least 21, at least 22, at least 23, at least 24, at least 25, at least 30, at least 35, or more consecutive nucleotides of a target RNA sequence. In some embodiments, siRNA molecules comprise an antisense strand having a nucleotide sequence that contains no more than 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 base mismatches compared to the portion of the consecutive nucleotides of target RNA sequence. In some embodiments, siRNA molecules comprise a nucleotide sequence that has up to 3 mismatches over 15 bases, or up to 4 mismatches over 10 bases with a target sequence. In some embodiments, siRNA molecules comprises an antisense strand having a nucleotide sequence that has up 0, 1, 2, or 3 mismatches over 15-22 bases with a target sequence. In some embodiments, siRNA molecules comprises an antisense strand having a nucleotide sequence that has 0, 1, or 2 mismatches over 15-22 bases with a target sequence. In some embodiments, siRNA molecules comprises an antisense strand having a nucleotide sequence that has 0 or 1 mismatch over 15-22 bases with a target sequence. In some embodiments, siRNA molecules comprises an antisense strand having a nucleotide sequence that has 0 mismatches over 15-22 bases with a target sequence. [00339] In various embodiments, siRNA molecules may comprise an antisense strand comprising a nucleotide sequence that is at least 70%, at least 75%, at least 85%, at least 90%, at least 95%, or 100% complementary to the target RNA sequence of the antisense oligonucleotides disclosed herein. In some embodiments, siRNA molecules comprise an antisense strand comprising a nucleotide sequence that is at least 70%, at least 75%, at least 85%, at least 90%, at least 95%, or 100% identical to any of the antisense oligonucleotides provided herein. In some embodiments, siRNA molecules comprise an antisense strand comprising at least 5, at least 6, at least 7, at least 8, at least 9, at least 10, at least 11, at least 12, at least 13, at least 14, at least 15, at least 16, at least 17, at least 18, at least 19, at least 20, at least 21, at least 22, at least 23, at least 24, at least 25, at least 30, at least 35, or more consecutive nucleotides of any of the antisense oligonucleotides provided herein. Attorney Docket No.250298.000780 [00340] In some embodiments, double-stranded siRNA can comprise sense and anti- sense RNA strands that are different lengths or the same length. In some embodiments, double-stranded siRNA molecules may also be generated from a single oligonucleotide in a stem-loop structure. The self-complementary sense and antisense regions of the siRNA molecule having a stem-loop structure may be linked by means of a nucleic acid based or a non-nucleic acid-based linker. In some embodiments, an siRNA having a stem-loop structure comprises a circular single-stranded RNA having two or more loop structures and a stem comprising self-complementary sense and antisense strands. In some embodiments, the circular RNA may be processed in vivo or in vitro to produce an active siRNA molecule which may be capable of mediating RNAi. Small hairpin RNA (shRNA) molecules are therefore also contemplated in the present disclosure. Such molecules may comprise a specific antisense sequence together with the reverse complement (sense) sequence, which may be separated by a spacer or loop sequence in some instances. A reverse complement described herein may comprise a sequence that is a complement sequence of a reference sequence, wherein the complement sequence is written in the reverse orientation. Due to codon usage redundancy, a reverse complement can diverge from a reference sequence that encodes the same polypeptide. As used herein, “reverse complement” also includes sequences that are, e.g., at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the reverse complement sequence of a reference sequence. Cleavage of the spacer or loop can provide a single- stranded RNA molecule and its reverse complement, such that they may anneal to form a dsRNA molecule. In various embodiments, additional optional processing steps may result in removal or addition of 1, 2, 3, 4, 5 or more nucleotides from the 3' end and/or the 5' end of one or both strands. A spacer may be of a suitable length to allow the antisense and sense sequences to anneal and form a double- stranded structure or stem prior to cleavage of the spacer. In certain embodiments subsequent optional processing steps may result in removal or addition of 1, 2, 3, 4, 5 or more nucleotides from the 3' end and/or the 5' end of one or both strands. In some embodiments, a spacer sequence can be an unrelated nucleotide sequence that may be, e.g., situated between two complementary nucleotide sequence regions that, when annealed into a double-stranded nucleic acid, can comprise a shRNA. [00341] The length of the siRNA molecules can vary from about 10 to about 120 nucleotides depending on the type of siRNA molecule being designed. Generally, between about 10 and about 55 of these nucleotides may be complementary to the RNA target Attorney Docket No.250298.000780 sequence. For instance, when the siRNA is a double-stranded siRNA or single-stranded siRNA, the length can vary from about 10 to about 55 nucleotides, whereas when the siRNA is a shRNA or circular molecule, the length can vary from about 30 nucleotides to about 110 nucleotides. [00342] In various embodiments, an siRNA molecule can comprise a 3' overhang at one end of the molecule. In some embodiments, the other end can be blunt-ended or may also comprise an overhang (e.g., 5' and/or 3'). When the siRNA molecule comprises an overhang at both ends of the molecule, the length of the overhangs may be different or the same. In some embodiments, an siRNA molecule described herein may comprises 3' overhangs of about 1 to about 3 nucleotides on both ends of the molecule. In some embodiments, the siRNA molecule comprises 3’ overhangs of about 1 to about 3 nucleotides on both the sense strand and the antisense strand. In some embodiments, the siRNA molecule comprises 3’ overhangs of about 1 to about 3 nucleotides on the antisense strand. In some embodiments, the siRNA molecule may comprise 3’ overhangs of about 1 to about 3 nucleotides on the sense strand. [00343] In various embodiments, the siRNA molecule comprises one or more modified nucleotides (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15 or more). In some embodiments, all of the nucleotides of the sense strand and/or the antisense strand of the siRNA molecule are modified. In certain embodiments, the siRNA molecule can comprise one or more modified nucleotides and/or one or more modified internucleotide linkages. In some embodiments, the siRNA molecule may comprise modified internucleotide linkages at the first and second internucleoside linkages at the 5′ end of the siRNA molecule sense strand. In some embodiments, the siRNA molecule may comprise modified internucleotide linkages at the first and second internucleoside linkages at the 5′ and 3′ ends of the siRNA molecule antisense strand. In some embodiments, the siRNA molecule may comprise modified internucleotide linkages at the first and second internucleoside linkages at the 5′ end of the siRNA molecule sense strand and at the first and second internucleoside linkages at the 5′ and 3′ ends of the siRNA molecule antisense strand. [00344] In some embodiments, the modified nucleotide may comprise a modified sugar moiety (e.g., a 2' modified nucleotide). In some embodiments, the siRNA molecule can comprise one or more 2’ modified nucleotides, e.g., a 2'-deoxy, 2'-fluoro (2’-F), 2'-O-methyl (2’-O-Me), 2'-O-methoxyethyl (2'-MOE), 2'-O-aminopropyl (2'-O-AP), 2'-O- dimethylaminoethyl (2'-O-DMAOE), 2'-O-dimethylaminopropyl (2'-O-DMAP), 2'-O- Attorney Docket No.250298.000780 dimethylaminoethyloxyethyl (2'-O-DMAEOE), or 2'-O-N-methylacetamido (2'-O-NMA). In various embodiments, each nucleotide of the siRNA molecule can a modified nucleotide (e.g., a 2'-modified nucleotide). In some embodiments, the siRNA molecule may comprise one or more phosphorodiamidate morpholinos. In some embodiments, each nucleotide of the siRNA molecule consists of a phosphorodiamidate morpholino. [00345] In various embodiments, the siRNA molecule may comprise a phosphorothioate or other modified internucleotide linkage. In various embodiments, the siRNA molecule may comprise, e.g., a phosphorothioate internucleoside linkage(s). In some embodiments, the siRNA molecule may comprise a phosphorothioate internucleoside linkage(s) between two or more nucleotides. In some embodiments, the siRNA molecule may comprise a phosphorothioate internucleoside linkage(s) between all nucleotides. In some embodiments, the siRNA molecule may comprise modified internucleotide linkages at the first, second, and/or third internucleoside linkage at the 5' or 3' end of the siRNA molecule. In some embodiments, the siRNA molecule may comprise modified internucleotide linkages at the first and second internucleoside linkages at the 5′ and/or 3′ end of the siRNA molecule. In some embodiments, the siRNA molecule may comprise modified internucleotide linkages at the first and second internucleoside linkages at the 5′ end of the siRNA molecule sense strand. In some embodiments, the siRNA molecule may comprise modified internucleotide linkages at the first and second internucleoside linkages at the 5′ and 3′ ends of the siRNA molecule antisense strand. In some embodiments, the siRNA molecule may comprise modified internucleotide linkages at the first and second internucleoside linkages at the 5′ end of the siRNA molecule sense strand and at the first and second internucleoside linkages at the 5′ and 3′ ends of the siRNA molecule antisense strand. In some embodiments, the siRNA molecule may comprise modified internucleotide linkages at the first internucleoside linkage at the 5′ and 3′ ends of the siRNA molecule sense strand, at the first, second, and third internucleoside linkages at the 5′ end of the siRNA molecule antisense strand, and at the first internucleoside linkage at the 3′ end of the siRNA molecule antisense strand. [00346] In various embodiments, the modified internucleotide linkages may comprise phosphorus-containing linkages. In some embodiments, phosphorus-containing linkages which may be used in the practice of the present disclosure include, without limitation, chiral phosphorothioates, phosphorothioates, phosphorodithioates, aminoalkylphosphotriesters, phosphotriesters, methyl and other alkyl phosphonates comprising 3'alkylene phosphonates and chiral phosphonates, phosphoramidates comprising 3'-amino phosphoramidate and Attorney Docket No.250298.000780 aminoalkylphosphoramidates, phosphinates, thionoalkylphosphonates, thionophosphoramidates, thionoalkylphosphotriesters, and boranophosphates having normal 3'-5' linkages, 2'-5' linked analogs of these, and those having inverted polarity wherein the adjacent pairs of nucleoside units are linked 3'-5' to 5'-3' or 2'-5' to 5'-2'; see US Patent Nos. 5,625,050; 3,687,808; 4,469,863; 4,476,301; 5,177,196; 5,455, 233; 5,264,423; 5,276,019; 5,278,302; 5,286,717; 5,321,131; 5,399,676; 5,405,939; 5,519,126; 5,453,496; 5,466,677; 5,476,925; 5,536,821; 5,023,243; 5,541,306; 5,550,111; 5,563, 253; 5,571,799; 5,587,361; and 5,188,897. [00347] Any of the various modified formats or chemistries of siRNA molecules disclosed herein may be combined together. For example, without limitation, 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 or more different types of modifications may be included within the same siRNA molecule. [00348] In various embodiments, the antisense strand may comprise one or more modified nucleotides (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15 or more). In some embodiments, the antisense strand may comprise one or more modified nucleotides and/or one or more modified internucleotide linkage(s). In some embodiments, the modified nucleotide may comprise a modified sugar moiety (e.g., a 2' modified nucleotide). In some embodiments, the antisense strand comprises one or more 2' modified nucleotides, e.g., a 2'-deoxy, 2'-fluoro (2’-F), 2'-O-methyl (2’-O-Me), 2'-O-methoxyethyl (2'-MOE), 2'-O- aminopropyl (2'-O-AP), 2'-O- dimethylaminoethyl (2'-O-DMAOE), 2'-O-dimethylaminopropyl (2'-O-DMAP), 2'-O- dimethylaminoethyloxyethyl (2'-O-DMAEOE), or 2'-O-N-methylacetamido (2'-O-NMA). In various embodiments, each nucleotide of the antisense strand can be a modified nucleotide (e.g., a 2'-modified nucleotide). In some embodiments, the antisense strand may comprise one or more phosphorodiamidate morpholinos. In some embodiments, the antisense strand consists of a phosphorodiamidate morpholino oligomer (PMO). [00349] In some embodiments, antisense strand contains a phosphorothioate or other modified internucleotide linkage. In some embodiments, the antisense strand may comprise phosphorothioate internucleoside linkage(s). In some embodiments, the antisense strand may comprise phosphorothioate internucleoside linkage(s) between two or more nucleotides. In some embodiments, the antisense strand may comprise phosphorothioate internucleoside linkage(s) between all nucleotides. In some embodiments, the antisense strand may comprise modified internucleotide linkages at the first, second, and/or third nucleotide at the 5' or 3' end of the antisense strand. In some embodiments, the antisense strand may comprise Attorney Docket No.250298.000780 modified internucleotide linkages at the first and second nucleotide positions (e.g., between the first and second and between the second and third nucleotides) at the 5′ and 3′ ends of the antisense strand. [00350] In various embodiments, the modified internucleotide linkages may comprise phosphorus-containing linkages of the antisense strand. In some embodiments, phosphorus- containing linkages which may be used in the practice of the present disclosure include, without limitation, chiral phosphorothioates, phosphorothioates, phosphorodithioates, aminoalkylphosphotriesters, phosphotriesters, methyl and other alkyl phosphonates comprising 3' alkylene phosphonates and chiral phosphonates, phosphoramidates comprising 3'-amino phosphoramidate and aminoalkylphosphoramidates, phosphinates, thionoalkylphosphonates, thionophosphoramidates, thionoalkylphosphotriesters, and boranophosphates having normal 3'-5' linkages, 2'-5' linked analogs of these, and those having inverted polarity wherein the adjacent pairs of nucleoside units are linked 3'-5' to 5'-3' or 2'-5' to 5'-2'; see US Patent Nos.5,625,050; 3,687,808; 4,469,863; 4,476,301; 5,177,196; 5,455, 233; 5,264,423; 5,276,019; 5,278,302; 5,286,717; 5,321,131; 5,399,676; 5,405,939; 5,519,126; 5,453,496; 5,466,677; 5,476,925; 5,536,821; 5,023,243; 5,541,306; 5,550,111; 5,563, 253; 5,571,799; 5,587,361; and 5,188,897. [00351] Any of the modified formats or chemistries of the antisense strand disclosed herein may be combined together. For example, without limitation, 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 or more different types of modifications may be included within the same antisense strand. [00352] In some embodiments, the sense strand comprises one or more modified nucleotides (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 11, 12, 13, 14, 15 or more). In some embodiments, the antisense strand may comprise one or more modified nucleotides and/or one or more modified internucleotide linkage(s). In some embodiments, the modified nucleotide may comprise a modified sugar moiety (e.g., a 2' modified nucleotide). In some embodiments, the antisense strand comprises one or more 2' modified nucleotides, e.g., a 2'-deoxy, 2'-fluoro (2’-F), 2'-O-methyl (2’-O-Me), 2'-O-methoxyethyl (2'-MOE), 2'-O-aminopropyl (2'-O-AP), 2'-O- dimethylaminoethyl (2'-O-DMAOE), 2'-O-dimethylaminopropyl (2'-O-DMAP), 2'-O- dimethylaminoethyloxyethyl (2'-O-DMAEOE), or 2'-O-N-methylacetamido (2'-O-NMA). In various embodiments, each nucleotide of the antisense strand can be a modified nucleotide (e.g., a 2'-modified nucleotide). In some embodiments, the antisense strand may comprise one or more phosphorodiamidate morpholinos. In some embodiments, the antisense strand consists of a phosphorodiamidate morpholino oligomer (PMO). Attorney Docket No.250298.000780 [00353] In some embodiments, the sense strand contains a phosphorothioate or other modified internucleotide linkage. In some embodiments, the sense strand may comprise phosphorothioate internucleoside linkage(s). In some embodiments, the sense strand may comprise phosphorothioate internucleoside linkage(s) between two or more nucleotides. In some embodiments, the sense strand may comprise phosphorothioate internucleoside linkages between all nucleotides. For example, in some embodiments, the sense strand comprises modified internucleotide linkages at the first, second, and/or third nucleotide at the 5' or 3' end of the sense strand. In some embodiments, the sense strand may comprise modified internucleotide linkages at the first and second nucleotide positions (e.g., between the first and second and between the second and third nucleotides) at the 5′ end of the sense strand. [00354] In various embodiments, the modified internucleotide linkages may comprise phosphorus-containing linkages of the sense strand. In some embodiments, phosphorus- containing linkages which may be used in the practice of the present disclosure include, without limitation, chiral phosphorothioates, phosphorothioates, phosphorodithioates, aminoalkylphosphotriesters, phosphotriesters, methyl and other alkyl phosphonates comprising 3'alkylene phosphonates and chiral phosphonates, phosphoramidates comprising 3'-amino phosphoramidate and aminoalkylphosphoramidates, phosphinates, thionoalkylphosphonates, thionophosphoramidates, thionoalkylphosphotriesters, and boranophosphates having normal 3'-5' linkages, 2'-5' linked analogs of these, and those having inverted polarity wherein the adjacent pairs of nucleoside units are linked 3'-5' to 5'-3' or 2'-5' to 5'-2'; see U.S. Pat. Nos.5,625,050; 3,687,808; 4,469,863; 4,476,301; 5,177,196; 5,455, 233; 5,264,423; 5,276,019; 5,278,302; 5,286,717; 5,321,131; 5,399,676; 5,405,939; 5,519,126; 5,453,496; 5,466,677; 5,476,925; 5,536,821; 5,023,243; 5,541,306; 5,550,111; 5,563, 253; 5,571,799; 5,587,361; and 5,188,897. [00355] Any of the modified chemistries or formats of the sense strand described herein can be combined together. For example, without limitation, 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 or more different types of modifications may be included within the same sense strand. [00356] In various embodiments, the antisense and/or sense strand of the siRNA molecule may comprise one or more modifications capable of enhancing or reducing, e.g., RNA-induced silencing complex (RISC) loading. In some embodiments, the antisense strand of the siRNA molecule may comprise one or more modifications capable of enhancing RISC loading. In various embodiments, the sense strand of the siRNA molecule may comprise one Attorney Docket No.250298.000780 or more modifications capable of reducing RISC loading and/or reducing off-target effects. In various embodiments, the antisense strand of the siRNA molecule may comprise a 2'-O- methoxyethyl (2’-MOE) modification. In some embodiments, the addition of the 2'-O- methoxyethyl (2’-MOE) group, e.g., at the cleavage site may improve the silencing activity and/or specificity of siRNAs, e.g., by facilitating the oriented RNA-induced silencing complex (RISC) loading of the modified strand, e.g., as disclosed in Song et al., (2017) Mol Ther Nucleic Acids 9:242-250, incorporated herein by reference in its entirety. In various embodiments, the antisense strand of the siRNA molecule may comprise a 2'-O-Me- phosphorodithioate modification. In some embodiment, the 2'-O-Me-phosphorodithioate modification may increase RISC loading, e.g., as disclosed in Wu et al., (2014) Nat Commun 5:3459, incorporated herein by reference in its entirety. [00357] In various embodiments, the sense strand of the siRNA molecule may comprise a 5'-nitroindole modification. In some embodiments, the 5'-nitroindole modification may decrease the RNAi potency of the sense strand and/or reduces off-target effects, e.g., as disclosed in Zhang et al., (2012) Chembiochem 13(13): 1940-1945, incorporated herein by reference in its entirety. In various embodiments, the sense strand may comprise a 2’-O- methyl (2'-O-Me) modification. In some embodiments, the 2'- O-Me modification may reduce RISC loading and/or the off-target effects of the sense strand, e.g., as disclosed in Zheng et al., FASEB (2013) 27(10): 4017-4026, incorporated herein by reference in its entirety. In various embodiments, the sense strand of the siRNA molecule may be fully substituted with morpholino, 2'-MOE and/ or 2'-O-Me residues, and may not be recognized by RISC, e.g., as disclosed in Kole et al., (2012) Nature reviews. Drug Discovery 11(2): 125- 140, incorporated herein by reference in its entirety. [00358] In various embodiments, the sense strand of the siRNA molecule may comprise a 5'-morpholino modification. In various embodiments, the 5'-morpholino modification may reduce RISC loading of the sense strand and/or improves RNAi activity and/or antisense strand selection, e.g., as disclosed in Kumar et al., (2019) Chem Commun (Camb) 55(35):5139-5142, incorporated herein by reference in its entirety. In various embodiments, the sense strand of the siRNA molecule may be modified, for example, with a synthetic RNA-like high affinity nucleotide analogue called Locked Nucleic Acid (LNA) that may reduce RISC loading of the sense strand and promote antisense strand incorporation into RISC, e.g., as disclosed in Elman et al., (2005) Nucleic Acids Res. 33(1): 439-447, incorporated herein by reference in its entirety. In various embodiments, the sense strand of Attorney Docket No.250298.000780 the siRNA molecule may comprise a 5' unlocked nucleic acid (UNA) modification. In various embodiments, the 5' unlocked nucleic acid (UNA) modification may reduce RISC loading of the sense strand and/or improve silencing capability of the antisense strand, e.g., as disclosed in Snead et al., (2013) Mol Ther Nucleic Acids 2(7):e103, incorporated herein by reference in its entirety. [00359] In some embodiments, the antisense strand of the siRNA molecule may comprise a 2’-MOE modification and/or the sense strand may comprise an 2’-O-Me modification (see e.g., Song et al., (2017) Mol Ther Nucleic Acids 9:242-250). In some embodiments at least one (e.g., at least 2, at least 3, at least 4, at least 5, at least 6, at least 5, at least 8, at least 9, at least 10 or more) siRNA molecule may be conjugated, for example, covalently to an p75NTR binding protein described herein. In some embodiments, the p75NTR binding protein may be conjugated to the 5’ end of the sense strand of the siRNA molecule. In some embodiments, the p75NTR binding protein may be conjugated to the 3’ end of the sense strand of the siRNA molecule. In some embodiments, the p75NTR binding protein may be conjugated internally to the sense strand of the siRNA molecule. In some embodiments, the p75NTR binding protein may be conjugated to the 5’ end of the antisense strand of the siRNA molecule. In some embodiments, the p75NTR binding protein may be conjugated to the 3’ end of the antisense strand of the siRNA molecule. In some embodiments, the p75NTR binding protein be conjugated internally to the antisense strand of the siRNA molecule. [00360] In addition, an siRNA molecule may be modified or include nucleoside surrogates. Single stranded regions of an siRNA molecule may be modified or include nucleoside surrogates, e.g., the unpaired region or regions of a hairpin structure, e.g., a region which links two complementary regions, can have modifications or nucleoside surrogates. Modification to stabilize one or more 3'- or 5 '-termini of an siRNA molecule, e.g., against exonucleases, or to favor the antisense siRNA agent to enter into RISC are also useful. Modifications can include C3 (or C6, C7, C12) amino linkers, thiol linkers, carboxyl linkers, non-nucleotidic spacers (e.g., C3-C12 (e.g., C3, C6, C9, C12), abasic, tri ethylene glycol, hexaethylene glycol), biotin or fluorescein reagents that come as phosphoramidites and that have another DMT-protected hydroxyl group, allowing multiple couplings during RNA synthesis. [00361] In some embodiments, the sense strand is 23 nucleotides in length and the antisense strand is 21 nucleotides in length. In some embodiments, the sense strand is 23 nucleotides in length and the antisense strand is 21 nucleotides in length, wherein the 3′ and Attorney Docket No.250298.000780 5′ terminal nucleotide positions of the sense strand are inverted abasic residues. The sense strand 3′ and 5′ terminal inverted abasic residues may be overhangs. The inverted abasic residues may be linked via a 3′-3′ phosphodiester linkage. In some embodiments, the antisense strand of the siRNA molecule contains 1-2 phosphorothioate linkages at the 3′ and/or 5′ ends. In some embodiments, the antisense strand contain two or three phosphorothioate internucleotide linkages at the 5′-terminus and 1 phosphorothioate internucleotide linkage at the 3′-terminus. The siRNA molecule may be linked to a targeting moiety at the 5′ or 3′ end of the sense strand. [00362] In some embodiments, the sense strand is 21 nucleotides in length and the antisense strand is 23 nucleotides in length, wherein the antisense strand contains a 2 nucleobase 3′ overhang. In some embodiments, the antisense strand of the siRNA molecule contains 1-3 phosphorothioate linkages at the 3′ and 5′ ends and the sense strand of the siRNA molecule contains 1-2 phosphorothioate linkages at the 3′ end. In some embodiments, the antisense strand of the siRNA molecule contains 2-3 phosphorothioate linkages at the 5′ end and 2 phosphorothioate linkages at the 3′, and the sense strand of the siRNA molecule contains 2 phosphorothioate linkages at the 5′ end. The siRNA molecule may be linked to a targeting moiety at the 5′ or 3′ end of the sense strand. [00363] In some embodiments, the siRNA molecules described herein may be conjugated to a moiety that directs delivery to the CNS, e.g., a lipophilic ligand, optionally a C16 ligand, as described in WO2021119226A1, which is incorporated herein by reference in its entirety. In one embodiment, the lipophilic moiety is a lipid, cholesterol, retinoic acid, cholic acid, adamantane acetic acid, 1-pyrene butyric acid, dihydrotestosterone, l,3-bis- O(hexadecyl)glycerol, geranyloxyhexyanol, hexadecylglycerol, bomeol, menthol, 1,3- propanediol, heptadecyl group, palmitic acid, myristic acid, O3-(oleoyl)lithocholic acid, O3- (oleoyl)cholenic acid, dimethoxytrityl, or phenoxazine. [00364] In one embodiment, the lipophilic moiety contains a saturated or unsaturated C4-C30 hydrocarbon chain, and an optional functional group selected from the group consisting of hydroxyl, amine, carboxylic acid, sulfonate, phosphate, thiol, azide, and alkyne. In one embodiment, the lipophilic moiety contains a saturated or unsaturated C6-C18 hydrocarbon chain. In one embodiment, the lipophilic moiety contains a saturated or unsaturated C16 hydrocarbon chain. In one embodiment, the saturated or unsaturated C16 hydrocarbon chain is conjugated to position 6, from the 5 ’-end of the strand. Attorney Docket No.250298.000780 [00365] In one embodiment, the lipophilic moiety is conjugated via a carrier that replaces one or more nucleotide(s) in the internal position(s) or the double stranded region. In one embodiment, the carrier is a cyclic group selected from the group consisting of pyrrolidinyl, pyrazolinyl, pyrazolidinyl, imidazolinyl, imidazolidinyl, piperidinyl, piperazinyl, [l,3]dioxolanyl, oxazolidinyl, isoxazolidinyl, morpholinyl, thiazolidinyl, isothiazolidinyl, quinoxalinyl, pyridazinonyl, tetrahydrofuranyl, and decalinyl; or is an acyclic moiety based on a serinol backbone or a diethanolamine backbone. In one embodiment, the lipophilic moiety is conjugated to the double-stranded siRNA agent via a linker containing an ether, thioether, urea, carbonate, amine, amide, maleimide-thioether, disulfide, phosphodiester, sulfonamide linkage, a product of a click reaction, or carbamate. In one embodiment, the lipophilic moiety is conjugated to a nucleobase, sugar moiety, or intemucleosidic linkage. [00366] In one embodiment, the lipophilic moiety or targeting ligand is conjugated via a bio-cleavable linker selected from the group consisting of DNA, RNA, disulfide, amide, functionalized monosaccharides or oligosaccharides of galactosamine, glucosamine, glucose, galactose, mannose, and combinations thereof. [00367] In one embodiment, the 3 ’ end of the sense strand is protected via an end cap which is a cyclic group having an amine, said cyclic group being selected from the group consisting of pyrrolidinyl, pyrazolinyl, pyrazolidinyl, imidazolinyl, imidazolidinyl, piperidinyl, piperazinyl, [l,3]dioxolanyl, oxazolidinyl, isoxazolidinyl, morpholinyl, thiazolidinyl, isothiazolidinyl, quinoxalinyl, pyridazinonyl, tetrahydrofuranyl, and decalinyl. [00368] In some embodiments, the interfering nucleic acid molecule is a short hairpin RNA (shRNA). A “ small hairpin RNA ” or “short hairpin RNA” or “shRNA” described herein may include a short RNA sequence that makes a tight hairpin turn that can be used to silence gene expression via RNA interference. The shRNAs provided herein may be chemically synthesized or transcribed from a transcriptional cassette in a DNA plasmid. The shRNA hairpin structure may be cleaved by the cellular machinery into siRNA, which is then bound to the RNA-induced silencing complex (RISC). [00369] Non-limiting examples of shRNAs include a double-stranded polynucleotide molecule assembled from a single-stranded molecule, where the sense and antisense regions are linked by a nucleic acid-based or non-nucleic acid-based linker; and a double- stranded polynucleotide molecule with a hairpin secondary structure having self- complementary sense and antisense regions. In some embodiments, the sense and antisense strands of the shRNA are linked by a loop structure comprising from about 1 to Attorney Docket No.250298.000780 about 25 nucleotides, from about 2 to about 20 nucleotides, from about 4 to about 15 nucleotides, from about 5 to about 12 nucleotides, or 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, or more nucleotides. [00370] Additional embodiments related to the shRNAs, as well as methods of designing and synthesizing such shRNAs, are described in U.S. Patent Publication No. 2011/0071208, the disclosure of which is herein incorporated by reference in its entirety for all purposes. [00371] In some embodiments, the interfering nucleic acid molecule is a micro RNA (miRNA). miRNAs represent a large group of small RNAs produced naturally in organisms, some of which regulate the expression of target genes. miRNAs are short hairpin RNAs about 18 to about 25 nucleotides in length that function in RNA silencing and post-translational regulation of gene expression. Typically, miRNAs are generated from large RNA precursors (termed pri-miRNAs) that are processed in the nucleus into approximately 70 nucleotide pre- miRNAs, which fold into imperfect stem-loop structures. These pre-miRNAs typically undergo an additional processing step within the cytoplasm where mature miRNAs of 18-25 nucleotides in length are excised from one side of the pre-miRNA hairpin by an rNase III enzyme, Dicer. miRNAs are not translated into proteins, but instead bind to specific messenger RNAs, thereby blocking translation. In some embodiments, miRNAs base-pair imprecisely with their targets to inhibit translation. [00372] miRNAs as described herein can include pri-miRNA, pre-miRNA, mature miRNA or fragments of variants thereof that retain the biological activity of mature miRNA. In some embodiments, the size range of the miRNA can be from 21 nucleotides to 170 nucleotides. In one embodiment, the size range of the miRNA is from 70 to 170 nucleotides in length. In another embodiment, mature miRNAs of from 21 to 25 nucleotides in length can be used. [00373] In certain embodiments, the interfering nucleic acid molecule is an antisense oligonucleotide (ASO). An ASO can down regulate a target by inducing rNase H endonuclease cleavage of a target RNA, by steric hindrance of ribosomal activity, by inhibiting 5′ cap formation, or by altering splicing. An ASO can be, but is not limited to, a gapmer or a morpholino. An antisense oligonucleotide typically comprises a short nucleotide sequence which is substantially complementary to a target nucleotide sequence in a pre-mRNA molecule, heterogeneous nuclear RNA (hnRNA) or mRNA molecule. The degree of complementarity (or substantial complementarity) of the antisense sequence is preferably Attorney Docket No.250298.000780 such that a molecule comprising the antisense sequence can form a stable double stranded hybrid with the target nucleotide sequence in the RNA molecule under physiological conditions. Antisense oligonucleotides are often synthetic and chemically modified. [00374] Antisense oligonucleotides may be 100% complementary to the target sequence, or may include mismatches, e.g., to improve selective targeting of allele containing the disease-associated mutation, as long as a heteroduplex formed between the oligonucleotide and target sequence is sufficiently stable to withstand the action of cellular nucleases and other modes of degradation which may occur in vivo. Hence, certain oligonucleotides may have about or at least about 70% sequence complementarity, e.g, 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence complementarity, between the oligonucleotide and the target sequence. Oligonucleotide backbones that are less susceptible to cleavage by nucleases are discussed herein. Mismatches, if present, are typically less destabilizing toward the end regions of the hybrid duplex than in the middle. The number of mismatches allowed will depend on the length of the oligonucleotide, the percentage of G:C base pairs in the duplex, and the position of the mismatch(es) in the duplex, according to well understood principles of duplex stability. [00375] In some embodiments, an interfering nucleic acid molecule described herein is a gapmer. A “Gapmer” is oligonucleotide comprising an internal region having a plurality of nucleosides that support RNase H cleavage positioned between external regions having one or more nucleosides, wherein the nucleosides comprising the internal region are chemically distinct from the nucleoside or nucleosides comprising the external regions. The internal region may be referred to as the “gap” and the external regions may be referred to as the “wings.” A gapmer can have 5′ and 3′ wings each having 2-6 nucleotides and a gap having 7-12 nucleotides. In some embodiments, a gapmer can have a 3-10-3 configuration or a 5- 10-5 configuration. [00376] A gapmer commonly has the formula 5'-X-Y-Z-3', with X and Z as flanking regions around a gap region Y. In some embodiments, flanking region X of formula 5'-X-Y-Z- 3' is also called X region, flanking sequence X, 5' wing region X, or 5' wing segment. In some embodiments, flanking region Z of formula 5'-X-Y-Z-3' is also called Z region, flanking sequence Z, 3' wing region Z, or 3' wing segment. In some embodiments, gap region Y of formula 5'-X-Y-Z-3' is also called Y region, Y segment, gap-segment Y, gap segment, or gap region. In some embodiments, each nucleoside in the gap region Y is a 2'- Attorney Docket No.250298.000780 deoxyribonucleoside, and neither the 5' wing region X or the 3' wing region Z comprises any 2'-deoxyribonucleosides. [00377] In some embodiments, the gap region of the gapmer polynucleotide may contain modified nucleotides known to be acceptable for efficient rNase H action in addition to DNA nucleotides, such as C4'-substituted nucleotides, acyclic nucleotides, and arabino- configured nucleotides. In some embodiments, the gap region comprises one or more unmodified internucleosides. In some embodiments, one or both flanking regions each independently comprise one or more phosphorothioate internucleoside linkages (e.g., phosphorothioate internucleoside linkages or other linkages) between at least two, at least three, at least four, or at least five or more nucleotides. In some embodiments, each internucleotide linkage in the gap segment comprises a phosphorothioate linkage. In some embodiments, the gap region and two flanking regions each independently comprise modified internucleoside linkages (e.g., phosphorothioate internucleoside linkages or other linkages) between at least two, at least three, at least four, or at least five or more nucleotides. In some embodiments, each internucleotide linkage in the 5′ or 3′ wing region comprises a phosphorothioate linkage. In some embodiments, each internucleotide linkage in the gapmer comprises a phosphorothioate linkage. [00378] In some embodiments, the Y region may comprise a contiguous stretch of nucleotides, e.g., a region of 5 or more DNA nucleotides, which can be capable of recruiting an rNase including but not limited to rNase H. In some embodiments, the gapmer may bind to a target nucleic acid such that an rNase is recruited to cleave the target nucleic acid. In some embodiments, the Y region may be flanked both 5' and 3' by regions X and Z comprising high-affinity modified nucleosides, e.g., 1-10 high-affinity modified nucleosides. Exemplary high affinity modified nucleosides include, without limitation, 2'-4' bicyclic nucleosides (e.g., LNA, cEt, ENA) and 2'-modified nucleosides (e.g., 2'-MOE, 2'O-Me, 2'-F). In some embodiments, the flanking sequences X and Z may be of 1-30 nucleotides, 1-20 nucleotides, 1-10 nucleotides, or 1-5 nucleotides in length. The flanking sequences X and Z may be of similar length or of dissimilar lengths. In some embodiments, the flanking sequences X and Z are each 5 nucleotides in length. In some embodiments, the flanking sequences X and Z are each 3 nucleotides in length. In some embodiments, the gap-segment Y may be a nucleotide sequence of 5-30 nucleotides, 5-20 nucleotides, or 5-10 nucleotides in length. In some embodiments, the gap segment is 10 nucleotides in length. Attorney Docket No.250298.000780 [00379] A gapmer may be produced using suitable methods. Preparation of gapmers is described in, for example, U.S. Pat. Nos.10,260,069; 10,017,764; 9,695,418; 9,428,534; 9,428,534; 9,045,754; 8,580,756; 8,580,756; 7,750,131; 7,683,036; 7,569,686; 7,432,250; 7,399,845; 7,101,993; 7,015,315; 5,898,031; 5,700,922; 5,652,356; 5,652,355; 5,623,065; 5,565,350; 5,491,133; 5,403,711; 5,366,878; 5,256,775; 5,220,007; 5,149,797; and 5,013,830; U.S. Patent Publication Nos. US2010/0197762, US2005/0074801, US2009/0221685, US2009/0286969, and US2011/0112170; PCT Publication Nos. WO2005/023825, WO2004/069991, WO2008/049085 and WO2009/090182, each of which is herein incorporated by reference in its entirety. [00380] In some embodiments, a gapmer is 10-50 nucleosides in length. For example, a gapmer may be 10-50, 10-45, 10-40, 10-35, 10-30, 10-25, 10-20, 10-15, 15-40, 15-35, 15- 30, 15-25, 15-20, 20-40, 20-35, 20-30, 20-25, 25-40, 25-35, 25-30, 30-40, 30-35, or 35-40 nucleosides in length. In some embodiments, a gapmer is 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, or 40 nucleosides in length. In some embodiments, a gapmer is about 16 to about 20 nucleosides in length. In some embodiments, a gapmer is 16 nucleotides in length. In some embodiments, a gapmer is 20 nucleotides in length. [00381] In some embodiments, the 5' wing region and the 3' wing region of a gapmer are independently 1-20 nucleosides (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 nucleosides) long. For example, the 5' wing region and the 3' wing region of the gapmer may be independently 1- 20, 1-15, 1-10, 1-7, 1-5, 1-3, 1-2, 2-5, 2-7, 3-5, 3-7, 5- 20, 5-15, 5-10, 10-20, 10-15, or 15-20 nucleosides long. In some embodiments, the 5' wing region and the 3' wing region of the gapmer are of the same length. In some embodiments, the 5' wing region and the 3' wing region of a gapmer are of different lengths. In some embodiments, the 5' wing region is longer than the 3' wing region of a gapmer. In some embodiments, the 5' wing region is shorter than the 3' wing region of the gapmer. [00382] In some embodiments, the gap region in a gapmer is 5-20 nucleosides in length. For example, the gap region Y may be 5-20, 5-15, 5-10, 10-20, 10-15, or 15-20 nucleosides in length. In some embodiments, the gap region is 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 nucleosides in length. In some embodiments, one or more nucleosides in the gap region Y is a 2'-deoxyribonucleoside. In some embodiments, every nucleotide in the gap region is a deoxyribonucleoside. In some embodiments, one or more of the nucleosides in the gap region is a modified nucleoside (e.g., a 2' modified nucleoside Attorney Docket No.250298.000780 such as those described herein). In some embodiments, one or more cytosines in the gap region Y are 5-methyl-cytosines. In some embodiments, every cytosine in the gap region Y is a 5-methyl-cytosine. In some embodiments, every cytosine in a gapmer is a 5-methyl- cytosine. [00383] In some embodiments, one or more nucleosides in the 5' wing region or the 3' wing region of a gapmer are modified nucleotides. In some embodiments, the modified nucleotide may be a 2'- modified nucleoside, e.g., 2'-4' bicyclic nucleoside or a non-bicyclic 2'-modified nucleoside. In some embodiments, the nucleoside may be a 2'-4' bicyclic nucleoside (e.g., LNA, cEt, or ENA) or a non-bicyclic 2'-modified nucleoside (e.g., 2'-fluoro (2'-F), 2'-O-methyl (2'-O-Me), 2'-O-dimethylaminoethyl (2'-O-DMAOE), 2'-O- dimethylaminopropyl (2'-O-DMAP), 2'-O-methoxyethyl (2'-MOE), 2'-O-aminopropyl (2'-O- AP), 2'-O-dimethylaminoethyloxyethyl (2'-O-DMAEOE), or 2'-O-N-methylacetamido (2'-O- NMA)). In some embodiments, every nucleotide in a wing region is a modified nucleotide. In some embodiments, every nucleotide in a wing region is a 2′-MOE, LNA or cET nucleotide. [00384] In some embodiments, a gapmer of the present disclosure may comprises one or more modified nucleoside linkages in each of the X, Y, and Z regions. In some embodiments, each internucleoside linkage may comprise phosphorothioate linkage. In some embodiments, each of the X, Y, and Z regions independently comprises a combination of phosphodiester linkages and phosphorothioate linkages. In some embodiments, each internucleoside linkage in the gap region Y may be a phosphorothioate linkage, the 5' wing region X comprises a combination of phosphorothioate linkages and phosphodiester linkages, and the 3' wing region Z comprises a combination of phosphorothioate linkages and phosphodiester linkages. [00385] In some embodiments, each nucleotide in the gap region of a gapmer is a deoxyribonucleotide and each nucleotide in a wing region is a 2′-MOE nucleotide. In some embodiments, each nucleotide in the gap region of a gapmer is a deoxyribonucleotide, each nucleotide in a wing region is a 2′-MOE nucleotide, and every cytosine in the gapmer is a 5- methyl-cytosine. In some embodiments, each nucleotide in the gap region of a gapmer is a deoxyribonucleotide, each nucleotide in a wing region is a 2′-MOE nucleotide, every cytosine in the gapmer is a 5-methyl-cytosine and every internucleotide linkage is a phosphorothioate linkage. [00386] In some embodiments, each nucleotide in the gap region of a gapmer is a deoxyribonucleotide and each nucleotide in a wing region is a LNA nucleotide. In some Attorney Docket No.250298.000780 embodiments, each nucleotide in the gap region of a gapmer is a deoxyribonucleotide, each nucleotide in a wing region is a LNA nucleotide, and every cytosine in the gapmer is a 5- methyl-cytosine. In some embodiments, each nucleotide in the gap region of a gapmer is a deoxyribonucleotide, each nucleotide in a wing region is a LNA nucleotide, every cytosine in the gapmer is a 5-methyl-cytosine and every internucleotide linkage is a phosphorothioate linkage. In some embodiments, each nucleotide in the gap region of a gapmer is a deoxyribonucleotide and each nucleotide in a wing region is a cET nucleotide. In some embodiments, each nucleotide in the gap region of a gapmer is a deoxyribonucleotide, each nucleotide in a wing region is a cET nucleotide, and every cytosine in the gapmer is a 5- methyl-cytosine. In some embodiments, each nucleotide in the gap region of a gapmer is a deoxyribonucleotide, each nucleotide in a wing region is a cET nucleotide, every cytosine in the gapmer is a 5-methyl-cytosine and every internucleotide linkage is a phosphorothioate linkage. [00387] The interfering nucleic acids can employ a variety of oligonucleotide chemistries. Examples of oligonucleotide chemistries include, without limitation, peptide nucleic acid (PNA), locked nucleic acid (LNA), phosphorothioate, 2’-O-Me-modified oligonucleotides, and morpholino chemistries, including combinations of any of the foregoing. In general, PNA and LNA chemistries can utilize shorter targeting sequences because of their relatively high target binding strength relative to 2’-O-Me oligonucleotides. Phosphorothioate and 2’-O-Me-modified chemistries are often combined to generate 2’-O-Me-modified oligonucleotides having a phosphorothioate backbone. See, e.g., PCT Publication Nos. WO/2013/112053 and WO/2009/008725, incorporated by reference in their entireties. [00388] Peptide nucleic acids (PNAs) are analogs of DNA in which the backbone is structurally homomorphous with a deoxyribose backbone, consisting of N-(2-aminoethyl) glycine units to which pyrimidine or purine bases are attached. PNAs containing natural pyrimidine and purine bases hybridize to complementary oligonucleotides obeying Watson- Crick base-pairing rules, and mimic DNA in terms of base pair recognition (Egholm, Buchardt et al.1993). The backbone of PNAs is formed by peptide bonds rather than phosphodiester bonds, making them well-suited for antisense applications. The backbone is uncharged, resulting in PNA/DNA or PNA/RNA duplexes that exhibit greater than normal thermal stability. PNAs are not recognized by nucleases or proteases. [00389] Despite a radical structural change to the natural structure, PNAs are capable of sequence-specific binding in a helix form to DNA or RNA. Characteristics of PNAs include Attorney Docket No.250298.000780 a high binding affinity to complementary DNA or RNA, a destabilizing effect caused by single- base mismatch, resistance to nucleases and proteases, hybridization with DNA or RNA independent of salt concentration and triplex formation with homopurine DNA. PANAGENETM has developed its proprietary Bts PNA monomers (Bts; benzothiazole-2- sulfonyl group) and proprietary oligomerization process. The PNA oligomerization using Bts PNA monomers is composed of repetitive cycles of deprotection, coupling and capping. PNAs can be produced synthetically using any technique known in the art. See, e.g., U.S. Pat. Nos. 5,539,082; 5,714,331; and 5,719,262, 6,969,766, 7,211,668, 7,022,851, 7,125,994, 7,145,006 and 7,179,896. See also U.S. Pat. Nos.5,539,082; 5,714,331; and 5,719,262 for the preparation of PNAs. Further teaching of PNA compounds can be found in Nielsen et al., Science, 254:1497-1500, 1991. Each of the foregoing is incorporated by reference in its entirety. [00390] Interfering nucleic acids described herein may also contain “locked nucleic acid” subunits (LNAs). “LNAs” are a member of a class of modifications called bridged nucleic acid (BNA). BNA is characterized by a covalent linkage that locks the conformation of the ribose ring in a C30-endo (northern) sugar pucker. For LNA, the bridge is composed of a methylene between the 2’-O and the 4’-C positions. LNA enhances backbone preorganization and base stacking to increase hybridization and thermal stability. [00391] The structures of LNAs can be found, for example, in Wengel, et al., Chemical Communications (1998) 455; Tetrahedron (1998) 54:3607, and Accounts of Chem. Research (1999) 32:301); Obika, et al., Tetrahedron Letters (1997) 38:8735; (1998) 39:5401, and Bioorganic Medicinal Chemistry (2008) 16:9230. Compounds provided herein may incorporate one or more LNAs; in some cases, the compounds may be entirely composed of LNAs. Methods for the synthesis of individual LNA nucleoside subunits and their incorporation into oligonucleotides are described, for example, in U.S. Pat. Nos. 7,572,582, 7,569,575, 7,084,125, 7,060,809, 7,053,207, 7,034,133, 6,794,499, and 6,670,461, each of which is incorporated by reference in its entirety. Typical intersubunit linkers include phosphodiester and phosphorothioate moieties. Alternatively, non-phosphorous containing linkers may be employed. In some embodiments, an antisense oligonucleotide comprises an LNA containing compound where each LNA subunit is separated by a DNA subunit. Certain compounds are composed of alternating LNA and DNA subunits where the intersubunit linker is phosphorothioate. Attorney Docket No.250298.000780 [00392] “Phosphorothioates” (or S-oligos) are a variant of normal DNA in which one of the nonbridging oxygens is replaced by a sulfur. The sulfurization of the internucleotide bond reduces the action of endo-and exonucleases including 5’ to 3’ and 3’ to 5’ DNA POL 1 exonuclease, nucleases SI and PI, rNases, serum nucleases and snake venom phosphodiesterase. Phosphorothioates are made by two principal routes: by the action of a solution of elemental sulfur in carbon disulfide on a hydrogen phosphonate, or by the method of sulfurizing phosphite triesters with either tetraethylthiuram disulfide (TETD) or 3H-1, 2- bensodithiol-3-one 1, 1-dioxide (BDTD) (see, e.g., Iyer et al., J. Org. Chem.55, 4693-4699, 1990). The latter methods avoid the problem of elemental sulfur’s insolubility in most organic solvents and the toxicity of carbon disulfide. The TETD and BDTD methods also yield higher purity phosphorothioates. [00393] “2’ O-Me oligonucleotides” molecules carry a methyl group at the 2’-OH residue of the ribose molecule.2’-O-Me-RNAs show the same (or similar) behavior as DNA, but are protected against nuclease degradation. 2’-O-Me-RNAs can also be combined with phosphothioate oligonucleotides (PTOs) for further stabilization. 2’-O-Me oligonucleotides (phosphodiester or phosphothioate) can be synthesized according to routine techniques in the art (see, e.g., Yoo et al., Nucleic Acids Res.32:2008-16, 2004). [00394] Interfering nucleic acid molecules can be prepared, for example, by chemical synthesis, in vitro transcription, or digestion of long dsRNA by rNase III or Dicer. These can be introduced into cells by transfection, electroporation, or other methods known in the art. See Hannon, GJ, 2002, Nature 418: 244- 251; Bernstein E et al., 2002, RNA 7: 1509-1521; Hutvagner G et al., Curr. Opin. Genetics & Development 12: 225-232; Brummelkamp, 2002, Science 296: 550-553; Lee NS, et al.2002. Nature Biotechnol.20:500-505; Miyagishi M, and Taira K. 2002. Nature Biotechnol. 20:497-500; Paddison PJ, et al., 2002. Genes & Dev. 16:948-958; Paul CP, et al., 2002. Nature Biotechnol.20:505-508; Sui G et al., 2002. Proc. Natl. Acad. Sci. USA 99(6):5515-5520; Yu J-Y et al., 2002. Proc. Natl. Acad. Sci. USA 99(9):6047-6052. Each of the foregoing is incorporated by reference in its entirety. Guide RNAs [00395] In some embodiments, a conjugated molecular cargo comprises a guide RNA or a DNA encoding a guide RNA. A “guide RNA” or “gRNA” is an RNA molecule that binds to a Cas protein (e.g., Cas9 protein) and targets the Cas protein to a specific location within a target DNA. Guide RNAs can comprise two segments: a “DNA-targeting segment” (also Attorney Docket No.250298.000780 called “guide sequence”) and a “protein-binding segment.” “Segment” includes a section or region of a molecule, such as a contiguous stretch of nucleotides in an RNA. Some gRNAs, such as those for Cas9, can comprise two separate RNA molecules: an “activator-RNA” (e.g., tracrRNA) and a “targeter-RNA” (e.g., CRISPR RNA or crRNA). Other gRNAs are a single RNA molecule (single RNA polynucleotide), which can also be called a “single-molecule gRNA,” a “single-guide RNA,” or an “sgRNA.” See, e.g., WO 2013/176772, WO 2014/065596, WO 2014/089290, WO 2014/093622, WO 2014/099750, WO 2013/142578, and WO 2014/131833, each of which is herein incorporated by reference in its entirety for all purposes. A guide RNA can refer to either a CRISPR RNA (crRNA) or the combination of a crRNA and a trans-activating CRISPR RNA (tracrRNA). The crRNA and tracrRNA can be associated as a single RNA molecule (single guide RNA or sgRNA) or in two separate RNA molecules (dual guide RNA or dgRNA). For Cas9, for example, a single-guide RNA can comprise a crRNA fused to a tracrRNA (e.g., via a linker). For Cpf1 and CasΦ, for example, only a crRNA is needed to achieve binding to a target sequence. The terms “guide RNA” and “gRNA” include both double-molecule (i.e., modular) gRNAs and single-molecule gRNAs. In some of the methods and compositions disclosed herein, a gRNA is a S. pyogenes Cas9 gRNA or an equivalent thereof. In some of the methods and compositions disclosed herein, a gRNA is a S. aureus Cas9 gRNA or an equivalent thereof. [00396] An exemplary two-molecule gRNA comprises a crRNA-like (“CRISPR RNA” or “targeter-RNA” or “crRNA” or “crRNA repeat”) molecule and a corresponding tracrRNA-like (“trans-activating CRISPR RNA” or “activator-RNA” or “tracrRNA”) molecule. A crRNA comprises both the DNA-targeting segment (single-stranded) of the gRNA and a stretch of nucleotides that forms one half of the dsRNA duplex of the protein-binding segment of the gRNA. An example of a crRNA tail (e.g., for use with S. pyogenes Cas9), located downstream (3’) of the DNA-targeting segment, comprises, consists essentially of, or consists of GUUUUAGAGCUAUGCU (SEQ ID NO: 625) or GUUUUAGAGCUAUGCUGUUUUG (SEQ ID NO: 626). Any of the DNA-targeting segments disclosed herein can be joined to the 5’ end of SEQ ID NO: 625 or 626 to form a crRNA. [00397] A corresponding tracrRNA (activator-RNA) comprises a stretch of nucleotides that forms the other half of the dsRNA duplex of the protein-binding segment of the gRNA. A stretch of nucleotides of a crRNA are complementary to and hybridize with a stretch of nucleotides of a tracrRNA to form the dsRNA duplex of the protein-binding domain of the gRNA. As such, each crRNA can be said to have a corresponding tracrRNA. Examples of Attorney Docket No.250298.000780 tracrRNA sequences (e.g., for use with S. pyogenes Cas9) comprise, consist essentially of, or consist of any one of AGCAUAGCAAGUUAAAAUAAGGCUAGUCCGUUAUCAACUUGAAAAAGUGGCACCGAG UCGGUGCUUU (SEQ ID NO: 627), AAACAGCAUAGCAAGUUAAAAUAAGGCUAGUCCGUUAUCAACUUGAAAAAGUGGCAC CGAGUCGGUGCUUUU (SEQ ID NO: 628), or GUUGGAACCAUUCAAAACAGCAUAGCAAGUUAAAAUAAGGCUAGUCCGUUAUCAACU UGAAAAAGUGGCACCGAGUCGGUGC (SEQ ID NO: 629). [00398] In systems in which both a crRNA and a tracrRNA are needed, the crRNA and the corresponding tracrRNA hybridize to form a gRNA. In systems in which only a crRNA is needed, the crRNA can be the gRNA. The crRNA additionally provides the single-stranded DNA-targeting segment that hybridizes to the complementary strand of a target DNA. If used for modification within a cell, the exact sequence of a given crRNA or tracrRNA molecule can be designed to be specific to the species in which the RNA molecules will be used. See, e.g., Mali et al. (2013) Science 339(6121):823-826; Jinek et al. (2012) Science 337(6096):816- 821; Hwang et al. (2013) Nat. Biotechnol.31(3):227-229; Jiang et al. (2013) Nat. Biotechnol. 31(3):233-239; and Cong et al. (2013) Science 339(6121):819-823, each of which is herein incorporated by reference in its entirety for all purposes. [00399] The DNA-targeting segment (crRNA) of a given gRNA comprises a nucleotide sequence that is complementary to a sequence on the complementary strand of the target DNA, as described in more detail below. The DNA-targeting segment of a gRNA interacts with the target DNA in a sequence-specific manner via hybridization (i.e., base pairing). As such, the nucleotide sequence of the DNA-targeting segment may vary and determines the location within the target DNA with which the gRNA and the target DNA will interact. The DNA-targeting segment of a subject gRNA can be modified to hybridize to any desired sequence within a target DNA. Naturally occurring crRNAs differ depending on the CRISPR/Cas system and organism but often contain a targeting segment of between 21 to 72 nucleotides length, flanked by two direct repeats (DR) of a length of between 21 to 46 nucleotides (see, e.g., WO 2014/131833, herein incorporated by reference in its entirety for all purposes). In the case of S. pyogenes, the DRs are 36 nucleotides long and the targeting segment is 30 nucleotides long. The 3’ located DR is complementary to and hybridizes with the corresponding tracrRNA, which in turn binds to the Cas protein. Attorney Docket No.250298.000780 [00400] The DNA-targeting segment can have, for example, a length of at least about 12, at least about 15, at least about 17, at least about 18, at least about 19, at least about 20, at least about 25, at least about 30, at least about 35, or at least about 40 nucleotides. Such DNA-targeting segments can have, for example, a length from about 12 to about 100, from about 12 to about 80, from about 12 to about 50, from about 12 to about 40, from about 12 to about 30, from about 12 to about 25, or from about 12 to about 20 nucleotides. For example, the DNA targeting segment can be from about 15 to about 25 nucleotides (e.g., from about 17 to about 20 nucleotides, or about 17, 18, 19, or 20 nucleotides). See, e.g., US 2016/0024523, herein incorporated by reference in its entirety for all purposes. For Cas9 from S. pyogenes, a typical DNA-targeting segment is between 16 and 20 nucleotides in length or between 17 and 20 nucleotides in length. For Cas9 from S. aureus, a typical DNA-targeting segment is between 21 and 23 nucleotides in length. For Cpf1, a typical DNA-targeting segment is at least 16 nucleotides in length or at least 18 nucleotides in length. [00401] In one example, the DNA-targeting segment can be about 20 nucleotides in length. However, shorter and longer sequences can also be used for the targeting segment (e.g., 15-25 nucleotides in length, such as 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, or 25 nucleotides in length). The degree of identity between the DNA-targeting segment and the corresponding guide RNA target sequence (or degree of complementarity between the DNA- targeting segment and the other strand of the guide RNA target sequence) can be, for example, about 75%, about 80%, about 85%, about 90%, about 95%, or 100%. The DNA- targeting segment and the corresponding guide RNA target sequence can contain one or more mismatches. For example, the DNA-targeting segment of the guide RNA and the corresponding guide RNA target sequence can contain 1-4, 1-3, 1-2, 1, 2, 3, or 4 mismatches (e.g., where the total length of the guide RNA target sequence is at least 17, at least 18, at least 19, or at least 20 or more nucleotides). For example, the DNA-targeting segment of the guide RNA and the corresponding guide RNA target sequence can contain 1-4, 1-3, 1-2, 1, 2, 3, or 4 mismatches where the total length of the guide RNA target sequence 20 nucleotides. [00402] TracrRNAs can be in any form (e.g., full-length tracrRNAs or active partial tracrRNAs) and of varying lengths. They can include primary transcripts or processed forms. For example, tracrRNAs (as part of a single-guide RNA or as a separate molecule as part of a two-molecule gRNA) may comprise, consist essentially of, or consist of all or a portion of a wild type tracrRNA sequence (e.g., about or more than about 20, 26, 32, 45, 48, 54, 63, 67, 85, or more nucleotides of a wild type tracrRNA sequence). Examples of wild type tracrRNA Attorney Docket No.250298.000780 sequences from S. pyogenes include 171-nucleotide, 89-nucleotide, 75-nucleotide, and 65- nucleotide versions. See, e.g., Deltcheva et al. (2011) Nature 471(7340):602-607; WO 2014/093661, each of which is herein incorporated by reference in its entirety for all purposes. Examples of tracrRNAs within single-guide RNAs (sgRNAs) include the tracrRNA segments found within +48, +54, +67, and +85 versions of sgRNAs, where “+n” indicates that up to the +n nucleotide of wild type tracrRNA is included in the sgRNA. See US 8,697,359, herein incorporated by reference in its entirety for all purposes. [00403] The percent complementarity between the DNA-targeting segment of the guide RNA and the complementary strand of the target DNA can be at least 60% (e.g., at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100%). The percent complementarity between the DNA-targeting segment and the complementary strand of the target DNA can be at least 60% over about 20 contiguous nucleotides. As an example, the percent complementarity between the DNA-targeting segment and the complementary strand of the target DNA can be 100% over the 14 contiguous nucleotides at the 5’ end of the complementary strand of the target DNA and as low as 0% over the remainder. In such a case, the DNA-targeting segment can be considered to be 14 nucleotides in length. As another example, the percent complementarity between the DNA- targeting segment and the complementary strand of the target DNA can be 100% over the seven contiguous nucleotides at the 5’ end of the complementary strand of the target DNA and as low as 0% over the remainder. In such a case, the DNA-targeting segment can be considered to be 7 nucleotides in length. In some guide RNAs, at least 17 nucleotides within the DNA-targeting segment are complementary to the complementary strand of the target DNA. For example, the DNA-targeting segment can be 20 nucleotides in length and can comprise 1, 2, or 3 mismatches with the complementary strand of the target DNA. In one example, the mismatches are not adjacent to the region of the complementary strand corresponding to the protospacer adjacent motif (PAM) sequence (i.e., the reverse complement of the PAM sequence) (e.g., the mismatches are in the 5’ end of the DNA- targeting segment of the guide RNA, or the mismatches are at least 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, or 19 base pairs away from the region of the complementary strand corresponding to the PAM sequence). [00404] The protein-binding segment of a gRNA can comprise two stretches of nucleotides that are complementary to one another. The complementary nucleotides of the protein-binding segment hybridize to form a double-stranded RNA duplex (dsRNA). The Attorney Docket No.250298.000780 protein-binding segment of a subject gRNA interacts with a Cas protein, and the gRNA directs the bound Cas protein to a specific nucleotide sequence within target DNA via the DNA- targeting segment. [00405] Single-guide RNAs can comprise a DNA-targeting segment and a scaffold sequence (i.e., the protein-binding or Cas-binding sequence of the guide RNA). For example, such guide RNAs can have a 5’ DNA-targeting segment joined to a 3’ scaffold sequence. Exemplary scaffold sequences (e.g., for use with S. pyogenes Cas9) comprise, consist essentially of, or consist of: GUUUUAGAGCUAGAAAUAGCAAGUUAAAAUAAGGCUAGUCCGUUAUCAACUUGAAAA AGUGGCACCGAGUCGGUGCU (version 1; SEQ ID NO: 630); GUUGGAACCAUUCAAAACAGCAUAGCAAGUUAAAAUAAGGCUAGUCCGUUAUCAACU UGAAAAAGUGGCACCGAGUCGGUGC (version 2; SEQ ID NO: 629); GUUUUAGAGCUAGAAAUAGCAAGUUAAAAUAAGGCUAGUCCGUUAUCAACUUGAAAA AGUGGCACCGAGUCGGUGC (version 3; SEQ ID NO: 631); and GUUUAAGAGCUAUGCUGGAAACAGCAUAGCAAGUUUAAAUAAGGCUAGUCCGUUAU CAACUUGAAAAAGUGGCACCGAGUCGGUGC (version 4; SEQ ID NO: 632); GUUUUAGAGCUAGAAAUAGCAAGUUAAAAUAAGGCUAGUCCGUUAUCAACUUGAAAA AGUGGCACCGAGUCGGUGCUUUUUUU (version 5; SEQ ID NO: 633); GUUUUAGAGCUAGAAAUAGCAAGUUAAAAUAAGGCUAGUCCGUUAUCAACUUGAAAA AGUGGCACCGAGUCGGUGCUUUU (version 6; SEQ ID NO: 634); GUUUAAGAGCUAUGCUGGAAACAGCAUAGCAAGUUUAAAUAAGGCUAGUCCGUUAU CAACUUGAAAAAGUGGCACCGAGUCGGUGCUUUUUU (version 7; SEQ ID NO: 635); or GUUUUAGAGCUAGAAAUAGCAAGUUAAAAUAAGGCUAGUCCGUUAUCAACUUGGCA CCGAGUCGGUGC (version 8; SEQ ID NO: 636). In some guide sgRNAs, the four terminal U residues of version 6 are not present. In some sgRNAs, only 1, 2, or 3 of the four terminal U residues of version 6 are present. Guide RNAs targeting any of the guide RNA target sequences disclosed herein can include, for example, a DNA-targeting segment on the 5’ end of the guide RNA fused to any of the exemplary guide RNA scaffold sequences on the 3’ end of the guide RNA. That is, any of the DNA-targeting segments disclosed herein can be joined to the 5’ end of any one of the above scaffold sequences to form a single guide RNA (chimeric guide RNA). [00406] Guide RNAs can include modifications or sequences that provide for additional desirable features (e.g., modified or regulated stability; subcellular targeting; tracking with a Attorney Docket No.250298.000780 fluorescent label; a binding site for a protein or protein complex; and the like). That is, guide RNAs can include one or more modified nucleosides or nucleotides, or one or more non- naturally and/or naturally occurring components or configurations that are used instead of or in addition to the canonical A, G, C, and U residues. Examples of such modifications include, for example, a 5’ cap (e.g., a 7-methylguanylate cap (m7G)); a 3’ polyadenylated tail (i.e., a 3’ poly(A) tail); a riboswitch sequence (e.g., to allow for regulated stability and/or regulated accessibility by proteins and/or protein complexes); a stability control sequence; a sequence that forms a dsRNA duplex (i.e., a hairpin); a modification or sequence that targets the RNA to a subcellular location (e.g., nucleus, mitochondria, chloroplasts, and the like); a modification or sequence that provides for tracking (e.g., direct conjugation to a fluorescent molecule, conjugation to a moiety that facilitates fluorescent detection, a sequence that allows for fluorescent detection, and so forth); a modification or sequence that provides a binding site for proteins (e.g., proteins that act on DNA, including transcriptional activators, transcriptional repressors, DNA methyltransferases, DNA demethylases, histone acetyltransferases, histone deacetylases, and the like); and combinations thereof. Other examples of modifications include engineered stem loop duplex structures, engineered bulge regions, engineered hairpins 3’ of the stem loop duplex structure, or any combination thereof. See, e.g., US 2015/0376586, herein incorporated by reference in its entirety for all purposes. A bulge can be an unpaired region of nucleotides within the duplex made up of the crRNA- like region and the minimum tracrRNA-like region. A bulge can comprise, on one side of the duplex, an unpaired 5′-XXXY-3′ where X is any purine and Y can be a nucleotide that can form a wobble pair with a nucleotide on the opposite strand, and an unpaired nucleotide region on the other side of the duplex. [00407] In some cases, a guide RNA for use in a transcriptional activation system comprising a dCas9-VP64 fusion protein paired with MS2-p65-HSF1 can be used. Guide RNAs in such systems can be designed with aptamer sequences appended to sgRNA tetraloop and stem-loop 2 designed to bind dimerized MS2 bacteriophage coat proteins. See, e.g., Konermann et al. (2015) Nature 517(7536):583-588, herein incorporated by reference in its entirety for all purposes. [00408] Guide RNAs can comprise modified nucleosides and modified nucleotides including, for example, one or more of the following: (1) alteration or replacement of one or both of the non-linking phosphate oxygens and/or of one or more of the linking phosphate oxygens in the phosphodiester backbone linkage (an exemplary backbone modification); (2) Attorney Docket No.250298.000780 alteration or replacement of a constituent of the ribose sugar such as alteration or replacement of the 2’ hydroxyl on the ribose sugar (an exemplary sugar modification); (3) replacement (e.g., wholesale replacement) of the phosphate moiety with dephospho linkers (an exemplary backbone modification); (4) modification or replacement of a naturally occurring nucleobase, including with a non-canonical nucleobase (an exemplary base modification); (5) replacement or modification of the ribose-phosphate backbone (an exemplary backbone modification); (6) modification of the 3’ end or 5’ end of the oligonucleotide (e.g., removal, modification or replacement of a terminal phosphate group or conjugation of a moiety, cap, or linker (such 3’ or 5’ cap modifications may comprise a sugar and/or backbone modification); and (7) modification or replacement of the sugar (an exemplary sugar modification). Other possible guide RNA modifications include modifications of or replacement of uracils or poly-uracil tracts. See, e.g., WO 2015/048577 and US 2016/0237455, each of which is herein incorporated by reference in its entirety for all purposes. Similar modifications can be made to Cas-encoding nucleic acids, such as Cas mRNAs. For example, Cas mRNAs can be modified by depletion of uridine using synonymous codons. [00409] Chemical modifications such at hose listed above can be combined to provide modified gRNAs and/or mRNAs comprising residues (nucleosides and nucleotides) that can have two, three, four, or more modifications. For example, a modified residue can have a modified sugar and a modified nucleobase. In one example, every base of a gRNA is modified (e.g., all bases have a modified phosphate group, such as a phosphorothioate group). For example, all or substantially all of the phosphate groups of a gRNA can be replaced with phosphorothioate groups. Alternatively or additionally, a modified gRNA can comprise at least one modified residue at or near the 5’ end. Alternatively or additionally, a modified gRNA can comprise at least one modified residue at or near the 3’ end. [00410] Some gRNAs comprise one, two, three or more modified residues. For example, at least 5%, at least 10%, at least 15%, at least 20%, at least 25%, at least 30%, at least 35%, at least 40%, at least 45%, at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% of the positions in a modified gRNA can be modified nucleosides or nucleotides. [00411] Unmodified nucleic acids can be prone to degradation. Exogenous nucleic acids can also induce an innate immune response. Modifications can help introduce stability and reduce immunogenicity. Some gRNAs described herein can contain one or more Attorney Docket No.250298.000780 modified nucleosides or nucleotides to introduce stability toward intracellular or serum-based nucleases. Some modified gRNAs described herein can exhibit a reduced innate immune response when introduced into a population of cells. [00412] The gRNAs disclosed herein can comprise a backbone modification in which the phosphate group of a modified residue can be modified by replacing one or more of the oxygens with a different substituent. The modification can include the wholesale replacement of an unmodified phosphate moiety with a modified phosphate group as described herein. Backbone modifications of the phosphate backbone can also include alterations that result in either an uncharged linker or a charged linker with unsymmetrical charge distribution. [00413] Examples of modified phosphate groups include, phosphorothioate, phosphoroselenates, borano phosphates, borano phosphate esters, hydrogen phosphonates, phosphoroamidates, alkyl or aryl phosphonates and phosphotriesters. The phosphorous atom in an unmodified phosphate group is achiral. However, replacement of one of the non-bridging oxygens with one of the above atoms or groups of atoms can render the phosphorous atom chiral. The stereogenic phosphorous atom can possess either the “R” configuration (Rp) or the “S” configuration (Sp). The backbone can also be modified by replacement of a bridging oxygen, (i.e., the oxygen that links the phosphate to the nucleoside), with nitrogen (bridged phosphoroamidates), sulfur (bridged phosphorothioates) and carbon (bridged methylenephosphonates). The replacement can occur at either linking oxygen or at both of the linking oxygens. [00414] The phosphate group can be replaced by non-phosphorus containing connectors in certain backbone modifications. In some embodiments, the charged phosphate group can be replaced by a neutral moiety. Examples of moieties which can replace the phosphate group can include, without limitation, e.g., methyl phosphonate, hydroxylamino, siloxane, carbonate, carboxymethyl, carbamate, amide, thioether, ethylene oxide linker, sulfonate, sulfonamide, thioformacetal, formacetal, oxime, methyleneimino, methylenemethylimino, methylenehydrazo, methylenedimethylhydrazo and methyleneoxymethylimino. [00415] Scaffolds that can mimic nucleic acids can also be constructed wherein the phosphate linker and ribose sugar are replaced by nuclease resistant nucleoside or nucleotide surrogates. Such modifications may comprise backbone and sugar modifications. In some embodiments, the nucleobases can be tethered by a surrogate backbone. Examples Attorney Docket No.250298.000780 can include, without limitation, the morpholino, cyclobutyl, pyrrolidine and peptide nucleic acid (PNA) nucleoside surrogates. [00416] The modified nucleosides and modified nucleotides can include one or more modifications to the sugar group (a sugar modification). For example, the 2’ hydroxyl group (OH) can be modified (e.g., replaced with a number of different oxy or deoxy substituents. Modifications to the 2’ hydroxyl group can enhance the stability of the nucleic acid since the hydroxyl can no longer be deprotonated to form a 2’-alkoxide ion. [00417] Examples of 2’ hydroxyl group modifications can include alkoxy or aryloxy (OR, wherein “R” can be, e.g., alkyl, cycloalkyl, aryl, aralkyl, heteroaryl or a sugar); polyethyleneglycols (PEG), O(CH2CH2O)nCH2CH2OR wherein R can be, e.g., H or optionally substituted alkyl, and n can be an integer from 0 to 20 (e.g., from 0 to 4, from 0 to 8, from 0 to 10, from 0 to 16, from 1 to 4, from 1 to 8, from 1 to 10, from 1 to 16, from 1 to 20, from 2 to 4, from 2 to 8, from 2 to 10, from 2 to 16, from 2 to 20, from 4 to 8, from 4 to 10, from 4 to 16, and from 4 to 20). The 2’ hydroxyl group modification can be 2’-O-Me. Likewise, the 2’ hydroxyl group modification can be a 2’-fluoro modification, which replaces the 2’ hydroxyl group with a fluoride. The 2’ hydroxyl group modification can include locked nucleic acids (LNA) in which the 2’ hydroxyl can be connected, e.g., by a C1-6 alkylene or C1-6 heteroalkylene bridge, to the 4’ carbon of the same ribose sugar, where exemplary bridges can include methylene, propylene, ether, or amino bridges; O-amino (wherein amino can be, e.g., NH2; alkylamino, dialkylamino, heterocyclyl, arylamino, diarylamino, heteroarylamino, or diheteroarylamino, ethylenediamine, or polyamino) and aminoalkoxy, O(CH2)n-amino, (wherein amino can be, e.g., NH2; alkylamino, dialkylamino, heterocyclyl, arylamino, diarylamino, heteroarylamino, or diheteroarylamino, ethylenediamine, or polyamino). The 2’ hydroxyl group modification can include unlocked nucleic acids (UNA) in which the ribose ring lacks the C2’-C3’ bond. The 2’ hydroxyl group modification can include the methoxyethyl group (MOE), (OCH2CH2OCH3, e.g., a PEG derivative). [00418] Deoxy 2’ modifications can include hydrogen (i.e. deoxyribose sugars, e.g., at the overhang portions of partially dsRNA); halo (e.g., bromo, chloro, fluoro, or iodo); amino (wherein amino can be, e.g., NH2; alkylamino, dialkylamino, heterocyclyl, arylamino, diarylamino, heteroarylamino, diheteroarylamino, or amino acid); NH(CH2CH2NH)nCH2CH2- amino (wherein amino can be, e.g., as described herein), -NHC(O)R (wherein R can be, e.g., alkyl, cycloalkyl, aryl, aralkyl, heteroaryl or sugar), cyano; mercapto; alkyl-thio-alkyl; Attorney Docket No.250298.000780 thioalkoxy; and alkyl, cycloalkyl, aryl, alkenyl and alkynyl, which may be optionally substituted with e.g., an amino as described herein. [00419] The sugar modification can comprise a sugar group which may also contain one or more carbons that possess the opposite stereochemical configuration than that of the corresponding carbon in ribose. Thus, a modified nucleic acid can include nucleotides containing e.g., arabinose, as the sugar. The modified nucleic acids can also include abasic sugars. These abasic sugars can also be further modified at one or more of the constituent sugar atoms. The modified nucleic acids can also include one or more sugars that are in the L form (e.g. L- nucleosides). [00420] The modified nucleosides and modified nucleotides described herein, which can be incorporated into a modified nucleic acid, can include a modified base, also called a nucleobase. Examples of nucleobases include, but are not limited to, adenine (A), guanine (G), cytosine (C), and uracil (U). These nucleobases can be modified or wholly replaced to provide modified residues that can be incorporated into modified nucleic acids. The nucleobase of the nucleotide can be independently selected from a purine, a pyrimidine, a purine analog, or pyrimidine analog. In some embodiments, the nucleobase can include, for example, naturally-occurring and synthetic derivatives of a base. [00421] In a dual guide RNA, each of the crRNA and the tracrRNA can contain modifications. Such modifications may be at one or both ends of the crRNA and/or tracrRNA. In a sgRNA, one or more residues at one or both ends of the sgRNA may be chemically modified, and/or internal nucleosides may be modified, and/or the entire sgRNA may be chemically modified. Some gRNAs comprise a 5’ end modification. Some gRNAs comprise a 3’ end modification. [00422] The guide RNAs disclosed herein can comprise one of the modification patterns disclosed in WO 2018/107028 A1, herein incorporated by reference in its entirety for all purposes. The guide RNAs disclosed herein can also comprise one of the structures/modification patterns disclosed in US 2017/0114334, herein incorporated by reference in its entirety for all purposes. The guide RNAs disclosed herein can also comprise one of the structures/modification patterns disclosed in WO 2017/136794, WO 2017/004279, US 2018/0187186, or US 2019/0048338, each of which is herein incorporated by reference in its entirety for all purposes. [00423] As one example, nucleotides at the 5’ or 3’ end of a guide RNA can include phosphorothioate linkages (e.g., the bases can have a modified phosphate group that is a Attorney Docket No.250298.000780 phosphorothioate group). For example, a guide RNA can include phosphorothioate linkages between the 2, 3, or 4 terminal nucleotides at the 5’ or 3’ end of the guide RNA. As another example, nucleotides at the 5’ and/or 3’ end of a guide RNA can have 2’-O-methyl modifications. For example, a guide RNA can include 2’-O-methyl modifications at the 2, 3, or 4 terminal nucleotides at the 5’ and/or 3’ end of the guide RNA (e.g., the 5’ end). See, e.g., WO 2017/173054 A1 and Finn et al. (2018) Cell Rep. 22(9):2227-2235, each of which is herein incorporated by reference in its entirety for all purposes. Other possible modifications are described in more detail elsewhere herein. In a specific example, a guide RNA includes 2’-O-methyl analogs and 3’ phosphorothioate internucleotide linkages at the first three 5’ and 3’ terminal RNA residues. Such chemical modifications can, for example, provide greater stability and protection from exonucleases to guide RNAs, allowing them to persist within cells for longer than unmodified guide RNAs. Such chemical modifications can also, for example, protect against innate intracellular immune responses that can actively degrade RNA or trigger immune cascades that lead to cell death. [00424] As one example, any of the guide RNAs described herein can comprise at least one modification. In one example, the at least one modification comprises a 2’-O-methyl (2’- O-Me) modified nucleotide, a phosphorothioate (PS) bond between nucleotides, a 2’-fluoro (2’-F) modified nucleotide, or a combination thereof. For example, the at least one modification can comprise a 2’-O-methyl (2’-O-Me) modified nucleotide. Alternatively or additionally, the at least one modification can comprise a phosphorothioate (PS) bond between nucleotides. Alternatively or additionally, the at least one modification can comprise a 2’-fluoro (2’-F) modified nucleotide. In one example, a guide RNA described herein comprises one or more 2’-O-methyl (2’-O-Me) modified nucleotides and one or more phosphorothioate (PS) bonds between nucleotides. [00425] The modifications can occur anywhere in the guide RNA. As one example, the guide RNA comprises a modification at one or more of the first five nucleotides at the 5’ end of the guide RNA, the guide RNA comprises a modification at one or more of the last five nucleotides of the 3’ end of the guide RNA, or a combination thereof. For example, the guide RNA can comprise phosphorothioate bonds between the first four nucleotides of the guide RNA, phosphorothioate bonds between the last four nucleotides of the guide RNA, or a combination thereof. Alternatively or additionally, the guide RNA can comprise 2’-O-Me modified nucleotides at the first three nucleotides at the 5’ end of the guide RNA, can Attorney Docket No.250298.000780 comprise 2’-O-Me modified nucleotides at the last three nucleotides at the 3’ end of the guide RNA, or a combination thereof. [00426] In one example, a modified gRNA can comprise the following sequence: mN*mN*mN*NNNNNNNNNNNNNNNNNGUUUUAGAmGmCmUmAmGmAmAmAmUmAm GmCAAGUUAAAAUAAGGCUAGUCCGUUAUCAmAmCmUmUmGmAmAmAmAmAmGmU mGmGmCmAmCmCmGmAmGmUmCmGmGmUmGmCmU*mU*mU*mU (SEQ ID NO: 637), where “N” may be any natural or non-natural nucleotide. The totality of N residues can comprise a DNA-targeting segment as described herein. The terms “mA,” “mC,” “mU,” and “mG” denote a nucleotide (A, C, U, and G, respectively) that has been modified with 2’-O-Me. The symbol “*” depicts a phosphorothioate modification. In certain embodiments, A, C, G, U, and N independently denote a ribose sugar, i.e., 2’-OH. In certain embodiments in the context of a modified sequence, A, C, G, U, and N denote a ribose sugar, i.e., 2’-OH. A phosphorothioate linkage or bond refers to a bond where a sulfur is substituted for one nonbridging phosphate oxygen in a phosphodiester linkage, for example in the bonds between nucleotides bases. When phosphorothioates are used to generate oligonucleotides, the modified oligonucleotides may also be referred to as S-oligos. The terms A*, C*, U*, or G* denote a nucleotide that is linked to the next (e.g., 3’) nucleotide with a phosphorothioate bond. The terms “mA*,” “mC*,” “mU*,” and “mG*” denote a nucleotide (A, C, U, and G, respectively) that has been substituted with 2’-O-Me and that is linked to the next (e.g., 3’) nucleotide with a phosphorothioate bond. [00427] Another chemical modification that has been shown to influence nucleotide sugar rings is halogen substitution. For example, 2’-fluoro (2’-F) substitution on nucleotide sugar rings can increase oligonucleotide binding affinity and nuclease stability. Abasic nucleotides refer to those which lack nitrogenous bases. Inverted bases refer to those with linkages that are inverted from the normal 5’ to 3' linkage (i.e., either a 5’ to 5’ linkage or a 3’ to 3’ linkage). [00428] An abasic nucleotide can be attached with an inverted linkage. For example, an abasic nucleotide may be attached to the terminal 5’ nucleotide via a 5’ to 5’ linkage, or an abasic nucleotide may be attached to the terminal 3’ nucleotide via a 3’ to 3’ linkage. An inverted abasic nucleotide at either the terminal 5’ or 3’ nucleotide may also be called an inverted abasic end cap. [00429] In one example, one or more of the first three, four, or five nucleotides at the 5’ terminus, and one or more of the last three, four, or five nucleotides at the 3’ terminus are Attorney Docket No.250298.000780 modified. The modification can be, for example, a 2’-O-Me, 2’-F, inverted abasic nucleotide, phosphorothioate bond, or other nucleotide modification well known to increase stability and/or performance. [00430] In another example, the first four nucleotides at the 5’ terminus, and the last four nucleotides at the 3’ terminus can be linked with phosphorothioate bonds. [00431] In another example, the first three nucleotides at the 5’ terminus, and the last three nucleotides at the 3’ terminus can comprise a 2’-O-methyl (2’-O-Me) modified nucleotide. In another example, the first three nucleotides at the 5’ terminus, and the last three nucleotides at the 3’ terminus comprise a 2’-fluoro (2’-F) modified nucleotide. In another example, the first three nucleotides at the 5’ terminus, and the last three nucleotides at the 3’ terminus comprise an inverted abasic nucleotide. [00432] Guide RNAs can be provided in any form. For example, the gRNA can be conjugated to the p75NTR binding protein disclosed herein, such as an scFv or an antibody or an antigen-binding fragment thereof, in the form of RNA, either as two molecules (separate crRNA and tracrRNA) or as one molecule (sgRNA), and optionally in the form of a complex with a Cas protein. [00433] The gRNA can be conjugated to the p75NTR binding protein disclosed herein, such as an scFv or an antibody or an antigen-binding fragment thereof, in the form of DNA encoding the gRNA. The DNA encoding the gRNA can encode a single RNA molecule (sgRNA) or separate RNA molecules (e.g., separate crRNA and tracrRNA). In the latter case, the DNA encoding the gRNA can be provided as one DNA molecule or as separate DNA molecules encoding the crRNA and tracrRNA, respectively. [00434] Multiple gRNAs can be conjugated to the p75NTR binding protein disclosed herein, such as an scFv or an antibody or an antigen-binding fragment thereof. The gRNAs can be the same or different gRNAs, or can target the same gene or different genes. In some embodiments, 1, 2, 3, 4, 5 or more guide RNAs are conjugated to the p75NTR binding protein disclosed herein, such as an scFv or an antibody or an antigen-binding fragment thereof. [00435] Alternatively, the gRNA, either in the form of RNA or DNA, may be incorporated into a carrier (e.g., liposomes or LNPs) which is conjugated to the p75NTR binding protein disclosed herein, such as an scFv or an antibody or an antigen-binding fragment thereof. The carrier can further comprise a Cas protein, such as a Cas9 protein, or a nucleic acid (e.g., mRNA) encoding a Cas protein. Carriers such as liposomes or lipid nanoparticles are described in further detail below. Attorney Docket No.250298.000780 [00436] Multiple gRNAs can be incorporated into a carrier (e.g., liposome or LNP) which is conjugated to the p75NTR binding protein disclosed herein, such as an scFv or an antibody or an antigen-binding fragment thereof. The gRNAs can be the same or different gRNAs, or can target the same gene or different genes. In some embodiments, 1, 2, 3, 4, 5 or more guide RNAs are incorporated into a carrier (e.g., liposome or LNP) which is conjugated to the p75NTR binding protein disclosed herein, such as an scFv or an antibody or an antigen-binding fragment thereof. [00437] When a gRNA is provided in the form of DNA, the gRNA after being delivered to the target cell can be transiently, conditionally, or constitutively expressed in the cell. DNAs encoding gRNAs can be stably integrated into the genome of the cell and operably linked to a promoter active in the cell. Alternatively, DNAs encoding gRNAs can be operably linked to a promoter in an expression construct. For example, the DNA encoding the gRNA can be in a vector comprising a heterologous nucleic acid, such as a nucleic acid encoding a Cas protein. Alternatively, it can be in a vector or a plasmid that is separate from the vector comprising the nucleic acid encoding the Cas protein. Promoters that can be used in such expression constructs include promoters active, for example, in one or more of a eukaryotic cell, a human cell, a non-human cell, a mammalian cell, a non-human mammalian cell, a rodent cell, a mouse cell, a rat cell, a pluripotent cell, an embryonic stem (ES) cell, an adult stem cell, a developmentally restricted progenitor cell, an induced pluripotent stem (iPS) cell, or a one-cell stage embryo. Such promoters can be, for example, conditional promoters, inducible promoters, constitutive promoters, or tissue-specific promoters. Such promoters can also be, for example, bidirectional promoters. Specific examples of suitable promoters include an RNA polymerase III promoter, such as a human U6 promoter, a rat U6 polymerase III promoter, or a mouse U6 polymerase III promoter. [00438] Alternatively, gRNAs can be prepared by various other methods. For example, gRNAs can be prepared by in vitro transcription using, for example, T7 RNA polymerase (see, e.g., WO 2014/089290 and WO 2014/065596, each of which is herein incorporated by reference in its entirety for all purposes). Guide RNAs can also be a synthetically produced molecule prepared by chemical synthesis. For example, a guide RNA can be chemically synthesized to include 2’-O-methyl analogs and 3’ phosphorothioate internucleotide linkages at the first three 5’ and 3’ terminal RNA residues. [00439] Guide RNAs (or nucleic acids encoding guide RNAs) can be in compositions comprising one or more guide RNAs (e.g., 1, 2, 3, 4, or more guide RNAs) and a carrier Attorney Docket No.250298.000780 increasing the stability of the guide RNA (e.g., prolonging the period under given conditions of storage (e.g., -20°C, 4°C, or ambient temperature) for which degradation products remain below a threshold, such below 0.5% by weight of the starting nucleic acid or protein; or increasing the stability in vivo). Non-limiting examples of such carriers include poly(lactic acid) (PLA) microspheres, poly(D,L-lactic-coglycolic-acid) (PLGA) microspheres, liposomes, micelles, inverse micelles, lipid cochleates, and lipid microtubules. Such compositions can further comprise a Cas protein, such as a Cas9 protein, or a nucleic acid encoding a Cas protein. [00440] Target DNAs for guide RNAs include nucleic acid sequences present in a DNA to which a DNA-targeting segment of a gRNA will bind, provided sufficient conditions for binding exist. Suitable DNA/RNA binding conditions include physiological conditions normally present in a cell. Other suitable DNA/RNA binding conditions (e.g., conditions in a cell-free system) are known in the art (see, e.g., Molecular Cloning: A Laboratory Manual, 3rd Ed. (Sambrook et al., Harbor Laboratory Press 2001), herein incorporated by reference in its entirety for all purposes). The strand of the target DNA that is complementary to and hybridizes with the gRNA can be called the “complementary strand,” and the strand of the target DNA that is complementary to the “complementary strand” (and is therefore not complementary to the Cas protein or gRNA) can be called “noncomplementary strand” or “template strand”. [00441] The target DNA includes both the sequence on the complementary strand to which the guide RNA hybridizes and the corresponding sequence on the non-complementary strand (e.g., adjacent to the protospacer adjacent motif (PAM)). The term “guide RNA target sequence” as used herein refers specifically to the sequence on the non-complementary strand corresponding to (i.e., the reverse complement of) the sequence to which the guide RNA hybridizes on the complementary strand. That is, the guide RNA target sequence refers to the sequence on the non-complementary strand adjacent to the PAM (e.g., upstream or 5’ of the PAM in the case of Cas9). A guide RNA target sequence is equivalent to the DNA- targeting segment of a guide RNA, but with thymines instead of uracils. As one example, a guide RNA target sequence for an SpCas9 enzyme can refer to the sequence upstream of the 5’-NGG-3’ PAM on the non-complementary strand. A guide RNA is designed to have complementarity to the complementary strand of a target DNA, where hybridization between the DNA-targeting segment of the guide RNA and the complementary strand of the target DNA promotes the formation of a CRISPR complex. Full complementarity is not necessarily Attorney Docket No.250298.000780 required, provided that there is sufficient complementarity to cause hybridization and promote formation of a CRISPR complex. If a guide RNA is referred to herein as targeting a guide RNA target sequence, what is meant is that the guide RNA hybridizes to the complementary strand sequence of the target DNA that is the reverse complement of the guide RNA target sequence on the non-complementary strand. [00442] A target DNA or guide RNA target sequence can comprise any polynucleotide, and can be located, for example, in the nucleus or cytoplasm of a cell or within an organelle of a cell, such as a mitochondrion or chloroplast. A target DNA or guide RNA target sequence can be any nucleic acid sequence endogenous or exogenous to a cell. The guide RNA target sequence can be a sequence coding a gene product (e.g., a protein) or a non-coding sequence (e.g., a regulatory sequence) or can include both. [00443] The target sequence (e.g., guide RNA target sequence) for the DNA-binding protein can be anywhere within a targeted gene that is suitable for altering expression of the targeted gene. As one example, the target sequence can be within a regulatory element, such as an enhancer or promoter, or can be in proximity to a regulatory element. For example, the target sequence can be within about 10, 20, 30, 40, 50, 100, 200, 300, 400, 500, or 1,000 nucleotides of the start codon. [00444] Site-specific binding and cleavage of a target DNA by a Cas protein can occur at locations determined by both (i) base-pairing complementarity between the guide RNA and the complementary strand of the target DNA and (ii) a short motif, called the protospacer adjacent motif (PAM), in the non-complementary strand of the target DNA. The PAM can flank the guide RNA target sequence. Optionally, the guide RNA target sequence can be flanked on the 3’ end by the PAM (e.g., for Cas9). Alternatively, the guide RNA target sequence can be flanked on the 5’ end by the PAM (e.g., for Cpf1). For example, the cleavage site of Cas proteins can be about 1 to about 10 or about 2 to about 5 base pairs (e.g, 3 base pairs) upstream or downstream of the PAM sequence (e.g., within the guide RNA target sequence). In the case of SpCas9, the PAM sequence (i.e., on the non-complementary strand) can be 5’-NiGG-3’, where Ni is any DNA nucleotide, and where the PAM is immediately 3’ of the guide RNA target sequence on the non-complementary strand of the target DNA. As such, the sequence corresponding to the PAM on the complementary strand (i.e., the reverse complement) would be 5’-CCN2-3’, where N2 is any DNA nucleotide and is immediately 5’ of the sequence to which the DNA-targeting segment of the guide RNA hybridizes on the complementary strand of the target DNA. In some such cases, Ni and N2 can be Attorney Docket No.250298.000780 complementary and the Ni- N2 base pair can be any base pair (e.g., Ni=C and N2=G; Ni=G and N2=C; Ni=A and N2=T; or Ni=T, and N2=A). In the case of Cas9 from S. aureus, the PAM can be NNGRRT or NNGRR, where N can A, G, C, or T, and R can be G or A. In the case of Cas9 from C. jejuni, the PAM can be, for example, NNNNACAC or NNNNRYAC, where N can be A, G, C, or T, and R can be G or A. In some cases (e.g., for FnCpf1), the PAM sequence can be upstream of the 5’ end and have the sequence 5’-TTN-3. In the case of DpbCasX, the PAM can have the sequence 5’-TTCN-3’. In the case of CasΦ, the PAM can have the sequence 5’-TBN-3’, wherein B is G, T, or C. [00445] An example of a guide RNA target sequence is a 20-nucleotide DNA sequence immediately preceding an NGG motif recognized by an SpCas9 protein. The guanine at the 5’ end can facilitate transcription by RNA polymerase in cells. Other examples of guide RNA target sequences plus PAMs can include two guanine nucleotides at the 5’ end to facilitate efficient transcription by T7 polymerase in vitro. See, e.g., WO 2014/065596, herein incorporated by reference in its entirety for all purposes. Other guide RNA target sequences plus PAMs can have between 4-22 nucleotides in length, including the 5’ G or GG and the 3’ GG or NGG. Yet other guide RNA target sequences plus PAMs can have between 14 and 20 nucleotides in length. [00446] Formation of a CRISPR complex hybridized to a target DNA can result in cleavage of one or both strands of the target DNA within or near the region corresponding to the guide RNA target sequence (i.e., the guide RNA target sequence on the non- complementary strand of the target DNA and the reverse complement on the complementary strand to which the guide RNA hybridizes). For example, the cleavage site can be within the guide RNA target sequence (e.g., at a defined location relative to the PAM sequence). The “cleavage site” includes the position of a target DNA at which a Cas protein produces a single- strand break or a double-strand break. The cleavage site can be on only one strand (e.g., when a nickase is used) or on both strands of a double- stranded DNA. Cleavage sites can be at the same position on both strands (producing blunt ends; e.g., Cas9) or can be at different sites on each strand (producing staggered ends (i.e., overhangs); e.g., Cpf1). Staggered ends can be produced, for example, by using two Cas proteins, each of which produces a single-strand break at a different cleavage site on a different strand, thereby producing a double-strand break. For example, a first nickase can create a single-strand break on the first strand of double-stranded DNA (dsDNA), and a second nickase can create a single-strand break on the second strand of dsDNA such that overhanging sequences are Attorney Docket No.250298.000780 created. In some cases, the guide RNA target sequence or cleavage site of the nickase on the first strand is separated from the guide RNA target sequence or cleavage site of the nickase on the second strand by at least 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25, 30, 40, 50, 75, 100, 250, 500, or 1,000 base pairs. Other Types of Polynucleotide Molecules [00447] In some embodiments, a molecular cargo, e.g., a polynucleotide molecule described herein may comprise a ribozyme (ribonucleic acid enzyme). Without wishing to be bound by theory, a ribozyme is a molecule, commonly an RNA molecule, that is capable of performing specific biochemical reactions, akin to the action of protein enzymes. Ribozymes comprise molecules possessing catalytic activities such as, but not limited to, the capacity to cleave at specific phosphodiester linkages in RNA molecules to which they have hybridized, e.g., RNA-containing substrates, IncRNAs, mRNAs, and ribozymes. [00448] Ribozymes may take on one of several physical structures, one such structure is termed "hammerhead". A hammerhead ribozyme can comprise, e.g., a catalytic core comprising nine conserved bases, two regions complementary to the target RNA flanking regions the catalytic core, and a double-stranded stem and loop structure (stem-loop II).. The flanking regions may permit the binding of the ribozyme to the target RNA, in particular, by forming double-stranded stems I and III. Cleavage may occur in trans (cleavage of an RNA substrate other than that containing the ribozyme) or in cis (cleavage of the same RNA molecule that contains the hammerhead motif) adjacent to a specific ribonucleotide triplet by a transesterification reaction from a 3', 5'- phosphate diester to a 2', 3'-cyclic phosphate diester. In certain embodiments, this catalytic activity may require the presence of specific, highly conserved sequences in the catalytic region of the ribozyme. [00449] Modifications in ribozyme structure can include the replacement or substitution of non-core portions of the molecule with non-nucleotidic molecules. As a non-limiting example, Ma et al. (Biochem. (1993) 32:1751-1758; Nucleic Acids Res. (1993) 21:2585- 2589) replaced the six-nucleotide loop of the TAR ribozyme hairpin with non-nucleotidic, ethylene glycol-related linkers. Thomson et al. (Nucleic Acids Res. (1993) 21:5600-5603) replaced loop II with linear, non-nucleotidic linkers of 13, 17, and 19 atoms in length. Benseler et al. (J. Am. Chem. Soc. (1993) 115:8483-8484) describes hammerhead-like molecules where two of the base pairs of stem II, and all four of the nucleotides of loop II may be replaced Attorney Docket No.250298.000780 with non-nucleoside linkers based on bis(propanediol) phosphate, hexaethylene glycol, bis(triethylene glycol) phosphate, propanediol, or tris(propanediol)bisphosphate. [00450] Ribozyme polynucleotides may be generated using any of various suitable methods known in the art (see, e.g., U.S. Pat. Nos 5,436,143 and 5,650,502; and PCT Publications Nos. WO94/13688; WO91/18624, WO92/01806; and WO 92/07065) or can be obtained from commercial sources (e.g., US Biochemicals), the contents of each of which are incorporated herein by reference in their entirety. In some embodiments, the ribozyme polynucleotide described herein can incorporate nucleotide analogs, e.g., to increase the resistance of the oligonucleotide to degradation by nucleases in a cell. The ribozyme may be synthesized in any known manner, e.g., by use of a commercially available synthesizer produced, e.g., by Applied Biosystems, Inc. or Milligen. The ribozyme RNA sequences maybe synthesized conventionally, for example, by using RNA polymerases such as T7 or SP6.The ribozyme may also be produced in recombinant vectors by suitable means. [00451] In some embodiments, internucleotidic phosphorus atoms of the polynucleotide molecules disclosed herein may be chiral, and the properties of the polynucleotides by adjusted based on the configuration of the chiral phosphorus atoms. In some embodiments, appropriate methods may be used to synthesize P-chiral oligonucleotide analogs in a stereocontrolled manner (e.g., as described in Oka N, Wada T, Stereocontrolled synthesis of oligonucleotide analogs containing chiral internucleotidic phosphorus atoms. Chem Soc Rev.2011 Dec;40(12):5829-43, the contents of which are incorporated herein by reference in their entirety). In some embodiments, phosphorothioate-containing oligonucleotides may comprise nucleoside units that can be joined together by either substantially all Rp or substantially all Sp phosphorothioate inter-sugar linkages. In some embodiments, such phosphorothioate oligonucleotides comprising substantially chirally pure inter-sugar linkages may be produced via chemical synthesis or enzymatic approaches, as disclosed, e.g., in U.S. Patent No.5,587,261, the contents of which are incorporated herein by reference in their entirety. In some embodiments, chirally controlled polynucleotide molecules described may provide selective cleavage patterns of a target nucleic acid. As a non-limiting example, a chirally controlled polynucleotide molecule may provide single site cleavage within a complementary sequence of a nucleic acid, as disclosed, for example, in US Patent Publication No.2017/0037399, the contents of which are incorporated herein by reference in their entirety. Attorney Docket No.250298.000780 [00452] In some embodiments, the polynucleotide molecule described herein may be a morpholino-based compound. In some embodiments, the morpholino-based oligomeric compound is a phosphorodiamidate morpholino oligomer (PMO) (e.g., as described in Iverson, Curr. Opin. Mol. Ther., 3:235-238, 2001; and Wang et al., J. Gene Med., 12:354- 364, 2010; the disclosures of which are incorporated herein by reference in their entireties). Morpholino-based oligomeric compounds are also described in, e.g., U.S. Patent No. 5,034,506, and Genesis, volume 30, issue 3, 2001; Heasman, J., Dev. Biol., 2002, 243, 209- 214; Dwaine A. Braasch and David R. Corey, Biochemistry, 2002, 41(14), 4503-4510); Nasevicius et al., Nat. Genet., 2000, 26, 216-220; Lacerra et al., Proc. Natl. Acad. Sci., 2000, 97, 9591-9596, the disclosures of which are incorporated herein by reference in their entireties. [00453] In some embodiments, a polynucleotide molecule described herein may comprise an aptamer. An aptamer may comprise any nucleic acid which specifically binds specifically to a target, e.g., protein, a small molecule, nucleic acid in a cell. In some embodiments, the aptamer is a DNA aptamer or an RNA aptamer. In some embodiments, a nucleic acid aptamer may comprise a single-stranded RNA (ssDNA or ssRNA) or DNA. In certain embodiments, a single-stranded nucleic acid aptamer may form loop(s) and/or helice(s) structures. The nucleic acid that forms the nucleic acid aptamer may comprise naturally occurring nucleotides, modified nucleotides with hydrocarbon or PEG linkers inserted between one or more nucleotides, modified nucleotides, naturally occurring nucleotides with hydrocarbon linkers (e.g., an alkylene) or a polyether linker (e.g., a PEG linker) inserted between one or more nucleotides, or a combination of thereof. Aptamers and method of producing aptamers are described in, e.g., U.S. Patent Nos.8,318,438, 5,650,275; 5,683,867; 5,670,637; 5,696,249; 5,789,157; 5,843,653; 5,270,163; 5,567,588, 5,864,026; 5,989,823; 6,569,630; and PCT Publication No. WO 99/31275, Lorsch and Szostak, 1996; Jayasena, 1999; each incorporated herein by reference. [00454] In some embodiments, a polynucleotide molecule described herein may be a mixmer or comprise a mixmer sequence pattern. In some embodiments, mixmers can be polynucleotides that comprise both naturally and non-naturally occurring nucleosides or comprise two different types of non- naturally occurring nucleosides commonly in an alternating pattern. Mixmers may have higher binding affinity than unmodified polynucleotides and may be used, in particular, to specifically bind a target molecule, e.g., to block a binding site on the target molecule. In some embodiments, mixmers may not recruit an rNase to a Attorney Docket No.250298.000780 target molecule and hence do not promote cleavage of the target molecule. Such polynucleotides that may be incapable of recruiting, e.g., RNase H have been described, e.g., see WO2007/112753 or WO2007/112754. [00455] In some embodiments, a mixmer disclosed herein may comprise a repeating pattern of naturally occurring nucleosides and nucleoside analogues, or, e.g., one type of nucleoside analogue and a second type of nucleoside analogue. Yet, a mixmer need not comprise a repeating pattern and may instead comprise any arrangement of modified naturally occurring nucleosides and nucleosides or any arrangement of one type of modified nucleoside and a second type of modified nucleoside. Such repeating pattern, may, for example comprise every second or every third nucleoside as a modified nucleoside, e.g., LNA. In certain embodiments, the remaining nucleosides may be naturally occurring nucleosides, e.g., DNA, or may be a 2' substituted nucleoside analogue, e.g., 2' fluoro analogues or 2'-MOE, or any other some modified nucleoside(s) disclosed herein. It is understood that the repeating pattern of modified nucleoside, such as LNA units, may be combined with modified nucleoside at fixed positions (e.g., at the 5' and/or 3' termini). [00456] In some embodiments, a mixmer may not comprise a region of more than 6. more than 5, more than 4, more than 3, or more than 2 consecutive naturally occurring nucleosides (e.g., DNA nucleosides). In some embodiments, the mixmer may comprise at least a region comprising at least two consecutive modified nucleosides, for example, at least two consecutive LNAs. In some embodiments, the mixmer may comprise at least a region consisting of at least three consecutive modified nucleoside units, e.g., at least three consecutive LNAs. [00457] In some embodiments, the mixmer may not comprise a region of more than 8, more than 7, more than 6, more than 5, more than 4, more than 3, or more than 2 consecutive nucleoside analogues, e.g., LNAs. In some embodiments, LNA units may be replaced with other nucleoside analogues including, but not limited to, those referred to herein. [00458] In some embodiments, mixmers may be designed to comprise a mixture of affinity enhancing modified nucleosides, such as, without limitation, in LNA nucleosides and 2'-O-Me nucleosides. In some embodiments, a mixmer may comprise modified internucleoside linkages (e.g., phosphorothioate internucleoside linkages or other linkages) between at least two, at least three, at least four, at least five, at least six or more nucleosides. [00459] In some embodiments, a mixmer may comprise one or more morpholino nucleosides. In some embodiments, a mixmer may comprise morpholino nucleosides mixed Attorney Docket No.250298.000780 (e.g., in an alternating manner) with one or more other nucleosides (e.g., DNA, RNA nucleosides) or modified nucleosides (e.g., 2'-O-Me nucleosides, LNA). [00460] In some embodiments, mixmers may be useful for splice correcting or exon skipping, for example, as described in Chen S. et al., Molecules 2016, 21, 1582, Touznik A., et al., Scientific Reports, volume 7, Article number: 3672 (2017), the contents of each which are incorporated herein by reference. [00461] A mixmer may be produced using any suitable method. Preparation of mixmers is described in, for example, U.S. Patent No. 7687617, and U.S. Patent Application Publication Nos. US2012/0322851, US2009/0209748, US2009/0298916, US2006/0128646, and US2011/0077288. Additional examples of multimers are described, for example, in US Patent No.5,693,773, US Patent Application Publication Nos.2015/0247141; 2015/0315588; US 2011/0158937; the contents of each of which are incorporated herein by reference in their entireties. [00462] In some embodiments, polynucleotide molecules comprising molecular cargos disclosed herein may comprise multimers (e.g., concatemers) of two or more polynucleotide molecules connected, e.g., by a linker. Polynucleotides in a multimer may be the same or different (e.g., targeting different sites on the same gene different genes or products thereof). [00463] In some embodiments, multimers may comprise two or more polynucleotide molecules linked together by a cleavable linker. In some embodiments, multimers may comprise two or more polynucleotide molecules linked together, e.g., by a non-cleavable linker. In some embodiments, a multimer may comprise 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20 or more polynucleotide molecules linked together. In some embodiments, a multimer may comprises 2 to 5, 2 to 10, 4 to 20 or 5 to 30 polynucleotide molecules linked together. [00464] In some embodiments, a multimer may comprises two or more polynucleotide molecules linked in a linear arrangement, e.g., end-to-end. In some embodiments, a multimer may comprises two or more polynucleotide molecules linked end-to-end via a polynucleotide- based linker (e.g., an abasic linker, a poly-dT linker). In some embodiments, a multimer comprises a 3’ end of one polynucleotide linked to a 3’ end of another polynucleotide. In some embodiments, a multimer may comprise a 5’ end of one polynucleotide linked to a 3’ end of another polynucleotide. In some embodiments, a multimer comprises a 5’ end of one polynucleotide linked to a 5’ end of another polynucleotide . In some embodiments, multimers Attorney Docket No.250298.000780 may comprise a branched structure comprising multiple polynucleotides linked together by a branching linker. [00465] In some embodiments, a polynucleotide molecule of the present disclosure can target splicing. In some embodiments, the polynucleotide can targets splicing by inducing exon skipping and restoring the reading frame within a gene. For example, without limitation, the oligonucleotide may induce skipping of an exon encoding a frameshift mutation and/or an exon that encodes a premature stop codon. In some embodiments, a polynucleotide may induce exon skipping by, e.g., blocking spliceosome recognition of a splice site. In some embodiments, a polynucleotide molecule disclosed herein may induce inclusion of an exon by targeting a splice site inhibitory sequence. In some embodiments, the oligonucleotide promotes inclusion of a particular exon. In some embodiments, exon skipping results in a truncated but functional protein compared to the reference protein. [00466] In some embodiments, the polynucleotide molecule described herein may be a messenger RNA (mRNA). mRNAs comprise an open reading frame that can be translated into a polypeptide (i.e., can serve as a substrate for translation by a ribosome and amino- acylated tRNAs). mRNA can comprise a phosphate-sugar backbone including ribose residues or analogs thereof, e.g., 2’-methoxy ribose residues. In some embodiments, the sugars of an mRNA phosphate-sugar backbone consist essentially of ribose residues, 2’- methoxy ribose residues, or a combination thereof. Bases of an mRNA can be modified bases such as pseudouridine, N-1-methyl-pseudouridine, or other naturally occurring or non- naturally occurring bases. Polypeptide Molecules [00467] In some embodiments, the molecular cargo described herein comprises a polypeptide molecule. When an p75NTR binding protein (e.g., antibody or antigen-binding fragment) described herein is covalently conjugated to a polypeptide molecule, such conjugates may also be referred to as “fusion proteins”. The term “fused” with regard to fused polypeptides refers to polypeptides joined directly or indirectly (e.g., via a linker or other polypeptide). In one embodiment, the fusion protein is encoded by a single nucleic acid that encodes the p75NTR binding protein with the polypeptide molecule. In some embodiments, the polypeptide molecule is an enzyme, a neuroprotective molecule, or an antigen-binding protein that binds to a target other than p75NTR. In some embodiments, the polypeptide molecule is associated with pain, itch, and/or a neurological disease and/or disorder Attorney Docket No.250298.000780 described herein. In some embodiments, the polypeptide molecule is a neurotrophic factor, an antibody or antibody fragment, an antibody receptor fusion protein, or a suppressor of cytokine signaling. [00468] The anti-p75NTR fusion proteins may be useful, for example, for delivery of the fused polypeptide molecule to various tissues (e.g., nervous tissue) and/or cells in the body, including brain cells, spinal cord cells, peripheral nervous system cells e.g., sensory neurons (such as, but not limited to, dorsal root ganglion cells or trigeminal ganglion cells) and/or eye cells (e.g., retinal cells). [00469] Non-limiting examples of polypeptide molecules that can be fused with an p75NTR binding protein described herein can include, e.g., enzymes, neuroprotective proteins and molecules, or other antigen-binding proteins (e.g., antibodies and antigen-binding fragments thereof). Enzymes can include, without limitation, a hydrolase, including esterases, glycosylases, hydrolases that act on ether bonds, peptidases, linear amidases, diphosphatases, ketone hydrolases, halogenases, phosphoamidases, sulfohydrolases, sulfinases, desulfinases, and the like. In some embodiments, the enzyme is a glycosylase, including glycosidases and N-glycosylases. In some embodiments, the enzyme is a glycosidase, including alpha-amylase, beta-amylase, glucan 1,4-alpha-glucosidase, cellulose, endo-1,3(4)-beta-glucanase, inulinase, endo-1,4-beta-xylanase, endo-1,4-b- xylanase, dextranase, chitinase, polygalacturonidase, lysozyme, exo-alpha-sialidase, alpha- glucosidase, beta-glucosidase, alpha-galactosidase, beta-galactosidase, alpha- mannosidase, beta-mannosidase, beta-fructofuranosidase, alpha,alpha-trehalose, beta- glucuronidase, xylan endo-1,3-beta-xylosidase, amylo-alpha-1,6-glucosidase, hyaluronoglucosaminidase, hyaluronoglucuronidase, and the like. [00470] In some embodiments, the present disclosure includes anti-p75NTR fusion proteins, e.g., wherein the antigen-binding protein of the fusion is an antibody or antigen- binding fragment thereof set forth herein, and wherein the molecular cargo is a therapeutic agent useful for treating or preventing pain, itch, e.g., a chronic itch, and/or a neurological disease or disorder. In some embodiments, the neurological disease or disorder is a neurodegenerative disease or disorder, a neurodevelopmental disease or disorder, a chronic neuropathic pain, a chronic ataxia, a physical injury, a neuropsychiatric disease or disorder, or a neurological cancer. In some embodiments, the neurodegenerative disease or disorder is Alzheimer’s disease (AD), Parkinson’s disease (PD), amyotrophic lateral sclerosis (ALS) or multiple sclerosis (MS). In some embodiments, the physical injury is traumatic brain injury, Attorney Docket No.250298.000780 spinal cord injury, stroke, or brain edema. In some embodiments, the neurological cancer is a brain cancer or a peripheral nerve cancer. [00471] In some embodiments, the pain is peripheral chronic pain, a chronic neuropathic pain, somatic pain, chronic post-operative pain, chronic itch, small fiber peripheral neuropathy, chemotherapy-induced neuropathy, painful diabetic-induced neuropathy, post-herpetic neuralgia, osteoarthritis, back pain, joint pain, trigeminal neuralgia, trigeminal pain, temporo-mandibular pain, migraine, dysautonomia, myofascial pain syndrome, or myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). In some embodiments, the chronic neuropathic pain is trigeminal pain or trigeminal neuralgia. [00472] Example methods for preparing a fusion protein comprising an antigen-binding protein are described in, e.g., US Patent No. 11,208,458, US Patent Publication No. US 2019/0112588, and Baik et al., Mol Ther. 2021 Dec 1;29(12):3512-3524; the contents of all of which are incorporated herein by reference in their entireties. [00473] The p75NTR binding proteins may also be fused to other polypeptide molecules such as, but are not limited to, an epitope (e.g., FLAG) or a tag sequence (e.g., His6 (SEQ ID NO: 619), and the like) to allow for the detection and/or isolation of the anti-p75NTR antigen binding protein; a ligand or a portion thereof which binds to a transmembrane receptor protein; an enzyme or portion thereof which is catalytically active; a polypeptide or peptide which promotes oligomerization, such as a leucine zipper domain; a polypeptide or peptide which increases stability, such as an immunoglobulin constant region (e.g., an Fc domain); a half- life extending polypeptide (e.g., albumin or albumin-binding peptides/proteins); a functional or non-functional antibody, or a heavy or light chain thereof; and a polypeptide which has an activity, such as a therapeutic activity, different from the anti-p75NTR antigen binding protein of the present disclosure. [00474] In some embodiments, the polypeptide molecule can be a gene editing nuclease, such as Cas protein, ZFN, TALEN. Gene editing nucleases are described in further details below. [00475] In some embodiments, anti-p75NTR fusion proteins can be made by fusing the heterologous polypeptide molecule at either the N-terminus or at the C-terminus of the anti- p75NTR antigen binding protein (e.g., the heavy chain and/or light chain). Heterologous sequences can be fused either directly to the anti-p75NTR antigen binding protein, either chemically or by recombinant expression from a single polynucleotide or they may be joined via a linker or adapter molecule. A peptidyl linker or adapter molecule can be one or more Attorney Docket No.250298.000780 amino acid residues (or -mers), e.g., 1, 2, 3, 4, 5, 6, 7, 8, or 9 residues (or -mers), preferably from 10 to 50 amino acid residues (or -mers), e.g., 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 25, 30, 35, 40, 45, or 50 residues (or -mers), and more preferably from 15 to 35 amino acid residues (or -mers). A linker or adapter molecule can also be designed with a cleavage site for a protease to allow for the separation of the fused moieties. [00476] When forming the fusion proteins of the present disclosure, a linker can be employed. The linker can be made up of amino acids linked together by peptide bonds, i.e., a peptidyl linker. In some embodiments, the linker is made up of from 1 to 20 or more amino acids linked by peptide bonds, wherein the amino acids are selected from the 20 naturally occurring amino acids. In some embodiments, the amino acids are selected from the amino acids glycine, serine, and glutamate. In some embodiments, suitable linkers include, for example, GSGEGEGSEGSG (SEQ ID NO: 642); GGSEGEGSEGGS (SEQ ID NO: 643); GGGGS (SEQ ID NO: 644), GGGS (SEQ ID NO: 645), and (GGGGS)n (SEQ ID NO: 668); wherein n is 1-10.The present disclosure contemplates linkers of any length or composition. Liposomes, Lipid Nanoparticles and Other Carriers [00477] In some embodiments, a conjugated molecular cargo described herein comprises a carrier, for example, a lipid-based carrier, such as a lipid nanoparticle (LNP), a liposome, a lipidoid, or a lipoplex, a polymeric nanoparticle, an inorganic nanoparticle, a peptide carrier, a nanoparticle mimic, or a nanotube. [00478] In some embodiments, a conjugated molecular cargo described herein comprises a liposome or LNP. Liposomes and LNPs are vesicles including one or more lipid bilayers. In some embodiments, a liposome or LNP includes two or more concentric bilayers separated by aqueous compartments. Lipid bilayers can be functionalized and/or crosslinked to one another. Lipid bilayers can include one or more proteins, polysaccharides or other molecules. [00479] Lipid formulations can protect biological molecules from degradation while improving their cellular uptake. Liposomes or LNPs are particles comprising a plurality of lipid molecules physically associated with each other by intermolecular forces. These include microspheres (including unilamellar and multilamellar vesicles, e.g., liposomes), a dispersed phase in an emulsion, micelles, or an internal phase in a suspension. Such liposomes or LNPs can be used to encapsulate one or more nucleic acids or proteins for delivery. Formulations which contain cationic lipids are useful for delivering polyanions such as nucleic Attorney Docket No.250298.000780 acids. Other lipids that can be included are neutral lipids (i.e., uncharged or zwitterionic lipids), anionic lipids, helper lipids that enhance transfection, and stealth lipids that increase the length of time for which nanoparticles can exist in vivo. Examples of suitable cationic lipids, neutral lipids, anionic lipids, helper lipids, and stealth lipids can be found in WO 2016/010840 A1 and WO 2017/173054 A1, each of which is herein incorporated by reference in its entirety for all purposes. An exemplary lipid nanoparticle can comprise a cationic lipid and one or more other components. In one example, the other component can comprise a helper lipid such as cholesterol. In another example, the other components can comprise a helper lipid such as cholesterol and a neutral lipid such as distearoylphosphatidylcholine (DSPC). In another example, the other components can comprise a helper lipid such as cholesterol, an optional neutral lipid such as DSPC, and a stealth lipid such as S010, S024, S027, S031, or S033. [00480] Liposomes are amphiphilic lipids which can form bilayers in an aqueous environment to encapsulate an aqueous core. The polypeptide (e.g., Cas protein) or polynucleotide (e.g., guide RNA) may be incorporated into the aqueous core. These lipids can have an anionic, cationic or zwitterionic hydrophilic head group. Liposomes can be formed from a single lipid or from a mixture of lipids. A mixture may comprise (1) a mixture of anionic lipids; (2) a mixture of cationic lipids; (3) a mixture of zwitterionic lipids; (4) a mixture of anionic lipids and cationic lipids; (5) a mixture of anionic lipids and zwitterionic lipids; (6) a mixture of zwitterionic lipids and cationic lipids; or (7) a mixture of anionic lipids, cationic lipids and zwitterionic lipids. Similarly, a mixture may comprise both saturated and unsaturated lipids. Exemplary phospholipids include, but are not limited to, phosphatidylethanolamines, phosphatidylcholines, phosphatidylserines, and phosphatidylglycerols. Cationic lipids include, but are not limited to, 1,2-distearyloxy-N,N-dimethyl-3-aminopropane (DSDMA), dioleoyl trimethylammonium propane (DOTAP), 1,2-dioleyloxy-N,Ndimethyl-3-aminopropane (DODMA), 1,2-dilinoleyloxy-N,N-dimethyl-3-aminopropane (DLinDMA), 1,2-dilinolenyloxy- N,N-dimethyl-3-aminopropane (DLenDMA). Zwitterionic lipids include, but are not limited to, acyl zwitterionic lipids and ether zwitterionic lipids. Examples of useful zwitterionic lipids include dodecylphosphocholine, DPPC, and DOPC. [00481] The liposomes or LNPs may contain one or more or all of the following: (i) a lipid for encapsulation and for endosomal escape; (ii) a neutral lipid for stabilization; (iii) a helper lipid for stabilization; and (iv) a stealth lipid. See, e.g., Finn et al. (2018) Cell Rep. Attorney Docket No.250298.000780 22(9):2227-2235 and WO 2017/173054 A1, each of which is herein incorporated by reference in its entirety for all purposes. [00482] In some examples, the liposomes or LNPs comprise cationic lipids. In some examples, the liposomes or LNPs comprise (9Z,12Z)-3-((4,4-bis(octyloxy)butanoyl)oxy)-2- ((((3- (diethylamino)propoxy)carbonyl)oxy)methyl)propyl octadeca-9,12-dienoate, also called 3-((4,4-bis(octyloxy)butanoyl)oxy)-2-((((3-(diethylamino)propoxy)carbonyl)oxy)methyl)propyl (9Z,12Z)-octadeca-9,12-dienoate) or another ionizable lipid. See, e.g., WO 2019/067992, WO 2017/173054, WO 2015/095340, and WO 2014/136086, each of which is herein incorporated by reference in its entirety for all purposes. In some examples, the LNPs comprise molar ratios of a cationic lipid amine to RNA phosphate (N:P) of about 4.5, about 5.0, about 5.5, about 6.0, or about 6.5. In some examples, the terms cationic and ionizable in the context of LNP lipids are interchangeable (e.g., wherein ionizable lipids are cationic depending on the pH). [00483] The lipid for encapsulation and endosomal escape can be a cationic lipid. The lipid can also be a biodegradable lipid, such as a biodegradable ionizable lipid. One example of a suitable lipid is Lipid A or LP01, which is (9Z,12Z)-3-((4,4-bis(octyloxy)butanoyl)oxy)-2- ((((3-(diethylamino)propoxy)carbonyl)oxy)methyl)propyl octadeca-9,12-dienoate, also called 3-((4,4-bis(octyloxy)butanoyl)oxy)-2-((((3-(diethylamino)propoxy)carbonyl)oxy)methyl)propyl (9Z,12Z)-octadeca-9,12-dienoate. See, e.g., Finn et al. (2018) Cell Rep.22(9):2227-2235 and WO 2017/173054 A1, each of which is herein incorporated by reference in its entirety for all purposes. Another example of a suitable lipid is Lipid B, which is ((5-((dimethylamino)methyl)- 1,3-phenylene)bis(oxy))bis(octane-8,1-diyl)bis(decanoate), also called ((5- ((dimethylamino)methyl)-1,3-phenylene)bis(oxy))bis(octane-8,1-diyl)bis(decanoate). Another example of a suitable lipid is Lipid C, which is 2-((4-(((3- (dimethylamino)propoxy)carbonyl)oxy)hexadecanoyl)oxy)propane-1,3-diyl(9Z,9'Z,12Z,12'Z)- bis(octadeca-9,12-dienoate). Another example of a suitable lipid is Lipid D, which is 3-(((3- (dimethylamino)propoxy)carbonyl)oxy)-13-(octanoyloxy)tridecyl 3-octylundecanoate. Other suitable lipids include heptatriaconta-6,9,28,31-tetraen-19-yl 4-(dimethylamino)butanoate (also known as [(6Z,9Z,28Z,31Z)-heptatriaconta-6,9,28,31-tetraen-19-yl] 4- (dimethylamino)butanoate or Dlin-MC3-DMA (MC3))). [00484] Additional suitable cationic lipids include, but are not limited to 1,2- DiLinoleyloxy-N,N-dimethylaminopropane (DLinDMA), 1,2-Dilinolenyloxy-N,N- dimethylaminopropane (DLenDMA), dioctadecyldimethylammonium (DODMA), Attorney Docket No.250298.000780 distearyldimethylammonium (DSDMA), N,N-dioleyl-N,N-dimethylammonium chloride (DODAC); N-(2,3-dioleyloxy)propyl)-N,N,N-trimethylammonium chloride (DOTMA); N,N- distearyl-N,N-dimethylammonium bromide (DDAB); N-(2,3-dioleoyloxy)propyl)-N,N,N- trimethylammonium chloride (DOTAP); 3-(N(N′,N′-dimethylaminoethane)- carbamoyl)cholesterol (DC-Chol), and N-(1,2-dimyristyloxyprop-3-yl)-N,N-dimethyl-N- hydroxyethyl ammonium bromide (DMRIE). For example, cationic lipids that have a positive charge at below physiological pH include, but are not limited to, DODAP, DODMA, and DMDMA. In some embodiments, the cationic lipids comprise C18 alkyl chains, ether linkages between the head group and alkyl chains, and 0 to 3 double bonds. Such lipids include, e.g., DSDMA, DLinDMA, DLenDMA, and DODMA. The cationic lipids may comprise ether linkages and pH titratable head groups. Such lipids include, e.g., DODMA. Additional cationic lipids are described in U.S. Patent Nos. 7,745,651; 5,208,036; 5,264,618; 5,279,833; 5,283,185; 5,753,613; and 5,785,992, incorporated herein by reference. [00485] In some embodiments, the cationic lipids may comprise a protonatable tertiary amine head group. Such lipids are referred to herein as ionizable lipids. Ionizable lipids refer to lipid species comprising an ionizable amine head group and typically comprising a pKa of less than about 7. In environments with an acidic pH, the ionizable amine head group is protonated such that the ionizable lipid preferentially interacts with negatively charged molecules (e.g., nucleic acids such as the recombinant polynucleotides described herein) thus facilitating liposome or LNP assembly and encapsulation. Therefore, in some embodiments, ionizable lipids can increase the loading of nucleic acids into liposomes or LNPs. In environments where the pH is greater than about 7 (e.g., physiologic pH of 7.4), the ionizable lipid comprises a neutral charge. When particles comprising ionizable lipids are taken up into the low pH environment of an endosome (e.g., pH<7), the ionizable lipid is again protonated and associates with the anionic endosomal membranes, promoting release of the contents encapsulated by the particle. [00486] In some embodiments, the liposomes or LNPs may comprise one or more non- cationic helper lipids. Exemplary helper lipids include (1,2-dilauroyl-sn-glycero-3- phosphoethanolamine) (DLPE), 1,2-diphytanoyl-sn-glycero-3-phosphoethanolamine (D iPPE), 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC), 1,2-dipalmitoyl-sn-glycero-3- phosphocholine (DPPC), 1,2-dioleyl-sn-glycero-3-phosphoethanolamine (DOPE), 1,2- dipalmitoyl-sn-glycero-3-phosphoethanolamine (DPPE), 1,2-dimyristoyl-sn-glycero-3- phosphoethanolamine (DMPE), (1,2-dioleoyl-sn-glycero-3-phospho-(1′-rac-glycerol) Attorney Docket No.250298.000780 (DOPG), 1,2-distearoyl-sn-glycero-3-phosphoethanolamine (DSPE), ceramides, sphingomyelins, and cholesterol. [00487] Some such lipids suitable for use in the liposomes or LNPs described herein are biodegradable in vivo. Examples of biodegradable lipids include, but are not limited to, (9Z,12Z)-3-((4,4-bis(octyloxy)butanoyl)oxy)-2-((((3-20 (diethylamino)propoxy)carbonyl)oxy)methyl)propyl octadeca-9,12-dienoate, also called 3- ((4,4-bis(octyloxy)butanoyl)oxy)-2-((((3- (diethylamino)propoxy)carbonyl)oxy)methyl)propyl(9Z,12Z)-octadeca-9,12-dienoate) or another ionizable lipid. See, e.g., PCT Publication Nos. WO2017/173054, WO2015/095340, and WO2014/136086. In some embodiments, the term cationic and ionizable in the context of liposome or LNP lipids is interchangeable, e.g., wherein ionizable lipids are cationic depending on the pH. [00488] Such lipids may be ionizable depending upon the pH of the medium they are in. For example, in a slightly acidic medium, the lipids may be protonated and thus bear a positive charge. Conversely, in a slightly basic medium, such as, for example, blood where pH is approximately 7.35, the lipids may not be protonated and thus bear no charge. In some embodiments, the lipids may be protonated at a pH of at least about 9, 9.5, or 10. The ability of such a lipid to bear a charge is related to its intrinsic pKa. For example, the lipid may, independently, have a pKa in the range of from about 5.8 to about 6.2. [00489] Neutral lipids function to stabilize and improve processing of the liposomes or LNPs. Examples of suitable neutral lipids include a variety of neutral, uncharged or zwitterionic lipids. Examples of neutral phospholipids suitable for use in the present disclosure include, but are not limited to, 5-heptadecylbenzene-1,3-diol (resorcinol), dipalmitoylphosphatidylcholine (DPPC), distearoylphosphatidylcholine or 1,2-distearoyl-sn- glycero-3-phosphocholine (DSPC), phosphocholine (DOPC), dimyristoylphosphatidylcholine (DMPC), phosphatidylcholine (PLPC), 1,2-diarachidonoyl-sn-glycero-3-phosphocholine (DAPC), phosphatidylethanolamine (PE), egg phosphatidylcholine (EPC), dilauryloylphosphatidylcholine (DLPC), dimyristoylphosphatidylcholine (DMPC), 1-myristoyl- 2-palmitoyl phosphatidylcholine (MPPC), 1-palmitoyl-2-myristoyl phosphatidylcholine (PMPC), 1-palmitoyl-2-stearoyl phosphatidylcholine (PSPC), 1,2-diarachidoyl-sn-glycero-3- phosphocholine (DBPC), 1-stearoyl-2-palmitoyl phosphatidylcholine (SPPC), 1,2- dieicosenoyl-sn-glycero-3-phosphocholine (DEPC), palmitoyloleoyl phosphatidylcholine (POPC), lysophosphatidyl choline, dioleoyl phosphatidylethanolamine (DOPE), Attorney Docket No.250298.000780 dilinoleoylphosphatidylcholine distearoylphosphatidylethanolamine (DSPE), dimyristoyl phosphatidylethanolamine (DMPE), dipalmitoyl phosphatidylethanolamine (DPPE), palmitoyloleoyl phosphatidylethanolamine (POPE), lysophosphatidylethanolamine, 1- stearoyl-2-oleoyl-sn-glycero-3-phosphocholine (SOPC), and combinations thereof. For example, the neutral phospholipid may be selected from the group consisting of distearoylphosphatidylcholine (DSPC) and dimyristoyl phosphatidyl ethanolamine (DMPE). [00490] Helper lipids include lipids that enhance transfection. The mechanism by which the helper lipid enhances transfection can include enhancing particle stability. In certain cases, the helper lipid can enhance membrane fusogenicity. Helper lipids include steroids, sterols, and alkyl resorcinols. Examples of suitable helper lipids suitable include cholesterol, 5-heptadecylresorcinol, and cholesterol hemisuccinate. In one example, the helper lipid may be cholesterol or cholesterol hemisuccinate. [00491] Stealth lipids include lipids that alter the length of time the nanoparticles can exist in vivo. Stealth lipids may assist in the formulation process by, for example, reducing particle aggregation and controlling particle size. Stealth lipids may modulate pharmacokinetic properties of the liposomes or LNPs. Suitable stealth lipids include lipids having a hydrophilic head group linked to a lipid moiety. [00492] The hydrophilic head group of stealth lipid can comprise, for example, a polymer moiety selected from polymers based on PEG (sometimes referred to as poly(ethylene oxide)), poly(oxazoline), poly(vinyl alcohol), poly(glycerol), poly(N- vinylpyrrolidone), polyaminoacids, and poly N-(2-hydroxypropyl)methacrylamide. The term PEG means any polyethylene glycol or other polyalkylene ether polymer. In certain liposome or LNP formulations, the PEG, is a PEG-2K, also termed PEG 2000, which has an average molecular weight of about 2,000 daltons. See, e.g., WO 2017/173054 A1, herein incorporated by reference in its entirety for all purposes. [00493] The lipid moiety of the stealth lipid may be derived, for example, from diacylglycerol or diacylglycamide, including those comprising a dialkylglycerol or dialkylglycamide group having alkyl chain length independently comprising from about C4 to about C40 saturated or unsaturated carbon atoms, wherein the chain may comprise one or more functional groups such as, for example, an amide or ester. The dialkylglycerol or dialkylglycamide group can further comprise one or more substituted alkyl groups. [00494] As one example, the stealth lipid may be selected from PEG-dilauroylglycerol, PEG-dimyristoylglycerol (PEG-DMG), PEG-dipalmitoylglycerol, PEG-distearoylglycerol Attorney Docket No.250298.000780 (PEG- DSPE), PEG-dilaurylglycamide, PEG- dimyristylglycamide, PEG- dipalmitoylglycamide, and PEG-distearoylglycamide, PEG- cholesterol (l-[8'-(Cholest-5-en- 3[beta]-oxy)carboxamido-3',6'- dioxaoctanyl]carbamoyl-[omega]-methyl-poly(ethylene glycol), PEG-DMB (3,4- ditetradecoxylbenzyl-[omega]-methyl-poly(ethylene glycol)ether), 1,2-dimyristoyl-sn- glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-2000] (PEG2k- DMG), 1,2- distearoyl-sn-glycero-3-phosphoethanolamine-N- [methoxy(polyethylene glycol)-2000] (PEG2k-DSPE), 1,2-distearoyl-sn-glycerol, methoxypoly ethylene glycol (PEG2k-DSG), poly(ethylene glycol)-2000-dimethacrylate (PEG2k-DMA), and 1,2- distearyloxypropyl-3-amine-N-[methoxy(polyethylene glycol)-2000] (PEG2k-DSA). In one particular example, the stealth lipid may be PEG2k-DMG. [00495] In some embodiments, the liposomes or LNPs may further comprise one or more of PEG-modified lipids that comprise a poly(ethylene)glycol chain of up to 5 kDa in length covalently attached to a lipid comprising one or more C6-C20 alkyls. In some embodiments, the liposomes or LNPs further comprise 1,2-Distearoyl-sn-glycero-3- phosphoethanolamine-Poly(ethylene glycol) (DSPE-PEG), or 1,2-distearoyl-sn-glycero-3- phosphoethanolamine-N-[amino(polyethylene glycol)] (DSPE-PEG-amine). In some embodiments, the PEG-modified lipid comprises about 0.1% to about 1% of the total lipid content in a lipid nanoparticle. In some embodiments, the PEG-modified lipid comprises about 0.1%, about 0.2% about 0.3%, about 0.4%, about 0.5%, about 0.6%, about 0.7%, about 0.8%, about 0.9%, or about 1.0%, of the total lipid content in the liposome or lipid nanoparticle. [00496] In some embodiments, a liposome or LNP described herein may comprise a conjugated lipid that inhibits aggregation of lipid particles. Such lipid conjugates include, but are not limited to, PEG- lipid conjugates such as, e.g, PEG coupled to dialkyloxypropyls (e.g, PEG-DAA conjugates), PEG coupled to diacylglycerols (e.g, PEG-DAG conjugates), PEG coupled to cholesterol, PEG coupled to phosphatidylethanolamines, and PEG conjugated to ceramides (see, e.g., U.S. Patent No.5,885,613), cationic PEG lipids, polyoxazoline (POZ)- lipid conjugates (e.g., POZ-DAA conjugates), polyamide oligomers (e.g, ATTA-lipid conjugates), and mixtures thereof. Additional examples of POZ-lipid conjugates are described in PCT Publication No. WO 2010/006282. PEG or POZ can be conjugated directly to the lipid or may be linked to the lipid via a linker moiety. Any linker moiety suitable for coupling the PEG or the POZ to a lipid can be used including, e.g., non-ester containing linker moieties and ester-containing linker moieties. In certain embodiments, non-ester containing linker moieties, such as amides or carbamates, are used. Attorney Docket No.250298.000780 [00497] The liposomes or LNPs can comprise different respective molar ratios of the component lipids in the formulation. The mol-% of the CCD lipid may be, for example, from about 30 mol-% to about 60 mol-%. The mol-% of the helper lipid may be, for example, from about 30 mol-% to about 60 mol-%. The mol-% of the neutral lipid may be, for example, from about 1 mol-% to about 20 mol-%. The mol-% of the stealth lipid may be, for example, from about 1 mol-% to about 10 mol-% [00498] The liposomes or LNPs can have different ratios between the positively charged amine groups of the biodegradable lipid (N) and the negatively charged phosphate groups (P) of the nucleic acid to be encapsulated. This may be mathematically represented by the equation N/P. For example, the N/P ratio may be from about 0.5 to about 100. The N/P ratio can also be from about 4 to about 6. [00499] In some embodiments, the liposome or LNP can comprise a polynucleotide molecule and/or a polypeptide molecule. In some embodiments, the liposome or LNP can one or more components of a gene editing system. In some embodiments, the liposome or LNP can comprise (a) a Cas nuclease, or a nucleic acid encoding the Cas nuclease, and/or (b) a guide RNA, or one or more DNAs encoding the guide RNA. [00500] In some embodiments, the liposome or LNP can comprise a nuclease agent (e.g., CRISPR/Cas system, ZFN, or TALEN), can comprise a polynucleotide molecule (e.g., guide RNA), can comprise a nucleic acid construct encoding a polypeptide of interest (e.g., multidomain therapeutic protein), or can comprise both a nuclease agent (e.g., a CRISPR/Cas system) and a nucleic acid construct encoding a polypeptide of interest (e.g., a donor template for use in gene editing). Regarding CRISPR/Cas systems, the liposomes or LNPs can comprise the Cas protein in any form (e.g., protein, DNA, or mRNA) and/or can comprise the guide RNA(s) in any form (e.g., DNA or RNA). In one example, the liposomes or LNPs comprise the Cas protein in the form of mRNA (e.g., a modified RNA as described herein) and the guide RNA(s) in the form of RNA (e.g., a modified guide RNA as disclosed herein). As another example, the liposomes or LNPs can comprise the Cas protein in the form of protein and the guide RNA(s) in the form of RNA). In one example, the guide RNA and the Cas protein are each introduced in the form of RNA via LNP-mediated delivery in the same LNP. As discussed in more detail elsewhere herein, one or more of the RNAs can be modified. For example, guide RNAs can be modified to comprise one or more stabilizing end modifications at the 5’ end and/or the 3’ end. Such modifications can include, for example, one or more phosphorothioate linkages at the 5’ end and/or the 3’ end and/or one or more 2’- Attorney Docket No.250298.000780 O-methyl modifications at the 5’ end and/or the 3’ end. As another example, Cas mRNA modifications can include substitution with pseudouridine (e.g., fully substituted with pseudouridine), 5’ caps, and polyadenylation. Other modifications are also contemplated as disclosed elsewhere herein. Delivery through such methods can result in transient Cas expression and/or transient presence of the guide RNA, and the biodegradable lipids improve clearance, improve tolerability, and decrease immunogenicity. [00501] In certain liposomes or LNPs, the cargo can include a guide RNA or a nucleic acid encoding a guide RNA. In certain liposomes or LNPs, the cargo can include an mRNA encoding a Cas nuclease, such as Cas9, and a guide RNA or a nucleic acid encoding a guide RNA. In certain liposomes or LNPs, the cargo can include a nucleic acid construct encoding a polypeptide of interest (e.g., multidomain therapeutic protein) as described elsewhere herein. In certain liposomes or LNPs, the cargo can include an mRNA encoding a Cas nuclease, such as Cas9, a guide RNA or a nucleic acid encoding a guide RNA, and a nucleic acid construct encoding a polypeptide of interest (e.g., multidomain therapeutic protein). In some liposomes or LNPs, the lipid component comprises an amine lipid such as a biodegradable, ionizable lipid. In some instances, the lipid component comprises biodegradable, ionizable lipid, cholesterol, DSPC, and PEG-DMG. For example, Cas9 mRNA and gRNA can be delivered to cells and animals utilizing lipid formulations comprising ionizable lipid ((9Z,12Z)-3-((4,4-bis(octyloxy)butanoyl)oxy)-2-((((3- (diethylamino)propoxy)carbonyl)oxy)methyl)propyl octadeca-9,12-dienoate, also called 3- ((4,4-bis(octyloxy)butanoyl)oxy)-2-((((3-(diethylamino)propoxy)carbonyl)oxy)methyl)propyl (9Z, 12Z)-octadeca-9,12-dienoate), cholesterol, DSPC, and PEG2k-DMG. [00502] In some liposomes or LNPs, the cargo can comprise Cas mRNA (e.g., Cas9 mRNA) and gRNA. The Cas mRNA and gRNAs can be in different ratios. For example, the LNP formulation can include a ratio of Cas mRNA to gRNA nucleic acid ranging from about 25:1 to about 1:25. Alternatively, the liposome or LNP formulation can include a ratio of Cas mRNA to gRNA nucleic acid of from about 2:1 to about 1:2. In specific examples, the ratio of Cas mRNA to gRNA can be about 2:1. [00503] In some liposomes or LNPs, the cargo can comprise a nucleic acid construct encoding a polypeptide of interest (e.g., multidomain therapeutic protein) and gRNA. The nucleic acid construct encoding a polypeptide of interest (e.g., multidomain therapeutic protein) and gRNAs can be in different ratios. For example, the liposome or LNP formulation Attorney Docket No.250298.000780 can include a ratio of nucleic acid construct to gRNA nucleic acid ranging from about 25:1 to about 1:25. [00504] A specific example of a suitable LNP has a nitrogen-to-phosphate (N/P) ratio of about 4.5 and contains biodegradable cationic lipid, cholesterol, DSPC, and PEG2k-DMG in an about 45:44:9:2 molar ratio (about 45:about 44:about 9:about 2). The biodegradable cationic lipid can be (9Z,12Z)-3-((4,4-bis(octyloxy)butanoyl)oxy)-2-((((3- (diethylamino)propoxy)carbonyl)oxy)methyl)propyl octadeca-9,12-dienoate, also called 3- ((4,4-bis(octyloxy)butanoyl)oxy)-2-((((3-(diethylamino)propoxy)carbonyl)oxy)methyl)propyl (9Z,12Z)-octadeca-9,12-dienoate. See, e.g., Finn et al. (2018) Cell Rep. 22(9):2227-2235, herein incorporated by reference in its entirety for all purposes. The Cas9 mRNA can be in an about 1:1 (about 1:about 1) ratio by weight to the guide RNA. Another specific example of a suitable LNP contains Dlin-MC3-DMA (MC3), cholesterol, DSPC, and PEG-DMG in an about 50:38.5:10:1.5 molar ratio (about 50:about 38.5:about 10:about 1.5). The Cas9 mRNA can be in an about 1:2 ratio (about 1:about 2) by weight to the guide RNA. The Cas9 mRNA can be in an about 1:1 ratio (about 1:about 1) by weight to the guide RNA. The Cas9 mRNA can be in an about 2:1 ratio (about 2:about 1) by weight to the guide RNA. [00505] Another specific example of a suitable LNP has a nitrogen-to-phosphate (N/P) ratio of about 6 and contains biodegradable cationic lipid, cholesterol, DSPC, and PEG2k- DMG in an about 50:38:9:3 molar ratio (about 50:about 38:about 9:about 3). The biodegradable cationic lipid can be Lipid A ((9Z,12Z)-3-((4,4-bis(octyloxy)butanoyl)oxy)-2- ((((3-(diethylamino)propoxy)carbonyl)oxy)methyl)propyl octadeca-9,12-dienoate, also called 3-((4,4-bis(octyloxy)butanoyl)oxy)-2-((((3-(diethylamino)propoxy)carbonyl)oxy)methyl)propyl (9Z,12Z)-octadeca-9,12-dienoate). The Cas9 mRNA can be in an about 1:2 ratio (about 1:about 2) by weight to the guide RNA. The Cas9 mRNA can be in an about 1:1 ratio (about 1:about 1)by weight to the guide RNA. The Cas9 mRNA can be in an about 2:1 (about 2:about 1) ratio by weight to the guide RNA. [00506] Another specific example of a suitable LNP has a nitrogen-to-phosphate (N/P) ratio of about 3 and contains a cationic lipid, a structural lipid, cholesterol (e.g., cholesterol (ovine) (Avanti 700000)), and PEG2k-DMG (e.g., PEG-DMG 2000 (NOF America- SUNBRIGHT® GM-020(DMG-PEG)) in an about 50:10:38.5:1.5 ratio (about 50:about 10:about 38.5:about 1.5) or an about 47:10:42:1 ratio (about 47:about 10:about 42:about 1). The structural lipid can be, for example, DSPC (e.g., DSPC (Avanti 850365)), SOPC, DOPC, or DOPE. The cationic/ionizable lipid can be, for example, Dlin-MC3-DMA (e.g., Dlin-MC3- Attorney Docket No.250298.000780 DMA (Biofine International)). The Cas9 mRNA can be in an about 1:2 ratio (about 1:about 2) by weight to the guide RNA. The Cas9 mRNA can be in an about 1:1 ratio (about 1:about 1) by weight to the guide RNA. The Cas9 mRNA can be in an about 2:1 ratio (about 2:about 1) by weight to the guide RNA. [00507] Another specific example of a suitable LNP contains Dlin-MC3-DMA, DSPC, cholesterol, and a PEG lipid in an about 45:9:44:2 ratio (about 45:about 9:about 44:about 2). Another specific example of a suitable LNP contains Dlin-MC3-DMA, DOPE, cholesterol, and PEG lipid or PEG DMG in an about 50:10:39:1 ratio (about 50:about 10:about 39:about 1). Another specific example of a suitable LNP has Dlin-MC3-DMA, DSPC, cholesterol, and PEG2k-DMG at an about 55:10:32.5:2.5 ratio (about 55:about 10:about 32.5:about 2.5). Another specific example of a suitable LNP has Dlin-MC3-DMA, DSPC, cholesterol, and PEG-DMG in an about 50:10:38.5:1.5 ratio (about 50:about 10:about 38.5:about 1.5). Another specific example of a suitable LNP has Dlin-MC3-DMA, DSPC, cholesterol, and PEG-DMG in an about 50:10:38.5:1.5 ratio (about 50:about 10:about 38.5:about 1.5). The Cas9 mRNA can be in an about 1:2 ratio (about 1:about 2) by weight to the guide RNA. The Cas9 mRNA can be in an about 1:1 ratio (about 1:about 1) by weight to the guide RNA. The Cas9 mRNA can be in an about 2:1 ratio (about 2:about 1) by weight to the guide RNA. [00508] Other examples of suitable LNPs can be found, e.g., in WO 2019/067992, WO 2020/082042, US 2020/0270617, WO 2020/082041, US 2020/0268906, WO 2020/082046 (see, e.g., pp. 85-86), and US 2020/0289628, each of which is herein incorporated by reference in its entirety for all purposes. [00509] Dynamic Light Scattering ("DLS") can be used to characterize the polydispersity index ("PDI") and size of the liposomes and LNPs. In some embodiments, the PDI may range from about 0.005 to about 0.75. In some embodiments, the PDI may range from about 0.01 to about 0.5. In some embodiments, the PDI may range from about 0.02 to about 0.4. In some embodiments, the PDI may range from about 0.03 to about 0.35. In some embodiments, the PDI may range from about 0.1 to about 0.35. [00510] The LNPs disclosed herein may have a size of about 1 to about 250 nm. In some embodiments, the LNPs may have a size of about 10 to about 200 nm. In some embodiments, the LNPs may have a size of about 20 to about 150 nm. In some embodiments, the LNPs may have a size of about 50 to about 150 nm. In some embodiments, the LNPs may have a size of about 50 to about 100 nm. In some embodiments, the LNPs may have a size of about 50 to about 120 nm. In some embodiments, the LNPs may have a size of about Attorney Docket No.250298.000780 75 to about 150 nm. In some embodiments, the LNPs may have a size of about 30 to about 200 nm. In some embodiments, the average sizes (diameters) of the fully formed nanoparticles are measured by dynamic light scattering on a Malvern Zetasizer (e.g., the nanoparticle sample may be diluted in phosphate buffered saline (PBS) so that the count rate is approximately 200-400 kcts, and the data may be presented as a weighted-average of the intensity measure). [00511] In some embodiments, the liposomes or LNPs may be formed with an average encapsulation efficiency ranging from about 50% to about 100%. In some embodiments, the liposomes or LNPs may be formed with an average encapsulation efficiency ranging from about 50% to about 70%. In some embodiments, the liposomes or LNPs may be formed with an average encapsulation efficiency ranging from about 70% to about 90%. In some embodiments, the liposomes or LNPs may be formed with an average encapsulation efficiency ranging from about 90% to about 100%. In some embodiments, the liposomes or LNPs may be formed with an average encapsulation efficiency ranging from about 75% to about 95%. [00512] In addition to liposomes and LNPs, an p75NTR binding protein disclosed herein, such as an scFv or an antibody or an antigen-binding fragment thereof, may be conjugated to other carriers for delivery of nucleic acid and/ protein molecules. Examples of other suitable carriers include, but are not limited to, lipoids and lipoplexes, particulate or polymeric nanoparticles, inorganic nanoparticles, peptide carriers, nanoparticle mimics, nanotubes, conjugates, immune stimulating complexes (ISCOM), virus-like particles (VLPs), self- assembling proteins, or emulsion delivery systems such as cationic submicron oil-in-water emulsions. [00513] Polymeric microparticles or nanoparticles can also be used to encapsulate or adsorb a polypeptide (e.g., Cas protein) or polynucleotide (e.g., guide RNA). The particles may be substantially non-toxic and biodegradable. The particles useful for delivering a polynucleotide (e.g., guide RNA) may have an optimal size and zeta potential. For example, the microparticles may have a diameter in the range of 0.02 μm to 8 μm. In the instances when the composition has a population of micro- or nanoparticles with different diameters, at least 80%, 85%, 90%, or 95% of those particles ideally have diameters in the range of 0.03- 7 μm. The particles may also have a zeta potential of between 40-100 mV, in order to provide maximal adsorption of the polynucleotide (e.g., guide RNA) to the particles. Attorney Docket No.250298.000780 [00514] Non-toxic and biodegradable polymers include, but are not limited to, poly(ahydroxy acids), polyhydroxy butyric acids, polylactones (including polycaprolactones), polydioxanones, polyvalerolactone, polyorthoesters, polyanhydrides, polycyanoacrylates, tyrosine-derived polycarbonates, polyvinyl-pyrrolidinones or polyester-amides, one or more natural polymers such as a polysaccharide, for example pullulan, alginate, inulin, and chitosan, and combinations thereof. In some embodiments, the particles are formed from poly(ahydroxy acids), such as a poly(lactides) (PLA), poly(g-glutamic acid) (g-PGA), poly(ethylene glycol) (PEG), polystyrene, copolymers of lactide and glycolide such as a poly(D,L-lactide-co-glycolide) (PLG), and copolymers of D,L-lactide and caprolactone. Useful PLG polymers can include those having a lactide/glycolide molar ratio ranging, for example, from 20:80 to 80:20 e.g., 25:75, 40:60, 45:55, 55:45, 60:40, 75:25. Useful PLG polymers include those having a molecular weight between, for example, 5,000-200,000 Da e.g., between 10,000-100,000, 20,000-70,000, 40,000-50,000 Da. [00515] The polymeric nanoparticle may also form hydrogel nanoparticles, hydrophilic three-dimensional polymer networks with favorable properties including flexible mesh size, large surface area for multivalent conjugation, high water content, and high loading capacity for antigens. Polymers such as Poly(L-lactic acid) (PLA), PLGA, PEG, and polysaccharides are suitable for forming hydrogel nanoparticles. [00516] For example, the inorganic nanoparticles may be calcium phosphate nanoparticles, silicon nanoparticles or gold nanoparticles. Inorganic nanoparticles typically have a rigid structure and comprise a shell in which a polypeptide or polynucleotide is encapsulated or a core to which the polypeptide or polynucleotide may be covalently attached. The core may comprise one or more atoms such as gold (Au), silver (Ag), copper (Cu) atoms, Au/Ag, Au/Cu, Au/Ag/Cu, Au/Pt, Au/Pd or Au/Ag/Cu/Pd or calcium phosphate (CaP). [00517] Other molecules suitable for complexing with the polypeptides or polynucleotides of the disclosure include cationic molecules, such as, polyamidoamine, dendritic polylysine, polyethylene irinine or polypropylene imine, polylysine, chitosan, DNA- gelatin coarcervates, DEAE dextran, dendrimers, or polyethylenimine (PEI). [00518] In some embodiments, polypeptides or polynucleotides of the present disclosure can be conjugated to nanoparticles. Nanoparticles that may be used for conjugation with antigens and/or antibodies of the present disclosure include but not are limited to chitosan-shelled nanoparticles, carbon nanotubes, PEGylated liposomes, poly(d,l- Attorney Docket No.250298.000780 lactide-co-glycolide)/montmorillonite (PLGA/MMT) nanoparticles, poly(lactide-co-glycolide) (PLGA) nanoparticles, poly-(malic acid)-based nanoparticles, and other inorganic nanoparticles (e.g., nanoparticles made of magnesium–aluminium layered double hydroxides with disuccinimidyl carbonate (DSC), and TiO2 nanoparticles). Nanoparticles can be developed and conjugated to antigens and/or antibodies contained in a composition for targeting virus-infected cells. [00519] Oil-in-water emulsions may also be used for delivering a polypeptide or polynucleotide (e.g., mRNA) to a subject. Examples of oils useful for making the emulsions include animal (e.g., fish) oil or vegetable oil (e.g., nuts, grains and seeds). The oil may be biodegradable and biocompatible. Exemplary oils include, but are not limited to, tocopherols and squalene, a shark liver oil which is a branched, unsaturated terpenoid and combinations thereof. Terpenoids are branched chain oils that are synthesized biochemically in 5-carbon isoprene units. [00520] The aqueous component of the emulsion can be water or can be water in which additional components have been added. For example, it may include salts to form a buffer e.g., citrate or phosphate salts, such as sodium salts. Exemplary buffers include a borate buffer, a citrate buffer, a histidine buffer a phosphate buffer, a Tris buffer, or a succinate buffer. [00521] In some embodiments, the oil-in water emulsions include one or more cationic molecules. For example, a cationic lipid can be included in the emulsion to provide a positively charged droplet surface to which negatively-charged polynucleotide (e.g., mRNA) can attach. Exemplary cationic lipids include, but are not limited to: 1,2-dioleoyloxy-3- (trimethylammonio)propane (DOTAP), 1,2-Dimyristoyl-3-Trimethyl-AmmoniumPropane (DMTAP), 3’-[N-(N’,N’-Dimethylaminoethane)-carbamoyl]Cholesterol (DC Cholesterol), dimethyldioctadecyl-ammonium (DDA e.g., the bromide), dipalmitoyl(C16:0)trimethyl ammonium propane (DPTAP), distearoyltrimethylammonium propane (DSTAP). Other useful cationic lipids include benzalkonium chloride (BAK), benzethonium chloride, cholesterol hemisuccinate choline ester, lipopolyamines (e.g., dioctadecylamidoglycylspermine (DOGS), dipalmitoyl phosphatidylethanol-amidospermine (DPPES)), cetramide, cetylpyridinium chloride (CPC), cetyl trimethylammonium chloride (CTAC), cationic derivatives of cholesterol (e.g., cholesteryl-3.beta.-oxysuccinamidoethylenetrimethylammonium salt, cholesteryl- 3.beta.-oxysuccinamidoethylene-dimethylamine, cholesteryl-3.beta.- carboxyamidoethylenetrimethylammonium salt, and cholesteryl-3.beta.- Attorney Docket No.250298.000780 carboxyamidoethylenedimethylamine), N,N’,N’-polyoxyethylene (10)-N-tallow-1,3- diaminopropane, dodecyltrimethylammonium bromide, hexadecyltrimethyl-ammonium bromide, mixed alkyl-trimethyl-ammonium bromide, benzyldimethyldodecylammonium chloride, benzyldimethylhexadecyl-ammonium chloride, benzyltrimethylammonium methoxide, cetyldimethylethylammonium bromide, dimethyldioctadecyl ammonium bromide (DDAB), methylbenzethonium chloride, decamethonium chloride, methyl mixed trialkyl ammonium chloride, methyl trioctylammonium chloride), N,N-dimethyl-N-[2 (2-methyl-4- (1,1,3,3tetramethylbutyl)-phenoxy]-ethoxy)ethyl]-benzenemetha-naminium chloride (DEBDA), cholesteryl (4’-trimethylammonio) butanoate), N-alkyl pyridinium salts (e.g., cetylpyridinium bromide and cetylpyridinium chloride), N-alkylpiperidinium salts, dicationic bolaform electrolytes (C12Me6; C12BU6), dialkylglycetylphosphorylcholine, lysolecithin, L- alpha.dioleoylphosphatidylethanolamine, lipopoly-L (or D)-lysine (LPLL, LPDL), poly(L (or D)- lysine conjugated to N-glutarylphosphatidylethanolamine, dialkyldimethylammonium salts, [1- (2,3-dioleyloxy)-propyl]-N,N,N,trimethylammonium chloride, 1,2-diacyl-3-(trimethylammonio) propane (acyl group can be dimyristoyl, dipalmitoyl, distearoyl, or dioleoyl), 1,2-diacyl-3 (dimethylammonio)propane (acyl group can be dimyristoyl, dipalmitoyl, distearoyl, or dioleoyl), 1,2-dioleoyl-3-(4’-trimethyl-ammonio)butanoyl-sn-glycerol, 1,2-dioleoyl 3-succinyl- sn-glycerol choline ester, didodecyl glutamate ester with pendant amino group (C GluPhCnN), and ditetradecyl glutamate ester with pendant amino group (C14GluCnN+). [00522] In some embodiments, in addition to the oil and cationic lipid, an emulsion can also include a non-ionic surfactant and/or a zwitterionic surfactant. Examples of useful surfactants include, but are not limited to: the polyoxyethylene sorbitan esters surfactants, e.g., polysorbate 20 and polysorbate 80; copolymers of ethylene oxide, propylene oxide, and/or butylene oxide, linear block copolymers; phospholipids, e.g., phosphatidylcholine; polyoxyethylene fatty ethers derived from lauryl, cetyl, stearyl and oleyl alcohols; polyoxyethylene-9-lauryl ether; octoxynols; (octylphenoxy)polyethoxyethanol;and sorbitan esters. [00523] In some embodiments, a polynucleotide described herein may be incorporated into polynucleotide complexes, such as, but not limited to, nanoparticles (e.g., polynucleotide self-assembled nanoparticles, polymer-based self-assembled nanoparticles, inorganic nanoparticles, lipid nanoparticles, semiconductive/metallic nanoparticles), gels and hydrogels, polynucleotide complexes with cations and anions, microparticles, and any combination thereof. The polynucleotide complexes may be conjugated to an p75NTR binding Attorney Docket No.250298.000780 protein described herein, e.g., via linkage to the polynucleotide or nanoparticle/hydrogel/microparticle. [00524] In some embodiments, the polynucleotides disclosed herein may be formulated as self-assembled nanoparticles. As a non-limiting example, polynucleotides may be used to make nanoparticles which may be used in a delivery system for the polynucleotides (See e.g., PCT Publication No. WO2012/125987). In some embodiments, the polynucleotide self- assembled nanoparticles may comprise a core of the polynucleotides disclosed herein and a polymer shell. The polymer shell may be any of the polymers described herein and are known in the art. In an additional embodiment, the polymer shell may be used to protect the polynucleotides in the core. [00525] In some embodiments, self-assembled nanoparticles may be microsponges formed of long polymers of polynucleotide hairpins which form into crystalline “pleated” sheets before self-assembling into microsponges. These microsponges are densely-packed sponge like microparticles which may function as an efficient carrier and may be able to deliver cargo to a cell. The microsponges may be from 1 μm to 300 nm in diameter. The microsponges may be complexed with other agents known in the art to form larger microsponges. As a non- limiting example, the microsponge may be complexed with an agent to form an outer layer to promote cellular uptake such as polycation polyethyleneime (PEI). This complex can form a 250-nm diameter particle that can remain stable at high temperatures (150ºC) (Grabow and Jaegar, Nature Materials 2012, 11:269-269). Additionally, these microsponges may be able to exhibit an extraordinary degree of protection from degradation by ribonucleases. In an embodiment, the polymer-based self-assembled nanoparticles such as, but not limited to, microsponges, may be fully programmable nanoparticles. The geometry, size and stoichiometry of the nanoparticle may be precisely controlled to create the optimal nanoparticle for delivery of cargo such as, but not limited to, polynucleotides. [00526] In some embodiments, a polynucleotide disclosed herein may be formulated in inorganic nanoparticles (see U.S. Patent. No.8,257,745). The inorganic nanoparticles may include, but are not limited to, clay substances that are water swellable. As a non-limiting example, the inorganic nanoparticle may include synthetic smectite clays which are made from simple silicates (See U.S. Patent Nos.5,585,108 and 8,257,745). [00527] In some embodiments, a polynucleotide disclosed herein may be formulated in water-dispersible nanoparticle comprising a semiconductive or metallic material (U.S. Patent Application Publication No.2012/0228565; herein incorporated by reference in its entirety) or Attorney Docket No.250298.000780 formed in a magnetic nanoparticle (U.S. Patent Application Publication No. 2012/0265001 and 2012/0283503). The water-dispersible nanoparticles may be hydrophobic nanoparticles or hydrophilic nanoparticles. [00528] In some embodiments, the polynucleotides disclosed herein may be encapsulated into any hydrogel known in the art which may form a gel when injected into a subject. Hydrogels are a network of polymer chains that are hydrophilic, and are sometimes found as a colloidal gel in which water is the dispersion medium. Hydrogels are highly absorbent (they can contain over 99% water) natural or synthetic polymers. Hydrogels also possess a degree of flexibility very similar to natural tissue, due to their significant water content. The hydrogel described herein may be used to encapsulate lipid nanoparticles which are biocompatible, biodegradable and/or porous. [00529] As a non-limiting example, the hydrogel may be an aptamer-functionalized hydrogel. The aptamer-functionalized hydrogel may be programmed to release one or more polynucleotides using polynucleotide hybridization. (Battig et al., J. Am. Chem. Society.2012 134:12410-12413). In some embodiments, the polynucleotide may be encapsulated in a lipid nanoparticle and then the lipid nanoparticle may be encapsulated into a hydrogel. [00530] In some embodiments, the polynucleotides disclosed herein may be encapsulated into a fibrin gel, fibrin hydrogel or fibrin glue. In another embodiment, the polynucleotides may be formulated in a lipid nanoparticle or a rapidly eliminated lipid nanoparticle prior to being encapsulated into a fibrin gel, fibrin hydrogel or a fibrin glue. In yet another embodiment, the polynucleotides may be formulated as a lipoplex prior to being encapsulated into a fibrin gel, hydrogel or a fibrin glue. Fibrin gels, hydrogels and glues comprise two components, a fibrinogen solution and a thrombin solution which is rich in calcium (See e.g., Spicer and Mikos, Journal of Controlled Release 2010.148: 49-55; Kidd et al. Journal of Controlled Release 2012.157:80-85). The concentration of the components of the fibrin gel, hydrogel and/or glue can be altered to change the characteristics, the network mesh size, and/or the degradation characteristics of the gel, hydrogel and/or glue such as, but not limited to changing the release characteristics of the fibrin gel, hydrogel and/or glue. (See e.g., Spicer and Mikos, Journal of Controlled Release 2010. 148: 49-55; Kidd et al. Journal of Controlled Release 2012. 157:80-85; Catelas et al. Tissue Engineering 2008. 14:119-128). This feature may be advantageous when used to deliver the polynucleotide disclosed herein. (See e.g., Kidd et al. Journal of Controlled Release 2012. 157:80-85; Catelas et al. Tissue Engineering 2008.14:119-128). Attorney Docket No.250298.000780 [00531] In some embodiments, a polynucleotide disclosed herein may include cations or anions. In one embodiment, the formulations include metal cations such as, but not limited to, Zn2+, Ca2+, Cu2+, Mg2+ and combinations thereof. As a non-limiting example, formulations may include polymers and a polynucleotide complexed with a metal cation (See U.S. Patent Nos.6,265,389 and 6,555,525). [00532] In some embodiments, a polynucleotide may be formulated in nanoparticles and/or microparticles. These nanoparticles and/or microparticles may be molded into any size shape and chemistry. As an example, the nanoparticles and/or microparticles may be made using the PRINT® technology by LIQUIDA TECHNOLOGIES (Morrisville, N.C.) (See e.g., International Pub. Publication No. WO2007/024323). [00533] In some embodiments, the polynucleotides disclosed herein may be formulated in NanoJackets and NanoLiposomes by Keystone Nano (State College, Pa.). NanoJackets are made of compounds that are naturally found in the body including calcium, phosphate and may also include a small amount of silicates. Nanojackets may range in size from 5 to 50 nm and may be used to deliver hydrophilic and hydrophobic compounds such as, but not limited to, polynucleotides, primary constructs and/or polynucleotide. NanoLiposomes are made of lipids such as, but not limited to, lipids which naturally occur in the body. NanoLiposomes may range in size from 60-80 nm and may be used to deliver hydrophilic and hydrophobic compounds such as, but not limited to, polynucleotides, primary constructs and/or polynucleotide. In one aspect, the polynucleotides disclosed herein are formulated in a NanoLiposome such as, but not limited to, Ceramide NanoLiposomes. In some embodiments, the anti-p75-LNP disclosed herein may comprise mCherry mRNA. In some embodiments, the anti-p75-LNP disclosed herein Cas9 mRNA and gRNA. Gene Editing System [00534] In various embodiments, a molecular cargo of the present disclosure can include a gene editing system or components of such systems. Various known gene editing systems can be used in the practice of the present disclosure, including, e.g., a Clustered Regularly Interspersed Short Palindromic Repeats (CRISPR)/Cas system; zinc finger nuclease (ZFN) system; transcription activator-like effector nuclease (TALEN) system, or systems using meganucleases, restriction endonucleases, or recombinases. Generally, these gene editing systems are used to modify a genome within a cell by inducing a double strand break (DSB) or a nick (e.g., a single strand break, or SSB) in a target DNA sequence. Attorney Docket No.250298.000780 Cleavage or nicking can occur through the use of specific nucleases such as engineered ZFN, TALENs, or using the CRISPR/Cas system with an engineered guide RNA (gRNA) to guide specific cleavage or nicking of a target DNA sequence. Further, targeted nucleases have been developed, and additional nucleases are being developed, for example based on the Argonaute system (e.g., from T. thermophilus, known as ‘TtAgo’, see Swarts et al (2014) Nature 507(7491): 258-261), which also may have the potential for uses in genome editing and gene therapy. [00535] Deletion of DNA may be performed using a gene editing system to knock-out or disrupt a target gene. A knock-out can be a gene knock-down or the gene can be knocked out by a mutation such as, a point mutation, an insertion, a deletion, a frameshift, or a missense mutation by techniques known in the art. Alternatively, a knock-in of an exogenous gene or replacement of a defective gene with a corrective gene can also be achieved with a gene editing system. In such instances, a donor template carrying an heterologous gene to be inserted into a genomic locus is provided along with a gene editing system. The donor template would typically include homology arms corresponding to the genomic locus which is targeted by a gene editing system. [00536] There are various ways to incorporate a gene editing system or component(s) thereof (e.g., Cas protein, guide RNA) to an anti-p75NTR protein-drug conjugate described herein. In some embodiments, a gene editing system or component(s) thereof (e.g., Cas protein or nucleic acid (e.g., mRNA or DNA) encoding, guide RNA or DNA encoding) are loaded to a carrier described, such as a liposome, LNP, or encoded in the genome of a viral particle (e.g., AAV), which is conjugated to an p75NTR binding protein described herein. In some embodiments, a guide RNA or a DNA encoding the guide RNA is conjugated to an p75NTR binding protein described herein. In some embodiments, a gene editing nuclease (e.g., Cas protein, ZFN, TALEN) or one or more nucleic acids (e.g., mRNA or DNA) encoding the gene editing nuclease is conjugated to p75NTR binding protein described herein. In some embodiments, both a guide RNA (or DNA encoding) and a Cas protein (or nucleic acid (e.g., mRNA or DNA) encoding) may be conjugated to an p75NTR binding protein described herein. In some embodiments, a guide RNA (or DNA encoding) is conjugated to an p75NTR binding protein described herein, and a Cas protein (or nucleic acid (e.g., mRNA or DNA) encoding) is loaded to a carrier described, such as a liposome or LNP, which is conjugated to an p75NTR binding protein described herein. In some embodiments, a Cas protein (or nucleic acid (e.g., mRNA or DNA) encoding) is conjugated to an p75NTR binding protein described herein, and Attorney Docket No.250298.000780 a guide RNA (or DNA encoding) is loaded to a carrier described, such as a liposome or LNP, which is conjugated to an p75NTR binding protein described herein. [00537] In some embodiments, the molecular cargo disclosed herein can comprise a CRISPR/Cas system or components of such systems. CRISPR/Cas systems include transcripts and other elements involved in the expression of, or directing the activity of, Cas genes. A CRISPR/Cas system can be, for example, a type I, a type II, or a type III system. Alternatively, a CRISPR/Cas system can be a type V system (e.g., subtype V-A or subtype V-B). The methods and compositions disclosed herein can employ CRISPR/Cas systems by utilizing CRISPR complexes (comprising a guide RNA (gRNA) complexed with a Cas protein) for site-directed cleavage of nucleic acids. [00538] Cas proteins generally comprise at least one RNA recognition or binding domain that can interact with guide RNAs. Cas proteins can also comprise nuclease domains (e.g., DNase domains or RNase domains), DNA-binding domains, helicase domains, protein- protein interaction domains, dimerization domains, and other domains. Some such domains (e.g., DNase domains) can be from a native Cas protein. Other such domains can be added to make a modified Cas protein. A nuclease domain possesses catalytic activity for nucleic acid cleavage, which includes the breakage of the covalent bonds of a nucleic acid molecule. Cleavage can produce blunt ends or staggered ends, and it can be single-stranded or double- stranded. For example, a wild type Cas9 protein will typically create a blunt cleavage product. Alternatively, a wild type Cpf1 protein (e.g., FnCpf1) can result in a cleavage product with a 5-nucleotide 5’ overhang, with the cleavage occurring after the 18th base pair from the PAM sequence on the non-targeted strand and after the 23rd base on the targeted strand. A Cas protein can have full cleavage activity to create a double-strand break at a target genomic locus (e.g., a double-strand break with blunt ends), or it can be a nickase that creates a single- strand break at a target genomic locus. [00539] Examples of Cas proteins include Cas1, Cas1B, Cas2, Cas3, Cas4, Cas5, Cas5e (CasD), Cas6, Cas6e, Cas6f, Cas7, Cas8a1, Cas8a2, Cas8b, Cas8c, Cas9 (Csn1 or Csx12), Cas10, Cas10d, CasF, CasG, CasH, Csy1, Csy2, Csy3, Cse1 (CasA), Cse2 (CasB), Cse3 (CasE), Cse4 (CasC), Csc1, Csc2, Csa5, Csn2, Csm2, Csm3, Csm4, Csm5, Csm6, Cmr1, Cmr3, Cmr4, Cmr5, Cmr6, Csb1, Csb2, Csb3, Csx17, Csx14, Csx10, Csx16, CsaX, Csx3, Csx1, Csx15, Csf1, Csf2, Csf3, Csf4, and Cu1966, and homologs or modified versions thereof. Attorney Docket No.250298.000780 [00540] An exemplary Cas protein is a Cas9 protein or a protein derived from a Cas9 protein. Cas9 proteins are from a type II CRISPR/Cas system and typically share four key motifs with a conserved architecture. Motifs 1, 2, and 4 are RuvC-like motifs, and motif 3 is an HNH motif. Exemplary Cas9 proteins are from Streptococcus pyogenes, Streptococcus thermophilus, Streptococcus sp., Staphylococcus aureus, Nocardiopsis dassonvillei, Streptomyces pristinaespiralis, Streptomyces viridochromogenes, Streptomyces viridochromogenes, Streptosporangium roseum, Streptosporangium roseum, Alicyclobacillus acidocaldarius, Bacillus pseudomycoides, Bacillus selenitireducens, Exiguobacterium sibiricum, Lactobacillus delbrueckii, Lactobacillus salivarius, Microscilla marina, Burkholderiales bacterium, Polaromonas naphthalenivorans, Polaromonas sp., Crocosphaera watsonii, Cyanothece sp., Microcystis aeruginosa, Synechococcus sp., Acetohalobium arabaticum, Ammonifex degensii, Caldicelulosiruptor becscii, Candidatus Desulforudis, Clostridium botulinum, Clostridium difficile, Finegoldia magna, Natranaerobius thermophilus, Pelotomaculum thermopropionicum, Acidithiobacillus caldus, Acidithiobacillus ferrooxidans, Allochromatium vinosum, Marinobacter sp., Nitrosococcus halophilus, Nitrosococcus watsoni, Pseudoalteromonas haloplanktis, Ktedonobacter racemifer, Methanohalobium evestigatum, Anabaena variabilis, Nodularia spumigena, Nostoc sp., Arthrospira maxima, Arthrospira platensis, Arthrospira sp., Lyngbya sp., Microcoleus chthonoplastes, Oscillatoria sp., Petrotoga mobilis, Thermosipho africanus, Acaryochloris marina, Neisseria meningitidis, or Campylobacter jejuni. Additional examples of the Cas9 family members are described in WO 2014/131833, herein incorporated by reference in its entirety for all purposes. Cas9 from S. pyogenes (SpCas9) (e.g., assigned UniProt accession number Q99ZW2) is an exemplary Cas9 protein. Smaller Cas9 proteins (e.g., Cas9 proteins whose coding sequences are compatible with the maximum AAV packaging capacity when combined with a guide RNA coding sequence and regulatory elements for the Cas9 and guide RNA, such as SaCas9 and CjCas9 and Nme2Cas9) are other exemplary Cas9 proteins. For example, Cas9 from S. aureus (SaCas9) (e.g., assigned UniProt accession number J7RUA5) is another exemplary Cas9 protein. Likewise, Cas9 from Campylobacter jejuni (CjCas9) (e.g., assigned UniProt accession number Q0P897) is another exemplary Cas9 protein. See, e.g., Kim et al. (2017) Nat. Commun.8:14500, herein incorporated by reference in its entirety for all purposes. SaCas9 is smaller than SpCas9, and CjCas9 is smaller than both SaCas9 and SpCas9. Cas9 from Neisseria meningitidis (Nme2Cas9) is another exemplary Cas9 protein. See, e.g., Edraki et al. (2019) Mol. Cell 73(4):714-726, herein incorporated by reference in its Attorney Docket No.250298.000780 entirety for all purposes. Cas9 proteins from Streptococcus thermophilus (e.g., Streptococcus thermophilus LMD-9 Cas9 encoded by the CRISPR1 locus (St1Cas9) or Streptococcus thermophilus Cas9 from the CRISPR3 locus (St3Cas9)) are other exemplary Cas9 proteins. Cas9 from Francisella novicida (FnCas9) or the RHA Francisella novicida Cas9 variant that recognizes an alternative PAM (E1369R/E1449H/R1556A substitutions) are other exemplary Cas9 proteins. These and other exemplary Cas9 proteins are reviewed, e.g., in Cebrian- Serrano and Davies (2017) Mamm. Genome 28(7):247-261, herein incorporated by reference in its entirety for all purposes. Examples of Cas9 coding sequences, Cas9 mRNAs, and Cas9 protein sequences are provided in WO 2013/176772, WO 2014/065596, WO 2016/106121, WO 2019/067910, WO 2020/082042, US 2020/0270617, WO 2020/082041, US 2020/0268906, WO 2020/082046, and US 2020/0289628, each of which is herein incorporated by reference in its entirety for all purposes. Specific examples of ORFs and Cas9 amino acid sequences are provided in Table 30 at paragraph [0449] WO 2019/067910, and specific examples of Cas9 mRNAs and ORFs are provided in paragraphs [0214]-[0234] of WO 2019/067910. See also WO 2020/082046 A2 (pp. 84-85) and Table 24 in WO 2020/069296, each of which is herein incorporated by reference in its entirety for all purposes. [00541] Another example of a Cas protein is a Cpf1 (CRISPR from Prevotella and Francisella 1) protein. Cpf1 is a large protein (about 1300 amino acids) that contains a RuvC- like nuclease domain homologous to the corresponding domain of Cas9 along with a counterpart to the characteristic arginine-rich cluster of Cas9. However, Cpf1 lacks the HNH nuclease domain that is present in Cas9 proteins, and the RuvC-like domain is contiguous in the Cpf1 sequence, in contrast to Cas9 where it contains long inserts including the HNH domain. See, e.g., Zetsche et al. (2015) Cell 163(3):759-771, herein incorporated by reference in its entirety for all purposes. Exemplary Cpf1 proteins are from Francisella tularensis 1, Francisella tularensis subsp. novicida, Prevotella albensis, Lachnospiraceae bacterium MC2017 1, Butyrivibrio proteoclasticus, Peregrinibacteria bacterium GW2011_GWA2_33_10, Parcubacteria bacterium GW2011_GWC2_44_17, Smithella sp. SCADC, Acidaminococcus sp. BV3L6, Lachnospiraceae bacterium MA2020, Candidatus Methanoplasma termitum, Eubacterium eligens, Moraxella bovoculi 237, Leptospira inadai, Lachnospiraceae bacterium ND2006, Porphyromonas crevioricanis 3, Prevotella disiens, and Porphyromonas macacae. Cpf1 from Francisella novicida U112 (FnCpf1; assigned UniProt accession number A0Q7Q2) is an exemplary Cpf1 protein. Attorney Docket No.250298.000780 [00542] Another example of a Cas protein is CasX (Cas12e). CasX is an RNA-guided DNA endonuclease that generates a staggered double-strand break in DNA. CasX is less than 1000 amino acids in size. Exemplary CasX proteins are from Deltaproteobacteria (DpbCasX or DpbCas12e) and Planctomycetes (PlmCasX or PlmCas12e). Like Cpf1, CasX uses a single RuvC active site for DNA cleavage. See, e.g., Liu et al. (2019) Nature 566(7743):218-223, herein incorporated by reference in its entirety for all purposes. [00543] Another example of a Cas protein is CasΦ (CasPhi or Cas12j), which is uniquely found in bacteriophages. CasΦ is less than 1000 amino acids in size (e.g., 700-800 amino acids). CasΦ cleavage generates staggered 5’ overhangs. A single RuvC active site in CasΦ is capable of crRNA processing and DNA cutting. See, e.g., Pausch et al. (2020) Science 369(6501):333-337, herein incorporated by reference in its entirety for all purposes. [00544] Cas proteins can be wild type proteins (i.e., those that occur in nature), modified Cas proteins (i.e., Cas protein variants), or fragments of wild type or modified Cas proteins. Cas proteins can also be active variants or fragments with respect to catalytic activity of wild type or modified Cas proteins. Active variants or fragments with respect to catalytic activity can comprise at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more sequence identity to the wild type or modified Cas protein or a portion thereof, wherein the active variants retain the ability to cut at a desired cleavage site and hence retain nick-inducing or double-strand-break-inducing activity. Assays for nick-inducing or double- strand-break-inducing activity are known and generally measure the overall activity and specificity of the Cas protein on DNA substrates containing the cleavage site. [00545] One example of a modified Cas protein is the modified SpCas9-HF1 protein, which is a high-fidelity variant of Streptococcus pyogenes Cas9 harboring alterations (N497A/R661A/Q695A/Q926A) designed to reduce non-specific DNA contacts. See, e.g., Kleinstiver et al. (2016) Nature 529(7587):490-495, herein incorporated by reference in its entirety for all purposes. Another example of a modified Cas protein is the modified eSpCas9 variant (K848A/K1003A/R1060A) designed to reduce off-target effects. See, e.g., Slaymaker et al. (2016) Science 351(6268):84-88, herein incorporated by reference in its entirety for all purposes. Other SpCas9 variants include K855A and K810A/K1003A/R1060A. These and other modified Cas proteins are reviewed, e.g., in Cebrian-Serrano and Davies (2017) Mamm. Genome 28(7):247-261, herein incorporated by reference in its entirety for all purposes. Another example of a modified Cas9 protein is xCas9, which is a SpCas9 variant that can Attorney Docket No.250298.000780 recognize an expanded range of PAM sequences. See, e.g., Hu et al. (2018) Nature 556:57- 63, herein incorporated by reference in its entirety for all purposes. [00546] Cas proteins can be modified to increase or decrease one or more of nucleic acid binding affinity, nucleic acid binding specificity, and enzymatic activity. Cas proteins can also be modified to change any other activity or property of the protein, such as stability. For example, one or more nuclease domains of the Cas protein can be modified, deleted, or inactivated, or a Cas protein can be truncated to remove domains that are not essential for the function of the protein or to optimize (e.g., enhance or reduce) the activity of or a property of the Cas protein. [00547] Cas proteins can comprise at least one nuclease domain, such as a dNase domain. For example, a wild type Cpf1 protein generally comprises a RuvC-like domain that cleaves both strands of target DNA, perhaps in a dimeric configuration. Likewise, CasX and CasΦ generally comprise a single RuvC-like domain that cleaves both strands of a target DNA. Cas proteins can also comprise at least two nuclease domains, such as dNase domains. For example, a wild type Cas9 protein generally comprises a RuvC-like nuclease domain and an HNH-like nuclease domain. The RuvC and HNH domains can each cut a different strand of double-stranded DNA to make a double-stranded break in the DNA. See, e.g., Jinek et al. (2012) Science 337(6096):816-821, herein incorporated by reference in its entirety for all purposes. [00548] One or more or all of the nuclease domains can be deleted or mutated so that they are no longer functional or have reduced nuclease activity. For example, if one of the nuclease domains is deleted or mutated in a Cas9 protein, the resulting Cas9 protein can be referred to as a nickase and can generate a single-strand break within a double-stranded target DNA but not a double-strand break (i.e., it can cleave the complementary strand or the non-complementary strand, but not both). If both of the nuclease domains are deleted or mutated, the resulting Cas protein (e.g., Cas9) will have a reduced ability to cleave both strands of a double-stranded DNA (e.g., a nuclease-null or nuclease-inactive Cas protein, or a catalytically dead Cas protein (dCas)). If none of the nuclease domains is deleted or mutated in a Cas9 protein, the Cas9 protein will retain double-strand-break-inducing activity. An example of a mutation that converts Cas9 into a nickase is a D10A (aspartate to alanine at position 10 of Cas9) mutation in the RuvC domain of Cas9 from S. pyogenes. Likewise, H939A (histidine to alanine at amino acid position 839), H840A (histidine to alanine at amino acid position 840), or N863A (asparagine to alanine at amino acid position N863) in the HNH Attorney Docket No.250298.000780 domain of Cas9 from S. pyogenes can convert the Cas9 into a nickase. Other examples of mutations that convert Cas9 into a nickase include the corresponding mutations to Cas9 from S. thermophilus. See, e.g., Sapranauskas et al. (2011) Nucleic Acids Res.39(21):9275-9282 and WO 2013/141680, each of which is herein incorporated by reference in its entirety for all purposes. Such mutations can be generated using methods such as site-directed mutagenesis, PCR-mediated mutagenesis, or total gene synthesis. Examples of other mutations creating nickases can be found, for example, in WO 2013/176772 and WO 2013/142578, each of which is herein incorporated by reference in its entirety for all purposes. If all of the nuclease domains are deleted or mutated in a Cas protein (e.g., both of the nuclease domains are deleted or mutated in a Cas9 protein), the resulting Cas protein (e.g., Cas9) will have a reduced ability to cleave both strands of a double-stranded DNA (e.g., a nuclease-null or nuclease-inactive Cas protein). One specific example is a D10A/H840A S. pyogenes Cas9 double mutant or a corresponding double mutant in a Cas9 from another species when optimally aligned with S. pyogenes Cas9. Another specific example is a D10A/N863A S. pyogenes Cas9 double mutant or a corresponding double mutant in a Cas9 from another species when optimally aligned with S. pyogenes Cas9. [00549] Examples of inactivating mutations in the catalytic domains of xCas9 are the same as those described above for SpCas9. Examples of inactivating mutations in the catalytic domains of Staphylococcus aureus Cas9 proteins are also known. For example, the Staphylococcus aureus Cas9 enzyme (SaCas9) may comprise a substitution at position N580 (e.g., N580A substitution) or a substitution at position D10 (e.g., D10A substitution) to generate a Cas nickase. See, e.g., WO 2016/106236, herein incorporated by reference in its entirety for all purposes. Examples of inactivating mutations in the catalytic domains of Nme2Cas9 are also known (e.g., D16A or H588A). Examples of inactivating mutations in the catalytic domains of St1Cas9 are also known (e.g., D9A, D598A, H599A, or N622A). Examples of inactivating mutations in the catalytic domains of St3Cas9 are also known (e.g., D10A or N870A). Examples of inactivating mutations in the catalytic domains of CjCas9 are also known (e.g., combination of D8A or H559A). Examples of inactivating mutations in the catalytic domains of FnCas9 and RHA FnCas9 are also known (e.g., N995A). [00550] Examples of inactivating mutations in the catalytic domains of Cpf1 proteins are also known. With reference to Cpf1 proteins from Francisella novicida U112 (FnCpf1), Acidaminococcus sp. BV3L6 (AsCpf1), Lachnospiraceae bacterium ND2006 (LbCpf1), and Moraxella bovoculi 237 (MbCpf1 Cpf1), such mutations can include mutations at positions Attorney Docket No.250298.000780 908, 993, or 1263 of AsCpf1 or corresponding positions in Cpf1 orthologs, or positions 832, 925, 947, or 1180 of LbCpf1 or corresponding positions in Cpf1 orthologs. Such mutations can include, for example one or more of mutations D908A, E993A, and D1263A of AsCpf1 or corresponding mutations in Cpf1 orthologs, or D832A, E925A, D947A, and D1180A of LbCpf1 or corresponding mutations in Cpf1 orthologs. See, e.g., US 2016/0208243, herein incorporated by reference in its entirety for all purposes. [00551] Examples of inactivating mutations in the catalytic domains of CasX proteins are also known. With reference to CasX proteins from Deltaproteobacteria, D672A, E769A, and D935A (individually or in combination) or corresponding positions in other CasX orthologs are inactivating. See, e.g., Liu et al. (2019) Nature 566(7743):218-223, herein incorporated by reference in its entirety for all purposes. [00552] Examples of inactivating mutations in the catalytic domains of CasΦ proteins are also known. For example, D371A and D394A, alone or in combination, are inactivating mutations. See, e.g., Pausch et al. (2020) Science 369(6501):333-337, herein incorporated by reference in its entirety for all purposes. [00553] Cas proteins can also be operably linked to heterologous polypeptides as fusion proteins. For example, a Cas nuclease can be fused to a cleavage domain, an epigenetic modification domain, a transcriptional activation domain, or a transcriptional repressor domain. See WO 2014/089290, herein incorporated by reference in its entirety for all purposes. Examples of transcriptional activation domains include a herpes simplex virus VP 16 activation domain, VP64 (which is a tetrameric derivative of VP 16), a NFKB p65 activation domain, p53 activation domains 1 and 2, a CREB (cAMP response element binding protein) activation domain, an E2A activation domain, and an NFAT (nuclear factor of activated T-cells) activation domain. Other examples include activation domains from Octl, Oct-2A, SP1, AP-2, CTF1, P300, CBP, PCAF, SRC1, PvALF, ERF-2, OsGAI, HALF-1, Cl, API, ARF-5, ARF-6, ARF-7, ARF-8, CPRF1, CPRF4, MYC- RP/GP, TRAB1PC4, and HSF1. See, e.g., US 2016/0237456, EP3045537, and WO 2011/146121, each of which is incorporated by reference in its entirety for all purposes. [00554] In some cases, a transcriptional activation system can be used comprising a dCas9-VP64 fusion protein paired with MS2-p65-HSFl. Guide RNAs in such systems can be designed with aptamer sequences appended to sgRNA tetraloop and stem-loop 2 designed to bind dimerized MS2 bacteriophage coat proteins. See, e.g., Konermann et al. (2015) Nature 517(7536):583-588, herein incorporated by reference in its entirety for all purposes. Attorney Docket No.250298.000780 [00555] Examples of transcriptional repressor domains include inducible cAMP early repressor (ICER) domains, Kruppel-associated box A (KRAB-A) repressor domains, YY 1 glycine rich repressor domains, Spl -like repressors, E(spl) repressors, IKB repressor, and MeCP2. Other examples include transcriptional repressor domains from A/B, KOX, TGF- beta-inducible early gene (TIEG), v-erbA, SID, SID4X, MBD2, MBD3, DNMT1, DNMG3A, DNMT3B, Rb, ROM2, See, e.g., EP3045537 and WO 2011/146121, each of which is incorporated by reference in its entirety for all purposes. Cas nucleases can also be fused to a heterologous polypeptide providing increased or decreased stability. The fused domain or heterologous polypeptide can be located at the N-terminus, the C-terminus, or internally within the Cas nuclease. [00556] As one example, a Cas protein can be fused to one or more heterologous polypeptides that provide for subcellular localization. Such heterologous polypeptides can include, for example, one or more nuclear localization signals (NLS) such as the monopartite SV40 NLS and/or a bipartite alpha-importin NLS for targeting to the nucleus, a mitochondrial localization signal for targeting to the mitochondria, an ER retention signal, and the like. See, e.g., Lange et al. (2007) J. Biol. Chem.282(8):5101-5105, herein incorporated by reference in its entirety for all purposes. Such subcellular localization signals can be located at the N- terminus, the C-terminus, or anywhere within the Cas protein. An NLS can comprise a stretch of basic amino acids, and can be a monopartite sequence or a bipartite sequence. Optionally, a Cas protein can comprise two or more NLSs, including an NLS (e.g., an alpha-importin NLS or a monopartite NLS) at the N-terminus and an NLS (e.g., an SV40 NLS or a bipartite NLS) at the C-terminus. A Cas protein can also comprise two or more NLSs at the N-terminus and/or two or more NLSs at the C-terminus. [00557] A Cas protein may, for example, be fused with 1-10 NLSs (e.g., fused with 1-5 NLSs or fused with one NLS. Where one NLS is used, the NLS may be linked at the N- terminus or the C-terminus of the Cas protein sequence. It may also be inserted within the Cas protein sequence. Alternatively, the Cas protein may be fused with more than one NLS. For example, the Cas protein may be fused with 2, 3, 4, or 5 NLSs. In a specific example, the Cas protein may be fused with two NLSs. In certain circumstances, the two NLSs may be the same (e.g., two SV40 NLSs) or different. For example, the Cas protein can be fused to two SV40 NLS sequences linked at the carboxy terminus. Alternatively, the Cas protein may be fused with two NLSs, one linked at the N-terminus and one at the C-terminus. In other examples, the Cas protein may be fused with 3 NLSs or with no NLS. The NLS may be a Attorney Docket No.250298.000780 monopartite sequence, such as, e.g., the SV40 NLS, PKKKRKV (SEQ ID NO: 646) or PKKKRRV (SEQ ID NO: 647). The NLS may be a bipartite sequence, such as the NLS of nucleoplasmin, KRPAATKKAGQAKKKK (SEQ ID NO: 648). In a specific example, a single PKKKRKV (SEQ ID NO: 646) NLS may be linked at the C-terminus of the Cas protein. One or more linkers are optionally included at the fusion site. [00558] Cas proteins can also be operably linked to a cell-penetrating domain or protein transduction domain. For example, the cell-penetrating domain can be derived from the HIV- 1 TAT protein, the TLM cell-penetrating motif from human hepatitis B virus, MPG, Pep-1, VP22, a cell penetrating peptide from Herpes simplex virus, or a polyarginine peptide sequence. See, e.g., WO 2014/089290 and WO 2013/176772, each of which is herein incorporated by reference in its entirety for all purposes. The cell-penetrating domain can be located at the N-terminus, the C-terminus, or anywhere within the Cas protein. [00559] Cas proteins can also be operably linked to a heterologous polypeptide for ease of tracking or purification, such as a fluorescent protein, a purification tag, or an epitope tag. Examples of fluorescent proteins include green fluorescent proteins (e.g., GFP, GFP-2, tagGFP, turboGFP, eGFP, Emerald, Azami Green, Monomeric Azami Green, CopGFP, AceGFP, ZsGreenl), yellow fluorescent proteins (e.g., YFP, eYFP, Citrine, Venus, yPet, PhiYFP, ZsYellowl), blue fluorescent proteins (e.g., eBFP, eBFP2, Azurite, mKalamal, GFPuv, Sapphire, T-sapphire), cyan fluorescent proteins (e.g., eCFP, Cerulean, CyPet, AmCyanl, Midoriishi-Cyan), red fluorescent proteins (e.g., mKate, mKate2, mPlum, DsRed monomer, mCherry, mRFP1, DsRed-Express, DsRed2, DsRed-Monomer, HcRed-Tandem, HcRedl, AsRed2, eqFP611, mRaspberry, mStrawberry, Jred), orange fluorescent proteins (e.g., mOrange, mKO, Kusabira-Orange, Monomeric Kusabira-Orange, mTangerine, tdTomato), and any other suitable fluorescent protein. Examples of tags include glutathione- S-transferase (GST), chitin binding protein (CBP), maltose binding protein, thioredoxin (TRX), poly(NANP), tandem affinity purification (TAP) tag, myc, AcV5, AU1, AU5, E, ECS, E2, FLAG, hemagglutinin (HA), nus, Softag 1, Softag 3, Strep, SBP, Glu-Glu, HSV, KT3, S, S1, T7, V5, VSV-G, histidine (His), biotin carboxyl carrier protein (BCCP), and calmodulin. [00560] Cas proteins can also be tethered to labeled nucleic acids. Such tethering (i.e., physical linking) can be achieved through covalent interactions or noncovalent interactions, and the tethering can be direct (e.g., through direct fusion or chemical conjugation, which can be achieved by modification of cysteine or lysine residues on the protein or intein modification), or can be achieved through one or more intervening linkers or adapter Attorney Docket No.250298.000780 molecules such as streptavidin or aptamers. See, e.g., Pierce et al. (2005) Mini Rev. Med. Chem. 5(1):41-55; Duckworth et al. (2007) Angew. Chem. Int. Ed. Engl.46(46):8819-8822; Schaeffer and Dixon (2009) Australian J. Chem. 62(10):1328-1332; Goodman et al. (2009) Chembiochem. 10(9):1551-1557; and Khatwani et al. (2012) Bioorg. Med. Chem. 20(14):4532-4539, each of which is herein incorporated by reference in its entirety for all purposes. Noncovalent strategies for synthesizing protein-nucleic acid conjugates include biotin-streptavidin and nickel-histidine methods. Covalent protein-nucleic acid conjugates can be synthesized by connecting appropriately functionalized nucleic acids and proteins using a wide variety of chemistries. Some of these chemistries involve direct attachment of the oligonucleotide to an amino acid residue on the protein surface (e.g., a lysine amine or a cysteine thiol), while other more complex schemes require post-translational modification of the protein or the involvement of a catalytic or reactive protein domain. Methods for covalent attachment of proteins to nucleic acids can include, for example, chemical cross-linking of oligonucleotides to protein lysine or cysteine residues, expressed protein-ligation, chemoenzymatic methods, and the use of photoaptamers. The labeled nucleic acid can be tethered to the C-terminus, the N-terminus, or to an internal region within the Cas protein. In one example, the labeled nucleic acid is tethered to the C-terminus or the N-terminus of the Cas protein. Likewise, the Cas protein can be tethered to the 5’ end, the 3’ end, or to an internal region within the labeled nucleic acid. That is, the labeled nucleic acid can be tethered in any orientation and polarity. For example, the Cas protein can be tethered to the 5’ end or the 3’ end of the labeled nucleic acid. [00561] Cas proteins can be provided in any form. For example, a Cas protein can be provided in the form of a protein, such as a Cas protein complexed with a gRNA. Alternatively, a Cas protein can be provided in the form of a nucleic acid encoding the Cas protein, such as an RNA (e.g., messenger RNA (mRNA)) or DNA. Optionally, the nucleic acid encoding the Cas protein can be codon optimized for efficient translation into protein in a particular cell or organism. For example, the nucleic acid encoding the Cas protein can be modified to substitute codons having a higher frequency of usage in a bacterial cell, a yeast cell, a human cell, a non-human cell, a mammalian cell, a rodent cell, a mouse cell, a rat cell, or any other host cell of interest, as compared to the naturally occurring polynucleotide sequence. In some embodiments, the nucleic acid encoding the Cas nuclease is codon-optimized for expression in a mammalian cell. In some embodiments, the nucleic acid encoding the Cas nuclease is codon-optimized for expression in a human cell. Codon usage tables are readily available, Attorney Docket No.250298.000780 for example, at the “Codon Usage Database.” These tables can be adapted in a number of ways. See Nakamura et al. (2000) Nucleic Acids Research 28:292, herein incorporated by reference in its entirety for all purposes. Computer algorithms for codon optimization of a particular sequence for expression in a particular host are also available (see, e.g., Gene Forge). Examples of codon-optimized Cas9 coding sequences, Cas9 mRNAs, and Cas9 protein sequences include those described in WO2013/176772, WO2014/065596, W02016/106121, and W02019/067910 are hereby incorporated by reference. In particular, the Cas9 coding sequences and Cas9 amino acid sequences of the table at paragraph [0449] WO2019/067910, and the Cas9 mRNAs and coding sequences of paragraphs [0214] - [0234] of WO2019/067910 are hereby incorporated by reference. When a nucleic acid encoding the Cas protein is introduced into the cell, the Cas protein can be transiently, conditionally, or constitutively expressed in the cell. [00562] Nucleic acids encoding Cas proteins can be stably integrated in the genome of a cell and operably linked to a promoter active in the cell. Alternatively, nucleic acids encoding Cas proteins can be operably linked to a promoter in an expression construct. Expression constructs include any nucleic acid constructs capable of directing expression of a gene or other nucleic acid sequence of interest (e.g., a Cas gene) and which can transfer such a nucleic acid sequence of interest to a target cell. For example, the nucleic acid encoding the Cas protein can be in a vector comprising a DNA encoding a gRNA. Alternatively, it can be in a vector or plasmid that is separate from the vector comprising the DNA encoding the gRNA. Promoters that can be used in an expression construct include promoters active, for example, in one or more of a eukaryotic cell, a human cell, a non-human cell, a mammalian cell, a non-human mammalian cell, a rodent cell, a mouse cell, a rat cell, a pluripotent cell, an embryonic stem (ES) cell, an adult stem cell, a developmentally restricted progenitor cell, an induced pluripotent stem (iPS) cell, or a one-cell stage embryo. Such promoters can be, for example, conditional promoters, inducible promoters, constitutive promoters, or tissue- specific promoters. Optionally, the promoter can be a bidirectional promoter driving expression of both a Cas protein in one direction and a guide RNA in the other direction. Such bidirectional promoters can consist of (1) a complete, conventional, unidirectional Pol III promoter that contains 3 external control elements: a distal sequence element (DSE), a proximal sequence element (PSE), and a TATA box; and (2) a second basic Pol III promoter that includes a PSE and a TATA box fused to the 5’ terminus of the DSE in reverse orientation. For example, in the H1 promoter, the DSE is adjacent to the PSE and the TATA box, and the Attorney Docket No.250298.000780 promoter can be rendered bidirectional by creating a hybrid promoter in which transcription in the reverse direction is controlled by appending a PSE and TATA box derived from the U6 promoter. See, e.g., US 2016/0074535, herein incorporated by references in its entirety for all purposes. Use of a bidirectional promoter to express genes encoding a Cas protein and a guide RNA simultaneously allow for the generation of compact expression cassettes to facilitate delivery. In preferred embodiments, promotors are accepted by regulatory authorities for use in humans. In certain embodiments, promotors drive expression in a liver cell. [00563] Different promoters can be used to drive Cas expression or Cas9 expression. In some methods, small promoters are used so that the Cas or Cas9 coding sequence can fit into an AAV construct. For example, Cas or Cas9 and one or more gRNAs (e.g., 1 gRNA or 2 gRNAs or 3 gRNAs or 4 gRNAs) can be delivered via LNP-mediated delivery (e.g., in the form of RNA). Different promoters can be used to drive expression of the gRNA, such as a U6 promoter or the small tRNA Gln. Likewise, different promoters can be used to drive Cas9 expression. [00564] Cas proteins provided as mRNAs can be modified for improved stability and/or immunogenicity properties. The modifications may be made to one or more nucleosides within the mRNA. Examples of chemical modifications to mRNA nucleobases include pseudouridine, 1-methyl-pseudouridine, and 5-methyl-cytidine. mRNA encoding Cas proteins can also be capped. The cap can be, for example, a cap 1 structure in which the +1 ribonucleotide is methylated at the 2’O position of the ribose. The capping can, for example, give superior activity in vivo (e.g., by mimicking a natural cap), can result in a natural structure that reduce stimulation of the innate immune system of the host (e.g., can reduce activation of pattern recognition receptors in the innate immune system). mRNA encoding Cas proteins can also be polyadenylated (to comprise a poly(A) tail). mRNA encoding Cas proteins can also be modified to include pseudouridine (e.g., can be fully substituted with pseudouridine). As another example, capped and polyadenylated Cas mRNA containing N1-methyl pseudouridine can be used. As another example, Cas mRNA fully substituted with pseudouridine can be used (i.e., all standard uracil residues are replaced with pseudouridine, a uridine isomer in which the uracil is attached with a carbon-carbon bond rather than nitrogen-carbon). Likewise, Cas mRNAs can be modified by depletion of uridine using synonymous codons. For example, capped and polyadenylated Cas mRNA fully substituted with pseudouridine can be used. Attorney Docket No.250298.000780 [00565] Cas mRNAs can comprise a modified uridine at least at one, a plurality of, or all uridine positions. The modified uridine can be a uridine modified at the 5’ position (e.g., with a halogen, methyl, or ethyl). The modified uridine can be a pseudouridine modified at the 1 position (e.g., with a halogen, methyl, or ethyl). The modified uridine can be, for example, pseudouridine, N1-methyl-pseudouridine, 5-methoxyuridine, 5-iodouridine, or a combination thereof. In some examples, the modified uridine is 5-methoxyuridine. In some examples, the modified uridine is 5-iodouridine. In some examples, the modified uridine is pseudouridine. In some examples, the modified uridine is N1-methyl-pseudouridine. In some examples, the modified uridine is a combination of pseudouridine and N1-methyl-pseudouridine. In some examples, the modified uridine is a combination of pseudouridine and 5-methoxyuridine. In some examples, the modified uridine is a combination of N1-methyl pseudouridine and 5- methoxyuridine. In some examples, the modified uridine is a combination of 5-iodouridine and N1-methyl-pseudouridine. In some examples, the modified uridine is a combination of pseudouridine and 5-iodouridine. In some examples, the modified uridine is a combination of 5-iodouridine and 5-methoxyuridine. [00566] Cas mRNAs disclosed herein can also comprise a 5’ cap, such as a Cap0, Cap1, or Cap2. A 5’ cap is generally a 7-methylguanine ribonucleotide (which may be further modified, e.g., with respect to ARCA) linked through a 5’-triphosphate to the 5’ position of the first nucleotide of the 5’-to-3’ chain of the mRNA (i.e., the first cap-proximal nucleotide). In Cap0, the riboses of the first and second cap-proximal nucleotides of the mRNA both comprise a 2’-hydroxyl. In Cap1, the riboses of the first and second transcribed nucleotides of the mRNA comprise a 2’-methoxy and a 2’-hydroxyl, respectively. In Cap2, the riboses of the first and second cap-proximal nucleotides of the mRNA both comprise a 2’-methoxy. See, e.g., Katibah et al. (2014) Proc. Natl. Acad. Sci. U.S.A. 111(33):12025-30 and Abbas et al. (2017) Proc. Natl. Acad. Sci. U.S.A. 114(11):E2106-E2115, each of which is herein incorporated by reference in its entirety for all purposes. Most endogenous higher eukaryotic mRNAs, including mammalian mRNAs such as human mRNAs, comprise Cap1 or Cap2. Cap0 and other cap structures differing from Cap1 and Cap2 may be immunogenic in mammals, such as humans, due to recognition as non-self by components of the innate immune system such as IFIT-1 and IFIT-5, which can result in elevated cytokine levels including type I interferon. Components of the innate immune system such as IFIT-1 and IFIT- 5 may also compete with eIF4E for binding of an mRNA with a cap other than Cap1 or Cap2, potentially inhibiting translation of the mRNA. Attorney Docket No.250298.000780 [00567] A cap can be included co-transcriptionally. For example, ARCA (anti-reverse cap analog; Thermo Fisher Scientific Cat. No. AM8045) is a cap analog comprising a 7- methylguanine 3’-methoxy-5’-triphosphate linked to the 5’ position of a guanine ribonucleotide which can be incorporated in vitro into a transcript at initiation. ARCA results in a Cap0 cap in which the 2’ position of the first cap-proximal nucleotide is hydroxyl. See, e.g., Stepinski et al. (2001) RNA 7:1486-1495, herein incorporated by reference in its entirety for all purposes. [00568] CleanCapTM AG (m7G(5’)ppp(5’)(2’oMeA)pG; TriLink Biotechnologies Cat. No. N-7113) or CleanCapTM GG (m7G(5’)ppp(5’)(2’oMeG)pG; TriLink Biotechnologies Cat. No. N-7133) can be used to provide a Cap1 structure co-transcriptionally. 3’-O-methylated versions of CleanCapTM AG and CleanCapTM GG are also available from TriLink Biotechnologies as Cat. Nos. N-7413 and N-7433, respectively. [00569] Alternatively, a cap can be added to an RNA post-transcriptionally. For example, Vaccinia capping enzyme is commercially available (New England Biolabs Cat. No. M2080S) and has RNA triphosphatase and guanylyltransferase activities, provided by its D1 subunit, and guanine methyltransferase, provided by its D12 subunit. As such, it can add a 7-methylguanine to an RNA, so as to give Cap0, in the presence of S-adenosyl methionine and GTP. See, e.g., Guo and Moss (1990) Proc. Natl. Acad. Sci. U.S.A.87:4023-4027 and Mao and Shuman (1994) J. Biol. Chem. 269:24472-24479, each of which is herein incorporated by reference in its entirety for all purposes. [00570] Cas mRNAs can further comprise a poly-adenylated (poly-A or poly(A) or poly- adenine) tail. The poly-A tail can, for example, comprise at least 20, at least 30, at least 40, at least 50, at least 60, at least 70, at least 80, at least 90, or at least 100 adenines, and optionally up to 300 adenines. For example, the poly-A tail can comprise 95, 96, 97, 98, 99, or 100 adenine nucleotides. [00571] In some embodiments, a CRISPR/Cas system can be used to create a site of insertion at a desired locus within a host genome, at which site a construct disclosed herein can be inserted to express one or more polypeptides of interest. Methods of designing suitable guide RNAs that target any desired locus of a host genome for insertion are well known in the art. A construct comprising a transgene may be heterologous with respect to its insertion site, for example, insertion of a heterologous transgene into a “safe harbor” locus. A construct comprising a transgene may be non-heterologous with respect to its insertion site, for example, insertion of a wild-type transgene into its endogenous locus. Attorney Docket No.250298.000780 [00572] Safe harbor loci include chromosomal loci where transgenes or other exogenous nucleic acid inserts can be stably and reliably expressed in all tissues of interest without overtly altering cell behavior or phenotype (i.e., without any deleterious effects on the host cell). See, e.g., Sadelain et al. (2012) Nat. Rev. Cancer 12:51-58, herein incorporated by reference in its entirety for all purposes. For example, the safe harbor locus can be one in which expression of the inserted gene sequence is not perturbed by any read-through expression from neighboring genes. For example, safe harbor loci can include chromosomal loci where exogenous DNA can integrate and function in a predictable manner without adversely affecting endogenous gene structure or expression. Safe harbor loci can include extragenic regions or intragenic regions such as, for example, loci within genes that are non- essential, dispensable, or able to be disrupted without overt phenotypic consequences. [00573] Such safe harbor loci can offer an open chromatin configuration in all tissues and can be ubiquitously expressed during embryonic development and in adults. See, e.g., Zambrowicz et al. (1997) Proc. Natl. Acad. Sci. U.S.A.94:3789-3794, herein incorporated by reference in its entirety for all purposes. In addition, the safe harbor loci can be targeted with high efficiency, and safe harbor loci can be disrupted with no overt phenotype. Examples of safe harbor loci include ALB, CCR5, HPRT, AAVS1 (PPP1 R12C), Rosa (e.g., Rosa26), AngptiS, ApoC3, ASGR2, FIX (F9), G6PC, Gys2, HGD, Lp(a), Pcsk9, SERPINA1, TF, and TTR. See, e.g., US Patent Nos. 7,888,121; 7,972,854; 7,914,796; 7,951,925; 8,110,379; 8,409,861; 8,586,526; and US Patent Publication Nos. 2003/0232410; 2005/0208489; 2005/0026157; 2006/0063231; 2008/0159996; 2010/00218264; 2012/0017290; 2011/0265198; 2013/0137104; 2013/0122591; 2013/0177983; 2013/0177960; and 2013/0122591, each of which is herein incorporated by reference in its entirety for all purposes. Other examples of target genomic loci include an ALB locus, a EESYR locus, a SARS locus, position 188,083,272 of human chromosome 1 or its non-human mammalian orthologue, position 3,046,320 of human chromosome 10 or its non-human mammalian orthologue, position 67, 328,980 of human chromosome 17 or its non-human mammalian orthologue, an adeno-associated virus site 1 (AAVS1) on chromosome, a naturally occurring site of integration of AAV virus on human chromosome 19 or its non-human mammalian orthologue, a chemokine receptor 5 (CCR5) gene, a chemokine receptor gene encoding an HIV-1 coreceptor, or a mouse Rosa26 locus or its non-murine mammalian orthologue. [00574] In some embodiments, the heterologous gene may be inserted into a safe harbor locus and use the safe harbor locus’s endogenous signal sequence. In some Attorney Docket No.250298.000780 embodiments, the heterologous gene may comprise its own signal sequence, may be inserted into the safe harbor locus, and may further use the safe harbor locus’s endogenous signal sequence. In some embodiments, the gene may comprise its own signal sequence and an internal ribosomal entry site (IRES), may be inserted into the safe harbor locus, and may further use the safe harbor locus’s endogenous signal sequence. In some embodiments, the gene may comprise its own signal sequence and IRES, may be inserted into the safe harbor locus, and does not use the safe harbor locus’s endogenous signal sequence. In some embodiments, the gene may be inserted into the safe harbor locus and may comprise an IRES and does not use any signal sequence. [00575] In some methods, two or more nuclease agents can be used. For example, two or more nuclease agents can be used, each targeting a nuclease target sequence including or proximate to the start codon. As another example, two nuclease agents can be used, one targeting a nuclease target sequence including or proximate to the start codon, and one targeting a nuclease target sequence including or proximate to the stop codon, wherein cleavage by the nuclease agents can result in deletion of the coding region between the two nuclease target sequences. As yet another example, three or more nuclease agents can be used, with one or more (e.g., two) targeting nuclease target sequences including or proximate to the start codon, and one or more (e.g., two) targeting nuclease target sequences including or proximate to the stop codon, wherein cleavage by the nuclease agents can result in deletion of the coding region between the nuclease target sequences including or proximate to the start codon and the nuclease target sequence including or proximate to the stop codon. [00576] In some embodiments, CRISPR/Cas systems used in the compositions and methods disclosed herein can be non-naturally occurring. [00577] In some embodiments, the Cas protein (e.g., Cas9) may be complexed with a gRNA to form a ribonucleoprotein complex (RNP). In some embodiments, a molecular cargo (e.g., liposome or LNP) of the present disclosure comprises a ribonucleoprotein complex (RNP) comprising a Cas protein (e.g., Cas9) and a gRNA. [00578] In some embodiments, a molecular cargo (e.g., liposomes and LNPs) described herein may comprise one or more components from gene editing systems other than a CRISPR/Cas system. In some embodiments, the molecular cargo is a nuclease, such as Zinc-finger nuclease (ZFN) or a TALEN, which is effective to bind and modify at a target gene. Attorney Docket No.250298.000780 [00579] Any nuclease molecular cargo that induces a nick or double-strand break into a desired target sequence or any DNA-binding protein that binds to a desired target sequence can be used in the methods and compositions disclosed herein. A naturally occurring or native nuclease molecular cargo can be employed so long as the nuclease molecular cargo induces a nick or double-strand break in a desired target sequence. Likewise, a naturally occurring or native DNA-binding protein can be employed so long as the DNA-binding protein binds to the desired target sequence. Alternatively, a modified or engineered nuclease molecular cargo or DNA-binding protein can be employed. An “engineered nuclease molecular cargo or DNA- binding protein” includes a nuclease molecular cargo or DNA-binding protein that is engineered (modified or derived) from its native form to specifically recognize a desired target sequence. Thus, an engineered nuclease molecular cargo or DNA-binding protein can be derived from a native, naturally occurring nuclease molecular cargo or DNA-binding protein or it can be artificially created or synthesized. The engineered nuclease molecular cargo or DNA-binding protein can recognize a target sequence, for example, wherein the target sequence is not a sequence that would have been recognized by a native (non-engineered or non-modified) nuclease molecular cargo or DNA-binding protein. The modification of the nuclease molecular cargo or DNA- binding protein can be as little as one amino acid in a protein cleavage molecular cargo or one nucleotide in a nucleic acid cleavage molecular cargo. Producing a nick or double-strand break in a target sequence or other DNA can be referred to herein as “cutting” or “cleaving” the target sequence or other DNA. [00580] Active variants and fragments of nuclease molecular cargoes or DNA-binding proteins (i.e., an engineered nuclease molecular cargo or DNA-binding protein) are also provided. Such active variants can comprise at least 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more sequence identity to the native nuclease molecular cargo or DNA-binding protein, wherein the active variants retain the ability to cut at a desired target sequence and hence retain nick or double-strand-break-inducing activity or retain the ability to bind a desired target sequence. For example, any of the nuclease molecular cargoes described herein can be modified from a native endonuclease sequence and designed to recognize and induce a nick or double-strand break at a target sequence that was not recognized by the native nuclease molecular cargo. Thus, some engineered nucleases have a specificity to induce a nick or double-strand break at a target sequence that is different from the corresponding native nuclease molecular cargo target sequence. Assays for nick or double- strand-break-inducing activity are known and generally measure the overall Attorney Docket No.250298.000780 activity and specificity of the endonuclease on DNA substrates containing the target sequence. The target sequence can be endogenous (or native) to the cell or the target sequence can be exogenous to the cell. A target sequence that is exogenous to the cell is not naturally occurring in the genome of the cell. The target sequence can also exogenous to the polynucleotides of interest that one desires to be positioned at the target locus. In some cases, the target sequence is present only once in the genome of the host cell. [00581] Active variants and fragments of the exemplified target sequences are also provided. Such active variants can comprise at least 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more sequence identity to the given target sequence, wherein the active variants retain biological activity and hence are capable of being recognized and cleaved by a nuclease molecular cargo in a sequence-specific manner. Assays to measure the double-strand break of a target sequence by a nuclease molecular cargo are known (e.g., TAQMAN® qPCR assay, Frendewey et al. (2010) Methods in Enzymology 476:295-307, herein incorporated by reference in its entirety for all purposes). [00582] The length of the target sequence can vary, and includes, for example, target sequences that are about 30-36 bp for a zinc finger nuclease (ZFN) pair (about 15-18 bp for each ZFN), about 36 bp for a Transcription Activator- Like Effector (TALE) protein or Transcription Activator-Like Effector Nuclease (TALEN), or about 20 bp for a CRISPR/Cas9 guide RNA. [00583] The target sequence of the DNA-binding protein or nuclease molecular cargo can be positioned anywhere in or near the target genomic locus. The target sequence can be located within a coding region of a gene, or within regulatory regions that influence the expression of the gene. A target sequence of the DNA-binding protein or nuclease molecular cargo can be located in an intron, an exon, a promoter, an enhancer, a regulatory region, or any non-protein coding region. [00584] One type of DNA-binding protein that can be employed in the various methods and compositions disclosed herein is a Transcription Activator-Like Effector (TALE). A TALE can be fused or linked to, for example, an epigenetic modification domain, a transcriptional activation domain, or a transcriptional repressor domain. Examples of such domains are described with respect to Cas proteins, below, and can also be found, for example, in WO 2011/145121, herein incorporated by reference in its entirety for all purposes. Correspondingly, one type of nuclease molecular cargo that can be employed in the various methods and compositions disclosed herein is a Transcription Activator-Like Effector Attorney Docket No.250298.000780 Nuclease (TALEN). TAL effector nucleases are a class of sequence-specific nucleases that can be used to make double-strand breaks at specific target sequences in the genome of a prokaryotic or eukaryotic organism. TAL effector nucleases are created by fusing a native or engineered transcription activator-like (TAL) effector, or functional part thereof, to the catalytic domain of an endonuclease such as Fokl. The unique, modular TAL effector DNA binding domain allows for the design of proteins with potentially any given DNA recognition specificity. Thus, the DNA binding domains of the TAL effector nucleases can be engineered to recognize specific DNA target sites and thus, used to make double-strand breaks at desired target sequences. See WO 2010/079430; Morbitzer et al. (2010) Proc. Natl. Acad. Sci. U.S.A. 107(50:21617- 21622; Scholze & Boch (2010) Virulence 1:428-432; Christian et al. (2010) Genetics 186:757-761; Li et al. (2011) Nucleic Acids Res. 39(l):359-372; and Miller et al. (2011) Nature Biotechnology 29: 143-148, each of which is herein incorporated by reference in its entirety for all purposes. [00585] The non-specific DNA cleavage domain from the end of the Fokl endonuclease can be used to construct hybrid nucleases that are active in a yeast assay. These molecular cargoes are also active in plant cells and in animal cells. The Fokl domain functions as a dimer, requiring two constructs with unique DNA binding domains for sites in the target genome with proper orientation and spacing. Both the number of amino acid residues between the TALEN DNA binding domain and the Fokl cleavage domain and the number of bases between the two individual TALEN binding sites are parameters for achieving high levels of activity. The number of amino acid residues between the TALEN DNA binding domain and the Fokl cleavage domain may be modified by introduction of a spacer (distinct from the spacer sequence) between the plurality of TAL effector repeat sequences and the Fokl endonuclease domain. The spacer sequence may be 12 to 30 nucleotides. [00586] The relationship between amino acid sequence and DNA recognition of the TALEN binding domain allows for designable proteins. In this case artificial gene synthesis is problematic because of improper annealing of the repetitive sequence found in the TALE binding domain. One solution to this is to use a publicly available software program (DNAWorks) to calculate oligonucleotides suitable for assembly in a two-step PCR; oligonucleotide assembly followed by whole gene amplification. A number of modular assembly schemes for generating engineered TALE constructs have also been reported. Both methods offer a systematic approach to engineering DNA binding domains that is Attorney Docket No.250298.000780 conceptually similar to the modular assembly method for generating zinc finger DNA recognition domains. [00587] Once the TALEN genes have been assembled, they are inserted into plasmids; the plasmids are then used to transfect the target cell where the gene products are expressed and enter the nucleus to access the genome. TALENs can be used to edit genomes by inducing double-strand breaks (DSB), which cells respond to with repair mechanisms. [00588] Examples of suitable TAL nucleases, and methods for preparing suitable TAL nucleases, are disclosed, e.g., in US 2011/0239315 Al, US 2011/0269234 A1, US 2011/0145940 A1, US 2003/0232410 A1, US 2005/0208489 A1, US 2005/0026157 A1, US 2005/0064474 A1, US 2006/0188987 A1, and US 2006/0063231 A1, each of which is herein incorporated by reference in its entirety for all purposes. In some embodiments, TAL effector nucleases are engineered that cut in or near a target nucleic acid sequence in, for example, a genomic locus of interest, wherein the target nucleic acid sequence is at or near a sequence to be modified. [00589] In some TALENs, each monomer of the TALEN comprises 33-35 TAL repeats that recognize a single base pair via two hypervariable residues. In some TALENs, the nuclease molecular cargo is a chimeric protein comprising a TAL-repeat-based DNA binding domain operably linked to an independent nuclease such as a Fokl endonuclease. For example, the nuclease molecular cargo can comprise a first TAL-repeat-based DNA binding domain and a second TAL-repeat-based DNA binding domain, wherein each of the first and the second TAL-repeat-based DNA binding domains is operably linked to a Fokl nuclease, wherein the first and the second TAL-repeat-based DNA binding domain recognize two contiguous target DNA sequences in each strand of the target DNA sequence separated by a spacer sequence of varying length (12-20 bp), and wherein the Fokl nuclease subunits dimerize to create an active nuclease that makes a double strand break at a target sequence. [00590] Transcription Activator-Like Effector Nucleases (TALENs) are artificial restriction enzymes generated by fusing the TAL effector DNA binding domain to a DNA cleavage domain. These molecular cargoes enable efficient, programmable, and specific DNA cleavage and represent powerful tools for genome editing in situ. Transcription activator- like effectors (TALEs) can be quickly engineered to bind practically any DNA sequence. The term TALEN, as used herein, is broad and includes a monomeric TALEN that can cleave double stranded DNA without assistance from another TALEN. The term TALEN is also used to refer to one or both members of a pair of TALENs that are engineered to work together to Attorney Docket No.250298.000780 cleave DNA at the same site. TALENs that work together may be referred to as a left-TALEN and a right-TALEN, which references the handedness of DNA. See U.S. Patent Nos. 8,586,363; 8,450,471; 8,440,431; 8,440,432; and 8,697,853, all of which are incorporated by reference herein in their entirety. [00591] Another example of a DNA-binding protein is a zinc finger protein. Such zinc finger proteins can be linked or fused to, for example, an epigenetic modification domain, a transcriptional activation domain, or a transcriptional repressor domain. Examples of such domains are described with respect to Cas proteins, below, and can also be found, for example, in WO 2011/145121, herein incorporated by reference in its entirety for all purposes. Correspondingly, another example of a nuclease molecular cargo that can be employed in the various methods and compositions disclosed herein is a zinc-finger nuclease (ZFN). In some ZFNs, each monomer of the ZFN comprises three or more zinc finger-based DNA binding domains, wherein each zinc finger-based DNA binding domain binds to a 3 bp subsite. In other ZFNs, the ZFN is a chimeric protein comprising a zinc finger-based DNA binding domain operably linked to an independent nuclease such as a Fokl endonuclease. For example, the nuclease molecular cargo can comprise a first ZFN and a second ZFN, wherein each of the first ZFN and the second ZFN is operably linked to a Fokl nuclease subunit, wherein the first and the second ZFN recognize two contiguous target DNA sequences in each strand of the target DNA sequence separated by about 5-7 bp spacer, and wherein the Fokl nuclease subunits dimerize to create an active nuclease that makes a double strand break. See, e.g., US 2006/0246567; US 2008/0182332; US 2002/0081614; US 2003/0021776; WO 2002/057308 A2; US 2013/0123484; US 2010/0291048; WO 2011/017293 A2; and Gaj et al. (2013) Trends in Biotechnology 31(7):397-405, each of which is herein incorporated by reference in its entirety for all purposes. Conjugation of Molecular Cargo to Antigen-binding Protein [00592] In some embodiments, a molecular cargo described herein, e.g., a polynucleotide molecule described herein, or a liposome or LNP, is conjugated to an p75NTR binding protein for delivery to a site of interest (e.g., brain or spinal cord). In some embodiments, the p75NTR binding protein is conjugated to at least one molecular cargo (e.g., polynucleotide molecule, polypeptide molecule, or liposome or LNP). Attorney Docket No.250298.000780 [00593] In some embodiments, an p75NTR binding protein is conjugated to the 5' terminus of a polynucleotide molecule, the 3' terminus of a polynucleotide molecule, an internal site on a polynucleotide molecule, or in any combinations thereof. [00594] In some embodiments, an p75NTR binding protein is conjugated to the N terminus of a polypeptide molecule, the C terminus of a polypeptide molecule, an internal site on a polypeptide molecule, or in any combinations thereof. [00595] In some embodiments, the p75NTR binding protein is conjugated to at least one molecular cargo (e.g., at least one polynucleotide molecule, polypeptide molecule and/ or liposome or LNP). In some embodiments, the p75NTR binding protein is conjugated to at least 2, 3, 4, 5, 6, 7, 8, 10, 12, 16, 20, 24, 30 or more molecular cargoes described herein (e.g., at least 2, 3, 4, 5, 6, 7, 8, 10, 12, 16, 20, 24, 30 or more polynucleotide molecules, polypeptide molecules, and/or liposomes or LNPs). [00596] In some embodiments, the p75NTR binding protein is conjugated to a molecular cargo (e.g., polynucleotide molecule, polypeptide molecule, or liposome or LNP) non- specifically. In some embodiments, the p75NTR binding protein is conjugated to a molecular cargo (e.g., polynucleotide molecule, polypeptide molecule, or liposome or LNP) via a lysine residue or a cysteine residue, in a non-site-specific manner. In some embodiments, the p75NTR binding protein is conjugated to a molecular cargo (e.g., polynucleotide molecule, polypeptide molecule, or liposome or LNP) via a lysine residue (e.g., lysine residue present in the p75NTR binding protein) in a non-site-specific manner. In some cases, the p75NTR binding protein is conjugated to a molecular cargo (e.g., polynucleotide molecule, or liposome or LNP) via a cysteine residue (e.g., cysteine residue present in the p75NTR binding protein ) in a non-site-specific manner. [00597] In some embodiments, the p75NTR binding protein is conjugated to a molecular cargo (e.g., polynucleotide molecule, polypeptide molecule, or liposome or LNP) in a site- specific manner. In some embodiments, the p75NTR binding protein is conjugated to a molecular cargo (e.g., polynucleotide molecule, polypeptide molecule, or liposome or LNP) through a lysine residue, a cysteine residue, at the N-terminus, at the C-terminus, an unnatural amino acid, or an enzyme-modified or enzyme-catalyzed residue, via a site-specific manner. In some embodiments, the p75NTR binding protein is conjugated to a molecular cargo (e.g., polynucleotide molecule, or liposome or LNP) through a lysine residue (e.g., lysine residue present in the p75NTR binding protein) via a site-specific manner. In some embodiments, the p75NTR binding protein is conjugated to a molecular cargo (e.g., Attorney Docket No.250298.000780 polynucleotide molecule, polypeptide molecule, or liposome or LNP) through a cysteine residue (e.g., cysteine residue present in the p75NTR binding protein) via a site-specific manner. In some embodiments, the p75NTR binding protein is conjugated to a molecular cargo (e.g., polynucleotide molecule, polypeptide molecule, or liposome or LNP) at the N-terminus via a site-specific manner. In some embodiments, the p75NTR binding protein is conjugated to a molecular cargo (e.g., polynucleotide molecule, polypeptide molecule, or liposome or LNP) at the C-terminus via a site-specific manner. In some embodiments, the p75NTR binding protein is conjugated to a molecular cargo (e.g., polynucleotide molecule, polypeptide molecule, or liposome or LNP) through an unnatural amino acid via a site-specific manner. In some embodiments, the p75NTR binding protein is conjugated to a molecular cargo (e.g., polynucleotide molecule, or liposome or LNP) through an enzyme-modified or enzyme- catalyzed residue via a site-specific manner. [00598] In some embodiments, one or more molecular cargoes (e.g., polynucleotide molecule, polypeptide molecule, and/or liposome or LNP) is conjugated to an FGFR3 binding protein . In some embodiments, about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 20, 24, 30, 36 or more molecular cargoes (e.g., polynucleotide molecule, polypeptide molecule, and/or liposome or LNP) are conjugated to one p75NTR binding protein. In some embodiments, 1 molecular cargo is conjugated to one p75NTR binding protein. In some embodiments, 2 molecular cargoes are conjugated to one p75NTR binding protein . In some embodiments, 3 molecular cargoes are conjugated to one p75NTR binding protein. In some embodiments, 4 molecular cargoes are conjugated to one p75NTR binding protein. In some embodiments, 5 molecular cargoes are conjugated to one p75NTR binding protein . In some embodiments, 6 molecular cargoes are conjugated to one p75NTR binding protein. In some embodiments, 7 molecular cargoes are conjugated to one p75NTR binding protein. In some embodiments, 8 molecular cargoes are conjugated to one p75NTR binding protein. In some embodiments, 9 molecular cargoes are conjugated to one p75NTR binding protein. In some embodiments, 10 molecular cargoes are conjugated to one p75NTR binding protein. In some embodiments, 11 molecular cargoes are conjugated to one p75NTR binding protein . In some embodiments, 12 molecular cargoes are conjugated to one p75NTR binding protein. In some embodiments, 13 molecular cargoes are conjugated to one p75NTR binding protein . In some embodiments, 14 molecular cargoes are conjugated to one p75NTR binding protein . In some embodiments, 15 molecular cargoes are conjugated to one p75NTR binding protein. In some embodiments, 16 molecular cargoes are conjugated to one p75NTR binding protein. In some cases, the one or Attorney Docket No.250298.000780 more molecular cargoes are the same. In other cases, the one or more molecular cargoes are different. [00599] In some embodiments, the number of molecular cargoes conjugated to an p75NTR binding protein forms a ratio. In some embodiments, the ratio is referred to as a DAR (drug-to-antibody) ratio, in which the drug as referred to herein is a molecular cargo described herein (e.g., polynucleotide molecule, polypeptide molecule, or liposome or LNP). In some embodiments, the DAR ratio of the molecular cargo to p75NTR binding protein is about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 20, 24, 30, 36 or greater. In some embodiments, the DAR ratio of the molecular cargo to p75NTR binding protein is about 1 or greater. In some embodiments, the DAR ratio of the molecular cargo to p75NTR binding protein is about 2 or greater. In some embodiments, the DAR ratio of the molecular cargo to p75NTR binding protein is about 3 or greater. In some embodiments, the DAR ratio of the molecular cargo to p75NTR binding protein is about 4 or greater. In some embodiments, the DAR ratio of the molecular cargo to p75NTR binding protein is about 5 or greater. In some embodiments, the DAR ratio of the molecular cargo to p75NTR binding protein is about 6 or greater. In some embodiments, the DAR ratio of the molecular cargo to p75NTR binding protein is about 7 or greater. In some embodiments, the DAR ratio of the molecular cargo to p75NTR binding protein is about 8 or greater. In some embodiments, the DAR ratio of the molecular cargo to p75NTR binding protein is about 9 or greater. In some embodiments, the DAR ratio of the molecular cargo to p75NTR binding protein is about 10 or greater. In some embodiments, the DAR ratio of the molecular cargo to p75NTR binding protein is about 11 or greater. In some embodiments, the DAR ratio of the molecular cargo to p75NTR binding protein is about 12 or greater. In some embodiments, the DAR ratio of the molecular cargo to p75NTR binding protein is about 16 or greater. In some embodiments, the DAR ratio of the molecular cargo to p75NTR binding protein is about 20 or greater. In some embodiments, the DAR ratio of the molecular cargo to p75NTR binding protein is about 24 or greater. [00600] In some embodiments, the DAR ratio of the molecular cargo to p75NTR binding protein is about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 20, 24, 30, or 36. In some embodiments, the DAR ratio of the molecular cargo to p75NTR binding protein is about 1. In some embodiments, the DAR ratio of the molecular cargo to p75NTR binding protein is about 2. In some embodiments, the DAR ratio of the molecular cargo to p75NTR binding protein is about 3. In some embodiments, the DAR ratio of the molecular cargo to p75NTR binding protein is about 4. In some embodiments, the DAR ratio of the molecular cargo to p75NTR binding Attorney Docket No.250298.000780 protein is about 5. In some embodiments, the DAR ratio of the molecular cargo to p75NTR binding protein is about 6. In some embodiments, the DAR ratio of the molecular cargo to p75NTR binding protein is about 7. In some embodiments, the DAR ratio of the molecular cargo to p75NTR binding protein is about 8. In some embodiments, the DAR ratio of the molecular cargo to p75NTR binding protein is about 9. In some embodiments, the DAR ratio of the molecular cargo to p75NTR binding protein is about 10. In some embodiments, the DAR ratio of the molecular cargo to p75NTR binding protein is about 11. In some embodiments, the DAR ratio of the molecular cargo to p75NTR binding protein is about 12. In some embodiments, the DAR ratio of the molecular cargo to p75NTR binding protein is about 13. In some embodiments, the DAR ratio of the molecular cargo to p75NTR binding protein is about 14. In some embodiments, the DAR ratio of the molecular cargo to p75NTR binding protein is about 15. In some embodiments, the DAR ratio of the molecular cargo to p75NTR binding protein is about 16. [00601] In some embodiments, liposome or LNP functionalization with binding moieties is carried out via the adsorption phenomenon, covalent-nature binding, or binding by the use of adapter molecules or linkers. Adsorption [00602] This phenomenon is a non-covalent immobilization strategy that comprises physical adsorption and ionic binding. Physical adsorption occurs via weak interactions such as hydrogen bonding, electrostatic, hydrophobic and Van der Waals attractive forces, while ionic binding occurs between the opposite charges of the p75NTR binding protein and liposome or LNP surfaces. However, when compared to other methodologies such as covalent binding, adsorption provides less stability. On the other hand, the fact that the interaction is non- covalent may allow easier release of the cargo in the tumor tissue. Covalent Strategies [00603] Covalent binding requires prior activation of the LNPs. In some embodiments, covalent strategies occur via carbodiimide chemistry, maleimide chemistry or “click chemistry”, as discussed in detail below. Conjugation Chemistry [00604] In some embodiments, a molecular cargo described herein (e.g., a polynucleotide molecule or polypeptide molecule described herein, or a liposome or LNP) is conjugated to an p75NTR binding protein . In some embodiments, a molecular cargo described herein (e.g., a polynucleotide molecule or polypeptide molecule described herein, or a Attorney Docket No.250298.000780 liposome or LNP) is conjugated to an p75NTR binding protein directly. In some embodiments, a molecular cargo described herein (e.g., a polynucleotide molecule or polypeptide molecule described herein, or a liposome or LNP) is conjugated to an p75NTR binding protein via a linker covalently connecting the p75NTR binding protein with the molecular cargo. In some embodiments, the p75NTR binding protein is an antibody or antigen binding fragment thereof (e.g., scFv or Fab). [00605] In some embodiments, the molecular cargo described herein (e.g., a polynucleotide molecule or polypeptide molecule described herein, or a liposome or LNP) is conjugated to the p75NTR binding protein by a chemical ligation process. In some embodiments, the molecular cargo described herein (e.g., a polynucleotide molecule or polypeptide molecule described herein, or a liposome or LNP) is conjugated to the p75NTR binding protein by a native ligation. In some embodiments, the conjugation is as described in: Dawson, et al. "Synthesis of proteins by native chemical ligation," Science 1994, 266, 776- 779; Dawson, et al. "Modulation of Reactivity in Native Chemical Ligation through the Use of Thiol Additives," J. Am. Chem. Soc.1997, 119, 4325-4329; Hackeng, et al. "Protein synthesis by native chemical ligation: Expanded scope by using straightforward methodology.," Proc. Natl. Acad. Sci. USA 1999, 96, 10068-10073; or Wu, et al. "Building complex glycopeptides: Development of a cysteine-free native chemical ligation protocol," Angew. Chem. Int. Ed. 2006, 45, 4116-4125. In some embodiments, the conjugation is as described in U.S. Patent No. 8,936,910. In some embodiments, the molecular cargo described herein (e.g., a polynucleotide molecule or polypeptide molecule, described herein, or a liposome or LNP) is conjugated to the p75NTR binding protein either site-specifically or non-specifically via native ligation chemistry. [00606] In some embodiments, the molecular cargo described herein (e.g., a polynucleotide molecule or polypeptide molecule described herein, or a liposome or LNP) is conjugated to the p75NTR binding protein by a site-directed method utilizing a "traceless" coupling technology (Philochem). In some embodiments, the "traceless" coupling technology utilizes an N-terminal 1,2-aminothiol group on the p75NTR binding protein which is then conjugated with a molecular cargo described herein (e.g., a polynucleotide molecule or polypeptide molecule described herein, or a liposome or LNP) containing an aldehyde group. (see Casi et al., "Site-specific traceless coupling of potent cytotoxic drugs to recombinant antibodies for pharmacodelivery," JACS 134(13): 5887-5892 (2012)). Attorney Docket No.250298.000780 [00607] In some embodiments, the molecular cargo described herein (e.g., a polynucleotide molecule or polypeptide molecule described herein, or a liposome or LNP) is conjugated to the p75NTR binding protein by a site-directed method utilizing an unnatural amino acid incorporated into the p75NTR binding protein . In some embodiments, the unnatural amino acid comprises p-acetylphenylalanine (pAcPhe). In some embodiments, the keto group of pAcPhe is selectively coupled to an alkoxy-amine derivatived conjugating moiety to form an oxime bond. (see Axup et al., "Synthesis of site-specific antibody-drug conjugates using unnatural amino acids, "PNAS 109(40): 16101-16106 (2012)). [00608] In some embodiments, the molecular cargo described herein (e.g., a polynucleotide molecule or polypeptide molecule described herein, or a liposome or LNP) is conjugated to the p75NTR binding protein by a site-directed method utilizing an enzyme- catalyzed process. In some embodiments, the site-directed method utilizes SMARTagTM technology (Catalent, Inc.). In some embodiments, the SMARTagTM technology comprises generation of a formylglycine (fGly) residue from cysteine by formylglycine-generating enzyme (FGE) through an oxidation process under the presence of an aldehyde tag and the subsequent conjugation of fGly to an alkylhydraine-functionalized molecular cargo described herein (e.g., a polynucleotide molecule or polypeptide molecule described herein, or a liposome or LNP) via hydrazino-Pictet-Spengler (HIPS) ligation. (see Wu et al., "Site-specific chemical modification of recombinant proteins produced in mammalian cells by using the genetically encoded aldehyde tag," PNAS 106(9): 3000-3005 (2009); Agarwal, et al., "A Pictet-Spengler ligation for protein chemical modification," PNAS 110(1): 46-51 (2013)) [00609] In some embodiments, the enzyme-catalyzed process comprises transglutaminase, e.g., microbial transglutaminase (mTG). In some cases, the molecular cargo described herein (e.g., a polynucleotide molecule or polypeptide molecule described herein, or a liposome or LNP) is conjugated to the p75NTR binding protein utilizing a microbial transglutaminase-catalyzed process. In some embodiments, mTG catalyzes the formation of a covalent bond between the amide side chain of a glutamine within the recognition sequence and a primary amine of a functionalized molecular cargo described herein (e.g., a polynucleotide molecule or polypeptide molecule described herein, or a liposome or LNP). In some embodiments, mTG is produced from Streptomyces mobarensis. (see Strop et al., "Location matters: site of conjugation modulates stability and pharmacokinetics of antibody drug conjugates," Chemistry and Biology 20(2) 161-167 (2013)). Attorney Docket No.250298.000780 [00610] In some embodiments, a sequence of amino acids comprising an acceptor glutamine residue are incorporated into (e.g., appended to) a polypeptide sequence, under suitable conditions, for recognition by a TG. This sequence leads to cross-linking by the TG through a reaction between an amino acid side chain within the sequence of amino acids and a reaction partner. The recognition tag may be a peptide sequence that is not naturally present in the polypeptide comprising the TG recognition tag. In some embodiments, the TG recognition tag comprises at least one Gln. In some embodiments, the tGase recognition tag comprises an amino acid sequence XXQX, wherein X is any amino acid (e.g., conventional amino acid Leu, Ala, Gly, Ser, Val, Phe, Tyr, His, Arg, Asn, Glu, Asp, Cys, Gln, Ile, Met, Pro, Thr, Lys, or Trp or nonconventional amino acid). In some embodiments, the acyl donor glutamine-containing tag comprises an amino acid sequence selected from the group consisting of LLQGG (SEQ ID NO: 650), LLQG (SEQ ID NO: 651), LSLSQG (SEQ ID NO: 652), gGGLLQGG (SEQ ID NO: 653), gLLQG (SEQ ID NO: 654), LLQ, gSPLAQSHGG (SEQ ID NO: 655), gLLQGGG (SEQ ID NO: 656), gLLQGG (SEQ ID NO: 657), gLLQ (SEQ ID NO: 658), LLQLLQGA (SEQ ID NO: 659), LLQGA (SEQ ID NO: 660), LLQYQGA (SEQ ID NO: 661), LLQGSG (SEQ ID NO: 624), LLQYQG (SEQ ID NO: 662), LLQLLQG (SEQ ID NO: 663), SLLQG (SEQ ID NO: 664), LLQLQ (SEQ ID NO: 665), LLQLLQ (SEQ ID NO: 666), and LLQGR (SEQ ID NO: 667). See, e.g., PCT Publication No. WO2012/059882. In some embodiments, the acyl donor glutamine-containing tag is present at the N-terminus of the antigen-binding protein. In some embodiments, the acyl donor glutamine-containing tag is present at the C-terminus of the antigen-binding protein. In some embodiments, the acyl donor glutamine-containing tag is present both at the N-terminus and the C-terminus of the antigen-binding protein. In some embodiments, the antigen-binding protein and the molecular cargo described herein are conjugated via a linker. [00611] In some embodiments, the molecular cargo described herein (e.g., a polynucleotide molecule or polypeptide molecule described herein, or a liposome or LNP) is conjugated to the p75NTR binding protein by a method as described in PCT Publication No. W02014/140317, which utilizes a sequence-specific transpeptidase. In some embodiments, the molecular cargo described herein (e.g., a polynucleotide molecule or polypeptide molecule described herein, or a liposome or LNP) is conjugated to the p75NTR binding protein by a method as described in U.S. Patent Publication Nos.2015/0105539 and 2015/0105540. [00612] In some embodiments, the molecular cargo described herein (e.g., a polynucleotide molecule or polypeptide molecule described herein, or a liposome or LNP) is Attorney Docket No.250298.000780 conjugated to the p75NTR binding protein utilizing Azide-Alkyne Cycloaddition (CuAAC) click chemistry. Azides and alkynes can undergo catalyst free [3+2] cycloaddition by a using the reaction of activated alkynes with azides. Such catalyst-free [3+2] cycloaddition can be used in the methods described herein to conjugate an p75NTR binding protein and the molecular cargo described herein (e.g., a polynucleotide molecule or polypeptide molecule described herein, or a liposome or LNP). Alkynes can be activated by ring strain such as, by way of example only, eight-membered ring structures, or nine-membered, appending electron- withdrawing groups to such alkyne rings, or alkynes can be activated by the addition of a Lewis acid such as, by way of example only, Au(I) or Au(III). [00613] Alkynes activated by ring strain have been described and used in "copperless" [3+2] cycloaddition. For example, the cyclooctynes and difluorocyclooctynes described by Agard et al., J. Am. Chem. Soc., 126 (46):15046-15047 (2004), the dibenzocyclooctynes described by Boons et al., PCT International Publication No. WO 2009/067663 Al (2009), the aza-dibenzocyclooctynes described by Debets et al., Chem. Comm., 46:97-99 (2010), and the cyclononynes described by Dommerholt et al., Angew. Chem.122:9612-9615 (2010)). In some embodiments, a tetrazine (Tzn)-activated p75NTR binding protein may be cross-linked to a trans-cyclooctene (TCO)-activated molecular cargo described herein (e.g., a polynucleotide molecule or polypeptide molecule described herein, or a liposome or LNP). In some embodiments, a TCO-activated p75NTR binding protein may be crosslinked to a Tzn- activated molecular cargo described herein (e.g., a polynucleotide molecule or polypeptide molecule described herein, or a liposome or LNP). Linkers [00614] Complexes described herein generally comprise a linker that connects a binding agent to a molecular cargo (e.g., a polynucleotide molecule, polypeptide molecule, a liposome or an LNP). A linker comprises at least one covalent bond. In some embodiments, a linker may be a single bond, e.g., a disulfide bond or disulfide bridge, that connects a binding agent to a polynucleotide molecule, polypeptide molecule, or a liposome or LNP. However, in some embodiments, a linker may connect a binding agent to a polynucleotide molecule, polypeptide molecule, or a liposome or LNP through multiple covalent bonds. A linker is generally stable in vitro and in vivo, and may be stable in certain cellular environments. Additionally, generally a linker does not negatively impact the functional properties of either the binding agent or the polynucleotide molecule, polypeptide molecule, or a liposome or LNP. Examples and methods of synthesis of linkers are known in the art (see, e.g. Kline, T. Attorney Docket No.250298.000780 et al. "Methods to Make Homogenous Antibody Drug Conjugates." Pharmaceutical Research, 2015, 32:11, 3480-3493; Jain, N. et al. "Current ADC Linker Chemistry" Pharm Res. 2015, 32:11, 3526-3540; McCombs, J. R. and Owen, S. C., "Antibody Drug Conjugates: Design and Selection of Linker, Payload and Conjugation Chemistry" AAPS J.2015, 17:2, 339-351). [00615] A precursor to a linker typically will contain two different reactive species that allow for attachment to both the binding agent and a polynucleotide molecule, polypeptide molecule, or a liposome or LNP. In some embodiments, the two different reactive species may be a nucleophile and/or an electrophile. In some embodiments, a linker is connected to a binding agent via conjugation to a lysine residue or a cysteine residue of the binding agent. In some embodiments, a linker is connected to a cysteine residue of a muscle-targeting agent via a maleimide-containing linker, wherein optionally the maleimide-containing linker comprises a maleimidocaproyl or maleimidomethyl cyclohexane- 1 -carboxylate group. In some embodiments, a linker is connected to a cysteine residue of a muscle-targeting agent or thiol functionalized molecular cargo via a 3-arylpropionitrile functional group. In some embodiments, a linker is connected to a binding agent and/or a polynucleotide molecule, polypeptide molecule or an LNP via an amide bond, a hydrazide, a triazole, a thioether or a disulfide bond. [00616] In some embodiments, a linker described herein is a cleavable linker or a non- cleavable linker. In some embodiments, the linker is a cleavable linker. In other embodiments, the linker is a non-cleavable linker. Cleavable Linkers [00617] A cleavable linker may be a protease-sensitive linker, a pH-sensitive linker, or a glutathione-sensitive linker. These linkers are generally cleavable only intracellularly and are preferably stable in extracellular environments. [00618] Protease-sensitive linkers are cleavable by protease enzymatic activity. These linkers typically comprise peptide sequences and may be 2-10 amino acids, about 2-5 amino acids, about 5-10 amino acids, about 10 amino acids, about 5 amino acids, about 3 amino acids, or about 2 amino acids in length. In some embodiments, a peptide sequence may comprise naturally-occurring amino acids, e.g. cysteine, alanine, or non-naturally-occurring or modified amino acids. Non-naturally occurring amino acids include 3-amino acids, homo- amino acids, proline derivatives, 3-substituted alanine derivatives, linear core amino acids, N-methyl amino acids, and others known in the art. In some embodiments, a protease- sensitive linker comprises a valine-citrulline or alanine-citrulline dipeptide sequence. In some Attorney Docket No.250298.000780 embodiments, a protease-sensitive linker can be cleaved by a lysosomal protease, e.g. cathepsin B, and/or an endosomal protease. [00619] A pH-sensitive linker is a covalent linkage that readily degrades in high or low pH environments. In some embodiments, a pH-sensitive linker may be cleaved at a pH in a range of 4 to 6. In some embodiments, a pH-sensitive linker comprises a hydrazone or cyclic acetal. In some embodiments, a pH-sensitive linker is cleaved within an endosome or a lysosome. [00620] In some embodiments, a glutathione-sensitive linker comprises a disulfide moiety. In some embodiments, a glutathione-sensitive linker is cleaved by an disulfide exchange reaction with a glutathione species inside a cell. In some embodiments, the disulfide moiety further comprises at least one amino acid, e.g. a cysteine residue. Non-Cleavable Linkers [00621] In some embodiments, non-cleavable linkers may be used. Generally, a non- cleavable linker cannot be readily degraded in a cellular or physiological environment. In some embodiments, a non-cleavable linker comprises an optionally substituted alkyl group, wherein the substitutions may include halogens, hydroxyl groups, oxygen species, and other common substitutions. In some embodiments, a linker may comprise an optionally substituted alkyl, an optionally substituted alkylene, an optionally substituted arylene, a heteroarylene, a peptide sequence comprising at least one non-natural amino acid, a truncated glycan, a sugar or sugars that cannot be enzymatically degraded, an azide, an alkyneazide, a peptide sequence comprising a LPXT sequence, a thioether, a biotin, a biphenyl, repeating units of polyethylene glycol or equivalent compounds, acid esters, acid amides, sulfamides, and/or an alkoxy-amine linker. In some embodiments, sortase-mediated ligation will be utilized to covalently link a muscle-targeting agent comprising a LPXT sequence to a molecular cargo comprising a (G), sequence (see, e.g. Proft T. Sortase-mediated protein ligation: an emerging biotechnology tool for protein modification and immobilization. Biotechnol Lett.2010, 32(1):1- 10). [00622] In some embodiments, a linker may comprise a substituted alkylene, an optionally substituted alkenylene, an optionally substituted alkynylene, an optionally substituted cycloalkylene, an optionally substituted cycloalkenylene, an optionally substituted arylene, an optionally substituted heteroarylene further comprising at least one heteroatom selected from N, O, and S; an optionally substituted heterocyclylene further comprising at least one heteroatom selected from N, O, and S; an imino, an optionally substituted nitrogen Attorney Docket No.250298.000780 species, an optionally substituted oxygen species, an optionally substituted sulfur species, or a poly(alkylene oxide), e.g. polyethylene oxide or polypropylene oxide. [00623] In some cases, the linker is a non-polymeric linker. A non-polymeric linker refers to a linker that does not contain a repeating unit of monomers generated by a polymerization process. Exemplary non-polymeric linkers include, but are not limited to, C1- C30 alkyl group (e.g., a C5, C4, C 3, C 2, or C1 alkyl group), homobifunctional cross linkers, heterobifunctional cross linkers, peptide linkers, traceless linkers, self-immolative linkers, maleimide-based linkers, or combinations thereof. In some cases, the non-polymeric linker comprises a C1-C30 alkyl group (e.g., a C5, C4, C 3, C 2, or C1 alkyl group), a homobifunctional cross linker, a heterobifunctional cross linker, a peptide linker, a traceless linker, a self-immolative linker, a maleimide-based linker, or a combination thereof. In additional cases, the non-polymeric linker does not comprise more than two of the same type of linkers, e.g., more than two homobifunctional cross linkers, or more than two peptide linkers. In further cases, the non-polymeric linker optionally comprises one or more reactive functional groups. In one embodiment, the linker has a . [00624] In some cases, the non-polymeric linker does oxide (e.g., PEG). In some cases, the non-polymeric linker does not encompass a PEG. [00625] In some embodiments, the linker comprises a homobifunctional linker. Exemplary homobifunctional linkers include, but are not limited to, organoazide, organoalkyne, Lomant's reagent dithiobis (succinimidylpropionate) DSP, 3'3'- dithiobis(sulfosuccinimidyl proprionate (DTSSP), disuccinimidyl suberate (DSS), bis(sulfosuccinimidyl)suberate (BS), disuccinimidyl tartrate (DST), disulfosuccinimidyl tartrate (sulfo DST), ethylene glycobis(succinimidylsuccinate) (EGS), disuccinimidyl glutarate (DSG), N,N'-disuccinimidyl carbonate (DSC), dimethyl adipimidate (DMA), dimethyl pimelimidate (DMP), dimethyl suberimidate (DMS), dimethyl-3,3'-dithiobispropionimidate (DTBP), 1,4-di- 3'-(2'-pyridyldithio)propionamido) butane (DPDPB), bismaleimidohexane (BMH), aryl halide- containing compound (DFDNB), such as e.g.1,5-difluoro-2,4-dinitrobenzene or 1,3-difluoro- 4,6-dinitrobenzene, 4,4'-difluoro-3,3'-dinitrophenylsulfone (DFDNPS), bis-113-(4- azidosalicylamido)ethyl]disulfide (BASED), formaldehyde, glutaraldehyde, 1,4-butanediol diglycidyl ether, adipic acid dihydrazide, carbohydrazide, o-toluidine, 3,3'-dimethylbenzidine, Attorney Docket No.250298.000780 benzidine, a,a'-p-diaminodiphenyl, diiodo-p-xylene sulfonic acid, N,N'-ethylene- bis(iodoacetamide), or N,N'-hexamethylene-bis(iodoacetamide). [00626] In some embodiments, the linker comprises a heterobifunctional linker. Exemplary heterobifunctional linker include, but are not limited to, amine-reactive and sulfhydryl cross-linkers such as N-succinimidyl 3-(2-pyridyldithio) propionate (sPDP), long- chain N-succinimidyl 3-(2-pyridyldithio) propionate (LC-sPDP), water-soluble-long-chain N- succinimidyl 3-(2-pyridyldithio) propionate (sulfo-LCsPDP), succinimidyloxycarbonyl-a- methyl-a-(2-pyridyldithio) toluene (sMPT), sulfosuccinimidy1-6-[a-methyl-a-(2- pyridyldithio)toluamido]hexanoate (sulfo-LC-sMPT), succinimidy1-4-(N-maleimidomethyl) cyclohexane-1-car-boxylate (sMCC), sulfosuccinimidyl-4-(N-maleimidomethyl) cyclohexane- 1-carboxylate (sulfo-sMCC), m-maleimidobenzoyl-N-hydroxysuccinimide ester (MBs), m- maleimidobenzoyl-N-hydroxysulfosuccinimide ester (sulfo-MB s), N-succinimidyl (4 - iodoacteyl)aminobenzoate (sIAB), sulfosuccinimidyl (4 -iodoacteyl)aminobenzoate (sulfo- sIAB), succinimidyl-4-(p-maleimidophenyl)butyrate (sMPB), sulfosuccinimidyl-4-(p- maleimidophenyl)butyrate (sulfo-sMPB), N-(y-maleimidobutyryloxy)succinimide ester [00627] (GMBs), N-(y-maleimidobutyryloxy)sulfosuccinimide ester (sulfo-GMBs), succinimidyl 6-((iodoacetyl)amino)hexanoate (sIAX), succinimidyl 6-[6-(((iodoacetyl)amino) hexanoyl)amino]hexanoate (sIAXX), succinimidyl 4-(((iodoacetyl) amino)methyl)cyclohexane-l-carboxylate (sIAC), succinimidyl 6-((((4- iodoacetyl)amino)methyl)cyclohexane-1 -carbonyl)amino) hexanoate (sIACX), p-nitrophenyl iodoacetate (NPIA), carbonyl-reactive and sulfhydrylreactive cross-linkers such as 4-(4-N- maleimidophenyl) butyric acid hydrazide (MPBH), 4-(N-maleimidomethyl) cyclohexane-l- carboxyl-hydrazide-8 (M2C2H), 3-(2- pyridyldithio)propionyl hydrazide (PDPH), amine- reactive and photoreactive cross-linkers such as N-hydroxysuccinimidyl-4-azidosalicylic acid (NHs-AsA), N-hydroxysulfosuccinimidyl-4-azidosalicylic acid (sulfo-NHs-AsA), sulfosuccinimidyl-(4-azidosalicylamido)hexanoate (sulfo-NHs-LC-AsA), sulfosuccinimidy1-2- (p-azidosalicylamido)ethyl1,3'-dithiopropionate (sAsD), N-hydroxysuccinimidyl-4- azidobenzoate (HsAB), N-hydroxysulfosuccinimidyl-4-azidobenzoate (sulfo-HsAB), N- succinimidyl-6-(4'-azido2'-nitrophenylamino)hexanoate (sANPAH), sulfo succinimidyl- 6- (4' - azido -2' -nitrophenylamino)hexanoate (sulfo-sANPAH), N-5-azido-2- nitrobenzoyloxysuccinimide (ANB-NOs), sulfosuccinimidy1-2-(m-azido-o-nitrobenzamido)- ethyl- 1 ,3'-dithiopropionate (sAND), N-succinimidyl-4(4-azidopheny1)1,3'-dithiopropionate Attorney Docket No.250298.000780 [00628] (sADP), N-sulfosuccinimidyl(4-azidophenyl)-1,3'-dithiopropionate (sulfo- sADP), sulfosuccinimidyl 4-(p-azidophenyl) butyrate (sulfo-sAPB), sulfosuccinimidyl 2-(7- azido-4-methylcoumarin-3-acetamide)ethy1-1,3'-dithiopropionate (sAED), sulfosuccinimidyl 7-azido-4-methylcoumain-3-acetate (sulfo-sAMCA), p-nitrophenyl diazopyruvate (pNPDP), p-nitrophenyl-2-diazo-3,3,3-trifluoropropionate (PNP-DTP), sulfhydryl-reactive and photoreactive crosslinkers such as 1-(p-Azidosalicylamido)-4-(iodoacetamido) butane (AsIB), N-[4-(p-azidosalicylamido)buty1]-3'-(2'-pyridyldithio)propionamide (APDP), benzophenone- 4-iodoacetamide, benzophenone-4-maleimide carbonylreactive and photoreactive cross- linkers such as p-azidobenzoyl hydrazide (ABH), carboxylate-reactive and photoreactive cross-linkers such as 4-(p-azidosalicylamido) butylamine (AsBA), and arginine-reactive and photoreactive cross-linkers such as p-azidophenyl glyoxal (APG). [00629] In some embodiments, the linker comprises a reactive functional group. In some cases, the reactive functional group comprises a nucleophilic group that is reactive to an electrophilic group present on an p75NTR binding protein . Exemplary electrophilic groups include carbonyl groups such as aldehyde, ketone, carboxylic acid, ester, amide, enone, acyl halide or acid anhydride. In some embodiments, the reactive functional group is aldehyde. Exemplary nucleophilic groups include hydrazide, oxime, amino, hydrazine, thiosemicarbazone, hydrazine carboxylate, and arylhydrazide. [00630] In some embodiments, the linker comprises a maleimide group. In some embodiments, the maleimide group is also referred to as a maleimide spacer. In some embodiments, the maleimide group further encompasses a caproic acid, forming maleimidocaproyl (mc). In some cases, the linker comprises maleimidocaproyl (mc). In some cases, the linker is maleimidocaproyl (mc). In other embodiments, the maleimide group comprises a maleimidomethyl group, such as succinimidy1-4-(N- maleimidomethyl)cyclohexane-l-carboxylate (sMCC) or sulfosuccinimidy1-4-(N- maleimidomethyl)cyclohexane-1 -carboxylate (sulfo-sMCC) described above. [00631] In some embodiments, the maleimide group is a self-stabilizing maleimide. In some embodiments, the self-stabilizing maleimide utilizes diaminopropionic acid (DPR) to incorporate a basic amino group adjacent to the maleimide to provide intramolecular catalysis of tiosuccinimide ring hydrolysis, thereby eliminating maleimide from undergoing an elimination reaction through a retro-Michael reaction. In some embodiments, the self- stabilizing maleimide is a maleimide group described in Lyon, et al., "Self-hydrolyzing maleimides improve the stability and pharmacological properties of antibody-drug Attorney Docket No.250298.000780 conjugates," Nat. Biotechnol. 32(10):1059-1062 (2014). In some embodiments, the linker comprises a self-stabilizing maleimide. In some embodiments, the linker is a self-stabilizing maleimide. [00632] In some embodiments, the linker comprises at least one azide moiety, e.g., as part of an organoazide moiety. In some embodiments, the linker comprises at least one alkyne moiety, e.g., as part of an organoalkyne moiety. In one embodiment, the alkyne is an activated alkyne. In some embodiments, the linker comprises a trizole (e.g., formed via a 1,3- cycloaddition reaction of an azide and an alkyne). In some embodiments, the linker comprises a Diels-Alder adduct. [00633] In some embodiments, the linker comprises a peptide moiety. In some embodiments, the peptide moiety comprises at least 2, 3, 4, 5, or 6 more amino acid residues. In some embodiments, the peptide moiety comprises at most 2, 3, 4, 5, 6, 7, or 8 amino acid residues. In some embodiments, the peptide moiety comprises about 2, about 3, about 4, about 5, or about 6 amino acid residues. In some embodiments, the peptide moiety is a cleavable peptide moiety (e.g., either enzymatically or chemically). In some embodiments, the peptide moiety is a non-cleavable peptide moiety. In some embodiments, the peptide moiety comprises Val-Cit (valine-citrulline), Gly-Gly-Phe-Gly (SEQ ID NO: 681), Phe-Lys, Val- Lys, Gly-Phe-Lys, Phe-Phe-Lys, Ala-Lys, Val-Arg, Phe-Cit, Phe-Arg, Leu-Cit, Ile-Cit, Trp-Cit, Phe-Ala, Ala-Leu-Ala-Leu (SEQ ID NO: 682), or Gly-Phe-Leu-Gly (SEQ ID NO: 683). In some embodiments, the linker comprises a peptide moiety such as: Val-Cit (valine-citrulline), Gly- Gly-Phe-Gly (SEQ ID NO: 681), Phe-Lys, Val-Lys, Gly-Phe-Lys, Phe-Phe-Lys, Ala-Lys, Val- Arg, Phe-Cit, Phe-Arg, Leu-Cit, Ile-Cit, Trp-Cit, Phe-Ala, Ala-Leu-Ala-Leu (SEQ ID NO: 682), or Gly-Phe-Leu-Gly (SEQ ID NO: 683). In some cases, the linker comprises Val-Cit. In some cases, the linker is Val-Cit. [00634] In some embodiments, the linker comprises a benzoic acid group, or its derivatives thereof. In some embodiments, the benzoic acid group or its derivatives thereof comprise paraaminobenzoic acid (PABA). In some embodiments, the benzoic acid group or its derivatives thereof comprise gamma-aminobutyric acid (GABA). [00635] In some embodiments, the linker comprises one or more of a maleimide group, a peptide moiety, and/or a benzoic acid group, in any combination. In some embodiments, the linker comprises a combination of a maleimide group, a peptide moiety, and/or a benzoic acid group. In some embodiments, the maleimide group is maleimidocaproyl (mc). In some embodiments, the peptide group is val-cit. In some embodiments, the benzoic acid group is Attorney Docket No.250298.000780 PABA. In some embodiments, the linker comprises a mc-val-cit group. In some cases, the linker comprises a val-cit-PABA group. In additional cases, the linker comprises a mc-val-cit- PABA group. [00636] In some embodiments, the linker is a self-immolative linker or a self-elimination linker. In some cases, the linker is a self-immolative linker. In other cases, the linker is a self- elimination linker (e.g., a cyclization self-elimination linker). In some embodiments, the linker comprises a linker described in U.S. Patent No. 9,089,614 or PCT Publication No. WO 2015/038426. [00637] In some embodiments, the linker is a dendritic type linker. In some embodiments, the dendritic type linker comprises a branching, multifunctional linker moiety. In some embodiments, the dendritic type linker is used to increase the molar ratio of polynucleotide B to the p75NTR binding protein . In some embodiments, the dendritic type linker comprises PAMAM dendrimers. In some embodiments, the dendritic type linker comprises triazoles. In some embodiments, the triazoles are connected by PEG links. In some embodiments, the linkers are as described in WO 2022/015656. [00638] In some embodiments, the linker is a traceless linker or a linker in which after cleavage does not leave behind a linker moiety (e.g., an atom or a linker group) to an p75NTR binding protein or a polynucleotide B. Exemplary traceless linkers include, but are not limited to, germanium linkers, silicium linkers, sulfur linkers, selenium linkers, nitrogen linkers, phosphorus linkers, boron linkers, chromium linkers, or phenylhydrazide linker. In some cases, the linker is a traceless aryl-triazene linker as described in Hejesen, et al., "A traceless aryl-triazene linker for DNA-directed chemistry," Org Biomol Chem 11(15): 2493-2497 (2013). In some embodiments, the linker is a traceless linker described in Blaney, et al., "Traceless solid-phase organic synthesis," Chem. Rev.102: 2607-2024 (2002). In some embodiments, a linker is a traceless linker as described in U.S. Patent No.6,821,783. [00639] In some embodiments, the linker is a linker described in U.S. Pat. Nos. 6,884,869; 7,498,298; 8,288,352; 8,609,105; or 8,697,688; U.S. Patent Publication Nos. US2014/0127239; US2013/028919; US2014/286970; US2013/0309256; US2015/037360; and US2014/0294851; or International Application Publication Nos. WO2015/057699; WO2014/080251; WO2014/197854; WO2014/145090; WO2014/177042, WO2022/015656. [00640] In some embodiments, a linker is a bond, i.e., a linker is absent. In some cases, a linker is a non-polymeric linker. In some cases, a linker is a polymeric linker. Attorney Docket No.250298.000780 [00641] In some embodiments, the linker comprises an alkyl group. In some embodiments, the linker comprises a C1-C30 alkyl group, or a C1-C24 alkyl group, or a C1- C20 alkyl group, or a C1-C16 alkyl group, or a C1-C12 alkyl group, or a C1-C10 alkyl group, or a C1-C8 alkyl group, or a C1-C6 alkyl group, or a C1-C4 alkyl group. In some cases, a linker is a C1-C6 alkyl group, such as for example, a C 3, C 4, C 3, C 2, or C1 alkyl group. In some cases, the C1-C6 alkyl group is an unsubstituted C1-C6 alkyl group. As used in the context of a linker, alkyl means a saturated straight or branched hydrocarbon radical containing up to six carbon atoms. In some embodiments, the linker comprises a homobifunctional linker or a heterobifunctional linker described supra. [00642] In some cases, a linker is an oligomeric or a polymeric linker. In some embodiments, a linker is a natural or synthetic oligomer or polymer, consisting of branched or unbranched monomers, and/or cross-linked network of monomers in two or three dimensions. In some embodiments, the linker comprises a polysaccharide, lignin, rubber, or polyalkylen oxide (e.g., polyethylene glycol). [00643] In some embodiments, the at least one polymeric linker includes, but is not limited to, alpha-, omega-dihydroxylpolyethyleneglycol, biodegradable lactone-based polymer, e.g. polyacrylic acid, polylactide acid (PLA), poly(glycolic acid) (PGA), polypropylene, polystyrene, polyolefin, polyamide, polycyanoacrylate, polyimide, polyethylene terephthalate (also known as poly(ethylene terephthalate), PET, PETG, or PETE), polytetramethylene glycol (PTG), or polyurethane as well as mixtures thereof. In some embodiments, the linker comprises polyalkylene oxide. In some embodiments, the linker comprises PEG. In some embodiments, the linker comprises polyethylene imide (PEI) or hydroxy ethyl starch (HES). [00644] In some embodiments, the linker comprises a polyalkylene oxide (e.g., PEG) comprising discrete ethylene oxide units. In some cases, the linker comprises between about 2 and about 48 ethylene oxide units. In some cases, the polymer moiety C comprises about 2, about 3, about 4, about 5, about 6, about 7, about 8, about 9, about 10, about 11, about 12, about 13, about 14, about 15, about 16, about 17, about 18, about 19, about 20, about 24, about 30, about 36, about 42, or about 48 ethylene oxide units. [00645] In some embodiments, the p75NTR binding protein is conjugated to the molecular cargo described herein (e.g., a polynucleotide molecule, polypeptide molecule described herein, or a liposome or LNP) using a protamine linker, as disclosed in the U.S. Patent Application Publication Nos. US2002/0132990, US2004/0023902, US2007/012152, Attorney Docket No.250298.000780 and US2010/0209440. In some embodiments, a protamine linker encompassed for use in the present disclosure comprises a sequence disclosed in US 2010/0209440. [00646] Acid cleavable linkers can also be used with the present disclosure and include, but are not limited to, bismaleimideothoxy propane, adipic acid dihydrazide linkers (see, e.g., Fattom et al., Infection & Immun.60:584589, 1992) and acid labile transferrin conjugates that contain a sufficient portion of transferrin to permit entry into the intracellular transferrin cycling pathway (see, e.g., Welhoner et al., J. Biol. Chem.266:43094314, 1991). Conjugates linked via acid cleavable linkers should be preferentially cleaved in acidic intracellular compartments, such as the endosome. [00647] Photocleavable linkers can also be used with the present disclosure. Photocleavable linkers are cleaved upon exposure to light (see, e.g., Goldmacher et al., Bioconj. Chem. 3:104-107, 1992), thereby releasing the targeted agent upon exposure to light. (Hazum et al., Proc. Eur. Pept. Symp., 16th, Brunfeldt, K (Ed), pp. 105 110, 1981; nitrobenzyl group as a photocleavable protective group for cysteine; Yen et al., Makromol. Chem 190:69 82, 1989; water soluble photocleavable copolymers, including hydroxypropylmethacrylamide copolymer, glycine copolymer, fluorescein copolymer and methylrhodamine copolymer; and Senter et al., Photochem. Photobiol. 42:231237, 1985; nitrobenzyloxy carbonyl chloride cross linking reagents that produce photocleavable linkages), relevant portions incorporated herein by reference. Such linkers are particularly useful in treating dermatological or ophthalmic conditions. In addition, other tissues, such as blood vessels that can be exposed to light using fiber-optics during angioplasty in the prevention or treatment of restenosis may benefit from the use of photocleavable linkers. After administration of the conjugate, the body part is exposed to light, resulting in release of the targeted moiety from the conjugate. Heat sensitive linkers would also have similar applicability. Polynucleotides and Methods of Making [00648] The present disclosure includes any polynucleotide described herein, for example, encoding an immunoglobulin VH, VL, HCDR, LCDR, HC or LC of REGN14148; REGN14149; REGN14150; REGN14151; REGN14152; REGN14153; REGN14154; REGN14155; REGN14156; REGN14157; REGN14158; REGN14159; REGN14160; REGN14161; REGN14162; REGN14163; REGN14164; REGN14165; REGN14175; REGN14176; REGN14177; REGN14178; REGN14179; REGN14180; REGN14181; Attorney Docket No.250298.000780 REGN14182; REGN14183; REGN14184; REGN14185; REGN14186; REGN14187; REGN14188; REGN14189; REGN14190; REGN14191; REGN19513; REGN19514; REGN19515; REGN19516; and/or REGN19517, optionally, which is operably linked to a promoter or other expression control sequence. For example, the present disclosure provides any polynucleotide (e.g., DNA) that includes a nucleotide sequence set forth in SEQ ID NO: 1; 3; 5; 7; 9; 11; 13; 15; 17; 19; 21; 23; 25; 27; 29; 31; 33; 35; 37; 39; 41; 43; 45; 47; 49; 51; 53; 55; 57; 59; 61; 63; 65; 67; 69; 71; 73; 75; 77; 79; 81; 83; 85; 87; 89; 91; 93; 95; 97; 99; 101; 103; 105; 107; 109; 111; 113; 115; 117; 119; 121; 123; 125; 127; 129; 131; 133; 135; 137; 139; 141; 143; 145; 147; 148; 150; 152; 154; 156; 157; 159; 161; 163; 165; 166; 168; 170; 172; 174; 176; 178; 180; 182; 184; 186; 188; 190; 192; 194; 196; 198; 200; 202; 204; 206; 208; 210; 212; 214; 216; 218; 220; 222; 224; 226; 228; 230; 232; 234; 236; 238; 240; 242; 244; 246; 248; 250; 252; 254; 256; 258; 260; 262; 264; 266; 268; 270; 272; 274; 276; 278; 280; 282; 284; 286; 288; 290; 292; 294; 296; 298; 300; 301; 303; 305; 306; 308; 310; 312; 314; 316; 318; 320; 322; 324; 326; 328; 330; 332; 334; 336; 338; 340; 342; 344; 346; 348; 350; 352; 354; 356; 358; 360; 362; 364; 366; 368; 370; 372; 374; 376; 378; 380; 382; 384; 386; 388; 390; 392; 394; 396; 398; 400; 402; 404; 406; 408; 410; 412; 414; 416; 418; 420; 422; 424; 426; 428; 430; 432; 434; 436; 438; 439; 440; 442; 444; 446; 448; 450; 452; 454; 456; 458; 460; 462; 464; 466; 468; 470; 472; 474; 476; 478; 479; 481; 483; 485; 487; 488; 490; 492; 494; 496; 498; 500; 502; 504; 506; 508; 510; 512; 514; 516; 518; 520; 522; 524; 526; 528; 530; 532; 534; 536; 538; 540; 542; 544; 546; 548; 550; 552; 554; 556; 558; 560; 562; 564; 566; 568; 570; 572; 574; 576; 578; 580; 582; 584; 586; 588; 590; 592; 594; 596; 598; 600; 602; 604; 606; 608; 610; 612; 614 or 616. In an embodiment, a polynucleotide of the present disclosure is fused to a secretion signal sequence. Polypeptides encoded by such polynucleotides are also within the scope of the present disclosure. A polynucleotide described herein can be DNA or RNA. [00649] Nucleotide sequences of HCVRs and LCVRs of anti-p75NTR protein-drug conjugates set forth herein are summarized below in Table 1-2. Polynucleotides encoding an anti-p75NTR protein-drug conjugates, or polypeptide portion(s) thereof, that include one or more of the HCVRs and/or LCVRs set forth in Table 1-2 form part of the present disclosure. Attorney Docket No.250298.000780 Table 1-2. SEQ ID NOs of DNA Sequences of Domains in Antibodies or Antigen- binding Fragments (e.g., Fabs or scFv Molecules) in Protein-Drug Conjugates of the Present Disclosure. anti-p75NTR # HCVR HCDR1 HCDR2 HCDR3 LCVR LCDR1 LCDR2 LCDR3 HC LC Molecule 3 3 2 0 6 4 4 2 8 6 4 2 Attorney Docket No.250298.000780 REGN14165 314 316 318 320 322 11 13 324 326 328 6 6 4 8 4 4 4 4 4 4 4 4 4 4 4 4 4 6 6 Attorney Docket No.250298.000780 REGN19515 568 570 572 574 576 578 580 582 584 586 6 6 an ^ a polynucleotide encoding a HCVR that comprises the nucleotide sequence set forth in SEQ ID NO: 1, and a polynucleotide encoding a LCVR that comprises the nucleotide sequence set forth in SEQ ID NO: 9; ^ a polynucleotide encoding a HCVR that comprises the nucleotide sequence set forth in SEQ ID NO: 21, and a polynucleotide encoding a LCVR that comprises the nucleotide sequence set forth in SEQ ID NO: 29; ^ a polynucleotide encoding a HCVR that comprises the nucleotide sequence set forth in SEQ ID NO: 41, and a polynucleotide encoding a LCVR that comprises the nucleotide sequence set forth in SEQ ID NO: 49; ^ a polynucleotide encoding a HCVR that comprises the nucleotide sequence set forth in SEQ ID NO: 57, and a polynucleotide encoding a LCVR that comprises the nucleotide sequence set forth in SEQ ID NO: 65; ^ a polynucleotide encoding a HCVR that comprises the nucleotide sequence set forth in SEQ ID NO: 77, and a polynucleotide encoding a LCVR that comprises the nucleotide sequence set forth in SEQ ID NO: 85; ^ a polynucleotide encoding a HCVR that comprises the nucleotide sequence set forth in SEQ ID NO: 97, and a polynucleotide encoding a LCVR that comprises the nucleotide sequence set forth in SEQ ID NO: 105; ^ a polynucleotide encoding a HCVR that comprises the nucleotide sequence set forth in SEQ ID NO: 115, and a polynucleotide encoding a LCVR that comprises the nucleotide sequence set forth in SEQ ID NO: 123; ^ a polynucleotide encoding a HCVR that comprises the nucleotide sequence set forth in SEQ ID NO: 135, and a polynucleotide encoding a LCVR that comprises the nucleotide sequence set forth in SEQ ID NO: 143; Attorney Docket No.250298.000780 ^ a polynucleotide encoding a HCVR that comprises the nucleotide sequence set forth in SEQ ID NO: 154, and a polynucleotide encoding a LCVR that comprises the nucleotide sequence set forth in SEQ ID NO: 161; ^ a polynucleotide encoding a HCVR that comprises the nucleotide sequence set forth in SEQ ID NO: 172, and a polynucleotide encoding a LCVR that comprises the nucleotide sequence set forth in SEQ ID NO: 178; ^ a polynucleotide encoding a HCVR that comprises the nucleotide sequence set forth in SEQ ID NO: 188, and a polynucleotide encoding a LCVR that comprises the nucleotide sequence set forth in SEQ ID NO: 196; ^ a polynucleotide encoding a HCVR that comprises the nucleotide sequence set forth in SEQ ID NO: 206, and a polynucleotide encoding a LCVR that comprises the nucleotide sequence set forth in SEQ ID NO: 214; ^ a polynucleotide encoding a HCVR that comprises the nucleotide sequence set forth in SEQ ID NO: 226, and a polynucleotide encoding a LCVR that comprises the nucleotide sequence set forth in SEQ ID NO: 234; ^ a polynucleotide encoding a HCVR that comprises the nucleotide sequence set forth in SEQ ID NO: 244, and a polynucleotide encoding a LCVR that comprises the nucleotide sequence set forth in SEQ ID NO: 250; ^ a polynucleotide encoding a HCVR that comprises the nucleotide sequence set forth in SEQ ID NO: 260, and a polynucleotide encoding a LCVR that comprises the nucleotide sequence set forth in SEQ ID NO: 268; ^ a polynucleotide encoding a HCVR that comprises the nucleotide sequence set forth in SEQ ID NO: 278, and a polynucleotide encoding a LCVR that comprises the nucleotide sequence set forth in SEQ ID NO: 286; ^ a polynucleotide encoding a HCVR that comprises the nucleotide sequence set forth in SEQ ID NO: 296, and a polynucleotide encoding a LCVR that comprises the nucleotide sequence set forth in SEQ ID NO: 303; ^ a polynucleotide encoding a HCVR that comprises the nucleotide sequence set forth in SEQ ID NO: 314, and a polynucleotide encoding a LCVR that comprises the nucleotide sequence set forth in SEQ ID NO: 322; Attorney Docket No.250298.000780 ^ a polynucleotide encoding a HCVR that comprises the nucleotide sequence set forth in SEQ ID NO: 330, and a polynucleotide encoding a LCVR that comprises the nucleotide sequence set forth in SEQ ID NO: 338; ^ a polynucleotide encoding a HCVR that comprises the nucleotide sequence set forth in SEQ ID NO: 348, and a polynucleotide encoding a LCVR that comprises the nucleotide sequence set forth in SEQ ID NO: 356; ^ a polynucleotide encoding a HCVR that comprises the nucleotide sequence set forth in SEQ ID NO: 368, and a polynucleotide encoding a LCVR that comprises the nucleotide sequence set forth in SEQ ID NO: 376; ^ a polynucleotide encoding a HCVR that comprises the nucleotide sequence set forth in SEQ ID NO: 386, and a polynucleotide encoding a LCVR that comprises the nucleotide sequence set forth in SEQ ID NO: 390; ^ a polynucleotide encoding a HCVR that comprises the nucleotide sequence set forth in SEQ ID NO: 400, and a polynucleotide encoding a LCVR that comprises the nucleotide sequence set forth in SEQ ID NO: 408; ^ a polynucleotide encoding a HCVR that comprises the nucleotide sequence set forth in SEQ ID NO: 416, and a polynucleotide encoding a LCVR that comprises the nucleotide sequence set forth in SEQ ID NO: 408; ^ a polynucleotide encoding a HCVR that comprises the nucleotide sequence set forth in SEQ ID NO: 426, and a polynucleotide encoding a LCVR that comprises the nucleotide sequence set forth in SEQ ID NO: 408; ^ a polynucleotide encoding a HCVR that comprises the nucleotide sequence set forth in SEQ ID NO: 436, and a polynucleotide encoding a LCVR that comprises the nucleotide sequence set forth in SEQ ID NO: 408; ^ a polynucleotide encoding a HCVR that comprises the nucleotide sequence set forth in SEQ ID NO: 444, and a polynucleotide encoding a LCVR that comprises the nucleotide sequence set forth in SEQ ID NO: 408; ^ a polynucleotide encoding a HCVR that comprises the nucleotide sequence set forth in SEQ ID NO: 454, and a polynucleotide encoding a LCVR that comprises the nucleotide sequence set forth in SEQ ID NO: 408; Attorney Docket No.250298.000780 ^ a polynucleotide encoding a HCVR that comprises the nucleotide sequence set forth in SEQ ID NO: 464, and a polynucleotide encoding a LCVR that comprises the nucleotide sequence set forth in SEQ ID NO: 408; ^ a polynucleotide encoding a HCVR that comprises the nucleotide sequence set forth in SEQ ID NO: 474, and a polynucleotide encoding a LCVR that comprises the nucleotide sequence set forth in SEQ ID NO: 408; ^ a polynucleotide encoding a HCVR that comprises the nucleotide sequence set forth in SEQ ID NO: 483, and a polynucleotide encoding a LCVR that comprises the nucleotide sequence set forth in SEQ ID NO: 408; ^ a polynucleotide encoding a HCVR that comprises the nucleotide sequence set forth in SEQ ID NO: 492, and a polynucleotide encoding a LCVR that comprises the nucleotide sequence set forth in SEQ ID NO: 408; ^ a polynucleotide encoding a HCVR that comprises the nucleotide sequence set forth in SEQ ID NO: 502, and a polynucleotide encoding a LCVR that comprises the nucleotide sequence set forth in SEQ ID NO: 408; ^ a polynucleotide encoding a HCVR that comprises the nucleotide sequence set forth in SEQ ID NO: 512, and a polynucleotide encoding a LCVR that comprises the nucleotide sequence set forth in SEQ ID NO: 408; ^ a polynucleotide encoding a HCVR that comprises the nucleotide sequence set forth in SEQ ID NO: 518, and a polynucleotide encoding a LCVR that comprises the nucleotide sequence set forth in SEQ ID NO: 408; ^ a polynucleotide encoding a HCVR that comprises the nucleotide sequence set forth in SEQ ID NO: 528, and a polynucleotide encoding a LCVR that comprises the nucleotide sequence set forth in SEQ ID NO: 536; ^ a polynucleotide encoding a HCVR that comprises the nucleotide sequence set forth in SEQ ID NO: 548, and a polynucleotide encoding a LCVR that comprises the nucleotide sequence set forth in SEQ ID NO: 556; ^ a polynucleotide encoding a HCVR that comprises the nucleotide sequence set forth in SEQ ID NO: 568, and a polynucleotide encoding a LCVR that comprises the nucleotide sequence set forth in SEQ ID NO: 576; Attorney Docket No.250298.000780 ^ a polynucleotide encoding a HCVR that comprises the nucleotide sequence set forth in SEQ ID NO: 588, and a polynucleotide encoding a LCVR that comprises the nucleotide sequence set forth in SEQ ID NO: 596; ^ a polynucleotide encoding a HCVR that comprises the nucleotide sequence set forth in SEQ ID NO: 608, and a polynucleotide encoding a LCVR that comprises the nucleotide sequence set forth in SEQ ID NO: 596; wherein the HCVR and LCVR are in either order. [00651] In some embodiments, a nucleic acid molecule as described herein comprises a nucleic acid sequence encoding any of the HCVR amino acid sequences listed in Table 1- 2; in certain embodiments the nucleic acid molecule comprises a polynucleotide sequence selected from any of the HCVR nucleic acid sequences listed in Table 1-2, or a substantially similar sequence thereof having at least 90%, at least 95%, at least 98% or at least 99% sequence identity thereto. [00652] In some embodiments, the nucleic acid molecule comprises a polynucleotide sequence selected from any of the LCVR nucleic acid sequences listed in Table 1-2, or a substantially similar sequence thereof having at least 90%, at least 95%, at least 98% or at least 99% sequence identity thereto. [00653] In some embodiments the nucleic acid molecule comprises a polynucleotide sequence selected from any of the HCDR1 nucleic acid sequences listed in Table 1-2, or a substantially similar sequence thereof having at least 90%, at least 95%, at least 98% or at least 99% sequence identity thereto. [00654] In some embodiments the nucleic acid molecule comprises a polynucleotide sequence selected from any of the HCDR2 nucleic acid sequences listed in Table 1-2, or a substantially similar sequence thereof having at least 90%, at least 95%, at least 98% or at least 99% sequence identity thereto. [00655] In some embodiments the nucleic acid molecule comprises a polynucleotide sequence selected from any of the HCDR3 nucleic acid sequences listed in Table 1-2, or a substantially similar sequence thereof having at least 90%, at least 95%, at least 98% or at least 99% sequence identity thereto. [00656] In some embodiments the nucleic acid molecule comprises a polynucleotide sequence selected from any of the LCDR1 nucleic acid sequences listed in Table 1-2, or a Attorney Docket No.250298.000780 substantially similar sequence thereof having at least 90%, at least 95%, at least 98% or at least 99% sequence identity thereto. [00657] In some embodiments the nucleic acid molecule comprises a polynucleotide sequence selected from any of the LCDR2 nucleic acid sequences listed in Table 1-2, or a substantially similar sequence thereof having at least 90%, at least 95%, at least 98% or at least 99% sequence identity thereto. [00658] In some embodiments the nucleic acid molecule comprises a polynucleotide sequence selected from any of the LCDR3 nucleic acid sequences listed in Table 1-2, or a substantially similar sequence thereof having at least 90%, at least 95%, at least 98% or at least 99% sequence identity thereto. [00659] In general, a "promoter" or "promoter sequence" is a DNA regulatory region capable of binding an RNA polymerase in a cell (e.g., directly or through other promoter- bound proteins or substances) and initiating transcription of a coding sequence. A promoter may be operably linked to other expression control sequences, including enhancer and repressor sequences and/or with a polynucleotide of the disclosure. Promoters which may be used to control gene expression include, but are not limited to, cytomegalovirus (CMV) promoter (U.S. Pat. Nos.5,385,839 and 5,168,062), the SV40 early promoter region (Benoist, et al., (1981) Nature 290:304-310), the promoter contained in the 3' long terminal repeat of Rous sarcoma virus (Yamamoto, et al., (1980) Cell 22:787-797), the herpes thymidine kinase promoter (Wagner, et al., (1981) Proc. Natl. Acad. Sci. USA 78:1441-1445), the regulatory sequences of the metallothionein gene (Brinster, et al., (1982) Nature 296:39-42); prokaryotic expression vectors such as the beta-lactamase promoter (VIIIa-Komaroff, et al., (1978) Proc. Natl. Acad. Sci. USA 75:3727-3731), or the tac promoter (DeBoer, et al., (1983) Proc. Natl. Acad. Sci. USA 80:21-25); see also "Useful proteins from recombinant bacteria" in Scientific American (1980) 242:74-94; and promoter elements from yeast or other fungi such as the Gal4 promoter, the ADC (alcohol dehydrogenase) promoter, PGK (phosphoglycerol kinase) promoter or the alkaline phosphatase promoter. [00660] A polynucleotide encoding a polypeptide is "operably linked" to a promoter or other expression control sequence when, in a cell or other expression system, the sequence directs RNA polymerase mediated transcription of the coding sequence into RNA, preferably mRNA, which then may be RNA spliced (if it contains introns) and, optionally, translated into a protein encoded by the coding sequence. Attorney Docket No.250298.000780 [00661] The present disclosure includes a polynucleotide comprising the following polynucleotide pairs encoding a VH and VL: SEQ ID NO: 1 and SEQ ID NO: 9; SEQ ID NO: 2 and SEQ ID NO: 29; SEQ ID NO: 41 and SEQ ID NO: 49; SEQ ID NO: 57 and SEQ ID NO: 65; SEQ ID NO: 77 and SEQ ID NO: 85; SEQ ID NO: 97 and SEQ ID NO: 105; SEQ ID NO: 115 and SEQ ID NO: 123; SEQ ID NO: 135 and SEQ ID NO: 143; SEQ ID NO: 154 and SEQ ID NO: 161; SEQ ID NO: 172 and SEQ ID NO: 178; SEQ ID NO: 188 and SEQ ID NO: 196; SEQ ID NO: 206 and SEQ ID NO: 214; SEQ ID NO: 226 and SEQ ID NO: 234; SEQ ID NO: 244 and SEQ ID NO: 250; SEQ ID NO: 260 and SEQ ID NO: 268; SEQ ID NO: 278 and SEQ ID NO: 286; SEQ ID NO: 296 and SEQ ID NO: 303; SEQ ID NO: 314 and SEQ ID NO: 322; SEQ ID NO: 330 and SEQ ID NO: 338; SEQ ID NO: 348 and SEQ ID NO: 356; SEQ ID NO: 368 and SEQ ID NO: 376; SEQ ID NO: 386 and SEQ ID NO: 390; SEQ ID NO: 400 and SEQ ID NO: 408; SEQ ID NO: 416 and SEQ ID NO: 408; SEQ ID NO: 426 and SEQ ID NO: 408; SEQ ID NO: 436 and SEQ ID NO: 408; SEQ ID NO: 444 and SEQ ID NO: 408; SEQ ID NO: 454 and SEQ ID NO: 408; SEQ ID NO: 464 and SEQ ID NO: 408; SEQ ID NO: 474 and SEQ ID NO: 408; SEQ ID NO: 483 and SEQ ID NO: 408; Attorney Docket No.250298.000780 SEQ ID NO: 492 and SEQ ID NO: 408; SEQ ID NO: 502 and SEQ ID NO: 408; SEQ ID NO: 512 and SEQ ID NO: 408; SEQ ID NO: 518 and SEQ ID NO: 408; SEQ ID NO: 528 and SEQ ID NO: 536; SEQ ID NO: 548 and SEQ ID NO: 556; SEQ ID NO: 568 and SEQ ID NO: 576; SEQ ID NO: 588 and SEQ ID NO: 596; and/or SEQ ID NO: 608 and SEQ ID NO: 596; or two separate polynucleotides, each including one of the sequences SEQ ID NO: 1 and SEQ ID NO: 9; SEQ ID NO: 2 and SEQ ID NO: 29; SEQ ID NO: 41 and SEQ ID NO: 49; SEQ ID NO: 57 and SEQ ID NO: 65; SEQ ID NO: 77 and SEQ ID NO: 85; SEQ ID NO: 97 and SEQ ID NO: 105; SEQ ID NO: 115 and SEQ ID NO: 123; SEQ ID NO: 135 and SEQ ID NO: 143; SEQ ID NO: 154 and SEQ ID NO: 161; SEQ ID NO: 172 and SEQ ID NO: 178; SEQ ID NO: 188 and SEQ ID NO: 196; SEQ ID NO: 206 and SEQ ID NO: 214; SEQ ID NO: 226 and SEQ ID NO: 234; SEQ ID NO: 244 and SEQ ID NO: 250; SEQ ID NO: 260 and SEQ ID NO: 268; SEQ ID NO: 278 and SEQ ID NO: 286; SEQ ID NO: 296 and SEQ ID NO: 303; SEQ ID NO: 314 and SEQ ID NO: 322; SEQ ID NO: 330 and SEQ ID NO: 338; SEQ ID NO: 348 and SEQ ID NO: 356; SEQ ID NO: 368 and SEQ ID NO: 376; SEQ ID NO: 386 and SEQ ID NO: 390; SEQ ID NO: 400 and SEQ ID NO: 408; Attorney Docket No.250298.000780 SEQ ID NO: 416 and SEQ ID NO: 408; SEQ ID NO: 426 and SEQ ID NO: 408; SEQ ID NO: 436 and SEQ ID NO: 408; SEQ ID NO: 444 and SEQ ID NO: 408; SEQ ID NO: 454 and SEQ ID NO: 408; SEQ ID NO: 464 and SEQ ID NO: 408; SEQ ID NO: 474 and SEQ ID NO: 408; SEQ ID NO: 483 and SEQ ID NO: 408; SEQ ID NO: 492 and SEQ ID NO: 408; SEQ ID NO: 502 and SEQ ID NO: 408; SEQ ID NO: 512 and SEQ ID NO: 408; SEQ ID NO: 518 and SEQ ID NO: 408; SEQ ID NO: 528 and SEQ ID NO: 536; SEQ ID NO: 548 and SEQ ID NO: 556; SEQ ID NO: 568 and SEQ ID NO: 576; SEQ ID NO: 588 and SEQ ID NO: 596; or SEQ ID NO: 608 and SEQ ID NO: 596. [00662] The present disclosure includes a polynucleotide comprising the following polynucleotide sets which encode a HCDR1, HCDR2, HCDR3, LCDR1, LCDR2 and LCDR3: SEQ ID NOs: 3, 5, 7, 11, 13 and 15; SEQ ID NOs: 23, 25, 27, 31, 33 and 35; SEQ ID NOs: 43, 45, 47, 11, 13 and 51; SEQ ID NOs: 59, 61, 63, 67, 69 and 71; SEQ ID NOs: 79, 81, 83, 87, 89 and 91; SEQ ID NOs: 99, 101, 103, 107, 33 and 109; SEQ ID NOs: 117, 119, 121, 125, 127 and 129; SEQ ID NOs: 137, 139, 141, 145, 147 and 148; SEQ ID NOs: 156, 157, 159, 163, 165 and 166; SEQ ID NOs: 156, 174, 176, 180, 69 and 182; SEQ ID NOs: 190, 192, 194, 198, 13 and 200; SEQ ID NOs: 208, 210, 212, 216, 218 and 220; SEQ ID NOs: 228, 230, 232, 236, 13 and 238; Attorney Docket No.250298.000780 SEQ ID NOs: 156, 246, 248, 252, 69 and 254; SEQ ID NOs: 262, 264, 266, 270, 165 and 272; SEQ ID NOs: 280, 282, 284, 288, 13 and 290; SEQ ID NOs: 298, 300, 301, 305, 306 and 308; SEQ ID NOs: 316, 318, 320, 11, 13 and 324; SEQ ID NOs: 332, 334, 336, 236, 340 and 342; SEQ ID NOs: 350, 352, 354, 358, 360 and 362; SEQ ID NOs: 370, 372, 374, 378, 165 and 380; SEQ ID NOs: 137, 318, 388, 392, 360 and 394; SEQ ID NOs: 402, 404, 406, 236, 13 and 410; SEQ ID NOs: 418, 420, 422, 236, 13 and 410; SEQ ID NOs: 428, 430, 432, 236, 13 and 410; SEQ ID NOs: 438, 439, 440, 236, 13 and 410; SEQ ID NOs: 446, 448, 450, 236, 13 and 410; SEQ ID NOs: 456, 458, 460, 236, 13 and 410; SEQ ID NOs: 466, 468, 470, 236, 13 and 410; SEQ ID NOs: 476, 478, 479, 236, 13 and 410; SEQ ID NOs: 485, 487, 488, 236, 13 and 410; SEQ ID NOs: 494, 496, 498, 236, 13 and 410; SEQ ID NOs: 504, 506, 508, 236, 13 and 410; SEQ ID NOs: 137, 318, 514, 236, 13 and 410; SEQ ID NOs: 520, 522, 524, 236, 13 and 410; SEQ ID NOs: 530, 532, 534, 538, 540 and 542; SEQ ID NOs: 550, 552, 554, 558, 560 and 562; SEQ ID NOs: 570, 572, 574, 578, 580 and 582; SEQ ID NOs: 590, 592, 594, 598, 600 and 602; and/or SEQ ID NOs: 610, 612, 614, 598, 600 and 602; or two separate polynucleotides, each including one of the sequences SEQ ID NOs: 3, 5, 7, 11, 13 and 15; SEQ ID NOs: 23, 25, 27, 31, 33 and 35; SEQ ID NOs: 43, 45, 47, 11, 13 and 51; SEQ ID NOs: 59, 61, 63, 67, 69 and 71; SEQ ID NOs: 79, 81, 83, 87, 89 and 91; Attorney Docket No.250298.000780 SEQ ID NOs: 99, 101, 103, 107, 33 and 109; SEQ ID NOs: 117, 119, 121, 125, 127 and 129; SEQ ID NOs: 137, 139, 141, 145, 147 and 148; SEQ ID NOs: 156, 157, 159, 163, 165 and 166; SEQ ID NOs: 156, 174, 176, 180, 69 and 182; SEQ ID NOs: 190, 192, 194, 198, 13 and 200; SEQ ID NOs: 208, 210, 212, 216, 218 and 220; SEQ ID NOs: 228, 230, 232, 236, 13 and 238; SEQ ID NOs: 156, 246, 248, 252, 69 and 254; SEQ ID NOs: 262, 264, 266, 270, 165 and 272; SEQ ID NOs: 280, 282, 284, 288, 13 and 290; SEQ ID NOs: 298, 300, 301, 305, 306 and 308; SEQ ID NOs: 316, 318, 320, 11, 13 and 324; SEQ ID NOs: 332, 334, 336, 236, 340 and 342; SEQ ID NOs: 350, 352, 354, 358, 360 and 362; SEQ ID NOs: 370, 372, 374, 378, 165 and 380; SEQ ID NOs: 137, 318, 388, 392, 360 and 394; SEQ ID NOs: 402, 404, 406, 236, 13 and 410; SEQ ID NOs: 418, 420, 422, 236, 13 and 410; SEQ ID NOs: 428, 430, 432, 236, 13 and 410; SEQ ID NOs: 438, 439, 440, 236, 13 and 410; SEQ ID NOs: 446, 448, 450, 236, 13 and 410; SEQ ID NOs: 456, 458, 460, 236, 13 and 410; SEQ ID NOs: 466, 468, 470, 236, 13 and 410; SEQ ID NOs: 476, 478, 479, 236, 13 and 410; SEQ ID NOs: 485, 487, 488, 236, 13 and 410; SEQ ID NOs: 494, 496, 498, 236, 13 and 410; SEQ ID NOs: 504, 506, 508, 236, 13 and 410; SEQ ID NOs: 137, 318, 514, 236, 13 and 410; SEQ ID NOs: 520, 522, 524, 236, 13 and 410; SEQ ID NOs: 530, 532, 534, 538, 540 and 542; SEQ ID NOs: 550, 552, 554, 558, 560 and 562; SEQ ID NOs: 570, 572, 574, 578, 580 and 582; Attorney Docket No.250298.000780 SEQ ID NOs: 590, 592, 594, 598, 600 and 602; or SEQ ID NOs: 610, 612, 614, 598, 600 and 602. [00663] The present disclosure includes a polynucleotide comprising the following polynucleotide pairs encoding a HC and LC: SEQ ID NO: 17 and SEQ ID NO: 19; SEQ ID NO: 37 and SEQ ID NO: 39; SEQ ID NO: 53 and SEQ ID NO: 55; SEQ ID NO: 73 and SEQ ID NO: 75; SEQ ID NO: 93 and SEQ ID NO: 95; SEQ ID NO: 111 and SEQ ID NO: 113; SEQ ID NO: 131 and SEQ ID NO: 133; SEQ ID NO: 150 and SEQ ID NO: 152; SEQ ID NO: 168 and SEQ ID NO: 170; SEQ ID NO: 184 and SEQ ID NO: 186; SEQ ID NO: 202 and SEQ ID NO: 204; SEQ ID NO: 222 and SEQ ID NO: 224; SEQ ID NO: 240 and SEQ ID NO: 242; SEQ ID NO: 256 and SEQ ID NO: 258; SEQ ID NO: 274 and SEQ ID NO: 276; SEQ ID NO: 292 and SEQ ID NO: 294; SEQ ID NO: 310 and SEQ ID NO: 312; SEQ ID NO: 326 and SEQ ID NO: 328; SEQ ID NO: 344 and SEQ ID NO: 346; SEQ ID NO: 364 and SEQ ID NO: 366; SEQ ID NO: 382 and SEQ ID NO: 384; SEQ ID NO: 396 and SEQ ID NO: 398; SEQ ID NO: 412 and SEQ ID NO: 414; SEQ ID NO: 424 and SEQ ID NO: 414; SEQ ID NO: 434 and SEQ ID NO: 414; SEQ ID NO: 442 and SEQ ID NO: 414; SEQ ID NO: 452 and SEQ ID NO: 414; SEQ ID NO: 462 and SEQ ID NO: 414; SEQ ID NO: 472 and SEQ ID NO: 414; Attorney Docket No.250298.000780 SEQ ID NO: 481 and SEQ ID NO: 414; SEQ ID NO: 490 and SEQ ID NO: 414; SEQ ID NO: 500 and SEQ ID NO: 414; SEQ ID NO: 510 and SEQ ID NO: 414; SEQ ID NO: 516 and SEQ ID NO: 414; SEQ ID NO: 526 and SEQ ID NO: 414; SEQ ID NO: 544 and SEQ ID NO: 546; SEQ ID NO: 564 and SEQ ID NO: 566; SEQ ID NO: 584 and SEQ ID NO: 586; SEQ ID NO: 604 and SEQ ID NO: 606; and/or SEQ ID NO: 616 and SEQ ID NO: 606; or two separate polynucleotides, each including one of the sequences SEQ ID NO: 17 and SEQ ID NO: 19; SEQ ID NO: 37 and SEQ ID NO: 39; SEQ ID NO: 53 and SEQ ID NO: 55; SEQ ID NO: 73 and SEQ ID NO: 75; SEQ ID NO: 93 and SEQ ID NO: 95; SEQ ID NO: 111 and SEQ ID NO: 113; SEQ ID NO: 131 and SEQ ID NO: 133; SEQ ID NO: 150 and SEQ ID NO: 152; SEQ ID NO: 168 and SEQ ID NO: 170; SEQ ID NO: 184 and SEQ ID NO: 186; SEQ ID NO: 202 and SEQ ID NO: 204; SEQ ID NO: 222 and SEQ ID NO: 224; SEQ ID NO: 240 and SEQ ID NO: 242; SEQ ID NO: 256 and SEQ ID NO: 258; SEQ ID NO: 274 and SEQ ID NO: 276; SEQ ID NO: 292 and SEQ ID NO: 294; SEQ ID NO: 310 and SEQ ID NO: 312; SEQ ID NO: 326 and SEQ ID NO: 328; SEQ ID NO: 344 and SEQ ID NO: 346; SEQ ID NO: 364 and SEQ ID NO: 366; SEQ ID NO: 382 and SEQ ID NO: 384; Attorney Docket No.250298.000780 SEQ ID NO: 396 and SEQ ID NO: 398; SEQ ID NO: 412 and SEQ ID NO: 414; SEQ ID NO: 424 and SEQ ID NO: 414; SEQ ID NO: 434 and SEQ ID NO: 414; SEQ ID NO: 442 and SEQ ID NO: 414; SEQ ID NO: 452 and SEQ ID NO: 414; SEQ ID NO: 462 and SEQ ID NO: 414; SEQ ID NO: 472 and SEQ ID NO: 414; SEQ ID NO: 481 and SEQ ID NO: 414; SEQ ID NO: 490 and SEQ ID NO: 414; SEQ ID NO: 500 and SEQ ID NO: 414; SEQ ID NO: 510 and SEQ ID NO: 414; SEQ ID NO: 516 and SEQ ID NO: 414; SEQ ID NO: 526 and SEQ ID NO: 414; SEQ ID NO: 544 and SEQ ID NO: 546; SEQ ID NO: 564 and SEQ ID NO: 566; SEQ ID NO: 584 and SEQ ID NO: 586; SEQ ID NO: 604 and SEQ ID NO: 606; and/or SEQ ID NO: 616 and SEQ ID NO: 606. [00664] Host cells including the two separate polynucleotides as discussed above, each integrated into chromosomal DNA of the host cell at different loci or ectopic, wherein such polynucleotide are maintained in separate genetic elements, are within the scope of the present disclosure. [00665] The present disclosure includes polynucleotides encoding immunoglobulin polypeptide chains which are variants of those whose nucleotide sequence is specifically set forth herein. A "variant" of a polynucleotide refers to a polynucleotide comprising a nucleotide sequence that is at least about 70-99.9% (e.g., 70, 72, 74, 75, 76, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 99.5, 99.9%) identical to a referenced nucleotide sequence that is set forth herein; when the comparison is performed by a BLAST algorithm wherein the parameters of the algorithm are selected to give the largest match between the respective sequences over the entire length of the respective reference sequences (e.g., expect threshold: 10; word size: 28; max matches in a query range: 0; match/mismatch scores: 1, -2; gap costs: linear). In an embodiment, a variant of a nucleotide Attorney Docket No.250298.000780 sequence specifically set forth herein comprises one or more (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 or 12) point mutations, insertions (e.g., in frame insertions) or deletions (e.g., in frame deletions) of one or more nucleotides. Such mutations may, in an embodiment, be missense or nonsense mutations. In an embodiment, such a variant polynucleotide encodes an immunoglobulin polypeptide chain which can be incorporated into an p75NTR binding protein, i.e., such that the protein retains specific binding to p75NTR. [00666] Eukaryotic and prokaryotic host cells, including mammalian cells, may be used as hosts for expression of an p75NTR binding protein (e.g., antibody or antigen-binding fragment thereof). Such host cells are well known in the art and many are available from the American Type Culture Collection (ATCC). These host cells include, inter alia, Chinese hamster ovary (CHO) cells, NSO, SP2 cells, HeLa cells, baby hamster kidney (BHK) cells, monkey kidney cells (COS), human hepatocellular carcinoma cells (e.g., Hep G2), A549 cells, 3T3 cells, HEK-293 cells and a number of other cell lines. Mammalian host cells include human, mouse, rat, dog, monkey, pig, goat, bovine, horse and hamster cells. Other cell lines that may be used are insect cell lines (e.g., Spodoptera frugiperda or Trichoplusia ni), amphibian cells, bacterial cells, plant cells and fungal cells. Fungal cells include yeast and filamentous fungus cells including, for example, Pichia, Pichia pastoris, Pichia finlandica, Pichia trehalophila, Pichia koclamae, Pichia membranaefaciens, Pichia minuta (Ogataea minuta, Pichia lindneri), Pichia opuntiae, Pichia thermotolerans, Pichia salictaria, Pichia guercuum, Pichia pijperi, Pichia stiptis, Pichia methanolica, Pichia sp., Saccharomyces cerevisiae, Saccharomyces sp., Hansenula polymorpha, Kluyveromyces sp., Kluyveromyces lactis, Candida albicans, Aspergillus nidulans, Aspergillus niger, Aspergillus oryzae, Trichoderma reesei, Chrysosporium lucknowense, Fusarium sp., Fusarium gramineum, Fusarium venenatum, Physcomitrella patens and Neurospora crassa. The present disclosure includes an isolated host cell (e.g., a CHO cell or any type of host cell set forth above) comprising an antigen-binding protein, a VH, VL, HC, LC or CDRs thereof (or variant thereof), such as REGN14148; REGN14149; REGN14150; REGN14151; REGN14152; REGN14153; REGN14154; REGN14155; REGN14156; REGN14157; REGN14158; REGN14159; REGN14160; REGN14161; REGN14162; REGN14163; REGN14164; REGN14165; REGN14175; REGN14176; REGN14177; REGN14178; REGN14179; REGN14180; REGN14181; REGN14182; REGN14183; REGN14184; REGN14185; REGN14186; REGN14187; REGN14188; REGN14189; REGN14190; REGN14191; REGN19513; REGN19514; REGN19515; REGN19516; or Attorney Docket No.250298.000780 REGN19517; and/or a polynucleotide encoding one or more immunoglobulin chains thereof (e.g., as discussed herein). In an embodiment, a host cell includes two separate polynucleotides, one encoding a VH and the other encoding a VL; or one encoding a HC and the other encoding a LC. [00667] The present disclosure also includes a cell which is expressing p75NTR or an antigenic fragment or fusion thereof (e.g., His6 (SEQ ID NO: 619), Fc (e.g., mouse Fc (mFc)), myc, or mycmycHis6 (mmh) (“His6” disclosed as SEQ ID NO: 619)) which is bound by an antigen-binding protein of the present disclosure (e.g., an antibody or antigen-binding fragment thereof), for example, REGN14148; REGN14149; REGN14150; REGN14151; REGN14152; REGN14153; REGN14154; REGN14155; REGN14156; REGN14157; REGN14158; REGN14159; REGN14160; REGN14161; REGN14162; REGN14163; REGN14164; REGN14165; REGN14175; REGN14176; REGN14177; REGN14178; REGN14179; REGN14180; REGN14181; REGN14182; REGN14183; REGN14184; REGN14185; REGN14186; REGN14187; REGN14188; REGN14189; REGN14190; REGN14191; REGN19513; REGN19514; REGN19515; REGN19516; or REGN19517, for example, wherein the cell is in the body of a subject or is in vitro. In addition, the present disclosure also provides a complex comprising an p75NTR binding protein, e.g., antibody or antigen-binding fragment thereof, as discussed herein complexed with p75NTR polypeptide or an antigenic fragment thereof or fusion thereof and/or with a secondary antibody or antigen- binding fragment thereof (e.g., detectably labeled secondary antibody) that binds specifically to the anti-p75NTR antibody or fragment. In an embodiment of the disclosure, the complex is in vitro (e.g., is immobilized to a solid substrate) or is in the body of a subject. [00668] In an embodiment, a myc tag has the amino acid sequence EQKLISEEDLGG (SEQ ID NO: 618), a His6 (SEQ ID NO: 619) or hexahis (SEQ ID NO: 619) or hexahistidine (SEQ ID NO: 619) tag has the amino acid sequence HHHHHH (SEQ ID NO: 619), an mmh tag has the amino acid sequence EQKLISEEDLGGEQKLISEEDLHHHHHH (SEQ ID NO: 620) and a mouse Fc tag has the amino acid sequence EPRGPTIKPCPPCKCPAPNLLGGPSVFIFPPKIKDVLMISLSPIVTCVVVDVSEDDPDVQISWFVNNVEVHTAQTQT HREDYNSTLRVVSALPIQHQDWMSGKEFKCKVNNKDLPAPIERTISKPKGSVRAPQVYVLPPPEEEMTKKQVTLTCM VTDFMPEDIYVEWTNNGKTELNYKNTEPVLDSDGSYFMYSKLRVEKKNWVERNSYSCSVVHEGLHNHHTTKSFSRTP GK (SEQ ID NO: 621). [00669] In addition, the present disclosure also provides a complex comprising an anti- p75NTR protein-drug conjugate, as discussed herein complexed with a p75NTR polypeptide or Attorney Docket No.250298.000780 an antigenic fragment thereof or fusion thereof and/or with a secondary antibody or antigen- binding fragment thereof (e.g., detectably labeled secondary antibody) that binds specifically to the anti-p75NTR protein-drug conjugate. In an embodiment, the complex is in vitro (e.g., is immobilized to a solid substrate) or is in the body of a subject. [00670] Recombinant p75NTR binding proteins, e.g., antibodies and antigen-binding fragments, or anti-p75NTR fusion proteins disclosed herein may also be produced in an E. coli/T7 expression system. In this embodiment, polynucleotides encoding the anti-p75NTR antibody immunoglobulin molecules described herein (e.g., HC, LC, VH and/or VL or CDRs thereof of (REGN14148; REGN14149; REGN14150; REGN14151; REGN14152; REGN14153; REGN14154; REGN14155; REGN14156; REGN14157; REGN14158; REGN14159; REGN14160; REGN14161; REGN14162; REGN14163; REGN14164; REGN14165; REGN14175; REGN14176; REGN14177; REGN14178; REGN14179; REGN14180; REGN14181; REGN14182; REGN14183; REGN14184; REGN14185; REGN14186; REGN14187; REGN14188; REGN14189; REGN14190; REGN14191; REGN19513; REGN19514; REGN19515; REGN19516; or REGN19517)) may be inserted into a pET-based plasmid and expressed in the E. coli/T7 system. For example, the present disclosure includes methods for expressing an antibody or antigen-binding fragment thereof or immunoglobulin chain thereof in a host cell (e.g., bacterial host cell such as E. coli such as BL21 or BL21DE3) comprising T7 RNA polymerase in the cell which also includes a polynucleotide encoding an immunoglobulin chain (e.g., including the nucleotide sequence in any one or more of SEQ ID NOs: 1, 3, 5, 7, 9, 11, 13, 15, 17 or 19; or a variant thereof) that is operably linked to a T7 promoter. For example, in an embodiment, a bacterial host cell, such as an E. coli, includes a polynucleotide encoding the T7 RNA polymerase gene operably linked to a lac promoter and expression of the polymerase and the chain is induced by incubation of the host cell with IPTG (isopropyl-beta-D-thiogalactopyranoside). See US4952496 and US5693489 or Studier & Moffatt, Use of bacteriophage T7 RNA polymerase to direct selective high-level expression of cloned genes, J. Mol. Biol. 1986 May 5;189(1): 113-30. [00671] There are several methods by which to produce recombinant antibodies which are known in the art. One example of a method for recombinant production of antibodies is disclosed in US Patent No.4,816,567. [00672] Transformation can be by any known method for introducing polynucleotides into a host cell. Methods for introduction of heterologous polynucleotides into mammalian Attorney Docket No.250298.000780 cells are well known in the art and include dextran-mediated transfection, calcium phosphate precipitation, polybrene-mediated transfection, protoplast fusion, electroporation, encapsulation of the polynucleotide(s) in liposomes, biolistic injection and direct microinjection of the DNA into nuclei. In addition, nucleic acid molecules may be introduced into mammalian cells by viral vectors. Methods of transforming cells are well known in the art. See, for example, U.S. Pat. Nos.4,399,216; 4,912,040; 4,740,461 and 4,959,455. Thus, the present disclosure includes recombinant methods for making an anti-p75NTR antigen- binding protein, such as an antibody or antigen-binding fragment thereof of the present disclosure, or an immunoglobulin chain thereof, comprising (i) introducing, into a host cell, one or more polynucleotides (e.g., including the nucleotide sequence in any one or more of SEQ ID NOs: 1, 9, 17 and/or 19; or a variant thereof) encoding light and/or heavy immunoglobulin chains of the antigen-binding protein, e.g., REGN14148; REGN14149; REGN14150; REGN14151; REGN14152; REGN14153; REGN14154; REGN14155; REGN14156; REGN14157; REGN14158; REGN14159; REGN14160; REGN14161; REGN14162; REGN14163; REGN14164; REGN14165; REGN14175; REGN14176; REGN14177; REGN14178; REGN14179; REGN14180; REGN14181; REGN14182; REGN14183; REGN14184; REGN14185; REGN14186; REGN14187; REGN14188; REGN14189; REGN14190; REGN14191; REGN19513; REGN19514; REGN19515; REGN19516; or REGN19517, for example, wherein the polynucleotide is in a vector; and/or integrates into the host cell chromosome and/or is operably linked to a promoter; (ii) culturing the host cell (e.g., CHO or Pichia or Pichia pastoris) under conditions favorable to expression of the polynucleotide and, (iii) optionally, isolating the antigen-binding protein (e.g., antibody or antigen-binding fragment) or chain from the host cell and/or medium in which the host cell is grown. When making an antigen-binding protein (e.g., antibody or antigen-binding fragment) comprising more than one immunoglobulin chain, e.g., an antibody that comprises two heavy immunoglobulin chains and two light immunoglobulin chains, co-expression of the chains in a single host cell leads to association of the chains, e.g., in the cell or on the cell surface or outside the cell if such chains are secreted, so as to form the antigen-binding protein (e.g., antibody or antigen-binding fragment). The methods of the present disclosure include those wherein only a heavy immunoglobulin chain or only a light immunoglobulin chain or both (e.g., any of those discussed herein including mature fragments and/or variable domains thereof) are expressed in a cell. Such single chains are useful, for example, as intermediates in the expression of an antibody or antigen-binding fragment that includes such Attorney Docket No.250298.000780 a chain. For example, the present disclosure also includes p75NTR binding proteins, such as antibodies and antigen-binding fragments thereof which are the product of the production methods set forth herein, and, optionally, the purification methods set forth herein. [00673] In an embodiment of the disclosure, a method for making an anti-p75NTR antigen-binding protein, e.g., antibody or antigen-binding fragment thereof, includes a method of purifying the antigen-binding protein, e.g., by column chromatography, precipitation and/or filtration. As discussed, the product of such a method also forms part of the present disclosure. [00674] In some embodiments, the present disclosure provides methods for making protein-drug conjugates described herein, the methods comprising (a) contacting the antigen- binding protein, with a molecular cargo described herein, under conditions favorable for conjugation of the antigen-binding protein to the molecular cargo; and (b) optionally, isolating the protein-drug conjugate produced in step (a). [00675] In some embodiments, the present disclosure provides methods for making protein-drug conjugates described herein, the method comprising (a) culturing a host cell described herein comprising a polynucleotide encoding the protein-drug conjugate described herein under conditions that allow expression of the protein-drug conjugate; and (b) optionally, isolating the protein-drug conjugate produced in step (a). Preparation of Human Antibodies [00676] The anti-p75NTR antibodies and antigen-binding fragments described herein (e.g., REGN14148; REGN14149; REGN14150; REGN14151; REGN14152; REGN14153; REGN14154; REGN14155; REGN14156; REGN14157; REGN14158; REGN14159; REGN14160; REGN14161; REGN14162; REGN14163; REGN14164; REGN14165; REGN14175; REGN14176; REGN14177; REGN14178; REGN14179; REGN14180; REGN14181; REGN14182; REGN14183; REGN14184; REGN14185; REGN14186; REGN14187; REGN14188; REGN14189; REGN14190; REGN14191; REGN19513; REGN19514; REGN19515; REGN19516; or REGN19517) can be fully human antibodies and fragments. Methods for generating monoclonal antibodies, including fully human monoclonal antibodies are known in the art. Any such known methods can be used in the context of the present disclosure to make human antibodies that specifically bind to p75NTR. [00677] Using VELOCIMMUNE™ technology, for example, or any other similar known method for generating fully human monoclonal antibodies, high affinity chimeric antibodies to Attorney Docket No.250298.000780 p75NTR are initially isolated having a human variable region and a mouse constant region. As in the experimental section below, the antibodies are characterized and selected for desirable characteristics, including affinity, ligand blocking activity, selectivity, epitope, etc. If necessary, mouse constant regions are replaced with a desired human constant region, for example wild-type or modified IgG1 or IgG4, to generate a fully human anti-p75NTR antibody. While the constant region selected may vary according to specific use, high affinity antigen- binding and target specificity characteristics reside in the variable region. In certain instances, fully human anti-p75NTR antibodies are isolated directly from antigen-positive B cells. See, for example, US Patent No.6,596,541, Regeneron Pharmaceuticals, VELOCIMMUNE®. Treatment and Administration [00678] The present disclosure provides anti-p75NTR antigen-binding proteins or antigen-binding fragments thereof, and protein-drug conjugates which can be used, for example, for delivering a molecular cargo to the body of a subject (e.g., the nervous system including the peripheral nervous system, autonomic nervous system, enteric nervous system, brain and the spinal cord, or eye, and, in particular, sensory neurons (such as, but not limited to, dorsal root ganglion cells or trigeminal ganglion cells) residing therein), for treating or preventing a disease or disorder (e.g., neurological disease or disorder), in the body of the subject. In some embodiments, the present disclosure provides methods for administering the protein-drug conjugates of the present disclosure to a subject, the methods comprising introducing the protein-drug conjugate into the body of the subject. [00679] In some embodiments, the present disclosure provides methods for administering antigen-binding proteins or antigen-binding fragments thereof (e.g., anti-p75NTR antibodies or antigen-binding fragments thereof) of the present disclosure to a subject, the methods comprising introducing the antigen-binding protein or antigen-binding fragment thereof into the body of the subject. [00680] In some embodiments, the administering of the protein-drug conjugates and/or antigen-binding proteins or antigen-binding fragments thereof to the subject described herein does not modulate (i.e., increase or decrease) the expression and/or activity of p75NTR, e.g., in regions or subregions of the nervous system that express p75NTR. [00681] In some embodiments, the disease or disorder being treated herein can present dysfunctional pathways in regions or subregions of the nervous system that express p75NTR. In some embodiments, the disease or disorder being treated herein can exhibit an Attorney Docket No.250298.000780 increase in expression and/or activity in p75NTR, e.g., in regions or subregions of the nervous system. In some embodiments, the disease or disorder being treated herein can be any disease or disorder for which p75NTR can be a biomarker.. [00682] In some embodiments, the disease or disorder being treated here can be a condition that is not mediated by the activity of p75NTR. [00683] In one aspect, the disclosure provides a pharmaceutical composition comprising an antigen-binding protein or antigen-binding fragment thereof (e.g., an anti- p75NTR or antigen-binding fragment thereof described herein) and/or a protein-drug conjugate described herein together with a pharmaceutically acceptable carrier and/or excipient. The phrase “pharmaceutically acceptable”, as used in connection with compositions described herein, refers to molecular entities and other ingredients of such compositions that are physiologically tolerable and do not typically produce untoward reactions when administered to a mammal (e.g., a human). Preferably, the term “pharmaceutically acceptable” means approved by a regulatory agency of the Federal or a state government or listed in the U.S. Pharmacopeia or other generally recognized pharmacopeia for use in mammals, and more particularly in humans. [00684] The pharmaceutical compositions of the disclosure may be in any suitable form (depending upon the desired method of administering to a patient). Suitable compositions and methods of administration are known to those skilled in the art, for example see, Johnson et al., Blood.2009; 114(3):535-46. [00685] The pharmaceutical compositions may comprise the antigen-binding protein or antigen-binding fragment thereof (e.g., the anti-p75NTR or antigen-binding fragment thereof described herein) and/or the protein-drug conjugates of the disclosure either in the free form or in the form of a pharmaceutically acceptable salt. The term “pharmaceutically acceptable salt” as used herein refers to a derivative of the disclosed protein-drug conjugates wherein the protein-drug conjugates is modified by making acid or base salts of the agent. For example, acid salts are prepared from the free base (typically wherein the neutral form of the drug has a neutral —NH2 group) involving reaction with a suitable acid. Suitable acids for preparing acid salts include both organic acids, e.g., acetic acid, benzoic acid, citric acid, propionic acid, glycolic acid, trifluoroacetic acid, pyruvic acid, oxalic acid, malic acid, malonic acid, maleic acid, succinic acid, fumaric acid, tartaric acid, cinnamic acid, mandelic acid, methanesulfonic acid, ethanesulfonic acid, p-toluenesulfonic acid, salicylic acid, and the like, as well as inorganic acids, e.g., hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid Attorney Docket No.250298.000780 phosphoric acid and the like. Conversely, preparation of basic salts of acid moieties which may be present on a protein-drug conjugates are prepared using a pharmaceutically acceptable base such as sodium hydroxide, potassium hydroxide, ammonium hydroxide, calcium hydroxide, trimethylamine or the like. [00686] In some embodiments, the protein-drug conjugates described herein may be present in a solution at a concentration of about 1 μg/mL to 50 mg/mL, for example, about 0.1 mg/mL to 10 mg/mL, about 0.2 mg/mL to 5 mg/mL, about 0.5 mg/mL to 8 mg/mL, about 0.8 mg/mL to 12 mg/mL, about 1 mg/mL to 15 mg/mL, about 2 mg/mL to 20 mg/mL, or about 5 mg/mL to 25 mg/mL, or about 0.1 mg/mL, 0.2 mg/mL, 0.3 mg/mL, 0.4 mg/mL, 0.5 mg/mL, 0.6 mg/mL, 0.7 mg/mL, 0.8 mg/mL, 0.9 mg/mL, 1 mg/mL, 1.25 mg/mL, 1.5 mg/mL, 1.75 mg/mL, 2 mg/mL, 2.25 mg/mL, 2.5 mg/mL, 2.75 mg/mL, 3 mg/mL, 3.25 mg/mL, 3.5 mg/mL, 3.75 mg/mL, 4 mg/mL, 5 mg/mL, 6 mg/mL, 7 mg/mL, 8 mg/mL, 9 mg/mL, 10 mg/mL, 11 mg/mL, 12 mg/mL, 13 mg/mL, 14 mg/mL, 15 mg/mL or 20 mg/mL. [00687] In some embodiments, the antigen-binding proteins or antigen-binding fragments thereof described herein may be present in a solution at a concentration of about 1 μg/mL to 50 mg/mL, for example, about 0.1 mg/mL to 10 mg/mL, about 0.2 mg/mL to 5 mg/mL, about 0.5 mg/mL to 8 mg/mL, about 0.8 mg/mL to 12 mg/mL, about 1 mg/mL to 15 mg/mL, about 2 mg/mL to 20 mg/mL, or about 5 mg/mL to 25 mg/mL, or about 0.1 mg/mL, 0.2 mg/mL, 0.3 mg/mL, 0.4 mg/mL, 0.5 mg/mL, 0.6 mg/mL, 0.7 mg/mL, 0.8 mg/mL, 0.9 mg/mL, 1 mg/mL, 1.25 mg/mL, 1.5 mg/mL, 1.75 mg/mL, 2 mg/mL, 2.25 mg/mL, 2.5 mg/mL, 2.75 mg/mL, 3 mg/mL, 3.25 mg/mL, 3.5 mg/mL, 3.75 mg/mL, 4 mg/mL, 5 mg/mL, 6 mg/mL, 7 mg/mL, 8 mg/mL, 9 mg/mL, 10 mg/mL, 11 mg/mL, 12 mg/mL, 13 mg/mL, 14 mg/mL, 15 mg/mL or 20 mg/mL. [00688] The pharmaceutical composition may be adapted for administration by any appropriate route such as, e.g., parenteral injections (including intrathecal, intracerebroventricular, intracisternal (e.g., cisterna magna), intraparenchymal injections) into the central nervous system. [00689] Such compositions may be prepared by any method known in the art of pharmacy, for example, by mixing the active ingredient with the carrier(s) or excipient(s) under sterile conditions. [00690] In addition, disclosed herein are pharmaceutical dosage forms comprising the antigen-binding proteins or antigen-binding fragments thereof and/or the protein-drug conjugates of the disclosure. Attorney Docket No.250298.000780 [00691] Pharmaceutical compositions based on the antigen-binding proteins or antigen-binding fragments thereof and/or protein-drug conjugates disclosed herein can be formulated in any conventional manner using one or more physiologically acceptable carriers and/or excipients. The antigen-binding proteins or antigen-binding fragments thereof and/or protein-drug conjugates may be formulated for administration by, for example, injection, inhalation, or insulation (either through the mouth or the nose) or by parenteral administration, or by administration directly to an organ or tissue. In some embodiments, the present disclosure provides methods for delivering a molecular cargo to a tissue or cell type expressing p75NTR in the body of a subject comprising administering to the subject the protein- drug conjugate of the present disclosure or the pharmaceutical compositions of the present disclosure. In some embodiments, the tissue is brain, spinal cord, peripheral nervous system, autonomic nervous system, enteric nervous system, and/or eye. In some embodiments, the cell type is a sensory neuron. In some embodiments, the cell type is a dorsal root ganglion cell or a trigeminal ganglion cell. [00692] The pharmaceutical compositions can be formulated for a variety of modes of administration, including systemic, topical, or localized administration. Techniques and formulations can be found in, for example, Remington's Pharmaceutical Sciences, Meade Publishing Co., Easton, Pa. In some embodiments, localized injection is used, including intrathecal, intracisternal (e.g., cisterna magna), intracerebroventricular, intraparenchymal injection. For the purposes of injection, the pharmaceutical compositions can be formulated in liquid solutions, preferably in physiologically compatible buffers, such as Hank’s solution or Ringer’s solution. In addition, the pharmaceutical compositions may be formulated in solid form and redissolved or suspended immediately prior to use. Lyophilized forms of the pharmaceutical composition are also suitable. [00693] In some embodiments, the pharmaceutical compositions of the present disclosure may be lyophilized. As a non-limiting example, the obtained lyophilizate can be reconstituted into a hydrous composition by adding a hydrous solvent. In some embodiments, the hydrous composition may be able to be directly administered parenterally (e.g., via intrathecal, intracisternal (e.g., cisterna magna), intracerebroventricular, or intraparenchymal injection) to a patient. Therefore, a further embodiment of the present disclosure is a hydrous pharmaceutical composition, obtainable via reconstitution of the lyophilizate with a hydrous solvent. Attorney Docket No.250298.000780 [00694] In some embodiments, the pharmaceutical composition disclosed herein may comprise a lyophilized formulation. As a non-limiting example, the lyophilization formulation may comprise antigen-binding proteins (e.g., antibodies or antigen-binding fragments thereof) and/or protein-drug conjugates of the disclosure, mannitol, and/or TWEEN 80®. As another non-limiting example, the lyophilization formulation may comprise antigen-binding proteins (e.g., antibodies or antigen-binding fragments thereof) and/or protein-drug conjugates disclosed herein, mannitol and poloxamer 188. In some embodiments, the pharmaceutical composition may comprise a lyophilization formulation comprising a reconstituted-liquid composition. [00695] In some embodiments, pharmaceutical compositions of the present disclosure may provide a formulation with an enhanced solubility and/or moistening of the lyophilizate over previously known compositions. As a non-limiting example, enhanced solubility and/or moistening of the lyophilizate may be achieved using an appropriate composition of excipients. In this way, pharmaceutical compositions of the present disclosure comprising antigen-binding proteins (e.g., antibodies or antigen-binding fragments thereof) and/or protein-drug conjugates described herein may be developed to show a desired shelf stability at (e.g., at −20° C, +5° C, or +25° C) and can be easily resolubilized such that the lyophilizate can be completely dissolved through the use of a buffer or other excipients from seconds up to two or more minutes, with or without the use of an of ultrasonic homogenizer. Furthermore, the composition can be easily provided to a patient in need of treatment via any appropriate delivery route disclosed herein, e.g., parenteral (including intrathecal, intracisternal (e.g., cisterna magna), intracerebroventricular, or intraparenchymal injections), enteral (including oral or rectal), inhalation, or intranasal routes. As a non-limiting example, the pH-value of the resulting solution may be between pH 2.7 and pH 9. [00696] In some embodiments, the pharmaceutical compositions of the present disclosure may be desiccated, e.g., freeze-dried, or a pharmaceutical formulation thereof that includes a pharmaceutically acceptable carrier but substantially lacks water. [00697] For oral administration, the pharmaceutical compositions may take the form of, for example, tablets or capsules prepared by conventional means with pharmaceutically acceptable excipients such as binding agents (e.g. pregelatinized maize starch, polyvinylpyrrolidone or hydroxypropyl methylcellulose); fillers (e.g. lactose, microcrystalline cellulose or calcium hydrogen phosphate); lubricants (e.g. magnesium stearate, talc or silica); disintegrants (e.g. potato starch or sodium starch glycolate); or wetting agents (e.g. sodium Attorney Docket No.250298.000780 lauryl sulfate). The tablets can also be coated by methods well known in the art. Liquid preparations for oral administration may take the form of, for example, solutions, syrups or suspensions, or they may be presented as a dry product for constitution with water or other suitable vehicle before use. Such liquid preparations may be prepared by conventional means with pharmaceutically acceptable additives such as suspending agents (e.g. sorbitol syrup, cellulose derivatives or hydrogenated edible fats); emulsifying agents (e.g. lecithin or acacia); non-aqueous vehicles (e.g. ationd oil, oily esters, ethyl alcohol or fractionated vegetable oils); and preservatives (e.g. methyl or propyl-p-hydroxybenzoates or sorbic acid). The preparations can also contain buffer salts, flavoring, coloring and sweetening agents as appropriate. [00698] The pharmaceutical compositions can be formulated for parenteral administration by injection, e.g. by bolus injection or continuous infusion. Formulations for injection can be presented in a unit dosage form, e.g. in ampoules or in multi-dose containers, with an optionally added preservative. The pharmaceutical compositions can further be formulated as suspensions, solutions or emulsions in oily or aqueous vehicles, and may contain other agents including suspending, stabilizing and/or dispersing agents. [00699] Additionally, the pharmaceutical compositions can also be formulated as a depot preparation. These long-acting formulations can be administered by implantation (e.g. subcutaneously or intramuscularly) or by intramuscular injection. Thus, for example, the compounds may be formulated with suitable polymeric or hydrophobic materials (e.g. as an emulsion in an acceptable oil) or ion exchange resins, or as sparingly soluble derivatives, for example, as a sparingly soluble salt. Other suitable delivery systems include microspheres, which offer the possibility of local noninvasive delivery of drugs over an extended period of time. This technology can include microspheres having a precapillary size, which can be injected via a coronary catheter into any selected part of an organ without causing inflammation or ischemia. The administered therapeutic is then slowly released from the microspheres and absorbed by the surrounding cells present in the selected tissue. [00700] Systemic administration can also be by transmucosal or transdermal means. For transmucosal or transdermal administration, penetrants appropriate to the barrier to be permeated are used in the formulation. Such penetrants are generally known in the art, and include, for example, for transmucosal administration, bile salts, and fusidic acid derivatives. In addition, detergents may be used to facilitate permeation. Transmucosal administration can occur using nasal sprays or suppositories. For topical administration, the vector particles Attorney Docket No.250298.000780 described herein can be formulated into ointments, salves, gels, or creams as generally known in the art. A wash solution can also be used locally to treat an injury or inflammation in order to accelerate healing. [00701] Pharmaceutical forms suitable for injectable use can include sterile aqueous solutions or dispersions; formulations including sesame oil, peanut oil or aqueous propylene glycol; and sterile powders for the extemporaneous preparation of sterile injectable solutions or dispersions. In all cases, the form must be sterile and must be fluid. It must be stable under the conditions of manufacture and certain storage parameters (e.g. refrigeration and freezing) and must be preserved against the contaminating action of microorganisms, such as bacteria and fungi. [00702] An antigen-binding protein (e.g., an antibody or antigen-binding fragment thereof) and/or a protein-drug conjugate described herein can be formulated into a composition in a neutral or salt form. Pharmaceutically acceptable salts, include the acid addition salts (formed with the free amino groups of the protein) and which are formed with inorganic acids such as, for example, hydrochloric or phosphoric acids, or such organic acids as acetic, oxalic, tartaric, mandelic, and the like. Salts formed with the free carboxyl groups can also be derived from inorganic bases such as, for example, sodium, potassium, ammonium, calcium, or ferric hydroxides, and such organic bases as isopropylamine, trimethylamine, histidine, procaine and the like. [00703] A pharmaceutically acceptable carrier can also be a solvent or dispersion medium containing, for example, water, ethanol, polyol (for example, glycerol, propylene glycol, and liquid polyethylene glycol, and the like), suitable mixtures thereof, and vegetable oils. The proper fluidity can be maintained, for example, by the use of a coating, such as lecithin, by the maintenance of the required particle size in the case of dispersion and by the use of surfactants. The prevention of the action of microorganisms can be brought about by various antibacterial and antifungal agents known in the art. In many cases, it will be preferable to include isotonic agents, for example, sugars or sodium chloride. Prolonged absorption of the injectable compositions can be brought about by the use in the compositions of agents delaying absorption, for example, aluminum monostearate and gelatin. [00704] Sterile injectable solutions can be prepared by incorporating the active compounds or constructs in the required amount in the appropriate solvent with various of the other ingredients enumerated above, as required, followed by filtered sterilization. Attorney Docket No.250298.000780 [00705] Upon formulation, solutions can be administered in a manner compatible with the dosage formulation and in such amount as is therapeutically effective. The formulations are easily administered in a variety of dosage forms, such as the type of injectable solutions described above, but slow-release capsules or microparticles and microspheres and the like can also be employed. [00706] For parenteral administration in an aqueous solution, for example, the solution should be suitably buffered if necessary and the liquid diluent first rendered isotonic with sufficient saline or glucose. In this context, sterile aqueous media that can be employed will be known to those of skill in the art in light of the present disclosure. For example, one dosage could be dissolved in 1 ml of isotonic NaCl solution and either added to 1000 ml of hypodermoclysis fluid or injected at the proposed site of infusion. [00707] The person responsible for administration will, in any event, determine the appropriate dose for the individual subject. For example, a subject may be administered the antigen-binding proteins (e.g., antibodies or antigen-binding fragments thereof) and/or protein-drug conjugates described herein on a daily or weekly basis for a time period or on a monthly, bi-yearly or yearly basis. [00708] In addition to the compounds formulated for parenteral administration, such as intrathecal, intracerebroventricular, intracisternal (e.g., cisterna magna), or intraparenchymal injection, other pharmaceutically acceptable forms include, e.g., tablets or other solids for oral administration; liposomal formulations; time release capsules; biodegradable and any other form currently used. [00709] One may also use intranasal or inhalable solutions or sprays, aerosols or inhalants. Nasal solutions can be aqueous solutions designed to be administered to the nasal passages in drops or sprays. Nasal solutions can be prepared so that they are similar in many respects to nasal secretions. Thus, the aqueous nasal solutions usually are isotonic and slightly buffered to maintain a pH of 5.5 to 7.5. In addition, antimicrobial preservatives, similar to those used in ophthalmic preparations, and appropriate drug stabilizers, if required, may be included in the formulation. Various commercial nasal preparations are known and can include, for example, antibiotics and antihistamines and are used for asthma prophylaxis. [00710] Oral formulations can include excipients as, for example, pharmaceutical grades of mannitol, lactose, starch, magnesium stearate, sodium saccharine, cellulose, magnesium carbonate and the like. These compositions take the form of solutions, suspensions, tablets, pills, capsules, sustained release formulations or powders. In certain Attorney Docket No.250298.000780 defined embodiments, oral pharmaceutical compositions will include an inert diluent or assimilable edible carrier, or they may be enclosed in hard or soft-shell gelatin capsule, or they may be compressed into tablets, or they may be incorporated directly with the food of the diet. For oral therapeutic administration, the active compounds may be incorporated with excipients and used in the form of ingestible tablets, buccal tablets, troches, capsules, elixirs, suspensions, syrups, wafers, and the like. [00711] The tablets, troches, pills, capsules and the like may also contain the following: a binder, as gum tragacanth, acacia, cornstarch, or gelatin; excipients, such as dicalcium phosphate; a disintegrating agent, such as corn starch, potato starch, alginic acid and the like; a lubricant, such as magnesium stearate; and a sweetening agent, such as sucrose, lactose or saccharin may be added or a flavoring agent, such as peppermint, oil of wintergreen, or cherry flavoring. When the dosage unit form is a capsule, it may contain, in addition to materials of the above type, a liquid carrier. Various other materials may be present as coatings or to otherwise modify the physical form of the dosage unit. For instance, tablets, pills, or capsules may be coated with shellac, sugar, or both. A syrup of elixir may contain the active compounds sucrose as a sweetening agent methyl and propylparabens as preservatives, a dye and flavoring, such as cherry or orange flavor. [00712] The mode of administration of the p75NTR binding proteins (e.g., the anti-p75NTR antibodies or antigen-binding fragments thereof described herein) and/or the anti-p75NTR protein-drug conjugates or composition thereof can vary. Routes of administration include parenteral, non-parenteral, oral, rectal, transmucosal, intestinal, parenteral; intramuscular, subcutaneous, intradermal, intramedullary, intrathecal, intracisternal (e.g., cisterna magna), intracerebroventricular, direct intraventricular, intravenous, intraperitoneal, intranasal, intraocular, inhalation, insufflation, topical, cutaneous, intraocular, intravitreal, transdermal or intra-arterial. [00713] Compositions may be administered to a subject intravenously, intratumorally, intradermally, intraarterially, intraperitoneally, intralesionally, intracranially, intraarticularly, intraprostaticaly, intrapleurally, intratracheally, intranasally, intravitreally, intravaginally, intrarectally, topically, intratumorally, intramuscularly, intrathecally, intracisternally, intracerebroventricularly, subcutaneously, subconjunctival, intravesicularlly, mucosally, intrapericardially, intraumbilically, intraocularly, orally, locally, by inhalation, by injection, by infusion, by continuous infusion, by localized perfusion, via a catheter, via a lavage, in a cream, or in a lipid composition. Attorney Docket No.250298.000780 [00714] Compositions as disclosed herein can also include adjuvants such as aluminum salts and other mineral adjuvants, tensoactive agents, bacterial derivatives, vehicles and cytokines. Adjuvants can also have antagonizing immunomodulating properties. Compositions and methods as disclosed herein can also include adjuvant therapy. [00715] The pharmaceutical compositions of the disclosure may be administered directly into the patient, into the affected organ or systemically, or applied ex vivo to cells derived from the patient or a human cell line which are subsequently administered to the patient, or used in vitro to select a subpopulation of cells derived from the patient, which are then re-administered to the patient. [00716] The present disclosure provides a vessel (e.g., a plastic or glass vial, e.g., with a cap or a chromatography column, hollow bore needle or a syringe cylinder) comprising any of the p75NTR binding proteins or antigen-binding fragments thereof and/or the anti-p75NTR protein-drug conjugates, or a pharmaceutical formulation comprising a pharmaceutically acceptable carrier thereof. [00717] In some embodiments, p75NTR binding proteins described herein (e.g., anti- p75NTR antibodies or antigen-binding fragments thereof described herein) and/or anti-p75NTR protein-drug conjugates described herein are used for treating or preventing a disease or disorder, such as but not limited to, a central nervous system (CNS) disease or disorder (e.g., a brain disease or disorder or a spinal cord disease or disorder), a peripheral nervous system disease or disorder, an autonomic nervous system disease or disorder, an enteric nervous system disease or disorder or an eye disease or disorder. [00718] In some embodiments, p75NTR binding proteins described herein (e.g., anti- p75NTR antibodies or antigen-binding fragments thereof described herein) and/or anti-p75NTR protein-drug conjugates described herein are used for treating or preventing pain. Non- limiting examples of pain include, but are not limited to, peripheral chronic pain (e.g., by delivering Nav1.7 siRNA or another siRNA targeting any other various gene or gene products associated with pain, e.g., chronic pain such as peripheral chronic pain, contemplated herein), somatic pain, small fiber peripheral neuropathy, chemotherapy-induced neuropathy, painful diabetic-induced neuropathy, chronic itch, trigeminal neuralgia, post-herpetic neuralgia, temporo-mandibular pain, migraine, dysautonomia, Sickle cell disease, joint pain, back pain, myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), myofascial pain syndrome, herpes zoster, or pelvic pain. Attorney Docket No.250298.000780 [00719] In some embodiments, p75NTR binding proteins described herein (e.g., anti- p75NTR antibodies or antigen-binding fragments thereof described herein) and/or anti-p75NTR protein-drug conjugates described herein are used for treating or preventing itch (e.g., chronic itch). [00720] In some embodiments, p75NTR binding proteins described herein (e.g., anti- p75NTR antibodies or antigen-binding fragments thereof described herein) and/or anti-p75NTR protein-drug conjugates described herein are used for treating or preventing a neurological disease or disorder. Non-limiting examples of neurological diseases or disorders include, but are not limited to, lysosomal storage diseases, amyloidosis, neuropathy, neurodegenerative diseases, leukodystrophy, neuropsychiatric diseases, traumatic brain injury, neurodevelopmental diseases, and neuromuscular diseases, seizure, behavioral disorders, ocular diseases or disorders, viral or microbial infections, inflammation, ischemia, and cancer. Specific examples of neurological disorders include, but are not limited to, neurodegenerative diseases (e.g., Parkinson's disease, striatonigral degeneration, Shy-Draeger syndrome, tauopathies (e.g., Alzheimer disease), motor neuron disease, and nervous system heterodegenerative disorders (e.g., Alexander's disease, Cockayne syndrome, Canavan disease, hepatolenticular degeneration, hereditary sensory ataxia, dementia (e.g., spinocerebellar ataxia), cancer (e.g., central nervous system (CNS) cancers, including brain metastases resulting from cancer elsewhere in the body). [00721] In some embodiments, the p75NTR binding proteins described herein (e.g., anti- p75NTR antibodies or antigen-binding fragments thereof described herein) and/or the p75NTR protein-drug conjugates described herein are used for treating or preventing, for example, without limitation, chronic pain (e.g., peripheral chronic pain), somatic pain, chronic itch, migraine, trigeminal neuralgia, post-herpetic neuralgia, joint pain, back pain, Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, myofascial pain syndrome, herpes zoster, and/or pelvic pain. [00722] In some embodiments, p75NTR binding proteins described herein (e.g., anti- p75NTR antibodies or antigen-binding fragments thereof described herein) and/or anti-p75NTR protein-drug conjugates described herein are used for treating or preventing glioblastoma multiforme (GBM). Glioblastoma multiforme (GBM) is a rapidly-growing type of tumor typically of the brain or spinal cord. It is the most common type of primary malignant brain tumor in adults. Only 25% of glioblastoma patients survive more than one year and 5% of patients survive more than five years. Symptoms of can depend on the brain region where the Attorney Docket No.250298.000780 glioblastoma is located. For instance, the tumor can grow in areas of the brain that lead to difficulties in forming words or in moving limbs. Expanding tumors can increase pressure within the skull, leading to headaches. Other symptoms include impaired vision, nausea and vomiting, loss of appetite; mood swings; loss of balance, problems with memory or concentration, problems speaking and/or seizures. [00723] As used herein, the term “subject” refers to a mammal (e.g., rat, mouse, cat, dog, cow, sheep, horse, goat, rabbit), preferably a human, for example, in need of prevention and/or treatment of a disease or disorder described herein. [00724] The present disclosure includes combinations including a p75NTR binding protein described herein (e.g., an anti-p75NTR antibody or antigen-binding fragment thereof described herein) and/or an anti-p75NTR protein-drug conjugate described herein, in association with one or more further therapeutic agents or treatments. A further therapeutic agent that is administered to a subject in association with a p75NTR binding protein described herein (e.g., an anti-p75NTR antibody or antigen-binding fragment thereof described herein) and/or an anti-p75NTR protein-drug conjugate is administered to the subject in accordance with the Physicians' Desk Reference 2003 (Thomson Healthcare; 57th edition (Nov.1, 2002)). The p75NTR binding protein and/or anti-p75NTR protein-drug conjugate and the further therapeutic agent can be in a single composition or in separate compositions. [00725] Methods for treating or preventing a disease or disorder in a subject in need of said treatment or prevention by administering a p75NTR binding protein (e.g., an anti-p75NTR antibody or antigen-binding fragment thereof described herein) and/or an anti-p75NTR protein- drug conjugate, in association with a further therapeutic agent are part of the present disclosure. Compositions comprising the p75NTR binding protein and/or the anti-p75NTR protein-drug conjugate in association with one or more further therapeutic agents also form part of the present disclosure. [00726] The term "in association with" indicates that components, an p75NTR binding protein, e.g., antibody or antigen-binding fragment thereof of the present disclosure, along with another agent such as methotrexate, can be formulated into a single composition, e.g., for simultaneous delivery, or formulated separately into two or more compositions (e.g., a kit including each component). Components administered in association with each another can be administered to a subject at a different time than when the other component is administered; for example, each administration may be given non-simultaneously (e.g., separately or sequentially) at intervals over a given period of time. Separate components Attorney Docket No.250298.000780 administered in association with each another may also be administered sequentially, though essentially simultaneously, during the same administration session. Moreover, the separate components administered in association with each another may be administered to a subject by the same or by a different route. [00727] In some embodiments, a p75NTR binding protein (e.g., an anti-p75NTR antibody or antigen-binding fragment thereof described herein) and/or an anti-p75NTR protein-drug conjugate may be administered in association with a further therapeutic agent such as an anesthetic or analgesic for the treatment of chronic and somatic pain. Suitable anesthetics include, but are not limited to, local anesthetics, general anesthetics, inhaled agents, intravenous agents, and muscle relaxants. Examples of local anesthetics include, but are not limited to, articaine, benzocaine, bupivacaine, cinchocaine/dibucaine, chloroprocaine, cocaine, cyclomethycaine, dimethocaine/loracaine, etidocaine, eugenol, lidocaine/lignocaine, mepivacaine, menthol, piperocaine, propoxycaine, procaine/novocaine, proparacaine, tetracaine/amethocaine, levobupivacaine, prilocaine, ropivacaine, trimecaine, saxitoxin, tetrodotoxin, and combinations and derivations thereof. Examples of general anesthetics include, but are not limited to, amobarbital, atracurium, alcuronium, alfentanil, butorphanol, cisatracurium, diamorphine, decamethonium, desflurane, diazepam, doxacurium, etomidate, enflurane, halothane, isoflurane, methoxyflurane, meperidine, methadone, morphine, nalbuphine, nitrous oxide, sevoflurane, methohexital, thiamylal, thiopental, lorazepam, midazolam, ketamine, propofol, fentanyl, remifentanil, sufentanil, buprenorphine, hydromorphone, levorphanol, oxycodone, oxymorphone, pentazocine, succinylcholine, mivacurium, rapacuronium, rocuronium, vecuronium, gallamine, metocurine, pancuronium, pipecuronium, tubocurarine, xenon, and combinations and derivations thereof. Other anesthesia includes, including, but not limited to, anesthesia that is administered orally, by dermal contact, subcutaneously, intravenously, by epidural means, spinally, and by inhalation. Examples of analgesics include, but are not limited to, opioids, such as codeine, dexamethasone, morphine, fentanyl, hydromorphone, hydrocodone, tramadol, oxycodone, ondansetron, methadone, alfentanil, remifentanil, and derivations thereof, and non-opioid analgesics, including acetaminophen, nonsteroidal anti-inflammatory drugs (NSAIDs), dexmedetomidine, clonidine, capsaicin, anti-convulsants such as gabapentin and pregabalin, steroids such as Dexamethasone, prednisone, prednisolone, and combinations and derivations thereof. Attorney Docket No.250298.000780 [00728] In some embodiments, a p75NTR binding protein (e.g., an anti-p75NTR antibody or antigen-binding fragment thereof described herein) and/or an anti-p75NTR protein-drug conjugate may be administered in association with a further therapeutic agent such as a pain reliever (e.g., aspirin or ibuprofen, acetaminophen), triptan (e.g., sumatriptan (Imitrex, Tosymra) and rizatriptan (Maxalt, Maxalt-MLT)), dihydroergotamine (Migranal, Trudhesa), Lasmiditan (Reyvow), oral calcitonin gene-related peptides antagonists (e.g, ubrogepant (Ubrelvy) and rimegepant (Nurtec ODT)), intranasal zavegepant (Zavzpret), an opioid medication, an anti-nausea drug (e.g., chlorpromazine, metoclopramide (Gimoti, Reglan) or prochlorperazine (Compro, Compazine)), beta blocker such as propranolol (Inderal, InnoPran), Hemangeol) and metoprolol (Lopressor), calcium channel blocker such as verapamil (Verelan, Calan), antidepressant (e.g., amitriptyline), an anti-seizure drug such as Valproate and topiramate (Topamax, Qudexy), onabotulinumtoxinA (Botox), calcitonin gene- related peptides (CGRP) monoclonal antibody such as Erenumab-aooe (Aimovig), fremanezumab-vfrm (Ajovy), galcanezumab-gnlm (Emgality), and eptinezumab-jjmr (Vyepti), atogepant (Qulipta), or rimegepant (Nurtec ODT) for the treatment of migraine. [00729] In some embodiments, a p75NTR binding protein (e.g., an anti-p75NTR antibody or antigen-binding fragment thereof described herein) and/or an anti-p75NTR protein-drug conjugate may be administered in association with a further therapeutic agent such as an anticonvulsant (e.g., carbamazepine (Tegretol, Carbatrol, others), oxcarbazepine (Trileptal, Oxtellar XR), lamotrigine (Lamictal), valproate and phenytoin (Dilantin, Phenytek, Cerebyx), clonazepam (Klonopin), topiramate (Qsymia, Topamax, others), pregabalin (Lyrica) and gabapentin (Neurontin, Gralise, Horizant)), a muscle relaxant (e.g., baclofen (Gablofen, Lioresal, Ozobax)), or onabotulinumtoxinA (Botox) for the treatment of trigeminal neuralgia. [00730] In some embodiments, a p75NTR binding protein (e.g., an anti-p75NTR antibody or antigen-binding fragment thereof described herein) and/or an anti-p75NTR protein-drug conjugate may be administered in association with a further therapeutic agent such as a pain reliever (e.g., NSAIDs), an anti-seizure medicine (e.g., gabapentin (Gralise, Neurontin, Horizant) and pregabalin (Lyrica)), a topical agent (e.g., lidocaine cream or patch), an antidepressant such as a tricyclic antidepressant (e.g., amitriptyline and nortriptyline (Pamelor)), or serotonin and norepinephrine reuptake inhibitor duloxetine (Cymbalta) and the extended-release antidepressant venlafaxine (Effexor XR) and desvenlafaxine (Pristiq)), a scrambler therapy, spinal cord stimulation, or plasma exchange, steroids and intravenous immune globulin for the treatment of chronic pain (e.g., peripheral chronic pain). Attorney Docket No.250298.000780 [00731] In some embodiments, a p75NTR binding protein (e.g., an anti-p75NTR antibody or antigen-binding fragment thereof described herein) and/or an anti-p75NTR protein-drug conjugate may be administered in association with a further therapeutic agent such as a nonsteroidal anti-inflammatory drug (NSAID), acetaminophen, a local anesthetic, capsaicin, a Cox-2 inhibitor, an antidepressant, an anti-seizure medication, an anti-epileptic medication, an opioid, a steroid, an anticonvulsant, a muscle relaxant, a triptan, dihydroergotamine, Lasmiditan, a calcitonin gene-related peptides antagonist, an anti-nausea drug, a beta blocker, a calcium channel blocker, a serotonin and norepinephrine reuptake inhibitor (SNRI), onabotulinumtoxinA, or a benzodiazepine, or a combination thereof. [00732] In some embodiments, a p75NTR binding protein (e.g., an anti-p75NTR antibody or antigen-binding fragment thereof described herein) and/or an anti-p75NTR protein-drug conjugate may be administered in association with a further therapeutic agent such as Aducanumab (Aduhelm™), Donepezil (Aricept®), Galantamine (Razadyne®), Lecanemab, Memantine (Namenda®), Rivastigmine (Exelon®), Donepezil and memantine (Namzaric®), Orexin receptor antagonist (Belsomra®), or Suvorexant (Belsomra®) for the treatment of Alzheimer’s disease. [00733] In some embodiments, a p75NTR binding protein (e.g., an anti-p75NTR antibody or antigen-binding fragment thereof described herein) and/or an anti-p75NTR protein-drug conjugate may be administered in association with a further therapeutic agent such as Carbidopa-levodopa (Sinemet), Carbidopa-levodopa (controlled release) (Sinemet CR), Carbidopa-levodopa (orally disintegrating tablet) (Parcopa), Carbidopa-levodopa (extended release capsules) (Rytary), Carbidopa-levodopa-entacapone (enteral suspension) (Duopa), Levodopa Inhalation powder (Inbrija), Entacapone (Comtan), Tolcapone (Tasmar), Opicapone (Ongentys), Carbidopa/Levodopa Entacapone (Stalevo), Pramipexole (Mirapex), Pramipexole (extended release) (Mirapex ER), Ropinirole (Requip), Ropinirole (extended release) (Requip XL), Apomorphine (injection) (Apokyn), Apomorphine sublingual film (Kynmobi), Rotigotine (transdermal patch) (Neupro), Selegiline (Eldepryl), Selegiline (orally disintegrating tablet) (Zelapar), Rasagiline (Azilect), Safinamide (Xadago), Amantadine (Symmetrel), Amantadine (extended release) (Gocovri), Amantadine (extended release) (Osmolex), Istradefylline (Nourianz), Trihexyphenidyl (Artane), or Benztropine (Cogentin) for the treatment of Parkinson’s disease. [00734] In some embodiments, a p75NTR binding protein (e.g., an anti-p75NTR antibody or antigen-binding fragment thereof described herein) and/or an anti-p75NTR protein-drug Attorney Docket No.250298.000780 conjugate may be administered in association with a further therapeutic agent such as Mannitol (Osmitrol, Resectisol), carbamazepine, Phenytoin (Dilantin, Phenytek), Valproate sodium, Gabapentin (Neurontin), Topiramate (Topamax), Carbamazepine (Equetro), Magnesium sulfate (NMDA), Potassium, Phosphate, Dextromethorphan/quinidine (Nuedexta), Pentobarbital sodium (Nembutal sodium), Nimodipine (Nymalize), Methylphenidate hydrochloride (Ritalin, Daytrana), Modafinil (Provigil), Levodopa, Sertraline hydrochloride (Zoloft), Citalopram hydrobromide (Celexa), Paroxetine hydrochloride (Paxil), Quetiapine fumarate (Seroquel), Tizanidine hydrochloride (Zanaflex), Baclofen (Lioresal), Dantrolene sodium (Dantrium), Diazepam (Valium, Diazepam Intensol), Cyclobenzaprine hydrochloride (Amrix), Acetaminophen (Tylenol), Ibuprofen (Advil, Motrin), or Naproxen sodium (Naprosyn, Aleve, Anaprox DS) for the treatment of Traumatic brain injury. [00735] In some embodiments, a p75NTR binding protein (e.g., an anti-p75NTR antibody or antigen-binding fragment thereof described herein) and/or an anti-p75NTR protein-drug conjugate may be administered in association with a further therapeutic agent such as Methylprednisolone, Tirilazad mesylate, Lyrica (pregabalin), Riluzole, GM1 ganglioside, Gacyclidine, or naloxone for the treatment of Spinal cord injury. [00736] In some embodiments, a p75NTR binding protein (e.g., an anti-p75NTR antibody or antigen-binding fragment thereof described herein) and/or an anti-p75NTR protein-drug conjugate may be administered in association with a further therapeutic agent such as Dexamethasone, Mannitol, Dexamethasone Intensol, Osmitrol, De-Sone LA, Dxevo, HiDex, or Zcort for the treatment of brain edema. [00737] An effective or therapeutically effective amount of p75NTR binding protein, e.g., antibody or antigen-binding fragment, for treating or preventing a disease or condition described herein refers to the amount of the antigen-binding protein sufficient to alleviate one or more signs and/or symptoms of the disease or condition in the treated subject, whether by inducing the regression or elimination of such signs and/or symptoms or by inhibiting the progression of such signs and/or symptoms. In an embodiment of the disclosure, an effective or therapeutically effective amount of p75NTR binding protein is about 2-30 mg/kg. This dose may be administered, for example, about once a month. The dose amount may vary depending upon the age and the size of a subject to be administered, target disease, conditions, route of administration, and the like. In certain embodiments, the initial dose may be followed by administration of a second or a plurality of subsequent doses of antigen- Attorney Docket No.250298.000780 binding protein in an amount that can be approximately the same or less or more than that of the initial dose, wherein the subsequent doses are separated by days or weeks or months. [00738] A symptom is a manifestation of disease apparent to the patient himself, while a sign is a manifestation of disease that the physician perceives. Reduction, fully or in part, of a sign or symptom may be referred to as alleviation of the sign or symptom. [00739] In an embodiment, an effective or therapeutically effective dose of p75NTR binding protein and/or anti-p75NTR protein-drug conjugate is about 1 mg/kg and 50 mg/kg body weight. The dose amount may vary depending upon the age and the size of a subject to be administered, target disease, conditions, route of administration, and the like. In certain embodiments, the initial dose may be followed by administration of a second or a plurality of subsequent doses of antigen-binding protein in an amount that can be approximately the same or less or more than that of the initial dose, wherein the subsequent doses are separated by days or weeks. EXAMPLES [00740] The present invention is also described and demonstrated by way of the following examples. However, the use of these and other examples anywhere in the specification is illustrative only and in no way limits the scope and meaning of the invention or of any exemplified term. Likewise, the invention is not limited to any particular preferred embodiments described here. Indeed, many modifications and variations of the invention may be apparent to those skilled in the art upon reading this specification, and such variations can be made without departing from the invention in spirit or in scope. The invention is therefore to be limited only by the terms of the appended claims along with the full scope of equivalents to which those claims are entitled. Example 1. Determination of the ability of anti-p75NTR (p75) monoclonal antibody supernatants to block binding of human p75 dimer to plate-coated human NT-3. Table 2-1. mAb clone IDs Corresponding L t # Cl n N me Attorney Docket No.250298.000780 REGN14152 REGN14152-L1 927-62-B09 REGN14153 REGN14153-L1 927-62-H09 Table 2-2. Reagents used and lot numbers Reagent Source Identifier Lot# Attorney Docket No.250298.000780 Proteins Human p75-ecto domain.mFc Regeneron REGN6869 REGN6869-L1 H NT 3 R&D S t 267N3025CF L1 [00741] An ELISA-based blocking assay was developed to determine the ability of anti- p75 monoclonal antibody supernatants to block the binding of the human p75 neurotrophin receptor mouse Fc dimer (human p75-mFc), to plate-coated human neurotrophin-3 (hNT-3). [00742] The recombinant human hp75-mFc protein (REGN6869) (SEQ ID NO: 675) used in the experiments comprises a portion of the human p75NTR extracellular domain (amino acids K29-N250) (REGN6869) (SEQ ID NO: 676), fused to the Fc portion of the mouse IgG2a at the C-terminus of human p75NTR (REGN6869) (SEQ ID NO: 621). The human NTF-3 (UniProt Attorney Docket No.250298.000780 accession number P20783.1) expressed with amino acids W139-T257 (K196R) (SEQ ID NO: 679) was commercially obtained from R&D Systems. [00743] In this assay, hNT-3 was passively absorbed at a concentration of 2 μg/mL in PBS on a 96-well microtiter plate overnight at 4°C. Nonspecific binding sites were subsequently blocked using a 0.5% (w/v) solution of BSA in PBS for 1 hour at room temperature. In a separate microtiter plate, a fixed amount of 1 nM human p75NTR-mFc was bound for one hour with anti- hp75 monoclonal antibody supernatants or sample media at a dilution of 1:5 or 0.5 ^g/ml of the control anti-human/canine NGFR-mIgG1 monoclonal antibody in assay buffer. The fixed concentration of human p75NTR-mFc was selected to be near the concentration that generated 50% of the maximal binding (EC50 value) to plate-adhered hNT-3 protein. After the incubation, the antibody-protein complexes were transferred to the microtiter plate coated with hNT-3. After one hour incubation at room temperature, the wells were washed, and hNT-3 bound human p75-mFc was detected with a horseradish peroxidase-conjugated goat anti-mouse IgG Fcγ fragment specific polyclonal antibody. The plates were then developed using TMB substrate solution (BD Biosciences) according to manufacturer’s recommendation and absorbance at 450 nm was measured on a Victor^ Multilabel Plate Reader (PerkinElmer^). [00744] Percent blocking for the tested anti-p75NTR monoclonal antibody supernatants was calculated using the formula below: [Experimental Signal (anti-p75NTR) – Background Signal (buffer)] % Blocking = 100 –( ) x100 [Maximum Signal (1nM hp75 NTR -mFc) – Background Signal (buffer)] [00745] For the purpose of this Example, antibodies that blocked binding of human p75NTR-mFc to human NT-3 with a value greater than or equal to 50% in the results presented in Table 2-3 were classified as blockers. [00746] The ability of thirty-five anti-p75NTR monoclonal antibody supernatants to block human p75-mFc binding to plate-coated human NT-3 was assessed using a sandwich ELISA- based blocking assay. The results are shown in Table 2-3. Table 2-3. Summary of anti-p75NTR antibody supernatants blocking human p75-mFc dimer binding to human NT-3 Attorney Docket No.250298.000780 REGN14149 REGN14149-L1 927-62-F02 76 REGN14150 REGN14150-L1 927-62-E06 121 Attorney Docket No.250298.000780 Human/Canine NGFR-mIgG1 N/A N/A 105 [00747 ] In the present assay, twenty-eight anti-p75 monoclonal antibody supernatants blocked human p75-mFc from binding to plate-coated human NT-3 with a percent blockade of greater than or equal to 50% and were classified as blockers. Seven anti- p75NTR monoclonal antibody supernatants were classified as non-blockers since their blockade was below 50%. In this assay the control anti-human/canine NGFR-mIgG1 antibody blocked the human p75 binding to human NT-3. Example 2. Anti-p75NTR (p75) monoclonal antibody supernatants binding to engineered cells expressing human p75NTR (hp75), monkey p75NTR (mfp75) or mouse p75NTR (mp75) using electrochemiluminescence. Table 3-1. Reagents used and lot numbers Cell Lines Source Identifier NIH3T3/hp75NTR Regeneron ACL16057 Attorney Docket No.250298.000780 Deep Well Dilution Plate VWR 10755-250 80841-931C-931 Milli t NA NA NA [00748] The same mAb clone IDs as used in Example 1 were used in the present Example. The ability of anti-human p75 monoclonal antibody supernatants to bind human p75 neurotrophin receptor (hp75) (NCBI accession number NP_002498.1) (SEQ ID NO: 669), or Macaca fascicularis p75 neurotrophin receptor (mfp75) (NCBI accession number XP_005583674.1) (SEQ ID NO: 671), or mouse neurotrophin receptor (mp75) (GenBank accession number AAH38365) (SEQ ID NO: 673) expressing cells was determined using an electrochemiluminescence based assay. [00749] Briefly, NIH3T3 cells were engineered to express hp75, or mfp75, or mp75 by transfecting the cells with hygromycin resistant pLVxEF1a.hNGFR expression plasmid encoding hp75 (amino acids M1-V399, NCBI accession number NP_002498.1) (SEQ ID NO: 669), or pLVx.mfNGFR expression plasmid encoding mfp75 (M1-V427, NCBI accession number XP_005583674.1) (SEQ ID NO: 671), or pLVxEF1a.mNGFR expression plasmid encoding mp75 (amino acids M1-V427, GenBank accession number AAH38365 (SEQ ID NO: 673). The p75 negative NIH3T3/SRELuc (NIH3T3/SRELuc) cells showed no detectable expression of p75 by fluorescence activated cell sorting (FACS) with a commercial p75 antibody and were included in the experiments as a background binding control. [00750] Experiments were carried out according to the following procedure. NIH3T3/hp75, NIH3T3/mfp75, NIH3T3/mp75 and NIH3T3/SRELuc cells cultured in flasks were rinsed once with 1xPBS buffer without Ca2+/Mg2+ and incubated for 10 minutes at 37°C with Enzyme Free Cell Dissociation Solution to detach cells. The cell pellets were washed once with 1xPBS with Ca2+/Mg2+ and counted with a CellometerTM Auto T4 cell counter (Nexcelom Bioscience, Lawrence, MA). Approximately 2.0x104 NIH3T3/hp75, NIH3T3/mfp75, NIH3T3/mp75 or NIH3T3/SRELuc cells per well were seeded separately onto 96-well carbon electrode plates (Meso Scale Discovery, Rockville, MD) and incubated for 1 hour at 37°C to allow the cells to Attorney Docket No.250298.000780 adhere. Nonspecific binding sites were blocked by incubating with 2% BSA (w/v) in 1xPBS with Ca2+/Mg2+ for 1 hour at room temperature. To the plate-bound cells, anti-p75 monoclonal antibody supernatants at a dilution of 1:10, 0.5 ^g/ml of the control antibody in assay buffer and buffer with no antibody were added followed by 1 hour incubation at room temperature. Plates were then washed to remove unbound antibodies using an AquaMax2000 plate washer with a cell washing head (MDS Analytical Technologies, Sunnyvale, CA). The plate-bound anti-p75-hIgG samples were detected with SULFO-TAGTM-conjugated goat polyclonal anti-human IgG antibody specific for heavy and light chains (Jackson Immunoresearch Labs, West Grove, PA) and the plate-bound anti-p75-mIgG (ME20.4 purified anti-hp75) was detected with SULFO-TAGTM-conjugated goat polyclonal anti-mouse IgG antibody specific for Fcγ fragment (Jackson Immunoresearch Labs, West Grove, PA) for 1 hour at room temperature. After washes, plates were developed with Read Buffer (Meso Scale Discovery, Rockville, MD) according to the manufacturer’s recommended procedure and luminescent signals were recorded with a SECTOR Imager 600 (Meso Scale Discovery, Rockville, MD). The ratio of binding signals on the NIH3T3/hp75, NIH3T3/mfp75, or NIH3T3/mp75 to NIH3T3/SRELuc was calculated and reported as an indication of the binding specificity of anti-p75 antibodies. Antibodies with binding signal on NIH3T3/hp75, NIH3T3/mfp75, or NIH3T3/mp75 cells greater than or equal to 200 RLU, with a binding ratio of greater than or equal to 3, were classified as specific binders. Antibodies with a binding signal less than 200 RLU or with a binding ratio less than 3 were classified as non-specific binders or non-binders. [00751] The ability of the anti-p75NTR monoclonal antibody supernatants to bind specifically to NIH3T3 cells expressing human, monkey or mouse p75 was evaluated using an electrochemiluminescence based binding assay. The experimental results are summarized in Table 3-2 and Table 3-3. Table 3-2. Summary of anti-p75NTR antibody supernatants binding to cells engineered to express human or monkey p75 Antibody Binding Signal (RLU) Ratio to 75 Attorney Docket No.250298.000780 REGN14153 REGN14153-L1 927-62-H09 24540 22368 628 39 36 REGN14154 REGN14154-L1 927-62-B10 29803 24819 891 33 28 Attorney Docket No.250298.000780 IgG, Fcγ Fragment Specific - Table 3-3. Summary of anti-p75NTR antibody supernatants binding to cells engineered to express mouse p75 Antibody Binding Signal (RLU) Ratio to NIH3T3/SRELuc Attorney Docket No.250298.000780 REGN14179 REGN14179-L1 927-68-D02 20374 636 32 REGN14180 REGN14180-L1 927-68-A05 18286 403 45 [00752] A total of 40 anti-p75NTR monoclonal antibodies in crude supernatants were tested for binding to NIH3T3/hp75, NIH3T3/mfp75, NIH3T3/mp75 and NIH3T3/SREluc cells. All tested anti-p75 monoclonal antibodies displayed binding signals greater than 3000 RLU on NIH3T3/hp75 cells with ratios of binding on NIH3T3/hp75 to NIH3T3/SREluc cells greater than 14 suggesting these antibodies are capable of specific binding to human p75. When tested for specific binding to NIH3T3/mfp75, all anti-p75 antibodies displayed binding signals Attorney Docket No.250298.000780 greater than 4000 RLU and ratio of binding on NIH3T3/mfp75 to NIH3T3/SRELuc cells greater than 11 and were characterized as mfp75 binders. [00753] These forty anti-p75 antibodies displayed binding signals greater than 1500 RLU on NIH3T3/mp75 cells with ratios of binding on NIH3T3/mp75 to NIH3T3/SREluc cells greater than 7 and were characterized as mouse p75 binders. [00754] The commercial positive control anti-p75-mIgG1 clone ME20.4 tested at 0.5 ^g/ml bound to NIH3T3/hp75 and NIH3T3/mfp75 cells with signals of 15897 RLU and 12505 RLU and with ratios of binding to negative NIH3T3/SRELuc cells of 230 and 181, respectively, and was classified as a hp75 and mfp75 specific binder. When tested for binding to NIH3T3/mp75, anti- p75-mIgG1 clone ME20.4 bound to NIH3T3/mp75 and NIH3T3/SRELuc cells with similar signals of 30 RLU and 29 RLU, respectively, suggesting that this antibody does not bind to mouse p75. [00755] Minimal binding signal was observed for the SULFO-TAGTM-conjugated goat polyclonal anti-human IgG and SULFO-TAGTM-conjugated goat polyclonal anti-mouse IgG detection antibodies. Example 3. Biacore binding kinetics of anti-p75NTR monoclonal antibodies binding to p75NTR reagents measured at 25°C. Table 4-1. mAb clone IDs Lot # Description REGN# l) Table 4-2. Reagents used and lot numbers Common Name REGN# L t# Attorney Docket No.250298.000780 [00756] Equilibrium dissociation constants (KD) for p75NTR binding to purified anti- p75NTR monoclonal antibodies were determined using a real-time surface plasmon resonance (SPR) based Biacore T200 biosensor. All binding studies were performed in 10 mM HEPES, 150 mM NaCl, 3 mM EDTA, 0.05% and 0.05% v/v surfactant Tween-20, pH 7.4 (HBS-EP) running buffer at 25°C. The Biacore CM5 sensor surface was first derivatized by amine coupling with a monoclonal mouse anti-human Fc antibody (REGN2567) to capture anti- p75NTR monoclonal antibodies. Different concentrations of p75NTR reagents, human p75NTR extracellular domain expressed with a C-terminal myc-myc-hexahistidine tag (“hexahistidine” disclosed as SEQ ID NO: 619) (hP75NTR-MMH; REGN6870), monkey p75NTR extracellular domain expressed with a C-terminal myc-myc-hexahistidine tag (“hexahistidine” disclosed as SEQ ID NO: 619) (mfP75NTR-MMH; REGN6942), mouse p75NTR extracellular domain expressed with a C-terminal myc-myc-hexahistidine tag (“hexahistidine” disclosed as SEQ ID NO: 619) (mp75NTR-MMH; REGN6871), mouse P75NTR extracellular domain expressed with a C-terminal mouse IgG2a Fc tag (mp75NTR-mFc; REGN6872), and human p75NTR extracellular domain expressed with a C-terminal mouse IgG2a Fc tag (hp75NTR-mFc; REGN6869) , at concentrations ranging from 1.56 nM to 100 nM in a series of 4-fold dilutions prepared in HBS-EP running buffer were injected at a flow rate of 50 µL/min for 2 minutes. The dissociation of different p75NTR reagents bound to anti-p75NTR monoclonal antibodies was monitored for 10 minutes in HBS-EP running buffer. At the end of each cycle, the anti-p75NTR monoclonal antibodies capture surface was regenerated using a 12 second injection of 20 mM H3PO4. The association rate (ka) and dissociation rate (kd) were determined by fitting the real-time binding sensorgrams to a 1:1 binding model with mass transport limitation using Scrubber 2.0c curve-fitting software. Binding dissociation equilibrium constant (KD) and dissociative half-life (t½) were calculated from the kinetic rates as: ^^^^ ^^^^(^^) KD = ^^^^ and t½ = [00757] The equilibrium and kinetic binding parameters for anti-p75NTR monoclonal antibodies binding to hp75NTR-MMH, mfp75NTR-MMH, hP75NTR-mFc, mp75NTR-MMH, and mp75NTR-mFc at 25°C are shown in Table 4-3 through Table 4-7, respectively. [00758] At 25°C, anti-p75NTR monoclonal antibodies bound to hp75NTR-MMH with KD values ranging from 151 pM to 2.84 nM, as shown in Table 4-3. Attorney Docket No.250298.000780 [00759] At 25°C, anti-p75NTR monoclonal antibodies bound to mfp75NTR-MMH with KD values ranging from 219 pM to 1.56 nM, as shown in Table 4-4. [00760] At 25°C, anti-p75NTR monoclonal antibodies bound to hp75NTR-mFc with KD values ranging from 27.2 pM to 378 pM, as shown in Table 4-5. [00761] At 25°C, anti-p75NTR monoclonal antibodies bound to mp75NTR-MMH with KD values ranging from 195 pM to 2.59 nM, as shown in Table 4-6. [00762] At 25°C, anti-p75NTR monoclonal antibodies bound to mp75NTR-mFc with KD values ranging from 6.99 pM to 94.0 pM, as shown in Table 4-7. Table 4-3. Kinetic binding parameters for the interaction of hp75NTR-MMH with anti- p75NTR monoclonal antibodies at 25°C. 100 nM mAb Ag ka kd KD t½ REGN# Capture ) T . anti- p75NTR monoclonal antibodies at 25°C. 25 nM mAb Ag ka kd KD t½ ) Attorney Docket No.250298.000780 Table 4-5. Kinetic binding parameters for the interaction of hp75NTR-mFc with anti- p75NTR monoclonal antibodies at 25°C. 100 nM mAb Ag ka kd KD t½ REGN# Capture Bound (1/Ms) (1/s) (M) (min) T nti- p75NTR monoclonal antibodies at 25°C. 100 nM mAb Ag ka kd KD t½ REGN# Ca ture ) . nti- p75NTR monoclonal antibodies at 25°C. 100 nM mAb A k k K t½ ) Attorney Docket No.250298.000780 REGN1945-L49 274 ± 0.1 8 NB NB NB NB antibodies. Table 5-1. mAb Clone IDs REGN# Lot # Description REGN14149 REGN14149L1 Bi l t hI G4P l) . g Common Name (Source) REGN# Lot# [00763] Binding competition between different anti-p75 monoclonal antibodies (mAbs) was determined using a real time, label-free bio-layer interferometry (BLI) assay on the Octet HTX biosensor platform (Pall ForteBio Corp.). The entire experiment was performed at 25°C in 10 mM HEPES buffer containing 150 mM NaCl, 3 mM EDTA, 1 mg/mL BSA, 0.02% NaN3, and 0.05% v/v Surfactant Tween-20 at pH7.4 (HBS-EP) with the plate shaking at a speed of 1000 rpm. To assess the ability of one antibody to compete with another antibody for binding to p75NTR, around 0.2 nm of recombinant human p75NTR extracellular domain expressed with a C-terminal myc-myc-hexahistidine (“hexahistidine” disclosed as SEQ ID NO: 619) (hp75NTR-MMH) (REGN6870) was first captured onto anti-Penta-His antibody coated Octet biosensor tips (Fortebio Inc, # 18-5122) by submerging the biosensor tips in wells containing 45 µg/mL solution of the hp75NTR-MMH for 120 seconds. The antigen captured biosensor tips were then saturated with a first anti-p75NTR monoclonal antibody (subsequently referred to as mAb-1) by dipping into wells containing 50 µg/mL solution of mAb-1 for 4 minutes. The biosensor tips were then subsequently dipped into wells containing 50 µg/mL solution of a second anti-p75NTR monoclonal antibody (subsequently referred to as mAb-2) for 3 minutes. The biosensor tips were washed in HBS-EBT buffer in between every Attorney Docket No.250298.000780 step of the experiment. The real-time binding response was monitored and the binding response at the end of every step was recorded. The response of mAb-2 binding to hp75NTR- MMH pre-complexed with mAb-1 was compared to the binding response hp75NTR-MMH alone (sample of isotype control), and if pre-bound mAb-1 reduced binding of mAb-2 by more than 50%, mAb-1 is considered as competitor to mAb-2. Competitors of each antibody tested are summarized in Table 5-3. Table 5-3. Cross-competition between different anti-p75NTR monoclonal antibodies for binding to hp75NTR-MMH mAb-2 blocked by Pre-bound mAb-1 mAb-1 (> 50%) Example 5. Biacore binding kinetics for the interaction of 35 anti-human p75NTR monoclonal antibodies from CHOt supernatants with p75NTR reagents at 25°C. Table 6-1. Reagent/mAb clone IDs Attorney Docket No.250298.000780 927-2-62E8 PN62937 REGN14151 primary sup 927-2-62B9 PN62939 REGN14152 primary sup Table 6-2. Reagents used and lot numbers Monomer Attorney Docket No.250298.000780 REGN6870 REGN6870-L1 p75NTR.mmh 27000 [00764] f anti-p75NTR monoclonal antibodies with human p75NTR ecto domain recombinant proteins were determined using a real-time surface plasmon resonance (SPR) based Biacore 8K biosensor. All binding studies were performed in 10 mM HEPES, 150 mM NaCl, 3 mM EDTA, and 0.05% v/v surfactant Tween-20, pH 7.4 (HBS-EP) running buffer at 25°C. The Biacore CM5 sensor surface was first derivatized by amine coupling with a monoclonal mouse anti-human Fc antibody (REGN2567) followed by a step to capture anti-p75NTR monoclonal antibodies in CHO conditioned media. Human p75NTR extracellular domain expressed with a C-terminal myc-myc-hexahistidine tag (“hexahistidine” disclosed as SEQ ID NO: 619) (hp75NTR-mmh; REGN6870) at concentrations of 100 nM in HBS-EP running buffer were injected at a flow rate of 50 µL/min for 1.5 minutes. The dissociation of p75NTR bound to anti-p75NTR monoclonal antibodies was monitored for 2 minutes in HBS-EP running buffer. At the end of each cycle, the anti-p75NTR monoclonal antibodies capture surface was regenerated using a 12-second injection of 20mM H3PO4. The association rate (ka) and dissociation rate (kd) were determined by fitting the real-time binding sensorgrams to a 1:1 binding model with mass transport limitation using Scrubber 2.0c software. The dissociation equilibrium constant (KD) and dissociative half-life (t½) were calculated from the kinetic rate constants as: ^^^^ ^^^^(^^) KD (M) = ^^^^ , and t½ (min) = [00765] The equilibrium binding constant and the kinetic binding constants are summarized in Table 6-3 for human p75NTR. At 25°C, anti-p75NTR monoclonal antibodies bound to p75NTR-mmh with KD values ranging from 373 pM to 82 nM, as shown in Table 6-3. Table 6-2. Equilibrium and kinetic binding parameters for the interaction of p75NTR- mmh with anti-p75NTR monoclonal antibodies at 25°C. mAb 100nM Ag REGN# AbID# CloneID# Capture Bound ka kd KD t½ ) Attorney Docket No.250298.000780 REGN14150 PN62934 927-2-62E6 190 45 5.68E+05 4.28E-04 7.53E-10 27 REGN14151 PN62937 927-2-62E8 996 76 1.11E+05 2.52E-04 2.26E-09 46 manually fixed at 1.00E-04 s-1 while fitting the real time binding sensorgrams to determine the ka value. Attorney Docket No.250298.000780 Example 6. Cell based assay testing regulation of TrkA signaling with NGF. Table 7-1. mAb Clone IDs REGN # Clone ID Ab PID REGN14160 927-1-61C4 PN62906 Attorney Docket No.250298.000780 REGN14183 927-8-69A2 PN63034 REGN14184 927-8-69H2 PN63037 abe - . eagens used Reagent Source Identification 0 Attorney Docket No.250298.000780 p75 NTR -mFc REGN6869, lot # Regeneron REGN6869-L1 REGN2390 Lot # rane receptor and a member of the tumor necrosis factor receptor (TNFR) superfamily that can bind neurotrophins. One of its functional roles may be to enhance signaling of neurotrophins via the tropomyosin receptor kinase (Trk) family of receptors (Conroy and Coulson, 2022, PMID: 35051416). Upon ligand binding, Trk receptors initiate signaling pathways, including the mitogen-activated protein kinase (MAPK) cascade. [00767] In order to assess the effects of anti-human p75NTR antibodies, bioassays were established in NIH/3T3 cells (mouse fibroblast cells, ATCC) that stably expressed the serum response element fused to firefly luciferase reporter (SRE-luc, which measures MAPK signaling pathway activation, SA Biosciences CLS-010L), along with full-length human TrkA (amino acids 1-790 of UniProt accession number P04629-2) (SEQ ID NO: 680). The cell line was single cell cloned and named 3T3/SRE-luc/hTrkA cl. C2.3T3/SRE-luc/hTrkA cl.C2 cells were further engineered to stably express full-length human p75NTR NCBI accession number NP_002498.1 (amino acids 1-427 of UniProt accession number P08138) (SEQ ID NO: 669) and the resulting cell line was named 3T3/SRE-luc/hTrkA cl.C2/hp75NTR. [00768] Cell based assay testing regulation of NGF-dependent TrkA signaling by the extracellular domain of p75NTR in the presence of various anti-p75NTR antibodies. [00769] 3T3/SRE-luc/hTrkA cl.C2 cells were plated at 20,000 cells per well in assay media (Opti-MEM media containing 0.1% fetal bovine serum and 1X Penicillin-Streptomycin- Glutamine) and incubated overnight at 37°C in 5% CO2. The following day, supernatants containing the antibodies of the invention (subclass hIgG1) or 100 nM of irrelevant IgG control antibody, REGN2390, were preincubated at room temperature for 30 minutes with 5 nM of the extracellular region human p75NTR (amino acids 1-250 of NCBI accession number NP_002498.1) (SEQ ID NO: 669) fused to the Fc domain of mouse IgG2a (amino acids 98- 330 of UniProt accession number P01863) (SEQ ID NO: 621), referred to hereafter as hp75NTR-mFc or REGN6869 (SEQ ID NO: 675). This was followed by an additional 30 minute incubation with 200 pM mature human nerve growth factor (NGF) β (hNGFβ) (amino acids 122-241 of UniProt accession number P01138) (SEQ ID NO: 677), referred to hereafter as NGF or REGN205, before adding to cells. To measure the extent of TrkA activation in the Attorney Docket No.250298.000780 absence of soluble p75NTR-mFc, 200 pM of NGF with 100 nM of irrelevant Fc fusion protein, REGN1666 (SEQ ID NO: 678), was added to the cells. After a 5 hour incubation at 37°C in 5% CO2, luciferase activity was evaluated by the addition of OneGlo™ luciferase assay system reagent (Promega, cat. #E6130) and Relative Luminescence Units (RLU) were measured using an Envision Plate reader (Perkin Elmer). Results were analyzed using the following equation: RLU % Inhibition = 100 X mAb − RLUsoluble p75 RLUNGF − RLUsoluble p75 [00770] In this equation, “RLUmAb” refers to RLU value from cells treated with supernatants containing antibodies of the invention, 5 nM p75NTR-mFc and 200 pM NGF. “RLUsoluble p75” refers to the RLU value from cells treated with 100nM irrelevant antibody, 5 nM p75NTR-mFc and 200pM NGF and is defined as 0% inhibition. “RLUNGF” refers to the RLU value from cells treated with 100 nM REGN1666 and 200 pM NGF and is defined as 100% inhibition. [00771] Cell based assay testing the effects of anti-p75NTR antibodies on NGF- dependent TrkA signaling when co-expressed with p75NTR. [00772] For the assay, 3T3/SRE-luc/hTrkA cl.C2 and 3T3/SRE-luc/hTrkA cl.C2/hp75NTR cells were plated at 20,000 cells per well in assay media and incubated overnight at 37^C in 5% CO2. The following day, supernatants containing the antibodies of the invention (subclass hIgG1) or control antibody, 40 nM REGN2390, were preincubated with 3T3/SRE-luc/hTrkA cl.C2 or 3T3/SRE-luc cl.C2/hp75NTR cells for 30 minutes at 37^C in 5%CO2 before the addition of 200 pM NGF (REGN205). To measure the extent of TrkA activation in the presence or absence of co-expressed p75NTR, the following conditions were included: no NGF, 200 pM and 50 nM NGF. After a 5 hour incubation at 37^C in 5% CO2, luciferase activity was evaluated by the addition of OneGlo™ luciferase assay system reagent (Promega, cat. #E6130) and RLUs were measured using an Envision Plate reader (Perkin Elmer). Results were analyzed using the following equations to calculate inhibition by anti- p75NTR antibodies: RLU % Activation [^] = 100 X η − RLUNGF min RLUNGF max − RLUNGF min Attorney Docket No.250298.000780 % Activation [200pM NGF]p75&Trk − % Activation [mAb] % Inhibition = 100 X A p75&TrkA % Activation [200pM NGF]p75&TrkA − % Activation [mAb]TrkA [00773] “RLU^” refers to RLU values for conditions containing 200 pM NGF alone, or antibody with 200 pM NGF (mAb). “RLUNGF min” and “RLUNGF max” refer to the minimum and maximum RLU values from cells alone without NGF and with 50 nM NGF, respectively. “p75&TrkA” and “TrkA” refer to cells co-expressing two receptors or TrkA alone. [00774] As shown in Table 7-3, 40 antibodies of the invention were each incubated with the soluble, extracellular domain of p75NTR, p75NTR-mFc, to examine effects on NGF dependent activation of TrkA signaling in 3T3/SRE-luc/hTrkA cl.C2 cells; blocking of p75NTR inhibition of TrkA signaling ranged from 2.76% to 112.50%. [00775] As shown in Table 7-4, 40 antibodies of the invention were tested for their effects on inhibiting the enhancement of NGF-dependent TrkA signaling when TrkA was co- expressed with p75NTR in 3T3/SRE-luc/hTrkA cl.C2/hp75NTR cells. Antibodies showed inhibition of TrkA signaling ranging from -61.42% to 189.33%. Irrelevant control antibody, REGN2390, showed -13.53% inhibition. Table 7-3. Effects of anti-p75NTR antibodies on the inhibition of NGF-dependent TrkA signaling by the extracellular domain of p75NTR in 3T3/SRE-luc/hTrkA cl.C2 cells Antibody clone ID PID % Inhibition Attorney Docket No.250298.000780 REGN14162 927-1-61D7 PN62916 91.35 REGN14150 927-2-62E6 PN62934 92.44 abe - . n b on o p 5 -dependen en ancemen o G -dependen rkA signaling in 3T3/SRE-luc/hTrkA cl.C2/hp75NTR cells co-expressing TrkA and p75NTR by various anti-p75NTR antibodies REGN# clone ID PID % Inhibition Attorney Docket No.250298.000780 REGN14152 927-2-62B9 PN62939 130.03 REGN14158 927-1-61F3 PN62903 109.19 Attorney Docket No.250298.000780 REGN19515 927-7-71F5 PN63075 -25.33 REGN19516 927-9-72A4 PN63091 36.50 Example 7. Cell-based cytotoxicity assay using a secondary antibody-drug conjugate to assess internalization of 6 anti-p75NTR antibodies in 3T3/p75NTR/SRE-luc cl.4B5 cells. Table 8-1. mAb Clone IDs REGN # Lot Clone ID Table 8-2. Reagents used Reagent Source Identification 9 Attorney Docket No.250298.000780 Control antibody #1 Regeneron REGN1945, lot REGN1945-L54 was performed to assess internalization of 6 anti-p75NTR antibodies in 3T3/p75NTR/SRE-luc cl.4B5 cells that stably express full-length human p75NTR NCBI accession number NP_002498.1 (amino acids 1-427 of UniProt accession number P08138) (SEQ ID NO: 427) and the SRE- luc reporter gene. [00777] For the assay, 3T3 parental (ATCC) and 3T3/p75NTR/SRE-luc cl.4B5 cells were plated at 1,000 cells per well in assay media (RPMI 1640 media containing 10% fetal bovine serum and 1X Penicillin-Streptomycin-Glutamine) and incubated overnight at 37^C in 5% CO2. The following day, antibodies of the invention or an hIgG4 subclass control antibody were serially diluted (1:3) from 5 nM to 0.762 pM (with an additional well without test molecule) and then added to the cells along with 20 nM of anti-human Fc-cleavable linker-duocarmycin conjugated (Moradec, cat#AH-202DD-20) secondary Fab. To measure the extent of killing driven by free soluble drug alone, duocarmycin free drug (REGN, lot#M0111-140610-2) was serially titrated (1:4) from 10 nM to 1.52 pM (with an additional well without test molecule) and then added to a separate set of cells. After a 72 hour incubation at 37^C in 5% CO2, cell viability was evaluated by the addition of CellTiterGlo™ luciferase assay system reagent (Promega, cat. #G7572) and RLUs were measured using an Envision Plate reader (Perkin Elmer). Results were analyzed using non-linear regression (4-parameter logistics) on Graphpad PRISM 9 to obtain IC50 values. The maximum percent cytotoxicity was calculated using the following equation: RLU ^^^^^^^^^^^^^^^^^^ (max) = X Secondary a − RLU % ^^^^^^ lone Min [00778] In this equation, “RLUSecondary alone” refers to the relative light unit (RLU) value of cells treated only with 20 nM anti-human Fc secondary Fab and “RLUMin” refers to the smallest RLU value from cells treated with serially diluted antibody and 20nM anti-human Fc secondary Fab. “RLUDuocarmycin min” refers to the smallest RLU value from cells treated with serially diluted duocarmycin free drug. Attorney Docket No.250298.000780 [00779] As shown in Table 8-3, anti-p75NTR antibodies of the invention showed maximum internalization and killing of 3T3/p75NTR/SRE-luc cl.4B5 cells with duocarmycin conjugated secondary Fab ranging from 41% to 60% with IC50 values ranging from 21 pM to 63 pM. Control antibody showed no internalization or killing of 3T3/p75NTR/SRE-luc cl.4B5 cells. Duocarmycin free drug showed 100% killing of both 3T3/p75NTR/SRE-luc cl.4B5 and 3T3 parental cells with IC50 values of 71 pM and 49 pM, respectively. The killing of 3T3 parental cells was between 14 and 27% for all antibodies including control antibody, with IC50 values that could not be determined due to lack of dose dependent response. Table 8-3. Quantification of 3T3/p75NTR/SRE-luc cl.4B5 cell cytotoxicity mediated by internalization of anti-p75NTR antibodies with duocarmycin conjugated secondary Fab 3T3/p75NTR cells 3T3 parental cells Antibody Clone ID Max. % IC [M] Max. C t t i it 50 C t t i it % IC50 [M] d d d d d d d E Table 9-1. mAb clone IDs: REGN# AbPID Lot # Description RE N1414 PN62928 L2 A i 7 A 47 Table 9-2. Reagents used and lot numbers Attorney Docket No.250298.000780 Reagent / Equipment Source Identifier Lot # Explant culture Attorney Docket No.250298.000780 Normal Goat Serum Invitrogen 01-6201 VA293799 Triton X-100 Sigma T9284 SLBZ2181 ants. [00781] To evaluate free antibody uptake in DRG neurons for the purpose of identifying potential receptors to cargo delivery, ex vivo DRG explants were used in conjunction with fluorescently tagged antibodies. [00782] Dorsal root ganglia (DRG) explants were plated in Ibidi µ-slide 8 well glass bottom dishes. Glass was coated with Poly-dl-Ornithine (0.5 mg/ml) and Laminin (10 μg/ml). Following CO2 euthanasia, DRGs were harvested from mice into ice cold L15+10% FBS. A thin layer of ice cold Matrigel was pipetted onto the bottom of each coated Ibidi well and 3 DRGs were placed onto the Matrigel immediately. Plates with DRGs were placed in the incubator at 37°C 5% CO2 for 15 minutes to allow polymerization. Then, just enough serum- containing media to cover the explant (Phenol red-free Neurobasal-A, 10% FBS, 2% B-27, 2 mM L-Glut, 1% P/S, 50 ng/ml NGF) was added to each well and explants were placed in incubator to allow tissue to adhere. After 2 hours, low serum media (Phenol red-free Neurobasal-A, 2% FBS, 2% B-27, 2 mM L-Glut, 1% P/S, 50 ng/ml NGF) was supplemented to fill the culture well. Media was exchanged 3 times a week. After 48-72 hours, time-lapse imaging of live explants was performed on a Zeiss LSM880 confocal with a full incubation chamber on the stage set to 37^C and 5% CO2. Once the system stabilized and multi-region positions were programmed for each explant location, 100 nM anti-p75NTR-A647 or anti-Fel D1-A647 were added directly to the explants in their native media on the stage and time- lapse acquisition was initiated. Imaging was performed with a 20X Plan-Apochromat 0.8 NA objective. Three optical slices 10 µm apart were acquired per explant with a 1 Airy diameter pinhole opening. After 18 hours of imaging, explants were fixed in 4% PFA in PBS for 20 minutes for post-fix imaging. [00783] In vivo detection of anti-p75NTR antibody distribution. [00784] To evaluate the ability of p75NTR antibodies to internalize in DRGs in vivo a comparison of various injection routes was tested. Attorney Docket No.250298.000780 [00785] For all in vivo antibody injections, animals were euthanized with CO2 in accordance with the guidelines approved by Regeneron Institutional Animal Care and Use Committee. Following euthanasia, DRGs, Trigeminal Ganglion (TG) and other tissue were collected into 4% PFA in PBS. DRG and TG were fixed for one hour at room temperature and other visceral and central nervous tissue were fixed overnight at 4°C. After fixation, tissues were washed and stored in PBS at 4°C. Prior to imaging, tissue were transferred into PBS + 1 µg/ml DAPI and for whole mount confocal imaging in PBS. DRG and TG were imaged on a Zeiss LSM880 at 10x with optical slices 10 µm apart. Brain and visceral organs were imaged on a Zeiss LSM900 at 5x and 10x. For all images, unless stated, the maximum projection of a Z stack collected with 1 Airy pinhole opening is presented. [00786] To evaluate anti-p75NTR delivery in comparison to the retrogradely travelling ligand Cholera Toxin Subunit B (CT-B), a mix of Alexa 647 fluorescent antibody and Alexa 488 fluorescent CT-B was injected in the foot pad or the gastrocnemius muscle. Tissue was collected five days later and fluorescence was evaluated in whole DRGs with confocal microscopy. [00787] For intraplantar injections, 3.5 month old male C57Bl/6J mice were injected in the right foot pad with 5 µg Cholera Toxin Subunit B conjugated to Alexa 488 (Molecular Probes) resuspended in PBS, mixed with 0.7 mg/kg Alexa 647-conjugated REGN antibodies. Five days post injection, mice were asphyxiated with CO2 and tissue was collected. [00788] For intramuscular injections, 4 month old male C57Bl/6J were placed under 2% Isoflurane anesthesia and received an injection into the right gastrocnemius muscle of 10 µg of Alexa 647-conjugated REGN antibody mixed with 5 µg Cholera Toxin Subunit B conjugated to Alexa 488. Tissue was collected after 5 days and processed as stated above. [00789] For subcutaneous injections, a pilot study was conducted with 2 mice injected with 0.7 mg/kg antibody and tissue was collected after 5 days. To compare 6 REGN anti- p75NTR antibodies injected subcutaneously, 3 month old female C57Bl/6J mice were injected into the ventral inguinal area with Alexa 647-conjugated REGN antibodies at a concentration of 0.5 mg/kg and tissue was collected after 3 days and processed as stated above. [00790] For intravenous injections, mice were restrained and 100 ul of Alexa 647- conjugated REGN antibodies were injected into the lateral caudal tail vein at a final concentration of 0.5 mg/kg. Tissue was collected after 3 days and processed as stated above. [00791] For intracerebroventricular (ICV) injections, mice were placed under 2% isoflurane anesthesia, lubricant was placed on their eyes and the injection area was sterilized Attorney Docket No.250298.000780 and injected with 2 mg/mg Lidocaine, 1 mg/kg Bupivacaine at the site of incision. Animals were placed in a stereotax instrument and a vertical 2-3 mm incision was made in the scalp over Bregma. After identifying the coordinates for Bregma, 2 µg Alexa 647-conjugated REGN antibodies were injected unilaterally into the lateral ventricle. Five minutes following the injection, the needle was removed slowly and the scalp was sutured shut. [00792] To confirm that anti-p75NTR antibodies internalized into DRG neurons, IHC was performed on sections of DRG that were harvested 5 days post 0.7 mg/kg subcutaneous injection of REGN14187. Tissue was cryoprotected by transferring to 30% sucrose overnight and then frozen in OCT on dry ice. 16 μm DRG sections were prepared on a cryostat and placed on slides. Sections were permeabilized in 0.1% Triton-X-100 for 10 minutes, then blocked with 10% Normal Goat Serum (NGS) with 0.1% Triton X-100 for 30 minutes. Sections were labeled with primary antibody against peripherin diluted 1:500 in 5% NGS overnight at 4°C. After washing in PBS for 10 minutes, sections were incubated with secondary antibody diluted 1:1000 for 3 hours at room temperature, then washed with PBS for 10 minutes and mounted with aquamount. [00793] Results. [00794] REGN14155 and REGN14187 anti-p75NTR antibodies were internalized in DRG neurons ex vivo. [00795] Anti-p75NTR-A647 was observed to bind to axons emanating from DRG explants within 5 minutes following addition of the fluorescently-conjugated antibody to the culture dish (Fig.1, REGN14152 and REGN14162 at 3 min. and Fig.2, REGN14152 and REGN14187 at 5 min). Time lapse acquisition revealed that anti-p75NTR-A647 fluorescence was detected intracellularly at the soma in neurons in explants around 1-4 hours after antibody addition (Fig.2B, close up of an ROI shown in the right box in Fig.2A, REGN14152). Bright internalization was observed in more than half the neurons by 17 hours after antibody addition. Isotype controls displayed no axonal labeling or internalization in neurons (Fig.1 Anti-EGFRVIII and Fig.2 REGN1945). [00796] Anti-p75NTR antibodies bind to DRGs in vivo following intraplantar and subcutaneous injections. [00797] Five days after intraplantar and intramuscular injections, whole mount imaging of harvested DRGs revealed Cholera Toxin B-A488 uptake in a small population of neurons in the Lumbar DRGs on the ipsilateral (Fig.3A-3C), but not the contralateral side (Figs.3D- 3F).5 days post intramuscular injection (Figs.5A-5B: ipsilateral; Figs.5C-5D: contralateral). Attorney Docket No.250298.000780 Conversely, anti-p75NTR was detected in a large percent of neurons in Lumbar DRGs on both sides (Figs. 3B, 3C, 3E, 3F) in addition to being detected in neurons in the Trigeminal Ganglion (TG) (Fig. 4B-4C, Fig. 5F). Intraplantar injection of fluorescent isotype control antibody, REGN1945, did not demonstrate labeling in DRGs or TG (Figs.3A-3D, Fig.4A, and Figs.5A, 5C, and 5E). [00798] A comparison of 6 REGN anti-p75NTR antibodies injected subcutaneously demonstrated that all of the antibodies tested exhibited similar uptake into lumbar DRGs (Fig. 6). [00799] Higher resolution imaging of L4 DRGs revealed punctate, intracellular distribution of anti-p75NTR in DRG neurons (Fig.7) [00800] REGN anti-p75NTR antibodies internalized into neurons in the DRG that were labeled by anti-peripherin (Fig.8). [00801] REGN anti-p75NTR antibodies internalized into neurons all along the anterior- posterior axis and were observed in cervical, thoracic and lumbar DRG (Figs.9B, 9D, and 9F). Fluorescent signal was also detected in the TG (Fig. 9B), myenteric plexus (parasympathetic neurons) (Figs. 9H and 9I), eye (Fig. 9K), sympathetic ganglia, for example, thoracic sympathetic ganglia (Fig. 9M) and superior cervical ganglia. Neuronal structures were labeled in the retina. REGN anti-Fel D1 did not show labeling following subcutaneous injection (Figs.9A, 9C, 9G, 9J, and 9L). [00802] Imaging in other tissues from the same animals injected subcutaneously with anti-p75NTR did not reveal significant biodistribution of REGN14155 or REGN14187 to the brain, with the exception of antibody detected in the choroid plexus (Fig.10H). No signal was detected in the liver (Fig.10J) or spinal cord (Fig.10L). Sparse signal was detected in the kidney (Fig.10I) and heart (Fig.10K). [00803] A closer look at the choroid plexus following subcutaneous injection of anti- p75NTR antibodies shows internalization in the choroid cells (Fig.11). [00804] ICV injection of REGN14187 labeled the choroid plexus, cortical regions and cells in ventral areas in the brain (Fig.12). REGN anti-Fel D1 did not show labeling aside from the site of injection at the ventricle (Fig.12B). [00805] Internalization of fluorescent REGN anti-p75NTR into neurons was observed following intravenous injection of REGN19516 in the Trigeminal ganglia (Fig.15D) and DRG (Fig. 15H, 15H). Intravenous injection of fluorescent isotype control antibody, REGN1945, did not demonstrate labeling in TG or DRGs (Figs.15B, Fig.15F). Attorney Docket No.250298.000780 [00806] Anti-p75NTR antibodies were internalized in DRG and TG neurons in vivo following a broad variety of injection routes. [00807] When injected unilaterally in foot pad or gastrocnemius muscle, anti-p75NTR antibodies were internalized in DRG neurons on both ipsilateral and contralateral sides, suggesting that uptake is driven by systemic delivery to the DRG and not solely by retrograde transport from the injection site. [00808] The REGN anti-p75NTR antibodies tested exhibited interference with downstream p75NTR signaling by weak or strong blocking of receptor activity. Antibody dependent prevention of NGF binding to p75NTR receptors and a reduction of downstream signaling may reduce the prosurvival effects of NGF in the homeostatic environment. Example 9. Fluorescent anti-p75NTR uptake in trigeminal ganglia with local subcutaneous (s.c.) injection. [00809] To evaluate anti-p75NTR delivery via retrograde transport, 2 µg of Alexa conjugated anti-p75 antibody (REGN19516) were unilaterally injected (s.c.) into the whisker pad of mice. Tissue was collected one day later, and fluorescence was evaluated in whole trigeminal ganglia (TG) with confocal microscopy. Alexa conjugated anti-p75 was detected in sensory neurons in trigeminal ganglia that were ipsilateral (Fig. 13A-13B), but not contralateral (Fig.13C-13D), to the injection site at sensory neuron terminals in the whisker pad, indicative of retrograde transport of the fluorescently conjugated antibodies along sensory neuron axons from the axon terminals to the sensory neuron cell body. Example 10. Intravenous delivery of anti-p75NTR antibody-Nav1.7 siRNA [00810] 8-month-old female Nav1.7 humanized mice were injected intravenously with two doses of 50mg/kg antibody-Nav1.7 siRNA conjugates, 1 week apart. Anti-p75 antibody (REGN14187) and an isotype control (REGN2759) IgG4 stealth mAbs were conjugated to siRNA RT3542 (human Scn9a-targeting siRNA: sequence obtained from Thermo) through cysteine interchain conjugation. Animals were euthanized by CO2 inhalation 14 days post the first I.V. injection, and trigeminal ganglia tissues were collected and placed in RNAlater™ Stabilization Solution (Thermo) for quantitative PCR processing. RNA was isolated using the Rneasy Plus Micro Kit (Qiagen) according to the manufacturer’s protocol. cDNA synthesis was performed with SuperScript™ III Reverse Transcriptase (Invitrogen) Attorney Docket No.250298.000780 and quantitative PCR was performed using the PrimeTime Gene Expression Master Mix (Integrated DNA Technologies) according to the manufacturers’ guidelines. [00811] The cysteine interchain conjugation consisted of two steps: step 1, reduction using TCEP; and step 2, conjugation with linker-payload. The reduction using TCEP was performed as follows: A 50 mM TCEP solution was prepared by diluting 0.5 M TCEP (Thermo Fisher Bond Breaker TCEP solution, catalog no.77720) with PBS, pH 7.2. The antibody was buffer exchanged to PBS, pH 7.2, 2 mM EDTA, and concentrated, if necessary, to less than 10 mg/ml. A 2.8 molar excess of the 50 mM TCEP solution was added to the antibody, ensuring that the reaction mixture also contained 2 mM EDTA. The mixture was incubated at 37 °C for 1 hour or at 30 °C for 2 hours. For the conjugation with the linker-payload, a 3 molar excess of the linker-payload was added to the antibody and incubated overnight at room temperature. Finally, the excess linker-payload was removed by buffer exchanging into the formulation buffer using a size-exclusion chromatography (SEC) column. Maleimide was used as the linker. [00812] As shown in Fig.14, anti-p75NTR antibody conjugation improves delivery of siRNAs to trigeminal ganglia tissues in the peripheral nervous system when delivered systemically, as evidenced by a 30% reduction of Scn9a RNA transcript in target tissues of interest compared to delivery of Scn9a siRNAs conjugated to isotype antibodies. ********* [00813] All references cited herein are incorporated by reference to the same extent as if each individual publication, database entry (e.g., GenBank sequences or GeneID entries), patent application, or patent, was specifically and individually indicated to be incorporated by reference. This statement of incorporation by reference is intended by Applicants to relate to each and every individual publication, database entry (e.g., GenBank sequences or GeneID entries), patent application, or patent, each of which is clearly identified in even if such citation is not immediately adjacent to a dedicated statement of incorporation by reference. The inclusion of dedicated statements of incorporation by reference, if any, within the specification does not in any way weaken this general statement of incorporation by reference. Citation of the references herein is not intended as an admission that the reference is pertinent prior art, nor does it constitute any admission as to the contents or date of these publications or documents. Attorney Docket No.250298.000780 List of Additional Sequences of the Disclosure SEQ ID NO: 618 myc tag, amino acid sequence EQKLISEEDLGG SEQ ID NO: 619 his6 tag sequence, amino acid sequence HHHHHH SEQ ID NO: 620 mmh tag , amino acid sequence EQKLISEEDLGGEQKLISEEDLHHHHHH SEQ ID NO: 621 mouse Fc tag, Fc portion of mIgG2a at C terminus of human p75 (REGN6869), amino acid sequence EPRGPTIKPCPPCKCPAPNLLGGPSVFIFPPKIKDVLMISLSPIVTCVVVDVSEDDPDVQISW FVNNVEVHTAQTQTHREDYNSTLRVVSALPIQHQDWMSGKEFKCKVNNKDLPAPIERTISK PKGSVRAPQVYVLPPPEEEMTKKQVTLTCMVTDFMPEDIYVEWTNNGKTELNYKNTEPVL DSDGSYFMYSKLRVEKKNWVERNSYSCSVVHEGLHNHHTTKSFSRTPGK SEQ ID NO: 622 signal peptide from Mus musculus Ror1 , amino acid sequence MHRPRRRGTRPPPLALLAALLLAARGADA SEQ ID NO: 623 linker, amino acid sequence (Gly4Ser)3 SEQ ID NO: 624 tag sequence, amino acid sequence LLQGSG SEQ ID NO: 625 crRNA tail , nucleotide sequence GUUUUAGAGCUAUGCU SEQ ID NO: 626 crRNA tail , nucleotide sequence GUUUUAGAGCUAUGCUGUUUUG SEQ ID NO: 627 tracrRNA sequences, nucleotide sequence Attorney Docket No.250298.000780 AGCAUAGCAAGUUAAAAUAAGGCUAGUCCGUUAUCAACUUGAAAAAGUGGCACCGAG UCGGUGCUUU SEQ ID NO: 628 tracrRNA sequences, nucleotide sequence AAACAGCAUAGCAAGUUAAAAUAAGGCUAGUCCGUUAUCAACUUGAAAAAGUGGCAC CGAGUCGGUGCUUUU SEQ ID NO: 629 tracrRNA sequences (scaffold sequence, v2, nucleotide sequence GUUGGAACCAUUCAAAACAGCAUAGCAAGUUAAAAUAAGGCUAGUCCGUUAUCAACU UGAAAAAGUGGCACCGAGUCGGUGC SEQ ID NO: 630 scaffold sequence, v1, nucleotide sequence GUUUUAGAGCUAGAAAUAGCAAGUUAAAAUAAGGCUAGUCCGUUAUCAACUUGAAAA AGUGGCACCGAGUCGGUGCU SEQ ID NO: 631 scaffold sequence, v3, nucleotide sequence GUUUUAGAGCUAGAAAUAGCAAGUUAAAAUAAGGCUAGUCCGUUAUCAACUUGAAAA AGUGGCACCGAGUCGGUGC SEQ ID NO: 632 scaffold sequence, v4, nucleotide sequence GUUUAAGAGCUAUGCUGGAAACAGCAUAGCAAGUUUAAAUAAGGCUAGUCCGUUAU CAACUUGAAAAAGUGGCACCGAGUCGGUGC SEQ ID NO: 633 scaffold sequence, v5, nucleotide sequence GUUUUAGAGCUAGAAAUAGCAAGUUAAAAUAAGGCUAGUCCGUUAUCAACUUGAAAA AGUGGCACCGAGUCGGUGCUUUUUUU SEQ ID NO: 634 scaffold sequence, v6, nucleotide sequence GUUUUAGAGCUAGAAAUAGCAAGUUAAAAUAAGGCUAGUCCGUUAUCAACUUGAAAA AGUGGCACCGAGUCGGUGCUUUU SEQ ID NO: 635 scaffold sequence, v7, nucleotide sequence Attorney Docket No.250298.000780 GUUUAAGAGCUAUGCUGGAAACAGCAUAGCAAGUUUAAAUAAGGCUAGUCCGUUAU CAACUUGAAAAAGUGGCACCGAGUCGGUGCUUUUUU SEQ ID NO: 636 scaffold sequence, v8, nucleotide sequence GUUUUAGAGCUAGAAAUAGCAAGUUAAAAUAAGGCUAGUCCGUUAUCAACUUGGCA CCGAGUCGGUGC SEQ ID NO: 637 modified gRNA , nucleotide sequence mN*mN*mN*NNNNNNNNNNNNNNNNNGUUUUAGAmGmCmUmAmGmAmAmAmUmAm GmCAAGUUAAAAUAAGGCUAGUCCGUUAUCAmAmCmUmUmGmAmAmAmAmAmGmU mGmGmCmAmCmCmGmAmGmUmCmGmGmUmGmCmU*mU*mU*mU SEQ ID NO: 642 linker, amino acid sequence GSGEGEGSEGSG SEQ ID NO: 643 linker, amino acid sequence GGSEGEGSEGGS SEQ ID NO: 644 linker, amino acid sequence GGGGS SEQ ID NO: 645 linker, amino acid sequence GGGS SEQ ID NO: 646 SV40 nuclear localization signal (NLS), amino acid sequence PKKKRKV SEQ ID NO: 647 SV40 nuclear localization signal (NLS), amino acid sequence PKKKRRV SEQ ID NO: 648 nuclear localization signal (NLS) of nucleoplasmin, amino acid sequence KRPAATKKAGQAKKKK Attorney Docket No.250298.000780 SEQ ID NO: 650 acyl donor glutamine-containing tag , amino acid sequence LLQGG SEQ ID NO: 651 acyl donor glutamine-containing tag , amino acid sequence LLQG SEQ ID NO: 652 acyl donor glutamine-containing tag , amino acid sequence LSLSQG SEQ ID NO: 653 acyl donor glutamine-containing tag , amino acid sequence gGGLLQGG SEQ ID NO: 654 acyl donor glutamine-containing tag , amino acid sequence gLLQG SEQ ID NO: 655 acyl donor glutamine-containing tag , amino acid sequence gSPLAQSHGG SEQ ID NO: 656 acyl donor glutamine-containing tag , amino acid sequence gLLQGGG SEQ ID NO: 657 acyl donor glutamine-containing tag , amino acid sequence gLLQGG SEQ ID NO: 658 acyl donor glutamine-containing tag , amino acid sequence gLLQ SEQ ID NO: 659 acyl donor glutamine-containing tag , amino acid sequence LLQLLQGA SEQ ID NO: 660 acyl donor glutamine-containing tag , amino acid sequence LLQGA Attorney Docket No.250298.000780 SEQ ID NO: 661 acyl donor glutamine-containing tag , amino acid sequence LLQYQGA SEQ ID NO: 662 acyl donor glutamine-containing tag , amino acid sequence LLQYQG SEQ ID NO: 663 acyl donor glutamine-containing tag , amino acid sequence LLQLLQG SEQ ID NO: 664 acyl donor glutamine-containing tag , amino acid sequence SLLQG SEQ ID NO: 665 acyl donor glutamine-containing tag , amino acid sequence LLQLQ SEQ ID NO: 666 acyl donor glutamine-containing tag , amino acid sequence LLQLLQ SEQ ID NO: 667 acyl donor glutamine-containing tag , amino acid sequence LLQGR SEQ ID NO: 668 linker, amino acid sequence (GGGGS)n SEQ ID NO: 669 human p75 neurotrophin receptor (NCBI accession number NP_002498.1) , amino acid sequence MGAGATGRAMDGPRLLLLLLLGVSLGGAKEACPTGLYTHSGECCKACNLGEGVAQPCGA NQTVCEPCLDSVTFSDVVSATEPCKPCTECVGLQSMSAPCVEADDAVCRCAYGYYQDET TGRCEACRVCEAGSGLVFSCQDKQNTVCEECPDGTYSDEANHVDPCLPCTVCEDTERQL RECTRWADAECEEIPGRWITRSTPPEGSDSTAPSTQEPEAPPEQDLIASTVAGVVTTVMG SSQPVVTRGTTDNLIPVYCSILAAVVVGLVAYIAFKRWNSCKQNKQGANSRPVNQTPPPEG EKLHSDSGISVDSQSLHDQQPHTQTASGQALKGDGGLYSSLPPAKREEVEKLLNGSAGDT Attorney Docket No.250298.000780 WRHLAGELGYQPEHIDSFTHEACPVRALLASWATQDSATLDALLAALRRIQRADLVESLCS ESTATSPV SEQ ID NO: 670 human p75 neurotrophin receptor (encodes NCBI accession number NP_002498.1) , nucleotide sequence ATGGGGGCAGGTGCCACCGGCCGCGCCATGGACGGGCCGCGCCTGCTGCTGTTGCT GCTTCTGGGGGTGTCCCTTGGAGGTGCCAAGGAGGCATGCCCCACAGGCCTGTACAC ACACAGCGGTGAGTGCTGCAAAGCCTGCAACCTGGGCGAGGGTGTGGCCCAGCCTT GTGGAGCCAACCAGACCGTGTGTGAGCCCTGCCTGGACAGCGTGACGTTCTCCGACG TGGTGAGCGCGACCGAGCCGTGCAAGCCGTGCACCGAGTGCGTGGGGCTCCAGAGC ATGTCGGCGCCGTGCGTGGAGGCCGACGACGCCGTGTGCCGCTGCGCCTACGGCTA CTACCAGGATGAGACGACTGGGCGCTGCGAGGCGTGCCGCGTGTGCGAGGCGGGCT CGGGCCTCGTGTTCTCCTGCCAGGACAAGCAGAACACCGTGTGCGAGGAGTGCCCCG ACGGCACGTATTCCGACGAGGCCAACCACGTGGACCCGTGCCTGCCCTGCACCGTGT GCGAGGACACCGAGCGCCAGCTCCGCGAGTGCACACGCTGGGCCGACGCCGAGTGC GAGGAGATCCCTGGCCGTTGGATTACACGGTCCACACCCCCAGAGGGCTCGGACAGC ACAGCCCCCAGCACCCAGGAGCCTGAGGCACCTCCAGAACAAGACCTCATAGCCAGC ACGGTGGCAGGTGTGGTGACCACAGTGATGGGCAGCTCCCAGCCCGTGGTGACCCG AGGCACCACCGACAACCTCATCCCTGTCTATTGCTCCATCCTGGCTGCTGTGGTTGTG GGCCTTGTGGCCTACATAGCCTTCAAGAGGTGGAACAGCTGCAAGCAGAACAAGCAA GGAGCCAACAGCCGGCCAGTGAACCAGACGCCCCCACCAGAGGGAGAAAAACTCCA CAGCGACAGTGGCATCTCCGTGGACAGCCAGAGCCTGCATGACCAGCAGCCCCACAC GCAGACAGCCTCGGGCCAGGCCCTCAAGGGTGACGGAGGCCTCTACAGCAGCCTGC CCCCAGCCAAGCGGGAGGAGGTGGAGAAGCTTCTCAACGGCTCTGCGGGGGACACC TGGCGGCACCTGGCGGGCGAGCTGGGCTACCAGCCCGAGCACATAGACTCCTTTACC CATGAGGCCTGCCCCGTTCGCGCCCTGCTTGCAAGCTGGGCCACCCAGGACAGCGC CACACTGGACGCCCTCCTGGCCGCCCTGCGCCGCATCCAGCGAGCCGACCTCGTGG AGAGTCTGTGCAGTGAGTCCACTGCCACATCCCCGGTG SEQ ID NO: 671 Macaca fascicularis p75 neurotrophin receptor (mfp75) (NCBI accession number XP_005583674.1), amino acid sequence MRAGATGRAMDGPRLLLLLLLGVSLGGAKEACPTGLYTHGGECCKACNLGEGVAQPCGA NQTVCEPCLDSVTFSDVVSATEPCKPCTECVGLQSMSAPCVEADDAVCRCAYGYYQDET Attorney Docket No.250298.000780 TGRCEACRVCEAGSGLVFSCQDKQNTVCEECPDGTYSDEANHVDPCLPCTVCEDTERQL RECTRWADAECEEIPGRWITRSTPPEGSDSTATSTQEPEAPPEQDLIASTVADVVTTVMG SSQPVVTRGTTDNLIPVYCSILAAVVVGLVAYIAFKRWNSCKQNKQGANSRPVNQTPPPEG EKLHSDSGISVDSQSLHDQQSHTQTASGQALKGDGGLYSSLPPAKREEVEKLLNGSAGDT WRHLAGELGYQPEHIDSFTHEACPVRALLASWATQDSATLDALLAALRRIQRADLVESLCS ESTATSPV SEQ ID NO: 672 Macaca fascicularis p75 neurotrophin receptor (mfp75) (encodes NCBI accession number XP_005583674.1), nucleotide sequence ATGAGGGCAGGTGCCACCGGCCGCGCCATGGACGGGCCGCGCCTGCTGCTGTTGCT GCTTCTGGGGGTGTCCCTTGGAGGTGCCAAGGAGGCATGCCCCACAGGCCTGTACAC ACACGGCGGCGAGTGCTGCAAAGCCTGCAACCTGGGCGAAGGTGTGGCCCAGCCTT GTGGAGCCAACCAGACCGTGTGTGAGCCCTGCCTGGACAGTGTGACGTTCTCCGACG TGGTGAGCGCGACGGAGCCGTGCAAGCCGTGCACTGAGTGCGTGGGGCTTCAGAGC ATGTCGGCGCCGTGCGTGGAGGCCGACGACGCCGTGTGCCGCTGTGCCTACGGCTA CTACCAGGACGAGACGACCGGGCGCTGCGAGGCGTGCCGCGTGTGCGAGGCGGGC TCGGGCCTCGTATTCTCGTGCCAGGACAAGCAGAACACCGTGTGCGAGGAGTGCCCC GACGGCACGTATTCAGATGAGGCCAACCACGTGGACCCGTGCCTGCCCTGCACCGTG TGCGAGGACACCGAGCGCCAGCTGCGCGAGTGCACACGCTGGGCCGACGCCGAGTG CGAGGAGATCCCTGGCCGTTGGATTACAAGGTCCACACCCCCCGAAGGCTCTGACAG CACAGCCACCAGCACCCAGGAGCCTGAGGCACCTCCAGAACAAGACCTCATAGCCAG CACGGTGGCAGATGTGGTGACCACAGTGATGGGCAGCTCCCAGCCCGTGGTAACCCG AGGCACCACCGACAACCTCATCCCCGTCTATTGCTCCATCCTGGCTGCTGTGGTGGTG GGCCTTGTGGCCTACATAGCCTTCAAGAGGTGGAACAGCTGCAAGCAGAACAAGCAA GGAGCCAACAGCCGGCCAGTGAACCAGACGCCCCCACCAGAGGGAGAAAAACTCCAT AGTGACAGTGGCATCTCCGTGGACAGCCAGAGCCTGCATGACCAGCAGTCCCACACG CAGACGGCCTCGGGCCAGGCCCTCAAGGGTGATGGAGGCCTCTACAGCAGCCTGCC CCCAGCCAAGCGGGAGGAGGTGGAGAAGCTTCTCAACGGGTCTGCGGGGGACACCT GGCGGCACCTGGCGGGCGAGCTGGGCTACCAGCCCGAGCACATAGACTCCTTTACC CACGAGGCCTGCCCCGTTCGTGCCCTGCTTGCAAGCTGGGCCACCCAGGACAGCGC CACACTGGACGCCCTCCTGGCCGCCCTGCGCCGCATCCAGCGAGCCGACCTCGTGG AGAGTCTGTGCAGTGAGTCCACTGCCACGTCCCCGGTG Attorney Docket No.250298.000780 SEQ ID NO: 673 mouse neurotrophin receptor (mp75) (GenBank accession number AAH38365), amino acid sequence MRRAGAACSAMDRLRLLLLLLLLLGVSFGGAKETCSTGMYTHSGECCKACNLGEGVAQP CGANQTVCEPCLDSVTFSDVVSATEPCKPCTECLGLQSMSAPCVEADDAVCRCSYGYYQ DEETGRCEACSVCGVGSGLVFSCQDKQNTVCEECPEGTYSDEANHVDPCLPCTVCEDTE RQLRECTPWADAECEEIPGRWITRSTPPEGSDVTTPSTQEPEAPPERDLIASTVADTVTTV MGSSQPVVTRGTADNLIPVYCSILAAVVVGLVAYIAFKRWNSCKQNKQGANSRPVNQTPP PEGEKLHSDSGISVDSQSLHDQQTHTQTASGQALKGDGNLYSSLPLTKREEVEKLLNGDT WRHLAGELGYQPEHIDSFTHEACPVRALLASWGAQDSATLDALLAALRRIQRADIVESLCS ESTATSPV SEQ ID NO: 674 mouse neurotrophin receptor (mp75) (encodes GenBank accession number AAH38365), nucleotide sequence ATGAGGAGGGCAGGTGCTGCCTGCAGCGCCATGGACCGGCTGCGCCTGCTGCTGCT GCTGCTGCTGCTTCTAGGGGTGTCCTTTGGAGGTGCCAAGGAGACATGTTCCACAGG CATGTACACCCACAGTGGAGAGTGCTGCAAAGCCTGCAACCTGGGCGAAGGTGTGGC CCAGCCTTGCGGAGCCAACCAGACCGTGTGTGAACCCTGCCTGGACAGTGTTACGTT CTCTGACGTGGTGAGCGCCACCGAGCCGTGCAAGCCGTGCACCGAGTGCCTGGGCC TGCAGAGTATGTCCGCTCCCTGTGTGGAGGCAGACGATGCCGTGTGCCGATGCTCCT ATGGCTACTACCAGGACGAGGAGACTGGCCGCTGCGAGGCTTGCAGCGTGTGCGGG GTGGGCTCAGGACTCGTGTTCTCCTGCCAGGACAAACAGAACACAGTGTGTGAAGAG TGCCCAGAGGGCACATACTCAGATGAAGCCAACCACGTGGACCCGTGCCTACCCTGC ACGGTGTGCGAGGACACTGAGCGCCAGTTACGCGAGTGCACGCCCTGGGCTGACGC CGAATGCGAGGAGATCCCTGGCCGATGGATCACAAGGTCTACGCCCCCGGAGGGCTC TGACGTCACAACACCCAGCACCCAGGAGCCGGAGGCACCTCCAGAGCGAGACCTCAT AGCCAGCACAGTGGCCGATACGGTGACCACTGTGATGGGCAGCTCCCAGCCTGTAGT GACCCGAGGCACCGCTGACAACCTCATTCCTGTCTATTGCTCCATCTTGGCTGCTGTG GTTGTGGGCCTTGTGGCCTATATTGCTTTCAAGAGATGGAACAGCTGCAAGCAAAATA AACAAGGAGCCAACAGCCGGCCGGTGAACCAGACACCCCCACCAGAGGGAGAGAAA CTGCACAGCGACAGCGGCATCTCTGTGGACAGCCAGAGCCTGCACGACCAGCAGACC CACACACAGACTGCCTCAGGCCAAGCCCTCAAGGGTGATGGCAACCTCTACAGTAGC CTGCCCCTGACCAAGCGTGAGGAGGTCGAGAAGCTGCTCAATGGTGACACCTGGCGA CATCTGGCAGGCGAGCTGGGCTACCAGCCGGAGCATATAGACTCCTTTACCCACGAG Attorney Docket No.250298.000780 GCCTGCCCAGTCCGAGCCCTGCTGGCCAGCTGGGGTGCCCAGGACAGCGCGACGCT CGATGCCCTTTTAGCCGCCCTGCGACGCATCCAGAGAGCTGACATTGTGGAGAGCCT GTGCAGCGAGTCCACTGCCACGTCCCCTGTG SEQ ID NO: 675 recombinant human hp75-mFc protein (REGN6869) , amino acid sequence KEACPTGLYTHSGECCKACNLGEGVAQPCGANQTVCEPCLDSVTFSDVVSATEPCKPCT ECVGLQSMSAPCVEADDAVCRCAYGYYQDETTGRCEACRVCEAGSGLVFSCQDKQNTV CEECPDGTYSDEANHVDPCLPCTVCEDTERQLRECTRWADAECEEIPGRWITRSTPPEG SDSTAPSTQEPEAPPEQDLIASTVAGVVTTVMGSSQPVVTRGTTDNEPRGPTIKPCPPCK CPAPNLLGGPSVFIFPPKIKDVLMISLSPIVTCVVVDVSEDDPDVQISWFVNNVEVHTAQTQ THREDYNSTLRVVSALPIQHQDWMSGKEFKCKVNNKDLPAPIERTISKPKGSVRAPQVYVL PPPEEEMTKKQVTLTCMVTDFMPEDIYVEWTNNGKTELNYKNTEPVLDSDGSYFMYSKLR VEKKNWVERNSYSCSVVHEGLHNHHTTKSFSRTPGK SEQ ID NO: 676 human p75NTR extracellular domain (amino acids K29-N250) (REGN6869), amino acid sequence KEACPTGLYTHSGECCKACNLGEGVAQPCGANQTVCEPCLDSVTFSDVVSATEPCKPCT ECVGLQSMSAPCVEADDAVCRCAYGYYQDETTGRCEACRVCEAGSGLVFSCQDKQNTV CEECPDGTYSDEANHVDPCLPCTVCEDTERQLRECTRWADAECEEIPGRWITRSTPPEG SDSTAPSTQEPEAPPEQDLIASTVAGVVTTVMGSSQPVVTRGTTDN SEQ ID NO: 677 hNGFβ (REGN205), amino acid sequence SSSHPIFHRGEFSVCDSVSVWVGDKTTATDIKGKEVMVLGEVNINNSVFKQYFFETKCRDP NPVDSGCRGIDSKHWNSYCTTTHTFVKALTMDGKQAAWRFIRIDTACVCVLSRKAVRRA SEQ ID NO: 678 irrelevant Fc fusion protein (REGN1666), amino acid sequence CPTSCKCSASRIWCSDPSPGIVAFPRLEPNSVDPENITEIFIANQKRLEIINEDDVEAYVGLR NLTIVDSGLKFVAHKAFLKNSNLQHINFTRNKLTSLSRKHFRHLDLSELILVGNPFTCSCDIM WIKTLQEAKSSPDTQDLYCLNESSKNIPLANLQIPNCGLPSANLAAPNLTVEEGKSITLSCSV AGDPVPNMYWDVGNLVSKHMNETSHTQGSLRITNISSDDSGKQISCVAENLVGEDQDSV NLTVHFAPTITFLESPTSDHHWCIPFTVKGNPKPALQWFYNGAILNESKYICTKIHVTNHTEY HGCLQLDNPTHMNNGDYTLIAKNEYGKDEKQISAHFMGWPGIDDGANPNYPDVIYEDYGT Attorney Docket No.250298.000780 AANDIGDTTNRSNEIPSTDVTDKTGREHDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMIS RTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDW LNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYP SDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALH NHYTQKSLSLSPGK SEQ ID NO: 679 human NTF-3 (UniProt accession number P20783-1), amino acid sequence MSILFYVIFLAYLRGIQGNNMDQRSLPEDSLNSLIIKLIQADILKNKLSKQMVDVKENYQSTLP KAEAPREPERGGPAKSAFQPVIAMDTELLRQQRRYNSPRVLLSDSTPLEPPPLYLMEDYV GSPVVANRTSRRKRYAEHKSHRGEYSVCDSESLWVTDKSSAIDIRGHQVTVLGEIKTGNS PVKQYFYETRCKEARPVKNGCRGIDDKHWNSQCKTSQTYVRALTSENNKLVGWRWIRID TSCVCALSRKIGRT SEQ ID NO: 680 human TrkA amino acid sequence (UniProt Accession number P04629-2), amino acid sequence MLRGGRRGQLGWHSWAAGPGSLLAWLILASAGAAPCPDACCPHGSSGLRCTRDGALDS LHHLPGAENLTELYIENQQHLQHLELRDLRGLGELRNLTIVKSGLRFVAPDAFHFTPRLSRL NLSFNALESLSWKTVQGLSLQELVLSGNPLHCSCALRWLQRWEEEGLGGVPEQKLQCHG QGPLAHMPNASCGVPTLKVQVPNASVDVGDDVLLRCQVEGRGLEQAGWILTELEQSATV MKSGGLPSLGLTLANVTSDLNRKNVTCWAENDVGRAEVSVQVNVSFPASVQLHTAVEMH HWCIPFSVDGQPAPSLRWLFNGSVLNETSFIFTEFLEPAANETVRHGCLRLNQPTHVNNG NYTLLAANPFGQASASIMAAFMDNPFEFNPEDPIPDTNSTSGDPVEKKDETPFGVSVAVGL AVFACLFLSTLLLVLNKCGRRNKFGINRPAVLAPEDGLAMSLHFMTLGGSSLSPTEGKGSG LQGHIIENPQYFSDACVHHIKRRDIVLKWELGEGAFGKVFLAECHNLLPEQDKMLVAVKALK EASESARQDFQREAELLTMLQHQHIVRFFGVCTEGRPLLMVFEYMRHGDLNRFLRSHGP DAKLLAGGEDVAPGPLGLGQLLAVASQVAAGMVYLAGLHFVHRDLATRNCLVGQGLVVKI GDFGMSRDIYSTDYYRVGGRTMLPIRWMPPESILYRKFTTESDVWSFGVVLWEIFTYGKQ PWYQLSNTEAIDCITQGRELERPRACPPEVYAIMRGCWQREPQQRHSIKDVHARLQALAQ APPVYLDVLG

Claims

Attorney Docket No.250298.000780 We claim: 1. An antigen-binding protein that binds to p75 neurotrophin receptor (p75NTR), wherein the antigen-binding protein exhibits less than 50% inhibition of an activity of the extracellular domain of human p75NTR, wherein the activity of the extracellular domain of p75NTR is the blocking of human nerve growth factor (NGF)-dependent activation of human tropomyosin receptor kinase A (TrkA) signaling, as measured in a cell-based assay. 2. The antigen-binding protein of claim 1, wherein the cell-based assay comprises the steps of: a) incubating a soluble extracellular domain of human p75NTR with mature human NGF in the presence of the antigen-binding protein, optionally the extracellular domain of human p75NTR is fused to an Fc domain of IgG, b) incubating the mixture of step (a) with a population of recombinant mammalian cells which stably expresses TrkA and a serum response element fused to a luciferase reporter. c) measuring luciferase activity in Relative Luminescence Units (RLU) from the mixture of step (b), and d) calculating % inhibition using the formula RLUantigen−b − RLU 100 X inding protein soluble p75 − wherein, RLUsoluble p75 same conditions with an antigen-binding protein which does not bind to p75NTR , and RLUNGF is the RLU value from cells treated with only the human mature NGF in the absence of the soluble extracellular domain of p75NTR . 3. The antigen-binding protein of claim 1 or claim 2, which comprises: (1) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 529, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 537, or a variant thereof; (2) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 549, or a variant thereof; and a LCVR Attorney Docket No.250298.000780 comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 557, or a variant thereof; (3) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 569, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 577, or a variant thereof; (4) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 589, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 597, or a variant thereof; and/or (5) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 609, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 597, or a variant thereof. 4. The antigen-binding protein of any one of claims 1-3, which comprises: (1) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 531, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 533, or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 535, or a variant thereof; and/or a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 539, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 541, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 543, or a variant thereof; (2) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 551, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 553, or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 555, or a variant thereof; and/or a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 559, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 561, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 563, or a variant thereof; Attorney Docket No.250298.000780 (3) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 571, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 573, or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 575, or a variant thereof; and/or a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 579, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 581, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 583, or a variant thereof; (4) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 591, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 593, or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 595, or a variant thereof; and/or a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 599, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 601, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 603, or a variant thereof; and/or (5) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 611, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 613 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 615, or a variant thereof; and/or a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 599, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 601, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 603, or a variant thereof. 5. The antigen-binding protein of any one of claims 1-4, which comprises: (1) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 529, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 537, or a variant thereof; (2) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 549, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 557, or a variant thereof; Attorney Docket No.250298.000780 (3) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 569, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 577, or a variant thereof; (4) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 589, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 597, or a variant thereof; and/or (5) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 609, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 597, or a variant thereof. 6. The antigen-binding protein of any one of claims 1-5, which comprises: (1) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 545, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 547, or a variant thereof; (2) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 565, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 567, or a variant thereof; (3) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 585, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 587, or a variant thereof; (4) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 605, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 607, or a variant thereof; and/or (5) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 617, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 607, or a variant thereof. 7. An antigen-binding protein that binds to p75 neurotrophin receptor (p75NTR), comprising: (i) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 2, 22, 42, 58, 78, 98, 116, 136, 155, 173, 189, 207, 227, 245, 261, 279, 297, 315, 331, 349, 369, 387, 401, 417, 427, 437, 445, 455, 465, 475, 484, 493, 503, 513, 519, 529, 549, 569, 589 or 609, or a variant thereof; and/or Attorney Docket No.250298.000780 (ii) a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 10, 30, 50, 66, 86, 106, 124, 144, 162, 179, 197, 215, 235, 251, 269, 287, 304, 323, 339, 357, 377, 391, 409, 537, 557, 577, or 597, or a variant thereof. 8. The antigen-binding protein of claim 7 which comprises: (1) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 2, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 10, or a variant thereof; (2) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 22, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 30, or a variant thereof; (3) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 42, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 50, or a variant thereof; (4) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 58, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 66, or a variant thereof; (5) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 78, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 86, or a variant thereof; (6) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 98, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 106, or a variant thereof; (7) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 116, or a variant thereof; and a LCVR Attorney Docket No.250298.000780 comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 124, or a variant thereof; (8) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 136, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 144, or a variant thereof; (9) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 155, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 162, or a variant thereof; (10) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 173, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 179, or a variant thereof; (11) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 189, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 197, or a variant thereof; (12) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 207, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 215, or a variant thereof; (13) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 227, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 235, or a variant thereof; (14) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 245, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 251, or a variant thereof; (15) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 261, or a variant thereof; and a Attorney Docket No.250298.000780 LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 269, or a variant thereof; (16) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 279, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 287, or a variant thereof; (17) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 297, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 304, or a variant thereof; (18) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 315, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 323, or a variant thereof; (19) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 331, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 339, or a variant thereof; (20) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 349, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 357, or a variant thereof; (21) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 369, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 377, or a variant thereof; (22) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 387, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 391, or a variant thereof; (23) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 401, or a variant thereof; and a Attorney Docket No.250298.000780 LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof; (24) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 417, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof; (25) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 427, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof; (26) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 437, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof; (27) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 445, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof; (28) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 455, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof; (29) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 465, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof; (30) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 475, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof; (31) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 484, or a variant thereof; and a Attorney Docket No.250298.000780 LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof; (32) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 493, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof; (33) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 503, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof; (34) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 513, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof; (35) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 519, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof; (36) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 529, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 537, or a variant thereof; (37) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 549, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 557, or a variant thereof; (38) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 569, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 577, or a variant thereof; (39) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 589, or a variant thereof; and a Attorney Docket No.250298.000780 LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 597, or a variant thereof; and/or (40) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 609, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 597, or a variant thereof. 9. The antigen-binding protein of claim 7 or claim 8 which comprises: (1) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 2, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 10, or a variant thereof; (2) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 22, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 30, or a variant thereof; (3) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 42, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 50, or a variant thereof; (4) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 58, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 66, or a variant thereof; (5) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 78, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 86, or a variant thereof; (6) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 98, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 106, or a variant thereof; Attorney Docket No.250298.000780 (7) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 116, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 124, or a variant thereof; (8) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 136, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 144, or a variant thereof; (9) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 155, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 162, or a variant thereof; (10) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 173, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 179, or a variant thereof; (11) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 207, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 215, or a variant thereof; (12) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 245, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 251, or a variant thereof; (13) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 279, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 287, or a variant thereof; (14) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 297, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 304, or a variant thereof; Attorney Docket No.250298.000780 (15) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 315, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 323, or a variant thereof; (16) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 349, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 357, or a variant thereof; (17) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 387, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 391, or a variant thereof; (18) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 417, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof; (19) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 427, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof; (20) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 437, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof; (21) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 445, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof; (22) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 455, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof; Attorney Docket No.250298.000780 (23) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 465, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof; (24) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 475, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof; (25) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 493, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof; (26) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 503, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof; (27) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 513, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof; and/or (28) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 519, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof. 10. The antigen-binding protein of claim 7 or claim 8 which comprises: (1) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 189, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 197, or a variant thereof; (2) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 227, or a variant thereof; and a LCVR Attorney Docket No.250298.000780 comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 235, or a variant thereof; (3) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 261, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 269, or a variant thereof; (4) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 331, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 339, or a variant thereof; (5) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 369, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 377, or a variant thereof; (6) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 401, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof; and/or (7) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 484, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof. 11. The antigen-binding protein of claim 7 or claim 8 which comprises: (1) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 22, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 30, or a variant thereof; (2) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 78, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 86, or a variant thereof; Attorney Docket No.250298.000780 (3) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 136, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 144, or a variant thereof; (4) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 261, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 269, or a variant thereof; (5) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 369, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 377, or a variant thereof; and/or (6) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 484, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof. 12. The antigen-binding protein of claim 7 or claim 8 which comprises: (1) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 4, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 6, or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 8, or a variant thereof; and a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 12, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 14, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 16, or a variant thereof; (2) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 24, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 26 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 28, or a variant thereof; and a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 32, or a variant thereof, a LCDR2 comprising the amino acid sequence set Attorney Docket No.250298.000780 forth in SEQ ID NO: 34, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 36, or a variant thereof; (3) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 44, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 46 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 48, or a variant thereof; and a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 12, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 14, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 52, or a variant thereof; (4) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 60, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 62 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 64, or a variant thereof; and a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 68, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 70, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 72, or a variant thereof; (5) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 80, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 82, or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 84, or a variant thereof; and a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 88, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 90, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 92, or a variant thereof; (6) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 100, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 102 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 104, or a variant thereof; and a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 108, or a variant thereof, a LCDR2 comprising the amino acid sequence set Attorney Docket No.250298.000780 forth in SEQ ID NO: 34, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 110, or a variant thereof; (7) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 118, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 120, or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 122, or a variant thereof; and a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 126, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 128, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 130, or a variant thereof; (8) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 138, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 140, or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 142, or a variant thereof; and a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 146, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 90, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 149, or a variant thereof; (9) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 100, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 158 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 160, or a variant thereof; and a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 164, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 90, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 167, or a variant thereof; (10) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 100, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 175 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 177, or a variant thereof; and a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 181, or a variant thereof, a LCDR2 comprising the amino acid sequence set Attorney Docket No.250298.000780 forth in SEQ ID NO: 70, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 183, or a variant thereof; (11) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 191, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 193 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 195, or a variant thereof; and a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 199, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 14, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 201, or a variant thereof; (12) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 209, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 211 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 213, or a variant thereof; and a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 217, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 219, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 221, or a variant thereof; (13) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 229, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 231 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 233, or a variant thereof; and a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 237, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 14, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 239, or a variant thereof; (14) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 100, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 247 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 249, or a variant thereof; and a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 253, or a variant thereof, a LCDR2 comprising the amino acid sequence set Attorney Docket No.250298.000780 forth in SEQ ID NO: 70, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 255, or a variant thereof; (15) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 263, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 265 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 267, or a variant thereof; and a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 271, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 90, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 273, or a variant thereof; (16) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 281, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 283 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 285, or a variant thereof; and a LCVR that comprises: an LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 289, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 14, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 291, or a variant thereof; (17) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 299, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 193 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 302, or a variant thereof; and a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 237, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 307, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 309, or a variant thereof; (18) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 317, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 319 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 321, or a variant thereof; and a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 12, or a variant thereof, a LCDR2 comprising the amino acid sequence set Attorney Docket No.250298.000780 forth in SEQ ID NO: 14, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 325, or a variant thereof; (19) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 333, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 335 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 337, or a variant thereof; and a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 237, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 341, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 343, or a variant thereof; (20) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 351, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 353 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 355, or a variant thereof; and a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 359, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 361, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 363, or a variant thereof; (21) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 371, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 373 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 375, or a variant thereof; and a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 379, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 90, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 381, or a variant thereof; (22) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 138, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 319 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 389, or a variant thereof; and a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 393, or a variant thereof, a LCDR2 comprising the amino acid sequence set Attorney Docket No.250298.000780 forth in SEQ ID NO: 361, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 395, or a variant thereof; (23) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 403, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 405 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 407, or a variant thereof; and a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 237, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 14, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 411, or a variant thereof; (24) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 419, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 421 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 423, or a variant thereof; and a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 237, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 14, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 411, or a variant thereof; (25) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 429, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 431 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 433, or a variant thereof; and a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 237, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 14, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 411, or a variant thereof; (26) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 191, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 335 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 441, or a variant thereof; and a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 237, or a variant thereof, a LCDR2 comprising the amino acid sequence set Attorney Docket No.250298.000780 forth in SEQ ID NO: 14, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 411, or a variant thereof; (27) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 447, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 449 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 451, or a variant thereof; and a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 237, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 14, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 411, or a variant thereof; (28) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 457, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 459 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 461, or a variant thereof; and a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 237, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 14, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 411, or a variant thereof; (29) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 467, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 469 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 471, or a variant thereof; and a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 237, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 14, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 411, or a variant thereof; (30) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 477, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 158 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 480, or a variant thereof; and a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 237, or a variant thereof, a LCDR2 comprising the amino acid sequence set Attorney Docket No.250298.000780 forth in SEQ ID NO: 14, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 411, or a variant thereof; (31) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 486, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 283 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 489, or a variant thereof; and a LCVR that comprises: LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 237, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 14, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 411, or a variant thereof; (32) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 495, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 497 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 499, or a variant thereof; and a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 237, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 14, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 411, or a variant thereof; (33) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 505, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 507 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 509, or a variant thereof; and a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 237, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 14, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 411, or a variant thereof; (34) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 138, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 319 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 515, or a variant thereof; and a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 237, or a variant thereof, a LCDR2 comprising the amino acid sequence set Attorney Docket No.250298.000780 forth in SEQ ID NO: 14, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 411, or a variant thereof; (35) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 521, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 523 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 525, or a variant thereof; and a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 237, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 14, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 411, or a variant thereof; (36) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 531, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 533 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 535, or a variant thereof; and a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 539, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 541, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 543, or a variant thereof; (37) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 551, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 553 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 555, or a variant thereof; and a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 559, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 561, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 563, or a variant thereof; (38) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 571, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 573 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 575, or a variant thereof; and a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 579, or a variant thereof, a LCDR2 comprising the amino acid sequence set Attorney Docket No.250298.000780 forth in SEQ ID NO: 581, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 583, or a variant thereof; (39) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 591, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 593 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 595, or a variant thereof; and a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 599, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 601, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 603, or a variant thereof; (40) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 611, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 613 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 615, or a variant thereof; and/or a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 599, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 601, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 603, or a variant thereof. 13. The antigen-binding protein of any one of claims 7-9 which comprises: (1) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 4, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 6 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 8, or a variant thereof; and/or a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 12, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 14, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 16, or a variant thereof; (2) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 24, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 26 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 28, or a variant thereof; and/or Attorney Docket No.250298.000780 a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 32, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 34, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 36, or a variant thereof; (3) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 44, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 46 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 48, or a variant thereof; and/or a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 12, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 14, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 52, or a variant thereof; (4) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 60, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 62 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 64, or a variant thereof; and/or a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 68, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 70, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 72, or a variant thereof; (5) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 80, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 82 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 84, or a variant thereof; and/or a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 88, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 90, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 92, or a variant thereof; (6) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 100, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 102 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 104, or a variant thereof; and/or Attorney Docket No.250298.000780 a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 108, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 34, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 110, or a variant thereof; (7) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 118, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 120 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 122, or a variant thereof; and/or a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 126, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 128, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 130, or a variant thereof; (8) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 138, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 140 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 142, or a variant thereof; and/or a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 146, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 90, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 149, or a variant thereof; (9) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 100, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 158 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 160, or a variant thereof; and/or a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 164, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 90, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 167, or a variant thereof; (10) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 100, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 175 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 177, or a variant thereof; and/or Attorney Docket No.250298.000780 a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 181, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 70, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 183, or a variant thereof; (11) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 209, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 211 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 213, or a variant thereof; and/or a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 217, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 219, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 221, or a variant thereof; (12) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 100, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 247 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 249, or a variant thereof; and/or a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 253, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 70, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 255, or a variant thereof; (13) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 281, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 283 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 285, or a variant thereof; and/or a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 289, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 14, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 291, or a variant thereof; (14) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 299, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 193 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 302, or a variant thereof; and/or Attorney Docket No.250298.000780 a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 237, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 307, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 309, or a variant thereof; (15) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 317, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 319 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 321, or a variant thereof; and/or a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 12, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 14, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 325, or a variant thereof; (16) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 351, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 353 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 355, or a variant thereof; and/or a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 359, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 361, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 363, or a variant thereof; (17) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 138, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 319 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 389, or a variant thereof; and/or a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 393, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 361, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 395, or a variant thereof; (18) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 419, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 421 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 423, or a variant thereof; and/or Attorney Docket No.250298.000780 a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 237, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 14, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 411, or a variant thereof; (19) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 429, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 431 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 433, or a variant thereof; and/or a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 237, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 14, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 411, or a variant thereof; (20) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 191, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 335 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 441, or a variant thereof; and/or a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 237, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 14, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 411, or a variant thereof; (21) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 447, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 449 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 451, or a variant thereof; and/or a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 237, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 14, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 411, or a variant thereof; (22) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 457, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 459 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 461, or a variant thereof; and/or Attorney Docket No.250298.000780 a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 237, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 14, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 411, or a variant thereof; (23) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 467, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 469 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 471, or a variant thereof; and/or a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 237, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 14, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 411, or a variant thereof; (24) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 477, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 158 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 480, or a variant thereof; and/or a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 237, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 14, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 411, or a variant thereof; (25) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 495, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 497 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 499, or a variant thereof; and/or a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 237, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 14, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 411, or a variant thereof; (26) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 505, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 507 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 509, or a variant thereof; and/or Attorney Docket No.250298.000780 a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 237, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 14, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 411, or a variant thereof; (27) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 138, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 319 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 515, or a variant thereof; and/or a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 237, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 14, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 411, or a variant thereof; and/or (28) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 521, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 523 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 525, or a variant thereof; and/or a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 237, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 14, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 411, or a variant thereof. 14. The antigen-binding protein of any one of claims 7-8 and 10 which comprises (1) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 191, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 193 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 195, or a variant thereof; and/or a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 199, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 14, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 201, or a variant thereof; (2) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 229, or a variant thereof, a HCDR2 comprising the amino acid sequence set Attorney Docket No.250298.000780 forth in SEQ ID NO: 231 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 233, or a variant thereof; and/or a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 237, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 14, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 239, or a variant thereof; (3) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 263, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 265 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 267, or a variant thereof; and/or a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 271, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 90, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 273, or a variant thereof; (4) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 333, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 335 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 337, or a variant thereof; and/or a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 237, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 341, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 343, or a variant thereof; (5) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 371, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 373 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 375, or a variant thereof; and/or a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 379, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 90, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 381, or a variant thereof; (6) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 403, or a variant thereof, a HCDR2 comprising the amino acid sequence set Attorney Docket No.250298.000780 forth in SEQ ID NO: 405 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 407, or a variant thereof; and/or a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 237, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 14, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 411, or a variant thereof; and/or (7) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 486, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 283 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 489, or a variant thereof; and/or a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 237, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 14, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 411, or a variant thereof. 15. The antigen-binding protein of any one of claims 7-8 and 11 which comprises: (1) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 24, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 26 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 28, or a variant thereof; and/or a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 32, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 34, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 36, or a variant thereof; (2) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 80, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 82 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 84, or a variant thereof; and/or a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 88, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 90, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 92, or a variant thereof; Attorney Docket No.250298.000780 (3) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 138, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 140 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 142, or a variant thereof; and/or a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 146, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 90, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 149, or a variant thereof; (4) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 263, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 265 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 267, or a variant thereof; and/or a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 271, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 90, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 273, or a variant thereof; (5) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 371, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 373 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 375, or a variant thereof; and/or a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 379, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 90, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 381, or a variant thereof; and/or (6) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 486, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 283 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 489, or a variant thereof; and/or a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 237, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 14, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 411, or a variant thereof. Attorney Docket No.250298.000780 16. The antigen-binding protein of any one of claims 7-8 and 12 which comprises: (1) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 2, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 10, or a variant thereof; (2) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 22, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 30, or a variant thereof; (3) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 42, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 50, or a variant thereof; (4) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 58, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 66, or a variant thereof; (5) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 78, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 86, or a variant thereof; (6) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 98, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 106, or a variant thereof; (7) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 116, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 124, or a variant thereof; (8) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 136, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 144, or a variant thereof; (9) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 155, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 162, or a variant thereof; (10) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 173, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 179, or a variant thereof; Attorney Docket No.250298.000780 (11) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 189, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 197, or a variant thereof; (12) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 207, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 215, or a variant thereof; (13) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 227, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 235, or a variant thereof; (14) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 245, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 251, or a variant thereof; (15) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 261, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 269, or a variant thereof; (16) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 279, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 287, or a variant thereof; (17) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 297, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 304, or a variant thereof; (18) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 315, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 323, or a variant thereof; (19) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 331, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 339, or a variant thereof; (20) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 349, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 357, or a variant thereof; (21) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 369, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 377, or a variant thereof; Attorney Docket No.250298.000780 (22) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 387, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 391, or a variant thereof; (23) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 401, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof; (24) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 417, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof; (25) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 427, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof; (26) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 437, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof; (27) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 445, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof; (28) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 455, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof; (29) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 465, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof; (30) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 475, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof; (31) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 484, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof; (32) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 493, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof; Attorney Docket No.250298.000780 (33) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 503, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof; (34) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 513, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof; (35) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 519, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof; (36) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 529, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 537, or a variant thereof; (37) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 549, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 557, or a variant thereof; (38) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 569, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 577, or a variant thereof; (39) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 589, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 597, or a variant thereof; and/or (40) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 609, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 597, or a variant thereof. 17. The antigen-binding protein of any one of claims 7-9, 12-13, and 16, which comprises: (1) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 2, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 10, or a variant thereof; (2) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 22, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 30, or a variant thereof; Attorney Docket No.250298.000780 (3) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 42, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 50, or a variant thereof; (4) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 58, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 66, or a variant thereof; (5) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 78, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 86, or a variant thereof; (6) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 98, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 106, or a variant thereof; (7) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 116, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 124, or a variant thereof; (8) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 136, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 144, or a variant thereof; (9) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 155, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 162, or a variant thereof; (10) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 173, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 179, or a variant thereof; (11) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 207, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 215, or a variant thereof; (12) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 245, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 251, or a variant thereof; (13) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 279, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 287, or a variant thereof; Attorney Docket No.250298.000780 (14) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 297, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 304, or a variant thereof; (15) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 315, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 323, or a variant thereof; (16) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 349, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 357, or a variant thereof; (17) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 387, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 391, or a variant thereof; (18) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 417, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof; (19) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 427, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof; (20) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 437, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof; (21) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 445, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof; (22) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 455, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof; (23) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 465, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof; (24) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 475, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof; Attorney Docket No.250298.000780 (25) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 493, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof; (26) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 503, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof; (27) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 513, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof; and/or 28) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 519, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof. 18. The antigen-binding protein of any one of claims 7-8, 10, 12, 14, and 16, which comprises: (1) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 189, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 197, or a variant thereof; (2) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 227, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 235, or a variant thereof; (3) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 261, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 269, or a variant thereof; (4) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 331, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 339, or a variant thereof; (5) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 369, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 377, or a variant thereof; (6) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 401, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof; and/or Attorney Docket No.250298.000780 (7) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 484, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof. 19. The antigen-binding protein of any one of claims 7-8, 11, 12, 15, and 16, which comprises: (1) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 22, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 30, or a variant thereof; (2) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 78, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 86, or a variant thereof; (3) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 136, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 144, or a variant thereof; (4) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 261, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 269, or a variant thereof; (5) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 369, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 377, or a variant thereof; and/or (6) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 484, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof. 20. The antigen-binding protein of any one of claims 7-8, 12, and 16, which comprises: (1) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 18, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 20, or a variant thereof; (2) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 38, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 40, or a variant thereof; Attorney Docket No.250298.000780 (3) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 54, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 56, or a variant thereof; (4) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 74, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 76, or a variant thereof; (5) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 94, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 96, or a variant thereof; (6) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 112, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 114, or a variant thereof; (7) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 132, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 134, or a variant thereof; (8) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 151, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 153, or a variant thereof; (9) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 169, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 171, or a variant thereof; (10) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 185, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 187, or a variant thereof; (11) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 203, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 205, or a variant thereof; (12) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 223, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 225, or a variant thereof; (13) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 241, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 243, or a variant thereof; Attorney Docket No.250298.000780 (14) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 257, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 259, or a variant thereof; (15) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 275, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 277, or a variant thereof; (16) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 293, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 295, or a variant thereof; (17) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 311, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 313, or a variant thereof; (18) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 327, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 329, or a variant thereof; (19) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 345, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 347, or a variant thereof; (20) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 365, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 367, or a variant thereof; (21) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 383, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 385, or a variant thereof; (22) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 397, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 399, or a variant thereof; (23) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 413, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 415, or a variant thereof; (24) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 425, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 415, or a variant thereof; Attorney Docket No.250298.000780 (25) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 435, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 415, or a variant thereof; (26) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 443, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 415, or a variant thereof; (27) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 453, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 415, or a variant thereof; (28) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 463, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 415, or a variant thereof; (29) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 473, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 415, or a variant thereof; (30) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 482, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 415, or a variant thereof; (31) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 491, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 415, or a variant thereof; (32) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 501, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 415, or a variant thereof; (33) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 511, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 415, or a variant thereof; (34) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 517, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 415, or a variant thereof; (35) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 527, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 415, or a variant thereof; Attorney Docket No.250298.000780 (36) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 545, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 547, or a variant thereof; (37) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 565, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 567, or a variant thereof; (38) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 585, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 587, or a variant thereof; (39) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 605, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 607, or a variant thereof; and/or (40) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 617, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 607, or a variant thereof. 21. The antigen-binding protein of any one of claims 7-9, 12-13, 16-17, and 20, which comprises: (1) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 18, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 20, or a variant thereof; (2) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 38, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 40, or a variant thereof; (3) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 54, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 56, or a variant thereof; (4) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 74, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 76, or a variant thereof; (5) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 94, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 96, or a variant thereof; Attorney Docket No.250298.000780 (6) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 112, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 114, or a variant thereof; (7) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 132, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 134, or a variant thereof; (8) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 151, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 153, or a variant thereof; (9) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 169, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 171, or a variant thereof; (10) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 185, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 187, or a variant thereof; (11) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 223, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 225, or a variant thereof; (12) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 257, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 259, or a variant thereof; (13) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 293, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 295, or a variant thereof; (14) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 311, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 313, or a variant thereof; (15) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 327, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 329, or a variant thereof; (16) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 365, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 367, or a variant thereof; Attorney Docket No.250298.000780 (17) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 397, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 399, or a variant thereof; (18) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 425, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 415, or a variant thereof; (19) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 435, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 415, or a variant thereof; (20) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 443, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 415, or a variant thereof; (21) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 453, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 415, or a variant thereof; (22) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 463, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 415, or a variant thereof; (23) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 473, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 415, or a variant thereof; (24) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 482, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 415, or a variant thereof; (25) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 501, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 415, or a variant thereof; (26) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 511, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 415, or a variant thereof; (27) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 517, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 415, or a variant thereof; and/or Attorney Docket No.250298.000780 (28) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 527, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 415, or a variant thereof. 22. The antigen-binding protein of any one of claims 7-8, 10, 12, 14, 16, 18, and 20, which comprises: (1) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 203, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 205, or a variant thereof; (2) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 241, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 243, or a variant thereof; (3) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 275, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 277, or a variant thereof; (4) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 345, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 347, or a variant thereof; (5) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 383, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 385, or a variant thereof; (6) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 413, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 415, or a variant thereof; and/or (7) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 491, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 415, or a variant thereof. 23. The antigen-binding protein of any one of claims 7-8, 11, 12, 15, 16, 19, and 20, which comprises: (1) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 38, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 40, or a variant thereof; Attorney Docket No.250298.000780 (2) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 94, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 96, or a variant thereof; (3) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 151, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 153, or a variant thereof; (4) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 275, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 277, or a variant thereof; (5) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 383, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 385, or a variant thereof; and/or (6) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 491, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 415, or a variant thereof. 24. The antigen binding protein of any one of claims 7-9, 12-13, 16-17, and 20-21, wherein the antigen-binding protein blocks the binding of a human neurotrophin receptor mouse Fc dimer (human p75-mFc) to human neurotrophin 3 (hNT-3) by at least about 50%. 25. The antigen binding protein of claims 7-8, 10, 12, 14, 16, 18, 20, and 22, wherein the antigen-binding protein blocks the binding of a human neurotrophin receptor mouse Fc dimer (human p75-mFc) to human neurotrophin 3 (hNT-3) by less than about 50%. 26. An antigen-binding protein that binds to the same epitope on p75NTR as an antibody comprising an HCVR/LCVR amino acid sequence pair as set forth in Table 1-1. 27. An antigen-binding protein that competes for binding to p75NTR with an antibody comprising an HCVR/LCVR amino acid sequence pair as set forth in Table 1-1. Attorney Docket No.250298.000780 28. The antigen-binding protein of any one of claims 1-27, wherein the antigen-binding protein comprises an antibody or antigen-binding fragment thereof. 29. The antigen-binding protein of any one of claims 1-27, wherein the antigen-binding protein is selected from a humanized antibody or antigen binding fragment thereof, human antibody or antigen binding fragment thereof, murine antibody or antigen binding fragment thereof, chimeric antibody or antigen binding fragment thereof, monovalent Fab', divalent Fab2, F(ab)'3 fragments, single-chain fragment variable (scFv), bis-scFv, (scFv)2, diabody, minibody, nanobody, triabody, tetrabody, disulfide stabilized Fv protein (dsFv), single-domain antibody (sdAb), Ig NAR, single heavy chain antibody, bispecific antibody or biding fragment thereof, bi-specific T-cell engager (BiTE), trispecific antibody, or chemically modified derivatives thereof. 30. The antigen-binding protein of claim 29, wherein the antigen-binding protein comprises a fragment antigen-binding region (Fab). 31. The antigen-binding protein of claim 29, wherein the antigen-binding protein comprises a single chain fragment variable (scFv). 32. The antigen-binding protein of claim 31, wherein the scFv comprises variable regions arranged in the following orientation from N-terminus to C-terminus: HCVR- LCVR. 33. The antigen-binding protein of claim 31, wherein the scFv comprises variable regions arranged in the following orientation from N-terminus to C-terminus: LCVR- HCVR. 34. The antigen-binding protein of any one of claims 31-33, wherein the variable regions in the scFv are connected by a linker. 35. The antigen-binding protein of claim 34, wherein the linker is a peptide linker. Attorney Docket No.250298.000780 36. The antigen-binding protein of claim 35, wherein the peptide linker is -(GGGGS)n- (SEQ ID NO: 668), wherein n is any integral selected from 1-10. 37. The antigen-binding protein of any one of claims 1-36, wherein the antigen-binding protein binds to human p75NTR. 38. The antigen-binding protein of claim 37, wherein the antigen-binding protein binds to human p75NTR with a KD of about 1X10-9 M or a stronger affinity. 39. An isolated polynucleotide encoding the antigen-binding protein of any one of claims 1-38. 40. A vector comprising the isolated polynucleotide of claims 39. 41. A host cell comprising the antigen-binding protein of any one of claims 1-38, the isolated polynucleotide of claim 39 or the vector of claim 40. 42. The host cell of claim 41 which is a Chinese hamster ovary (CHO) cell. 43. A protein-drug conjugate comprising an antigen-binding protein that binds to p75 neurotrophin receptor (p75NTR) and is conjugated to a molecular cargo. 44. The protein-drug conjugate of claim 43, wherein the antigen-binding protein comprises the antigen-binding protein of any one of claims 1-38. 45. The protein-drug conjugate of claim 43 or claim 44, wherein the antigen-binding protein and the molecular cargo are conjugated via a linker. 46. The protein-drug conjugate of any one of claims 43-45, wherein the molecular cargo comprises a polynucleotide molecule, a polypeptide molecule, a carrier, or a small molecule. Attorney Docket No.250298.000780 47. The protein-drug conjugate of claim 46, wherein the molecular cargo comprises a polynucleotide molecule. 48. The protein-drug conjugate of claim 47, wherein the polynucleotide molecule is an interfering nucleic acid molecule, a guide RNA, a ribozyme, an aptamer, a mixmer, a multimer, or an mRNA. 49. The protein-drug conjugate of claim 48, wherein the interfering nucleic acid molecule is an siRNA, an shRNA, a miRNA, an antisense oligonucleotide, or a gapmer. 50. The protein-drug conjugate of claim 49, wherein the interfering nucleic acid molecule is an siRNA. 51. The protein-drug conjugate of claim 50, wherein the siRNA comprises a sense strand of 21 nucleotides in length. 52. The protein-drug conjugate of claim 50 or claim 51, wherein the siRNA comprises an antisense strand of 23 nucleotides in length. 53. The protein-drug conjugate of any one of claims 50-52, wherein the siRNA comprises two phosphorothioate linkages at the first and second internucleoside linkages at the 5’ end of the sense strand. 54. The protein-drug conjugate of any one of claims 50-53, wherein the siRNA comprises two phosphorothioate linkages at the first and second internucleoside linkages at the 3’ and/or 5’ ends of the antisense strand. 55. The protein-drug conjugate of claim 49, wherein the interfering nucleic acid molecule is an antisense oligonucleotide. 56. The protein-drug conjugate of claim 48, wherein the polynucleotide molecule is a guide RNA. Attorney Docket No.250298.000780 57. The protein-drug conjugate of any one of claims 46-56, wherein the polynucleotide molecule targets a gene or gene product associated with pain, itch, or a neurological disease or disorder. 58. The protein-drug conjugate of claim 57, wherein the gene or gene product associated with pain, itch, or a neurological disease or disorder is voltage-gated sodium channel Nav1.7, voltage-gated sodium channel Nav1.8, voltage-gated sodium channel Nav1.9, voltage-gated sodium channel Nav1.6, tropomyosin receptor kinase A (TrkA), tropomyosin receptor kinase C (TRKC), acid-sensing ion channel subunit 1 (ASIC1), acid-sensing ion channel subunit 3 (ASIC3), transient receptor potential vanilloid 1 (TRPV1), transient receptor potential vanilloid 4 (TRPV4), transient receptor potential cation channel, subfamily A, member 1 (TRPA1), transient receptor potential cation channel subfamily M, member 8 (TRPM8), fatty acid amide hydrolase (FAAH), piezo type mechanosensitive ion channel component 1 (PIEZO1), piezo type mechanosensitive ion channel component 2 (PIEZO2), enkephalin, RET proto-oncogene (RET), interleukin 4 receptor (IL4R), interleukin 13 receptor (IL13R), interleukin 31 receptor (IL31R), interleukin 6 receptor alpha (IL6Ra), glycoprotein 130(gp130), FXYD domain containing ion transport regulator 2 (FXYD2), P2X purinoceptor 3 (P2X3), calcitonin gene-related peptide (CGRP), pituitary adenylate cyclase-activating polypeptide (PACAP), or interleukin 6 (IL6). 59. The protein-drug conjugate of any one of claims 46-58, wherein the polynucleotide molecule comprises one or more modified nucleotides. 60. The protein-drug conjugate of claim 46, wherein the molecular cargo comprises a polypeptide molecule. 61. The protein-drug conjugate of claim 60, wherein the polypeptide molecule is an enzyme, a neuroprotective molecule, or an antigen-binding protein that binds to a target other than p75NTR. Attorney Docket No.250298.000780 62. The protein-drug conjugate of claim 60 or claim 61, wherein the polypeptide molecule is associated with pain, itch, or a neurological disease or disorder. 63. The protein-drug conjugate of claim 62, wherein the polypeptide molecule is a neurotrophic factor, an antibody or antibody fragment, an antibody receptor fusion protein, or a suppressor of cytokine signaling. 64. The protein-drug conjugate of any one of claims 43-63 for use in treating or preventing pain, itch, or a neurological disease or disorder. 65. The protein-drug conjugate of any one of claims 57-58 and 62-64, wherein the pain is peripheral chronic pain, a chronic neuropathic pain, somatic pain, chronic post- operative pain, small fiber peripheral neuropathy, chemotherapy-induced neuropathy, painful diabetic-induced neuropathy, post-herpetic neuralgia, osteoarthritis, back pain, joint pain, trigeminal neuralgia, trigeminal pain, temporo- mandibular pain, migraine, dysautonomia, or myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). 66. The protein-drug conjugate of claim 65, wherein the chronic neuropathic pain is trigeminal pain or trigeminal neuralgia. 67. The protein-drug conjugate of any one of claims 57-58 and 62-64, wherein the itch is chronic itch. 68. The protein-drug conjugate of any one of claims 57-58 and 62-64, wherein the neurological disease or disorder is a neurodegenerative disease or disorder, a neurodevelopmental disease or disorder, a physical injury, a neuropsychiatric disease or disorder, or a neurological cancer. 69. The protein-drug conjugate of claim 68, wherein the neurodegenerative disease or disorder is Alzheimer’s disease (AD), Parkinson’s disease (PD), amyotrophic lateral sclerosis (ALS), or multiple sclerosis (MS). Attorney Docket No.250298.000780 70. The protein-drug conjugate of claim 68, wherein the physical injury is traumatic brain injury, spinal cord injury, stroke, or brain edema. 71. The protein-drug conjugate of claim 68, wherein the neurological cancer is a brain cancer or a peripheral nerve cancer. 72. The protein-drug conjugate of any one of claims 57-71, wherein the pain, itch, or neurological disease or disorder is associated with a sensory neuron, a dorsal root ganglion cell or a trigeminal ganglion cell, or a population thereof. 73. The protein-drug conjugate of claim 46, wherein the molecular cargo comprises a carrier. 74. The protein-drug conjugate of claim 73, wherein the carrier is a lipid-based carrier. 75. The protein-drug conjugate of claim 74, wherein the lipid-based carrier is a lipid nanoparticle (LNP), a liposome, a lipidoid, or a lipoplex. 76. The protein-drug conjugate of claim 75, wherein the lipid-based carrier is a LNP. 77. The protein-drug conjugate of claim 76, wherein the LNP further comprises a polynucleotide molecule and/or a polypeptide molecule. 78. The protein-drug conjugate of claim 76 or claim 77, wherein the LNP comprises one or more components of a gene editing system. 79. The protein-drug conjugate of claim 78, wherein the LNP comprises (a) a Cas nuclease, or a nucleic acid encoding the Cas nuclease, and/or (b) a guide RNA, or one or more DNAs encoding the guide RNA. 80. The protein-drug conjugate of claim 79, wherein the Cas nuclease is a Cas9 protein. Attorney Docket No.250298.000780 81. The protein-drug conjugate of claim 80, wherein the Cas9 protein is derived from a Streptococcus pyogenes Cas9 protein, a Staphylococcus aureus Cas9 protein, a Campylobacter jejuni Cas9 protein, a Streptococcus thermophilus Cas9 protein, or a Neisseria meningitidis Cas9 protein. 82. The protein-drug conjugate of any one of claims 79-81, wherein the nucleic acid encoding the Cas nuclease is codon-optimized for expression in a mammalian cell. 83. The protein-drug conjugate of claim 82, wherein the nucleic acid encoding the Cas nuclease is codon-optimized for expression in a human cell. 84. The protein-drug conjugate of any one of claims 79-83, wherein the nucleic acid encoding the Cas nuclease is an mRNA. 85. The protein-drug conjugate of any one of claims 48, 56-59, and 79-84, wherein the guide RNA is a single guide RNA (sgRNA). 86. The protein-drug conjugate of claim 78, wherein the LNP comprises a zinc finger nuclease (ZFN), or a transcription activator-like effector nuclease (TALEN). 87. The protein-drug conjugate of any one of claims 76-86, wherein the LNP comprises a cationic lipid, a neutral lipid, a helper lipid, a stealth lipid, or any combination thereof. 88. The protein-drug conjugate of claim 87, wherein the neutral lipid is distearoylphosphatidylcholine (DSPC). 89. The protein-drug conjugate of claim 87, wherein the helper lipid is cholesterol. 90. The protein-drug conjugate of claim 87, wherein the stealth lipid is PEG2k-DMG. 91. A pharmaceutical composition comprising the antigen-binding protein of any one of claims 1-38, the isolated polynucleotide of claim 39, the vector of claim 40, or the Attorney Docket No.250298.000780 protein-drug conjugate of any one of claims 43-90 and a pharmaceutically acceptable carrier. 92. A composition or kit comprising the antigen-binding protein of any one of claims 1- 38, the isolated polynucleotide of claim 39, the vector of claim 40, or the protein-drug conjugate of any one of claims 43-90 or pharmaceutical composition of claim 91 and a further therapeutic agent. 93. A complex comprising the antigen-binding protein of any one of claims 1-38 or the protein-drug conjugate of any one of claims 43-90 bound to a human p75 neurotrophin receptor (p75NTR) polypeptide. 94. A method for making the antigen-binding protein of any one of claims 1-38, comprising culturing a host cell comprising a polynucleotide that encodes the antigen-binding protein in a culture medium under conditions favorable to expression of the antigen-binding protein. 95. The method of claim 94 comprising the steps: (a) introducing said polynucleotide into a host cell; (b) culturing the host cell under conditions favorable to expression of the antigen- binding protein; (c) optionally, isolating the antigen-binding protein from the culture medium and/or host cell; and (d) optionally, conjugating the antigen-binding protein to a molecular cargo. 96. An antigen-binding protein which is produced by or obtainable by the method of claim 94 or claim 95. 97. A method for making a protein-drug conjugate of any one of claims 43-90 comprising (a) contacting the antigen-binding protein, with the molecular cargo under the conditions favorable for conjugation of the antigen-binding protein to the molecular cargo; and (b) optionally, isolating the protein-drug conjugate produced in step (a). Attorney Docket No.250298.000780 98. A method for making a protein-drug conjugate of any one of claims 43-90, wherein the molecular cargo comprises a polypeptide molecule, comprising (a) culturing a host cell comprising a polynucleotide encoding the protein-drug conjugate under conditions that allow expression of the protein-drug conjugate; and (b) optionally, isolating the protein-drug conjugate produced in step (a). 99. A protein-drug conjugate which is produced by or obtainable by the method of claim 97 or claim 98. 100. A vessel or injection device comprising the antigen-binding protein of any one of claims 1-38 and 96, the isolated polynucleotide of claim 39, the vector of claim 40, or the protein-drug conjugate of any one of claims 43-90 and 99. 101. A method for administering the antigen-binding protein of any one of claims 1-38 and 96, the isolated polynucleotide of claim 39, the vector of claim 40, or the protein-drug conjugate of any one of claims 43-90 and 99 to a subject comprising introducing the antigen-binding protein, the polynucleotide, the vector, or the protein-drug conjugate into the body of the subject. 102. The method of claim 101, wherein the antigen-binding protein, the polynucleotide, the vector, or the protein-drug conjugate is introduced into the body of the subject via subcutaneous, intramuscular, or intravenous administration. 103. The method of claim 101, wherein the antigen-binding protein, the polynucleotide, the vector, or the protein-drug conjugate is administered into the body of the subject via intrathecal, intracisternal, intracerebroventricular, or intraparenchymal administration. 104. The method of claim 101, wherein the antigen-binding protein, the polynucleotide, the vector, or the protein-drug conjugate is administered into the body of the subject via intravitreal administration into the eye. Attorney Docket No.250298.000780 105. A method for delivering a molecular cargo to a tissue or cell type expressing p75NTR in the body of a subject comprising administering to the subject the protein-drug conjugate of any one of claims 43-90 and 99, or the pharmaceutical composition of claim 91. 106. The method of claim 105, wherein the tissue is brain, spinal cord, peripheral nervous system, autonomic nervous system, enteric nervous system, or eye. 107. The method of claim 106, wherein the tissue is brain or spinal cord. 108. The method of claim 105, wherein the cell type is a sensory neuron. 109. The method of claim 105, wherein the cell type is a dorsal root ganglion cell or a trigeminal ganglion cell. 110. The method of any one of claims 105-109, wherein the protein-drug conjugate is introduced into the body of the subject via subcutaneous, intramuscular, or intravenous administration. 111. The method of any one of claims 105-109, wherein the protein-drug conjugate is administered into the body of the subject via subcutaneous, intrathecal, intracisternal, intracerebroventricular, or intraparenchymal administration. 112. The method of any one of claims 105-109, wherein the protein-drug conjugate is administered into the body of the subject via intravitreal administration into the eye. 113. The method of claim 107 or claim 110, wherein the protein-drug conjugate is administered into the body of the subject via subcutaneous administration. 114. The method of claim 107 or 111, wherein the protein-drug conjugate is administered into the body of the subject via intracerebroventricular administration. Attorney Docket No.250298.000780 115. A method for treating or preventing pain, itch, or a neurological disease or disorder in a subject in need thereof comprising administering to the subject an effective amount of the antigen-binding protein of any one of claims 1-38 and 96, the isolated polynucleotide of claim 39, the vector of claim 40, or the protein-drug conjugate of any one of claims 43-90 and 99, or the pharmaceutical composition of claim 91. 116. The method of claim 115, wherein the antigen-binding protein, the polynucleotide, the vector, or the protein-drug conjugate is administered via subcutaneous, intramuscular, or intravenous administration. 117. The method of claim 115, wherein the antigen-binding protein, the polynucleotide, the vector, or the protein-drug conjugate is administered into the body of the subject via intrathecal, intracisternal, intracerebroventricular, or intraparenchymal administration. 118. The method of claim 115, wherein the antigen-binding protein, the polynucleotide, the vector, or the protein-drug conjugate is administered into the body of the subject via intravitreal administration into the eye. 119. The method of any one of claims 115-118, wherein the pain is peripheral chronic pain, a chronic neuropathic pain, somatic pain, chronic post-operative pain, small fiber peripheral neuropathy, chemotherapy-induced neuropathy, painful diabetic- induced neuropathy, post-herpetic neuralgia, osteoarthritis, back pain, joint pain, trigeminal neuralgia, trigeminal pain, temporo-mandibular pain, migraine, dysautonomia, or myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). 120. The method of claim 119, wherein the chronic neuropathic pain is trigeminal pain or trigeminal neuralgia. 121. The method of any one of claims 115-118, wherein the itch is chronic itch. 122. The method of any one of claims 115-118, wherein the neurological disease or disorder is a neurodegenerative disease, a neurodevelopmental disease, a chronic Attorney Docket No.250298.000780 neuropathic pain, a physical injury, a neuropsychiatric disease, or a neurological cancer. 123. The method of claim 122, wherein the neurodegenerative disease or disorder is Alzheimer’s disease (AD), Parkinson’s disease (PD), amyotrophic lateral sclerosis (ALS), or multiple sclerosis (MS). 124. The method of claim 122, wherein the physical injury is traumatic brain injury, spinal cord injury, stroke, or brain edema. 125. The method of claim 122, wherein the neurological cancer is a brain cancer or a peripheral nerve cancer. 126. The method of any one of claims 115-125, wherein the pain, itch, or a neurological disease or disorder is associated with a sensory neuron, a dorsal root ganglion cell, a trigeminal ganglion cell, or a population thereof. 127. The method of any one of claims 101-126, further comprising administering an additional treatment to the subject. 128. The method of claim 127, wherein the additional treatment comprises administering comprises administering a nonsteroidal anti-inflammatory drug (NSAID), acetaminophen, a local anesthetic, capsaicin, a Cox-2 inhibitor, an antidepressant, an anti-seizure medication, an anti-epileptic medication, an opioid, a steroid, an anticonvulsant, a muscle relaxant, a triptan, dihydroergotamine, Lasmiditan, a calcitonin gene-related peptides antagonist, an anti-nausea drug, a beta blocker, a calcium channel blocker, a serotonin and norepinephrine reuptake inhibitor (SNRI), onabotulinumtoxinA, or a benzodiazepine, or a combination thereof.
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