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WO2025264972A1 - Antibodies that bind il-4r alpha and antibodies that bind - Google Patents

Antibodies that bind il-4r alpha and antibodies that bind

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Publication number
WO2025264972A1
WO2025264972A1 PCT/US2025/034460 US2025034460W WO2025264972A1 WO 2025264972 A1 WO2025264972 A1 WO 2025264972A1 US 2025034460 W US2025034460 W US 2025034460W WO 2025264972 A1 WO2025264972 A1 WO 2025264972A1
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Prior art keywords
seq
set forth
sequence set
cdr
amino acid
Prior art date
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Pending
Application number
PCT/US2025/034460
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French (fr)
Inventor
Hussam Hisham SHAHEEN
Kenneth Evan THOMPSON
Peter Evan HARWIN
Tomas KISELAK
Byong Ha KANG
Eric Franklin ZHU
Jason Zee Seug OH
Shawn Michael RUSSELL
Michael Henderson
Carl Linden DAMBKOWSKI
Rebecca Lucille DABORA
Aaron Noyes
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Apogee Therapeutics Inc
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Apogee Therapeutics Inc
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Publication of WO2025264972A1 publication Critical patent/WO2025264972A1/en
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Anticipated expiration legal-status Critical

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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
    • C07K16/24—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against cytokines, lymphokines or interferons
    • C07K16/244—Interleukins [IL]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/43—Enzymes; Proenzymes; Derivatives thereof
    • A61K38/46—Hydrolases (3)
    • A61K38/47—Hydrolases (3) acting on glycosyl compounds (3.2), e.g. cellulases, lactases
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • 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
    • C07K16/2866—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against receptors for cytokines, lymphokines, interferons
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Y—ENZYMES
    • C12Y302/00—Hydrolases acting on glycosyl compounds, i.e. glycosylases (3.2)
    • C12Y302/01—Glycosidases, i.e. enzymes hydrolysing O- and S-glycosyl compounds (3.2.1)
    • C12Y302/01035—Hyaluronoglucosaminidase (3.2.1.35), i.e. hyaluronidase
    • 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
    • A61K2039/505—Medicinal preparations containing antigens or antibodies comprising antibodies
    • 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
    • A61K2039/505—Medicinal preparations containing antigens or antibodies comprising antibodies
    • A61K2039/507—Comprising a combination of two or more separate antibodies
    • 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
    • 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
    • A61K39/39591—Stabilisation, fragmentation
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/20—Immunoglobulins specific features characterized by taxonomic origin
    • C07K2317/21—Immunoglobulins specific features characterized by taxonomic origin from primates, e.g. man
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/20—Immunoglobulins specific features characterized by taxonomic origin
    • C07K2317/24—Immunoglobulins specific features characterized by taxonomic origin containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
    • 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
    • C07K2317/31—Immunoglobulins specific features characterized by aspects of specificity or valency multispecific
    • 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
    • C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
    • C07K2317/52—Constant or Fc region; Isotype
    • 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
    • C07K2317/71—Decreased effector function due to an Fc-modification
    • 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
    • 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
    • C07K2317/94—Stability, e.g. half-life, pH, temperature or enzyme-resistance

Definitions

  • OX40L is the ligand for 0X40.
  • OX40L is expressed on antigen presenting cells and its interaction with 0X40 causes the accumulation of T cells by providing a survival signal.
  • OX40L by playing a role in activating T cells and reprogramming them into inflammatory subsets, contributes to immune overactivation in AD and other inflammatory conditions.
  • OX40L activation of 0X40 inhibits the expression of FOXP3 and the inhibitory function of regulatory T (Treg) cells. Treg cells suppress immune response, which leads to worse symptoms in inflammatory conditions.
  • OX40L blockade may lead to clinical benefit in AD and other inflammatory conditions by first suppressing inflammatory T cell activation, and next by increasing the proliferation of Treg cells, which can serve to further reduce inflammatory cells.
  • Amlitelimab, which targets OX40L, and rocatinlimab, which targets 0X40, have both demonstrated promising Phase 2 data in AD.
  • 0X40 L is the ligand for 0X40 expressed on antigen presenting cells. Its interaction with 0X40 causes the accumulation of T cells by providing a survival signal. T cells are important types of white blood cells of the immune system that play a central role in the immune response.
  • OX40L by playing a role in activating T cells and reprogramming them into inflammatory subsets, contributes to immune overactivation in AD and other inflammatory conditions, such as Systemic Lupus Erythematosus. Additionally, OX40L activation of OX40 inhibits the expression of Foxp3 and the inhibitory function of regulatory T (Treg) cells. Treg cells can suppress the immune response that leads to worsening symptoms in inflammatory conditions.
  • IL-4 interleukin 4
  • IL-13 interleukin 13
  • the Interleukin-4 Receptor Alpha (IL-4R ⁇ ) chain that pairs with distinct subunits (Nelms, K., et al. (1999) Annu. Rev.
  • IL-4R ⁇ pairs with the common ⁇ c chain to form a type I IL-4R complex that is found predominantly in hematopoietic cells and is exclusive for IL-4.
  • IL-4R ⁇ also pairs with the Interleukin-13 Receptor alpha 1 (IL-13R ⁇ 1) subunit to form a type II IL-4R that binds both IL-4 and IL-13.
  • the type II receptor is expressed on both hematopoietic and nonhematopoietic cells.
  • IL-4 (also known as B cell stimulating factor or BSF-1) was originally characterized by its ability to stimulate the proliferation of B cells in response to low concentrations of antibodies directed to surface immunoglobulin.
  • IL-4 has been shown to possess a broad spectrum of biological activities, including growth stimulation of T cells, mast cells, granulocytes, megakaryocytes and erythrocytes.
  • IL-4 induces the expression of class II major histocompatibility complex molecules in resting B cells and enhances the secretion of IgE and IgG1 isotypes by stimulated B cells.
  • the biological and immunological functions of B-lymphocytes, monocytes, dendritic cells, and fibroblasts are all affected by IL-4 and IL-13.
  • cytokines interact with IL-4R to initiate the type 2 inflammatory pathway, which results in Th2 cell differentiation, inflammation, and mucus production.
  • the type-2 inflammatory pathway is first activated in allergic illnesses by aberrant cytokine release resulting from an imbalance of Th1 and Th2 differentiation.
  • Th2 cells that have been activated release cytokines, including IL-4, IL-13, and IL-31, which prompt downstream B cells to undergo a change and produce IgE antibodies.
  • Mast cells and basophils are then called upon to degranulate and release inflammatory substances.
  • the secreted IL-4 and IL-13 continue to bind to their respective receptors, such as IL-4R ⁇ , that repeatedly promotes TH2 differentiation and subsequent inflammation.
  • IL-4R ⁇ The important role of IL-4 and IL-13 in the type-2 inflammation pathway identifies IL-4R ⁇ as a potential target for individuals who exhibit aberrant type-2 inflammatory responses. Unlike medications that target IL-4 and IL-13 exclusively, targeting IL-4R ⁇ would target both IL-4 and IL-13. [0008] In addition, because targeting each of OX40L and IL-4R ⁇ may lead to various clinical benefits in inflammatory conditions, there is a need in the art for improved therapeutics that target both OX40L and IL-4R ⁇ , such as recombinant antibodies and combinations thereof. There is also a need for delivering relatively large doses of these antibodies subcutaneously.
  • an isolated antibody, or an antigen binding fragment thereof, that binds OX40L comprising: a) a variable heavy (VH) chain sequence having three heavy chain CDR sequences, CDR-H1, CDR-H2, and CDR-H3; and b) a variable light (VL) chain sequence having three light chain CDR sequences, CDR-L1, CDR- L2, and CDR-L3; wherein the antibody, or antigen binding fragment thereof, that binds OX40L comprises: (i) a CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 2-4; a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 5-7; a CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 8-10; a CDR-L1 comprising the amino acid sequence set forth in any one of SEQ ID NOs:
  • the isolated antibody, or antigen binding fragment thereof, that binds IL-4R ⁇ comprises a CDR-H1, CDR-H2, CDR-H3, CDR-L1, CDR-L2, and CDR- L3 of an antibody selected from dupilumab, stapokibart, and 611.
  • the isolated antibody, or an antigen binding fragment thereof, that binds IL-4R ⁇ comprises: a) a VH chain sequence having three heavy chain CDR sequences, CDR-H1, CDR-H2, and CDR-H3; and b) a VL chain sequence having three light chain CDR sequences, CDR-L1, CDR-L2, and CDR-L3, wherein the isolated antibody, or antigen binding fragment thereof, that binds IL-4R ⁇ comprises: (i) a CDR-H1 comprising the sequence set forth in any one of SEQ ID NOs: 273, 274, and 275; a CDR-H2 comprising the sequence set forth in any one of SEQ ID NOs: 276, 277, and 278; a CDR-H3 comprising the sequence set forth in any one of SEQ ID NOs: 281 and 282; a CDR-L1 comprising the sequence set forth in any one of SEQ ID NOs: 285 and 286; a CDR-
  • an isolated antibody, or an antigen binding fragment thereof, that binds OX40L; and an isolated antibody, or an antigen binding fragment thereof, that binds IL-4R ⁇ comprising: a) a variable heavy (VH) chain sequence having three heavy chain CDR sequences, CDR-H1, CDR-H2, and CDR-H3; and b) a variable light (VL) chain sequence having three light chain CDR sequences, CDR-L1, CDR-L2, and CDR-L3; wherein the antibody, or antigen binding fragment thereof, that binds IL-4R ⁇ comprises: (i) a CDR-H1 comprising the sequence set forth in any one of SEQ ID NOs: 273, 274, and 275; a CDR-H2 comprising the sequence set forth in any one of SEQ ID NOs: 276, 277, and 278; a CDR-H3 comprising the sequence set forth in any one of SEQ ID NOs: 281 and 282
  • the isolated antibody, or antigen binding fragment thereof, that binds OX40L comprises a CDR-H1, CDR-H2, CDR-H3, CDR-L1, CDR-L2, and CDR- L3 of an antibody selected from amlitelimab and oxelumab.
  • the isolated antibody, or antigen binding fragment thereof, that binds OX40L comprises: a) a VH chain sequence having three heavy chain CDR sequences, CDR-H1, CDR-H2, and CDR-H3; and b) a VL chain sequence having three light chain CDR sequences, CDR-L1, CDR-L2, and CDR-L3, wherein the isolated antibody, or antigen binding fragment thereof, that binds OX40L comprises: (i) a CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 2-4; a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 5-7; a CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 8-10; a CDR-L1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 12-14; a CDR-L2 comprising the amino acid sequence set forth in any
  • the antibody, or antigen binding fragment thereof, that binds OX40L comprises: (i) a CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 2-4; a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 5-7; a CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 8-10; a CDR-L1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 12-14; a CDR-L2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 15-16; and a CDR-L3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 17-18; and (b) the antibody, or antigen binding fragment thereof, that binds IL-4R ⁇ comprises: (i) a CDR-H1 comprising the sequence set forth in any one of SEQ ID NOs:
  • the antibody, or antigen binding fragment thereof, that binds OX40L comprises: (ii) a CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 20-22; a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 23-25; a CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 26-28; a CDR-L1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 30-32; a CDR-L2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 33-34; and a CDR-L3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 35-36; and (b) the antibody, or antigen binding fragment thereof, that binds IL-4R ⁇ comprises: (i) a CDR-H1 comprising the sequence set forth in any one of SEQ ID NOs: 20-22; a CDR
  • the antibody, or antigen binding fragment thereof, that binds OX40L comprises: (iii) a CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 38-40; a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 41-43; a CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 44-46; a CDR-L1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 48-50; a CDR-L2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 51-52; and a CDR-L3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 53-54; and (b) the antibody, or antigen binding fragment thereof, that binds IL-4R ⁇ comprises: (i) a CDR-H1 comprising the sequence set forth in any one of
  • the antibody, or antigen binding fragment thereof, that binds OX40L comprises: (iv) a CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 56-58; a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 59-61; a CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 62-64; a CDR-L1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 66-68; a CDR-L2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 69-70; and a CDR-L3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 71-72; and (b) the antibody, or antigen binding fragment thereof, that binds IL-4R ⁇ comprises: (i) a CDR-H1 comprising the sequence
  • the antibody, or antigen binding fragment thereof, that binds OX40L comprises: (i) a CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 2-4; a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 5-7; a CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 8-10; a CDR-L1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 12-14; a CDR-L2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 15-16; and a CDR-L3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 17-18; and (b) the antibody, or antigen binding fragment thereof, that binds IL-4R ⁇ comprises: (ii) a CDR-H1 comprising the sequence set forth in any one of SEQ ID NOs
  • the antibody, or antigen binding fragment thereof, that binds OX40L comprises: (ii) a CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 20-22; a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 23-25; a CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 26-28; a CDR-L1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 30-32; a CDR-L2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 33-34; and a CDR-L3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 35-36; and (b) the antibody, or antigen binding fragment thereof, that binds IL-4R ⁇ comprises: (ii) a CDR-H1 comprising the sequence set forth in any one of SEQ ID NOs: 20-22; a C
  • the antibody, or antigen binding fragment thereof, that binds OX40L comprises: (iii) a CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 38-40; a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 41-43; a CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 44-46; a CDR-L1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 48-50; a CDR-L2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 51-52; and a CDR-L3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 53-54; and (b) the antibody, or antigen binding fragment thereof, that binds IL-4R ⁇ comprises: (ii) a CDR-H1 comprising the sequence set forth in any one of SEQ ID NOs: 38-40;
  • the antibody, or antigen binding fragment thereof, that binds OX40L comprises: (iv) a CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 56-58; a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 59-61; a CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 62-64; a CDR-L1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 66-68; a CDR-L2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 69-70; and a CDR-L3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 71-72; and (b) the antibody, or antigen binding fragment thereof, that binds IL-4R ⁇ comprises: (ii) a CDR-H1 comprising the
  • the antibody, or antigen binding fragment thereof, that binds OX40L comprises: (i) a CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 2-4; a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 5-7; a CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 8-10; a CDR-L1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 12-14; a CDR-L2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 15-16; and a CDR-L3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 17-18; and (b) the antibody, or antigen binding fragment thereof, that binds IL-4R ⁇ comprises: (iii) a CDR-H1 comprising the sequence set forth in any one of SEQ ID NOs: 2-4; a CDR-H
  • the antibody, or antigen binding fragment thereof, that binds OX40L comprises: (ii) a CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 20-22; a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 23-25; a CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 26-28; a CDR-L1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 30-32; a CDR-L2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 33-34; and a CDR-L3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 35-36; and (b) the antibody, or antigen binding fragment thereof, that binds IL-4R ⁇ comprises: ((iii) a CDR-H1 comprising the sequence set forth in any one of SEQ ID NOs: 20-22;
  • the antibody, or antigen binding fragment thereof, that binds OX40L comprises: (iii) a CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 38-40; a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 41-43; a CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 44-46; a CDR-L1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 48-50; a CDR-L2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 51-52; and a CDR-L3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 53-54; and (b) the antibody, or antigen binding fragment thereof, that binds IL-4R ⁇ comprises: (iii) a CDR-H1 comprising the sequence set forth in any one of SEQ ID NOs: 38-40;
  • the antibody, or antigen binding fragment thereof, that binds OX40L comprises: (iv) a CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 56-58; a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 59-61; a CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 62-64; a CDR-L1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 66-68; a CDR-L2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 69-70; and a CDR-L3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 71-72; and (b) the antibody, or antigen binding fragment thereof, that binds IL-4R ⁇ comprises: (iii) a CDR-H1 comprising
  • the antibody, or antigen binding fragment thereof, that binds OX40L comprises a heavy chain variable domain (VH) sequence comprising the amino acid sequence set forth in any one of SEQ ID NOs: 1, 19, 37, and 55.
  • the antibody, or antigen binding fragment thereof, that binds IL-4R ⁇ comprises a VH sequence comprising the amino acid sequence set forth in any one of SEQ ID NOs: 295-297.
  • the antibody, or antigen binding fragment thereof, that binds OX40L comprises a light chain variable domain (VL) sequence comprising the amino acid sequence set forth in any one of SEQ ID NOs: 11, 29, 47, and 65.
  • the antibody, or antigen binding fragment thereof, that binds IL-4R ⁇ comprises a VL sequence comprising the amino acid sequence set forth in any one of SEQ ID NOs: 298-300.
  • (a) the antibody, or antigen binding fragment thereof, that binds OX40L comprises: (i) a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 1; (ii) a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 19; (iii) a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 37; or (iv) a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 55; and/or (v) a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 11; (vi) a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 29; (vii) a VL sequence comprising the amino acid sequence
  • the antibody, or antigen binding fragment thereof, that binds OX40L comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 1; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 11.
  • the antibody, or antigen binding fragment thereof, that binds OX40L comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 19; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 29.
  • the antibody, or antigen binding fragment thereof, that binds OX40L comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 37; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 47.
  • the antibody, or antigen binding fragment thereof, that binds OX40L comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 55; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 65.
  • the antibody, or antigen binding fragment thereof, that binds IL-4R ⁇ comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 295; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 298.
  • the antibody, or antigen binding fragment thereof, that binds IL-4R ⁇ comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 296; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 299.
  • the antibody, or antigen binding fragment thereof, that binds IL-4R ⁇ comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 297; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 300.
  • the antibody, or antigen binding fragment thereof, that binds OX40L comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 1; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 11; and the antibody, or antigen binding fragment thereof, that binds IL-4R ⁇ comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 295; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 298.
  • the antibody, or antigen binding fragment thereof, that binds OX40L comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 1; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 11; and the antibody, or antigen binding fragment thereof, that binds IL-4R ⁇ comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 296; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 299.
  • the antibody, or antigen binding fragment thereof, that binds OX40L comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 1; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 11; and the antibody, or antigen binding fragment thereof, that binds IL-4R ⁇ comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 297; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 300.
  • the antibody, or antigen binding fragment thereof, that binds OX40L comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 19; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 29; and the antibody, or antigen binding fragment thereof, that binds IL-4R ⁇ comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 295; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 298.
  • the antibody, or antigen binding fragment thereof, that binds OX40L comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 19; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 29; and the antibody, or antigen binding fragment thereof, that binds IL-4R ⁇ comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 296; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 299.
  • the antibody, or antigen binding fragment thereof, that binds OX40L comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 19; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 29; and the antibody, or antigen binding fragment thereof, that binds IL-4R ⁇ comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 297; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 300.
  • the antibody, or antigen binding fragment thereof, that binds OX40L comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 37; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 47; and the antibody, or antigen binding fragment thereof, that binds IL-4R ⁇ comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 295; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 298.
  • the antibody, or antigen binding fragment thereof, that binds OX40L comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 37; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 47; and the antibody, or antigen binding fragment thereof, that binds IL-4R ⁇ comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 296; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 299.
  • the antibody, or antigen binding fragment thereof, that binds OX40L comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 37; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 47; and the antibody, or antigen binding fragment thereof, that binds IL-4R ⁇ comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 297; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 300.
  • the antibody, or antigen binding fragment thereof, that binds OX40L comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 55; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 65; and the antibody, or antigen binding fragment thereof, that binds IL-4R ⁇ comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 295; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 298.
  • the antibody, or antigen binding fragment thereof, that binds OX40L comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 55; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 65; and the antibody, or antigen binding fragment thereof, that binds IL-4R ⁇ comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 296; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 299.
  • the antibody, or antigen binding fragment thereof, that binds OX40L comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 55; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 65; and the antibody, or antigen binding fragment thereof, that binds IL-4R ⁇ comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 297; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 300.
  • the antibody, or antigen binding fragment thereof, that binds OX40L and/or the antibody, or antigen binding fragment thereof, that binds IL-4R ⁇ is a humanized, human, or chimeric antibody.
  • the antibody, or antigen binding fragment thereof, that binds OX40L and/or the antibody, or antigen binding fragment thereof, that binds IL-4R ⁇ is a humanized antibody.
  • the antibody, or antigen binding fragment thereof, that binds OX40L and/or the antibody, or antigen binding fragment thereof, that binds IL-4R ⁇ comprises a heavy chain human constant region of a class selected from IgG, IgA, IgD, IgE, and IgM.
  • the antibody, or antigen binding fragment thereof, that binds OX40L and/or the antibody, or antigen binding fragment thereof, that binds IL-4R ⁇ comprises a human Fc region, and the human Fc region comprises a human heavy chain constant region of the class IgG and a subclass selected from IgG1, IgG2, IgG3, and IgG4.
  • the human Fc region of the antibody, or antigen binding fragment thereof, that binds OX40L and/or the antibody, or antigen binding fragment thereof, that binds IL-4R ⁇ comprises a human IgG1 Fc region.
  • the human Fc region of the antibody, or antigen binding fragment thereof, that binds OX40L and/or the antibody, or antigen binding fragment thereof, that binds IL-4R ⁇ comprises a human IgG4 Fc region.
  • the human Fc region of the antibody, or antigen binding fragment thereof, that binds OX40L and/or the antibody, or antigen binding fragment thereof, that binds IL-4R ⁇ comprises a human IgG2 Fc region.
  • the antibody, or antigen binding fragment thereof, that binds OX40L and/or the antibody, or antigen binding fragment thereof, that binds IL-4R ⁇ comprises a heavy chain comprising constant heavy chain sequence selected from the amino acid sequences set forth in any one of SEQ ID NOs: 637-737 and 847-1070.
  • the antibody, or antigen binding fragment thereof, that binds OX40L and/or the antibody, or antigen binding fragment thereof, that binds IL-4R ⁇ comprises a light chain comprising constant light chain sequence selected from the sequences set forth in SEQ ID NOs: 738 and 1071.
  • the antibody, or antigen binding fragment thereof, that binds OX40L and/or the antibody, or antigen binding fragment thereof, that binds IL-4R ⁇ comprises a heavy chain constant domain having a means for increasing the half-life of the antibody.
  • the antibody, or antigen binding fragment thereof, that binds OX40L and/or the antibody, or antigen binding fragment thereof, that binds IL-4R ⁇ comprises an Fc region comprising one or more amino acid substitutions, wherein the one or more substitutions result in an increase in one or more of antibody half-life, ADCC activity, ADCP activity, or CDC activity compared to an antibody comprising an Fc region without the one or more amino acid substitutions (e.g., a wild-type Fc region).
  • the antibody, or antigen binding fragment thereof, that binds OX40L and/or the antibody, or antigen binding fragment thereof, that binds IL-4R ⁇ comprises an Fc region comprising one or more amino acid substitutions, wherein the one or more substitutions result in a decrease in one or more of, ADCC activity, ADCP activity or CDC activity compared to an antibody comprising an Fc region without the one or more amino acid substitutions, (e.g., a wild-type Fc region).
  • the one or more amino acid substitutions is selected from the group consisting of S228P, M252Y, S254T, T256E, T256D, T250Q, H285D, T307A, T307Q, T307R, T307W, L309D, Q411H, Q311V, A378V, E380A, M428L, N434A, N434S, N297A, D265A, L234A, L235A, and N434W; optionally, wherein the one or more amino acid substitutions comprises a plurality of amino acid substitutions selected from the group consisting of M428L/N434S (LS), M252Y/S254T/T256E (YTE), T250Q/M428L, T307A/E380A/N434A, T256D/T307Q (DQ), T256D/T307W (DW), M252Y/T256D (LS), M252Y/S
  • the one or more amino acid substitutions is selected from the group consisting of LS, YTE, T250Q/M428L, T307A/E380A/N434A, DQ, DW, YD, QVV, DHS, LA, D265A/YTE, LALA/YTE, LAGA/YTE, LALAGA/YTE, LALAPG/YTE, N297A/LS, D265A/LS, LALA/LS, LALAGA/LS, LALAPG/LS, N297A/DHS, D265A/DHS, LALA/DHS, LAGA/DHS, LALAGA/DHS, LALAPG/DHS, SP/YTE, SPLE/YTE, SP/LS, SPLE/LS, SP/DHS, SPLE/DHS, N297A/LA, D265A/LA, LALA/LA, LAGA/LA, LALAGA/LA, LALAPG/LA, N297A/DQ, D265
  • an antibody described herein comprises an Fc region with YTE mutations at positions 253/255/257 or 260/262/264, respectively.
  • an antibody described herein comprises an Fc region with LALA mutations at positions 235/236 or 242/243, respectively.
  • an antibody described herein comprises an Fc region with YTE mutations at positions 253/255/257 and with LALA mutations at positions 235/236.
  • an antibody described herein comprises an Fc region with YTE mutations at positions 260/262/264 and with LALA mutations at positions 242/243.
  • the OX40L antibody described herein comprises the VH and VL of Construct 114 and an Fc region comprising YTE mutations at positions 253/255/257, respectively and with LALA mutations at positions 235/236, respectively.
  • the IL-4R ⁇ antibody described herein comprises the VH and VL of Construct 38 (mAb 471) and an Fc region comprising YTE mutations at positions 260/262/264, respectively and with LALA mutations at positions 242/243, respectively.
  • the antibody, or antigen binding fragment thereof, that binds OX40L comprises a VH domain comprising the amino acid sequence set forth in SEQ ID NO: 1, a VL domain comprising the amino acid sequence set forth in SEQ ID NO: 11, and a human IgG1 Fc region comprising LALA and YTE mutations.
  • the antibody, or antigen binding fragment thereof, that binds OX40L comprises a VH domain comprising the amino acid sequence set forth in SEQ ID NO: 1, a VL domain comprising the amino acid sequence set forth in SEQ ID NO: 11, a constant heavy chain sequence set forth in SEQ ID NO: 651 and/or a constant heavy chain sequence set forth in SEQ ID NO: 973, and a constant light chain sequence set forth in SEQ ID NO: 738.
  • the antibody, or antigen binding fragment thereof, that binds OX40L comprises a VH domain comprising the amino acid sequence set forth in SEQ ID NO: 1, a VL domain comprising the amino acid sequence set forth in SEQ ID NO: 11, a constant heavy chain sequence set forth in SEQ ID NO: 973, and a constant light chain sequence set forth in SEQ ID NO: 738.
  • the antibody, or antigen binding fragment thereof, that binds OX40L comprises a VH domain comprising the amino acid sequence set forth in SEQ ID NO: 1, a VL domain comprising the amino acid sequence set forth in SEQ ID NO: 11, a constant heavy chain sequence set forth in SEQ ID NO: 651, and a constant light chain sequence set forth in SEQ ID NO: 738.
  • the antibody, or antigen binding fragment thereof, that binds OX40L comprises a heavy chain sequence set forth in SEQ ID NO: 839 and/or SEQ ID NO: 840 and a light chain sequence set forth in SEQ ID NO: 841.
  • the antibody, or antigen binding fragment thereof, that binds OX40L comprises a heavy chain sequence set forth in SEQ ID NO: 839 and a light chain sequence set forth in SEQ ID NO: 841. In some embodiments, the antibody that binds OX40L is Construct 114. [0066] In some embodiments, the antibody, or antigen binding fragment thereof, that binds IL-4R ⁇ comprises a VH domain comprising the amino acid sequence set forth in SEQ ID NO: 297, a VL domain comprising the amino acid sequence set forth in SEQ ID NO: 300, and a human IgG1 Fc region comprising LALA and YTE mutations.
  • the antibody, or antigen binding fragment thereof, that binds IL-4R ⁇ comprises a VH domain comprising the amino acid sequence set forth in SEQ ID NO: 297, a VL domain comprising the amino acid sequence set forth in SEQ ID NO: 300, a constant heavy chain sequence set forth in SEQ ID NO: 651 and/or a constant heavy chain sequence set forth in SEQ ID NO: 973, and a constant light chain sequence set forth in SEQ ID NO: 738.
  • the antibody, or antigen binding fragment thereof, that binds IL-4R ⁇ comprises a VH domain comprising the amino acid sequence set forth in SEQ ID NO: 297, a VL domain comprising the amino acid sequence set forth in SEQ ID NO: 300, a constant heavy chain sequence set forth in SEQ ID NO: 973, and a constant light chain sequence set forth in SEQ ID NO: 738.
  • the antibody, or antigen binding fragment thereof, that binds IL-4R ⁇ comprises a VH domain comprising the amino acid sequence set forth in SEQ ID NO: 297, a VL domain comprising the amino acid sequence set forth in SEQ ID NO: 300, a constant heavy chain sequence set forth in SEQ ID NO: 651, and a constant light chain sequence set forth in SEQ ID NO: 738.
  • the antibody, or antigen binding fragment thereof, that binds IL-4R ⁇ comprises a heavy chain sequence set forth in SEQ ID NO: 836 and/or SEQ ID NO: 837 and a light chain sequence set forth in SEQ ID NO: 838.
  • the antibody, or antigen binding fragment thereof, that binds IL-4R ⁇ comprises a heavy chain sequence set forth in SEQ ID NO: 836 and a light chain sequence set forth in SEQ ID NO: 838.
  • the antibody that binds IL-4R ⁇ is Construct 38 (mAb 471).
  • the antibody that binds OX40L is Construct 114 and the antibody that binds IL-4R ⁇ is Construct 38 (mAb 471).
  • the antibody that binds OX40L is Construct 114 and the antibody that binds IL-4R ⁇ is dupilumab, stapokibart, or 611.
  • the antibody that binds OX40L is amlitelimab or oxelumab and the antibody that binds IL-4R ⁇ is Construct 38 (mAb 471).
  • the Fc region of the antibody, or antigen binding fragment thereof, that binds OX40L and/or the antibody, or antigen binding fragment thereof, that binds IL-4R ⁇ binds to Neonatal Fc receptor (FcRn).
  • the Fc region of the antibody, or antigen binding fragment thereof, that binds OX40L and/or the antibody, or antigen binding fragment thereof, that binds IL-4R ⁇ binds an FcRn with higher affinity at pH 6.0 compared to an antibody comprising a wild-type Fc region.
  • the Fc region of the antibody, or antigen binding fragment thereof, that binds OX40L and/or the antibody, or antigen binding fragment thereof, that binds IL-4R ⁇ binds to FcRn with a KD of ⁇ 1 x 10 -7 M at pH 6.0.
  • the antibody, or antigen binding fragment thereof, that binds OX40L and/or the antibody, or antigen binding fragment thereof, that binds IL-4R ⁇ is a monoclonal antibody.
  • the antibody, or antigen binding fragment thereof, that binds OX40L binds an OX40L sequence set forth in the amino acid sequence of SEQ ID NO: 739.
  • the antibody, or antigen binding fragment thereof, that binds IL-4R ⁇ binds an IL-4R ⁇ sequence set forth in any one of the amino acid sequences of SEQ ID NOs: 301-303.
  • the disclosure relates to the isolated antibodies, or antigen binding fragments thereof, of any one of the preceding aspects or embodiments for use in the treatment of an inflammatory disorder or disease (e.g., combined in a single formulation or administered in separate formulations).
  • the disclosure relates to the isolated antibodies, or antigen binding fragments thereof, of any one of the preceding aspects or embodiments for use in the treatment of atopic dermatitis (AD).
  • AD atopic dermatitis
  • the treatment reduces disease severity in a patient and wherein disease severity is assessed by an atopic dermatitis disease severity outcome measure.
  • the disclosure relates to the isolated antibodies, or antigen binding fragments thereof, of any one of the preceding aspects or embodiments for use in the treatment of asthma, chronic sinusitis with nasal polyps; Chronic Rhinosinusitis without Nasal Polyps (CRSsNP); eosinophilic esophagitis (EoE); an Eosinophilic gastrointestinal disorder or disease (EGID), such as Eosinophilic Gastritis (EoG), Eosinophilic Enteritis (EoN), Eosinophilic Colitis (EoC), or Eosinophilic Gastroenteritis (EGE); Churg-Strauss syndrome/Eosinophilic granulomatosis with polyangiitis (EGPA); Prurigo Nodularis (PN); Chronic Spontaneous Urticaria (CSU); Chronic Pruritis of Unknown Origin (CPUO); Bullous Pemphigoid (BP); Cold Inducible Urticaria (Cold
  • a multi-specific antibody comprising: a first antigen binding region that binds OX40L and comprises: a) a variable heavy (VH) chain sequence having three heavy chain CDR sequences, CDR-H1, CDR-H2, and CDR-H3; and b) a variable light (VL) chain sequence having three light chain CDR sequences, CDR-L1, CDR-L2, and CDR-L3; wherein the antigen binding region that binds OX40L comprises: (i) a CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 2-4; a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 5-7; a CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 8-10; a CDR-L1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 12-14; a CDR-
  • the antigen binding region that binds IL-4R ⁇ comprises a CDR-H1, CDR-H2, CDR-H3, CDR-L1, CDR-L2, and CDR-L3 of an antibody selected from dupilumab, stapokibart, and 611.
  • the antigen binding region that binds IL-4R ⁇ comprises: a) a VH chain sequence having three heavy chain CDR sequences, CDR-H1, CDR-H2, and CDR-H3; and b) a VL chain sequence having three light chain CDR sequences, CDR-L1, CDR-L2, and CDR-L3, wherein the antigen binding region that binds IL-4R ⁇ comprises: (i) a CDR-H1 comprising the sequence set forth in any one of SEQ ID NOs: 273, 274, and 275; a CDR-H2 comprising the sequence set forth in any one of SEQ ID NOs: 276, 277, and 278; a CDR-H3 comprising the sequence set forth in any one of SEQ ID NOs: 281 and 282; a CDR- L1 comprising the sequence set forth in any one of SEQ ID NOs: 285 and 286; a CDR-L2 comprising the sequence set forth in SEQ ID NO
  • a multi-specific antibody comprising: a first antigen binding region that binds OX40L; and a second antigen binding region that binds IL- 4R ⁇ and comprises: a) a variable heavy (VH) chain sequence having three heavy chain CDR sequences, CDR-H1, CDR-H2, and CDR-H3; and b) a variable light (VL) chain sequence having three light chain CDR sequences, CDR-L1, CDR-L2, and CDR-L3; wherein the antigen binding region that binds IL-4R ⁇ comprises: (i) a CDR-H1 comprising the sequence set forth in any one of SEQ ID NOs: 273, 274, and 275; a CDR-H2 comprising the sequence set forth in any one of SEQ ID NOs: 276, 277, and 278; a CDR-H3 comprising the sequence set forth in any one of SEQ ID NOs: 281 and 282; a CDR-
  • the antigen binding region that binds OX40L comprises a CDR-H1, CDR-H2, CDR-H3, CDR-L1, CDR-L2, and CDR-L3 of an antibody selected from amlitelimab and oxelumab.
  • the antigen binding region that binds OX40L comprises: a) a VH chain sequence having three heavy chain CDR sequences, CDR-H1, CDR-H2, and CDR-H3; and b) a VL chain sequence having three light chain CDR sequences, CDR-L1, CDR-L2, and CDR-L3, wherein the antigen binding region that binds OX40L comprises: (i) a CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 2-4; a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 5-7; a CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 8-10; a CDR-L1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 12-14; a CDR-L2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 15-16; and
  • the antigen binding region that binds OX40L comprises: (i) a CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 2-4; a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 5-7; a CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 8-10; a CDR-L1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 12-14; a CDR-L2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 15-16; and a CDR-L3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 17-18; and (b) the antigen binding region that binds IL-4R ⁇ comprises: (i) a CDR- H1 comprising the sequence set forth in any one of SEQ ID NOs: 273, 274, and 275; a
  • the antigen binding region that binds OX40L comprises: (ii) a CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 20-22; a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 23-25; a CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 26-28; a CDR-L1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 30-32; a CDR-L2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 33-34; and a CDR-L3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 35-36; and (b) the antigen binding region that binds IL-4R ⁇ comprises: (i) a CDR-H1 comprising the sequence set forth in any one of SEQ ID NOs: 273, 274, and
  • the antigen binding region that binds OX40L comprises: (iii) a CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 38-40; a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 41-43; a CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 44-46; a CDR-L1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 48-50; a CDR-L2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 51-52; and a CDR-L3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 53-54; and (b) the antigen binding region that binds IL-4R ⁇ comprises: (i) a CDR-H1 comprising the sequence set forth in any one of SEQ ID NOs: 273, 274,
  • the antigen binding region that binds OX40L comprises: (iv) a CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 56-58; a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 59-61; a CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 62-64; a CDR-L1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 66-68; a CDR-L2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 69-70; and a CDR-L3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 71-72; and (b) the antigen binding region that binds IL-4R ⁇ comprises: (i) a CDR-H1 comprising the sequence set forth in any one of SEQ ID NOs: 56-58; a CDR-
  • the antigen binding region that binds OX40L comprises: (i) a CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 2-4; a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 5-7; a CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 8-10; a CDR-L1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 12-14; a CDR-L2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 15-16; and a CDR-L3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 17-18; and (b) the antigen binding region that binds IL-4R ⁇ comprises: (ii) a CDR- H1 comprising the sequence set forth in any one of SEQ ID NOs: 273, 274, and 275;
  • the antigen binding region that binds OX40L comprises: (ii) a CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 20-22; a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 23-25; a CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 26-28; a CDR-L1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 30-32; a CDR-L2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 33-34; and a CDR-L3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 35-36; and (b) the antigen binding region that binds IL-4R ⁇ comprises: ((ii) a CDR-H1 comprising the sequence set forth in any one of SEQ ID NOs: 273, 274,
  • the antigen binding region that binds OX40L comprises: (iii) a CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 38-40; a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 41-43; a CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 44-46; a CDR-L1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 48-50; a CDR-L2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 51-52; and a CDR-L3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 53-54; and (b) the antigen binding region that binds IL-4R ⁇ comprises: (ii) a CDR-H1 comprising the sequence set forth in any one of SEQ ID NOs: 273, 27
  • the antigen binding region that binds OX40L comprises: (iv) a CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 56-58; a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 59-61; a CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 62-64; a CDR-L1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 66-68; a CDR-L2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 69-70; and a CDR-L3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 71-72; and (b) the antigen binding region that binds IL-4R ⁇ comprises: (ii) a CDR-H1 comprising the sequence set forth in any one of SEQ ID NOs: 56-58; a CDR
  • the antigen binding region that binds OX40L comprises: (i) a CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 2-4; a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 5-7; a CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 8-10; a CDR-L1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 12-14; a CDR-L2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 15-16; and a CDR-L3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 17-18; and (b) the antigen binding region that binds IL-4R ⁇ comprises: (iii) a CDR- H1 comprising the sequence set forth in any one of SEQ ID NOs: 273, 274, and 275;
  • the antigen binding region that binds OX40L comprises: (ii) a CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 20-22; a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 23-25; a CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 26-28; a CDR-L1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 30-32; a CDR-L2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 33-34; and a CDR-L3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 35-36; and (b) the antigen binding region that binds IL-4R ⁇ comprises: (iii) a CDR-H1 comprising the sequence set forth in any one of SEQ ID NOs: 273, 274,
  • the antigen binding region that binds OX40L comprises: (iii) a CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 38-40; a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 41-43; a CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 44-46; a CDR-L1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 48-50; a CDR-L2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 51-52; and a CDR-L3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 53-54; and (b) the antigen binding region that binds IL-4R ⁇ comprises: (iii) a CDR-H1 comprising the sequence set forth in any one of SEQ ID NOs: 273,
  • the antigen binding region that binds OX40L comprises: (iv) a CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 56-58; a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 59-61; a CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 62-64; a CDR-L1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 66-68; a CDR-L2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 69-70; and a CDR-L3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 71-72; and (b) the antigen binding region that binds IL-4R ⁇ comprises: (iii) a CDR-H1 comprising the sequence set forth in any one of SEQ ID NOs: 56-58; a C
  • the antigen binding region that binds OX40L comprises a heavy chain variable domain (VH) sequence comprising the amino acid sequence set forth in any one of SEQ ID NOs: 1, 19, 37, and 55.
  • the antigen binding region that binds IL-4R ⁇ comprises a VH sequence comprising the amino acid sequence set forth in any one of SEQ ID NOs: 295- 297.
  • the antigen binding region that binds OX40L comprises a light chain variable domain (VL) sequence comprising the amino acid sequence set forth in any one of SEQ ID NOs: 11, 29, 47, and 65.
  • the antigen binding region that binds IL-4R ⁇ comprises a VL sequence comprising the amino acid sequence set forth in any one of SEQ ID NOs: 298- 300.
  • (a) the antigen binding region that binds OX40L comprises: (i) a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 1; (ii) a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 19; (iii) a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 37; or (iv) a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 55; and/or (v) a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 11; (vi) a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 29;(vii) a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 47;
  • the antigen binding region that binds OX40L comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 1; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 11.
  • the antigen binding region that binds OX40L comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 19; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 29.
  • the antigen binding region that binds OX40L comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 37; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 47.
  • the antigen binding region that binds OX40L comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 55; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 65.
  • the antigen binding region that binds IL-4R ⁇ comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 295; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 298.
  • the antigen binding region that binds IL-4R ⁇ comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 296; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 299.
  • the antigen binding region that binds IL-4R ⁇ comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 297; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 300.
  • the antigen binding region that binds OX40L comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 1; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 11; and the antigen binding region that binds IL-4R ⁇ comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 295; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 298.
  • the antigen binding region that binds OX40L comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 1; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 11; and the antigen binding region that binds IL-4R ⁇ comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 296; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 299.
  • the antigen binding region that binds OX40L comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 1; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 11; and the antigen binding region that binds IL-4R ⁇ comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 297; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 300.
  • the antigen binding region that binds OX40L comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 19; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 29; and the antigen binding region that binds IL-4R ⁇ comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 295; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 298.
  • the antigen binding region that binds OX40L comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 19; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 29; and the antigen binding region that binds IL-4R ⁇ comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 296; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 299.
  • the antigen binding region that binds OX40L comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 19; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 29; and the antigen binding region that binds IL-4R ⁇ comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 297; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 300.
  • the antigen binding region that binds OX40L comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 37; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 47; and the antigen binding region that binds IL-4R ⁇ comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 295; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 298.
  • the antigen binding region that binds OX40L comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 37; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 47; and the antigen binding region that binds IL-4R ⁇ comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 296; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 299.
  • the antigen binding region that binds OX40L comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 37; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 47; and the antigen binding region that binds IL-4R ⁇ comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 297; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 300.
  • the antigen binding region that binds OX40L comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 55; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 65; and the antigen binding region that binds IL-4R ⁇ comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 295; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 298.
  • the antigen binding region that binds OX40L comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 55; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 65; and the antigen binding region that binds IL-4R ⁇ comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 296; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 299.
  • the antigen binding region that binds OX40L comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 55; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 65; and the antigen binding region that binds IL-4R ⁇ comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 297; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 300.
  • the antigen binding region that binds OX40L and/or the antigen binding region that binds IL-4R ⁇ is humanized, human, or chimeric.
  • the antigen binding region that binds OX40L and/or the antigen binding region that binds IL-4R ⁇ is humanized.
  • the multi-specific antibody comprises a heavy chain human constant region of a class selected from IgG, IgA, IgD, IgE, and IgM.
  • the multi-specific antibody comprises a human Fc region, and the human Fc region comprises a human heavy chain constant region of the class IgG and a subclass selected from IgG1, IgG2, IgG3, and IgG4.
  • the human Fc region comprises a human IgG1 Fc region.
  • the human Fc region comprises a human IgG4 Fc region.
  • the human Fc region comprises a human IgG2 Fc region.
  • the multi-specific antibody comprises a heavy chain comprising a constant heavy chain sequence selected from the amino acid sequences set forth in any one of SEQ ID NOs: 427, 439, 440, 446, 457, 460, 637-737, and 847-1070.
  • the multi-specific antibody comprises a heavy chain constant domain having a means for increasing the half-life of the antibody.
  • the multi-specific antibody comprises a light chain comprising a constant light chain sequence selected from the sequences set forth in SEQ ID NOs: 469 and 1071.
  • the multi-specific antibody comprises an Fc region comprising one or more amino acid substitutions, wherein the one or more substitutions result in an increase in one or more of antibody half-life, ADCC activity, ADCP activity, or CDC activity compared with the Fc without the one or more substitutions.
  • the multi-specific antibody comprises an Fc region comprising one or more amino acid substitutions, wherein the one or more substitutions result in a decrease in one or more of, ADCC activity, ADCP activity or CDC activity compared to an antibody comprising a wild-type Fc region.
  • the one or more amino acid substitutions is selected from the group consisting of S228P, M252Y, S254T, T256E, T256D, T250Q, H285D, T307A, T307Q, T307R, T307W, L309D, Q411H, Q311V, A378V, E380A, M428L, N434A, N434S, N297A, D265A, L234A, L235A, and N434W; optionally, wherein the one or more amino acid substitutions comprises a plurality of amino acid substitutions selected from the group consisting of M428L/N434S (LS), M252Y/S254T/T256E (YTE), T250Q/M428L, T307A/E380A/N434A, T256D/T307Q (DQ), T256D/T307W (DW), M252Y/T256D (LS), M252Y/S
  • the one or more amino acid substitutions is selected from the group consisting of LS, YTE, T250Q/M428L, T307A/E380A/N434A, DQ, DW, YD, QVV, DHS, LA, D265A/YTE, LALA/YTE, LAGA/YTE, LALAGA/YTE, LALAPG/YTE, N297A/LS, D265A/LS, LALA/LS, LALAGA/LS, LALAPG/LS, N297A/DHS, D265A/DHS, LALA/DHS, LAGA/DHS, LALAGA/DHS, LALAPG/DHS, SP/YTE, SPLE/YTE, SP/LS, SPLE/LS, SP/DHS, SPLE/DHS, N297A/LA, D265A/LA, LALA/LA, LAGA/LA, LALAGA/LA, LALAPG/LA, N297A/DQ, D265
  • an antibody described herein comprises an Fc region with YTE mutations at positions 253/255/257 or 260/262/264, respectively.
  • an antibody described herein comprises an Fc region with LALA mutations at positions 235/236 or 242/243, respectively.
  • an antibody described herein comprises an Fc region with YTE mutations at positions 253/255/257 and with LALA mutations at positions 235/236.
  • an antibody described herein comprises an Fc region with YTE mutations at positions 260/262/264 and with LALA mutations at positions 242/243.
  • the OX40L antibody described herein comprises the VH and VL of Construct 114 and an Fc region comprising YTE mutations at positions 253/255/257, respectively and with LALA mutations at positions 235/236, respectively.
  • the IL-4R ⁇ antibody described herein comprises the VH and VL of Construct 38 (mAb 471) and an Fc region comprising YTE mutations at positions 260/262/264, respectively and with LALA mutations at positions 242/243, respectively.
  • the multi-specific antibody comprising an antigen binding region that binds OX40L comprises a VH domain comprising the amino acid sequence set forth in SEQ ID NO: 1, a VL domain comprising the amino acid sequence set forth in SEQ ID NO: 11, a constant heavy chain sequence set forth in any one of SEQ ID NOs: 651 and 973, and a constant light chain sequence set forth in SEQ ID NO: 738.
  • the multi-specific antibody comprising an antigen binding region that binds IL-4R ⁇ comprises a VH domain comprising the amino acid sequence set forth in SEQ ID NO: 297, a VL domain comprising the amino acid sequence set forth in SEQ ID NO: 300, a heavy chain sequence set forth in any one of SEQ ID NOs: 651 and 973, and a light chain sequence set forth in SEQ ID NO: 738.
  • the Fc region of the multi-specific antibody binds to Neonatal Fc receptor (FcRn).
  • the Fc region of the multi-specific antibody binds an FcRn with higher affinity at pH 6.0 compared to an antibody comprising a wild-type Fc region.
  • the Fc region of the multi-specific antibody binds to FcRn with a K D of ⁇ 1 x 10 -7 M at pH 6.0.
  • the antigen binding region that binds OX40L and/or the antigen binding region that binds IL-4R ⁇ is monoclonal.
  • the antigen binding region that binds OX40L binds an OX40L sequence set forth in the amino acid sequence of SEQ ID NO: 739.
  • the antigen binding region that binds IL-4R ⁇ binds an IL- 4R ⁇ sequence set forth in any one of the amino acid sequences of SEQ ID NOs: 301-303.
  • the disclosure relates to the multi-specific antibodies of any one of the foregoing aspects or embodiments for use in the treatment of an inflammatory disorder or disease.
  • the disclosure relates to the multi-specific antibodies of any one of the foregoing aspects or embodiments for use in the treatment of atopic dermatitis (AD).
  • the treatment reduces disease severity in a patient and wherein disease severity is assessed by an atopic dermatitis disease severity outcome measure.
  • the disclosure relates to the multi-specific antibodies of any one of the foregoing aspects or embodiments for use in the treatment of asthma; chronic sinusitis with nasal polyps; Chronic Rhinosinusitis without Nasal Polyps (CRSsNP); eosinophilic esophagitis (EoE); an Eosinophilic gastrointestinal disorder or disease (EGID), such as Eosinophilic Gastritis (EoG), Eosinophilic Enteritis (EoN), Eosinophilic Colitis (EoC), or Eosinophilic Gastroenteritis (EGE); Churg-Strauss syndrome/Eosinophilic granulomatosis with polyangiitis (EGPA); Prurigo Nodularis (PN); Chronic Spontaneous Urticaria (CSU); Chronic Pruritis of Unknown Origin (CPUO); Bullous Pemphigoid (BP); Cold Inducible Urticaria (ColdU); Allergic Fungal
  • EGPA Eo
  • the disclosure relates to an isolated polynucleotide or set of polynucleotides encoding the isolated antibodies or multi-specific antibodies of any one of the preceding aspects or embodiments, a VH thereof, a VL thereof, a light chain thereof, a heavy chain thereof, or an antigen-binding portion thereof, and optionally, wherein the polynucleotide or set of polynucleotides comprises cDNA.
  • the disclosure relates to a vector or set of vectors comprising the polynucleotide or set of polynucleotides of any one of the preceding aspects or embodiments.
  • the disclosure relates to a host cell comprising the polynucleotide or set of polynucleotides of any one of the preceding aspects or embodiments or the vector or set of vectors of any one of the preceding aspects or embodiments.
  • the disclosure relates to a method of producing one or more of the isolated antibodies or multi-specific antibody of any one of the preceding aspects or embodiments, the method comprising expressing one or more of the isolated antibodies or multi-specific antibody within the host cell of any one of the preceding aspects or embodiments and isolating the one or more expressed antibodies.
  • the disclosure relates to a pharmaceutical composition comprising the isolated antibodies or multi-specific antibody of any one of the preceding aspects or embodiments and a pharmaceutically acceptable excipient.
  • the disclosure relates to a kit comprising the isolated antibodies or multi-specific antibody of any one of any one of the preceding aspects or embodiments or the pharmaceutical composition of any one of the preceding aspects or embodiments and instructions for use.
  • the disclosure relates to a method for treating an inflammatory disorder or disease in a mammalian subject in need thereof, the method comprising administering to the mammalian subject a therapeutically effective amount of the isolated antibodies or multi-specific antibody of any one of the preceding aspects or embodiments; a therapeutically effective amount of the pharmaceutical composition of any one of the preceding aspects or embodiments; or a therapeutically effective amount of a pharmaceutical composition comprising an isolated antibody, or an antigen binding fragment thereof, that binds OX40L and a pharmaceutically acceptable excipient and a therapeutically effective amount of a pharmaceutical composition comprising an antibody, or an antigen binding fragment thereof, that binds IL-4R ⁇ and a pharmaceutically acceptable excipient137.
  • the mammalian subject is a human.
  • the inflammatory disorder or disease is atopic dermatitis.
  • the inflammatory disorder or disease is asthma.
  • the inflammatory disorder or disease is chronic sinusitis with nasal polyps; Chronic Rhinosinusitis without Nasal Polyps (CRSsNP); eosinophilic esophagitis (EoE); an Eosinophilic gastrointestinal disorder or disease (EGID), such as Eosinophilic Gastritis (EoG), Eosinophilic Enteritis (EoN), Eosinophilic Colitis (EoC), or Eosinophilic Gastroenteritis (EGE); Churg-Strauss syndrome/Eosinophilic granulomatosis with polyangiitis (EGPA); Prurigo Nodularis (PN); Chronic Spontaneous Urticaria (CSU);
  • CRSsNP Chronic Rhinosinusitis without Nasal Polyps
  • EoE eos
  • the disclosure relates to a method for treating a pathology associated with elevated levels of OX40L and/or IL-4R ⁇ in a mammalian subject in need thereof, the method comprising administering to the mammalian subject a therapeutically effective amount the isolated antibodies or multi-specific antibody of any one of the foregoing aspects or embodiments, the pharmaceutical composition of any one of the foregoing aspects or embodiments, or a therapeutically effective amount of a pharmaceutical composition comprising an isolated antibody, or an antigen binding fragment thereof, that binds OX40L and a pharmaceutically acceptable excipient and a therapeutically effective amount of a pharmaceutical composition comprising an isolated antibody, or an antigen binding fragment thereof, that binds IL-4R ⁇ and a pharmaceutically acceptable excipient.
  • the disclosure relates to a method of reducing biological activity of OX40L and/or IL-4R ⁇ in a mammalian subject in need thereof, the method comprising administering to the mammalian subject a therapeutically effective amount the isolated antibodies or multi-specific antibody of any one of the foregoing aspects or embodiments, the pharmaceutical composition of any one of the foregoing aspects or embodiments, or a therapeutically effective amount of a pharmaceutical composition comprising an isolated antibody, or an antigen binding fragment thereof, that binds OX40L and a pharmaceutically acceptable excipient and a therapeutically effective amount of a pharmaceutical composition comprising an isolated antibody, or an antigen binding fragment thereof, that binds IL-4R ⁇ and a pharmaceutically acceptable excipient.
  • the mammalian subject is a human.
  • the disclosure relates to a pharmaceutical composition
  • the disclosure relates to a pharmaceutical composition
  • a multi-specific antibody comprising: an antigen binding region that binds OX40L comprises a VH domain comprising the amino acid sequence set forth in SEQ ID NO: 1, a VL domain comprising the amino acid sequence set forth in SEQ ID NO: 11, a constant heavy chain sequence set forth in any one of SEQ ID NOs: 651 and 973, and a constant light chain sequence set forth in SEQ ID NO: 738; an antigen binding region that binds IL-4R ⁇ comprises a VH domain comprising the amino acid sequence set forth in SEQ ID NO: 297, a VL domain comprising the amino acid sequence set forth in SEQ ID NO: 300, a constant heavy chain sequence set forth in any one of SEQ ID NOs: 651 and 973, and a constant light chain sequence set forth in SEQ ID NO: 738; and a pharmaceutically acceptable excipient.
  • the pharmaceutical composition comprises a means for increasing the bioavailability of the isolated antibody, or antigen binding region thereof, that binds OX40L and/or the isolated antibody, or antigen binding region thereof, that binds IL- 4R ⁇ or the multi-specific antibody.
  • described herein are compositions comprising an isolated antibody, or an antigen binding fragment thereof, that binds OX40L, an isolated antibody, or an antigen binding fragment thereof, that binds Interleukin-4 Receptor Alpha (IL-4R ⁇ ), and a hyaluronidase or variant thereof.
  • compositions comprising any one of the antibodies, or an antigen binding fragment thereof, described herein that binds OX40L, any one of the antibodies, or an antigen binding fragment thereof, described herein that binds IL-4R ⁇ , and any one of the hyaluronidases or variants thereof described herein.
  • compositions comprising hyaluronidase or a variant thereof and a multi-specific antibody comprising a first antigen binding region that binds OX40L and a second antigen binding region that binds IL-4R ⁇ .
  • described herein are a combination of an antibody, or an antigen binding fragment thereof, that binds OX40L, an antibody, or an antigen binding fragment thereof, that binds IL-4R ⁇ , and a hyaluronidase or variant thereof.
  • described herein are a combination of any one of the antibodies, or an antigen binding fragment thereof, described herein that binds OX40L, any one of the antibodies, or an antigen binding fragment thereof, described herein that binds IL-4R ⁇ , and a hyaluronidase or a variant thereof.
  • described herein are combinations comprising hyaluronidase or a variant thereof and a multi-specific antibody comprising a first antigen binding region that binds OX40L and a second antigen binding region that binds IL-4R ⁇ .
  • described herein are methods of treating an inflammatory disorder or disease in a human patient comprising co-administering to the patient an isolated antibody, or an antigen binding fragment thereof, that binds OX40L, an isolated antibody, or an antigen binding fragment thereof, that binds IL-4R ⁇ , and a hyaluronidase or a variant thereof.
  • described herein are methods of treating an inflammatory disorder or disease in a human patient comprising co-administering to the patient any one of the antibodies, or an antigen binding fragment thereof, described herein that binds OX40L, any one of the antibodies, or an antigen binding fragment thereof, described herein that binds IL- 4R ⁇ , and any one of the hyaluronidases or variants thereof described herein.
  • Described herein are methods of treating an inflammatory disorder or disease in a human patient comprising co-administering to the patient hyaluronidase or a variant thereof and a multi-specific antibody comprising a first antigen binding region that binds OX40L and a second antigen binding region that binds IL-4R ⁇ .
  • described herein are methods of treating an inflammatory disorder or disease in a human patient comprising co-administering to the patient any one of the hyaluronidases or variants thereof described herein and any one of the multi-specific antibodies described herein (e.g., comprising a first antigen binding region that binds OX40L and a second antigen binding region that binds IL-4R ⁇ ).
  • the antibody, or an antigen binding fragment thereof, that binds OX40L and/or the antibody, or an antigen binding fragment thereof, that binds IL- 4R ⁇ is a humanized, human, or chimeric antibody.
  • the antibody, or an antigen binding fragment thereof is a monoclonal antibody.
  • the antibody, or an antigen binding fragment thereof comprises a heavy chain human constant region of a class selected from IgG, IgA, IgD, IgE, and IgM.
  • the antibody, or an antigen binding fragment thereof comprises a human Fc region comprising a human heavy chain constant region of the class IgG and a subclass selected from IgG1, IgG2, IgG3, and IgG4.
  • the human Fc region comprises a human IgG1 Fc region [00172]
  • the human Fc region comprises a human IgG1 Fc region with LALA mutations.
  • the human Fc region comprises a human IgG1 Fc region with YTE mutations. In certain embodiments the human Fc region comprises a human IgG1 Fc region with LALA and YTE mutations. In certain embodiments, when direct numbering is used these “YTE” and “LALA” mutations can be located at different amino acid position numbers. For example, in one embodiment, the human Fc region comprises a human IgG1 Fc region with LALA mutations at L235A/L236A and/or YTE mutations at M253Y/S255T/T257E.
  • the human Fc region comprises a human IgG1 Fc region with LALA mutations at L242A/L243A and/or YTE mutations at M260Y/S262T/T264E.
  • the antibody, or an antigen binding fragment thereof, that binds OX40L comprises a CDR-H1 comprising the sequence set forth in SEQ ID NO: 2; a CDR-H2 comprising the sequence set forth in SEQ ID NO: 5; a CDR-H3 comprising the sequence set forth in SEQ ID NO: 8; a CDR-L1 comprising the sequence set forth in SEQ ID NO: 12; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 15; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 17.
  • the antibody, or an antigen binding fragment thereof, that binds OX40L comprises a VH sequence set forth in SEQ ID NO: 1 and a VL sequence set forth in SEQ ID NO: 11.
  • the heavy chain of the antibody that binds OX40L comprises a constant heavy chain sequence set forth in SEQ ID NO: 651.
  • the heavy chain of the antibody that binds OX40L comprises a constant heavy chain sequence set forth in SEQ ID NO: 973.
  • the light chain of the antibody, or an antigen binding fragment thereof, that binds OX40L comprises a constant light chain sequence set forth in SEQ ID NO: 738.
  • the heavy chain of the antibody, or an antigen binding fragment thereof, that binds OX40L comprises a sequence set forth in SEQ ID NO: 839 and/or SEQ ID NO: 840.
  • the light chain of the antibody, or an antigen binding fragment thereof, that binds OX40L comprises a sequence set forth in SEQ ID NO: 841.
  • the heavy chain of the antibody, or an antigen binding fragment thereof, that binds OX40L comprises a sequence set forth in SEQ ID NO: 839 and the light chain of the antibody, or antigen binding fragment thereof that binds OX40L, comprises a sequence set forth in SEQ ID NO: 841.
  • the antibody, or an antigen binding fragment thereof, that binds IL-4R ⁇ comprises a CDR-H1 comprising the sequence set forth in SEQ ID NO: 273; a CDR-H2 comprising the sequence set forth in SEQ ID NO: 279; a CDR-H3 comprising the sequence set forth in SEQ ID NO: 281; a CDR-L1 comprising the sequence set forth in SEQ ID NO: 289; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 290; and a CDR- L3 comprising the sequence set forth in SEQ ID NO: 293.
  • the antibody, or an antigen binding fragment thereof, that binds IL-4R ⁇ comprises a VH sequence set forth in SEQ ID NO: 297 and a VL sequence set forth in SEQ ID NO: 300.
  • the heavy chain of the antibody, or an antigen binding fragment thereof, that binds IL-4R ⁇ comprises a constant heavy chain sequence set forth in SEQ ID NO: 651.
  • the heavy chain of the antibody, or an antigen binding fragment thereof, that binds IL-4R ⁇ comprises a constant heavy chain sequence set forth in SEQ ID NO: 973.
  • the light chain of the antibody, or an antigen binding fragment thereof, that binds IL-4R ⁇ comprises a constant light chain sequence set forth in SEQ ID NO: 738.
  • the heavy chain of the antibody, or an antigen binding fragment thereof, that binds IL-4R ⁇ comprises a sequence set forth in SEQ ID NO: 836 and/or SEQ ID NO: 837.
  • the light chain of the antibody, or an antigen binding fragment thereof, that binds IL-4R ⁇ comprises a sequence set forth in SEQ ID NO: 838.
  • the heavy chain of the antibody, or an antigen binding fragment thereof, that binds IL-4R ⁇ comprises a sequence set forth in SEQ ID NO: 836 and the light chain of the antibody, or antigen binding fragment thereof that binds IL-4R ⁇ , comprises a sequence set forth in SEQ ID NO: 838.
  • a multi-specific antibody comprising a first antigen binding region that binds OX40L and a second antigen binding region that binds IL-4R ⁇ is provided.
  • the antigen binding region that binds OX40L comprises a CDR-H1 comprising the sequence set forth in SEQ ID NO: 2; a CDR-H2 comprising the sequence set forth in SEQ ID NO: 5; a CDR-H3 comprising the sequence set forth in SEQ ID NO: 8; a CDR-L1 comprising the sequence set forth in SEQ ID NO: 12; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 15; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 17.
  • the antigen binding region that binds OX40L comprises a VH sequence set forth in SEQ ID NO: 1 and a VL sequence set forth in SEQ ID NO: 11.
  • the antigen binding region that binds IL- 4R ⁇ comprises a CDR-H1 comprising the sequence set forth in SEQ ID NO: 273; a CDR-H2 comprising the sequence set forth in SEQ ID NO: 279; a CDR-H3 comprising the sequence set forth in SEQ ID NO: 281; a CDR-L1 comprising the sequence set forth in SEQ ID NO: 289; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 290; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 293.
  • the antibody that binds IL-4R ⁇ comprises a VH sequence set forth in SEQ ID NO: 297 and a VL sequence set forth in SEQ ID NO: 300.
  • the antibody or antigen binding region that binds OX40L and/or the antibody or antigen binding region that binds IL-4R ⁇ comprises a heavy chain human constant region of a class selected from IgG, IgA, IgD, IgE, and IgM.
  • the antibody or antigen binding region that binds OX40L and/or the antibody or antigen binding region that binds IL-4R ⁇ comprises a human Fc region
  • the human Fc region comprises a human heavy chain constant region of the class IgG and a subclass selected from IgG1, IgG2, IgG3, and IgG4.
  • the human Fc region of the antibody that binds OX40L and/or the antibody that binds IL-4R ⁇ comprises a human IgG1 Fc region.
  • the human Fc region of the antibody that binds OX40L and/or the antibody that binds IL-4R ⁇ comprises a human IgG4 Fc region.
  • the human Fc region of the antibody or antigen binding region that binds OX40L and/or the antibody or antigen binding region that binds IL-4R ⁇ comprises a human IgG2 Fc region.
  • the human Fc region comprises a human IgG1 Fc region with LALA mutations.
  • the human Fc region comprises a human IgG1 Fc region with YTE mutations.
  • the human Fc region comprises a human IgG1 Fc region with LALA and YTE mutations.
  • when direct numbering is used these “YTE” and “LALA” mutations can be located at different amino acid position numbers.
  • the human Fc region comprises a human IgG1 Fc region with LALA mutations at L235A/L236A and/or YTE mutations at M253Y/S255T/T257E.
  • the human Fc region comprises a human IgG1 Fc region with LALA mutations at L242A/L243A and/or YTE mutations at M260Y/S262T/T264E.
  • the Fc region of the antibody or antigen binding region that binds OX40L and/or the antibody or antigen binding region that binds IL-4R ⁇ binds to Neonatal Fc receptor (FcRn).
  • the Fc region of the antibody or antigen binding region that binds OX40L and/or the antibody or antigen binding region that binds IL-4R ⁇ binds an FcRn with higher affinity at pH 6.0 compared to an antibody comprising a wild-type Fc region.
  • the Fc region of the antibody or antigen binding region that binds OX40L and/or the antibody or antigen binding region that binds IL-4R ⁇ binds to FcRn with a K D of ⁇ 1 x 10 -7 M at pH 6.0.
  • the antibody or antigen binding region that binds OX40L and/or the antibody or antigen binding region that binds IL-4R ⁇ is a monoclonal antibody.
  • the antibody or antigen binding region that binds OX40L binds an OX40L sequence set forth in the amino acid sequence of SEQ ID NO: 739.
  • the antibody or antigen binding region that binds IL-4R ⁇ binds an IL- 4R ⁇ sequence set forth in any one of the amino acid sequences of SEQ ID NOs: 301-303.
  • Any suitable hyaluronidase or variant thereof can be used in the compositions, combinations, and methods described herein.
  • the hyaluronidase is a recombinant human hyaluronidase.
  • the recombinant human hyaluronidase comprises the amino acid sequence set forth in any one of SEQ ID NOs: 1076- 1085 and 1087-1142.
  • the recombinant human hyaluronidase is rHuPH20.
  • the rHuPH20 formulation is ENHANZE®.
  • the recombinant human hyaluronidase includes a sequence of amino acids in any one of SEQ ID NOs: 1076-1085 and 1087-1142, or has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 95%, 97%, 98%, or 99% sequence identity to a sequence of amino acids included in any one of SEQ ID NO: 1076-1085 and 1087-1142 and retains hyaluronidase activity.
  • the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1076.
  • the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1076. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1078. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1078. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1079. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1079.
  • the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1080. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1080. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1081. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1081. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1082.
  • the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1082. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1083. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1083. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1084. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1084.
  • the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1085. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1085. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1087. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1087. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1088.
  • the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1088. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1089. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1089. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1090. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1090.
  • the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1091. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1091. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1093. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1093. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1094.
  • the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1094. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1095. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1095. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1096. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1096.
  • the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1097. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1097. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1098. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1098. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1099.
  • the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1099. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1100. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1100. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1101. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1101.
  • the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1102. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1102. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1103. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1103. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1104.
  • the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1104. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1105. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1105. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1106. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1106.
  • the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1107. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1107. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1108. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1108. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1109.
  • the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1109. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1110. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1110. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1111. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1111.
  • the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1112. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1112. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1113. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1113. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1114.
  • the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1114. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1115. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1115. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1116. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1116.
  • the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1117. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1117. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1118. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1118. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1119.
  • the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1119. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1120. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1120. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1121. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1121.
  • the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1122. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1122. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1123. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1123. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1124.
  • the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1124. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1125. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1125. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1126. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1126.
  • the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1127. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1127. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1128. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1128. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1129.
  • the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1129. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1130. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1130. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1131. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1131.
  • the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1132. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1132. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1133. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1133. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1134.
  • the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1134. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1135. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1135. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1136. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1136.
  • the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1137. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1137. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1138. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1138. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1139.
  • the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1139. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1140. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1140. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1141. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1141.
  • the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1142. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1142. [00183] In certain embodiments, the hyaluronidase or variant thereof and antibodies (i.e., anti- IL-4R ⁇ antibody, or antigen binding fragment thereof, and anti-OX40L antibody, or antigen binding fragment thereof) or multi-specific antibody (i.e., comprising a first antigen binding region that binds OX40L and a second antigen binding region that binds IL-4R ⁇ ) are administered in separate formulations.
  • antibodies i.e., anti- IL-4R ⁇ antibody, or antigen binding fragment thereof, and anti-OX40L antibody, or antigen binding fragment thereof
  • multi-specific antibody i.e., comprising a first antigen binding region that binds OX40L and a second anti
  • the hyaluronidase or variant thereof and antibodies or multi-specific antibody are administered simultaneously in separate formulations.
  • the hyaluronidase or variant thereof is administered to the patient prior to administration of the antibodies or multi-specific antibody.
  • the hyaluronidase or variant thereof is administered to the patient after administration of the antibodies or multi-specific antibody.
  • the hyaluronidase or variant thereof is administered to the patient after administration of one of the antibodies (either the OX40L antibody or the IL-4R ⁇ antibody) but is administered before the administration of the second of the antibodies (either the OX40L antibody or the IL-4R ⁇ antibody).
  • the hyaluronidase or variant thereof and the antibodies or multi-specific antibody are mixed and administered in a single formulation. In certain embodiments, the hyaluronidase or variant thereof and the antibodies or multi-specific antibody are administered by subcutaneous injection. In certain embodiments, the hyaluronidase or variant thereof and the antibodies or multi-specific antibody are administered by intravenous injection.
  • the hyaluronidase is rHuPH20 (ENHANZE®) administered at a concentration of 5,000, 6,000, 7,000, 8,000, 9,000, 10,000, 11,000, 12,000, 13,000, 14,000, 15,000, 16,000, 17,000, 18,000, 19,000, 20,000, 21,000, 22,000, 23,000, 24,000, 25,000, 26,000, 27,000, 28,000, 29,000, 30,000, 31,000, 32,000, 33,000, 34,000, 35,000, 36,000, 37,000, 38,000, 39,000, or 40,000 units.
  • methods of treating an inflammatory disorder or disease in a human patient comprising co-administering to the patient any one of the antibodies that bind OX40L described herein and any one of the antibodies that bind IL-4R ⁇ described herein in combination with a hyaluronidase or variant thereof.
  • methods of treating an inflammatory disorder or disease in a human patient are provided, wherein the method comprises co-administering to the patient any one of the multi-specific antibodies described herein in combination with a hyaluronidase or variant thereof.
  • the inflammatory disorder or disease is atopic dermatitis.
  • the treatment reduces disease severity in the patient and disease severity is assessed by an atopic dermatitis disease severity outcome measure.
  • the inflammatory disorder or disease is asthma; chronic sinusitis with nasal polyps; Chronic Rhinosinusitis without Nasal Polyps (CRSsNP); eosinophilic esophagitis (EoE); an Eosinophilic gastrointestinal disorder or disease (EGID), such as Eosinophilic Gastritis (EoG), Eosinophilic Enteritis (EoN), Eosinophilic Colitis (EoC), or Eosinophilic Gastroenteritis (EGE); Churg-Strauss syndrome/Eosinophilic granulomatosis with polyangiitis (EGPA); Prurigo Nodularis (PN); Chronic Spontaneous Urticaria (CSU); Chronic Pruritis of Unknown Origin (CPUO); Bullous Pemphigoid (BP); Cold Inducible Urticaria
  • compositions comprising an isolated antibody, or antigen binding region thereof, that binds OX40L, an isolated antibody, or antigen binding region thereof, that binds IL-4R ⁇ , and a hyaluronidase or variant thereof.
  • compositions comprising an isolated antibody, or antigen binding region thereof, that binds OX40L, an isolated antibody, or antigen binding region thereof, that binds IL-4R ⁇ , and a hyaluronidase or variant thereof, wherein the antibody that binds OX40L comprises a CDR-H1 comprising the sequence set forth in SEQ ID NO: 2; a CDR-H2 comprising the sequence set forth in SEQ ID NO: 5; a CDR-H3 comprising the sequence set forth in SEQ ID NO: 8; a CDR-L1 comprising the sequence set forth in SEQ ID NO: 12; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 15; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 17.
  • compositions comprising an isolated antibody, or antigen binding region thereof, that binds OX40L, an isolated antibody, or antigen binding region thereof, that binds IL-4R ⁇ , and a hyaluronidase or variant thereof, wherein the antibody that binds OX40L comprises a VH sequence set forth in SEQ ID NO: 1 and a VL sequence set forth in SEQ ID NO: 11.
  • compositions comprising an isolated antibody, or antigen binding region thereof, that binds OX40L, an isolated antibody, or antigen binding region thereof, that binds IL-4R ⁇ , and a hyaluronidase or variant thereof, wherein the antibody that binds IL-4R ⁇ comprises a CDR-H1 comprising the sequence set forth in SEQ ID NO: 273; a CDR-H2 comprising the sequence set forth in SEQ ID NO: 279; a CDR-H3 comprising the sequence set forth in SEQ ID NO: 281; a CDR-L1 comprising the sequence set forth in SEQ ID NO: 289; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 290; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 293.
  • compositions comprising an isolated antibody, or antigen binding region thereof, that binds OX40L, an isolated antibody, or antigen binding region thereof, that binds IL-4R ⁇ , and a hyaluronidase or variant thereof, wherein the antibody that binds IL-4R ⁇ comprises a VH sequence set forth in SEQ ID NO: 297 and a VL sequence set forth in SEQ ID NO: 300.
  • compositions comprising an isolated antibody, or an antigen binding fragment thereof, that binds OX40L, an isolated antibody, or an antigen binding fragment thereof, that binds IL-4R ⁇ , and a hyaluronidase or variant thereof, wherein the antibody, or an antigen binding fragment thereof, that binds OX40L comprises a CDR-H1 comprising the sequence set forth in SEQ ID NO: 2; a CDR-H2 comprising the sequence set forth in SEQ ID NO: 5; a CDR-H3 comprising the sequence set forth in SEQ ID NO: 8; a CDR-L1 comprising the sequence set forth in SEQ ID NO: 12; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 15; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 17, and wherein the antibody, or an antigen binding fragment thereof, that binds IL-4R ⁇ comprises a CDR-H1 comprising
  • compositions comprising an isolated antibody, or an antigen binding fragment thereof, that binds OX40L, an isolated antibody, or an antigen binding fragment thereof, that binds IL-4R ⁇ , and a hyaluronidase or variant thereof, wherein the antibody, or an antigen binding fragment thereof, that binds OX40L comprises a VH sequence set forth in SEQ ID NO: 1 and a VL sequence set forth in SEQ ID NO: 11; and wherein the antibody, or an antigen binding fragment thereof, that binds IL-4R ⁇ comprises a VH sequence set forth in SEQ ID NO: 297 and a VL sequence set forth in SEQ ID NO: 300.
  • compositions comprising hyaluronidase or a variant thereof and a multi-specific antibody comprising a first antigen binding region that binds OX40L and a second antigen binding region that binds IL-4R ⁇ , wherein the antigen binding region that binds OX40L comprises a VH sequence set forth in SEQ ID NO: 1 and a VL sequence set forth in SEQ ID NO: 11; and wherein the antigen binding region that binds IL-4R ⁇ comprises a VH sequence set forth in SEQ ID NO: 297 and a VL sequence set forth in SEQ ID NO: 300.
  • a CDR-H1 comprising the sequence set forth in SEQ ID NO: 2
  • a CDR-H2 comprising the sequence set forth in SEQ ID NO: 5
  • a CDR-H3 comprising the sequence set forth in SEQ ID NO: 8
  • a CDR-L1 comprising the sequence set forth in SEQ ID NO: 12
  • a CDR-L2 comprising the sequence set forth in SEQ ID NO: 15
  • a CDR-L3 comprising the sequence set forth in SEQ ID NO: 17, and wherein the antibody, or an antigen binding fragment thereof, that binds IL-4R ⁇ comprises a CDR-H1 comprising the
  • hyaluronidase or a variant thereof and a multi-specific antibody comprising a first antigen binding region that binds OX40L and a second antigen binding region that binds IL-4R ⁇
  • the antigen binding region that binds OX40L comprises a CDR-H1 comprising the sequence set forth in SEQ ID NO: 2; a CDR-H2 comprising the sequence set forth in SEQ ID NO: 5; a CDR-H3 comprising the sequence set forth in SEQ ID NO: 8; a CDR-L1 comprising the sequence set forth in SEQ ID NO: 12; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 15; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 17, and wherein the antigen binding region that binds IL-4R ⁇ comprises a CDR-H1 comprising the sequence set forth in SEQ ID NO: 273; a CDR-H2 comprising the sequence set forth in SEQ ID NO
  • hyaluronidase or a variant thereof and a multi-specific antibody comprising a first antigen binding region that binds OX40L and a second antigen binding region that binds IL-4R ⁇ , wherein the antigen binding region that binds OX40L comprises a VH sequence set forth in SEQ ID NO: 1 and a VL sequence set forth in SEQ ID NO: 11; and wherein the antigen binding region that binds IL-4R ⁇ comprises a VH sequence set forth in SEQ ID NO: 297 and a VL sequence set forth in SEQ ID NO: 300.
  • Describe herein are methods of treating an inflammatory disorder or disease in a human patient comprising administering to the patient an isolated antibody, or an antigen binding fragment thereof, that binds OX40L, an isolated antibody, or an antigen binding fragment thereof, that binds IL-4R ⁇ , and a hyaluronidase or a variant thereof, wherein the antibody, or an antigen binding fragment thereof, that binds OX40L comprises a CDR-H1 comprising the sequence set forth in SEQ ID NO: 2; a CDR-H2 comprising the sequence set forth in SEQ ID NO: 5; a CDR-H3 comprising the sequence set forth in SEQ ID NO: 8; a CDR-L1 comprising the sequence set forth in SEQ ID NO: 12; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 15; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 17, and wherein the antibody, or an antigen binding fragment thereof,
  • Described herein are methods of treating an inflammatory disorder or disease in a human patient comprising administering to the patient an isolated antibody, or an antigen binding fragment thereof, that binds OX40L, an isolated antibody, or an antigen binding fragment thereof, that binds IL-4R ⁇ , and a hyaluronidase or a variant thereof, wherein the antibody, or an antigen binding fragment thereof, that binds OX40L comprises a VH sequence set forth in SEQ ID NO: 1 and a VL sequence set forth in SEQ ID NO: 11; and wherein the antibody, or an antigen binding fragment thereof, that binds IL-4R ⁇ comprises a VH sequence set forth in SEQ ID NO: 297 and a VL sequence set forth in SEQ ID NO: 300.
  • Describe herein are methods of treating an inflammatory disorder or disease in a human patient comprising administering to the patient hyaluronidase or a variant thereof and a multi-specific antibody comprising a first antigen binding region that binds OX40L and a second antigen binding region that binds IL-4R ⁇ , wherein the antigen binding region that binds OX40L comprises a CDR-H1 comprising the sequence set forth in SEQ ID NO: 2; a CDR-H2 comprising the sequence set forth in SEQ ID NO: 5; a CDR-H3 comprising the sequence set forth in SEQ ID NO: 8; a CDR-L1 comprising the sequence set forth in SEQ ID NO: 12; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 15; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 17, and wherein the antigen binding region that binds IL-4R ⁇ comprises a CDR-H1
  • Described herein are methods of treating an inflammatory disorder or disease in a human patient comprising administering to the patient hyaluronidase or a variant thereof and a multi-specific antibody comprising a first antigen binding region that binds OX40L and a second antigen binding region that binds IL-4R ⁇ , wherein the antigen binding region that binds OX40L comprises a VH sequence set forth in SEQ ID NO: 1 and a VL sequence set forth in SEQ ID NO: 11; and wherein the antigen binding region that binds IL-4R ⁇ comprises a VH sequence set forth in SEQ ID NO: 297 and a VL sequence set forth in SEQ ID NO: 300.
  • the hyaluronidase is a recombinant human hyaluronidase or variant thereof. In certain embodiments, the hyaluronidase is a recombinant human hyaluronidase. In certain embodiments, the recombinant human hyaluronidase comprises the amino acid sequence set forth in any one of SEQ ID NOs: 1076-1142 and 1087-1142. In certain embodiments, the recombinant human hyaluronidase is rHuPH20. In certain embodiments, the rHuPH20 formulation is ENHANZE®.
  • the antibodies or multi-specific antibody and hyaluronidase or a variant thereof are for use in treating an inflammatory disorder or disease.
  • the inflammatory disorder or disease is atopic dermatitis.
  • the inflammatory disorder or disease is asthma; chronic sinusitis with nasal polyps; Chronic Rhinosinusitis without Nasal Polyps (CRSsNP); eosinophilic esophagitis (EoE); an Eosinophilic gastrointestinal disorder or disease (EGID), such as Eosinophilic Gastritis (EoG), Eosinophilic Enteritis (EoN), Eosinophilic Colitis (EoC), or Eosinophilic Gastroenteritis (EGE); Churg-Strauss syndrome/Eosinophilic granulomatosis with polyangiitis (EGPA); Prurigo Nodularis (PN); Chronic Spontaneous Urticaria (CSU); Chronic Prusinophilic granulomatosis with polyangi
  • FIGURE 1 is a graph showing the ability of exemplary anti-hOX40L antibodies to bind to hOX40L-expressing CHO cells.
  • FIGURE 2 is a graph showing the OD450-540 value with increasing concentration of the indicated antibody in the presence of hOX40L to determine the ability of the indicated antibodies to block the binding of hOX40L to hOX40.
  • FIGURE 3 is a graph showing the luminescence units (RLU) with increasing concentration of the indicated antibody in the presence of cells that express hOX40 to determine the ability of the indicated antibodies to block the binding of hOX40L to hOX40.
  • RLU luminescence units
  • FIGURE 4A and FIGURE 4B are graphs showing the percent inhibition of OX40L and OX40L binding by the indicated antibody compared to a positive control.
  • FIGURE 5A - FIGURE 5C are graphs showing inhibition of IFNgamma response in PBMC-CD4 T cell mixed lymphocyte reaction (MLR) with 100 nM, 20 nM and 4 nM concentrations of indicated antibodies.
  • FIGURE 6A and FIGURE 6B are a set of graphs showing the concentration of the indicated antibody over time in the serum of cynomolgus monkeys after receiving a single dose of the indicated antibody.
  • FIGURE 7A and FIGURE 7B show the ability of exemplary antibodies and dupilumab to inhibit IL-4 and IL-13 binding.
  • FIGURE 8A and FIGURE 8B show the ability of exemplary antibodies and dupilumab to inhibit IL-4-induced and IL-13-induced STAT6 phosphorylation (pSTAT6).
  • FIGURE 9A and FIGURE 9B show the ability of exemplary antibodies and dupilumab to inhibit IL-4- and/or IL-13-induced TARC secretion.
  • FIGURE 10A and FIGURE 10B show the ability of exemplary antibodies and dupilumab to inhibit IL-4-induced and IL-13-induced proliferation of TF-1 cells.
  • FIGURE 11A and FIGURE 11B show the serum concentration of exemplary antibodies (Construct 13 (mAb422), Construct 38 (mAb471), and dupilumab) over time after a single intravenous (FIGURE 11A) or subcutaneous (FIGURE 11B) administration of 25 mg/kg in non-human primates.
  • FIGURE 12 is a heatmap depicting the changes in cytokine/chemokine levels of thymus and activation regulated chemokine (TARC), macrophage-derived chemokine (MDC), interleukin (IL)-13, IL-5, interferon gamma (IFNg), tumor necrosis factor alpha (TNFa), IL-31, and granulocyte-macrophage colony-stimulating factor (GM-CSF) in allogeneic lymphocyte reaction experiments performed on myeloid dendritic cells (mDCs) primed with recombinant human TSLP and allogeneic CD4-positive cells from four healthy volunteers treated with test article, Construct 38, Construct 114, a combination of Construct 38 and Construct 114, dupilumab, or amlitelimab, or unstimulated.
  • TARC thymus and activation regulated chemokine
  • MDC macrophage-derived chemokine
  • IFNg interleuk
  • composition when a composition is described as “consisting essentially of” the listed components, the composition contains the components listed, and may contain other components which do not substantially affect the condition being treated, but do not contain any other components which substantially affect the condition being treated other than those components expressly listed; or, if the composition does contain extra components other than those listed which substantially affect the condition being treated, the composition does not contain a sufficient concentration or amount of the extra components to substantially affect the condition being treated.
  • a method is described as “consisting essentially of” the listed steps, the method contains the steps listed, and may contain other steps that do not substantially affect the condition being treated, but the method does not contain any other steps which substantially affect the condition being treated other than those steps expressly listed.
  • the terms “increase” and “activate” refer to an increase of 10%, 20%, 30%, 40%, 50%, 60%, 70%, 75%, 80%, 85%, 90%, 95%, 100%, 2-fold, 3-fold, 4-fold, 5-fold, 10-fold, 20-fold, 50-fold, 100-fold, or greater in a recited variable.
  • the terms “reduce” and “inhibit” refer to a decrease of 10%, 20%, 30%, 40%, 50%, 60%, 70%, 75%, 80%, 85%, 90%, 95%, 2-fold, 3-fold, 4-fold, 5-fold, 10-fold, 20-fold, 50-fold, 100-fold, or greater in a recited variable.
  • an “antagonist” is an entity that binds to and antagonizes a receptor.
  • an “antagonist” is an entity that binds to and antagonizes a receptor.
  • methods of determining these characteristics are known in the art.
  • the term “optionally” is meant, when used sequentially, to include from one to all of the enumerated combinations and contemplates all sub-combinations.
  • amino acid refers to the twenty common naturally occurring amino acids.
  • Naturally occurring amino acids include alanine (Ala; A), arginine (Arg; R), asparagine (Asn; N), aspartic acid (Asp; D), cysteine (Cys; C); glutamic acid (Glu; E), glutamine (Gln; Q), Glycine (Gly; G); histidine (His; H), isoleucine (Ile; I), leucine (Leu; L), lysine (Lys; K), methionine (Met; M), phenylalanine (Phe; F), proline (Pro; P), serine (Ser; S), threonine (Thr; T), tryptophan (Trp; W), tyrosine (Tyr; Y), and valine (Val; V).
  • affinity refers to the strength of the sum total of non-covalent interactions between a single binding site of a molecule (e.g., an antibody) and its binding partner (e.g., an antigen or epitope). Unless indicated otherwise, as used herein, “affinity” refers to intrinsic binding affinity, which reflects a 1:1 interaction between members of a binding pair (e.g., antibody and antigen or epitope).
  • kd (sec-1), as used herein, refers to the dissociation rate constant of a particular antibody- antigen interaction. This value is also referred to as the koff value.
  • ka M-1 ⁇ sec-1
  • KD Kd/ka.
  • affinity of an antibody is described in terms of the KD for an interaction between such antibody and its antigen. For clarity, as known in the art, a smaller KD value indicates a higher affinity interaction, while a larger KD value indicates a lower affinity interaction.
  • the terms “conservative mutation,” “conservative substitution,” and “conservative amino acid substitution” refer to a substitution of one or more amino acids for one or more different amino acids that exhibit similar physicochemical properties, such as polarity, electrostatic charge, and steric volume. These properties are summarized for each of the twenty naturally occurring amino acids in TABLE 1 below. TABLE 1.
  • human antibody refers to an antibody which possesses an amino acid sequence corresponding to that of an antibody produced by a human or a human cell, or derived from a non-human source that utilizes a human antibody repertoire or human antibody-encoding sequences (e.g., obtained from human sources or designed de novo). Human antibodies specifically exclude humanized antibodies.
  • humanized antibody refers to a protein having a sequence that differs from the sequence of an antibody derived from a non-human species by one or more amino acid substitutions, deletions, and/or additions, such that the humanized antibody is less likely to induce an immune response, and/or induces a less severe immune response, as compared to the non-human species antibody, when it is administered to a human subject.
  • multispecific antibody refers to an antibody that comprises two or more different antigen-binding domains that collectively specifically bind two or more different epitopes.
  • a “monospecific antibody” is an antibody that comprises one or more binding sites that specifically bind to a single epitope.
  • a monospecific antibody is a naturally occurring IgG molecule which, while divalent (i.e., having two antigen-binding domains), recognizes the same epitope at each of the two antigen-binding domains.
  • the binding specificity may be present in any suitable valency.
  • the term “monoclonal antibody” refers to an antibody from a population of substantially homogeneous antibodies.
  • a population of substantially homogeneous antibodies comprises antibodies that are substantially similar and that bind the same epitope(s), except for variants that may normally arise during production of the monoclonal antibody. Such variants are generally present in only minor amounts.
  • a monoclonal antibody is typically obtained by a process that includes the selection of a single antibody from a plurality of antibodies.
  • the selection process can be the selection of a unique clone from a plurality of clones, such as a pool of hybridoma clones, phage clones, yeast clones, bacterial clones, or other recombinant DNA clones.
  • the selected antibody can be further altered, for example, to improve affinity for the target (“affinity maturation”), to humanize the antibody, to improve its production in cell culture, and/or to reduce its immunogenicity in a subject.
  • affinity maturation affinity for the target
  • single-chain refers to a molecule comprising amino acid monomers linearly linked by peptide bonds.
  • an scFv has a variable domain of light chain (VL) connected from its C-terminus to the N-terminal end of a variable domain of heavy chain (VH) by a polypeptide chain.
  • VL variable domain of light chain
  • VH variable domain of heavy chain
  • the scFv comprises of polypeptide chain where in the C-terminal end of the VH is connected to the N-terminal end of VL by a polypeptide chain.
  • the “Fab fragment” (also referred to as fragment antigen-binding) contains the constant domain (CL) of the light chain and the first constant domain (CH1) of the heavy chain along with the variable domains VL and VH on the light and heavy chains respectively.
  • the variable domains comprise the complementarity determining loops (CDR, also referred to as hypervariable region) that are involved in antigen-binding.
  • CDR complementarity determining loops
  • Fab′ fragments differ from Fab fragments by the addition of a few residues at the carboxy terminus of the heavy chain CH1 domain including one or more cysteines from the antibody hinge region.
  • “F(ab’)2” fragments contain two Fab’ fragments joined, near the hinge region, by disulfide bonds.
  • F(ab’)2 fragments may be generated, for example, by recombinant methods or by pepsin digestion of an intact antibody.
  • the F(ab’) fragments can be dissociated, for example, by treatment with ß-mercaptoethanol.
  • “Fv” fragments comprise a non-covalently-linked dimer of one heavy chain variable domain and one light chain variable domain.
  • Single-chain Fv or “sFv” or “scFv” includes the VH and VL domains of an antibody, wherein these domains are present in a single polypeptide chain.
  • the Fv polypeptide further comprises a polypeptide linker between the VH and VL domains which enables the scFv to form the desired structure for antigen-binding.
  • a polypeptide linker between the VH and VL domains which enables the scFv to form the desired structure for antigen-binding.
  • an Fc domain may be attached to the C-terminal of the scFv.
  • the Fc domain may follow the VH or VL, depending on the orientation of the variable domains in the scFv (i.e., VH-VL or VL- VH). Any suitable Fc domain known in the art or described herein may be used.
  • the Fc domain comprises an IgG4 Fc domain.
  • single domain antibody or “sdAb” refers to a molecule in which one variable domain of an antibody specifically binds to an antigen without the presence of the other variable domain.
  • Single domain antibodies are described in Arabi Ghahroudi et al., FEBS Letters, 1998, 414:521-526 and Muyldermans et al., Trends in Biochem. Sci., 2001, 26:230-245, each of which is incorporated by reference in its entirety.
  • Single domain antibodies are also known as sdAbs or nanobodies. SdAbs are fairly stable and easy to express as fusion partner with the Fc chain of an antibody (Harmsen MM, De Haard HJ (2007). “Properties, production, and applications of camelid single-domain antibody fragments”. Appl. Microbiol Biotechnol.77(1): 13-22).
  • full length antibody “intact antibody,” and “whole antibody” are used herein interchangeably to refer to an antibody having a structure substantially similar to a naturally occurring antibody structure and having heavy chains that comprise an Fc region.
  • a “full length antibody” is an antibody that comprises two heavy chains and two light chains.
  • antibody fragment refers to an antibody that comprises a portion of an intact antibody, such as the antigen-binding or variable region of an intact antibody.
  • a native cell, or host cell in the case of a recombinantly produced antibody that in certain embodiments, is substantially free of cellular material includes preparations of protein having less than about 30%, less than about 25%, less than about 20%, less than about 15%, less than about 10%, less than about 5%, less than about 4%, less than about 3%, less than about 2%, or less than about 1% (by dry weight) of contaminating protein.
  • percent “identity,” in the context of two or more nucleic acid or polypeptide sequences, refer to two or more sequences or subsequences that have a specified percentage of nucleotides or amino acid residues that are the same, when compared and aligned for maximum correspondence, as measured using one of the sequence comparison algorithms described below (e.g., using publicly available computer software such as BLAST, BLASTP, BLASTN, BLAST-2, ALIGN, MEGALIGN (DNASTAR), CLUSTALW, CLUSTAL OMEGA, or MUSCLE software or other algorithms available to persons of skill) or by visual inspection.
  • sequence comparison algorithms e.g., using publicly available computer software such as BLAST, BLASTP, BLASTN, BLAST-2, ALIGN, MEGALIGN (DNASTAR), CLUSTALW, CLUSTAL OMEGA, or MUSCLE software or other algorithms available to persons of skill
  • sequence comparison typically one sequence acts as a reference sequence to which test sequences are compared.
  • test and reference sequences are input into a computer, subsequence coordinates are designated, if necessary, and sequence algorithm program parameters are designated.
  • sequence comparison algorithm calculates the percent sequence identity for the test sequence(s) relative to the reference sequence, based on the designated program parameters.
  • Optimal alignment of sequences for comparison can be conducted, e.g., by the local homology algorithm of Smith & Waterman, Adv. Appl. Math.2:482 (1981), by the homology alignment algorithm of Needleman & Wunsch, J. Mol. Biol.48:443 (1970), by the search for similarity method of Pearson & Lipman, Proc. Nat’l. Acad. Sci.
  • a range of 1 to 50 is understood to include any number, combination of numbers, or sub-range from the group consisting of 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, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, and 50.
  • atopic dermatitis disease severity outcome measure refers to a determination of certain signs, symptoms, features or parameters that have been associated with atopic dermatitis and that can be quantitatively or qualitatively assessed.
  • exemplary atopic dermatitis disease severity outcome measures include "Eczema Area and Severity Index” (EASI), "Severity Scoring of Atopic Dermatitis” (SCORAD), "Validated Investigator Global Assessment-Atopic Dermatitis” (vIGA-AD), “Investigator Global Assessment of Signs” (IGSA), Rajka/Langeland Atopic Dermatitis Severity Score, “Body Surface Area” (BSA), and Patient-Reported Outcomes including Pruritus Visual Analog Scale (an aspect of disease severity assessed as part of SCORAD), Sleep Loss Visual Analog Scale (an aspect of disease severity assessed as part of SCORAD), Atopic Dermatitis Symptom Diary (ADSD), Atopic Dermatitis Impact Questionnaire (ADIQ), Dermatology Life Quality Index (EASI), S
  • Hyaluronidases refers to an enzyme that degrades hyaluronic acid, which constitutes an essential part of the extracellular matrix. Included in this definition are naturally occurring hyaluronidases, recombinant hyaluronidases, both human and from other sources, as well as variants thereof.
  • hyaluronidases include, but are not limited to, nonhuman hyaluronidases, including bacterial hyaluronidases, bovine hyaluronidases, ovine hyaluronidases, and variants thereof. Reference to hyaluronidase refers to all forms, including variants. [00287] Hyaluronidases were initially discovered in bacteria, and are now known to be widely distributed in nature and have been found in many different species, including insects, snakes, and mammals.
  • Human hyaluronidase is present both in organs (e.g., testis, spleen, skin, eyes, liver, kidneys, uterus, and placenta) and in body fluids (e.g., tears, blood, and semen).
  • organs e.g., testis, spleen, skin, eyes, liver, kidneys, uterus, and placenta
  • body fluids e.g., tears, blood, and semen.
  • HYAL1-4, HYAL-P1 and PH-20 six different hyaluronidases, HYAL1-4, HYAL-P1 and PH-20, have been identified.
  • PH-20 exerts the strongest biologic activity, is found in high concentrations in the testicles, and can be localized on the head and the acrosome of human spermatozoa (see, e.g., Weber GC, et al., Adv. Exp. Med. Biol.2019;1148:255-2
  • Hyaluronidases are classified into three categories according to their mechanism of action (see, e.g., Jung H., Arch. Plast. Surg.2020 Jul;47(4):297-300).
  • mammalian hyaluronidases are endo- ⁇ -N-acetylhexosaminidases that break down ⁇ -1,4 glycosidic linkages to form tetrasaccharides.
  • leech/hookworm hyaluronidases are endo- ⁇ -D- glucuronidases that break down ⁇ -1,3 glycosidic bonds to form pentasaccharides and hexasaccharides.
  • Hyaluronidases are classified as hyaluronate lyases. Unlike other hyaluronidases, they do not catalyze hydrolysis reactions. Instead, they produce unsaturated disaccharides through a ⁇ -elimination reaction at ⁇ -1,4 glycosidic linkage. [00289] Hyaluronidases can also be classified into two types according to the pH at which they are most active (see, e.g., Jung H., Arch. Plast. Surg.2020 Jul;47(4):297-300). Acid- active hyaluronidases are activated at a pH of 3 to 4.
  • Neutral-active hyaluronidases which include the hyaluronidase enzymes found in snake and bee venom, are activated at a pH of 5 to 8 (see, e.g., Cavallini M, et al., Aesthet. Surg. J.2013;33:1167–74).
  • Hyaluronidase use has become more diverse and widespread in clinical practice.
  • chondroitinases that are hyaluronan degrading enzymes include, but are not limited to, chondroitin ABC lyase (also known as chondroitinase ABC), chondroitin AC lyase (also known as chondroitin sulfate lyase or chondroitin sulfate eliminase) and chondroitin C lyase.
  • Chondroitin ABC lyase comprises two enzymes, chondroitin-sulfate-ABC endolyase (EC 4.2.2.20) and chondroitin-sulfate-ABC exolyase (EC 4.2.2.21).
  • chondroitin- sulfate-ABC endolyases and chondroitin-sulfate-ABC exolyases include, but are not limited to, those from Proteus vulgaris and Flavobacterium heparinum (the Proteus vulgaris chondroitin-sulfate-ABC endolyase (e.g., see Sato et al. (1994) Appl. Microbiol. Biotechnol. 41(1):39-46)).
  • Exemplary chondroitinase AC enzymes from the bacteria include, but are not limited to, those from Flavobacterium heparinum, Victivallis vadensis, and Arthrobacter aurescens (see, e.g., Tkalec et al. (2000) Applied and Environmental Microbiology 66(1):29- 35; Ernst et al. (1995) Critical Reviews in Biochemistry and Molecular Biology 30(5):387- 444).
  • Exemplary chondroitinase C enzymes from the bacteria include, but are not limited to, those from Streptococcus and Flavobacterium (Hibi et al. (1989) FEMS-Microbiol-Lett. 48(2):121-4; Michelacci et al.
  • Hyaluronidases include bacterial hyaluronidases (EC 4.2.2.1 or EC 4.2.99.1), hyaluronidases from leeches, other parasites, and crustaceans (EC 3.2.1.36), and mammalian- type hyaluronidases (EC 3.2.1.35).
  • Hyaluronidases include any of non-human origin including, but not limited to, murine, canine, feline, leporine, avian, bovine, ovine, porcine, equine, piscine, ranine, bacterial, and any from leeches, other parasites, and crustaceans.
  • Exemplary non-human hyaluronidases include, hyaluronidases from cows (SEQ ID NOs:10, 11, 64 of US Patent No.: 8,568,713) and BH55 (U.S. Pat.
  • strain FB24 (SEQ ID NO:67 of US Patent No.: 8,568,713), Bdellovibrio bacteriovorus (SEQ ID NO:68 of US Patent No.: 8,568,713), Propionibacterium acnes (SEQ ID NO:69 of US Patent No.: 8,568,713), Streptococcus agalactiae ((SEQ ID NO:70 of US Patent No.: 8,568,713); 18RS21 (SEQ ID NO:71 of US Patent No.: 8,568,713 ); serotype Ia (SEQ ID NO:72 of US Patent No.: 8,568,713); serotype III (SEQ ID NO:73 of US Patent No.: 8,568,713), Staphylococcus aureus (strain COL) (SEQ ID NO:74 of US Patent No.: 8,568,713 ); strain MRSA252 (SEQ ID NOs:75 and 76 of US Patent No.: 8,568,713 of US Patent No.: 8,568,71
  • Hyaluronidases also include those of human origin.
  • Exemplary human hyaluronidases include PH20, HYAL1 (SEQ ID NO:36 of US Patent No.: 8,568,713), HYAL2 (SEQ ID NO:37 of US Patent No.: 8,568,713), HYAL3 (SEQ ID NO:38 of US Patent No.: 8,568,713), and HYAL4 (SEQ ID NO:36 of US Patent No.: 8,568,713).
  • the sequences and contents of US Patent No.8,568,713 are expressly incorporated herein by reference.
  • soluble hyaluronidases include, ovine and bovine PH20, soluble human PH20 and soluble rHuPH20.
  • bovine or ovine soluble hyaluronidases are Vitrase® (ovine hyaluronidase) and Amphadase ® (bovine hyaluronidase).
  • Hyaluronidases as described herein include precursor hyaluronan degrading enzyme polypeptides and mature hyaluronan degrading enzyme polypeptides (such as those in which a signal sequence has been removed), truncated forms thereof that have activity, and includes allelic variants and species variants, variants encoded by splice variants, and other variants, including polypeptides that have at least 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or more sequence identity to the polypeptides set forth in SEQ ID NOs:1076-1085 and 1087-1142.
  • Hyaluronidases also include those that contain chemical or posttranslational modifications and those that do not contain chemical or posttranslational modifications. Such modifications include, but are not limited to, pegylation, albumination, glycosylation, farnesylation, carboxylation, hydroxylation, phosphorylation, and other polypeptide modifications known in the art.
  • a soluble hyaluronidase refers to a polypeptide characterized by its solubility under physiologic conditions. Soluble hyaluronidases can be distinguished, for example, by its partitioning into the aqueous phase of a Triton X-114 solution warmed to 37 oC.
  • Membrane-anchored such as lipid anchored hyaluronidases, will partition into the detergent rich phase, but will partition into the detergent-poor or aqueous phase following treatment with Phospholipase-C.
  • soluble hyaluronidases include membrane anchored hyaluronidases in which one or more regions associated with anchoring of the hyaluronidase to the membrane has been removed or modified, where the soluble form retains hyaluronidase activity.
  • Soluble hyaluronidases include recombinant soluble hyaluronidases and those contained in or purified from natural sources.
  • activity refers to a functional activity or activities of a polypeptide or portion thereof associated with a full-length (complete) protein. Functional activities include, but are not limited to, biological activity, catalytic or enzymatic activity, antigenicity (ability to bind or compete with a polypeptide for binding to an anti-polypeptide antibody), immunogenicity, ability to form multimers, and the ability to specifically bind to a receptor or ligand for the polypeptide.
  • hyaluronidase activity refers to the ability to enzymatically catalyze the cleavage of hyaluronic acid.
  • USP United States Pharmacopeia
  • HA hyaluronan
  • a Reference Standard solution can be used in an assay to ascertain the relative activity, in units, of any hyaluronidase.
  • In vitro assays to determine the hyaluronidase activity of hyaluronidases, such as soluble rHuPH20, are known in the art.
  • Exemplary assays include the microturbidity assay (see e.g., Example 3 of US Patent No.:8,568,713) that measures cleavage of hyaluronic acid by hyaluronidase indirectly by detecting the insoluble precipitate formed when the uncleaved hyaluronic acid binds with serum albumin.
  • Reference Standards can be used, for example, to generate a standard curve to determine the activity in Units of the hyaluronidase being tested.
  • "functionally equivalent amount” or grammatical variations thereof, with reference to a hyaluronan degrading enzyme refers to the amount of hyaluronan degrading enzyme that achieves the same effect as an amount (such as a known number of Units of hyaluronidase activity) of a reference enzyme, such as a hyaluronidase.
  • the activity of any hyaluronan degrading enzyme can be compared to the activity of rHuPH20 to determine the functionally equivalent amount of a hyaluronan degrading enzyme that would achieve the same effect as a known amount of rHuPH20.
  • the ability of a hyaluronan degrading enzyme to act as a spreading or diffusing agent can be assessed by injecting it into the lateral skin of mice with trypan blue (see e.g. U.S. Pat. Publication No. 20050260186), and the amount of hyaluronan degrading enzyme required to achieve the same amount of diffusion as, for example, 100 units of a Hyaluronidase Reference Standard, can be determined.
  • hyaluronan degrading enzymes are hyaluronidases, particularly soluble hyaluronidases, such as a PH20, or a truncated or variant form thereof.
  • the PH20 can be, for example, an ovine, bovine or truncated human PH20.
  • the human PH20 mRNA transcript is normally translated to generate a 509 amino acid precursor polypeptide (SEQ ID NO:1076; and replicated below) containing a 35 amino acid signal sequence at the N-terminus (amino acid residue positions 1-35) and a 19 amino acid glycosylphosphatidylinositol (GPI) anchor attachment signal sequence at the C-terminus (amino acid residue positions 491-509).
  • the mature PH20 is, therefore, a 474 amino acid polypeptide set forth in SEQ ID NO:1077.
  • the C-terminal GPI-attachment signal peptide is cleaved to facilitate covalent attachment of a GPI anchor to the newly-formed C-terminal amino acid at the amino acid position corresponding to position 490 of the precursor polypeptide set forth in SEQ ID NO:1076.
  • a 474 amino acid GPI-anchored mature polypeptide with an amino acid sequence set forth in SEQ ID NO:1077 is produced.
  • the amino acid sequence of the human PH20 precursor polypeptide (SEQ ID NO: 1076; 509 amino acids) is as follows: MGVLKFKHIFFRSFVKSSGVSQIVFTFLLIPCCLTLNFRAPPVIPNVPFLWAWNAPSEF CLGKFDEPLDMSLFSFIGSPRINATGQGVTIFYVDRLGYYPYIDSITGVTVNGGIPQKIS LQDHLDKAKKDITFYMPVDNLGMAVIDWEEWRPTWARNWKPKDVYKNRSIELVQ QQNVQLSLTEATEKAKQEFEKAGKDFLVETIKLGKLLRPNHLWGYYLFPDCYNHHY KKPGYNGSCFNVEIKRNDDLSWLWNESTALYPSIYLNTQQSPVAATLYVRNRVREAI RVSKIPDAKSPLPVFAYTRIVFTDQVLKFLSQDELVYTFGETVALGASGIVIWGTLSIM RSMKSCLLLDNYMETILNPYIINVTLA
  • amino acid sequence of the mature PH20 polypeptide (SEQ ID NO: 1077; 474 amino acids) is as follows: LNFRAPPVIPNVPFLWAWNAPSEFCLGKFDEPLDMSLFSFIGSPRINATGQGVTIFYVD RLGYYPYIDSITGVTVNGGIPQKISLQDHLDKAKKDITFYMPVDNLGMAVIDWEEWR PTWARNWKPKDVYKNRSIELVQQQNVQLSLTEATEKAKQEFEKAGKDFLVETIKLG KLLRPNHLWGYYLFPDCYNHHYKKPGYNGSCFNVEIKRNDDLSWLWNESTALYPSI YLNTQQSPVAATLYVRNRVREAIRVSKIPDAKSPLPVFAYTRIVFTDQVLKFLSQDEL VYTFGETVALGASGIVIWGTLSIMRSMKSCLLLDNYMETILNPYIINVTLAAKMCSQV LCQEQGVCIRKNWNSSDYLHLNPDN
  • the Peptide 3 region which corresponds to amino acid positions 242-262 of the mature polypeptide set forth in SEQ ID NO:1077, and positions 277-297 of the precursor polypeptide set forth in SEQ ID NO:1076, appears to be important for enzyme activity at acidic pH. Within this region, amino acids at positions 249 and 252 of the mature PH20 polypeptide appear to be essential for activity, and mutagenesis of either one results in a polypeptide essentially devoid of activity (Arming et al., (1997) Eur. J. Biochem.247:810- 814). [00303] In addition to the catalytic sites, PH20 also contains a hyaluronan-binding site.
  • soluble recombinant human PH20 refers to a soluble form of human PH20 that is recombinantly expressed in Chinese Hamster Ovary (CHO) cells.
  • Soluble human PH20 or sHuPH20 includes mature polypeptides lacking all or a portion of the glycosylphospatidylinositol (GPI) attachment site at the C-terminus such that upon expression, the polypeptides are soluble.
  • Soluble rHuPH20 is encoded by a nucleic acid that includes the signal sequence and is set forth in SEQ ID NO:1086. Also included are DNA molecules that are allelic variants thereof and other soluble variants. The nucleic acid encoding soluble rHuPH20 is expressed in CHO cells which secrete the mature polypeptide.
  • exemplary sHuPH20 polypeptides include mature polypeptides having an amino acid sequence set forth in any one of SEQ ID NOs:1078-1085 and 1087-1142.
  • Other variants can have 60%, 70%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more sequence identity to any of SEQ ID NOs: 1078-1085 and 1087-1142, as long they retain a hyaluronidase activity and are soluble.
  • allelic variants and other variants also are included, including those corresponding to the precursor human PH20 polypeptide set forth in SEQ ID NO: 1076 and the mature human PH20 polypeptide set forth in SEQ ID NO: 1077.
  • rHuPH20 was approved by the US Food and Drug Administration in 2005 as an adjuvant to increase the dispersion and absorption of other injected drugs.
  • Recombinant human hyaluronidase PH20 is a transiently and locally-acting permeation enhancer that increases the dispersion and absorption of other injected agents.
  • rHuPH20 is a glycosylated single chain protein with up to 447 amino acids, synthesized in CHO cells. Recombinant human hyaluronidase PH20 degrades HA under physiologic conditions and acts as a spreading factor in vivo.
  • rHUPH20 when combined (co- mixed) or co-formulated with certain injectable drugs, rHUPH20 facilitates the absorption and dispersion of these drugs by temporarily reducing resistance to bulk fluid flow in the subcutaneous space. The permeability barrier in these tissues is restored to pre-injection levels within 24 to 48 hours after injection of rHuPH20.
  • any suitable hyaluronidase e.g., a recombinant human hyaluronidase
  • hyaluronidase e.g., a recombinant human hyaluronidase
  • US Patent No.: 7,767,429 e.g., SEQ ID NO:1
  • US Patent No.: 7,846,431 e.g., SEQ ID NO:1
  • US Patent No.: 7,871,607 e.g., SEQ ID NO:1
  • US Patent No.: 8,105,586 e.g., SEQ ID NO:1
  • US Patent No.: 8,202,517 e.g., SEQ ID NO:1
  • US Patent No.: 8,257,699 e.g., SEQ ID NO:1
  • US Patent No.: 8,450,470 e.g., SEQ ID NO:1
  • US Patent No.: 8,431,124 e.g., SEQ ID NO
  • An exemplary recombinant human hyaluronidase is rHuPH20, i.e., the active ingredient in the commercial product Hylenex® recombinant (hyaluronidase human injection), which is supplied as ENHANZE® drug product.
  • Hyaluronidases that have altered properties, such as increased stability and/or activity, have been produced and can also be used, including, but not limited to those described in U.S. Pat. No.9,447,401, U.S. Pat. No.10,865,400, and U.S. Pat. No. 11,041,149, the contents of each of which are expressly incorporated herein by reference. These patents provide about 7000 examples in which the effects of replacing each amino acid with 15 other amino acids on activity and stability were identified and described. [00312] Other variants are known to those of skill in the art including those described, for example, in WO2020/022791 and WO2020197230A, the contents of each of which are expressly incorporated herein by reference.
  • variant polypeptides include replacements, insertions, and deletions, including one or more amino acid residues S343E, M345T, K349E, L353A, L354I, N356E, and 136 IT. Variants that contain such modifications and others are set forth in SEQ ID NOs: 60-115 from WO2020/022791. WO2021/150079 also provides variant polypeptides described as having increased stability.
  • the recombinant human hyaluronidase includes a sequence of amino acids in any one of SEQ ID NOs: 1076-1085 and 1087-1142, or has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 95%, 97%, 98%, or 99% sequence identity to a sequence of amino acids included in SEQ ID NO: 1076- 1085 and 1087-1142 and retains hyaluronidase activity.
  • the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1076. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1076. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1078. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1078. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1079.
  • the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1079. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1080. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1080. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1081. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1081.
  • the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1082. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1082. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1083. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1083. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1084.
  • the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1084. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1085. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1085. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1087. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1087.
  • the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1088. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1088. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1089. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1089. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1090.
  • the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1090. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1091. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1091. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1092. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1092.
  • the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1093. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1093. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1094. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1094. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1095.
  • the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1095. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1096. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1096. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1097. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1097.
  • the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1098. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1098. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1099. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1099. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1100.
  • the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1100. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1101. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1101. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1102. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1102.
  • the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1103. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1103. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1104. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1104. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1105.
  • the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1105. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1106. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1106. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1107. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1107.
  • the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1108. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1108. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1109. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1109. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1110.
  • the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1110. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1111. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1111. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1112. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1112.
  • the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1113. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1113. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1114. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1114. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1115.
  • the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1115. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1116. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1116. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1117. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1117.
  • the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1118. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1118. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1119. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1119. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1120.
  • the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1120. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1121. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1121. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1122. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1122.
  • the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1123. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1123. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1124. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1124. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1125.
  • the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1125. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1126. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1126. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1127. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1127.
  • the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1128. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1128. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1129. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1129. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1130.
  • the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1130. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1131. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1131. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1132. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1132.
  • the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1133. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1133. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1134. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1134. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1135.
  • the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1135. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1136. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1136. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1137. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1137.
  • the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1138. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1138. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1139. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1139. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1140.
  • the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1140. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1141. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1141. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1142. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1142.
  • the recognized immunoglobulin genes include the kappa, lambda, alpha, gamma, delta, epsilon and mu constant region genes, as well as the myriad immunoglobulin variable region genes.
  • Light chains are classified as either kappa or lambda.
  • the “class” of an antibody or immunoglobulin refers to the type of constant domain or constant region possessed by its heavy chain. There are five major classes of antibodies: IgA, IgD, IgE, IgG, and IgM, and several of these may be further divided into subclasses (isotypes), e.g., IgG1, IgG2, IgG3, IgG4, IgA1, and IgA2.
  • the heavy chain constant domains that correspond to the different classes of immunoglobulins are called ⁇ , ⁇ , ⁇ , and ⁇ , respectively.
  • An exemplary immunoglobulin (antibody) structural unit is composed of two pairs of polypeptide chains, each pair having one “light” (about 25 kD) and one “heavy” chain (about 50-70 kD).
  • the N-terminal domain of each chain defines a variable region of about 100 to 110 or more amino acids primarily responsible for antigen recognition.
  • the terms variable light chain (VL) and variable heavy chain (VH) refer to these light and heavy chain domains respectively.
  • the IgG1 heavy chain comprises of the VH, CH1, CH2 and CH3 domains respectively from the N to C-terminus.
  • the light chain comprises of the VL and CL domains from N to C terminus.
  • the IgG1 heavy chain comprises a hinge between the CH1 and CH2 domains.
  • the immunoglobulin constructs comprise at least one immunoglobulin domain from IgG, IgM, IgA, IgD, or IgE connected to a therapeutic polypeptide.
  • the immunoglobulin domain found in an antibody provided herein is from or derived from an immunoglobulin-based construct such as a diabody, or a nanobody.
  • the immunoglobulin constructs described herein comprise at least one immunoglobulin domain from a heavy chain antibody such as a camelid antibody.
  • the immunoglobulin constructs provided herein comprise at least one immunoglobulin domain from a mammalian antibody such as a bovine antibody, a human antibody, a camelid antibody, a mouse antibody or any chimeric antibody.
  • the antibodies provided herein comprise a heavy chain.
  • the heavy chain is an IgA.
  • the heavy chain is an IgD.
  • the heavy chain is an IgE.
  • the heavy chain is an IgG.
  • the heavy chain is an IgM.
  • the heavy chain is an IgG1.
  • the heavy chain is an IgG2.
  • the heavy chain is an IgG3.
  • the heavy chain is an IgG4. In one embodiment, the heavy chain is an IgA1. In one embodiment, the heavy chain is an IgA2. [00318] In some embodiments, an antibody is an IgG1 antibody. In some embodiments, an antibody is an IgG3 antibody. In some embodiments, an antibody is an IgG2 antibody. In some embodiments, an antibody is an IgG4 antibody. [00319] Generally, native four-chain antibodies comprise six HVRs; three in the VH (H1, H2, H3), and three in the VL (L1, L2, L3).
  • HVRs generally comprise amino acid residues from the hypervariable loops and/or from the complementarity determining regions (CDRs), the latter being of highest sequence variability and/or involved in antigen recognition. With the exception of CDR1 in VH, CDRs generally comprise the amino acid residues that form the hypervariable loops.
  • CDRs complementarity determining regions
  • Hypervariable regions (HVRs) are also referred to as “complementarity determining regions” (CDRs), and these terms are used herein interchangeably in reference to portions of the variable region that form the antigen-binding regions. This particular region has been described by Kabat et al., U.S. Dept.
  • amino acid sequence boundaries of a CDR can be determined by one of skill in the art using any of a number of known numbering schemes, including those described by Kabat et al., supra (“Kabat” numbering scheme); Al-Lazikani et al., 1997, J. Mol. Biol., 273:927-948 (“Chothia” numbering scheme); MacCallum et al., 1996, J. Mol. Biol.262:732- 745 (“Contact” numbering scheme); Lefranc et al., Dev. Comp. Immunol., 2003, 27:55-77 (“IMGT” numbering scheme); and Honegge and Plückthun, J. Mol.
  • an antigen-binding domain is an antigen-binding domain formed by a VH-VL dimer of an antibody.
  • an antigen-binding domain is an antigen-binding domain formed by diversification of certain loops from the tenth fibronectin type III domain of an Adnectin.
  • An antigen-binding domain can include CDRs 1, 2, and 3 from a heavy chain in that order; and CDRs 1, 2, and 3 from a light chain in that order.
  • Epitopes frequently consist of surface-accessible amino acid residues and/or sugar side chains and may have specific three-dimensional structural characteristics, as well as specific charge characteristics. Conformational and non-conformational epitopes are distinguished in that the binding to the former but not the latter may be lost in the presence of denaturing solvents.
  • An epitope may comprise amino acid residues that are directly involved in the binding, and other amino acid residues, which are not directly involved in the binding.
  • the epitope to which an antibody binds can be determined using known techniques for epitope determination such as, for example, testing for antibody binding to OX40L or IL- 4R ⁇ , to OX40L or IL-4R ⁇ variants with different point-mutations, or to chimeric OX40L or IL-4R ⁇ variants.
  • an antibody of interest e.g., OX40L or IL-4R ⁇
  • a routine cross-blocking assay such as that described in Antibodies, A Laboratory Manual, Cold Spring Harbor Laboratory, Ed Harlow and David Lane (1988)
  • epitope mapping can be performed by methods known in the art.
  • Anti-OX40L Antibodies [00327] The present application provides antibodies or antigen binding fragments thereof and compositions comprising an antibody, or an antigen binding fragment thereof, which binds OX40L.
  • an anti-OX40L antibody, or an antigen binding fragment thereof, described herein is selected from amlitelimab and oxelumab.
  • amlitelimab comprises a variable heavy (VH) chain sequence having the amino acid sequence of SEQ ID NO: 832 and a variable light (VL) chain sequence having the amino acid sequence of SEQ ID NO: 833.
  • VH variable heavy
  • VL variable light
  • oxelumab comprises a VH chain sequence having the amino acid sequence of SEQ ID NO: 834 and a VL chain sequence having the amino acid sequence of SEQ ID NO: 835.
  • amlitelimab comprises a heavy chain having the amino acid sequence of SEQ ID NO: 842 and a light chain sequence having the amino acid sequence of SEQ ID NO: 843.
  • oxelumab comprises a heavy chain having the amino acid sequence of SEQ ID NO: 1072 and a light chain sequence having the amino acid sequence of SEQ ID NO: 1073, or a VH and/or VL therein. See also PCT Application No. PCT/US2024/026854 (corresponding to PCT Publication No. WO2024227174), which is incorporated herein by reference in its entirety.
  • an anti-OX40L antibody, or an antigen binding fragment thereof, described herein is selected from an anti-OX40L antibody described therein.
  • Anti-OX40L antibodies or an antigen binding fragments thereof can include those described herein such as the clones set forth in the drawings and/or tables.
  • the antibody comprises an alternative scaffold.
  • the antibody consists of an alternative scaffold.
  • the antibody consists essentially of an alternative scaffold.
  • the antibody comprises an antibody fragment.
  • the antibody consists of an antibody fragment.
  • the antibody consists essentially of an antibody fragment.
  • the antibodies are monoclonal antibodies.
  • the antibodies are polyclonal antibodies. [00331] In some embodiments, the antibodies are produced by hybridomas. In other embodiments, the antibodies are produced by recombinant cells engineered to express the desired variable and constant domains. [00332] In some embodiments, the antibodies may be single chain antibodies or other antibody derivatives retaining the antigen specificity and the lower hinge region or a variant thereof. [00333] In some embodiments, the antibodies may be polyfunctional antibodies, recombinant antibodies, human antibodies, humanized antibodies, fragments or variants thereof. In particular embodiments, the antibody fragment or a derivative thereof is selected from a Fab fragment, a Fab′2 fragment, a CDR and ScFv.
  • the antibodies are capable of forming an immune complex.
  • sequence comparison typically one sequence acts as a reference sequence to which test sequences are compared.
  • test and reference sequences are input into a computer, subsequence coordinates are designated, if necessary, and sequence algorithm program parameters are designated.
  • sequence comparison algorithm then calculates the percent sequence identity for the test sequence(s) relative to the reference sequence, based on the designated program parameters.
  • Optimal alignment of sequences for comparison can be conducted, e.g., by the local homology algorithm of Smith & Waterman, Adv. Appl. Math.2:482 (1981), by the homology alignment algorithm of Needleman & Wunsch, J. Mol.
  • an antibody, or an antigen binding fragment thereof, provided herein comprises a VH sequence selected from any one of SEQ ID NOs: 1, 19, 37, and 55.
  • an antibody, or an antigen binding fragment thereof, provided herein comprises a VH sequence having at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to an illustrative VH sequence selected from any one of SEQ ID NOs: 1, 19, 37, and 55.
  • an antibody, or an antigen binding fragment thereof, provided herein comprises a VH sequence selected from any one of SEQ ID NOs: 1, 19, 37, and 55, with up to 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 amino acid substitutions.
  • the amino acid substitutions are conservative amino acid substitutions.
  • an antibody, or an antigen binding fragment thereof, provided herein comprises a VL sequence selected from any one of SEQ ID NOs: 11, 29, 47, and 65.
  • an antibody, or an antigen binding fragment thereof, provided herein comprises a VL sequence having at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to a VL sequence selected from any one of SEQ ID NOs: 11, 29, 47, and 65.
  • an antibody, or an antigen binding fragment thereof, provided herein comprises a VL sequence selected from any one of SEQ ID NOs: 11, 29, 47, and 65, with up to 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 amino acid substitutions.
  • the amino acid substitutions are conservative amino acid substitutions.
  • the antibodies described in this paragraph are referred to herein as “variants.”
  • such variants are derived from a sequence provided herein, for example, by affinity maturation, site directed mutagenesis, random mutagenesis, or any other method known in the art or described herein.
  • such variants are not derived from a sequence provided herein and may, for example, be isolated de novo according to the methods provided herein for obtaining antibodies.
  • an antibody, or an antigen binding fragment thereof, provided herein comprises a VH sequence selected from any one of SEQ ID NOs: 1, 19, 37, and 55; and a VL sequence selected from any one of SEQ ID NOs: 11, 29, 47, and 65.
  • a VH sequence selected from any one of SEQ ID NOs: 1, 19, 37, and 55 can be combined with a VL sequence selected from any one of SEQ ID NOs: 11, 29, 47, and 65.
  • an antibody, or an antigen binding fragment thereof, provided herein comprises a VH sequence and a VL sequence of a construct provided in TABLE 3 (e.g., a VH sequence and a VL sequence from the same row of TABLE 3) or in PCT Application No. PCT/US2024/026854 (corresponding to PCT Publication No. WO2024227174), incorporated by reference herein in its entirety.
  • an antibody, or antigen binding fragment thereof, provided herein comprises a VH sequence and a VL sequence from Table 2 in PCT Application No. PCT/US2024/026854 (e.g., a VH sequence and a VL sequence from the same row of Table 2).
  • an antibody, or an antigen binding fragment thereof, provided herein comprises a VH sequence having at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to a VH sequence selected from any one of SEQ ID NOs: 1, 19, 37, and 55; and a VL sequence having at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to a VL sequence selected from any one of SEQ ID NOs: 11, 29, 47, and 65.
  • an antibody, or an antigen binding fragment thereof, provided herein comprises a VH sequence selected from any one of SEQ ID NOs: 1, 19, 37, and 55, with up to 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 amino acid substitutions, and a VL sequence selected from any one of SEQ ID NOs: 11, 29, 47, and 65, with up to 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 amino acid substitutions.
  • the amino acid substitutions are conservative amino acid substitutions.
  • the antibodies described in this paragraph are referred to herein as “variants.”
  • such variants are derived from a sequence provided herein, for example, by affinity maturation, site directed mutagenesis, random mutagenesis, or any other method known in the art or described herein.
  • such variants are not derived from a sequence provided herein and may, for example, be isolated de novo according to the methods provided herein for obtaining antibodies.
  • the antibody, or an antigen binding fragment thereof comprises a VH sequence set forth in SEQ ID NO: 1 and a VL sequence set forth in SEQ ID NO: 11.
  • the antibody, or an antigen binding fragment thereof comprises a VH sequence set forth in SEQ ID NO: 19 and a VL sequence set forth in SEQ ID NO: 29.
  • the antibody, or an antigen binding fragment thereof comprises a VH sequence set forth in SEQ ID NO: 37 and a VL sequence set forth in SEQ ID NO: 47.
  • the antibody, or an antigen binding fragment thereof comprises a VH sequence set forth in SEQ ID NO: 55 and a VL sequence set forth in SEQ ID NO: 65.
  • an antibody, or an antigen binding fragment thereof comprises any of the VH and VL combinations described above and further comprises a heavy chain comprising a human IgG sequence selected from a sequence set forth in any one of SEQ ID NOs: 637-737 and SEQ ID NOs: 847-1070 or a sequence having at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity thereto.
  • an antibody comprises any of the VH and VL combinations described above and further comprises a heavy chain comprising a constant heavy chain sequence set forth in SEQ ID NO: 651 or a sequence having at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity thereto.
  • an antibody comprises any of the VH and VL combinations described above and further comprises a constant heavy chain comprising a constant heavy chain sequence set forth in SEQ ID NO: 973 or a sequence having at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity thereto.
  • an antibody comprises any of the VH and VL combinations described above and further comprises a human constant light chain sequence set forth in SEQ ID NO: 738 or a sequence having at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity thereto.
  • an antibody comprises any of the VH and VL combinations described above and further comprises a constant heavy chain sequence set forth in SEQ ID NO: 651 or a sequence having at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity thereto and a human constant light chain sequence set forth in SEQ ID NO: 738 or a sequence having at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity thereto.
  • an antibody comprises any of the VH and VL combinations described above and further comprises a constant heavy chain sequence set forth in SEQ ID NO: 973 or a sequence having at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity thereto and a human constant light chain sequence set forth in SEQ ID NO: 738 or a sequence having at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity thereto.
  • a C-terminal lysine may be present in the corresponding coding sequence of the constant heavy chain region (e.g., in a sequence encoding any one of SEQ ID NOs: 959-1070), it may be cleaved off during manufacture or after administration (resulting in, e.g., a constant heavy chain sequence of any one of SEQ ID NOs: 637-737 and 847-958).
  • any of the antibodies or antigen binding fragments thereof described above may comprise a human IgG sequence containing a C-terminal lysine (e.g., any one of SEQ ID NOs: 959-1070), a human IgG sequence lacking a C-terminal lysine (e.g., any one of SEQ ID NOs: 637-737 and 847-958), or a mixture thereof (e.g., a mixture of the same heavy chain constant sequence with and without a C-terminal lysine, such as a mixture of SEQ ID NO: 973 and SEQ ID NO: 651).
  • a human IgG sequence containing a C-terminal lysine e.g., any one of SEQ ID NOs: 959-1070
  • a human IgG sequence lacking a C-terminal lysine e.g., any one of SEQ ID NOs: 637-737 and 847-958
  • a mixture thereof e.g., a mixture of the
  • Anti-OX40L CDRs [00352] In some embodiments, disclosed herein is an antibody, or an antigen binding fragment thereof, comprising 1, 2, 3, 4, 5, or 6 of the CDRs of TABLE 3. In some embodiments, disclosed herein is an antibody, or an antigen binding fragment thereof, comprising 6 of the Kabat CDRs of TABLE 3. In some embodiments, disclosed herein is an antibody, or an antigen binding fragment thereof, comprising 1, 2, 3, 4, 5, or 6 of the Chothia CDRs of TABLE 3. In some embodiments, disclosed herein is an antibody, or an antigen binding fragment thereof, comprising 1, 2, 3, 4, 5, or 6 of the IMGT CDRs of TABLE 3.
  • the antibody, or an antigen binding fragment thereof comprises 6 of the Kabat CDRs, 6 of the Chothia CDRs, or 6 of the IMGT CDRs from a single row of TABLE 3 (e.g., 6 CDRs from the same antibody).
  • an antibody, or an antigen binding fragment thereof comprising 1, 2, 3, 4, 5, or 6 of the CDRs of an antibody provided in PCT Application No. PCT/US2024/026854 (corresponding to PCT Publication No. WO2024227174, incorporated by reference herein in its entirety, such as 1, 2, 3, 4, 5, or 6 of the CDRs in Table 2 in PCT Application No. PCT/US2024/026854.
  • an antibody, or an antigen binding fragment thereof comprising 1, 2, 3, 4, 5, or 6 of the Kabat CDRs of an antibody, or an antigen binding fragment thereof, provided in PCT Application No. PCT/US2024/026854.
  • an antibody, or an antigen binding fragment thereof comprising 1, 2, 3, 4, 5, or 6 of the Chothia CDRs of an antibody, or an antigen binding fragment thereof, provided in PCT Application No. PCT/US2024/026854.
  • an antibody, or an antigen binding fragment thereof comprising 1, 2, 3, 4, 5, or 6 of the IMGT CDRs of an antibody provided in PCT Application No. PCT/US2024/026854.
  • the antibody, or an antigen binding fragment thereof comprises 6 of the Kabat CDRs, 6 of the Chothia CDRs, or 6 of the IMGT CDRs from a single row of Table 2 in in PCT Application No. PCT/US2024/026854 (e.g., 6 CDRs from the same antibody).
  • an antibody, or an antigen binding fragment thereof, provided herein comprises three CDRs of a VH domain selected from SEQ ID NOs: 1, 19, 37, and 55.
  • the CDRs are exemplary CDRs.
  • the CDRs are Kabat CDRs.
  • the CDRs are Chothia CDRs.
  • the CDRs are IMGT CDRs. In some aspects, the CDRs are AbM CDRs. In some aspects, the CDRs are Contact CDRs. [00355] In some embodiments, the CDRs are CDRs having at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity to a CDR-H1, CDR-H2, or CDR-H3 selected from SEQ ID NOs: 2-10, 12-18, 20-28, 30-36, 38-46, 48-54, 56-64, and 66-72.
  • the CDR-H1 is a CDR-H1 of a VH domain selected from SEQ ID NOs: 1, 19, 37, and 55, with up to 1, 2, 3, 4, or 5 amino acid substitutions.
  • the CDR-H2 is a CDR-H2 of a VH domain selected from SEQ ID NOs: 1, 19, 37, and 55, with up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions.
  • the CDR-H3 is a CDR-H3 of a VH domain selected from SEQ ID NOs: 1, 19, 37, and 55, with up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions.
  • the amino acid substitutions are conservative amino acid substitutions.
  • the antibodies described in this paragraph are referred to herein as “variants.”
  • such variants are derived from a sequence provided herein, for example, by affinity maturation, site directed mutagenesis, random mutagenesis, or any other method known in the art or described herein.
  • such variants are not derived from a sequence provided herein and may, for example, be isolated de novo according to the methods provided herein for obtaining antibodies.
  • an antibody, or an antigen binding fragment thereof, provided herein comprises three CDRs of a VL domain selected from SEQ ID NOs: 11, 29, 47, and 65.
  • the CDRs are exemplary CDRs.
  • the CDRs are Kabat CDRs. In some aspects, the CDRs are Chothia CDRs. In some aspects, the CDRs are IMGT CDRs. In some aspects, the CDRs are AbM CDRs. In some aspects, the CDRs are Contact CDRs.
  • the CDRs are CDRs having at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity to a CDR-L1, CDR-L2, or CDR-L3 selected from SEQ ID NOs: 2-10, 12-18, 20-28, 30-36, 38-46, 48-54, 56-64, and 66- 72,
  • the CDR-L1 is a CDR-L1 of a VL domain selected from SEQ ID NOs: 11, 29, 47, and 65, with up to 1, 2, 3, 4, or 5 amino acid substitutions.
  • the CDR-L2 is a CDR-L2 of a VL domain selected from SEQ ID NOs: 11, 29, 47, and 65, with up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions.
  • the CDR-L3 is a CDR-L3 of a VL domain selected from SEQ ID NOs: 11, 29, 47, and 65, with up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions.
  • the amino acid substitutions are conservative amino acid substitutions.
  • an antibody, or an antigen binding fragment thereof, provided herein comprises three CDRs of a VH domain selected from SEQ ID NOs: 1, 19, 37, and 55 and three CDRs of a VL domain selected from SEQ ID NOs: 11, 29, 47, and 65.
  • the CDRs are exemplary CDRs. In some aspects, the CDRs are Kabat CDRs. In some aspects, the CDRs are Chothia CDRs. In some aspects, the CDRs are IMGT CDRs. In some aspects, the CDRs are AbM CDRs. In some aspects, the CDRs are Contact CDRs. [00359] In some embodiments, an antibody, or an antigen binding fragment thereof, provided herein comprises a CDR-H3 selected from SEQ ID NOs: 8-10, 26-28, 44-46, and 62-64.
  • the CDR-H3 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to a CDR-H3 selected from SEQ ID NOs: 8-10, 26-28, 44-46, and 62-64.
  • the CDR-H3 is a CDR-H3 selected from SEQ ID NOs: 8-10, 26-28, 44-46, and 62-64, with up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions.
  • the amino acid substitutions are conservative amino acid substitutions.
  • the antibodies described in this paragraph are referred to herein as “variants.”
  • such variants are derived from a sequence provided herein, for example, by affinity maturation, site directed mutagenesis, random mutagenesis, or any other method known in the art or described herein.
  • such variants are not derived from a sequence provided herein and may, for example, be isolated de novo according to the methods provided herein for obtaining antibodies.
  • an antibody, or an antigen binding fragment thereof, provided herein comprises a CDR-H1 selected from SEQ ID NOs: 2-4, 20-22, 38-40, and 56- 58.
  • the CDR-H1 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to a CDR-H1 selected from SEQ ID NOs: 2-4, 20-22, 38-40, and 56-58.
  • the CDR-H1 is a CDR-H1 selected from SEQ ID NOs: 2- 4, 20-22, 38-40, and 56-58, with up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions.
  • the amino acid substitutions are conservative amino acid substitutions.
  • an antibody, or an antigen binding fragment thereof, provided herein comprises a CDR-H2 selected from SEQ ID NOs: 5-7, 23-25, 41-43, and 59- 61.
  • the CDR-H2 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to a CDR-H2 selected from SEQ ID NOs: 5-7, 23-25, 41-43, and 59-61.
  • the CDR-H2 is a CDR-H2 selected from SEQ ID NOs: 5- 7, 23-25, 41-43, and 59-61, with up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions.
  • the amino acid substitutions are conservative amino acid substitutions.
  • an antibody, or an antigen binding fragment thereof, provided herein comprises a CDR-L3 selected from SEQ ID NOs: 17-18, 35-36, 53-54, and 71-72.
  • the CDR-L3 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to a CDR-L3 selected from SEQ ID NOs: 17-18, 35- 36, 53-54, and 71-72.
  • the CDR-L3 is a CDR-L3 selected from SEQ ID NOs: 17-18, 35-36, 53-54, and 71-72, with up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions.
  • the amino acid substitutions are conservative amino acid substitutions.
  • an antibody, or an antigen binding fragment thereof, provided herein comprises a CDR-L2 selected from SEQ ID NOs: 15-16, 33-34, 51-52, and 69-70.
  • the CDR-L2 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to a CDR-L2 selected from SEQ ID NOs: 15-16, 33- 34, 51-52, and 69-70.
  • the CDR-L2 is a CDR-L2 selected from SEQ ID NOs: 15-16, 33-34, 51-52, and 69-70, with up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions.
  • the amino acid substitutions are conservative amino acid substitutions.
  • an antibody, or an antigen binding fragment thereof, provided herein comprises a CDR-L1 selected from SEQ ID NOs: 12-14, 30-32, 48-50, and 66-68.
  • the CDR-L1 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to a CDR-L1 selected from SEQ ID NOs: 12-14, 30- 32, 48-50, and 66-68.
  • the CDR-L1 is a CDR-L1 selected from SEQ ID NOs: 12-14, 30-32, 48-50, and 66-68, with up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions.
  • the amino acid substitutions are conservative amino acid substitutions.
  • the antibodies described in this paragraph are referred to herein as “variants.”
  • such variants are derived from a sequence provided herein, for example, by affinity maturation, site directed mutagenesis, random mutagenesis, or any other method known in the art or described herein.
  • such variants are not derived from a sequence provided herein and may, for example, be isolated de novo according to the methods provided herein for obtaining antibodies.
  • an antibody, or an antigen binding fragment thereof comprises a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 2; a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 5; a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 8; a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 12; a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 15; and a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 17.
  • an antibody, or an antigen binding fragment thereof comprises a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 3; a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 6; a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 9; a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 13; a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 16; and a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 18.
  • an antibody, or an antigen binding fragment thereof comprises a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 4; a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 7; a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 10; a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 14; a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 16; and a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 17.
  • an antibody, or an antigen binding fragment thereof comprises a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 20; a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 23; a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 26; a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 30; a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 33; and a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 35.
  • an antibody, or an antigen binding fragment thereof comprises a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 21; a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 24; a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 27; a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 31; a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 34; and a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 36.
  • an antibody, or an antigen binding fragment thereof comprises a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 22; a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 25; a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 27; a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 32; a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 34; and a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 35.
  • an antibody, or an antigen binding fragment thereof comprises a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 38; a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 41; a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 44; a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 48; a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 51; and a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 53.
  • an antibody, or an antigen binding fragment thereof comprises a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 39; a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 42; a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 45; a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 49; a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 52; and a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 54.
  • an antibody, or an antigen binding fragment thereof comprises a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 40; a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 43; a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 46; a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 50; a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 52; and a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 53.
  • an antibody, or an antigen binding fragment thereof comprises a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 56; a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 59; a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 62; a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 66; a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 69; and a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 71.
  • an antibody, or an antigen binding fragment thereof comprises a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 58; a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 61; a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 64; a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 68; a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 70; and a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 71.
  • any of the antibodies or antigen binding fragments thereof described above further comprises a heavy chain comprising a human IgG sequence selected from a sequence set forth in any one of SEQ ID NOs: 637-737 and SEQ ID NOs: 847-1070 or a sequence having at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity thereto.
  • any of the antibodies described above further comprises a constant heavy chain sequence set forth in SEQ ID NO: 651 or a sequence having at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity thereto.
  • any of the antibodies described above further comprises a constant heavy chain sequence set forth in SEQ ID NO: 651 or a sequence having at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity thereto and a human constant light chain sequence set forth in SEQ ID NO: 738 or a sequence having at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity thereto.
  • any of the antibodies described above further comprises a constant heavy chain sequence set forth in SEQ ID NO: 973 or a sequence having at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity thereto and a human constant light chain sequence set forth in SEQ ID NO: 738 or a sequence having at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity thereto.
  • any of the antibodies or antigen binding fragments thereof described above may comprise a human IgG sequence containing a C-terminal lysine (e.g., any one of SEQ ID NOs: 959-1070), a human IgG sequence lacking a C-terminal lysine (e.g., any one of SEQ ID NOs: 637-737 and 847-958), or a mixture thereof (e.g., a mixture of the same heavy chain constant sequence with and without a C-terminal lysine, such as a mixture of SEQ ID NO: 973 and SEQ ID NO: 651).
  • the amino acid substitutions are conservative amino acid substitutions.
  • the antibodies described in this disclosure are referred to herein as “variants” or “clones”.
  • variants or clones are derived from a sequence provided herein, for example, by affinity maturation, site directed mutagenesis, random mutagenesis, or any other method known in the art or described herein.
  • variants or cones are not derived from a sequence provided herein and may, for example, be isolated de novo according to the methods provided herein for obtaining antibodies.
  • Fc Region [00380] The structures of the Fc regions of various immunoglobulins, and the glycosylation sites contained therein, are known in the art. See Schroeder et al. (2010) Allergy Clin.
  • the Fc region may be a naturally occurring Fc region, or an Fc region modified as described in the art or elsewhere in this disclosure.
  • numbering of amino acid residues in the Fc region or constant region is according to the EU numbering system, also called the EU index, as described in Kabat et al., Sequences of Proteins of Immunological Interest, 5th Ed. Public Health Service, National Institutes of Health, Bethesda, MD, 1991.
  • An "Fc polypeptide" of a dimeric Fc as used herein refers to one of the two polypeptides forming the dimeric Fc domain, i.e.
  • an Fc polypeptide of a dimeric IgG Fc comprises an IgG CH2 and an IgG CH3 constant domain sequence.
  • An Fc can be of the class IgA, IgD, IgE, IgG, and IgM, and several of these may be further divided into subclasses (isotypes), e.g., IgG1, IgG2, IgG3, IgG4, IgA1, and IgA2.
  • the terms “Fc receptor” and “FcR” are used to describe a receptor that binds to the Fc region of an antibody.
  • Immunoglobulins of other isotypes can also be bound by certain FcRs (see, e.g., Janeway et al., Immuno Biology: the immune system in health and disease, (Elsevier Science Ltd., NY) (4th ed., 1999)).
  • Activating receptor Fc ⁇ RIIA contains an immunoreceptor tyrosine-based activation motif (ITAM) in its cytoplasmic domain.
  • Inhibiting receptor Fc ⁇ RIIB contains an immunoreceptor tyrosine-based inhibition motif (ITIM) in its cytoplasmic domain (reviewed in Da ⁇ ron, Annu. Rev. Immunol.15:203-234 (1997)).
  • FcRs are reviewed in Ravetch and Kinet, Annu. Rev.
  • Modifications in the CH2 domain can affect the binding of FcRs to the Fc.
  • a number of amino acid modifications in the Fc region are known that can selectively alter the affinity of the Fc for different Fcgamma receptors.
  • the Fc comprises one or more modifications designed to promote selective binding of Fc-gamma receptors.
  • any of the antibodies or antigen binding fragments thereof described above further comprises a heavy chain comprising a constant heavy chain sequence selected from an amino acid sequence set forth in any one of SEQ ID NOs: 637-737 and SEQ ID NOs: 847-1070, or an amino acid sequence having 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%, or at least 99% sequence identity thereto.
  • an antibody, or an antigen binding fragment thereof, described herein includes modifications designed to improve its ability to mediate effector function.
  • modifications that can have this effect are known in the art and include afucosylation, or engineering of the affinity of the Fc towards an activating receptor, mainly FCGR3a for ADCC, and towards C1q for CDC.
  • FCGR3a for ADCC
  • C1q for CDC.
  • TABLE 4 summarizes various designs reported in the literature for effector function engineering.
  • Methods of producing antibodies with little or no fucose on the Fc glycosylation site (Asn 297 EU numbering) without altering the amino acid sequence are well known in the art.
  • the GlymaxX® technology (ProBioGen AG) is based on the introduction of a gene for an enzyme which deflects the cellular pathway of fucose biosynthesis into cells used for antibody production. This prevents the addition of the sugar “fucose” to the N-linked antibody carbohydrate part by antibody-producing cells (von Horsten et al. (2010) Glycobiology.2010 Dec; 20 (12):1607-18).
  • Examples of cell lines capable of producing defucosylated antibody include CHO-DG44 with stable overexpression of the bacterial oxidoreductase GDP-6-deoxy-D-lyxo-4-hexylose reductase (RMD) (see von Horsten et al.
  • Lec13 CHO cells which are deficient in protein fucosylation (see Ripka et al. (1986) Arch. Biochem. Biophys.249:533-545; U.S. Pat. Pub. No.2003/0157108; WO 2004/056312; each of which is incorporated by reference in its entirety), and knockout cell lines, such as alpha-1,6-fucosyltransferase gene or FUT8 knockout CHO cells (see Yamane- Ohnuki et al. (2004) Biotech. Bioeng.87: 614-622; Kanda et al. (2006) Biotechnol. Bioeng.
  • Antibodies can be fully afucosylated (meaning they contain no detectable fucose) or they can be partially afucosylated, meaning that the isolated antibody contains less than 95%, less than 85%, less than 75%, less than 65%, less than 55%, less than 45%, less than 35%, less than 25%, less than 15% or less than 5% of the amount of fucose normally detected for a similar antibody produced by a mammalian expression system.
  • an antibody, or an antigen binding fragment thereof, provided herein comprises an IgG1 domain with reduced fucose content at position Asn 297 compared to a naturally occurring IgG1 domain. Such Fc domains can have improved ADCC.
  • an antibody, or an antigen binding fragment thereof, provided herein comprises an Fc region with one or more amino acid substitutions which improve ADCC, such as a substitution at one or more of positions 298, 333, and 334 of the Fc region.
  • an antibody, or an antigen binding fragment thereof, provided herein comprises an Fc region with one or more amino acid substitutions at positions 239, 332, and 330, as described in Lazar et al. (2006) Proc. Natl. Acad. Sci. USA 103:4005-4010, incorporated by reference in its entirety.
  • Other illustrative glycosylation variants which may be incorporated into the antibodies provided herein are described, for example, in U.S. Pat. Pub.
  • an antibody, or an antigen binding fragment thereof, provided herein comprises an Fc region with at least one galactose residue in the oligosaccharide attached to the Fc region.
  • Such antibody variants may have improved CDC function. Examples of such antibody variants are described, for example, in WO 1997/30087; WO 1998/58964; and WO 1999/22764; each of which is incorporated by reference in its entirety.
  • an antibody described herein can include a dimeric Fc that comprises one or more amino acid modifications as noted in TABLE 4 that may confer improved effector function.
  • the antibody can be afucosylated to improve effector function. TABLE 4.
  • a a o y, o a a ge ding fragment thereof comprises one or more alterations that is designed to improve or diminish C1q binding and/or CDC. See U.S. Pat. No.6,194,551; WO 99/51642; and Idusogie et al. (2000) J. Immunol.164:4178-4184; each of which is incorporated by reference in its entirety.
  • the heavy chain comprises a constant heavy chain sequence selected from the sequences set forth in SEQ ID NOs: 637-737 and SEQ ID NOs: 847-1070.
  • the Fc region comprises one or more amino acid substitutions, wherein the one or more substitutions result in an increase in one or more of antibody half-life, ADCC activity, ADCP activity, or CDC activity compared with the Fc without the one or more substitutions.
  • the one or more amino acid substitutions results in increased antibody half-life at pH 6.0 compared to an antibody comprising a wild-type Fc region.
  • the antibody has an increased half-life that is about 10,000-fold, 1,000-fold, 500-fold, 100-fold, 50-fold, 20-fold, 10-fold, 9- fold, 8-fold, 7-fold, 6-fold, 5-fold, 4.5-fold, 4-fold, 3.5-fold, 3-fold, 2.5-fold, 2-fold, 1.95- fold, 1.9-fold, 1.85-fold, 1.8-fold, 1.75-fold, 1.7-fold, 1.65-fold, 1.6-fold, 1.55-fold, 1.50-fold, 1.45-fold, 1.4-fold, 1.35-fold, 1.3-fold, 1.25-fold, 1.2-fold, 1.15-fold, 1.1-fold, or 1.05-fold longer compared to an antibody comprising a wild-type Fc region.
  • the antibody has an increased half-life that is about 10,000-fold, 1,000-fold, 500-fold, 100- fold, 50-fold, 20-fold, 10-fold, 9-fold, 8-fold, 7-fold, 6-fold, 5-fold, 4.5-fold, 4-fold, 3.5-fold, 3-fold, 2.5-fold, 2-fold, 1.95-fold, 1.9-fold, 1.85-fold, 1.8-fold, 1.75-fold, 1.7-fold, 1.65-fold, 1.6-fold, 1.55-fold, 1.50-fold, 1.45-fold, 1.4-fold, 1.35-fold, 1.3-fold, 1.25-fold, 1.2-fold, 1.15-fold, 1.1-fold, or 1.05-fold longer compared to amlitelimab.
  • the Fc region comprises one or more amino acid substitutions, wherein the one or more substitutions result in a decrease in one or more of ADCC activity, ADCP activity, or CDC activity compared with the Fc without the one or more substitutions.
  • the one or more amino acid substitutions is selected from the group consisting of S228P (SP), M252Y, S254T, T256E, T256D, T250Q, H285D, T307A, T307Q, T307R, T307W, L309D, Q411H, Q311V, A378V, E380A, M428L, N434A, N434S, N297A, D265A, L234A, L235A, and N434W.
  • SP S228P
  • M252Y S254T
  • T256E T256D
  • T250Q H285D
  • T307A, T307Q, T307R, T307W L309D
  • Q411H, Q311V, A378V, E380A M428L, N434A, N434S, N297A, D265A, L234A, L235A, and N434W.
  • the one or more amino acid substitutions comprises a specific combination of amino acid substitutions selected from the group consisting of M428L/N434S (LS), M252Y/S254T/T256E (YTE), T250Q/M428L, T307A/E380A/N434A, T256D/T307Q (DQ), T256D/T307W (DW), M252Y/T256D (YD), T307Q/Q311V/A378V (QVV), T256D/H285D/T307R/Q311V/A378V (DDRVV), L309D/Q311H/N434S (DHS), S228P/L235E (SPLE), L234A/L235A (LALA), M428L/N434A (LA), L235A/G237A (LAGA), L234A/L235A/G237A (LALAGA), L234A/L/L/L
  • an antibody described herein comprises an Fc region with YTE mutations at positions 253, 255 and 257.
  • an antibody described herein comprises an Fc region with LALA mutations at positions 235 and 236, respectively.
  • an antibody described herein comprises an Fc region with YTE mutations at positions 253, 255 and 257 and with LALA mutations at positions 235 and 236.
  • the OX40L antibody described herein comprises the heavy and light chain variable regions of Construct 114 and an Fc region comprising YTE mutations at positions 253, 255 and 257, respectively and with LALA mutations at positions 235 and 236, respectively (e.g., as shown in the heavy chain sequences of SEQ ID NOs: 839 and 840).
  • the human Fc region comprises a human IgG1 Fc with LALA mutations.
  • the human Fc region comprises a human IgG1 Fc with YTE mutations.
  • the human Fc region comprises a human IgG1 Fc with LALA and YTE mutations.
  • YTE and “LALA” mutations can be located at different amino acid position numbers.
  • a human Fc region can comprise a human IgG1 Fc with LALA mutations at L235A/L236A and/or YTE mutations at M253Y/S255T/T257E.
  • the OX40L antibody, or antigen binding fragment thereof comprises a heavy chain variable region sequence comprising an amino acid sequence set forth in SEQ ID NO:1, a constant heavy chain sequence set forth in SEQ ID NO: 651, a light chain variable region sequence comprising an amino acid sequence set forth in SEQ ID NO:11, and a constant light chain sequence set forth in SEQ ID NO: 738.
  • the OX40L antibody, or antigen binding fragment thereof comprises a heavy chain variable region sequence comprising an amino acid sequence set forth in SEQ ID NO:1, a constant heavy chain sequence set forth in SEQ ID NO: 973, a light chain variable region sequence comprising an amino acid sequence set forth in SEQ ID NO:11, and a constant light chain sequence set forth in SEQ ID NO: 738.
  • the C-terminal Lys330 of the constant heavy chain sequence of SEQ ID NO: 973 may or may not be present.
  • the disclosure specifically contemplates SEQ ID NO: 973 that does not include the C-terminal Lys corresponding to Lys330 (as set forth in SEQ ID NO: 651).
  • a polypeptide comprising SEQ ID NO: 973 may be expressed including a C-terminal Lys330 which then may be proteolytically cleaved upon expression of the polypeptide (e.g., a polypeptide comprising SEQ ID NO: 973 is expressed using a nucleic acid construct encoding the polypeptide including a C-terminal lysine residue, which may then be removed via cleavage to produce a polypeptide in which the constant heavy chain has the sequence of SEQ ID NO: 651, such as the polypeptide of SEQ ID NO: 840).
  • the OX40L antibody that is administered can have the constant heavy chain sequence of SEQ ID NO: 973, SEQ ID NO: 651, or a mixture thereof.
  • the OX40L antibody comprises a light chain comprising the sequence set forth in SEQ ID NO: 841.
  • the OX40L antibody comprises a heavy chain comprising the sequence set forth in SEQ ID NO: 839 or SEQ ID NO: 840.
  • the OX40L antibody comprises a heavy chain comprising the sequence set forth in SEQ ID NO: 839.
  • the OX40L antibody comprises a heavy chain comprising the sequence set forth in SEQ ID NO: 840.
  • the OX40L antibody comprises a light chain comprising the sequence set forth in SEQ ID NO: 841 and a heavy chain comprising the sequence set forth in SEQ ID NO: 839. In some embodiments, the OX40L antibody comprises a light chain comprising the sequence set forth in SEQ ID NO: 841 and a heavy chain comprising the sequence set forth in SEQ ID NO: 840. [00407] In certain embodiments, the Fc region binds an Fc ⁇ Receptor selected from the group consisting of: Fc ⁇ RI, Fc ⁇ RIIa, Fc ⁇ RIIb, Fc ⁇ RIIc, Fc ⁇ RIIIa, and Fc ⁇ RIIIb.
  • the Fc region binds an Fc ⁇ Receptor with higher affinity at pH 6.0 compared to an antibody comprising a wild-type Fc region.
  • Binding [00408]
  • the affinity of a molecule X for its partner Y can be represented by the dissociation equilibrium constant (KD).
  • KD dissociation equilibrium constant
  • the kinetic components that contribute to the dissociation equilibrium constant are described in more detail below.
  • Affinity can be measured by common methods known in the art, including those described herein, such as surface plasmon resonance (SPR) technology (e.g., BIACORE®) or biolayer interferometry (e.g., FORTEBIO®).
  • SPR surface plasmon resonance
  • BIACORE® BIACORE®
  • biolayer interferometry e.g., FORTEBIO®
  • the terms “bind,” “specific binding,” “specifically binds to,” “specific for,” “selectively binds,” and “selective for” a particular antigen (e.g., a polypeptide target) or an epitope on a particular antigen mean binding that is measurably different from a non-specific or non-selective interaction (e.g., with a non-target molecule).
  • Specific binding can be measured, for example, by measuring binding to a target molecule (i.e., OX40L) and comparing it to binding to a non-target molecule.
  • Specific binding can also be determined by competition with a control molecule that mimics the epitope recognized on the target molecule. In that case, specific binding is indicated if the binding of the antibody to the target molecule is competitively inhibited by the control molecule.
  • the affinity of an anti-OX40L antibody, or an antigen binding fragment thereof, for a non-target molecule is less than about 50% of the affinity for OX40L. In some embodiments, the affinity of an anti-OX40L antibody, or an antigen binding fragment thereof, for a non-target molecule is less than about 40% of the affinity for OX40L.
  • the affinity of an anti-OX40L antibody, or an antigen binding fragment thereof, for a non-target molecule is less than about 30% of the affinity for OX40L. In some embodiments, the affinity of an anti-OX40L antibody, or an antigen binding fragment thereof, for a non-target molecule is less than about 20% of the affinity for OX40L. In some embodiments, the affinity of an anti-OX40L antibody, or an antigen binding fragment thereof, for a non-target molecule is less than about 10% of the affinity for OX40L. In some embodiments, the affinity of an anti-OX40L antibody, or an antigen binding fragment thereof, for a non-target molecule is less than about 1% of the affinity for OX40L.
  • the affinity of an anti-OX40L antibody, or an antigen binding fragment thereof, for a non-target molecule is less than about 0.1% of the affinity for OX40L.
  • the antibody, or an antigen binding fragment thereof binds an OX40L sequence set forth in SEQ ID NO: 739.
  • the antibody, or an antigen binding fragment thereof binds to an OX40L sequence set forth in SEQ ID NO: 739 with a KD of less than or equal to about 1, 2, 3, 4, 5, 6, 7, 8, 9 x 10 -9 M, as measured by surface plasmon resonance (SPR).
  • the antibody, or an antigen binding fragment thereof binds to an OX40L sequence set forth in SEQ ID NO: 739 with a KD of less than or equal to about 1 x 10 -10 M, as measured by surface plasmon resonance (SPR). In certain embodiments, the antibody, or an antigen binding fragment thereof, binds to human OX40L with a KD of less than or equal to about 1 x 10 -9 M, as measured by surface plasmon resonance (SPR).
  • an antibody, or an antigen binding fragment thereof, provided herein binds OX40L with a K D of less than or equal to about 0.01, 0.02, 0.03, 0.04, 0.05, 0.06, 0.07, 0.08, 0.09, 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1, 1.1, 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, 1.9, 1.95, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 7, 8, 9, or 10 x 10 -8 M, as measured by ELISA or any other suitable method known in the art.
  • an antibody, or an antigen binding fragment thereof, provided herein binds OX40L with a K D of less than or equal to about 0.01, 0.02, 0.03, 0.04, 0.05, 0.06, 0.07, 0.08, 0.09, 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1, 1.1, 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, 1.9, 1.95, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 7, 8, 9, or 10 x 10 -9 M, as measured by ELISA or any other suitable method known in the art.
  • the K D of the antibody, or an antigen binding fragment thereof, provided herein for the binding of OX40L is between about 0.001-0.01, 0.01-0.1, 0.01-0.05, 0.05-0.1, 0.1-0.5, 0.5-1, 0.25-0.75, 0.25-0.5, 0.5-0.75, 0.75-1, 0.75-2, 1.1-1.2, 1.2- 1.3, 1.3-1.4, 1.4-1.5, 1.5-1.6, 1.6-1.7, 1.7-1.8, 1.8-1.9, 1.9-2, 1-2, 1-5, 2-7, 3-8, 3-5, 4-6, 5-7, 6-8, 7-9, 7-10, or 5-10 x 10 -8 M, as measured by ELISA or any other suitable method known in the art.
  • an antibody, or an antigen binding fragment thereof, provided herein binds OX40L with a K D of less than or equal to about 1 x 10 -8 M, or less than or equal to about 1 x 10 -9 M as measured by ELISA or any other suitable method known in the art.
  • the antibody, or an antigen binding fragment thereof, provided herein binds OX40L with a KD of less than or equal to about 10, 9, 8, 7, 6, 5, 4.5, 4, 3.5, 3, 2.5, 2, 1.98, 1.95, 1.9, 1.85, 1.8, 1.75, 1.7, 1.65, 1.6, 1.55, 1.50, 1.45, 1.4, 1.3, 1.2, 1.1, 1, 0.9, 0.85, 0.8, 0.75, 0.7, 0.65, 0.6, 0.55, 0.5, 0.45, 0.4, 0.35, 0.3, 0.25, 0.2, 0.15, 0.1, 0.05, 0.01, 0.005, 0.001, 0.0005, or 0.0001 x 10 -8 M, or less, as measured by ELISA or any other suitable method known in the art .
  • the antibody, or an antigen binding fragment thereof, provided herein binds OX40L with a KD between 5-3, 4-2, 3-1, 1.9-1.8, 1.8-1.7, 1.7-1.6, 1.6-1.5, 1.9-1.5, 1.5-1, 1-0.8, 1-0.5, 0.9-0.6, 0.7-0.4, 0.6-0.2, 0.5-0.3, 0.3-0.2, 0.2-0.1, 0.1-0.01, 0.01-0.001, or 0.001-0.0001 x 10 -8 M as measured by ELISA or any other suitable method known in the art.
  • the antibody, or an antigen binding fragment thereof, provided herein binds FcRn with an affinity at pH 7.4 compared to pH 6.0 at a ratio (pH 7.4/pH 6.0) of about 10,000, 1,000, 500, 100, 50, 20, 10, 9, 8, 7, 6, 5, 4.5, 4, 3.5, 3, 2.5, 2, 1.95, 1.9, 1.85, 1.8, 1.75, 1.7, 1.65, 1.6, 1.55, 1.50, 1.45, 1.4, 1.3, 1.2, 1.1, or 1.05, as measured by ELISA or any other suitable method known in the art.
  • the antibody, or an antigen binding fragment thereof, provided herein binds FcRn with an affinity at pH 6.0 compared to pH 7.4 at a ratio (pH 6.0/pH 7.4) of about 1-0.8, 1-0.5, 0.9-0.6, 0.7-0.4, 0.6-0.2, 0.5-0.3, 0.3-0.2, 0.2-0.1, 0.1-0.01, 0.01-0.001, or 0.001-0.0001 x 10 -8 M as measured by ELISA or any other suitable method known in the art.
  • Function [00416] “Effector functions” refer to those biological activities mediated by the Fc region of an antibody, which activities may vary depending on the antibody isotype.
  • antibody effector functions include receptor ligand blocking, agonism, or antagonism, C1q binding to activate complement dependent cytotoxicity (CDC), Fc receptor binding to activate antibody-dependent cellular cytotoxicity (ADCC), and antibody dependent cellular phagocytosis (ADCP).
  • Anti-IL-4R ⁇ Antibodies [00417] The present application provides antibodies, or antigen binding fragments thereof, and compositions comprising an antibody, or an antigen binding fragment thereof, which binds IL-4R ⁇ . See also PCT Application No. PCT/US2024/016235 (corresponding to PCT Publication No. WO2024173847), which is incorporated herein by reference in its entirety.
  • an anti-IL-4R ⁇ antibody, or an antigen binding fragment thereof, described herein is selected from an anti-IL-4R ⁇ antibody described therein.
  • an anti-IL-4R ⁇ antibody, or an antigen binding fragment thereof, described herein is selected from dupilumab, stapokibart, and 611.
  • dupilumab comprises a variable heavy (VH) chain sequence having the amino acid sequence of SEQ ID NO: 113 and a variable light (VL) chain sequence having the amino acid sequence of SEQ ID NO: 146.
  • dupilumab comprises a heavy chain having the amino acid sequence of SEQ ID NO: 147 and a light chain sequence having the amino acid sequence of SEQ ID NO: 148.
  • stapokibart comprises a heavy chain having the amino acid sequence of SEQ ID NO: 1074 and a light chain sequence having the amino acid sequence of SEQ ID NO: 1075, or a VH and/or VL therein (e.g., a VH having the sequence of SEQ ID NO: 844 and a VL having the sequence of SEQ ID NO: 845).
  • Anti-IL-4R ⁇ antibodies can include those described herein such as the clones set forth in the drawings and/or tables.
  • the antibody comprises an alternative scaffold. In some embodiments, the antibody consists of an alternative scaffold. In some embodiments, the antibody consists essentially of an alternative scaffold. In some embodiments, the antibody comprises an antibody fragment. In some embodiments, the antibody consists of an antibody fragment. In some embodiments, the antibody consists essentially of an antibody fragment. [00420] In some embodiments the antibodies are monoclonal antibodies. [00421] In some embodiments the antibodies are polyclonal antibodies. [00422] In some embodiments the antibodies are produced by hybridomas. In other embodiments, the antibodies are produced by recombinant cells engineered to express the desired variable and constant domains.
  • the antibodies may be single chain antibodies or other antibody derivatives retaining the antigen specificity and the lower hinge region or a variant thereof.
  • the antibodies may be polyfunctional antibodies, recombinant antibodies, human antibodies, humanized antibodies, fragments or variants thereof.
  • the antibody fragment or a derivative thereof is selected from a Fab fragment, a Fab′2 fragment, a CDR, and scFv.
  • the antibodies are capable of forming an immune complex.
  • For sequence comparison typically one sequence acts as a reference sequence to which test sequences are compared.
  • test and reference sequences are input into a computer, subsequence coordinates are designated, if necessary, and sequence algorithm program parameters are designated.
  • sequence comparison algorithm calculates the percent sequence identity for the test sequence(s) relative to the reference sequence, based on the designated program parameters.
  • Optimal alignment of sequences for comparison can be conducted, e.g., by the local homology algorithm of Smith & Waterman, Adv. Appl. Math.2:482 (1981), by the homology alignment algorithm of Needleman & Wunsch, J. Mol. Biol.48:443 (1970), by the search for similarity method of Pearson & Lipman, Proc. Nat’l. Acad. Sci.
  • an antibody, or an antigen binding fragment thereof, provided herein comprises a VH sequence selected from any one of SEQ ID NOs: 295-297.
  • an antibody, or an antigen binding fragment thereof, provided herein comprises a VH sequence having at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to an illustrative VH sequence selected from any one of SEQ ID NOs: 295-297.
  • an antibody, or an antigen binding fragment thereof, provided herein comprises a VH sequence selected from any one of SEQ ID NOs: 295-297, with up to 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 amino acid substitutions.
  • the amino acid substitutions are conservative amino acid substitutions.
  • the antibodies described in this paragraph are referred to herein as “variants.”
  • such variants are derived from a sequence provided herein, for example, by affinity maturation, site directed mutagenesis, random mutagenesis, or any other method known in the art or described herein.
  • such variants are not derived from a sequence provided herein and may, for example, be isolated de novo according to the methods provided herein for obtaining antibodies.
  • Anti-IL-4R ⁇ VL Domains [00431]
  • an antibody, or an antigen binding fragment thereof, provided herein comprises a VL sequence selected from any one of SEQ ID NOs: 298-300.
  • an antibody, or an antigen binding fragment thereof, provided herein comprises a VL sequence having at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to a VL sequence selected from any one of SEQ ID NOs: 298-300.
  • an antibody, or an antigen binding fragment thereof, provided herein comprises a VL sequence selected from any one of SEQ ID NOs: 298-300, with up to 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 amino acid substitutions.
  • the amino acid substitutions are conservative amino acid substitutions.
  • the antibodies described in this paragraph are referred to herein as “variants.”
  • such variants are derived from a sequence provided herein, for example, by affinity maturation, site directed mutagenesis, random mutagenesis, or any other method known in the art or described herein.
  • such variants are not derived from a sequence provided herein and may, for example, be isolated de novo according to the methods provided herein for obtaining antibodies.
  • an antibody, or an antigen binding fragment thereof, provided herein comprises a VH sequence selected from any one of SEQ ID NOs: 295-297; and a VL sequence selected from any one of SEQ ID NOs: 298-300.
  • a VH sequence selected from any one of SEQ ID NOs: 295-297 can be combined with a VL sequence selected from any one of SEQ ID NOs: 298-300.
  • an antibody provided herein comprises a VH sequence and a VL sequence of a construct provided in TABLE 6 or a VH sequence and a VL sequence of a construct provided in PCT Application No.
  • an antibody, or antigen binding fragment thereof, provided herein comprises a VH sequence and a VL sequence from Table 2 in PCT Application No. PCT/US2024/016235 (e.g., a VH sequence and a VL sequence from the same row of Table 2).
  • an antibody, or an antigen binding fragment thereof, provided herein comprises a VH sequence having at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to a VH sequence selected from any one of SEQ ID NOs: 295-297; and a VL sequence having at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to a VL sequence selected from any one of SEQ ID NOs: 298-300.
  • an antibody, or an antigen binding fragment thereof, provided herein comprises a VH sequence selected from any one of SEQ ID NOs: 295-297, with up to 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 amino acid substitutions, and a VL sequence selected from any one of SEQ ID NOs: 298-300, with up to 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 amino acid substitutions.
  • the amino acid substitutions are conservative amino acid substitutions.
  • the antibodies described in this paragraph are referred to herein as “variants.”
  • such variants are derived from a sequence provided herein, for example, by affinity maturation, site directed mutagenesis, random mutagenesis, or any other method known in the art or described herein.
  • such variants are not derived from a sequence provided herein and may, for example, be isolated de novo according to the methods provided herein for obtaining antibodies.
  • the antibody, or an antigen binding fragment thereof comprises a VH sequence set forth in SEQ ID NO: 295 and a VL sequence set forth in SEQ ID NO: 298.
  • the antibody, or an antigen binding fragment thereof comprises a VH sequence set forth in SEQ ID NO: 296 and a VL sequence set forth in SEQ ID NO: 299. [00439] In certain embodiments, the antibody, or an antigen binding fragment thereof, comprises a VH sequence set forth in SEQ ID NO: 297 and a VL sequence set forth in SEQ ID NO: 300.
  • an antibody, or an antigen binding fragment thereof comprises any of the VH and VL combinations described above and further comprises a heavy chain comprising a human IgG sequence selected from a sequence set forth in SEQ ID NOs: 847-1070 or a sequence having at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity thereto.
  • an antibody comprises any of the VH and VL combinations described above and further comprises a heavy chain comprising a constant heavy chain sequence set forth in SEQ ID NO: 651 or a sequence having at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity thereto.
  • an antibody comprises any of the VH and VL combinations described above and further comprises a constant heavy chain comprising a constant heavy chain sequence set forth in SEQ ID NO: 973 or a sequence having at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity thereto.
  • an antibody comprises any of the VH and VL combinations described above and further comprises a human constant light chain sequence set forth in SEQ ID NO: 738 or a sequence having at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity thereto.
  • an antibody comprises any of the VH and VL combinations described above and further comprises a constant heavy chain sequence set forth in SEQ ID NO: 651 or a sequence having at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity thereto and a human constant light chain sequence set forth in SEQ ID NO: 738 or a sequence having at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity thereto.
  • an antibody comprises any of the VH and VL combinations described above and further comprises a constant heavy chain sequence set forth in SEQ ID NO: 973 or a sequence having at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity thereto and a human constant light chain sequence set forth in SEQ ID NO: 738 or a sequence having at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity thereto.
  • a C-terminal lysine may be present in the corresponding coding sequence of the constant heavy chain region (e.g., in a sequence encoding any one of SEQ ID NOs: 959-1070), it may be cleaved off during manufacture or after administration (resulting in, e.g., a constant heavy chain sequence of any one of SEQ ID NOs: 637-737 and 847-958).
  • any of the antibodies or antigen binding fragments thereof described above may comprise a human IgG sequence containing a C-terminal lysine (e.g., any one of SEQ ID NOs: 959-1070), a human IgG sequence lacking a C-terminal lysine (e.g., any one of SEQ ID NOs: 637-737 and 847-958), or a mixture thereof (e.g., a mixture of the same heavy chain constant sequence with and without a C-terminal lysine, such as a mixture of SEQ ID NO: 973 and SEQ ID NO: 651).
  • a human IgG sequence containing a C-terminal lysine e.g., any one of SEQ ID NOs: 959-1070
  • a human IgG sequence lacking a C-terminal lysine e.g., any one of SEQ ID NOs: 637-737 and 847-958
  • a mixture thereof e.g., a mixture of the
  • Anti-IL4R ⁇ CDRs [00442] In some embodiments, disclosed herein is an antibody, or an antigen binding fragment thereof, comprising 1, 2, 3, 4, 5, or 6 of the CDRs of TABLE 6. In some embodiments, disclosed herein is an antibody, or an antigen binding fragment thereof, comprising 6 of the Kabat CDRs of TABLE 6. In some embodiments, disclosed herein is an antibody, or an antigen binding fragment thereof, comprising 1, 2, 3, 4, 5, or 6 of the Chothia CDRs of TABLE 6. In some embodiments, disclosed herein is an antibody, or an antigen binding fragment thereof, comprising 1, 2, 3, 4, 5, or 6 of the IMGT CDRs of TABLE 6.
  • the antibody, or an antigen binding fragment thereof comprises 6 of the Kabat CDRs, 6 of the Chothia CDRs, or 6 of the IMGT CDRs from a single row of TABLE 6 (e.g., 6 CDRs from the same antibody).
  • an antibody, or an antigen binding fragment thereof comprising 1, 2, 3, 4, 5, or 6 of the CDRs of an antibody provided in PCT Application No. PCT/US2024/016235 (corresponding to PCT Publication No. WO2024173847), incorporated by reference herein in its entirety.
  • an antibody, or an antigen binding fragment thereof comprising 1, 2, 3, 4, 5, or 6 of the Kabat CDRs of an antibody provided in PCT Application No. PCT/US2024/016235.
  • an antibody, or an antigen binding fragment thereof comprising 1, 2, 3, 4, 5, or 6 of the Chothia CDRs of an antibody provided in PCT Application No. PCT/US2024/016235.
  • an antibody, or an antigen binding fragment thereof comprising 1, 2, 3, 4, 5, or 6 of the IMGT CDRs of an antibody provided in PCT Application No. PCT/US2024/016235.
  • the antibody, or an antigen binding fragment thereof comprises 6 of the Kabat CDRs, 6 of the Chothia CDRs, or 6 of the IMGT CDRs from a single row of Table 2 of PCT Application No. PCT/US2024/016235 (e.g., 6 CDRs from the same antibody).
  • an antibody, or an antigen binding fragment thereof, provided herein comprises three CDRs of a VH domain selected from SEQ ID NOs: 295-297.
  • the CDRs are exemplary CDRs.
  • the CDRs are Kabat CDRs.
  • the CDRs are Chothia CDRs.
  • the CDRs are IMGT CDRs. In some aspects, the CDRs are AbM CDRs. In some aspects, the CDRs are Contact CDRs. [00445] In some embodiments, the CDRs are CDRs having at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity to a CDR-H1, CDR-H2, or CDR-H3 selected from SEQ ID NOs: 273-293 and 295-300. In some embodiments, the CDR-H1 is a CDR-H1 of a VH domain selected from SEQ ID NOs: 295-297, with up to 1, 2, 3, 4, or 5 amino acid substitutions.
  • the CDR-H2 is a CDR-H2 of a VH domain selected from SEQ ID NOs: 295-297, with up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions.
  • the CDR-H3 is a CDR-H3 of a VH domain selected from SEQ ID NOs: 295-297, with up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions.
  • the amino acid substitutions are conservative amino acid substitutions.
  • the antibodies described in this paragraph are referred to herein as “variants.”
  • such variants are derived from a sequence provided herein, for example, by affinity maturation, site directed mutagenesis, random mutagenesis, or any other method known in the art or described herein.
  • such variants are not derived from a sequence provided herein and may, for example, be isolated de novo according to the methods provided herein for obtaining antibodies.
  • an antibody, or an antigen binding fragment thereof, provided herein comprises three CDRs of a VL domain selected from SEQ ID NOs: 298-300.
  • the CDRs are exemplary CDRs.
  • the CDRs are Kabat CDRs. In some aspects, the CDRs are Chothia CDRs. In some aspects, the CDRs are IMGT CDRs. In some aspects, the CDRs are AbM CDRs. In some aspects, the CDRs are Contact CDRs.
  • the CDRs are CDRs having at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity to a CDR-L1, CDR-L2, or CDR-L3 selected from SEQ ID NOs: 273-293 and 295-300
  • the CDR- L1 is a CDR-L1 of a VL domain selected from SEQ ID NOs: 298-300, with up to 1, 2, 3, 4, or 5 amino acid substitutions.
  • the CDR-L2 is a CDR-L2 of a VL domain selected from SEQ ID NOs: 298-300, with up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions.
  • the CDR-L3 is a CDR-L3 of a VL domain selected from SEQ ID NOs: 298-300, with up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions.
  • the amino acid substitutions are conservative amino acid substitutions.
  • an antibody, or an antigen binding fragment thereof, provided herein comprises three CDRs of a VH domain selected from SEQ ID NOs: 295-297 and three CDRs of a VL domain selected from SEQ ID NOs: 298-300.
  • the CDRs are exemplary CDRs. In some aspects, the CDRs are Kabat CDRs. In some aspects, the CDRs are Chothia CDRs. In some aspects, the CDRs are IMGT CDRs. In some aspects, the CDRs are AbM CDRs. In some aspects, the CDRs are Contact CDRs. [00449] In some embodiments, an antibody, or an antigen binding fragment thereof, provided herein comprises a CDR-H3 selected from SEQ ID NOs: 281-284.
  • the CDR-H3 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to a CDR-H3 selected from SEQ ID NOs: 281-284.
  • the CDR-H3 is a CDR-H3 selected from SEQ ID NOs: 281-284, with up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions.
  • the amino acid substitutions are conservative amino acid substitutions.
  • the antibodies described in this paragraph are referred to herein as “variants.”
  • such variants are derived from a sequence provided herein, for example, by affinity maturation, site directed mutagenesis, random mutagenesis, or any other method known in the art or described herein.
  • such variants are not derived from a sequence provided herein and may, for example, be isolated de novo according to the methods provided herein for obtaining antibodies.
  • an antibody, or an antigen binding fragment thereof, provided herein comprises a CDR-H1 selected from SEQ ID NOs: 273-275.
  • the CDR-H1 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to a CDR-H1 selected from SEQ ID NOs: 273-275.
  • the CDR-H1 is a CDR-H1 selected from SEQ ID NOs: 273-275, with up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions.
  • the amino acid substitutions are conservative amino acid substitutions.
  • the antibodies described in this paragraph are referred to herein as “variants.”
  • such variants are derived from a sequence provided herein, for example, by affinity maturation, site directed mutagenesis, random mutagenesis, or any other method known in the art or described herein.
  • such variants are not derived from a sequence provided herein and may, for example, be isolated de novo according to the methods provided herein for obtaining antibodies.
  • an antibody, or an antigen binding fragment thereof, provided herein comprises a CDR-H2 selected from SEQ ID NOs: 276-282.
  • the CDR-H2 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to a CDR-H2 H2 selected from SEQ ID NOs: 276-282.
  • the CDR-H2 is a CDR-H2 selected from SEQ ID NOs: 276-282, with up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions.
  • the amino acid substitutions are conservative amino acid substitutions.
  • the antibodies described in this paragraph are referred to herein as “variants.”
  • such variants are derived from a sequence provided herein, for example, by affinity maturation, site directed mutagenesis, random mutagenesis, or any other method known in the art or described herein.
  • such variants are not derived from a sequence provided herein and may, for example, be isolated de novo according to the methods provided herein for obtaining antibodies.
  • an antibody, or an antigen binding fragment thereof, provided herein comprises a CDR-L3 of SEQ ID NO: 293.
  • the CDR-L3 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to a CDR-L3 of SEQ ID NO: 293.
  • the CDR-L3 is a CDR-L3 of SEQ ID NO: 293, with up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions.
  • the amino acid substitutions are conservative amino acid substitutions.
  • an antibody, or an antigen binding fragment thereof, provided herein comprises a CDR-L2 selected from SEQ ID NOs: 290-292 and the amino acid sequence LG or EG.
  • the CDR-L2 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to a CDR-L2 selected from SEQ ID NOs: 290-292 and the amino acid sequence LG or EG.
  • the CDR-L2 is a CDR-L2 selected from SEQ ID NOs: 290-292 and the amino acid sequence LG or EG, with up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions.
  • the amino acid substitutions are conservative amino acid substitutions.
  • the antibodies described in this paragraph are referred to herein as “variants.”
  • such variants are derived from a sequence provided herein, for example, by affinity maturation, site directed mutagenesis, random mutagenesis, or any other method known in the art or described herein.
  • such variants are not derived from a sequence provided herein and may, for example, be isolated de novo according to the methods provided herein for obtaining antibodies.
  • an antibody, or an antigen binding fragment thereof, provided herein comprises a CDR-L1 selected from SEQ ID NOs: 285-289.
  • the CDR-L1 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to a CDR-L1 selected from SEQ ID NOs: 285-289.
  • the CDR-L1 is a CDR-L1 selected from SEQ ID NOs: 285-289, with up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions.
  • the amino acid substitutions are conservative amino acid substitutions.
  • the antibodies described in this paragraph are referred to herein as “variants.”
  • such variants are derived from a sequence provided herein, for example, by affinity maturation, site directed mutagenesis, random mutagenesis, or any other method known in the art or described herein.
  • such variants are not derived from a sequence provided herein and may, for example, be isolated de novo according to the methods provided herein for obtaining antibodies.
  • an antibody, or an antigen binding fragment thereof comprises a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 273; a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 276; a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 281; a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 285; a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 292; and a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 293.
  • an antibody, or an antigen binding fragment thereof comprises a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 274; a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 277; a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 281; a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 285; a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 292; and a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 293.
  • an antibody, or an antigen binding fragment thereof comprises a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 275; a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 278; a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 282; a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 286; a CDR-L2 comprising the amino acid sequence LG; and a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 293.
  • an antibody, or an antigen binding fragment thereof comprises a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 273; a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 279; a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 283; a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 287; a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 291; and a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 293.
  • an antibody, or an antigen binding fragment thereof comprises a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 274; a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 277; a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 283; a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 287; a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 291; and a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 293.
  • an antibody, or an antigen binding fragment thereof comprises a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 275; a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 280; a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 284; a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 288; a CDR-L2 comprising the amino acid sequence LG; and a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 293.
  • an antibody, or an antigen binding fragment thereof comprises a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 273; a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 279; a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 281; a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 289; a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 290; and a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 293.
  • an antibody, or an antigen binding fragment thereof comprises a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 274; a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 277; a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 281; a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 289; a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 290; and a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 293.
  • an antibody, or an antigen binding fragment thereof comprises a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 275; a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 280; a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 282; a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 288; a CDR-L2 comprising the amino acid sequence EG; and a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 293.
  • any of the antibodies or antigen binding fragments thereof described above further comprises a heavy chain comprising a human IgG sequence selected from a sequence set forth in any one of SEQ ID NOs: 847-1070 or a sequence having at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity thereto.
  • any of the antibodies or antigen binding fragments thereof described above further comprises a constant heavy chain sequence set forth in SEQ ID NO: 651 or a sequence having at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity thereto.
  • any of the antibodies or antigen binding fragments thereof described above further comprises a constant heavy chain sequence set forth in SEQ ID NO: 973 or a sequence having at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity thereto.
  • any of the antibodies or antigen binding fragments thereof described above further comprises a human constant light chain sequence set forth in SEQ ID NO: 738 or a sequence having at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity thereto.
  • any of the antibodies or antigen binding fragments thereof described above further comprises a constant heavy chain sequence set forth in SEQ ID NO: 651 or a sequence having at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity thereto and a human constant light chain sequence set forth in SEQ ID NO: 738 or a sequence having at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity thereto.
  • any of the antibodies or antigen binding fragments thereof described above further comprises a constant heavy chain sequence set forth in SEQ ID NO: 973 or a sequence having at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity thereto and a human constant light chain sequence set forth in SEQ ID NO: 738 or a sequence having at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity thereto.
  • a C-terminal lysine may be present in the corresponding coding sequence of the constant heavy chain region (e.g., in a sequence encoding any one of SEQ ID NOs: 959-1070), it may be cleaved off during manufacture or after administration (resulting in, e.g., a constant heavy chain sequence of any one of SEQ ID NOs: 637-737 and 847-958).
  • any of the antibodies or antigen binding fragments thereof described above may comprise a human IgG sequence containing a C-terminal lysine (e.g., any one of SEQ ID NOs: 959-1070), a human IgG sequence lacking a C-terminal lysine (e.g., any one of SEQ ID NOs: 637-737 and 847-958), or a mixture thereof (e.g., a mixture of the same heavy chain constant sequence with and without a C-terminal lysine, such as a mixture of SEQ ID NO: 973 and SEQ ID NO: 651).
  • the amino acid substitutions are conservative amino acid substitutions.
  • the antibodies described in this disclosure are referred to herein as “variants” or “clones”.
  • variants or clones are derived from a sequence provided herein, for example, by affinity maturation, site directed mutagenesis, random mutagenesis, or any other method known in the art or described herein.
  • variants or cones are not derived from a sequence provided herein and may, for example, be isolated de novo according to the methods provided herein for obtaining antibodies.
  • Fc Region [00467] The structures of the Fc regions of various immunoglobulins, and the glycosylation sites contained therein, are known in the art. See Schroeder and Cavacini, J. Allergy Clin.
  • the Fc region may be a naturally occurring Fc region or an Fc region modified as described in the art or elsewhere in this disclosure.
  • numbering of amino acid residues in the Fc region or constant region is according to the EU numbering system, also called the EU index, as described in Kabat et al., Sequences of Proteins of Immunological Interest, 5th Ed. Public Health Service, National Institutes of Health, Bethesda, MD, 1991.
  • an “Fc polypeptide” of a dimeric Fc as used herein refers to one of the two polypeptides forming the dimeric Fc domain, i.e., a polypeptide comprising C-terminal constant regions of an immunoglobulin heavy chain, capable of stable self-association.
  • an Fc polypeptide of a dimeric IgG Fc comprises an IgG CH2 and an IgG CH3 constant domain sequence.
  • An Fc can be of the class IgA, IgD, IgE, IgG, and IgM, and several of these may be further divided into subclasses (isotypes), e.g., IgG 1 , IgG 2 , IgG 3 , IgG 4 , IgA 1 , and IgA 2 .
  • the terms “Fc receptor” and “FcR” are used to describe a receptor that binds to the Fc region of an antibody.
  • an FcR can be a native sequence human FcR.
  • an FcR is one which binds an IgG antibody (a gamma receptor) and includes receptors of the Fc ⁇ RI, Fc ⁇ RII, and Fc ⁇ RIII subclasses, including allelic variants and alternatively spliced forms of these receptors.
  • Fc ⁇ RII receptors include Fc ⁇ RIIA (an “activating receptor”) and Fc ⁇ RIIB (an “inhibiting receptor”), which have similar amino acid sequences that differ primarily in the cytoplasmic domains thereof.
  • Immunoglobulins of other isotypes can also be bound by certain FcRs (see, e.g., Janeway et al., Immuno Biology: the immune system in health and disease, (Elsevier Science Ltd., NY) (4th ed., 1999)).
  • Activating receptor Fc ⁇ RIIA contains an immunoreceptor tyrosine-based activation motif (ITAM) in its cytoplasmic domain.
  • Inhibiting receptor Fc ⁇ RIIB contains an immunoreceptor tyrosine-based inhibition motif (ITIM) in its cytoplasmic domain (reviewed in Da ⁇ ron, Annu. Rev. Immunol.15:203-234 (1997)).
  • FcRs are reviewed in Ravetch and Kinet, Annu. Rev.
  • FcR FcR
  • FcRn neonatal receptor
  • Fc comprises one or more modifications designed to promote selective binding of Fc-gamma receptors.
  • Exemplary mutations that may alter the binding of FcRs to the Fc are listed below (in EU numbering format): • S298A/E333A/K334A, S298A/E333A/K334A/K326A (Lu Y, Vernes JM, Chiang N, et al., J Immunol Methods.2011 Feb 28;365(1-2):132-41); • F243L/R292P/Y300L/V305I/P396L, F243L/R292P/Y300L/L235V/P396L (Stavenhagen JB, Gorlatov S, Tuaillon N, et al., Cancer Res.2007 Sep 15;67(18):8882-
  • an antibody, or an antigen binding fragment thereof, described herein includes modifications designed to improve its ability to mediate effector function. Such modifications that can have this effect are known in the art and include afucosylation, or engineering of the affinity of the Fc towards an activating receptor, mainly FCGR3a for ADCC, and towards C1q for CDC.
  • modifications designed to improve its ability to mediate effector function.
  • modifications that can have this effect are known in the art and include afucosylation, or engineering of the affinity of the Fc towards an activating receptor, mainly FCGR3a for ADCC, and towards C1q for CDC.
  • Examples of cell lines capable of producing defucosylated antibody include CHO-DG44 with stable overexpression of the bacterial oxidoreductase GDP-6-deoxy-D-lyxo-4-hexylose reductase (RMD) (see von Horsten et al. (2010) supra) or Lec13 CHO cells, which are deficient in protein fucosylation (see Ripka et al. (1986) Arch. Biochem. Biophys.249:533-545; U.S. Pat. Pub.
  • RMD bacterial oxidoreductase GDP-6-deoxy-D-lyxo-4-hexylose reductase
  • Antibodies can be fully afucosylated (meaning they contain no detectable fucose) or they can be partially afucosylated, meaning that the isolated antibody contains less than 95%, less than 85%, less than 75%, less than 65%, less than 55%, less than 45%, less than 35%, less than 25%, less than 15% or less than 5% of the amount of fucose normally detected for a similar antibody produced by a mammalian expression system.
  • an antibody, or an antigen binding fragment thereof, provided herein comprises an IgG1 domain with reduced fucose content at position Asn 297 compared to a naturally occurring IgG1 domain. Such Fc domains can have improved ADCC.
  • an antibody, or an antigen binding fragment thereof, provided herein comprises an Fc region with one or more amino acid substitutions which improve ADCC, such as a substitution at one or more of positions 298, 333, and 334 of the Fc region.
  • an antibody, or an antigen binding fragment thereof, provided herein comprises an Fc region with one or more amino acid substitutions at positions 239, 332, and 330, as described in Lazar et al. (2006) Proc. Natl. Acad. Sci. USA 103:4005-4010, incorporated by reference in its entirety.
  • Other illustrative glycosylation variants which may be incorporated into the antibodies provided herein are described, for example, in U.S. Pat. Pub.
  • an antibody, or an antigen binding fragment thereof, provided herein comprises an Fc region with at least one galactose residue in the oligosaccharide attached to the Fc region.
  • Such antibody variants may have improved CDC function. Examples of such antibody variants are described, for example, in WO 1997/30087; WO 1998/58964; and WO 1999/22764; each of which is incorporated by reference in its entirety.
  • an antibody described herein can include a dimeric Fc that comprises one or more amino acid modifications as noted in TABLE 7 that may confer improved effector function.
  • the antibody can be afucosylated to improve effector function. TABLE 7.
  • an antibody, or an antigen binding fragment thereof, provided herein comprises one or more alterations that is designed to improve or diminish C1q binding and/or CDC. See U.S. Pat. No.6,194,551; WO 99/51642; and Idusogie et al., J. Immunol., 2000, 164:4178-4184; each of which is incorporated by reference in its entirety.
  • an antibody provided herein comprises a heavy chain comprising a constant heavy chain sequence selected from the sequences set forth in any one of SEQ ID NOs: 847-1070.
  • the antibody comprises a VH sequence set forth in SEQ ID NO: 295 and a VL sequence set forth in SEQ ID NO: 298; and the constant heavy chain comprises a human IgG sequence selected from a sequence set forth in any one of SEQ ID NOs: 847-1070 (e.g., SEQ ID NO: 973 or SEQ ID NO: 861).
  • the antibody comprises a VH sequence set forth in SEQ ID NO: 296 and a VL sequence set forth in SEQ ID NO: 299; and the constant heavy chain comprises a human IgG sequence selected from a sequence set forth in any one of SEQ ID NOs: 847-1070 (e.g., SEQ ID NO: 973 or SEQ ID NO: 861).
  • the antibody comprises a VH sequence set forth in SEQ ID NO: 297 and a VL sequence set forth in SEQ ID NO: 300; and the constant heavy chain comprises a human IgG sequence selected from a sequence set forth in any one of SEQ ID NOs: 847-1070 (e.g., SEQ ID NO: 973 or SEQ ID NO: 861).
  • the Fc region comprises one or more amino acid substitutions, wherein the one or more substitutions result in increased antibody half-life, increased ADCC activity, increased ADCP activity, or increased CDC activity compared with the Fc without the one or more substitutions.
  • the one or more amino acid substitutions results in increased antibody half-life at pH 6.0 compared to an antibody comprising a wild-type Fc region.
  • the isolated antibody comprising an Fc region with one or more amino acid substitutions has a half-life of about 20 to 60 days in a human.
  • the antibody has an increased half-life that is about 10,000-fold, 1,000-fold, 500-fold, 100-fold, 50-fold, 20-fold, 10-fold, 9-fold, 8-fold, 7-fold, 6-fold, 5-fold, 4.5-fold, 4-fold, 3.5-fold, 3-fold, 2.5-fold, 2-fold, 1.95-fold, 1.9-fold, 1.85- fold, 1.8-fold, 1.75-fold, 1.7-fold, 1.65-fold, 1.6-fold, 1.55-fold, 1.50-fold, 1.45-fold, 1.4-fold, 1.35-fold, 1.3-fold, 1.25-fold, 1.2-fold, 1.15-fold, 1.1-fold, or 1.05-fold longer compared to an antibody comprising a wild-type Fc region.
  • the antibody has an increased half-life that is about 10,000-fold, 1,000-fold, 500-fold, 100-fold, 50-fold, 20-fold, 10-fold, 9-fold, 8-fold, 7-fold, 6-fold, 5-fold, 4.5-fold, 4-fold, 3.5-fold, 3-fold, 2.5-fold, 2- fold, 1.95-fold, 1.9-fold, 1.85-fold, 1.8-fold, 1.75-fold, 1.7-fold, 1.65-fold, 1.6-fold, 1.55-fold, 1.50-fold, 1.45-fold, 1.4-fold, 1.35-fold, 1.3-fold, 1.25-fold, 1.2-fold, 1.15-fold, 1.1-fold, or 1.05-fold longer compared to dupilumab.
  • the Fc region comprises one or more amino acid substitutions, wherein the one or more substitutions result in increased antibody half-life, and a decrease in one or more of ADCC activity, ADCP activity, or CDC activity compared with the Fc without the one or more substitutions.
  • the one or more amino acid substitutions results in increased antibody half-life at pH 6.0 compared to an antibody comprising a wild-type Fc region.
  • the isolated antibody comprising an Fc region with one or more amino acid substitutions has a half-life of about 20 to 60 days in a human.
  • the one or more amino acid substitutions is selected from the group consisting of S228P (SP), M252Y, S254T, T256E, T256D, T250Q, H285D, T307A, T307Q, T307R, T307W, L309D, Q411H, Q311V, A378V, E380A, M428L, N434A, N434S, N297A, D265A, L234A, L235A, and N434W.
  • SP S228P
  • M252Y S254T
  • T256E T256D
  • T250Q H285D
  • T307A, T307Q, T307R, T307W L309D
  • Q411H, Q311V, A378V, E380A M428L, N434A, N434S, N297A, D265A, L234A, L235A, and N434W.
  • the one or more amino acid substitutions comprises a plurality of amino acid substitutions selected from the group consisting of M428L/N434S (LS), M252Y/S254T/T256E (YTE), T250Q/M428L, T307A/E380A/N434A, T256D/T307Q (DQ), T256D/T307W (DW), M252Y/T256D (YD), T307Q/Q311V/A378V (QVV), T256D/H285D/T307R/Q311V/A378V (DDRVV), L309D/Q311H/N434S (DHS), S228P/L235E (SPLE), L234A/L235A (LALA), M428L/N434A (LA), L235A/G237A(LAGA), L234A/L235A/G237A (LALAGA), L234A/L/L, L
  • the one or more amino acid substitutions is selected from the group consisting of LALA/YTE, LAGA/YTE, LALA/LS, YTE, and LS. [00490] In certain embodiments, the one or more amino acid substitutions comprises or consists of LALA/YTE. In certain embodiments, the one or more amino acid substitutions comprises or consists of LAGA/YTE. In certain embodiments, the one or more amino acid substitutions comprises or consists of LALA/LS. In certain embodiments, the one or more amino acid substitutions comprises or consists of YTE. In certain embodiments, the one or more amino acid substitutions comprises or consists of LS.
  • an antibody described herein comprises an Fc region with YTE mutations at positions 260, 262, and 264.
  • an antibody described herein comprises an Fc region with LALA mutations at positions 242 and 243, respectively.
  • an antibody described herein comprises an Fc region with YTE mutations at positions 260, 262, and 264 and with LALA mutations at positions 242 and 243.
  • the IL-4R ⁇ antibody described herein comprises the heavy and light chain variable regions of Construct 38 and an Fc region comprising YTE mutations at positions 260, 262, and 264, respectively and with LALA mutations at positions 242 and 243, respectively (e.g., as shown in the heavy chain sequences of SEQ ID NOs: 836 and 837).
  • the human Fc region comprises a human IgG1 Fc with LALA mutations.
  • the human Fc region comprises a human IgG1 Fc with YTE mutations.
  • the human Fc region comprises a human IgG1 Fc with LALA and YTE mutations.
  • YTE and “LALA” mutations can be located at different amino acid position numbers.
  • a human Fc region can comprise a human IgG1 Fc with LALA mutations at L242A/L243A and/or YTE mutations at M260Y/S262T/T264E.
  • the IL-4R ⁇ antibody, or antigen binding fragment thereof comprises a heavy chain variable region sequence comprising an amino acid sequence set forth in SEQ ID NO: 297, a constant heavy chain sequence set forth in SEQ ID NO: 651, a light chain variable region sequence comprising an amino acid sequence set forth in SEQ ID NO: 300, and a constant light chain sequence set forth in SEQ ID NO: 738.
  • the IL-4R ⁇ antibody comprises a heavy chain variable region sequence comprising an amino acid sequence set forth in SEQ ID NO: 297, a constant heavy chain sequence set forth in SEQ ID NO: 973, a light chain variable region sequence comprising an amino acid sequence set forth in SEQ ID NO: 300, and a constant light chain sequence set forth in SEQ ID NO: 738.
  • the C-terminal Lys330 of the constant heavy chain sequence of SEQ ID NO: 973 may or may not be present.
  • the disclosure specifically contemplates SEQ ID NO: 973 that does not include the C-terminal Lys corresponding to Lys330 (as set forth in SEQ ID NO: 651).
  • a polypeptide comprising SEQ ID NO: 973 may be expressed including a C-terminal Lys330 which then may be proteolytically cleaved upon expression of the polypeptide (e.g., a polypeptide comprising SEQ ID NO: 973 is expressed using a nucleic acid construct encoding the polypeptide including a C-terminal lysine residue, which may then be removed via cleavage to produce a polypeptide in which the constant heavy chain has the sequence of SEQ ID NO: 651, such as the polypeptide of SEQ ID NO: 837).
  • the IL-4R ⁇ antibody that is administered can have the constant heavy chain sequence of SEQ ID NO: 973, SEQ ID NO: 651, or a mixture thereof.
  • the IL-4R ⁇ antibody comprises a light chain comprising the sequence set forth in SEQ ID NO: 838.
  • the IL-4R ⁇ antibody comprises a heavy chain comprising the sequence set forth in SEQ ID NO: 836 or SEQ ID NO: 837.
  • the IL-4R ⁇ antibody comprises a heavy chain comprising the sequence set forth in SEQ ID NO: 836.
  • the IL-4R ⁇ antibody comprises a heavy chain comprising the sequence set forth in SEQ ID NO: 837.
  • the IL-4R ⁇ antibody comprises a light chain comprising the sequence set forth in SEQ ID NO: 838 and a heavy chain comprising the sequence set forth in SEQ ID NO: 836. In some embodiments, the IL-4R ⁇ antibody comprises a light chain comprising the sequence set forth in SEQ ID NO: 838 and a heavy chain comprising the sequence set forth in SEQ ID NO: 837. [00497] In certain embodiments, the Fc region binds an Fc ⁇ Receptor selected from the group consisting of: Fc ⁇ RI, Fc ⁇ RIIa, Fc ⁇ RIIb, Fc ⁇ RIIc, Fc ⁇ RIIIa, and Fc ⁇ RIIIb.
  • the Fc region binds an Fc ⁇ Receptor with higher affinity at pH 6.0 compared to an antibody comprising a wild-type Fc region.
  • Binding [00498]
  • the affinity of a molecule X for its partner Y can be represented by the dissociation equilibrium constant (K D ).
  • K D dissociation equilibrium constant
  • the kinetic components that contribute to the dissociation equilibrium constant are described in more detail below.
  • Affinity can be measured by common methods known in the art, including those described herein, such as surface plasmon resonance (SPR) technology (e.g., BIACORE®) or biolayer interferometry (e.g., FORTEBIO®).
  • the terms “bind,” “specific binding,” “specifically binds to,” “specific for,” “selectively binds,” and “selective for” a particular antigen (e.g., a polypeptide target) or an epitope on a particular antigen mean binding that is measurably different from a non-specific or non-selective interaction (e.g., with a non-target molecule).
  • Specific binding can be measured, for example, by measuring binding to a target molecule (i.e., IL-4R ⁇ ) and comparing it to binding to a non-target molecule.
  • Specific binding can also be determined by competition with a control molecule that mimics the epitope recognized on the target molecule. In that case, specific binding is indicated if the binding of the antibody to the target molecule is competitively inhibited by the control molecule.
  • the affinity of an anti-IL-4R ⁇ antibody, or an antigen binding fragment thereof, for a non-target molecule is less than about 50% of the affinity for IL-4R ⁇ . In some embodiments, the affinity of an anti-IL-4R ⁇ antibody, or an antigen binding fragment thereof, for a non-target molecule is less than about 40% of the affinity for IL-4R ⁇ .
  • the affinity of an anti-IL-4R ⁇ antibody, or an antigen binding fragment thereof, for a non-target molecule is less than about 30% of the affinity for IL-4R ⁇ . In some embodiments, the affinity of an anti-IL-4R ⁇ antibody, or an antigen binding fragment thereof, for a non-target molecule is less than about 20% of the affinity for IL-4R ⁇ . In some embodiments, the affinity of an anti-IL-4R ⁇ antibody, or an antigen binding fragment thereof, for a non-target molecule is less than about 10% of the affinity for IL-4R ⁇ .
  • the affinity of an anti-IL-4R ⁇ antibody, or an antigen binding fragment thereof, for a non-target molecule is less than about 1% of the affinity for IL-4R ⁇ . In some embodiments, the affinity of an anti-IL-4R ⁇ antibody, or an antigen binding fragment thereof, for a non-target molecule is less than about 0.1% of the affinity for IL-4R ⁇ . [00500] In certain embodiments, the antibody, or an antigen binding fragment thereof, binds a human IL-4R ⁇ . [00501] In certain embodiments, the antibody, or an antigen binding fragment thereof, binds an IL-4R ⁇ sequence set forth in any one of SEQ ID NOs: 301-303.
  • the antibody is cross-reactive to cynomolgus monkey IL- 4R ⁇ .
  • the antibody, or an antigen binding fragment thereof binds to an IL-4R ⁇ sequence set forth in SEQ ID NOs: 301-303 with a KD of less than or equal to about 1, 2, 3, 4, 5, 6, 7, 8, 9 x 10 -9 M, as measured by SPR.
  • the antibody, or an antigen binding fragment thereof binds to an IL-4R ⁇ sequence set forth in SEQ ID NOs: 301-303 with a KD of less than or equal to about 1 x 10 -10 M, as measured by SPR.
  • the antibody, or an antigen binding fragment thereof binds to human IL-4R ⁇ with a KD of less than or equal to about 1 x 10 -9 M, as measured by SPR.
  • an antibody, or an antigen binding fragment thereof, provided herein binds IL-4R ⁇ with a KD of less than or equal to about 0.01, 0.02, 0.03, 0.04, 0.05, 0.06, 0.07, 0.08, 0.09, 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1, 1.1, 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, 1.9, 1.95, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 7, 8, 9, or 10 x 10 -8 M, as measured by ELISA or any other suitable method known in the art.
  • an antibody, or an antigen binding fragment thereof, provided herein binds IL-4R ⁇ with a KD of less than or equal to about 0.01, 0.02, 0.03, 0.04, 0.05, 0.06, 0.07, 0.08, 0.09, 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1, 1.1, 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, 1.9, 1.95, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 7, 8, 9, or 10 x 10 -9 M, as measured by ELISA or any other suitable method known in the art.
  • the KD of the antibody, or an antigen binding fragment thereof, provided herein for the binding of IL-4R ⁇ is between about 0.001-0.01, 0.01-0.1, 0.01-0.05, 0.05-0.1, 0.1-0.5, 0.5-1, 0.25-0.75, 0.25-0.5, 0.5-0.75, 0.75-1, 0.75-2, 1.1-1.2, 1.2- 1.3, 1.3-1.4, 1.4-1.5, 1.5-1.6, 1.6-1.7, 1.7-1.8, 1.8-1.9, 1.9-2, 1-2, 1-5, 2-7, 3-8, 3-5, 4-6, 5-7, 6-8, 7-9, 7-10, or 5-10 x 10 -8 M, as measured by ELISA or any other suitable method known in the art.
  • an antibody, or an antigen binding fragment thereof, provided herein binds IL-4R ⁇ with a KD of less than or equal to about 1 x 10 -8 M, or less than or equal to about 1 x 10 -9 M as measured by ELISA or any other suitable method known in the art.
  • the antibody, or an antigen binding fragment thereof, provided herein binds IL-4R ⁇ with a KD of less than or equal to about 10, 9, 8, 7, 6, 5, 4.5, 4, 3.5, 3, 2.5, 2, 1.98, 1.95, 1.9, 1.85, 1.8, 1.75, 1.7, 1.65, 1.6, 1.55, 1.50, 1.45, 1.4, 1.3, 1.2, 1.1, 1, 0.9, 0.85, 0.8, 0.75, 0.7, 0.65, 0.6, 0.55, 0.5, 0.45, 0.4, 0.35, 0.3, 0.25, 0.2, 0.15, 0.1, 0.05, 0.01, 0.005, 0.001, 0.0005, or 0.0001 x 10 -8 M, or less, as measured by ELISA or any other suitable method known in the art .
  • the antibody, or an antigen binding fragment thereof, provided herein binds IL-4R ⁇ with a K D between 5-3, 4-2, 3-1, 1.9-1.8, 1.8- 1.7, 1.7-1.6, 1.6-1.5, 1.9-1.5, 1.5-1, 1-0.8, 1-0.5, 0.9-0.6, 0.7-0.4, 0.6-0.2, 0.5-0.3, 0.3-0.2, 0.2-0.1, 0.1-0.01, 0.01-0.001, or 0.001-0.0001 x 10 -8 M as measured by ELISA or any other suitable method known in the art.
  • the antibody, or an antigen binding fragment thereof, provided herein binds FcRn with an affinity at pH 7.4 compared to pH 6.0 at a ratio (pH 7.4/pH 6.0) of about 10,000, 1,000, 500, 100, 50, 20, 10, 9, 8, 7, 6, 5, 4.5, 4, 3.5, 3, 2.5, 2, 1.95, 1.9, 1.85, 1.8, 1.75, 1.7, 1.65, 1.6, 1.55, 1.50, 1.45, 1.4, 1.3, 1.2, 1.1, or 1.05, as measured by ELISA or any other suitable method known in the art.
  • the antibody, or an antigen binding fragment thereof, provided herein binds FcRn with an affinity at pH 6.0 compared to pH 7.4 at a ratio (pH 6.0/pH 7.4) of about 1-0.8, 1-0.5, 0.9-0.6, 0.7-0.4, 0.6-0.2, 0.5-0.3, 0.3-0.2, 0.2-0.1, 0.1-0.01, 0.01-0.001, or 0.001-0.0001 x 10 -8 M as measured by ELISA or any other suitable method known in the art.
  • Function [00508] “Effector functions” refer to those biological activities mediated by the Fc region of an antibody, which activities may vary depending on the antibody isotype.
  • antibody effector functions include receptor ligand blocking, agonism, or antagonism, C1q binding to activate complement dependent cytotoxicity (CDC), Fc receptor binding to activate antibody-dependent cellular cytotoxicity (ADCC), and antibody dependent cellular phagocytosis (ADCP).
  • the effector function of the anti-IL-4R ⁇ antibody described herein is antagonism and blocks the IL-4R ⁇ receptor binding to IL-4R ⁇ .
  • Multi-Specific Antibodies [00509] The present application provides multi-specific antibodies which comprises at least two distinct antigen binding regions; wherein at least one antigen binding region binds OX40L and at least one antigen binding region binds IL-4R ⁇ .
  • a multi-specific antibody of the disclosure is a bispecific antibody.
  • Multi-specific antibodies of the present disclosure can comprise any antigen binding region of any antibody or antibody fragment format that binds to an antigen.
  • suitable antibody or antibody fragment formats include, without limitation, a monoclonal antibody, a polyclonal antibody, a recombinant antibody, a bispecific antibody, a conjugated antibody, a human antibody, a humanized antibody, and a functional fragment of an antibody, including but not limited to a single-domain antibody (sdAb) also referred to interchangeably herein as a variable domain (VHH) of camelid derived nanobody, a heavy chain variable domain (VH), a light chain variable domain (VL), and an alternative scaffold known in the art to function as antigen binding region, such as a recombinant fibronectin domain, a T cell receptor (TCR), a recombinant TCR with enhanced affinity, or a fragment thereof, e.g.,
  • the antigen binding region is beneficial for the antigen binding region to be derived from the same species in which the multi-specific antibody will ultimately be used in.
  • the antigen binding region of the multi-specific antibody comprises human or humanized residues for the antigen binding region of an antibody or antibody fragment.
  • the multi-specific antibody comprises an antibody (e.g., an IgG).
  • a multi-specific antibody of the disclosure comprises a bispecific antibody (e.g., a bispecific IgG).
  • the antibody is a human antibody.
  • the antibody is a humanized antibody.
  • the antibody is a chimeric antibody.
  • the antigen binding region comprises an antigen binding fragment of an antibody.
  • the antigen binding region is part of a F(ab) fragment.
  • the antigen binding region is part of a F(ab′) fragment.
  • the antigen binding region is part of an scFv (e.g., scFv or scdsFv).
  • the antigen binding region is part of two single chain variable fragments (scFvs or scdsFvs). In some embodiments, each of the two scFvs binds to a distinct epitope on the same antigen.
  • the antigen binding region is part of a first scFv and a second scFv. In some embodiments, the first scFv and the second scFv bind different antigens.
  • the scFv is a human scFv. In some embodiments, the scFv is a humanized scFv. In some embodiments, the scFv is a chimeric scFv. In some embodiments, the scFv comprises a heavy chain variable domain (VH) and a light chain variable domain (VL). In some embodiments, the VH and VL are separated by a peptide linker.
  • the scFv comprises the structure VH-L-VL or VL-L-VH, wherein VH is the heavy chain variable domain, L is the peptide linker, and VL is the light chain variable domain.
  • a multi-specific antibody of the disclosure is a tetrabody comprising a heavy chain and scFv (e.g., scFv or scdsFv) fusion.
  • each of the one or more scFvs comprises the structure VH-L-VL or VL-L-VH, wherein VH is the heavy chain variable domain, L is the peptide linker, and VL is the light chain variable domain.
  • each scFv can be linked to the next scFv with a peptide linker.
  • each of the one or more scFvs is separated by a peptide linker.
  • each of the two scFvs binds to a distinct epitope on the same antigen.
  • the antigen binding region is part of a single-domain antibody (sdAb; also known as VHH).
  • the sdAb is a humanized sdAb.
  • the sdAb is a chimeric sdAb.
  • a multi-specific antibody of the disclosure is a tetrabody comprising a heavy chain and sdAb fusion.
  • a multi-specific antibody of the present disclosure may comprise two or more antigen-binding domains, three or more antigen-binding domains, four or more antigen-binding domains, five or more antigen-binding domains, six or more antigen- binding domains, seven or more antigen-binding domains, eight or more antigen-binding domains, nine or more antigen-binding domains, or ten or more antigen-binding domains.
  • each of the two or more antigen-binding domains binds the same antigen.
  • each of the two or more antigen-binding domains binds a different epitope of the same antigen. In some embodiments, each of the two or more antigen- binding domains binds a different antigen. In some embodiments, the two or more antigen- binding domains provide the multi-specific antibody with logic gating, such as ‘or’ logic gating. [00517] In some embodiments, the multi-specific antibody comprises two or more (e.g., four) antigen binding regions. In some embodiments, two or more antigen binding regions are attached to one another via a flexible linker.
  • antigen binding regions are part of an antibody format selected from an antibody (e.g., an IgG), an antigen binding fragment of an antibody, an scFv (e.g., scFv or scdsFv), a Fab, a sdAb (VHH), or a recombinant fibronectin domain.
  • an antibody e.g., an IgG
  • an scFv e.g., scFv or scdsFv
  • Fab a sdAb
  • VHH a recombinant fibronectin domain
  • one or two of the two or more antigen binding regions are part of an IgG antibody.
  • one or two of the two or more antigen binding regions are part of a scFv (e.g., scFv or scdsFv).
  • one or two of the two or more antigen binding regions are part of a Fab.
  • the multi-specific antibody comprises an antibody fragment (e.g., scFv).
  • the VH can be upstream or downstream of the VL.
  • the upstream antibody or antibody fragment (e.g., scFv) is arranged with its VH (VH1) upstream of its VL (VL1) and the downstream antibody or antibody fragment (e.g., scFv) is arranged with its VL (VL2) upstream of its VH (VH2), such that the overall multi-specific antibody has the arrangement VH1-VL1-VL2-VH2.
  • the upstream antibody or antibody fragment (e.g., scFv) is arranged with its VL (VL1) upstream of its VH (VH1) and the downstream antibody or antibody fragment (e.g., scFv) is arranged with its VH (VH2) upstream of its VL (VL2), such that the overall multi- specific antibody has the arrangement VL1-VH1-VH2-VL2.
  • a linker is disposed between the two antibodies or antibody fragments (e.g., scFvs), for example, between VL1 and VL2 if the construct is arranged as VH1-VL1-VL2-VH2, or between VH1 and VH2 if the construct is arranged as VL1-VH1-VH2-VL2.
  • the linker may be a linker as described herein, e.g., a (Gly 4 -Ser)n linker (SEQ ID NO: 1143), wherein n is 1, 2, 3, 4, 5, or 6.
  • the linker is GS.
  • the linker between the two scFvs should be long enough to avoid mispairing between the domains of the two scFvs.
  • a linker is disposed between the VL and VH of the first scFv.
  • a linker is disposed between the VL and VH of the second scFv.
  • any two or more of the linkers may be the same or different.
  • a multi-specific antibody comprises VLs, VHs, and may further comprise one or more linkers in an arrangement as described herein.
  • An exemplary immunoglobulin (antibody) structural unit is composed of two pairs of polypeptide chains, each pair having one “light” (about 25 kD) and one “heavy” chain (about 50-70 kD).
  • the N-terminal domain of each chain defines a variable region of about 100 to 110 or more amino acids primarily responsible for antigen recognition.
  • the terms variable light chain (VL) and variable heavy chain (VH) refer to these light and heavy chain domains, respectively.
  • the IgG1 heavy chain comprises the VH, CH1, CH2 and CH3 domains, respectively, from the N to C-terminus.
  • the light chain comprises the VL and CL domains from N to C terminus.
  • the IgG1 heavy chain comprises a hinge between the CH1 and CH2 domains.
  • the immunoglobulin constructs comprise at least one immunoglobulin domain from IgG, IgM, IgA, IgD, or IgE connected to a therapeutic polypeptide.
  • the immunoglobulin domain found in a multi-specific antibody provided herein is from or derived from an immunoglobulin-based construct such as a diabody or a nanobody.
  • the immunoglobulin constructs described herein comprise at least one immunoglobulin domain from a heavy chain antibody such as a camelid antibody.
  • the immunoglobulin constructs provided herein comprise at least one immunoglobulin domain from a mammalian antibody such as a bovine antibody, a human antibody, a camelid antibody, a mouse antibody, or any chimeric antibody.
  • the multi-specific antibodies provided herein comprise one or more heavy chains.
  • the heavy chain is an IgA.
  • the heavy chain is an IgD.
  • the heavy chain is an IgE.
  • the heavy chain is an IgG.
  • the heavy chain is an IgM.
  • the heavy chain is an IgG1.
  • the heavy chain is an IgG2.
  • the heavy chain is an IgG3. In some embodiments, the heavy chain is an IgG4. In some embodiments, the heavy chain is an IgA1. In some embodiments, the heavy chain is an IgA2. [00521] In some embodiments, the multi-specific antibody comprises an IgG1 antibody. In some embodiments, the multi-specific antibody comprises an IgG3 antibody. In some embodiments, the multi-specific antibody comprises an IgG2 antibody. In some embodiments, the multi-specific antibody comprises an IgG4 antibody.
  • the two or more different epitopes may be epitopes on the same antigen (e.g., a single OX40L molecule expressed by a cell) or on different antigens (e.g., different OX40L molecules expressed by the same cell, or a OX40L molecule and an IL-4R ⁇ molecule).
  • a multi-specific antibody binds two different epitopes (i.e., a “bispecific antibody” or “bispecific antibody”).
  • a multi-specific antibody binds three different epitopes (i.e., a “trispecific antibody”).
  • the antigen binding regions of the multi-specific antibodies can include an antigen binding region or variable domain described herein such as the antigen binding region of the clones set forth in the drawings and/or tables.
  • the multi- specific antibody comprises an alternative scaffold.
  • the multi-specific antibody consists of an alternative scaffold.
  • the multi-specific antibody consists essentially of an alternative scaffold.
  • the multi- specific antibody comprises two or more antibody fragments.
  • the multi-specific antibody consists of two or more antibody fragments.
  • the multi-specific antibody consists essentially of two or more antibody fragments.
  • the multi-specific antibody or antigen binding region thereof is produced by hybridomas.
  • the antibodies are produced by recombinant cells engineered to express the desired variable and constant domains.
  • the multi-specific antibody comprises one or more single chain antibodies or other antibody derivatives retaining the antigen specificity and the lower hinge region or a variant thereof.
  • the multi-specific antibody may be polyfunctional antibodies, recombinant antibodies, human antibodies, humanized antibodies, fragments or variants thereof.
  • the multi-specific antibody comprises antibody fragments or a derivative thereof, which can be selected from a Fab fragment, a Fab′2 fragment, a CDR, and scFv (e.g., heavy chain and scFv fusions).
  • multi-specific antibodies of the disclosure comprise amino acid substitutions to enable heterodimerization of two heavy chains, such as with a knob-into- hole approach, and/or CrossMAb technology to enable light chain pairing yet prevent unspecific binding of the light chains.
  • Sequences of OX40L Antigen Binding Regions [00528]
  • an anti-OX40L antigen binding region included in a multi- specific antibody described herein is an antigen binding region included in amlitelimab or oxelumab.
  • amlitelimab comprises a variable heavy (VH) chain sequence having the amino acid sequence of SEQ ID NO: 832 and a variable light (VL) chain sequence having the amino acid sequence of SEQ ID NO: 833.
  • oxelumab comprises a VH sequence having the amino acid sequence of SEQ ID NO: 834 and a VL sequence having the amino acid sequence of SEQ ID NO: 835.
  • oxelumab comprises a heavy chain having the amino acid sequence of SEQ ID NO: 1072 and a light chain sequence having the amino acid sequence of SEQ ID NO: 1073, or a VH and/or VL therein. See also PCT Application No.
  • an anti-OX40L antigen binding region included in a multi-specific antibody described herein is selected from an anti-OX40L antibody or antigen binding region described therein.
  • an OX40L antigen binding region provided herein comprises a CDR, VH, and/or VL sequence described herein. TABLE 9.
  • a multi-specific antibody comprises a VH sequence selected from any one of SEQ ID NOs: 1, 19, 37, and 55.
  • a multi-specific antibody provided herein comprises a VH sequence having at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to an illustrative VH sequence selected from any one of SEQ ID NOs: 1, 19, 37, and 55.
  • a multi-specific antibody provided herein comprises a VH sequence selected from any one of SEQ ID NOs: 1, 19, 37, and 55, with up to 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 amino acid substitutions.
  • the amino acid substitutions are conservative amino acid substitutions.
  • the antibodies described in this paragraph are referred to herein as “variants.”
  • such variants are derived from a sequence provided herein, for example, by affinity maturation, site directed mutagenesis, random mutagenesis, or any other method known in the art or described herein.
  • such variants are not derived from a sequence provided herein and may, for example, be isolated de novo according to the methods provided herein for obtaining antibodies.
  • OX40L Antigen Binding Region VL Domains [00532]
  • a multi-specific antibody provided herein comprises a VL sequence selected from any one of SEQ ID NOs: 11, 29, 47, and 65.
  • a multi-specific antibody provided herein comprises a VL sequence having at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to a VL sequence selected from any one of SEQ ID NOs: 11, 29, 47, and 65.
  • a multi-specific antibody provided herein comprises a VL sequence selected from any one of SEQ ID NOs: 11, 29, 47, and 65, with up to 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 amino acid substitutions.
  • the amino acid substitutions are conservative amino acid substitutions.
  • the antibodies described in this paragraph are referred to herein as “variants.”
  • such variants are derived from a sequence provided herein, for example, by affinity maturation, site directed mutagenesis, random mutagenesis, or any other method known in the art or described herein.
  • such variants are not derived from a sequence provided herein and may, for example, be isolated de novo according to the methods provided herein for obtaining antibodies.
  • a multi-specific antibody provided herein comprises a VH sequence selected from any one of SEQ ID NOs: 1, 19, 37, and 55; and a VL sequence selected from any one of SEQ ID NOs: 11, 29, 47, and 65.
  • a VH sequence selected from any one of SEQ ID NOs: 1, 19, 37, and 55 can be combined with a VL sequence selected from any one of SEQ ID NOs: 11, 29, 47, and 65.
  • a multi-specific antibody provided herein comprises a VH sequence and a VL sequence of a construct provided in TABLE 9 (e.g., a VH sequence and a VL sequence from the same row of TABLE 9).
  • a multi-specific antibody provided herein comprises a VH sequence and a VL sequence of a construct provided in PCT Application No. PCT/US2024/026854 (corresponding to PCT Publication No. WO2024227174), incorporated by reference herein in its entirety.
  • a multi-specific antibody provided herein comprises a VH sequence and a VL sequence from Table 2 in PCT Application No.
  • a multi-specific antibody provided herein comprises a VH sequence having at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to a VH sequence selected from any one of SEQ ID NOs: 1, 19, 37, and 55; and a VL sequence having at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to a VL sequence selected from any one of SEQ ID NOs: 11, 29, 47, and 65.
  • a multi-specific antibody provided herein comprises a VH sequence selected from any one of SEQ ID NOs: 1, 19, 37, and 55, with up to 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 amino acid substitutions, and a VL sequence selected from any one of SEQ ID NOs: 11, 29, 47, and 65, with up to 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 amino acid substitutions.
  • the amino acid substitutions are conservative amino acid substitutions.
  • the antibodies described in this paragraph are referred to herein as “variants.”
  • such variants are derived from a sequence provided herein, for example, by affinity maturation, site directed mutagenesis, random mutagenesis, or any other method known in the art or described herein.
  • such variants are not derived from a sequence provided herein and may, for example, be isolated de novo according to the methods provided herein for obtaining antibodies.
  • the multi-specific antibody comprises a VH sequence set forth in SEQ ID NO: 1 and a VL sequence set forth in SEQ ID NO: 11.
  • the multi-specific antibody comprises a VH sequence set forth in SEQ ID NO: 19 and a VL sequence set forth in SEQ ID NO: 29. [00541] In certain embodiments, the multi-specific antibody comprises a VH sequence set forth in SEQ ID NO: 37 and a VL sequence set forth in SEQ ID NO: 47. [00542] In certain embodiments, the multi-specific antibody comprises a VH sequence set forth in SEQ ID NO: 55 and a VL sequence set forth in SEQ ID NO: 65.
  • a multi-specific antibody comprises any of the VH and VL combinations described above and further comprises a heavy chain comprising a human IgG sequence selected from a sequence set forth in any one of SEQ ID NOs: 637-737 and 847-1070 or a sequence having at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity thereto.
  • a multi-specific antibody comprises any of the VH and VL combinations described above and further comprises a heavy chain comprising a constant heavy chain sequence set forth in SEQ ID NO: 651 or a sequence having at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity thereto.
  • a multi-specific antibody comprises any of the VH and VL combinations described above and further comprises a heavy chain comprising a constant heavy chain sequence set forth in SEQ ID NO: 973 or a sequence having at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity thereto.
  • a multi-specific antibody comprises any of the VH and VL combinations described above and further comprises a human constant light chain sequence set forth in SEQ ID NO: 738 or a sequence having at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity thereto.
  • a multi-specific antibody comprises any of the VH and VL combinations described above and further comprises a constant heavy chain sequence set forth in SEQ ID NO: 651 or a sequence having at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity thereto and a human constant light chain sequence set forth in SEQ ID NO: 738 or a sequence having at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity thereto.
  • a multi-specific antibody comprises any of the VH and VL combinations described above and further comprises a constant heavy chain sequence set forth in SEQ ID NO: 973 or a sequence having at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity thereto and a human constant light chain sequence set forth in SEQ ID NO: 738 or a sequence having at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity thereto.
  • a C-terminal lysine may be present in the corresponding coding sequence of the constant heavy chain region (e.g., in a sequence encoding any one of SEQ ID NOs: 959-1070), it may be cleaved off during manufacture or after administration (resulting in, e.g., a constant heavy chain sequence of any one of SEQ ID NOs: 637-737 and 847-958).
  • any of the multi-specific antibodies described above may comprise a human IgG sequence containing a C-terminal lysine (e.g., any one of SEQ ID NOs: 959-1070), a human IgG sequence lacking a C-terminal lysine (e.g., any one of SEQ ID NOs: 637-737 and 847-958), or a mixture thereof (e.g., a mixture of the same heavy chain constant sequence with and without a C-terminal lysine, such as a mixture of SEQ ID NO: 973 and SEQ ID NO: 651).
  • a human IgG sequence containing a C-terminal lysine e.g., any one of SEQ ID NOs: 959-1070
  • a human IgG sequence lacking a C-terminal lysine e.g., any one of SEQ ID NOs: 637-737 and 847-958
  • a mixture thereof e.g., a mixture of the same heavy chain constant
  • OX40L Antigen Binding Region CDRs [00545]
  • a multi-specific antibody comprising 1, 2, 3, 4, 5, or 6 of the CDRs of TABLE 9.
  • a multi-specific antibody comprising 6 of the Kabat CDRs of TABLE 9, 6 of the Chothia CDRs of TABLE 9, or 6 of the IMGT CDRs of TABLE 9.
  • the multi-specific antibody comprises 6 of the Kabat CDRs, 6 of the Chothia CDRs, or 6 of the IMGT CDRs from a single row of TABLE 9 (e.g., 6 CDRs from the same antibody).
  • a multi-specific antibody comprising 1, 2, 3, 4, 5, or 6 of the CDRs of an antibody provided in PCT Application No. PCT/US2024/026854 (corresponding to PCT Publication No. WO2024227174), incorporated by reference herein in its entirety, such as 1, 2, 3, 4, 5, or 6 of the CDRs in Table 2 in PCT Application No. PCT/US2024/026854.
  • a multi- specific antibody comprising 1, 2, 3, 4, 5, or 6 of the Kabat CDRs of an antibody, or an antigen binding fragment thereof, provided in PCT Application No. PCT/US2024/026854.
  • a multi-specific antibody comprising 1, 2, 3, 4, 5, or 6 of the Chothia CDRs of an antibody, or an antigen binding fragment thereof, provided in PCT Application No. PCT/US2024/026854.
  • a multi-specific antibody comprising 1, 2, 3, 4, 5, or 6 of the IMGT CDRs of an antibody provided in PCT Application No. PCT/US2024/026854.
  • the multi-specific antibody comprises 6 of the Kabat CDRs, 6 of the Chothia CDRs, or 6 of the IMGT CDRs from a single row of Table 2 in in PCT Application No.
  • a multi-specific antibody provided herein comprises three CDRs of a VH domain selected from SEQ ID NOs: 1, 19, 37, and 55.
  • the CDRs are exemplary CDRs.
  • the CDRs are Kabat CDRs.
  • the CDRs are Chothia CDRs.
  • the CDRs are IMGT CDRs.
  • the CDRs are AbM CDRs.
  • the CDRs are Contact CDRs.
  • the CDRs are CDRs having at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity to a CDR-H1, CDR-H2, or CDR-H3 selected from SEQ ID NOs: 2-10, 12-18, 20-28, 30-36, 38-46, 48-54, 56-64, and 66-72.
  • the CDR-H1 is a CDR-H1 of a VH domain selected from SEQ ID NOs: 1, 19, 37, and 55, with up to 1, 2, 3, 4, or 5 amino acid substitutions.
  • the CDR-H2 is a CDR-H2 of a VH domain selected from SEQ ID NOs: 1, 19, 37, and 55, with up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions.
  • the CDR-H3 is a CDR-H3 of a VH domain selected from SEQ ID NOs: 1, 19, 37, and 55, with up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions.
  • the amino acid substitutions are conservative amino acid substitutions.
  • the antibodies described in this paragraph are referred to herein as “variants.”
  • such variants are derived from a sequence provided herein, for example, by affinity maturation, site directed mutagenesis, random mutagenesis, or any other method known in the art or described herein.
  • such variants are not derived from a sequence provided herein and may, for example, be isolated de novo according to the methods provided herein for obtaining antibodies.
  • a multi-specific antibody provided herein comprises three CDRs of a VL domain selected from SEQ ID NOs: 11, 29, 47, and 65.
  • the CDRs are exemplary CDRs.
  • the CDRs are Kabat CDRs.
  • the CDRs are Chothia CDRs. In some aspects, the CDRs are IMGT CDRs. In some aspects, the CDRs are AbM CDRs. In some aspects, the CDRs are Contact CDRs. [00550] In some embodiments, the CDRs are CDRs having at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity to a CDR-L1, CDR-L2, or CDR-L3 selected from SEQ ID NOs: 2-10, 12-18, 20-28, 30-36, 38-46, 48-54, 56-64, and 66- 72, In some embodiments, the CDR-L1 is a CDR-L1 of a VL domain selected from SEQ ID NOs: 11, 29, 47, and 65, with up to 1, 2, 3, 4, or 5 amino acid substitutions.
  • the CDR-L2 is a CDR-L2 of a VL domain selected from SEQ ID NOs: 11, 29, 47, and 65, with up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions.
  • the CDR-L3 is a CDR-L3 of a VL domain selected from SEQ ID NOs: 11, 29, 47, and 65, with up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions.
  • the amino acid substitutions are conservative amino acid substitutions.
  • the antibodies described in this paragraph are referred to herein as “variants.”
  • such variants are derived from a sequence provided herein, for example, by affinity maturation, site directed mutagenesis, random mutagenesis, or any other method known in the art or described herein.
  • such variants are not derived from a sequence provided herein and may, for example, be isolated de novo according to the methods provided herein for obtaining antibodies.
  • a multi-specific antibody provided herein comprises three CDRs of a VH domain selected from SEQ ID NOs: 1, 19, 37, and 55 and three CDRs of a VL domain selected from SEQ ID NOs: 11, 29, 47, and 65.
  • the CDRs are exemplary CDRs. In some aspects, the CDRs are Kabat CDRs. In some aspects, the CDRs are Chothia CDRs. In some aspects, the CDRs are IMGT CDRs. In some aspects, the CDRs are AbM CDRs. In some aspects, the CDRs are Contact CDRs. [00552] In some embodiments, a multi-specific antibody provided herein comprises a CDR-H3 selected from SEQ ID NOs: 8-10, 26-28, 44-46, and 62-64.
  • the CDR-H3 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to a CDR-H3 selected from SEQ ID NOs: 8-10, 26-28, 44-46, and 62-64.
  • the CDR-H3 is a CDR-H3 selected from SEQ ID NOs: 8-10, 26-28, 44-46, and 62-64, with up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions.
  • the amino acid substitutions are conservative amino acid substitutions.
  • the antibodies described in this paragraph are referred to herein as “variants.”
  • such variants are derived from a sequence provided herein, for example, by affinity maturation, site directed mutagenesis, random mutagenesis, or any other method known in the art or described herein.
  • such variants are not derived from a sequence provided herein and may, for example, be isolated de novo according to the methods provided herein for obtaining antibodies.
  • a multi-specific antibody provided herein comprises a CDR-H1 selected from SEQ ID NOs: 2-4, 20-22, 38-40, and 56-58.
  • the CDR-H1 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to a CDR-H1 selected from SEQ ID NOs: 2-4, 20-22, 38-40, and 56-58.
  • the CDR-H1 is a CDR-H1 selected from SEQ ID NOs: 2-4, 20-22, 38-40, and 56-58, with up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions.
  • the amino acid substitutions are conservative amino acid substitutions.
  • the antibodies described in this paragraph are referred to herein as “variants.”
  • such variants are derived from a sequence provided herein, for example, by affinity maturation, site directed mutagenesis, random mutagenesis, or any other method known in the art or described herein.
  • such variants are not derived from a sequence provided herein and may, for example, be isolated de novo according to the methods provided herein for obtaining antibodies.
  • a multi-specific antibody provided herein comprises a CDR-H2 selected from SEQ ID NOs: 5-7, 23-25, 41-43, and 59-61.
  • the CDR-H2 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to a CDR-H2 H2 selected from SEQ ID NOs: 5-7, 23-25, 41-43, and 59-61.
  • the CDR-H2 is a CDR-H2 selected from SEQ ID NOs: 5-7, 23-25, 41-43, and 59-61, with up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions.
  • the amino acid substitutions are conservative amino acid substitutions.
  • the antibodies described in this paragraph are referred to herein as “variants.”
  • such variants are derived from a sequence provided herein, for example, by affinity maturation, site directed mutagenesis, random mutagenesis, or any other method known in the art or described herein.
  • such variants are not derived from a sequence provided herein and may, for example, be isolated de novo according to the methods provided herein for obtaining antibodies.
  • a multi-specific antibody provided herein comprises a CDR-L3 selected from SEQ ID NOs: 17-18, 35-36, 53-54, and 71-72.
  • the CDR-L3 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to a CDR-L3 selected from SEQ ID NOs: 17-18, 35-36, 53-54, and 71-72.
  • the CDR-L3 is a CDR-L3 selected from SEQ ID NOs: 17-18, 35-36, 53-54, and 71-72, with up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions.
  • the amino acid substitutions are conservative amino acid substitutions.
  • the antibodies described in this paragraph are referred to herein as “variants.”
  • such variants are derived from a sequence provided herein, for example, by affinity maturation, site directed mutagenesis, random mutagenesis, or any other method known in the art or described herein.
  • such variants are not derived from a sequence provided herein and may, for example, be isolated de novo according to the methods provided herein for obtaining antibodies.
  • a multi-specific antibody provided herein comprises a CDR-L2 selected from SEQ ID NOs: 15-16, 33-34, 51-52, and 69-70.
  • the CDR-L2 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to a CDR-L2 selected from SEQ ID NOs: 15-16, 33-34, 51-52, and 69-70.
  • the CDR-L2 is a CDR-L2 selected from SEQ ID NOs: 15-16, 33-34, 51-52, and 69-70, with up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions.
  • the amino acid substitutions are conservative amino acid substitutions.
  • the antibodies described in this paragraph are referred to herein as “variants.”
  • such variants are derived from a sequence provided herein, for example, by affinity maturation, site directed mutagenesis, random mutagenesis, or any other method known in the art or described herein.
  • such variants are not derived from a sequence provided herein and may, for example, be isolated de novo according to the methods provided herein for obtaining antibodies.
  • a multi-specific antibody provided herein comprises a CDR-L1 selected from SEQ ID NOs: 12-14, 30-32, 48-50, and 66-68.
  • the CDR-L1 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to a CDR-L1 selected from SEQ ID NOs: 12-14, 30-32, 48-50, and 66-68.
  • the CDR-L1 is a CDR-L1 selected from SEQ ID NOs: 12-14, 30-32, 48-50, and 66-68, with up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions.
  • the amino acid substitutions are conservative amino acid substitutions.
  • the antibodies described in this paragraph are referred to herein as “variants.”
  • such variants are derived from a sequence provided herein, for example, by affinity maturation, site directed mutagenesis, random mutagenesis, or any other method known in the art or described herein.
  • such variants are not derived from a sequence provided herein and may, for example, be isolated de novo according to the methods provided herein for obtaining antibodies.
  • a multi-specific antibody provided herein comprises a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 2; a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 5; a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 8; a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 12; a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 15; and a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 17.
  • a multi-specific antibody provided herein comprises a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 3; a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 6; a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 9; a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 13; a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 16; and a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 18.
  • a multi-specific antibody provided herein comprises a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 4; a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 7; a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 10; a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 14; a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 16; and a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 17.
  • a multi-specific antibody provided herein comprises a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 20; a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 23; a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 26; a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 30; a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 33; and a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 35.
  • a multi-specific antibody provided herein comprises a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 21; a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 24; a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 27; a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 31; a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 34; and a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 36.
  • a multi-specific antibody provided herein comprises a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 22; a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 25; a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 27; a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 32; a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 34; and a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 35.
  • a multi-specific antibody provided herein comprises a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 38; a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 41; a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 44; a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 48; a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 51; and a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 53.
  • a multi-specific antibody provided herein comprises a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 39; a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 42; a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 45; a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 49; a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 52; and a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 54.
  • a multi-specific antibody provided herein comprises a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 40; a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 43; a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 46; a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 50; a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 52; and a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 53.
  • a multi-specific antibody provided herein comprises a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 56; a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 59; a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 62; a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 66; a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 69; and a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 71.
  • a multi-specific antibody provided herein comprises a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 57; a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 60; a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 63; a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 67; a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 70; and a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 72.
  • a multi-specific antibody provided herein comprises a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 58; a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 61; a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 64; a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 68; a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 70; and a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 71.
  • any of the multi-specific antibodies described above further comprises a heavy chain comprising a human IgG sequence selected from a sequence set forth in any one of SEQ ID NOs: 637-737 and SEQ ID NOs: 847-1070 or a sequence having at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity thereto.
  • any of the multi-specific antibodies described above further comprises a constant heavy chain sequence set forth in SEQ ID NO: 651 or a sequence having at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity thereto.
  • any of the multi-specific antibodies described above further comprises a constant heavy chain sequence set forth in SEQ ID NO: 973 or a sequence having at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity thereto.
  • any of the multi-specific antibodies described above further comprises a human constant light chain sequence set forth in SEQ ID NO: 738 or a sequence having at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity thereto.
  • any of the multi-specific antibodies described above further comprises a constant heavy chain sequence set forth in SEQ ID NO: 651 or a sequence having at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity thereto and a human constant light chain sequence set forth in SEQ ID NO: 738 or a sequence having at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity thereto.
  • any of the multi-specific antibodies described above further comprises a constant heavy chain sequence set forth in SEQ ID NO: 973 or a sequence having at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity thereto and a human constant light chain sequence set forth in SEQ ID NO: 738 or a sequence having at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity thereto.
  • a C-terminal lysine may be present in the corresponding coding sequence of the constant heavy chain region (e.g., in a sequence encoding any one of SEQ ID NOs: 959-1070), it may be cleaved off during manufacture or after administration (resulting in, e.g., a constant heavy chain sequence of any one of SEQ ID NOs: 637-737 and 847-958).
  • any of the multi-specific antibodies described above may comprise a human IgG sequence containing a C-terminal lysine (e.g., any one of SEQ ID NOs: 959-1070), a human IgG sequence lacking a C-terminal lysine (e.g., any one of SEQ ID NOs: 637-737 and 847-958), or a mixture thereof (e.g., a mixture of the same heavy chain constant sequence with and without a C-terminal lysine, such as a mixture of SEQ ID NO: 973 and SEQ ID NO: 651).
  • the amino acid substitutions are conservative amino acid substitutions.
  • the antibodies described in this disclosure are referred to herein as “variants” or “clones”.
  • variants or clones are derived from a sequence provided herein, for example, by affinity maturation, site directed mutagenesis, random mutagenesis, or any other method known in the art or described herein.
  • variants or cones are not derived from a sequence provided herein and may, for example, be isolated de novo according to the methods provided herein for obtaining antibodies.
  • Sequences of IL-4R ⁇ Antigen Binding Regions [00573] The present application provides multi-specific antibodies and compositions comprising an antigen binding region which binds IL-4R ⁇ . See also PCT Application No.
  • an anti-IL-4R ⁇ antigen binding region described herein is selected from an anti-IL-4R ⁇ antigen binding region described therein.
  • an anti-IL-4R ⁇ antigen binding region described herein is selected from an antigen binding region included in dupilumab, stapokibart, and 611.
  • dupilumab comprises a variable heavy (VH) chain sequence having the amino acid sequence of SEQ ID NO: 113 and a variable light (VL) chain sequence having the amino acid sequence of SEQ ID NO: 146.
  • dupilumab comprises a heavy chain having the amino acid sequence of SEQ ID NO: 147 and a light chain sequence having the amino acid sequence of SEQ ID NO: 148.
  • stapokibart comprises a heavy chain having the amino acid sequence of SEQ ID NO: 1074 and a light chain sequence having the amino acid sequence of SEQ ID NO: 1075, or a VH and/or VL therein (e.g., a VH having the sequence of SEQ ID NO: 844 and a VL having the sequence of SEQ ID NO: 845).
  • an IL-4R ⁇ antigen binding region provided herein comprises a CDR, VH, and/or VL sequence described herein.
  • a multi-specific antibody comprises a VH sequence selected from any one of SEQ ID NOs: 295-297.
  • a multi-specific antibody provided herein comprises a VH sequence having at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to an illustrative VH sequence selected from any one of SEQ ID NOs: 295-297.
  • a multi-specific antibody provided herein comprises a VH sequence selected from any one of SEQ ID NOs: 295-297, with up to 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 amino acid substitutions.
  • the amino acid substitutions are conservative amino acid substitutions.
  • the antibodies described in this paragraph are referred to herein as “variants.”
  • such variants are derived from a sequence provided herein, for example, by affinity maturation, site directed mutagenesis, random mutagenesis, or any other method known in the art or described herein.
  • such variants are not derived from a sequence provided herein and may, for example, be isolated de novo according to the methods provided herein for obtaining antibodies.
  • IL-4R ⁇ Antigen Binding Region VL Domains [00578]
  • a multi-specific antibody provided herein comprises a VL sequence selected from any one of SEQ ID NOs: 298-300.
  • a multi-specific antibody provided herein comprises a VL sequence having at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to a VL sequence selected from any one of SEQ ID NOs: 298-300.
  • a multi-specific antibody provided herein comprises a VL sequence selected from any one of SEQ ID NOs: 298-300, with up to 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 amino acid substitutions.
  • the amino acid substitutions are conservative amino acid substitutions.
  • the antibodies described in this paragraph are referred to herein as “variants.”
  • such variants are derived from a sequence provided herein, for example, by affinity maturation, site directed mutagenesis, random mutagenesis, or any other method known in the art or described herein.
  • such variants are not derived from a sequence provided herein and may, for example, be isolated de novo according to the methods provided herein for obtaining antibodies.
  • a multi-specific antibody provided herein comprises a VH sequence selected from any one of SEQ ID NOs: 295-297; and a VL sequence selected from any one of SEQ ID NOs: 298-300.
  • a VH sequence selected from any one of SEQ ID NOs: 295-297 can be combined with a VL sequence selected from any one of SEQ ID NOs: 298-300.
  • a multi-specific antibody provided herein comprises a VH sequence and a VL sequence of a construct provided in TABLE 10 (e.g., a VH sequence and VL sequence from the same row of TABLE 10).
  • a multi-specific antibody provided herein comprises a VH sequence and a VL sequence of a construct provided in PCT Application No. PCT/US2024/016235 (corresponding to PCT Publication No. WO2024173847), incorporated by reference herein in its entirety.
  • a multi-specific antibody provided herein comprises a VH sequence and a VL sequence from Table 2 in PCT Application No.
  • a multi-specific antibody provided herein comprises a VH sequence having at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to a VH sequence selected from any one of SEQ ID NOs: 295-297; and a VL sequence having at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to a VL sequence selected from any one of SEQ ID NOs: 298-300.
  • a multi-specific antibody provided herein comprises a VH sequence selected from any one of SEQ ID NOs: 295-297, with up to 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 amino acid substitutions, and a VL sequence selected from any one of SEQ ID NOs: 298-300, with up to 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 amino acid substitutions.
  • the amino acid substitutions are conservative amino acid substitutions.
  • the antibodies described in this paragraph are referred to herein as “variants.”
  • such variants are derived from a sequence provided herein, for example, by affinity maturation, site directed mutagenesis, random mutagenesis, or any other method known in the art or described herein.
  • such variants are not derived from a sequence provided herein and may, for example, be isolated de novo according to the methods provided herein for obtaining antibodies.
  • the multi-specific antibody comprises a VH sequence set forth in SEQ ID NO: 295 and a VL sequence set forth in SEQ ID NO: 298.
  • the multi-specific antibody comprises a VH sequence set forth in SEQ ID NO: 296 and a VL sequence set forth in SEQ ID NO: 299. [00587] In certain embodiments, the multi-specific antibody comprises a VH sequence set forth in SEQ ID NO: 297 and a VL sequence set forth in SEQ ID NO: 300.
  • a multi-specific antibody comprises any of the VH and VL combinations described above and further comprises a heavy chain comprising a human IgG sequence selected from a sequence set forth in SEQ ID NOs: 847-1070 or a sequence having at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity thereto.
  • any of the multi-specific antibodies described above further comprises a constant heavy chain sequence set forth in SEQ ID NO: 973 or a sequence having at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity thereto.
  • any of the multi-specific antibodies described above further comprises a human constant light chain sequence set forth in SEQ ID NO: 738 or a sequence having at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity thereto.
  • any of the multi-specific antibodies described above further comprises a constant heavy chain sequence set forth in SEQ ID NO: 973 or a sequence having at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity thereto and a human constant light chain sequence set forth in SEQ ID NO: 738 or a sequence having at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity thereto.
  • a C-terminal lysine may be present in the corresponding coding sequence of the constant heavy chain region (e.g., in a sequence encoding any one of SEQ ID NOs: 959-1070), it may be cleaved off during manufacture or after administration (resulting in, e.g., a constant heavy chain sequence of any one of SEQ ID NOs: 847-958).
  • any of the multi-specific antibodies described above may comprise a human IgG sequence containing a C-terminal lysine (e.g., any one of SEQ ID NOs: 959-1070), a human IgG sequence lacking a C-terminal lysine (e.g., any one of SEQ ID NOs: 847-958), or a mixture thereof (e.g., a mixture of the same heavy chain constant sequence with and without a C- terminal lysine, such as a mixture of SEQ ID NO: 973 and SEQ ID NO: 861).
  • a human IgG sequence containing a C-terminal lysine e.g., any one of SEQ ID NOs: 959-1070
  • a human IgG sequence lacking a C-terminal lysine e.g., any one of SEQ ID NOs: 847-958
  • a mixture thereof e.g., a mixture of the same heavy chain constant sequence with and without a C- terminal
  • IL-4R ⁇ Antigen Binding Region CDRs [00590] In some embodiments, disclosed herein is a multi-specific antibody comprising 1, 2, 3, 4, 5, or 6 of the CDRs of TABLE 10. In some embodiments, disclosed herein is a multi-specific antibody comprising 6 of the Kabat CDRs of TABLE 10. In some embodiments, disclosed herein is a multi-specific antibody comprising 1, 2, 3, 4, 5, or 6 of the Chothia CDRs of TABLE 10. In some embodiments, disclosed herein is a multi-specific antibody comprising 1, 2, 3, 4, 5, or 6 of the IMGT CDRs of TABLE 10.
  • the multi-specific antibody comprises 6 of the Kabat CDRs, 6 of the Chothia CDRs, or 6 of the IMGT CDRs from a single row of TABLE 10 (e.g., 6 CDRs from the same antibody).
  • a multi-specific antibody comprising 1, 2, 3, 4, 5, or 6 of the CDRs of a multi-specific antibody provided in PCT Application No. PCT/US2024/016235 (corresponding to PCT Publication No. WO2024173847), incorporated by reference herein in its entirety.
  • a multi-specific antibody comprising 1, 2, 3, 4, 5, or 6 of the Kabat CDRs of a multi-specific antibody provided in PCT Application No. PCT/US2024/016235. In some embodiments, disclosed herein is a multi-specific antibody comprising 1, 2, 3, 4, 5, or 6 of the Chothia CDRs of a multi-specific antibody provided in PCT Application No. PCT/US2024/016235. In some embodiments, disclosed herein is a multi-specific antibody comprising 1, 2, 3, 4, 5, or 6 of the IMGT CDRs of a multi-specific antibody provided in PCT Application No. PCT/US2024/016235.
  • the multi-specific antibody comprises 6 of the Kabat CDRs, 6 of the Chothia CDRs, or 6 of the IMGT CDRs from a single row of Table 2 of PCT Application No. PCT/US2024/016235 (e.g., 6 CDRs from the same antibody).
  • a multi-specific antibody provided herein comprises three CDRs of a VH domain selected from SEQ ID NOs: 295-297.
  • the CDRs are exemplary CDRs.
  • the CDRs are Kabat CDRs.
  • the CDRs are Chothia CDRs.
  • the CDRs are IMGT CDRs.
  • the CDRs are AbM CDRs. In some aspects, the CDRs are Contact CDRs. [00592] In some embodiments, the CDRs are CDRs having at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity to a CDR-H1, CDR-H2, or CDR-H3 selected from SEQ ID NOs: 273-293 and 295-300. In some embodiments, the CDR-H1 is a CDR-H1 of a VH domain selected from SEQ ID NOs: 295-297, with up to 1, 2, 3, 4, or 5 amino acid substitutions.
  • the CDR-H2 is a CDR-H2 of a VH domain selected from SEQ ID NOs: 295-297, with up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions.
  • the CDR-H3 is a CDR-H3 of a VH domain selected from SEQ ID NOs: 295-297, with up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions.
  • the amino acid substitutions are conservative amino acid substitutions.
  • the antibodies described in this paragraph are referred to herein as “variants.”
  • such variants are derived from a sequence provided herein, for example, by affinity maturation, site directed mutagenesis, random mutagenesis, or any other method known in the art or described herein.
  • such variants are not derived from a sequence provided herein and may, for example, be isolated de novo according to the methods provided herein for obtaining antibodies.
  • a multi-specific antibody provided herein comprises three CDRs of a VL domain selected from SEQ ID NOs: 298-300.
  • the CDRs are exemplary CDRs.
  • the CDRs are Kabat CDRs.
  • the CDRs are Chothia CDRs. In some aspects, the CDRs are IMGT CDRs. In some aspects, the CDRs are AbM CDRs. In some aspects, the CDRs are Contact CDRs. [00594] In some embodiments, the CDRs are CDRs having at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity to a CDR-L1, CDR-L2, or CDR-L3 selected from SEQ ID NOs: 273-293 and 295-300, In some embodiments, the CDR- L1 is a CDR-L1 of a VL domain selected from SEQ ID NOs: 298-300, with up to 1, 2, 3, 4, or 5 amino acid substitutions.
  • the CDR-L2 is a CDR-L2 of a VL domain selected from SEQ ID NOs: 298-300, with up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions.
  • the CDR-L3 is a CDR-L3 of a VL domain selected from SEQ ID NOs: 298-300, with up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions.
  • the amino acid substitutions are conservative amino acid substitutions.
  • the antibodies described in this paragraph are referred to herein as “variants.”
  • such variants are derived from a sequence provided herein, for example, by affinity maturation, site directed mutagenesis, random mutagenesis, or any other method known in the art or described herein.
  • such variants are not derived from a sequence provided herein and may, for example, be isolated de novo according to the methods provided herein for obtaining antibodies.
  • a multi-specific antibody provided herein comprises three CDRs of a VH domain selected from SEQ ID NOs: 295-297 and three CDRs of a VL domain selected from SEQ ID NOs: 298-300..
  • the CDRs are exemplary CDRs. In some aspects, the CDRs are Kabat CDRs. In some aspects, the CDRs are Chothia CDRs. In some aspects, the CDRs are IMGT CDRs. In some aspects, the CDRs are AbM CDRs. In some aspects, the CDRs are Contact CDRs. [00596] In some embodiments, a multi-specific antibody provided herein comprises a CDR-H3 selected from SEQ ID NOs: 281-284.
  • the CDR-H3 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to a CDR-H3 selected from SEQ ID NOs: 281-284.
  • the CDR-H3 is a CDR-H3 selected from SEQ ID NOs: 281-284, with up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions.
  • the amino acid substitutions are conservative amino acid substitutions.
  • the antibodies described in this paragraph are referred to herein as “variants.”
  • such variants are derived from a sequence provided herein, for example, by affinity maturation, site directed mutagenesis, random mutagenesis, or any other method known in the art or described herein.
  • such variants are not derived from a sequence provided herein and may, for example, be isolated de novo according to the methods provided herein for obtaining antibodies.
  • a multi-specific antibody provided herein comprises a CDR-H1 selected from SEQ ID NOs: 273-275.
  • the CDR-H1 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to a CDR-H1 selected from SEQ ID NOs: 273-275.
  • the CDR-H1 is a CDR-H1 selected from SEQ ID NOs: 273-275, with up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions.
  • the amino acid substitutions are conservative amino acid substitutions.
  • the antibodies described in this paragraph are referred to herein as “variants.”
  • such variants are derived from a sequence provided herein, for example, by affinity maturation, site directed mutagenesis, random mutagenesis, or any other method known in the art or described herein.
  • such variants are not derived from a sequence provided herein and may, for example, be isolated de novo according to the methods provided herein for obtaining antibodies.
  • a multi-specific antibody provided herein comprises a CDR-H2 selected from SEQ ID NOs: 276-282.
  • the CDR-H2 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to a CDR-H2 selected from SEQ ID NOs: 276-282.
  • the CDR-H2 is a CDR-H2 selected from SEQ ID NOs: 276-282, with up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions.
  • the amino acid substitutions are conservative amino acid substitutions.
  • the antibodies described in this paragraph are referred to herein as “variants.”
  • such variants are derived from a sequence provided herein, for example, by affinity maturation, site directed mutagenesis, random mutagenesis, or any other method known in the art or described herein.
  • such variants are not derived from a sequence provided herein and may, for example, be isolated de novo according to the methods provided herein for obtaining antibodies.
  • a multi-specific antibody provided herein comprises a CDR-L3 of SEQ ID NO: 293.
  • the CDR-L3 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to a CDR-L3 of SEQ ID NO: 293.
  • the CDR-L3 is a CDR-L3 of SEQ ID NO: 293, with up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions.
  • the amino acid substitutions are conservative amino acid substitutions.
  • the antibodies described in this paragraph are referred to herein as “variants.”
  • such variants are derived from a sequence provided herein, for example, by affinity maturation, site directed mutagenesis, random mutagenesis, or any other method known in the art or described herein.
  • such variants are not derived from a sequence provided herein and may, for example, be isolated de novo according to the methods provided herein for obtaining antibodies.
  • a multi-specific antibody provided herein comprises a CDR-L2 selected from SEQ ID NOs: 290-292 and the amino acid sequence LG or EG.
  • the CDR-L2 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to a CDR-L2 selected from SEQ ID NOs: 290-292 and the amino acid sequence LG or EG.
  • the CDR-L2 is a CDR-L2 selected from SEQ ID NOs: 290-292 and the amino acid sequence LG or EG, with up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions.
  • the amino acid substitutions are conservative amino acid substitutions.
  • the antibodies described in this paragraph are referred to herein as “variants.”
  • such variants are derived from a sequence provided herein, for example, by affinity maturation, site directed mutagenesis, random mutagenesis, or any other method known in the art or described herein.
  • such variants are not derived from a sequence provided herein and may, for example, be isolated de novo according to the methods provided herein for obtaining antibodies.
  • a multi-specific antibody provided herein comprises a CDR-L1 selected from SEQ ID NOs: 285-289.
  • the CDR-L1 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to a CDR-L1 selected from SEQ ID NOs: 285-289.
  • the CDR-L1 is a CDR-L1 selected from SEQ ID NOs: 285-289, with up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions.
  • the amino acid substitutions are conservative amino acid substitutions.
  • the antibodies described in this paragraph are referred to herein as “variants.”
  • such variants are derived from a sequence provided herein, for example, by affinity maturation, site directed mutagenesis, random mutagenesis, or any other method known in the art or described herein.
  • such variants are not derived from a sequence provided herein and may, for example, be isolated de novo according to the methods provided herein for obtaining antibodies.
  • a multi-specific antibody provided herein comprises a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 273; a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 276; a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 281; a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 285; a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 292; and a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 293.
  • a multi-specific antibody provided herein comprises a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 274; a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 277; a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 281; a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 285; a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 292; and a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 293.
  • a multi-specific antibody provided herein comprises a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 275; a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 278; a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 282; a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 286; a CDR-L2 comprising the amino acid sequence LG; and a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 293.
  • a multi-specific antibody provided herein comprises a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 273; a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 279; a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 283; a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 287; a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 291; and a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 293.
  • a multi-specific antibody provided herein comprises a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 274; a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 277; a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 283; a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 287; a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 291; and a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 293.
  • a multi-specific antibody provided herein comprises a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 275; a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 280; a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 284; a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 288; a CDR-L2 comprising the amino acid sequence LG; and a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 293.
  • a multi-specific antibody provided herein comprises a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 273; a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 279; a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 281; a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 289; a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 290; and a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 293.
  • a multi-specific antibody provided herein comprises a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 274; a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 277; a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 281; a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 289; a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 290; and a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 293.
  • a multi-specific antibody provided herein comprises a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 275; a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 280; a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 282; a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 288; a CDR-L2 comprising the amino acid sequence EG; and a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 293.
  • any of the multi-specific antibodies described above further comprises a heavy chain comprising a human IgG sequence selected from a sequence set forth in any one of SEQ ID NOs: 847-1070 or a sequence having at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity thereto.
  • any of the multi-specific antibodies described above further comprises a constant heavy chain sequence set forth in SEQ ID NO: 973 or a sequence having at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity thereto.
  • any of the multi-specific antibodies described above further comprises a human constant light chain sequence set forth in SEQ ID NO: 738 or a sequence having at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity thereto.
  • any of the multi-specific antibodies described above further comprises a constant heavy chain sequence set forth in SEQ ID NO: 973 or a sequence having at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity thereto and a human constant light chain sequence set forth in SEQ ID NO: 738 or a sequence having at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity thereto.
  • a C-terminal lysine may be present in the corresponding coding sequence of the constant heavy chain region (e.g., in a sequence encoding any one of SEQ ID NOs: 959-1070), it may be cleaved off during manufacture or after administration (resulting in, e.g., a constant heavy chain sequence of any one of SEQ ID NOs: 847-958).
  • any of the multi-specific antibodies described above may comprise a human IgG sequence containing a C-terminal lysine (e.g., any one of SEQ ID NOs: 959-1070), a human IgG sequence lacking a C-terminal lysine (e.g., any one of SEQ ID NOs: 847-958), or a mixture thereof (e.g., a mixture of the same heavy chain constant sequence with and without a C- terminal lysine, such as a mixture of SEQ ID NO: 973 and SEQ ID NO: 861).
  • the amino acid substitutions are conservative amino acid substitutions.
  • the antibodies described in this disclosure are referred to herein as “variants” or “clones”.
  • variants or clones are derived from a sequence provided herein, for example, by affinity maturation, site directed mutagenesis, random mutagenesis, or any other method known in the art or described herein.
  • variants or cones are not derived from a sequence provided herein and may, for example, be isolated de novo according to the methods provided herein for obtaining antibodies.
  • compositions comprising the antibodies or antigen binding fragments thereof described herein, including pharmaceutical compositions comprising an OX40L antibody, or an antigen binding fragment thereof, and/or an IL-4R ⁇ antibody, or an antigen binding fragment thereof, or a multi-specific antibody comprising an OX40L antigen binding region and an IL-4R ⁇ antigen binding region described herein with one or more pharmaceutically acceptable excipients.
  • the composition is sterile.
  • compositions generally comprise an effective amount of an OX40L antibody, or an antigen binding fragment thereof, and/or an IL-4R ⁇ antibody, or an antigen binding fragment thereof, or a multi-specific antibody comprising an OX40L antigen binding region and an IL-4R ⁇ antigen binding region.
  • compositions can comprise, in addition to the OX40L antibody, or an antigen binding fragment thereof, and/or the IL-4R ⁇ antibody, or an antigen binding fragment thereof, or the multi-specific antibody comprising an OX40L antigen binding region and an IL-4R ⁇ antigen binding region disclosed herein, a pharmaceutically acceptable excipient, carrier, buffer, stabilizer or other materials well known to those skilled in the art.
  • compositions for oral administration can be in tablet, capsule, powder or liquid form.
  • a tablet can include a solid carrier such as gelatin or an adjuvant.
  • Liquid pharmaceutical compositions generally include a liquid carrier such as water, petroleum, animal or vegetable oils, mineral oil or synthetic oil. Physiological saline solution, dextrose or other saccharide solution or glycols such as ethylene glycol, propylene glycol or polyethylene glycol can be included.
  • the active ingredient will be in the form of a parenterally acceptable aqueous solution which is pyrogen-free and has suitable pH, isotonicity and stability.
  • a parenterally acceptable aqueous solution which is pyrogen-free and has suitable pH, isotonicity and stability.
  • Those of relevant skill in the art can prepare suitable solutions using, for example, isotonic vehicles such as Sodium Chloride Injection, Ringer's Injection, Lactated Ringer's Injection.
  • Preservatives, stabilizers, buffers, antioxidants and/or other additives can be included, as required.
  • administration is preferably in a “therapeutically effective amount” or “prophylactically effective amount” (as the case can be, although prophylaxis can be considered therapy), this being sufficient to show benefit to the individual.
  • a “therapeutically effective amount” or “prophylactically effective amount” as the case can be, although prophylaxis can be considered therapy
  • the actual amount administered, and rate and time-course of administration will depend on a number of factors, e.g., the nature and severity of the disease being treated. Prescription of treatment, e.g.
  • a composition can be administered alone or in combination with other treatments, either simultaneously or sequentially dependent upon the condition to be treated.
  • Methods Methods of Preparation [00620] Antibodies, or antigen binding fragments thereof, and multi-specific antibodies described herein can be produced using recombinant methods and compositions, e.g., as described in U.S. Pat.
  • an isolated nucleic acid encoding an antibody, or an antigen binding fragment thereof, described herein is provided.
  • Such nucleic acid may encode an amino acid sequence comprising the VL and/or an amino acid sequence comprising the VH of the antibody (e.g., the light and/or heavy chains of the antibody) or an amino acid sequence comprising the VHH of a single domain antibody.
  • one or more vectors e.g., expression vectors
  • the nucleic acid is provided in a multicistronic vector.
  • a host cell comprising such nucleic acid is provided.
  • a host cell comprises (e.g., has been transformed with): (1) a vector comprising a nucleic acid that encodes an amino acid sequence comprising the VL of the antibody and an amino acid sequence comprising the VH of the antibody , or (2) a first vector comprising a nucleic acid that encodes an amino acid sequence comprising the VL of the antigen-binding polypeptide construct and a second vector comprising a nucleic acid that encodes an amino acid sequence comprising the VH of the antigen-binding polypeptide construct.
  • the host cell is eukaryotic, e.g.
  • a method of making an antibody comprises culturing a host cell comprising nucleic acid encoding the antibody, as provided above, under conditions suitable for expression of the antibody, and optionally recovering the antibody from the host cell (or host cell culture medium).
  • nucleic acid encoding an antibody e.g., as described above, is isolated and inserted into one or more vectors for further cloning and/or expression in a host cell.
  • nucleic acid may be readily isolated and sequenced using conventional procedures (e.g., by using oligonucleotide probes that are capable of binding specifically to genes encoding the heavy and light chains of the antibody).
  • the protein in certain embodiments is present at about 30%, about 25%, about 20%, about 15%, about 10%, about 5%, about 4%, about 3%, about 2%, or about 1% or less of the dry weight of the cells.
  • the protein in certain embodiments, is present in the culture medium at about 5 g/L, about 4 g/L, about 3 g/L, about 2 g/L, about 1 g/L, about 750 mg/L, about 500 mg/L, about 250 mg/L, about 100 mg/L, about 50 mg/L, about 10 mg/L, or about 1 mg/L or less of the dry weight of the cells.
  • substantially purified antibody produced by the methods described herein has a purity level of at least about 30%, at least about 35%, at least about 40%, at least about 45%, at least about 50%, at least about 55%, at least about 60%, at least about 65%, at least about 70%, specifically, a purity level of at least about 75%, 80%, 85%, and more specifically, a purity level of at least about 90%, a purity level of at least about 95%, a purity level of at least about 99% or greater as determined by appropriate methods such as SDS/PAGE analysis, RP-HPLC, SEC, and capillary electrophoresis.
  • Suitable host cells for cloning or expression of antibody-encoding vectors include prokaryotic or eukaryotic cells described herein.
  • Recombinant host cells or host cells are cells that include an exogenous polynucleotide, regardless of the method used for insertion, for example, direct uptake, transduction, f-mating, or other methods known in the art to create recombinant host cells.
  • the exogenous polynucleotide may be maintained as a nonintegrated vector, for example, a plasmid, or alternatively, may be integrated into the host genome.
  • Host cells can include CHO, derivatives of CHO, NS0, Sp2O, CV-1, VERO-76, HeLa, HepG2, Per.C6, or BHK.
  • an antibody may be produced in bacteria, in particular when glycosylation and Fc effector function are not needed.
  • expression of antibody fragments and polypeptides in bacteria see, e.g., U.S. Pat. Nos.5,648,237, 5,789,199, and 5,840,523. (See also Charlton, Methods in Molecular Biology, Vol.248 (B.K.C. Lo, ed., Humana Press, Totowa, N.J., 2003), pp.245-254, describing expression of antibody fragments in E.
  • the antibody may be isolated from the bacterial cell paste in a soluble fraction and can be further purified.
  • eukaryotic microbes such as filamentous fungi or yeast are suitable cloning or expression hosts for antibody-encoding vectors, including fungi and yeast strains whose glycosylation pathways have been “humanized,” resulting in the production of an antibody with a partially or fully human glycosylation pattern. See Gerngross, Nat. Biotech.22:1409-1414 (2004), and Li et al., Nat. Biotech.24:210-215 (2006).
  • Suitable host cells for the expression of glycosylated antibodies are also derived from multicellular organisms (invertebrates and vertebrates). Examples of invertebrate cells include plant and insect cells. Numerous baculoviral strains have been identified which may be used in conjunction with insect cells, particularly for transfection of Spodoptera frugiperda cells.
  • Plant cell cultures can also be utilized as hosts. See, e.g., U.S. Pat. Nos.5,959,177, 6,040,498, 6,420,548, 7,125,978, and 6,417,429 (describing PLANTIBODIESTM technology for producing antibodies in transgenic plants).
  • Vertebrate cells may also be used as hosts.
  • mammalian cell lines that are adapted to grow in suspension may be useful.
  • useful mammalian host cell lines are monkey kidney CV1 line transformed by SV40 (COS-7); human embryonic kidney line (293 or 293 cells as described, e.g., in Graham et al., J. Gen Virol. 36:59 (1977)); baby hamster kidney cells (BHK); mouse sertoli cells (TM4 cells as described, e.g., in Mather, Biol.
  • monkey kidney cells (CV1); African green monkey kidney cells (VERO-76); human cervical carcinoma cells (HELA); canine kidney cells (MDCK; buffalo rat liver cells (BRL 3A); human lung cells (W138); human liver cells (Hep G2); mouse mammary tumor (MMT 060562); TRI cells, as described, e.g., in Mather et al., Annals N.Y. Acad. Sci.383:44-68 (1982); MRC 5 cells; and FS4 cells.
  • Other useful mammalian host cell lines include Chinese hamster ovary (CHO) cells, including DHFR ⁇ CHO cells (Urlaub et al. (1980) Proc. Natl. Acad.
  • the antibodies described herein are produced in stable mammalian cells, by a method comprising: transfecting at least one stable mammalian cell with: nucleic acid encoding the antibody, in a predetermined ratio; and expressing the nucleic acid in the at least one mammalian cell.
  • the predetermined ratio of nucleic acid is determined in transient transfection experiments to determine the relative ratio of input nucleic acids that results in the highest percentage of the antibody in the expressed product.
  • the method of producing an antibody in stable mammalian cells as described herein results in an expression product of the at least one stable mammalian cell comprising a larger percentage of the desired glycosylated antibody as compared to the monomeric heavy or light chain polypeptides, or other antibodies.
  • the method of producing a glycosylated antibody in stable mammalian cells described herein comprises identifying and purifying the desired glycosylated antibody.
  • the said identification is by one or both of liquid chromatography and mass spectrometry.
  • the antibodies can be purified or isolated after expression. Proteins may be isolated or purified in a variety of ways known to those skilled in the art. Standard purification methods include chromatographic techniques, including ion exchange, hydrophobic interaction, affinity, sizing or gel filtration, and reversed-phase, carried out at atmospheric pressure or at high pressure using systems such as FPLC and HPLC. Purification methods also include electrophoretic, immunological, precipitation, dialysis, and chromatofocusing techniques. Ultrafiltration and diafiltration techniques, in conjunction with protein concentration, are also useful.
  • the bacterial proteins A and G bind to the Fc region.
  • the bacterial protein L binds to the Fab region of some antibodies. Purification can often be enabled by a particular fusion partner. For example, antibodies may be purified using glutathione resin if a GST fusion is employed, Ni +2 affinity chromatography if a His-tag is employed or immobilized anti-flag antibody if a flag-tag is used. For general guidance in suitable purification techniques, see, e.g.
  • the antibodies are purified using Anion Exchange Chromatography including, but not limited to, chromatography on Q-sepharose, DEAE sepharose, poros HQ, poros DEAF, Toyopearl Q, Toyopearl QAE, Toyopearl DEAE, Resource/Source Q and DEAE, Fractogel Q and DEAE columns.
  • Anion Exchange Chromatography including, but not limited to, chromatography on Q-sepharose, DEAE sepharose, poros HQ, poros DEAF, Toyopearl Q, Toyopearl QAE, Toyopearl DEAE, Resource/Source Q and DEAE, Fractogel Q and DEAE columns.
  • the proteins described herein are purified using Cation Exchange Chromatography including, but not limited to, SP-sepharose, CM sepharose, poros HS, poros CM, Toyopearl SP, Toyopearl CM, Resource/Source S and CM, Fractogel S and CM columns and their equivalents and comparables.
  • Cation Exchange Chromatography including, but not limited to, SP-sepharose, CM sepharose, poros HS, poros CM, Toyopearl SP, Toyopearl CM, Resource/Source S and CM, Fractogel S and CM columns and their equivalents and comparables.
  • antibodies described herein can be chemically synthesized using techniques known in the art (e.g., see Creighton, 1983, Proteins: Structures and Molecular Principles, W. H. Freeman & Co., N.Y and Hunkapiller et al., Nature, 310:105-111 (1984)).
  • polypeptide corresponding to a fragment of a polypeptide can be synthesized by use of a peptide synthesizer.
  • nonclassical amino acids or chemical amino acid analogs can be introduced as a substitution or addition into the polypeptide sequence.
  • Non-classical amino acids include, but are not limited to, to the D-isomers of the common amino acids, 2,4diaminobutyric acid, alpha-amino isobutyric acid, 4aminobutyric acid, Abu, 2-amino butyric acid, g-Abu, e-Ahx, 6amino hexanoic acid, Aib, 2-amino isobutyric acid, 3-amino propionic acid, ornithine, norleucine, norvaline, hydroxyproline, sarcosine, citrulline, homocitrulline, cysteic acid, t-butylglycine, t-butylalanine, phenylglycine, cyclohexylalanine, alanine, fluoro-amino acids, designer amino acids such as methyl amino acids, C-methyl amino acids, N-methyl amino acids, and amino acid analogs in general.
  • the amino acid can be D (dextrorotary) or L (levorotary).
  • Methods of Use [00637]
  • the present application provides methods of contacting OX40L with an anti-OX40L antibody, or an antigen binding fragment thereof, such as a human or humanized antibody, which results in inhibition of OX40 binding to OX40L expressed on antigen presenting cells.
  • the present application provides methods of using the isolated anti- OX40L antibodies, or antigen binding fragments thereof, described herein for treatment of a disorder or disease in a subject.
  • described herein is a method for treating a subject in need thereof with an anti-OX40L antibody, or an antigen binding fragment thereof, the method comprising administering to the subject (e.g., a mammalian subject) a therapeutically effective amount of an anti-OX40L antibody, or an antigen binding fragment thereof, or pharmaceutical composition comprising an anti-OX40L antibody, or an antigen binding fragment thereof, described herein.
  • the present application provides methods of treating a disorder or disease associated with elevated levels of OX40L and/or IgE in a subject.
  • described herein are methods for treating a pathology associated with OX40L activity, the method comprising administering to a mammalian subject a therapeutically effective amount an isolated anti-OX40L antibody, or an antigen binding fragment thereof, or a pharmaceutical composition comprising an isolated anti- OX40L antibody, or an antigen binding fragment thereof, described herein.
  • the present application provides methods of contacting IL-4R ⁇ with an anti-IL-4R ⁇ antibody, or an antigen binding fragment thereof, such as a human or humanized antibody, which results in inhibition of IL-4 and IL-13 signaling to an IL-4R ⁇ receptor expressed on a cell (e.g., by preventing IL-4R ⁇ and IL-13R ⁇ 1 heterodimer formation).
  • the present application provides methods of contacting OX40L and IL-4R ⁇ with a multi-specific OX40L and IL-4R ⁇ antibody, which results in inhibition of OX40L and/or IL-4 signaling to an OX40 and/or IL-4R ⁇ receptor expressed on a cell.
  • the present application provides methods of using the isolated anti- IL-4R ⁇ antibodies, or antigen binding fragments thereof, described herein for treatment of a disorder or disease in a subject.
  • described herein is a method for treating a subject in need thereof with an anti-IL-4R ⁇ antibody, or an antigen binding fragment thereof, the method comprising administering to the subject (e.g., a mammalian subject) a therapeutically effective amount of an anti-IL-4R ⁇ antibody, or an antigen binding fragment thereof, or pharmaceutical composition comprising an anti-IL-4R ⁇ antibody, or an antigen binding fragment thereof, described herein.
  • the present application provides methods of treating a disorder or disease associated with elevated levels of IL-4, IL- 13, and/or IgE in a subject.
  • methods for treating a pathology associated with IL-4, IL-13, and/or IL-4R ⁇ activity comprising administering to a mammalian subject a therapeutically effective amount an isolated anti-IL-4R ⁇ antibody, or an antigen binding fragment thereof, or a pharmaceutical composition comprising an isolated anti-IL-4R ⁇ antibody, or an antigen binding fragment thereof, described herein.
  • the present application provides methods of contacting OX40L and IL-4R ⁇ with an anti-OX40L antibody, or an antigen binding fragment thereof, and an anti-IL- 4R ⁇ antibody, or an antigen binding fragment thereof, respectively (e.g., via administration of a single composition containing both antibodies or antigen binding fragments thereof or by administration of two different compositions, one containing the anti-OX40L antibody, or an antigen binding fragment thereof and the other containing an anti- IL-4R ⁇ antibody or an antigen binding fragment thereof), such as a human or humanized antibody, which results in inhibition of OX40L and/or IL-4 signaling to an OX40 and/or IL-4R ⁇ receptor expressed on a cell.
  • the present application provides methods of using the isolated anti- IL-4R ⁇ antibodies, or antigen binding fragments thereof, and isolated OX40L antibodies, or antigen binding fragments thereof, described herein in combination for treatment of a disorder or disease in a subject.
  • described herein is a method for treating a subject in need thereof with an anti-OX40L antibody, or an antigen binding fragment thereof, and an anti-IL-4R ⁇ antibody, or an antigen binding fragment thereof, the method comprising administering to a mammalian subject a therapeutically effective amount of an anti-IL-4R ⁇ antibody, or an antigen binding fragment thereof, and a therapeutically effective amount of an anti-OX40L antibody, or an antigen binding fragment thereof, or pharmaceutical composition comprising such antibodies described herein (e.g., via administration of a single composition containing both antibodies or antigen binding fragments thereof or by administration of two different compositions, one containing the anti-OX40L antibody, or an antigen binding fragment thereof and the other containing an anti- IL-4R ⁇ antibody or an antigen binding fragment thereof).
  • the present application provides methods of treating a disorder or disease associated with elevated levels of OX40L, IL-4, IL-13, and/or IgE in a subject.
  • a therapeutically effective amount of each antibody may be different when the antibody is administered in combination with the other antibody or another therapeutic agent.
  • the present application provides methods of using the multi-specific OX40L and IL-4R ⁇ antibody described herein for treatment of a disorder or disease in a subject.
  • described herein is a method for treating a subject in need thereof with a multi-specific OX40L and IL-4R ⁇ antibody, the method comprising administering to a mammalian subject a therapeutically effective amount of the multi-specific OX40L and IL- 4R ⁇ antibody or pharmaceutical composition comprising such an antibody described herein.
  • the present application provides methods of treating a disorder or disease associated with elevated levels of OX40L, IL-4, IL-13, and/or IgE in a subject.
  • a therapeutically effective amount of the multi-specific OX40L and IL-4R ⁇ antibody may be different than a therapeutically effect amount of either an isolated anti- OX40L antibody, or an antigen binding fragment thereof, and/or an isolated anti-IL-4R ⁇ antibody, or an antigen binding fragment thereof.
  • described herein are methods for treating a pathology associated with OX40L and/or IL-4R ⁇ activity, the method comprising administering to a mammalian subject a therapeutically effective amount an isolated anti-IL-4R ⁇ antibody, or an antigen binding fragment thereof, and a therapeutically effective amount of an isolated anti- OX40L antibody, or an antigen binding fragment thereof, or a pharmaceutical composition comprising such antibodies described herein (e.g., via administration of a single composition containing both antibodies or antigen binding fragments thereof or by administration of two different compositions, one containing the anti-OX40L antibody, or an antigen binding fragment thereof and the other containing an anti- IL-4R ⁇ antibody or an antigen binding fragment thereof).
  • a therapeutically effective amount of each antibody may be different when the antibody is administered in combination with the other antibody or another therapeutic agent.
  • the combination of antibodies, or antigen binding fragments thereof, or. the multi-specific antibody is used in the treatment of an inflammatory disorder or disease.
  • the combination of antibodies, or antigen binding fragments thereof, or the multi-specific antibody is used in the treatment of atopic dermatitis.
  • the treatment reduces disease severity in a patient and disease severity is assessed by an atopic dermatitis disease severity outcome measure.
  • the combination of antibodies, or antigen binding fragments thereof, or the multi-specific antibody is used in the treatment of idiopathic pulmonary fibrosis.
  • the combination of antibodies, or antigen binding fragments thereof, or the multi-specific antibody is used in the treatment of alopecia areata. In certain embodiments, the combination of antibodies, or antigen binding fragments thereof, or the multi-specific antibody is used in the treatment of asthma. In certain embodiments, the combination of antibodies, or antigen binding fragments thereof, or the multi-specific antibody is used in the treatment of chronic sinusitis with nasal polyps. In certain embodiments, the combination of antibodies, or antigen binding fragments thereof, or the multi-specific antibody is used in the treatment of Chronic Rhinosinusitis without Nasal Polyps (CRSsNP).
  • CRSsNP Chronic Rhinosinusitis without Nasal Polyps
  • the combination of antibodies, or antigen binding fragments thereof, or the multi-specific antibody is used in the treatment of eosinophilic esophagitis (EoE).
  • EoE eosinophilic esophagitis
  • the combination of antibodies, or antigen binding fragments thereof, or the multi-specific antibody is used in the treatment of an Eosinophilic gastrointestinal disorder or disease (EGID) selected from the group consisting of Eosinophilic Gastritis (EoG), Eosinophilic Enteritis (EoN), Eosinophilic Colitis (EoC), and Eosinophilic Gastroenteritis (EGE).
  • Eosinophilic gastrointestinal disorder or disease selected from the group consisting of Eosinophilic Gastritis (EoG), Eosinophilic Enteritis (EoN), Eosinophilic Colitis (EoC), and Eosinophilic Gastroenteritis (EGE).
  • the combination of antibodies, or antigen binding fragments thereof, or the multi-specific antibody is used in the treatment of Churg- Strauss syndrome/Eosinophilic granulomatosis with polyangiitis (EGPA).
  • the combination of antibodies, or antigen binding fragments thereof, or the multi-specific antibody is used in the treatment of Prurigo Nodularis (PN).
  • the combination of antibodies, or antigen binding fragments thereof, or the multi-specific antibody is used in the treatment of Chronic Spontaneous Urticaria (CSU).
  • CSU Chronic Spontaneous Urticaria
  • the combination of antibodies, or antigen binding fragments thereof, or the multi-specific antibody is used in the treatment of Chronic Pruritis of Unknown Origin (CPUO).
  • the combination of antibodies, or antigen binding fragments thereof, or the multi-specific antibody is used in the treatment of Bullous Pemphigoid (BP). In certain embodiments, the combination of antibodies, or antigen binding fragments thereof, or the multi-specific antibody is used in the treatment of Cold Inducible Urticaria (ColdU). In certain embodiments, the combination of antibodies, or antigen binding fragments thereof, or the multi-specific antibody is used in the treatment of Allergic Fungal Rhinosinusitis (AFRS). In certain embodiments, the combination of antibodies, or antigen binding fragments thereof, or the multi-specific antibody is used in the treatment of Allergic Bronchopulmonary Aspergillosis (ABPA).
  • BP Bullous Pemphigoid
  • ColdU Cold Inducible Urticaria
  • AFRS Allergic Fungal Rhinosinusitis
  • the combination of antibodies, or antigen binding fragments thereof, or the multi-specific antibody is used in the treatment of Allergic Bronchopulmonary Aspergillos
  • the combination of antibodies, or antigen binding fragments thereof, or the multi-specific antibody is used in the treatment of Chronic Obstructive Pulmonary Disease (COPD).
  • COPD Chronic Obstructive Pulmonary Disease
  • the combination of antibodies, or antigen binding fragments thereof, or the multi-specific antibody is used in the treatment of inflammatory bowel disease, such as Crohn’s disease or ulcerative colitis.
  • the combination of antibodies, or antigen binding fragments thereof, or the multi-specific antibody is used in the treatment of psoriasis.
  • the combination of antibodies, or antigen binding fragments thereof, or the multi-specific antibody is used in the treatment of lupus.
  • the combination of antibodies, or antigen binding fragments thereof, or the multi-specific antibody is used in the treatment of rheumatoid arthritis. In certain embodiments, the combination of antibodies, or antigen binding fragments thereof, or the multi-specific antibody is used in the treatment of hidradenitis suppurativa. In certain embodiments, the combination of antibodies, or antigen binding fragments thereof, or the multi-specific antibody is used in the treatment of celiac disease. In certain embodiments, the combination of antibodies, or antigen binding fragments thereof, or the multi-specific antibody is used in the treatment of systemic sclerosis. In certain embodiments, the combination of antibodies, or antigen binding fragments thereof, or the multi-specific antibody is used in the treatment of allergic rhinitis.
  • the combination of antibodies, or antigen binding fragments thereof, or the multi-specific antibody is used in the treatment of eosinophilic fasciitis. In certain embodiments, the combination of antibodies, or antigen binding fragments thereof, or the multi-specific antibody is used in the treatment of scleromyxedema. In certain embodiments, the combination of antibodies, or antigen binding fragments thereof, or the multi-specific antibody is used in the treatment of scleredema. In certain embodiments, the combination of antibodies, or antigen binding fragments thereof, or the multi-specific antibody is used in the treatment of nephrogenic systemic fibrosis.
  • a method for treating an inflammatory disorder or disease in a mammalian subject in need thereof comprising administering to the mammalian subject a therapeutically effective amount of a combination of antibodies, or antigen binding fragments thereof, or a multi-specific antibody described herein or a pharmaceutical composition of such antibody or antibodies described herein.
  • the inflammatory disorder or disease is atopic dermatitis.
  • the inflammatory disorder or disease is asthma.
  • the inflammatory disorder or disease is idiopathic pulmonary fibrosis.
  • the inflammatory disorder or disease is alopecia areata.
  • the inflammatory disorder or disease is chronic sinusitis with nasal polyps. In certain embodiments, the inflammatory disorder or disease is Chronic Rhinosinusitis without Nasal Polyps (CRSsNP). In certain embodiments, the inflammatory disorder or disease is eosinophilic esophagitis (EoE). In certain embodiments, the inflammatory disorder or disease is an Eosinophilic gastrointestinal disorder or disease (EGID) selected from the group consisting of Eosinophilic Gastritis (EoG), Eosinophilic Enteritis (EoN), Eosinophilic Colitis (EoC), and Eosinophilic Gastroenteritis (EGE).
  • EoG Eosinophilic Gastritis
  • EoN Eosinophilic Enteritis
  • EoC Eosinophilic Colitis
  • EGE Eosinophilic Gastroenteritis
  • the inflammatory disorder or disease is Churg-Strauss syndrome/Eosinophilic granulomatosis with polyangiitis (EGPA).
  • the inflammatory disorder or disease is Prurigo Nodularis (PN).
  • the inflammatory disorder or disease is Chronic Spontaneous Urticaria (CSU).
  • the inflammatory disorder or disease is Chronic Pruritis of Unknown Origin (CPUO).
  • the inflammatory disorder or disease is Bullous Pemphigoid (BP).
  • the inflammatory disorder or disease is Cold Inducible Urticaria (ColdU).
  • the inflammatory disorder or disease is Allergic Fungal Rhinosinusitis (AFRS).
  • the inflammatory disorder or disease is Allergic Bronchopulmonary Aspergillosis (ABPA). In certain embodiments, the inflammatory disorder or disease is Chronic Obstructive Pulmonary Disease (COPD). In certain embodiments, the inflammatory disorder or disease is inflammatory bowel disease, such as Crohn’s disease or ulcerative colitis. In certain embodiments, the inflammatory disorder or disease is psoriasis. In certain embodiments, the inflammatory disorder or disease is lupus. In certain embodiments, the inflammatory disorder or disease is rheumatoid arthritis. In certain embodiments, the inflammatory disorder or disease is celiac disease. In certain embodiments, the inflammatory disorder or disease is hidradenitis suppurativa.
  • ABPA Allergic Bronchopulmonary Aspergillosis
  • COPD Chronic Obstructive Pulmonary Disease
  • the inflammatory disorder or disease is inflammatory bowel disease, such as Crohn’s disease or ulcerative colitis.
  • the inflammatory disorder or disease is psoriasis.
  • the inflammatory disorder or disease is systemic sclerosis. In certain embodiments, the inflammatory disorder or disease is allergic rhinitis. In certain embodiments, the inflammatory disorder or disease is eosinophilic fasciitis. In certain embodiments, the inflammatory disorder or disease is scleromyxedema. In certain embodiments, the inflammatory disorder or disease is scleredema. In certain embodiments, the inflammatory disorder or disease is nephrogenic systemic fibrosis.
  • described herein are methods for treating a pathology associated with elevated levels of OX40L in a mammalian subject in need thereof, the method comprising administering to the mammalian subject a therapeutically effective amount of a combination of antibodies, or antigen binding fragments thereof, or a multi- specific antibody or a pharmaceutical composition described herein.
  • described herein are methods of reducing biological activity of OX40L in a mammalian subject in need thereof, the method comprising administering to the mammalian subject a therapeutically effective amount of a combination of antibodies, or antigen binding fragments thereof, or a multi-specific antibody or a pharmaceutical composition described herein.
  • described herein are methods for treating a pathology associated with elevated levels of IL-4 or IL-13 in a mammalian subject in need thereof, the method comprising administering to the mammalian subject a therapeutically effective amount of a combination of antibodies, or antigen binding fragments thereof, or a multi- specific antibody or a pharmaceutical composition described herein.
  • described herein are methods of reducing biological activity of IL-4, IL-13, and/or IL-4R ⁇ in a mammalian subject in need thereof, the method comprising administering to the mammalian subject a therapeutically effective amount of a combination of antibodies, or antigen binding fragments thereof, or a multi-specific antibody or a pharmaceutical composition described herein.
  • described herein are methods for reducing or inhibiting the TH2 type (Type 2) allergic response in a mammalian subject in need thereof, the method comprising administering to the mammalian subject a therapeutically effective amount of a combination of antibodies, or antigen binding fragments thereof, or a multi-specific antibody or a pharmaceutical composition described herein.
  • described herein are methods for inhibiting IL-4R ⁇ -induced phosphorylation of STAT6 in a cell, the method comprising contacting the cell with a combination of antibodies, or antigen binding fragments thereof, or a multi-specific antibody or a pharmaceutical composition described herein.
  • TARC Thymus and Activation Regulated Chemokine
  • cytokines and/or chemokines e.g., TNF ⁇ , MDC, IL-13, and/or IL-5
  • the method comprising administering to the mammalian subject a therapeutically effective amount of a combination of antibodies or a multi-specific antibody or a pharmaceutical composition described herein.
  • described herein are methods for reducing levels of interferon- gamma (IFN ⁇ ) in a mammalian subject in need thereof, the method comprising administering to the mammalian subject a therapeutically effective amount of a combination of antibodies, or antigen binding fragments thereof, or a multi-specific antibody or a pharmaceutical composition described herein.
  • IFN ⁇ interferon- gamma
  • described herein are methods for reducing levels of IL-2 in a mammalian subject in need thereof, the method comprising administering to the mammalian subject a therapeutically effective amount of a combination of antibodies, or antigen binding fragments thereof, or a multi-specific antibody or a pharmaceutical composition described herein.
  • described herein are methods of preventing an inflammatory disorder or disease in a mammalian subject in need thereof, the method comprising administering to the mammalian subject a therapeutically effective amount of a combination of antibodies or a multi-specific antibody or a pharmaceutical composition described herein.
  • Methods of Administration [00661]
  • the methods provided herein are useful for the treatment of a disease or disorder in an individual, e.g., a human.
  • the individual has received an anti-IL-4R ⁇ antibody, or an antigen binding fragment thereof, and the method includes administering an anti-OX40L antibody, or an antigen binding fragment thereof, described herein.
  • the individual has received an anti-OX40L antibody, or an antigen binding fragment thereof, and the method includes administering an anti-IL-4R ⁇ antibody, or an antigen binding fragment thereof, described herein.
  • the individual is administered an anti-OX40L antibody, or an antigen binding fragment thereof, and an anti-IL-4R ⁇ antibody, or an antigen binding fragment thereof.
  • the treatment regimen of the present invention may involve administering the anti-OX40L antibody, or an antigen binding fragment thereof, and the anti-IL-4R ⁇ antibody, or an antigen binding fragment thereof, at the same time.
  • compositions or formulations may be administered before the anti-IL-4R ⁇ antibody, or an antigen binding fragment thereof, by intervals ranging from minutes, hours, days to weeks, or the anti-IL-4R ⁇ antibody, or an antigen binding fragment thereof, may be administered before the anti-OX40L antibody, or an antigen binding fragment thereof, by intervals ranging from minutes, hours days to weeks.
  • the individual is administered a combination of antibodies, or antigen binding fragments thereof, or a multi-specific antibody described herein.
  • a combination of antibodies, or antigen binding fragments thereof, or a multi-specific antibody is administered intravenously, intramuscularly, subcutaneously, topically, orally, transdermally, intraperitoneally, intraorbitally, by implantation, by inhalation, intrathecally, intraventricularly, or intranasally.
  • An effective amount of an anti-OX40L antibody, or an antigen binding fragment thereof, and an anti-IL- 4R ⁇ antibody, or an antigen binding fragment thereof may be administered for the treatment of a disease or disorder.
  • the appropriate dosage of the anti-OX40L antibody, or an antigen binding fragment thereof, and the anti-IL-4R ⁇ antibody, or an antigen binding fragment thereof may be determined based on, e.g., the type of disease or disorder to be treated, the type of the anti-OX40L antibody, the type of anti-IL-4R ⁇ antibody, the severity and course of the disease or disorder, the clinical condition of the individual, the individual’s clinical history and response to the treatment, and the discretion of the attending physician.
  • the combination of antibodies, or antigen binding fragments thereof, or a multi-specific antibody provided herein are administered with at least one additional therapeutic agent.
  • any suitable additional therapeutic or immunotherapeutic agent may be administered with a combination of antibodies or a multi-specific antibody provided herein.
  • Additional therapeutic agents include agents that are used to treat or prevent a disease or disorder such as, but not limited to, an inflammatory disease or disorder associated with elevated levels of OX40L, IL-4 IL-13, and/or IgE.
  • the additional therapeutic agent can be administered by any suitable means.
  • the antibodies, or antigen binding fragments thereof, or multi-specific antibody and the additional therapeutic agent are included in the same pharmaceutical composition.
  • the antibodies, or antigen binding fragments thereof, or multi-specific antibody provided herein and the additional therapeutic agent are included in different pharmaceutical compositions.
  • administration of the antibodies, or antigen binding fragments thereof, or multi-specific antibody and the additional therapeutic agent can occur prior to, simultaneously, and/or following, administration of the additional therapeutic agent.
  • administration of the antibodies, or antigen binding fragments thereof, or multi-specific antibody provided herein and the additional therapeutic agent occur within about one month of each other.
  • administration of the antibodies, or antigen binding fragments thereof, or multi-specific antibody provided herein and the additional therapeutic agent occur within about one week of each other.
  • administration of the antibodies, or antigen binding fragments thereof, or multi-specific antibody provided herein and the additional therapeutic agent occur within about one day of each other. In some embodiments, administration of the antibodies, or antigen binding fragments thereof, or multi-specific antibody provided herein and the additional therapeutic agent occur within about twelve hours of each other. In some embodiments, administration of the antibodies, or antigen binding fragments thereof, or multi-specific antibody provided herein and the additional therapeutic agent occur within about one hour of each other. [00668] In some embodiments, the method further comprises administration of a hyaluronidase or variant thereof.
  • the hyaluronidase or variant thereof is included in the same composition with one or more of the antibodies (i.e., anti- IL-4R ⁇ antibody, or an antigen binding fragment thereof, and anti-OX40L antibody, or an antigen binding fragment thereof) or the multi-specific antibody (i.e., comprising a first antigen binding region that binds OX40L and a second antigen binding region that binds IL-4R ⁇ ).
  • the hyaluronidase or variant there is administered in a separate formulation.
  • the hyaluronidase or variant thereof and antibodies or multi-specific antibody are administered simultaneously in separate formulations (e.g., via two formulations: one containing the hyaluronidase or variant thereof and the other containing the multi-specific antibody or combination of the OX40L antibody, or an antigen binding fragment thereof, and IL-4R ⁇ antibody, or an antigen binding fragment thereof, or via three formulations: one containing the hyaluronidase or variant thereof, another containing the OX40L antibody, or an antigen binding fragment thereof, and another containing the IL-4R ⁇ antibody, or an antigen binding fragment thereof).
  • the hyaluronidase or variant thereof is administered to the patient prior to administration of the antibodies or multi-specific antibody. In certain embodiments, the hyaluronidase or variant thereof is administered to the patient after administration of the antibodies or multi-specific antibody. In certain embodiments, the hyaluronidase or variant thereof is administered to the patient after administration of one of the antibodies (either the OX40L antibody, or an antigen binding fragment thereof, or the IL-4R ⁇ antibody, or an antigen binding fragment thereof) but is administered before the administration of the second of the antibodies (either the OX40L antibody, or an antigen binding fragment thereof, or the IL-4R ⁇ antibody, or an antigen binding fragment thereof).
  • compositions comprising an isolated antibody that binds OX40L, or an antigen binding fragment thereof, an isolated antibody that binds Interleukin-4 Receptor Alpha (IL-4R ⁇ ), or an antigen binding fragment thereof, and a hyaluronidase or variant thereof.
  • IL-4R ⁇ Interleukin-4 Receptor Alpha
  • compositions comprising any one of the antibodies, or antigen binding fragments thereof, described herein that binds OX40L, any one of the antibodies, or antigen binding fragments thereof, described herein that binds IL-4R ⁇ , and any of the hyaluronidases or variants thereof described herein.
  • compositions comprising hyaluronidase or a variant thereof and a multi-specific antibody comprising a first antigen binding region that binds OX40L and a second antigen binding region that binds IL-4R ⁇ .
  • described herein are a combination of an antibody that binds OX40L, or an antigen binding fragment thereof, an antibody that binds IL-4R ⁇ , or an antigen binding fragment thereof, and a hyaluronidase or variant thereof.
  • described herein are a combination of any one of the antibodies, or antigen binding fragments thereof, described herein that binds OX40L, any one of the antibodies, or antigen binding fragments thereof, described herein that binds IL-4R ⁇ , and a hyaluronidase or a variant thereof.
  • described herein are combinations comprising hyaluronidase or a variant thereof and a multi-specific antibody comprising a first antigen binding region that binds OX40L and a second antigen binding region that binds IL-4R ⁇ .
  • described herein are methods of treating an inflammatory disorder or disease in a human patient comprising co-administering to the patient an isolated antibody, or an antigen binding fragment thereof, that binds OX40L, an isolated antibody, or an antigen binding fragment thereof, that binds IL-4R ⁇ , and a hyaluronidase or a variant thereof.
  • described herein are methods of treating an inflammatory disorder or disease in a human patient comprising co-administering to the patient any one of the antibodies, or antigen binding fragments thereof, described herein that binds OX40L, any one of the antibodies, or antigen binding fragments thereof, described herein that binds IL-4R ⁇ , and any of the hyaluronidases or variants thereof described herein.
  • Described herein are methods of treating an inflammatory disorder or disease in a human patient comprising co-administering to the patient a hyaluronidase or a variant thereof and a multi-specific antibody comprising a first antigen binding region that binds OX40L and a second antigen binding region that binds IL-4R ⁇ .
  • described herein are methods of treating an inflammatory disorder or disease in a human patient comprising co-administering to the patient any of the hyaluronidases or variants thereof described herein and any one of the multi-specific antibodies described herein (e.g., comprising a first antigen binding region that binds OX40L and a second antigen binding region that binds IL-4R ⁇ ).
  • the antibody, or antigen binding region thereof, that binds OX40L and/or the antibody, or antigen binding region thereof, that binds IL-4R ⁇ is a humanized, human, or chimeric antibody.
  • the antibody is a monoclonal antibody.
  • the antibody comprises a heavy chain human constant region of a class selected from IgG, IgA, IgD, IgE, and IgM.
  • the antibody comprises a human Fc region comprising a human heavy chain constant region of the class IgG and a subclass selected from IgG1, IgG2, IgG3, and IgG4.
  • the human Fc region comprises a human IgG1 Fc region.
  • the human Fc region comprises a human IgG1 Fc region with LALA (L234A/L235A) mutations.
  • the human Fc region comprises a human IgG1 Fc with YTE (M252Y/S254T/T256E) mutations. In certain embodiments the human Fc region comprises a human IgG1 Fc with LALA (L234A/L235A) and YTE (M252Y/S254T/T256E) mutations. In certain embodiments, when direct numbering is used these “YTE” and “LALA” mutations can be located at different amino acid position numbers.
  • the human Fc region comprises a human IgG1 Fc region with LALA mutations at L235A/L236A and/or YTE mutations at M253Y/S255T/T257E (see, e.g., SEQ ID NO: 839 and 840).
  • the human Fc region comprises a human IgG1 Fc region with LALA mutations at L242A/L243A and/or YTE mutations at M260Y/S262T/T264E (see, e.g., SEQ ID NO: 836 or 837).
  • the antibody, or antigen binding region thereof, that binds OX40L comprises a CDR-H1 comprising the sequence set forth in SEQ ID NO: 2; a CDR- H2 comprising the sequence set forth in SEQ ID NO: 5; a CDR-H3 comprising the sequence set forth in SEQ ID NO: 8; a CDR-L1 comprising the sequence set forth in SEQ ID NO: 12; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 15; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 17.
  • the antibody, or antigen binding region thereof, that binds OX40L comprises a VH sequence set forth in SEQ ID NO: 1 and a VL sequence set forth in SEQ ID NO: 11.
  • the heavy chain of the antibody, or antigen binding region thereof, that binds OX40L comprises a constant heavy chain sequence set forth in SEQ ID NO: 651.
  • the heavy chain of the antibody, or antigen binding region thereof, that binds OX40L comprises a constant heavy chain sequence set forth in SEQ ID NO: 973.
  • the light chain of the antibody, or antigen binding region thereof, that binds OX40L comprises a constant light chain sequence set forth in SEQ ID NO: 738.
  • the heavy chain of the antibody, or antigen binding region thereof, that binds OX40L has the sequence set forth in SEQ ID NO: 839.
  • the light chain of the antibody, or antigen binding region thereof, that binds OX40L has the sequence set forth in SEQ ID NO: 841.
  • the C- terminal lysine in SEQ ID NO: 839 may not be present if cleavage occurs during manufacture or after administration (which would result in the heavy chain sequence of SEQ ID NO: 840).
  • the antibody, or antigen binding region thereof, that binds IL-4R ⁇ comprises a CDR-H1 comprising the sequence set forth in SEQ ID NO: 273; a CDR- H2 comprising the sequence set forth in SEQ ID NO: 279; a CDR-H3 comprising the sequence set forth in SEQ ID NO: 281; a CDR-L1 comprising the sequence set forth in SEQ ID NO: 289; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 290; and a CDR- L3 comprising the sequence set forth in SEQ ID NO: 293.
  • the antibody, or antigen binding region thereof, that binds IL-4R ⁇ comprises a VH sequence set forth in SEQ ID NO: 297 and a VL sequence set forth in SEQ ID NO: 300.
  • the heavy chain of the antibody, or antigen binding region thereof, that binds IL-4R ⁇ comprises a constant heavy chain sequence set forth in SEQ ID NO: 651.
  • the heavy chain of the antibody, or antigen binding region thereof, that binds IL-4R ⁇ comprises a constant heavy chain sequence set forth in SEQ ID NO: 973.
  • the light chain of the antibody, or antigen binding region thereof, that binds IL-4R ⁇ comprises a constant light chain sequence set forth in SEQ ID NO: 738.
  • the heavy chain of the antibody, or antigen binding region thereof, that binds IL-4R ⁇ has the sequence set forth in SEQ ID NO: 836.
  • the light chain of the antibody, or antigen binding region thereof, that binds IL-4R ⁇ has the sequence set forth in SEQ ID NO: 838.
  • the C-terminal lysine in SEQ ID NO: 836 may not be present if cleavage occurs during manufacture or after administration (which would result in the heavy chain sequence of SEQ ID NO: 837).
  • a multi-specific antibody comprising a first antigen binding region that binds OX40L and a second antigen binding region that binds IL-4R ⁇ is provided.
  • the antigen binding region that binds OX40L comprises a CDR-H1 comprising the sequence set forth in SEQ ID NO: 2; a CDR-H2 comprising the sequence set forth in SEQ ID NO: 5; a CDR-H3 comprising the sequence set forth in SEQ ID NO: 8; a CDR-L1 comprising the sequence set forth in SEQ ID NO: 12; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 15; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 17.
  • the antigen binding region that binds OX40L comprises a VH sequence set forth in SEQ ID NO: 1 and a VL sequence set forth in SEQ ID NO: 11.
  • the antigen binding region that binds IL- 4R ⁇ comprises a CDR-H1 comprising the sequence set forth in SEQ ID NO: 273; a CDR-H2 comprising the sequence set forth in SEQ ID NO: 279; a CDR-H3 comprising the sequence set forth in SEQ ID NO: 281; a CDR-L1 comprising the sequence set forth in SEQ ID NO: 289; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 290; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 293.
  • the antibody that binds IL-4R ⁇ comprises a VH sequence set forth in SEQ ID NO: 297 and a VL sequence set forth in SEQ ID NO: 300.
  • the antibody or antigen binding region that binds OX40L and/or the antibody or antigen binding region that binds IL-4R ⁇ comprises a heavy chain human constant region of a class selected from IgG, IgA, IgD, IgE, and IgM.
  • the antibody or antigen binding region that binds OX40L and/or the antibody or antigen binding region that binds IL-4R ⁇ comprises a human Fc region
  • the human Fc region comprises a human heavy chain constant region of the class IgG and a subclass selected from IgG1, IgG2, IgG3, and IgG4.
  • the human Fc region of the antibody that binds OX40L and/or the antibody that binds IL-4R ⁇ comprises a human IgG1 Fc region.
  • the human Fc region comprises a human IgG1 Fc with LALA (L234A/L235A) mutations.
  • the human Fc region comprises a human IgG1 Fc with YTE (M252Y/S254T/T256E) mutations. In certain embodiments the human Fc region comprises a human IgG1 Fc with LALA (L234A/L235A) and YTE (M252Y/S254T/T256E) mutations. In certain embodiments, when direct numbering is used these “YTE” and “LALA” mutations can be located at different amino acid position numbers.
  • the human Fc region comprises a human IgG1 Fc region with LALA mutations at L235A/L236A and/or YTE mutations at M253Y/S255T/T257E (see, e.g., SEQ ID NO: 839 and 840).
  • the human Fc region comprises a human IgG1 Fc region with LALA mutations at L242A/L243A and/or YTE mutations at M260Y/S262T/T264E (see, e.g., SEQ ID NO: 836 or 837).
  • the human Fc region of the antibody that binds OX40L and/or the antibody that binds IL-4R ⁇ comprises a human IgG4 Fc region. In certain embodiments, the human Fc region of the antibody or antigen binding region that binds OX40L and/or the antibody or antigen binding region that binds IL-4R ⁇ comprises a human IgG2 Fc region. [00681] In certain embodiments, the Fc region of the antibody or antigen binding region that binds OX40L and/or the antibody or antigen binding region that binds IL-4R ⁇ binds to Neonatal Fc receptor (FcRn).
  • FcRn Neonatal Fc receptor
  • the Fc region of the antibody or antigen binding region that binds OX40L and/or the antibody or antigen binding region that binds IL-4R ⁇ binds an FcRn with higher affinity at pH 6.0 compared to an antibody comprising a wild-type Fc region.
  • the Fc region of the antibody or antigen binding region that binds OX40L and/or the antibody or antigen binding region that binds IL-4R ⁇ binds to FcRn with a K D of ⁇ 1 x 10 -7 M at pH 6.0.
  • the antibody or antigen binding region that binds OX40L and/or the antibody or antigen binding region that binds IL-4R ⁇ is a monoclonal antibody.
  • the antibody or antigen binding region that binds OX40L binds an OX40L sequence set forth in the amino acid sequence of SEQ ID NO: 739.
  • the antibody or antigen binding region that binds IL-4R ⁇ binds an IL- 4R ⁇ sequence set forth in any one of the amino acid sequences of SEQ ID NOs: 301-303.
  • Any suitable hyaluronidase or variant thereof can be used in the compositions, combinations, and methods described herein.
  • the hyaluronidase is a recombinant human hyaluronidase.
  • the recombinant human hyaluronidase comprises the amino acid sequence set forth in any one of SEQ ID NOs: 1076- 1085 and 1087-1142.
  • the recombinant human hyaluronidase is rHuPH20.
  • the rHuPH20 formulation is ENHANZE®.
  • the recombinant human hyaluronidase includes a sequence of amino acids in any one of SEQ ID NOs: 1076-1085 and 1087-1142, or has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 95%, 97%, 98%, or 99% sequence identity to a sequence of amino acids included in SEQ ID NO: 1076- 1085 and 1087-1142 and retains hyaluronidase activity.
  • the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1076.
  • the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1076. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1078. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1078. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1079. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1079.
  • the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1080. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1080. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1081. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1081. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1082.
  • the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1082. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1083. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1083. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1084. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1084.
  • the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1085. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1085. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1087. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1087. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1088.
  • the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1088. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1089. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1089. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1090. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1090.
  • the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1091. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1091. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1092. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1092. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1093.
  • the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1093. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1094. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1094. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1095. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1095.
  • the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1096. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1096. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1097. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1097. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1098.
  • the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1098. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1099. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1099. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1100. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1100.
  • the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1101. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1101. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1102. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1102. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1103.
  • the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1103. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1104. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1104. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1105. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1105.
  • the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1106. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1106. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1107. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1107. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1108.
  • the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1108. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1109. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1109. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1110. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1110.
  • the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1111. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1111. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1112. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1112. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1113.
  • the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1113. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1114. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1114. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1115. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1115.
  • the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1116. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1116. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1117. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1117. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1118.
  • the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1118. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1119. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1119. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1120. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1120.
  • the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1121. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1121. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1122. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1122. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1123.
  • the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1123. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1124. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1124. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1125. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1125.
  • the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1126. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1126. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1127. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1127. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1128.
  • the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1128. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1129. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1129. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1130. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1130.
  • the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1131. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1131. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1132. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1132. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1133.
  • the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1133. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1134. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1134. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1135. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1135.
  • the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1136. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1136. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1137. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1137. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1138.
  • the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1138. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1139. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1139. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1140. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1140.
  • the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1141. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1141. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1142. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1142.
  • the hyaluronidase or variant thereof and antibodies i.e., anti- IL-4R ⁇ antibody, or an antigen binding fragment thereof, and anti-OX40L antibody, or an antigen binding fragment thereof,
  • multi-specific antibody i.e., comprising a first antigen binding region that binds OX40L and a second antigen binding region that binds IL- 4R ⁇
  • the hyaluronidase or variant thereof and antibodies i.e., anti- IL-4R ⁇ antibody, or an antigen binding fragment thereof, and anti-OX40L antibody, or an antigen binding fragment thereof,
  • multi-specific antibody i.e., comprising a first antigen binding region that binds OX40L and a second antigen binding region that binds IL- 4R ⁇
  • the hyaluronidase or variant thereof and antibodies i.e., anti- IL-4R ⁇ antibody, or an antigen binding fragment thereof, and antigen binding fragment thereof, or an antigen
  • the hyaluronidase or variant thereof and antibodies or multi-specific antibody are administered simultaneously in separate formulations. In certain embodiments, the hyaluronidase or variant thereof is administered to the patient prior to administration of the antibodies or multi-specific antibody. In certain embodiments, the hyaluronidase or variant thereof is administered to the patient after administration of the antibodies or multi-specific antibody.
  • the hyaluronidase or variant thereof is administered to the patient after administration of one of the antibodies (either the OX40L antibody, or an antigen binding fragment thereof, or the IL- 4R ⁇ antibody, or an antigen binding fragment thereof) but is administered before the administration of the second of the antibodies (either the OX40L antibody, or an antigen binding fragment thereof, or the IL-4R ⁇ antibody, or an antigen binding fragment thereof).
  • the hyaluronidase or variant thereof and the antibodies or multi- specific antibody are mixed and administered in a single formulation.
  • the hyaluronidase or variant thereof and the antibodies or multi-specific antibody are administered by subcutaneous injection.
  • the hyaluronidase or variant thereof and the antibodies or multi-specific antibody are administered by intravenous injection.
  • the hyaluronidase is rHuPH20 (ENHANZE®) administered at a concentration of 5,000, 6,000, 7,000, 8,000, 9,000, 10,000, 11,000, 12,000, 13,000, 14,000, 15,000, 16,000, 17,000, 18,000, 19,000, 20,000, 21,000, 22,000, 23,000, 24,000, 25,000, 26,000, 27,000, 28,000, 29,000, 30,000, 31,000, 32,000, 33,000, 34,000, 35,000, 36,000, 37,000, 38,000, 39,000, or 40,000 units.
  • methods of treating an inflammatory disorder or disease in a human patient comprising co-administering to the patient any one of the antibodies, or antigen binding fragments thereof, that bind OX40L described herein and any one of the antibodies, or antigen binding fragments thereof, that bind IL-4R ⁇ described herein in combination with a hyaluronidase or variant thereof.
  • methods of treating an inflammatory disorder or disease in a human patient are provided, wherein the method comprises co-administering to the patient any one of the multi-specific antibodies described herein in combination with a hyaluronidase or variant thereof.
  • the inflammatory disorder or disease is atopic dermatitis.
  • the treatment reduces disease severity in the patient and wherein disease severity is assessed by an atopic dermatitis disease severity outcome measure.
  • the inflammatory disorder or disease is asthma; chronic sinusitis with nasal polyps; Chronic Rhinosinusitis without Nasal Polyps (CRSsNP); eosinophilic esophagitis (EoE); an Eosinophilic gastrointestinal disorder or disease (EGID) selected from the group consisting of Eosinophilic Gastritis (EoG), Eosinophilic Enteritis (EoN), Eosinophilic Colitis (EoC), and Eosinophilic Gastroenteritis (EGE); Churg-Strauss syndrome/Eosinophilic granulomatosis with polyangiitis (EGPA); Prurigo Nodularis (PN); Chronic Spontaneous Urticaria (CSU); Chronic Pruritis of Unknown Origin (CPUO); Bullous Pemphigoid (BP);
  • compositions comprising an isolated antibody, or antigen binding region thereof, that binds OX40L, an isolated antibody, or antigen binding region thereof, that binds IL-4R ⁇ , and a hyaluronidase or variant thereof.
  • compositions comprising an isolated antibody, or antigen binding region thereof, that binds OX40L, an isolated antibody, or antigen binding region thereof, that binds IL-4R ⁇ , and a hyaluronidase or variant thereof, wherein the antibody, or antigen binding region thereof, that binds OX40L comprises a CDR- H1 comprising the sequence set forth in SEQ ID NO: 2; a CDR-H2 comprising the sequence set forth in SEQ ID NO: 5; a CDR-H3 comprising the sequence set forth in SEQ ID NO: 8; a CDR-L1 comprising the sequence set forth in SEQ ID NO: 12; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 15; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 17.
  • compositions comprising an isolated antibody, or antigen binding region thereof, that binds OX40L, an isolated antibody, or antigen binding region thereof, that binds IL-4R ⁇ , and a hyaluronidase or variant thereof, wherein the antibody, or antigen binding region thereof, that binds OX40L comprises a VH sequence set forth in SEQ ID NO: 1 and a VL sequence set forth in SEQ ID NO: 11.
  • compositions comprising an isolated antibody, or antigen binding region thereof, that binds OX40L, an isolated antibody, or antigen binding region thereof, that binds IL-4R ⁇ , and a hyaluronidase or variant thereof, wherein the antibody that binds IL-4R ⁇ , or antigen binding region thereof, comprises a CDR- H1 comprising the sequence set forth in SEQ ID NO: 273; a CDR-H2 comprising the sequence set forth in SEQ ID NO: 279; a CDR-H3 comprising the sequence set forth in SEQ ID NO: 281; a CDR-L1 comprising the sequence set forth in SEQ ID NO: 289; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 290; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 293.
  • compositions comprising an isolated antibody, or antigen binding region thereof, that binds OX40L, an isolated antibody, or antigen binding region thereof, that binds IL-4R ⁇ , and a hyaluronidase or variant thereof, wherein the antibody, or antigen binding region thereof, that binds IL-4R ⁇ comprises a VH sequence set forth in SEQ ID NO: 297 and a VL sequence set forth in SEQ ID NO: 300.
  • compositions comprising an isolated antibody, or antigen binding region thereof, that binds OX40L, an isolated antibody, or antigen binding region thereof, that binds IL-4R ⁇ , and a hyaluronidase or variant thereof, wherein the antibody, or antigen binding region thereof, that binds OX40L comprises a CDR- H1 comprising the sequence set forth in SEQ ID NO: 2; a CDR-H2 comprising the sequence set forth in SEQ ID NO: 5; a CDR-H3 comprising the sequence set forth in SEQ ID NO: 8; a CDR-L1 comprising the sequence set forth in SEQ ID NO: 12; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 15; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 17, and wherein the antibody, or antigen binding region thereof, that binds IL- 4R ⁇ comprises a CDR-H1 comprising the sequence
  • compositions comprising an isolated antibody, or antigen binding region thereof, that binds OX40L, an isolated antibody, or antigen binding region thereof, that binds IL-4R ⁇ , and a hyaluronidase or variant thereof, wherein the antibody, or antigen binding region thereof, that binds OX40L comprises a VH sequence set forth in SEQ ID NO: 1 and a VL sequence set forth in SEQ ID NO: 11; and wherein the antibody, or antigen binding region thereof, that binds IL-4R ⁇ comprises a VH sequence set forth in SEQ ID NO: 297 and a VL sequence set forth in SEQ ID NO: 300.
  • compositions comprising hyaluronidase or a variant thereof and a multi-specific antibody comprising a first antigen binding region that binds OX40L and a second antigen binding region that binds IL-4R ⁇
  • the antigen binding region that binds OX40L comprises a CDR-H1 comprising the sequence set forth in SEQ ID NO: 2; a CDR-H2 comprising the sequence set forth in SEQ ID NO: 5; a CDR-H3 comprising the sequence set forth in SEQ ID NO: 8; a CDR-L1 comprising the sequence set forth in SEQ ID NO: 12; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 15; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 17, and wherein the antigen binding region that binds IL-4R ⁇ comprises a CDR-H1 comprising the sequence set forth in SEQ ID NO: 273;
  • compositions comprising hyaluronidase or a variant thereof and a multi-specific antibody comprising a first antigen binding region that binds OX40L and a second antigen binding region that binds IL-4R ⁇ , wherein the antigen binding region that binds OX40L comprises a VH sequence set forth in SEQ ID NO: 1 and a VL sequence set forth in SEQ ID NO: 11; and wherein the antigen binding region that binds IL-4R ⁇ comprises a VH sequence set forth in SEQ ID NO: 297 and a VL sequence set forth in SEQ ID NO: 300.
  • a CDR- H1 comprising the sequence set forth in SEQ ID NO: 2
  • a CDR-H2 comprising the sequence set forth in SEQ ID NO: 5
  • a CDR-H3 comprising the sequence set forth in SEQ ID NO: 8
  • a CDR-L1 comprising the sequence set forth in SEQ ID NO: 12
  • a CDR-L2 comprising the sequence set forth in SEQ ID NO: 15
  • a CDR-L3 comprising the sequence set forth in SEQ ID NO: 17, and wherein the antibody, or antigen binding region thereof, that binds IL- 4R ⁇ comprises a CDR-H1 comprising the sequence set
  • hyaluronidase or a variant thereof and a multi-specific antibody comprising a first antigen binding region that binds OX40L and a second antigen binding region that binds IL-4R ⁇
  • the antigen binding region that binds OX40L comprises a CDR-H1 comprising the sequence set forth in SEQ ID NO: 2; a CDR-H2 comprising the sequence set forth in SEQ ID NO: 5; a CDR-H3 comprising the sequence set forth in SEQ ID NO: 8; a CDR-L1 comprising the sequence set forth in SEQ ID NO: 12; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 15; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 17, and wherein the antigen binding region that binds IL-4R ⁇ comprises a CDR-H1 comprising the sequence set forth in SEQ ID NO: 273; a CDR-H2 comprising the sequence set forth in SEQ ID NO
  • hyaluronidase or a variant thereof and a multi-specific antibody comprising a first antigen binding region that binds OX40L and a second antigen binding region that binds IL-4R ⁇ , wherein the antigen binding region that binds OX40L comprises a VH sequence set forth in SEQ ID NO: 1 and a VL sequence set forth in SEQ ID NO: 11; and wherein the antigen binding region that binds IL-4R ⁇ comprises a VH sequence set forth in SEQ ID NO: 297 and a VL sequence set forth in SEQ ID NO: 300.
  • Described herein are methods of treating an inflammatory disorder or disease in a human patient comprising administering to the patient an isolated antibody, or antigen binding region thereof, that binds OX40L, an isolated antibody, or antigen binding region thereof, that binds IL-4R ⁇ , and a hyaluronidase or a variant thereof, wherein the antibody, or antigen binding region thereof, that binds OX40L comprises a VH sequence set forth in SEQ ID NO: 1 and a VL sequence set forth in SEQ ID NO: 11; and wherein the antibody, or antigen binding region thereof, that binds IL-4R ⁇ comprises a VH sequence set forth in SEQ ID NO: 297 and a VL sequence set forth in SEQ ID NO: 300.
  • Describe herein are methods of treating an inflammatory disorder or disease in a human patient comprising administering to the patient hyaluronidase or a variant thereof and a multi-specific antibody comprising a first antigen binding region that binds OX40L and a second antigen binding region that binds IL-4R ⁇ , wherein the antigen binding region that binds OX40L comprises a CDR-H1 comprising the sequence set forth in SEQ ID NO: 2; a CDR-H2 comprising the sequence set forth in SEQ ID NO: 5; a CDR-H3 comprising the sequence set forth in SEQ ID NO: 8; a CDR-L1 comprising the sequence set forth in SEQ ID NO: 12; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 15; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 17, and wherein the antigen binding region that binds IL-4R ⁇ comprises a CDR-H
  • Described herein are methods of treating an inflammatory disorder or disease in a human patient comprising administering to the patient hyaluronidase or a variant thereof and a multi-specific antibody comprising a first antigen binding region that binds OX40L and a second antigen binding region that binds IL-4R ⁇ , wherein the antigen binding region that binds OX40L comprises a VH sequence set forth in SEQ ID NO: 1 and a VL sequence set forth in SEQ ID NO: 11; and wherein the antigen binding region that binds IL-4R ⁇ comprises a VH sequence set forth in SEQ ID NO: 297 and a VL sequence set forth in SEQ ID NO: 300.
  • the hyaluronidase is a recombinant human hyaluronidase or variant thereof. In certain embodiments, the hyaluronidase is a recombinant human hyaluronidase. In certain embodiments, the recombinant human hyaluronidase comprises the amino acid sequence set forth in any one of SEQ ID NOs: 1076-1085 and 1087-1142. In certain embodiments, the recombinant human hyaluronidase is rHuPH20. In certain embodiments, the rHuPH20 formulation is ENHANZE®.
  • kits comprising any one or more of the antibodies, or antigen binding regions thereof, or multi-specific antibody compositions described herein and instructions for use.
  • the kits further contain a component selected from any of secondary antibodies, additional therapeutic agents, reagents for immunohistochemistry analysis, pharmaceutically acceptable excipient and instruction manual and any combination thereof.
  • the kit comprises a pharmaceutical composition comprising any one or more of the antibodies, or antigen binding regions thereof, or multi-specific antibody compositions described herein, with one or more pharmaceutically acceptable excipients.
  • kits for treating an inflammatory disorder or disease in a human patient comprising: (a) a dose of an antibody, or antigen binding region thereof, that binds OX40L (e.g., an antibody, or an antigen binding region thereof, that binds OX40L in unit dosage form); (b) a dose of an antibody, or antigen binding region thereof, that binds IL-4R ⁇ (e.g., an antibody, or an antigen binding region thereof, that binds IL-4R ⁇ in unit dosage form); (c) a dose of a hyaluronidase or variant thereof (e.g., a hyaluronidase or a variant thereof in unit dosage form); and (d) instructions.
  • OX40L e.g., an antibody, or an antigen binding region thereof, that binds OX40L in unit dosage form
  • IL-4R ⁇ e.g., an antibody, or an antigen binding region thereof, that binds IL-4R ⁇ in unit dosage form
  • kits for treating an inflammatory disorder or disease in a human patient comprising: (a) a dose of an antibody, or antigen binding region thereof, that binds OX40L (e.g., an antibody, or an antigen binding region thereof, that binds OX40L in unit dosage form), wherein the antibody, or antigen binding region thereof, comprises a CDR-H1 comprising the sequence set forth in SEQ ID NO: 2; a CDR-H2 comprising the sequence set forth in SEQ ID NO: 5; a CDR-H3 comprising the sequence set forth in SEQ ID NO: 8; a CDR-L1 comprising the sequence set forth in SEQ ID NO: 12; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 15; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 17; (b) a dose of an antibody, or antigen binding region thereof, that binds IL-4R ⁇ (
  • kits for treating an inflammatory disorder or disease in a human patient comprising: (a) a dose of an antibody, or antigen binding region thereof, that binds OX40L (e.g., an antibody, or an antigen binding region thereof, that binds OX40L in unit dosage form), wherein the antibody, or antigen binding region thereof, comprises a VH sequence set forth in SEQ ID NO: 1 and a VL sequence set forth in SEQ ID NO: 11; (b) a dose of an antibody, or antigen binding region thereof, that binds IL-4R ⁇ (e.g., an antibody, or an antigen binding region thereof, that binds IL-4R ⁇ in unit dosage form), wherein the antibody, or antigen binding region thereof, comprises a VH sequence set forth in SEQ ID NO: 297 and a VL sequence set forth in SEQ ID NO: 300; (c) a dose of a hyaluronidase or variant thereof (e.
  • kits for treating an inflammatory disorder or disease in a human patient comprising: (a) a dose of a multi-specific antibody comprising a first antigen binding region that binds OX40L and a second antigen binding region that binds IL-4R ⁇ (e.g., a multi-specific antibody in unit dosage form); (b) a dose of a hyaluronidase or variant thereof (e.g., a hyaluronidase or a variant thereof in unit dosage form); and (c) instructions.
  • a dose of a multi-specific antibody comprising a first antigen binding region that binds OX40L and a second antigen binding region that binds IL-4R ⁇
  • a dose of a hyaluronidase or variant thereof e.g., a hyaluronidase or a variant thereof in unit dosage form
  • instructions e.g., a hyaluronidase or a variant thereof in unit dosage form
  • kits for treating an inflammatory disorder or disease in a human patient comprising: (a) a dose of a multi-specific antibody comprising a first antigen binding region that binds OX40L and a second antigen binding region that binds IL-4R ⁇ (e.g., a multi-specific antibody in unit dosage form), wherein the antigen binding region that binds OX40L comprises a VH sequence set forth in SEQ ID NO: 1 and a VL sequence set forth in SEQ ID NO: 11; and wherein the antigen binding region that binds IL-4R ⁇ comprises a VH sequence set forth in SEQ ID NO: 297 and a VL sequence set forth in SEQ ID NO: 300; (b) a dose of a hyaluronidase or variant thereof (e.g., a hyaluronidase or a variant thereof in unit dosage form); and (c) instructions.
  • a dose of a multi-specific antibody comprising a first antigen binding region that binds O
  • the hyaluronidase is a recombinant human hyaluronidase or variant thereof. In certain embodiments, the hyaluronidase is a recombinant human hyaluronidase. In certain embodiments, the recombinant human hyaluronidase comprises the amino acid sequence set forth in any one of SEQ ID NOs: 1076-1085 and 1087-1142. In certain embodiments, the recombinant human hyaluronidase is rHuPH20. In certain embodiments, the rHuPH20 formulation is ENHANZE®. [00714] In certain embodiments, the kit is for use in treating an inflammatory disorder or disease.
  • the inflammatory disorder or disease is atopic dermatitis; asthma, chronic sinusitis with nasal polyps; Chronic Rhinosinusitis without Nasal Polyps (CRSsNP); eosinophilic esophagitis (EoE); an Eosinophilic gastrointestinal disorder or disease (EGID) selected from the group consisting of Eosinophilic Gastritis (EoG), Eosinophilic Enteritis (EoN), Eosinophilic Colitis (EoC), and Eosinophilic Gastroenteritis (EGE); Churg-Strauss syndrome/Eosinophilic granulomatosis with polyangiitis (EGPA); Prurigo Nodularis (PN); Chronic Spontaneous Urticaria (CSU); Chronic Pruritis of Unknown Origin (CPUO); Bullous Pemphigoid (BP); Cold Inducible Urticaria (ColdU); Allergic Fungal Rhinosinusitis (AFRS);
  • Example 1 Generation of anti-hOX40L antibodies
  • Alloy ATX mice expressing chimeric antibodies with fully-human variable regions were immunized with recombinant human OX40L (hOX40L) protein and/or DNA encoding hOX40L.
  • the serum was used to measure titers against hOX40L by ELISA.
  • Splenic and lymph node cells from immunized mice were fused with fusion partner cells to generate hybridomas. Upon expansion, the supernatants were screened for binding to recombinant hOX40L protein by ELISA and hOX40L-expressing CHO cells by flow cytometry.
  • the coding sequences for HC and LC of the antibody were generated by DNA synthesis and PCR, subsequently subcloned into an expression vector for protein expression in mammalian cell system. The gene sequences in the expression vectors were confirmed by DNA sequencing.
  • Example 2 Production and purification of recombinant anti-hOX40L antibodies [00723] To produce fully-human anti-hOX40L antibodies, DNA sequences encoding heavy and light variable regions of hybridoma and plasma cells of interest were recombinantly assembled into separate mammalian cell expression vectors with the mutant human IgG1 constant region comprising LALA/YTE mutations (SEQ ID NO: 973) and wild- type human IgK constant region (SEQ ID NO: 738), respectively.
  • ExpiCHO cells were transiently transfected and supernatants containing antibodies were harvested after up to 14 days.
  • Protein purification by affinity chromatography, and ion exchange chromatography was performed using an AKTA pure instrument (GE Lifesciences).
  • Conditional medium expressing target antibody was harvested by centrifugation at 4000 rpm, 50 min, and filtered with a 0.22 ⁇ m filter.
  • the harvested supernatants were loaded to a column of HiTrap MabselectTM SuReTM Protein A and polished by size-exclusion chromatography with HiLoadTM 26/200 SuperdexTM 200 pg.
  • the protein was eluted with Buffer B (1 M Glycine, pH 2.7), and immediately neutralized with 1/10 volume of Buffer D (1 M sodium citrate, pH 6.0).
  • Buffer A PBS, PH 7.4
  • Buffer B 1 M Glycine, pH 2.7
  • Buffer D 1 M sodium citrate, pH 6.0
  • the affinity purified antibody was then buffer exchanged into 20 mM sodium acetate pH 5.5.
  • Example 3 Determination of antibody affinity to hOX40L Measuring Antibody-OX-40L Binding Kinetics Using Surface Plasmon Resonance
  • a Biacore 8K SPR system (GE HealthCare) equipped with Series S Sensor Chip Protein G (Cytiva, Cat.29179315) was used to determine the binding kinetic rate and affinity constants at 25 ⁇ C and in a running buffer of HBS-EP+ (10 mM HEPES pH 7.4, 150 mM NaCl, 3 mM EDTA, 0.05% Surfactant P20).
  • the anti-OX40L mAb constructs (diluted to 1 ⁇ g/mL) were captured onto flow cell 2 (active) for 60 sec at a flow rate of 10 ⁇ L/min.
  • Recombinant Human OX40L Protein, His Tag (Acro Cat. IL3-H52H4) was prepared at concentrations of 0, 0.39, 0.78, 1.56, 3.13, 6.25, 12.5 and 0 nM and injected over flow cell 1 (reference) and flow cell 2 (active) for 180 sec at a flow rate of 30 ⁇ L/min.
  • Recombinant non-human primate (NHP) Cynomolgus OX40L Protein, His Tag was prepared at concentrations of 0, 0.39, 0.78, 1.56, 3.13, 6.25, 12.5, 25 and 0 nM and injected over flow cell 1 (reference) and flow cell 2 (active) for 180 sec at a flow rate of 30 ⁇ L/min. Samples were injected in a multi- cycle manner over freshly captured mAb, by regenerating the capture surfaces with injection of glycine pH 1.5 for 30 sec at a flow rate of 30 ⁇ L/min. The data was processed and analyzed with Biacore Insight Evaluation Software Version 2.0.15.12933 (GE Healthcare) as follows.
  • CM5 Series S sensor chip functionalized with anti-human IgG Fc or anti-mouse IgG Fc antibody by amine coupling was used to capture antibodies at 20 nM. Subsequently, concentrations of hOX40L ranging from 500 nM to 31.25 nM were injected at 30 ⁇ L/min. The chip was regenerated with 10 mM glycine pH 1.5 between runs. Results are summarized in TABLE 11. TABLE 11.
  • KD Binding affinity of antibodies to human and NHP OX40L Human OX40L NHP (Cynomolgus) OX40L 1 1 Human OX40L NHP (Cynomolgus) OX40L kon (M- kon (M- 11 11 11 11 co espo g o u ca o o. , c s co po a e e e y reference in its entirety n.d.: No data.
  • Example 4 Binding of hOX40L-
  • CHO cells were transduced to generate a pool of cells overexpressing hOX40L.
  • Single clones were isolated and expanded to select a clone stably expressing hOX40L.
  • a positive control based on the sequences of the anti-hOX40L antibody amlitelimab (called “positive control” throughout the anti-OX40L antibody-related Examples and Figures) was also generated.
  • the cells were incubated with titrated anti-hOX40L antibodies, then with fluorophore-labeled goat anti-human IgG secondary antibody to detect bound antibodies by flow cytometry. Nonlinear regression was performed on geometric mean fluorescence intensity (gMFI) values to determine EC50 values (FIGURE 1, TABLE 12).
  • gMFI geometric mean fluorescence intensity
  • the exemplary anti-hOX40L antibodies bound hOX40L-expressing CHO cells with an EC 50 less than 5 nM. Furthermore, clones 105 and 114 exhibited higher gMFI at maximum concentration tested suggesting an increased capacity to bind cell surface OX40L compared to positive control (FIGURE 1). TABLE 12. Binding of OX40L antibodies to hOX40L-expressing CHO cells Clone EC50 (nM) 105 3.43 114 4.04 Positive Control 3.49 See construct sequences in TABLE 3 Example 5: Blocking activity of anti-hOX40L antibodies [00728] Anti-hOX40L antibodies were assessed for their ability to block hOX40L-hOX40 interaction by ELISA.
  • Exemplary anti-hOX40L antibodies inhibited human OX40L binding to OX40 in a concentration-dependent manner.
  • Blockade of the hOX40/hOX40L interaction by anti-hOX40L antibodies Clone IC50 (nM) 105 1.41 114 1.12 122 1.57 128 7.52 130 12.99 231 28.5 328 5.99 Pos. Ctrl. 0.62 Iso. Ctrl. N/A See construct sequences in TABLE 3 and in PCT Application No. PCT/US2024/026854 (corresponding to PCT Publication No. WO2024227174), which is incorporated herein by reference in its entirety N/A: No data.
  • Example 6 Signaling activity of anti-hOX40L antibodies in hOX40 reporter assay
  • Anti-hOX40L antibodies were assessed for their functional blockade of the OX40- OX40L interaction using an OX40 bioassay.
  • hOX40 cells are commercial cells that overexpress OX40 and have a downstream element that drives luciferase expression under hOX40L stimulation. These cells were used to determine the ability of anti-hOX40L antibodies to block hOX40-mediated signaling.
  • hOX40 cells were incubated with 50 ng/mL hOX40L and titrated anti-hOX40L antibodies for 3-5 hours, and Bio-Glo reagent was added to quantify luminescence (RLU). Nonlinear regression was performed on the luminescence values to determine the IC50 value (FIGURE 3, TABLE 14), which were calculated to be less than 5 nM for all the tested clones.
  • Exemplary anti-hOX40L antibodies blocked human OX40L-induced activation of OX40 reporter cells. TABLE 14.
  • Example 7 Functional activity of anti-hOX40L antibodies in human CD4+ T cell IL-2 release assay
  • Anti-hOX40L antibodies were assessed for their ability to block the interaction between exogenous OX40L and OX40L expressed on activated CD4+ T cells, thereby inhibiting the release of cytokine interleukin-2 (IL-2).
  • CD4+ T cells were isolated from PBMCs from 3 different donors using an isolation kit, such as EasySepTM Human CD4+ T Cell Isolation Kit.
  • CD4+ T cells were cultured with 2 ⁇ g/mL PHA-L and 20 IU/mL recombinant human IL-2 in complete RPMI culture medium for 3 days.
  • Microplates were coated with OKT3 (5 ⁇ g/mL) at 4 °C overnight and pre-activated CD4+ T cells were seeded at 3 ⁇ 10 4 cells per well.
  • Serially-diluted antibodies with human OX40L at a final concentration of 20 ng/mL were added and the cells were cultured at 37 °C for 3 days.
  • Microplates were centrifuged and supernatant was collected to measure the amount of IL-2 by ELISA. Nonlinear regression was performed to determine the IC50 values (FIGURES 4A-4B, TABLE 15).
  • Exemplary anti-hOX40L antibodies blocked OX40L-induced IL-2 release from primary CD4+ cells from three healthy donors. TABLE 15. Exemplary anti-hOX40L antibodies blocked OX40L-induced IL-2 release Donor 1 IC 50 Donor 2 IC 50 Donor 3 IC 50 Clone (nM) (nM) (nM) 105 1.37 1.33 1.00 114 1.25 1.19 1.18 Pos. Ctrl. 0.96 – 1.02 0.94 – 0.89 0.70 – 0.49 See construct sequences in TABLE 3 Example 8.
  • Binding affinity (KD) of antibodies to human Fc ⁇ receptors (CD64, CD32a 167H, CD32a 167R, CD32b, CD16a 176F, CD16a 176V, and CD16b) (TABLE 18) and mean response unit (RU) to C1q at 25 nM (TABLE 19) was determined by surface plasmon resonance, as described in Example 3, using Biacore 8K+. Briefly, a CM5 Series S sensor chip functionalized with anti-human IgG Fc antibody was used to capture antibodies at 5 ⁇ g/mL.
  • concentrations of human CD64 ranging from 12.5 nM to 0.3906 nM, CD32a 167H and 167R from 8 ⁇ M to 250 nM, CD32b from 18 ⁇ M to 562.5 nM, CD16a 176F and 176V from 6 ⁇ M to 187.5 nM, CD16b from 10 ⁇ M to 312.5 nM, and C1q from 25 nM to 0.7813 nM were injected at 30 ⁇ L/min.
  • the chip was regenerated with 10 mM glycine pH 1.5 and 10 mM NaOH between runs.
  • Rituximab an anti-CD20 antibody, was included for comparison.
  • TABLE 18 shows that while Rituximab displayed measurable binding to the various human Fc ⁇ receptors, the tested anti-OX40L antibodies containing LALA/YTE substitutions displayed no significant binding to any of the human Fc ⁇ receptors (TABLE 18). Further, while Rituximab displayed C1q binding, none of the tested anti-OX40L antibodies containing LALA/YTE substitutions displayed C1q binding. (TABLE 19). TABLE 18.
  • Anti-hOX40L antibodies were assessed for their ability to block the interaction between exogenous OX40L and OX40L expressed on activated CD4+ T cells from human donors, thereby inhibiting the release of interferon gamma (IFN ⁇ ) in mixed allogeneic lymphocyte reaction (ALR).
  • PBMCs were preincubated with mitomycin C at 10 ⁇ g/mL for 37 °C for 1 h.
  • Allogeneic CD4+ T cells were isolated from PBMCs using an isolation kit, such as EasySepTM Human CD4+ T Cell Isolation Kit.
  • Antibodies 100 nM, 20 nM, or 4 nM
  • recombinant OX40L final concentration 1000 ng/mL
  • mitomycin C-treated PBMCs (1 ⁇ 10 5 cells/well
  • CD4+ T cells (1 ⁇ 10 5 cells/well) were added to microplates sequentially and co-cultured for 5 days at 37 °C.
  • Supernatant was collected and IFN ⁇ was measured by an ELISA detection kit.
  • Data was collected on 6 different donor pairs in triplicate (FIGURES 5A-C, TABLE 21). As shown in FIGURES 5A-5C and TABLE 20, tested anti-OX40L antibodies inhibited IFN ⁇ to a similar extent as the positive control at higher antibody concentrations, such as 100 nM.
  • Anti-hOX40L antibodies inhibited IFN ⁇ release from allogeneic mixed lymphocytes in a concentration dependent manner in all five evaluable donor pairs.
  • AOJ-010PC AOE-007WO TABLE 20. Suppression of IFN ⁇ Release (pg/mL) by anti-hOX40L Antibodies Across Multiple Donor Pairs (Mean +/- SEM) Donor pairing 3 4 1 5 6 8 4 24.1 10.3 17.3 10.0 159.0 72.7 40.6 28.9 TA conc. Test antibody concentration; nM
  • Example 11 Pharmacokinetic profiles of anti-hOX40L antibodies in cynomolgus monkeys [00739] Anti-hOX40L antibodies were evaluated for their pharmacokinetic profiles following single intravenous (IV) or subcutaneous (SC) administration to na ⁇ ve male cynomolgus monkeys as shown in TABLE 21. An n of 4 was used for each group. TABLE 21.
  • PK analyses were performed on serum concentration versus time data using linear trapezoidal rule for AUC calculations (TABLE 22, FIGURE 6A, FIGURE 6B). Nominal dose values and sampling times were used for calculations. Bioavailability was calculated by dividing the mean dose-normalized AUC 0-inf following subcutaneous administration by the mean dose- normalized AUC0-inf following intravenous administration. The normalization of doses was done using doses based on measured formulation concentration and body weights of the subjects. For PK calculations and serum concentration descriptive statistics, any concentration reported as below the limit of quantification (BLQ) was set equal to zero. As shown in FIGURE 6A and FIGURE 6B, the tested antibodies exhibited a longer half-life than did the positive control.
  • BLQ limit of quantification
  • Example 12 Affinity maturation of anti-IL-4R ⁇ antibody
  • Dupilumab (based on the published sequence) was used as a parental antibody for further CDR diversification to identify clones with improvements in potency, manufacturability, and pharmacokinetics.
  • various mutations in all CDRs of both heavy and light chain were made. Site-directed PCR mutagenesis was employed to generate distinct libraries for each CDR in both heavy and light chain, resulting in 6 unique libraries with an average of 2-3 amino acid substitutions per chain.
  • mutants were displayed as Fabs in a phage display system and within each library, mutants were panned through two rounds of selection.
  • the first round of selection consisted of 1 nM biotinylated hIL-4R ⁇ and the output of that round was subsequently split into four distinct secondary rounds of parallel selection consisting of A) 1 nM biotinylated hIL-4R ⁇ while also being washed for 4 hours at room temperature in buffer containing 100 nM of unlabeled hIL- 4R ⁇ , B) 0.1 nM biotinylated hIL-4R ⁇ while also being washed for 4 hours at room temperature in buffer containing 10 nM of unlabeled hIL-4R ⁇ , C) 50 nM biotinylated cyIL-4R ⁇ with no wash, and D) 5 nM biotinylated cyIL-4R ⁇ with no wash.
  • Mutant clones from the output of each arm of secondary selection were analyzed for koff as a proxy for binding affinity by using periplasmic extracts of each mutant clone using surface plasmon resonance (SPR) and comparing to dupilumab, as well as bioinformatic analyses of sequences to identify patterns of enrichment. Mutants that exhibited no loss or improved binding relative to dupilumab as well as population enrichment throughout the selection were combined into a single library comprising all mutants in both the heavy and light chain. Fabs containing a random combinatorial mix of these individual CDR mutants were again screened in a phage display system, with multiple combinations of selection strategies outlined in TABLE 23. TABLE 23.
  • Selection strategies for anti-IL-4R ⁇ antibody clones Strategy Round 1 Selection Round 2 Selection Strategy 1 Antigen: 50 nM biotinylated cyIL-4R ⁇ Antigen: 50 nM biotinylated cyIL-4R ⁇ Wash: No wash Wash: 2 hr R.T. w/ 500 nM unlabeled cyIL-4R ⁇ Strategy Antigen: 50 nM biotinylated cyIL-4R ⁇ Antigen: 5 nM biotinylated cyIL-4R ⁇ 2* Wash: No wash Wash: 2 hr R.T.
  • Example 7 Determination of antibody affinity to IL-4R ⁇ [00744] Binding affinity (KD) of anti-IL-4R ⁇ antibodies to human and cynomolgus monkey IL-4R ⁇ was determined through surface plasmon resonance (SPR) using a Carterra LSA. The anti-IL-4R ⁇ mAb referred to as dupilumab was based on the published sequence. Briefly, an HC30M sensor chip that was previously functionalized with a polyclonal mixture of goat anti- human Fc antibody was used to capture purified antibodies at a level between 100-1000 RLU. Subsequently, concentrations of antigen ranging from 200 nM to 0.13 nM were injected over the surface at a rate of 2 mL/min.
  • SPR surface plasmon resonance
  • an SPR chip functionalized with Protein G is used to capture purified antibodies normalized to 0.5 mg/mL, at a flow rate of 10 ⁇ L/min for 60 seconds.
  • a paired channel with only buffer is used as reference.
  • concentrations of human or cyno FcRn ranging from 25 nM to 0.39 nM are injected over the surface with captured purified antibody as well as the reference channel.
  • Affinity measurement as described is done at both pH 7.4 and pH 6.0. Association and dissociation rate constants are subsequently determined through fitting to a 1:1 Langmuir binding model using the BIACORE® Insight Evaluation Software from which a KD value is derived.
  • Example 14 Inhibition of IL-13 and IL-4 binding to hIL-13R ⁇ /hIL-4R ⁇ with an anti- IL- 4R ⁇ antibody [00747] IL-13 and IL-4 binding to cells overexpressing hIL-13Ra/hIL-4R ⁇ were used to evaluate the functional blockade of anti-IL-4R ⁇ antibodies against this binding interaction.
  • HEK293 previously transduced to stably express both hIL-13R ⁇ and hIL-4R ⁇ were cultured and harvested. Cells were seeded at 200,000 cells in 100 ⁇ L per well. Cells were washed and the supernatant discarded. A 100 ⁇ L mixture of biotinylated hIL-13 OR biotinylated hIL-4 and purified antibody (1:1 by volume) that had been previously made and incubated for 1 hour was added to resuspend the cells, resulting in a final concentration of 0.05 ⁇ g/mL of hIL-13 OR 0.04 ⁇ g/mL of hIL-4 and 0-100 nM of purified antibody.
  • the cells were stained in this mixture at 4 °C for 1 hour. Cells were then washed and stained with 100 ⁇ L of Alexa Fluor 488- conjugated streptavidin at a 1:1000 dilution to detect binding of biotinylated hIL-13 OR biotinylated hIL-4 on the cell surface. Cells were incubated 4 °C for 1 hour, protected from light. Cells were then washed and the MFI of cells in each well were recorded by FACS using a BD FACSCanto II. Subsequent data were analyzed using GraphPad Prism.
  • IC50 values were determined as the concentration of antibody required to inhibit 50% of the maximum MFI of biotinylated hIL-13 OR biotinylated hIL-4 surface detected with incubation of 0.05 ⁇ g/mL of hIL-13 OR 0.04 ⁇ g/mL hIL-4 alone.
  • the anti-IL-4R ⁇ mAb referred to as dupilumab was based on the published sequence. Results are summarized in TABLE 25, TABLE 26, FIGURE 7A and FIGURE 7B. TABLE 25.
  • Example 15 Inhibition of STAT6 phosphorylation in HT-29 cells with an anti-IL-4R ⁇ antibody
  • Inhibition of STAT6 phosphorylation in HT-29 cells was used to evaluate the functional activity of anti-IL-4R ⁇ antibodies to block IL-13-induced and IL-4-induced biological activity. Briefly, HT-29 cells were starved in RMPI 1640 + 0.1% FBS overnight. Cells were collected and seeded at 50,000 cells per well in 100 ⁇ L.
  • a 100 ⁇ L mixture of hIL- 13 OR hIL-4 and purified antibody (1:1 by volume) was added to the same well, resulting in a final concentration of 10 ng/mL of hIL-13 OR 5 ng/mL of hIL-4 and 0-50 nM of purified antibody.
  • Cells were incubated at 37 °C for 1 hour and subsequently fixed, permeabilized, and stained with a PE-conjugated anti-pSTAT6 antibody.
  • the MFI of cells in each well were recorded by FACS using a BD FACSCanto II and subsequent data were analyzed using GraphPad Prism.
  • IC50 values were determined as the concentration of antibody required to inhibit 50% of the maximum MFI of pSTAT6 detected with incubation of 10 ng/mL of hIL-13 OR 5 ng/mL of hIL-4 alone.
  • the anti-IL-4R ⁇ mAb referred to as dupilumab was based on the published sequence. Results are summarized in TABLE 27, TABLE 28, FIGURE 8A, and FIGURE 8B. [00750] As shown in TABLE 27, clones were identified that demonstrated more effective inhibition of IL-13 and/or IL-4 induced phosphorylation of STAT6 as compared to dupilumab by up to about 2-fold (such as, for example, Construct 24). TABLE 27.
  • Example 16 Inhibition of IL-13-induced or IL-4-induced Release of TARC from A549 cells with an anti-IL-4R ⁇ antibody
  • Inhibition of TARC secretion by A549 cells was used to evaluate the functional activity of anti-IL-4R ⁇ antibodies to block IL-13-induced or IL-4-induced biological activity. Briefly, A549 cells were seeded at 20,000 cells in 100 ⁇ L of DMEM + 10% FBS and cultured overnight at 37 °C. The next day, the cell culture media was discarded and cells were gently washed with fresh media.
  • Cells were incubated in this mixture at 37 °C for 20-24 hours. Following incubation, culture supernatant was collected and the amount of TARC present was analyzed using a commercial TARC ELISA kit (R&D Systems), analyzed according to manufacturer’s instructions.
  • TARC concentration of TARC in each well were analyzed using GraphPad Prism. IC50 values were determined as the concentration of antibody required to inhibit 50% of the maximum TARC concentration detected with incubation of only 20 ng/mL of hIL-13 and 200 ng/mL hTNFa OR 1.5 ng/mL hIL-4 and 50 ng/mL hTNFa.
  • the anti-IL-4R ⁇ mAb referred to as dupilumab was based on the published sequence. Results are summarized in TABLE 29, TABLE 30, FIGURE 9A, and FIGURE 9B.
  • Example 17 Inhibition of IL-13-induced or IL-4-induced proliferation of TF-1 cells with an anti-IL-4R ⁇ antibody
  • the proliferation or inhibition thereof of TF-1 cells was used to evaluate the functional activity of antibodies to block IL-13-induced or IL-4-induced biological activity. Briefly, TF-1 cells were harvested and starved in RPMI1640 +10% FBS without additional cytokine for 4 hours. During this time, a mixture of hIL-13 OR hIL-4 and purified anti-IL-4R ⁇ antibody (1:1 by volume) was prepared 50 ⁇ L was added per well.
  • TF-1 cells were again harvested and seeded at 15,000 cells in 50 ⁇ L per well, resulting in a final concentration of 4 ng/mL of hIL-13 OR 0.5 ng/mL of hIL-4 and 0-5 nM purified antibody. Cells were subsequently incubated at 37 °C for 72 hours and proliferation of cells was quantified using CellTiter-Glo (Promega) according to manufacturer’s instructions. Luminescence was recorded by SpectraMax M5 Multimode Plate Reader and data was analyzed using GraphPad Prism.
  • IC50 values were determined as the concentration of antibody required to result in 50% of the maximum luminescence detected when TF-1 cells are incubated and cultured with 4 ng/mL of hIL-13 OR 0.5 ng/mL of hIL-4 alone.
  • the anti-IL-4R ⁇ mAb referred to as dupilumab was based on the published sequence. Results are summarized in TABLE 31, TABLE 32, FIGURE 10A, and FIGURE 10B. TABLE 31.
  • a Baculovirus Particle assay was used to assess non-specific binding by ELISA. Briefly, 96-well plates were coated with a 0.15% baculovirus particle (BVP) suspension and incubated at 4 °C, overnight.
  • Binding affinity (KD) of exemplary antibodies to human IL-4R ⁇ was determined using the Kinetic Exclusion Assay (KinExA).
  • KinExA Kinetic Exclusion Assay
  • the anti-IL-4R ⁇ mAb referred to as dupilumab was based on the published sequence. Briefly, antibody and recombinant human IL-4R ⁇ were equilibrated in solution.
  • equilibration samples were done with a fixed concentration of the antibody ranging from 2.27 pm to 100 pM and a titration of recombinant human IL-4R ⁇ generated from a starting concentration ranging from 9.78 pM to 1.00 nM with 2- fold dilutions for a total set of dilutions ranging from 11 to 13 concentrations. Samples were incubated for a time period ranging from 3.5 hours to 340 hours, to fully reach equilibrium. Once samples reached equilibrium, azlactone beads previously coated with recombinant human IL-4R ⁇ were used to capture any free antibody from the equilibrated solution.
  • PCT/US2024/016235 (corresponding to PCT Publication No. WO2024173847), which is incorporated herein by reference in its entirety
  • the majority of exemplary antibodies bind to human IL-4R ⁇ with femtomolar affinity compared to dupilumab that binds with low picomolar affinity.
  • Example 20 Pharmacokinetic analysis of anti-IL-4R ⁇ antibodies
  • In vivo pharmacokinetic (PK) studies were performed to evaluate the half-life extension of IgG1 LALA-YTE anti-IL-4R ⁇ antibodies compared to dupilumab, based on the published sequence.
  • PK parameters were determined from cynomolgus serum samples up to day 91.
  • the PK analysis demonstrated that Construct 13 and Construct 38 had a half-life of 17.62 and 25.60 days, respectively, compared with 10.88 days for dupilumab (25 mg/kg, IV).
  • the results are summarized in TABLE 35.
  • the PK analysis demonstrated that the exemplary antibodies, Construct 13 (mAb422) and Construct 38 (mAb471), had improved half-life compared to those of dupilumab (TABLE 35, FIGURE 11A, and FIGURE 11B) across different routes of administration.
  • Example 21 Binning experiments with anti-IL-4R ⁇ antibodies compared to dupilumab Epitope binning is a technique used to cluster different mAbs based on the specific region of the antigen (in this case IL-4R ⁇ ) that is recognized by the antibody.
  • any suitable anti-OX40L and anti-IL-4R ⁇ antibody or antigen binding fragment or domain thereof, such as those described herein, can be used.
  • Plasmid cDNA are co-transfected into a mammalian CHO expression platform, and the bispecific antibody is purified. The purity of the final product can be determined by, for example, SEC HPLC. Binding activity for OX40L and IL-4R ⁇ can be assessed with, for example, Octet Biolayer Interferometry (BLI) to confirm that the constructed bispecific IgG binds both OX40L and IL-4R ⁇ antigens.
  • BBI Octet Biolayer Interferometry
  • Construct 114 that binds OX40L and has a VH domain comprising the amino acid sequence set forth in SEQ ID NO: 1, a VL domain comprising the amino acid sequence set forth in SEQ ID NO: 11, a constant heavy chain sequence set forth in any one of SEQ ID NOs: 651 and 973, and a constant light chain sequence set forth in SEQ ID NO: 738 is administered in one pharmaceutical composition simultaneously with a pharmaceutical composition comprising Construct 38 that binds IL-4R ⁇ and has a VH domain comprising the amino acid sequence set forth in SEQ ID NO: 297, a VL domain comprising the amino acid sequence set forth in SEQ ID NO: 300, a constant heavy chain sequence set forth in any one of SEQ ID NOs: 651 and 973, and a constant light chain sequence set forth in SEQ ID NO: 738.
  • a practitioner of skill in the art can monitor the subject’s response to co-administration of the OX40L antibody and the IL-4R ⁇ antibody to determine whether co-administration results in a change in efficacy (e.g., increased efficacy) and/or allows for a change in dosing (e.g., less frequent dosing) as compared to treatment with just one of the antibodies alone.
  • Example 24 Combination of an anti-OX40L antibody and an anti-IL-4R ⁇ antibody – co- administration in a single composition [00767] Two antibodies, one that binds OX40L and one that binds IL-4R ⁇ , are selected and formulated into a single composition that is then administered to a subject.
  • Construct 114 that binds OX40L and has VH domain comprising the amino acid sequence set forth in SEQ ID NO: 1, a VL domain comprising the amino acid sequence set forth in SEQ ID NO: 11, a constant heavy chain sequence set forth in any one of SEQ ID NOs: 651 and 973, and a constant light chain sequence set forth in SEQ ID NO: 738 is co-formulated with Construct 38 that binds IL-4R ⁇ and has a VH domain comprising the amino acid sequence set forth in SEQ ID NO: 297, a VL domain comprising the amino acid sequence set forth in SEQ ID NO: 300, a constant heavy chain sequence set forth in any one of SEQ ID NOs: 651 and 973, and a constant light chain sequence set forth in SEQ ID NO: 738.
  • Example 25 Clinical Study [00768] A clinical study is conducted to assess the safety, tolerability, pharmacokinetics, pharmacodynamics, and immunogenicity of an isolated antibody, or antigen binding fragment thereof, that binds OX40L and an isolated antibody, or antigen binding fragment thereof, that binds IL-4R ⁇ administered in combination with hyaluronidase or a variant thereof.
  • the antibody, or antigen binding fragment thereof, that binds OX40L comprises a CDR-H1 comprising the sequence set forth in SEQ ID NO: 2; a CDR-H2 comprising the sequence set forth in SEQ ID NO: 5; a CDR-H3 comprising the sequence set forth in SEQ ID NO: 8; a CDR-L1 comprising the sequence set forth in SEQ ID NO: 12; a CDR- L2 comprising the sequence set forth in SEQ ID NO: 15; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 17.
  • the antibody, or antigen binding fragment thereof, that binds OX40L comprises a VH sequence set forth in SEQ ID NO: 1 and a VL sequence set forth in SEQ ID NO: 11.
  • the heavy chain of the antibody that binds OX40L comprises a constant heavy chain sequence set forth in SEQ ID NO: 651.
  • the heavy chain of the antibody that binds OX40L comprises a constant heavy chain sequence set forth in SEQ ID NO: 973.
  • the light chain of the antibody that binds OX40L comprises a constant light chain sequence set forth in SEQ ID NO: 738.
  • a C-terminal lysine is present in SEQ ID NO: 973, which may be cleaved off during manufacture or after administration, resulting in the sequence of SEQ ID NO: 651.
  • a composition comprising an antibody comprising the constant heavy chain of SEQ ID NO: 973 that is administered to a subject may comprise antibodies having the constant heavy chain sequence set forth in SEQ ID NO: 973 or SEQ ID NO: 651, or a mixture thereof (e.g., a composition comprising anti-OX40L antibodies may contain a mixture of antibodies having either a constant heavy chain sequence of SEQ ID NO: 973 or a constant heavy chain sequence of SEQ ID NO: 651 and/or antibodies containing both constant heavy chain sequences (e.g., in a single antibody containing two constant heavy chain sequences)).
  • the heavy chain of the antibody that binds OX40L comprises the heavy chain sequence set forth in SEQ ID NO: 839 and the light chain sequence set forth in SEQ ID NO: 841.
  • the C-terminal lysine in SEQ ID NO: 839 may not be present if cleavage occurs during manufacture or after administration (which would result in the heavy chain sequence of SEQ ID NO: 840).
  • the antibody, or antigen binding fragment thereof, that binds IL- 4R ⁇ comprises a CDR-H1 comprising the sequence set forth in SEQ ID NO: 273; a CDR-H2 comprising the sequence set forth in SEQ ID NO: 279; a CDR-H3 comprising the sequence set forth in SEQ ID NO: 281; a CDR-L1 comprising the sequence set forth in SEQ ID NO: 289; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 290; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 293.
  • the antibody, or antigen binding fragment thereof, that binds IL-4R ⁇ comprises a VH sequence set forth in SEQ ID NO: 297 and a VL sequence set forth in SEQ ID NO: 300.
  • the heavy chain of the antibody that binds IL-4R ⁇ comprises a constant heavy chain sequence set forth in SEQ ID NO: 651.
  • the heavy chain of the antibody that binds IL-4R ⁇ comprises a constant heavy chain sequence set forth in SEQ ID NO: 973.
  • the light chain of the antibody that binds IL-4R ⁇ comprises a constant light chain sequence set forth in SEQ ID NO: 738.
  • a C-terminal lysine is present in SEQ ID NO: 973, which may be cleaved off during manufacture or after administration, resulting in the sequence of SEQ ID NO: 651.
  • a composition comprising an antibody comprising the constant heavy chain of SEQ ID NO: 973 that is administered to a subject may comprise antibodies having the constant heavy chain sequence set forth in SEQ ID NO: 973 or SEQ ID NO: 651, or a mixture thereof (e.g., a composition comprising anti-IL-4R ⁇ antibodies may contain a mixture of antibodies having either a constant heavy chain sequence of SEQ ID NO: 973 or a constant heavy chain sequence of SEQ ID NO: 651 and/or antibodies containing both constant heavy chain sequences (e.g., in a single antibody containing two constant heavy chain sequences)).
  • the heavy chain of the antibody that binds IL-4R ⁇ comprises the heavy chain sequence set forth in SEQ ID NO: 836 and the light chain sequence set forth in SEQ ID NO: 838.
  • the C-terminal lysine in SEQ ID NO: 836 may not be present if cleavage occurs during manufacture or after administration (which would result in the heavy chain sequence of SEQ ID NO: 837).
  • a multi-specific antibody comprising a first antigen binding region that binds OX40L and a second antigen binding region that binds IL-4R ⁇ is administered in combination with hyaluronidase or a variant thereof.
  • the antigen binding region that binds OX40L comprises a CDR- H1 comprising the sequence set forth in SEQ ID NO: 2; a CDR-H2 comprising the sequence set forth in SEQ ID NO: 5; a CDR-H3 comprising the sequence set forth in SEQ ID NO: 8; a CDR- L1 comprising the sequence set forth in SEQ ID NO: 12; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 15; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 17.
  • the antigen binding region that binds OX40L comprises a VH sequence set forth in SEQ ID NO: 1 and a VL sequence set forth in SEQ ID NO: 11.
  • the antigen binding region that binds IL-4R ⁇ comprises a CDR- H1 comprising the sequence set forth in SEQ ID NO: 273; a CDR-H2 comprising the sequence set forth in SEQ ID NO: 279; a CDR-H3 comprising the sequence set forth in SEQ ID NO: 281; a CDR-L1 comprising the sequence set forth in SEQ ID NO: 289; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 290; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 293.
  • the antigen binding region that binds IL-4R ⁇ comprises a VH sequence set forth in SEQ ID NO: 297 and a VL sequence set forth in SEQ ID NO: 300.
  • the hyaluronidase is a recombinant human hyaluronidase, such as rHuPH20.
  • the rHuPH20 formulation is ENHANZE®.
  • the recombinant human hyaluronidase comprises the amino acid sequence set forth in any one of SEQ ID NOs: 1076-1085 and 1087-1142.
  • the hyaluronidase or variant thereof and the antibodies or multi-specific antibody are administered in separate formulations.
  • the hyaluronidase or variant thereof and the antibodies or multi-specific antibody are administered simultaneously in separate formulations (e.g., one formulation containing the hyaluronidase or a variant thereof and a second formulation containing the antibodies or multi-specific antibody; or one formulation containing the hyaluronidase or a variant thereof, another formulation containing the OX40 antibody, or an antigen binding fragment thereof, and another formulation containing the IL-4R ⁇ antibody, or an antigen binding fragment thereof).
  • the hyaluronidase or variant thereof is administered to the patient prior to administration of the antibodies or multi-specific antibody. In certain embodiments, the hyaluronidase or variant thereof is administered to the patient after administration of one of the antibodies (either the OX40L antibody, or an antigen binding fragment thereof, or the IL-4R ⁇ antibody, or an antigen binding fragment thereof) but is administered before the administration of the second of the antibodies (either the OX40L antibody, or an antigen binding fragment thereof, or the IL-4R ⁇ antibody, or an antigen binding fragment thereof). In certain embodiments, the hyaluronidase or variant thereof is administered to the patient after administration of the antibodies or multi-specific antibody.
  • the hyaluronidase or variant thereof and the antibodies or multi-specific antibody are mixed and administered in a single formulation. In certain embodiments, the hyaluronidase or variant thereof and the antibodies or multi-specific antibody are administered by subcutaneous injection. In certain embodiments, the hyaluronidase or variant thereof and the antibodies or multi-specific antibody are administered by intravenous injection.
  • the hyaluronidase is rHuPH20 (ENHANZE®) administered at a concentration of 5,000, 6,000, 7,000, 8,000, 9,000, 10,000, 11,000, 12,000, 13,000, 14,000, 15,000, 16,000, 17,000, 18,000, 19,000, 20,000, 21,000, 22,000, 23,000, 24,000, 25,000, 26,000, 27,000, 28,000, 29,000, 30,000, 31,000, 32,000, 33,000, 34,000, 35,000, 36,000, 37,000, 38,000, 39,000, or 40,000 units.
  • Example 26 Impact of the effect of the combination of an anti-IL-4R ⁇ antibody and an anti-OX40L antibody on markers of inflammation as compared to single agents in an immune co-culture assay [00777]
  • ALR allogeneic lymphocyte reaction
  • mDCs Myeloid dendritic cells
  • PBMCs peripheral blood mononuclear cells
  • mDCs monoclonal antibodies
  • mDCs were primed for 24 hours with recombinant human TSLP (5 ng/mL). Allogeneic CD4-positive cells were isolated from PBMCs using a negative selection magnetic bead-based enrichment kit. Primed mDCs were then washed, pretreated once more with mAbs at 300 nM for 30 min at 37 °C, and mixed with the allogeneic CD4-positive lymphocytes in a 1:3 mDC:CD4-positive cell ratio. After a 5-day incubation, the supernatant was collected and cytokines and chemokines were measured using a multi-analyte detection kit (MesoScale Discovery).
  • the Construct 114 + Construct 38 combination broadly inhibited Type 1 and 2 cytokine/chemokine responses, and inhibited Type 1 and Type 2 cytokine/chemokine responses to a greater extent than single agents and benchmarks, dupilumab and amlitelimab, for several cytokines (e.g., TNFa, MDC, IL-13, IL-5). Exemplary embodiments of the invention are described in the enumerated paragraphs below. E1.
  • a composition comprising an isolated antibody, or an antigen binding fragment thereof, that binds OX40L, comprising: a) a variable heavy (VH) chain sequence having three heavy chain CDR sequences, CDR-H1, CDR-H2, and CDR-H3; and b) a variable light (VL) chain sequence having three light chain CDR sequences, CDR-L1, CDR-L2, and CDR-L3; wherein the antibody, or antigen binding fragment thereof, that binds OX40L comprises: (i) a CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 2-4; a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 5-7; a CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 8-10; a CDR-L1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 12-14; a CDR-L2 comprising the
  • composition of E1, wherein the isolated antibody, or antigen binding fragment thereof, that binds IL-4R ⁇ comprises a CDR-H1, CDR-H2, CDR-H3, CDR-L1, CDR-L2, and CDR-L3 of an antibody selected from dupilumab, stapokibart, and 611.
  • composition of E1, wherein the isolated antibody, or antigen binding fragment thereof, that binds IL-4R ⁇ comprises: a) a VH chain sequence having three heavy chain CDR sequences, CDR-H1, CDR-H2, and CDR-H3; and b) a VL chain sequence having three light chain CDR sequences, CDR-L1, CDR-L2, and CDR-L3, wherein the isolated antibody, or antigen binding fragment thereof, that binds IL-4R ⁇ comprises: (i) a CDR-H1 comprising the sequence set forth in any one of SEQ ID NOs: 273, 274, and 275; a CDR-H2 comprising the sequence set forth in any one of SEQ ID NOs: 276, 277, and 278; a CDR-H3 comprising the sequence set forth in any one of SEQ ID NOs: 281 and 282; a CDR-L1 comprising the sequence set forth in any one of SEQ ID NOs: 285 and 286; a CDR-L2 compris
  • a composition comprising an isolated antibody, or an antigen binding fragment thereof, that binds OX40L; and an isolated antibody, or an antigen binding fragment thereof, that binds IL-4R ⁇ , comprising: a) a variable heavy (VH) chain sequence having three heavy chain CDR sequences, CDR-H1, CDR-H2, and CDR-H3; and b) a variable light (VL) chain sequence having three light chain CDR sequences, CDR-L1, CDR-L2, and CDR- L3; wherein the isolated antibody, or antigen binding fragment thereof, that binds IL-4R ⁇ comprises: (i) a CDR-H1 comprising the sequence set forth in any one of SEQ ID NOs: 273, 274, and 275; a CDR-H2 comprising the sequence set forth in any one of SEQ ID NOs: 276, 277, and 278; a CDR-H3 comprising the sequence set forth in any one of SEQ ID NOs: 281 and 282; a CDR
  • composition of E4, wherein the isolated antibody, or antigen binding fragment thereof, that binds OX40L comprises a CDR-H1, CDR-H2, CDR-H3, CDR-L1, CDR- L2, and CDR-L3 of an antibody selected from amlitelimab and oxelumab.
  • E6 The composition of E4, wherein the isolated antibody, or antigen binding fragment thereof, that binds OX40L comprises a CDR-H1, CDR-H2, CDR-H3, CDR-L1, CDR- L2, and CDR-L3 of an antibody selected from amlitelimab and oxelumab.
  • composition of E4, wherein the isolated antibody, or antigen binding fragment thereof, that binds OX40L comprises: a) a VH chain sequence having three heavy chain CDR sequences, CDR-H1, CDR-H2, and CDR-H3; and b) a VL chain sequence having three light chain CDR sequences, CDR-L1, CDR-L2, and CDR-L3, wherein the isolated antibody, or antigen binding fragment thereof, that binds OX40L comprises: (i) a CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 2-4; a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 5-7; a CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 8-10; a CDR-L1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 12-14; a CDR-L2 comprising the amino acid sequence set forth in any one of
  • composition of E3 or E6, wherein: (a) the antibody, or antigen binding fragment thereof, that binds OX40L comprises: (i) a CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 2-4; a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 5-7; a CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 8-10; a CDR-L1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 12-14; a CDR-L2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 15-16; and a CDR-L3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 17-18; and (b) the antibody, or antigen binding fragment thereof, that binds IL-4R ⁇ comprises: (i) a CDR-H1 comprising the sequence set forth in any one of SEQ ID NO
  • composition of E3 or E6, wherein: (a) the antibody, or antigen binding fragment thereof, that binds OX40L comprises: (ii) a CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 20-22; a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 23-25; a CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 26-28; a CDR-L1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 30-32; a CDR-L2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 33-34; and a CDR-L3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 35-36; and (b) the antibody, or antigen binding fragment thereof, that binds IL-4R ⁇ comprises: (i) a CDR-H1 comprising the sequence set forth in any one of
  • composition of E3 or E6, wherein: (a) the antibody, or antigen binding fragment thereof, that binds OX40L comprises: (iii) a CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 38-40; a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 41-43; a CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 44-46; a CDR-L1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 48-50; a CDR-L2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 51-52; and a CDR-L3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 53-54; and (b) the antibody, or antigen binding fragment thereof, that binds IL-4R ⁇ comprises: (i) a CDR-H1 comprising the sequence set forth in any
  • composition of E3 or E6, wherein: (a) the antibody, or antigen binding fragment thereof, that binds OX40L comprises: (iv) a CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 56-58; a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 59-61; a CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 62-64; a CDR-L1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 66-68; a CDR-L2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 69-70; and a CDR-L3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 71-72; and (b) the antibody, or antigen binding fragment thereof, that binds IL-4R ⁇ comprises: (i) a CDR-H1 comprising
  • composition of E3 or E6, wherein: (a) the antibody, or antigen binding fragment thereof, that binds OX40L comprises: (i) a CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 2-4; a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 5-7; a CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 8-10; a CDR-L1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 12-14; a CDR-L2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 15-16; and a CDR-L3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 17-18; and (b) the antibody, or antigen binding fragment thereof, that binds IL-4R ⁇ comprises: (ii) a CDR-H1 comprising the sequence set forth in any one of SEQ ID
  • composition of E3 or E6, wherein: (a) the antibody, or antigen binding fragment thereof, that binds OX40L comprises: (ii) a CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 20-22; a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 23-25; a CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 26-28; a CDR-L1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 30-32; a CDR-L2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 33-34; and a CDR-L3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 35-36; and (b) the antibody, or antigen binding fragment thereof, that binds IL-4R ⁇ comprises: (ii) a CDR-H1 comprising the sequence set forth in any one
  • composition of E3 or E6, wherein: (a) the antibody, or antigen binding fragment thereof, that binds OX40L comprises: (iii) a CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 38-40; a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 41-43; a CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 44-46; a CDR-L1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 48-50; a CDR-L2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 51-52; and a CDR-L3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 53-54; and (b) the antibody, or antigen binding fragment thereof, that binds IL-4R ⁇ comprises: (ii) a CDR-H1 comprising the sequence
  • composition of E3 or E6, wherein: (a) the antibody, or antigen binding fragment thereof, that binds OX40L comprises: (iv) a CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 56-58; a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 59-61; a CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 62-64; a CDR-L1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 66-68; a CDR-L2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 69-70; and a CDR-L3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 71-72; and (b) the antibody, or antigen binding fragment thereof, that binds IL-4R ⁇ comprises: (ii) a CDR-H1 compris
  • composition of E3 or E6, wherein: (a) the antibody, or antigen binding fragment thereof, that binds OX40L comprises: (i) a CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 2-4; a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 5-7; a CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 8-10; a CDR-L1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 12-14; a CDR-L2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 15-16; and a CDR-L3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 17-18; and (b) the antibody, or antigen binding fragment thereof, that binds IL-4R ⁇ comprises: (iii) a CDR-H1 comprising the sequence set forth in any one of SEQ
  • composition of E3 or E6, wherein: (a) the antibody, or antigen binding fragment thereof, that binds OX40L comprises: (ii) a CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 20-22; a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 23-25; a CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 26-28; a CDR-L1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 30-32; a CDR-L2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 33-34; and a CDR-L3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 35-36; and (b) the antibody, or antigen binding fragment thereof, that binds IL-4R ⁇ comprises: (iii) a CDR-H1 comprising the sequence set forth in any
  • composition of E3 or E6, wherein: (a) the antibody, or antigen binding fragment thereof, that binds OX40L comprises: (iii) a CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 38-40; a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 41-43; a CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 44-46; a CDR-L1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 48-50; a CDR-L2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 51-52; and a CDR-L3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 53-54; and (b) the antibody, or antigen binding fragment thereof, that binds IL-4R ⁇ comprises: (iii) a CDR-H1 comprising the
  • composition of E3 or E6, wherein: (a) the antibody, or antigen binding fragment thereof, that binds OX40L comprises: (iv) a CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 56-58; a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 59-61; a CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 62-64; a CDR-L1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 66-68; a CDR-L2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 69-70; and a CDR-L3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 71-72; and (b) the antibody, or antigen binding fragment thereof, that binds IL-4R ⁇ comprises: (iii) a CDR
  • E19 The composition of any one of E1-E4 and E6-E18, wherein the antibody, or antigen binding fragment thereof, that binds OX40L comprises a heavy chain variable domain (VH) sequence comprising the amino acid sequence set forth in any one of SEQ ID NOs: 1, 19, 37, and 55.
  • VH heavy chain variable domain
  • E20 The composition of any one of E1 and E3-E19, wherein the antibody, or antigen binding fragment thereof, that binds IL-4R ⁇ comprises a VH sequence comprising the amino acid sequence set forth in any one of SEQ ID NOs: 295-297.
  • E21 The composition of any one of E1-E4 and E6-E18, wherein the antibody, or antigen binding fragment thereof, that binds OX40L comprises a heavy chain variable domain (VH) sequence comprising the amino acid sequence set forth in any one of SEQ ID NOs: 1, 19, 37, and 55.
  • composition of any one of E1-E4 and E6-E20, wherein the antibody, or antigen binding fragment thereof, that binds OX40L comprises a light chain variable domain (VL) sequence comprising the amino acid sequence set forth in any one of SEQ ID NOs: 11, 29, 47, and 65.
  • VL light chain variable domain
  • the composition of any one of E1 and E3-E21, wherein the antibody, or antigen binding fragment thereof, that binds IL-4R ⁇ comprises a VL sequence comprising the amino acid sequence set forth in any one of SEQ ID NOs: 298-300.
  • composition of any one of E19-E22, wherein: (a) the antibody, or antigen binding fragment thereof, that binds OX40L comprises: (i) a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 1; (ii) a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 19; (iii) a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 37; or (iv) a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 55; and/or (v) a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 11; (vi) a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 29; (vii) a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 47; or (viii) a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 65; and/or (b) the antibody that binds IL-4
  • composition of E23, wherein the antibody, or antigen binding fragment thereof, that binds OX40L comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 1; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 11.
  • the composition of E23, wherein the antibody, or antigen binding fragment thereof, that binds OX40L comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 19; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 29.
  • composition of E23, wherein the antibody, or antigen binding fragment thereof, that binds OX40L comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 37; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 47.
  • the composition of E23, wherein the antibody, or antigen binding fragment thereof, that binds OX40L comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 55; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 65.
  • composition of E23, wherein the antibody, or antigen binding fragment thereof, that binds IL-4R ⁇ comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 295; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 298.
  • the composition of E23, wherein the antibody, or antigen binding fragment thereof, that binds IL-4R ⁇ comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 296; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 299.
  • composition of E23, wherein the antibody, or antigen binding fragment thereof, that binds IL-4R ⁇ comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 297; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 300.
  • composition of E23, wherein the antibody, or antigen binding fragment thereof, that binds OX40L comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 1; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 11; and wherein the antibody, or antigen binding fragment thereof, that binds IL- 4R ⁇ comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 295; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 298.
  • composition of E23, wherein the antibody, or antigen binding fragment thereof, that binds OX40L comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 1; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 11; and wherein the antibody, or antigen binding fragment thereof, that binds IL- 4R ⁇ comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 296; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 299.
  • composition of E23, wherein the antibody, or antigen binding fragment thereof, that binds OX40L comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 1; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 11; and wherein the antibody, or antigen binding fragment thereof, that binds IL- 4R ⁇ comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 297; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 300.
  • composition of E23, wherein the antibody, or antigen binding fragment thereof, that binds OX40L comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 19; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 29; and wherein the antibody, or antigen binding fragment thereof, that binds IL-4R ⁇ comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 295; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 298.
  • composition of E23, wherein the antibody, or antigen binding fragment thereof, that binds OX40L comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 19; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 29; and wherein the antibody, or antigen binding fragment thereof, that binds IL-4R ⁇ comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 296; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 299.
  • composition of E23, wherein the antibody, or antigen binding fragment thereof, that binds OX40L comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 19; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 29; and wherein the antibody, or antigen binding fragment thereof, that binds IL-4R ⁇ comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 297; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 300.
  • composition of E23, wherein the antibody, or antigen binding fragment thereof, that binds OX40L comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 37; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 47; and wherein the antibody, or antigen binding fragment thereof, that binds IL-4R ⁇ comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 295; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 298.
  • composition of E23, wherein the antibody, or antigen binding fragment thereof, that binds OX40L comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 37; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 47; and wherein the antibody, or antigen binding fragment thereof, that binds IL-4R ⁇ comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 296; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 299.
  • composition of E23, wherein the antibody, or antigen binding fragment thereof, that binds OX40L comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 37; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 47; and wherein the antibody, or antigen binding fragment thereof, that binds IL-4R ⁇ comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 297; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 300.
  • composition of E23, wherein the antibody, or antigen binding fragment thereof, that binds OX40L comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 55; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 65; and wherein the antibody, or antigen binding fragment thereof, that binds IL-4R ⁇ comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 295; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 298.
  • composition of E23, wherein the antibody, or antigen binding fragment thereof, that binds OX40L comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 55; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 65; and wherein the antibody, or antigen binding fragment thereof, that binds IL-4R ⁇ comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 296; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 299.

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Abstract

Described herein are antibodies, or antigen binding fragments thereof, that bind OX40L and IL-4Rα in combination and methods of use thereof. In certain aspects, described herein are methods of inhibiting OX40L and IL-4Rα biological activity. In certain aspects, described herein are pharmaceutical compositions comprising the anti-OX40L and anti-IL-4Rα antibodies, or antigen binding fragments thereof. In certain aspects, the antibodies and methods described herein are used for treatment of an inflammatory disease or disorder (e.g., associated with elevated levels of OX40L and/or IL-4). Also described herein are compositions and combinations comprising an antibody or antigen binding region that binds OX40L, an antibody or antigen binding region that binds IL-4Rα, and a hyaluronidase or variant thereof, as well as related methods of treating an inflammatory disorder or disease in a human patient by administering such compositions and combinations.

Description

ANTIBODIES THAT BIND IL-4R ALPHA AND ANTIBODIES THAT BIND
CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] This application claims priority to, and the benefit of, U.S. Provisional Application No. 63/662,968 (filed June 21, 2024) and U.S. Provisional Application No. 63/708,879 (filed October 18, 2024). The entire contents of the aforementioned applications is incorporated herein by reference.
SEQUENCE LISTING
[0002] The instant application contains a Sequence Listing which has been submitted electronically in ASCII format and is hereby incorporated by reference in its entirety. Said ASCII copy, created on June 19, 2025, is named AOJ-010PC_SL.txt and is 717,774 bytes in size.
BACKGROUND
[0003] An emerging mechanism in treatments for atopic dermatitis (AD) is targeting 0X40 or OX40L. OX40L is the ligand for 0X40. OX40L is expressed on antigen presenting cells and its interaction with 0X40 causes the accumulation of T cells by providing a survival signal. OX40L, by playing a role in activating T cells and reprogramming them into inflammatory subsets, contributes to immune overactivation in AD and other inflammatory conditions. Additionally, OX40L activation of 0X40 inhibits the expression of FOXP3 and the inhibitory function of regulatory T (Treg) cells. Treg cells suppress immune response, which leads to worse symptoms in inflammatory conditions. Therefore, OX40L blockade may lead to clinical benefit in AD and other inflammatory conditions by first suppressing inflammatory T cell activation, and next by increasing the proliferation of Treg cells, which can serve to further reduce inflammatory cells. Amlitelimab, which targets OX40L, and rocatinlimab, which targets 0X40, have both demonstrated promising Phase 2 data in AD. [0004] 0X40 L is the ligand for 0X40 expressed on antigen presenting cells. Its interaction with 0X40 causes the accumulation of T cells by providing a survival signal. T cells are important types of white blood cells of the immune system that play a central role in the immune response. OX40L, by playing a role in activating T cells and reprogramming them into inflammatory subsets, contributes to immune overactivation in AD and other inflammatory conditions, such as Systemic Lupus Erythematosus. Additionally, OX40L activation of OX40 inhibits the expression of Foxp3 and the inhibitory function of regulatory T (Treg) cells. Treg cells can suppress the immune response that leads to worsening symptoms in inflammatory conditions. [0005] Meanwhile, interleukin 4 (IL-4) and interleukin 13 (IL-13) share a common receptor component. The Interleukin-4 Receptor Alpha (IL-4Rα) chain, that pairs with distinct subunits (Nelms, K., et al. (1999) Annu. Rev. Immunol.17:701–738) and (Jensen, P.L. (2000) Stem Cells.18:61–62). IL-4Rα pairs with the common γc chain to form a type I IL-4R complex that is found predominantly in hematopoietic cells and is exclusive for IL-4. IL-4Rα also pairs with the Interleukin-13 Receptor alpha 1 (IL-13Rα1) subunit to form a type II IL-4R that binds both IL-4 and IL-13. The type II receptor is expressed on both hematopoietic and nonhematopoietic cells. IL-4, (also known as B cell stimulating factor or BSF-1) was originally characterized by its ability to stimulate the proliferation of B cells in response to low concentrations of antibodies directed to surface immunoglobulin. IL-4 has been shown to possess a broad spectrum of biological activities, including growth stimulation of T cells, mast cells, granulocytes, megakaryocytes and erythrocytes. IL-4 induces the expression of class II major histocompatibility complex molecules in resting B cells and enhances the secretion of IgE and IgG1 isotypes by stimulated B cells. [0006] The biological and immunological functions of B-lymphocytes, monocytes, dendritic cells, and fibroblasts are all affected by IL-4 and IL-13. These cytokines interact with IL-4R to initiate the type 2 inflammatory pathway, which results in Th2 cell differentiation, inflammation, and mucus production. The type-2 inflammatory pathway is first activated in allergic illnesses by aberrant cytokine release resulting from an imbalance of Th1 and Th2 differentiation. Th2 cells that have been activated release cytokines, including IL-4, IL-13, and IL-31, which prompt downstream B cells to undergo a change and produce IgE antibodies. Mast cells and basophils are then called upon to degranulate and release inflammatory substances. Simultaneously, the secreted IL-4 and IL-13 continue to bind to their respective receptors, such as IL-4Rα, that repeatedly promotes TH2 differentiation and subsequent inflammation. [0007] The important role of IL-4 and IL-13 in the type-2 inflammation pathway identifies IL-4Rα as a potential target for individuals who exhibit aberrant type-2 inflammatory responses. Unlike medications that target IL-4 and IL-13 exclusively, targeting IL-4Rα would target both IL-4 and IL-13. [0008] In addition, because targeting each of OX40L and IL-4Rα may lead to various clinical benefits in inflammatory conditions, there is a need in the art for improved therapeutics that target both OX40L and IL-4Rα, such as recombinant antibodies and combinations thereof. There is also a need for delivering relatively large doses of these antibodies subcutaneously. SUMMARY [0009] In a first aspect, disclosed herein is an isolated antibody, or an antigen binding fragment thereof, that binds OX40L, comprising: a) a variable heavy (VH) chain sequence having three heavy chain CDR sequences, CDR-H1, CDR-H2, and CDR-H3; and b) a variable light (VL) chain sequence having three light chain CDR sequences, CDR-L1, CDR- L2, and CDR-L3; wherein the antibody, or antigen binding fragment thereof, that binds OX40L comprises: (i) a CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 2-4; a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 5-7; a CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 8-10; a CDR-L1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 12-14; a CDR-L2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 15-16; and a CDR-L3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 17-18; (ii) a CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 20-22; a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 23-25; a CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 26-28; a CDR-L1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 30-32; a CDR-L2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 33-34; and a CDR-L3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 35-36; (iii) a CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 38-40; a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 41-43; a CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 44-46; a CDR-L1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 48-50; a CDR-L2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 51-52; and a CDR-L3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 53-54; or (iv) a CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 56-58; a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 59-61; a CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 62-64; a CDR-L1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 66-68; a CDR-L2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 69-70; and a CDR-L3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 71-72; and an isolated antibody that binds IL-4Rα. [0010] In some embodiments, the isolated antibody, or antigen binding fragment thereof, that binds IL-4Rα comprises a CDR-H1, CDR-H2, CDR-H3, CDR-L1, CDR-L2, and CDR- L3 of an antibody selected from dupilumab, stapokibart, and 611. [0011] In some embodiments, the isolated antibody, or an antigen binding fragment thereof, that binds IL-4Rα comprises: a) a VH chain sequence having three heavy chain CDR sequences, CDR-H1, CDR-H2, and CDR-H3; and b) a VL chain sequence having three light chain CDR sequences, CDR-L1, CDR-L2, and CDR-L3, wherein the isolated antibody, or antigen binding fragment thereof, that binds IL-4Rα comprises: (i) a CDR-H1 comprising the sequence set forth in any one of SEQ ID NOs: 273, 274, and 275; a CDR-H2 comprising the sequence set forth in any one of SEQ ID NOs: 276, 277, and 278; a CDR-H3 comprising the sequence set forth in any one of SEQ ID NOs: 281 and 282; a CDR-L1 comprising the sequence set forth in any one of SEQ ID NOs: 285 and 286; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 292 or the amino acid sequence LG; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 293; (ii) a CDR-H1 comprising the sequence set forth in any one of SEQ ID NOs: 273, 274, and 275; a CDR-H2 comprising the sequence set forth in any one of SEQ ID NOs: 279, 277, and 280; a CDR-H3 comprising the sequence set forth in any one of SEQ ID NOs: 283 and 284; a CDR-L1 comprising the sequence set forth in any one of SEQ ID NOs: 287 and 288; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 291 or the amino acid sequence LG; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 293; or (iii) a CDR-H1 comprising the sequence set forth in any one of SEQ ID NOs: 273, 274, and 275; a CDR-H2 comprising the sequence set forth in any one of SEQ ID NOs: 279, 277, and 280; a CDR-H3 comprising the sequence set forth in any one of SEQ ID NOs: 281 and 282; a CDR-L1 comprising the sequence set forth in any one of SEQ ID NOs: 289 and 288; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 290 or the amino acid sequence EG; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 293. [0012] In another aspect, disclosed herein is an isolated antibody, or an antigen binding fragment thereof, that binds OX40L; and an isolated antibody, or an antigen binding fragment thereof, that binds IL-4Rα, comprising: a) a variable heavy (VH) chain sequence having three heavy chain CDR sequences, CDR-H1, CDR-H2, and CDR-H3; and b) a variable light (VL) chain sequence having three light chain CDR sequences, CDR-L1, CDR-L2, and CDR-L3; wherein the antibody, or antigen binding fragment thereof, that binds IL-4Rα comprises: (i) a CDR-H1 comprising the sequence set forth in any one of SEQ ID NOs: 273, 274, and 275; a CDR-H2 comprising the sequence set forth in any one of SEQ ID NOs: 276, 277, and 278; a CDR-H3 comprising the sequence set forth in any one of SEQ ID NOs: 281 and 282; a CDR- L1 comprising the sequence set forth in any one of SEQ ID NOs: 285 and 286; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 292 or the amino acid sequence LG; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 293; (ii) a CDR-H1 comprising the sequence set forth in any one of SEQ ID NOs: 273, 274, and 275; a CDR-H2 comprising the sequence set forth in any one of SEQ ID NOs: 279, 277, and 280; a CDR-H3 comprising the sequence set forth in any one of SEQ ID NOs: 283 and 284; a CDR-L1 comprising the sequence set forth in any one of SEQ ID NOs: 287 and 288; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 291 or the amino acid sequence LG; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 293; or (iii) a CDR-H1 comprising the sequence set forth in any one of SEQ ID NOs: 273, 274, and 275; a CDR-H2 comprising the sequence set forth in any one of SEQ ID NOs: 279, 277, and 280; a CDR-H3 comprising the sequence set forth in any one of SEQ ID NOs: 281 and 282; a CDR-L1 comprising the sequence set forth in any one of SEQ ID NOs: 289 and 288; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 290 or the amino acid sequence EG; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 293. [0013] In some embodiments, the isolated antibody, or antigen binding fragment thereof, that binds OX40L comprises a CDR-H1, CDR-H2, CDR-H3, CDR-L1, CDR-L2, and CDR- L3 of an antibody selected from amlitelimab and oxelumab. [0014] In some embodiments, the isolated antibody, or antigen binding fragment thereof, that binds OX40L comprises: a) a VH chain sequence having three heavy chain CDR sequences, CDR-H1, CDR-H2, and CDR-H3; and b) a VL chain sequence having three light chain CDR sequences, CDR-L1, CDR-L2, and CDR-L3, wherein the isolated antibody, or antigen binding fragment thereof, that binds OX40L comprises: (i) a CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 2-4; a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 5-7; a CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 8-10; a CDR-L1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 12-14; a CDR-L2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 15-16; and a CDR-L3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 17-18; (i) a CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 20-22; a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 23-25; a CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 26-28; a CDR-L1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 30-32; a CDR-L2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 33-34; and a CDR- L3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 35-36; (iii) a CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 38-40; a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 41-43; a CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 44-46; a CDR-L1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 48-50; a CDR-L2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 51-52; and a CDR-L3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 53- 54; or (iv) a CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 56-58; a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 59-61; a CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 62-64; a CDR-L1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 66-68; a CDR-L2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 69-70; and a CDR-L3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 71-72. [0015] In some embodiments, (a) the antibody, or antigen binding fragment thereof, that binds OX40L comprises: (i) a CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 2-4; a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 5-7; a CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 8-10; a CDR-L1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 12-14; a CDR-L2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 15-16; and a CDR-L3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 17-18; and (b) the antibody, or antigen binding fragment thereof, that binds IL-4Rα comprises: (i) a CDR-H1 comprising the sequence set forth in any one of SEQ ID NOs: 273, 274, and 275; a CDR-H2 comprising the sequence set forth in any one of SEQ ID NOs: 276, 277, and 278; a CDR-H3 comprising the sequence set forth in any one of SEQ ID NOs: 281 and 282; a CDR-L1 comprising the sequence set forth in any one of SEQ ID NOs: 285 and 286; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 292 or the amino acid sequence LG; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 293. [0016] In some embodiments, (a) the antibody, or antigen binding fragment thereof, that binds OX40L comprises: (ii) a CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 20-22; a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 23-25; a CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 26-28; a CDR-L1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 30-32; a CDR-L2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 33-34; and a CDR-L3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 35-36; and (b) the antibody, or antigen binding fragment thereof, that binds IL-4Rα comprises: (i) a CDR-H1 comprising the sequence set forth in any one of SEQ ID NOs: 273, 274, and 275; a CDR-H2 comprising the sequence set forth in any one of SEQ ID NOs: 276, 277, and 278; a CDR-H3 comprising the sequence set forth in any one of SEQ ID NOs: 281 and 282; a CDR-L1 comprising the sequence set forth in any one of SEQ ID NOs: 285 and 286; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 292 or the amino acid sequence LG; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 293. [0017] In some embodiments, (a) the antibody, or antigen binding fragment thereof, that binds OX40L comprises: (iii) a CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 38-40; a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 41-43; a CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 44-46; a CDR-L1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 48-50; a CDR-L2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 51-52; and a CDR-L3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 53-54; and (b) the antibody, or antigen binding fragment thereof, that binds IL-4Rα comprises: (i) a CDR-H1 comprising the sequence set forth in any one of SEQ ID NOs: 273, 274, and 275; a CDR-H2 comprising the sequence set forth in any one of SEQ ID NOs: 276, 277, and 278; a CDR-H3 comprising the sequence set forth in any one of SEQ ID NOs: 281 and 282; a CDR-L1 comprising the sequence set forth in any one of SEQ ID NOs: 285 and 286; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 292 or the amino acid sequence LG; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 293. [0018] In some embodiments, (a) the antibody, or antigen binding fragment thereof, that binds OX40L comprises: (iv) a CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 56-58; a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 59-61; a CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 62-64; a CDR-L1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 66-68; a CDR-L2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 69-70; and a CDR-L3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 71-72; and (b) the antibody, or antigen binding fragment thereof, that binds IL-4Rα comprises: (i) a CDR-H1 comprising the sequence set forth in any one of SEQ ID NOs: 273, 274, and 275; a CDR-H2 comprising the sequence set forth in any one of SEQ ID NOs: 276, 277, and 278; a CDR-H3 comprising the sequence set forth in any one of SEQ ID NOs: 281 and 282; a CDR-L1 comprising the sequence set forth in any one of SEQ ID NOs: 285 and 286; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 292 or the amino acid sequence LG; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 293. [0019] In some embodiments, (a) the antibody, or antigen binding fragment thereof, that binds OX40L comprises: (i) a CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 2-4; a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 5-7; a CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 8-10; a CDR-L1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 12-14; a CDR-L2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 15-16; and a CDR-L3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 17-18; and (b) the antibody, or antigen binding fragment thereof, that binds IL-4Rα comprises: (ii) a CDR-H1 comprising the sequence set forth in any one of SEQ ID NOs: 273, 274, and 275; a CDR-H2 comprising the sequence set forth in any one of SEQ ID NOs: 279, 277, and 280; a CDR-H3 comprising the sequence set forth in any one of SEQ ID NOs: 283 and 284; a CDR-L1 comprising the sequence set forth in any one of SEQ ID NOs: 287 and 288; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 291 or the amino acid sequence LG; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 293. [0020] In some embodiments, (a) the antibody, or antigen binding fragment thereof, that binds OX40L comprises: (ii) a CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 20-22; a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 23-25; a CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 26-28; a CDR-L1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 30-32; a CDR-L2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 33-34; and a CDR-L3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 35-36; and (b) the antibody, or antigen binding fragment thereof, that binds IL-4Rα comprises: (ii) a CDR-H1 comprising the sequence set forth in any one of SEQ ID NOs: 273, 274, and 275; a CDR-H2 comprising the sequence set forth in any one of SEQ ID NOs: 279, 277, and 280; a CDR-H3 comprising the sequence set forth in any one of SEQ ID NOs: 283 and 284; a CDR-L1 comprising the sequence set forth in any one of SEQ ID NOs: 287 and 288; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 291 or the amino acid sequence LG; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 293. [0021] In some embodiments, (a) the antibody, or antigen binding fragment thereof, that binds OX40L comprises: (iii) a CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 38-40; a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 41-43; a CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 44-46; a CDR-L1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 48-50; a CDR-L2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 51-52; and a CDR-L3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 53-54; and (b) the antibody, or antigen binding fragment thereof, that binds IL-4Rα comprises: (ii) a CDR-H1 comprising the sequence set forth in any one of SEQ ID NOs: 273, 274, and 275; a CDR-H2 comprising the sequence set forth in any one of SEQ ID NOs: 279, 277, and 280; a CDR-H3 comprising the sequence set forth in any one of SEQ ID NOs: 283 and 284; a CDR-L1 comprising the sequence set forth in any one of SEQ ID NOs: 287 and 288; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 291 or the amino acid sequence LG; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 293. [0022] In some embodiments, (a) the antibody, or antigen binding fragment thereof, that binds OX40L comprises: (iv) a CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 56-58; a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 59-61; a CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 62-64; a CDR-L1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 66-68; a CDR-L2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 69-70; and a CDR-L3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 71-72; and (b) the antibody, or antigen binding fragment thereof, that binds IL-4Rα comprises: (ii) a CDR-H1 comprising the sequence set forth in any one of SEQ ID NOs: 273, 274, and 275; a CDR-H2 comprising the sequence set forth in any one of SEQ ID NOs: 279, 277, and 280; a CDR-H3 comprising the sequence set forth in any one of SEQ ID NOs: 283 and 284; a CDR-L1 comprising the sequence set forth in any one of SEQ ID NOs: 287 and 288; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 291 or the amino acid sequence LG; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 293. [0023] In some embodiments, (a) the antibody, or antigen binding fragment thereof, that binds OX40L comprises: (i) a CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 2-4; a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 5-7; a CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 8-10; a CDR-L1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 12-14; a CDR-L2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 15-16; and a CDR-L3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 17-18; and (b) the antibody, or antigen binding fragment thereof, that binds IL-4Rα comprises: (iii) a CDR-H1 comprising the sequence set forth in any one of SEQ ID NOs: 273, 274, and 275; a CDR-H2 comprising the sequence set forth in any one of SEQ ID NOs: 279, 277, and 280; a CDR-H3 comprising the sequence set forth in any one of SEQ ID NOs: 281 and 282; a CDR-L1 comprising the sequence set forth in any one of SEQ ID NOs: 289 and 288; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 290 or the amino acid sequence EG; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 293. [0024] In some embodiments, (a) the antibody, or antigen binding fragment thereof, that binds OX40L comprises: (ii) a CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 20-22; a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 23-25; a CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 26-28; a CDR-L1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 30-32; a CDR-L2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 33-34; and a CDR-L3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 35-36; and (b) the antibody, or antigen binding fragment thereof, that binds IL-4Rα comprises: ((iii) a CDR-H1 comprising the sequence set forth in any one of SEQ ID NOs: 273, 274, and 275; a CDR-H2 comprising the sequence set forth in any one of SEQ ID NOs: 279, 277, and 280; a CDR-H3 comprising the sequence set forth in any one of SEQ ID NOs: 281 and 282; a CDR-L1 comprising the sequence set forth in any one of SEQ ID NOs: 289 and 288; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 290 or the amino acid sequence EG; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 293. [0025] In some embodiments, (a) the antibody, or antigen binding fragment thereof, that binds OX40L comprises: (iii) a CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 38-40; a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 41-43; a CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 44-46; a CDR-L1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 48-50; a CDR-L2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 51-52; and a CDR-L3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 53-54; and (b) the antibody, or antigen binding fragment thereof, that binds IL-4Rα comprises: (iii) a CDR-H1 comprising the sequence set forth in any one of SEQ ID NOs: 273, 274, and 275; a CDR-H2 comprising the sequence set forth in any one of SEQ ID NOs: 279, 277, and 280; a CDR-H3 comprising the sequence set forth in any one of SEQ ID NOs: 281 and 282; a CDR-L1 comprising the sequence set forth in any one of SEQ ID NOs: 289 and 288; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 290 or the amino acid sequence EG; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 293. [0026] In some embodiments, (a) the antibody, or antigen binding fragment thereof, that binds OX40L comprises: (iv) a CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 56-58; a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 59-61; a CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 62-64; a CDR-L1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 66-68; a CDR-L2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 69-70; and a CDR-L3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 71-72; and (b) the antibody, or antigen binding fragment thereof, that binds IL-4Rα comprises: (iii) a CDR-H1 comprising the sequence set forth in any one of SEQ ID NOs: 273, 274, and 275; a CDR-H2 comprising the sequence set forth in any one of SEQ ID NOs: 279, 277, and 280; a CDR-H3 comprising the sequence set forth in any one of SEQ ID NOs: 281 and 282; a CDR-L1 comprising the sequence set forth in any one of SEQ ID NOs: 289 and 288; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 290 or the amino acid sequence EG; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 293. [0027] In some embodiments, the antibody, or antigen binding fragment thereof, that binds OX40L comprises a heavy chain variable domain (VH) sequence comprising the amino acid sequence set forth in any one of SEQ ID NOs: 1, 19, 37, and 55. [0028] In some embodiments, the antibody, or antigen binding fragment thereof, that binds IL-4Rα comprises a VH sequence comprising the amino acid sequence set forth in any one of SEQ ID NOs: 295-297. [0029] In some embodiments, the antibody, or antigen binding fragment thereof, that binds OX40L comprises a light chain variable domain (VL) sequence comprising the amino acid sequence set forth in any one of SEQ ID NOs: 11, 29, 47, and 65. [0030] In some embodiments, the antibody, or antigen binding fragment thereof, that binds IL-4Rα comprises a VL sequence comprising the amino acid sequence set forth in any one of SEQ ID NOs: 298-300. [0031] In some embodiments, (a) the antibody, or antigen binding fragment thereof, that binds OX40L comprises: (i) a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 1; (ii) a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 19; (iii) a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 37; or (iv) a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 55; and/or (v) a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 11; (vi) a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 29; (vii) a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 47; or (viii) a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 65; and/or (b) the antibody, or antigen binding fragment thereof, that binds IL-4Rα comprises: (i) a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 295; (ii) a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 296; or (iii) a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 297; and/or (iv) a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 298; (v) a VL sequence comprising the amino acid sequence set forth in SEQ ID NO:299; or (vi) a VL sequence comprising the amino acid sequence set forth in SEQ ID NO:300. [0032] In some embodiments, the antibody, or antigen binding fragment thereof, that binds OX40L comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 1; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 11. [0033] In some embodiments, the antibody, or antigen binding fragment thereof, that binds OX40L comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 19; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 29. [0034] In some embodiments, the antibody, or antigen binding fragment thereof, that binds OX40L comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 37; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 47. [0035] In some embodiments, the antibody, or antigen binding fragment thereof, that binds OX40L comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 55; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 65. [0036] In some embodiments, the antibody, or antigen binding fragment thereof, that binds IL-4Rα comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 295; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 298. [0037] In some embodiments, the antibody, or antigen binding fragment thereof, that binds IL-4Rα comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 296; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 299. [0038] In some embodiments, the antibody, or antigen binding fragment thereof, that binds IL-4Rα comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 297; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 300. [0039] In some embodiments, the antibody, or antigen binding fragment thereof, that binds OX40L comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 1; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 11; and the antibody, or antigen binding fragment thereof, that binds IL-4Rα comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 295; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 298. [0040] In some embodiments, the antibody, or antigen binding fragment thereof, that binds OX40L comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 1; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 11; and the antibody, or antigen binding fragment thereof, that binds IL-4Rα comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 296; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 299. [0041] In some embodiments, the antibody, or antigen binding fragment thereof, that binds OX40L comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 1; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 11; and the antibody, or antigen binding fragment thereof, that binds IL-4Rα comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 297; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 300. [0042] In some embodiments, the antibody, or antigen binding fragment thereof, that binds OX40L comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 19; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 29; and the antibody, or antigen binding fragment thereof, that binds IL-4Rα comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 295; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 298. [0043] In some embodiments, the antibody, or antigen binding fragment thereof, that binds OX40L comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 19; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 29; and the antibody, or antigen binding fragment thereof, that binds IL-4Rα comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 296; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 299. [0044] In some embodiments, the antibody, or antigen binding fragment thereof, that binds OX40L comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 19; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 29; and the antibody, or antigen binding fragment thereof, that binds IL-4Rα comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 297; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 300. [0045] In some embodiments, the antibody, or antigen binding fragment thereof, that binds OX40L comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 37; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 47; and the antibody, or antigen binding fragment thereof, that binds IL-4Rα comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 295; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 298. [0046] In some embodiments, the antibody, or antigen binding fragment thereof, that binds OX40L comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 37; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 47; and the antibody, or antigen binding fragment thereof, that binds IL-4Rα comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 296; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 299. [0047] In some embodiments, the antibody, or antigen binding fragment thereof, that binds OX40L comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 37; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 47; and the antibody, or antigen binding fragment thereof, that binds IL-4Rα comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 297; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 300. [0048] In some embodiments, the antibody, or antigen binding fragment thereof, that binds OX40L comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 55; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 65; and the antibody, or antigen binding fragment thereof, that binds IL-4Rα comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 295; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 298. [0049] In some embodiments, the antibody, or antigen binding fragment thereof, that binds OX40L comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 55; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 65; and the antibody, or antigen binding fragment thereof, that binds IL-4Rα comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 296; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 299. [0050] In some embodiments, the antibody, or antigen binding fragment thereof, that binds OX40L comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 55; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 65; and the antibody, or antigen binding fragment thereof, that binds IL-4Rα comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 297; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 300. [0051] In some embodiments, the antibody, or antigen binding fragment thereof, that binds OX40L and/or the antibody, or antigen binding fragment thereof, that binds IL-4Rα is a humanized, human, or chimeric antibody. [0052] In some embodiments, the antibody, or antigen binding fragment thereof, that binds OX40L and/or the antibody, or antigen binding fragment thereof, that binds IL-4Rα is a humanized antibody. [0053] In some embodiments, the antibody, or antigen binding fragment thereof, that binds OX40L and/or the antibody, or antigen binding fragment thereof, that binds IL-4Rα comprises a heavy chain human constant region of a class selected from IgG, IgA, IgD, IgE, and IgM. [0054] In some embodiments, the antibody, or antigen binding fragment thereof, that binds OX40L and/or the antibody, or antigen binding fragment thereof, that binds IL-4Rα comprises a human Fc region, and the human Fc region comprises a human heavy chain constant region of the class IgG and a subclass selected from IgG1, IgG2, IgG3, and IgG4. [0055] In some embodiments, the human Fc region of the antibody, or antigen binding fragment thereof, that binds OX40L and/or the antibody, or antigen binding fragment thereof, that binds IL-4Rα comprises a human IgG1 Fc region. [0056] In some embodiments, the human Fc region of the antibody, or antigen binding fragment thereof, that binds OX40L and/or the antibody, or antigen binding fragment thereof, that binds IL-4Rα comprises a human IgG4 Fc region. [0057] In some embodiments, the human Fc region of the antibody, or antigen binding fragment thereof, that binds OX40L and/or the antibody, or antigen binding fragment thereof, that binds IL-4Rα comprises a human IgG2 Fc region. [0058] In some embodiments, the antibody, or antigen binding fragment thereof, that binds OX40L and/or the antibody, or antigen binding fragment thereof, that binds IL-4Rα comprises a heavy chain comprising constant heavy chain sequence selected from the amino acid sequences set forth in any one of SEQ ID NOs: 637-737 and 847-1070. [0059] In some embodiments, the antibody, or antigen binding fragment thereof, that binds OX40L and/or the antibody, or antigen binding fragment thereof, that binds IL-4Rα comprises a light chain comprising constant light chain sequence selected from the sequences set forth in SEQ ID NOs: 738 and 1071. [0060] In some embodiments, the antibody, or antigen binding fragment thereof, that binds OX40L and/or the antibody, or antigen binding fragment thereof, that binds IL-4Rα comprises a heavy chain constant domain having a means for increasing the half-life of the antibody. [0061] In some embodiments, the antibody, or antigen binding fragment thereof, that binds OX40L and/or the antibody, or antigen binding fragment thereof, that binds IL-4Rα comprises an Fc region comprising one or more amino acid substitutions, wherein the one or more substitutions result in an increase in one or more of antibody half-life, ADCC activity, ADCP activity, or CDC activity compared to an antibody comprising an Fc region without the one or more amino acid substitutions (e.g., a wild-type Fc region). [0062] In some embodiments, the antibody, or antigen binding fragment thereof, that binds OX40L and/or the antibody, or antigen binding fragment thereof, that binds IL-4Rα comprises an Fc region comprising one or more amino acid substitutions, wherein the one or more substitutions result in a decrease in one or more of, ADCC activity, ADCP activity or CDC activity compared to an antibody comprising an Fc region without the one or more amino acid substitutions, (e.g., a wild-type Fc region). [0063] In some embodiments, the one or more amino acid substitutions is selected from the group consisting of S228P, M252Y, S254T, T256E, T256D, T250Q, H285D, T307A, T307Q, T307R, T307W, L309D, Q411H, Q311V, A378V, E380A, M428L, N434A, N434S, N297A, D265A, L234A, L235A, and N434W; optionally, wherein the one or more amino acid substitutions comprises a plurality of amino acid substitutions selected from the group consisting of M428L/N434S (LS), M252Y/S254T/T256E (YTE), T250Q/M428L, T307A/E380A/N434A, T256D/T307Q (DQ), T256D/T307W (DW), M252Y/T256D (YD), T307Q/Q311V/A378V (QVV), T256D/H285D/T307R/Q311V/A378V (DDRVV), L309D/Q311H/N434S (DHS), S228P/L235E (SPLE), L234A/L235A (LALA), M428L/N434A (LA), L235A/G237A (LAGA), L234A/L235A/G237A (LALAGA), L234A/L235A/P329G (LALAPG), D265A/YTE, LALA/YTE, LAGA/YTE, LALAGA/YTE, LALAPG/YTE, N297A/LS, D265A/LS, LALA/LS, LALAGA/LS, LALAPG/LS, N297A/DHS, D265A/DHS, LALA/DHS, LAGA/DHS, LALAGA/DHS, LALAPG/DHS, SP/YTE, SPLE/YTE, SP/LS, SPLE/LS, SP/DHS, SPLE/DHS, N297A/LA, D265A/LA, LALA/LA, LAGA/LA, LALAGA/LA, LALAPG/LA, N297A/N434A, D265A/N434A, LALA/N434A, LAGA/N434A, LALAGA/N434A, LALAPG/N434A, N297A/N434W, D265A/N434W, LALA/N434W, LAGA/N434W, LALAGA/N434W, LALAPG/N434W, N297A/DQ, D265A/DQ, LALA/DQ, LAGA/DQ, LALAGA/DQ, LALAPG/DQ, N297A/DW, D265A/DW, LALA/DW, LAGA/DW, LALAGA/DW, LALAPG/DW, N297A/YD, D265A/YD, LALA/YD, LAGA/YD, LALAGA/YD, LALAPG/YD, T307Q/Q311V/A378V (QVV), N297A/QVV, D265A/QVV, LALA/QVV, LAGA/QVV, LALAGA/QVV, LALAPG/QVV, DDRVV, N297A/DDRVV, D265A/DDRVV, LALA/DDRVV, LAGA/DDRVV, LALAGA/DDRVV, and LALAPG/DDRVV. In some embodiments, the one or more amino acid substitutions is selected from the group consisting of LS, YTE, T250Q/M428L, T307A/E380A/N434A, DQ, DW, YD, QVV, DHS, LA, D265A/YTE, LALA/YTE, LAGA/YTE, LALAGA/YTE, LALAPG/YTE, N297A/LS, D265A/LS, LALA/LS, LALAGA/LS, LALAPG/LS, N297A/DHS, D265A/DHS, LALA/DHS, LAGA/DHS, LALAGA/DHS, LALAPG/DHS, SP/YTE, SPLE/YTE, SP/LS, SPLE/LS, SP/DHS, SPLE/DHS, N297A/LA, D265A/LA, LALA/LA, LAGA/LA, LALAGA/LA, LALAPG/LA, N297A/DQ, D265A/DQ, LALA/DQ, LAGA/DQ, LALAGA/DQ, LALAPG/DQ, N297A/DW, D265A/DW, LALA/DW, LAGA/DW, LALAGA/DW, LALAPG/DW, N297A/YD, D265A/YD, LALA/YD, LAGA/YD, LALAGA/YD, LALAPG/YD, N297A/QVV, D265A/QVV, LALA/QVV, LAGA/QVV, LALAGA/QVV, and LALAPG/QVV. [0064] Although the EU numbering system is typically used to identify the positions of the various Fc mutations described herein, direct numbering can also be used. For example, in certain embodiments, an antibody described herein comprises an Fc region with YTE mutations at positions 253/255/257 or 260/262/264, respectively. In certain embodiments, an antibody described herein comprises an Fc region with LALA mutations at positions 235/236 or 242/243, respectively. In certain embodiments, an antibody described herein comprises an Fc region with YTE mutations at positions 253/255/257 and with LALA mutations at positions 235/236. In certain embodiments, an antibody described herein comprises an Fc region with YTE mutations at positions 260/262/264 and with LALA mutations at positions 242/243. In certain embodiments, the OX40L antibody described herein comprises the VH and VL of Construct 114 and an Fc region comprising YTE mutations at positions 253/255/257, respectively and with LALA mutations at positions 235/236, respectively. In certain embodiments, the IL-4Rα antibody described herein comprises the VH and VL of Construct 38 (mAb 471) and an Fc region comprising YTE mutations at positions 260/262/264, respectively and with LALA mutations at positions 242/243, respectively. [0065] In some embodiments, the antibody, or antigen binding fragment thereof, that binds OX40L comprises a VH domain comprising the amino acid sequence set forth in SEQ ID NO: 1, a VL domain comprising the amino acid sequence set forth in SEQ ID NO: 11, and a human IgG1 Fc region comprising LALA and YTE mutations. In some embodiments, the antibody, or antigen binding fragment thereof, that binds OX40L comprises a VH domain comprising the amino acid sequence set forth in SEQ ID NO: 1, a VL domain comprising the amino acid sequence set forth in SEQ ID NO: 11, a constant heavy chain sequence set forth in SEQ ID NO: 651 and/or a constant heavy chain sequence set forth in SEQ ID NO: 973, and a constant light chain sequence set forth in SEQ ID NO: 738. In some embodiments, the antibody, or antigen binding fragment thereof, that binds OX40L comprises a VH domain comprising the amino acid sequence set forth in SEQ ID NO: 1, a VL domain comprising the amino acid sequence set forth in SEQ ID NO: 11, a constant heavy chain sequence set forth in SEQ ID NO: 973, and a constant light chain sequence set forth in SEQ ID NO: 738. In some embodiments, the antibody, or antigen binding fragment thereof, that binds OX40L comprises a VH domain comprising the amino acid sequence set forth in SEQ ID NO: 1, a VL domain comprising the amino acid sequence set forth in SEQ ID NO: 11, a constant heavy chain sequence set forth in SEQ ID NO: 651, and a constant light chain sequence set forth in SEQ ID NO: 738. In some embodiments, the antibody, or antigen binding fragment thereof, that binds OX40L comprises a heavy chain sequence set forth in SEQ ID NO: 839 and/or SEQ ID NO: 840 and a light chain sequence set forth in SEQ ID NO: 841. In some embodiments, the antibody, or antigen binding fragment thereof, that binds OX40L comprises a heavy chain sequence set forth in SEQ ID NO: 839 and a light chain sequence set forth in SEQ ID NO: 841. In some embodiments, the antibody that binds OX40L is Construct 114. [0066] In some embodiments, the antibody, or antigen binding fragment thereof, that binds IL-4Rα comprises a VH domain comprising the amino acid sequence set forth in SEQ ID NO: 297, a VL domain comprising the amino acid sequence set forth in SEQ ID NO: 300, and a human IgG1 Fc region comprising LALA and YTE mutations. In some embodiments, the antibody, or antigen binding fragment thereof, that binds IL-4Rα comprises a VH domain comprising the amino acid sequence set forth in SEQ ID NO: 297, a VL domain comprising the amino acid sequence set forth in SEQ ID NO: 300, a constant heavy chain sequence set forth in SEQ ID NO: 651 and/or a constant heavy chain sequence set forth in SEQ ID NO: 973, and a constant light chain sequence set forth in SEQ ID NO: 738. In some embodiments, the antibody, or antigen binding fragment thereof, that binds IL-4Rα comprises a VH domain comprising the amino acid sequence set forth in SEQ ID NO: 297, a VL domain comprising the amino acid sequence set forth in SEQ ID NO: 300, a constant heavy chain sequence set forth in SEQ ID NO: 973, and a constant light chain sequence set forth in SEQ ID NO: 738. In some embodiments, the antibody, or antigen binding fragment thereof, that binds IL-4Rα comprises a VH domain comprising the amino acid sequence set forth in SEQ ID NO: 297, a VL domain comprising the amino acid sequence set forth in SEQ ID NO: 300, a constant heavy chain sequence set forth in SEQ ID NO: 651, and a constant light chain sequence set forth in SEQ ID NO: 738. In some embodiments, the antibody, or antigen binding fragment thereof, that binds IL-4Rα comprises a heavy chain sequence set forth in SEQ ID NO: 836 and/or SEQ ID NO: 837 and a light chain sequence set forth in SEQ ID NO: 838. In some embodiments, the antibody, or antigen binding fragment thereof, that binds IL-4Rα comprises a heavy chain sequence set forth in SEQ ID NO: 836 and a light chain sequence set forth in SEQ ID NO: 838. In some embodiments, the antibody that binds IL-4Rα is Construct 38 (mAb 471). [0067] In some embodiments, the antibody that binds OX40L is Construct 114 and the antibody that binds IL-4Rα is Construct 38 (mAb 471). [0068] In some embodiments, the antibody that binds OX40L is Construct 114 and the antibody that binds IL-4Rα is dupilumab, stapokibart, or 611. [0069] In some embodiments, the antibody that binds OX40L is amlitelimab or oxelumab and the antibody that binds IL-4Rα is Construct 38 (mAb 471). [0070] In some embodiments, the Fc region of the antibody, or antigen binding fragment thereof, that binds OX40L and/or the antibody, or antigen binding fragment thereof, that binds IL-4Rα binds to Neonatal Fc receptor (FcRn). [0071] In some embodiments, the Fc region of the antibody, or antigen binding fragment thereof, that binds OX40L and/or the antibody, or antigen binding fragment thereof, that binds IL-4Rα binds an FcRn with higher affinity at pH 6.0 compared to an antibody comprising a wild-type Fc region. [0072] In some embodiments, the Fc region of the antibody, or antigen binding fragment thereof, that binds OX40L and/or the antibody, or antigen binding fragment thereof, that binds IL-4Rα binds to FcRn with a KD of <1 x 10-7 M at pH 6.0. [0073] In some embodiments, the antibody, or antigen binding fragment thereof, that binds OX40L and/or the antibody, or antigen binding fragment thereof, that binds IL-4Rα is a monoclonal antibody. [0074] In some embodiments, the antibody, or antigen binding fragment thereof, that binds OX40L binds an OX40L sequence set forth in the amino acid sequence of SEQ ID NO: 739. [0075] In some embodiments, the antibody, or antigen binding fragment thereof, that binds IL-4Rα binds an IL-4Rα sequence set forth in any one of the amino acid sequences of SEQ ID NOs: 301-303. [0076] In another aspect, the disclosure relates to the isolated antibodies, or antigen binding fragments thereof, of any one of the preceding aspects or embodiments for use in the treatment of an inflammatory disorder or disease (e.g., combined in a single formulation or administered in separate formulations). [0077] In another aspect, the disclosure relates to the isolated antibodies, or antigen binding fragments thereof, of any one of the preceding aspects or embodiments for use in the treatment of atopic dermatitis (AD). [0078] In some embodiments, the treatment reduces disease severity in a patient and wherein disease severity is assessed by an atopic dermatitis disease severity outcome measure. [0079] In another aspect, the disclosure relates to the isolated antibodies, or antigen binding fragments thereof, of any one of the preceding aspects or embodiments for use in the treatment of asthma, chronic sinusitis with nasal polyps; Chronic Rhinosinusitis without Nasal Polyps (CRSsNP); eosinophilic esophagitis (EoE); an Eosinophilic gastrointestinal disorder or disease (EGID), such as Eosinophilic Gastritis (EoG), Eosinophilic Enteritis (EoN), Eosinophilic Colitis (EoC), or Eosinophilic Gastroenteritis (EGE); Churg-Strauss syndrome/Eosinophilic granulomatosis with polyangiitis (EGPA); Prurigo Nodularis (PN); Chronic Spontaneous Urticaria (CSU); Chronic Pruritis of Unknown Origin (CPUO); Bullous Pemphigoid (BP); Cold Inducible Urticaria (ColdU); Allergic Fungal Rhinosinusitis (AFRS); Allergic Bronchopulmonary Aspergillosis (ABPA); Chronic Obstructive Pulmonary Disease (COPD); an inflammatory bowel disease, such as Crohn’s disease or ulcerative colitis; lupus; rheumatoid arthritis (RA); psoriasis; hidradenitis suppurativa; celiac disease; systemic sclerosis; idiopathic pulmonary fibrosis; alopecia areata; allergic rhinitis; eosinophilic fasciitis; scleromyxedema; scleredema; or nephrogenic systemic fibrosis. [0080] In another aspect, disclosed herein is a multi-specific antibody comprising: a first antigen binding region that binds OX40L and comprises: a) a variable heavy (VH) chain sequence having three heavy chain CDR sequences, CDR-H1, CDR-H2, and CDR-H3; and b) a variable light (VL) chain sequence having three light chain CDR sequences, CDR-L1, CDR-L2, and CDR-L3; wherein the antigen binding region that binds OX40L comprises: (i) a CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 2-4; a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 5-7; a CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 8-10; a CDR-L1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 12-14; a CDR-L2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 15-16; and a CDR-L3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 17- 18; (ii) a CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 20-22; a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 23-25; a CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 26-28; a CDR-L1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 30-32; a CDR-L2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 33-34; and a CDR-L3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 35-36; (iii) a CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 38-40; a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NO: s 41-43; a CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 44-46; a CDR-L1 comprising the amino acid sequence set forth in any one of SEQ ID NO: s 48-50; a CDR-L2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 51-52; and a CDR-L3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 53-54; or (iv) a CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 56-58; a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 59-61; a CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 62-64; a CDR-L1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 66-68; a CDR-L2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 69-70; and a CDR-L3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 71-72; and a second antigen binding region that binds IL-4Rα. [0081] In some embodiments, the antigen binding region that binds IL-4Rα comprises a CDR-H1, CDR-H2, CDR-H3, CDR-L1, CDR-L2, and CDR-L3 of an antibody selected from dupilumab, stapokibart, and 611. [0082] In some embodiments, the antigen binding region that binds IL-4Rα comprises: a) a VH chain sequence having three heavy chain CDR sequences, CDR-H1, CDR-H2, and CDR-H3; and b) a VL chain sequence having three light chain CDR sequences, CDR-L1, CDR-L2, and CDR-L3, wherein the antigen binding region that binds IL-4Rα comprises: (i) a CDR-H1 comprising the sequence set forth in any one of SEQ ID NOs: 273, 274, and 275; a CDR-H2 comprising the sequence set forth in any one of SEQ ID NOs: 276, 277, and 278; a CDR-H3 comprising the sequence set forth in any one of SEQ ID NOs: 281 and 282; a CDR- L1 comprising the sequence set forth in any one of SEQ ID NOs: 285 and 286; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 292 or the amino acid sequence LG; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 293; (ii) a CDR-H1 comprising the sequence set forth in any one of SEQ ID NOs: 273, 274, and 275; a CDR-H2 comprising the sequence set forth in any one of SEQ ID NOs: 279, 277, and 280; a CDR-H3 comprising the sequence set forth in any one of SEQ ID NOs: 283 and 284; a CDR-L1 comprising the sequence set forth in any one of SEQ ID NOs: 287 and 288; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 291 or the amino acid sequence LG; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 293; or (iii) a CDR-H1 comprising the sequence set forth in any one of SEQ ID NOs: 273, 274, and 275; a CDR-H2 comprising the sequence set forth in any one of SEQ ID NOs: 279, 277, and 280; a CDR-H3 comprising the sequence set forth in any one of SEQ ID NOs: 281 and 282; a CDR-L1 comprising the sequence set forth in any one of SEQ ID NOs: 289 and 288; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 290 or the amino acid sequence EG; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 293. [0083] In another aspect, disclosed herein is a multi-specific antibody comprising: a first antigen binding region that binds OX40L; and a second antigen binding region that binds IL- 4Rα and comprises: a) a variable heavy (VH) chain sequence having three heavy chain CDR sequences, CDR-H1, CDR-H2, and CDR-H3; and b) a variable light (VL) chain sequence having three light chain CDR sequences, CDR-L1, CDR-L2, and CDR-L3; wherein the antigen binding region that binds IL-4Rα comprises: (i) a CDR-H1 comprising the sequence set forth in any one of SEQ ID NOs: 273, 274, and 275; a CDR-H2 comprising the sequence set forth in any one of SEQ ID NOs: 276, 277, and 278; a CDR-H3 comprising the sequence set forth in any one of SEQ ID NOs: 281 and 282; a CDR-L1 comprising the sequence set forth in any one of SEQ ID NOs: 285 and 286; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 292 or the amino acid sequence LG; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 293; (ii) a CDR-H1 comprising the sequence set forth in any one of SEQ ID NOs: 273, 274, and 275; a CDR-H2 comprising the sequence set forth in any one of SEQ ID NOs: 279, 277, and 280; a CDR-H3 comprising the sequence set forth in any one of SEQ ID NOs: 283 and 284; a CDR-L1 comprising the sequence set forth in any one of SEQ ID NOs: 287 and 288; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 291 or the amino acid sequence LG; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 293; or (iii) a CDR-H1 comprising the sequence set forth in any one of SEQ ID NOs: 273, 274, and 275; a CDR-H2 comprising the sequence set forth in any one of SEQ ID NOs: 279, 277, and 280; a CDR-H3 comprising the sequence set forth in any one of SEQ ID NOs: 281 and 282; a CDR-L1 comprising the sequence set forth in any one of SEQ ID NOs: 289 and 288; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 290 or the amino acid sequence EG; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 293. [0084] In some embodiments, the antigen binding region that binds OX40L comprises a CDR-H1, CDR-H2, CDR-H3, CDR-L1, CDR-L2, and CDR-L3 of an antibody selected from amlitelimab and oxelumab. [0085] In some embodiments, the antigen binding region that binds OX40L comprises: a) a VH chain sequence having three heavy chain CDR sequences, CDR-H1, CDR-H2, and CDR-H3; and b) a VL chain sequence having three light chain CDR sequences, CDR-L1, CDR-L2, and CDR-L3, wherein the antigen binding region that binds OX40L comprises: (i) a CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 2-4; a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 5-7; a CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 8-10; a CDR-L1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 12-14; a CDR-L2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 15-16; and a CDR-L3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 17- 18; (ii) a CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 20-22; a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 23-25; a CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 26-28; a CDR-L1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 30-32; a CDR-L2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 33-34; and a CDR-L3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 35-36; (iii) a CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 38-40; a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 41-43; a CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 44-46; a CDR-L1 comprising the amino acid sequence set forth in any one of SEQ ID NO: s 48-50; a CDR-L2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 51-52; and a CDR-L3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 53-54; or (iv) a CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 56-58; a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 59-61; a CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 62-64; a CDR-L1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 66-68; a CDR-L2 comprising the amino acid sequence set forth in any one of SEQ ID NO: 69-70s; and a CDR-L3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 71-72. [0086] In some embodiments, (a) the antigen binding region that binds OX40L comprises: (i) a CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 2-4; a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 5-7; a CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 8-10; a CDR-L1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 12-14; a CDR-L2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 15-16; and a CDR-L3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 17-18; and (b) the antigen binding region that binds IL-4Rα comprises: (i) a CDR- H1 comprising the sequence set forth in any one of SEQ ID NOs: 273, 274, and 275; a CDR- H2 comprising the sequence set forth in any one of SEQ ID NOs: 276, 277, and 278; a CDR- H3 comprising the sequence set forth in any one of SEQ ID NOs: 281 and 282; a CDR-L1 comprising the sequence set forth in any one of SEQ ID NOs: 285 and 286; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 292 or the amino acid sequence LG; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 293. [0087] In some embodiments, (a) the antigen binding region that binds OX40L comprises: (ii) a CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 20-22; a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 23-25; a CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 26-28; a CDR-L1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 30-32; a CDR-L2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 33-34; and a CDR-L3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 35-36; and (b) the antigen binding region that binds IL-4Rα comprises: (i) a CDR-H1 comprising the sequence set forth in any one of SEQ ID NOs: 273, 274, and 275; a CDR-H2 comprising the sequence set forth in any one of SEQ ID NOs: 276, 277, and 278; a CDR-H3 comprising the sequence set forth in any one of SEQ ID NOs: 281 and 282; a CDR- L1 comprising the sequence set forth in any one of SEQ ID NOs: 285 and 286; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 292 or the amino acid sequence LG; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 293. [0088] In some embodiments, (a) the antigen binding region that binds OX40L comprises: (iii) a CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 38-40; a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 41-43; a CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 44-46; a CDR-L1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 48-50; a CDR-L2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 51-52; and a CDR-L3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 53-54; and (b) the antigen binding region that binds IL-4Rα comprises: (i) a CDR-H1 comprising the sequence set forth in any one of SEQ ID NOs: 273, 274, and 275; a CDR-H2 comprising the sequence set forth in any one of SEQ ID NOs: 276, 277, and 278; a CDR-H3 comprising the sequence set forth in any one of SEQ ID NOs: 281 and 282; a CDR- L1 comprising the sequence set forth in any one of SEQ ID NOs: 285 and 286; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 292 or the amino acid sequence LG; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 293. [0089] In some embodiments, (a) the antigen binding region that binds OX40L comprises: (iv) a CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 56-58; a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 59-61; a CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 62-64; a CDR-L1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 66-68; a CDR-L2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 69-70; and a CDR-L3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 71-72; and (b) the antigen binding region that binds IL-4Rα comprises: (i) a CDR-H1 comprising the sequence set forth in any one of SEQ ID NOs: 273, 274, and 275; a CDR-H2 comprising the sequence set forth in any one of SEQ ID NOs: 276, 277, and 278; a CDR-H3 comprising the sequence set forth in any one of SEQ ID NOs: 281 and 282; a CDR- L1 comprising the sequence set forth in any one of SEQ ID NOs: 285 and 286; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 292 or the amino acid sequence LG; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 293. [0090] In some embodiments, (a) the antigen binding region that binds OX40L comprises: (i) a CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 2-4; a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 5-7; a CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 8-10; a CDR-L1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 12-14; a CDR-L2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 15-16; and a CDR-L3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 17-18; and (b) the antigen binding region that binds IL-4Rα comprises: (ii) a CDR- H1 comprising the sequence set forth in any one of SEQ ID NOs: 273, 274, and 275; a CDR- H2 comprising the sequence set forth in any one of SEQ ID NOs: 279, 277, and 280; a CDR- H3 comprising the sequence set forth in any one of SEQ ID NOs: 283 and 284; a CDR-L1 comprising the sequence set forth in any one of SEQ ID NOs: 287 and 288; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 291 or the amino acid sequence LG; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 293. [0091] In some embodiments, (a) the antigen binding region that binds OX40L comprises: (ii) a CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 20-22; a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 23-25; a CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 26-28; a CDR-L1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 30-32; a CDR-L2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 33-34; and a CDR-L3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 35-36; and (b) the antigen binding region that binds IL-4Rα comprises: ((ii) a CDR-H1 comprising the sequence set forth in any one of SEQ ID NOs: 273, 274, and 275; a CDR-H2 comprising the sequence set forth in any one of SEQ ID NOs: 279, 277, and 280; a CDR-H3 comprising the sequence set forth in any one of SEQ ID NOs: 283 and 284; a CDR- L1 comprising the sequence set forth in any one of SEQ ID NOs: 287 and 288; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 291 or the amino acid sequence LG; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 293. [0092] In some embodiments, (a) the antigen binding region that binds OX40L comprises: (iii) a CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 38-40; a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 41-43; a CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 44-46; a CDR-L1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 48-50; a CDR-L2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 51-52; and a CDR-L3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 53-54; and (b) the antigen binding region that binds IL-4Rα comprises: (ii) a CDR-H1 comprising the sequence set forth in any one of SEQ ID NOs: 273, 274, and 275; a CDR-H2 comprising the sequence set forth in any one of SEQ ID NOs: 279, 277, and 280; a CDR-H3 comprising the sequence set forth in any one of SEQ ID NOs: 283 and 284; a CDR- L1 comprising the sequence set forth in any one of SEQ ID NOs: 287 and 288; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 291 or the amino acid sequence LG; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 293. [0093] In some embodiments, (a) the antigen binding region that binds OX40L comprises: (iv) a CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 56-58; a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 59-61; a CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 62-64; a CDR-L1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 66-68; a CDR-L2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 69-70; and a CDR-L3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 71-72; and (b) the antigen binding region that binds IL-4Rα comprises: (ii) a CDR-H1 comprising the sequence set forth in any one of SEQ ID NOs: 273, 274, and 275; a CDR-H2 comprising the sequence set forth in any one of SEQ ID NOs: 279, 277, and 280; a CDR-H3 comprising the sequence set forth in any one of SEQ ID NOs: 283 and 284; a CDR- L1 comprising the sequence set forth in any one of SEQ ID NOs: 287 and 288; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 291 or the amino acid sequence LG; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 293. [0094] In some embodiments, (a) the antigen binding region that binds OX40L comprises: (i) a CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 2-4; a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 5-7; a CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 8-10; a CDR-L1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 12-14; a CDR-L2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 15-16; and a CDR-L3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 17-18; and (b) the antigen binding region that binds IL-4Rα comprises: (iii) a CDR- H1 comprising the sequence set forth in any one of SEQ ID NOs: 273, 274, and 275; a CDR- H2 comprising the sequence set forth in any one of SEQ ID NOs: 279, 277, and 280; a CDR- H3 comprising the sequence set forth in any one of SEQ ID NOs: 281 and 282; a CDR-L1 comprising the sequence set forth in any one of SEQ ID NOs: 289 and 288; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 290 or the amino acid sequence EG; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 293. [0095] In some embodiments, (a) the antigen binding region that binds OX40L comprises: (ii) a CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 20-22; a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 23-25; a CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 26-28; a CDR-L1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 30-32; a CDR-L2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 33-34; and a CDR-L3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 35-36; and (b) the antigen binding region that binds IL-4Rα comprises: (iii) a CDR-H1 comprising the sequence set forth in any one of SEQ ID NOs: 273, 274, and 275; a CDR-H2 comprising the sequence set forth in any one of SEQ ID NOs: 279, 277, and 280; a CDR-H3 comprising the sequence set forth in any one of SEQ ID NOs: 281 and 282; a CDR- L1 comprising the sequence set forth in any one of SEQ ID NOs: 289 and 288; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 290 or the amino acid sequence EG; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 293. [0096] In some embodiments, (a) the antigen binding region that binds OX40L comprises: (iii) a CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 38-40; a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 41-43; a CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 44-46; a CDR-L1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 48-50; a CDR-L2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 51-52; and a CDR-L3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 53-54; and (b) the antigen binding region that binds IL-4Rα comprises: (iii) a CDR-H1 comprising the sequence set forth in any one of SEQ ID NOs: 273, 274, and 275; a CDR-H2 comprising the sequence set forth in any one of SEQ ID NOs: 279, 277, and 280; a CDR-H3 comprising the sequence set forth in any one of SEQ ID NOs: 281 and 282; a CDR- L1 comprising the sequence set forth in any one of SEQ ID NOs: 289 and 288; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 290 or the amino acid sequence EG; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 293. [0097] In some embodiments, (a) the antigen binding region that binds OX40L comprises: (iv) a CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 56-58; a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 59-61; a CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 62-64; a CDR-L1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 66-68; a CDR-L2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 69-70; and a CDR-L3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 71-72; and (b) the antigen binding region that binds IL-4Rα comprises: (iii) a CDR-H1 comprising the sequence set forth in any one of SEQ ID NOs: 273, 274, and 275; a CDR-H2 comprising the sequence set forth in any one of SEQ ID NOs: 279, 277, and 280; a CDR-H3 comprising the sequence set forth in any one of SEQ ID NOs: 281 and 282; a CDR- L1 comprising the sequence set forth in any one of SEQ ID NOs: 289 and 288; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 290 or the amino acid sequence EG; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 293. [0098] In some embodiments, the antigen binding region that binds OX40L comprises a heavy chain variable domain (VH) sequence comprising the amino acid sequence set forth in any one of SEQ ID NOs: 1, 19, 37, and 55. [0099] In some embodiments, the antigen binding region that binds IL-4Rα comprises a VH sequence comprising the amino acid sequence set forth in any one of SEQ ID NOs: 295- 297. [00100] In some embodiments, the antigen binding region that binds OX40L comprises a light chain variable domain (VL) sequence comprising the amino acid sequence set forth in any one of SEQ ID NOs: 11, 29, 47, and 65. [00101] In some embodiments, the antigen binding region that binds IL-4Rα comprises a VL sequence comprising the amino acid sequence set forth in any one of SEQ ID NOs: 298- 300. [00102] In some embodiments, (a) the antigen binding region that binds OX40L comprises: (i) a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 1; (ii) a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 19; (iii) a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 37; or (iv) a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 55; and/or (v) a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 11; (vi) a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 29;(vii) a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 47; or (viii) a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 65; and/or (b) the antigen binding region that binds IL-4Rα comprises: (i) a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 295; (ii) a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 296; or (iii) a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 297; and/or (iv) a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 298; (v) a VL sequence comprising the amino acid sequence set forth in SEQ ID NO:299; or (vi) a VL sequence comprising the amino acid sequence set forth in SEQ ID NO:300. [00103] In some embodiments, the antigen binding region that binds OX40L comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 1; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 11. [00104] In some embodiments, the antigen binding region that binds OX40L comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 19; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 29. [00105] In some embodiments, the antigen binding region that binds OX40L comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 37; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 47. [00106] In some embodiments, the antigen binding region that binds OX40L comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 55; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 65. [00107] In some embodiments, the antigen binding region that binds IL-4Rα comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 295; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 298. [00108] In some embodiments, the antigen binding region that binds IL-4Rα comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 296; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 299. [00109] In some embodiments, the antigen binding region that binds IL-4Rα comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 297; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 300. [00110] In some embodiments, the antigen binding region that binds OX40L comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 1; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 11; and the antigen binding region that binds IL-4Rα comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 295; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 298. [00111] In some embodiments, the antigen binding region that binds OX40L comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 1; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 11; and the antigen binding region that binds IL-4Rα comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 296; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 299. [00112] In some embodiments, the antigen binding region that binds OX40L comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 1; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 11; and the antigen binding region that binds IL-4Rα comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 297; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 300. [00113] In some embodiments, the antigen binding region that binds OX40L comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 19; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 29; and the antigen binding region that binds IL-4Rα comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 295; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 298. [00114] In some embodiments, the antigen binding region that binds OX40L comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 19; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 29; and the antigen binding region that binds IL-4Rα comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 296; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 299. [00115] In some embodiments, the antigen binding region that binds OX40L comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 19; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 29; and the antigen binding region that binds IL-4Rα comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 297; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 300. [00116] In some embodiments, the antigen binding region that binds OX40L comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 37; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 47; and the antigen binding region that binds IL-4Rα comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 295; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 298. [00117] In some embodiments, the antigen binding region that binds OX40L comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 37; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 47; and the antigen binding region that binds IL-4Rα comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 296; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 299. [00118] In some embodiments, the antigen binding region that binds OX40L comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 37; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 47; and the antigen binding region that binds IL-4Rα comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 297; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 300. [00119] In some embodiments, the antigen binding region that binds OX40L comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 55; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 65; and the antigen binding region that binds IL-4Rα comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 295; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 298. [00120] In some embodiments, the antigen binding region that binds OX40L comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 55; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 65; and the antigen binding region that binds IL-4Rα comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 296; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 299. [00121] In some embodiments, the antigen binding region that binds OX40L comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 55; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 65; and the antigen binding region that binds IL-4Rα comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 297; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 300. [00122] In some embodiments, the antigen binding region that binds OX40L and/or the antigen binding region that binds IL-4RΑ is humanized, human, or chimeric. [00123] In some embodiments, the antigen binding region that binds OX40L and/or the antigen binding region that binds IL-4RΑ is humanized. [00124] In some embodiments, the multi-specific antibody comprises a heavy chain human constant region of a class selected from IgG, IgA, IgD, IgE, and IgM. [00125] In some embodiments, the multi-specific antibody comprises a human Fc region, and the human Fc region comprises a human heavy chain constant region of the class IgG and a subclass selected from IgG1, IgG2, IgG3, and IgG4. [00126] In some embodiments, the human Fc region comprises a human IgG1 Fc region. [00127] In some embodiments, the human Fc region comprises a human IgG4 Fc region. [00128] In some embodiments, the human Fc region comprises a human IgG2 Fc region. [00129] In some embodiments, the multi-specific antibody comprises a heavy chain comprising a constant heavy chain sequence selected from the amino acid sequences set forth in any one of SEQ ID NOs: 427, 439, 440, 446, 457, 460, 637-737, and 847-1070. [00130] In some embodiments, the multi-specific antibody comprises a heavy chain constant domain having a means for increasing the half-life of the antibody. [00131] In some embodiments, the multi-specific antibody comprises a light chain comprising a constant light chain sequence selected from the sequences set forth in SEQ ID NOs: 469 and 1071. [00132] In some embodiments, the multi-specific antibody comprises an Fc region comprising one or more amino acid substitutions, wherein the one or more substitutions result in an increase in one or more of antibody half-life, ADCC activity, ADCP activity, or CDC activity compared with the Fc without the one or more substitutions. [00133] In some embodiments, the multi-specific antibody comprises an Fc region comprising one or more amino acid substitutions, wherein the one or more substitutions result in a decrease in one or more of, ADCC activity, ADCP activity or CDC activity compared to an antibody comprising a wild-type Fc region. [00134] In some embodiments, the one or more amino acid substitutions is selected from the group consisting of S228P, M252Y, S254T, T256E, T256D, T250Q, H285D, T307A, T307Q, T307R, T307W, L309D, Q411H, Q311V, A378V, E380A, M428L, N434A, N434S, N297A, D265A, L234A, L235A, and N434W; optionally, wherein the one or more amino acid substitutions comprises a plurality of amino acid substitutions selected from the group consisting of M428L/N434S (LS), M252Y/S254T/T256E (YTE), T250Q/M428L, T307A/E380A/N434A, T256D/T307Q (DQ), T256D/T307W (DW), M252Y/T256D (YD), T307Q/Q311V/A378V (QVV), T256D/H285D/T307R/Q311V/A378V (DDRVV), L309D/Q311H/N434S (DHS), S228P/L235E (SPLE), L234A/L235A (LALA), M428L/N434A (LA), L235A/G237A (LAGA), L234A/L235A/G237A (LALAGA), L234A/L235A/P329G (LALAPG), D265A/YTE, LALA/YTE, LAGA/YTE, LALAGA/YTE, LALAPG/YTE, N297A/LS, D265A/LS, LALA/LS, LALAGA/LS, LALAPG/LS, N297A/DHS, D265A/DHS, LALA/DHS, LAGA/DHS, LALAGA/DHS, LALAPG/DHS, SP/YTE, SPLE/YTE, SP/LS, SPLE/LS, SP/DHS, SPLE/DHS, N297A/LA, D265A/LA, LALA/LA, LAGA/LA, LALAGA/LA, LALAPG/LA, N297A/N434A, D265A/N434A, LALA/N434A, LAGA/N434A, LALAGA/N434A, LALAPG/N434A, N297A/N434W, D265A/N434W, LALA/N434W, LAGA/N434W, LALAGA/N434W, LALAPG/N434W, N297A/DQ, D265A/DQ, LALA/DQ, LAGA/DQ, LALAGA/DQ, LALAPG/DQ, N297A/DW, D265A/DW, LALA/DW, LAGA/DW, LALAGA/DW, LALAPG/DW, N297A/YD, D265A/YD, LALA/YD, LAGA/YD, LALAGA/YD, LALAPG/YD, T307Q/Q311V/A378V (QVV), N297A/QVV, D265A/QVV, LALA/QVV, LAGA/QVV, LALAGA/QVV, LALAPG/QVV, DDRVV, N297A/DDRVV, D265A/DDRVV, LALA/DDRVV, LAGA/DDRVV, LALAGA/DDRVV, and LALAPG/DDRVV. In some embodiments, the one or more amino acid substitutions is selected from the group consisting of LS, YTE, T250Q/M428L, T307A/E380A/N434A, DQ, DW, YD, QVV, DHS, LA, D265A/YTE, LALA/YTE, LAGA/YTE, LALAGA/YTE, LALAPG/YTE, N297A/LS, D265A/LS, LALA/LS, LALAGA/LS, LALAPG/LS, N297A/DHS, D265A/DHS, LALA/DHS, LAGA/DHS, LALAGA/DHS, LALAPG/DHS, SP/YTE, SPLE/YTE, SP/LS, SPLE/LS, SP/DHS, SPLE/DHS, N297A/LA, D265A/LA, LALA/LA, LAGA/LA, LALAGA/LA, LALAPG/LA, N297A/DQ, D265A/DQ, LALA/DQ, LAGA/DQ, LALAGA/DQ, LALAPG/DQ, N297A/DW, D265A/DW, LALA/DW, LAGA/DW, LALAGA/DW, LALAPG/DW, N297A/YD, D265A/YD, LALA/YD, LAGA/YD, LALAGA/YD, LALAPG/YD, N297A/QVV, D265A/QVV, LALA/QVV, LAGA/QVV, LALAGA/QVV, and LALAPG/QVV. [00135] Although the EU numbering system is typically used to identify the positions of the various Fc mutations described herein, direct numbering can also be used. For example, in certain embodiments, an antibody described herein comprises an Fc region with YTE mutations at positions 253/255/257 or 260/262/264, respectively. In certain embodiments, an antibody described herein comprises an Fc region with LALA mutations at positions 235/236 or 242/243, respectively. In certain embodiments, an antibody described herein comprises an Fc region with YTE mutations at positions 253/255/257 and with LALA mutations at positions 235/236. In certain embodiments, an antibody described herein comprises an Fc region with YTE mutations at positions 260/262/264 and with LALA mutations at positions 242/243. In certain embodiments, the OX40L antibody described herein comprises the VH and VL of Construct 114 and an Fc region comprising YTE mutations at positions 253/255/257, respectively and with LALA mutations at positions 235/236, respectively. In certain embodiments, the IL-4Rα antibody described herein comprises the VH and VL of Construct 38 (mAb 471) and an Fc region comprising YTE mutations at positions 260/262/264, respectively and with LALA mutations at positions 242/243, respectively. [00136] In some embodiments, the multi-specific antibody comprising an antigen binding region that binds OX40L comprises a VH domain comprising the amino acid sequence set forth in SEQ ID NO: 1, a VL domain comprising the amino acid sequence set forth in SEQ ID NO: 11, a constant heavy chain sequence set forth in any one of SEQ ID NOs: 651 and 973, and a constant light chain sequence set forth in SEQ ID NO: 738. [00137] In some embodiments, the multi-specific antibody comprising an antigen binding region that binds IL-4Rα comprises a VH domain comprising the amino acid sequence set forth in SEQ ID NO: 297, a VL domain comprising the amino acid sequence set forth in SEQ ID NO: 300, a heavy chain sequence set forth in any one of SEQ ID NOs: 651 and 973, and a light chain sequence set forth in SEQ ID NO: 738. [00138] In some embodiments, the Fc region of the multi-specific antibody binds to Neonatal Fc receptor (FcRn). [00139] In some embodiments, the Fc region of the multi-specific antibody binds an FcRn with higher affinity at pH 6.0 compared to an antibody comprising a wild-type Fc region. [00140] In some embodiments, the Fc region of the multi-specific antibody binds to FcRn with a KD of <1 x 10-7 M at pH 6.0. [00141] In some embodiments, the antigen binding region that binds OX40L and/or the antigen binding region that binds IL-4Rα is monoclonal. [00142] In some embodiments, the antigen binding region that binds OX40L binds an OX40L sequence set forth in the amino acid sequence of SEQ ID NO: 739. [00143] In some embodiments, the antigen binding region that binds IL-4Rα binds an IL- 4Rα sequence set forth in any one of the amino acid sequences of SEQ ID NOs: 301-303. [00144] In another aspect, the disclosure relates to the multi-specific antibodies of any one of the foregoing aspects or embodiments for use in the treatment of an inflammatory disorder or disease. [00145] In another aspect, the disclosure relates to the multi-specific antibodies of any one of the foregoing aspects or embodiments for use in the treatment of atopic dermatitis (AD). [00146] In some embodiments, the treatment reduces disease severity in a patient and wherein disease severity is assessed by an atopic dermatitis disease severity outcome measure. [00147] In another aspect, the disclosure relates to the multi-specific antibodies of any one of the foregoing aspects or embodiments for use in the treatment of asthma; chronic sinusitis with nasal polyps; Chronic Rhinosinusitis without Nasal Polyps (CRSsNP); eosinophilic esophagitis (EoE); an Eosinophilic gastrointestinal disorder or disease (EGID), such as Eosinophilic Gastritis (EoG), Eosinophilic Enteritis (EoN), Eosinophilic Colitis (EoC), or Eosinophilic Gastroenteritis (EGE); Churg-Strauss syndrome/Eosinophilic granulomatosis with polyangiitis (EGPA); Prurigo Nodularis (PN); Chronic Spontaneous Urticaria (CSU); Chronic Pruritis of Unknown Origin (CPUO); Bullous Pemphigoid (BP); Cold Inducible Urticaria (ColdU); Allergic Fungal Rhinosinusitis (AFRS); Allergic Bronchopulmonary Aspergillosis (ABPA); Chronic Obstructive Pulmonary Disease (COPD); an inflammatory bowel disease, such as Crohn’s disease or ulcerative colitis; lupus; rheumatoid arthritis (RA); psoriasis; hidradenitis suppurativa; celiac disease; systemic sclerosis; idiopathic pulmonary fibrosis; alopecia areata; allergic rhinitis; eosinophilic fasciitis; scleromyxedema; scleredema; or nephrogenic systemic fibrosis. [00148] In another aspect, the disclosure relates to an isolated polynucleotide or set of polynucleotides encoding the isolated antibodies or multi-specific antibodies of any one of the preceding aspects or embodiments, a VH thereof, a VL thereof, a light chain thereof, a heavy chain thereof, or an antigen-binding portion thereof, and optionally, wherein the polynucleotide or set of polynucleotides comprises cDNA. [00149] In another aspect, the disclosure relates to a vector or set of vectors comprising the polynucleotide or set of polynucleotides of any one of the preceding aspects or embodiments. [00150] In another aspect, the disclosure relates to a host cell comprising the polynucleotide or set of polynucleotides of any one of the preceding aspects or embodiments or the vector or set of vectors of any one of the preceding aspects or embodiments. [00151] In another aspect, the disclosure relates to a method of producing one or more of the isolated antibodies or multi-specific antibody of any one of the preceding aspects or embodiments, the method comprising expressing one or more of the isolated antibodies or multi-specific antibody within the host cell of any one of the preceding aspects or embodiments and isolating the one or more expressed antibodies. [00152] In another aspect, the disclosure relates to a pharmaceutical composition comprising the isolated antibodies or multi-specific antibody of any one of the preceding aspects or embodiments and a pharmaceutically acceptable excipient. [00153] In another aspect, the disclosure relates to a kit comprising the isolated antibodies or multi-specific antibody of any one of any one of the preceding aspects or embodiments or the pharmaceutical composition of any one of the preceding aspects or embodiments and instructions for use. [00154] In another aspect, the disclosure relates to a method for treating an inflammatory disorder or disease in a mammalian subject in need thereof, the method comprising administering to the mammalian subject a therapeutically effective amount of the isolated antibodies or multi-specific antibody of any one of the preceding aspects or embodiments; a therapeutically effective amount of the pharmaceutical composition of any one of the preceding aspects or embodiments; or a therapeutically effective amount of a pharmaceutical composition comprising an isolated antibody, or an antigen binding fragment thereof, that binds OX40L and a pharmaceutically acceptable excipient and a therapeutically effective amount of a pharmaceutical composition comprising an antibody, or an antigen binding fragment thereof, that binds IL-4RΑ and a pharmaceutically acceptable excipient137. [00155] In some embodiments, the mammalian subject is a human. [00156] In some embodiments, the inflammatory disorder or disease is atopic dermatitis. [00157] In some embodiments, the inflammatory disorder or disease is asthma. [00158] In some embodiments, the inflammatory disorder or disease is chronic sinusitis with nasal polyps; Chronic Rhinosinusitis without Nasal Polyps (CRSsNP); eosinophilic esophagitis (EoE); an Eosinophilic gastrointestinal disorder or disease (EGID), such as Eosinophilic Gastritis (EoG), Eosinophilic Enteritis (EoN), Eosinophilic Colitis (EoC), or Eosinophilic Gastroenteritis (EGE); Churg-Strauss syndrome/Eosinophilic granulomatosis with polyangiitis (EGPA); Prurigo Nodularis (PN); Chronic Spontaneous Urticaria (CSU); Chronic Pruritis of Unknown Origin (CPUO); Bullous Pemphigoid (BP); Cold Inducible Urticaria (ColdU); Allergic Fungal Rhinosinusitis (AFRS); Allergic Bronchopulmonary Aspergillosis (ABPA); Chronic Obstructive Pulmonary Disease (COPD); celiac disease; an inflammatory bowel disease, such as Crohn’s disease or ulcerative colitis; lupus; rheumatoid arthritis (RA); psoriasis; hidradenitis suppurativa; systemic sclerosis; idiopathic pulmonary fibrosis; alopecia areata; allergic rhinitis; eosinophilic fasciitis; scleromyxedema; scleredema; or nephrogenic systemic fibrosis. [00159] In another aspect, the disclosure relates to a method for treating a pathology associated with elevated levels of OX40L and/or IL-4Rα in a mammalian subject in need thereof, the method comprising administering to the mammalian subject a therapeutically effective amount the isolated antibodies or multi-specific antibody of any one of the foregoing aspects or embodiments, the pharmaceutical composition of any one of the foregoing aspects or embodiments, or a therapeutically effective amount of a pharmaceutical composition comprising an isolated antibody, or an antigen binding fragment thereof, that binds OX40L and a pharmaceutically acceptable excipient and a therapeutically effective amount of a pharmaceutical composition comprising an isolated antibody, or an antigen binding fragment thereof, that binds IL-4Rα and a pharmaceutically acceptable excipient. [00160] In another aspect, the disclosure relates to a method of reducing biological activity of OX40L and/or IL-4RΑ in a mammalian subject in need thereof, the method comprising administering to the mammalian subject a therapeutically effective amount the isolated antibodies or multi-specific antibody of any one of the foregoing aspects or embodiments, the pharmaceutical composition of any one of the foregoing aspects or embodiments, or a therapeutically effective amount of a pharmaceutical composition comprising an isolated antibody, or an antigen binding fragment thereof, that binds OX40L and a pharmaceutically acceptable excipient and a therapeutically effective amount of a pharmaceutical composition comprising an isolated antibody, or an antigen binding fragment thereof, that binds IL-4Rα and a pharmaceutically acceptable excipient. [00161] In some embodiments, the mammalian subject is a human. [00162] In another aspect, the disclosure relates to a pharmaceutical composition comprising: an isolated antibody, or an antigen binding fragment thereof, that binds OX40L comprising a VH domain comprising the amino acid sequence set forth in SEQ ID NO: 1, a VL domain comprising the amino acid sequence set forth in SEQ ID NO: 11, a constant heavy chain sequence set forth in any one of SEQ ID NOs: 651 and 973, and a constant light chain sequence set forth in SEQ ID NO: 738; an isolated antibody, or an antigen binding fragment thereof, that binds IL-4Rα comprising a VH domain comprising the amino acid sequence set forth in SEQ ID NO: 297, a VL domain comprising the amino acid sequence set forth in SEQ ID NO: 300, a constant heavy chain sequence set forth in any one of SEQ ID NOs: 651 and 973, and a constant light chain sequence set forth in SEQ ID NO: 738; and a pharmaceutically acceptable excipient. [00163] In another aspect, the disclosure relates to a pharmaceutical composition comprising: a multi-specific antibody comprising: an antigen binding region that binds OX40L comprises a VH domain comprising the amino acid sequence set forth in SEQ ID NO: 1, a VL domain comprising the amino acid sequence set forth in SEQ ID NO: 11, a constant heavy chain sequence set forth in any one of SEQ ID NOs: 651 and 973, and a constant light chain sequence set forth in SEQ ID NO: 738; an antigen binding region that binds IL-4Rα comprises a VH domain comprising the amino acid sequence set forth in SEQ ID NO: 297, a VL domain comprising the amino acid sequence set forth in SEQ ID NO: 300, a constant heavy chain sequence set forth in any one of SEQ ID NOs: 651 and 973, and a constant light chain sequence set forth in SEQ ID NO: 738; and a pharmaceutically acceptable excipient. [00164] In some embodiments, the pharmaceutical composition comprises a means for increasing the bioavailability of the isolated antibody, or antigen binding region thereof, that binds OX40L and/or the isolated antibody, or antigen binding region thereof, that binds IL- 4Rα or the multi-specific antibody. [00165] In certain aspects, described herein are compositions comprising an isolated antibody, or an antigen binding fragment thereof, that binds OX40L, an isolated antibody, or an antigen binding fragment thereof, that binds Interleukin-4 Receptor Alpha (IL-4Rα), and a hyaluronidase or variant thereof. In certain aspects, described herein are compositions comprising any one of the antibodies, or an antigen binding fragment thereof, described herein that binds OX40L, any one of the antibodies, or an antigen binding fragment thereof, described herein that binds IL-4Rα, and any one of the hyaluronidases or variants thereof described herein. [00166] In certain aspects, described herein are compositions comprising hyaluronidase or a variant thereof and a multi-specific antibody comprising a first antigen binding region that binds OX40L and a second antigen binding region that binds IL-4Rα. [00167] In certain aspects, described herein are a combination of an antibody, or an antigen binding fragment thereof, that binds OX40L, an antibody, or an antigen binding fragment thereof, that binds IL-4Rα, and a hyaluronidase or variant thereof. In certain aspects, described herein are a combination of any one of the antibodies, or an antigen binding fragment thereof, described herein that binds OX40L, any one of the antibodies, or an antigen binding fragment thereof, described herein that binds IL-4Rα, and a hyaluronidase or a variant thereof. [00168] In certain aspects, described herein are combinations comprising hyaluronidase or a variant thereof and a multi-specific antibody comprising a first antigen binding region that binds OX40L and a second antigen binding region that binds IL-4Rα. [00169] In certain aspects, described herein are methods of treating an inflammatory disorder or disease in a human patient comprising co-administering to the patient an isolated antibody, or an antigen binding fragment thereof, that binds OX40L, an isolated antibody, or an antigen binding fragment thereof, that binds IL-4Rα, and a hyaluronidase or a variant thereof. In certain aspects, described herein are methods of treating an inflammatory disorder or disease in a human patient comprising co-administering to the patient any one of the antibodies, or an antigen binding fragment thereof, described herein that binds OX40L, any one of the antibodies, or an antigen binding fragment thereof, described herein that binds IL- 4Rα, and any one of the hyaluronidases or variants thereof described herein. [00170] In certain aspects, described herein are methods of treating an inflammatory disorder or disease in a human patient comprising co-administering to the patient hyaluronidase or a variant thereof and a multi-specific antibody comprising a first antigen binding region that binds OX40L and a second antigen binding region that binds IL-4Rα. In certain aspects, described herein are methods of treating an inflammatory disorder or disease in a human patient comprising co-administering to the patient any one of the hyaluronidases or variants thereof described herein and any one of the multi-specific antibodies described herein (e.g., comprising a first antigen binding region that binds OX40L and a second antigen binding region that binds IL-4Rα). [00171] In certain embodiments, the antibody, or an antigen binding fragment thereof, that binds OX40L and/or the antibody, or an antigen binding fragment thereof, that binds IL- 4Rα is a humanized, human, or chimeric antibody. In certain embodiments, the antibody, or an antigen binding fragment thereof, is a monoclonal antibody. In certain embodiments, the antibody, or an antigen binding fragment thereof, comprises a heavy chain human constant region of a class selected from IgG, IgA, IgD, IgE, and IgM. In certain embodiments, the antibody, or an antigen binding fragment thereof, comprises a human Fc region comprising a human heavy chain constant region of the class IgG and a subclass selected from IgG1, IgG2, IgG3, and IgG4. In certain embodiments, the human Fc region comprises a human IgG1 Fc region [00172] In certain embodiments the human Fc region comprises a human IgG1 Fc region with LALA mutations. In certain embodiments the human Fc region comprises a human IgG1 Fc region with YTE mutations. In certain embodiments the human Fc region comprises a human IgG1 Fc region with LALA and YTE mutations. In certain embodiments, when direct numbering is used these “YTE” and “LALA” mutations can be located at different amino acid position numbers. For example, in one embodiment, the human Fc region comprises a human IgG1 Fc region with LALA mutations at L235A/L236A and/or YTE mutations at M253Y/S255T/T257E. In another embodiment, the human Fc region comprises a human IgG1 Fc region with LALA mutations at L242A/L243A and/or YTE mutations at M260Y/S262T/T264E. [00173] In certain embodiments, the antibody, or an antigen binding fragment thereof, that binds OX40L comprises a CDR-H1 comprising the sequence set forth in SEQ ID NO: 2; a CDR-H2 comprising the sequence set forth in SEQ ID NO: 5; a CDR-H3 comprising the sequence set forth in SEQ ID NO: 8; a CDR-L1 comprising the sequence set forth in SEQ ID NO: 12; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 15; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 17. In one embodiment, the antibody, or an antigen binding fragment thereof, that binds OX40L comprises a VH sequence set forth in SEQ ID NO: 1 and a VL sequence set forth in SEQ ID NO: 11. In one embodiment, the heavy chain of the antibody that binds OX40L comprises a constant heavy chain sequence set forth in SEQ ID NO: 651. In one embodiment, the heavy chain of the antibody that binds OX40L comprises a constant heavy chain sequence set forth in SEQ ID NO: 973. In one embodiment, the light chain of the antibody, or an antigen binding fragment thereof, that binds OX40L comprises a constant light chain sequence set forth in SEQ ID NO: 738. In one embodiment, the heavy chain of the antibody, or an antigen binding fragment thereof, that binds OX40L comprises a sequence set forth in SEQ ID NO: 839 and/or SEQ ID NO: 840. In one embodiment, the light chain of the antibody, or an antigen binding fragment thereof, that binds OX40L comprises a sequence set forth in SEQ ID NO: 841. In one embodiment, the heavy chain of the antibody, or an antigen binding fragment thereof, that binds OX40L comprises a sequence set forth in SEQ ID NO: 839 and the light chain of the antibody, or antigen binding fragment thereof that binds OX40L, comprises a sequence set forth in SEQ ID NO: 841. [00174] In certain embodiments, the antibody, or an antigen binding fragment thereof, that binds IL-4Rα comprises a CDR-H1 comprising the sequence set forth in SEQ ID NO: 273; a CDR-H2 comprising the sequence set forth in SEQ ID NO: 279; a CDR-H3 comprising the sequence set forth in SEQ ID NO: 281; a CDR-L1 comprising the sequence set forth in SEQ ID NO: 289; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 290; and a CDR- L3 comprising the sequence set forth in SEQ ID NO: 293. In one embodiment, the antibody, or an antigen binding fragment thereof, that binds IL-4Rα comprises a VH sequence set forth in SEQ ID NO: 297 and a VL sequence set forth in SEQ ID NO: 300. In one embodiment, the heavy chain of the antibody, or an antigen binding fragment thereof, that binds IL-4Rα comprises a constant heavy chain sequence set forth in SEQ ID NO: 651. In one embodiment, the heavy chain of the antibody, or an antigen binding fragment thereof, that binds IL-4Rα comprises a constant heavy chain sequence set forth in SEQ ID NO: 973. In one embodiment, the light chain of the antibody, or an antigen binding fragment thereof, that binds IL-4Rα comprises a constant light chain sequence set forth in SEQ ID NO: 738. In one embodiment, the heavy chain of the antibody, or an antigen binding fragment thereof, that binds IL-4Rα comprises a sequence set forth in SEQ ID NO: 836 and/or SEQ ID NO: 837. In one embodiment, the light chain of the antibody, or an antigen binding fragment thereof, that binds IL-4Rα comprises a sequence set forth in SEQ ID NO: 838. In one embodiment, the heavy chain of the antibody, or an antigen binding fragment thereof, that binds IL-4Rα comprises a sequence set forth in SEQ ID NO: 836 and the light chain of the antibody, or antigen binding fragment thereof that binds IL-4Rα, comprises a sequence set forth in SEQ ID NO: 838. [00175] In certain embodiments, a multi-specific antibody comprising a first antigen binding region that binds OX40L and a second antigen binding region that binds IL-4Rα is provided. In one embodiment, the antigen binding region that binds OX40L comprises a CDR-H1 comprising the sequence set forth in SEQ ID NO: 2; a CDR-H2 comprising the sequence set forth in SEQ ID NO: 5; a CDR-H3 comprising the sequence set forth in SEQ ID NO: 8; a CDR-L1 comprising the sequence set forth in SEQ ID NO: 12; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 15; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 17. In one embodiment, the antigen binding region that binds OX40L comprises a VH sequence set forth in SEQ ID NO: 1 and a VL sequence set forth in SEQ ID NO: 11.In another embodiment, the antigen binding region that binds IL- 4Rα comprises a CDR-H1 comprising the sequence set forth in SEQ ID NO: 273; a CDR-H2 comprising the sequence set forth in SEQ ID NO: 279; a CDR-H3 comprising the sequence set forth in SEQ ID NO: 281; a CDR-L1 comprising the sequence set forth in SEQ ID NO: 289; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 290; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 293. In one embodiment, the antibody that binds IL-4Rα comprises a VH sequence set forth in SEQ ID NO: 297 and a VL sequence set forth in SEQ ID NO: 300. [00176] In certain embodiments, the antibody or antigen binding region that binds OX40L and/or the antibody or antigen binding region that binds IL-4Rα comprises a heavy chain human constant region of a class selected from IgG, IgA, IgD, IgE, and IgM. In certain embodiments, the antibody or antigen binding region that binds OX40L and/or the antibody or antigen binding region that binds IL-4Rα comprises a human Fc region, and the human Fc region comprises a human heavy chain constant region of the class IgG and a subclass selected from IgG1, IgG2, IgG3, and IgG4. In certain embodiments, the human Fc region of the antibody that binds OX40L and/or the antibody that binds IL-4Rα comprises a human IgG1 Fc region. In certain embodiments, the human Fc region of the antibody that binds OX40L and/or the antibody that binds IL-4Rα comprises a human IgG4 Fc region. In certain embodiments, the human Fc region of the antibody or antigen binding region that binds OX40L and/or the antibody or antigen binding region that binds IL-4Rα comprises a human IgG2 Fc region. [00177] In certain embodiments the human Fc region comprises a human IgG1 Fc region with LALA mutations. In certain embodiments the human Fc region comprises a human IgG1 Fc region with YTE mutations. In certain embodiments the human Fc region comprises a human IgG1 Fc region with LALA and YTE mutations. In certain embodiments, when direct numbering is used these “YTE” and “LALA” mutations can be located at different amino acid position numbers. For example, in one embodiment, the human Fc region comprises a human IgG1 Fc region with LALA mutations at L235A/L236A and/or YTE mutations at M253Y/S255T/T257E. In another embodiment, the human Fc region comprises a human IgG1 Fc region with LALA mutations at L242A/L243A and/or YTE mutations at M260Y/S262T/T264E. [00178] In certain embodiments, the Fc region of the antibody or antigen binding region that binds OX40L and/or the antibody or antigen binding region that binds IL-4Rα binds to Neonatal Fc receptor (FcRn). In certain embodiments, the Fc region of the antibody or antigen binding region that binds OX40L and/or the antibody or antigen binding region that binds IL-4Rα binds an FcRn with higher affinity at pH 6.0 compared to an antibody comprising a wild-type Fc region. In certain embodiments, the Fc region of the antibody or antigen binding region that binds OX40L and/or the antibody or antigen binding region that binds IL-4Rα binds to FcRn with a KD of <1 x 10-7 M at pH 6.0. [00179] In certain embodiments, the antibody or antigen binding region that binds OX40L and/or the antibody or antigen binding region that binds IL-4Rα is a monoclonal antibody. [00180] In certain embodiments, the antibody or antigen binding region that binds OX40L binds an OX40L sequence set forth in the amino acid sequence of SEQ ID NO: 739. In certain embodiments, the antibody or antigen binding region that binds IL-4Rα binds an IL- 4Rα sequence set forth in any one of the amino acid sequences of SEQ ID NOs: 301-303. [00181] Any suitable hyaluronidase or variant thereof can be used in the compositions, combinations, and methods described herein. In certain embodiments, the hyaluronidase is a recombinant human hyaluronidase. In certain embodiments, the recombinant human hyaluronidase comprises the amino acid sequence set forth in any one of SEQ ID NOs: 1076- 1085 and 1087-1142. In certain embodiments, the recombinant human hyaluronidase is rHuPH20. In certain embodiments, the rHuPH20 formulation is ENHANZE®. [00182] In one embodiment, the recombinant human hyaluronidase includes a sequence of amino acids in any one of SEQ ID NOs: 1076-1085 and 1087-1142, or has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 95%, 97%, 98%, or 99% sequence identity to a sequence of amino acids included in any one of SEQ ID NO: 1076-1085 and 1087-1142 and retains hyaluronidase activity. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1076. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1076. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1078. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1078. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1079. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1079. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1080. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1080. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1081. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1081. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1082. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1082. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1083. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1083. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1084. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1084. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1085. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1085. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1087. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1087. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1088. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1088. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1089. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1089. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1090. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1090. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1091. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1091. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1093. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1093. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1094. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1094. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1095. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1095. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1096. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1096. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1097. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1097. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1098. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1098. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1099. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1099. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1100. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1100. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1101. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1101. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1102. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1102. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1103. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1103. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1104. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1104. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1105. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1105. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1106. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1106. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1107. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1107. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1108. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1108. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1109. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1109. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1110. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1110. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1111. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1111. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1112. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1112. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1113. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1113. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1114. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1114. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1115. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1115. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1116. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1116. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1117. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1117. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1118. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1118. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1119. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1119. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1120. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1120. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1121. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1121. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1122. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1122. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1123. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1123. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1124. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1124. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1125. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1125. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1126. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1126. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1127. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1127. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1128. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1128. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1129. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1129. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1130. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1130. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1131. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1131. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1132. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1132. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1133. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1133. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1134. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1134. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1135. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1135. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1136. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1136. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1137. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1137. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1138. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1138. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1139. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1139. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1140. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1140. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1141. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1141. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1142. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1142. [00183] In certain embodiments, the hyaluronidase or variant thereof and antibodies (i.e., anti- IL-4Rα antibody, or antigen binding fragment thereof, and anti-OX40L antibody, or antigen binding fragment thereof) or multi-specific antibody (i.e., comprising a first antigen binding region that binds OX40L and a second antigen binding region that binds IL-4Rα) are administered in separate formulations. In certain embodiments, the hyaluronidase or variant thereof and antibodies or multi-specific antibody are administered simultaneously in separate formulations. In certain embodiments, the hyaluronidase or variant thereof is administered to the patient prior to administration of the antibodies or multi-specific antibody. In certain embodiments, the hyaluronidase or variant thereof is administered to the patient after administration of the antibodies or multi-specific antibody. In certain embodiments, the hyaluronidase or variant thereof is administered to the patient after administration of one of the antibodies (either the OX40L antibody or the IL-4Rα antibody) but is administered before the administration of the second of the antibodies (either the OX40L antibody or the IL-4Rα antibody). In certain embodiments, the hyaluronidase or variant thereof and the antibodies or multi-specific antibody are mixed and administered in a single formulation. In certain embodiments, the hyaluronidase or variant thereof and the antibodies or multi-specific antibody are administered by subcutaneous injection. In certain embodiments, the hyaluronidase or variant thereof and the antibodies or multi-specific antibody are administered by intravenous injection. [00184] In certain embodiments, the hyaluronidase is rHuPH20 (ENHANZE®) administered at a concentration of 5,000, 6,000, 7,000, 8,000, 9,000, 10,000, 11,000, 12,000, 13,000, 14,000, 15,000, 16,000, 17,000, 18,000, 19,000, 20,000, 21,000, 22,000, 23,000, 24,000, 25,000, 26,000, 27,000, 28,000, 29,000, 30,000, 31,000, 32,000, 33,000, 34,000, 35,000, 36,000, 37,000, 38,000, 39,000, or 40,000 units. [00185] In certain embodiments, methods of treating an inflammatory disorder or disease in a human patient are provided, wherein the method comprises co-administering to the patient any one of the antibodies that bind OX40L described herein and any one of the antibodies that bind IL-4Rα described herein in combination with a hyaluronidase or variant thereof. In certain embodiments, methods of treating an inflammatory disorder or disease in a human patient are provided, wherein the method comprises co-administering to the patient any one of the multi-specific antibodies described herein in combination with a hyaluronidase or variant thereof. In certain embodiments, the inflammatory disorder or disease is atopic dermatitis. In certain embodiments, the treatment reduces disease severity in the patient and disease severity is assessed by an atopic dermatitis disease severity outcome measure. In certain embodiments, the inflammatory disorder or disease is asthma; chronic sinusitis with nasal polyps; Chronic Rhinosinusitis without Nasal Polyps (CRSsNP); eosinophilic esophagitis (EoE); an Eosinophilic gastrointestinal disorder or disease (EGID), such as Eosinophilic Gastritis (EoG), Eosinophilic Enteritis (EoN), Eosinophilic Colitis (EoC), or Eosinophilic Gastroenteritis (EGE); Churg-Strauss syndrome/Eosinophilic granulomatosis with polyangiitis (EGPA); Prurigo Nodularis (PN); Chronic Spontaneous Urticaria (CSU); Chronic Pruritis of Unknown Origin (CPUO); Bullous Pemphigoid (BP); Cold Inducible Urticaria (ColdU); Allergic Fungal Rhinosinusitis (AFRS); Allergic Bronchopulmonary Aspergillosis (ABPA); Chronic Obstructive Pulmonary Disease (COPD); an inflammatory bowel disease, such as Crohn’s disease or ulcerative colitis; lupus; rheumatoid arthritis (RA); psoriasis; ulcerative colitis; hidradenitis suppurativa; celiac disease; systemic sclerosis; idiopathic pulmonary fibrosis; alopecia areata; allergic rhinitis; eosinophilic fasciitis; scleromyxedema; scleredema; or nephrogenic systemic fibrosis. [00186] In certain aspects, described herein are compositions comprising an isolated antibody, or antigen binding region thereof, that binds OX40L, an isolated antibody, or antigen binding region thereof, that binds IL-4Rα, and a hyaluronidase or variant thereof. [00187] In certain aspects, described herein are compositions comprising an isolated antibody, or antigen binding region thereof, that binds OX40L, an isolated antibody, or antigen binding region thereof, that binds IL-4Rα, and a hyaluronidase or variant thereof, wherein the antibody that binds OX40L comprises a CDR-H1 comprising the sequence set forth in SEQ ID NO: 2; a CDR-H2 comprising the sequence set forth in SEQ ID NO: 5; a CDR-H3 comprising the sequence set forth in SEQ ID NO: 8; a CDR-L1 comprising the sequence set forth in SEQ ID NO: 12; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 15; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 17. [00188] In certain aspects, described herein are compositions comprising an isolated antibody, or antigen binding region thereof, that binds OX40L, an isolated antibody, or antigen binding region thereof, that binds IL-4Rα, and a hyaluronidase or variant thereof, wherein the antibody that binds OX40L comprises a VH sequence set forth in SEQ ID NO: 1 and a VL sequence set forth in SEQ ID NO: 11. [00189] In certain aspects, described herein are compositions comprising an isolated antibody, or antigen binding region thereof, that binds OX40L, an isolated antibody, or antigen binding region thereof, that binds IL-4Rα, and a hyaluronidase or variant thereof, wherein the antibody that binds IL-4Rα comprises a CDR-H1 comprising the sequence set forth in SEQ ID NO: 273; a CDR-H2 comprising the sequence set forth in SEQ ID NO: 279; a CDR-H3 comprising the sequence set forth in SEQ ID NO: 281; a CDR-L1 comprising the sequence set forth in SEQ ID NO: 289; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 290; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 293. [00190] In certain aspects, described herein are compositions comprising an isolated antibody, or antigen binding region thereof, that binds OX40L, an isolated antibody, or antigen binding region thereof, that binds IL-4Rα, and a hyaluronidase or variant thereof, wherein the antibody that binds IL-4Rα comprises a VH sequence set forth in SEQ ID NO: 297 and a VL sequence set forth in SEQ ID NO: 300. [00191] In certain aspects, described herein are compositions comprising an isolated antibody, or an antigen binding fragment thereof, that binds OX40L, an isolated antibody, or an antigen binding fragment thereof, that binds IL-4Rα, and a hyaluronidase or variant thereof, wherein the antibody, or an antigen binding fragment thereof, that binds OX40L comprises a CDR-H1 comprising the sequence set forth in SEQ ID NO: 2; a CDR-H2 comprising the sequence set forth in SEQ ID NO: 5; a CDR-H3 comprising the sequence set forth in SEQ ID NO: 8; a CDR-L1 comprising the sequence set forth in SEQ ID NO: 12; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 15; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 17, and wherein the antibody, or an antigen binding fragment thereof, that binds IL-4Rα comprises a CDR-H1 comprising the sequence set forth in SEQ ID NO: 273; a CDR-H2 comprising the sequence set forth in SEQ ID NO: 279; a CDR-H3 comprising the sequence set forth in SEQ ID NO: 281; a CDR-L1 comprising the sequence set forth in SEQ ID NO: 289; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 290; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 293. [00192] In certain aspects, described herein are compositions comprising an isolated antibody, or an antigen binding fragment thereof, that binds OX40L, an isolated antibody, or an antigen binding fragment thereof, that binds IL-4Rα, and a hyaluronidase or variant thereof, wherein the antibody, or an antigen binding fragment thereof, that binds OX40L comprises a VH sequence set forth in SEQ ID NO: 1 and a VL sequence set forth in SEQ ID NO: 11; and wherein the antibody, or an antigen binding fragment thereof, that binds IL-4Rα comprises a VH sequence set forth in SEQ ID NO: 297 and a VL sequence set forth in SEQ ID NO: 300. [00193] In certain aspects, described herein are compositions comprising hyaluronidase or a variant thereof and a multi-specific antibody comprising a first antigen binding region that binds OX40L and a second antigen binding region that binds IL-4Rα, wherein the antigen binding region that binds OX40L comprises a CDR-H1 comprising the sequence set forth in SEQ ID NO: 2; a CDR-H2 comprising the sequence set forth in SEQ ID NO: 5; a CDR-H3 comprising the sequence set forth in SEQ ID NO: 8; a CDR-L1 comprising the sequence set forth in SEQ ID NO: 12; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 15; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 17, and wherein the antigen binding region that binds IL-4Rα comprises a CDR-H1 comprising the sequence set forth in SEQ ID NO: 273; a CDR-H2 comprising the sequence set forth in SEQ ID NO: 279; a CDR- H3 comprising the sequence set forth in SEQ ID NO: 281; a CDR-L1 comprising the sequence set forth in SEQ ID NO: 289; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 290; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 293. [00194] In certain aspects, described herein are compositions comprising hyaluronidase or a variant thereof and a multi-specific antibody comprising a first antigen binding region that binds OX40L and a second antigen binding region that binds IL-4Rα, wherein the antigen binding region that binds OX40L comprises a VH sequence set forth in SEQ ID NO: 1 and a VL sequence set forth in SEQ ID NO: 11; and wherein the antigen binding region that binds IL-4Rα comprises a VH sequence set forth in SEQ ID NO: 297 and a VL sequence set forth in SEQ ID NO: 300. [00195] In certain aspects, described herein are combinations comprising an isolated antibody, or an antigen binding fragment thereof, that binds OX40L, an isolated antibody, or an antigen binding fragment thereof, that binds IL-4Rα, and a hyaluronidase or variant thereof, wherein the antibody, or an antigen binding fragment thereof, that binds OX40L comprises a CDR-H1 comprising the sequence set forth in SEQ ID NO: 2; a CDR-H2 comprising the sequence set forth in SEQ ID NO: 5; a CDR-H3 comprising the sequence set forth in SEQ ID NO: 8; a CDR-L1 comprising the sequence set forth in SEQ ID NO: 12; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 15; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 17, and wherein the antibody, or an antigen binding fragment thereof, that binds IL-4Rα comprises a CDR-H1 comprising the sequence set forth in SEQ ID NO: 273; a CDR-H2 comprising the sequence set forth in SEQ ID NO: 279; a CDR-H3 comprising the sequence set forth in SEQ ID NO: 281; a CDR-L1 comprising the sequence set forth in SEQ ID NO: 289; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 290; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 293 [00196] In certain aspects, described herein are combinations comprising an isolated antibody, or an antigen binding fragment thereof, that binds OX40L, an isolated antibody, or an antigen binding fragment thereof, that binds IL-4Rα, and a hyaluronidase or variant thereof, wherein the antibody, or an antigen binding fragment thereof, that binds OX40L comprises a VH sequence set forth in SEQ ID NO: 1 and a VL sequence set forth in SEQ ID NO: 11; and wherein the antibody, or an antigen binding fragment thereof, that IL-4Rα comprises a VH sequence set forth in SEQ ID NO: 297 and a VL sequence set forth in SEQ ID NO: 300. [00197] In certain aspects, described herein are combinations comprising hyaluronidase or a variant thereof and a multi-specific antibody comprising a first antigen binding region that binds OX40L and a second antigen binding region that binds IL-4Rα, wherein the antigen binding region that binds OX40L comprises a CDR-H1 comprising the sequence set forth in SEQ ID NO: 2; a CDR-H2 comprising the sequence set forth in SEQ ID NO: 5; a CDR-H3 comprising the sequence set forth in SEQ ID NO: 8; a CDR-L1 comprising the sequence set forth in SEQ ID NO: 12; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 15; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 17, and wherein the antigen binding region that binds IL-4Rα comprises a CDR-H1 comprising the sequence set forth in SEQ ID NO: 273; a CDR-H2 comprising the sequence set forth in SEQ ID NO: 279; a CDR- H3 comprising the sequence set forth in SEQ ID NO: 281; a CDR-L1 comprising the sequence set forth in SEQ ID NO: 289; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 290; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 293. [00198] In certain aspects, described herein are combinations comprising hyaluronidase or a variant thereof and a multi-specific antibody comprising a first antigen binding region that binds OX40L and a second antigen binding region that binds IL-4Rα, wherein the antigen binding region that binds OX40L comprises a VH sequence set forth in SEQ ID NO: 1 and a VL sequence set forth in SEQ ID NO: 11; and wherein the antigen binding region that binds IL-4Rα comprises a VH sequence set forth in SEQ ID NO: 297 and a VL sequence set forth in SEQ ID NO: 300. [00199] In certain aspects, described herein are methods of treating an inflammatory disorder or disease in a human patient comprising administering to the patient an isolated antibody, or an antigen binding fragment thereof, that binds OX40L, an isolated antibody, or an antigen binding fragment thereof, that binds IL-4Rα, and a hyaluronidase or a variant thereof, wherein the antibody, or an antigen binding fragment thereof, that binds OX40L comprises a CDR-H1 comprising the sequence set forth in SEQ ID NO: 2; a CDR-H2 comprising the sequence set forth in SEQ ID NO: 5; a CDR-H3 comprising the sequence set forth in SEQ ID NO: 8; a CDR-L1 comprising the sequence set forth in SEQ ID NO: 12; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 15; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 17, and wherein the antibody, or an antigen binding fragment thereof, that binds IL-4Rα comprises a CDR-H1 comprising the sequence set forth in SEQ ID NO: 273; a CDR-H2 comprising the sequence set forth in SEQ ID NO: 279; a CDR-H3 comprising the sequence set forth in SEQ ID NO: 281; a CDR-L1 comprising the sequence set forth in SEQ ID NO: 289; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 290; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 293. [00200] In certain aspects, described herein are methods of treating an inflammatory disorder or disease in a human patient comprising administering to the patient an isolated antibody, or an antigen binding fragment thereof, that binds OX40L, an isolated antibody, or an antigen binding fragment thereof, that binds IL-4Rα, and a hyaluronidase or a variant thereof, wherein the antibody, or an antigen binding fragment thereof, that binds OX40L comprises a VH sequence set forth in SEQ ID NO: 1 and a VL sequence set forth in SEQ ID NO: 11; and wherein the antibody, or an antigen binding fragment thereof, that binds IL-4Rα comprises a VH sequence set forth in SEQ ID NO: 297 and a VL sequence set forth in SEQ ID NO: 300. [00201] In certain aspects, described herein are methods of treating an inflammatory disorder or disease in a human patient comprising administering to the patient hyaluronidase or a variant thereof and a multi-specific antibody comprising a first antigen binding region that binds OX40L and a second antigen binding region that binds IL-4Rα, wherein the antigen binding region that binds OX40L comprises a CDR-H1 comprising the sequence set forth in SEQ ID NO: 2; a CDR-H2 comprising the sequence set forth in SEQ ID NO: 5; a CDR-H3 comprising the sequence set forth in SEQ ID NO: 8; a CDR-L1 comprising the sequence set forth in SEQ ID NO: 12; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 15; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 17, and wherein the antigen binding region that binds IL-4Rα comprises a CDR-H1 comprising the sequence set forth in SEQ ID NO: 273; a CDR-H2 comprising the sequence set forth in SEQ ID NO: 279; a CDR-H3 comprising the sequence set forth in SEQ ID NO: 281; a CDR-L1 comprising the sequence set forth in SEQ ID NO: 289; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 290; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 293. [00202] In certain aspects, described herein are methods of treating an inflammatory disorder or disease in a human patient comprising administering to the patient hyaluronidase or a variant thereof and a multi-specific antibody comprising a first antigen binding region that binds OX40L and a second antigen binding region that binds IL-4Rα, wherein the antigen binding region that binds OX40L comprises a VH sequence set forth in SEQ ID NO: 1 and a VL sequence set forth in SEQ ID NO: 11; and wherein the antigen binding region that binds IL-4Rα comprises a VH sequence set forth in SEQ ID NO: 297 and a VL sequence set forth in SEQ ID NO: 300. [00203] In certain embodiments, the hyaluronidase is a recombinant human hyaluronidase or variant thereof. In certain embodiments, the hyaluronidase is a recombinant human hyaluronidase. In certain embodiments, the recombinant human hyaluronidase comprises the amino acid sequence set forth in any one of SEQ ID NOs: 1076-1142 and 1087-1142. In certain embodiments, the recombinant human hyaluronidase is rHuPH20. In certain embodiments, the rHuPH20 formulation is ENHANZE®. [00204] In certain embodiments, the antibodies or multi-specific antibody and hyaluronidase or a variant thereof are for use in treating an inflammatory disorder or disease. In certain embodiments, the inflammatory disorder or disease is atopic dermatitis. In certain embodiments, the inflammatory disorder or disease is asthma; chronic sinusitis with nasal polyps; Chronic Rhinosinusitis without Nasal Polyps (CRSsNP); eosinophilic esophagitis (EoE); an Eosinophilic gastrointestinal disorder or disease (EGID), such as Eosinophilic Gastritis (EoG), Eosinophilic Enteritis (EoN), Eosinophilic Colitis (EoC), or Eosinophilic Gastroenteritis (EGE); Churg-Strauss syndrome/Eosinophilic granulomatosis with polyangiitis (EGPA); Prurigo Nodularis (PN); Chronic Spontaneous Urticaria (CSU); Chronic Pruritis of Unknown Origin (CPUO); Bullous Pemphigoid (BP); Cold Inducible Urticaria (ColdU); Allergic Fungal Rhinosinusitis (AFRS); Allergic Bronchopulmonary Aspergillosis (ABPA); Chronic Obstructive Pulmonary Disease (COPD); an inflammatory bowel disease, such as Crohn’s disease or ulcerative colitis; lupus; rheumatoid arthritis (RA); psoriasis; hidradenitis suppurativa; celiac disease; systemic sclerosis; idiopathic pulmonary fibrosis; alopecia areata; allergic rhinitis; eosinophilic fasciitis; scleromyxedema; scleredema; or nephrogenic systemic fibrosis. BRIEF DESCRIPTION OF THE FIGURES [00205] FIGURE 1 is a graph showing the ability of exemplary anti-hOX40L antibodies to bind to hOX40L-expressing CHO cells. [00206] FIGURE 2 is a graph showing the OD450-540 value with increasing concentration of the indicated antibody in the presence of hOX40L to determine the ability of the indicated antibodies to block the binding of hOX40L to hOX40. [00207] FIGURE 3 is a graph showing the luminescence units (RLU) with increasing concentration of the indicated antibody in the presence of cells that express hOX40 to determine the ability of the indicated antibodies to block the binding of hOX40L to hOX40. [00208] FIGURE 4A and FIGURE 4B are graphs showing the percent inhibition of OX40L and OX40L binding by the indicated antibody compared to a positive control. [00209] FIGURE 5A - FIGURE 5C are graphs showing inhibition of IFNgamma response in PBMC-CD4 T cell mixed lymphocyte reaction (MLR) with 100 nM, 20 nM and 4 nM concentrations of indicated antibodies. [00210] FIGURE 6A and FIGURE 6B are a set of graphs showing the concentration of the indicated antibody over time in the serum of cynomolgus monkeys after receiving a single dose of the indicated antibody. [00211] FIGURE 7A and FIGURE 7B show the ability of exemplary antibodies and dupilumab to inhibit IL-4 and IL-13 binding. [00212] FIGURE 8A and FIGURE 8B show the ability of exemplary antibodies and dupilumab to inhibit IL-4-induced and IL-13-induced STAT6 phosphorylation (pSTAT6). [00213] FIGURE 9A and FIGURE 9B show the ability of exemplary antibodies and dupilumab to inhibit IL-4- and/or IL-13-induced TARC secretion. [00214] FIGURE 10A and FIGURE 10B show the ability of exemplary antibodies and dupilumab to inhibit IL-4-induced and IL-13-induced proliferation of TF-1 cells. [00215] FIGURE 11A and FIGURE 11B show the serum concentration of exemplary antibodies (Construct 13 (mAb422), Construct 38 (mAb471), and dupilumab) over time after a single intravenous (FIGURE 11A) or subcutaneous (FIGURE 11B) administration of 25 mg/kg in non-human primates. [00216] FIGURE 12 is a heatmap depicting the changes in cytokine/chemokine levels of thymus and activation regulated chemokine (TARC), macrophage-derived chemokine (MDC), interleukin (IL)-13, IL-5, interferon gamma (IFNg), tumor necrosis factor alpha (TNFa), IL-31, and granulocyte-macrophage colony-stimulating factor (GM-CSF) in allogeneic lymphocyte reaction experiments performed on myeloid dendritic cells (mDCs) primed with recombinant human TSLP and allogeneic CD4-positive cells from four healthy volunteers treated with test article, Construct 38, Construct 114, a combination of Construct 38 and Construct 114, dupilumab, or amlitelimab, or unstimulated. Values are normalized to isotype control. DETAILED DESCRIPTION Definitions [00217] Unless otherwise defined, all terms of art, notations and other scientific terminology used herein are intended to have the meanings commonly understood by those of skill in the art. In some cases, terms with commonly understood meanings are defined herein for clarity and/or for ready reference, and the inclusion of such definitions herein should not necessarily be construed to represent a difference over what is generally understood in the art. The techniques and procedures described or referenced herein are generally well understood and commonly employed using conventional methodologies by those skilled in the art, such as, for example, the widely utilized molecular cloning methodologies described in Sambrook et al., Molecular Cloning: A Laboratory Manual 4th ed. (2012) Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY. As appropriate, procedures involving the use of commercially available kits and reagents are generally carried out in accordance with manufacturer-defined protocols and conditions unless otherwise noted. [00218] As used herein, the singular forms “a”, “an”, and “the” include plural references unless indicated otherwise. [00219] It is understood that aspects and embodiments of the invention described herein include “comprising,” “consisting,” and “consisting essentially of” aspects and embodiments. [00220] For all compositions described herein, and all methods using a composition described herein, the compositions can either comprise the listed components or steps, or can “consist essentially of” the listed components or steps. When a composition is described as “consisting essentially of” the listed components, the composition contains the components listed, and may contain other components which do not substantially affect the condition being treated, but do not contain any other components which substantially affect the condition being treated other than those components expressly listed; or, if the composition does contain extra components other than those listed which substantially affect the condition being treated, the composition does not contain a sufficient concentration or amount of the extra components to substantially affect the condition being treated. When a method is described as “consisting essentially of” the listed steps, the method contains the steps listed, and may contain other steps that do not substantially affect the condition being treated, but the method does not contain any other steps which substantially affect the condition being treated other than those steps expressly listed. As a non-limiting specific example, when a composition is described as ‘consisting essentially of’ a component, the composition may additionally contain any amount of pharmaceutically acceptable carriers, vehicles, or diluents and other such components which do not substantially affect the condition being treated. [00221] The term “vector,” as used herein, refers to a nucleic acid molecule capable of propagating another nucleic acid to which it is linked. The term includes the vector as a self- replicating nucleic acid structure as well as the vector incorporated into the genome of a host cell into which it has been introduced. Certain vectors are capable of directing the expression of nucleic acids to which they are operatively linked. Such vectors are referred to herein as “expression vectors.” [00222] The terms “host cell,” “host cell line,” and “host cell culture” are used interchangeably and refer to cells into which an exogenous nucleic acid has been introduced, and the progeny of such cells. Host cells include “transformants” (or “transformed cells”) and “transfectants” (or “transfected cells”), which each include the primary transformed or transfected cell and progeny derived therefrom. Such progeny may not be completely identical in nucleic acid content to a parent cell, and may contain mutations. A “recombinant host cell” or “host cell” refers to a cell that includes an exogenous polynucleotide, regardless of the method used for insertion, for example, direct uptake, transduction, f-mating, or other methods known in the art to create recombinant host cells. [00223] As used herein, the term “eukaryote” refers to organisms belonging to the phylogenetic domain Eukarya such as animals (including but not limited to, mammals, insects, reptiles, birds, etc.), ciliates, plants (including but not limited to, monocots, dicots, algae, etc.), fungi, yeasts, flagellates, microsporidia, protists, etc. [00224] As used herein, the term “prokaryote” refers to prokaryotic organisms. For example, a non-eukaryotic organism can belong to the Eubacteria (including but not limited to, Escherichia coli, Thermus thermophilus, Bacillus stearothermophilus, Pseudomonas fluorescens, Pseudomonas aeruginosa, Pseudomonas putida, etc.) phylogenetic domain, or the Archaea (including but not limited to, Methanococcus jannaschii, Methanobacterium thermoautotrophicum, Halobacterium such as Haloferax volcanii and Halobacterium species NRC-1, Archaeoglobus fulgidus, Pyrococcus furiosus, Pyrococcus horikoshii, Aeuropyrum pernix, etc.) phylogenetic domain. [00225] An “effective amount” or “therapeutically effective amount” as used herein refers to an amount of therapeutic compound, such as an anti-OX40L antibody, or an antigen binding fragment thereof, or an anti-IL-4Rα antibody, or an antigen binding fragment thereof, administered to an individual, either as a single dose or as part of a series of doses, which is effective to produce or contribute to a desired therapeutic effect, either alone or in combination with another therapeutic modality. Examples of a desired therapeutic effect are reducing an aberrant immune response, slowing or delaying disease development; stabilization of disease; and amelioration of one or more symptoms. An effective amount may be given in one or more dosages. [00226] The term “treating” (and variations thereof such as “treat” or “treatment”) refers to clinical intervention in an attempt to alter the natural course of a disease or condition in a subject in need thereof. Treatment can be performed during the course of clinical pathology. Desirable effects of treatment include preventing recurrence of disease, alleviation of symptoms, diminishment of any direct or indirect pathological consequences of the disease, preventing metastasis, decreasing the rate of disease progression, amelioration or palliation of the disease state, and remission or improved prognosis. [00227] The term “sufficient amount” means an amount sufficient to produce a desired effect, e.g., an amount sufficient to modulate an immune response in a subject. [00228] As used herein, the term “subject,” “patient,” or “individual” means a mammalian subject. Exemplary subjects include humans, monkeys, dogs, cats, mice, rats, cows, horses, camels, goats, rabbits, and sheep. In certain embodiments, the subject is a human. In some embodiments the subject has a disease or condition that can be treated with an antibody provided herein. In some aspects, the disease or condition is atopic dermatitis. In some aspects, the disease or condition is asthma. [00229] The term “in vitro” refers to processes that occur in a living cell growing separate from a living organism, e.g., growing in tissue culture. [00230] The term “in vivo” refers to processes that occur in a living organism. [00231] The term “package insert” is used to refer to instructions customarily included in commercial packages of therapeutic or diagnostic products (e.g., kits) that contain information about the indications, usage, dosage, administration, combination therapy, contraindications and/or warnings concerning the use of such therapeutic or diagnostic products. [00232] The term “pharmaceutical composition” refers to a preparation which is in such form as to permit the biological activity of one or more active ingredient(s) contained therein to be effective in treating a subject. [00233] As used herein, the term “pharmaceutically acceptable” refers to those compounds, materials, compositions and/or dosage forms, which are suitable for contact with the tissues of a subject, such as a mammal (e.g., a human) without excessive toxicity, irritation, allergic response and other problem complications commensurate with a reasonable benefit/risk ratio. 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. [00234] The terms “co-administration”, “co-administer”, and “in combination with” include the administration of two or more therapeutic agents either simultaneously, concurrently or sequentially within no specific time limits. In one embodiment, the agents are present in the cell or in the subject’s body at the same time or exert their biological or therapeutic effect at the same time. In one embodiment, the therapeutic agents are in the same composition or unit dosage form. In other embodiments, the therapeutic agents are in separate compositions or unit dosage forms. In certain embodiments, a first agent can be administered prior to the administration of a second therapeutic agent. [00235] The terms “modulate” and “modulation” refer to reducing or inhibiting or, alternatively, activating or increasing, a recited variable. [00236] The terms “increase” and “activate” refer to an increase of 10%, 20%, 30%, 40%, 50%, 60%, 70%, 75%, 80%, 85%, 90%, 95%, 100%, 2-fold, 3-fold, 4-fold, 5-fold, 10-fold, 20-fold, 50-fold, 100-fold, or greater in a recited variable. [00237] The terms “reduce” and “inhibit” refer to a decrease of 10%, 20%, 30%, 40%, 50%, 60%, 70%, 75%, 80%, 85%, 90%, 95%, 2-fold, 3-fold, 4-fold, 5-fold, 10-fold, 20-fold, 50-fold, 100-fold, or greater in a recited variable. [00238] The term “about” indicates and encompasses an indicated value and a range above and below that value. In certain embodiments, the term “about” indicates the designated value ± 10%, ± 5%, or ± 1%. In certain embodiments, where applicable, the term “about” indicates the designated value(s) ± one standard deviation of that value(s). [00239] The term “agonize” refers to the activation of receptor signaling to induce a biological response associated with activation of the receptor. An “agonist” is an entity that binds to and agonizes a receptor. [00240] The term “antagonize” refers to the inhibition of receptor signaling to inhibit a biological response associated with activation of the receptor. An “antagonist” is an entity that binds to and antagonizes a receptor. [00241] For any of the structural and functional characteristics described herein, methods of determining these characteristics are known in the art. [00242] The term “optionally” is meant, when used sequentially, to include from one to all of the enumerated combinations and contemplates all sub-combinations. [00243] The term “amino acid” refers to the twenty common naturally occurring amino acids. Naturally occurring amino acids include alanine (Ala; A), arginine (Arg; R), asparagine (Asn; N), aspartic acid (Asp; D), cysteine (Cys; C); glutamic acid (Glu; E), glutamine (Gln; Q), Glycine (Gly; G); histidine (His; H), isoleucine (Ile; I), leucine (Leu; L), lysine (Lys; K), methionine (Met; M), phenylalanine (Phe; F), proline (Pro; P), serine (Ser; S), threonine (Thr; T), tryptophan (Trp; W), tyrosine (Tyr; Y), and valine (Val; V). [00244] The term “affinity” refers to the strength of the sum total of non-covalent interactions between a single binding site of a molecule (e.g., an antibody) and its binding partner (e.g., an antigen or epitope). Unless indicated otherwise, as used herein, “affinity” refers to intrinsic binding affinity, which reflects a 1:1 interaction between members of a binding pair (e.g., antibody and antigen or epitope). [00245] The term “kd” (sec-1), as used herein, refers to the dissociation rate constant of a particular antibody- antigen interaction. This value is also referred to as the koff value. [00246] The term “ka” (M-1×sec-1), as used herein, refers to the association rate constant of a particular antibody-antigen interaction. This value is also referred to as the kon value. [00247] The term “KD” (M), as used herein, refers to the dissociation equilibrium constant of a particular antibody-antigen interaction. KD = kd/ka. In some embodiments, the affinity of an antibody is described in terms of the KD for an interaction between such antibody and its antigen. For clarity, as known in the art, a smaller KD value indicates a higher affinity interaction, while a larger KD value indicates a lower affinity interaction. [00248] The term “KA” (M-1), as used herein, refers to the association equilibrium constant of a particular antibody-antigen interaction. KA = ka/kd. [00249] As used herein, “administration” refers to providing or giving a subject a therapeutic agent (e.g., an anti-OX40L antibody, or an antigen binding fragment thereof, or an anti- IL-4Rα antibody, or an antigen binding fragment thereof, described herein) by any effective route. Exemplary routes of administration are described herein below. [00250] As used herein, the term “polypeptide” describes a single polymer in which the monomers are amino acid residues which are covalently conjugated together through amide bonds. A polypeptide is intended to encompass any amino acid sequence, either naturally occurring, recombinant, or synthetically produced. [00251] As used herein, the terms “nucleic acid” and “polynucleotide,” used interchangeably herein, refer to a polymeric form of nucleosides in any length. Typically, a polynucleotide is composed of nucleosides that are naturally found in DNA or RNA (e.g., adenosine, thymidine, guanosine, cytidine, uridine, deoxyadenosine, deoxythymidine, deoxyguanosine, and deoxycytidine) joined by phosphodiester bonds. The term encompasses molecules comprising nucleosides or nucleoside analogs containing chemically or biologically modified bases, modified backbones, etc., whether or not found in naturally occurring nucleic acids, and such molecules may be preferred for certain applications. Where this application refers to a polynucleotide it is understood that both DNA, RNA, and in each case both single- and double-stranded forms (and complements of each single-stranded molecule) are provided. [00252] As used herein, the terms “conservative mutation,” “conservative substitution,” and “conservative amino acid substitution” refer to a substitution of one or more amino acids for one or more different amino acids that exhibit similar physicochemical properties, such as polarity, electrostatic charge, and steric volume. These properties are summarized for each of the twenty naturally occurring amino acids in TABLE 1 below. TABLE 1. Representative physicochemical properties of naturally occurring amino acids Amino Acid 3 Letter 1 Letter Side-chain Electrostatic Steric Code Code Polarity character at Volume† te te te te te te te te From this table it is appreciated that the conservative amino acid families include (i) G, A, V, L and I; (ii) D and E; (iii) C, S and T; (iv) H, K and R; (v) N and Q; and (vi) F, Y and W. A conservative mutation or substitution is therefore one that substitutes one amino acid for a member of the same amino acid family (e.g., a substitution of Ser for Thr or Lys for Arg). [00253] The term “antibody” is used herein in its broadest sense and includes certain types of immunoglobulin molecules comprising one or more antigen-binding domains that specifically bind to an antigen or epitope. An antibody specifically includes intact antibodies (e.g., intact immunoglobulins), antibody fragments, and multi-specific antibodies. [00254] A “anti-OX40L antibody,” “OX40L antibody,” or “OX40L specific antibody” is an antibody, as provided herein, which specifically binds to the antigen OX40L. [00255] A “OX40L antigen binding region,” “anti-OX40L antigen binding region,” or “OX40L-specific antigen binding region” is an antigen binding region of a multi-specific antibody, as provided herein, which specifically binds to the antigen OX40L. In some embodiments, the OX40L antigen binding region binds the extracellular domain of OX40L. [00256] A “anti-IL-4Rα antibody,” “IL-4Rα antibody,” or “IL-4Rα specific antibody” is an antibody, as provided herein, which specifically binds to the antigen IL-4Rα. [00257] A “IL-4Rα antigen binding region,” “anti-IL-4Rα antigen binding region,” or “IL- 4Rα-specific antigen binding region” is an antigen binding region of a multi-specific antibody, as provided herein, which specifically binds to the antigen IL-4Rα. [00258] The term “multi-specific antibody” is used herein in its broadest sense to include molecules comprising polypeptides that have the capability of binding to two or more distinct antigens. Multi-specific antibodies include antibodies comprising two or more antigen binding domains that have affinity to one or more antigens, such as, for example, a bispecific antibody. [00259] The term “epitope” means a portion of an antigen that specifically binds to an antibody. [00260] The term “hypervariable region” or “HVR”, as used herein, refers to each of the regions of an antibody variable domain which are hypervariable in sequence and/or form structurally defined loops (“hypervariable loops”). [00261] The term “antigen-binding domain” means the portion of an antibody that is capable of specifically binding to an antigen or epitope. [00262] The term “chimeric antibody” refers to an antibody in which a portion of the heavy and/or light chain is derived from a particular source or species, while the remainder of the heavy and/or light chain is derived from a different source or species. [00263] The term “human antibody” refers to an antibody which possesses an amino acid sequence corresponding to that of an antibody produced by a human or a human cell, or derived from a non-human source that utilizes a human antibody repertoire or human antibody-encoding sequences (e.g., obtained from human sources or designed de novo). Human antibodies specifically exclude humanized antibodies. [00264] The term “humanized antibody” refers to a protein having a sequence that differs from the sequence of an antibody derived from a non-human species by one or more amino acid substitutions, deletions, and/or additions, such that the humanized antibody is less likely to induce an immune response, and/or induces a less severe immune response, as compared to the non-human species antibody, when it is administered to a human subject. [00265] The term “multispecific antibody” refers to an antibody that comprises two or more different antigen-binding domains that collectively specifically bind two or more different epitopes. [00266] A “monospecific antibody” is an antibody that comprises one or more binding sites that specifically bind to a single epitope. An example of a monospecific antibody is a naturally occurring IgG molecule which, while divalent (i.e., having two antigen-binding domains), recognizes the same epitope at each of the two antigen-binding domains. The binding specificity may be present in any suitable valency. [00267] The term “monoclonal antibody” refers to an antibody from a population of substantially homogeneous antibodies. A population of substantially homogeneous antibodies comprises antibodies that are substantially similar and that bind the same epitope(s), except for variants that may normally arise during production of the monoclonal antibody. Such variants are generally present in only minor amounts. A monoclonal antibody is typically obtained by a process that includes the selection of a single antibody from a plurality of antibodies. For example, the selection process can be the selection of a unique clone from a plurality of clones, such as a pool of hybridoma clones, phage clones, yeast clones, bacterial clones, or other recombinant DNA clones. The selected antibody can be further altered, for example, to improve affinity for the target (“affinity maturation”), to humanize the antibody, to improve its production in cell culture, and/or to reduce its immunogenicity in a subject. [00268] The term “single-chain” refers to a molecule comprising amino acid monomers linearly linked by peptide bonds. In a particular such embodiment, the C-terminus of the Fab light chain is connected to the N-terminus of the Fab heavy chain in the single-chain Fab molecule. As described in more detail herein, an scFv has a variable domain of light chain (VL) connected from its C-terminus to the N-terminal end of a variable domain of heavy chain (VH) by a polypeptide chain. Alternately the scFv comprises of polypeptide chain where in the C-terminal end of the VH is connected to the N-terminal end of VL by a polypeptide chain. [00269] The “Fab fragment” (also referred to as fragment antigen-binding) contains the constant domain (CL) of the light chain and the first constant domain (CH1) of the heavy chain along with the variable domains VL and VH on the light and heavy chains respectively. The variable domains comprise the complementarity determining loops (CDR, also referred to as hypervariable region) that are involved in antigen-binding. Fab′ fragments differ from Fab fragments by the addition of a few residues at the carboxy terminus of the heavy chain CH1 domain including one or more cysteines from the antibody hinge region. [00270] “F(ab’)2” fragments contain two Fab’ fragments joined, near the hinge region, by disulfide bonds. F(ab’)2 fragments may be generated, for example, by recombinant methods or by pepsin digestion of an intact antibody. The F(ab’) fragments can be dissociated, for example, by treatment with ß-mercaptoethanol. [00271] “Fv” fragments comprise a non-covalently-linked dimer of one heavy chain variable domain and one light chain variable domain. [00272] “Single-chain Fv” or “sFv” or “scFv” includes the VH and VL domains of an antibody, wherein these domains are present in a single polypeptide chain. In one embodiment, the Fv polypeptide further comprises a polypeptide linker between the VH and VL domains which enables the scFv to form the desired structure for antigen-binding. For a review of scFv see Pluckthun in The Pharmacology of Monoclonal Antibodies, vol.113, Rosenburg and Moore eds., Springer-Verlag, New York, pp.269-315 (1994). HER2 antibody scFv fragments are described in WO93/16185; U.S. Pat. No.5,571,894; and U.S. Pat. No. 5,587,458. [00273] “scFv-Fc” fragments comprise an scFv attached to an Fc domain. For example, an Fc domain may be attached to the C-terminal of the scFv. The Fc domain may follow the VH or VL, depending on the orientation of the variable domains in the scFv (i.e., VH-VL or VL- VH). Any suitable Fc domain known in the art or described herein may be used. In some cases, the Fc domain comprises an IgG4 Fc domain. [00274] The term “single domain antibody” or “sdAb” refers to a molecule in which one variable domain of an antibody specifically binds to an antigen without the presence of the other variable domain. Single domain antibodies, and fragments thereof, are described in Arabi Ghahroudi et al., FEBS Letters, 1998, 414:521-526 and Muyldermans et al., Trends in Biochem. Sci., 2001, 26:230-245, each of which is incorporated by reference in its entirety. Single domain antibodies are also known as sdAbs or nanobodies. SdAbs are fairly stable and easy to express as fusion partner with the Fc chain of an antibody (Harmsen MM, De Haard HJ (2007). “Properties, production, and applications of camelid single-domain antibody fragments”. Appl. Microbiol Biotechnol.77(1): 13-22). [00275] The terms “full length antibody,” “intact antibody,” and “whole antibody” are used herein interchangeably to refer to an antibody having a structure substantially similar to a naturally occurring antibody structure and having heavy chains that comprise an Fc region. For example, when used to refer to an IgG molecule, a “full length antibody” is an antibody that comprises two heavy chains and two light chains. [00276] The term “antibody fragment” refers to an antibody that comprises a portion of an intact antibody, such as the antigen-binding or variable region of an intact antibody. Antibody fragments include, for example, Fv fragments, Fab fragments, F(ab’)2 fragments, Fab’ fragments, scFv (sFv) fragments, and scFv-Fc fragments. [00277] The term “Fc domain” or “Fc region” herein is used to define a C-terminal region of an immunoglobulin heavy chain that contains at least a portion of the constant region. The term includes native sequence Fc regions and variant Fc regions. [00278] The term “substantially purified” refers to a construct described herein, or variant thereof that may be substantially or essentially free of components that normally accompany or interact with the protein as found in its naturally occurring environment, i.e. a native cell, or host cell in the case of a recombinantly produced antibody, that in certain embodiments, is substantially free of cellular material includes preparations of protein having less than about 30%, less than about 25%, less than about 20%, less than about 15%, less than about 10%, less than about 5%, less than about 4%, less than about 3%, less than about 2%, or less than about 1% (by dry weight) of contaminating protein. [00279] The term percent “identity,” in the context of two or more nucleic acid or polypeptide sequences, refer to two or more sequences or subsequences that have a specified percentage of nucleotides or amino acid residues that are the same, when compared and aligned for maximum correspondence, as measured using one of the sequence comparison algorithms described below (e.g., using publicly available computer software such as BLAST, BLASTP, BLASTN, BLAST-2, ALIGN, MEGALIGN (DNASTAR), CLUSTALW, CLUSTAL OMEGA, or MUSCLE software or other algorithms available to persons of skill) or by visual inspection. Software for performing BLAST analyses is publicly available through the National Center for Biotechnology Information (ncbi.nlm.nih.gov). Those skilled in the art can determine appropriate parameters for aligning sequences, including any algorithms needed to achieve maximal alignment over the full length of the sequences being compared. Depending on the application, the percent “identity” can exist over a region of the sequence being compared, e.g., over a functional domain, or, alternatively, exist over the full length of the two sequences to be compared. [00280] For sequence comparison, typically one sequence acts as a reference sequence to which test sequences are compared. When using a sequence comparison algorithm, test and reference sequences are input into a computer, subsequence coordinates are designated, if necessary, and sequence algorithm program parameters are designated. The sequence comparison algorithm then calculates the percent sequence identity for the test sequence(s) relative to the reference sequence, based on the designated program parameters. [00281] Optimal alignment of sequences for comparison can be conducted, e.g., by the local homology algorithm of Smith & Waterman, Adv. Appl. Math.2:482 (1981), by the homology alignment algorithm of Needleman & Wunsch, J. Mol. Biol.48:443 (1970), by the search for similarity method of Pearson & Lipman, Proc. Nat’l. Acad. Sci. USA 85:2444 (1988), by computerized implementations of these algorithms (GAP, BESTFIT, FASTA, and TFASTA in the Wisconsin Genetics Software Package, Genetics Computer Group, 575 Science Dr., Madison, Wis.), or by visual inspection (see generally Ausubel et al., infra). [00282] Ranges recited herein are understood to be shorthand for all of the values within the range, inclusive of the recited endpoints. For example, a range of 1 to 50 is understood to include any number, combination of numbers, or sub-range from the group consisting of 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, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, and 50. [00283] It must be noted that, as used in the specification and the appended claims, the singular forms “a,” “an” and “the” include plural referents unless the context clearly dictates otherwise. [00284] The term "atopic dermatitis disease severity outcome measure" refers to a determination of certain signs, symptoms, features or parameters that have been associated with atopic dermatitis and that can be quantitatively or qualitatively assessed. Exemplary atopic dermatitis disease severity outcome measures include "Eczema Area and Severity Index" (EASI), "Severity Scoring of Atopic Dermatitis" (SCORAD), "Validated Investigator Global Assessment-Atopic Dermatitis" (vIGA-AD), "Investigator Global Assessment of Signs" (IGSA), Rajka/Langeland Atopic Dermatitis Severity Score, “Body Surface Area” (BSA), and Patient-Reported Outcomes including Pruritus Visual Analog Scale (an aspect of disease severity assessed as part of SCORAD), Sleep Loss Visual Analog Scale (an aspect of disease severity assessed as part of SCORAD), Atopic Dermatitis Symptom Diary (ADSD), Atopic Dermatitis Impact Questionnaire (ADIQ), Dermatology Life Quality Index (DLQI) (Finlay and Khan, Clin Exper Dermatol 1994;19:210), 5-D Itch Scale (Elman et al., Br J Dermatol 2010;162(3):587-593), Itch Numeric Rating Scale (I-NRS) (see Naegeli et al., International Journal of Dermatology.2015;54(6):715-722; and Newton L, et al., J. Patient Rep. Outcomes.2019;3(1):42), and the Patient-Oriented Eczema Measure (POEM) (www.nottingham.ac.uk/research/groups/cebd/resources/poem.aspx). [00285] Hyaluronidases [00286] As used herein, “hyaluronidase” refers to an enzyme that degrades hyaluronic acid, which constitutes an essential part of the extracellular matrix. Included in this definition are naturally occurring hyaluronidases, recombinant hyaluronidases, both human and from other sources, as well as variants thereof. Such hyaluronidases include, but are not limited to, nonhuman hyaluronidases, including bacterial hyaluronidases, bovine hyaluronidases, ovine hyaluronidases, and variants thereof. Reference to hyaluronidase refers to all forms, including variants. [00287] Hyaluronidases were initially discovered in bacteria, and are now known to be widely distributed in nature and have been found in many different species, including insects, snakes, and mammals. Human hyaluronidase is present both in organs (e.g., testis, spleen, skin, eyes, liver, kidneys, uterus, and placenta) and in body fluids (e.g., tears, blood, and semen). In the human, six different hyaluronidases, HYAL1-4, HYAL-P1 and PH-20, have been identified. PH-20 exerts the strongest biologic activity, is found in high concentrations in the testicles, and can be localized on the head and the acrosome of human spermatozoa (see, e.g., Weber GC, et al., Adv. Exp. Med. Biol.2019;1148:255-277). [00288] Hyaluronidases are classified into three categories according to their mechanism of action (see, e.g., Jung H., Arch. Plast. Surg.2020 Jul;47(4):297-300). First, mammalian hyaluronidases are endo-β-N-acetylhexosaminidases that break down β-1,4 glycosidic linkages to form tetrasaccharides. Second, leech/hookworm hyaluronidases are endo-β-D- glucuronidases that break down β-1,3 glycosidic bonds to form pentasaccharides and hexasaccharides. Finally, microbial hyaluronidases are classified as hyaluronate lyases. Unlike other hyaluronidases, they do not catalyze hydrolysis reactions. Instead, they produce unsaturated disaccharides through a β-elimination reaction at β-1,4 glycosidic linkage. [00289] Hyaluronidases can also be classified into two types according to the pH at which they are most active (see, e.g., Jung H., Arch. Plast. Surg.2020 Jul;47(4):297-300). Acid- active hyaluronidases are activated at a pH of 3 to 4. Neutral-active hyaluronidases, which include the hyaluronidase enzymes found in snake and bee venom, are activated at a pH of 5 to 8 (see, e.g., Cavallini M, et al., Aesthet. Surg. J.2013;33:1167–74). [00290] Hyaluronidase use has become more diverse and widespread in clinical practice. Today, animal-derived bovine or ovine testicular hyaluronidases, as well as synthetic hyaluronidases, are clinically applied as adjuncts to increase the bioavailability of drugs, for the therapy of extravasations, or for the management of complications associated with the aesthetic injection of hyaluronic acid-based fillers. [00291] Examples of hyaluronan degrading enzymes are hyaluronidases, and particular chondroitinases and lyases that have the ability to depolymerize hyaluronan. Exemplary chondroitinases that are hyaluronan degrading enzymes include, but are not limited to, chondroitin ABC lyase (also known as chondroitinase ABC), chondroitin AC lyase (also known as chondroitin sulfate lyase or chondroitin sulfate eliminase) and chondroitin C lyase. Chondroitin ABC lyase comprises two enzymes, chondroitin-sulfate-ABC endolyase (EC 4.2.2.20) and chondroitin-sulfate-ABC exolyase (EC 4.2.2.21). Exemplary chondroitin- sulfate-ABC endolyases and chondroitin-sulfate-ABC exolyases include, but are not limited to, those from Proteus vulgaris and Flavobacterium heparinum (the Proteus vulgaris chondroitin-sulfate-ABC endolyase (e.g., see Sato et al. (1994) Appl. Microbiol. Biotechnol. 41(1):39-46)). Exemplary chondroitinase AC enzymes from the bacteria include, but are not limited to, those from Flavobacterium heparinum, Victivallis vadensis, and Arthrobacter aurescens (see, e.g., Tkalec et al. (2000) Applied and Environmental Microbiology 66(1):29- 35; Ernst et al. (1995) Critical Reviews in Biochemistry and Molecular Biology 30(5):387- 444). Exemplary chondroitinase C enzymes from the bacteria include, but are not limited to, those from Streptococcus and Flavobacterium (Hibi et al. (1989) FEMS-Microbiol-Lett. 48(2):121-4; Michelacci et al. (1976) J. Biol. Chem.251:1154-8; Tsuda et al. (1999) Eur. J. Biochem.262:127-133). [00292] Hyaluronidases include bacterial hyaluronidases (EC 4.2.2.1 or EC 4.2.99.1), hyaluronidases from leeches, other parasites, and crustaceans (EC 3.2.1.36), and mammalian- type hyaluronidases (EC 3.2.1.35). Hyaluronidases include any of non-human origin including, but not limited to, murine, canine, feline, leporine, avian, bovine, ovine, porcine, equine, piscine, ranine, bacterial, and any from leeches, other parasites, and crustaceans. Exemplary non-human hyaluronidases include, hyaluronidases from cows (SEQ ID NOs:10, 11, 64 of US Patent No.: 8,568,713) and BH55 (U.S. Pat. Nos.5,747,027 and 5,827,721), yellow jacket wasp (SEQ ID NOs:12 and 13 of US Patent No.: 8,568,713), honey bee (SEQ ID NO:14 of US Patent No.: 8,568,713), white-face hornet (SEQ ID NO:15 of US Patent No.: 8,568,713), paper wasp (SEQ ID NO:16 of US Patent No.: 8,568,713), mouse (SEQ ID NOs:17-19, and 32 of US Patent No.: 8,568,713), pig (SEQ ID NOs:20-21of US Patent No.: 8,568,713), rat (SEQ ID NOs:22-24, and 31 of US Patent No.: 8,568,713), rabbit (SEQ ID NO:25 of US Patent No.: 8,568,713), sheep (SEQ ID NOs:26, 27, 63 and 65 of US Patent No.: 8,568,713), orangutan (SEQ ID NO:28 of US Patent No.: 8,568,713), cynomolgus monkey (SEQ ID NO:29 of US Patent No.: 8,568,713), guinea pig (SEQ ID NO:30 of US Patent No.: 8,568,713), Arthrobacter sp. (strain FB24) (SEQ ID NO:67 of US Patent No.: 8,568,713), Bdellovibrio bacteriovorus (SEQ ID NO:68 of US Patent No.: 8,568,713), Propionibacterium acnes (SEQ ID NO:69 of US Patent No.: 8,568,713), Streptococcus agalactiae ((SEQ ID NO:70 of US Patent No.: 8,568,713); 18RS21 (SEQ ID NO:71 of US Patent No.: 8,568,713 ); serotype Ia (SEQ ID NO:72 of US Patent No.: 8,568,713); serotype III (SEQ ID NO:73 of US Patent No.: 8,568,713), Staphylococcus aureus (strain COL) (SEQ ID NO:74 of US Patent No.: 8,568,713 ); strain MRSA252 (SEQ ID NOs:75 and 76 of US Patent No.: 8,568,713 of US Patent No.: 8,568,713); strain MSSA476 (SEQ ID NO:77 of US Patent No.: 8,568,713); strain NCTC 8325 (SEQ ID NO:78 of US Patent No.: 8,568,713 ); strain bovine RF122 (SEQ ID NOs:79 and 80 of US Patent No.: 8,568,713); strain USA300 (SEQ ID NO:81 of US Patent No.: 8,568,713), Streptococcus pneumoniae (SEQ ID NO:82 of US Patent No.: 8,568,713); strain ATCC BAA-255/R6 (SEQ ID NO:83 of US Patent No.: 8,568,713); serotype 2, strain D39/NCTC 7466 (SEQ ID NO:84 of US Patent No.: 8,568,713), Streptococcus pyogenes (serotype (SEQ ID NO:85 of US Patent No.: 8,568,713); serotype M2, strain MGAS10270 (SEQ ID NO:86 of US Patent No.: 8,568,713); serotype M4, strain MGAS10750 (SEQ ID NO:87 of US Patent No.: 8,568,713); serotype M6 (SEQ ID NO:88 of US Patent No.: 8,568,713); serotype M12, strain MGAS2096 (SEQ ID NOs:89 and 90 of US Patent No.: 8,568,713); serotype M12, strain MGAS9429 (SEQ ID NO:91 of US Patent No.: 8,568,713); serotype M28 (SEQ ID NO:92 of US Patent No.: 8,568,713); Streptococcus suis (SEQ ID NOs:93-95 of US Patent No.: 8,568,713 ); Vibrio fischeri (strain ATCC 700601/ES114 (SEQ ID NO:96 of US Patent No.: 8,568,713), and the Streptomyces hyaluronolyticus hyaluronidase enzyme, which is specific for hyaluronic acid and does not cleave chondroitin or chondroitin sulfate (Ohya, T. and Kaneko, Y. (1970) Biochim. Biophys. Acta 198:607). Hyaluronidases also include those of human origin. Exemplary human hyaluronidases include PH20, HYAL1 (SEQ ID NO:36 of US Patent No.: 8,568,713), HYAL2 (SEQ ID NO:37 of US Patent No.: 8,568,713), HYAL3 (SEQ ID NO:38 of US Patent No.: 8,568,713), and HYAL4 (SEQ ID NO:36 of US Patent No.: 8,568,713). The sequences and contents of US Patent No.8,568,713 are expressly incorporated herein by reference. Also included amongst hyaluronidases are soluble hyaluronidases, including, ovine and bovine PH20, soluble human PH20 and soluble rHuPH20. Examples of commercially available bovine or ovine soluble hyaluronidases are Vitrase® (ovine hyaluronidase) and Amphadase ® (bovine hyaluronidase). [00293] Hyaluronidases as described herein include precursor hyaluronan degrading enzyme polypeptides and mature hyaluronan degrading enzyme polypeptides (such as those in which a signal sequence has been removed), truncated forms thereof that have activity, and includes allelic variants and species variants, variants encoded by splice variants, and other variants, including polypeptides that have at least 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or more sequence identity to the polypeptides set forth in SEQ ID NOs:1076-1085 and 1087-1142. Hyaluronidases also include those that contain chemical or posttranslational modifications and those that do not contain chemical or posttranslational modifications. Such modifications include, but are not limited to, pegylation, albumination, glycosylation, farnesylation, carboxylation, hydroxylation, phosphorylation, and other polypeptide modifications known in the art. [00294] As used herein, a soluble hyaluronidase refers to a polypeptide characterized by its solubility under physiologic conditions. Soluble hyaluronidases can be distinguished, for example, by its partitioning into the aqueous phase of a Triton X-114 solution warmed to 37 ºC. (Bordier et al., (1981) J. Biol. Chem., 256:1604-7). Membrane-anchored, such as lipid anchored hyaluronidases, will partition into the detergent rich phase, but will partition into the detergent-poor or aqueous phase following treatment with Phospholipase-C. Included among soluble hyaluronidases are membrane anchored hyaluronidases in which one or more regions associated with anchoring of the hyaluronidase to the membrane has been removed or modified, where the soluble form retains hyaluronidase activity. Soluble hyaluronidases include recombinant soluble hyaluronidases and those contained in or purified from natural sources. [00295] As used herein, activity refers to a functional activity or activities of a polypeptide or portion thereof associated with a full-length (complete) protein. Functional activities include, but are not limited to, biological activity, catalytic or enzymatic activity, antigenicity (ability to bind or compete with a polypeptide for binding to an anti-polypeptide antibody), immunogenicity, ability to form multimers, and the ability to specifically bind to a receptor or ligand for the polypeptide. [00296] As used herein, hyaluronidase activity refers to the ability to enzymatically catalyze the cleavage of hyaluronic acid. The United States Pharmacopeia (USP) XXII assay for hyaluronidase determines hyaluronidase activity indirectly by measuring the amount of higher molecular weight hyaluronic acid, or hyaluronan, (HA) substrate remaining after the enzyme is allowed to react with the HA for 30 min at 37 ºC (USP XXII-NF XVII (1990) 644- 645 United States Pharmacopeia Convention, Inc, Rockville, Md.). A Reference Standard solution can be used in an assay to ascertain the relative activity, in units, of any hyaluronidase. In vitro assays to determine the hyaluronidase activity of hyaluronidases, such as soluble rHuPH20, are known in the art. Exemplary assays include the microturbidity assay (see e.g., Example 3 of US Patent No.:8,568,713) that measures cleavage of hyaluronic acid by hyaluronidase indirectly by detecting the insoluble precipitate formed when the uncleaved hyaluronic acid binds with serum albumin. Reference Standards can be used, for example, to generate a standard curve to determine the activity in Units of the hyaluronidase being tested. [00297] As used herein, "functionally equivalent amount" or grammatical variations thereof, with reference to a hyaluronan degrading enzyme, refers to the amount of hyaluronan degrading enzyme that achieves the same effect as an amount (such as a known number of Units of hyaluronidase activity) of a reference enzyme, such as a hyaluronidase. For example, the activity of any hyaluronan degrading enzyme can be compared to the activity of rHuPH20 to determine the functionally equivalent amount of a hyaluronan degrading enzyme that would achieve the same effect as a known amount of rHuPH20. For example, the ability of a hyaluronan degrading enzyme to act as a spreading or diffusing agent can be assessed by injecting it into the lateral skin of mice with trypan blue (see e.g. U.S. Pat. Publication No. 20050260186), and the amount of hyaluronan degrading enzyme required to achieve the same amount of diffusion as, for example, 100 units of a Hyaluronidase Reference Standard, can be determined. The amount of hyaluronan degrading enzyme required is, therefore, functionally equivalent to 100 units. [00298] Exemplary hyaluronan degrading enzymes are hyaluronidases, particularly soluble hyaluronidases, such as a PH20, or a truncated or variant form thereof. The PH20 can be, for example, an ovine, bovine or truncated human PH20. The human PH20 mRNA transcript is normally translated to generate a 509 amino acid precursor polypeptide (SEQ ID NO:1076; and replicated below) containing a 35 amino acid signal sequence at the N-terminus (amino acid residue positions 1-35) and a 19 amino acid glycosylphosphatidylinositol (GPI) anchor attachment signal sequence at the C-terminus (amino acid residue positions 491-509). The mature PH20 is, therefore, a 474 amino acid polypeptide set forth in SEQ ID NO:1077. Following transport of the precursor polypeptide to the ER and removal of the signal peptide, the C-terminal GPI-attachment signal peptide is cleaved to facilitate covalent attachment of a GPI anchor to the newly-formed C-terminal amino acid at the amino acid position corresponding to position 490 of the precursor polypeptide set forth in SEQ ID NO:1076. Thus, a 474 amino acid GPI-anchored mature polypeptide with an amino acid sequence set forth in SEQ ID NO:1077 is produced. [00299] The amino acid sequence of the human PH20 precursor polypeptide (SEQ ID NO: 1076; 509 amino acids) is as follows: MGVLKFKHIFFRSFVKSSGVSQIVFTFLLIPCCLTLNFRAPPVIPNVPFLWAWNAPSEF CLGKFDEPLDMSLFSFIGSPRINATGQGVTIFYVDRLGYYPYIDSITGVTVNGGIPQKIS LQDHLDKAKKDITFYMPVDNLGMAVIDWEEWRPTWARNWKPKDVYKNRSIELVQ QQNVQLSLTEATEKAKQEFEKAGKDFLVETIKLGKLLRPNHLWGYYLFPDCYNHHY KKPGYNGSCFNVEIKRNDDLSWLWNESTALYPSIYLNTQQSPVAATLYVRNRVREAI RVSKIPDAKSPLPVFAYTRIVFTDQVLKFLSQDELVYTFGETVALGASGIVIWGTLSIM RSMKSCLLLDNYMETILNPYIINVTLAAKMCSQVLCQEQGVCIRKNWNSSDYLHLNP DNFAIQLEKGGKFTVRGKPTLEDLEQFSEKFYCSCYSTLSCKEKADVKDTDAVDVCI ADGVCIDAFLKPPMETEEPQIFYN ASPSTLSATMFIVSILFLIISSVASL. [00300] The amino acid sequence of the mature PH20 polypeptide (SEQ ID NO: 1077; 474 amino acids) is as follows: LNFRAPPVIPNVPFLWAWNAPSEFCLGKFDEPLDMSLFSFIGSPRINATGQGVTIFYVD RLGYYPYIDSITGVTVNGGIPQKISLQDHLDKAKKDITFYMPVDNLGMAVIDWEEWR PTWARNWKPKDVYKNRSIELVQQQNVQLSLTEATEKAKQEFEKAGKDFLVETIKLG KLLRPNHLWGYYLFPDCYNHHYKKPGYNGSCFNVEIKRNDDLSWLWNESTALYPSI YLNTQQSPVAATLYVRNRVREAIRVSKIPDAKSPLPVFAYTRIVFTDQVLKFLSQDEL VYTFGETVALGASGIVIWGTLSIMRSMKSCLLLDNYMETILNPYIINVTLAAKMCSQV LCQEQGVCIRKNWNSSDYLHLNPDNFAIQLEKGGKFTVRGKPTLEDLEQFSEKFYCS CYSTLSCKEKADVKDTDAVDVCIADGVCIDAFLKPPMETEEPQIFYNASPSTLSATMF IVSILFLIISSVASL. [00301] Human PH20 exhibits hyaluronidase activity at both neutral and acid pH. In one aspect, human PH20 is the prototypical neutral-active hyaluronidase that is generally locked to the plasma membrane via a GPI anchor. In another aspect, PH20 is expressed on the inner acrosomal membrane where it has hyaluronidase activity at both neutral and acid pH. It appears that PH20 contains two catalytic sites at distinct regions of the polypeptide: the Peptide 1 and Peptide 3 regions (Cherr et al., (2001) Matrix Biology 20:515-525). Evidence suggests that the Peptide 1 region of PH20, which corresponds to amino acid positions 107- 137 of the mature polypeptide set forth in SEQ ID NO:1077 and positions 142-172 of the precursor polypeptide set forth in SEQ ID NO:1076, is required for enzyme activity at neutral pH. Amino acids at positions 111 and 113 (corresponding to the mature PH20 polypeptide set forth in SEQ ID NO:1077) within this region appear to be important for activity, as mutagenesis by amino acid replacement results in PH20 polypeptides with 3% hyaluronidase activity or undetectable hyaluronidase activity, respectively, compared to the wild-type PH20 (Arming et al., (1997) Eur. J. Biochem.247:810-814) [00302] The Peptide 3 region, which corresponds to amino acid positions 242-262 of the mature polypeptide set forth in SEQ ID NO:1077, and positions 277-297 of the precursor polypeptide set forth in SEQ ID NO:1076, appears to be important for enzyme activity at acidic pH. Within this region, amino acids at positions 249 and 252 of the mature PH20 polypeptide appear to be essential for activity, and mutagenesis of either one results in a polypeptide essentially devoid of activity (Arming et al., (1997) Eur. J. Biochem.247:810- 814). [00303] In addition to the catalytic sites, PH20 also contains a hyaluronan-binding site. Experimental evidence suggest that this site is located in the Peptide 2 region, which corresponds to amino acid positions 205-235 of the precursor polypeptide set forth in SEQ ID NO:1076 and positions 170-200 of the mature polypeptide set forth in SEQ ID NO:1077. This region is highly conserved among hyaluronidases and is similar to the heparin binding motif. Mutation of the arginine residue at position 176 (corresponding to the mature PH20 polypeptide set forth in SEQ ID NO:1077) to a glycine results in a polypeptide with only about 1% of the hyaluronidase activity of the wild type polypeptide (Arming et al., (1997) Eur. J. Biochem.247:810-814). [00304] There are seven potential N-linked glycosylation sites in human PH20 at N82, N166, N235, N254, N368, N393, N490 of the polypeptide exemplified in SEQ ID NO:1076. Because amino acids 36 to 464 of SEQ ID NO:1076 appear to contain the minimally active human PH20 hyaluronidase domain, the N-linked glycosylation site N-490 is not required for proper hyaluronidase activity. There are six disulfide bonds in human PH20. Two disulfide bonds between the cysteine residues C60 and C351 and between C224 and C238 of the polypeptide exemplified in SEQ ID NO:1076 (corresponding to residues C25 and C316, and C189 and C203 of the mature polypeptide set forth in SEQ ID NO:1077, respectively). A further four disulfide bonds are formed between the cysteine residues C376 and C387; between C381 and C435; between C437 and C443; and between C458 and C464 of the polypeptide exemplified in SEQ ID NO: 1076 (corresponding to residues C341 and C352; between C346 and C400; between C402 and C408; and between C423 and C429 of the mature polypeptide set forth in SEQ ID NO:1077, respectively). [00305] As used herein, soluble recombinant human PH20 (rHuPH20) refers to a soluble form of human PH20 that is recombinantly expressed in Chinese Hamster Ovary (CHO) cells. Soluble human PH20 or sHuPH20 includes mature polypeptides lacking all or a portion of the glycosylphospatidylinositol (GPI) attachment site at the C-terminus such that upon expression, the polypeptides are soluble. [00306] Soluble rHuPH20 is encoded by a nucleic acid that includes the signal sequence and is set forth in SEQ ID NO:1086. Also included are DNA molecules that are allelic variants thereof and other soluble variants. The nucleic acid encoding soluble rHuPH20 is expressed in CHO cells which secrete the mature polypeptide. Accordingly, exemplary sHuPH20 polypeptides include mature polypeptides having an amino acid sequence set forth in any one of SEQ ID NOs:1078-1085 and 1087-1142. Other variants can have 60%, 70%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more sequence identity to any of SEQ ID NOs: 1078-1085 and 1087-1142, as long they retain a hyaluronidase activity and are soluble. Corresponding allelic variants and other variants also are included, including those corresponding to the precursor human PH20 polypeptide set forth in SEQ ID NO: 1076 and the mature human PH20 polypeptide set forth in SEQ ID NO: 1077. [00307] rHuPH20 was approved by the US Food and Drug Administration in 2005 as an adjuvant to increase the dispersion and absorption of other injected drugs. Recombinant human hyaluronidase PH20 is a transiently and locally-acting permeation enhancer that increases the dispersion and absorption of other injected agents. Recombinant human hyaluronidase PH20 depolymerizes hyaluronic acid (HA) at the injection site causing rapid decrease in the viscosity of the extracellular matrix, allowing bulk fluid flow and facilitating dispersion and absorption of coadministered agents (rHuPH20 Investigator’s Brochure, 2018). [00308] rHuPH20 is a glycosylated single chain protein with up to 447 amino acids, synthesized in CHO cells. Recombinant human hyaluronidase PH20 degrades HA under physiologic conditions and acts as a spreading factor in vivo. Therefore, when combined (co- mixed) or co-formulated with certain injectable drugs, rHUPH20 facilitates the absorption and dispersion of these drugs by temporarily reducing resistance to bulk fluid flow in the subcutaneous space. The permeability barrier in these tissues is restored to pre-injection levels within 24 to 48 hours after injection of rHuPH20. [00309] Any suitable hyaluronidase (e.g., a recombinant human hyaluronidase) can be used in the methods described herein, including, but not limited to, those described in US Patent No.: 7,767,429 (e.g., SEQ ID NO:1), US Patent No.: 7,846,431 (e.g., SEQ ID NO:1), US Patent No.: 7,871,607 (e.g., SEQ ID NO:1), US Patent No.: 8,105,586 (e.g., SEQ ID NO:1), US Patent No.: 8,202,517 (e.g., SEQ ID NO:1), US Patent No.: 8,257,699 (e.g., SEQ ID NO:1), US Patent No.: 8,450,470 (e.g., SEQ ID NO:1), US Patent No.: 8,431,124 (e.g., SEQ ID NO:1),US Patent No.: 8,431,380 (e.g., SEQ ID NO:1), US Patent No.: 8,580,252 (e.g., SEQ ID NO:1), US Patent No.: US 8,765,685 (e.g., SEQ ID NO:1), US Patent No.: US 8,772,246 (e.g., SEQ ID NO:1),US Patent No.: US 9,211,315 (e.g., SEQ ID NO:1), US Patent No.: US 9,562,223 (e.g., SEQ ID NO:1), US Patent No.: US 9,677,061 (e.g., SEQ ID NO:1), US Patent No.: US 9,677,062 (e.g., SEQ ID NO:1), US Patent No.: US 5,721,348 (e.g., SEQ ID NO:6), US 20210155913, US 20210363270, and US 20220289864, the contents of each of which are expressly incorporated herein by reference. The generation of such recombinant human hyaluronidases is described in U.S. Patent No.: 7,767,429; U.S. Patent No.: 7,871,607; and US20060104968, the contents of each of which are expressly incorporated herein by reference. [00310] An exemplary recombinant human hyaluronidase is rHuPH20, i.e., the active ingredient in the commercial product Hylenex® recombinant (hyaluronidase human injection), which is supplied as ENHANZE® drug product. [00311] Hyaluronidases that have altered properties, such as increased stability and/or activity, have been produced and can also be used, including, but not limited to those described in U.S. Pat. No.9,447,401, U.S. Pat. No.10,865,400, and U.S. Pat. No. 11,041,149, the contents of each of which are expressly incorporated herein by reference. These patents provide about 7000 examples in which the effects of replacing each amino acid with 15 other amino acids on activity and stability were identified and described. [00312] Other variants are known to those of skill in the art including those described, for example, in WO2020/022791 and WO2020197230A, the contents of each of which are expressly incorporated herein by reference. These variant polypeptides include replacements, insertions, and deletions, including one or more amino acid residues S343E, M345T, K349E, L353A, L354I, N356E, and 136 IT. Variants that contain such modifications and others are set forth in SEQ ID NOs: 60-115 from WO2020/022791. WO2021/150079 also provides variant polypeptides described as having increased stability. [00313] In one embodiment, the recombinant human hyaluronidase includes a sequence of amino acids in any one of SEQ ID NOs: 1076-1085 and 1087-1142, or has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 95%, 97%, 98%, or 99% sequence identity to a sequence of amino acids included in SEQ ID NO: 1076- 1085 and 1087-1142 and retains hyaluronidase activity. [00314] In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1076. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1076. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1078. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1078. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1079. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1079. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1080. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1080. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1081. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1081. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1082. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1082. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1083. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1083. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1084. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1084. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1085. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1085. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1087. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1087. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1088. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1088. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1089. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1089. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1090. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1090. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1091. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1091. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1092. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1092. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1093. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1093. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1094. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1094. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1095. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1095. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1096. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1096. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1097. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1097. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1098. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1098. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1099. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1099. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1100. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1100. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1101. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1101. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1102. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1102. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1103. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1103. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1104. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1104. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1105. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1105. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1106. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1106. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1107. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1107. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1108. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1108. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1109. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1109. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1110. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1110. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1111. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1111. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1112. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1112. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1113. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1113. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1114. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1114. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1115. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1115. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1116. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1116. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1117. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1117. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1118. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1118. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1119. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1119. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1120. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1120. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1121. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1121. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1122. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1122. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1123. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1123. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1124. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1124. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1125. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1125. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1126. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1126. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1127. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1127. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1128. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1128. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1129. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1129. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1130. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1130. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1131. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1131. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1132. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1132. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1133. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1133. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1134. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1134. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1135. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1135. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1136. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1136. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1137. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1137. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1138. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1138. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1139. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1139. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1140. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1140. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1141. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1141. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1142. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1142. Antibodies [00315] The recognized immunoglobulin genes include the kappa, lambda, alpha, gamma, delta, epsilon and mu constant region genes, as well as the myriad immunoglobulin variable region genes. Light chains are classified as either kappa or lambda. The “class” of an antibody or immunoglobulin refers to the type of constant domain or constant region possessed by its heavy chain. There are five major classes of antibodies: IgA, IgD, IgE, IgG, and IgM, and several of these may be further divided into subclasses (isotypes), e.g., IgG1, IgG2, IgG3, IgG4, IgA1, and IgA2. The heavy chain constant domains that correspond to the different classes of immunoglobulins are called α, δ, ε, γ, and μ, respectively. [00316] An exemplary immunoglobulin (antibody) structural unit is composed of two pairs of polypeptide chains, each pair having one “light” (about 25 kD) and one “heavy” chain (about 50-70 kD). The N-terminal domain of each chain defines a variable region of about 100 to 110 or more amino acids primarily responsible for antigen recognition. The terms variable light chain (VL) and variable heavy chain (VH) refer to these light and heavy chain domains respectively. The IgG1 heavy chain comprises of the VH, CH1, CH2 and CH3 domains respectively from the N to C-terminus. The light chain comprises of the VL and CL domains from N to C terminus. The IgG1 heavy chain comprises a hinge between the CH1 and CH2 domains. In certain embodiments, the immunoglobulin constructs comprise at least one immunoglobulin domain from IgG, IgM, IgA, IgD, or IgE connected to a therapeutic polypeptide. In some embodiments, the immunoglobulin domain found in an antibody provided herein, is from or derived from an immunoglobulin-based construct such as a diabody, or a nanobody. In certain embodiments, the immunoglobulin constructs described herein comprise at least one immunoglobulin domain from a heavy chain antibody such as a camelid antibody. In certain embodiments, the immunoglobulin constructs provided herein comprise at least one immunoglobulin domain from a mammalian antibody such as a bovine antibody, a human antibody, a camelid antibody, a mouse antibody or any chimeric antibody. [00317] In some embodiments, the antibodies provided herein comprise a heavy chain. In one embodiment, the heavy chain is an IgA. In one embodiment, the heavy chain is an IgD. In one embodiment, the heavy chain is an IgE. In one embodiment, the heavy chain is an IgG. In one embodiment, the heavy chain is an IgM. In one embodiment, the heavy chain is an IgG1. In one embodiment, the heavy chain is an IgG2. In one embodiment, the heavy chain is an IgG3. In one embodiment, the heavy chain is an IgG4. In one embodiment, the heavy chain is an IgA1. In one embodiment, the heavy chain is an IgA2. [00318] In some embodiments, an antibody is an IgG1 antibody. In some embodiments, an antibody is an IgG3 antibody. In some embodiments, an antibody is an IgG2 antibody. In some embodiments, an antibody is an IgG4 antibody. [00319] Generally, native four-chain antibodies comprise six HVRs; three in the VH (H1, H2, H3), and three in the VL (L1, L2, L3). HVRs generally comprise amino acid residues from the hypervariable loops and/or from the complementarity determining regions (CDRs), the latter being of highest sequence variability and/or involved in antigen recognition. With the exception of CDR1 in VH, CDRs generally comprise the amino acid residues that form the hypervariable loops. Hypervariable regions (HVRs) are also referred to as “complementarity determining regions” (CDRs), and these terms are used herein interchangeably in reference to portions of the variable region that form the antigen-binding regions. This particular region has been described by Kabat et al., U.S. Dept. of Health and Human Services, Sequences of Proteins of Immunological Interest (1983) and by Chothia et al., J Mol Biol 196:901-917 (1987), where the definitions include overlapping or subsets of amino acid residues when compared against each other. Nevertheless, application of either definition to refer to a CDR of an antibody or variants thereof is intended to be within the scope of the term as defined and used herein. The exact residue numbers which encompass a particular CDR will vary depending on the sequence and size of the CDR. Those skilled in the art can routinely determine which residues comprise a particular CDR given the variable region amino acid sequence of the antibody. [00320] The amino acid sequence boundaries of a CDR can be determined by one of skill in the art using any of a number of known numbering schemes, including those described by Kabat et al., supra (“Kabat” numbering scheme); Al-Lazikani et al., 1997, J. Mol. Biol., 273:927-948 (“Chothia” numbering scheme); MacCallum et al., 1996, J. Mol. Biol.262:732- 745 (“Contact” numbering scheme); Lefranc et al., Dev. Comp. Immunol., 2003, 27:55-77 (“IMGT” numbering scheme); and Honegge and Plückthun, J. Mol. Biol., 2001, 309:657-70 (“aHo” numbering scheme); each of which is incorporated by reference in its entirety. [00321] TABLE 2 provides the positions of CDR-L1, CDR-L2, CDR-L3, CDR-H1, CDR- H2, and CDR-H3 as identified by the Kabat and Chothia schemes. For CDR-H1, residue numbering is provided using both the Kabat and Chothia numbering schemes. [00322] CDRs may be assigned, for example, using antibody numbering software, such as Abnum, available at www.bioinf.org.uk/abs/abnum/, and described in Abhinandan and Martin, Immunology, 2008, 45:3832-3839, incorporated by reference in its entirety. TABLE 2. Residues in CDRs according to Kabat and Chothia numbering schemes CDR Kabat Chothia convention, varies between H32 and H34, depending on the length of the CDR. [00323] The “EU numbering scheme” is generally used when referring to a residue in an antibody heavy chain constant region (e.g., as reported in Kabat et al., supra). Unless stated otherwise, the EU numbering scheme is used to refer to residues in antibody heavy chain constant regions described herein. [00324] One example of an antigen-binding domain is an antigen-binding domain formed by a VH-VL dimer of an antibody. Another example of an antigen-binding domain is an antigen-binding domain formed by diversification of certain loops from the tenth fibronectin type III domain of an Adnectin. An antigen-binding domain can include CDRs 1, 2, and 3 from a heavy chain in that order; and CDRs 1, 2, and 3 from a light chain in that order. [00325] Epitopes frequently consist of surface-accessible amino acid residues and/or sugar side chains and may have specific three-dimensional structural characteristics, as well as specific charge characteristics. Conformational and non-conformational epitopes are distinguished in that the binding to the former but not the latter may be lost in the presence of denaturing solvents. An epitope may comprise amino acid residues that are directly involved in the binding, and other amino acid residues, which are not directly involved in the binding. The epitope to which an antibody binds can be determined using known techniques for epitope determination such as, for example, testing for antibody binding to OX40L or IL- 4Rα, to OX40L or IL-4Rα variants with different point-mutations, or to chimeric OX40L or IL-4Rα variants. [00326] To screen for antibodies which bind to an epitope on a target antigen bound by an antibody of interest (e.g., OX40L or IL-4Rα), a routine cross-blocking assay such as that described in Antibodies, A Laboratory Manual, Cold Spring Harbor Laboratory, Ed Harlow and David Lane (1988), can be performed. Alternatively, or additionally, epitope mapping can be performed by methods known in the art. Anti-OX40L Antibodies [00327] The present application provides antibodies or antigen binding fragments thereof and compositions comprising an antibody, or an antigen binding fragment thereof, which binds OX40L. In some embodiments, an anti-OX40L antibody, or an antigen binding fragment thereof, described herein is selected from amlitelimab and oxelumab. In some embodiments, amlitelimab comprises a variable heavy (VH) chain sequence having the amino acid sequence of SEQ ID NO: 832 and a variable light (VL) chain sequence having the amino acid sequence of SEQ ID NO: 833. In some embodiments, oxelumab comprises a VH chain sequence having the amino acid sequence of SEQ ID NO: 834 and a VL chain sequence having the amino acid sequence of SEQ ID NO: 835. In some embodiments, amlitelimab comprises a heavy chain having the amino acid sequence of SEQ ID NO: 842 and a light chain sequence having the amino acid sequence of SEQ ID NO: 843. In some embodiments, oxelumab comprises a heavy chain having the amino acid sequence of SEQ ID NO: 1072 and a light chain sequence having the amino acid sequence of SEQ ID NO: 1073, or a VH and/or VL therein. See also PCT Application No. PCT/US2024/026854 (corresponding to PCT Publication No. WO2024227174), which is incorporated herein by reference in its entirety. In some embodiments, an anti-OX40L antibody, or an antigen binding fragment thereof, described herein is selected from an anti-OX40L antibody described therein. [00328] Anti-OX40L antibodies or an antigen binding fragments thereof can include those described herein such as the clones set forth in the drawings and/or tables. In some embodiments, the antibody comprises an alternative scaffold. In some embodiments, the antibody consists of an alternative scaffold. In some embodiments, the antibody consists essentially of an alternative scaffold. In some embodiments, the antibody comprises an antibody fragment. In some embodiments, the antibody consists of an antibody fragment. In some embodiments, the antibody consists essentially of an antibody fragment. [00329] In some embodiments, the antibodies are monoclonal antibodies. [00330] In some embodiments, the antibodies are polyclonal antibodies. [00331] In some embodiments, the antibodies are produced by hybridomas. In other embodiments, the antibodies are produced by recombinant cells engineered to express the desired variable and constant domains. [00332] In some embodiments, the antibodies may be single chain antibodies or other antibody derivatives retaining the antigen specificity and the lower hinge region or a variant thereof. [00333] In some embodiments, the antibodies may be polyfunctional antibodies, recombinant antibodies, human antibodies, humanized antibodies, fragments or variants thereof. In particular embodiments, the antibody fragment or a derivative thereof is selected from a Fab fragment, a Fab′2 fragment, a CDR and ScFv. [00334] In some embodiments, the antibodies are capable of forming an immune complex. [00335] For sequence comparison, typically one sequence acts as a reference sequence to which test sequences are compared. When using a sequence comparison algorithm, test and reference sequences are input into a computer, subsequence coordinates are designated, if necessary, and sequence algorithm program parameters are designated. The sequence comparison algorithm then calculates the percent sequence identity for the test sequence(s) relative to the reference sequence, based on the designated program parameters. [00336] Optimal alignment of sequences for comparison can be conducted, e.g., by the local homology algorithm of Smith & Waterman, Adv. Appl. Math.2:482 (1981), by the homology alignment algorithm of Needleman & Wunsch, J. Mol. Biol.48:443 (1970), by the search for similarity method of Pearson & Lipman, Proc. Nat’l. Acad. Sci. USA 85:2444 (1988), by computerized implementations of these algorithms (GAP, BESTFIT, FASTA, and TFASTA in the Wisconsin Genetics Software Package, Genetics Computer Group, 575 Science Dr., Madison, Wis.), or by visual inspection (see generally Ausubel et al., infra). [00337] One example of an algorithm that is suitable for determining percent sequence identity and sequence similarity is the BLAST algorithm, which is described in Altschul et al., J. Mol. Biol.215:403-410 (1990). Software for performing BLAST analyses is publicly available through the National Center for Biotechnology Information (www.ncbi.nlm.nih.gov/). Sequences of OX40L Antibodies TABLE 3. Sequences of OX40L antibody constructs – VH, VL, and associated CDRs Identifier VH and Heavy Chain CDRs VL and Light Chain CDRs 114 VH SE ID NO 1 VL SE ID NO 11 Identifier VH and Heavy Chain CDRs VL and Light Chain CDRs IMGT (SEQ ID NO: 25) IMGT (SEQ ID NO: 34) Identifier VH and Heavy Chain CDRs VL and Light Chain CDRs Oxelumab VH (SEQ ID NO: 834) VL (SEQ ID NO: 835) [00338] In some embodiments, an antibody, or an antigen binding fragment thereof, provided herein comprises a VH sequence selected from any one of SEQ ID NOs: 1, 19, 37, and 55. [00339] In some embodiments, an antibody, or an antigen binding fragment thereof, provided herein comprises a VH sequence having at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to an illustrative VH sequence selected from any one of SEQ ID NOs: 1, 19, 37, and 55. In some embodiments, an antibody, or an antigen binding fragment thereof, provided herein comprises a VH sequence selected from any one of SEQ ID NOs: 1, 19, 37, and 55, with up to 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 amino acid substitutions. In some aspects, the amino acid substitutions are conservative amino acid substitutions. In some embodiments, the antibodies described in this paragraph are referred to herein as “variants.” In some embodiments, such variants are derived from a sequence provided herein, for example, by affinity maturation, site directed mutagenesis, random mutagenesis, or any other method known in the art or described herein. In some embodiments, such variants are not derived from a sequence provided herein and may, for example, be isolated de novo according to the methods provided herein for obtaining antibodies. Anti-OX40L VL Domains [00340] In some embodiments, an antibody, or an antigen binding fragment thereof, provided herein comprises a VL sequence selected from any one of SEQ ID NOs: 11, 29, 47, and 65. [00341] In some embodiments, an antibody, or an antigen binding fragment thereof, provided herein comprises a VL sequence having at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to a VL sequence selected from any one of SEQ ID NOs: 11, 29, 47, and 65. In some embodiments, an antibody, or an antigen binding fragment thereof, provided herein comprises a VL sequence selected from any one of SEQ ID NOs: 11, 29, 47, and 65, with up to 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 amino acid substitutions. In some aspects, the amino acid substitutions are conservative amino acid substitutions. In some embodiments, the antibodies described in this paragraph are referred to herein as “variants.” In some embodiments, such variants are derived from a sequence provided herein, for example, by affinity maturation, site directed mutagenesis, random mutagenesis, or any other method known in the art or described herein. In some embodiments, such variants are not derived from a sequence provided herein and may, for example, be isolated de novo according to the methods provided herein for obtaining antibodies. Anti-OX40L VH-VL Combinations [00342] In some embodiments, an antibody, or an antigen binding fragment thereof, provided herein comprises a VH sequence selected from any one of SEQ ID NOs: 1, 19, 37, and 55; and a VL sequence selected from any one of SEQ ID NOs: 11, 29, 47, and 65. [00343] In certain aspects, a VH sequence selected from any one of SEQ ID NOs: 1, 19, 37, and 55 can be combined with a VL sequence selected from any one of SEQ ID NOs: 11, 29, 47, and 65. [00344] In certain aspects, an antibody, or an antigen binding fragment thereof, provided herein comprises a VH sequence and a VL sequence of a construct provided in TABLE 3 (e.g., a VH sequence and a VL sequence from the same row of TABLE 3) or in PCT Application No. PCT/US2024/026854 (corresponding to PCT Publication No. WO2024227174), incorporated by reference herein in its entirety. In certain aspects, an antibody, or antigen binding fragment thereof, provided herein comprises a VH sequence and a VL sequence from Table 2 in PCT Application No. PCT/US2024/026854 (e.g., a VH sequence and a VL sequence from the same row of Table 2). [00345] In some embodiments, an antibody, or an antigen binding fragment thereof, provided herein comprises a VH sequence having at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to a VH sequence selected from any one of SEQ ID NOs: 1, 19, 37, and 55; and a VL sequence having at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to a VL sequence selected from any one of SEQ ID NOs: 11, 29, 47, and 65. In some embodiments, an antibody, or an antigen binding fragment thereof, provided herein comprises a VH sequence selected from any one of SEQ ID NOs: 1, 19, 37, and 55, with up to 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 amino acid substitutions, and a VL sequence selected from any one of SEQ ID NOs: 11, 29, 47, and 65, with up to 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 amino acid substitutions. In some aspects, the amino acid substitutions are conservative amino acid substitutions. In some embodiments, the antibodies described in this paragraph are referred to herein as “variants.” In some embodiments, such variants are derived from a sequence provided herein, for example, by affinity maturation, site directed mutagenesis, random mutagenesis, or any other method known in the art or described herein. In some embodiments, such variants are not derived from a sequence provided herein and may, for example, be isolated de novo according to the methods provided herein for obtaining antibodies. [00346] In certain embodiments, the antibody, or an antigen binding fragment thereof, comprises a VH sequence set forth in SEQ ID NO: 1 and a VL sequence set forth in SEQ ID NO: 11. [00347] In certain embodiments, the antibody, or an antigen binding fragment thereof, comprises a VH sequence set forth in SEQ ID NO: 19 and a VL sequence set forth in SEQ ID NO: 29. [00348] In certain embodiments, the antibody, or an antigen binding fragment thereof, comprises a VH sequence set forth in SEQ ID NO: 37 and a VL sequence set forth in SEQ ID NO: 47. [00349] In certain embodiments, the antibody, or an antigen binding fragment thereof, comprises a VH sequence set forth in SEQ ID NO: 55 and a VL sequence set forth in SEQ ID NO: 65. [00350] In certain embodiments, an antibody, or an antigen binding fragment thereof, comprises any of the VH and VL combinations described above and further comprises a heavy chain comprising a human IgG sequence selected from a sequence set forth in any one of SEQ ID NOs: 637-737 and SEQ ID NOs: 847-1070 or a sequence having at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity thereto. In certain embodiments, an antibody comprises any of the VH and VL combinations described above and further comprises a heavy chain comprising a constant heavy chain sequence set forth in SEQ ID NO: 651 or a sequence having at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity thereto. In certain embodiments, an antibody comprises any of the VH and VL combinations described above and further comprises a constant heavy chain comprising a constant heavy chain sequence set forth in SEQ ID NO: 973 or a sequence having at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity thereto. In certain embodiments, an antibody comprises any of the VH and VL combinations described above and further comprises a human constant light chain sequence set forth in SEQ ID NO: 738 or a sequence having at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity thereto. In certain embodiments, an antibody comprises any of the VH and VL combinations described above and further comprises a constant heavy chain sequence set forth in SEQ ID NO: 651 or a sequence having at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity thereto and a human constant light chain sequence set forth in SEQ ID NO: 738 or a sequence having at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity thereto. In certain embodiments, an antibody comprises any of the VH and VL combinations described above and further comprises a constant heavy chain sequence set forth in SEQ ID NO: 973 or a sequence having at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity thereto and a human constant light chain sequence set forth in SEQ ID NO: 738 or a sequence having at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity thereto. [00351] Although a C-terminal lysine may be present in the corresponding coding sequence of the constant heavy chain region (e.g., in a sequence encoding any one of SEQ ID NOs: 959-1070), it may be cleaved off during manufacture or after administration (resulting in, e.g., a constant heavy chain sequence of any one of SEQ ID NOs: 637-737 and 847-958). Accordingly, any of the antibodies or antigen binding fragments thereof described above may comprise a human IgG sequence containing a C-terminal lysine (e.g., any one of SEQ ID NOs: 959-1070), a human IgG sequence lacking a C-terminal lysine (e.g., any one of SEQ ID NOs: 637-737 and 847-958), or a mixture thereof (e.g., a mixture of the same heavy chain constant sequence with and without a C-terminal lysine, such as a mixture of SEQ ID NO: 973 and SEQ ID NO: 651). Anti-OX40L CDRs [00352] In some embodiments, disclosed herein is an antibody, or an antigen binding fragment thereof, comprising 1, 2, 3, 4, 5, or 6 of the CDRs of TABLE 3. In some embodiments, disclosed herein is an antibody, or an antigen binding fragment thereof, comprising 6 of the Kabat CDRs of TABLE 3. In some embodiments, disclosed herein is an antibody, or an antigen binding fragment thereof, comprising 1, 2, 3, 4, 5, or 6 of the Chothia CDRs of TABLE 3. In some embodiments, disclosed herein is an antibody, or an antigen binding fragment thereof, comprising 1, 2, 3, 4, 5, or 6 of the IMGT CDRs of TABLE 3. In some embodiments, the antibody, or an antigen binding fragment thereof, comprises 6 of the Kabat CDRs, 6 of the Chothia CDRs, or 6 of the IMGT CDRs from a single row of TABLE 3 (e.g., 6 CDRs from the same antibody). [00353] In some embodiments, disclosed herein is an antibody, or an antigen binding fragment thereof, comprising 1, 2, 3, 4, 5, or 6 of the CDRs of an antibody provided in PCT Application No. PCT/US2024/026854 (corresponding to PCT Publication No. WO2024227174, incorporated by reference herein in its entirety, such as 1, 2, 3, 4, 5, or 6 of the CDRs in Table 2 in PCT Application No. PCT/US2024/026854. In some embodiments, disclosed herein is an antibody, or an antigen binding fragment thereof, comprising 1, 2, 3, 4, 5, or 6 of the Kabat CDRs of an antibody, or an antigen binding fragment thereof, provided in PCT Application No. PCT/US2024/026854. In some embodiments, disclosed herein is an antibody, or an antigen binding fragment thereof, comprising 1, 2, 3, 4, 5, or 6 of the Chothia CDRs of an antibody, or an antigen binding fragment thereof, provided in PCT Application No. PCT/US2024/026854. In some embodiments, disclosed herein is an antibody, or an antigen binding fragment thereof, comprising 1, 2, 3, 4, 5, or 6 of the IMGT CDRs of an antibody provided in PCT Application No. PCT/US2024/026854. In some embodiments, the antibody, or an antigen binding fragment thereof, comprises 6 of the Kabat CDRs, 6 of the Chothia CDRs, or 6 of the IMGT CDRs from a single row of Table 2 in in PCT Application No. PCT/US2024/026854 (e.g., 6 CDRs from the same antibody). [00354] In some embodiments, an antibody, or an antigen binding fragment thereof, provided herein comprises three CDRs of a VH domain selected from SEQ ID NOs: 1, 19, 37, and 55. In some aspects, the CDRs are exemplary CDRs. In some aspects, the CDRs are Kabat CDRs. In some aspects, the CDRs are Chothia CDRs. In some aspects, the CDRs are IMGT CDRs. In some aspects, the CDRs are AbM CDRs. In some aspects, the CDRs are Contact CDRs. [00355] In some embodiments, the CDRs are CDRs having at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity to a CDR-H1, CDR-H2, or CDR-H3 selected from SEQ ID NOs: 2-10, 12-18, 20-28, 30-36, 38-46, 48-54, 56-64, and 66-72. In some embodiments, the CDR-H1 is a CDR-H1 of a VH domain selected from SEQ ID NOs: 1, 19, 37, and 55, with up to 1, 2, 3, 4, or 5 amino acid substitutions. In some embodiments, the CDR-H2 is a CDR-H2 of a VH domain selected from SEQ ID NOs: 1, 19, 37, and 55, with up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions. In some embodiments, the CDR-H3 is a CDR-H3 of a VH domain selected from SEQ ID NOs: 1, 19, 37, and 55, with up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions. In some aspects, the amino acid substitutions are conservative amino acid substitutions. In some embodiments, the antibodies described in this paragraph are referred to herein as “variants.” In some embodiments, such variants are derived from a sequence provided herein, for example, by affinity maturation, site directed mutagenesis, random mutagenesis, or any other method known in the art or described herein. In some embodiments, such variants are not derived from a sequence provided herein and may, for example, be isolated de novo according to the methods provided herein for obtaining antibodies. [00356] In some embodiments, an antibody, or an antigen binding fragment thereof, provided herein comprises three CDRs of a VL domain selected from SEQ ID NOs: 11, 29, 47, and 65. In some aspects, the CDRs are exemplary CDRs. In some aspects, the CDRs are Kabat CDRs. In some aspects, the CDRs are Chothia CDRs. In some aspects, the CDRs are IMGT CDRs. In some aspects, the CDRs are AbM CDRs. In some aspects, the CDRs are Contact CDRs. [00357] In some embodiments, the CDRs are CDRs having at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity to a CDR-L1, CDR-L2, or CDR-L3 selected from SEQ ID NOs: 2-10, 12-18, 20-28, 30-36, 38-46, 48-54, 56-64, and 66- 72, In some embodiments, the CDR-L1 is a CDR-L1 of a VL domain selected from SEQ ID NOs: 11, 29, 47, and 65, with up to 1, 2, 3, 4, or 5 amino acid substitutions. In some embodiments, the CDR-L2 is a CDR-L2 of a VL domain selected from SEQ ID NOs: 11, 29, 47, and 65, with up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions. In some embodiments, the CDR-L3 is a CDR-L3 of a VL domain selected from SEQ ID NOs: 11, 29, 47, and 65, with up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions. In some aspects, the amino acid substitutions are conservative amino acid substitutions. In some embodiments, the antibodies described in this paragraph are referred to herein as “variants.” In some embodiments, such variants are derived from a sequence provided herein, for example, by affinity maturation, site directed mutagenesis, random mutagenesis, or any other method known in the art or described herein. In some embodiments, such variants are not derived from a sequence provided herein and may, for example, be isolated de novo according to the methods provided herein for obtaining antibodies. [00358] In some embodiments, an antibody, or an antigen binding fragment thereof, provided herein comprises three CDRs of a VH domain selected from SEQ ID NOs: 1, 19, 37, and 55 and three CDRs of a VL domain selected from SEQ ID NOs: 11, 29, 47, and 65. In some aspects, the CDRs are exemplary CDRs. In some aspects, the CDRs are Kabat CDRs. In some aspects, the CDRs are Chothia CDRs. In some aspects, the CDRs are IMGT CDRs. In some aspects, the CDRs are AbM CDRs. In some aspects, the CDRs are Contact CDRs. [00359] In some embodiments, an antibody, or an antigen binding fragment thereof, provided herein comprises a CDR-H3 selected from SEQ ID NOs: 8-10, 26-28, 44-46, and 62-64. In some aspects, the CDR-H3 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to a CDR-H3 selected from SEQ ID NOs: 8-10, 26-28, 44-46, and 62-64. In some embodiments, the CDR-H3 is a CDR-H3 selected from SEQ ID NOs: 8-10, 26-28, 44-46, and 62-64, with up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions. In some aspects, the amino acid substitutions are conservative amino acid substitutions. In some embodiments, the antibodies described in this paragraph are referred to herein as “variants.” In some embodiments, such variants are derived from a sequence provided herein, for example, by affinity maturation, site directed mutagenesis, random mutagenesis, or any other method known in the art or described herein. In some embodiments, such variants are not derived from a sequence provided herein and may, for example, be isolated de novo according to the methods provided herein for obtaining antibodies. [00360] In some embodiments, an antibody, or an antigen binding fragment thereof, provided herein comprises a CDR-H1 selected from SEQ ID NOs: 2-4, 20-22, 38-40, and 56- 58. In some aspects, the CDR-H1 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to a CDR-H1 selected from SEQ ID NOs: 2-4, 20-22, 38-40, and 56-58. In some embodiments, the CDR-H1 is a CDR-H1 selected from SEQ ID NOs: 2- 4, 20-22, 38-40, and 56-58, with up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions. In some aspects, the amino acid substitutions are conservative amino acid substitutions. In some embodiments, the antibodies described in this paragraph are referred to herein as “variants.” In some embodiments, such variants are derived from a sequence provided herein, for example, by affinity maturation, site directed mutagenesis, random mutagenesis, or any other method known in the art or described herein. In some embodiments, such variants are not derived from a sequence provided herein and may, for example, be isolated de novo according to the methods provided herein for obtaining antibodies. [00361] In some embodiments, an antibody, or an antigen binding fragment thereof, provided herein comprises a CDR-H2 selected from SEQ ID NOs: 5-7, 23-25, 41-43, and 59- 61. In some aspects, the CDR-H2 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to a CDR-H2 selected from SEQ ID NOs: 5-7, 23-25, 41-43, and 59-61. In some embodiments, the CDR-H2 is a CDR-H2 selected from SEQ ID NOs: 5- 7, 23-25, 41-43, and 59-61, with up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions. In some aspects, the amino acid substitutions are conservative amino acid substitutions. In some embodiments, the antibodies described in this paragraph are referred to herein as “variants.” In some embodiments, such variants are derived from a sequence provided herein, for example, by affinity maturation, site directed mutagenesis, random mutagenesis, or any other method known in the art or described herein. In some embodiments, such variants are not derived from a sequence provided herein and may, for example, be isolated de novo according to the methods provided herein for obtaining antibodies. [00362] In some embodiments, an antibody, or an antigen binding fragment thereof, provided herein comprises a CDR-L3 selected from SEQ ID NOs: 17-18, 35-36, 53-54, and 71-72. In some aspects, the CDR-L3 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to a CDR-L3 selected from SEQ ID NOs: 17-18, 35- 36, 53-54, and 71-72. In some embodiments, the CDR-L3 is a CDR-L3 selected from SEQ ID NOs: 17-18, 35-36, 53-54, and 71-72, with up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions. In some aspects, the amino acid substitutions are conservative amino acid substitutions. In some embodiments, the antibodies described in this paragraph are referred to herein as “variants.” In some embodiments, such variants are derived from a sequence provided herein, for example, by affinity maturation, site directed mutagenesis, random mutagenesis, or any other method known in the art or described herein. In some embodiments, such variants are not derived from a sequence provided herein and may, for example, be isolated de novo according to the methods provided herein for obtaining antibodies. [00363] In some embodiments, an antibody, or an antigen binding fragment thereof, provided herein comprises a CDR-L2 selected from SEQ ID NOs: 15-16, 33-34, 51-52, and 69-70. In some aspects, the CDR-L2 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to a CDR-L2 selected from SEQ ID NOs: 15-16, 33- 34, 51-52, and 69-70. In some embodiments, the CDR-L2 is a CDR-L2 selected from SEQ ID NOs: 15-16, 33-34, 51-52, and 69-70, with up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions. In some aspects, the amino acid substitutions are conservative amino acid substitutions. In some embodiments, the antibodies described in this paragraph are referred to herein as “variants.” In some embodiments, such variants are derived from a sequence provided herein, for example, by affinity maturation, site directed mutagenesis, random mutagenesis, or any other method known in the art or described herein. In some embodiments, such variants are not derived from a sequence provided herein and may, for example, be isolated de novo according to the methods provided herein for obtaining antibodies. [00364] In some embodiments, an antibody, or an antigen binding fragment thereof, provided herein comprises a CDR-L1 selected from SEQ ID NOs: 12-14, 30-32, 48-50, and 66-68. In some aspects, the CDR-L1 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to a CDR-L1 selected from SEQ ID NOs: 12-14, 30- 32, 48-50, and 66-68. In some embodiments, the CDR-L1 is a CDR-L1 selected from SEQ ID NOs: 12-14, 30-32, 48-50, and 66-68, with up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions. In some aspects, the amino acid substitutions are conservative amino acid substitutions. In some embodiments, the antibodies described in this paragraph are referred to herein as “variants.” In some embodiments, such variants are derived from a sequence provided herein, for example, by affinity maturation, site directed mutagenesis, random mutagenesis, or any other method known in the art or described herein. In some embodiments, such variants are not derived from a sequence provided herein and may, for example, be isolated de novo according to the methods provided herein for obtaining antibodies. [00365] In some embodiments, an antibody, or an antigen binding fragment thereof, provided herein comprises a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 2; a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 5; a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 8; a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 12; a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 15; and a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 17. [00366] In some embodiments, an antibody, or an antigen binding fragment thereof, provided herein comprises a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 3; a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 6; a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 9; a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 13; a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 16; and a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 18. [00367] In some embodiments, an antibody, or an antigen binding fragment thereof, provided herein comprises a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 4; a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 7; a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 10; a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 14; a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 16; and a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 17. [00368] In some embodiments, an antibody, or an antigen binding fragment thereof, provided herein comprises a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 20; a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 23; a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 26; a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 30; a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 33; and a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 35. [00369] In some embodiments, an antibody, or an antigen binding fragment thereof, provided herein comprises a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 21; a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 24; a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 27; a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 31; a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 34; and a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 36. [00370] In some embodiments, an antibody, or an antigen binding fragment thereof, provided herein comprises a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 22; a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 25; a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 27; a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 32; a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 34; and a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 35. [00371] In some embodiments, an antibody, or an antigen binding fragment thereof, provided herein comprises a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 38; a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 41; a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 44; a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 48; a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 51; and a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 53. [00372] In some embodiments, an antibody, or an antigen binding fragment thereof, provided herein comprises a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 39; a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 42; a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 45; a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 49; a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 52; and a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 54. [00373] In some embodiments, an antibody, or an antigen binding fragment thereof, provided herein comprises a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 40; a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 43; a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 46; a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 50; a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 52; and a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 53. [00374] In some embodiments, an antibody, or an antigen binding fragment thereof, provided herein comprises a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 56; a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 59; a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 62; a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 66; a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 69; and a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 71. [00375] In some embodiments, an antibody, or an antigen binding fragment thereof, provided herein comprises a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 57; a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 60; a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 63; a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 67; a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 70; and a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 72. [00376] In some embodiments, an antibody, or an antigen binding fragment thereof, provided herein comprises a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 58; a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 61; a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 64; a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 68; a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 70; and a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 71. [00377] In certain embodiments, any of the antibodies or antigen binding fragments thereof described above further comprises a heavy chain comprising a human IgG sequence selected from a sequence set forth in any one of SEQ ID NOs: 637-737 and SEQ ID NOs: 847-1070 or a sequence having at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity thereto. In certain embodiments, any of the antibodies described above further comprises a constant heavy chain sequence set forth in SEQ ID NO: 651 or a sequence having at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity thereto. In certain embodiments, any of the antibodies described above further comprises a constant heavy chain sequence set forth in SEQ ID NO: 973 or a sequence having at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity thereto. In certain embodiments, any of the antibodies described above further comprises a human constant light chain sequence set forth in SEQ ID NO: 738 or a sequence having at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity thereto. In certain embodiments, any of the antibodies described above further comprises a constant heavy chain sequence set forth in SEQ ID NO: 651 or a sequence having at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity thereto and a human constant light chain sequence set forth in SEQ ID NO: 738 or a sequence having at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity thereto. In certain embodiments, any of the antibodies described above further comprises a constant heavy chain sequence set forth in SEQ ID NO: 973 or a sequence having at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity thereto and a human constant light chain sequence set forth in SEQ ID NO: 738 or a sequence having at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity thereto. [00378] Although a C-terminal lysine may be present in the corresponding coding sequence of the constant heavy chain region (e.g., in a sequence encoding any one of SEQ ID NOs: 959-1070), it may be cleaved off during manufacture or after administration (resulting in, e.g., a constant heavy chain sequence of any one of SEQ ID NOs: 637-737 and 847-958). Accordingly, any of the antibodies or antigen binding fragments thereof described above may comprise a human IgG sequence containing a C-terminal lysine (e.g., any one of SEQ ID NOs: 959-1070), a human IgG sequence lacking a C-terminal lysine (e.g., any one of SEQ ID NOs: 637-737 and 847-958), or a mixture thereof (e.g., a mixture of the same heavy chain constant sequence with and without a C-terminal lysine, such as a mixture of SEQ ID NO: 973 and SEQ ID NO: 651). [00379] In some aspects, the amino acid substitutions are conservative amino acid substitutions. In some embodiments, the antibodies described in this disclosure are referred to herein as “variants” or “clones”. In some embodiments, such variants or clones are derived from a sequence provided herein, for example, by affinity maturation, site directed mutagenesis, random mutagenesis, or any other method known in the art or described herein. In some embodiments, such variants or cones are not derived from a sequence provided herein and may, for example, be isolated de novo according to the methods provided herein for obtaining antibodies. Fc Region [00380] The structures of the Fc regions of various immunoglobulins, and the glycosylation sites contained therein, are known in the art. See Schroeder et al. (2010) Allergy Clin. Immunol.125:S41-52, incorporated by reference in its entirety. The Fc region may be a naturally occurring Fc region, or an Fc region modified as described in the art or elsewhere in this disclosure. [00381] Unless otherwise specified herein, numbering of amino acid residues in the Fc region or constant region is according to the EU numbering system, also called the EU index, as described in Kabat et al., Sequences of Proteins of Immunological Interest, 5th Ed. Public Health Service, National Institutes of Health, Bethesda, MD, 1991. An "Fc polypeptide" of a dimeric Fc as used herein refers to one of the two polypeptides forming the dimeric Fc domain, i.e. a polypeptide comprising C-terminal constant regions of an immunoglobulin heavy chain, capable of stable self-association. For example, an Fc polypeptide of a dimeric IgG Fc comprises an IgG CH2 and an IgG CH3 constant domain sequence. An Fc can be of the class IgA, IgD, IgE, IgG, and IgM, and several of these may be further divided into subclasses (isotypes), e.g., IgG1, IgG2, IgG3, IgG4, IgA1, and IgA2. [00382] The terms “Fc receptor” and “FcR” are used to describe a receptor that binds to the Fc region of an antibody. For example, an FcR can be a native sequence human FcR. Generally, an FcR is one which binds an IgG antibody (a gamma receptor) and includes receptors of the FcγRI, FcγRII, and FcγRIII subclasses, including allelic variants and alternatively spliced forms of these receptors. FcγRII receptors include FcγRIIA (an “activating receptor”) and FcγRIIB (an “inhibiting receptor”), which have similar amino acid sequences that differ primarily in the cytoplasmic domains thereof. Immunoglobulins of other isotypes can also be bound by certain FcRs (see, e.g., Janeway et al., Immuno Biology: the immune system in health and disease, (Elsevier Science Ltd., NY) (4th ed., 1999)). Activating receptor FcγRIIA contains an immunoreceptor tyrosine-based activation motif (ITAM) in its cytoplasmic domain. Inhibiting receptor FcγRIIB contains an immunoreceptor tyrosine-based inhibition motif (ITIM) in its cytoplasmic domain (reviewed in Daëron, Annu. Rev. Immunol.15:203-234 (1997)). FcRs are reviewed in Ravetch and Kinet, Annu. Rev. Immunol 9:457-92 (1991); Capel et al., Immunomethods 4:25-34 (1994); and de Haas et al., J. Lab. Clin. Med.126:330-41 (1995). Other FcRs, including those to be identified in the future, are encompassed by the term “FcR” herein. The term also includes the neonatal receptor, FcRn, which is responsible for the transfer of maternal IgGs to the fetus (Guyer et al., J. Immunol.117:587 (1976); and Kim et al., J. Immunol.24:249 (1994)). [00383] Modifications in the CH2 domain can affect the binding of FcRs to the Fc. A number of amino acid modifications in the Fc region are known that can selectively alter the affinity of the Fc for different Fcgamma receptors. In some aspects, the Fc comprises one or more modifications designed to promote selective binding of Fc-gamma receptors. [00384] Exemplary mutations that may alter the binding of FcRs to the Fc are listed below (in EU numbering format): • S298A/E333A/K334A, S298A/E333A/K334A/K326A (Lu Y, Vernes JM, Chiang N, et al., J Immunol Methods.2011 Feb 28;365(1-2):132-41); • F243L/R292P/Y300L/V305I/P396L, F243L/R292P/Y300L/L235V/P396L (Stavenhagen JB, Gorlatov S, Tuaillon N, et al., Cancer Res.2007 Sep 15;67(18):8882-90; Nordstrom JL, Gorlatov S, Zhang W, et al., Breast Cancer Res. 2011 Nov 30;13(6):R123); • F243L (Stewart R, Thom G, Levens M, et al., Protein Eng Des Sel.2011 Sep;24(9):671-8.), S298A/E333A/K334A (Shields RL, Namenuk AK, Hong K, et al., J Biol Chem.2001 Mar 2;276(9):6591-604); • S239D/I332E/A330L, S239D/I332E (Lazar et al., (2006) Proc Natl Acad Sci U S A. 103(11):4005-10); • S239D/S267E, S267E/L328F (Chu et al., (2008) Mol Immunol.45(15):3926-33); • S239D/D265S/S298A/I332E, S239E/S298A/K326A/A327H, G237F/S298A/A330L/I 332E, S239D/I332E/S298A, S239D/K326E/A330L/I332E/S298A, G236A/S239D/D2 70L/I332E, S239E/S267E/H268D, L234F/S267E/N325L, G237F/V266L/S267D and other mutations listed in WO2011/120134 and WO2011/120135, herein incorporated by reference. Therapeutic Antibody Engineering (by William R. Strohl and Lila M. Strohl, Woodhead Publishing series in Biomedicine No 11, ISBN 1907568379, Oct 2012) lists mutations on page 283. [00385] In some embodiments, any of the antibodies or antigen binding fragments thereof described above further comprises a heavy chain comprising a constant heavy chain sequence selected from an amino acid sequence set forth in any one of SEQ ID NOs: 637-737 and SEQ ID NOs: 847-1070, or an amino acid sequence having 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%, or at least 99% sequence identity thereto. [00386] In some embodiments, an antibody, or an antigen binding fragment thereof, described herein includes modifications designed to improve its ability to mediate effector function. Such modifications that can have this effect are known in the art and include afucosylation, or engineering of the affinity of the Fc towards an activating receptor, mainly FCGR3a for ADCC, and towards C1q for CDC. The following TABLE 4 summarizes various designs reported in the literature for effector function engineering. [00387] Methods of producing antibodies with little or no fucose on the Fc glycosylation site (Asn 297 EU numbering) without altering the amino acid sequence are well known in the art. The GlymaxX® technology (ProBioGen AG) is based on the introduction of a gene for an enzyme which deflects the cellular pathway of fucose biosynthesis into cells used for antibody production. This prevents the addition of the sugar “fucose” to the N-linked antibody carbohydrate part by antibody-producing cells (von Horsten et al. (2010) Glycobiology.2010 Dec; 20 (12):1607-18). Examples of cell lines capable of producing defucosylated antibody include CHO-DG44 with stable overexpression of the bacterial oxidoreductase GDP-6-deoxy-D-lyxo-4-hexylose reductase (RMD) (see von Horsten et al. (2010) supra) or Lec13 CHO cells, which are deficient in protein fucosylation (see Ripka et al. (1986) Arch. Biochem. Biophys.249:533-545; U.S. Pat. Pub. No.2003/0157108; WO 2004/056312; each of which is incorporated by reference in its entirety), and knockout cell lines, such as alpha-1,6-fucosyltransferase gene or FUT8 knockout CHO cells (see Yamane- Ohnuki et al. (2004) Biotech. Bioeng.87: 614-622; Kanda et al. (2006) Biotechnol. Bioeng. 94:680-688; and WO 2003/085107; each of which is incorporated by reference in its entirety). Another approach to obtaining antibodies with lowered levels of fucosylation can be found in U.S. Patent No.8,409,572, which teaches selecting cell lines for antibody production for their ability to yield lower levels of fucosylation on antibodies. [00388] Antibodies can be fully afucosylated (meaning they contain no detectable fucose) or they can be partially afucosylated, meaning that the isolated antibody contains less than 95%, less than 85%, less than 75%, less than 65%, less than 55%, less than 45%, less than 35%, less than 25%, less than 15% or less than 5% of the amount of fucose normally detected for a similar antibody produced by a mammalian expression system. [00389] In some aspects, an antibody, or an antigen binding fragment thereof, provided herein comprises an IgG1 domain with reduced fucose content at position Asn 297 compared to a naturally occurring IgG1 domain. Such Fc domains can have improved ADCC. See Shields et al. (2002) J. Biol. Chem.277:26733-26740, incorporated by reference in its entirety. In some aspects, such antibodies do not comprise any fucose at position Asn 297. The amount of fucose may be determined using any suitable method, for example as described in WO 2008/077546, incorporated by reference in its entirety. [00390] In certain embodiments, an antibody, or an antigen binding fragment thereof, provided herein comprises an Fc region with one or more amino acid substitutions which improve ADCC, such as a substitution at one or more of positions 298, 333, and 334 of the Fc region. In some embodiments, an antibody, or an antigen binding fragment thereof, provided herein comprises an Fc region with one or more amino acid substitutions at positions 239, 332, and 330, as described in Lazar et al. (2006) Proc. Natl. Acad. Sci. USA 103:4005-4010, incorporated by reference in its entirety. [00391] Other illustrative glycosylation variants which may be incorporated into the antibodies provided herein are described, for example, in U.S. Pat. Pub. Nos.2003/0157108, 2004/0093621, 2003/0157108, 2003/0115614, 2002/0164328, 2004/0093621, 2004/0132140, 2004/0110704, 2004/0110282, 2004/0109865; International Pat. Pub. Nos.2000/61739, 2001/29246, 2003/085119, 2003/084570, 2005/035586, 2005/035778; 2005/053742, 2002/031140; Okazaki et al., J. Mol. Biol., 2004, 336:1239-1249; and Yamane-Ohnuki et al. (2004) supra; each of which is incorporated by reference in its entirety. [00392] In some embodiments, an antibody, or an antigen binding fragment thereof, provided herein comprises an Fc region with at least one galactose residue in the oligosaccharide attached to the Fc region. Such antibody variants may have improved CDC function. Examples of such antibody variants are described, for example, in WO 1997/30087; WO 1998/58964; and WO 1999/22764; each of which is incorporated by reference in its entirety. [00393] Thus, in one embodiment, an antibody described herein can include a dimeric Fc that comprises one or more amino acid modifications as noted in TABLE 4 that may confer improved effector function. In another embodiment, the antibody can be afucosylated to improve effector function. TABLE 4. CH2 domains and effector function engineering Reference Mutations Effect C C C C C C C C C C C [00394] Fc modifications designed to reduce FcgR and/or complement binding and/or effector function are known in the art. Recent publications describe strategies that have been used to engineer antibodies with reduced or silenced effector activity (see Strohl, WR (2009) Curr Opin Biotech 20:685-691, and Strohl, WR and Strohl LM, “Antibody Fc engineering for optimal antibody performance” In Therapeutic Antibody Engineering, Cambridge: Woodhead Publishing (2012), pp 225-249). These strategies include reduction of effector function through modification of glycosylation, use of IgG2/IgG4 scaffolds, or the introduction of mutations in the hinge or CH2 regions of the Fc. For example, U.S. Patent Publication No.2011/0212087 (Strohl), International Patent Publication No. WO 2006/105338 (Xencor), U.S. Patent Publication No.2012/0225058 (Xencor), U.S. Patent Publication No.2012/0251531 (Genentech), and Strop et al., ((2012) J. Mol. Biol.420: 204- 219), each of which is incorporated by reference in its entirety, describe specific modifications designed to reduce FcgR or complement binding to the Fc. [00395] Specific, non-limiting examples of amino acid modifications designed to reduce FcgR or complement binding to the Fc include those identified in the following TABLE 5: TABLE 5. Modifications designed to reduce FcgR or complement binding to the Fc Mutations Mutations [00396] In some embo e s, a a o y, o a a ge ding fragment thereof, provided herein comprises one or more alterations that is designed to improve or diminish C1q binding and/or CDC. See U.S. Pat. No.6,194,551; WO 99/51642; and Idusogie et al. (2000) J. Immunol.164:4178-4184; each of which is incorporated by reference in its entirety. [00397] In certain embodiments, the heavy chain comprises a constant heavy chain sequence selected from the sequences set forth in SEQ ID NOs: 637-737 and SEQ ID NOs: 847-1070. [00398] In certain embodiments, the Fc region comprises one or more amino acid substitutions, wherein the one or more substitutions result in an increase in one or more of antibody half-life, ADCC activity, ADCP activity, or CDC activity compared with the Fc without the one or more substitutions. In certain embodiments, the one or more amino acid substitutions results in increased antibody half-life at pH 6.0 compared to an antibody comprising a wild-type Fc region. In certain embodiments, the antibody has an increased half-life that is about 10,000-fold, 1,000-fold, 500-fold, 100-fold, 50-fold, 20-fold, 10-fold, 9- fold, 8-fold, 7-fold, 6-fold, 5-fold, 4.5-fold, 4-fold, 3.5-fold, 3-fold, 2.5-fold, 2-fold, 1.95- fold, 1.9-fold, 1.85-fold, 1.8-fold, 1.75-fold, 1.7-fold, 1.65-fold, 1.6-fold, 1.55-fold, 1.50-fold, 1.45-fold, 1.4-fold, 1.35-fold, 1.3-fold, 1.25-fold, 1.2-fold, 1.15-fold, 1.1-fold, or 1.05-fold longer compared to an antibody comprising a wild-type Fc region. In certain embodiments, the antibody has an increased half-life that is about 10,000-fold, 1,000-fold, 500-fold, 100- fold, 50-fold, 20-fold, 10-fold, 9-fold, 8-fold, 7-fold, 6-fold, 5-fold, 4.5-fold, 4-fold, 3.5-fold, 3-fold, 2.5-fold, 2-fold, 1.95-fold, 1.9-fold, 1.85-fold, 1.8-fold, 1.75-fold, 1.7-fold, 1.65-fold, 1.6-fold, 1.55-fold, 1.50-fold, 1.45-fold, 1.4-fold, 1.35-fold, 1.3-fold, 1.25-fold, 1.2-fold, 1.15-fold, 1.1-fold, or 1.05-fold longer compared to amlitelimab. [00399] In certain embodiments, the Fc region comprises one or more amino acid substitutions, wherein the one or more substitutions result in a decrease in one or more of ADCC activity, ADCP activity, or CDC activity compared with the Fc without the one or more substitutions. [00400] In certain embodiments, the one or more amino acid substitutions is selected from the group consisting of S228P (SP), M252Y, S254T, T256E, T256D, T250Q, H285D, T307A, T307Q, T307R, T307W, L309D, Q411H, Q311V, A378V, E380A, M428L, N434A, N434S, N297A, D265A, L234A, L235A, and N434W. In certain embodiments, the one or more amino acid substitutions comprises a specific combination of amino acid substitutions selected from the group consisting of M428L/N434S (LS), M252Y/S254T/T256E (YTE), T250Q/M428L, T307A/E380A/N434A, T256D/T307Q (DQ), T256D/T307W (DW), M252Y/T256D (YD), T307Q/Q311V/A378V (QVV), T256D/H285D/T307R/Q311V/A378V (DDRVV), L309D/Q311H/N434S (DHS), S228P/L235E (SPLE), L234A/L235A (LALA), M428L/N434A (LA), L235A/G237A (LAGA), L234A/L235A/G237A (LALAGA), L234A/L235A/P329G (LALAPG), D265A/YTE, LALA/YTE, LAGA/YTE, LALAGA/YTE, LALAPG/YTE, N297A/LS, D265A/LS, LALA/LS, LALAGA/LS, LALAPG/LS, N297A/DHS, D265A/DHS, LALA/DHS, LAGA/DHS, LALAGA/DHS, LALAPG/DHS, SP/YTE, SPLE/YTE, SP/LS, SPLE/LS, SP/DHS, SPLE/DHS, N297A/LA, D265A/LA, LALA/LA, LAGA/LA, LALAGA/LA, LALAPG/LA, N297A/N434A, D265A/N434A, LALA/N434A, LAGA/N434A, LALAGA/N434A, LALAPG/N434A, N297A/N434W, D265A/N434W, LALA/N434W, LAGA/N434W, LALAGA/N434W, LALAPG/N434W, N297A/DQ, D265A/DQ, LALA/DQ, LAGA/DQ, LALAGA/DQ, LALAPG/DQ, N297A/DW, D265A/DW, LALA/DW, LAGA/DW, LALAGA/DW, LALAPG/DW, N297A/YD, D265A/YD, LALA/YD, LAGA/YD, LALAGA/YD, LALAPG/YD, T307Q/Q311V/A378V (QVV), N297A/QVV, D265A/QVV, LALA/QVV, LAGA/QVV, LALAGA/QVV, LALAPG/QVV, DDRVV, N297A/DDRVV, D265A/DDRVV, LALA/DDRVV, LAGA/DDRVV, LALAGA/DDRVV, and LALAPG/DDRVV. [00401] Although the EU numbering system is typically used to identify the positions of the various Fc mutations described herein, direct numbering can also be used. For example, in certain embodiments, an antibody described herein comprises an Fc region with YTE mutations at positions 253, 255 and 257. In certain embodiments, an antibody described herein comprises an Fc region with LALA mutations at positions 235 and 236, respectively. In certain embodiments, an antibody described herein comprises an Fc region with YTE mutations at positions 253, 255 and 257 and with LALA mutations at positions 235 and 236. In certain embodiments, the OX40L antibody described herein comprises the heavy and light chain variable regions of Construct 114 and an Fc region comprising YTE mutations at positions 253, 255 and 257, respectively and with LALA mutations at positions 235 and 236, respectively (e.g., as shown in the heavy chain sequences of SEQ ID NOs: 839 and 840). [00402] In certain embodiments the human Fc region comprises a human IgG1 Fc with LALA mutations. In certain embodiments, the human Fc region comprises a human IgG1 Fc with YTE mutations. In certain embodiments, the human Fc region comprises a human IgG1 Fc with LALA and YTE mutations. In certain embodiments, when direct numbering is used, “YTE” and “LALA” mutations can be located at different amino acid position numbers. For example, a human Fc region can comprise a human IgG1 Fc with LALA mutations at L235A/L236A and/or YTE mutations at M253Y/S255T/T257E. [00403] In some embodiments, the OX40L antibody, or antigen binding fragment thereof, comprises a heavy chain variable region sequence comprising an amino acid sequence set forth in SEQ ID NO:1, a constant heavy chain sequence set forth in SEQ ID NO: 651, a light chain variable region sequence comprising an amino acid sequence set forth in SEQ ID NO:11, and a constant light chain sequence set forth in SEQ ID NO: 738. In some embodiments, the OX40L antibody, or antigen binding fragment thereof, comprises a heavy chain variable region sequence comprising an amino acid sequence set forth in SEQ ID NO:1, a constant heavy chain sequence set forth in SEQ ID NO: 973, a light chain variable region sequence comprising an amino acid sequence set forth in SEQ ID NO:11, and a constant light chain sequence set forth in SEQ ID NO: 738. [00404] The C-terminal Lys330 of the constant heavy chain sequence of SEQ ID NO: 973 may or may not be present. The disclosure specifically contemplates SEQ ID NO: 973 that does not include the C-terminal Lys corresponding to Lys330 (as set forth in SEQ ID NO: 651). A polypeptide comprising SEQ ID NO: 973 (e.g., the polypeptide of SEQ ID NO: 839) may be expressed including a C-terminal Lys330 which then may be proteolytically cleaved upon expression of the polypeptide (e.g., a polypeptide comprising SEQ ID NO: 973 is expressed using a nucleic acid construct encoding the polypeptide including a C-terminal lysine residue, which may then be removed via cleavage to produce a polypeptide in which the constant heavy chain has the sequence of SEQ ID NO: 651, such as the polypeptide of SEQ ID NO: 840). Accordingly, the OX40L antibody that is administered can have the constant heavy chain sequence of SEQ ID NO: 973, SEQ ID NO: 651, or a mixture thereof. [00405] In some embodiments, the OX40L antibody comprises a light chain comprising the sequence set forth in SEQ ID NO: 841. In some embodiments, the OX40L antibody comprises a heavy chain comprising the sequence set forth in SEQ ID NO: 839 or SEQ ID NO: 840. In some embodiments, the OX40L antibody comprises a heavy chain comprising the sequence set forth in SEQ ID NO: 839. In some embodiments, the OX40L antibody comprises a heavy chain comprising the sequence set forth in SEQ ID NO: 840. [00406] In some embodiments, the OX40L antibody comprises a light chain comprising the sequence set forth in SEQ ID NO: 841 and a heavy chain comprising the sequence set forth in SEQ ID NO: 839. In some embodiments, the OX40L antibody comprises a light chain comprising the sequence set forth in SEQ ID NO: 841 and a heavy chain comprising the sequence set forth in SEQ ID NO: 840. [00407] In certain embodiments, the Fc region binds an Fcγ Receptor selected from the group consisting of: FcγRI, FcγRIIa, FcγRIIb, FcγRIIc, FcγRIIIa, and FcγRIIIb. In certain embodiments, the Fc region binds an Fcγ Receptor with higher affinity at pH 6.0 compared to an antibody comprising a wild-type Fc region. Binding [00408] The affinity of a molecule X for its partner Y can be represented by the dissociation equilibrium constant (KD). The kinetic components that contribute to the dissociation equilibrium constant are described in more detail below. Affinity can be measured by common methods known in the art, including those described herein, such as surface plasmon resonance (SPR) technology (e.g., BIACORE®) or biolayer interferometry (e.g., FORTEBIO®). [00409] With regard to the binding of an antibody to a target molecule, the terms “bind,” “specific binding,” “specifically binds to,” “specific for,” “selectively binds,” and “selective for” a particular antigen (e.g., a polypeptide target) or an epitope on a particular antigen mean binding that is measurably different from a non-specific or non-selective interaction (e.g., with a non-target molecule). Specific binding can be measured, for example, by measuring binding to a target molecule (i.e., OX40L) and comparing it to binding to a non-target molecule. Specific binding can also be determined by competition with a control molecule that mimics the epitope recognized on the target molecule. In that case, specific binding is indicated if the binding of the antibody to the target molecule is competitively inhibited by the control molecule. In some embodiments, the affinity of an anti-OX40L antibody, or an antigen binding fragment thereof, for a non-target molecule is less than about 50% of the affinity for OX40L. In some embodiments, the affinity of an anti-OX40L antibody, or an antigen binding fragment thereof, for a non-target molecule is less than about 40% of the affinity for OX40L. In some embodiments, the affinity of an anti-OX40L antibody, or an antigen binding fragment thereof, for a non-target molecule is less than about 30% of the affinity for OX40L. In some embodiments, the affinity of an anti-OX40L antibody, or an antigen binding fragment thereof, for a non-target molecule is less than about 20% of the affinity for OX40L. In some embodiments, the affinity of an anti-OX40L antibody, or an antigen binding fragment thereof, for a non-target molecule is less than about 10% of the affinity for OX40L. In some embodiments, the affinity of an anti-OX40L antibody, or an antigen binding fragment thereof, for a non-target molecule is less than about 1% of the affinity for OX40L. In some embodiments, the affinity of an anti-OX40L antibody, or an antigen binding fragment thereof, for a non-target molecule is less than about 0.1% of the affinity for OX40L. [00410] In certain embodiments, the antibody, or an antigen binding fragment thereof, binds an OX40L sequence set forth in SEQ ID NO: 739. [00411] In certain embodiments, the antibody, or an antigen binding fragment thereof, binds to an OX40L sequence set forth in SEQ ID NO: 739 with a KD of less than or equal to about 1, 2, 3, 4, 5, 6, 7, 8, 9 x 10-9 M, as measured by surface plasmon resonance (SPR). In certain embodiments, the antibody, or an antigen binding fragment thereof, binds to an OX40L sequence set forth in SEQ ID NO: 739 with a KD of less than or equal to about 1 x 10-10 M, as measured by surface plasmon resonance (SPR). In certain embodiments, the antibody, or an antigen binding fragment thereof, binds to human OX40L with a KD of less than or equal to about 1 x 10-9 M, as measured by surface plasmon resonance (SPR). [00412] In some embodiments, an antibody, or an antigen binding fragment thereof, provided herein binds OX40L with a KD of less than or equal to about 0.01, 0.02, 0.03, 0.04, 0.05, 0.06, 0.07, 0.08, 0.09, 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1, 1.1, 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, 1.9, 1.95, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 7, 8, 9, or 10 x 10-8 M, as measured by ELISA or any other suitable method known in the art. In some embodiments, an antibody, or an antigen binding fragment thereof, provided herein binds OX40L with a KD of less than or equal to about 0.01, 0.02, 0.03, 0.04, 0.05, 0.06, 0.07, 0.08, 0.09, 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1, 1.1, 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, 1.9, 1.95, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 7, 8, 9, or 10 x 10-9 M, as measured by ELISA or any other suitable method known in the art. [00413] In some embodiments, the KD of the antibody, or an antigen binding fragment thereof, provided herein for the binding of OX40L is between about 0.001-0.01, 0.01-0.1, 0.01-0.05, 0.05-0.1, 0.1-0.5, 0.5-1, 0.25-0.75, 0.25-0.5, 0.5-0.75, 0.75-1, 0.75-2, 1.1-1.2, 1.2- 1.3, 1.3-1.4, 1.4-1.5, 1.5-1.6, 1.6-1.7, 1.7-1.8, 1.8-1.9, 1.9-2, 1-2, 1-5, 2-7, 3-8, 3-5, 4-6, 5-7, 6-8, 7-9, 7-10, or 5-10 x 10-8 M, as measured by ELISA or any other suitable method known in the art. In some embodiments, an antibody, or an antigen binding fragment thereof, provided herein binds OX40L with a KD of less than or equal to about 1 x 10-8 M, or less than or equal to about 1 x 10-9 M as measured by ELISA or any other suitable method known in the art. [00414] In some embodiments, the antibody, or an antigen binding fragment thereof, provided herein binds OX40L with a KD of less than or equal to about 10, 9, 8, 7, 6, 5, 4.5, 4, 3.5, 3, 2.5, 2, 1.98, 1.95, 1.9, 1.85, 1.8, 1.75, 1.7, 1.65, 1.6, 1.55, 1.50, 1.45, 1.4, 1.3, 1.2, 1.1, 1, 0.9, 0.85, 0.8, 0.75, 0.7, 0.65, 0.6, 0.55, 0.5, 0.45, 0.4, 0.35, 0.3, 0.25, 0.2, 0.15, 0.1, 0.05, 0.01, 0.005, 0.001, 0.0005, or 0.0001 x 10-8 M, or less, as measured by ELISA or any other suitable method known in the art . In some embodiments, the antibody, or an antigen binding fragment thereof, provided herein binds OX40L with a KD between 5-3, 4-2, 3-1, 1.9-1.8, 1.8-1.7, 1.7-1.6, 1.6-1.5, 1.9-1.5, 1.5-1, 1-0.8, 1-0.5, 0.9-0.6, 0.7-0.4, 0.6-0.2, 0.5-0.3, 0.3-0.2, 0.2-0.1, 0.1-0.01, 0.01-0.001, or 0.001-0.0001 x 10-8 M as measured by ELISA or any other suitable method known in the art. [00415] In some embodiments, the antibody, or an antigen binding fragment thereof, provided herein binds FcRn with an affinity at pH 7.4 compared to pH 6.0 at a ratio (pH 7.4/pH 6.0) of about 10,000, 1,000, 500, 100, 50, 20, 10, 9, 8, 7, 6, 5, 4.5, 4, 3.5, 3, 2.5, 2, 1.95, 1.9, 1.85, 1.8, 1.75, 1.7, 1.65, 1.6, 1.55, 1.50, 1.45, 1.4, 1.3, 1.2, 1.1, or 1.05, as measured by ELISA or any other suitable method known in the art. In some embodiments, the antibody, or an antigen binding fragment thereof, provided herein binds FcRn with an affinity at pH 6.0 compared to pH 7.4 at a ratio (pH 6.0/pH 7.4) of about 1-0.8, 1-0.5, 0.9-0.6, 0.7-0.4, 0.6-0.2, 0.5-0.3, 0.3-0.2, 0.2-0.1, 0.1-0.01, 0.01-0.001, or 0.001-0.0001 x 10-8 M as measured by ELISA or any other suitable method known in the art. Function [00416] “Effector functions” refer to those biological activities mediated by the Fc region of an antibody, which activities may vary depending on the antibody isotype. Examples of antibody effector functions include receptor ligand blocking, agonism, or antagonism, C1q binding to activate complement dependent cytotoxicity (CDC), Fc receptor binding to activate antibody-dependent cellular cytotoxicity (ADCC), and antibody dependent cellular phagocytosis (ADCP). Anti-IL-4Rα Antibodies [00417] The present application provides antibodies, or antigen binding fragments thereof, and compositions comprising an antibody, or an antigen binding fragment thereof, which binds IL-4Rα. See also PCT Application No. PCT/US2024/016235 (corresponding to PCT Publication No. WO2024173847), which is incorporated herein by reference in its entirety. In some embodiments, an anti-IL-4Rα antibody, or an antigen binding fragment thereof, described herein is selected from an anti-IL-4Rα antibody described therein. [00418] In some embodiments, an anti-IL-4Rα antibody, or an antigen binding fragment thereof, described herein is selected from dupilumab, stapokibart, and 611. In some embodiments, dupilumab comprises a variable heavy (VH) chain sequence having the amino acid sequence of SEQ ID NO: 113 and a variable light (VL) chain sequence having the amino acid sequence of SEQ ID NO: 146. In some embodiments, dupilumab comprises a heavy chain having the amino acid sequence of SEQ ID NO: 147 and a light chain sequence having the amino acid sequence of SEQ ID NO: 148. In some embodiments, stapokibart comprises a heavy chain having the amino acid sequence of SEQ ID NO: 1074 and a light chain sequence having the amino acid sequence of SEQ ID NO: 1075, or a VH and/or VL therein (e.g., a VH having the sequence of SEQ ID NO: 844 and a VL having the sequence of SEQ ID NO: 845). [00419] Anti-IL-4Rα antibodies can include those described herein such as the clones set forth in the drawings and/or tables. In some embodiments, the antibody comprises an alternative scaffold. In some embodiments, the antibody consists of an alternative scaffold. In some embodiments, the antibody consists essentially of an alternative scaffold. In some embodiments, the antibody comprises an antibody fragment. In some embodiments, the antibody consists of an antibody fragment. In some embodiments, the antibody consists essentially of an antibody fragment. [00420] In some embodiments the antibodies are monoclonal antibodies. [00421] In some embodiments the antibodies are polyclonal antibodies. [00422] In some embodiments the antibodies are produced by hybridomas. In other embodiments, the antibodies are produced by recombinant cells engineered to express the desired variable and constant domains. [00423] In some embodiments the antibodies may be single chain antibodies or other antibody derivatives retaining the antigen specificity and the lower hinge region or a variant thereof. [00424] In some embodiments the antibodies may be polyfunctional antibodies, recombinant antibodies, human antibodies, humanized antibodies, fragments or variants thereof. In particular embodiments, the antibody fragment or a derivative thereof is selected from a Fab fragment, a Fab′2 fragment, a CDR, and scFv. [00425] In some embodiments, the antibodies are capable of forming an immune complex. [00426] For sequence comparison, typically one sequence acts as a reference sequence to which test sequences are compared. When using a sequence comparison algorithm, test and reference sequences are input into a computer, subsequence coordinates are designated, if necessary, and sequence algorithm program parameters are designated. The sequence comparison algorithm then calculates the percent sequence identity for the test sequence(s) relative to the reference sequence, based on the designated program parameters. [00427] Optimal alignment of sequences for comparison can be conducted, e.g., by the local homology algorithm of Smith & Waterman, Adv. Appl. Math.2:482 (1981), by the homology alignment algorithm of Needleman & Wunsch, J. Mol. Biol.48:443 (1970), by the search for similarity method of Pearson & Lipman, Proc. Nat’l. Acad. Sci. USA 85:2444 (1988), by computerized implementations of these algorithms (GAP, BESTFIT, FASTA, and TFASTA in the Wisconsin Genetics Software Package, Genetics Computer Group, 575 Science Dr., Madison, Wis.), or by visual inspection (see generally Ausubel et al., infra). [00428] One example of an algorithm that is suitable for determining percent sequence identity and sequence similarity is the BLAST algorithm, which is described in Altschul et al., J. Mol. Biol.215:403-410 (1990). Software for performing BLAST analyses is publicly available through the National Center for Biotechnology Information (www.ncbi.nlm.nih.gov/). Sequences of IL-4Rα Antibodies TABLE 6. Sequences of IL-4Rα antibody constructs – VH, VL, and associated CDRs Identifier VH and Heavy Chain CDRs VL and Light Chain CDRs mAb422 VH (SEQ ID NO: 295) VL (SEQ ID NO: 298) Identifier VH and Heavy Chain CDRs VL and Light Chain CDRs IMGT (SEQ ID NO: 280) IMGT (amino acid sequence EG) [00429] In some embodiments, an antibody, or an antigen binding fragment thereof, provided herein comprises a VH sequence selected from any one of SEQ ID NOs: 295-297. [00430] In some embodiments, an antibody, or an antigen binding fragment thereof, provided herein comprises a VH sequence having at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to an illustrative VH sequence selected from any one of SEQ ID NOs: 295-297. In some embodiments, an antibody, or an antigen binding fragment thereof, provided herein comprises a VH sequence selected from any one of SEQ ID NOs: 295-297, with up to 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 amino acid substitutions. In some aspects, the amino acid substitutions are conservative amino acid substitutions. In some embodiments, the antibodies described in this paragraph are referred to herein as “variants.” In some embodiments, such variants are derived from a sequence provided herein, for example, by affinity maturation, site directed mutagenesis, random mutagenesis, or any other method known in the art or described herein. In some embodiments, such variants are not derived from a sequence provided herein and may, for example, be isolated de novo according to the methods provided herein for obtaining antibodies. Anti-IL-4Rα VL Domains [00431] In some embodiments, an antibody, or an antigen binding fragment thereof, provided herein comprises a VL sequence selected from any one of SEQ ID NOs: 298-300. [00432] In some embodiments, an antibody, or an antigen binding fragment thereof, provided herein comprises a VL sequence having at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to a VL sequence selected from any one of SEQ ID NOs: 298-300. In some embodiments, an antibody, or an antigen binding fragment thereof, provided herein comprises a VL sequence selected from any one of SEQ ID NOs: 298-300, with up to 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 amino acid substitutions. In some aspects, the amino acid substitutions are conservative amino acid substitutions. In some embodiments, the antibodies described in this paragraph are referred to herein as “variants.” In some embodiments, such variants are derived from a sequence provided herein, for example, by affinity maturation, site directed mutagenesis, random mutagenesis, or any other method known in the art or described herein. In some embodiments, such variants are not derived from a sequence provided herein and may, for example, be isolated de novo according to the methods provided herein for obtaining antibodies. Anti-IL-4Rα VH-VL Combinations [00433] In some embodiments, an antibody, or an antigen binding fragment thereof, provided herein comprises a VH sequence selected from any one of SEQ ID NOs: 295-297; and a VL sequence selected from any one of SEQ ID NOs: 298-300. [00434] In certain aspects, a VH sequence selected from any one of SEQ ID NOs: 295-297 can be combined with a VL sequence selected from any one of SEQ ID NOs: 298-300. [00435] In certain aspects, an antibody provided herein comprises a VH sequence and a VL sequence of a construct provided in TABLE 6 or a VH sequence and a VL sequence of a construct provided in PCT Application No. PCT/US2024/016235 (corresponding to PCT Publication No. WO2024173847), incorporated by reference herein in its entirety. In certain aspects, an antibody, or antigen binding fragment thereof, provided herein comprises a VH sequence and a VL sequence from Table 2 in PCT Application No. PCT/US2024/016235 (e.g., a VH sequence and a VL sequence from the same row of Table 2). [00436] In some embodiments, an antibody, or an antigen binding fragment thereof, provided herein comprises a VH sequence having at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to a VH sequence selected from any one of SEQ ID NOs: 295-297; and a VL sequence having at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to a VL sequence selected from any one of SEQ ID NOs: 298-300. In some embodiments, an antibody, or an antigen binding fragment thereof, provided herein comprises a VH sequence selected from any one of SEQ ID NOs: 295-297, with up to 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 amino acid substitutions, and a VL sequence selected from any one of SEQ ID NOs: 298-300, with up to 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 amino acid substitutions. In some aspects, the amino acid substitutions are conservative amino acid substitutions. In some embodiments, the antibodies described in this paragraph are referred to herein as “variants.” In some embodiments, such variants are derived from a sequence provided herein, for example, by affinity maturation, site directed mutagenesis, random mutagenesis, or any other method known in the art or described herein. In some embodiments, such variants are not derived from a sequence provided herein and may, for example, be isolated de novo according to the methods provided herein for obtaining antibodies. [00437] In certain embodiments, the antibody, or an antigen binding fragment thereof, comprises a VH sequence set forth in SEQ ID NO: 295 and a VL sequence set forth in SEQ ID NO: 298. [00438] In certain embodiments, the antibody, or an antigen binding fragment thereof, comprises a VH sequence set forth in SEQ ID NO: 296 and a VL sequence set forth in SEQ ID NO: 299. [00439] In certain embodiments, the antibody, or an antigen binding fragment thereof, comprises a VH sequence set forth in SEQ ID NO: 297 and a VL sequence set forth in SEQ ID NO: 300. [00440] In certain embodiments, an antibody, or an antigen binding fragment thereof, comprises any of the VH and VL combinations described above and further comprises a heavy chain comprising a human IgG sequence selected from a sequence set forth in SEQ ID NOs: 847-1070 or a sequence having at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity thereto. In certain embodiments, an antibody comprises any of the VH and VL combinations described above and further comprises a heavy chain comprising a constant heavy chain sequence set forth in SEQ ID NO: 651 or a sequence having at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity thereto. In certain embodiments, an antibody comprises any of the VH and VL combinations described above and further comprises a constant heavy chain comprising a constant heavy chain sequence set forth in SEQ ID NO: 973 or a sequence having at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity thereto. In certain embodiments, an antibody comprises any of the VH and VL combinations described above and further comprises a human constant light chain sequence set forth in SEQ ID NO: 738 or a sequence having at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity thereto. In certain embodiments, an antibody comprises any of the VH and VL combinations described above and further comprises a constant heavy chain sequence set forth in SEQ ID NO: 651 or a sequence having at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity thereto and a human constant light chain sequence set forth in SEQ ID NO: 738 or a sequence having at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity thereto. In certain embodiments, an antibody comprises any of the VH and VL combinations described above and further comprises a constant heavy chain sequence set forth in SEQ ID NO: 973 or a sequence having at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity thereto and a human constant light chain sequence set forth in SEQ ID NO: 738 or a sequence having at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity thereto. [00441] Although a C-terminal lysine may be present in the corresponding coding sequence of the constant heavy chain region (e.g., in a sequence encoding any one of SEQ ID NOs: 959-1070), it may be cleaved off during manufacture or after administration (resulting in, e.g., a constant heavy chain sequence of any one of SEQ ID NOs: 637-737 and 847-958). Accordingly, any of the antibodies or antigen binding fragments thereof described above may comprise a human IgG sequence containing a C-terminal lysine (e.g., any one of SEQ ID NOs: 959-1070), a human IgG sequence lacking a C-terminal lysine (e.g., any one of SEQ ID NOs: 637-737 and 847-958), or a mixture thereof (e.g., a mixture of the same heavy chain constant sequence with and without a C-terminal lysine, such as a mixture of SEQ ID NO: 973 and SEQ ID NO: 651). Anti-IL4Rα CDRs [00442] In some embodiments, disclosed herein is an antibody, or an antigen binding fragment thereof, comprising 1, 2, 3, 4, 5, or 6 of the CDRs of TABLE 6. In some embodiments, disclosed herein is an antibody, or an antigen binding fragment thereof, comprising 6 of the Kabat CDRs of TABLE 6. In some embodiments, disclosed herein is an antibody, or an antigen binding fragment thereof, comprising 1, 2, 3, 4, 5, or 6 of the Chothia CDRs of TABLE 6. In some embodiments, disclosed herein is an antibody, or an antigen binding fragment thereof, comprising 1, 2, 3, 4, 5, or 6 of the IMGT CDRs of TABLE 6. In some embodiments, the antibody, or an antigen binding fragment thereof, comprises 6 of the Kabat CDRs, 6 of the Chothia CDRs, or 6 of the IMGT CDRs from a single row of TABLE 6 (e.g., 6 CDRs from the same antibody). [00443] In some embodiments, disclosed herein is an antibody, or an antigen binding fragment thereof, comprising 1, 2, 3, 4, 5, or 6 of the CDRs of an antibody provided in PCT Application No. PCT/US2024/016235 (corresponding to PCT Publication No. WO2024173847), incorporated by reference herein in its entirety. In some embodiments, disclosed herein is an antibody, or an antigen binding fragment thereof, comprising 1, 2, 3, 4, 5, or 6 of the Kabat CDRs of an antibody provided in PCT Application No. PCT/US2024/016235. In some embodiments, disclosed herein is an antibody, or an antigen binding fragment thereof, comprising 1, 2, 3, 4, 5, or 6 of the Chothia CDRs of an antibody provided in PCT Application No. PCT/US2024/016235. In some embodiments, disclosed herein is an antibody, or an antigen binding fragment thereof, comprising 1, 2, 3, 4, 5, or 6 of the IMGT CDRs of an antibody provided in PCT Application No. PCT/US2024/016235. In some embodiments, the antibody, or an antigen binding fragment thereof, comprises 6 of the Kabat CDRs, 6 of the Chothia CDRs, or 6 of the IMGT CDRs from a single row of Table 2 of PCT Application No. PCT/US2024/016235 (e.g., 6 CDRs from the same antibody). [00444] In some embodiments, an antibody, or an antigen binding fragment thereof, provided herein comprises three CDRs of a VH domain selected from SEQ ID NOs: 295-297. In some aspects, the CDRs are exemplary CDRs. In some aspects, the CDRs are Kabat CDRs. In some aspects, the CDRs are Chothia CDRs. In some aspects, the CDRs are IMGT CDRs. In some aspects, the CDRs are AbM CDRs. In some aspects, the CDRs are Contact CDRs. [00445] In some embodiments, the CDRs are CDRs having at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity to a CDR-H1, CDR-H2, or CDR-H3 selected from SEQ ID NOs: 273-293 and 295-300. In some embodiments, the CDR-H1 is a CDR-H1 of a VH domain selected from SEQ ID NOs: 295-297, with up to 1, 2, 3, 4, or 5 amino acid substitutions. In some embodiments, the CDR-H2 is a CDR-H2 of a VH domain selected from SEQ ID NOs: 295-297, with up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions. In some embodiments, the CDR-H3 is a CDR-H3 of a VH domain selected from SEQ ID NOs: 295-297, with up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions. In some aspects, the amino acid substitutions are conservative amino acid substitutions. In some embodiments, the antibodies described in this paragraph are referred to herein as “variants.” In some embodiments, such variants are derived from a sequence provided herein, for example, by affinity maturation, site directed mutagenesis, random mutagenesis, or any other method known in the art or described herein. In some embodiments, such variants are not derived from a sequence provided herein and may, for example, be isolated de novo according to the methods provided herein for obtaining antibodies. [00446] In some embodiments, an antibody, or an antigen binding fragment thereof, provided herein comprises three CDRs of a VL domain selected from SEQ ID NOs: 298-300. In some aspects, the CDRs are exemplary CDRs. In some aspects, the CDRs are Kabat CDRs. In some aspects, the CDRs are Chothia CDRs. In some aspects, the CDRs are IMGT CDRs. In some aspects, the CDRs are AbM CDRs. In some aspects, the CDRs are Contact CDRs. [00447] In some embodiments, the CDRs are CDRs having at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity to a CDR-L1, CDR-L2, or CDR-L3 selected from SEQ ID NOs: 273-293 and 295-300, In some embodiments, the CDR- L1 is a CDR-L1 of a VL domain selected from SEQ ID NOs: 298-300, with up to 1, 2, 3, 4, or 5 amino acid substitutions. In some embodiments, the CDR-L2 is a CDR-L2 of a VL domain selected from SEQ ID NOs: 298-300, with up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions. In some embodiments, the CDR-L3 is a CDR-L3 of a VL domain selected from SEQ ID NOs: 298-300, with up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions. In some aspects, the amino acid substitutions are conservative amino acid substitutions. In some embodiments, the antibodies described in this paragraph are referred to herein as “variants.” In some embodiments, such variants are derived from a sequence provided herein, for example, by affinity maturation, site directed mutagenesis, random mutagenesis, or any other method known in the art or described herein. In some embodiments, such variants are not derived from a sequence provided herein and may, for example, be isolated de novo according to the methods provided herein for obtaining antibodies. [00448] In some embodiments, an antibody, or an antigen binding fragment thereof, provided herein comprises three CDRs of a VH domain selected from SEQ ID NOs: 295-297 and three CDRs of a VL domain selected from SEQ ID NOs: 298-300. In some aspects, the CDRs are exemplary CDRs. In some aspects, the CDRs are Kabat CDRs. In some aspects, the CDRs are Chothia CDRs. In some aspects, the CDRs are IMGT CDRs. In some aspects, the CDRs are AbM CDRs. In some aspects, the CDRs are Contact CDRs. [00449] In some embodiments, an antibody, or an antigen binding fragment thereof, provided herein comprises a CDR-H3 selected from SEQ ID NOs: 281-284. In some aspects, the CDR-H3 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to a CDR-H3 selected from SEQ ID NOs: 281-284. In some embodiments, the CDR-H3 is a CDR-H3 selected from SEQ ID NOs: 281-284, with up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions. In some aspects, the amino acid substitutions are conservative amino acid substitutions. In some embodiments, the antibodies described in this paragraph are referred to herein as “variants.” In some embodiments, such variants are derived from a sequence provided herein, for example, by affinity maturation, site directed mutagenesis, random mutagenesis, or any other method known in the art or described herein. In some embodiments, such variants are not derived from a sequence provided herein and may, for example, be isolated de novo according to the methods provided herein for obtaining antibodies. [00450] In some embodiments, an antibody, or an antigen binding fragment thereof, provided herein comprises a CDR-H1 selected from SEQ ID NOs: 273-275. In some aspects, the CDR-H1 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to a CDR-H1 selected from SEQ ID NOs: 273-275. In some embodiments, the CDR-H1 is a CDR-H1 selected from SEQ ID NOs: 273-275, with up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions. In some aspects, the amino acid substitutions are conservative amino acid substitutions. In some embodiments, the antibodies described in this paragraph are referred to herein as “variants.” In some embodiments, such variants are derived from a sequence provided herein, for example, by affinity maturation, site directed mutagenesis, random mutagenesis, or any other method known in the art or described herein. In some embodiments, such variants are not derived from a sequence provided herein and may, for example, be isolated de novo according to the methods provided herein for obtaining antibodies. [00451] In some embodiments, an antibody, or an antigen binding fragment thereof, provided herein comprises a CDR-H2 selected from SEQ ID NOs: 276-282. In some aspects, the CDR-H2 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to a CDR-H2 H2 selected from SEQ ID NOs: 276-282. In some embodiments, the CDR-H2 is a CDR-H2 selected from SEQ ID NOs: 276-282, with up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions. In some aspects, the amino acid substitutions are conservative amino acid substitutions. In some embodiments, the antibodies described in this paragraph are referred to herein as “variants.” In some embodiments, such variants are derived from a sequence provided herein, for example, by affinity maturation, site directed mutagenesis, random mutagenesis, or any other method known in the art or described herein. In some embodiments, such variants are not derived from a sequence provided herein and may, for example, be isolated de novo according to the methods provided herein for obtaining antibodies. [00452] In some embodiments, an antibody, or an antigen binding fragment thereof, provided herein comprises a CDR-L3 of SEQ ID NO: 293. In some aspects, the CDR-L3 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to a CDR-L3 of SEQ ID NO: 293. In some embodiments, the CDR-L3 is a CDR-L3 of SEQ ID NO: 293, with up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions. In some aspects, the amino acid substitutions are conservative amino acid substitutions. In some embodiments, the antibodies described in this paragraph are referred to herein as “variants.” In some embodiments, such variants are derived from a sequence provided herein, for example, by affinity maturation, site directed mutagenesis, random mutagenesis, or any other method known in the art or described herein. In some embodiments, such variants are not derived from a sequence provided herein and may, for example, be isolated de novo according to the methods provided herein for obtaining antibodies. [00453] In some embodiments, an antibody, or an antigen binding fragment thereof, provided herein comprises a CDR-L2 selected from SEQ ID NOs: 290-292 and the amino acid sequence LG or EG. In some aspects, the CDR-L2 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to a CDR-L2 selected from SEQ ID NOs: 290-292 and the amino acid sequence LG or EG. In some embodiments, the CDR-L2 is a CDR-L2 selected from SEQ ID NOs: 290-292 and the amino acid sequence LG or EG, with up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions. In some aspects, the amino acid substitutions are conservative amino acid substitutions. In some embodiments, the antibodies described in this paragraph are referred to herein as “variants.” In some embodiments, such variants are derived from a sequence provided herein, for example, by affinity maturation, site directed mutagenesis, random mutagenesis, or any other method known in the art or described herein. In some embodiments, such variants are not derived from a sequence provided herein and may, for example, be isolated de novo according to the methods provided herein for obtaining antibodies. [00454] In some embodiments, an antibody, or an antigen binding fragment thereof, provided herein comprises a CDR-L1 selected from SEQ ID NOs: 285-289. In some aspects, the CDR-L1 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to a CDR-L1 selected from SEQ ID NOs: 285-289. In some embodiments, the CDR-L1 is a CDR-L1 selected from SEQ ID NOs: 285-289, with up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions. In some aspects, the amino acid substitutions are conservative amino acid substitutions. In some embodiments, the antibodies described in this paragraph are referred to herein as “variants.” In some embodiments, such variants are derived from a sequence provided herein, for example, by affinity maturation, site directed mutagenesis, random mutagenesis, or any other method known in the art or described herein. In some embodiments, such variants are not derived from a sequence provided herein and may, for example, be isolated de novo according to the methods provided herein for obtaining antibodies. [00455] In some embodiments, an antibody, or an antigen binding fragment thereof, provided herein comprises a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 273; a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 276; a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 281; a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 285; a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 292; and a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 293. [00456] In some embodiments, an antibody, or an antigen binding fragment thereof, provided herein comprises a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 274; a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 277; a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 281; a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 285; a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 292; and a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 293. [00457] In some embodiments, an antibody, or an antigen binding fragment thereof, provided herein comprises a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 275; a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 278; a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 282; a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 286; a CDR-L2 comprising the amino acid sequence LG; and a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 293. [00458] In some embodiments, an antibody, or an antigen binding fragment thereof, provided herein comprises a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 273; a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 279; a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 283; a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 287; a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 291; and a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 293. [00459] In some embodiments, an antibody, or an antigen binding fragment thereof, provided herein comprises a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 274; a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 277; a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 283; a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 287; a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 291; and a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 293. [00460] In some embodiments, an antibody, or an antigen binding fragment thereof, provided herein comprises a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 275; a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 280; a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 284; a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 288; a CDR-L2 comprising the amino acid sequence LG; and a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 293. [00461] In some embodiments, an antibody, or an antigen binding fragment thereof, provided herein comprises a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 273; a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 279; a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 281; a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 289; a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 290; and a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 293. [00462] In some embodiments, an antibody, or an antigen binding fragment thereof, provided herein comprises a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 274; a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 277; a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 281; a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 289; a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 290; and a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 293. [00463] In some embodiments, an antibody, or an antigen binding fragment thereof, provided herein comprises a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 275; a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 280; a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 282; a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 288; a CDR-L2 comprising the amino acid sequence EG; and a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 293. [00464] In certain embodiments, any of the antibodies or antigen binding fragments thereof described above further comprises a heavy chain comprising a human IgG sequence selected from a sequence set forth in any one of SEQ ID NOs: 847-1070 or a sequence having at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity thereto. In certain embodiments, any of the antibodies or antigen binding fragments thereof described above further comprises a constant heavy chain sequence set forth in SEQ ID NO: 651 or a sequence having at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity thereto. In certain embodiments, any of the antibodies or antigen binding fragments thereof described above further comprises a constant heavy chain sequence set forth in SEQ ID NO: 973 or a sequence having at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity thereto. In certain embodiments, any of the antibodies or antigen binding fragments thereof described above further comprises a human constant light chain sequence set forth in SEQ ID NO: 738 or a sequence having at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity thereto. In certain embodiments, any of the antibodies or antigen binding fragments thereof described above further comprises a constant heavy chain sequence set forth in SEQ ID NO: 651 or a sequence having at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity thereto and a human constant light chain sequence set forth in SEQ ID NO: 738 or a sequence having at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity thereto. In certain embodiments, any of the antibodies or antigen binding fragments thereof described above further comprises a constant heavy chain sequence set forth in SEQ ID NO: 973 or a sequence having at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity thereto and a human constant light chain sequence set forth in SEQ ID NO: 738 or a sequence having at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity thereto. [00465] Although a C-terminal lysine may be present in the corresponding coding sequence of the constant heavy chain region (e.g., in a sequence encoding any one of SEQ ID NOs: 959-1070), it may be cleaved off during manufacture or after administration (resulting in, e.g., a constant heavy chain sequence of any one of SEQ ID NOs: 637-737 and 847-958). Accordingly, any of the antibodies or antigen binding fragments thereof described above may comprise a human IgG sequence containing a C-terminal lysine (e.g., any one of SEQ ID NOs: 959-1070), a human IgG sequence lacking a C-terminal lysine (e.g., any one of SEQ ID NOs: 637-737 and 847-958), or a mixture thereof (e.g., a mixture of the same heavy chain constant sequence with and without a C-terminal lysine, such as a mixture of SEQ ID NO: 973 and SEQ ID NO: 651). [00466] In some aspects, the amino acid substitutions are conservative amino acid substitutions. In some embodiments, the antibodies described in this disclosure are referred to herein as “variants” or “clones”. In some embodiments, such variants or clones are derived from a sequence provided herein, for example, by affinity maturation, site directed mutagenesis, random mutagenesis, or any other method known in the art or described herein. In some embodiments, such variants or cones are not derived from a sequence provided herein and may, for example, be isolated de novo according to the methods provided herein for obtaining antibodies. Fc Region [00467] The structures of the Fc regions of various immunoglobulins, and the glycosylation sites contained therein, are known in the art. See Schroeder and Cavacini, J. Allergy Clin. Immunol., 2010, 125:S41-52, incorporated by reference in its entirety. The Fc region may be a naturally occurring Fc region or an Fc region modified as described in the art or elsewhere in this disclosure. [00468] Unless otherwise specified herein, numbering of amino acid residues in the Fc region or constant region is according to the EU numbering system, also called the EU index, as described in Kabat et al., Sequences of Proteins of Immunological Interest, 5th Ed. Public Health Service, National Institutes of Health, Bethesda, MD, 1991. An “Fc polypeptide” of a dimeric Fc as used herein refers to one of the two polypeptides forming the dimeric Fc domain, i.e., a polypeptide comprising C-terminal constant regions of an immunoglobulin heavy chain, capable of stable self-association. For example, an Fc polypeptide of a dimeric IgG Fc comprises an IgG CH2 and an IgG CH3 constant domain sequence. An Fc can be of the class IgA, IgD, IgE, IgG, and IgM, and several of these may be further divided into subclasses (isotypes), e.g., IgG1, IgG2, IgG3, IgG4, IgA1, and IgA2. [00469] The terms “Fc receptor” and “FcR” are used to describe a receptor that binds to the Fc region of an antibody. For example, an FcR can be a native sequence human FcR. Generally, an FcR is one which binds an IgG antibody (a gamma receptor) and includes receptors of the FcγRI, FcγRII, and FcγRIII subclasses, including allelic variants and alternatively spliced forms of these receptors. FcγRII receptors include FcγRIIA (an “activating receptor”) and FcγRIIB (an “inhibiting receptor”), which have similar amino acid sequences that differ primarily in the cytoplasmic domains thereof. Immunoglobulins of other isotypes can also be bound by certain FcRs (see, e.g., Janeway et al., Immuno Biology: the immune system in health and disease, (Elsevier Science Ltd., NY) (4th ed., 1999)). Activating receptor FcγRIIA contains an immunoreceptor tyrosine-based activation motif (ITAM) in its cytoplasmic domain. Inhibiting receptor FcγRIIB contains an immunoreceptor tyrosine-based inhibition motif (ITIM) in its cytoplasmic domain (reviewed in Daëron, Annu. Rev. Immunol.15:203-234 (1997)). FcRs are reviewed in Ravetch and Kinet, Annu. Rev. Immunol 9:457-92 (1991); Capel et al., Immunomethods 4:25-34 (1994); and de Haas et al., J. Lab. Clin. Med.126:330-41 (1995). Other FcRs, including those to be identified in the future, are encompassed by the term “FcR” herein. The term also includes the neonatal receptor, FcRn, which is responsible for the transfer of maternal IgGs to the fetus (Guyer et al., J. Immunol.117:587 (1976); and Kim et al., J. Immunol.24:249 (1994)). [00470] Modifications in the CH2 domain can affect the binding of FcRs to the Fc. A number of amino acid modifications in the Fc region are known that can selectively alter the affinity of the Fc for different Fcgamma receptors. In some embodiments, the Fc comprises one or more modifications designed to promote selective binding of Fc-gamma receptors. [00471] Exemplary mutations that may alter the binding of FcRs to the Fc are listed below (in EU numbering format): • S298A/E333A/K334A, S298A/E333A/K334A/K326A (Lu Y, Vernes JM, Chiang N, et al., J Immunol Methods.2011 Feb 28;365(1-2):132-41); • F243L/R292P/Y300L/V305I/P396L, F243L/R292P/Y300L/L235V/P396L (Stavenhagen JB, Gorlatov S, Tuaillon N, et al., Cancer Res.2007 Sep 15;67(18):8882-90; Nordstrom JL, Gorlatov S, Zhang W, et al., Breast Cancer Res. 2011 Nov 30;13(6):R123); • F243L (Stewart R, Thom G, Levens M, et al., Protein Eng Des Sel.2011 Sep;24(9):671-8.), S298A/E333A/K334A (Shields RL, Namenuk AK, Hong K, et al., J Biol Chem.2001 Mar 2;276(9):6591-604); • S239D/I332E/A330L, S239D/I332E (Lazar et al., (2006) Proc Natl Acad Sci U S A. 103(11):4005-10); • S239D/S267E, S267E/L328F (Chu et al., (2008) Mol Immunol.45(15):3926-33); • S239D/D265S/S298A/I332E, S239E/S298A/K326A/A327H, G237F/S298A/A330L/I 332E, S239D/I332E/S298A, S239D/K326E/A330L/I332E/S298A, G236A/S239D/D2 70L/I332E, S239E/S267E/H268D, L234F/S267E/N325L, G237F/V266L/S267D and other mutations listed in WO2011/120134 and WO2011/120135, herein incorporated by reference. Therapeutic Antibody Engineering (by William R. Strohl and Lila M. Strohl, Woodhead Publishing series in Biomedicine No 11, ISBN 1907568379, Oct 2012) lists mutations on page 283. [00472] In some embodiments an antibody, or an antigen binding fragment thereof, described herein includes modifications designed to improve its ability to mediate effector function. Such modifications that can have this effect are known in the art and include afucosylation, or engineering of the affinity of the Fc towards an activating receptor, mainly FCGR3a for ADCC, and towards C1q for CDC. The following TABLE 7 summarizes various designs reported in the literature for effector function engineering. [00473] Methods of producing antibodies with little or no fucose on the Fc glycosylation site (Asn 297 EU numbering) without altering the amino acid sequence are well known in the art. The GlymaxX® technology (ProBioGen AG) is based on the introduction of a gene for an enzyme which deflects the cellular pathway of fucose biosynthesis into cells used for antibody production. This prevents the addition of the sugar “fucose” to the N-linked antibody carbohydrate part by antibody-producing cells (von Horsten et al. (2010) Glycobiology.2010 Dec; 20 (12):1607-18). Examples of cell lines capable of producing defucosylated antibody include CHO-DG44 with stable overexpression of the bacterial oxidoreductase GDP-6-deoxy-D-lyxo-4-hexylose reductase (RMD) (see von Horsten et al. (2010) supra) or Lec13 CHO cells, which are deficient in protein fucosylation (see Ripka et al. (1986) Arch. Biochem. Biophys.249:533-545; U.S. Pat. Pub. No.2003/0157108; WO 2004/056312; each of which is incorporated by reference in its entirety), and knockout cell lines, such as alpha-1,6-fucosyltransferase gene or FUT8 knockout CHO cells (see Yamane- Ohnuki et al. (2004) Biotech. Bioeng.87: 614-622; Kanda et al. (2006) Biotechnol. Bioeng. 94:680-688; and WO 2003/085107; each of which is incorporated by reference in its entirety). Another approach to obtaining antibodies with lowered levels of fucosylation can be found in U.S. Patent No.8,409,572, which teaches selecting cell lines for antibody production for their ability to yield lower levels of fucosylation on antibodies. [00474] Antibodies can be fully afucosylated (meaning they contain no detectable fucose) or they can be partially afucosylated, meaning that the isolated antibody contains less than 95%, less than 85%, less than 75%, less than 65%, less than 55%, less than 45%, less than 35%, less than 25%, less than 15% or less than 5% of the amount of fucose normally detected for a similar antibody produced by a mammalian expression system. [00475] In some aspects, an antibody, or an antigen binding fragment thereof, provided herein comprises an IgG1 domain with reduced fucose content at position Asn 297 compared to a naturally occurring IgG1 domain. Such Fc domains can have improved ADCC. See Shields et al. (2002) J. Biol. Chem.277:26733-26740, incorporated by reference in its entirety. In some aspects, such antibodies do not comprise any fucose at position Asn 297. The amount of fucose may be determined using any suitable method, for example as described in WO 2008/077546, incorporated by reference in its entirety. [00476] In certain embodiments, an antibody, or an antigen binding fragment thereof, provided herein comprises an Fc region with one or more amino acid substitutions which improve ADCC, such as a substitution at one or more of positions 298, 333, and 334 of the Fc region. In some embodiments, an antibody, or an antigen binding fragment thereof, provided herein comprises an Fc region with one or more amino acid substitutions at positions 239, 332, and 330, as described in Lazar et al. (2006) Proc. Natl. Acad. Sci. USA 103:4005-4010, incorporated by reference in its entirety. [00477] Other illustrative glycosylation variants which may be incorporated into the antibodies provided herein are described, for example, in U.S. Pat. Pub. Nos.2003/0157108, 2004/0093621, 2003/0157108, 2003/0115614, 2002/0164328, 2004/0093621, 2004/0132140, 2004/0110704, 2004/0110282, 2004/0109865; International Pat. Pub. Nos.2000/61739, 2001/29246, 2003/085119, 2003/084570, 2005/035586, 2005/035778; 2005/053742, 2002/031140; Okazaki et al., J. Mol. Biol., 2004, 336:1239-1249; and Yamane-Ohnuki et al. (2004) supra; each of which is incorporated by reference in its entirety. [00478] In some embodiments, an antibody, or an antigen binding fragment thereof, provided herein comprises an Fc region with at least one galactose residue in the oligosaccharide attached to the Fc region. Such antibody variants may have improved CDC function. Examples of such antibody variants are described, for example, in WO 1997/30087; WO 1998/58964; and WO 1999/22764; each of which is incorporated by reference in its entirety. [00479] Thus, in one embodiment, an antibody described herein can include a dimeric Fc that comprises one or more amino acid modifications as noted in TABLE 7 that may confer improved effector function. In another embodiment, the antibody can be afucosylated to improve effector function. TABLE 7. CH2 domains and effector function engineering Reference Mutations Effect Lu (2011) supra Ferrara Afucosylated Increased ADCC C C C C C C C C C C [00480] Fc modifications that are designed to reduce FcgR and/or complement binding and/or effector function are known in the art. Recent publications describe strategies that have been used to engineer antibodies with reduced or silenced effector activity (see Strohl, WR (2009), Curr Opin Biotech 20:685-691, and Strohl, WR and Strohl LM, “Antibody Fc engineering for optimal antibody performance” In Therapeutic Antibody Engineering, Cambridge: Woodhead Publishing (2012), pp 225-249). These strategies include reduction of effector function through modification of glycosylation, use of IgG2/IgG4 scaffolds, or the introduction of mutations in the hinge or CH2 regions of the Fc. For example, U.S. Patent Publication No.2011/0212087 (Strohl), International Patent Publication No. WO 2006/105338 (Xencor), U.S. Patent Publication No.2012/0225058 (Xencor), U.S. Patent Publication No.2012/0251531 (Genentech), and Strop et al. ((2012) J. Mol. Biol.420: 204- 219), each of which is incorporated by reference in its entirety, describe specific modifications designed to reduce FcgR or complement binding to the Fc. [00481] Specific, non-limiting examples of amino acid modifications designed to reduce FcgR or complement binding to the Fc include those identified in the following TABLE 8: TABLE 8. Modifications designed to reduce FcgR or complement binding to the Fc Mutations Mutations [00482] In some embodiments, an antibody, or an antigen binding fragment thereof, provided herein comprises one or more alterations that is designed to improve or diminish C1q binding and/or CDC. See U.S. Pat. No.6,194,551; WO 99/51642; and Idusogie et al., J. Immunol., 2000, 164:4178-4184; each of which is incorporated by reference in its entirety. [00483] In certain embodiments, an antibody provided herein comprises a heavy chain comprising a constant heavy chain sequence selected from the sequences set forth in any one of SEQ ID NOs: 847-1070. [00484] In certain embodiments, the antibody comprises a VH sequence set forth in SEQ ID NO: 295 and a VL sequence set forth in SEQ ID NO: 298; and the constant heavy chain comprises a human IgG sequence selected from a sequence set forth in any one of SEQ ID NOs: 847-1070 (e.g., SEQ ID NO: 973 or SEQ ID NO: 861). In certain embodiments, the antibody comprises a VH sequence set forth in SEQ ID NO: 296 and a VL sequence set forth in SEQ ID NO: 299; and the constant heavy chain comprises a human IgG sequence selected from a sequence set forth in any one of SEQ ID NOs: 847-1070 (e.g., SEQ ID NO: 973 or SEQ ID NO: 861). In certain embodiments, the antibody comprises a VH sequence set forth in SEQ ID NO: 297 and a VL sequence set forth in SEQ ID NO: 300; and the constant heavy chain comprises a human IgG sequence selected from a sequence set forth in any one of SEQ ID NOs: 847-1070 (e.g., SEQ ID NO: 973 or SEQ ID NO: 861). [00485] In certain embodiments, the Fc region comprises one or more amino acid substitutions, wherein the one or more substitutions result in increased antibody half-life, increased ADCC activity, increased ADCP activity, or increased CDC activity compared with the Fc without the one or more substitutions. In certain embodiments, the one or more amino acid substitutions results in increased antibody half-life at pH 6.0 compared to an antibody comprising a wild-type Fc region. In certain embodiments, the isolated antibody comprising an Fc region with one or more amino acid substitutions has a half-life of about 20 to 60 days in a human. [00486] In certain embodiments, the antibody has an increased half-life that is about 10,000-fold, 1,000-fold, 500-fold, 100-fold, 50-fold, 20-fold, 10-fold, 9-fold, 8-fold, 7-fold, 6-fold, 5-fold, 4.5-fold, 4-fold, 3.5-fold, 3-fold, 2.5-fold, 2-fold, 1.95-fold, 1.9-fold, 1.85- fold, 1.8-fold, 1.75-fold, 1.7-fold, 1.65-fold, 1.6-fold, 1.55-fold, 1.50-fold, 1.45-fold, 1.4-fold, 1.35-fold, 1.3-fold, 1.25-fold, 1.2-fold, 1.15-fold, 1.1-fold, or 1.05-fold longer compared to an antibody comprising a wild-type Fc region. In certain embodiments, the antibody has an increased half-life that is about 10,000-fold, 1,000-fold, 500-fold, 100-fold, 50-fold, 20-fold, 10-fold, 9-fold, 8-fold, 7-fold, 6-fold, 5-fold, 4.5-fold, 4-fold, 3.5-fold, 3-fold, 2.5-fold, 2- fold, 1.95-fold, 1.9-fold, 1.85-fold, 1.8-fold, 1.75-fold, 1.7-fold, 1.65-fold, 1.6-fold, 1.55-fold, 1.50-fold, 1.45-fold, 1.4-fold, 1.35-fold, 1.3-fold, 1.25-fold, 1.2-fold, 1.15-fold, 1.1-fold, or 1.05-fold longer compared to dupilumab. [00487] In certain embodiments, the Fc region comprises one or more amino acid substitutions, wherein the one or more substitutions result in increased antibody half-life, and a decrease in one or more of ADCC activity, ADCP activity, or CDC activity compared with the Fc without the one or more substitutions. In certain embodiments, the one or more amino acid substitutions results in increased antibody half-life at pH 6.0 compared to an antibody comprising a wild-type Fc region. In certain embodiments, the isolated antibody comprising an Fc region with one or more amino acid substitutions has a half-life of about 20 to 60 days in a human. [00488] In certain embodiments, the one or more amino acid substitutions is selected from the group consisting of S228P (SP), M252Y, S254T, T256E, T256D, T250Q, H285D, T307A, T307Q, T307R, T307W, L309D, Q411H, Q311V, A378V, E380A, M428L, N434A, N434S, N297A, D265A, L234A, L235A, and N434W. In certain embodiments, the one or more amino acid substitutions comprises a plurality of amino acid substitutions selected from the group consisting of M428L/N434S (LS), M252Y/S254T/T256E (YTE), T250Q/M428L, T307A/E380A/N434A, T256D/T307Q (DQ), T256D/T307W (DW), M252Y/T256D (YD), T307Q/Q311V/A378V (QVV), T256D/H285D/T307R/Q311V/A378V (DDRVV), L309D/Q311H/N434S (DHS), S228P/L235E (SPLE), L234A/L235A (LALA), M428L/N434A (LA), L235A/G237A(LAGA), L234A/L235A/G237A (LALAGA), L234A/L235A/P329G (LALAPG)), N297A, D265A/YTE, LALA/YTE, LAGA/YTE, LALAGA/YTE, LALAPG/YTE, N297A/LS, D265A/LS, LALA/LS, LALAGA/LS, LALAPG/LS, N297A/DHS, D265A/DHS, LALA/DHS, LAGA/DHS, LALAGA/DHS, LALAPG/DHS, SP/YTE, SPLE/YTE, SP/LS, SPLE/LS, SP/DHS, SPLE/DHS, N297A/LA, D265A/LA, LALA/LA, LAGA/LA, LALAGA/LA, LALAPG/LA, N297A/N434A, D265A/N434A; LALA/N434A, LAGA/N434A, LALAGA/N434A, LALAPG/N434A, N297A/N434W, D265A/N434W, LALA/N434W, LAGA/N434W, LALAGA/N434W, LALAPG/N434W, N297A/DQ, D265A/DQ, LALA/DQ, LAGA/DQ, LALAGA/DQ, LALAPG/DQ, N297A/DW, D265A/DW, LALA/DW, LAGA/DW, LALAGA/DW, LALAPG/DW N297A/YD, D265A/YD, LALA/YD, LAGA/YD, LALAGA/YD, LALAPG/YD, T307Q/Q311V/A378V (QVV), N297A/QVV, D265A/QVV, LALA/QVV, LAGA/QVV, LALAGA/QVV, LALAPG/QVV, DDRVV, N297A/DDRVV, D265A/DDRVV, LALA/DDRVV, LAGA/DDRVV, LALAGA/DDRVV, and LALAPG/DDRVV. [00489] In certain embodiments, the one or more amino acid substitutions is selected from the group consisting of LALA/YTE, LAGA/YTE, LALA/LS, YTE, and LS. [00490] In certain embodiments, the one or more amino acid substitutions comprises or consists of LALA/YTE. In certain embodiments, the one or more amino acid substitutions comprises or consists of LAGA/YTE. In certain embodiments, the one or more amino acid substitutions comprises or consists of LALA/LS. In certain embodiments, the one or more amino acid substitutions comprises or consists of YTE. In certain embodiments, the one or more amino acid substitutions comprises or consists of LS. [00491] Although the EU numbering system is typically used to identify the positions of the various Fc mutations described herein, direct numbering can also be used. For example, in certain embodiments, an antibody described herein comprises an Fc region with YTE mutations at positions 260, 262, and 264. In certain embodiments, an antibody described herein comprises an Fc region with LALA mutations at positions 242 and 243, respectively. In certain embodiments, an antibody described herein comprises an Fc region with YTE mutations at positions 260, 262, and 264 and with LALA mutations at positions 242 and 243. In certain embodiments, the IL-4Rα antibody described herein comprises the heavy and light chain variable regions of Construct 38 and an Fc region comprising YTE mutations at positions 260, 262, and 264, respectively and with LALA mutations at positions 242 and 243, respectively (e.g., as shown in the heavy chain sequences of SEQ ID NOs: 836 and 837). [00492] In certain embodiments the human Fc region comprises a human IgG1 Fc with LALA mutations. In certain embodiments, the human Fc region comprises a human IgG1 Fc with YTE mutations. In certain embodiments, the human Fc region comprises a human IgG1 Fc with LALA and YTE mutations. In certain embodiments, when direct numbering is used, “YTE” and “LALA” mutations can be located at different amino acid position numbers. For example, a human Fc region can comprise a human IgG1 Fc with LALA mutations at L242A/L243A and/or YTE mutations at M260Y/S262T/T264E. [00493] In some embodiments, the IL-4Rα antibody, or antigen binding fragment thereof, comprises a heavy chain variable region sequence comprising an amino acid sequence set forth in SEQ ID NO: 297, a constant heavy chain sequence set forth in SEQ ID NO: 651, a light chain variable region sequence comprising an amino acid sequence set forth in SEQ ID NO: 300, and a constant light chain sequence set forth in SEQ ID NO: 738. In some embodiments, the IL-4Rα antibody comprises a heavy chain variable region sequence comprising an amino acid sequence set forth in SEQ ID NO: 297, a constant heavy chain sequence set forth in SEQ ID NO: 973, a light chain variable region sequence comprising an amino acid sequence set forth in SEQ ID NO: 300, and a constant light chain sequence set forth in SEQ ID NO: 738. [00494] The C-terminal Lys330 of the constant heavy chain sequence of SEQ ID NO: 973 may or may not be present. The disclosure specifically contemplates SEQ ID NO: 973 that does not include the C-terminal Lys corresponding to Lys330 (as set forth in SEQ ID NO: 651). A polypeptide comprising SEQ ID NO: 973 (e.g., the polypeptide of SEQ ID NO: 836) may be expressed including a C-terminal Lys330 which then may be proteolytically cleaved upon expression of the polypeptide (e.g., a polypeptide comprising SEQ ID NO: 973 is expressed using a nucleic acid construct encoding the polypeptide including a C-terminal lysine residue, which may then be removed via cleavage to produce a polypeptide in which the constant heavy chain has the sequence of SEQ ID NO: 651, such as the polypeptide of SEQ ID NO: 837). Accordingly, the IL-4Rα antibody that is administered can have the constant heavy chain sequence of SEQ ID NO: 973, SEQ ID NO: 651, or a mixture thereof. [00495] In some embodiments, the IL-4Rα antibody comprises a light chain comprising the sequence set forth in SEQ ID NO: 838. In some embodiments, the IL-4Rα antibody comprises a heavy chain comprising the sequence set forth in SEQ ID NO: 836 or SEQ ID NO: 837. In some embodiments, the IL-4Rα antibody comprises a heavy chain comprising the sequence set forth in SEQ ID NO: 836. In some embodiments, the IL-4Rα antibody comprises a heavy chain comprising the sequence set forth in SEQ ID NO: 837. [00496] In some embodiments, the IL-4Rα antibody comprises a light chain comprising the sequence set forth in SEQ ID NO: 838 and a heavy chain comprising the sequence set forth in SEQ ID NO: 836. In some embodiments, the IL-4Rα antibody comprises a light chain comprising the sequence set forth in SEQ ID NO: 838 and a heavy chain comprising the sequence set forth in SEQ ID NO: 837. [00497] In certain embodiments, the Fc region binds an Fcγ Receptor selected from the group consisting of: FcγRI, FcγRIIa, FcγRIIb, FcγRIIc, FcγRIIIa, and FcγRIIIb. In certain embodiments, the Fc region binds an Fcγ Receptor with higher affinity at pH 6.0 compared to an antibody comprising a wild-type Fc region. Binding [00498] The affinity of a molecule X for its partner Y can be represented by the dissociation equilibrium constant (KD). The kinetic components that contribute to the dissociation equilibrium constant are described in more detail below. Affinity can be measured by common methods known in the art, including those described herein, such as surface plasmon resonance (SPR) technology (e.g., BIACORE®) or biolayer interferometry (e.g., FORTEBIO®). [00499] With regard to the binding of an antibody to a target molecule, the terms “bind,” “specific binding,” “specifically binds to,” “specific for,” “selectively binds,” and “selective for” a particular antigen (e.g., a polypeptide target) or an epitope on a particular antigen mean binding that is measurably different from a non-specific or non-selective interaction (e.g., with a non-target molecule). Specific binding can be measured, for example, by measuring binding to a target molecule (i.e., IL-4Rα) and comparing it to binding to a non-target molecule. Specific binding can also be determined by competition with a control molecule that mimics the epitope recognized on the target molecule. In that case, specific binding is indicated if the binding of the antibody to the target molecule is competitively inhibited by the control molecule. In some embodiments, the affinity of an anti-IL-4Rα antibody, or an antigen binding fragment thereof, for a non-target molecule is less than about 50% of the affinity for IL-4Rα. In some embodiments, the affinity of an anti-IL-4Rα antibody, or an antigen binding fragment thereof, for a non-target molecule is less than about 40% of the affinity for IL-4Rα. In some embodiments, the affinity of an anti-IL-4Rα antibody, or an antigen binding fragment thereof, for a non-target molecule is less than about 30% of the affinity for IL-4Rα. In some embodiments, the affinity of an anti-IL-4Rα antibody, or an antigen binding fragment thereof, for a non-target molecule is less than about 20% of the affinity for IL-4Rα. In some embodiments, the affinity of an anti-IL-4Rα antibody, or an antigen binding fragment thereof, for a non-target molecule is less than about 10% of the affinity for IL-4Rα. In some embodiments, the affinity of an anti-IL-4Rα antibody, or an antigen binding fragment thereof, for a non-target molecule is less than about 1% of the affinity for IL-4Rα. In some embodiments, the affinity of an anti-IL-4Rα antibody, or an antigen binding fragment thereof, for a non-target molecule is less than about 0.1% of the affinity for IL-4Rα. [00500] In certain embodiments, the antibody, or an antigen binding fragment thereof, binds a human IL-4Rα. [00501] In certain embodiments, the antibody, or an antigen binding fragment thereof, binds an IL-4Rα sequence set forth in any one of SEQ ID NOs: 301-303. [00502] In certain embodiments, the antibody is cross-reactive to cynomolgus monkey IL- 4Rα. [00503] In certain embodiments, the antibody, or an antigen binding fragment thereof, binds to an IL-4Rα sequence set forth in SEQ ID NOs: 301-303 with a KD of less than or equal to about 1, 2, 3, 4, 5, 6, 7, 8, 9 x 10-9 M, as measured by SPR. In certain embodiments, the antibody, or an antigen binding fragment thereof, binds to an IL-4Rα sequence set forth in SEQ ID NOs: 301-303 with a KD of less than or equal to about 1 x 10-10 M, as measured by SPR. In certain embodiments, the antibody, or an antigen binding fragment thereof, binds to human IL-4Rα with a KD of less than or equal to about 1 x 10-9 M, as measured by SPR. [00504] In some embodiments, an antibody, or an antigen binding fragment thereof, provided herein binds IL-4Rα with a KD of less than or equal to about 0.01, 0.02, 0.03, 0.04, 0.05, 0.06, 0.07, 0.08, 0.09, 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1, 1.1, 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, 1.9, 1.95, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 7, 8, 9, or 10 x 10-8 M, as measured by ELISA or any other suitable method known in the art. In some embodiments, an antibody, or an antigen binding fragment thereof, provided herein binds IL-4Rα with a KD of less than or equal to about 0.01, 0.02, 0.03, 0.04, 0.05, 0.06, 0.07, 0.08, 0.09, 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1, 1.1, 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, 1.9, 1.95, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 7, 8, 9, or 10 x 10-9 M, as measured by ELISA or any other suitable method known in the art. [00505] In some embodiments, the KD of the antibody, or an antigen binding fragment thereof, provided herein for the binding of IL-4Rα is between about 0.001-0.01, 0.01-0.1, 0.01-0.05, 0.05-0.1, 0.1-0.5, 0.5-1, 0.25-0.75, 0.25-0.5, 0.5-0.75, 0.75-1, 0.75-2, 1.1-1.2, 1.2- 1.3, 1.3-1.4, 1.4-1.5, 1.5-1.6, 1.6-1.7, 1.7-1.8, 1.8-1.9, 1.9-2, 1-2, 1-5, 2-7, 3-8, 3-5, 4-6, 5-7, 6-8, 7-9, 7-10, or 5-10 x 10-8 M, as measured by ELISA or any other suitable method known in the art. In some embodiments, an antibody, or an antigen binding fragment thereof, provided herein binds IL-4Rα with a KD of less than or equal to about 1 x 10-8 M, or less than or equal to about 1 x 10-9 M as measured by ELISA or any other suitable method known in the art. [00506] In some embodiments, the antibody, or an antigen binding fragment thereof, provided herein binds IL-4Rα with a KD of less than or equal to about 10, 9, 8, 7, 6, 5, 4.5, 4, 3.5, 3, 2.5, 2, 1.98, 1.95, 1.9, 1.85, 1.8, 1.75, 1.7, 1.65, 1.6, 1.55, 1.50, 1.45, 1.4, 1.3, 1.2, 1.1, 1, 0.9, 0.85, 0.8, 0.75, 0.7, 0.65, 0.6, 0.55, 0.5, 0.45, 0.4, 0.35, 0.3, 0.25, 0.2, 0.15, 0.1, 0.05, 0.01, 0.005, 0.001, 0.0005, or 0.0001 x 10-8 M, or less, as measured by ELISA or any other suitable method known in the art . In some embodiments, the antibody, or an antigen binding fragment thereof, provided herein binds IL-4Rα with a KD between 5-3, 4-2, 3-1, 1.9-1.8, 1.8- 1.7, 1.7-1.6, 1.6-1.5, 1.9-1.5, 1.5-1, 1-0.8, 1-0.5, 0.9-0.6, 0.7-0.4, 0.6-0.2, 0.5-0.3, 0.3-0.2, 0.2-0.1, 0.1-0.01, 0.01-0.001, or 0.001-0.0001 x 10-8 M as measured by ELISA or any other suitable method known in the art. [00507] In some embodiments, the antibody, or an antigen binding fragment thereof, provided herein binds FcRn with an affinity at pH 7.4 compared to pH 6.0 at a ratio (pH 7.4/pH 6.0) of about 10,000, 1,000, 500, 100, 50, 20, 10, 9, 8, 7, 6, 5, 4.5, 4, 3.5, 3, 2.5, 2, 1.95, 1.9, 1.85, 1.8, 1.75, 1.7, 1.65, 1.6, 1.55, 1.50, 1.45, 1.4, 1.3, 1.2, 1.1, or 1.05, as measured by ELISA or any other suitable method known in the art. In some embodiments, the antibody, or an antigen binding fragment thereof, provided herein binds FcRn with an affinity at pH 6.0 compared to pH 7.4 at a ratio (pH 6.0/pH 7.4) of about 1-0.8, 1-0.5, 0.9-0.6, 0.7-0.4, 0.6-0.2, 0.5-0.3, 0.3-0.2, 0.2-0.1, 0.1-0.01, 0.01-0.001, or 0.001-0.0001 x 10-8 M as measured by ELISA or any other suitable method known in the art. Function [00508] “Effector functions” refer to those biological activities mediated by the Fc region of an antibody, which activities may vary depending on the antibody isotype. Examples of antibody effector functions include receptor ligand blocking, agonism, or antagonism, C1q binding to activate complement dependent cytotoxicity (CDC), Fc receptor binding to activate antibody-dependent cellular cytotoxicity (ADCC), and antibody dependent cellular phagocytosis (ADCP). In some embodiments, the effector function of the anti-IL-4Rα antibody described herein is antagonism and blocks the IL-4Rα receptor binding to IL-4Rα. Multi-Specific Antibodies [00509] The present application provides multi-specific antibodies which comprises at least two distinct antigen binding regions; wherein at least one antigen binding region binds OX40L and at least one antigen binding region binds IL-4Rα. In some embodiments, a multi- specific antibody of the disclosure is a bispecific antibody. [00510] Multi-specific antibodies of the present disclosure can comprise any antigen binding region of any antibody or antibody fragment format that binds to an antigen. In some embodiments, suitable antibody or antibody fragment formats include, without limitation, a monoclonal antibody, a polyclonal antibody, a recombinant antibody, a bispecific antibody, a conjugated antibody, a human antibody, a humanized antibody, and a functional fragment of an antibody, including but not limited to a single-domain antibody (sdAb) also referred to interchangeably herein as a variable domain (VHH) of camelid derived nanobody, a heavy chain variable domain (VH), a light chain variable domain (VL), and an alternative scaffold known in the art to function as antigen binding region, such as a recombinant fibronectin domain, a T cell receptor (TCR), a recombinant TCR with enhanced affinity, or a fragment thereof, e.g., single chain TCR, and the like. In some embodiments, it is beneficial for the antigen binding region to be derived from the same species in which the multi-specific antibody will ultimately be used in. For example, for use in humans, it is beneficial for the antigen binding region of the multi-specific antibody to comprise human or humanized residues for the antigen binding region of an antibody or antibody fragment. [00511] In some embodiments, the multi-specific antibody comprises an antibody (e.g., an IgG). In some embodiments, a multi-specific antibody of the disclosure comprises a bispecific antibody (e.g., a bispecific IgG). In some embodiments, the antibody is a human antibody. In some embodiments, the antibody is a humanized antibody. In some embodiments, the antibody is a chimeric antibody. [00512] In some embodiments, the antigen binding region comprises an antigen binding fragment of an antibody. In some embodiments, the antigen binding region is part of a F(ab) fragment. In some embodiments, the antigen binding region is part of a F(ab′) fragment. In some embodiments, the antigen binding region is part of an scFv (e.g., scFv or scdsFv). In some embodiments, the antigen binding region is part of two single chain variable fragments (scFvs or scdsFvs). In some embodiments, each of the two scFvs binds to a distinct epitope on the same antigen. In some embodiments, the antigen binding region is part of a first scFv and a second scFv. In some embodiments, the first scFv and the second scFv bind different antigens. In some embodiments, the scFv is a human scFv. In some embodiments, the scFv is a humanized scFv. In some embodiments, the scFv is a chimeric scFv. In some embodiments, the scFv comprises a heavy chain variable domain (VH) and a light chain variable domain (VL). In some embodiments, the VH and VL are separated by a peptide linker. In some embodiments, the scFv comprises the structure VH-L-VL or VL-L-VH, wherein VH is the heavy chain variable domain, L is the peptide linker, and VL is the light chain variable domain. [00513] In some embodiments, a multi-specific antibody of the disclosure is a tetrabody comprising a heavy chain and scFv (e.g., scFv or scdsFv) fusion. In some embodiments, each of the one or more scFvs comprises the structure VH-L-VL or VL-L-VH, wherein VH is the heavy chain variable domain, L is the peptide linker, and VL is the light chain variable domain. When there are two or more scFv linked together, each scFv can be linked to the next scFv with a peptide linker. In some embodiments, each of the one or more scFvs is separated by a peptide linker. In some embodiments, each of the two scFvs binds to a distinct epitope on the same antigen. [00514] In some embodiments, the antigen binding region is part of a single-domain antibody (sdAb; also known as VHH). In some embodiments, the sdAb is a humanized sdAb. In some embodiments, the sdAb is a chimeric sdAb. [00515] In some embodiments, a multi-specific antibody of the disclosure is a tetrabody comprising a heavy chain and sdAb fusion. [00516] In some embodiments, a multi-specific antibody of the present disclosure may comprise two or more antigen-binding domains, three or more antigen-binding domains, four or more antigen-binding domains, five or more antigen-binding domains, six or more antigen- binding domains, seven or more antigen-binding domains, eight or more antigen-binding domains, nine or more antigen-binding domains, or ten or more antigen-binding domains. In some embodiments, each of the two or more antigen-binding domains binds the same antigen. In some embodiments, each of the two or more antigen-binding domains binds a different epitope of the same antigen. In some embodiments, each of the two or more antigen- binding domains binds a different antigen. In some embodiments, the two or more antigen- binding domains provide the multi-specific antibody with logic gating, such as ‘or’ logic gating. [00517] In some embodiments, the multi-specific antibody comprises two or more (e.g., four) antigen binding regions. In some embodiments, two or more antigen binding regions are attached to one another via a flexible linker. In some embodiments, antigen binding regions are part of an antibody format selected from an antibody (e.g., an IgG), an antigen binding fragment of an antibody, an scFv (e.g., scFv or scdsFv), a Fab, a sdAb (VHH), or a recombinant fibronectin domain. In some embodiments, one or two of the two or more antigen binding regions are part of an IgG antibody. In some embodiments, one or two of the two or more antigen binding regions are part of a scFv (e.g., scFv or scdsFv). In some embodiments, one or two of the two or more antigen binding regions are part of a Fab. In some embodiments, one or two of the two or more antigen binding regions are part of sdAbs. [00518] In some embodiments, the multi-specific antibody comprises an antibody fragment (e.g., scFv). In some embodiments, within each antibody or antibody fragment (e.g., scFv or scdsFv) of a bispecific antibody, the VH can be upstream or downstream of the VL. In some embodiments, the upstream antibody or antibody fragment (e.g., scFv) is arranged with its VH (VH1) upstream of its VL (VL1) and the downstream antibody or antibody fragment (e.g., scFv) is arranged with its VL (VL2) upstream of its VH (VH2), such that the overall multi-specific antibody has the arrangement VH1-VL1-VL2-VH2. In some embodiments, the upstream antibody or antibody fragment (e.g., scFv) is arranged with its VL (VL1) upstream of its VH (VH1) and the downstream antibody or antibody fragment (e.g., scFv) is arranged with its VH (VH2) upstream of its VL (VL2), such that the overall multi- specific antibody has the arrangement VL1-VH1-VH2-VL2. In some embodiments, a linker is disposed between the two antibodies or antibody fragments (e.g., scFvs), for example, between VL1 and VL2 if the construct is arranged as VH1-VL1-VL2-VH2, or between VH1 and VH2 if the construct is arranged as VL1-VH1-VH2-VL2. The linker may be a linker as described herein, e.g., a (Gly4-Ser)n linker (SEQ ID NO: 1143), wherein n is 1, 2, 3, 4, 5, or 6. In some embodiments, the linker is GS. In general, the linker between the two scFvs should be long enough to avoid mispairing between the domains of the two scFvs. In some embodiments, a linker is disposed between the VL and VH of the first scFv. In some embodiments, a linker is disposed between the VL and VH of the second scFv. In constructs that have multiple linkers, any two or more of the linkers may be the same or different. Accordingly, in some embodiments, a multi-specific antibody comprises VLs, VHs, and may further comprise one or more linkers in an arrangement as described herein. [00519] An exemplary immunoglobulin (antibody) structural unit is composed of two pairs of polypeptide chains, each pair having one “light” (about 25 kD) and one “heavy” chain (about 50-70 kD). The N-terminal domain of each chain defines a variable region of about 100 to 110 or more amino acids primarily responsible for antigen recognition. The terms variable light chain (VL) and variable heavy chain (VH) refer to these light and heavy chain domains, respectively. The IgG1 heavy chain comprises the VH, CH1, CH2 and CH3 domains, respectively, from the N to C-terminus. The light chain comprises the VL and CL domains from N to C terminus. The IgG1 heavy chain comprises a hinge between the CH1 and CH2 domains. In some embodiments, the immunoglobulin constructs comprise at least one immunoglobulin domain from IgG, IgM, IgA, IgD, or IgE connected to a therapeutic polypeptide. In some embodiments, the immunoglobulin domain found in a multi-specific antibody provided herein is from or derived from an immunoglobulin-based construct such as a diabody or a nanobody. In some embodiments, the immunoglobulin constructs described herein comprise at least one immunoglobulin domain from a heavy chain antibody such as a camelid antibody. In some embodiments, the immunoglobulin constructs provided herein comprise at least one immunoglobulin domain from a mammalian antibody such as a bovine antibody, a human antibody, a camelid antibody, a mouse antibody, or any chimeric antibody. [00520] In some embodiments, the multi-specific antibodies provided herein comprise one or more heavy chains. In some embodiments, the heavy chain is an IgA. In some embodiments, the heavy chain is an IgD. In some embodiments, the heavy chain is an IgE. In some embodiments, the heavy chain is an IgG. In some embodiments, the heavy chain is an IgM. In some embodiments, the heavy chain is an IgG1. In some embodiments, the heavy chain is an IgG2. In some embodiments, the heavy chain is an IgG3. In some embodiments, the heavy chain is an IgG4. In some embodiments, the heavy chain is an IgA1. In some embodiments, the heavy chain is an IgA2. [00521] In some embodiments, the multi-specific antibody comprises an IgG1 antibody. In some embodiments, the multi-specific antibody comprises an IgG3 antibody. In some embodiments, the multi-specific antibody comprises an IgG2 antibody. In some embodiments, the multi-specific antibody comprises an IgG4 antibody. [00522] The two or more different epitopes may be epitopes on the same antigen (e.g., a single OX40L molecule expressed by a cell) or on different antigens (e.g., different OX40L molecules expressed by the same cell, or a OX40L molecule and an IL-4Rα molecule). In some embodiments, a multi-specific antibody binds two different epitopes (i.e., a “bispecific antibody” or “bispecific antibody”). In some aspects, a multi-specific antibody binds three different epitopes (i.e., a “trispecific antibody”). [00523] The antigen binding regions of the multi-specific antibodies can include an antigen binding region or variable domain described herein such as the antigen binding region of the clones set forth in the drawings and/or tables. In some embodiments, the multi- specific antibody comprises an alternative scaffold. In some embodiments, the multi-specific antibody consists of an alternative scaffold. In some embodiments, the multi-specific antibody consists essentially of an alternative scaffold. In some embodiments, the multi- specific antibody comprises two or more antibody fragments. In some embodiments, the multi-specific antibody consists of two or more antibody fragments. In some embodiments, the multi-specific antibody consists essentially of two or more antibody fragments. [00524] In some embodiments the multi-specific antibody or antigen binding region thereof is produced by hybridomas. In some embodiments, the antibodies are produced by recombinant cells engineered to express the desired variable and constant domains. [00525] In some embodiments the multi-specific antibody comprises one or more single chain antibodies or other antibody derivatives retaining the antigen specificity and the lower hinge region or a variant thereof. [00526] In some embodiments the multi-specific antibody may be polyfunctional antibodies, recombinant antibodies, human antibodies, humanized antibodies, fragments or variants thereof. In some embodiments, the multi-specific antibody comprises antibody fragments or a derivative thereof, which can be selected from a Fab fragment, a Fab′2 fragment, a CDR, and scFv (e.g., heavy chain and scFv fusions). [00527] In some embodiments, multi-specific antibodies of the disclosure comprise amino acid substitutions to enable heterodimerization of two heavy chains, such as with a knob-into- hole approach, and/or CrossMAb technology to enable light chain pairing yet prevent unspecific binding of the light chains. Sequences of OX40L Antigen Binding Regions [00528] In some embodiments, an anti-OX40L antigen binding region included in a multi- specific antibody described herein is an antigen binding region included in amlitelimab or oxelumab. In some embodiments, amlitelimab comprises a variable heavy (VH) chain sequence having the amino acid sequence of SEQ ID NO: 832 and a variable light (VL) chain sequence having the amino acid sequence of SEQ ID NO: 833. In some embodiments, oxelumab comprises a VH sequence having the amino acid sequence of SEQ ID NO: 834 and a VL sequence having the amino acid sequence of SEQ ID NO: 835. In some embodiments, oxelumab comprises a heavy chain having the amino acid sequence of SEQ ID NO: 1072 and a light chain sequence having the amino acid sequence of SEQ ID NO: 1073, or a VH and/or VL therein. See also PCT Application No. PCT/US2024/026854 (corresponding to PCT Publication No. WO2024227174), which is incorporated herein by reference in its entirety. In some embodiments, an anti-OX40L antigen binding region included in a multi-specific antibody described herein is selected from an anti-OX40L antibody or antigen binding region described therein. [00529] In some embodiments, an OX40L antigen binding region provided herein comprises a CDR, VH, and/or VL sequence described herein. TABLE 9. Sequences of OX40L Antigen Binding Regions Constructs – VH, VL, and Associated CDRs Identifier VH and Heavy chain CDRs VL and Light chain CDRs Identifier VH and Heavy chain CDRs VL and Light chain CDRs Chothia (SEQ ID NO: 24) Chothia (SEQ ID NO: 34) Identifier VH and Heavy chain CDRs VL and Light chain CDRs Amlitelimab VH (SEQ ID NO: 832) VL (SEQ ID NO: 833) [00530] In some embodiments, a multi-specific antibody provided herein comprises a VH sequence selected from any one of SEQ ID NOs: 1, 19, 37, and 55. [00531] In some embodiments, a multi-specific antibody provided herein comprises a VH sequence having at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to an illustrative VH sequence selected from any one of SEQ ID NOs: 1, 19, 37, and 55. In some embodiments, a multi-specific antibody provided herein comprises a VH sequence selected from any one of SEQ ID NOs: 1, 19, 37, and 55, with up to 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 amino acid substitutions. In some aspects, the amino acid substitutions are conservative amino acid substitutions. In some embodiments, the antibodies described in this paragraph are referred to herein as “variants.” In some embodiments, such variants are derived from a sequence provided herein, for example, by affinity maturation, site directed mutagenesis, random mutagenesis, or any other method known in the art or described herein. In some embodiments, such variants are not derived from a sequence provided herein and may, for example, be isolated de novo according to the methods provided herein for obtaining antibodies. OX40L Antigen Binding Region VL Domains [00532] In some embodiments, a multi-specific antibody provided herein comprises a VL sequence selected from any one of SEQ ID NOs: 11, 29, 47, and 65. [00533] In some embodiments, a multi-specific antibody provided herein comprises a VL sequence having at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to a VL sequence selected from any one of SEQ ID NOs: 11, 29, 47, and 65. In some embodiments, a multi-specific antibody provided herein comprises a VL sequence selected from any one of SEQ ID NOs: 11, 29, 47, and 65, with up to 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 amino acid substitutions. In some aspects, the amino acid substitutions are conservative amino acid substitutions. In some embodiments, the antibodies described in this paragraph are referred to herein as “variants.” In some embodiments, such variants are derived from a sequence provided herein, for example, by affinity maturation, site directed mutagenesis, random mutagenesis, or any other method known in the art or described herein. In some embodiments, such variants are not derived from a sequence provided herein and may, for example, be isolated de novo according to the methods provided herein for obtaining antibodies. OX40L Antigen Binding Region VH-VL Combinations [00534] In some embodiments, a multi-specific antibody provided herein comprises a VH sequence selected from any one of SEQ ID NOs: 1, 19, 37, and 55; and a VL sequence selected from any one of SEQ ID NOs: 11, 29, 47, and 65. [00535] In certain aspects, a VH sequence selected from any one of SEQ ID NOs: 1, 19, 37, and 55 can be combined with a VL sequence selected from any one of SEQ ID NOs: 11, 29, 47, and 65. [00536] In certain aspects, a multi-specific antibody provided herein comprises a VH sequence and a VL sequence of a construct provided in TABLE 9 (e.g., a VH sequence and a VL sequence from the same row of TABLE 9). [00537] In certain aspects, a multi-specific antibody provided herein comprises a VH sequence and a VL sequence of a construct provided in PCT Application No. PCT/US2024/026854 (corresponding to PCT Publication No. WO2024227174), incorporated by reference herein in its entirety. In certain aspects, a multi-specific antibody provided herein comprises a VH sequence and a VL sequence from Table 2 in PCT Application No. PCT/US2024/026854 (e.g., a VH sequence and a VL sequence from the same row of Table 2). [00538] In some embodiments, a multi-specific antibody provided herein comprises a VH sequence having at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to a VH sequence selected from any one of SEQ ID NOs: 1, 19, 37, and 55; and a VL sequence having at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to a VL sequence selected from any one of SEQ ID NOs: 11, 29, 47, and 65. In some embodiments, a multi-specific antibody provided herein comprises a VH sequence selected from any one of SEQ ID NOs: 1, 19, 37, and 55, with up to 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 amino acid substitutions, and a VL sequence selected from any one of SEQ ID NOs: 11, 29, 47, and 65, with up to 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 amino acid substitutions. In some aspects, the amino acid substitutions are conservative amino acid substitutions. In some embodiments, the antibodies described in this paragraph are referred to herein as “variants.” In some embodiments, such variants are derived from a sequence provided herein, for example, by affinity maturation, site directed mutagenesis, random mutagenesis, or any other method known in the art or described herein. In some embodiments, such variants are not derived from a sequence provided herein and may, for example, be isolated de novo according to the methods provided herein for obtaining antibodies. [00539] In certain embodiments, the multi-specific antibody comprises a VH sequence set forth in SEQ ID NO: 1 and a VL sequence set forth in SEQ ID NO: 11. [00540] In certain embodiments, the multi-specific antibody comprises a VH sequence set forth in SEQ ID NO: 19 and a VL sequence set forth in SEQ ID NO: 29. [00541] In certain embodiments, the multi-specific antibody comprises a VH sequence set forth in SEQ ID NO: 37 and a VL sequence set forth in SEQ ID NO: 47. [00542] In certain embodiments, the multi-specific antibody comprises a VH sequence set forth in SEQ ID NO: 55 and a VL sequence set forth in SEQ ID NO: 65. [00543] In certain embodiments, a multi-specific antibody comprises any of the VH and VL combinations described above and further comprises a heavy chain comprising a human IgG sequence selected from a sequence set forth in any one of SEQ ID NOs: 637-737 and 847-1070 or a sequence having at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity thereto. In certain embodiments, a multi-specific antibody comprises any of the VH and VL combinations described above and further comprises a heavy chain comprising a constant heavy chain sequence set forth in SEQ ID NO: 651 or a sequence having at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity thereto. In certain embodiments, a multi-specific antibody comprises any of the VH and VL combinations described above and further comprises a heavy chain comprising a constant heavy chain sequence set forth in SEQ ID NO: 973 or a sequence having at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity thereto. In certain embodiments, a multi-specific antibody comprises any of the VH and VL combinations described above and further comprises a human constant light chain sequence set forth in SEQ ID NO: 738 or a sequence having at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity thereto. In certain embodiments, a multi-specific antibody comprises any of the VH and VL combinations described above and further comprises a constant heavy chain sequence set forth in SEQ ID NO: 651 or a sequence having at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity thereto and a human constant light chain sequence set forth in SEQ ID NO: 738 or a sequence having at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity thereto. In certain embodiments, a multi-specific antibody comprises any of the VH and VL combinations described above and further comprises a constant heavy chain sequence set forth in SEQ ID NO: 973 or a sequence having at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity thereto and a human constant light chain sequence set forth in SEQ ID NO: 738 or a sequence having at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity thereto. [00544] Although a C-terminal lysine may be present in the corresponding coding sequence of the constant heavy chain region (e.g., in a sequence encoding any one of SEQ ID NOs: 959-1070), it may be cleaved off during manufacture or after administration (resulting in, e.g., a constant heavy chain sequence of any one of SEQ ID NOs: 637-737 and 847-958). Accordingly, any of the multi-specific antibodies described above may comprise a human IgG sequence containing a C-terminal lysine (e.g., any one of SEQ ID NOs: 959-1070), a human IgG sequence lacking a C-terminal lysine (e.g., any one of SEQ ID NOs: 637-737 and 847-958), or a mixture thereof (e.g., a mixture of the same heavy chain constant sequence with and without a C-terminal lysine, such as a mixture of SEQ ID NO: 973 and SEQ ID NO: 651). OX40L Antigen Binding Region CDRs [00545] In some embodiments, disclosed herein is a multi-specific antibody comprising 1, 2, 3, 4, 5, or 6 of the CDRs of TABLE 9. In some embodiments, disclosed herein is a multi- specific antibody comprising 6 of the Kabat CDRs of TABLE 9, 6 of the Chothia CDRs of TABLE 9, or 6 of the IMGT CDRs of TABLE 9. In some embodiments, the multi-specific antibody comprises 6 of the Kabat CDRs, 6 of the Chothia CDRs, or 6 of the IMGT CDRs from a single row of TABLE 9 (e.g., 6 CDRs from the same antibody). [00546] In some embodiments, disclosed herein is a multi-specific antibody comprising 1, 2, 3, 4, 5, or 6 of the CDRs of an antibody provided in PCT Application No. PCT/US2024/026854 (corresponding to PCT Publication No. WO2024227174), incorporated by reference herein in its entirety, such as 1, 2, 3, 4, 5, or 6 of the CDRs in Table 2 in PCT Application No. PCT/US2024/026854. In some embodiments, disclosed herein is a multi- specific antibody comprising 1, 2, 3, 4, 5, or 6 of the Kabat CDRs of an antibody, or an antigen binding fragment thereof, provided in PCT Application No. PCT/US2024/026854. In some embodiments, disclosed herein is a multi-specific antibody comprising 1, 2, 3, 4, 5, or 6 of the Chothia CDRs of an antibody, or an antigen binding fragment thereof, provided in PCT Application No. PCT/US2024/026854. In some embodiments, disclosed herein is a multi- specific antibody comprising 1, 2, 3, 4, 5, or 6 of the IMGT CDRs of an antibody provided in PCT Application No. PCT/US2024/026854. In some embodiments, the multi-specific antibody comprises 6 of the Kabat CDRs, 6 of the Chothia CDRs, or 6 of the IMGT CDRs from a single row of Table 2 in in PCT Application No. PCT/US2024/026854 (e.g., 6 CDRs from the same antibody). [00547] In some embodiments, a multi-specific antibody provided herein comprises three CDRs of a VH domain selected from SEQ ID NOs: 1, 19, 37, and 55. In some aspects, the CDRs are exemplary CDRs. In some aspects, the CDRs are Kabat CDRs. In some aspects, the CDRs are Chothia CDRs. In some aspects, the CDRs are IMGT CDRs. In some aspects, the CDRs are AbM CDRs. In some aspects, the CDRs are Contact CDRs. [00548] In some embodiments, the CDRs are CDRs having at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity to a CDR-H1, CDR-H2, or CDR-H3 selected from SEQ ID NOs: 2-10, 12-18, 20-28, 30-36, 38-46, 48-54, 56-64, and 66-72. In some embodiments, the CDR-H1 is a CDR-H1 of a VH domain selected from SEQ ID NOs: 1, 19, 37, and 55, with up to 1, 2, 3, 4, or 5 amino acid substitutions. In some embodiments, the CDR-H2 is a CDR-H2 of a VH domain selected from SEQ ID NOs: 1, 19, 37, and 55, with up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions. In some embodiments, the CDR-H3 is a CDR-H3 of a VH domain selected from SEQ ID NOs: 1, 19, 37, and 55, with up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions. In some aspects, the amino acid substitutions are conservative amino acid substitutions. In some embodiments, the antibodies described in this paragraph are referred to herein as “variants.” In some embodiments, such variants are derived from a sequence provided herein, for example, by affinity maturation, site directed mutagenesis, random mutagenesis, or any other method known in the art or described herein. In some embodiments, such variants are not derived from a sequence provided herein and may, for example, be isolated de novo according to the methods provided herein for obtaining antibodies. [00549] In some embodiments, a multi-specific antibody provided herein comprises three CDRs of a VL domain selected from SEQ ID NOs: 11, 29, 47, and 65. In some aspects, the CDRs are exemplary CDRs. In some aspects, the CDRs are Kabat CDRs. In some aspects, the CDRs are Chothia CDRs. In some aspects, the CDRs are IMGT CDRs. In some aspects, the CDRs are AbM CDRs. In some aspects, the CDRs are Contact CDRs. [00550] In some embodiments, the CDRs are CDRs having at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity to a CDR-L1, CDR-L2, or CDR-L3 selected from SEQ ID NOs: 2-10, 12-18, 20-28, 30-36, 38-46, 48-54, 56-64, and 66- 72, In some embodiments, the CDR-L1 is a CDR-L1 of a VL domain selected from SEQ ID NOs: 11, 29, 47, and 65, with up to 1, 2, 3, 4, or 5 amino acid substitutions. In some embodiments, the CDR-L2 is a CDR-L2 of a VL domain selected from SEQ ID NOs: 11, 29, 47, and 65, with up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions. In some embodiments, the CDR-L3 is a CDR-L3 of a VL domain selected from SEQ ID NOs: 11, 29, 47, and 65, with up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions. In some aspects, the amino acid substitutions are conservative amino acid substitutions. In some embodiments, the antibodies described in this paragraph are referred to herein as “variants.” In some embodiments, such variants are derived from a sequence provided herein, for example, by affinity maturation, site directed mutagenesis, random mutagenesis, or any other method known in the art or described herein. In some embodiments, such variants are not derived from a sequence provided herein and may, for example, be isolated de novo according to the methods provided herein for obtaining antibodies. [00551] In some embodiments, a multi-specific antibody provided herein comprises three CDRs of a VH domain selected from SEQ ID NOs: 1, 19, 37, and 55 and three CDRs of a VL domain selected from SEQ ID NOs: 11, 29, 47, and 65. In some aspects, the CDRs are exemplary CDRs. In some aspects, the CDRs are Kabat CDRs. In some aspects, the CDRs are Chothia CDRs. In some aspects, the CDRs are IMGT CDRs. In some aspects, the CDRs are AbM CDRs. In some aspects, the CDRs are Contact CDRs. [00552] In some embodiments, a multi-specific antibody provided herein comprises a CDR-H3 selected from SEQ ID NOs: 8-10, 26-28, 44-46, and 62-64. In some aspects, the CDR-H3 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to a CDR-H3 selected from SEQ ID NOs: 8-10, 26-28, 44-46, and 62-64. In some embodiments, the CDR-H3 is a CDR-H3 selected from SEQ ID NOs: 8-10, 26-28, 44-46, and 62-64, with up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions. In some aspects, the amino acid substitutions are conservative amino acid substitutions. In some embodiments, the antibodies described in this paragraph are referred to herein as “variants.” In some embodiments, such variants are derived from a sequence provided herein, for example, by affinity maturation, site directed mutagenesis, random mutagenesis, or any other method known in the art or described herein. In some embodiments, such variants are not derived from a sequence provided herein and may, for example, be isolated de novo according to the methods provided herein for obtaining antibodies. [00553] In some embodiments, a multi-specific antibody provided herein comprises a CDR-H1 selected from SEQ ID NOs: 2-4, 20-22, 38-40, and 56-58. In some aspects, the CDR-H1 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to a CDR-H1 selected from SEQ ID NOs: 2-4, 20-22, 38-40, and 56-58. In some embodiments, the CDR-H1 is a CDR-H1 selected from SEQ ID NOs: 2-4, 20-22, 38-40, and 56-58, with up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions. In some aspects, the amino acid substitutions are conservative amino acid substitutions. In some embodiments, the antibodies described in this paragraph are referred to herein as “variants.” In some embodiments, such variants are derived from a sequence provided herein, for example, by affinity maturation, site directed mutagenesis, random mutagenesis, or any other method known in the art or described herein. In some embodiments, such variants are not derived from a sequence provided herein and may, for example, be isolated de novo according to the methods provided herein for obtaining antibodies. [00554] In some embodiments, a multi-specific antibody provided herein comprises a CDR-H2 selected from SEQ ID NOs: 5-7, 23-25, 41-43, and 59-61. In some aspects, the CDR-H2 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to a CDR-H2 H2 selected from SEQ ID NOs: 5-7, 23-25, 41-43, and 59-61. In some embodiments, the CDR-H2 is a CDR-H2 selected from SEQ ID NOs: 5-7, 23-25, 41-43, and 59-61, with up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions. In some aspects, the amino acid substitutions are conservative amino acid substitutions. In some embodiments, the antibodies described in this paragraph are referred to herein as “variants.” In some embodiments, such variants are derived from a sequence provided herein, for example, by affinity maturation, site directed mutagenesis, random mutagenesis, or any other method known in the art or described herein. In some embodiments, such variants are not derived from a sequence provided herein and may, for example, be isolated de novo according to the methods provided herein for obtaining antibodies. [00555] In some embodiments, a multi-specific antibody provided herein comprises a CDR-L3 selected from SEQ ID NOs: 17-18, 35-36, 53-54, and 71-72. In some aspects, the CDR-L3 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to a CDR-L3 selected from SEQ ID NOs: 17-18, 35-36, 53-54, and 71-72. In some embodiments, the CDR-L3 is a CDR-L3 selected from SEQ ID NOs: 17-18, 35-36, 53-54, and 71-72, with up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions. In some aspects, the amino acid substitutions are conservative amino acid substitutions. In some embodiments, the antibodies described in this paragraph are referred to herein as “variants.” In some embodiments, such variants are derived from a sequence provided herein, for example, by affinity maturation, site directed mutagenesis, random mutagenesis, or any other method known in the art or described herein. In some embodiments, such variants are not derived from a sequence provided herein and may, for example, be isolated de novo according to the methods provided herein for obtaining antibodies. [00556] In some embodiments, a multi-specific antibody provided herein comprises a CDR-L2 selected from SEQ ID NOs: 15-16, 33-34, 51-52, and 69-70. In some aspects, the CDR-L2 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to a CDR-L2 selected from SEQ ID NOs: 15-16, 33-34, 51-52, and 69-70. In some embodiments, the CDR-L2 is a CDR-L2 selected from SEQ ID NOs: 15-16, 33-34, 51-52, and 69-70, with up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions. In some aspects, the amino acid substitutions are conservative amino acid substitutions. In some embodiments, the antibodies described in this paragraph are referred to herein as “variants.” In some embodiments, such variants are derived from a sequence provided herein, for example, by affinity maturation, site directed mutagenesis, random mutagenesis, or any other method known in the art or described herein. In some embodiments, such variants are not derived from a sequence provided herein and may, for example, be isolated de novo according to the methods provided herein for obtaining antibodies. [00557] In some embodiments, a multi-specific antibody provided herein comprises a CDR-L1 selected from SEQ ID NOs: 12-14, 30-32, 48-50, and 66-68. In some aspects, the CDR-L1 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to a CDR-L1 selected from SEQ ID NOs: 12-14, 30-32, 48-50, and 66-68. In some embodiments, the CDR-L1 is a CDR-L1 selected from SEQ ID NOs: 12-14, 30-32, 48-50, and 66-68, with up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions. In some aspects, the amino acid substitutions are conservative amino acid substitutions. In some embodiments, the antibodies described in this paragraph are referred to herein as “variants.” In some embodiments, such variants are derived from a sequence provided herein, for example, by affinity maturation, site directed mutagenesis, random mutagenesis, or any other method known in the art or described herein. In some embodiments, such variants are not derived from a sequence provided herein and may, for example, be isolated de novo according to the methods provided herein for obtaining antibodies. [00558] In some embodiments, a multi-specific antibody provided herein comprises a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 2; a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 5; a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 8; a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 12; a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 15; and a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 17. [00559] In some embodiments, a multi-specific antibody provided herein comprises a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 3; a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 6; a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 9; a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 13; a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 16; and a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 18. [00560] In some embodiments, a multi-specific antibody provided herein comprises a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 4; a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 7; a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 10; a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 14; a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 16; and a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 17. [00561] In some embodiments, a multi-specific antibody provided herein comprises a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 20; a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 23; a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 26; a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 30; a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 33; and a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 35. [00562] In some embodiments, a multi-specific antibody provided herein comprises a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 21; a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 24; a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 27; a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 31; a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 34; and a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 36. [00563] In some embodiments, a multi-specific antibody provided herein comprises a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 22; a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 25; a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 27; a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 32; a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 34; and a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 35. [00564] In some embodiments, a multi-specific antibody provided herein comprises a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 38; a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 41; a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 44; a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 48; a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 51; and a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 53. [00565] In some embodiments, a multi-specific antibody provided herein comprises a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 39; a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 42; a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 45; a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 49; a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 52; and a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 54. [00566] In some embodiments, a multi-specific antibody provided herein comprises a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 40; a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 43; a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 46; a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 50; a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 52; and a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 53. [00567] In some embodiments, a multi-specific antibody provided herein comprises a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 56; a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 59; a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 62; a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 66; a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 69; and a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 71. [00568] In some embodiments, a multi-specific antibody provided herein comprises a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 57; a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 60; a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 63; a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 67; a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 70; and a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 72. [00569] In some embodiments, a multi-specific antibody provided herein comprises a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 58; a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 61; a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 64; a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 68; a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 70; and a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 71. [00570] In certain embodiments, any of the multi-specific antibodies described above further comprises a heavy chain comprising a human IgG sequence selected from a sequence set forth in any one of SEQ ID NOs: 637-737 and SEQ ID NOs: 847-1070 or a sequence having at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity thereto. In certain embodiments, any of the multi-specific antibodies described above further comprises a constant heavy chain sequence set forth in SEQ ID NO: 651 or a sequence having at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity thereto. In certain embodiments, any of the multi-specific antibodies described above further comprises a constant heavy chain sequence set forth in SEQ ID NO: 973 or a sequence having at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity thereto. In certain embodiments, any of the multi-specific antibodies described above further comprises a human constant light chain sequence set forth in SEQ ID NO: 738 or a sequence having at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity thereto. In certain embodiments, any of the multi-specific antibodies described above further comprises a constant heavy chain sequence set forth in SEQ ID NO: 651 or a sequence having at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity thereto and a human constant light chain sequence set forth in SEQ ID NO: 738 or a sequence having at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity thereto. In certain embodiments, any of the multi-specific antibodies described above further comprises a constant heavy chain sequence set forth in SEQ ID NO: 973 or a sequence having at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity thereto and a human constant light chain sequence set forth in SEQ ID NO: 738 or a sequence having at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity thereto. [00571] Although a C-terminal lysine may be present in the corresponding coding sequence of the constant heavy chain region (e.g., in a sequence encoding any one of SEQ ID NOs: 959-1070), it may be cleaved off during manufacture or after administration (resulting in, e.g., a constant heavy chain sequence of any one of SEQ ID NOs: 637-737 and 847-958). Accordingly, any of the multi-specific antibodies described above may comprise a human IgG sequence containing a C-terminal lysine (e.g., any one of SEQ ID NOs: 959-1070), a human IgG sequence lacking a C-terminal lysine (e.g., any one of SEQ ID NOs: 637-737 and 847-958), or a mixture thereof (e.g., a mixture of the same heavy chain constant sequence with and without a C-terminal lysine, such as a mixture of SEQ ID NO: 973 and SEQ ID NO: 651). [00572] In some aspects, the amino acid substitutions are conservative amino acid substitutions. In some embodiments, the antibodies described in this disclosure are referred to herein as “variants” or “clones”. In some embodiments, such variants or clones are derived from a sequence provided herein, for example, by affinity maturation, site directed mutagenesis, random mutagenesis, or any other method known in the art or described herein. In some embodiments, such variants or cones are not derived from a sequence provided herein and may, for example, be isolated de novo according to the methods provided herein for obtaining antibodies. Sequences of IL-4Rα Antigen Binding Regions [00573] The present application provides multi-specific antibodies and compositions comprising an antigen binding region which binds IL-4Rα. See also PCT Application No. PCT/US2024/016235 (corresponding to PCT Publication No. WO2024173847), which is incorporated herein by reference in its entirety. In some embodiments, an anti-IL-4Rα antigen binding region described herein is selected from an anti-IL-4Rα antigen binding region described therein. [00574] In some embodiments, an anti-IL-4Rα antigen binding region described herein is selected from an antigen binding region included in dupilumab, stapokibart, and 611. In some embodiments, dupilumab comprises a variable heavy (VH) chain sequence having the amino acid sequence of SEQ ID NO: 113 and a variable light (VL) chain sequence having the amino acid sequence of SEQ ID NO: 146. In some embodiments, dupilumab comprises a heavy chain having the amino acid sequence of SEQ ID NO: 147 and a light chain sequence having the amino acid sequence of SEQ ID NO: 148. In some embodiments, stapokibart comprises a heavy chain having the amino acid sequence of SEQ ID NO: 1074 and a light chain sequence having the amino acid sequence of SEQ ID NO: 1075, or a VH and/or VL therein (e.g., a VH having the sequence of SEQ ID NO: 844 and a VL having the sequence of SEQ ID NO: 845). [00575] In some embodiments, an IL-4Rα antigen binding region provided herein comprises a CDR, VH, and/or VL sequence described herein. TABLE 10. Sequences of IL-4Rα antigen binding regions – VH, VL, and associated CDRs Identifier VH and Heavy Chain CDRs VL and Light Chain CDRs Identifier VH and Heavy Chain CDRs VL and Light Chain CDRs mAb432 VH (SEQ ID NO: 296) VL (SEQ ID NO: 299) IL-4Rα Antigen Binding Region VH Domains [00576] In some embodiments, a multi-specific antibody provided herein comprises a VH sequence selected from any one of SEQ ID NOs: 295-297. [00577] In some embodiments, a multi-specific antibody provided herein comprises a VH sequence having at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to an illustrative VH sequence selected from any one of SEQ ID NOs: 295-297. In some embodiments, a multi-specific antibody provided herein comprises a VH sequence selected from any one of SEQ ID NOs: 295-297, with up to 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 amino acid substitutions. In some aspects, the amino acid substitutions are conservative amino acid substitutions. In some embodiments, the antibodies described in this paragraph are referred to herein as “variants.” In some embodiments, such variants are derived from a sequence provided herein, for example, by affinity maturation, site directed mutagenesis, random mutagenesis, or any other method known in the art or described herein. In some embodiments, such variants are not derived from a sequence provided herein and may, for example, be isolated de novo according to the methods provided herein for obtaining antibodies. IL-4Rα Antigen Binding Region VL Domains [00578] In some embodiments, a multi-specific antibody provided herein comprises a VL sequence selected from any one of SEQ ID NOs: 298-300. [00579] In some embodiments, a multi-specific antibody provided herein comprises a VL sequence having at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to a VL sequence selected from any one of SEQ ID NOs: 298-300. In some embodiments, a multi-specific antibody provided herein comprises a VL sequence selected from any one of SEQ ID NOs: 298-300, with up to 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 amino acid substitutions. In some aspects, the amino acid substitutions are conservative amino acid substitutions. In some embodiments, the antibodies described in this paragraph are referred to herein as “variants.” In some embodiments, such variants are derived from a sequence provided herein, for example, by affinity maturation, site directed mutagenesis, random mutagenesis, or any other method known in the art or described herein. In some embodiments, such variants are not derived from a sequence provided herein and may, for example, be isolated de novo according to the methods provided herein for obtaining antibodies. IL-4Rα Antigen Binding Region VH-VL Combinations [00580] In some embodiments, a multi-specific antibody provided herein comprises a VH sequence selected from any one of SEQ ID NOs: 295-297; and a VL sequence selected from any one of SEQ ID NOs: 298-300. [00581] In certain aspects, a VH sequence selected from any one of SEQ ID NOs: 295-297 can be combined with a VL sequence selected from any one of SEQ ID NOs: 298-300. [00582] In certain aspects, a multi-specific antibody provided herein comprises a VH sequence and a VL sequence of a construct provided in TABLE 10 (e.g., a VH sequence and VL sequence from the same row of TABLE 10). [00583] In some embodiments, a multi-specific antibody provided herein comprises a VH sequence and a VL sequence of a construct provided in PCT Application No. PCT/US2024/016235 (corresponding to PCT Publication No. WO2024173847), incorporated by reference herein in its entirety. In certain aspects, a multi-specific antibody provided herein comprises a VH sequence and a VL sequence from Table 2 in PCT Application No. PCT/US2024/016235 (e.g., a VH sequence and a VL sequence from the same row of Table 2). [00584] In some embodiments, a multi-specific antibody provided herein comprises a VH sequence having at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to a VH sequence selected from any one of SEQ ID NOs: 295-297; and a VL sequence having at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to a VL sequence selected from any one of SEQ ID NOs: 298-300. In some embodiments, a multi-specific antibody provided herein comprises a VH sequence selected from any one of SEQ ID NOs: 295-297, with up to 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 amino acid substitutions, and a VL sequence selected from any one of SEQ ID NOs: 298-300, with up to 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 amino acid substitutions. In some aspects, the amino acid substitutions are conservative amino acid substitutions. In some embodiments, the antibodies described in this paragraph are referred to herein as “variants.” In some embodiments, such variants are derived from a sequence provided herein, for example, by affinity maturation, site directed mutagenesis, random mutagenesis, or any other method known in the art or described herein. In some embodiments, such variants are not derived from a sequence provided herein and may, for example, be isolated de novo according to the methods provided herein for obtaining antibodies. [00585] In certain embodiments, the multi-specific antibody comprises a VH sequence set forth in SEQ ID NO: 295 and a VL sequence set forth in SEQ ID NO: 298. [00586] In certain embodiments, the multi-specific antibody comprises a VH sequence set forth in SEQ ID NO: 296 and a VL sequence set forth in SEQ ID NO: 299. [00587] In certain embodiments, the multi-specific antibody comprises a VH sequence set forth in SEQ ID NO: 297 and a VL sequence set forth in SEQ ID NO: 300. [00588] In certain embodiments, a multi-specific antibody comprises any of the VH and VL combinations described above and further comprises a heavy chain comprising a human IgG sequence selected from a sequence set forth in SEQ ID NOs: 847-1070 or a sequence having at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity thereto. In certain embodiments, any of the multi-specific antibodies described above further comprises a constant heavy chain sequence set forth in SEQ ID NO: 973 or a sequence having at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity thereto. In certain embodiments, any of the multi-specific antibodies described above further comprises a human constant light chain sequence set forth in SEQ ID NO: 738 or a sequence having at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity thereto. In certain embodiments, any of the multi-specific antibodies described above further comprises a constant heavy chain sequence set forth in SEQ ID NO: 973 or a sequence having at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity thereto and a human constant light chain sequence set forth in SEQ ID NO: 738 or a sequence having at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity thereto. [00589] Although a C-terminal lysine may be present in the corresponding coding sequence of the constant heavy chain region (e.g., in a sequence encoding any one of SEQ ID NOs: 959-1070), it may be cleaved off during manufacture or after administration (resulting in, e.g., a constant heavy chain sequence of any one of SEQ ID NOs: 847-958). Accordingly, any of the multi-specific antibodies described above may comprise a human IgG sequence containing a C-terminal lysine (e.g., any one of SEQ ID NOs: 959-1070), a human IgG sequence lacking a C-terminal lysine (e.g., any one of SEQ ID NOs: 847-958), or a mixture thereof (e.g., a mixture of the same heavy chain constant sequence with and without a C- terminal lysine, such as a mixture of SEQ ID NO: 973 and SEQ ID NO: 861). IL-4Rα Antigen Binding Region CDRs [00590] In some embodiments, disclosed herein is a multi-specific antibody comprising 1, 2, 3, 4, 5, or 6 of the CDRs of TABLE 10. In some embodiments, disclosed herein is a multi- specific antibody comprising 6 of the Kabat CDRs of TABLE 10. In some embodiments, disclosed herein is a multi-specific antibody comprising 1, 2, 3, 4, 5, or 6 of the Chothia CDRs of TABLE 10. In some embodiments, disclosed herein is a multi-specific antibody comprising 1, 2, 3, 4, 5, or 6 of the IMGT CDRs of TABLE 10. In some embodiments, the multi-specific antibody comprises 6 of the Kabat CDRs, 6 of the Chothia CDRs, or 6 of the IMGT CDRs from a single row of TABLE 10 (e.g., 6 CDRs from the same antibody). [00591] In some embodiments, disclosed herein is a multi-specific antibody comprising 1, 2, 3, 4, 5, or 6 of the CDRs of a multi-specific antibody provided in PCT Application No. PCT/US2024/016235 (corresponding to PCT Publication No. WO2024173847), incorporated by reference herein in its entirety. In some embodiments, disclosed herein is a multi-specific antibody comprising 1, 2, 3, 4, 5, or 6 of the Kabat CDRs of a multi-specific antibody provided in PCT Application No. PCT/US2024/016235. In some embodiments, disclosed herein is a multi-specific antibody comprising 1, 2, 3, 4, 5, or 6 of the Chothia CDRs of a multi-specific antibody provided in PCT Application No. PCT/US2024/016235. In some embodiments, disclosed herein is a multi-specific antibody comprising 1, 2, 3, 4, 5, or 6 of the IMGT CDRs of a multi-specific antibody provided in PCT Application No. PCT/US2024/016235. In some embodiments, the multi-specific antibody comprises 6 of the Kabat CDRs, 6 of the Chothia CDRs, or 6 of the IMGT CDRs from a single row of Table 2 of PCT Application No. PCT/US2024/016235 (e.g., 6 CDRs from the same antibody). In some embodiments, a multi-specific antibody provided herein comprises three CDRs of a VH domain selected from SEQ ID NOs: 295-297. In some aspects, the CDRs are exemplary CDRs. In some aspects, the CDRs are Kabat CDRs. In some aspects, the CDRs are Chothia CDRs. In some aspects, the CDRs are IMGT CDRs. In some aspects, the CDRs are AbM CDRs. In some aspects, the CDRs are Contact CDRs. [00592] In some embodiments, the CDRs are CDRs having at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity to a CDR-H1, CDR-H2, or CDR-H3 selected from SEQ ID NOs: 273-293 and 295-300. In some embodiments, the CDR-H1 is a CDR-H1 of a VH domain selected from SEQ ID NOs: 295-297, with up to 1, 2, 3, 4, or 5 amino acid substitutions. In some embodiments, the CDR-H2 is a CDR-H2 of a VH domain selected from SEQ ID NOs: 295-297, with up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions. In some embodiments, the CDR-H3 is a CDR-H3 of a VH domain selected from SEQ ID NOs: 295-297, with up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions. In some aspects, the amino acid substitutions are conservative amino acid substitutions. In some embodiments, the antibodies described in this paragraph are referred to herein as “variants.” In some embodiments, such variants are derived from a sequence provided herein, for example, by affinity maturation, site directed mutagenesis, random mutagenesis, or any other method known in the art or described herein. In some embodiments, such variants are not derived from a sequence provided herein and may, for example, be isolated de novo according to the methods provided herein for obtaining antibodies. [00593] In some embodiments, a multi-specific antibody provided herein comprises three CDRs of a VL domain selected from SEQ ID NOs: 298-300. In some aspects, the CDRs are exemplary CDRs. In some aspects, the CDRs are Kabat CDRs. In some aspects, the CDRs are Chothia CDRs. In some aspects, the CDRs are IMGT CDRs. In some aspects, the CDRs are AbM CDRs. In some aspects, the CDRs are Contact CDRs. [00594] In some embodiments, the CDRs are CDRs having at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity to a CDR-L1, CDR-L2, or CDR-L3 selected from SEQ ID NOs: 273-293 and 295-300, In some embodiments, the CDR- L1 is a CDR-L1 of a VL domain selected from SEQ ID NOs: 298-300, with up to 1, 2, 3, 4, or 5 amino acid substitutions. In some embodiments, the CDR-L2 is a CDR-L2 of a VL domain selected from SEQ ID NOs: 298-300, with up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions. In some embodiments, the CDR-L3 is a CDR-L3 of a VL domain selected from SEQ ID NOs: 298-300, with up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions. In some aspects, the amino acid substitutions are conservative amino acid substitutions. In some embodiments, the antibodies described in this paragraph are referred to herein as “variants.” In some embodiments, such variants are derived from a sequence provided herein, for example, by affinity maturation, site directed mutagenesis, random mutagenesis, or any other method known in the art or described herein. In some embodiments, such variants are not derived from a sequence provided herein and may, for example, be isolated de novo according to the methods provided herein for obtaining antibodies. [00595] In some embodiments, a multi-specific antibody provided herein comprises three CDRs of a VH domain selected from SEQ ID NOs: 295-297 and three CDRs of a VL domain selected from SEQ ID NOs: 298-300.. In some aspects, the CDRs are exemplary CDRs. In some aspects, the CDRs are Kabat CDRs. In some aspects, the CDRs are Chothia CDRs. In some aspects, the CDRs are IMGT CDRs. In some aspects, the CDRs are AbM CDRs. In some aspects, the CDRs are Contact CDRs. [00596] In some embodiments, a multi-specific antibody provided herein comprises a CDR-H3 selected from SEQ ID NOs: 281-284. In some aspects, the CDR-H3 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to a CDR-H3 selected from SEQ ID NOs: 281-284. In some embodiments, the CDR-H3 is a CDR-H3 selected from SEQ ID NOs: 281-284, with up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions. In some aspects, the amino acid substitutions are conservative amino acid substitutions. In some embodiments, the antibodies described in this paragraph are referred to herein as “variants.” In some embodiments, such variants are derived from a sequence provided herein, for example, by affinity maturation, site directed mutagenesis, random mutagenesis, or any other method known in the art or described herein. In some embodiments, such variants are not derived from a sequence provided herein and may, for example, be isolated de novo according to the methods provided herein for obtaining antibodies. [00597] In some embodiments, a multi-specific antibody provided herein comprises a CDR-H1 selected from SEQ ID NOs: 273-275. In some aspects, the CDR-H1 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to a CDR-H1 selected from SEQ ID NOs: 273-275. In some embodiments, the CDR-H1 is a CDR-H1 selected from SEQ ID NOs: 273-275, with up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions. In some aspects, the amino acid substitutions are conservative amino acid substitutions. In some embodiments, the antibodies described in this paragraph are referred to herein as “variants.” In some embodiments, such variants are derived from a sequence provided herein, for example, by affinity maturation, site directed mutagenesis, random mutagenesis, or any other method known in the art or described herein. In some embodiments, such variants are not derived from a sequence provided herein and may, for example, be isolated de novo according to the methods provided herein for obtaining antibodies. [00598] In some embodiments, a multi-specific antibody provided herein comprises a CDR-H2 selected from SEQ ID NOs: 276-282. In some aspects, the CDR-H2 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to a CDR-H2 selected from SEQ ID NOs: 276-282. In some embodiments, the CDR-H2 is a CDR-H2 selected from SEQ ID NOs: 276-282, with up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions. In some aspects, the amino acid substitutions are conservative amino acid substitutions. In some embodiments, the antibodies described in this paragraph are referred to herein as “variants.” In some embodiments, such variants are derived from a sequence provided herein, for example, by affinity maturation, site directed mutagenesis, random mutagenesis, or any other method known in the art or described herein. In some embodiments, such variants are not derived from a sequence provided herein and may, for example, be isolated de novo according to the methods provided herein for obtaining antibodies. [00599] In some embodiments, a multi-specific antibody provided herein comprises a CDR-L3 of SEQ ID NO: 293. In some aspects, the CDR-L3 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to a CDR-L3 of SEQ ID NO: 293. In some embodiments, the CDR-L3 is a CDR-L3 of SEQ ID NO: 293, with up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions. In some aspects, the amino acid substitutions are conservative amino acid substitutions. In some embodiments, the antibodies described in this paragraph are referred to herein as “variants.” In some embodiments, such variants are derived from a sequence provided herein, for example, by affinity maturation, site directed mutagenesis, random mutagenesis, or any other method known in the art or described herein. In some embodiments, such variants are not derived from a sequence provided herein and may, for example, be isolated de novo according to the methods provided herein for obtaining antibodies. [00600] In some embodiments, a multi-specific antibody provided herein comprises a CDR-L2 selected from SEQ ID NOs: 290-292 and the amino acid sequence LG or EG. In some aspects, the CDR-L2 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to a CDR-L2 selected from SEQ ID NOs: 290-292 and the amino acid sequence LG or EG. In some embodiments, the CDR-L2 is a CDR-L2 selected from SEQ ID NOs: 290-292 and the amino acid sequence LG or EG, with up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions. In some aspects, the amino acid substitutions are conservative amino acid substitutions. In some embodiments, the antibodies described in this paragraph are referred to herein as “variants.” In some embodiments, such variants are derived from a sequence provided herein, for example, by affinity maturation, site directed mutagenesis, random mutagenesis, or any other method known in the art or described herein. In some embodiments, such variants are not derived from a sequence provided herein and may, for example, be isolated de novo according to the methods provided herein for obtaining antibodies. [00601] In some embodiments, a multi-specific antibody provided herein comprises a CDR-L1 selected from SEQ ID NOs: 285-289. In some aspects, the CDR-L1 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to a CDR-L1 selected from SEQ ID NOs: 285-289. In some embodiments, the CDR-L1 is a CDR-L1 selected from SEQ ID NOs: 285-289, with up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions. In some aspects, the amino acid substitutions are conservative amino acid substitutions. In some embodiments, the antibodies described in this paragraph are referred to herein as “variants.” In some embodiments, such variants are derived from a sequence provided herein, for example, by affinity maturation, site directed mutagenesis, random mutagenesis, or any other method known in the art or described herein. In some embodiments, such variants are not derived from a sequence provided herein and may, for example, be isolated de novo according to the methods provided herein for obtaining antibodies. [00602] In some embodiments, a multi-specific antibody provided herein comprises a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 273; a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 276; a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 281; a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 285; a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 292; and a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 293. [00603] In some embodiments, a multi-specific antibody provided herein comprises a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 274; a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 277; a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 281; a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 285; a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 292; and a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 293. [00604] In some embodiments, a multi-specific antibody provided herein comprises a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 275; a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 278; a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 282; a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 286; a CDR-L2 comprising the amino acid sequence LG; and a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 293. [00605] In some embodiments, a multi-specific antibody provided herein comprises a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 273; a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 279; a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 283; a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 287; a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 291; and a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 293. [00606] In some embodiments, a multi-specific antibody provided herein comprises a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 274; a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 277; a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 283; a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 287; a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 291; and a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 293. [00607] In some embodiments, a multi-specific antibody provided herein comprises a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 275; a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 280; a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 284; a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 288; a CDR-L2 comprising the amino acid sequence LG; and a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 293. [00608] In some embodiments, a multi-specific antibody provided herein comprises a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 273; a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 279; a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 281; a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 289; a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 290; and a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 293. [00609] In some embodiments, a multi-specific antibody provided herein comprises a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 274; a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 277; a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 281; a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 289; a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 290; and a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 293. [00610] In some embodiments, a multi-specific antibody provided herein comprises a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 275; a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 280; a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 282; a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 288; a CDR-L2 comprising the amino acid sequence EG; and a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 293. [00611] In certain embodiments, any of the multi-specific antibodies described above further comprises a heavy chain comprising a human IgG sequence selected from a sequence set forth in any one of SEQ ID NOs: 847-1070 or a sequence having at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity thereto. In certain embodiments, any of the multi-specific antibodies described above further comprises a constant heavy chain sequence set forth in SEQ ID NO: 973 or a sequence having at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity thereto. In certain embodiments, any of the multi-specific antibodies described above further comprises a human constant light chain sequence set forth in SEQ ID NO: 738 or a sequence having at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity thereto. In certain embodiments, any of the multi-specific antibodies described above further comprises a constant heavy chain sequence set forth in SEQ ID NO: 973 or a sequence having at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity thereto and a human constant light chain sequence set forth in SEQ ID NO: 738 or a sequence having at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity thereto. [00612] Although a C-terminal lysine may be present in the corresponding coding sequence of the constant heavy chain region (e.g., in a sequence encoding any one of SEQ ID NOs: 959-1070), it may be cleaved off during manufacture or after administration (resulting in, e.g., a constant heavy chain sequence of any one of SEQ ID NOs: 847-958). Accordingly, any of the multi-specific antibodies described above may comprise a human IgG sequence containing a C-terminal lysine (e.g., any one of SEQ ID NOs: 959-1070), a human IgG sequence lacking a C-terminal lysine (e.g., any one of SEQ ID NOs: 847-958), or a mixture thereof (e.g., a mixture of the same heavy chain constant sequence with and without a C- terminal lysine, such as a mixture of SEQ ID NO: 973 and SEQ ID NO: 861). [00613] In some aspects, the amino acid substitutions are conservative amino acid substitutions. In some embodiments, the antibodies described in this disclosure are referred to herein as “variants” or “clones”. In some embodiments, such variants or clones are derived from a sequence provided herein, for example, by affinity maturation, site directed mutagenesis, random mutagenesis, or any other method known in the art or described herein. In some embodiments, such variants or cones are not derived from a sequence provided herein and may, for example, be isolated de novo according to the methods provided herein for obtaining antibodies. Pharmaceutical compositions [00614] The present application provides compositions comprising the antibodies or antigen binding fragments thereof described herein, including pharmaceutical compositions comprising an OX40L antibody, or an antigen binding fragment thereof, and/or an IL-4Rα antibody, or an antigen binding fragment thereof, or a multi-specific antibody comprising an OX40L antigen binding region and an IL-4Rα antigen binding region described herein with one or more pharmaceutically acceptable excipients. In some embodiments the composition is sterile. The pharmaceutical compositions generally comprise an effective amount of an OX40L antibody, or an antigen binding fragment thereof, and/or an IL-4Rα antibody, or an antigen binding fragment thereof, or a multi-specific antibody comprising an OX40L antigen binding region and an IL-4Rα antigen binding region. [00615] These compositions can comprise, in addition to the OX40L antibody, or an antigen binding fragment thereof, and/or the IL-4Rα antibody, or an antigen binding fragment thereof, or the multi-specific antibody comprising an OX40L antigen binding region and an IL-4Rα antigen binding region disclosed herein, a pharmaceutically acceptable excipient, carrier, buffer, stabilizer or other materials well known to those skilled in the art. Such materials should be non-toxic and should not interfere with the efficacy of the active ingredient. The precise nature of the carrier or other material can depend on the route of administration, e.g. oral, intravenous, cutaneous or subcutaneous, nasal, intramuscular, intraperitoneal routes. [00616] Pharmaceutical compositions for oral administration can be in tablet, capsule, powder or liquid form. A tablet can include a solid carrier such as gelatin or an adjuvant. Liquid pharmaceutical compositions generally include a liquid carrier such as water, petroleum, animal or vegetable oils, mineral oil or synthetic oil. Physiological saline solution, dextrose or other saccharide solution or glycols such as ethylene glycol, propylene glycol or polyethylene glycol can be included. [00617] For intravenous, cutaneous or subcutaneous injection, or injection at the site of affliction, the active ingredient will be in the form of a parenterally acceptable aqueous solution which is pyrogen-free and has suitable pH, isotonicity and stability. Those of relevant skill in the art can prepare suitable solutions using, for example, isotonic vehicles such as Sodium Chloride Injection, Ringer's Injection, Lactated Ringer's Injection. Preservatives, stabilizers, buffers, antioxidants and/or other additives can be included, as required. [00618] For the anti-OX40L antibody, or an antigen binding fragment thereof, and/or anti- IL-4Rα antibody, or an antigen binding fragment thereof, or the multi-specific antibody comprising an OX40L antigen binding region and an IL-4Rα antigen binding region that are to be given to an individual, administration is preferably in a “therapeutically effective amount” or “prophylactically effective amount” (as the case can be, although prophylaxis can be considered therapy), this being sufficient to show benefit to the individual. The actual amount administered, and rate and time-course of administration, will depend on a number of factors, e.g., the nature and severity of the disease being treated. Prescription of treatment, e.g. decisions on dosage etc., can be within the responsibility of general practitioners and other medical doctors, and typically takes account of e.g., the disorder to be treated, the condition of the individual patient, the site of delivery, the method of administration and other factors known to practitioners. Examples of the techniques and protocols mentioned above can be found in Remington's Pharmaceutical Sciences, 16th edition, Osol, A. (ed), 1980. [00619] A composition can be administered alone or in combination with other treatments, either simultaneously or sequentially dependent upon the condition to be treated. Methods Methods of Preparation [00620] Antibodies, or antigen binding fragments thereof, and multi-specific antibodies described herein can be produced using recombinant methods and compositions, e.g., as described in U.S. Pat. No.4,816,567. In one embodiment, an isolated nucleic acid encoding an antibody, or an antigen binding fragment thereof, described herein is provided. Such nucleic acid may encode an amino acid sequence comprising the VL and/or an amino acid sequence comprising the VH of the antibody (e.g., the light and/or heavy chains of the antibody) or an amino acid sequence comprising the VHH of a single domain antibody. In a further embodiment, one or more vectors (e.g., expression vectors) comprising such nucleic acid are provided. In one embodiment, the nucleic acid is provided in a multicistronic vector. In a further embodiment, a host cell comprising such nucleic acid is provided. In one such embodiment, a host cell comprises (e.g., has been transformed with): (1) a vector comprising a nucleic acid that encodes an amino acid sequence comprising the VL of the antibody and an amino acid sequence comprising the VH of the antibody , or (2) a first vector comprising a nucleic acid that encodes an amino acid sequence comprising the VL of the antigen-binding polypeptide construct and a second vector comprising a nucleic acid that encodes an amino acid sequence comprising the VH of the antigen-binding polypeptide construct. In one embodiment, the host cell is eukaryotic, e.g. a Chinese Hamster Ovary (CHO) cell, or human embryonic kidney (HEK) cell, or lymphoid cell (e.g., Y0, NS0, Sp20 cell). In one embodiment, a method of making an antibody is provided, wherein the method comprises culturing a host cell comprising nucleic acid encoding the antibody, as provided above, under conditions suitable for expression of the antibody, and optionally recovering the antibody from the host cell (or host cell culture medium). [00621] For recombinant production of the antibody, nucleic acid encoding an antibody, e.g., as described above, is isolated and inserted into one or more vectors for further cloning and/or expression in a host cell. Such nucleic acid may be readily isolated and sequenced using conventional procedures (e.g., by using oligonucleotide probes that are capable of binding specifically to genes encoding the heavy and light chains of the antibody). [00622] When an antibody or variant thereof is recombinantly produced by the host cells, the protein in certain embodiments is present at about 30%, about 25%, about 20%, about 15%, about 10%, about 5%, about 4%, about 3%, about 2%, or about 1% or less of the dry weight of the cells. When the antibody or variant thereof is recombinantly produced by the host cells, the protein, in certain embodiments, is present in the culture medium at about 5 g/L, about 4 g/L, about 3 g/L, about 2 g/L, about 1 g/L, about 750 mg/L, about 500 mg/L, about 250 mg/L, about 100 mg/L, about 50 mg/L, about 10 mg/L, or about 1 mg/L or less of the dry weight of the cells. In certain embodiments, “substantially purified” antibody produced by the methods described herein, has a purity level of at least about 30%, at least about 35%, at least about 40%, at least about 45%, at least about 50%, at least about 55%, at least about 60%, at least about 65%, at least about 70%, specifically, a purity level of at least about 75%, 80%, 85%, and more specifically, a purity level of at least about 90%, a purity level of at least about 95%, a purity level of at least about 99% or greater as determined by appropriate methods such as SDS/PAGE analysis, RP-HPLC, SEC, and capillary electrophoresis. [00623] Suitable host cells for cloning or expression of antibody-encoding vectors include prokaryotic or eukaryotic cells described herein. [00624] Recombinant host cells or host cells are cells that include an exogenous polynucleotide, regardless of the method used for insertion, for example, direct uptake, transduction, f-mating, or other methods known in the art to create recombinant host cells. The exogenous polynucleotide may be maintained as a nonintegrated vector, for example, a plasmid, or alternatively, may be integrated into the host genome. Host cells can include CHO, derivatives of CHO, NS0, Sp2O, CV-1, VERO-76, HeLa, HepG2, Per.C6, or BHK. [00625] For example, an antibody may be produced in bacteria, in particular when glycosylation and Fc effector function are not needed. For expression of antibody fragments and polypeptides in bacteria, see, e.g., U.S. Pat. Nos.5,648,237, 5,789,199, and 5,840,523. (See also Charlton, Methods in Molecular Biology, Vol.248 (B.K.C. Lo, ed., Humana Press, Totowa, N.J., 2003), pp.245-254, describing expression of antibody fragments in E. coli.) After expression, the antibody may be isolated from the bacterial cell paste in a soluble fraction and can be further purified. [00626] In addition to prokaryotes, eukaryotic microbes such as filamentous fungi or yeast are suitable cloning or expression hosts for antibody-encoding vectors, including fungi and yeast strains whose glycosylation pathways have been “humanized,” resulting in the production of an antibody with a partially or fully human glycosylation pattern. See Gerngross, Nat. Biotech.22:1409-1414 (2004), and Li et al., Nat. Biotech.24:210-215 (2006). [00627] Suitable host cells for the expression of glycosylated antibodies are also derived from multicellular organisms (invertebrates and vertebrates). Examples of invertebrate cells include plant and insect cells. Numerous baculoviral strains have been identified which may be used in conjunction with insect cells, particularly for transfection of Spodoptera frugiperda cells. [00628] Plant cell cultures can also be utilized as hosts. See, e.g., U.S. Pat. Nos.5,959,177, 6,040,498, 6,420,548, 7,125,978, and 6,417,429 (describing PLANTIBODIES™ technology for producing antibodies in transgenic plants). [00629] Vertebrate cells may also be used as hosts. For example, mammalian cell lines that are adapted to grow in suspension may be useful. Other examples of useful mammalian host cell lines are monkey kidney CV1 line transformed by SV40 (COS-7); human embryonic kidney line (293 or 293 cells as described, e.g., in Graham et al., J. Gen Virol. 36:59 (1977)); baby hamster kidney cells (BHK); mouse sertoli cells (TM4 cells as described, e.g., in Mather, Biol. Reprod.23:243-251 (1980)); monkey kidney cells (CV1); African green monkey kidney cells (VERO-76); human cervical carcinoma cells (HELA); canine kidney cells (MDCK; buffalo rat liver cells (BRL 3A); human lung cells (W138); human liver cells (Hep G2); mouse mammary tumor (MMT 060562); TRI cells, as described, e.g., in Mather et al., Annals N.Y. Acad. Sci.383:44-68 (1982); MRC 5 cells; and FS4 cells. Other useful mammalian host cell lines include Chinese hamster ovary (CHO) cells, including DHFR− CHO cells (Urlaub et al. (1980) Proc. Natl. Acad. Sci. USA 77:4216); and myeloma cell lines such as Y0, NS0 and Sp2/0. For a review of certain mammalian host cell lines suitable for antibody production, see, e.g., Yazaki and Wu, Methods in Molecular Biology, Vol.248 (B.K.C. Lo, ed., Humana Press, Totowa, N.J.), pp.255-268 (2003). [00630] In one embodiment, the antibodies described herein are produced in stable mammalian cells, by a method comprising: transfecting at least one stable mammalian cell with: nucleic acid encoding the antibody, in a predetermined ratio; and expressing the nucleic acid in the at least one mammalian cell. In some embodiments, the predetermined ratio of nucleic acid is determined in transient transfection experiments to determine the relative ratio of input nucleic acids that results in the highest percentage of the antibody in the expressed product. [00631] In some embodiments, the method of producing an antibody in stable mammalian cells as described herein results in an expression product of the at least one stable mammalian cell comprising a larger percentage of the desired glycosylated antibody as compared to the monomeric heavy or light chain polypeptides, or other antibodies. [00632] In some embodiments, the method of producing a glycosylated antibody in stable mammalian cells described herein comprises identifying and purifying the desired glycosylated antibody. In some embodiments, the said identification is by one or both of liquid chromatography and mass spectrometry. [00633] If required, the antibodies can be purified or isolated after expression. Proteins may be isolated or purified in a variety of ways known to those skilled in the art. Standard purification methods include chromatographic techniques, including ion exchange, hydrophobic interaction, affinity, sizing or gel filtration, and reversed-phase, carried out at atmospheric pressure or at high pressure using systems such as FPLC and HPLC. Purification methods also include electrophoretic, immunological, precipitation, dialysis, and chromatofocusing techniques. Ultrafiltration and diafiltration techniques, in conjunction with protein concentration, are also useful. As is well known in the art, a variety of natural proteins bind Fc and antibodies, and these proteins can find use in the present invention for purification of antibodies. For example, the bacterial proteins A and G bind to the Fc region. Likewise, the bacterial protein L binds to the Fab region of some antibodies. Purification can often be enabled by a particular fusion partner. For example, antibodies may be purified using glutathione resin if a GST fusion is employed, Ni+2 affinity chromatography if a His-tag is employed or immobilized anti-flag antibody if a flag-tag is used. For general guidance in suitable purification techniques, see, e.g. incorporated entirely by reference Protein Purification: Principles and Practice, 3rd Ed., Scopes, Springer-Verlag, NY, 1994, incorporated entirely by reference. The degree of purification necessary will vary depending on the use of the antibodies. In some instances, no purification is necessary. [00634] In certain embodiments, the antibodies are purified using Anion Exchange Chromatography including, but not limited to, chromatography on Q-sepharose, DEAE sepharose, poros HQ, poros DEAF, Toyopearl Q, Toyopearl QAE, Toyopearl DEAE, Resource/Source Q and DEAE, Fractogel Q and DEAE columns. [00635] In specific embodiments, the proteins described herein are purified using Cation Exchange Chromatography including, but not limited to, SP-sepharose, CM sepharose, poros HS, poros CM, Toyopearl SP, Toyopearl CM, Resource/Source S and CM, Fractogel S and CM columns and their equivalents and comparables. [00636] In addition, antibodies described herein can be chemically synthesized using techniques known in the art (e.g., see Creighton, 1983, Proteins: Structures and Molecular Principles, W. H. Freeman & Co., N.Y and Hunkapiller et al., Nature, 310:105-111 (1984)). For example, a polypeptide corresponding to a fragment of a polypeptide can be synthesized by use of a peptide synthesizer. Furthermore, if desired, nonclassical amino acids or chemical amino acid analogs can be introduced as a substitution or addition into the polypeptide sequence. Non-classical amino acids include, but are not limited to, to the D-isomers of the common amino acids, 2,4diaminobutyric acid, alpha-amino isobutyric acid, 4aminobutyric acid, Abu, 2-amino butyric acid, g-Abu, e-Ahx, 6amino hexanoic acid, Aib, 2-amino isobutyric acid, 3-amino propionic acid, ornithine, norleucine, norvaline, hydroxyproline, sarcosine, citrulline, homocitrulline, cysteic acid, t-butylglycine, t-butylalanine, phenylglycine, cyclohexylalanine, alanine, fluoro-amino acids, designer amino acids such as methyl amino acids, C-methyl amino acids, N-methyl amino acids, and amino acid analogs in general. Furthermore, the amino acid can be D (dextrorotary) or L (levorotary). Methods of Use [00637] In an aspect, the present application provides methods of contacting OX40L with an anti-OX40L antibody, or an antigen binding fragment thereof, such as a human or humanized antibody, which results in inhibition of OX40 binding to OX40L expressed on antigen presenting cells. [00638] In an aspect, the present application provides methods of using the isolated anti- OX40L antibodies, or antigen binding fragments thereof, described herein for treatment of a disorder or disease in a subject. In certain aspects, described herein is a method for treating a subject in need thereof with an anti-OX40L antibody, or an antigen binding fragment thereof, the method comprising administering to the subject (e.g., a mammalian subject) a therapeutically effective amount of an anti-OX40L antibody, or an antigen binding fragment thereof, or pharmaceutical composition comprising an anti-OX40L antibody, or an antigen binding fragment thereof, described herein. In certain embodiments, the present application provides methods of treating a disorder or disease associated with elevated levels of OX40L and/or IgE in a subject. [00639] In certain aspects, described herein are methods for treating a pathology associated with OX40L activity, the method comprising administering to a mammalian subject a therapeutically effective amount an isolated anti-OX40L antibody, or an antigen binding fragment thereof, or a pharmaceutical composition comprising an isolated anti- OX40L antibody, or an antigen binding fragment thereof, described herein. [00640] In an aspect, the present application provides methods of contacting IL-4Rα with an anti-IL-4Rα antibody, or an antigen binding fragment thereof, such as a human or humanized antibody, which results in inhibition of IL-4 and IL-13 signaling to an IL-4Rα receptor expressed on a cell (e.g., by preventing IL-4Rα and IL-13Rα1 heterodimer formation). [00641] In an aspect, the present application provides methods of contacting OX40L and IL-4Rα with a multi-specific OX40L and IL-4Rα antibody, which results in inhibition of OX40L and/or IL-4 signaling to an OX40 and/or IL-4Rα receptor expressed on a cell. [00642] In an aspect, the present application provides methods of using the isolated anti- IL-4Rα antibodies, or antigen binding fragments thereof, described herein for treatment of a disorder or disease in a subject. In certain aspects, described herein is a method for treating a subject in need thereof with an anti-IL-4Rα antibody, or an antigen binding fragment thereof, the method comprising administering to the subject (e.g., a mammalian subject) a therapeutically effective amount of an anti-IL-4Rα antibody, or an antigen binding fragment thereof, or pharmaceutical composition comprising an anti-IL-4Rα antibody, or an antigen binding fragment thereof, described herein. In certain embodiments, the present application provides methods of treating a disorder or disease associated with elevated levels of IL-4, IL- 13, and/or IgE in a subject. [00643] In certain aspects, described herein are methods for treating a pathology associated with IL-4, IL-13, and/or IL-4Rα activity, the method comprising administering to a mammalian subject a therapeutically effective amount an isolated anti-IL-4Rα antibody, or an antigen binding fragment thereof, or a pharmaceutical composition comprising an isolated anti-IL-4Rα antibody, or an antigen binding fragment thereof, described herein. [00644] In an aspect, the present application provides methods of contacting OX40L and IL-4Rα with an anti-OX40L antibody, or an antigen binding fragment thereof, and an anti-IL- 4Rα antibody, or an antigen binding fragment thereof, respectively (e.g., via administration of a single composition containing both antibodies or antigen binding fragments thereof or by administration of two different compositions, one containing the anti-OX40L antibody, or an antigen binding fragment thereof and the other containing an anti- IL-4Rα antibody or an antigen binding fragment thereof), such as a human or humanized antibody, which results in inhibition of OX40L and/or IL-4 signaling to an OX40 and/or IL-4Rα receptor expressed on a cell. [00645] In an aspect, the present application provides methods of using the isolated anti- IL-4Rα antibodies, or antigen binding fragments thereof, and isolated OX40L antibodies, or antigen binding fragments thereof, described herein in combination for treatment of a disorder or disease in a subject. In certain aspects, described herein is a method for treating a subject in need thereof with an anti-OX40L antibody, or an antigen binding fragment thereof, and an anti-IL-4Rα antibody, or an antigen binding fragment thereof, the method comprising administering to a mammalian subject a therapeutically effective amount of an anti-IL-4Rα antibody, or an antigen binding fragment thereof, and a therapeutically effective amount of an anti-OX40L antibody, or an antigen binding fragment thereof, or pharmaceutical composition comprising such antibodies described herein (e.g., via administration of a single composition containing both antibodies or antigen binding fragments thereof or by administration of two different compositions, one containing the anti-OX40L antibody, or an antigen binding fragment thereof and the other containing an anti- IL-4Rα antibody or an antigen binding fragment thereof). In certain embodiments, the present application provides methods of treating a disorder or disease associated with elevated levels of OX40L, IL-4, IL-13, and/or IgE in a subject. In certain cases, a therapeutically effective amount of each antibody may be different when the antibody is administered in combination with the other antibody or another therapeutic agent. [00646] In an aspect, the present application provides methods of using the multi-specific OX40L and IL-4Rα antibody described herein for treatment of a disorder or disease in a subject. In certain aspects, described herein is a method for treating a subject in need thereof with a multi-specific OX40L and IL-4Rα antibody, the method comprising administering to a mammalian subject a therapeutically effective amount of the multi-specific OX40L and IL- 4Rα antibody or pharmaceutical composition comprising such an antibody described herein. In certain embodiments, the present application provides methods of treating a disorder or disease associated with elevated levels of OX40L, IL-4, IL-13, and/or IgE in a subject. In certain cases, a therapeutically effective amount of the multi-specific OX40L and IL-4Rα antibody may be different than a therapeutically effect amount of either an isolated anti- OX40L antibody, or an antigen binding fragment thereof, and/or an isolated anti-IL-4Rα antibody, or an antigen binding fragment thereof. [00647] In certain aspects, described herein are methods for treating a pathology associated with OX40L and/or IL-4Rα activity, the method comprising administering to a mammalian subject a therapeutically effective amount an isolated anti-IL-4Rα antibody, or an antigen binding fragment thereof, and a therapeutically effective amount of an isolated anti- OX40L antibody, or an antigen binding fragment thereof, or a pharmaceutical composition comprising such antibodies described herein (e.g., via administration of a single composition containing both antibodies or antigen binding fragments thereof or by administration of two different compositions, one containing the anti-OX40L antibody, or an antigen binding fragment thereof and the other containing an anti- IL-4Rα antibody or an antigen binding fragment thereof). In certain cases, a therapeutically effective amount of each antibody may be different when the antibody is administered in combination with the other antibody or another therapeutic agent. [00648] In certain embodiments, the combination of antibodies, or antigen binding fragments thereof, or. the multi-specific antibody is used in the treatment of an inflammatory disorder or disease. In certain embodiments, the combination of antibodies, or antigen binding fragments thereof, or the multi-specific antibody is used in the treatment of atopic dermatitis. In certain embodiments, the treatment reduces disease severity in a patient and disease severity is assessed by an atopic dermatitis disease severity outcome measure. In certain embodiments, the combination of antibodies, or antigen binding fragments thereof, or the multi-specific antibody is used in the treatment of idiopathic pulmonary fibrosis. In certain embodiments, the combination of antibodies, or antigen binding fragments thereof, or the multi-specific antibody is used in the treatment of alopecia areata. In certain embodiments, the combination of antibodies, or antigen binding fragments thereof, or the multi-specific antibody is used in the treatment of asthma. In certain embodiments, the combination of antibodies, or antigen binding fragments thereof, or the multi-specific antibody is used in the treatment of chronic sinusitis with nasal polyps. In certain embodiments, the combination of antibodies, or antigen binding fragments thereof, or the multi-specific antibody is used in the treatment of Chronic Rhinosinusitis without Nasal Polyps (CRSsNP). In certain embodiments, the combination of antibodies, or antigen binding fragments thereof, or the multi-specific antibody is used in the treatment of eosinophilic esophagitis (EoE). In certain embodiments, the combination of antibodies, or antigen binding fragments thereof, or the multi-specific antibody is used in the treatment of an Eosinophilic gastrointestinal disorder or disease (EGID) selected from the group consisting of Eosinophilic Gastritis (EoG), Eosinophilic Enteritis (EoN), Eosinophilic Colitis (EoC), and Eosinophilic Gastroenteritis (EGE). In certain embodiments, the combination of antibodies, or antigen binding fragments thereof, or the multi-specific antibody is used in the treatment of Churg- Strauss syndrome/Eosinophilic granulomatosis with polyangiitis (EGPA). In certain embodiments, the combination of antibodies, or antigen binding fragments thereof, or the multi-specific antibody is used in the treatment of Prurigo Nodularis (PN). In certain embodiments, the combination of antibodies, or antigen binding fragments thereof, or the multi-specific antibody is used in the treatment of Chronic Spontaneous Urticaria (CSU). In certain embodiments, the combination of antibodies, or antigen binding fragments thereof, or the multi-specific antibody is used in the treatment of Chronic Pruritis of Unknown Origin (CPUO). In certain embodiments, the combination of antibodies, or antigen binding fragments thereof, or the multi-specific antibody is used in the treatment of Bullous Pemphigoid (BP). In certain embodiments, the combination of antibodies, or antigen binding fragments thereof, or the multi-specific antibody is used in the treatment of Cold Inducible Urticaria (ColdU). In certain embodiments, the combination of antibodies, or antigen binding fragments thereof, or the multi-specific antibody is used in the treatment of Allergic Fungal Rhinosinusitis (AFRS). In certain embodiments, the combination of antibodies, or antigen binding fragments thereof, or the multi-specific antibody is used in the treatment of Allergic Bronchopulmonary Aspergillosis (ABPA). In certain embodiments, the combination of antibodies, or antigen binding fragments thereof, or the multi-specific antibody is used in the treatment of Chronic Obstructive Pulmonary Disease (COPD). In certain embodiments, the combination of antibodies, or antigen binding fragments thereof, or the multi-specific antibody is used in the treatment of inflammatory bowel disease, such as Crohn’s disease or ulcerative colitis. In certain embodiments, the combination of antibodies, or antigen binding fragments thereof, or the multi-specific antibody is used in the treatment of psoriasis. In certain embodiments, the combination of antibodies, or antigen binding fragments thereof, or the multi-specific antibody is used in the treatment of lupus. In certain embodiments, the combination of antibodies, or antigen binding fragments thereof, or the multi-specific antibody is used in the treatment of rheumatoid arthritis. In certain embodiments, the combination of antibodies, or antigen binding fragments thereof, or the multi-specific antibody is used in the treatment of hidradenitis suppurativa. In certain embodiments, the combination of antibodies, or antigen binding fragments thereof, or the multi-specific antibody is used in the treatment of celiac disease. In certain embodiments, the combination of antibodies, or antigen binding fragments thereof, or the multi-specific antibody is used in the treatment of systemic sclerosis. In certain embodiments, the combination of antibodies, or antigen binding fragments thereof, or the multi-specific antibody is used in the treatment of allergic rhinitis. In certain embodiments, the combination of antibodies, or antigen binding fragments thereof, or the multi-specific antibody is used in the treatment of eosinophilic fasciitis. In certain embodiments, the combination of antibodies, or antigen binding fragments thereof, or the multi-specific antibody is used in the treatment of scleromyxedema. In certain embodiments, the combination of antibodies, or antigen binding fragments thereof, or the multi-specific antibody is used in the treatment of scleredema. In certain embodiments, the combination of antibodies, or antigen binding fragments thereof, or the multi-specific antibody is used in the treatment of nephrogenic systemic fibrosis. [00649] In certain aspects, described herein is a method for treating an inflammatory disorder or disease in a mammalian subject in need thereof, the method comprising administering to the mammalian subject a therapeutically effective amount of a combination of antibodies, or antigen binding fragments thereof, or a multi-specific antibody described herein or a pharmaceutical composition of such antibody or antibodies described herein. In certain embodiments of the methods described herein, the inflammatory disorder or disease is atopic dermatitis. In certain embodiments, the inflammatory disorder or disease is asthma. In certain embodiments, the inflammatory disorder or disease is idiopathic pulmonary fibrosis. In certain embodiments of the methods described herein, the inflammatory disorder or disease is alopecia areata. In certain embodiments, the inflammatory disorder or disease is chronic sinusitis with nasal polyps. In certain embodiments, the inflammatory disorder or disease is Chronic Rhinosinusitis without Nasal Polyps (CRSsNP). In certain embodiments, the inflammatory disorder or disease is eosinophilic esophagitis (EoE). In certain embodiments, the inflammatory disorder or disease is an Eosinophilic gastrointestinal disorder or disease (EGID) selected from the group consisting of Eosinophilic Gastritis (EoG), Eosinophilic Enteritis (EoN), Eosinophilic Colitis (EoC), and Eosinophilic Gastroenteritis (EGE). In certain embodiments, the inflammatory disorder or disease is Churg-Strauss syndrome/Eosinophilic granulomatosis with polyangiitis (EGPA). In certain embodiments, the inflammatory disorder or disease is Prurigo Nodularis (PN). In certain embodiments, the inflammatory disorder or disease is Chronic Spontaneous Urticaria (CSU). In certain embodiments, the inflammatory disorder or disease is Chronic Pruritis of Unknown Origin (CPUO). In certain embodiments, the inflammatory disorder or disease is Bullous Pemphigoid (BP). In certain embodiments, the inflammatory disorder or disease is Cold Inducible Urticaria (ColdU). In certain embodiments, the inflammatory disorder or disease is Allergic Fungal Rhinosinusitis (AFRS). In certain embodiments, the inflammatory disorder or disease is Allergic Bronchopulmonary Aspergillosis (ABPA). In certain embodiments, the inflammatory disorder or disease is Chronic Obstructive Pulmonary Disease (COPD). In certain embodiments, the inflammatory disorder or disease is inflammatory bowel disease, such as Crohn’s disease or ulcerative colitis. In certain embodiments, the inflammatory disorder or disease is psoriasis. In certain embodiments, the inflammatory disorder or disease is lupus. In certain embodiments, the inflammatory disorder or disease is rheumatoid arthritis. In certain embodiments, the inflammatory disorder or disease is celiac disease. In certain embodiments, the inflammatory disorder or disease is hidradenitis suppurativa. In certain embodiments, the inflammatory disorder or disease is systemic sclerosis. In certain embodiments, the inflammatory disorder or disease is allergic rhinitis. In certain embodiments, the inflammatory disorder or disease is eosinophilic fasciitis. In certain embodiments, the inflammatory disorder or disease is scleromyxedema. In certain embodiments, the inflammatory disorder or disease is scleredema. In certain embodiments, the inflammatory disorder or disease is nephrogenic systemic fibrosis. [00650] In certain aspects, described herein are methods for treating a pathology associated with elevated levels of OX40L in a mammalian subject in need thereof, the method comprising administering to the mammalian subject a therapeutically effective amount of a combination of antibodies, or antigen binding fragments thereof, or a multi- specific antibody or a pharmaceutical composition described herein. [00651] In certain aspects, described herein are methods of reducing biological activity of OX40L in a mammalian subject in need thereof, the method comprising administering to the mammalian subject a therapeutically effective amount of a combination of antibodies, or antigen binding fragments thereof, or a multi-specific antibody or a pharmaceutical composition described herein. [00652] In certain aspects, described herein are methods for treating a pathology associated with elevated levels of IL-4 or IL-13 in a mammalian subject in need thereof, the method comprising administering to the mammalian subject a therapeutically effective amount of a combination of antibodies, or antigen binding fragments thereof, or a multi- specific antibody or a pharmaceutical composition described herein. [00653] In certain aspects, described herein are methods of reducing biological activity of IL-4, IL-13, and/or IL-4Rα in a mammalian subject in need thereof, the method comprising administering to the mammalian subject a therapeutically effective amount of a combination of antibodies, or antigen binding fragments thereof, or a multi-specific antibody or a pharmaceutical composition described herein. [00654] In certain aspects, described herein are methods for reducing or inhibiting the TH2 type (Type 2) allergic response in a mammalian subject in need thereof, the method comprising administering to the mammalian subject a therapeutically effective amount of a combination of antibodies, or antigen binding fragments thereof, or a multi-specific antibody or a pharmaceutical composition described herein. [00655] In certain aspects, described herein are methods for inhibiting IL-4Rα-induced phosphorylation of STAT6 in a cell, the method comprising contacting the cell with a combination of antibodies, or antigen binding fragments thereof, or a multi-specific antibody or a pharmaceutical composition described herein. [00656] In certain aspects, described herein are methods for reducing levels of Thymus and Activation Regulated Chemokine (TARC)/CCL17 in a mammalian subject in need thereof, the method comprising administering to the mammalian subject a therapeutically effective amount of a combination of antibodies or a multi-specific antibody or a pharmaceutical composition described herein. [00657] In certain aspects, described herein are methods for reducing levels of Type 1 and Type 2 cytokines and/or chemokines (e.g., TNFα, MDC, IL-13, and/or IL-5) in a mammalian subject in need thereof, the method comprising administering to the mammalian subject a therapeutically effective amount of a combination of antibodies or a multi-specific antibody or a pharmaceutical composition described herein. [00658] In certain aspects, described herein are methods for reducing levels of interferon- gamma (IFNγ) in a mammalian subject in need thereof, the method comprising administering to the mammalian subject a therapeutically effective amount of a combination of antibodies, or antigen binding fragments thereof, or a multi-specific antibody or a pharmaceutical composition described herein. [00659] In certain aspects, described herein are methods for reducing levels of IL-2 in a mammalian subject in need thereof, the method comprising administering to the mammalian subject a therapeutically effective amount of a combination of antibodies, or antigen binding fragments thereof, or a multi-specific antibody or a pharmaceutical composition described herein. [00660] In certain aspects, described herein are methods of preventing an inflammatory disorder or disease in a mammalian subject in need thereof, the method comprising administering to the mammalian subject a therapeutically effective amount of a combination of antibodies or a multi-specific antibody or a pharmaceutical composition described herein. Methods of Administration [00661] In some embodiments, the methods provided herein are useful for the treatment of a disease or disorder in an individual, e.g., a human. In an embodiment, the individual has received an anti-IL-4Rα antibody, or an antigen binding fragment thereof, and the method includes administering an anti-OX40L antibody, or an antigen binding fragment thereof, described herein. [00662] In an embodiment, the individual has received an anti-OX40L antibody, or an antigen binding fragment thereof, and the method includes administering an anti-IL-4Rα antibody, or an antigen binding fragment thereof, described herein. [0001] In an embodiment, the individual is administered an anti-OX40L antibody, or an antigen binding fragment thereof, and an anti-IL-4Rα antibody, or an antigen binding fragment thereof. In certain embodiments, the treatment regimen of the present invention may involve administering the anti-OX40L antibody, or an antigen binding fragment thereof, and the anti-IL-4Rα antibody, or an antigen binding fragment thereof, at the same time. This may be achieved by administering a single composition or pharmacological formulation that includes both agents, or by administering two distinct compositions or formulations, at the same time, wherein one composition includes the anti-OX40L antibody, or an antigen binding fragment thereof, and the other includes the anti-IL-4Rα antibody, or an antigen binding fragment thereof. Alternatively, the anti-OX40L antibody, or an antigen binding fragment thereof, may be administered before the anti-IL-4Rα antibody, or an antigen binding fragment thereof, by intervals ranging from minutes, hours, days to weeks, or the anti-IL-4Rα antibody, or an antigen binding fragment thereof, may be administered before the anti-OX40L antibody, or an antigen binding fragment thereof, by intervals ranging from minutes, hours days to weeks. [00663] In an embodiment, the individual is administered a combination of antibodies, or antigen binding fragments thereof, or a multi-specific antibody described herein. [00664] In some embodiments, a combination of antibodies, or antigen binding fragments thereof, or a multi-specific antibody is administered intravenously, intramuscularly, subcutaneously, topically, orally, transdermally, intraperitoneally, intraorbitally, by implantation, by inhalation, intrathecally, intraventricularly, or intranasally. An effective amount of an anti-OX40L antibody, or an antigen binding fragment thereof, and an anti-IL- 4Rα antibody, or an antigen binding fragment thereof, may be administered for the treatment of a disease or disorder. The appropriate dosage of the anti-OX40L antibody, or an antigen binding fragment thereof, and the anti-IL-4Rα antibody, or an antigen binding fragment thereof, may be determined based on, e.g., the type of disease or disorder to be treated, the type of the anti-OX40L antibody, the type of anti-IL-4Rα antibody, the severity and course of the disease or disorder, the clinical condition of the individual, the individual’s clinical history and response to the treatment, and the discretion of the attending physician. [00665] In some embodiments, the combination of antibodies, or antigen binding fragments thereof, or a multi-specific antibody provided herein are administered with at least one additional therapeutic agent. Any suitable additional therapeutic or immunotherapeutic agent may be administered with a combination of antibodies or a multi-specific antibody provided herein. Additional therapeutic agents include agents that are used to treat or prevent a disease or disorder such as, but not limited to, an inflammatory disease or disorder associated with elevated levels of OX40L, IL-4 IL-13, and/or IgE. [00666] The additional therapeutic agent can be administered by any suitable means. In some embodiments, the antibodies, or antigen binding fragments thereof, or multi-specific antibody and the additional therapeutic agent are included in the same pharmaceutical composition. In some embodiments, the antibodies, or antigen binding fragments thereof, or multi-specific antibody provided herein and the additional therapeutic agent are included in different pharmaceutical compositions. [00667] In embodiments where the antibodies, or antigen binding fragments thereof, or multi-specific antibody and the additional therapeutic agent are included in different pharmaceutical compositions, administration of the antibodies, or antigen binding fragments thereof, or multi-specific antibody can occur prior to, simultaneously, and/or following, administration of the additional therapeutic agent. In some embodiments, administration of the antibodies, or antigen binding fragments thereof, or multi-specific antibody provided herein and the additional therapeutic agent occur within about one month of each other. In some embodiments, administration of the antibodies, or antigen binding fragments thereof, or multi-specific antibody provided herein and the additional therapeutic agent occur within about one week of each other. In some embodiments, administration of the antibodies, or antigen binding fragments thereof, or multi-specific antibody provided herein and the additional therapeutic agent occur within about one day of each other. In some embodiments, administration of the antibodies, or antigen binding fragments thereof, or multi-specific antibody provided herein and the additional therapeutic agent occur within about twelve hours of each other. In some embodiments, administration of the antibodies, or antigen binding fragments thereof, or multi-specific antibody provided herein and the additional therapeutic agent occur within about one hour of each other. [00668] In some embodiments, the method further comprises administration of a hyaluronidase or variant thereof. In certain embodiments, the hyaluronidase or variant thereof is included in the same composition with one or more of the antibodies (i.e., anti- IL-4Rα antibody, or an antigen binding fragment thereof, and anti-OX40L antibody, or an antigen binding fragment thereof) or the multi-specific antibody (i.e., comprising a first antigen binding region that binds OX40L and a second antigen binding region that binds IL-4Rα). In certain embodiments, the hyaluronidase or variant there if is administered in a separate formulation. In certain embodiments, the hyaluronidase or variant thereof and antibodies or multi-specific antibody are administered simultaneously in separate formulations (e.g., via two formulations: one containing the hyaluronidase or variant thereof and the other containing the multi-specific antibody or combination of the OX40L antibody, or an antigen binding fragment thereof, and IL-4Rα antibody, or an antigen binding fragment thereof, or via three formulations: one containing the hyaluronidase or variant thereof, another containing the OX40L antibody, or an antigen binding fragment thereof, and another containing the IL-4Rα antibody, or an antigen binding fragment thereof). In certain embodiments, the hyaluronidase or variant thereof is administered to the patient prior to administration of the antibodies or multi-specific antibody. In certain embodiments, the hyaluronidase or variant thereof is administered to the patient after administration of the antibodies or multi-specific antibody. In certain embodiments, the hyaluronidase or variant thereof is administered to the patient after administration of one of the antibodies (either the OX40L antibody, or an antigen binding fragment thereof, or the IL-4Rα antibody, or an antigen binding fragment thereof) but is administered before the administration of the second of the antibodies (either the OX40L antibody, or an antigen binding fragment thereof, or the IL-4Rα antibody, or an antigen binding fragment thereof). In certain embodiments, the hyaluronidase or variant thereof and the antibodies or multi-specific antibody are mixed and administered in a single formulation. [00669] Compositions, Combinations, and Methods Involving Co-Administration [00670] In certain aspects, described herein are compositions comprising an isolated antibody that binds OX40L, or an antigen binding fragment thereof, an isolated antibody that binds Interleukin-4 Receptor Alpha (IL-4Rα), or an antigen binding fragment thereof, and a hyaluronidase or variant thereof. In certain aspects, described herein are compositions comprising any one of the antibodies, or antigen binding fragments thereof, described herein that binds OX40L, any one of the antibodies, or antigen binding fragments thereof, described herein that binds IL-4Rα, and any of the hyaluronidases or variants thereof described herein. [00671] In certain aspects, described herein are compositions comprising hyaluronidase or a variant thereof and a multi-specific antibody comprising a first antigen binding region that binds OX40L and a second antigen binding region that binds IL-4Rα. [00672] In certain aspects, described herein are a combination of an antibody that binds OX40L, or an antigen binding fragment thereof, an antibody that binds IL-4Rα, or an antigen binding fragment thereof, and a hyaluronidase or variant thereof. In certain aspects, described herein are a combination of any one of the antibodies, or antigen binding fragments thereof, described herein that binds OX40L, any one of the antibodies, or antigen binding fragments thereof, described herein that binds IL-4Rα, and a hyaluronidase or a variant thereof. [00673] In certain aspects, described herein are combinations comprising hyaluronidase or a variant thereof and a multi-specific antibody comprising a first antigen binding region that binds OX40L and a second antigen binding region that binds IL-4Rα. [00674] In certain aspects, described herein are methods of treating an inflammatory disorder or disease in a human patient comprising co-administering to the patient an isolated antibody, or an antigen binding fragment thereof, that binds OX40L, an isolated antibody, or an antigen binding fragment thereof, that binds IL-4Rα, and a hyaluronidase or a variant thereof. In certain aspects, described herein are methods of treating an inflammatory disorder or disease in a human patient comprising co-administering to the patient any one of the antibodies, or antigen binding fragments thereof, described herein that binds OX40L, any one of the antibodies, or antigen binding fragments thereof, described herein that binds IL-4Rα, and any of the hyaluronidases or variants thereof described herein. [00675] In certain aspects, described herein are methods of treating an inflammatory disorder or disease in a human patient comprising co-administering to the patient a hyaluronidase or a variant thereof and a multi-specific antibody comprising a first antigen binding region that binds OX40L and a second antigen binding region that binds IL-4Rα. In certain aspects, described herein are methods of treating an inflammatory disorder or disease in a human patient comprising co-administering to the patient any of the hyaluronidases or variants thereof described herein and any one of the multi-specific antibodies described herein (e.g., comprising a first antigen binding region that binds OX40L and a second antigen binding region that binds IL-4Rα). [00676] In certain embodiments, the antibody, or antigen binding region thereof, that binds OX40L and/or the antibody, or antigen binding region thereof, that binds IL-4Rα is a humanized, human, or chimeric antibody. In certain embodiments, the antibody is a monoclonal antibody. In certain embodiments, the antibody comprises a heavy chain human constant region of a class selected from IgG, IgA, IgD, IgE, and IgM. In certain embodiments, the antibody comprises a human Fc region comprising a human heavy chain constant region of the class IgG and a subclass selected from IgG1, IgG2, IgG3, and IgG4. In certain embodiments, the human Fc region comprises a human IgG1 Fc region. In certain embodiments the human Fc region comprises a human IgG1 Fc region with LALA (L234A/L235A) mutations. In certain embodiments the human Fc region comprises a human IgG1 Fc with YTE (M252Y/S254T/T256E) mutations. In certain embodiments the human Fc region comprises a human IgG1 Fc with LALA (L234A/L235A) and YTE (M252Y/S254T/T256E) mutations. In certain embodiments, when direct numbering is used these “YTE” and “LALA” mutations can be located at different amino acid position numbers. For example, in one embodiment, the human Fc region comprises a human IgG1 Fc region with LALA mutations at L235A/L236A and/or YTE mutations at M253Y/S255T/T257E (see, e.g., SEQ ID NO: 839 and 840). In another embodiment, the human Fc region comprises a human IgG1 Fc region with LALA mutations at L242A/L243A and/or YTE mutations at M260Y/S262T/T264E (see, e.g., SEQ ID NO: 836 or 837). [00677] In certain embodiments, the antibody, or antigen binding region thereof, that binds OX40L comprises a CDR-H1 comprising the sequence set forth in SEQ ID NO: 2; a CDR- H2 comprising the sequence set forth in SEQ ID NO: 5; a CDR-H3 comprising the sequence set forth in SEQ ID NO: 8; a CDR-L1 comprising the sequence set forth in SEQ ID NO: 12; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 15; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 17. In one embodiment, the antibody, or antigen binding region thereof, that binds OX40L comprises a VH sequence set forth in SEQ ID NO: 1 and a VL sequence set forth in SEQ ID NO: 11. In one embodiment, the heavy chain of the antibody, or antigen binding region thereof, that binds OX40L comprises a constant heavy chain sequence set forth in SEQ ID NO: 651. In one embodiment, the heavy chain of the antibody, or antigen binding region thereof, that binds OX40L comprises a constant heavy chain sequence set forth in SEQ ID NO: 973. In one embodiment, the light chain of the antibody, or antigen binding region thereof, that binds OX40L comprises a constant light chain sequence set forth in SEQ ID NO: 738. In one embodiment, the heavy chain of the antibody, or antigen binding region thereof, that binds OX40L has the sequence set forth in SEQ ID NO: 839. In one embodiment, the light chain of the antibody, or antigen binding region thereof, that binds OX40L has the sequence set forth in SEQ ID NO: 841. The C- terminal lysine in SEQ ID NO: 839 may not be present if cleavage occurs during manufacture or after administration (which would result in the heavy chain sequence of SEQ ID NO: 840). [00678] In certain embodiments, the antibody, or antigen binding region thereof, that binds IL-4Rα comprises a CDR-H1 comprising the sequence set forth in SEQ ID NO: 273; a CDR- H2 comprising the sequence set forth in SEQ ID NO: 279; a CDR-H3 comprising the sequence set forth in SEQ ID NO: 281; a CDR-L1 comprising the sequence set forth in SEQ ID NO: 289; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 290; and a CDR- L3 comprising the sequence set forth in SEQ ID NO: 293. In one embodiment, the antibody, or antigen binding region thereof, that binds IL-4Rα comprises a VH sequence set forth in SEQ ID NO: 297 and a VL sequence set forth in SEQ ID NO: 300. In one embodiment, the heavy chain of the antibody, or antigen binding region thereof, that binds IL-4Rα comprises a constant heavy chain sequence set forth in SEQ ID NO: 651. In one embodiment, the heavy chain of the antibody, or antigen binding region thereof, that binds IL-4Rα comprises a constant heavy chain sequence set forth in SEQ ID NO: 973. In one embodiment, the light chain of the antibody, or antigen binding region thereof, that binds IL-4Rα comprises a constant light chain sequence set forth in SEQ ID NO: 738. In one embodiment, the heavy chain of the antibody, or antigen binding region thereof, that binds IL-4Rα has the sequence set forth in SEQ ID NO: 836. In one embodiment, the light chain of the antibody, or antigen binding region thereof, that binds IL-4Rα has the sequence set forth in SEQ ID NO: 838. The C-terminal lysine in SEQ ID NO: 836 may not be present if cleavage occurs during manufacture or after administration (which would result in the heavy chain sequence of SEQ ID NO: 837). [00679] In certain embodiments, a multi-specific antibody comprising a first antigen binding region that binds OX40L and a second antigen binding region that binds IL-4Rα is provided. In one embodiment, the antigen binding region that binds OX40L comprises a CDR-H1 comprising the sequence set forth in SEQ ID NO: 2; a CDR-H2 comprising the sequence set forth in SEQ ID NO: 5; a CDR-H3 comprising the sequence set forth in SEQ ID NO: 8; a CDR-L1 comprising the sequence set forth in SEQ ID NO: 12; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 15; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 17. In one embodiment, the antigen binding region that binds OX40L comprises a VH sequence set forth in SEQ ID NO: 1 and a VL sequence set forth in SEQ ID NO: 11. In another embodiment, the antigen binding region that binds IL- 4Rα comprises a CDR-H1 comprising the sequence set forth in SEQ ID NO: 273; a CDR-H2 comprising the sequence set forth in SEQ ID NO: 279; a CDR-H3 comprising the sequence set forth in SEQ ID NO: 281; a CDR-L1 comprising the sequence set forth in SEQ ID NO: 289; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 290; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 293. In one embodiment, the antibody that binds IL-4Rα comprises a VH sequence set forth in SEQ ID NO: 297 and a VL sequence set forth in SEQ ID NO: 300. [00680] In certain embodiments, the antibody or antigen binding region that binds OX40L and/or the antibody or antigen binding region that binds IL-4Rα comprises a heavy chain human constant region of a class selected from IgG, IgA, IgD, IgE, and IgM. In certain embodiments, the antibody or antigen binding region that binds OX40L and/or the antibody or antigen binding region that binds IL-4Rα comprises a human Fc region, and the human Fc region comprises a human heavy chain constant region of the class IgG and a subclass selected from IgG1, IgG2, IgG3, and IgG4. In certain embodiments, the human Fc region of the antibody that binds OX40L and/or the antibody that binds IL-4Rα comprises a human IgG1 Fc region. In certain embodiments the human Fc region comprises a human IgG1 Fc with LALA (L234A/L235A) mutations. In certain embodiments the human Fc region comprises a human IgG1 Fc with YTE (M252Y/S254T/T256E) mutations. In certain embodiments the human Fc region comprises a human IgG1 Fc with LALA (L234A/L235A) and YTE (M252Y/S254T/T256E) mutations. In certain embodiments, when direct numbering is used these “YTE” and “LALA” mutations can be located at different amino acid position numbers. For example, in one embodiment, the human Fc region comprises a human IgG1 Fc region with LALA mutations at L235A/L236A and/or YTE mutations at M253Y/S255T/T257E (see, e.g., SEQ ID NO: 839 and 840). In another embodiment, the human Fc region comprises a human IgG1 Fc region with LALA mutations at L242A/L243A and/or YTE mutations at M260Y/S262T/T264E (see, e.g., SEQ ID NO: 836 or 837). In certain embodiments, the human Fc region of the antibody that binds OX40L and/or the antibody that binds IL-4Rα comprises a human IgG4 Fc region. In certain embodiments, the human Fc region of the antibody or antigen binding region that binds OX40L and/or the antibody or antigen binding region that binds IL-4Rα comprises a human IgG2 Fc region. [00681] In certain embodiments, the Fc region of the antibody or antigen binding region that binds OX40L and/or the antibody or antigen binding region that binds IL-4Rα binds to Neonatal Fc receptor (FcRn). In certain embodiments, the Fc region of the antibody or antigen binding region that binds OX40L and/or the antibody or antigen binding region that binds IL-4Rα binds an FcRn with higher affinity at pH 6.0 compared to an antibody comprising a wild-type Fc region. In certain embodiments, the Fc region of the antibody or antigen binding region that binds OX40L and/or the antibody or antigen binding region that binds IL-4Rα binds to FcRn with a KD of <1 x 10-7 M at pH 6.0. [00682] In certain embodiments, the antibody or antigen binding region that binds OX40L and/or the antibody or antigen binding region that binds IL-4Rα is a monoclonal antibody. [00683] In certain embodiments, the antibody or antigen binding region that binds OX40L binds an OX40L sequence set forth in the amino acid sequence of SEQ ID NO: 739. In certain embodiments, the antibody or antigen binding region that binds IL-4Rα binds an IL- 4Rα sequence set forth in any one of the amino acid sequences of SEQ ID NOs: 301-303. [00684] Any suitable hyaluronidase or variant thereof can be used in the compositions, combinations, and methods described herein. In certain embodiments, the hyaluronidase is a recombinant human hyaluronidase. In certain embodiments, the recombinant human hyaluronidase comprises the amino acid sequence set forth in any one of SEQ ID NOs: 1076- 1085 and 1087-1142. In certain embodiments, the recombinant human hyaluronidase is rHuPH20. In certain embodiments, the rHuPH20 formulation is ENHANZE®. [00685] In one embodiment, the recombinant human hyaluronidase includes a sequence of amino acids in any one of SEQ ID NOs: 1076-1085 and 1087-1142, or has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 95%, 97%, 98%, or 99% sequence identity to a sequence of amino acids included in SEQ ID NO: 1076- 1085 and 1087-1142 and retains hyaluronidase activity. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1076. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1076. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1078. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1078. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1079. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1079. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1080. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1080. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1081. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1081. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1082. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1082. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1083. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1083. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1084. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1084. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1085. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1085. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1087. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1087. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1088. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1088. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1089. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1089. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1090. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1090. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1091. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1091. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1092. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1092. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1093. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1093. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1094. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1094. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1095. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1095. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1096. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1096. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1097. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1097. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1098. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1098. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1099. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1099. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1100. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1100. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1101. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1101. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1102. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1102. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1103. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1103. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1104. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1104. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1105. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1105. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1106. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1106. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1107. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1107. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1108. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1108. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1109. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1109. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1110. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1110. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1111. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1111. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1112. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1112. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1113. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1113. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1114. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1114. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1115. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1115. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1116. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1116. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1117. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1117. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1118. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1118. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1119. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1119. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1120. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1120. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1121. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1121. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1122. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1122. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1123. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1123. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1124. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1124. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1125. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1125. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1126. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1126. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1127. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1127. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1128. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1128. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1129. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1129. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1130. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1130. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1131. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1131. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1132. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1132. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1133. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1133. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1134. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1134. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1135. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1135. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1136. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1136. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1137. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1137. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1138. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1138. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1139. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1139. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1140. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1140. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1141. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1141. In another embodiment, the recombinant human hyaluronidase comprises the amino acid sequence set forth in SEQ ID NO:1142. In another embodiment, the recombinant human hyaluronidase consists of the amino acid sequence set forth in SEQ ID NO:1142. [00686] In certain embodiments, the hyaluronidase or variant thereof and antibodies (i.e., anti- IL-4Rα antibody, or an antigen binding fragment thereof, and anti-OX40L antibody, or an antigen binding fragment thereof,) or multi-specific antibody (i.e., comprising a first antigen binding region that binds OX40L and a second antigen binding region that binds IL- 4Rα) are administered in separate formulations (e.g., via two formulations: one containing the hyaluronidase or variant thereof and the other containing the multi-specific antibody or combination of the OX40L antibody, or an antigen binding fragment thereof, and IL-4Rα antibody, or an antigen binding fragment thereof, or via three formulations: one containing the hyaluronidase or variant thereof, another containing the OX40L antibody, or an antigen binding fragment thereof, and another containing the IL-4Rα antibody, or an antigen binding fragment thereof). In certain embodiments, the hyaluronidase or variant thereof and antibodies or multi-specific antibody are administered simultaneously in separate formulations. In certain embodiments, the hyaluronidase or variant thereof is administered to the patient prior to administration of the antibodies or multi-specific antibody. In certain embodiments, the hyaluronidase or variant thereof is administered to the patient after administration of the antibodies or multi-specific antibody. In certain embodiments, the hyaluronidase or variant thereof is administered to the patient after administration of one of the antibodies (either the OX40L antibody, or an antigen binding fragment thereof, or the IL- 4Rα antibody, or an antigen binding fragment thereof) but is administered before the administration of the second of the antibodies (either the OX40L antibody, or an antigen binding fragment thereof, or the IL-4Rα antibody, or an antigen binding fragment thereof). In certain embodiments, the hyaluronidase or variant thereof and the antibodies or multi- specific antibody are mixed and administered in a single formulation. In certain embodiments, the hyaluronidase or variant thereof and the antibodies or multi-specific antibody are administered by subcutaneous injection. In certain embodiments, the hyaluronidase or variant thereof and the antibodies or multi-specific antibody are administered by intravenous injection. [00687] In certain embodiments, the hyaluronidase is rHuPH20 (ENHANZE®) administered at a concentration of 5,000, 6,000, 7,000, 8,000, 9,000, 10,000, 11,000, 12,000, 13,000, 14,000, 15,000, 16,000, 17,000, 18,000, 19,000, 20,000, 21,000, 22,000, 23,000, 24,000, 25,000, 26,000, 27,000, 28,000, 29,000, 30,000, 31,000, 32,000, 33,000, 34,000, 35,000, 36,000, 37,000, 38,000, 39,000, or 40,000 units. [00688] In certain embodiments, methods of treating an inflammatory disorder or disease in a human patient are provided, wherein the method comprises co-administering to the patient any one of the antibodies, or antigen binding fragments thereof, that bind OX40L described herein and any one of the antibodies, or antigen binding fragments thereof, that bind IL-4Rα described herein in combination with a hyaluronidase or variant thereof. In certain embodiments, methods of treating an inflammatory disorder or disease in a human patient are provided, wherein the method comprises co-administering to the patient any one of the multi-specific antibodies described herein in combination with a hyaluronidase or variant thereof. In certain embodiments, the inflammatory disorder or disease is atopic dermatitis. In certain embodiments, the treatment reduces disease severity in the patient and wherein disease severity is assessed by an atopic dermatitis disease severity outcome measure. In certain embodiments, the inflammatory disorder or disease is asthma; chronic sinusitis with nasal polyps; Chronic Rhinosinusitis without Nasal Polyps (CRSsNP); eosinophilic esophagitis (EoE); an Eosinophilic gastrointestinal disorder or disease (EGID) selected from the group consisting of Eosinophilic Gastritis (EoG), Eosinophilic Enteritis (EoN), Eosinophilic Colitis (EoC), and Eosinophilic Gastroenteritis (EGE); Churg-Strauss syndrome/Eosinophilic granulomatosis with polyangiitis (EGPA); Prurigo Nodularis (PN); Chronic Spontaneous Urticaria (CSU); Chronic Pruritis of Unknown Origin (CPUO); Bullous Pemphigoid (BP); Cold Inducible Urticaria (ColdU); Allergic Fungal Rhinosinusitis (AFRS); Allergic Bronchopulmonary Aspergillosis (ABPA); Chronic Obstructive Pulmonary Disease (COPD); an inflammatory bowel disease, such as Crohn’s disease or ulcerative colitis; lupus; rheumatoid arthritis (RA); psoriasis; hidradenitis suppurativa; celiac disease; systemic sclerosis; idiopathic pulmonary fibrosis; alopecia areata; allergic rhinitis; eosinophilic fasciitis; scleromyxedema; scleredema; or nephrogenic systemic fibrosis. [00689] In certain aspects, described herein are compositions comprising an isolated antibody, or antigen binding region thereof, that binds OX40L, an isolated antibody, or antigen binding region thereof, that binds IL-4Rα, and a hyaluronidase or variant thereof. [00690] In certain aspects, described herein are compositions comprising an isolated antibody, or antigen binding region thereof, that binds OX40L, an isolated antibody, or antigen binding region thereof, that binds IL-4Rα, and a hyaluronidase or variant thereof, wherein the antibody, or antigen binding region thereof, that binds OX40L comprises a CDR- H1 comprising the sequence set forth in SEQ ID NO: 2; a CDR-H2 comprising the sequence set forth in SEQ ID NO: 5; a CDR-H3 comprising the sequence set forth in SEQ ID NO: 8; a CDR-L1 comprising the sequence set forth in SEQ ID NO: 12; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 15; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 17. [00691] In certain aspects, described herein are compositions comprising an isolated antibody, or antigen binding region thereof, that binds OX40L, an isolated antibody, or antigen binding region thereof, that binds IL-4Rα, and a hyaluronidase or variant thereof, wherein the antibody, or antigen binding region thereof, that binds OX40L comprises a VH sequence set forth in SEQ ID NO: 1 and a VL sequence set forth in SEQ ID NO: 11. [00692] In certain aspects, described herein are compositions comprising an isolated antibody, or antigen binding region thereof, that binds OX40L, an isolated antibody, or antigen binding region thereof, that binds IL-4Rα, and a hyaluronidase or variant thereof, wherein the antibody that binds IL-4Rα, or antigen binding region thereof, comprises a CDR- H1 comprising the sequence set forth in SEQ ID NO: 273; a CDR-H2 comprising the sequence set forth in SEQ ID NO: 279; a CDR-H3 comprising the sequence set forth in SEQ ID NO: 281; a CDR-L1 comprising the sequence set forth in SEQ ID NO: 289; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 290; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 293. [00693] In certain aspects, described herein are compositions comprising an isolated antibody, or antigen binding region thereof, that binds OX40L, an isolated antibody, or antigen binding region thereof, that binds IL-4Rα, and a hyaluronidase or variant thereof, wherein the antibody, or antigen binding region thereof, that binds IL-4Rα comprises a VH sequence set forth in SEQ ID NO: 297 and a VL sequence set forth in SEQ ID NO: 300. [00694] In certain aspects, described herein are compositions comprising an isolated antibody, or antigen binding region thereof, that binds OX40L, an isolated antibody, or antigen binding region thereof, that binds IL-4Rα, and a hyaluronidase or variant thereof, wherein the antibody, or antigen binding region thereof, that binds OX40L comprises a CDR- H1 comprising the sequence set forth in SEQ ID NO: 2; a CDR-H2 comprising the sequence set forth in SEQ ID NO: 5; a CDR-H3 comprising the sequence set forth in SEQ ID NO: 8; a CDR-L1 comprising the sequence set forth in SEQ ID NO: 12; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 15; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 17, and wherein the antibody, or antigen binding region thereof, that binds IL- 4Rα comprises a CDR-H1 comprising the sequence set forth in SEQ ID NO: 273; a CDR-H2 comprising the sequence set forth in SEQ ID NO: 279; a CDR-H3 comprising the sequence set forth in SEQ ID NO: 281; a CDR-L1 comprising the sequence set forth in SEQ ID NO: 289; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 290; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 293. [00695] In certain aspects, described herein are compositions comprising an isolated antibody, or antigen binding region thereof, that binds OX40L, an isolated antibody, or antigen binding region thereof, that binds IL-4Rα, and a hyaluronidase or variant thereof, wherein the antibody, or antigen binding region thereof, that binds OX40L comprises a VH sequence set forth in SEQ ID NO: 1 and a VL sequence set forth in SEQ ID NO: 11; and wherein the antibody, or antigen binding region thereof, that binds IL-4Rα comprises a VH sequence set forth in SEQ ID NO: 297 and a VL sequence set forth in SEQ ID NO: 300. [00696] In certain aspects, described herein are compositions comprising hyaluronidase or a variant thereof and a multi-specific antibody comprising a first antigen binding region that binds OX40L and a second antigen binding region that binds IL-4Rα, wherein the antigen binding region that binds OX40L comprises a CDR-H1 comprising the sequence set forth in SEQ ID NO: 2; a CDR-H2 comprising the sequence set forth in SEQ ID NO: 5; a CDR-H3 comprising the sequence set forth in SEQ ID NO: 8; a CDR-L1 comprising the sequence set forth in SEQ ID NO: 12; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 15; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 17, and wherein the antigen binding region that binds IL-4Rα comprises a CDR-H1 comprising the sequence set forth in SEQ ID NO: 273; a CDR-H2 comprising the sequence set forth in SEQ ID NO: 279; a CDR- H3 comprising the sequence set forth in SEQ ID NO: 281; a CDR-L1 comprising the sequence set forth in SEQ ID NO: 289; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 290; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 293. [00697] In certain aspects, described herein are compositions comprising hyaluronidase or a variant thereof and a multi-specific antibody comprising a first antigen binding region that binds OX40L and a second antigen binding region that binds IL-4Rα, wherein the antigen binding region that binds OX40L comprises a VH sequence set forth in SEQ ID NO: 1 and a VL sequence set forth in SEQ ID NO: 11; and wherein the antigen binding region that binds IL-4Rα comprises a VH sequence set forth in SEQ ID NO: 297 and a VL sequence set forth in SEQ ID NO: 300. [00698] In certain aspects, described herein are combinations comprising an isolated antibody, or antigen binding region thereof, that binds OX40L, an isolated antibody, or antigen binding region thereof, that binds IL-4Rα, and a hyaluronidase or variant thereof, wherein the antibody, or antigen binding region thereof, that binds OX40L comprises a CDR- H1 comprising the sequence set forth in SEQ ID NO: 2; a CDR-H2 comprising the sequence set forth in SEQ ID NO: 5; a CDR-H3 comprising the sequence set forth in SEQ ID NO: 8; a CDR-L1 comprising the sequence set forth in SEQ ID NO: 12; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 15; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 17, and wherein the antibody, or antigen binding region thereof, that binds IL- 4Rα comprises a CDR-H1 comprising the sequence set forth in SEQ ID NO: 273; a CDR-H2 comprising the sequence set forth in SEQ ID NO: 279; a CDR-H3 comprising the sequence set forth in SEQ ID NO: 281; a CDR-L1 comprising the sequence set forth in SEQ ID NO: 289; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 290; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 293 [00699] In certain aspects, described herein are combinations comprising an isolated antibody, or antigen binding region thereof, that binds OX40L, an isolated antibody, or antigen binding region thereof, that binds IL-4Rα, and a hyaluronidase or variant thereof, wherein the antibody, or antigen binding region thereof, that binds OX40L comprises a VH sequence set forth in SEQ ID NO: 1 and a VL sequence set forth in SEQ ID NO: 11; and wherein the antibody, or antigen binding region thereof, that IL-4Rα comprises a VH sequence set forth in SEQ ID NO: 297 and a VL sequence set forth in SEQ ID NO: 300. [00700] In certain aspects, described herein are combinations comprising hyaluronidase or a variant thereof and a multi-specific antibody comprising a first antigen binding region that binds OX40L and a second antigen binding region that binds IL-4Rα, wherein the antigen binding region that binds OX40L comprises a CDR-H1 comprising the sequence set forth in SEQ ID NO: 2; a CDR-H2 comprising the sequence set forth in SEQ ID NO: 5; a CDR-H3 comprising the sequence set forth in SEQ ID NO: 8; a CDR-L1 comprising the sequence set forth in SEQ ID NO: 12; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 15; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 17, and wherein the antigen binding region that binds IL-4Rα comprises a CDR-H1 comprising the sequence set forth in SEQ ID NO: 273; a CDR-H2 comprising the sequence set forth in SEQ ID NO: 279; a CDR- H3 comprising the sequence set forth in SEQ ID NO: 281; a CDR-L1 comprising the sequence set forth in SEQ ID NO: 289; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 290; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 293. [00701] In certain aspects, described herein are combinations comprising hyaluronidase or a variant thereof and a multi-specific antibody comprising a first antigen binding region that binds OX40L and a second antigen binding region that binds IL-4Rα, wherein the antigen binding region that binds OX40L comprises a VH sequence set forth in SEQ ID NO: 1 and a VL sequence set forth in SEQ ID NO: 11; and wherein the antigen binding region that binds IL-4Rα comprises a VH sequence set forth in SEQ ID NO: 297 and a VL sequence set forth in SEQ ID NO: 300. [00702] In certain aspects, described herein are methods of treating an inflammatory disorder or disease in a human patient comprising administering to the patient an isolated antibody, or antigen binding region thereof, that binds OX40L, an isolated antibody, or antigen binding region thereof, that binds IL-4Rα, and a hyaluronidase or a variant thereof, wherein the antibody, or antigen binding region thereof, that binds OX40L comprises a CDR- H1 comprising the sequence set forth in SEQ ID NO: 2; a CDR-H2 comprising the sequence set forth in SEQ ID NO: 5; a CDR-H3 comprising the sequence set forth in SEQ ID NO: 8; a CDR-L1 comprising the sequence set forth in SEQ ID NO: 12; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 15; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 17, and wherein the antibody, or antigen binding region thereof, that binds IL- 4Rα comprises a CDR-H1 comprising the sequence set forth in SEQ ID NO: 273; a CDR-H2 comprising the sequence set forth in SEQ ID NO: 279; a CDR-H3 comprising the sequence set forth in SEQ ID NO: 281; a CDR-L1 comprising the sequence set forth in SEQ ID NO: 289; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 290; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 293. [00703] In certain aspects, described herein are methods of treating an inflammatory disorder or disease in a human patient comprising administering to the patient an isolated antibody, or antigen binding region thereof, that binds OX40L, an isolated antibody, or antigen binding region thereof, that binds IL-4Rα, and a hyaluronidase or a variant thereof, wherein the antibody, or antigen binding region thereof, that binds OX40L comprises a VH sequence set forth in SEQ ID NO: 1 and a VL sequence set forth in SEQ ID NO: 11; and wherein the antibody, or antigen binding region thereof, that binds IL-4Rα comprises a VH sequence set forth in SEQ ID NO: 297 and a VL sequence set forth in SEQ ID NO: 300. [00704] In certain aspects, described herein are methods of treating an inflammatory disorder or disease in a human patient comprising administering to the patient hyaluronidase or a variant thereof and a multi-specific antibody comprising a first antigen binding region that binds OX40L and a second antigen binding region that binds IL-4Rα, wherein the antigen binding region that binds OX40L comprises a CDR-H1 comprising the sequence set forth in SEQ ID NO: 2; a CDR-H2 comprising the sequence set forth in SEQ ID NO: 5; a CDR-H3 comprising the sequence set forth in SEQ ID NO: 8; a CDR-L1 comprising the sequence set forth in SEQ ID NO: 12; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 15; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 17, and wherein the antigen binding region that binds IL-4Rα comprises a CDR-H1 comprising the sequence set forth in SEQ ID NO: 273; a CDR-H2 comprising the sequence set forth in SEQ ID NO: 279; a CDR-H3 comprising the sequence set forth in SEQ ID NO: 281; a CDR-L1 comprising the sequence set forth in SEQ ID NO: 289; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 290; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 293. [00705] In certain aspects, described herein are methods of treating an inflammatory disorder or disease in a human patient comprising administering to the patient hyaluronidase or a variant thereof and a multi-specific antibody comprising a first antigen binding region that binds OX40L and a second antigen binding region that binds IL-4Rα, wherein the antigen binding region that binds OX40L comprises a VH sequence set forth in SEQ ID NO: 1 and a VL sequence set forth in SEQ ID NO: 11; and wherein the antigen binding region that binds IL-4Rα comprises a VH sequence set forth in SEQ ID NO: 297 and a VL sequence set forth in SEQ ID NO: 300. [00706] In certain embodiments, the hyaluronidase is a recombinant human hyaluronidase or variant thereof. In certain embodiments, the hyaluronidase is a recombinant human hyaluronidase. In certain embodiments, the recombinant human hyaluronidase comprises the amino acid sequence set forth in any one of SEQ ID NOs: 1076-1085 and 1087-1142. In certain embodiments, the recombinant human hyaluronidase is rHuPH20. In certain embodiments, the rHuPH20 formulation is ENHANZE®. Kits and Articles of Manufacture [00707] The present application provides kits comprising any one or more of the antibodies, or antigen binding regions thereof, or multi-specific antibody compositions described herein and instructions for use. In some embodiments, the kits further contain a component selected from any of secondary antibodies, additional therapeutic agents, reagents for immunohistochemistry analysis, pharmaceutically acceptable excipient and instruction manual and any combination thereof. In one specific embodiment, the kit comprises a pharmaceutical composition comprising any one or more of the antibodies, or antigen binding regions thereof, or multi-specific antibody compositions described herein, with one or more pharmaceutically acceptable excipients. [00708] The present application also provides articles of manufacture comprising any one of the antibodies, or antigen binding regions thereof, or multi-specific antibody compositions or kits described herein. Examples of an article of manufacture include vials (including sealed vials). [00709] In certain aspects, described herein are kits for treating an inflammatory disorder or disease in a human patient, the kit comprising: (a) a dose of an antibody, or antigen binding region thereof, that binds OX40L (e.g., an antibody, or an antigen binding region thereof, that binds OX40L in unit dosage form); (b) a dose of an antibody, or antigen binding region thereof, that binds IL-4Rα (e.g., an antibody, or an antigen binding region thereof, that binds IL-4Rα in unit dosage form); (c) a dose of a hyaluronidase or variant thereof (e.g., a hyaluronidase or a variant thereof in unit dosage form); and (d) instructions. [00710] In certain aspects, described herein are kits for treating an inflammatory disorder or disease in a human patient, the kit comprising: (a) a dose of an antibody, or antigen binding region thereof, that binds OX40L (e.g., an antibody, or an antigen binding region thereof, that binds OX40L in unit dosage form), wherein the antibody, or antigen binding region thereof, comprises a CDR-H1 comprising the sequence set forth in SEQ ID NO: 2; a CDR-H2 comprising the sequence set forth in SEQ ID NO: 5; a CDR-H3 comprising the sequence set forth in SEQ ID NO: 8; a CDR-L1 comprising the sequence set forth in SEQ ID NO: 12; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 15; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 17; (b) a dose of an antibody, or antigen binding region thereof, that binds IL-4Rα (e.g., an antibody, or an antigen binding region thereof, that binds IL-4Rα in unit dosage form), wherein the antibody, or antigen binding region thereof, comprises a CDR- H1 comprising the sequence set forth in SEQ ID NO: 273; a CDR-H2 comprising the sequence set forth in SEQ ID NO: 279; a CDR-H3 comprising the sequence set forth in SEQ ID NO: 281; a CDR-L1 comprising the sequence set forth in SEQ ID NO: 289; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 290; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 293; (c) a dose of a hyaluronidase or variant thereof (e.g., a hyaluronidase or a variant thereof in unit dosage form); and (d) instructions. [00711] In certain aspects, described herein are kits for treating an inflammatory disorder or disease in a human patient, the kit comprising: (a) a dose of an antibody, or antigen binding region thereof, that binds OX40L (e.g., an antibody, or an antigen binding region thereof, that binds OX40L in unit dosage form), wherein the antibody, or antigen binding region thereof, comprises a VH sequence set forth in SEQ ID NO: 1 and a VL sequence set forth in SEQ ID NO: 11; (b) a dose of an antibody, or antigen binding region thereof, that binds IL-4Rα (e.g., an antibody, or an antigen binding region thereof, that binds IL-4Rα in unit dosage form), wherein the antibody, or antigen binding region thereof, comprises a VH sequence set forth in SEQ ID NO: 297 and a VL sequence set forth in SEQ ID NO: 300; (c) a dose of a hyaluronidase or variant thereof (e.g., a hyaluronidase or a variant thereof in unit dosage form); and (d) instructions. [00712] In certain aspects, described herein are kits for treating an inflammatory disorder or disease in a human patient, the kit comprising: (a) a dose of a multi-specific antibody comprising a first antigen binding region that binds OX40L and a second antigen binding region that binds IL-4Rα (e.g., a multi-specific antibody in unit dosage form); (b) a dose of a hyaluronidase or variant thereof (e.g., a hyaluronidase or a variant thereof in unit dosage form); and (c) instructions. [00713] In certain aspects, described herein are kits for treating an inflammatory disorder or disease in a human patient, the kit comprising: (a) a dose of a multi-specific antibody comprising a first antigen binding region that binds OX40L and a second antigen binding region that binds IL-4Rα (e.g., a multi-specific antibody in unit dosage form), wherein the antigen binding region that binds OX40L comprises a VH sequence set forth in SEQ ID NO: 1 and a VL sequence set forth in SEQ ID NO: 11; and wherein the antigen binding region that binds IL-4Rα comprises a VH sequence set forth in SEQ ID NO: 297 and a VL sequence set forth in SEQ ID NO: 300; (b) a dose of a hyaluronidase or variant thereof (e.g., a hyaluronidase or a variant thereof in unit dosage form); and (c) instructions. In certain embodiments, the hyaluronidase is a recombinant human hyaluronidase or variant thereof. In certain embodiments, the hyaluronidase is a recombinant human hyaluronidase. In certain embodiments, the recombinant human hyaluronidase comprises the amino acid sequence set forth in any one of SEQ ID NOs: 1076-1085 and 1087-1142. In certain embodiments, the recombinant human hyaluronidase is rHuPH20. In certain embodiments, the rHuPH20 formulation is ENHANZE®. [00714] In certain embodiments, the kit is for use in treating an inflammatory disorder or disease. In certain embodiments, the inflammatory disorder or disease is atopic dermatitis; asthma, chronic sinusitis with nasal polyps; Chronic Rhinosinusitis without Nasal Polyps (CRSsNP); eosinophilic esophagitis (EoE); an Eosinophilic gastrointestinal disorder or disease (EGID) selected from the group consisting of Eosinophilic Gastritis (EoG), Eosinophilic Enteritis (EoN), Eosinophilic Colitis (EoC), and Eosinophilic Gastroenteritis (EGE); Churg-Strauss syndrome/Eosinophilic granulomatosis with polyangiitis (EGPA); Prurigo Nodularis (PN); Chronic Spontaneous Urticaria (CSU); Chronic Pruritis of Unknown Origin (CPUO); Bullous Pemphigoid (BP); Cold Inducible Urticaria (ColdU); Allergic Fungal Rhinosinusitis (AFRS); Allergic Bronchopulmonary Aspergillosis (ABPA); Chronic Obstructive Pulmonary Disease (COPD); inflammatory bowel disease, such as Crohn’s disease or ulcerative colitis; lupus; rheumatoid arthritis (RA); psoriasis; hidradenitis suppurativa; celiac disease; systemic sclerosis; idiopathic pulmonary fibrosis; alopecia areata; allergic rhinitis; eosinophilic fasciitis; scleromyxedema; scleredema; or nephrogenic systemic fibrosis. EXAMPLES [00715] Below are examples of specific embodiments for carrying out the present invention. These examples are offered for illustrative purposes only, and are not intended to limit the scope of the present invention in any way. Efforts have been made to ensure accuracy with respect to numbers used (e.g., amounts, temperatures, etc.), but some experimental error and deviation should, of course, be allowed for. [00716] The practice of the present invention will employ, unless otherwise indicated, conventional methods of protein chemistry, biochemistry, recombinant DNA techniques and pharmacology, within the skill of the art. Such techniques are explained fully in the literature. See, e.g., T.E. Creighton, Proteins: Structures and Molecular Properties (W.H. Freeman and Company, 1993); A.L. Lehninger, Biochemistry (Worth Publishers, Inc., current addition); Sambrook, et al., Molecular Cloning: A Laboratory Manual (2nd Edition, 1989); Methods In Enzymology (S. Colowick and N. Kaplan eds., Academic Press, Inc.); Remington's Pharmaceutical Sciences, 18th Edition (Easton, Pennsylvania: Mack Publishing Company, 1990); Carey and Sundberg Advanced Organic Chemistry 3rd Ed. (Plenum Press) Vols A and B(1992). Example 1: Generation of anti-hOX40L antibodies [00717] Alloy ATX mice expressing chimeric antibodies with fully-human variable regions were immunized with recombinant human OX40L (hOX40L) protein and/or DNA encoding hOX40L. During immunizations, the serum was used to measure titers against hOX40L by ELISA. [00718] Splenic and lymph node cells from immunized mice were fused with fusion partner cells to generate hybridomas. Upon expansion, the supernatants were screened for binding to recombinant hOX40L protein by ELISA and hOX40L-expressing CHO cells by flow cytometry. [00719] Alternatively, plasma cells from immunized mice were cultured as single cells and supernatants were screened for binding to recombinant hOX40L protein to identify anti- hOX40L-antibody producing cells. [00720] Total RNA was collected from hybridomas and plasma cells of interest to generate cDNA and heavy and light variable regions were PCR amplified and sequenced. [00721] The coding sequences for HC and LC of the antibody were generated by DNA synthesis and PCR, subsequently subcloned into an expression vector for protein expression in mammalian cell system. The gene sequences in the expression vectors were confirmed by DNA sequencing. [00722] For additional methods and anti-OX40L antibodies, see also PCT Application No. PCT/US2024/026854 (corresponding to PCT Publication No. WO2024227174), which is incorporated herein by reference in its entirety. Example 2: Production and purification of recombinant anti-hOX40L antibodies [00723] To produce fully-human anti-hOX40L antibodies, DNA sequences encoding heavy and light variable regions of hybridoma and plasma cells of interest were recombinantly assembled into separate mammalian cell expression vectors with the mutant human IgG1 constant region comprising LALA/YTE mutations (SEQ ID NO: 973) and wild- type human IgK constant region (SEQ ID NO: 738), respectively. ExpiCHO cells were transiently transfected and supernatants containing antibodies were harvested after up to 14 days. [00724] Protein purification by affinity chromatography, and ion exchange chromatography was performed using an AKTA pure instrument (GE Lifesciences). Conditional medium expressing target antibody was harvested by centrifugation at 4000 rpm, 50 min, and filtered with a 0.22 µm filter. The harvested supernatants were loaded to a column of HiTrap Mabselect™ SuRe™ Protein A and polished by size-exclusion chromatography with HiLoad™ 26/200 Superdex™ 200 pg. Alternatively, after washing the column with Buffer A (PBS, PH 7.4), the protein was eluted with Buffer B (1 M Glycine, pH 2.7), and immediately neutralized with 1/10 volume of Buffer D (1 M sodium citrate, pH 6.0). The affinity purified antibody was then buffer exchanged into 20 mM sodium acetate pH 5.5. Example 3: Determination of antibody affinity to hOX40L Measuring Antibody-OX-40L Binding Kinetics Using Surface Plasmon Resonance [00725] A Biacore 8K SPR system (GE HealthCare) equipped with Series S Sensor Chip Protein G (Cytiva, Cat.29179315) was used to determine the binding kinetic rate and affinity constants at 25˚C and in a running buffer of HBS-EP+ (10 mM HEPES pH 7.4, 150 mM NaCl, 3 mM EDTA, 0.05% Surfactant P20). Following a stabilization period in running buffer, the anti-OX40L mAb constructs (diluted to 1 μg/mL) were captured onto flow cell 2 (active) for 60 sec at a flow rate of 10 µL/min. Recombinant Human OX40L Protein, His Tag (Acro Cat. IL3-H52H4) was prepared at concentrations of 0, 0.39, 0.78, 1.56, 3.13, 6.25, 12.5 and 0 nM and injected over flow cell 1 (reference) and flow cell 2 (active) for 180 sec at a flow rate of 30 μL/min. Recombinant non-human primate (NHP) Cynomolgus OX40L Protein, His Tag (SINO BIOLOGICAL, Cat.11057-C07H) was prepared at concentrations of 0, 0.39, 0.78, 1.56, 3.13, 6.25, 12.5, 25 and 0 nM and injected over flow cell 1 (reference) and flow cell 2 (active) for 180 sec at a flow rate of 30 μL/min. Samples were injected in a multi- cycle manner over freshly captured mAb, by regenerating the capture surfaces with injection of glycine pH 1.5 for 30 sec at a flow rate of 30 μL/min. The data was processed and analyzed with Biacore Insight Evaluation Software Version 2.0.15.12933 (GE Healthcare) as follows. Responses from flow cell 1 (reference) were subtracted from the responses from flow cell 2 (active). The responses from the two buffer blank injections were then subtracted from the reference subtracted data (2–1) to yield double-referenced data, which were fit to a 1:1 binding model to determine the apparent association (ka) and dissociation rate constants (kd). Their ratio provided the apparent equilibrium dissociation constant or affinity constant (KD = kd/ka). [00726] Binding affinity (KD) of antibodies to hOX40L was determined by surface plasmon resonance using Biacore 8K+ (TABLE 11). Briefly, a CM5 Series S sensor chip functionalized with anti-human IgG Fc or anti-mouse IgG Fc antibody by amine coupling was used to capture antibodies at 20 nM. Subsequently, concentrations of hOX40L ranging from 500 nM to 31.25 nM were injected at 30 µL/min. The chip was regenerated with 10 mM glycine pH 1.5 between runs. Results are summarized in TABLE 11. TABLE 11. Binding affinity (KD) of antibodies to human and NHP OX40L Human OX40L NHP (Cynomolgus) OX40L 11 Human OX40L NHP (Cynomolgus) OX40L kon (M- kon (M- 11 11 11 11 co espo g o u ca o o. , c s co po a e e e y reference in its entirety n.d.: No data. Example 4. Binding of hOX40L-expressing CHO cells by anti-hOX40L antibodies [00727] Anti-hOX40L antibodies were assessed for their ability to bind hOX40L- expressing CHO cells. Briefly, CHO cells were transduced to generate a pool of cells overexpressing hOX40L. Single clones were isolated and expanded to select a clone stably expressing hOX40L. A positive control based on the sequences of the anti-hOX40L antibody amlitelimab (called “positive control” throughout the anti-OX40L antibody-related Examples and Figures) was also generated. The cells were incubated with titrated anti-hOX40L antibodies, then with fluorophore-labeled goat anti-human IgG secondary antibody to detect bound antibodies by flow cytometry. Nonlinear regression was performed on geometric mean fluorescence intensity (gMFI) values to determine EC50 values (FIGURE 1, TABLE 12). The exemplary anti-hOX40L antibodies bound hOX40L-expressing CHO cells with an EC50 less than 5 nM. Furthermore, clones 105 and 114 exhibited higher gMFI at maximum concentration tested suggesting an increased capacity to bind cell surface OX40L compared to positive control (FIGURE 1). TABLE 12. Binding of OX40L antibodies to hOX40L-expressing CHO cells Clone EC50 (nM) 105 3.43 114 4.04 Positive Control 3.49 See construct sequences in TABLE 3 Example 5: Blocking activity of anti-hOX40L antibodies [00728] Anti-hOX40L antibodies were assessed for their ability to block hOX40L-hOX40 interaction by ELISA. Plates were coated with hOX40-Fc and biotinylated hOX40L preincubated with titrated anti-hOX40L antibodies added to the plates. The binding of hOX40L to hOX40-Fc was detected with Extravidin-HRP. An isotype control was included as a control for no blocking of the binding of hOX40L to hOX40-Fc. Nonlinear regression was performed on optical density (OD) at A450 to determine the IC50 value, which was found to be less than 30 nM for all the tested clones (FIGURE 2, TABLE 13). [00729] Exemplary anti-hOX40L antibodies inhibited human OX40L binding to OX40 in a concentration-dependent manner. TABLE 13. Blockade of the hOX40/hOX40L interaction by anti-hOX40L antibodies Clone IC50 (nM) 105 1.41 114 1.12 122 1.57 128 7.52 130 12.99 231 28.5 328 5.99 Pos. Ctrl. 0.62 Iso. Ctrl. N/A See construct sequences in TABLE 3 and in PCT Application No. PCT/US2024/026854 (corresponding to PCT Publication No. WO2024227174), which is incorporated herein by reference in its entirety N/A: No data. Example 6: Signaling activity of anti-hOX40L antibodies in hOX40 reporter assay [00730] Anti-hOX40L antibodies were assessed for their functional blockade of the OX40- OX40L interaction using an OX40 bioassay. hOX40 cells are commercial cells that overexpress OX40 and have a downstream element that drives luciferase expression under hOX40L stimulation. These cells were used to determine the ability of anti-hOX40L antibodies to block hOX40-mediated signaling. hOX40 cells were incubated with 50 ng/mL hOX40L and titrated anti-hOX40L antibodies for 3-5 hours, and Bio-Glo reagent was added to quantify luminescence (RLU). Nonlinear regression was performed on the luminescence values to determine the IC50 value (FIGURE 3, TABLE 14), which were calculated to be less than 5 nM for all the tested clones. [00731] Exemplary anti-hOX40L antibodies blocked human OX40L-induced activation of OX40 reporter cells. TABLE 14. Inhibition of human OX40L-induced signaling by anti-hOX40L antibodies Clone IC50 (nM) 105 0.852 114 0.732 118 0.9123 122 1.141 127 1.715 128 1.656 130 1.647 231 0.9087 328 1.898 Pos. Ctrl. 1.171 See construct sequences in TABLE 3 and in PCT Application No. PCT/US2024/026854 (corresponding to PCT Publication No. WO2024227174), which is incorporated herein by reference in its entirety Example 7: Functional activity of anti-hOX40L antibodies in human CD4+ T cell IL-2 release assay [00732] Anti-hOX40L antibodies were assessed for their ability to block the interaction between exogenous OX40L and OX40L expressed on activated CD4+ T cells, thereby inhibiting the release of cytokine interleukin-2 (IL-2). CD4+ T cells were isolated from PBMCs from 3 different donors using an isolation kit, such as EasySep™ Human CD4+ T Cell Isolation Kit. CD4+ T cells were cultured with 2 μg/mL PHA-L and 20 IU/mL recombinant human IL-2 in complete RPMI culture medium for 3 days. Microplates were coated with OKT3 (5 μg/mL) at 4 °C overnight and pre-activated CD4+ T cells were seeded at 3 × 104 cells per well. Serially-diluted antibodies with human OX40L at a final concentration of 20 ng/mL were added and the cells were cultured at 37 °C for 3 days. Microplates were centrifuged and supernatant was collected to measure the amount of IL-2 by ELISA. Nonlinear regression was performed to determine the IC50 values (FIGURES 4A-4B, TABLE 15). [00733] Exemplary anti-hOX40L antibodies blocked OX40L-induced IL-2 release from primary CD4+ cells from three healthy donors. TABLE 15. Exemplary anti-hOX40L antibodies blocked OX40L-induced IL-2 release Donor 1 IC50 Donor 2 IC50 Donor 3 IC50 Clone (nM) (nM) (nM) 105 1.37 1.33 1.00 114 1.25 1.19 1.18 Pos. Ctrl. 0.96 – 1.02 0.94 – 0.89 0.70 – 0.49 See construct sequences in TABLE 3 Example 8. Determination of anti-hOX40L antibody affinity to human and cynomolgus FcRn [00734] The binding affinity (KD) of antibodies to human (TABLE 16) and NHP (cynomolgus) neonatal Fc receptor (FcRn) (TABLE 17) at pH 5.8 and 7.4 was determined by surface plasmon resonance, as described in Example 3, using Biacore 8K+. Briefly, a CM5 Series S sensor chip functionalized with anti-human kappa antibody was used to capture antibodies at 5 μg/mL. Subsequently, concentrations of human FcRn ranging from 1.5 μM to 47 nM and cynomolgus FcRn from 1.0 μM to 31 nM were injected at 30 µL/min. The chip was regenerated with 10 mM glycine pH 1.5 and 10 mM NaOH between runs. The tested anti-OX40L antibodies bound human FcRn and cynomolgus FcRn with similar binding kinetics at pH 5.8. [00735] Exemplary anti-hOX40L antibodies containing LALA/YTE substitutions had increased binding to human and NHP FcRn under acidic pH conditions. (TABLE 16, TABLE 17). TABLE 16. Enhanced binding of anti-hOX40L antibodies to hFcRn under acidic pH Human FcRn H H 74 ) n.b.: No binding. TABLE 17. Enhanced binding of anti-hOX40L antibodies to NHP FcRn under acidic pH NHP (Cynomolgus) FcRn n.b.: No binding. Example 9. Determination of anti-hOX40L antibody affinity to human Fcγ receptors and C1q [00736] Binding affinity (KD) of antibodies to human Fcγ receptors (CD64, CD32a 167H, CD32a 167R, CD32b, CD16a 176F, CD16a 176V, and CD16b) (TABLE 18) and mean response unit (RU) to C1q at 25 nM (TABLE 19) was determined by surface plasmon resonance, as described in Example 3, using Biacore 8K+. Briefly, a CM5 Series S sensor chip functionalized with anti-human IgG Fc antibody was used to capture antibodies at 5 μg/mL. Subsequently, concentrations of human CD64 ranging from 12.5 nM to 0.3906 nM, CD32a 167H and 167R from 8 μM to 250 nM, CD32b from 18 μM to 562.5 nM, CD16a 176F and 176V from 6 μM to 187.5 nM, CD16b from 10 μM to 312.5 nM, and C1q from 25 nM to 0.7813 nM were injected at 30 µL/min. The chip was regenerated with 10 mM glycine pH 1.5 and 10 mM NaOH between runs. Rituximab, an anti-CD20 antibody, was included for comparison. TABLE 18 shows that while Rituximab displayed measurable binding to the various human Fcγ receptors, the tested anti-OX40L antibodies containing LALA/YTE substitutions displayed no significant binding to any of the human Fcγ receptors (TABLE 18). Further, while Rituximab displayed C1q binding, none of the tested anti-OX40L antibodies containing LALA/YTE substitutions displayed C1q binding. (TABLE 19). TABLE 18. Binding of anti-hOX40L antibodies to Fcγ Receptors compared to positive control (rituximab) KD (M) CD32a CD32a CD16a CD16a Clone CD64 CD32b CD16b 167H 167R 176F 176V 2.81 × 10- 4.21 × 10-62.67 × 10-6 7.4 -6 -6 -7 -6 10 0 × 10 2.18 × 10 8.97 × 10 1.48 × 10 Rituximab 105 n.b. n.b. n.b. n.b. n.b. n.b. n.b. 114 n.b. n.b. n.b. n.b. n.b. n.b. n.b. 231 n.b. n.b. n.b. n.b. n.b. n.b. n.b. 328 n.b. n.b. n.b. n.b. n.b. n.b. n.b. See construct sequences in TABLE 3 n.b.: No binding. TABLE 19. Binding of anti-hOX40L antibodies to C1q compared to positive control (rituximab) RU at 25 nM Clone C1q Rituximab 386.1 105 -3.6 114 -4.8 231 1.8 328 0.2 See construct sequences in TABLE 3 Example 10. Functional activity of anti-hOX40L antibodies in allogeneic immune cell co-culture [00737] Anti-hOX40L antibodies were assessed for their ability to block the interaction between exogenous OX40L and OX40L expressed on activated CD4+ T cells from human donors, thereby inhibiting the release of interferon gamma (IFNγ) in mixed allogeneic lymphocyte reaction (ALR). PBMCs were preincubated with mitomycin C at 10 μg/mL for 37 °C for 1 h. Allogeneic CD4+ T cells were isolated from PBMCs using an isolation kit, such as EasySep™ Human CD4+ T Cell Isolation Kit. Antibodies (100 nM, 20 nM, or 4 nM), recombinant OX40L (final concentration 1000 ng/mL), mitomycin C-treated PBMCs (1 × 105 cells/well), and CD4+ T cells (1 × 105 cells/well) were added to microplates sequentially and co-cultured for 5 days at 37 °C. Supernatant was collected and IFNγ was measured by an ELISA detection kit. Data was collected on 6 different donor pairs in triplicate (FIGURES 5A-C, TABLE 21). As shown in FIGURES 5A-5C and TABLE 20, tested anti-OX40L antibodies inhibited IFNγ to a similar extent as the positive control at higher antibody concentrations, such as 100 nM. [00738] Anti-hOX40L antibodies inhibited IFNγ release from allogeneic mixed lymphocytes in a concentration dependent manner in all five evaluable donor pairs. AOJ-010PC AOE-007WO TABLE 20. Suppression of IFNγ Release (pg/mL) by anti-hOX40L Antibodies Across Multiple Donor Pairs (Mean +/- SEM) Donor pairing 3 4 1 5 6 8 4 24.1 10.3 17.3 10.0 159.0 72.7 40.6 28.9 TA conc. = Test antibody concentration; nM
AOJ-010PC AOE-007WO Mean = Mean IFNγ concentration, pg/ml SEM = Standard error of the mean See construct sequences in TABLE 3
Example 11. Pharmacokinetic profiles of anti-hOX40L antibodies in cynomolgus monkeys [00739] Anti-hOX40L antibodies were evaluated for their pharmacokinetic profiles following single intravenous (IV) or subcutaneous (SC) administration to naïve male cynomolgus monkeys as shown in TABLE 21. An n of 4 was used for each group. TABLE 21. Experimental set-up for anti-OX40L antibody NHP PK study Fc Group # Clone Route Dosage Isotype Mutations E E E E E E E E See const [00740] Serum samples were collected from individual animals pre-dose, and at the time points post dose of 10 min, 1 h, 4 h, 8 h, 24 h, and days 2, 4, 7, 14, 21, 28, 35, 42, 49, 56, 63, 77, and 91. Standard curves were generated for each antibody, which were diluted in 2-10% pooled monkey serum, by ELISA to calculate antibody concentration based on ELISA measurements. Three different antibody concentrations were tested by ELISA for quality control purposes of the accuracy of the standard curves. PK analyses were performed on serum concentration versus time data using linear trapezoidal rule for AUC calculations (TABLE 22, FIGURE 6A, FIGURE 6B). Nominal dose values and sampling times were used for calculations. Bioavailability was calculated by dividing the mean dose-normalized AUC0-inf following subcutaneous administration by the mean dose- normalized AUC0-inf following intravenous administration. The normalization of doses was done using doses based on measured formulation concentration and body weights of the subjects. For PK calculations and serum concentration descriptive statistics, any concentration reported as below the limit of quantification (BLQ) was set equal to zero. As shown in FIGURE 6A and FIGURE 6B, the tested antibodies exhibited a longer half-life than did the positive control.
AOJ-010PC AOE-007WO TABLE 22. Results from anti-OX40L PK study in NHP Test Pos Con 1 1 2 3 . . . . . . . . . . . . . Tmax = peak time Cmax = peak concentration AUC = area under the curve F = fraction absorbed CL = clearance
AOJ-010PC AOE-007WO Vss = volume of distribution under steady state conditions See construct sequences in TABLE 3
Example 12: Affinity maturation of anti-IL-4Rα antibody [00741] Dupilumab (based on the published sequence) was used as a parental antibody for further CDR diversification to identify clones with improvements in potency, manufacturability, and pharmacokinetics. [00742] In order to diversify CDRs while at least maintaining the potency of dupilumab, various mutations in all CDRs of both heavy and light chain were made. Site-directed PCR mutagenesis was employed to generate distinct libraries for each CDR in both heavy and light chain, resulting in 6 unique libraries with an average of 2-3 amino acid substitutions per chain. Individual mutants were displayed as Fabs in a phage display system and within each library, mutants were panned through two rounds of selection. The first round of selection consisted of 1 nM biotinylated hIL-4Rα and the output of that round was subsequently split into four distinct secondary rounds of parallel selection consisting of A) 1 nM biotinylated hIL-4Rα while also being washed for 4 hours at room temperature in buffer containing 100 nM of unlabeled hIL- 4Rα, B) 0.1 nM biotinylated hIL-4Rα while also being washed for 4 hours at room temperature in buffer containing 10 nM of unlabeled hIL-4Rα, C) 50 nM biotinylated cyIL-4Rα with no wash, and D) 5 nM biotinylated cyIL-4Rα with no wash. [00743] Mutant clones from the output of each arm of secondary selection were analyzed for koff as a proxy for binding affinity by using periplasmic extracts of each mutant clone using surface plasmon resonance (SPR) and comparing to dupilumab, as well as bioinformatic analyses of sequences to identify patterns of enrichment. Mutants that exhibited no loss or improved binding relative to dupilumab as well as population enrichment throughout the selection were combined into a single library comprising all mutants in both the heavy and light chain. Fabs containing a random combinatorial mix of these individual CDR mutants were again screened in a phage display system, with multiple combinations of selection strategies outlined in TABLE 23. TABLE 23. Selection strategies for anti-IL-4Rα antibody clones Strategy Round 1 Selection Round 2 Selection Strategy 1 Antigen: 50 nM biotinylated cyIL-4Rα Antigen: 50 nM biotinylated cyIL-4Rα Wash: No wash Wash: 2 hr R.T. w/ 500 nM unlabeled cyIL-4Rα Strategy Antigen: 50 nM biotinylated cyIL-4Rα Antigen: 5 nM biotinylated cyIL-4Rα 2* Wash: No wash Wash: 2 hr R.T. w/ 100 nM unlabeled cyIL-4Rα Strategy 3 Antigen: 10-2 nM biotinylated hIL-4Rα Antigen: 10-2 nM biotinylated hIL-4Rα Wash: 2 hr R.T. w/ 1 nM unlabeled Wash: 24 hr R.T. w/ 1 nM unlabeled hIL- hIL-4Rα 4Rα Strategy 4 Antigen: 10-2 nM biotinylated hIL-4Rα Antigen: 10-3 nM biotinylated hIL-4Rα Wash: 2 hr R.T. w/ 1 nM unlabeled Wash: 24 hr R.T. w/ 0.1 nM unlabeled hIL-4Rα hIL-4Rα Strategy 5 Antigen: 10-2 nM biotinylated hIL-4Rα Antigen: 10-4 nM biotinylated hIL-4Rα Wash: 2 hr R.T. w/ 1 nM unlabeled Wash: 24 hr R.T. w/ 0.01 nM unlabeled hIL-4Rα hIL-4Rα *Outputs from Round 2 selection in this strategy were selected in a third round consisting of 5 nM biotinylated cyIL-4Rα with a 16 hour room temperature wash with 500 nM unlabeled cyIL- 4Rα. Example 7: Determination of antibody affinity to IL-4Rα [00744] Binding affinity (KD) of anti-IL-4Rα antibodies to human and cynomolgus monkey IL-4Rα was determined through surface plasmon resonance (SPR) using a Carterra LSA. The anti-IL-4Rα mAb referred to as dupilumab was based on the published sequence. Briefly, an HC30M sensor chip that was previously functionalized with a polyclonal mixture of goat anti- human Fc antibody was used to capture purified antibodies at a level between 100-1000 RLU. Subsequently, concentrations of antigen ranging from 200 nM to 0.13 nM were injected over the surface at a rate of 2 mL/min. Regeneration of the chip between different concentrations of antigen was performed with 200 mM phosphoric acid and antibody was captured again as previously described. Association and dissociation rate constants were subsequently determined through fitting to a 1:1 Langmuir binding model using the Kinetics Software from Carterra from which a KD value was derived. Results are summarized in TABLE 24. [00745] The majority of antibodies bind to human IL-4Rα with low picomolar affinity comparable to dupilumab. Additionally, a number of antibodies demonstrated improved cross- reactivity to cynomolgus monkey IL-4Rα, some with low-nanomolar affinities. TABLE 24. Binding affinity of anti-IL-4Rα antibodies for human and cyno IL-4Rα SPR Hu IL-4Rα Relative to SPR Cyno IL-4Rα Relative to Antibody KD (pM) Dupilumab KD (nM) Dupilumab Dupilumab 11.29 1.00 628.82 1.00 Construct 13 (mAb422) 7.37 0.65 12.63 0.02 Construct 24 (mAb432) 8.91 0.79 66.90 0.11 Construct 38 (mAb471) 5.89 0.52 249.24 0.40 Construct 15 (mAb423) 13.68 1.21 24.59 0.04 Construct 31 (mAb443) 8.29 0.73 421.26 0.67 W.S. Weak Signal, below Carterra sensitivity. Relative values to Dupilumab, <1.00 is tighter affinity. See construct sequences in TABLE 6 and in PCT Application No. PCT/US2024/016235 (corresponding to PCT Publication No. WO2024173847), which is incorporated herein by reference in its entirety Example 13: Improvement of IL-4Rα antibody affinity to human and cyno FcRn at pH 6.0 [00746] Binding affinity (KD) of antibodies to human and cynomolgus monkey FcRn at pH 6.0 is a reliable correlate of half-life in vivo. KD of purified antibodies to FcRn is determined through surface plasmon resonance (SPR) using a BIACORE® 8K. Briefly, an SPR chip functionalized with Protein G is used to capture purified antibodies normalized to 0.5 mg/mL, at a flow rate of 10 µL/min for 60 seconds. A paired channel with only buffer is used as reference. Subsequently, concentrations of human or cyno FcRn ranging from 25 nM to 0.39 nM are injected over the surface with captured purified antibody as well as the reference channel.. Affinity measurement as described is done at both pH 7.4 and pH 6.0. Association and dissociation rate constants are subsequently determined through fitting to a 1:1 Langmuir binding model using the BIACORE® Insight Evaluation Software from which a KD value is derived. It is expected that all improved antibodies show enhanced binding to FcRn at pH 6.0 relative to dupilumab, which is a strong indicator that such antibodies would have increased half-life in vivo. This can be further confirmed in a pharmacokinetics study in cynomolgus monkey. Example 14: Inhibition of IL-13 and IL-4 binding to hIL-13Rα/hIL-4Rα with an anti- IL- 4Rα antibody [00747] IL-13 and IL-4 binding to cells overexpressing hIL-13Ra/hIL-4Rα were used to evaluate the functional blockade of anti-IL-4Rα antibodies against this binding interaction. Briefly, HEK293 previously transduced to stably express both hIL-13Rα and hIL-4Rα were cultured and harvested. Cells were seeded at 200,000 cells in 100 µL per well. Cells were washed and the supernatant discarded. A 100 µL mixture of biotinylated hIL-13 OR biotinylated hIL-4 and purified antibody (1:1 by volume) that had been previously made and incubated for 1 hour was added to resuspend the cells, resulting in a final concentration of 0.05 µg/mL of hIL-13 OR 0.04 µg/mL of hIL-4 and 0-100 nM of purified antibody. The cells were stained in this mixture at 4 °C for 1 hour. Cells were then washed and stained with 100 µL of Alexa Fluor 488- conjugated streptavidin at a 1:1000 dilution to detect binding of biotinylated hIL-13 OR biotinylated hIL-4 on the cell surface. Cells were incubated 4 °C for 1 hour, protected from light. Cells were then washed and the MFI of cells in each well were recorded by FACS using a BD FACSCanto II. Subsequent data were analyzed using GraphPad Prism. IC50 values were determined as the concentration of antibody required to inhibit 50% of the maximum MFI of biotinylated hIL-13 OR biotinylated hIL-4 surface detected with incubation of 0.05 µg/mL of hIL-13 OR 0.04 µg/mL hIL-4 alone. The anti-IL-4Rα mAb referred to as dupilumab was based on the published sequence. Results are summarized in TABLE 25, TABLE 26, FIGURE 7A and FIGURE 7B. TABLE 25. Inhibition of IL-13 or IL-4 binding to IL-13Ra1/IL-4Rα overexpressing cells by anti-IL-4Rα antibodies (values normalized to dupilumab) Relative Blockade of IL- Relative Blockade of IL-4 Antibody 13 Binding IC50 (nM) Binding IC50 (nM) Dupilumab 1.000 1.000 Construct 1 (mAb410) 0.968 1.099 Construct 13 (mAb422) 0.882 1.023 Construct 24 (mAb432) 0.825 0.973 Construct 38 (mAb471) 0.996 0.981 Construct 15 (mAb423) 0.876 0.660 Construct 31 (mAb443) 0.964 1.012 All values relative to dupilumab. <1.000 is more potent. See construct sequences in TABLE 6 and in PCT Application No. PCT/US2024/016235 (corresponding to PCT Publication No. WO2024173847), which is incorporated herein by reference in its entirety [00748] Certain anti-IL-4Rα constructs, shown in TABLE 26, were modified to replace the IgG4 YTE heavy chain constant region with an IgG1 YTE LALA heavy chain constant region (SEQ ID NO: 973). These antibodies were tested for their ability to inhibit IL-13 and IL-4 binding to hIL-13Rα/hIL-4Rα as compared to dupilumab. Methods were as described above. The results are summarized in TABLE 256 The values reflect absolute IC50 measurements. TABLE 26. Inhibition of IL-13 or IL-4 binding to IL-13Ra1/IL-4Rα overexpressing cells by anti-IL-4Rα antibodies (absolute IC50-- not normalized to dupilumab) Blockade of IL-13 Blockade of IL-4 Binding Antibody Binding IC50 (nM) IC50 (nM) Dupilumab 0.274 0.251 Construct 13 (mAb422) 0.235 0.238 Construct 15 (mAb423) 0.204 0.230 Construct 24 (mAb432) 0.234 0.234 Construct 31 (mAb443) 0.209 0.279 Construct 38 (mAb471) 0.226 0.271 See construct sequences in TABLE 6 and in PCT Application No. PCT/US2024/016235 (corresponding to PCT Publication No. WO2024173847), which is incorporated herein by reference in its entirety Example 15: Inhibition of STAT6 phosphorylation in HT-29 cells with an anti-IL-4Rα antibody [00749] Inhibition of STAT6 phosphorylation in HT-29 cells was used to evaluate the functional activity of anti-IL-4Rα antibodies to block IL-13-induced and IL-4-induced biological activity. Briefly, HT-29 cells were starved in RMPI 1640 + 0.1% FBS overnight. Cells were collected and seeded at 50,000 cells per well in 100 µL. Concurrently, a 100 µL mixture of hIL- 13 OR hIL-4 and purified antibody (1:1 by volume) was added to the same well, resulting in a final concentration of 10 ng/mL of hIL-13 OR 5 ng/mL of hIL-4 and 0-50 nM of purified antibody. Cells were incubated at 37 °C for 1 hour and subsequently fixed, permeabilized, and stained with a PE-conjugated anti-pSTAT6 antibody. The MFI of cells in each well were recorded by FACS using a BD FACSCanto II and subsequent data were analyzed using GraphPad Prism. IC50 values were determined as the concentration of antibody required to inhibit 50% of the maximum MFI of pSTAT6 detected with incubation of 10 ng/mL of hIL-13 OR 5 ng/mL of hIL-4 alone. The anti-IL-4Rα mAb referred to as dupilumab was based on the published sequence. Results are summarized in TABLE 27, TABLE 28, FIGURE 8A, and FIGURE 8B. [00750] As shown in TABLE 27, clones were identified that demonstrated more effective inhibition of IL-13 and/or IL-4 induced phosphorylation of STAT6 as compared to dupilumab by up to about 2-fold (such as, for example, Construct 24). TABLE 27. Inhibition of IL-4- or IL-13-induced pSTAT6 by anti-IL-4Rα antibodies (values normalized to dupilumab) Antibody Relative Inhibition of IL-13 Relative Inhibition of IL-4 induced pSTAT6 IC50 (nM) induced pSTAT6 IC50 (nM) Dupilumab 1.000 1.000 Construct 13 (mAb422) 0.824 0.415 Construct 24 (mAb432) 0.586 0.629 Construct 38 (mAb471) 1.561 0.723 Construct 15 (mAb423) 0.468 0.285 Construct 31 (mAb443) 1.607 1.233 All values relative to dupilumab. <1.000 is more potent. See construct sequences in TABLE 6 and in PCT Application No. PCT/US2024/016235 (corresponding to PCT Publication No. WO2024173847), which is incorporated herein by reference in its entirety [00751] The constructs shown in TABLE 28 were modified to replace the IgG4 YTE heavy chain constant region with an IgG1 YTE LALA constant region. These constructs were tested for their ability to inhibit IL-13 and/or IL-4 induced phosphorylation of STAT6 as compared to dupilumab. These results are summarized in TABLE 28. The values reflect absolute IC50 measurements. TABLE 28. Inhibition of IL-4- or IL-13-induced pSTAT6 by anti-IL-4Rα antibodies (absolute IC50 values, not normalized to dupilumab) Antibody Inhibition of IL-13 induced Inhibition of IL-4 induced pSTAT6 IC50 (nM) pSTAT6 IC50 (nM) Construct 15 (mAb423) 0.599 0.122 Construct 24 (mAb432) 1.089 0.269 Construct 31 (mAb443) 0.916 0.452 Construct 38 (mAb471) 1.046 0.248 See construct sequences in TABLE 6 and in PCT Application No. PCT/US2024/016235 (corresponding to PCT Publication No. WO2024173847), which is incorporated herein by reference in its entirety Example 16: Inhibition of IL-13-induced or IL-4-induced Release of TARC from A549 cells with an anti-IL-4Rα antibody [00752] Inhibition of TARC secretion by A549 cells was used to evaluate the functional activity of anti-IL-4Rα antibodies to block IL-13-induced or IL-4-induced biological activity. Briefly, A549 cells were seeded at 20,000 cells in 100 µL of DMEM + 10% FBS and cultured overnight at 37 °C. The next day, the cell culture media was discarded and cells were gently washed with fresh media. A 150 µL mixture of hIL-13, purified antibody, and hTNFa (1:1:1 by volume) were added to the wells, resulting in a final concentration of 20 ng/mL hIL-13, 0-100 nM purified antibody, and 200 ng/mL hTNFa OR 1.5 ng/mL hIL-4, 0-100 nM purified antibody, and 50 ng/mL TNFa. Cells were incubated in this mixture at 37 °C for 20-24 hours. Following incubation, culture supernatant was collected and the amount of TARC present was analyzed using a commercial TARC ELISA kit (R&D Systems), analyzed according to manufacturer’s instructions. The determined concentrations of TARC in each well were analyzed using GraphPad Prism. IC50 values were determined as the concentration of antibody required to inhibit 50% of the maximum TARC concentration detected with incubation of only 20 ng/mL of hIL-13 and 200 ng/mL hTNFa OR 1.5 ng/mL hIL-4 and 50 ng/mL hTNFa. The anti-IL-4Rα mAb referred to as dupilumab was based on the published sequence. Results are summarized in TABLE 29, TABLE 30, FIGURE 9A, and FIGURE 9B. [00753] As shown in TABLE 29, clones were identified that demonstrated more effective inhibition of IL-13 and/or IL-4 induced TARC as compared to dupilumab by up to about 3-fold (such as, for example: Construct 2, and Construct 15). TABLE 29. Inhibition of IL-13- or IL-4 induced TARC release from A549 by anti-IL-4Rα antibodies (values normalized to dupilumab) Antibody Relative Inhibition of IL- Relative Inhibition of IL-4 13 induced TARC IC50 induced TARC IC50 (nM) (nM) Construct 24 (mAb432) 0.594 0.445 Construct 38 (mAb471) 1.634 1.17 Construct 15 (mAb423) 0.350 0.453 Construct 31 (mAb443) 0.703 1.37 All values relative to dupilumab. <1.000 is more potent. See construct sequences in TABLE 6 and in PCT Application No. PCT/US2024/016235 (corresponding to PCT Publication No. WO2024173847), which is incorporated herein by reference in its entirety [00754] The anti-IL4Rα constructs shown in TABLE 30 were modified to replace the IgG4 YTE heavy chain constant region with an IgG1 YTE LALA heavy chain constant region. These constructs were tested for their ability to inhibit IL-13 and/or IL-4 induced TARC as compared to dupilumab. These results are summarized in TABLE 30. The values reflect absolute IC50 measurements. TABLE 30. Inhibition of IL-13- or IL-4 induced TARC release from A549 by anti-IL-4Rα antibodies (absolute IC50 values, not normalized to dupilumab) Antibody Inhibition of IL-13 Inhibition of IL-4 induced induced TARC IC50 (nM) TARC IC50 (nM) Dupilumab 0.612 0.382 Construct 13 (mAb422) 0.261 0.179 Construct 15 (mAb423) 0.212 0.127 Construct 24 (mAb432) 0.361 0.222 Construct 31 (mAb443) 0.456 0.228 Construct 38 (mAb471) 0.527 0.259 See construct sequences in TABLE 6 and in PCT Application No. PCT/US2024/016235 (corresponding to PCT Publication No. WO2024173847), which is incorporated herein by reference in its entirety Example 17: Inhibition of IL-13-induced or IL-4-induced proliferation of TF-1 cells with an anti-IL-4Rα antibody [00755] The proliferation or inhibition thereof of TF-1 cells was used to evaluate the functional activity of antibodies to block IL-13-induced or IL-4-induced biological activity. Briefly, TF-1 cells were harvested and starved in RPMI1640 +10% FBS without additional cytokine for 4 hours. During this time, a mixture of hIL-13 OR hIL-4 and purified anti-IL-4Rα antibody (1:1 by volume) was prepared 50 µL was added per well. Following starvation, TF-1 cells were again harvested and seeded at 15,000 cells in 50 µL per well, resulting in a final concentration of 4 ng/mL of hIL-13 OR 0.5 ng/mL of hIL-4 and 0-5 nM purified antibody. Cells were subsequently incubated at 37 °C for 72 hours and proliferation of cells was quantified using CellTiter-Glo (Promega) according to manufacturer’s instructions. Luminescence was recorded by SpectraMax M5 Multimode Plate Reader and data was analyzed using GraphPad Prism. IC50 values were determined as the concentration of antibody required to result in 50% of the maximum luminescence detected when TF-1 cells are incubated and cultured with 4 ng/mL of hIL-13 OR 0.5 ng/mL of hIL-4 alone. The anti-IL-4Rα mAb referred to as dupilumab was based on the published sequence. Results are summarized in TABLE 31, TABLE 32, FIGURE 10A, and FIGURE 10B. TABLE 31. Inhibition of IL-13- or IL-4-induced proliferation of TF-1 cells by an anti-IL- 4Rα antibody (values normalized to dupilumab) Relative Inhibition of IL-13 induced Relative Inhibition of IL-4 TF-1 Proliferation IC50 (nM) induced TF-1 Proliferation IC50 Antibody (nM) Dupilumab 1.000 1.000 Construct 13 (mAb422) 0.794 0.675 Construct 24 (mAb432) 0.693 1.033 Construct 38 (mAb471) 1.202 1.044 Construct 15 (mAb423) 0.710 0.281 Construct 31 (mAb443) 1.237 1.251 All values relative to dupilumab. <1.000 is more potent. See construct sequences in TABLE 6 and in PCT Application No. PCT/US2024/016235 (corresponding to PCT Publication No. WO2024173847), which is incorporated herein by reference in its entirety [00756] The IL-4Rα constructs shown in TABLE 32 were modified to replace the IgG4 YTE heavy chain constant region with an IgG1 YTE LALA heavy chain constant region (SEQ ID NO: 973). These constructs were tested for their ability to inhibit IL-13 induced TF-1 proliferation as compared to dupilumab. These results are summarized in TABLE 32. The values reflect absolute IC50 measurements. TABLE 32. Inhibition of IL-13- or IL-4-induced proliferation of TF-1 cells by an anti-IL- 4Rα antibody (absolute IC50 values, not normalized to dupilumab) Inhibition of IL-13 induced Inhibition of IL-4 induced Antibody TF-1 Proliferation IC50 (nM) TF-1 Proliferation IC50 (nM) Dupilumab 0.164 0.059 Construct 13 (mAb422) 0.119 0.038 Construct 15 (mAb423) 0.117 0.028 Construct 24 (mAb432) 0.166 0.052 Construct 31 (mAb443) 0.175 0.058 Construct 38 (mAb471) 0.161 0.052 See construct sequences in TABLE 6 and in PCT Application No. PCT/US2024/016235 (corresponding to PCT Publication No. WO2024173847), which is incorporated herein by reference in its entirety Example 18: Improving developability of anti-IL-4Rα antibodies [00757] The manufacturing and clinical performance of antibodies are often improved when the antibodies themselves have improved biophysical characteristics. In order to assess some of these characteristics, purified anti-IL-4Rα antibodies were analyzed for their hydrophobic quality and non-specificity. The anti-IL-4Rα mAb referred to as dupilumab was based on the published sequence. Briefly, for hydrophobic quality, 10 µg of purified antibodies were injected into a hydrophobic interaction chromatography (HIC) Butyl 1.7 µm column in a mobile phase of sodium phosphate to capture antibodies to the column followed by elution of antibodies using ammonium sulphate. Retention time of antibody was used as a directly proportional measurement of hydrophobicity, i.e., a lower retention time indicates an antibody of lower hydrophobic character. [00758] A Baculovirus Particle assay (BVP) was used to assess non-specific binding by ELISA. Briefly, 96-well plates were coated with a 0.15% baculovirus particle (BVP) suspension and incubated at 4 °C, overnight. Plates were blocked with 1% BSA for 2 hours at 37 °C.200 nM of purified antibodies were added and incubated for 1 hour at 37 °C. An HRP-conjugated goat anti-human IgG Fc antibody was used to detect binding of purified antibodies, incubated for 0.5 hour at 37 °C. Between all steps, plates were washed multiple times in PBS-T. Plates were developed using the substrate TMB over the course of 15 minutes, with the reaction being halted through the addition of 1N HCl. Absorbance at 450nm was recorded by SpectraMax Plus 384 Microplate Reader and data was analyzed using GraphPad Prism. Absorbance of 450nm of each antibody was used as a directly proportional measurement of non-specificity, i.e., a lower absorbance indicates an antibody with expected low non-specific binding. Results are summarized in TABLE 33. [00759] As shown in TABLE 33 below, nearly all of the antibodies show lower HIC and BVP scores than dupilumab. TABLE 33. Assessment of hydrophobic quality and non-specific binding for anti-IL-4Rα antibodies Hydrophobic Interaction Retention Baculovirus Particle 200 nM Antibody Time (min) ELISA Score Dupilumab 9.24 9.8 Construct 13 (mAb422) 8.39 3.2 Construct 24 (mAb432) 7.81 3.7 Construct 38 (mAb471) 6.54 1.5 Construct 15 (mAb423) 8.13 2.3 Construct 31 (mAb443) 7.34 1.6 N.T.: Not Tested See construct sequences in TABLE 6 and in PCT Application No. PCT/US2024/016235 (corresponding to PCT Publication No. WO2024173847), which is incorporated herein by reference in its entirety Example 19. Determination of antibody affinity to IL-4Rα [00760] Binding affinity (KD) of exemplary antibodies to human IL-4Rα was determined using the Kinetic Exclusion Assay (KinExA). The anti-IL-4Rα mAb referred to as dupilumab was based on the published sequence. Briefly, antibody and recombinant human IL-4Rα were equilibrated in solution. For each antibody, equilibration samples were done with a fixed concentration of the antibody ranging from 2.27 pm to 100 pM and a titration of recombinant human IL-4Rα generated from a starting concentration ranging from 9.78 pM to 1.00 nM with 2- fold dilutions for a total set of dilutions ranging from 11 to 13 concentrations. Samples were incubated for a time period ranging from 3.5 hours to 340 hours, to fully reach equilibrium. Once samples reached equilibrium, azlactone beads previously coated with recombinant human IL-4Rα were used to capture any free antibody from the equilibrated solution. Captured antibody was then detected with an Alexa Fluor 647-labeled Goat Anti-Human IgG. The KinExA 4000 instrument was used to capture fluorescent signal and convert to a voltage signal that is directly proportional to the amount of free antibody in all the equilibrated samples, allowing for the determination of the apparent affinity of the antibody. Results are summarized in TABLE 34. TABLE 34. Binding affinity of exemplary IL-4Rα antibodies to human IL-4Rα Hu IL-4Rα KD 95% Confidence Relative to Antibody (fM) Interval (fM) Dupilumab Dupilumab 1120 644 – 1760 1.00 Construct 13 (mAb422) 299 160 – 482 0.267 Construct 15 (mAb423) 10.9 2.4 – 26 0.010 Construct 24 (mAb432) 118 52.6 – 199 0.105 Construct 31 (mAb443) 282 138 - 492 0.252 Construct 38 (mAb471) 421 256 - 636 0.376 See construct sequences in TABLE 6 and in PCT Application No. PCT/US2024/016235 (corresponding to PCT Publication No. WO2024173847), which is incorporated herein by reference in its entirety [00761] The majority of exemplary antibodies bind to human IL-4Rα with femtomolar affinity compared to dupilumab that binds with low picomolar affinity. Example 20. Pharmacokinetic analysis of anti-IL-4Rα antibodies [00762] In vivo pharmacokinetic (PK) studies were performed to evaluate the half-life extension of IgG1 LALA-YTE anti-IL-4Rα antibodies compared to dupilumab, based on the published sequence. Studies were performed using cynomolgus monkey (Macaca fascicularis), and antibodies were administered by subcutaneous (SC) or intravenous (IV) injection. All animals were males, ranging from 2.52 to 3.86 kg in weight (n=4 or 5/group). Animals were administered dupilumab, the exemplary antibody Construct 13 (mAb422), or the exemplary antibody Construct 38 (mAb471), where the IgG4 YTE constant heavy chain regions of Construct 13 and Construct 38 were replaced by IgG1 YTE LALA constant regions (SEQ ID NO: 973), by intravenous (IV) bolus or subcutaneous (SC) injection on Day 0 at a dose of 1, 5 or 25 mg/kg, as shown in TABLE 35, and serum samples were taken regularly throughout the study. TABLE 35. Half-life of anti-IL-4Rα antibodies in NHP Antibody Group Dose Route of Half-Life (mg/kg) Administration N (Days) [00763] PK parameters were determined from cynomolgus serum samples up to day 91. The PK analysis demonstrated that Construct 13 and Construct 38 had a half-life of 17.62 and 25.60 days, respectively, compared with 10.88 days for dupilumab (25 mg/kg, IV). The results are summarized in TABLE 35. The PK analysis demonstrated that the exemplary antibodies, Construct 13 (mAb422) and Construct 38 (mAb471), had improved half-life compared to those of dupilumab (TABLE 35, FIGURE 11A, and FIGURE 11B) across different routes of administration. The half-life of Construct 38 when dosed at 5 and 1 mg/kg, IV, remained superior to dupilumab when dosed at 25 mg/kg, IV. The increased half-life of the exemplary antibodies may enable less frequent dosing compared with currently available treatment protocols, reducing the burden of injection and increasing compliance for patients living with COPD and Type 2-mediated diseases. [00764] In cases where bioavailability (F) is determined, antibodies disclosed herein are shown to possess equivalent bioavailability to that of dupilumab. The results for the exemplary antibodies and dupilumab are summarized in TABLE 36. Construct 38 (mAb471) showed comparable bioavailability to dupilumab. TABLE 36. Bioavailability of anti-IL-4Rα antibodies administered SC in NHP Antibody Bioavailability (%) Dupilumab 100% Example 21. Binning experiments with anti-IL-4Rα antibodies compared to dupilumab Epitope binning is a technique used to cluster different mAbs based on the specific region of the antigen (in this case IL-4Rα) that is recognized by the antibody. In binning studies with immobilized dupilumab based on published sequence, no response was observed for constructs mAb410, mAb411, mAb412, mAb413, mAb414, mAb415, mAb416, mAb417, mAb418, mAb419, mAb420, mAb421, mAb422, mAb422B, mAb423, mAb424, mAb425, mAb426, mAb427, mAb428, mAb429, mAb431, mAb432, mAb433, mAb434, mAb435, mAb436, mAb437, mAb439, mAb443, mAb450, mAb470, mAb471, and mAb476 (see construct sequences in TABLE 6 and in PCT Application No. PCT/US2024/016235 (corresponding to PCT Publication No. WO2024173847), which is incorporated herein by reference in its entirety). This indicated that the recited mAbs and dupilumab binned together and provides evidence that the mAbs likely bind to a similar or the same epitope on IL-4Rα and therefore they are more likely to have the same biological effect. Example 22. Design of bispecific anti-OX40L and anti-IL-4Rα IgG Materials & Methods [00765] A bispecific IgG is constructed using the Genscript Clone EZ method, and the designed bispecific IgG includes knob-into-holes and CrossMAb approaches to ensure appropriate heavy and light chain pairing. It will be understood by one of skill in the art that any suitable anti-OX40L and anti-IL-4Rα antibody or antigen binding fragment or domain thereof, such as those described herein, can be used. Plasmid cDNA are co-transfected into a mammalian CHO expression platform, and the bispecific antibody is purified. The purity of the final product can be determined by, for example, SEC HPLC. Binding activity for OX40L and IL-4Rα can be assessed with, for example, Octet Biolayer Interferometry (BLI) to confirm that the constructed bispecific IgG binds both OX40L and IL-4Rα antigens. Example 23. Combination of an anti-OX40L antibody and an anti-IL-4Rα antibody – co- administration via different compositions [00766] Two antibodies, one that binds OX40L and one that binds IL-4Rα, are selected and simultaneously administered to a subject via different compositions. For example, Construct 114 that binds OX40L and has a VH domain comprising the amino acid sequence set forth in SEQ ID NO: 1, a VL domain comprising the amino acid sequence set forth in SEQ ID NO: 11, a constant heavy chain sequence set forth in any one of SEQ ID NOs: 651 and 973, and a constant light chain sequence set forth in SEQ ID NO: 738, is administered in one pharmaceutical composition simultaneously with a pharmaceutical composition comprising Construct 38 that binds IL-4Rα and has a VH domain comprising the amino acid sequence set forth in SEQ ID NO: 297, a VL domain comprising the amino acid sequence set forth in SEQ ID NO: 300, a constant heavy chain sequence set forth in any one of SEQ ID NOs: 651 and 973, and a constant light chain sequence set forth in SEQ ID NO: 738. A practitioner of skill in the art can monitor the subject’s response to co-administration of the OX40L antibody and the IL-4Rα antibody to determine whether co-administration results in a change in efficacy (e.g., increased efficacy) and/or allows for a change in dosing (e.g., less frequent dosing) as compared to treatment with just one of the antibodies alone. Example 24. Combination of an anti-OX40L antibody and an anti-IL-4Rα antibody – co- administration in a single composition [00767] Two antibodies, one that binds OX40L and one that binds IL-4Rα, are selected and formulated into a single composition that is then administered to a subject. For example, Construct 114 that binds OX40L and has VH domain comprising the amino acid sequence set forth in SEQ ID NO: 1, a VL domain comprising the amino acid sequence set forth in SEQ ID NO: 11, a constant heavy chain sequence set forth in any one of SEQ ID NOs: 651 and 973, and a constant light chain sequence set forth in SEQ ID NO: 738 is co-formulated with Construct 38 that binds IL-4Rα and has a VH domain comprising the amino acid sequence set forth in SEQ ID NO: 297, a VL domain comprising the amino acid sequence set forth in SEQ ID NO: 300, a constant heavy chain sequence set forth in any one of SEQ ID NOs: 651 and 973, and a constant light chain sequence set forth in SEQ ID NO: 738. A practitioner of skill in the art can monitor the subject’s response to administration of the co-formulated composition to determine whether the co-formulated composition results in a change in efficacy (e.g., increased efficacy) and/or allows for a change in dosing (e.g., less frequent dosing) as compared to treatment with just one of the antibodies alone. Example 25: Clinical Study [00768] A clinical study is conducted to assess the safety, tolerability, pharmacokinetics, pharmacodynamics, and immunogenicity of an isolated antibody, or antigen binding fragment thereof, that binds OX40L and an isolated antibody, or antigen binding fragment thereof, that binds IL-4Rα administered in combination with hyaluronidase or a variant thereof. [00769] In one embodiment, the antibody, or antigen binding fragment thereof, that binds OX40L comprises a CDR-H1 comprising the sequence set forth in SEQ ID NO: 2; a CDR-H2 comprising the sequence set forth in SEQ ID NO: 5; a CDR-H3 comprising the sequence set forth in SEQ ID NO: 8; a CDR-L1 comprising the sequence set forth in SEQ ID NO: 12; a CDR- L2 comprising the sequence set forth in SEQ ID NO: 15; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 17. In one embodiment, the antibody, or antigen binding fragment thereof, that binds OX40L comprises a VH sequence set forth in SEQ ID NO: 1 and a VL sequence set forth in SEQ ID NO: 11. In one embodiment, the heavy chain of the antibody that binds OX40L comprises a constant heavy chain sequence set forth in SEQ ID NO: 651. In one embodiment, the heavy chain of the antibody that binds OX40L comprises a constant heavy chain sequence set forth in SEQ ID NO: 973. In one embodiment, the light chain of the antibody that binds OX40L comprises a constant light chain sequence set forth in SEQ ID NO: 738. A C-terminal lysine is present in SEQ ID NO: 973, which may be cleaved off during manufacture or after administration, resulting in the sequence of SEQ ID NO: 651. Accordingly, a composition comprising an antibody comprising the constant heavy chain of SEQ ID NO: 973 that is administered to a subject may comprise antibodies having the constant heavy chain sequence set forth in SEQ ID NO: 973 or SEQ ID NO: 651, or a mixture thereof (e.g., a composition comprising anti-OX40L antibodies may contain a mixture of antibodies having either a constant heavy chain sequence of SEQ ID NO: 973 or a constant heavy chain sequence of SEQ ID NO: 651 and/or antibodies containing both constant heavy chain sequences (e.g., in a single antibody containing two constant heavy chain sequences)). In one embodiment, the heavy chain of the antibody that binds OX40L comprises the heavy chain sequence set forth in SEQ ID NO: 839 and the light chain sequence set forth in SEQ ID NO: 841. The C-terminal lysine in SEQ ID NO: 839 may not be present if cleavage occurs during manufacture or after administration (which would result in the heavy chain sequence of SEQ ID NO: 840). [00770] In one embodiment, the antibody, or antigen binding fragment thereof, that binds IL- 4Rα comprises a CDR-H1 comprising the sequence set forth in SEQ ID NO: 273; a CDR-H2 comprising the sequence set forth in SEQ ID NO: 279; a CDR-H3 comprising the sequence set forth in SEQ ID NO: 281; a CDR-L1 comprising the sequence set forth in SEQ ID NO: 289; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 290; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 293. In one embodiment, the antibody, or antigen binding fragment thereof, that binds IL-4Rα comprises a VH sequence set forth in SEQ ID NO: 297 and a VL sequence set forth in SEQ ID NO: 300. In one embodiment, the heavy chain of the antibody that binds IL-4Rα comprises a constant heavy chain sequence set forth in SEQ ID NO: 651. In one embodiment, the heavy chain of the antibody that binds IL-4Rα comprises a constant heavy chain sequence set forth in SEQ ID NO: 973. In one embodiment, the light chain of the antibody that binds IL-4Rα comprises a constant light chain sequence set forth in SEQ ID NO: 738. A C-terminal lysine is present in SEQ ID NO: 973, which may be cleaved off during manufacture or after administration, resulting in the sequence of SEQ ID NO: 651. Accordingly, a composition comprising an antibody comprising the constant heavy chain of SEQ ID NO: 973 that is administered to a subject may comprise antibodies having the constant heavy chain sequence set forth in SEQ ID NO: 973 or SEQ ID NO: 651, or a mixture thereof (e.g., a composition comprising anti-IL-4Rα antibodies may contain a mixture of antibodies having either a constant heavy chain sequence of SEQ ID NO: 973 or a constant heavy chain sequence of SEQ ID NO: 651 and/or antibodies containing both constant heavy chain sequences (e.g., in a single antibody containing two constant heavy chain sequences)). In one embodiment, the heavy chain of the antibody that binds IL-4Rα comprises the heavy chain sequence set forth in SEQ ID NO: 836 and the light chain sequence set forth in SEQ ID NO: 838. The C-terminal lysine in SEQ ID NO: 836 may not be present if cleavage occurs during manufacture or after administration (which would result in the heavy chain sequence of SEQ ID NO: 837). [00771] Alternatively, a multi-specific antibody comprising a first antigen binding region that binds OX40L and a second antigen binding region that binds IL-4Rα is administered in combination with hyaluronidase or a variant thereof. [00772] In one embodiment, the antigen binding region that binds OX40L comprises a CDR- H1 comprising the sequence set forth in SEQ ID NO: 2; a CDR-H2 comprising the sequence set forth in SEQ ID NO: 5; a CDR-H3 comprising the sequence set forth in SEQ ID NO: 8; a CDR- L1 comprising the sequence set forth in SEQ ID NO: 12; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 15; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 17. In one embodiment, the antigen binding region that binds OX40L comprises a VH sequence set forth in SEQ ID NO: 1 and a VL sequence set forth in SEQ ID NO: 11. [00773] In one embodiment, the antigen binding region that binds IL-4Rα comprises a CDR- H1 comprising the sequence set forth in SEQ ID NO: 273; a CDR-H2 comprising the sequence set forth in SEQ ID NO: 279; a CDR-H3 comprising the sequence set forth in SEQ ID NO: 281; a CDR-L1 comprising the sequence set forth in SEQ ID NO: 289; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 290; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 293. In one embodiment, the antigen binding region that binds IL-4Rα comprises a VH sequence set forth in SEQ ID NO: 297 and a VL sequence set forth in SEQ ID NO: 300. [00774] In one embodiment, the hyaluronidase is a recombinant human hyaluronidase, such as rHuPH20. In certain embodiments, the rHuPH20 formulation is ENHANZE®. In certain embodiments, the recombinant human hyaluronidase comprises the amino acid sequence set forth in any one of SEQ ID NOs: 1076-1085 and 1087-1142. [00775] In certain embodiments, the hyaluronidase or variant thereof and the antibodies or multi-specific antibody are administered in separate formulations. In certain embodiments, the hyaluronidase or variant thereof and the antibodies or multi-specific antibody are administered simultaneously in separate formulations (e.g., one formulation containing the hyaluronidase or a variant thereof and a second formulation containing the antibodies or multi-specific antibody; or one formulation containing the hyaluronidase or a variant thereof, another formulation containing the OX40 antibody, or an antigen binding fragment thereof, and another formulation containing the IL-4Rα antibody, or an antigen binding fragment thereof). In certain embodiments, the hyaluronidase or variant thereof is administered to the patient prior to administration of the antibodies or multi-specific antibody. In certain embodiments, the hyaluronidase or variant thereof is administered to the patient after administration of one of the antibodies (either the OX40L antibody, or an antigen binding fragment thereof, or the IL-4Rα antibody, or an antigen binding fragment thereof) but is administered before the administration of the second of the antibodies (either the OX40L antibody, or an antigen binding fragment thereof, or the IL-4Rα antibody, or an antigen binding fragment thereof). In certain embodiments, the hyaluronidase or variant thereof is administered to the patient after administration of the antibodies or multi-specific antibody. In certain embodiments, the hyaluronidase or variant thereof and the antibodies or multi-specific antibody are mixed and administered in a single formulation. In certain embodiments, the hyaluronidase or variant thereof and the antibodies or multi-specific antibody are administered by subcutaneous injection. In certain embodiments, the hyaluronidase or variant thereof and the antibodies or multi-specific antibody are administered by intravenous injection. [00776] In certain embodiments, the hyaluronidase is rHuPH20 (ENHANZE®) administered at a concentration of 5,000, 6,000, 7,000, 8,000, 9,000, 10,000, 11,000, 12,000, 13,000, 14,000, 15,000, 16,000, 17,000, 18,000, 19,000, 20,000, 21,000, 22,000, 23,000, 24,000, 25,000, 26,000, 27,000, 28,000, 29,000, 30,000, 31,000, 32,000, 33,000, 34,000, 35,000, 36,000, 37,000, 38,000, 39,000, or 40,000 units. Example 26: Impact of the effect of the combination of an anti-IL-4Rα antibody and an anti-OX40L antibody on markers of inflammation as compared to single agents in an immune co-culture assay [00777] To explore the combination effect on human cytokine and chemokine release from immune cells, allogeneic lymphocyte reaction (ALR) experiments were performed on four donor pairs using primary human leukocytes from healthy volunteers. Myeloid dendritic cells (mDCs) were isolated from peripheral blood mononuclear cells (PBMCs) using a negative selection magnetic bead-based enrichment kit. Once isolated, mDCs were pretreated with monoclonal antibodies (mAbs) and controls at 300 nM for 30 minutes at 37 °C. After pretreatment, mDCs were primed for 24 hours with recombinant human TSLP (5 ng/mL). Allogeneic CD4-positive cells were isolated from PBMCs using a negative selection magnetic bead-based enrichment kit. Primed mDCs were then washed, pretreated once more with mAbs at 300 nM for 30 min at 37 °C, and mixed with the allogeneic CD4-positive lymphocytes in a 1:3 mDC:CD4-positive cell ratio. After a 5-day incubation, the supernatant was collected and cytokines and chemokines were measured using a multi-analyte detection kit (MesoScale Discovery). Concentration values (pg/mL) from each analyte were normalized within each donor pair to the isotype control and the mean across all donor pairs was reported in a heatmap as the % response with 100% being the maximal cytokine secretion from the isotype control group. Benchmark mAbs dupilumab (anti-IL-4Rα), amlitelimab (Anti-OX40L) were produced based on publicly available sequences. [00778] As shown in FIGURE 12, TSLP priming of mDCs induced a greater inflammatory response than unprimed mDCs. The Construct 114 + Construct 38 combination broadly inhibited Type 1 and 2 cytokine/chemokine responses, and inhibited Type 1 and Type 2 cytokine/chemokine responses to a greater extent than single agents and benchmarks, dupilumab and amlitelimab, for several cytokines (e.g., TNFa, MDC, IL-13, IL-5). Exemplary embodiments of the invention are described in the enumerated paragraphs below. E1. A composition comprising an isolated antibody, or an antigen binding fragment thereof, that binds OX40L, comprising: a) a variable heavy (VH) chain sequence having three heavy chain CDR sequences, CDR-H1, CDR-H2, and CDR-H3; and b) a variable light (VL) chain sequence having three light chain CDR sequences, CDR-L1, CDR-L2, and CDR-L3; wherein the antibody, or antigen binding fragment thereof, that binds OX40L comprises: (i) a CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 2-4; a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 5-7; a CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 8-10; a CDR-L1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 12-14; a CDR-L2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 15-16; and a CDR-L3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 17-18; (ii) a CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 20-22; a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 23-25; a CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 26-28; a CDR-L1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 30-32; a CDR-L2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 33-34; and a CDR-L3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 35-36; (iii) a CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 38-40; a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 41-43; a CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 44-46; a CDR-L1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 48-50; a CDR-L2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 51-52; and a CDR-L3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 53-54; or (iv) a CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 56-58; a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 59-61; a CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 62-64; a CDR-L1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 66-68; a CDR-L2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 69-70; and a CDR-L3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 71-72; and an isolated antibody, or an antigen binding fragment thereof, that binds IL-4Rα. E2. The composition of E1, wherein the isolated antibody, or antigen binding fragment thereof, that binds IL-4Rα comprises a CDR-H1, CDR-H2, CDR-H3, CDR-L1, CDR-L2, and CDR-L3 of an antibody selected from dupilumab, stapokibart, and 611. E3. The composition of E1, wherein the isolated antibody, or antigen binding fragment thereof, that binds IL-4Rα comprises: a) a VH chain sequence having three heavy chain CDR sequences, CDR-H1, CDR-H2, and CDR-H3; and b) a VL chain sequence having three light chain CDR sequences, CDR-L1, CDR-L2, and CDR-L3, wherein the isolated antibody, or antigen binding fragment thereof, that binds IL-4Rα comprises: (i) a CDR-H1 comprising the sequence set forth in any one of SEQ ID NOs: 273, 274, and 275; a CDR-H2 comprising the sequence set forth in any one of SEQ ID NOs: 276, 277, and 278; a CDR-H3 comprising the sequence set forth in any one of SEQ ID NOs: 281 and 282; a CDR-L1 comprising the sequence set forth in any one of SEQ ID NOs: 285 and 286; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 292 or the amino acid sequence LG; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 293; (ii) a CDR-H1 comprising the sequence set forth in any one of SEQ ID NOs: 273, 274, and 275; a CDR-H2 comprising the sequence set forth in any one of SEQ ID NOs: 279, 277, and 280; a CDR-H3 comprising the sequence set forth in any one of SEQ ID NOs: 283 and 284; a CDR-L1 comprising the sequence set forth in any one of SEQ ID NOs: 287 and 288; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 291 or the amino acid sequence LG; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 293; or (iii) a CDR-H1 comprising the sequence set forth in any one of SEQ ID NOs: 273, 274, and 275; a CDR-H2 comprising the sequence set forth in any one of SEQ ID NOs: 279, 277, and 280; a CDR-H3 comprising the sequence set forth in any one of SEQ ID NOs: 281 and 282; a CDR-L1 comprising the sequence set forth in any one of SEQ ID NOs: 289 and 288; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 290 or the amino acid sequence EG; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 293. E4. A composition comprising an isolated antibody, or an antigen binding fragment thereof, that binds OX40L; and an isolated antibody, or an antigen binding fragment thereof, that binds IL-4Rα, comprising: a) a variable heavy (VH) chain sequence having three heavy chain CDR sequences, CDR-H1, CDR-H2, and CDR-H3; and b) a variable light (VL) chain sequence having three light chain CDR sequences, CDR-L1, CDR-L2, and CDR- L3; wherein the isolated antibody, or antigen binding fragment thereof, that binds IL-4Rα comprises: (i) a CDR-H1 comprising the sequence set forth in any one of SEQ ID NOs: 273, 274, and 275; a CDR-H2 comprising the sequence set forth in any one of SEQ ID NOs: 276, 277, and 278; a CDR-H3 comprising the sequence set forth in any one of SEQ ID NOs: 281 and 282; a CDR-L1 comprising the sequence set forth in any one of SEQ ID NOs: 285 and 286; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 292 or the amino acid sequence LG; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 293; (ii) a CDR-H1 comprising the sequence set forth in any one of SEQ ID NOs: 273, 274, and 275; a CDR-H2 comprising the sequence set forth in any one of SEQ ID NOs: 279, 277, and 280; a CDR-H3 comprising the sequence set forth in any one of SEQ ID NOs: 283 and 284; a CDR-L1 comprising the sequence set forth in any one of SEQ ID NOs: 287 and 288; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 291 or the amino acid sequence LG; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 293; or (iii) a CDR-H1 comprising the sequence set forth in any one of SEQ ID NOs: 273, 274, and 275; a CDR-H2 comprising the sequence set forth in any one of SEQ ID NOs: 279, 277, and 280; a CDR-H3 comprising the sequence set forth in any one of SEQ ID NOs: 281 and 282; a CDR-L1 comprising the sequence set forth in any one of SEQ ID NOs: 289 and 288; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 290 or the amino acid sequence EG; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 293. E5. The composition of E4, wherein the isolated antibody, or antigen binding fragment thereof, that binds OX40L comprises a CDR-H1, CDR-H2, CDR-H3, CDR-L1, CDR- L2, and CDR-L3 of an antibody selected from amlitelimab and oxelumab. E6. The composition of E4, wherein the isolated antibody, or antigen binding fragment thereof, that binds OX40L comprises: a) a VH chain sequence having three heavy chain CDR sequences, CDR-H1, CDR-H2, and CDR-H3; and b) a VL chain sequence having three light chain CDR sequences, CDR-L1, CDR-L2, and CDR-L3, wherein the isolated antibody, or antigen binding fragment thereof, that binds OX40L comprises: (i) a CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 2-4; a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 5-7; a CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 8-10; a CDR-L1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 12-14; a CDR-L2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 15-16; and a CDR-L3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 17-18; (ii) a CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 20-22; a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 23-25; a CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 26-28; a CDR-L1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 30-32; a CDR-L2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 33-34; and a CDR-L3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 35-36; (iii) a CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 38-40; a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 41-43; a CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 44-46; a CDR-L1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 48-50; a CDR-L2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 51-52; and a CDR-L3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 53-54; or (iv) a CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 56-58; a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 59-61; a CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 62-64; a CDR-L1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 66-68; a CDR-L2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 69-70; and a CDR-L3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 71-72. E7. The composition of E3 or E6, wherein: (a) the antibody, or antigen binding fragment thereof, that binds OX40L comprises: (i) a CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 2-4; a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 5-7; a CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 8-10; a CDR-L1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 12-14; a CDR-L2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 15-16; and a CDR-L3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 17-18; and (b) the antibody, or antigen binding fragment thereof, that binds IL-4Rα comprises: (i) a CDR-H1 comprising the sequence set forth in any one of SEQ ID NOs: 273, 274, and 275; a CDR-H2 comprising the sequence set forth in any one of SEQ ID NOs: 276, 277, and 278; a CDR-H3 comprising the sequence set forth in any one of SEQ ID NOs: 281 and 282; a CDR-L1 comprising the sequence set forth in any one of SEQ ID NOs: 285 and 286; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 292 or the amino acid sequence LG; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 293. E8. The composition of E3 or E6, wherein: (a) the antibody, or antigen binding fragment thereof, that binds OX40L comprises: (ii) a CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 20-22; a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 23-25; a CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 26-28; a CDR-L1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 30-32; a CDR-L2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 33-34; and a CDR-L3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 35-36; and (b) the antibody, or antigen binding fragment thereof, that binds IL-4Rα comprises: (i) a CDR-H1 comprising the sequence set forth in any one of SEQ ID NOs: 273, 274, and 275; a CDR-H2 comprising the sequence set forth in any one of SEQ ID NOs: 276, 277, and 278; a CDR-H3 comprising the sequence set forth in any one of SEQ ID NOs: 281 and 282; a CDR-L1 comprising the sequence set forth in any one of SEQ ID NOs: 285 and 286; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 292 or the amino acid sequence LG; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 293. E9. The composition of E3 or E6, wherein: (a) the antibody, or antigen binding fragment thereof, that binds OX40L comprises: (iii) a CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 38-40; a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 41-43; a CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 44-46; a CDR-L1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 48-50; a CDR-L2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 51-52; and a CDR-L3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 53-54; and (b) the antibody, or antigen binding fragment thereof, that binds IL-4Rα comprises: (i) a CDR-H1 comprising the sequence set forth in any one of SEQ ID NOs: 273, 274, and 275; a CDR-H2 comprising the sequence set forth in any one of SEQ ID NOs: 276, 277, and 278; a CDR-H3 comprising the sequence set forth in any one of SEQ ID NOs: 281 and 282; a CDR-L1 comprising the sequence set forth in any one of SEQ ID NOs: 285 and 286; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 292 or the amino acid sequence LG; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 293. E10. The composition of E3 or E6, wherein: (a) the antibody, or antigen binding fragment thereof, that binds OX40L comprises: (iv) a CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 56-58; a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 59-61; a CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 62-64; a CDR-L1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 66-68; a CDR-L2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 69-70; and a CDR-L3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 71-72; and (b) the antibody, or antigen binding fragment thereof, that binds IL-4Rα comprises: (i) a CDR-H1 comprising the sequence set forth in any one of SEQ ID NOs: 273, 274, and 275; a CDR-H2 comprising the sequence set forth in any one of SEQ ID NOs: 276, 277, and 278; a CDR-H3 comprising the sequence set forth in any one of SEQ ID NOs: 281 and 282; a CDR-L1 comprising the sequence set forth in any one of SEQ ID NOs: 285 and 286; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 292 or the amino acid sequence LG; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 293. E11. The composition of E3 or E6, wherein: (a) the antibody, or antigen binding fragment thereof, that binds OX40L comprises: (i) a CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 2-4; a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 5-7; a CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 8-10; a CDR-L1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 12-14; a CDR-L2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 15-16; and a CDR-L3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 17-18; and (b) the antibody, or antigen binding fragment thereof, that binds IL-4Rα comprises: (ii) a CDR-H1 comprising the sequence set forth in any one of SEQ ID NOs: 273, 274, and 275; a CDR-H2 comprising the sequence set forth in any one of SEQ ID NOs: 279, 277, and 280; a CDR-H3 comprising the sequence set forth in any one of SEQ ID NOs: 283 and 284; a CDR-L1 comprising the sequence set forth in any one of SEQ ID NOs: 287 and 288; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 291 or the amino acid sequence LG; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 293. E12. The composition of E3 or E6, wherein: (a) the antibody, or antigen binding fragment thereof, that binds OX40L comprises: (ii) a CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 20-22; a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 23-25; a CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 26-28; a CDR-L1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 30-32; a CDR-L2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 33-34; and a CDR-L3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 35-36; and (b) the antibody, or antigen binding fragment thereof, that binds IL-4Rα comprises: (ii) a CDR-H1 comprising the sequence set forth in any one of SEQ ID NOs: 273, 274, and 275; a CDR-H2 comprising the sequence set forth in any one of SEQ ID NOs: 279, 277, and 280; a CDR-H3 comprising the sequence set forth in any one of SEQ ID NOs: 283 and 284; a CDR-L1 comprising the sequence set forth in any one of SEQ ID NOs: 287 and 288; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 291 or the amino acid sequence LG; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 293. E13. The composition of E3 or E6, wherein: (a) the antibody, or antigen binding fragment thereof, that binds OX40L comprises: (iii) a CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 38-40; a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 41-43; a CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 44-46; a CDR-L1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 48-50; a CDR-L2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 51-52; and a CDR-L3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 53-54; and (b) the antibody, or antigen binding fragment thereof, that binds IL-4Rα comprises: (ii) a CDR-H1 comprising the sequence set forth in any one of SEQ ID NOs: 273, 274, and 275; a CDR-H2 comprising the sequence set forth in any one of SEQ ID NOs: 279, 277, and 280; a CDR-H3 comprising the sequence set forth in any one of SEQ ID NOs: 283 and 284; a CDR-L1 comprising the sequence set forth in any one of SEQ ID NOs: 287 and 288; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 291 or the amino acid sequence LG; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 293. E14. The composition of E3 or E6, wherein: (a) the antibody, or antigen binding fragment thereof, that binds OX40L comprises: (iv) a CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 56-58; a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 59-61; a CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 62-64; a CDR-L1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 66-68; a CDR-L2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 69-70; and a CDR-L3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 71-72; and (b) the antibody, or antigen binding fragment thereof, that binds IL-4Rα comprises: (ii) a CDR-H1 comprising the sequence set forth in any one of SEQ ID NOs: 273, 274, and 275; a CDR-H2 comprising the sequence set forth in any one of SEQ ID NOs: 279, 277, and 280; a CDR-H3 comprising the sequence set forth in any one of SEQ ID NOs: 283 and 284; a CDR-L1 comprising the sequence set forth in any one of SEQ ID NOs: 287 and 288; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 291 or the amino acid sequence LG; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 293. E15. The composition of E3 or E6, wherein: (a) the antibody, or antigen binding fragment thereof, that binds OX40L comprises: (i) a CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 2-4; a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 5-7; a CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 8-10; a CDR-L1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 12-14; a CDR-L2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 15-16; and a CDR-L3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 17-18; and (b) the antibody, or antigen binding fragment thereof, that binds IL-4Rα comprises: (iii) a CDR-H1 comprising the sequence set forth in any one of SEQ ID NOs: 273, 274, and 275; a CDR-H2 comprising the sequence set forth in any one of SEQ ID NOs: 279, 277, and 280; a CDR-H3 comprising the sequence set forth in any one of SEQ ID NOs: 281 and 282; a CDR-L1 comprising the sequence set forth in any one of SEQ ID NOs: 289 and 288; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 290 or the amino acid sequence EG; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 293. E16. The composition of E3 or E6, wherein: (a) the antibody, or antigen binding fragment thereof, that binds OX40L comprises: (ii) a CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 20-22; a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 23-25; a CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 26-28; a CDR-L1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 30-32; a CDR-L2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 33-34; and a CDR-L3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 35-36; and (b) the antibody, or antigen binding fragment thereof, that binds IL-4Rα comprises: (iii) a CDR-H1 comprising the sequence set forth in any one of SEQ ID NOs: 273, 274, and 275; a CDR-H2 comprising the sequence set forth in any one of SEQ ID NOs: 279, 277, and 280; a CDR-H3 comprising the sequence set forth in any one of SEQ ID NOs: 281 and 282; a CDR-L1 comprising the sequence set forth in any one of SEQ ID NOs: 289 and 288; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 290 or the amino acid sequence EG; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 293. E17. The composition of E3 or E6, wherein: (a) the antibody, or antigen binding fragment thereof, that binds OX40L comprises: (iii) a CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 38-40; a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 41-43; a CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 44-46; a CDR-L1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 48-50; a CDR-L2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 51-52; and a CDR-L3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 53-54; and (b) the antibody, or antigen binding fragment thereof, that binds IL-4Rα comprises: (iii) a CDR-H1 comprising the sequence set forth in any one of SEQ ID NOs: 273, 274, and 275; a CDR-H2 comprising the sequence set forth in any one of SEQ ID NOs: 279, 277, and 280; a CDR-H3 comprising the sequence set forth in any one of SEQ ID NOs: 281 and 282; a CDR-L1 comprising the sequence set forth in any one of SEQ ID NOs: 289 and 288; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 290 or the amino acid sequence EG; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 293. E18. The composition of E3 or E6, wherein: (a) the antibody, or antigen binding fragment thereof, that binds OX40L comprises: (iv) a CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 56-58; a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 59-61; a CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 62-64; a CDR-L1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 66-68; a CDR-L2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 69-70; and a CDR-L3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 71-72; and (b) the antibody, or antigen binding fragment thereof, that binds IL-4Rα comprises: (iii) a CDR-H1 comprising the sequence set forth in any one of SEQ ID NOs: 273, 274, and 275; a CDR-H2 comprising the sequence set forth in any one of SEQ ID NOs: 279, 277, and 280; a CDR-H3 comprising the sequence set forth in any one of SEQ ID NOs: 281 and 282; a CDR-L1 comprising the sequence set forth in any one of SEQ ID NOs: 289 and 288; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 290 or the amino acid sequence EG; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 293. E19. The composition of any one of E1-E4 and E6-E18, wherein the antibody, or antigen binding fragment thereof, that binds OX40L comprises a heavy chain variable domain (VH) sequence comprising the amino acid sequence set forth in any one of SEQ ID NOs: 1, 19, 37, and 55. E20. The composition of any one of E1 and E3-E19, wherein the antibody, or antigen binding fragment thereof, that binds IL-4Rα comprises a VH sequence comprising the amino acid sequence set forth in any one of SEQ ID NOs: 295-297. E21. The composition of any one of E1-E4 and E6-E20, wherein the antibody, or antigen binding fragment thereof, that binds OX40L comprises a light chain variable domain (VL) sequence comprising the amino acid sequence set forth in any one of SEQ ID NOs: 11, 29, 47, and 65. E22. The composition of any one of E1 and E3-E21, wherein the antibody, or antigen binding fragment thereof, that binds IL-4Rα comprises a VL sequence comprising the amino acid sequence set forth in any one of SEQ ID NOs: 298-300. E23. The composition of any one of E19-E22, wherein: (a) the antibody, or antigen binding fragment thereof, that binds OX40L comprises: (i) a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 1; (ii) a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 19; (iii) a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 37; or (iv) a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 55; and/or (v) a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 11; (vi) a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 29; (vii) a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 47; or (viii) a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 65; and/or (b) the antibody that binds IL-4Rα comprises: (i) a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 295; (ii) a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 296; or (iii) a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 297; and/or (iv) a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 298; (v) a VL sequence comprising the amino acid sequence set forth in SEQ ID NO:299; or (vi) a VL sequence comprising the amino acid sequence set forth in SEQ ID NO:300. E24. The composition of E23, wherein the antibody, or antigen binding fragment thereof, that binds OX40L comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 1; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 11. E25. The composition of E23, wherein the antibody, or antigen binding fragment thereof, that binds OX40L comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 19; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 29. E26. The composition of E23, wherein the antibody, or antigen binding fragment thereof, that binds OX40L comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 37; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 47. E27. The composition of E23, wherein the antibody, or antigen binding fragment thereof, that binds OX40L comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 55; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 65. E28. The composition of E23, wherein the antibody, or antigen binding fragment thereof, that binds IL-4Rα comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 295; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 298. E29. The composition of E23, wherein the antibody, or antigen binding fragment thereof, that binds IL-4Rα comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 296; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 299. E30. The composition of E23, wherein the antibody, or antigen binding fragment thereof, that binds IL-4Rα comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 297; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 300. E31. The composition of E23, wherein the antibody, or antigen binding fragment thereof, that binds OX40L comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 1; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 11; and wherein the antibody, or antigen binding fragment thereof, that binds IL- 4Rα comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 295; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 298. E32. The composition of E23, wherein the antibody, or antigen binding fragment thereof, that binds OX40L comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 1; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 11; and wherein the antibody, or antigen binding fragment thereof, that binds IL- 4Rα comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 296; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 299. E33. The composition of E23, wherein the antibody, or antigen binding fragment thereof, that binds OX40L comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 1; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 11; and wherein the antibody, or antigen binding fragment thereof, that binds IL- 4Rα comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 297; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 300. E34. The composition of E23, wherein the antibody, or antigen binding fragment thereof, that binds OX40L comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 19; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 29; and wherein the antibody, or antigen binding fragment thereof, that binds IL-4Rα comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 295; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 298. E35. The composition of E23, wherein the antibody, or antigen binding fragment thereof, that binds OX40L comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 19; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 29; and wherein the antibody, or antigen binding fragment thereof, that binds IL-4Rα comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 296; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 299. E36. The composition of E23, wherein the antibody, or antigen binding fragment thereof, that binds OX40L comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 19; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 29; and wherein the antibody, or antigen binding fragment thereof, that binds IL-4Rα comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 297; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 300. E37. The composition of E23, wherein the antibody, or antigen binding fragment thereof, that binds OX40L comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 37; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 47; and wherein the antibody, or antigen binding fragment thereof, that binds IL-4Rα comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 295; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 298. E38. The composition of E23, wherein the antibody, or antigen binding fragment thereof, that binds OX40L comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 37; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 47; and wherein the antibody, or antigen binding fragment thereof, that binds IL-4Rα comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 296; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 299. E39. The composition of E23, wherein the antibody, or antigen binding fragment thereof, that binds OX40L comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 37; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 47; and wherein the antibody, or antigen binding fragment thereof, that binds IL-4Rα comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 297; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 300. E40. The composition of E23, wherein the antibody, or antigen binding fragment thereof, that binds OX40L comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 55; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 65; and wherein the antibody, or antigen binding fragment thereof, that binds IL-4Rα comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 295; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 298. E41. The composition of E23, wherein the antibody, or antigen binding fragment thereof, that binds OX40L comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 55; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 65; and wherein the antibody, or antigen binding fragment thereof, that binds IL-4Rα comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 296; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 299. E42. The composition of E23, wherein the antibody, or antigen binding fragment thereof, that binds OX40L comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 55; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 65; and wherein the antibody, or antigen binding fragment thereof, that binds IL-4Rα comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 297; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 300. E43. The composition of any one of E1-E42, wherein the antibody, or antigen binding fragment thereof, that binds OX40L and/or the antibody, or antigen binding fragment thereof, that binds IL-4Rα is a humanized, human, or chimeric antibody. E44. The composition of any one of E1-E43, wherein the antibody, or antigen binding fragment thereof, that binds OX40L and/or the antibody, or antigen binding fragment thereof, that binds IL-4Rα is a humanized antibody. E45. The composition of any one of E1-E44, wherein the antibody, or antigen binding fragment thereof, that binds OX40L and/or the antibody, or antigen binding fragment thereof, that binds IL-4Rα comprises a heavy chain human constant region of a class selected from IgG, IgA, IgD, IgE, and IgM. E46. The composition of any one of E1-E45, wherein the antibody, or antigen binding fragment thereof, that binds OX40L and/or the antibody, or antigen binding fragment thereof, that binds IL-4Rα comprises a human Fc region, and wherein the human Fc region comprises a human heavy chain constant region of the class IgG and a subclass selected from IgG1, IgG2, IgG3, and IgG4. E47. The composition of E46, wherein the human Fc region of the antibody, or antigen binding fragment thereof, that binds OX40L and/or the antibody, or antigen binding fragment thereof, that binds IL-4Rα comprises a human IgG1 Fc region E48. The composition of E46, wherein the human Fc region of the antibody, or antigen binding fragment thereof, that binds OX40L and/or the antibody, or antigen binding fragment thereof, that binds IL-4Rα comprises a human IgG4 Fc region. E49. The composition of E46, wherein the human Fc region of the antibody, or antigen binding fragment thereof, that binds OX40L and/or the antibody, or antigen binding fragment thereof, that binds IL-4Rα comprises a human IgG2 Fc region. E50. The composition of any one of E1-E49, wherein the heavy chain of the antibody that binds OX40L and/or the antibody that binds IL-4Rα comprises a constant heavy chain sequence selected from the amino acid sequences set forth in any one of SEQ ID NOs: 637-737 and 847-1070. E51. The composition of any one of E1-E50, wherein the light chain of the antibody, or antigen binding fragment thereof, that binds OX40L and/or the antibody, or antigen binding fragment thereof, that binds IL-4Rα comprises a constant light chain sequence selected from the sequences set forth in SEQ ID NOs: 738 and 1072. E52. The composition of any one of E1-E51, wherein the antibody, or antigen binding fragment thereof, that binds OX40L and/or the antibody, or antigen binding fragment thereof, that binds IL-4Rα comprises an Fc region comprising one or more amino acid substitutions, wherein the one or more substitutions result in an increase in one or more of antibody half-life, ADCC activity, ADCP activity, or CDC activity compared with the Fc without the one or more substitutions. E53. The composition of any one of E1-E51, wherein the antibody, or antigen binding fragment thereof, that binds OX40L and/or the antibody, or antigen binding fragment thereof, that binds IL-4Rα comprises an Fc region comprising one or more amino acid substitutions, wherein the one or more substitutions result in a decrease in one or more of, ADCC activity, ADCP activity or CDC activity compared to an antibody comprising a wild-type Fc region. E54. The composition of E52 or E53, wherein the one or more amino acid substitutions is selected from the group consisting of S228P, M252Y, S254T, T256E, T256D, T250Q, H285D, T307A, T307Q, T307R, T307W, L309D, Q411H, Q311V, A378V, E380A, M428L, N434A, N434S, N297A, D265A, L234A, L235A, and N434W; optionally, wherein the one or more amino acid substitutions comprises a plurality of amino acid substitutions selected from the group consisting of M428L/N434S (LS), M252Y/S254T/T256E (YTE), T250Q/M428L, T307A/E380A/N434A, T256D/T307Q (DQ), T256D/T307W (DW), M252Y/T256D (YD), T307Q/Q311V/A378V (QVV), T256D/H285D/T307R/Q311V/A378V (DDRVV), L309D/Q311H/N434S (DHS), S228P/L235E (SPLE), L234A/L235A (LALA), M428L/N434A (LA), L235A/G237A (LAGA), L234A/L235A/G237A (LALAGA), L234A/L235A/P329G (LALAPG), D265A/YTE, LALA/YTE, LAGA/YTE, LALAGA/YTE, LALAPG/YTE, N297A/LS, D265A/LS, LALA/LS, LALAGA/LS, LALAPG/LS, N297A/DHS, D265A/DHS, LALA/DHS, LAGA/DHS, LALAGA/DHS, LALAPG/DHS, SP/YTE, SPLE/YTE, SP/LS, SPLE/LS, SP/DHS, SPLE/DHS, N297A/LA, D265A/LA, LALA/LA, LAGA/LA, LALAGA/LA, LALAPG/LA, N297A/N434A, D265A/N434A, LALA/N434A, LAGA/N434A, LALAGA/N434A, LALAPG/N434A, N297A/N434W, D265A/N434W, LALA/N434W, LAGA/N434W, LALAGA/N434W, LALAPG/N434W, N297A/DQ, D265A/DQ, LALA/DQ, LAGA/DQ, LALAGA/DQ, LALAPG/DQ, N297A/DW, D265A/DW, LALA/DW, LAGA/DW, LALAGA/DW, LALAPG/DW, N297A/YD, D265A/YD, LALA/YD, LAGA/YD, LALAGA/YD, LALAPG/YD, T307Q/Q311V/A378V (QVV), N297A/QVV, D265A/QVV, LALA/QVV, LAGA/QVV, LALAGA/QVV, LALAPG/QVV, DDRVV, N297A/DDRVV, D265A/DDRVV, LALA/DDRVV, LAGA/DDRVV, LALAGA/DDRVV, and LALAPG/DDRVV. E55. The composition of E54, wherein the one or more amino acid substitutions is selected from the group consisting of LS, YTE, T250Q/M428L, T307A/E380A/N434A, DQ, DW, YD, QVV, DHS, LA, D265A/YTE, LALA/YTE, LAGA/YTE, LALAGA/YTE, LALAPG/YTE, N297A/LS, D265A/LS, LALA/LS, LALAGA/LS, LALAPG/LS, N297A/DHS, D265A/DHS, LALA/DHS, LAGA/DHS, LALAGA/DHS, LALAPG/DHS, SP/YTE, SPLE/YTE, SP/LS, SPLE/LS, SP/DHS, SPLE/DHS, N297A/LA, D265A/LA, LALA/LA, LAGA/LA, LALAGA/LA, LALAPG/LA, N297A/DQ, D265A/DQ, LALA/DQ, LAGA/DQ, LALAGA/DQ, LALAPG/DQ, N297A/DW, D265A/DW, LALA/DW, LAGA/DW, LALAGA/DW, LALAPG/DW, N297A/YD, D265A/YD, LALA/YD, LAGA/YD, LALAGA/YD, LALAPG/YD, N297A/QVV, D265A/QVV, LALA/QVV, LAGA/QVV, LALAGA/QVV, and LALAPG/QVV. E56. The composition of any one of E1-E4 and E5-E55, wherein the antibody, or antigen binding fragment thereof, that binds OX40L comprises a VH domain comprising the amino acid sequence set forth in SEQ ID NO: 1, a VL domain comprising the amino acid sequence set forth in SEQ ID NO: 11, and a human IgG1 Fc region comprising LALA and YTE substitutions. E57. The composition of any one of E1-E4 and E5-E56, wherein the antibody, or antigen binding fragment thereof, that binds OX40L comprises a VH domain comprising the amino acid sequence set forth in SEQ ID NO: 1, a VL domain comprising the amino acid sequence set forth in SEQ ID NO: 11, a constant heavy chain sequence set forth in SEQ ID NO: 651 and/or a constant heavy chain sequence set forth in SEQ ID NO: 973, and a constant light chain sequence set forth in SEQ ID NO: 738. E58. The composition of E57, wherein the antibody, or antigen binding fragment thereof, that binds OX40L comprises a VH domain comprising the amino acid sequence set forth in SEQ ID NO: 1, a VL domain comprising the amino acid sequence set forth in SEQ ID NO: 11, a constant heavy chain sequence set forth in SEQ ID NO: 973, and a light chain sequence set forth in SEQ ID NO: 738 (e.g., a heavy chain set forth in SEQ ID NO: 839 and a light chain set forth in SEQ ID NO: 841). E59. The composition of E57, wherein the antibody, or antigen binding fragment thereof, that binds OX40L comprises a VH domain comprising the amino acid sequence set forth in SEQ ID NO: 1, a VL domain comprising the amino acid sequence set forth in SEQ ID NO: 11, a constant heavy chain sequence set forth in SEQ ID NO: 651, and a constant light chain sequence set forth in SEQ ID NO: 738 (e.g., a heavy chain set forth in SEQ ID NO: 840 and a light chain set forth in SEQ ID NO: 841). E60. The composition of any one of E1 and E3-E59, wherein the antibody, or antigen binding fragment thereof, that binds IL-4Rα comprises a VH domain comprising the amino acid sequence set forth in SEQ ID NO: 297, a VL domain comprising the amino acid sequence set forth in SEQ ID NO: 300, and a human IgG1 Fc region comprising LALA and YTE substitutions. E61. The composition of any one of E1 and E3-E60, wherein the antibody, or antigen binding fragment thereof, that binds IL-4Rα comprises a VH domain comprising the amino acid sequence set forth in SEQ ID NO: 297, a VL domain comprising the amino acid sequence set forth in SEQ ID NO: 300, a constant heavy chain sequence set forth in SEQ ID NO: 651 and/or a constant heavy chain sequence set forth in SEQ ID NO: 973, and a constant light chain sequence set forth in SEQ ID NO: 738. E62. The composition of E61, wherein the antibody, or antigen binding fragment thereof, that binds IL-4Rα comprises a VH domain comprising the amino acid sequence set forth in SEQ ID NO: 297, a VL domain comprising the amino acid sequence set forth in SEQ ID NO: 300, a constant heavy chain sequence set forth in SEQ ID NO: 973, and a constant light chain sequence set forth in SEQ ID NO: 738 (e.g., a heavy chain set forth in SEQ ID NO: 836 and a light chain set forth in SEQ ID NO: 838). E63. The composition of E61, wherein the antibody, or antigen binding fragment thereof, that binds IL-4Rα comprises a VH domain comprising the amino acid sequence set forth in SEQ ID NO: 297, a VL domain comprising the amino acid sequence set forth in SEQ ID NO: 300, a constant heavy chain sequence set forth in SEQ ID NO: 651, and a constant light chain sequence set forth in SEQ ID NO: 738 (e.g., a heavy chain set forth in SEQ ID NO: 837 and a light chain set forth in SEQ ID NO: 838). E64. The composition of any one of E1-E63, wherein the Fc region of the antibody, or antigen binding fragment thereof, that binds OX40L and/or the antibody, or antigen binding fragment thereof, that binds IL-4Rα binds to Neonatal Fc receptor (FcRn). E65. The composition of E64, wherein the Fc region of the antibody, or antigen binding fragment thereof, that binds OX40L and/or the antibody, or antigen binding fragment thereof, that binds IL-4Rα binds an FcRn with higher affinity at pH 6.0 compared to an antibody comprising a wild-type Fc region. E66. The composition of E64 or E65, wherein the Fc region of the antibody, or antigen binding fragment thereof, that binds OX40L and/or the antibody, or antigen binding fragment thereof, that binds IL-4Rα binds to FcRn with a KD of <1 x 10-7 M at pH 6.0. E67. The composition of any one of E1-E66, wherein the antibody, or antigen binding fragment thereof, that binds OX40L and/or the antibody, or antigen binding fragment thereof, that binds IL-4Rα is a monoclonal antibody. E68. The composition of any one of E1-E67, wherein the antibody, or antigen binding fragment thereof, that binds OX40L binds an OX40L sequence set forth in the amino acid sequence of SEQ ID NO: 739. E69. The composition of any one of E1-E68, wherein the antibody, or antigen binding fragment thereof, that binds IL-4Rα binds an IL-4Rα sequence set forth in the amino acid sequence of any one of SEQ ID NOs: 301-303. E70. The composition of any one of E1-E69, wherein the composition further comprises a hyaluronidase or variant thereof. E71. The composition of any one of E1-E70 for use in the treatment of an inflammatory disorder or disease. E72. The composition for use according to E71, wherein the composition is for use in the treatment of atopic dermatitis (AD). E73. The composition for use according to E72, wherein the treatment reduces disease severity in a patient and wherein disease severity is assessed by an atopic dermatitis disease severity outcome measure. E74. The composition for use according to E71, wherein the composition is for use in the treatment of asthma; chronic sinusitis with nasal polyps; Chronic Rhinosinusitis without Nasal Polyps (CRSsNP); eosinophilic esophagitis (EoE); an Eosinophilic gastrointestinal disorder or disease (EGID), such as Eosinophilic Gastritis (EoG), Eosinophilic Enteritis (EoN), Eosinophilic Colitis (EoC), or Eosinophilic Gastroenteritis (EGE); Churg-Strauss syndrome/Eosinophilic granulomatosis with polyangiitis (EGPA); Prurigo Nodularis (PN); Chronic Spontaneous Urticaria (CSU); Chronic Pruritis of Unknown Origin (CPUO); Bullous Pemphigoid (BP); Cold Inducible Urticaria (ColdU); Allergic Fungal Rhinosinusitis (AFRS); Allergic Bronchopulmonary Aspergillosis (ABPA); Chronic Obstructive Pulmonary Disease (COPD); an inflammatory bowel disease, such as Crohn’s disease or ulcerative colitis; lupus; rheumatoid arthritis (RA); psoriasis; hidradenitis suppurativa; celiac disease; systemic sclerosis; idiopathic pulmonary fibrosis; alopecia areata, allergic rhinitis; eosinophilic fasciitis; scleromyxedema; scleredema; or nephrogenic systemic fibrosis. E75. A multi-specific antibody comprising: a first antigen binding region that binds OX40L and comprises: a) a variable heavy (VH) chain sequence having three heavy chain CDR sequences, CDR-H1, CDR-H2, and CDR- H3; and b) a variable light (VL) chain sequence having three light chain CDR sequences, CDR-L1, CDR-L2, and CDR-L3; wherein the antigen binding region that binds OX40L comprises: (i) a CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 2-4; a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 5-7; a CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 8-10; a CDR-L1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 12-14; a CDR-L2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 15-16; and a CDR-L3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 17-18; (ii) a CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 20-22; a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 23-25; a CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 26-28; a CDR-L1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 30-32; a CDR-L2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 33-34; and a CDR-L3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 35-36; (iii) a CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 38-40; a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NO:s 41-43; a CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 44-46; a CDR-L1 comprising the amino acid sequence set forth in any one of SEQ ID NO:s 48-50; a CDR-L2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 51-52; and a CDR-L3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 53-54; or (iv) a CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 56-58; a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 59-61; a CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 62-64; a CDR-L1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 66-68; a CDR-L2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 69-70; and a CDR-L3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 71-72; and a second antigen binding region that binds IL-4Rα. E76. The multi-specific antibody of E75, wherein the antigen binding region that binds IL- 4Rα comprises a CDR-H1, CDR-H2, CDR-H3, CDR-L1, CDR-L2, and CDR-L3 of an antibody selected from dupilumab, stapokibart, and 611. E77. The multi-specific antibody of E75, wherein the antigen binding region that binds IL- 4Rα comprises: a) a VH chain sequence having three heavy chain CDR sequences, CDR- H1, CDR-H2, and CDR-H3; and b) a VL chain sequence having three light chain CDR sequences, CDR-L1, CDR-L2, and CDR-L3, wherein the antigen binding region that binds IL-4Rα comprises: (i) a CDR-H1 comprising the sequence set forth in any one of SEQ ID NOs: 273, 274, and 275; a CDR-H2 comprising the sequence set forth in any one of SEQ ID NOs: 276, 277, and 278; a CDR-H3 comprising the sequence set forth in any one of SEQ ID NOs: 281 and 282; a CDR-L1 comprising the sequence set forth in any one of SEQ ID NOs: 285 and 286; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 292 or the amino acid sequence LG; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 293; (ii) a CDR-H1 comprising the sequence set forth in any one of SEQ ID NOs: 273, 274, and 275; a CDR-H2 comprising the sequence set forth in any one of SEQ ID NOs: 279, 277, and 280; a CDR-H3 comprising the sequence set forth in any one of SEQ ID NOs: 283 and 284; a CDR-L1 comprising the sequence set forth in any one of SEQ ID NOs: 287 and 288; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 291 or the amino acid sequence LG; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 293; or (iii) a CDR-H1 comprising the sequence set forth in any one of SEQ ID NOs: 273, 274, and 275; a CDR-H2 comprising the sequence set forth in any one of SEQ ID NOs: 279, 277, and 280; a CDR-H3 comprising the sequence set forth in any one of SEQ ID NOs: 281 and 282; a CDR-L1 comprising the sequence set forth in any one of SEQ ID NOs: 289 and 288; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 290 or the amino acid sequence EG; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 293. E78. A multi-specific antibody comprising: a first antigen binding region that binds OX40L; and a second antigen binding region that binds IL-4Rα and comprises: a) a variable heavy (VH) chain sequence having three heavy chain CDR sequences, CDR-H1, CDR-H2, and CDR-H3; and b) a variable light (VL) chain sequence having three light chain CDR sequences, CDR-L1, CDR-L2, and CDR-L3; wherein the antigen binding region that binds IL-4Rα comprises: (i) a CDR-H1 comprising the sequence set forth in any one of SEQ ID NOs: 273, 274, and 275; a CDR-H2 comprising the sequence set forth in any one of SEQ ID NOs: 276, 277, and 278; a CDR-H3 comprising the sequence set forth in any one of SEQ ID NOs: 281 and 282; a CDR-L1 comprising the sequence set forth in any one of SEQ ID NOs: 285 and 286; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 292 or the amino acid sequence LG; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 293; (ii) a CDR-H1 comprising the sequence set forth in any one of SEQ ID NOs: 273, 274, and 275; a CDR-H2 comprising the sequence set forth in any one of SEQ ID NOs: 279, 277, and 280; a CDR-H3 comprising the sequence set forth in any one of SEQ ID NOs: 283 and 284; a CDR-L1 comprising the sequence set forth in any one of SEQ ID NOs: 287 and 288; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 291 or the amino acid sequence LG; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 293; or (iii) a CDR-H1 comprising the sequence set forth in any one of SEQ ID NOs: 273, 274, and 275; a CDR-H2 comprising the sequence set forth in any one of SEQ ID NOs: 279, 277, and 280; a CDR-H3 comprising the sequence set forth in any one of SEQ ID NOs: 281 and 282; a CDR-L1 comprising the sequence set forth in any one of SEQ ID NOs: 289 and 288; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 290 or the amino acid sequence EG; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 293. E79. The multi-specific antibody of E78, wherein the antigen binding region that binds OX40L comprises a CDR-H1, CDR-H2, CDR-H3, CDR-L1, CDR-L2, and CDR-L3 of an antibody selected from amlitelimab and oxelumab. E80. The multi-specific antibody of E78, wherein the antigen binding region that binds OX40L comprises: a) a VH chain sequence having three heavy chain CDR sequences, CDR-H1, CDR-H2, and CDR-H3; and b) a VL chain sequence having three light chain CDR sequences, CDR-L1, CDR-L2, and CDR-L3, wherein the antigen binding region that binds OX40L comprises: (i) a CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 2-4; a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 5-7; a CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 8-10; a CDR-L1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 12-14; a CDR-L2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 15-16; and a CDR-L3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 17-18; (ii) a CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 20-22; a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 23-25; a CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 26-28; a CDR-L1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 30-32; a CDR-L2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 33-34; and a CDR-L3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 35-36; (iii) a CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 38-40; a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 41-43; a CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 44-46; a CDR-L1 comprising the amino acid sequence set forth in any one of SEQ ID NO:s 48-50; a CDR-L2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 51-52; and a CDR-L3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 53-54; or (iv) a CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 56-58; a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 59-61; a CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 62-64; a CDR-L1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 66-68; a CDR-L2 comprising the amino acid sequence set forth in any one of SEQ ID NO: 69-70s; and a CDR-L3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 71-72. E81. The multi-specific antibody of E77 or E80, wherein: (a) the antigen binding region that binds OX40L comprises: (i) a CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 2-4; a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 5-7; a CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 8-10; a CDR-L1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 12-14; a CDR-L2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 15-16; and a CDR-L3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 17-18; and (b) the antigen binding region that binds IL-4Rα comprises: (i) a CDR-H1 comprising the sequence set forth in any one of SEQ ID NOs: 273, 274, and 275; a CDR-H2 comprising the sequence set forth in any one of SEQ ID NOs: 276, 277, and 278; a CDR-H3 comprising the sequence set forth in any one of SEQ ID NOs: 281 and 282; a CDR-L1 comprising the sequence set forth in any one of SEQ ID NOs: 285 and 286; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 292 or the amino acid sequence LG; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 293. E82. The multi-specific antibody of E77 or E80, wherein: (a) the antigen binding region that binds OX40L comprises: (ii) a CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 20-22; a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 23-25; a CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 26-28; a CDR-L1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 30-32; a CDR-L2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 33-34; and a CDR-L3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 35-36; and (b) the antigen binding region that binds IL-4Rα comprises: (i) a CDR-H1 comprising the sequence set forth in any one of SEQ ID NOs: 273, 274, and 275; a CDR-H2 comprising the sequence set forth in any one of SEQ ID NOs: 276, 277, and 278; a CDR-H3 comprising the sequence set forth in any one of SEQ ID NOs: 281 and 282; a CDR-L1 comprising the sequence set forth in any one of SEQ ID NOs: 285 and 286; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 292 or the amino acid sequence LG; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 293. E83. The multi-specific antibody of E77 or E80, wherein: (a) the antigen binding region that binds OX40L comprises: (iii) a CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 38-40; a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 41-43; a CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 44-46; a CDR-L1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 48-50; a CDR-L2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 51-52; and a CDR-L3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 53-54; and (b) the antigen binding region that binds IL-4Rα comprises: (i) a CDR-H1 comprising the sequence set forth in any one of SEQ ID NOs: 273, 274, and 275; a CDR-H2 comprising the sequence set forth in any one of SEQ ID NOs: 276, 277, and 278; a CDR-H3 comprising the sequence set forth in any one of SEQ ID NOs: 281 and 282; a CDR-L1 comprising the sequence set forth in any one of SEQ ID NOs: 285 and 286; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 292 or the amino acid sequence LG; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 293. E84. The multi-specific antibody of E77 or E80, wherein: (a) the antigen binding region that binds OX40L comprises: (iv) a CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 56-58; a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 59-61; a CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 62-64; a CDR-L1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 66-68; a CDR-L2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 69-70; and a CDR-L3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 71-72; and (b) the antigen binding region that binds IL-4Rα comprises: (i) a CDR-H1 comprising the sequence set forth in any one of SEQ ID NOs: 273, 274, and 275; a CDR-H2 comprising the sequence set forth in any one of SEQ ID NOs: 276, 277, and 278; a CDR-H3 comprising the sequence set forth in any one of SEQ ID NOs: 281 and 282; a CDR-L1 comprising the sequence set forth in any one of SEQ ID NOs: 285 and 286; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 292 or the amino acid sequence LG; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 293. E85. The multi-specific antibody of E77 or E80, wherein: (a) the antigen binding region that binds OX40L comprises: (i) a CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 2-4; a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 5-7; a CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 8-10; a CDR-L1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 12-14; a CDR-L2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 15-16; and a CDR-L3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 17-18; and (b) the antigen binding region that binds IL-4Rα comprises: (ii) a CDR-H1 comprising the sequence set forth in any one of SEQ ID NOs: 273, 274, and 275; a CDR-H2 comprising the sequence set forth in any one of SEQ ID NOs: 279, 277, and 280; a CDR-H3 comprising the sequence set forth in any one of SEQ ID NOs: 283 and 284; a CDR-L1 comprising the sequence set forth in any one of SEQ ID NOs: 287 and 288; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 291 or the amino acid sequence LG; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 293. E86. The multi-specific antibody of E77 or E80, wherein: (a) the antigen binding region that binds OX40L comprises: (ii) a CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 20-22; a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 23-25; a CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 26-28; a CDR-L1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 30-32; a CDR-L2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 33-34; and a CDR-L3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 35-36; and (b) the antigen binding region that binds IL-4Rα comprises: (ii) a CDR-H1 comprising the sequence set forth in any one of SEQ ID NOs: 273, 274, and 275; a CDR-H2 comprising the sequence set forth in any one of SEQ ID NOs: 279, 277, and 280; a CDR-H3 comprising the sequence set forth in any one of SEQ ID NOs: 283 and 284; a CDR-L1 comprising the sequence set forth in any one of SEQ ID NOs: 287 and 288; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 291 or the amino acid sequence LG; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 293. E87. The multi-specific antibody of E77 or E80, wherein: (a) the antigen binding region that binds OX40L comprises: (iii) a CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 38-40; a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 41-43; a CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 44-46; a CDR-L1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 48-50; a CDR-L2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 51-52; and a CDR-L3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 53-54; and (b) the antigen binding region that binds IL-4Rα comprises: (ii) a CDR-H1 comprising the sequence set forth in any one of SEQ ID NOs: 273, 274, and 275; a CDR-H2 comprising the sequence set forth in any one of SEQ ID NOs: 279, 277, and 280; a CDR-H3 comprising the sequence set forth in any one of SEQ ID NOs: 283 and 284; a CDR-L1 comprising the sequence set forth in any one of SEQ ID NOs: 287 and 288; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 291 or the amino acid sequence LG; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 293. E88. The multi-specific antibody of E77 or E80, wherein: (a) the antigen binding region that binds OX40L comprises: (iv) a CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 56-58; a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 59-61; a CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 62-64; a CDR-L1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 66-68; a CDR-L2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 69-70; and a CDR-L3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 71-72; and (b) the antigen binding region that binds IL-4Rα comprises: (ii) a CDR-H1 comprising the sequence set forth in any one of SEQ ID NOs: 273, 274, and 275; a CDR-H2 comprising the sequence set forth in any one of SEQ ID NOs: 279, 277, and 280; a CDR-H3 comprising the sequence set forth in any one of SEQ ID NOs: 283 and 284; a CDR-L1 comprising the sequence set forth in any one of SEQ ID NOs: 287 and 288; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 291 or the amino acid sequence LG; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 293. E89. The multi-specific antibody of E77 or E80, wherein: (a) the antigen binding region that binds OX40L comprises: (i) a CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 2-4; a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 5-7; a CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 8-10; a CDR-L1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 12-14; a CDR-L2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 15-16; and a CDR-L3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 17-18; and (b) the antigen binding region that binds IL-4Rα comprises: (iii) a CDR-H1 comprising the sequence set forth in any one of SEQ ID NOs: 273, 274, and 275; a CDR-H2 comprising the sequence set forth in any one of SEQ ID NOs: 279, 277, and 280; a CDR-H3 comprising the sequence set forth in any one of SEQ ID NOs: 281 and 282; a CDR-L1 comprising the sequence set forth in any one of SEQ ID NOs: 289 and 288; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 290 or the amino acid sequence EG; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 293. E90. The multi-specific antibody of E77 or E80, wherein: (a) the antigen binding region that binds OX40L comprises: (ii) a CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 20-22; a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 23-25; a CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 26-28; a CDR-L1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 30-32; a CDR-L2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 33-34; and a CDR-L3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 35-36; and (b) the antigen binding region that binds IL-4Rα comprises: (iii) a CDR-H1 comprising the sequence set forth in any one of SEQ ID NOs: 273, 274, and 275; a CDR-H2 comprising the sequence set forth in any one of SEQ ID NOs: 279, 277, and 280; a CDR-H3 comprising the sequence set forth in any one of SEQ ID NOs: 281 and 282; a CDR-L1 comprising the sequence set forth in any one of SEQ ID NOs: 289 and 288; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 290 or the amino acid sequence EG; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 293. E91. The multi-specific antibody of E77 or E80, wherein: (a) the antigen binding region that binds OX40L comprises: (iii) a CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 38-40; a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 41-43; a CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 44-46; a CDR-L1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 48-50; a CDR-L2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 51-52; and a CDR-L3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 53-54; and (b) the antigen binding region that binds IL-4Rα comprises: (iii) a CDR-H1 comprising the sequence set forth in any one of SEQ ID NOs: 273, 274, and 275; a CDR-H2 comprising the sequence set forth in any one of SEQ ID NOs: 279, 277, and 280; a CDR-H3 comprising the sequence set forth in any one of SEQ ID NOs: 281 and 282; a CDR-L1 comprising the sequence set forth in any one of SEQ ID NOs: 289 and 288; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 290 or the amino acid sequence EG; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 293. E92. The multi-specific antibody of E77 or E80, wherein: (a) the antigen binding region that binds OX40L comprises: (iv) a CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 56-58; a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 59-61; a CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 62-64; a CDR-L1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 66-68; a CDR-L2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 69-70; and a CDR-L3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 71-72; and (b) the antigen binding region that binds IL-4Rα comprises: (iii) a CDR-H1 comprising the sequence set forth in any one of SEQ ID NOs: 273, 274, and 275; a CDR-H2 comprising the sequence set forth in any one of SEQ ID NOs: 279, 277, and 280; a CDR-H3 comprising the sequence set forth in any one of SEQ ID NOs: 281 and 282; a CDR-L1 comprising the sequence set forth in any one of SEQ ID NOs: 289 and 288; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 290 or the amino acid sequence EG; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 293. E93. The multi-specific antibody of any one of E75-E78 and E80-E92, wherein the antigen binding region that binds OX40L comprises a heavy chain variable domain (VH) sequence comprising the amino acid sequence set forth in any one of SEQ ID NOs: 1, 19, 37, and 55. E94. The multi-specific antibody of any one of E75 and E77-E93, wherein the antigen binding region that binds IL-4Rα comprises a VH sequence comprising the amino acid sequence set forth in any one of SEQ ID NOs: 295-297. E95. The multi-specific antibody of any one of E75-E78 and E80-E94, wherein the antigen binding region that binds OX40L comprises a light chain variable domain (VL) sequence comprising the amino acid sequence set forth in any one of SEQ ID NOs: 11, 29, 47, and 65. E96. The multi-specific antibody of any one of E75 and E77-E95, wherein the antigen binding region that binds IL-4Rα comprises a VL sequence comprising the amino acid sequence set forth in any one of SEQ ID NOs: 298-300. E97. The multi-specific antibody of any one of E93-E96, wherein: (a) the antigen binding region that binds OX40L comprises: (i) a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 1; (ii) a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 19; (iii) a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 37; or (iv) a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 55; and/or (v) a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 11; (vi) a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 29; (vii) a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 47; or (viii) a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 65; and/or (b) the antigen binding region that binds IL-4Rα comprises: (i) a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 295; (ii) a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 296; or (iii) a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 297; and/or (iv) a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 298; (v) a VL sequence comprising the amino acid sequence set forth in SEQ ID NO:299; or (vi) a VL sequence comprising the amino acid sequence set forth in SEQ ID NO:300. E98. The multi-specific antibody of E97, wherein the antigen binding region that binds OX40L comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 1; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 11. E99. The multi-specific antibody of E97, wherein the antigen binding region that binds OX40L comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 19; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 29. E100. The multi-specific antibody of E97, wherein the antigen binding region that binds OX40L comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 37; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 47. E101. The multi-specific antibody of E97, wherein the antigen binding region that binds OX40L comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 55; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 65. E102. The multi-specific antibody of E97, wherein the antigen binding region that binds IL- 4Rα comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 295; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 298. E103. The multi-specific antibody of E97, wherein the antigen binding region that binds IL- 4Rα comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 296; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 299. E104. The multi-specific antibody of E97, wherein the antigen binding region that binds IL- 4Rα comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 297; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 300. E105. The multi-specific antibody of E97, wherein the antigen binding region that binds OX40L comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 1; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 11; and wherein the antigen binding region that binds IL-4Rα comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 295; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 298. E106. The multi-specific antibody of E97, wherein the antigen binding region that binds OX40L comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 1; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 11; and wherein the antigen binding region that binds IL-4Rα comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 296; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 299. E107. The multi-specific antibody of E97, wherein the antigen binding region that binds OX40L comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 1; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 11; and wherein the antigen binding region that binds IL-4Rα comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 297; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 300. E108. The multi-specific antibody of E97, wherein the antigen binding region that binds OX40L comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 19; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 29; and wherein the antigen binding region that binds IL-4Rα comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 295; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 298. E109. The multi-specific antibody of E97, wherein the antigen binding region that binds OX40L comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 19; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 29; and wherein the antigen binding region that binds IL-4Rα comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 296; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 299. E110. The multi-specific antibody of E97, wherein the antigen binding region that binds OX40L comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 19; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 29; and wherein the antigen binding region that binds IL-4Rα comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 297; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 300. E111. The multi-specific antibody of E97, wherein the antigen binding region that binds OX40L comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 37; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 47; and wherein the antigen binding region that binds IL-4Rα comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 295; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 298. E112. The multi-specific antibody of E97, wherein the antigen binding region that binds OX40L comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 37; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 47; and wherein the antigen binding region that binds IL-4Rα comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 296; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 299. E113. The multi-specific antibody of E97, wherein the antigen binding region that binds OX40L comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 37; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 47; and wherein the antigen binding region that binds IL-4Rα comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 297; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 300. E114. The multi-specific antibody of E97, wherein the antigen binding region that binds OX40L comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 55; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 65; and wherein the antigen binding region that binds IL-4Rα comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 295; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 298. E115. The multi-specific antibody of E97, wherein the antigen binding region that binds OX40L comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 55; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 65; and wherein the antigen binding region that binds IL-4Rα comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 296; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 299. E116. The multi-specific antibody of E97, wherein the antigen binding region that binds OX40L comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 55; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 65; and wherein the antigen binding region that binds IL-4Rα comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 297; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 300. E117. The multi-specific antibody of any one of E75-E116, wherein the antigen binding region that binds OX40L and/or the antigen binding region that binds IL-4Rα is a humanized, human, or chimeric antigen binding region. E118. The multi-specific antibody of any one of E75-E117, wherein the antigen binding region that binds OX40L and/or the antigen binding region that binds IL-4Rα is a humanized antigen binding region. E119. The multi-specific antibody of any one of E75-E118, wherein the multi-specific antibody comprises a heavy chain human constant region of a class selected from IgG, IgA, IgD, IgE, and IgM. E120. The multi-specific antibody of any one of E75-E119, wherein the multi-specific antibody comprises a human Fc region, and wherein the human Fc region comprises a human heavy chain constant region of the class IgG and a subclass selected from IgG1, IgG2, IgG3, and IgG4. E121. The multi-specific antibody of E120, wherein the human Fc region comprises a human IgG1 Fc region. E122. The multi-specific antibody of E120, wherein the human Fc region comprises a human IgG4 Fc region. E123. The multi-specific antibody of E120, wherein the human Fc region comprises a human IgG2 Fc region. E124. The multi-specific antibody of any one of E75-E123, wherein the multi-specific antibody comprises a heavy chain comprising a constant heavy chain sequence selected from the amino acid sequences set forth in any one of SEQ ID NOs: 637-737 and 847-1070. E125. The multi-specific antibody of any one of E75-E124, wherein the multi-specific antibody comprises a light chain comprising a constant light chain sequence selected from the sequences set forth in SEQ ID NOs: 738 and 1071. E126. The multi-specific antibody of any one of E75-E125, wherein the multi-specific antibody comprises an Fc region comprising one or more amino acid substitutions, wherein the one or more substitutions result in an increase in one or more of antibody half-life, ADCC activity, ADCP activity, or CDC activity compared with the Fc without the one or more substitutions. E127. The multi-specific antibody of any one of E66-E125, wherein the multi-specific antibody comprises an Fc region comprising one or more amino acid substitutions, wherein the one or more substitutions result in a decrease in one or more of, ADCC activity, ADCP activity or CDC activity compared to an antibody comprising a wild-type Fc region. E128. The multi-specific antibody of E126 or E127, wherein the one or more amino acid substitutions is selected from the group consisting of S228P, M252Y, S254T, T256E, T256D, T250Q, H285D, T307A, T307Q, T307R, T307W, L309D, Q411H, Q311V, A378V, E380A, M428L, N434A, N434S, N297A, D265A, L234A, L235A, and N434W; optionally, wherein the one or more amino acid substitutions comprises a plurality of amino acid substitutions selected from the group consisting of M428L/N434S (LS), M252Y/S254T/T256E (YTE), T250Q/M428L, T307A/E380A/N434A, T256D/T307Q (DQ), T256D/T307W (DW), M252Y/T256D (YD), T307Q/Q311V/A378V (QVV), T256D/H285D/T307R/Q311V/A378V (DDRVV), L309D/Q311H/N434S (DHS), S228P/L235E (SPLE), L234A/L235A (LALA), M428L/N434A (LA), L235A/G237A (LAGA), L234A/L235A/G237A (LALAGA), L234A/L235A/P329G (LALAPG), D265A/YTE, LALA/YTE, LAGA/YTE, LALAGA/YTE, LALAPG/YTE, N297A/LS, D265A/LS, LALA/LS, LALAGA/LS, LALAPG/LS, N297A/DHS, D265A/DHS, LALA/DHS, LAGA/DHS, LALAGA/DHS, LALAPG/DHS, SP/YTE, SPLE/YTE, SP/LS, SPLE/LS, SP/DHS, SPLE/DHS, N297A/LA, D265A/LA, LALA/LA, LAGA/LA, LALAGA/LA, LALAPG/LA, N297A/N434A, D265A/N434A, LALA/N434A, LAGA/N434A, LALAGA/N434A, LALAPG/N434A, N297A/N434W, D265A/N434W, LALA/N434W, LAGA/N434W, LALAGA/N434W, LALAPG/N434W, N297A/DQ, D265A/DQ, LALA/DQ, LAGA/DQ, LALAGA/DQ, LALAPG/DQ, N297A/DW, D265A/DW, LALA/DW, LAGA/DW, LALAGA/DW, LALAPG/DW, N297A/YD, D265A/YD, LALA/YD, LAGA/YD, LALAGA/YD, LALAPG/YD, T307Q/Q311V/A378V (QVV), N297A/QVV, D265A/QVV, LALA/QVV, LAGA/QVV, LALAGA/QVV, LALAPG/QVV, DDRVV, N297A/DDRVV, D265A/DDRVV, LALA/DDRVV, LAGA/DDRVV, LALAGA/DDRVV, and LALAPG/DDRVV. E129. The multi-specific antibody of E128, wherein the one or more amino acid substitutions is selected from the group consisting of LS, YTE, T250Q/M428L, T307A/E380A/N434A, DQ, DW, YD, QVV, DHS, LA, D265A/YTE, LALA/YTE, LAGA/YTE, LALAGA/YTE, LALAPG/YTE, N297A/LS, D265A/LS, LALA/LS, LALAGA/LS, LALAPG/LS, N297A/DHS, D265A/DHS, LALA/DHS, LAGA/DHS, LALAGA/DHS, LALAPG/DHS, SP/YTE, SPLE/YTE, SP/LS, SPLE/LS, SP/DHS, SPLE/DHS, N297A/LA, D265A/LA, LALA/LA, LAGA/LA, LALAGA/LA, LALAPG/LA, N297A/DQ, D265A/DQ, LALA/DQ, LAGA/DQ, LALAGA/DQ, LALAPG/DQ, N297A/DW, D265A/DW, LALA/DW, LAGA/DW, LALAGA/DW, LALAPG/DW, N297A/YD, D265A/YD, LALA/YD, LAGA/YD, LALAGA/YD, LALAPG/YD, N297A/QVV, D265A/QVV, LALA/QVV, LAGA/QVV, LALAGA/QVV, and LALAPG/QVV. E130. The multi-specific antibody of any one of E75-E78 and E80-E129, wherein the antigen binding region that binds OX40L comprises VH domain comprising the amino acid sequence set forth in SEQ ID NO: 1, a VL domain comprising the amino acid sequence set forth in SEQ ID NO: 11, and a human IgG1 Fc region comprising LALA and YTE substitutions. E131. The multi-specific antibody of any one of E75-E78 and E80-E130, wherein the antigen binding region that binds OX40L comprises VH domain comprising the amino acid sequence set forth in SEQ ID NO: 1, a VL domain comprising the amino acid sequence set forth in SEQ ID NO: 11, a constant heavy chain sequence set forth in SEQ ID NO: 651 and/or a constant heavy chain sequence set forth in SEQ ID NO: 973, and a constant light chain sequence set forth in SEQ ID NO: 738. E132. The multi-specific antibody of E131, wherein the antigen binding region that binds OX40L comprises VH domain comprising the amino acid sequence set forth in SEQ ID NO: 1, a VL domain comprising the amino acid sequence set forth in SEQ ID NO: 11, a constant heavy chain sequence set forth in SEQ ID NO: 973, and a constant light chain sequence set forth in SEQ ID NO: 738. E133. The multi-specific antibody of E131, wherein the antigen binding region that binds OX40L comprises VH domain comprising the amino acid sequence set forth in SEQ ID NO: 1, a VL domain comprising the amino acid sequence set forth in SEQ ID NO: 11, a constant heavy chain sequence set forth in SEQ ID NO: 651, and a constant light chain sequence set forth in SEQ ID NO: 738. E134. The multi-specific antibody of any one of E75 and E77-E133, wherein the antigen binding region that binds IL-4Rα comprises a VH domain comprising the amino acid sequence set forth in SEQ ID NO: 73, a VL domain comprising the amino acid sequence set forth in SEQ ID NO: 83, and a human IgG1 Fc region comprising LALA and YTE substitutions. E135. The multi-specific antibody of any one of E75 and E77-E134, wherein the antigen binding region that binds IL-4Rα comprises a VH domain comprising the amino acid sequence set forth in SEQ ID NO: 297, a VL domain comprising the amino acid sequence set forth in SEQ ID NO: 300, a constant heavy chain sequence set forth in SEQ ID NO: 651 and/or a constant heavy chain sequence set forth in SEQ ID NO: 973, and a constant light chain sequence set forth in SEQ ID NO: 738. E136. The multi-specific antibody of E135, wherein the antigen binding region that binds IL- 4Rα comprises a VH domain comprising the amino acid sequence set forth in SEQ ID NO: 297, a VL domain comprising the amino acid sequence set forth in SEQ ID NO: 300, a constant heavy chain sequence set forth in SEQ ID NO: 973, and a constant light chain sequence set forth in SEQ ID NO: 738. E137. The multi-specific antibody of E135, wherein the antigen binding region that binds IL- 4Rα comprises a VH domain comprising the amino acid sequence set forth in SEQ ID NO: 297, a VL domain comprising the amino acid sequence set forth in SEQ ID NO: 300, a constant heavy chain sequence set forth in SEQ ID NO: 651, and a constant light chain sequence set forth in SEQ ID NO: 738. E138. The multi-specific antibody of any one of E75-E137, wherein the Fc region of the multi- specific antibody binds to Neonatal Fc receptor (FcRn). E139. The multi-specific antibody of E138, wherein the Fc region of the multi-specific antibody binds an FcRn with higher affinity at pH 6.0 compared to an antibody comprising a wild-type Fc region. E140. The multi-specific antibody of E138 or E139, wherein the Fc region of the multi-specific antibody binds to FcRn with a KD of <1 x 10-7 M at pH 6.0. E141. The multi-specific antibody of any one of E75-E140, wherein the antigen binding region that binds OX40L and/or the antigen binding region that binds IL-4Rα is a monoclonal antigen binding region. E142. The multi-specific antibody of any one of E75-E141, wherein the antigen binding region that binds OX40L binds an OX40L sequence set forth in the amino acid sequence of SEQ ID NO: 739. E143. The multi-specific antibody of any one of E75-E142, wherein the antigen binding region that binds IL-4Rα binds an IL-4Rα sequence set forth in the amino acid sequence of any one of SEQ ID NOs: 301-303. E144. A composition comprising the multi-specific antibody of any one of E75-E143 and a hyaluronidase or variant thereof. E145. The multi-specific antibody of any one of E75-E143 or the composition of E144 for use in the treatment of an inflammatory disorder or disease. E146. The multi-specific antibody or composition for use according to E145, wherein the use is the treatment of atopic dermatitis (AD). E147. The multi-specific antibody or composition for use according to E146, wherein the treatment reduces disease severity in a patient and wherein disease severity is assessed by an atopic dermatitis disease severity outcome measure. E148. The multi-specific antibody or composition for use according to E145, wherein the use is for the treatment of asthma; chronic sinusitis with nasal polyps; Chronic Rhinosinusitis without Nasal Polyps (CRSsNP); eosinophilic esophagitis (EoE); an Eosinophilic gastrointestinal disorder or disease (EGID), such as Eosinophilic Gastritis (EoG), Eosinophilic Enteritis (EoN), Eosinophilic Colitis (EoC), or Eosinophilic Gastroenteritis (EGE); Churg-Strauss syndrome/Eosinophilic granulomatosis with polyangiitis (EGPA); Prurigo Nodularis (PN); Chronic Spontaneous Urticaria (CSU); Chronic Pruritis of Unknown Origin (CPUO); Bullous Pemphigoid (BP); Cold Inducible Urticaria (ColdU); Allergic Fungal Rhinosinusitis (AFRS); Allergic Bronchopulmonary Aspergillosis (ABPA); Chronic Obstructive Pulmonary Disease (COPD); an inflammatory bowel disease, such as Crohn’s disease or ulcerative colitis; lupus; rheumatoid arthritis (RA); psoriasis; hidradenitis suppurativa; celiac disease; systemic sclerosis; idiopathic pulmonary fibrosis; alopecia areata, allergic rhinitis; eosinophilic fasciitis; scleromyxedema; scleredema; or nephrogenic systemic fibrosis. E149. An isolated polynucleotide or set of polynucleotides encoding the isolated antibodies or multi-specific antibodies of any one of E1-E70 and E75-E143, a VH thereof, a VL thereof, a light chain thereof, a heavy chain thereof, or an antigen-binding portion thereof, optionally, wherein the polynucleotide or set of polynucleotides comprises cDNA. E150. A vector or set of vectors comprising the polynucleotide or set of polynucleotides of E149. E151. A host cell comprising the polynucleotide or set of polynucleotides of E149 or the vector or set of vectors of E150. E152. A method of producing one or more of the isolated antibodies or multi-specific antibody of any one of E1-E70 and E75-E143, the method comprising expressing one or more of the isolated antibodies or multi-specific antibody within the host cell of E151 and isolating the one or more expressed antibodies. E153. A pharmaceutical composition comprising the composition of any one of E1-E70 and E144 and a pharmaceutically acceptable excipient. E154. A pharmaceutical composition comprising the multi-specific antibody of any one of E75- E143 and a pharmaceutically acceptable excipient. E155. A kit comprising the composition of any one of E1-E70 and E144, the multi-specific antibody of any one of E75-E143, or the pharmaceutical composition of E153 or E154 and instructions for use. E156. A method for treating an inflammatory disorder or disease in a mammalian subject in need thereof, the method comprising administering to the mammalian subject a therapeutically effective amount of the composition of any one of E1-E70 and E144, the multi-specific antibody of any one of E75-E143, or the pharmaceutical composition of E153 or E154. E157. A method for treating a pathology associated with elevated levels of OX40L and/or IL-4 in a mammalian subject in need thereof, the method comprising administering to the mammalian subject a therapeutically effective amount of the composition of any one of E1-E70 and E144, the multi-specific antibody of any one of E75-E143, or the pharmaceutical composition of E153 or E154. E158. A method of reducing biological activity of OX40L and/or IL-4Rα in a mammalian subject in need thereof, the method comprising administering to the mammalian subject a therapeutically effective amount of the composition of any one of E1-E70 and E144, the multi-specific antibody of any one of E75-E143, or the pharmaceutical composition of E153 or E154. E159. A method for treating an inflammatory disorder or disease in a mammalian subject in need thereof, the method comprising administering to the mammalian subject a therapeutically effective amount of a pharmaceutical composition comprising an isolated antibody, or antigen binding fragment thereof, that binds OX40L and a pharmaceutically acceptable excipient and a therapeutically effective amount of a pharmaceutical composition comprising an antibody, or antigen binding fragment thereof, that binds IL- 4Rα and a pharmaceutically acceptable excipient. E160. A method for treating a pathology associated with elevated levels of OX40L and/or IL-4 in a mammalian subject in need thereof, the method comprising administering to the mammalian subject a therapeutically effective amount of a pharmaceutical composition comprising an isolated antibody, or antigen binding fragment thereof, that binds OX40L and a pharmaceutically acceptable excipient and a therapeutically effective amount of a pharmaceutical composition comprising an antibody, or antigen binding fragment thereof, that binds IL-4Rα and a pharmaceutically acceptable excipient. E161. A method of reducing biological activity of OX40L and/or IL-4Rα in a mammalian subject in need thereof, the method comprising administering to the mammalian subject a therapeutically effective amount of a pharmaceutical composition comprising an isolated antibody, or antigen binding fragment thereof, that binds OX40L and a pharmaceutically acceptable excipient and a therapeutically effective amount of a pharmaceutical composition comprising an antibody, or antigen binding fragment thereof, that binds IL- 4Rα and a pharmaceutically acceptable excipient. E162. The method of E156 or E159, wherein the inflammatory disorder or disease is atopic dermatitis. E163. The method of E156 or E159, wherein the inflammatory disorder or disease is asthma. E164. The method of E156 or E159, wherein the inflammatory disorder or disease is chronic sinusitis with nasal polyps; Chronic Rhinosinusitis without Nasal Polyps (CRSsNP); eosinophilic esophagitis (EoE); an Eosinophilic gastrointestinal disorder or disease (EGID) selected from the group consisting of Eosinophilic Gastritis (EoG), Eosinophilic Enteritis (EoN), Eosinophilic Colitis (EoC), and Eosinophilic Gastroenteritis (EGE); Churg-Strauss syndrome/Eosinophilic granulomatosis with polyangiitis (EGPA); Prurigo Nodularis (PN); Chronic Spontaneous Urticaria (CSU); Chronic Pruritis of Unknown Origin (CPUO); Bullous Pemphigoid (BP); Cold Inducible Urticaria (ColdU); Allergic Fungal Rhinosinusitis (AFRS); Allergic Bronchopulmonary Aspergillosis (ABPA); Chronic Obstructive Pulmonary Disease (COPD); celiac disease; Crohn’s disease; lupus; rheumatoid arthritis (RA); psoriasis; ulcerative colitis; hidradenitis suppurativa; systemic sclerosis; idiopathic pulmonary fibrosis; alopecia areata, allergic rhinitis; eosinophilic fasciitis; scleromyxedema; scleredema; or nephrogenic systemic fibrosis. E165. The method of any one of E159-E164, wherein the isolated antibody, or an antigen binding fragment thereof, that binds OX40L, comprises: a) a variable heavy (VH) chain sequence having three heavy chain CDR sequences, CDR-H1, CDR-H2, and CDR-H3; and b) a variable light (VL) chain sequence having three light chain CDR sequences, CDR-L1, CDR-L2, and CDR-L3; and wherein the antibody, or antigen binding fragment thereof, that binds OX40L comprises: (i) a CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 2-4; a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 5-7; a CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 8-10; a CDR-L1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 12-14; a CDR-L2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 15-16; and a CDR-L3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 17-18; (ii) a CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 20-22; a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 23-25; a CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 26-28; a CDR-L1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 30-32; a CDR-L2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 33-34; and a CDR-L3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 35-36; (iii) a CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 38-40; a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 41-43; a CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 44-46; a CDR-L1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 48-50; a CDR-L2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 51-52; and a CDR-L3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 53-54; or (iv) a CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 56-58; a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 59-61; a CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 62-64; a CDR-L1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 66-68; a CDR-L2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 69-70; and a CDR-L3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 71-72. E166. The method of any one of E159-E164, wherein the isolated antibody, or antigen binding fragment thereof, that binds OX40L comprises a CDR-H1, CDR-H2, CDR-H3, CDR-L1, CDR-L2, and CDR-L3 of an antibody selected from amlitelimab and oxelumab. E167. The method of any one of E159-E166, wherein the isolated antibody, or antigen binding fragment thereof, that binds IL-4Rα comprises a CDR-H1, CDR-H2, CDR-H3, CDR-L1, CDR-L2, and CDR-L3 of an antibody selected from dupilumab, stapokibart, and 611. E168. The method of any one of E159-E166, wherein the isolated antibody, or antigen binding fragment thereof, that binds IL-4Rα comprises: a) a VH chain sequence having three heavy chain CDR sequences, CDR-H1, CDR-H2, and CDR-H3; and b) a VL chain sequence having three light chain CDR sequences, CDR-L1, CDR-L2, and CDR-L3, wherein the isolated antibody, or antigen binding fragment thereof, that binds IL-4Rα comprises: (i) a CDR-H1 comprising the sequence set forth in any one of SEQ ID NOs: 273, 274, and 275; a CDR-H2 comprising the sequence set forth in any one of SEQ ID NOs: 276, 277, and 278; a CDR-H3 comprising the sequence set forth in any one of SEQ ID NOs: 281 and 282; a CDR-L1 comprising the sequence set forth in any one of SEQ ID NOs: 285 and 286; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 292 or the amino acid sequence LG; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 293; (ii) a CDR-H1 comprising the sequence set forth in any one of SEQ ID NOs: 273, 274, and 275; a CDR-H2 comprising the sequence set forth in any one of SEQ ID NOs: 279, 277, and 280; a CDR-H3 comprising the sequence set forth in any one of SEQ ID NOs: 283 and 284; a CDR-L1 comprising the sequence set forth in any one of SEQ ID NOs: 287 and 288; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 291 or the amino acid sequence LG; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 293; or (iii) a CDR-H1 comprising the sequence set forth in any one of SEQ ID NOs: 273, 274, and 275; a CDR-H2 comprising the sequence set forth in any one of SEQ ID NOs: 279, 277, and 280; a CDR-H3 comprising the sequence set forth in any one of SEQ ID NOs: 281 and 282; a CDR-L1 comprising the sequence set forth in any one of SEQ ID NOs: 289 and 288; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 290 or the amino acid sequence EG; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 293. E169. The method of E165 or E168, wherein: (a) the antibody, or antigen binding fragment thereof, that binds OX40L comprises: (i) a CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 2-4; a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 5-7; a CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 8-10; a CDR-L1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 12-14; a CDR-L2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 15-16; and a CDR-L3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 17-18; and (b) the antibody, or antigen binding fragment thereof, that binds IL-4Rα comprises: (i) a CDR-H1 comprising the sequence set forth in any one of SEQ ID NOs: 273, 274, and 275; a CDR-H2 comprising the sequence set forth in any one of SEQ ID NOs: 276, 277, and 278; a CDR-H3 comprising the sequence set forth in any one of SEQ ID NOs: 281 and 282; a CDR-L1 comprising the sequence set forth in any one of SEQ ID NOs: 285 and 286; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 292 or the amino acid sequence LG; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 293. E170. The method of E165 or E168, wherein: (a) the antibody, or antigen binding fragment thereof, that binds OX40L comprises: (ii) a CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 20-22; a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 23-25; a CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 26-28; a CDR-L1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 30-32; a CDR-L2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 33-34; and a CDR-L3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 35-36; and (b) the antibody, or antigen binding fragment thereof, that binds IL-4Rα comprises: (i) a CDR-H1 comprising the sequence set forth in any one of SEQ ID NOs: 273, 274, and 275; a CDR-H2 comprising the sequence set forth in any one of SEQ ID NOs: 276, 277, and 278; a CDR-H3 comprising the sequence set forth in any one of SEQ ID NOs: 281 and 282; a CDR-L1 comprising the sequence set forth in any one of SEQ ID NOs: 285 and 286; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 292 or the amino acid sequence LG; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 293. E171. The method of E165 or E168, wherein: (a) the antibody, or antigen binding fragment thereof, that binds OX40L comprises: (iii) a CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 38-40; a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 41-43; a CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 44-46; a CDR-L1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 48-50; a CDR-L2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 51-52; and a CDR-L3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 53-54; and (b) the antibody, or antigen binding fragment thereof, that binds IL-4Rα comprises: (i) a CDR-H1 comprising the sequence set forth in any one of SEQ ID NOs: 273, 274, and 275; a CDR-H2 comprising the sequence set forth in any one of SEQ ID NOs: 276, 277, and 278; a CDR-H3 comprising the sequence set forth in any one of SEQ ID NOs: 281 and 282; a CDR-L1 comprising the sequence set forth in any one of SEQ ID NOs: 285 and 286; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 292 or the amino acid sequence LG; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 293. E172. The method of E165 or E168, wherein: (a) the antibody, or antigen binding fragment thereof, that binds OX40L comprises: (iv) a CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 56-58; a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 59-61; a CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 62-64; a CDR-L1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 66-68; a CDR-L2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 69-70; and a CDR-L3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 71-72; and (b) the antibody, or antigen binding fragment thereof, that binds IL-4Rα comprises: (i) a CDR-H1 comprising the sequence set forth in any one of SEQ ID NOs: 273, 274, and 275; a CDR-H2 comprising the sequence set forth in any one of SEQ ID NOs: 276, 277, and 278; a CDR-H3 comprising the sequence set forth in any one of SEQ ID NOs: 281 and 282; a CDR-L1 comprising the sequence set forth in any one of SEQ ID NOs: 285 and 286; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 292 or the amino acid sequence LG; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 293. E173. The method of E165 or E168, wherein: (a) the antibody, or antigen binding fragment thereof, that binds OX40L comprises: (i) a CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 2-4; a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 5-7; a CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 8-10; a CDR-L1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 12-14; a CDR-L2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 15-16; and a CDR-L3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 17-18; and (b) the antibody, or antigen binding fragment thereof, that binds IL-4Rα comprises: (ii) a CDR-H1 comprising the sequence set forth in any one of SEQ ID NOs: 273, 274, and 275; a CDR-H2 comprising the sequence set forth in any one of SEQ ID NOs: 279, 277, and 280; a CDR-H3 comprising the sequence set forth in any one of SEQ ID NOs: 283 and 284; a CDR-L1 comprising the sequence set forth in any one of SEQ ID NOs: 287 and 288; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 291 or the amino acid sequence LG; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 293. E174. The method of E165 or E168, wherein: (a) the antibody, or antigen binding fragment thereof, that binds OX40L comprises: (ii) a CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 20-22; a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 23-25; a CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 26-28; a CDR-L1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 30-32; a CDR-L2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 33-34; and a CDR-L3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 35-36; and (b) the antibody, or antigen binding fragment thereof, that binds IL-4Rα comprises: (ii) a CDR-H1 comprising the sequence set forth in any one of SEQ ID NOs: 273, 274, and 275; a CDR-H2 comprising the sequence set forth in any one of SEQ ID NOs: 279, 277, and 280; a CDR-H3 comprising the sequence set forth in any one of SEQ ID NOs: 283 and 284; a CDR-L1 comprising the sequence set forth in any one of SEQ ID NOs: 287 and 288; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 291 or the amino acid sequence LG; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 293. E175. The method of E165 or E168, wherein: (a) the antibody, or antigen binding fragment thereof, that binds OX40L comprises: (iii) a CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 38-40; a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 41-43; a CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 44-46; a CDR-L1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 48-50; a CDR-L2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 51-52; and a CDR-L3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 53-54; and (b) the antibody, or antigen binding fragment thereof, that binds IL-4Rα comprises: (ii) a CDR-H1 comprising the sequence set forth in any one of SEQ ID NOs: 273, 274, and 275; a CDR-H2 comprising the sequence set forth in any one of SEQ ID NOs: 279, 277, and 280; a CDR-H3 comprising the sequence set forth in any one of SEQ ID NOs: 283 and 284; a CDR-L1 comprising the sequence set forth in any one of SEQ ID NOs: 287 and 288; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 291 or the amino acid sequence LG; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 293. E176. The method of E165 or E168, wherein: (a) the antibody, or antigen binding fragment thereof, that binds OX40L comprises: (iv) a CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 56-58; a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 59-61; a CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 62-64; a CDR-L1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 66-68; a CDR-L2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 69-70; and a CDR-L3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 71-72; and (b) the antibody, or antigen binding fragment thereof, that binds IL-4Rα comprises: (ii) a CDR-H1 comprising the sequence set forth in any one of SEQ ID NOs: 273, 274, and 275; a CDR-H2 comprising the sequence set forth in any one of SEQ ID NOs: 279, 277, and 280; a CDR-H3 comprising the sequence set forth in any one of SEQ ID NOs: 283 and 284; a CDR-L1 comprising the sequence set forth in any one of SEQ ID NOs: 287 and 288; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 291 or the amino acid sequence LG; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 293. E177. The method of E165 or E168, wherein: (a) the antibody, or antigen binding fragment thereof, that binds OX40L comprises: (i) a CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 2-4; a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 5-7; a CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 8-10; a CDR-L1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 12-14; a CDR-L2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 15-16; and a CDR-L3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 17-18; and (b) the antibody, or antigen binding fragment thereof, that binds IL-4Rα comprises: (iii) a CDR-H1 comprising the sequence set forth in any one of SEQ ID NOs: 273, 274, and 275; a CDR-H2 comprising the sequence set forth in any one of SEQ ID NOs: 279, 277, and 280; a CDR-H3 comprising the sequence set forth in any one of SEQ ID NOs: 281 and 282; a CDR-L1 comprising the sequence set forth in any one of SEQ ID NOs: 289 and 288; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 290 or the amino acid sequence EG; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 293. E178. The method of E165 or E168, wherein: (a) the antibody, or antigen binding fragment thereof, that binds OX40L comprises: (ii) a CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 20-22; a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 23-25; a CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 26-28; a CDR-L1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 30-32; a CDR-L2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 33-34; and a CDR-L3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 35-36; and (b) the antibody, or antigen binding fragment thereof, that binds IL-4Rα comprises: (iii) a CDR-H1 comprising the sequence set forth in any one of SEQ ID NOs: 273, 274, and 275; a CDR-H2 comprising the sequence set forth in any one of SEQ ID NOs: 279, 277, and 280; a CDR-H3 comprising the sequence set forth in any one of SEQ ID NOs: 281 and 282; a CDR-L1 comprising the sequence set forth in any one of SEQ ID NOs: 289 and 288; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 290 or the amino acid sequence EG; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 293. E179. The method of E165 or E168, wherein: (a) the antibody, or antigen binding fragment thereof, that binds OX40L comprises: (iii) a CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 38-40; a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 41-43; a CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 44-46; a CDR-L1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 48-50; a CDR-L2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 51-52; and a CDR-L3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 53-54; and (b) the antibody, or antigen binding fragment thereof, that binds IL-4Rα comprises: (iii) a CDR-H1 comprising the sequence set forth in any one of SEQ ID NOs: 273, 274, and 275; a CDR-H2 comprising the sequence set forth in any one of SEQ ID NOs: 279, 277, and 280; a CDR-H3 comprising the sequence set forth in any one of SEQ ID NOs: 281 and 282; a CDR-L1 comprising the sequence set forth in any one of SEQ ID NOs: 289 and 288; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 290 or the amino acid sequence EG; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 293. E180. The method of E165 or E168, wherein: (a) the antibody, or antigen binding fragment thereof, that binds OX40L comprises: (iv) a CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 56-58; a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 59-61; a CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 62-64; a CDR-L1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 66-68; a CDR-L2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 69-70; and a CDR-L3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 71-72; and (b) the antibody, or antigen binding fragment thereof, that binds IL-4Rα comprises: (iii) a CDR-H1 comprising the sequence set forth in any one of SEQ ID NOs: 273, 274, and 275; a CDR-H2 comprising the sequence set forth in any one of SEQ ID NOs: 279, 277, and 280; a CDR-H3 comprising the sequence set forth in any one of SEQ ID NOs: 281 and 282; a CDR-L1 comprising the sequence set forth in any one of SEQ ID NOs: 289 and 288; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 290 or the amino acid sequence EG; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 293. E181. The method of any one of E165 and E168-E180, wherein the antibody, or antigen binding fragment thereof, that binds OX40L comprises a heavy chain variable domain (VH) sequence comprising the amino acid sequence set forth in any one of SEQ ID NOs: 1, 19, 37, and 55. E182. The method of any one of E165 and E168-E181, wherein the antibody, or antigen binding fragment thereof, that binds IL-4Rα comprises a VH sequence comprising the amino acid sequence set forth in any one of SEQ ID NOs: 295-297. E183. The method of any one of E165 and E168-E183, wherein the antibody, or antigen binding fragment thereof, that binds OX40L comprises a light chain variable domain (VL) sequence comprising the amino acid sequence set forth in any one of SEQ ID NOs: 11, 29, 47, and 65. E184. The method of any one of E165 and E168-E183, wherein the antibody, or antigen binding fragment thereof, that binds IL-4Rα comprises a VL sequence comprising the amino acid sequence set forth in any one of SEQ ID NOs: 298-300. E185. The method of any one of E181-E184, wherein: (a) the antibody, or antigen binding fragment thereof, that binds OX40L comprises: (i) a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 1; (ii) a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 19; (iii) a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 37; or (iv) a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 55; and/or (v) a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 11; (vi) a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 29; (vii) a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 47; or (viii) a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 65; and/or (b) the antibody that binds IL-4Rα comprises: (i) a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 295; (ii) a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 296; or (iii) a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 297; and/or (iv) a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 298; (v) a VL sequence comprising the amino acid sequence set forth in SEQ ID NO:299; or (vi) a VL sequence comprising the amino acid sequence set forth in SEQ ID NO:300. E186. The method of E185, wherein the antibody, or antigen binding fragment thereof, that binds OX40L comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 1; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 11. E187. The method of E185, wherein the antibody, or antigen binding fragment thereof, that binds OX40L comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 19; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 29. E188. The method of E185, wherein the antibody, or antigen binding fragment thereof, that binds OX40L comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 37; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 47. E189. The method of E185, wherein the antibody, or antigen binding fragment thereof, that binds OX40L comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 55; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 65. E190. The method of E185, wherein the antibody, or antigen binding fragment thereof, that binds IL-4Rα comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 295; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 298. E191. The method of E185, wherein the antibody, or antigen binding fragment thereof, that binds IL-4Rα comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 296; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 299. E192. The method of E185, wherein the antibody, or antigen binding fragment thereof, that binds IL-4Rα comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 297; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 300. E193. The method of E185, wherein the antibody, or antigen binding fragment thereof, that binds OX40L comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 1; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 11; and wherein the antibody, or antigen binding fragment thereof, that binds IL- 4Rα comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 295; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 298. E194. The method of E185, wherein the antibody, or antigen binding fragment thereof, that binds OX40L comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 1; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 11; and wherein the antibody, or antigen binding fragment thereof, that binds IL- 4Rα comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 296; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 299. E195. The method of E185, wherein the antibody, or antigen binding fragment thereof, that binds OX40L comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 1; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 11; and wherein the antibody, or antigen binding fragment thereof, that binds IL- 4Rα comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 297; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 300. E196. The method of E185, wherein the antibody, or antigen binding fragment thereof, that binds OX40L comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 19; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 29; and wherein the antibody, or antigen binding fragment thereof, that binds IL-4Rα comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 295; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 298. E197. The method of E185, wherein the antibody, or antigen binding fragment thereof, that binds OX40L comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 19; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 29; and wherein the antibody, or antigen binding fragment thereof, that binds IL-4Rα comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 296; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 299. E198. The method of E185, wherein the antibody, or antigen binding fragment thereof, that binds OX40L comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 19; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 29; and wherein the antibody, or antigen binding fragment thereof, that binds IL-4Rα comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 297; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 300. E199. The method of E185, wherein the antibody, or antigen binding fragment thereof, that binds OX40L comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 37; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 47; and wherein the antibody, or antigen binding fragment thereof, that binds IL-4Rα comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 295; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 298. E200. The method of E185, wherein the antibody, or antigen binding fragment thereof, that binds OX40L comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 37; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 47; and wherein the antibody, or antigen binding fragment thereof, that binds IL-4Rα comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 296; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 299. E201. The method of E185, wherein the antibody, or antigen binding fragment thereof, that binds OX40L comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 37; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 47; and wherein the antibody, or antigen binding fragment thereof, that binds IL-4Rα comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 297; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 300. E202. The method of E185, wherein the antibody, or antigen binding fragment thereof, that binds OX40L comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 55; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 65; and wherein the antibody, or antigen binding fragment thereof, that binds IL-4Rα comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 295; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 298. E203. The method of E185, wherein the antibody, or antigen binding fragment thereof, that binds OX40L comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 55; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 65; and wherein the antibody, or antigen binding fragment thereof, that binds IL-4Rα comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 296; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 299. E204. The method of E185, wherein the antibody, or antigen binding fragment thereof, that binds OX40L comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 55; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 65; and wherein the antibody, or antigen binding fragment thereof, that binds IL-4Rα comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 297; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 300. E205. The method of any one of E159-E204, wherein the antibody, or antigen binding fragment thereof, that binds OX40L and/or the antibody, or antigen binding fragment thereof, that binds IL-4Rα is a humanized, human, or chimeric antibody. E206. The method of any one of E159-E205, wherein the antibody, or antigen binding fragment thereof, that binds OX40L and/or the antibody, or antigen binding fragment thereof, that binds IL-4Rα is a humanized antibody. E207. The method of any one of E159-E206, wherein the antibody, or antigen binding fragment thereof, that binds OX40L and/or the antibody, or antigen binding fragment thereof, that binds IL-4Rα comprises a heavy chain human constant region of a class selected from IgG, IgA, IgD, IgE, and IgM. E208. The method of any one of E159-E207, wherein the antibody, or antigen binding fragment thereof, that binds OX40L and/or the antibody, or antigen binding fragment thereof, that binds IL-4Rα comprises a human Fc region, and wherein the human Fc region comprises a human heavy chain constant region of the class IgG and a subclass selected from IgG1, IgG2, IgG3, and IgG4. E209. The method of E208, wherein the human Fc region of the antibody, or antigen binding fragment thereof, that binds OX40L and/or the antibody, or antigen binding fragment thereof, that binds IL-4Rα comprises a human IgG1 Fc region E210. The method of E208, wherein the human Fc region of the antibody, or antigen binding fragment thereof, that binds OX40L and/or the antibody, or antigen binding fragment thereof, that binds IL-4Rα comprises a human IgG4 Fc region. E211. The method of E208, wherein the human Fc region of the antibody, or antigen binding fragment thereof, that binds OX40L and/or the antibody, or antigen binding fragment thereof, that binds IL-4Rα comprises a human IgG2 Fc region. E212. The method of any one of E159-E211, wherein the heavy chain of the antibody that binds OX40L and/or the antibody that binds IL-4Rα comprises a constant heavy chain sequence selected from the amino acid sequences set forth in any one of SEQ ID NOs: 637-737 and 847-1070. E213. The method of any one of E159-E212, wherein the light chain of the antibody, or antigen binding fragment thereof, that binds OX40L and/or the antibody, or antigen binding fragment thereof, that binds IL-4Rα comprises a constant light chain sequence selected from the sequences set forth in SEQ ID NOs: 738 and 1071. E214. The method of any one of E159-E213, wherein the antibody, or antigen binding fragment thereof, that binds OX40L and/or the antibody, or antigen binding fragment thereof, that binds IL-4Rα comprises an Fc region comprising one or more amino acid substitutions, wherein the one or more substitutions result in an increase in one or more of antibody half-life, ADCC activity, ADCP activity, or CDC activity compared with the Fc without the one or more substitutions. E215. The method of any one of E159-E214, wherein the antibody, or antigen binding fragment thereof, that binds OX40L and/or the antibody, or antigen binding fragment thereof, that binds IL-4Rα comprises an Fc region comprising one or more amino acid substitutions, wherein the one or more substitutions result in a decrease in one or more of, ADCC activity, ADCP activity or CDC activity compared to an antibody comprising a wild-type Fc region. E216. The method of E214 or E215, wherein the one or more amino acid substitutions is selected from the group consisting of S228P, M252Y, S254T, T256E, T256D, T250Q, H285D, T307A, T307Q, T307R, T307W, L309D, Q411H, Q311V, A378V, E380A, M428L, N434A, N434S, N297A, D265A, L234A, L235A, and N434W; optionally, wherein the one or more amino acid substitutions comprises a plurality of amino acid substitutions selected from the group consisting of M428L/N434S (LS), M252Y/S254T/T256E (YTE), T250Q/M428L, T307A/E380A/N434A, T256D/T307Q (DQ), T256D/T307W (DW), M252Y/T256D (YD), T307Q/Q311V/A378V (QVV), T256D/H285D/T307R/Q311V/A378V (DDRVV), L309D/Q311H/N434S (DHS), S228P/L235E (SPLE), L234A/L235A (LALA), M428L/N434A (LA), L235A/G237A (LAGA), L234A/L235A/G237A (LALAGA), L234A/L235A/P329G (LALAPG), D265A/YTE, LALA/YTE, LAGA/YTE, LALAGA/YTE, LALAPG/YTE, N297A/LS, D265A/LS, LALA/LS, LALAGA/LS, LALAPG/LS, N297A/DHS, D265A/DHS, LALA/DHS, LAGA/DHS, LALAGA/DHS, LALAPG/DHS, SP/YTE, SPLE/YTE, SP/LS, SPLE/LS, SP/DHS, SPLE/DHS, N297A/LA, D265A/LA, LALA/LA, LAGA/LA, LALAGA/LA, LALAPG/LA, N297A/N434A, D265A/N434A, LALA/N434A, LAGA/N434A, LALAGA/N434A, LALAPG/N434A, N297A/N434W, D265A/N434W, LALA/N434W, LAGA/N434W, LALAGA/N434W, LALAPG/N434W, N297A/DQ, D265A/DQ, LALA/DQ, LAGA/DQ, LALAGA/DQ, LALAPG/DQ, N297A/DW, D265A/DW, LALA/DW, LAGA/DW, LALAGA/DW, LALAPG/DW, N297A/YD, D265A/YD, LALA/YD, LAGA/YD, LALAGA/YD, LALAPG/YD, T307Q/Q311V/A378V (QVV), N297A/QVV, D265A/QVV, LALA/QVV, LAGA/QVV, LALAGA/QVV, LALAPG/QVV, DDRVV, N297A/DDRVV, D265A/DDRVV, LALA/DDRVV, LAGA/DDRVV, LALAGA/DDRVV, and LALAPG/DDRVV. E217. The method of E216, wherein the one or more amino acid substitutions is selected from the group consisting of LS, YTE, T250Q/M428L, T307A/E380A/N434A, DQ, DW, YD, QVV, DHS, LA, D265A/YTE, LALA/YTE, LAGA/YTE, LALAGA/YTE, LALAPG/YTE, N297A/LS, D265A/LS, LALA/LS, LALAGA/LS, LALAPG/LS, N297A/DHS, D265A/DHS, LALA/DHS, LAGA/DHS, LALAGA/DHS, LALAPG/DHS, SP/YTE, SPLE/YTE, SP/LS, SPLE/LS, SP/DHS, SPLE/DHS, N297A/LA, D265A/LA, LALA/LA, LAGA/LA, LALAGA/LA, LALAPG/LA, N297A/DQ, D265A/DQ, LALA/DQ, LAGA/DQ, LALAGA/DQ, LALAPG/DQ, N297A/DW, D265A/DW, LALA/DW, LAGA/DW, LALAGA/DW, LALAPG/DW, N297A/YD, D265A/YD, LALA/YD, LAGA/YD, LALAGA/YD, LALAPG/YD, N297A/QVV, D265A/QVV, LALA/QVV, LAGA/QVV, LALAGA/QVV, and LALAPG/QVV. E218. The method of any one of E159-E217, wherein the antibody, or antigen binding fragment thereof, that binds OX40L comprises a VH domain comprising the amino acid sequence set forth in SEQ ID NO: 1, a VL domain comprising the amino acid sequence set forth in SEQ ID NO: 11, and a human IgG1 Fc region comprising LALA and YTE substitutions. E219. The method of any one of E159-E218, wherein the antibody, or antigen binding fragment thereof, that binds OX40L comprises a VH domain comprising the amino acid sequence set forth in SEQ ID NO: 1, a VL domain comprising the amino acid sequence set forth in SEQ ID NO: 11, a constant heavy chain sequence set forth in SEQ ID NO: 651 and/or a constant heavy chain sequence set forth in SEQ ID NO: 973, and a constant light chain sequence set forth in SEQ ID NO: 738. E220. The method of E219, wherein the antibody, or antigen binding fragment thereof, that binds OX40L comprises a VH domain comprising the amino acid sequence set forth in SEQ ID NO: 1, a VL domain comprising the amino acid sequence set forth in SEQ ID NO: 11, a constant heavy chain sequence set forth in SEQ ID NO: 973, and a light chain sequence set forth in SEQ ID NO: 738. E221. The method of E219, wherein the antibody, or antigen binding fragment thereof, that binds OX40L comprises a VH domain comprising the amino acid sequence set forth in SEQ ID NO: 1, a VL domain comprising the amino acid sequence set forth in SEQ ID NO: 11, a constant heavy chain sequence set forth in SEQ ID NO: 651, and a constant light chain sequence set forth in SEQ ID NO: 738. E222. The method of any one of E159-E221, wherein the antibody, or antigen binding fragment thereof, that binds IL-4Rα comprises a VH domain comprising the amino acid sequence set forth in SEQ ID NO: 297, a VL domain comprising the amino acid sequence set forth in SEQ ID NO: 300, and a human IgG1 Fc region comprising LALA and YTE substitutions. E223. The method of any one of E159-E222, wherein the antibody, or antigen binding fragment thereof, that binds IL-4Rα comprises a VH domain comprising the amino acid sequence set forth in SEQ ID NO: 297, a VL domain comprising the amino acid sequence set forth in SEQ ID NO: 300, a constant heavy chain sequence set forth in SEQ ID NO: 651 and/or a constant heavy chain sequence set forth in SEQ ID NO: 973, and a constant light chain sequence set forth in SEQ ID NO: 738. E224. The method of E223, wherein the antibody, or antigen binding fragment thereof, that binds IL-4Rα comprises a VH domain comprising the amino acid sequence set forth in SEQ ID NO: 297, a VL domain comprising the amino acid sequence set forth in SEQ ID NO: 300, a constant heavy chain sequence set forth in SEQ ID NO: 973, and a constant light chain sequence set forth in SEQ ID NO: 738. E225. The method of E223, wherein the antibody, or antigen binding fragment thereof, that binds IL-4Rα comprises a VH domain comprising the amino acid sequence set forth in SEQ ID NO: 297, a VL domain comprising the amino acid sequence set forth in SEQ ID NO: 300, a constant heavy chain sequence set forth in SEQ ID NO: 651, and a constant light chain sequence set forth in SEQ ID NO: 738. E226. The method of any one of E159-E225, wherein the Fc region of the antibody, or antigen binding fragment thereof, that binds OX40L and/or the antibody, or antigen binding fragment thereof, that binds IL-4Rα binds to Neonatal Fc receptor (FcRn). E227. The method of E226, wherein the Fc region of the antibody, or antigen binding fragment thereof, that binds OX40L and/or the antibody, or antigen binding fragment thereof, that binds IL-4Rα binds an FcRn with higher affinity at pH 6.0 compared to an antibody comprising a wild-type Fc region. E228. The method of E226 or E227, wherein the Fc region of the antibody, or antigen binding fragment thereof, that binds OX40L and/or the antibody, or antigen binding fragment thereof, that binds IL-4Rα binds to FcRn with a KD of <1 x 10-7 M at pH 6.0. E229. The method of any one of E159-E228, wherein the antibody, or antigen binding fragment thereof, that binds OX40L and/or the antibody, or antigen binding fragment thereof, that binds IL-4Rα is a monoclonal antibody. E230. The method of any one of E159-E229, wherein the antibody, or antigen binding fragment thereof, that binds OX40L binds an OX40L sequence set forth in the amino acid sequence of SEQ ID NO: 739. E231. The method of any one of E159-E230, wherein the antibody, or antigen binding fragment thereof, that binds IL-4Rα binds an IL-4Rα sequence set forth in the amino acid sequence of any one of SEQ ID NOs: 301-303. E232. The method of any one of E159-E231, wherein the OX40L antibody is Construct 114 and the IL-4Rα antibody is Construct 38. E233. The method of any one of E159-E168, wherein the OX40L antibody is Construct 114 and the IL-4Rα antibody is dupilumab, stapokibart, or 611. E234. The method of any one of E159-E168, wherein the OX40L antibody is amlitelimab or oxelumab and the IL-4Rα antibody is Construct 38. E235. The method of any one of E159-E234, wherein the pharmaceutical composition comprising the OX40L antibody or antigen binding fragment thereof is administered before the pharmaceutical composition comprising the IL-4Rα antibody or antigen binding fragment thereof. E236. The method of any one of E159-E234, wherein the pharmaceutical composition comprising the IL-4Rα antibody or antigen binding fragment thereof is administered before the pharmaceutical composition comprising the OX40L antibody or antigen binding fragment thereof. E237. The method of any one of E159-E234, wherein the pharmaceutical composition comprising the IL-4Rα antibody or antigen binding fragment thereof is administered at about the same time as the pharmaceutical composition comprising the OX40L antibody or antigen binding fragment thereof. E238. The method of any one of E159-E237, wherein the method further comprises administering a hyaluronidase or variant thereof. E239. The method of E238, wherein the hyaluronidase or variant thereof is administered before the pharmaceutical composition comprising the IL-4Rα antibody or antigen binding fragment thereof and the pharmaceutical composition comprising the OX40L antibody or antigen binding fragment thereof. E240. The method of E238, wherein the hyaluronidase or variant thereof is administered after the pharmaceutical composition comprising the IL-4Rα antibody or antigen binding fragment thereof and the pharmaceutical composition comprising the OX40L antibody or antigen binding fragment thereof. E241. The method of E238, wherein the hyaluronidase or variant thereof is administered after the pharmaceutical composition comprising the IL-4Rα antibody or antigen binding fragment thereof and before the pharmaceutical composition comprising the OX40L antibody or antigen binding fragment thereof. E242. The method of E238, wherein the hyaluronidase or variant thereof is administered after the pharmaceutical composition comprising the OX40L antibody or antigen binding fragment thereof and before the pharmaceutical composition comprising the IL-4Rα antibody or antigen binding fragment thereof. E243. A pharmaceutical composition comprising: an isolated antibody, or antigen binding fragment thereof, that binds OX40L comprising a VH domain comprising the amino acid sequence set forth in SEQ ID NO: 1, a VL domain comprising the amino acid sequence set forth in SEQ ID NO: 11, a constant heavy chain sequence set forth in any one of SEQ ID NOs: 651 and 973, and a constant light chain sequence set forth in SEQ ID NO: 738; an isolated antibody, or antigen binding fragment thereof, that binds IL-4Rα comprising a VH domain comprising the amino acid sequence set forth in SEQ ID NO: 297, a VL domain comprising the amino acid sequence set forth in SEQ ID NO: 300, a constant heavy chain sequence set forth in any one of SEQ ID NOs: 651 and 973, and a constant light chain sequence set forth in SEQ ID NO: 738; and a pharmaceutically acceptable excipient. E244. A pharmaceutical composition comprising: a multi-specific antibody comprising: an antigen binding region that binds OX40L comprising a VH domain comprising the amino acid sequence set forth in SEQ ID NO: 1, a VL domain comprising the amino acid sequence set forth in SEQ ID NO: 11, a constant heavy chain sequence set forth in any one of SEQ ID NOs: 651 and 973, and a constant light chain sequence set forth in SEQ ID NO: 738; an antigen binding region that binds IL-4Rα comprising a VH domain comprising the amino acid sequence set forth in SEQ ID NO: 297, a VL domain comprising the amino acid sequence set forth in SEQ ID NO: 300, a constant heavy chain sequence set forth in any one of SEQ ID NOs: 651 and 973, and a constant light chain sequence set forth in SEQ ID NO: 738; and a pharmaceutically acceptable excipient. E245. A composition comprising an isolated antibody, or antigen binding region thereof, that binds OX40L, an isolated antibody, or antigen binding region thereof, that binds Interleukin-4 Receptor Alpha (IL-4Rα), and a hyaluronidase or variant thereof. E246. A composition comprising an isolated antibody, or antigen binding region thereof, that binds OX40L, an isolated antibody, or antigen binding region thereof, that binds Interleukin-4 Receptor Alpha (IL-4Rα), and a hyaluronidase or variant thereof, wherein the antibody that binds OX40L comprises a CDR-H1 comprising the sequence set forth in SEQ ID NO: 2; a CDR-H2 comprising the sequence set forth in SEQ ID NO: 5; a CDR-H3 comprising the sequence set forth in SEQ ID NO: 8; a CDR-L1 comprising the sequence set forth in SEQ ID NO: 12; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 15; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 17. E247. The composition of E246, wherein the antibody that binds OX40L comprises a VH sequence set forth in SEQ ID NO: 1 and a VL sequence set forth in SEQ ID NO: 11. E248. A composition comprising an isolated antibody, or antigen binding region thereof, that binds OX40L, an isolated antibody, or antigen binding region thereof, that binds Interleukin-4 Receptor Alpha (IL-4Rα), and a hyaluronidase or variant thereof, wherein the antibody, or antigen binding region thereof, that binds IL-4Rα comprises a CDR-H1 comprising the sequence set forth in SEQ ID NO: 273; a CDR-H2 comprising the sequence set forth in SEQ ID NO: 279; a CDR-H3 comprising the sequence set forth in SEQ ID NO: 281; a CDR-L1 comprising the sequence set forth in SEQ ID NO: 289; a CDR-L2 comprising the sequence set. E249. The composition of E248 wherein the antibody that binds IL-4Rα comprises a VH sequence set forth in SEQ ID NO: 297 and a VL sequence set forth in SEQ ID NO: 300. E250. A composition comprising an isolated antibody, or antigen binding region thereof, that binds OX40L, an isolated antibody, or antigen binding region thereof, that binds Interleukin-4 Receptor Alpha (IL-4Rα), and a hyaluronidase or variant thereof, wherein the antibody, or antigen binding region thereof, that binds OX40L comprises a CDR-H1 comprising the sequence set forth in SEQ ID NO: 2; a CDR-H2 comprising the sequence set forth in SEQ ID NO: 5; a CDR-H3 comprising the sequence set forth in SEQ ID NO: 8; a CDR-L1 comprising the sequence set forth in SEQ ID NO: 12; a CDR- L2 comprising the sequence set forth in SEQ ID NO: 15; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 17, and wherein the antibody, or antigen binding region thereof, that binds IL-4Rα comprises a CDR-H1 comprising the sequence set forth in SEQ ID NO: 273; a CDR-H2 comprising the sequence set forth in SEQ ID NO: 279; a CDR-H3 comprising the sequence set forth in SEQ ID NO: 281; a CDR-L1 comprising the sequence set forth in SEQ ID NO: 289; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 290; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 293. E251. The composition of E250, wherein the antibody, or antigen binding region thereof, that binds OX40L comprises a VH sequence set forth in SEQ ID NO: 1 and a VL sequence set forth in SEQ ID NO: 11; and wherein the antibody, or antigen binding region thereof, that binds IL-4Rα comprises a VH sequence set forth in SEQ ID NO: 297 and a VL sequence set forth in SEQ ID NO: 300. E252. A composition comprising a hyaluronidase or variant thereof and a multi-specific antibody comprising a first antigen binding region that binds OX40L and a second antigen binding region that binds IL-4Rα, wherein the antigen binding region that binds OX40L comprises a CDR-H1 comprising the sequence set forth in SEQ ID NO: 2; a CDR-H2 comprising the sequence set forth in SEQ ID NO: 5; a CDR-H3 comprising the sequence set forth in SEQ ID NO: 8; a CDR- L1 comprising the sequence set forth in SEQ ID NO: 12; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 15; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 17, and wherein the antigen binding region that binds IL-4Rα comprises a CDR-H1 comprising the sequence set forth in SEQ ID NO: 273; a CDR-H2 comprising the sequence set forth in SEQ ID NO: 279; a CDR-H3 comprising the sequence set forth in SEQ ID NO: 281; a CDR-L1 comprising the sequence set forth in SEQ ID NO: 289; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 290; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 293. E253. The composition of E252,wherein the antigen binding region that binds OX40L comprises a VH sequence set forth in SEQ ID NO: 1 and a VL sequence set forth in SEQ ID NO: 11; and wherein the antigen binding region that binds IL-4Rα comprises a VH sequence set forth in SEQ ID NO: 297 and a VL sequence set forth in SEQ ID NO: 300. E254. A combination comprising an isolated antibody, or antigen binding region thereof, that binds OX40L, an isolated antibody, or antigen binding region thereof, that binds IL-4Rα, and a hyaluronidase or variant thereof, wherein the antibody, or antigen binding region thereof, that binds OX40L comprises a CDR-H1 comprising the sequence set forth in SEQ ID NO: 2; a CDR-H2 comprising the sequence set forth in SEQ ID NO: 5; a CDR-H3 comprising the sequence set forth in SEQ ID NO: 8; a CDR-L1 comprising the sequence set forth in SEQ ID NO: 12; a CDR- L2 comprising the sequence set forth in SEQ ID NO: 15; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 17, and wherein the antibody, or antigen binding region thereof, that binds IL-4Rα comprises a CDR-H1 comprising the sequence set forth in SEQ ID NO: 273; a CDR-H2 comprising the sequence set forth in SEQ ID NO: 279; a CDR-H3 comprising the sequence set forth in SEQ ID NO: 281; a CDR-L1 comprising the sequence set forth in SEQ ID NO: 289; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 290; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 293. E255. The combination of E254, wherein the antibody, or antigen binding region thereof, that binds OX40L comprises a VH sequence set forth in SEQ ID NO: 1 and a VL sequence set forth in SEQ ID NO: 11; and wherein the antibody, or antigen binding region thereof, that binds IL-4Rα comprises a VH sequence set forth in SEQ ID NO: 297 and a VL sequence set forth in SEQ ID NO: 300. E256. A combination comprising a hyaluronidase or a variant thereof and a multi-specific antibody comprising a first antigen binding region that binds OX40L and a second antigen binding region that binds IL-4Rα, wherein the antigen binding region that binds OX40L comprises a CDR-H1 comprising the sequence set forth in SEQ ID NO: 2; a CDR-H2 comprising the sequence set forth in SEQ ID NO: 5; a CDR-H3 comprising the sequence set forth in SEQ ID NO: 8; a CDR- L1 comprising the sequence set forth in SEQ ID NO: 12; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 15; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 17, and wherein the antigen binding region that binds IL-4Rα comprises a CDR-H1 comprising the sequence set forth in SEQ ID NO: 273; a CDR-H2 comprising the sequence set forth in SEQ ID NO: 279; a CDR-H3 comprising the sequence set forth in SEQ ID NO: 281; a CDR-L1 comprising the sequence set forth in SEQ ID NO: 289; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 290; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 293. E257. The combination of E256,wherein the antigen binding region that binds OX40L comprises a VH sequence set forth in SEQ ID NO: 1 and a VL sequence set forth in SEQ ID NO: 11; and wherein the antigen binding region that binds IL-4Rα comprises a VH sequence set forth in SEQ ID NO: 297 and a VL sequence set forth in SEQ ID NO: 300. E258. A method of treating an inflammatory disorder or disease in a human patient comprising administering to the patient an isolated antibody, or antigen binding region thereof, that binds OX40L, an isolated antibody, or antigen binding region thereof, that binds IL-4Rα, and a hyaluronidase or variant thereof, wherein the antibody, or antigen binding region thereof, that binds OX40L comprises a CDR-H1 comprising the sequence set forth in SEQ ID NO: 2; a CDR-H2 comprising the sequence set forth in SEQ ID NO: 5; a CDR-H3 comprising the sequence set forth in SEQ ID NO: 8; a CDR-L1 comprising the sequence set forth in SEQ ID NO: 12; a CDR- L2 comprising the sequence set forth in SEQ ID NO: 15; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 17, and wherein the antibody, or antigen binding region thereof, that binds IL-4Rα comprises a CDR-H1 comprising the sequence set forth in SEQ ID NO: 273; a CDR-H2 comprising the sequence set forth in SEQ ID NO: 279; a CDR-H3 comprising the sequence set forth in SEQ ID NO: 281; a CDR-L1 comprising the sequence set forth in SEQ ID NO: 289; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 290; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 293. E259. A method of treating an inflammatory disorder or disease in a human patient comprising administering to the patient an isolated antibody, or antigen binding region thereof, that binds OX40L, an isolated antibody, or antigen binding region thereof, that binds IL-4Rα, and a hyaluronidase or variant thereof, wherein the antibody, or antigen binding region thereof, that binds OX40L comprises a VH sequence set forth in SEQ ID NO: 1 and a VL sequence set forth in SEQ ID NO: 11; and wherein the antibody, or antigen binding region thereof, that binds IL-4Rα comprises a VH sequence set forth in SEQ ID NO: 297 and a VL sequence set forth in SEQ ID NO: 300. E260. A method of treating an inflammatory disorder or disease in a human patient comprising administering to the patient a hyaluronidase or a variant thereof and a multi-specific antibody comprising a first antigen binding region that binds OX40L and a second antigen binding region that binds IL-4Rα, wherein the antigen binding region that binds OX40L comprises a CDR-H1 comprising the sequence set forth in SEQ ID NO: 2; a CDR-H2 comprising the sequence set forth in SEQ ID NO: 5; a CDR-H3 comprising the sequence set forth in SEQ ID NO: 8; a CDR- L1 comprising the sequence set forth in SEQ ID NO: 12; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 15; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 17, and wherein the antigen binding region that binds IL-4Rα comprises a CDR-H1 comprising the sequence set forth in SEQ ID NO: 273; a CDR-H2 comprising the sequence set forth in SEQ ID NO: 279; a CDR-H3 comprising the sequence set forth in SEQ ID NO: 281; a CDR-L1 comprising the sequence set forth in SEQ ID NO: 289; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 290; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 293. E261. A method of treating an inflammatory disorder or disease in a human patient comprising administering to the patient a hyaluronidase or a variant thereof and a multi-specific antibody comprising a first antigen binding region that binds OX40L and a second antigen binding region that binds IL-4Rα, wherein the antigen binding region that binds OX40L comprises a VH sequence set forth in SEQ ID NO: 1 and a VL sequence set forth in SEQ ID NO: 11; and wherein the antigen binding region that binds IL-4Rα comprises a VH sequence set forth in SEQ ID NO: 297 and a VL sequence set forth in SEQ ID NO: 300. E262. The composition of any one of E245-E253, the combination of any one of E254-E257, or the method of any one of E258-E261, wherein the antibody or antigen binding region that binds OX40L and/or the antibody or antigen binding region that binds IL-4Rα comprises a human Fc region, and wherein the human Fc region comprises a human IgG1 Fc region. E263. The composition of any one of E245-E253, the combination of any one of E254-E257, or the method of any one of E258-E261, wherein the antibody or antigen binding region that binds OX40L and/or the antibody or antigen binding region that binds IL-4Rα comprises a human IgG1 Fc region with LALA and YTE mutations. E264. The composition of any one of E245-E253, the combination of any one of E254-E257, or the method of any one of E258-E261, wherein the antibody or antigen binding region that binds OX40L and/or the antibody or antigen binding region that binds IL-4Rα comprises a human Fc region, and wherein the human Fc region of the antibody or antigen binding region that binds OX40L comprises a human IgG1 Fc with LALA mutations (L235A/L236A by direct numbering) and YTE mutations (M253Y/S255T/T257E by direct numbering) and/or the human Fc region of the antibody or antigen binding region that binds IL-4Rα comprises a human IgG1 Fc with LALA mutations (L242A/L243A by direct numbering) and YTE mutations (M260Y/S262T/T264E by direct numbering). E265. The composition of any one of E245-E253, the combination of any one of E254-E257, or the method of any one of E258-E261, wherein the antibody or antigen binding region that binds OX40L comprises a heavy chain comprising a constant heavy chain sequence set forth in SEQ ID NO: 651 and/or SEQ ID NO: 973. E266. The composition, combination, or the method of E265, wherein the antibody or antigen binding region that binds OX40L comprises a heavy chain comprising a constant heavy chain sequence set forth in SEQ ID NO: 973. E267. The composition, combination, or the method of E265, wherein the antibody or antigen binding region that binds OX40L comprises a heavy chain comprising a constant heavy chain sequence set forth in SEQ ID NO: 651. E268. The composition of any one of E245-E253, the combination of any one of E254-E257, or the method of any one of E258-E261, wherein the antibody or antigen binding region that binds OX40L comprises a light chain comprising a constant light chain sequence set forth in SEQ ID NO: 738. E269. The composition of any one of E245-E253, the combination of any one of E254-E257, or the method of any one of E258-E261, wherein the antibody or antigen binding region that binds IL-4Rα comprises a heavy chain comprising a constant heavy chain sequence set forth in SEQ ID NO: 651 and/or SEQ ID NO: 973. E270. The composition, combination, or the method of E269, wherein the antibody or antigen binding region that binds IL-4Rα comprises a heavy chain comprising a constant heavy chain sequence set forth in SEQ ID NO: 973. E271. The composition, combination, or the method of E269, wherein the antibody or antigen binding region that binds IL-4Rα comprises a heavy chain comprising a constant heavy chain sequence set forth in SEQ ID NO: 651. E272. The composition of any one of E245-E253, the combination of any one of E254-E257, or the method of any one of E258-E261, wherein antibody or antigen binding region that binds IL-4Rα comprises a light chain of comprising a constant light chain sequence set forth in SEQ ID NO: 738. E273. The composition of any one of E245-E253, the combination of any one of E254-E257, or the method of any one of E258-E261, wherein the antibody or antigen binding region that binds OX40L is Construct 114 and the antibody or antigen binding region that binds IL-4Rα is Construct 38. E274. The composition of any one of E70, E144, and E245-E253, the combination of any one of E254-E257, or the method of any one of E238-E152 and E258-E261, wherein the hyaluronidase is a recombinant human hyaluronidase. E275. The composition, combination, or method of E274, wherein the recombinant human hyaluronidase comprises the amino acid sequence set forth in any one of SEQ ID NOs: 1082-1091 and 1093-1148 (e.g., SEQ ID NO: 1084). E276. The composition, combination, or method of E274, wherein the recombinant human hyaluronidase is rHuPH20. E277. The composition, combination, or method of E276, wherein the rHuPH20 formulation is ENHANZE®. E278. The composition of any one of E70, E144, and E245-E253, the combination of any one of E254-E257, or the method of any one of E238-E152 and E258-E261, wherein the hyaluronidase and antibody or antibodies are administered in separate formulations. E279. The composition of any one of E70, E144, and E245-E253, the combination of any one of E254-E257, or the method of any one of E238-E152 and E258-E261, wherein the hyaluronidase and antibody or antibodies are administered simultaneously in separate formulations. E280. The composition, combination, or method of E278, wherein the hyaluronidase is administered to the patient prior to administration of the antibody or antibodies. E281. The composition, combination, or method of E278, wherein the hyaluronidase is administered to the patient after administration of the antibody or antibodies. E282. The composition, combination, or method of E278, wherein the hyaluronidase is administered to the patient after administration of one of the antibodies, but before administration of the other antibody. E283. The composition of any one of E70, E144, and E245-E253, the combination of any one of E254-E257, or the method of any one of E238-E152 and E258-E261, wherein the hyaluronidase and antibody or antibodies are mixed and administered in a single formulation. E284. The composition of any one of E70, E144, and E245-E253, the combination of any one of E254-E257, or the method of any one of E238-E152 and E258-E261, wherein the hyaluronidase and antibody or antibodies are administered by subcutaneous injection. E285. The composition of any one of E70, E144, and E245-E253, the combination of any one of E254-E257, or the method of any one of E238-E152 and E258-E261, wherein the hyaluronidase and antibody or antibodies are administered by intravenous injection. E286. The composition of any one of E70, E144, and E245-E253, the combination of any one of E254-E257, or the method of any one of E238-E152 and E258-E261, wherein the hyaluronidase is rHuPH20 (ENHANZE®) administered at a concentration of 5,000, 6,000, 7,000, 8,000, 9,000, 10,000, 11,000, 12,000, 13,000, 14,000, 15,000, 16,000, 17,000, 18,000, 19,000, 20,000, 21,000, 22,000, 23,000, 24,000, 25,000, 26,000, 27,000, 28,000, 29,000, 30,000, 31,000, 32,000, 33,000, 34,000, 35,000, 36,000, 37,000, 38,000, 39,000, or 40,000 units. E287. The method of any one of E258-E261, wherein the inflammatory disorder or disease is atopic dermatitis. E288. The method of any one of E258-E261, wherein the inflammatory disorder or disease is asthma; chronic sinusitis with nasal polyps; Chronic Rhinosinusitis without Nasal Polyps (CRSsNP); eosinophilic esophagitis (EoE); an Eosinophilic gastrointestinal disorder or disease (EGID) selected from the group consisting of Eosinophilic Gastritis (EoG), Eosinophilic Enteritis (EoN), Eosinophilic Colitis (EoC), and Eosinophilic Gastroenteritis (EGE); Churg-Strauss syndrome/Eosinophilic granulomatosis with polyangiitis (EGPA); Prurigo Nodularis (PN); Chronic Spontaneous Urticaria (CSU); Chronic Pruritis of Unknown Origin (CPUO); Bullous Pemphigoid (BP); Cold Inducible Urticaria (ColdU); Allergic Fungal Rhinosinusitis (AFRS); Allergic Bronchopulmonary Aspergillosis (ABPA); Chronic Obstructive Pulmonary Disease (COPD); Crohn’s disease; lupus; rheumatoid arthritis (RA); psoriasis; ulcerative colitis; hidradenitis suppurativa; celiac disease; systemic sclerosis; idiopathic pulmonary fibrosis; alopecia areata, allergic rhinitis; eosinophilic fasciitis; scleromyxedema; scleredema; or nephrogenic systemic fibrosis. E289. A kit for treating an inflammatory disorder or disease in a human patient, the kit comprising: (a) an antibody, or antigen binding fragment thereof, that binds OX40L in unit dosage form, wherein the antibody comprises a VH sequence set forth in SEQ ID NO: 1 and a VL sequence set forth in SEQ ID NO: 11; (b) an antibody, or antigen binding fragment thereof, that binds IL-4Rα in unit dosage form, wherein the antibody comprises a VH sequence set forth in SEQ ID NO: 297 and a VL sequence set forth in SEQ ID NO: 300; (c) a hyaluronidase or variant thereof in unit dosage form; and (d) instructions. E290. The kit of E289, wherein the hyaluronidase is a recombinant human hyaluronidase. E291. The kit of E290, wherein the recombinant human hyaluronidase comprises the amino acid sequence set forth in any one of SEQ ID NOs: 1082-1091 and 1093-1148. E292. The kit of E290, wherein the recombinant human hyaluronidase is rHuPH20. E293. The kit of E292, wherein the rHuPH20 formulation is ENHANZE®. E294. The kit of E289, for use in treating an inflammatory disorder or disease. E295. The kit of E294, wherein the inflammatory disorder or disease is atopic dermatitis. E296. The kit of E294, wherein the inflammatory disorder or disease is asthma; chronic sinusitis with nasal polyps; Chronic Rhinosinusitis without Nasal Polyps (CRSsNP); eosinophilic esophagitis (EoE); an Eosinophilic gastrointestinal disorder or disease (EGID) selected from the group consisting of Eosinophilic Gastritis (EoG), Eosinophilic Enteritis (EoN), Eosinophilic Colitis (EoC), and Eosinophilic Gastroenteritis (EGE); Churg-Strauss syndrome/Eosinophilic granulomatosis with polyangiitis (EGPA); Prurigo Nodularis (PN); Chronic Spontaneous Urticaria (CSU); Chronic Pruritis of Unknown Origin (CPUO); Bullous Pemphigoid (BP); Cold Inducible Urticaria (ColdU); Allergic Fungal Rhinosinusitis (AFRS); Allergic Bronchopulmonary Aspergillosis (ABPA); Chronic Obstructive Pulmonary Disease (COPD); Crohn’s disease; lupus; rheumatoid arthritis (RA); psoriasis; ulcerative colitis; hidradenitis suppurativa; celiac disease; systemic sclerosis; idiopathic pulmonary fibrosis; alopecia areata, allergic rhinitis; eosinophilic fasciitis; scleromyxedema; scleredema; or nephrogenic systemic fibrosis. INCORPORATION BY REFERENCE [00779] The entire disclosure of each of the patent and scientific documents referred to herein is incorporated by reference for all purposes. EQUIVALENTS [00780] The invention may be embodied in other specific forms without departing from the spirit or essential characteristics thereof. The foregoing embodiments are therefore to be considered in all respects illustrative rather than limiting on the invention described herein. Scope of the invention is thus indicated by the appended claims rather than by the foregoing description, and all changes that come within the meaning and range of equivalency of the claims are intended to be embraced therein.
INFORMAL SEQUENCE LISTING SEQ ID Description Sequence NO OX40L Construct 114 DIQMTQSPSSLSASVGDRVTITCRASQDIRNDLAWYQQKPGK OX40L Antibody 231 OX40L Antibody 231 OX40L Antibody 328 OX40L Antibody 328 OX40L 65 Antibody 105 DIQMTQSPSSLSASVGDRVTITCRASQGIRNDLGWYQQKPGK SSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSW NSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCN IL4-Rα Kabat 283 and Chothia EVQLVESGGGLEQPGGSLRLSCAGSGFTFRDFAMTWVRQAP 295 IL4-Rα Heavy GKGLEWVSSVSGSGGNTYYADSVKGRFTISRDNSKNTLYLQ GTQASAVVGLGPPGEAGYKAFSSLLASSAVSPEKCGFGASSG EEGYKPFQDLIPGCPGDPAPVPVPLFTFGLDREPPRSPQSSHLP AGWCPMEVSRTVLWPENVSVSVVRCMELFEAPVQNVEEEE DEIVKEDLSMSPENSGGCGFQESQADIMARLTENLFSDLLEA ASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNS GALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNV NAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSN KALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCL ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWN SGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNV NAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSN KALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCL ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWN SGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNV NAKTKPREEQYNSTYRVVSVLTVDHHDWLNGKEYKCKVSN KALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCL ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWN SGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNV KPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPS SIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFY ASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNS GALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNV TKPREEQFNSTFRVVSVLTVDHHDWLNGKEYKCKVSNKGLP APIEKTISKTKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGF ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWN SGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNV NAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSN KALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCL ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWN SGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNV NAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSN KALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCL ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWN SGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNV NAKTKPREEQYNSTYRVVSVLQVLHQDWLNGKEYKCKVSN KALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCL ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWN SGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNV NAKTKPREEQYNSTYRVVSVLWVLHQDWLNGKEYKCKVSN KALGAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCL ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWN SGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNV NAKTKPREEQYASTYRVVSVLQVLHVDWLNGKEYKCKVSN KALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCL ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWN SGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNV NAKTKPREEQYNSTYRVVSVLRVLHVDWLNGKEYKCKVSN KALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCL EVQLVESGGGLVQPGGSLRLSCAASGFTFSNYAMNWVRQAP GKGLEWVSTISGSGGATRYADSVKGRFTISRDNSRNTVYLQ Construct 38 DIVMTQSPLSLPVTPGEPASISCRSSQSLLYSIGKNYVDWYLQ (mAb471) light KSGQSPQLLIYEGNKRASGVPDRFSGSGSGTDFTLKISRVEAE MNSLRVEDTAVFYCTKDRLIMATVRGPYYYGMDVWGQGTT VTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVT YPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDK SRWQEGNVFSCSVMHEALHNHYTQKSLSLSLG hIgG1-D265A NHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFP PKPKDTLMISRTPEVTCVVVAVSHEDPEVKFNWYVDGVEVH VKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKL TVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG hIgG1- NHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELAGAPSVFLFP LAGA/YTE PKPKDTLYITREPEVTCVVVDVSHEDPEVKFNWYVDGVEVH VKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKL TVDKSRWQQGNVFSCSVLHEALHSHYTQKSLSLSPG hIgG1- NHKPSNTKVDKKVEPKSCDKTHTCPPCPAPEAAGGPSVFLFP LALAPG/LS PKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVH VKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKL TVDKSRWQQGNVFSCSVMHEALHSHYTQKSLSLSPG hIgG4-SP/YTE DHKPSNTKVDKRVESKYGPPCPPCPAPEFLGGPSVFLFPPKPK DTLYITREPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKT YPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDK SRWQEGNVFSCSVLHEALHSHYTQKSLSLSLGK hIgG2-LS DHKPSNTKVDKTVERKCCVECPPCPAPPVAGPSVFLFPPKPK DTLMISRTPEVTCVVVDVSHEDPEVQFNWYVDGVEVHNAK VKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKL TVDKSRWQQGNVFSCSVLHEALHAHYTQKSLSLSPG hIgG1- NHKPSNTKVDKKVEPKSCDKTHTCPPCPAPEAAGGPSVFLFP LALAPG/LA PKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVH VKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKL TVDKSRWQQGNVFSCSVMHEALHAHYTQKSLSLSPG hIgG1-N297A/ NHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFP N434W PKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVH VKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKL TVDKSRWQQGNVFSCSVMHEALHWHYTQKSLSLSPG hIgG1- NHKPSNTKVDKKVEPKSCDKTHTCPPCPAPEAAGGPSVFLFP LALA/DQ PKPKDTLMISRDPEVTCVVVDVSHEDPEVKFNWYVDGVEVH VKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKL TVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG hIgG1- NHKPSNTKVDKKVEPKSCDKTHTCPPCPAPEAAGAPSVFLFP LALAGA/DW PKPKDTLMISRDPEVTCVVVDVSHEDPEVKFNWYVDGVEVH ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWN SGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNV Heavy Chain NHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELAGAPSVFLFP VKGFYPSDIVVEWESNGQPENNYKTTPPVLDSDGSFFLYSKL TVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWN hIgG1- KALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCL LALA/DDRVV VKGFYPSDIVVEWESNGQPENNYKTTPPVLDSDGSFFLYSKL TVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG IgG4- DTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAK SPLE/Q311R/M TKPREEQFNSTYRVVSVLTVLHRDWLNGKEYKCKVSNKGLP 428L SSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGF Constant Region NHKPSNTKVDKKVEPKSCDKTHTCPPCPAPEAAGGPSVFLFP hIgG1- PKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVH NAKTKPREEQYNSTYRVVSVLTVLHRDWLNGKEYKCKVSN ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWN SGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNV NHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFP VKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKL TVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWN KALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCL VKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKL TVDKSRWQQGNVFSCSVLHEALHSHYTQKSLSLSPGK hIgG1- NAKTKPREEQYASTYRVVSVLTVDHHDWLNGKEYKCKVSN N297A/DHS KALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCL VKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKL hIgG4-SP/YTE DTLYITREPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKT KPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPS SIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFY Constant Region DHKPSNTKVDKRVESKYGPPCPPCPAPEELGGPSVFLFPPKPK hIgG4- DTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAK TKPREEQFNSTYRVVSVLTVDHHDWLNGKEYKCKVSNKGL ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWN SGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNV NHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFP VKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKL TVDKSRWQQGNVFSCSVMHEALHAHYTQKSLSLSPGK ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWN KALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCL VKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKL TVDKSRWQQGNVFSCSVMHEALHWHYTQKSLSLSPGK hIgG1- NAKTKPREEQYASTYRVVSVLQVLHQDWLNGKEYKCKVSN N297A/DQ KALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCL VKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKL hIgG1- PKPKDTLMISRDPEVTCVVVDVSHEDPEVKFNWYVDGVEVH N297A/DW NAKTKPREEQYASTYRVVSVLWVLHQDWLNGKEYKCKVSN KALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCL ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWN SGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNV NHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFP VKGFYPSDIVVEWESNGQPENNYKTTPPVLDSDGSFFLYSKL TVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWN KALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCL VKGFYPSDIVVEWESNGQPENNYKTTPPVLDSDGSFFLYSKL TVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK hIgG1- NAKTKPREEQYNSTYRVVSVLTVLHRDWLNGKEYKCKVSN Q311R/M428L KALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCL VKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKL Heavy Chain ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWN Constant Region SGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNV NHKPSNTKVDKKVEPKSCDKTHTCPPCPAPEAAGGPSVFLFP MNSLRAEDTAVYYCARATARATEFAYWGQGTLVTVSSAST KGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGA LTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDH ces set forth in the table above, and either a SRDEL allotype heavy chain constant region sequence or a SREEM allotype heavy chain constant region sequence may be included in an anti-OX40L antibody, an anti-IL-4Rα antibody, or a multi-specific antibody described herein. SEQ ID NO: 1076 I I G Y T C SEQ ID NO: 1079 LNFRAPPVIPNVPFLWAWNAPSEFCLGKFDEPLDMSLFSFIGSPRINATGQGVTIFYVDRLGYYPYI I G Y T C I I G Y T C I I G Y T C I I G Y T C I I G Y T C I I G Y T C SEQ ID NO: 1085 LNFRAPPVIPNVPFLWAWNAPSEFCLGKFDEPLDMSLFSFIGSPRINATGQGVTIFYVDRLGYYPYI I G Y T C
SEQ ID NO: 1087 L A Ph A Al P P Vl Il P A Vl P Ph L T
SEQ ID NO: 1088 L A Ph A Al P P Vl Il P A Vl P Ph L T
SEQ ID NO: 1089 L A Ph A Al P P Vl Il P A Vl P Ph L T
SEQ ID NO: 1090 L A Ph A Al P P Vl Il P A Vl P Ph L T
SEQ ID NO: 1091 L A Ph A Al P P Vl Il P A Vl P Ph L T
SEQ ID NO: 1092 L A Ph A Al P P Vl Il P A Vl P Ph L T
SEQ ID NO: 1093
SEQ ID NO: 1094 L A Ph A Al P P Vl Il P A Vl P Ph L T
SEQ ID NO: 1095 L A Ph A Al P P Vl Il P A Vl P Ph L T
SEQ ID NO: 1096 L A Ph A Al P P Vl Il P A Vl P Ph L T
SEQ ID NO: 1097 L A Ph A Al P P Vl Il P A Vl P Ph L T
SEQ ID NO: 1098 Ph A Al P P Vl Il P A Vl P Ph L T Al T
SEQ ID NO: 1099 L A Ph A Al P P Vl Il P A Vl P Ph L T
SEQ ID NO: 1100
SEQ ID NO: 1101 L A Ph A Al P P Vl Il P A Vl P Ph L T
SEQ ID NO: 1102 Ph A l P L L P A A P Ph L T Al T A
SEQ ID NO: 1103 Ph A l P L L P A A P Ph Th Th Vl T A
SEQ ID NO: 1104 Ph A Al P P Vl Il P A Vl P Ph L T Al T
SEQ ID NO: 1105 Ph A Al P P Vl Il P A Vl P Ph L T Al T
SEQ ID NO: 1106 L A Ph A Al P P Vl Il P A Vl P Ph L T
SEQ ID NO: 1107 Al P P Vl Il P A Vl P Ph L T Al T A Al
SEQ ID NO: 1108 P Vl Il P A Vl P Ph L T Al T A Al P
SEQ ID NO: 1109 L A Ph A Al P P Vl Il P A Vl P Ph L T
SEQ ID NO: 1110 L A Ph A Al P P Vl Il P A Vl P Ph L T
SEQ ID NO: 1111 L A Ph A Al P P Vl Il P A Vl P Ph L T
SEQ ID NO: 1112 L A Ph A Al P P Vl Il P A Vl P Ph L T
SEQ ID NO: 1113 L A Ph A Al P P Vl Il P A Vl P Ph L T
SEQ ID NO: 1114 Ph A Al P P Vl Il P A Vl P Ph L T Al T
SEQ ID NO: 1115 Ph A Al P P Vl Il P A Vl P Ph L T Al T
SEQ ID NO: 1116 Ph A Al P P Vl Il P A Vl P Ph L T Al T
SEQ ID NO: 1117 Ph A Al P P Vl Il P A Vl P Ph L T Al T
SEQ ID NO: 1118 Ph A Al P P Vl Il P A Vl P Ph L T Al T
SEQ ID NO: 1119 Ph A Al P P Vl Il P A Vl P Ph L T Al T
SEQ ID NO: 1120
SEQ ID NO: 1121 A Al P P Vl Il P A Vl P Ph L T Al T A
SEQ ID NO: 1122 P P Vl Il P A Vl P Ph L T Al T A Al P
SEQ ID NO: 1123 Ph A Al P P Vl Il P A Vl P Ph L T Al T
SEQ ID NO: 1124 Ph A Al P P Vl Il P A Vl P Ph L T Al T
SEQ ID NO: 1125 Ph A Al P P Vl Il P A Vl P Ph L T Al T
SEQ ID NO: 1126 Ph A Al P P Vl Il P A Vl P Ph L T Al T
SEQ ID NO: 1127 Ph A Al P P Vl Il P A Vl P Ph L T Al T
SEQ ID NO: 1128 Ph A Al P P Vl Il P A Vl P Ph L T Al T
SEQ ID NO: 1129 Ph A Al P P Vl Il P A Vl P Ph L T Al T
SEQ ID NO: 1130 Ph A Al P P Vl Il P A Vl P Ph L T Al T
SEQ ID NO: 1131 Ph A Al P P Vl Il P A Vl P Ph L T Al T
SEQ ID NO: 1132 Ph A Al P P Vl Il P A Vl P Ph L T Al T
SEQ ID NO: 1133 L A Ph A Al P P Vl Il P A Vl P Ph L T
SEQ ID NO: 1134 L A Ph A Al P P Vl Il P A Vl P Ph L T
SEQ ID NO: 1135 L A Ph A Al P P Vl Il P A Vl P Ph L T
SEQ ID NO: 1136 L A Ph A Al P P Vl Il P A Vl P Ph L T
SEQ ID NO: 1137 Ph A Al P P Vl Il P A Vl P Ph L T Al T
SEQ ID NO: 1138 Ph A Al P P Vl Il P A Vl P Ph L T Al T
SEQ ID NO: 1139 Ph A Al P P Vl Il P A Vl P Ph L T Al T
SEQ ID NO: 1140 Ph A Al P P Vl Il P A Vl P Ph L T Al T
SEQ ID NO: 1141 Ph A l P P Vl Il P A Vl P Ph L T Al T
SEQ ID NO: 1142 Ph A l P P Vl Il P A Vl P Ph L T Al T

Claims

CLAIMS 1. An isolated antibody, or an antigen binding fragment thereof, that binds OX40L, comprising: a) a variable heavy (VH) chain sequence having three heavy chain CDR sequences, CDR-H1, CDR-H2, and CDR-H3; and b) a variable light (VL) chain sequence having three light chain CDR sequences, CDR-L1, CDR-L2, and CDR-L3; wherein the antibody, or an antigen binding fragment thereof, that binds OX40L comprises: (i) a CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 2-4; a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 5-7; a CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 8-10; a CDR-L1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 12-14; a CDR-L2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 15-16; and a CDR-L3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 17-18; (ii) a CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 20-22; a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 23-25; a CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 26-28; a CDR-L1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 30-32; a CDR-L2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 33-34; and a CDR-L3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 35-36; (iii) a CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 38-40; a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 41-43; a CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 44-46; a CDR-L1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 48-50; a CDR-L2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 51-52; and a CDR-L3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 53-54; or (iv) a CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 56-58; a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 59-61; a CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 62-64; a CDR-L1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 66-68; a CDR-L2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 69-70; and a CDR-L3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 71-72; and an isolated antibody, or an antigen binding fragment thereof, that binds IL-4Rα. 2. The isolated antibodies of claim 1, wherein the isolated antibody, or antigen binding fragment thereof, that binds IL-4Rα comprises a CDR-H1, CDR-H2, CDR-H3, CDR-L1, CDR- L2, and CDR-L3 of an antibody selected from dupilumab, stapokibart, and 611. 3. The isolated antibodies of claim 1, wherein the isolated antibody, or antigen binding fragment thereof, that binds IL-4Rα comprises: a) a VH chain sequence having three heavy chain CDR sequences, CDR-H1, CDR-H2, and CDR-H3; and b) a VL chain sequence having three light chain CDR sequences, CDR-L1, CDR-L2, and CDR-L3, wherein the isolated antibody, or antigen binding fragment thereof, that binds IL-4Rα comprises: (i) a CDR-H1 comprising the sequence set forth in any one of SEQ ID NOs: 273, 274, and 275; a CDR-H2 comprising the sequence set forth in any one of SEQ ID NOs: 276, 277, and 278; a CDR-H3 comprising the sequence set forth in any one of SEQ ID NOs: 281 and 282; a CDR-L1 comprising the sequence set forth in any one of SEQ ID NOs: 285 and 286; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 292 or the amino acid sequence LG; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 293; (ii) a CDR-H1 comprising the sequence set forth in any one of SEQ ID NOs: 273, 274, and 275; a CDR-H2 comprising the sequence set forth in any one of SEQ ID NOs: 279, 277, and 280; a CDR-H3 comprising the sequence set forth in any one of SEQ ID NOs: 283 and 284; a CDR-L1 comprising the sequence set forth in any one of SEQ ID NOs: 287 and 288; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 291 or the amino acid sequence LG; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 293; or (iii) a CDR-H1 comprising the sequence set forth in any one of SEQ ID NOs: 273, 274, and 275; a CDR-H2 comprising the sequence set forth in any one of SEQ ID NOs: 279, 277, and 280; a CDR-H3 comprising the sequence set forth in any one of SEQ ID NOs: 281 and 282; a CDR-L1 comprising the sequence set forth in any one of SEQ ID NOs: 289 and 288; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 290 or the amino acid sequence EG; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 293. 4. An isolated antibody that binds OX40L, or an antigen binding fragment thereof; and an isolated antibody that binds IL-4Rα, or an antigen binding fragment thereof, comprising: a) a variable heavy (VH) chain sequence having three heavy chain CDR sequences, CDR-H1, CDR- H2, and CDR-H3; and b) a variable light (VL) chain sequence having three light chain CDR sequences, CDR-L1, CDR-L2, and CDR-L3; wherein the antibody, or antigen binding fragment thereof, that binds IL-4Rα comprises: (i) a CDR-H1 comprising the sequence set forth in any one of SEQ ID NOs: 273, 274, and 275; a CDR-H2 comprising the sequence set forth in any one of SEQ ID NOs: 276, 277, and 278; a CDR-H3 comprising the sequence set forth in any one of SEQ ID NOs: 281 and 282; a CDR-L1 comprising the sequence set forth in any one of SEQ ID NOs: 285 and 286; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 292 or the amino acid sequence LG; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 293; (ii) a CDR-H1 comprising the sequence set forth in any one of SEQ ID NOs: 273, 274, and 275; a CDR-H2 comprising the sequence set forth in any one of SEQ ID NOs: 279, 277, and 280; a CDR-H3 comprising the sequence set forth in any one of SEQ ID NOs: 283 and 284; a CDR-L1 comprising the sequence set forth in any one of SEQ ID NOs: 287 and 288; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 291 or the amino acid sequence LG; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 293; or (iii) a CDR-H1 comprising the sequence set forth in any one of SEQ ID NOs: 273, 274, and 275; a CDR-H2 comprising the sequence set forth in any one of SEQ ID NOs: 279, 277, and 280; a CDR-H3 comprising the sequence set forth in any one of SEQ ID NOs: 281 and 282; a CDR-L1 comprising the sequence set forth in any one of SEQ ID NOs: 289 and 288; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 290 or the amino acid sequence EG; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 293. 5. The isolated antibodies of claim 4, wherein the isolated antibody, or antigen binding fragment thereof, that binds OX40L comprises a CDR-H1, CDR-H2, CDR-H3, CDR-L1, CDR- L2, and CDR-L3 of an antibody selected from amlitelimab and oxelumab. 6. The isolated antibodies of claim 4, wherein the isolated antibody, or antigen binding fragment thereof, that binds OX40L comprises: a) a VH chain sequence having three heavy chain CDR sequences, CDR-H1, CDR-H2, and CDR-H3; and b) a VL chain sequence having three light chain CDR sequences, CDR-L1, CDR-L2, and CDR-L3, wherein the isolated antibody, or antigen binding fragment thereof, that binds OX40L comprises: (i) a CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 2-4; a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 5-7; a CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 8-10; a CDR-L1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 12-14; a CDR-L2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 15-16; and a CDR-L3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 17-18; (i) a CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 20-22; a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 23-25; a CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 26-28; a CDR-L1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 30-32; a CDR-L2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 33-34; and a CDR-L3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 35-36; (iii) a CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 38-40; a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 41-43; a CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 44-46; a CDR-L1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 48-50; a CDR-L2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 51-52; and a CDR-L3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 53-54; or (iv) a CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 56-58; a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 59-61; a CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 62-64; a CDR-L1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 66-68; a CDR-L2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 69-70; and a CDR-L3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 71-72. 7. The isolated antibodies of claim 3 or 6, wherein: (a) the antibody, or antigen binding fragment thereof, that binds OX40L comprises: (i) a CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 2-4; a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 5-7; a CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 8-10; a CDR-L1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 12-14; a CDR-L2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 15-16; and a CDR-L3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 17-18; and (b) the antibody, or antigen binding fragment thereof, that binds IL-4Rα comprises: (i) a CDR-H1 comprising the sequence set forth in any one of SEQ ID NOs: 273, 274, and 275; a CDR-H2 comprising the sequence set forth in any one of SEQ ID NOs: 276, 277, and 278; a CDR-H3 comprising the sequence set forth in any one of SEQ ID NOs: 281 and 282; a CDR-L1 comprising the sequence set forth in any one of SEQ ID NOs: 285 and 286; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 292 or the amino acid sequence LG; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 293. 8. The isolated antibodies of claim 3 or 6, wherein: (a) the antibody, or antigen binding fragment thereof, that binds OX40L comprises: (ii) a CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 20-22; a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 23-25; a CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 26-28; a CDR-L1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 30-32; a CDR-L2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 33-34; and a CDR-L3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 35-36; and (b) the antibody, or antigen binding fragment thereof, that binds IL-4Rα comprises: (i) a CDR-H1 comprising the sequence set forth in any one of SEQ ID NOs: 273, 274, and 275; a CDR-H2 comprising the sequence set forth in any one of SEQ ID NOs: 276, 277, and 278; a CDR-H3 comprising the sequence set forth in any one of SEQ ID NOs: 281 and 282; a CDR-L1 comprising the sequence set forth in any one of SEQ ID NOs: 285 and 286; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 292 or the amino acid sequence LG; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 293. 9. The isolated antibodies of claim 3 or 6, wherein: (a) the antibody, or antigen binding fragment thereof, that binds OX40L comprises: (iii) a CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 38-40; a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 41-43; a CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 44-46; a CDR-L1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 48-50; a CDR-L2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 51-52; and a CDR-L3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 53-54; and (b) the antibody, or antigen binding fragment thereof, that binds IL-4Rα comprises: (i) a CDR-H1 comprising the sequence set forth in any one of SEQ ID NOs: 273, 274, and 275; a CDR-H2 comprising the sequence set forth in any one of SEQ ID NOs: 276, 277, and 278; a CDR-H3 comprising the sequence set forth in any one of SEQ ID NOs: 281 and 282; a CDR-L1 comprising the sequence set forth in any one of SEQ ID NOs: 285 and 286; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 292 or the amino acid sequence LG; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 293. 10. The isolated antibodies of claim 3 or 6, wherein: (a) the antibody, or antigen binding fragment thereof, that binds OX40L comprises: (iv) a CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 56-58; a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 59-61; a CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 62-64; a CDR-L1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 66-68; a CDR-L2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 69-70; and a CDR-L3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 71-72; and (b) the antibody, or antigen binding fragment thereof, that binds IL-4Rα comprises: (i) a CDR-H1 comprising the sequence set forth in any one of SEQ ID NOs: 273, 274, and 275; a CDR-H2 comprising the sequence set forth in any one of SEQ ID NOs: 276, 277, and 278; a CDR-H3 comprising the sequence set forth in any one of SEQ ID NOs: 281 and 282; a CDR-L1 comprising the sequence set forth in any one of SEQ ID NOs: 285 and 286; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 292 or the amino acid sequence LG; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 293. 11. The isolated antibodies of claim 3 or 6, wherein: (a) the antibody, or antigen binding fragment thereof, that binds OX40L comprises: (i) a CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 2-4; a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 5-7; a CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 8-10; a CDR-L1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 12-14; a CDR-L2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 15-16; and a CDR-L3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 17-18; and (b) the antibody, or antigen binding fragment thereof, that binds IL-4Rα comprises: (ii) a CDR-H1 comprising the sequence set forth in any one of SEQ ID NOs: 273, 274, and 275; a CDR-H2 comprising the sequence set forth in any one of SEQ ID NOs: 279, 277, and 280; a CDR-H3 comprising the sequence set forth in any one of SEQ ID NOs: 283 and 284; a CDR-L1 comprising the sequence set forth in any one of SEQ ID NOs: 287 and 288; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 291 or the amino acid sequence LG; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 293. 12. The isolated antibodies of claim 3 or 6, wherein: (a) the antibody, or antigen binding fragment thereof, that binds OX40L comprises: (ii) a CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 20-22; a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 23-25; a CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 26-28; a CDR-L1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 30-32; a CDR-L2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 33-34; and a CDR-L3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 35-36; and (b) the antibody, or antigen binding fragment thereof, that binds IL-4Rα comprises: (ii) a CDR-H1 comprising the sequence set forth in any one of SEQ ID NOs: 273, 274, and 275; a CDR-H2 comprising the sequence set forth in any one of SEQ ID NOs: 279, 277, and 280; a CDR-H3 comprising the sequence set forth in any one of SEQ ID NOs: 283 and 284; a CDR-L1 comprising the sequence set forth in any one of SEQ ID NOs: 287 and 288; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 291 or the amino acid sequence LG; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 293. 13. The isolated antibodies of claim 3 or 6, wherein: (a) the antibody, or antigen binding fragment thereof, that binds OX40L comprises: (iii) a CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 38-40; a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 41-43; a CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 44-46; a CDR-L1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 48-50; a CDR-L2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 51-52; and a CDR-L3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 53-54; and (b) the antibody, or antigen binding fragment thereof, that binds IL-4Rα comprises: (ii) a CDR-H1 comprising the sequence set forth in any one of SEQ ID NOs: 273, 274, and 275; a CDR-H2 comprising the sequence set forth in any one of SEQ ID NOs: 279, 277, and 280; a CDR-H3 comprising the sequence set forth in any one of SEQ ID NOs: 283 and 284; a CDR-L1 comprising the sequence set forth in any one of SEQ ID NOs: 287 and 288; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 291 or the amino acid sequence LG; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 293. 14. The isolated antibodies of claim 3 or 6, wherein: (a) the antibody, or antigen binding fragment thereof, that binds OX40L comprises: (iv) a CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 56-58; a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 59-61; a CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 62-64; a CDR-L1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 66-68; a CDR-L2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 69-70; and a CDR-L3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 71-72; and (b) the antibody, or antigen binding fragment thereof, that binds IL-4Rα comprises: (ii) a CDR-H1 comprising the sequence set forth in any one of SEQ ID NOs: 273, 274, and 275; a CDR-H2 comprising the sequence set forth in any one of SEQ ID NOs: 279, 277, and 280; a CDR-H3 comprising the sequence set forth in any one of SEQ ID NOs: 283 and 284; a CDR-L1 comprising the sequence set forth in any one of SEQ ID NOs: 287 and 288; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 291 or the amino acid sequence LG; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 293. 15. The isolated antibodies of claim 3 or 6, wherein: (a) the antibody, or antigen binding fragment thereof, that binds OX40L comprises: (i) a CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 2-4; a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 5-7; a CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 8-10; a CDR-L1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 12-14; a CDR-L2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 15-16; and a CDR-L3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 17-18; and (b) the antibody, or antigen binding fragment thereof, that binds IL-4Rα comprises: (iii) a CDR-H1 comprising the sequence set forth in any one of SEQ ID NOs: 273, 274, and 275; a CDR-H2 comprising the sequence set forth in any one of SEQ ID NOs: 279, 277, and 280; a CDR-H3 comprising the sequence set forth in any one of SEQ ID NOs: 281 and 282; a CDR-L1 comprising the sequence set forth in any one of SEQ ID NOs: 289 and 288; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 290 or the amino acid sequence EG; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 293. 16. The isolated antibodies of claim 3 or 6, wherein: (a) the antibody, or antigen binding fragment thereof, that binds OX40L comprises: (ii) a CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 20-22; a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 23-25; a CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 26-28; a CDR-L1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 30-32; a CDR-L2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 33-34; and a CDR-L3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 35-36; and (b) the antibody, or antigen binding fragment thereof, that binds IL-4Rα comprises: (iii) a CDR-H1 comprising the sequence set forth in any one of SEQ ID NOs: 273, 274, and 275; a CDR-H2 comprising the sequence set forth in any one of SEQ ID NOs: 279, 277, and 280; a CDR-H3 comprising the sequence set forth in any one of SEQ ID NOs: 281 and 282; a CDR-L1 comprising the sequence set forth in any one of SEQ ID NOs: 289 and 288; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 290 or the amino acid sequence EG; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 293. 17. The isolated antibodies of claim 3 or 6, wherein: (a) the antibody, or antigen binding fragment thereof, that binds OX40L comprises: (iii) a CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 38-40; a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 41-43; a CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 44-46; a CDR-L1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 48-50; a CDR-L2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 51-52; and a CDR-L3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 53-54; and (b) the antibody, or antigen binding fragment thereof, that binds IL-4Rα comprises: (iii) a CDR-H1 comprising the sequence set forth in any one of SEQ ID NOs: 273, 274, and 275; a CDR-H2 comprising the sequence set forth in any one of SEQ ID NOs: 279, 277, and 280; a CDR-H3 comprising the sequence set forth in any one of SEQ ID NOs: 281 and 282; a CDR-L1 comprising the sequence set forth in any one of SEQ ID NOs: 289 and 288; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 290 or the amino acid sequence EG; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 293. 18. The isolated antibodies of claim 3 or 6, wherein: (a) the antibody, or antigen binding fragment thereof, that binds OX40L comprises: (iv) a CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 56-58; a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 59-61; a CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 62-64; a CDR-L1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 66-68; a CDR-L2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 69-70; and a CDR-L3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 71-72; and (b) the antibody, or antigen binding fragment thereof, that binds IL-4Rα comprises: (iii) a CDR-H1 comprising the sequence set forth in any one of SEQ ID NOs: 273, 274, and 275; a CDR-H2 comprising the sequence set forth in any one of SEQ ID NOs: 279, 277, and 280; a CDR-H3 comprising the sequence set forth in any one of SEQ ID NOs: 281 and 282; a CDR-L1 comprising the sequence set forth in any one of SEQ ID NOs: 289 and 288; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 290 or the amino acid sequence EG; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 293. 19. The isolated antibodies of any one of the preceding claims, wherein the antibody, or antigen binding fragment thereof, that binds OX40L comprises a heavy chain variable domain (VH) sequence comprising the amino acid sequence set forth in any one of SEQ ID NOs: 1, 19, 37, and 55. 20. The isolated antibodies of any one of the preceding claims, wherein the antibody, or antigen binding fragment thereof, that binds IL-4Rα comprises a VH sequence comprising the amino acid sequence set forth in any one of SEQ ID NOs: 295-297. 21. The isolated antibodies of any one of the preceding claims, wherein the antibody, or antigen binding fragment thereof, that binds OX40L comprises a light chain variable domain (VL) sequence comprising the amino acid sequence set forth in any one of SEQ ID NOs: 11, 29, 47, and 65. 22. The isolated antibodies of any one of the preceding claims, wherein the antibody, or antigen binding fragment thereof, that binds IL-4Rα comprises a VL sequence comprising the amino acid sequence set forth in any one of SEQ ID NOs: 298-300. 23. The isolated antibodies of any one of claims 19-22, wherein: (a) the antibody, or antigen binding fragment thereof, that binds OX40L comprises: (i) a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 1; (ii) a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 19; (iii) a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 37; or (iv) a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 55; and/or (v) a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 11; (vi) a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 29; (vii) a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 47; or (viii) a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 65; and/or (b) the antibody that binds IL-4Rα comprises: (i) a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 295; (ii) a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 296; or (iii) a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 297; and/or (iv) a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 298; (v) a VL sequence comprising the amino acid sequence set forth in SEQ ID NO:299; or (vi) a VL sequence comprising the amino acid sequence set forth in SEQ ID NO:300. 24. The isolated antibodies of claim 23, wherein the antibody, or antigen binding fragment thereof, that binds OX40L comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 1; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 11. 25. The isolated antibodies of claim 23, wherein the antibody, or antigen binding fragment thereof, that binds OX40L comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 19; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 29. 26. The isolated antibodies of claim 23, wherein the antibody, or antigen binding fragment thereof, that binds OX40L comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 37; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 47. 27. The isolated antibodies of claim 23, wherein the antibody, or antigen binding fragment thereof, that binds OX40L comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 55; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 65. 28. The isolated antibodies of claim 23, wherein the antibody, or antigen binding fragment thereof, that binds IL-4Rα comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 295; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 298. 29. The isolated antibodies of claim 23, wherein the antibody, or antigen binding fragment thereof, that binds IL-4Rα comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 296; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 299. 30. The isolated antibodies of claim 23, wherein the antibody, or antigen binding fragment thereof, that binds IL-4Rα comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 297; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 300. 31. The isolated antibodies of claim 23, wherein the antibody, or antigen binding fragment thereof, that binds OX40L comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 1; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 11; and wherein the antibody, or antigen binding fragment thereof, that binds IL-4Rα comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 295; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 298. 32. The isolated antibodies of claim 23, wherein the antibody, or antigen binding fragment thereof, that binds OX40L comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 1; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 11; and wherein the antibody, or antigen binding fragment thereof, that binds IL-4Rα comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 296; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 299. 33. The isolated antibodies of claim 23, wherein the antibody, or antigen binding fragment thereof, that binds OX40L comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 1; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 11; and wherein the antibody, or antigen binding fragment thereof, that binds IL-4Rα comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 297; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 300. 34. The isolated antibodies of claim 23, wherein the antibody, or antigen binding fragment thereof, that binds OX40L comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 19; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 29; and wherein the antibody, or antigen binding fragment thereof, that binds IL- 4Rα comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 295; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 298. 35. The isolated antibodies of claim 23, wherein the antibody, or antigen binding fragment thereof, that binds OX40L comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 19; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 29; and wherein the antibody, or antigen binding fragment thereof, that binds IL- 4Rα comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 296; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 299. 36. The isolated antibodies of claim 23, wherein the antibody, or antigen binding fragment thereof, that binds OX40L comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 19; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 29; and wherein the antibody, or antigen binding fragment thereof, that binds IL- 4Rα comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 297; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 300. 37. The isolated antibodies of claim 23, wherein the antibody, or antigen binding fragment thereof, that binds OX40L comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 37; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 47; and wherein the antibody, or antigen binding fragment thereof, that binds IL- 4Rα comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 295; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 298. 38. The isolated antibodies of claim 23, wherein the antibody, or antigen binding fragment thereof, that binds OX40L comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 37; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 47; and wherein the antibody, or antigen binding fragment thereof, that binds IL- 4Rα comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 296; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 299. 39. The isolated antibodies of claim 23, wherein the antibody, or antigen binding fragment thereof, that binds OX40L comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 37; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 47; and wherein the antibody, or antigen binding fragment thereof, that binds IL- 4Rα comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 297; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 300. 40. The isolated antibodies of claim 23, wherein the antibody, or antigen binding fragment thereof, that binds OX40L comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 55; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 65; and wherein the antibody, or antigen binding fragment thereof, that binds IL- 4Rα comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 295; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 298. 41. The isolated antibodies of claim 23, wherein the antibody, or antigen binding fragment thereof, that binds OX40L comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 55; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 65; and wherein the antibody, or antigen binding fragment thereof, that binds IL- 4Rα comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 296; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 299. 42. The isolated antibodies of claim 23, wherein the antibody, or antigen binding fragment thereof, that binds OX40L comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 55; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 65; and wherein the antibody, or antigen binding fragment thereof, that binds IL- 4Rα comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 297; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 300. 43. The isolated antibodies of any one of the preceding claims, wherein the antibody, or antigen binding fragment thereof, that binds OX40L and/or the antibody, or antigen binding fragment thereof, that binds IL-4Rα is a humanized, human, or chimeric antibody. 44. The isolated antibodies of any one of the preceding claims, wherein the antibody, or antigen binding fragment thereof, that binds OX40L and/or the antibody, or antigen binding fragment thereof, that binds IL-4Rα is a humanized antibody. 45. The isolated antibodies of any one of the preceding claims, wherein the antibody, or antigen binding fragment thereof, that binds OX40L and/or the antibody, or antigen binding fragment thereof, that binds IL-4Rα comprises a heavy chain human constant region of a class selected from IgG, IgA, IgD, IgE, and IgM. 46. The isolated antibodies of any one of the preceding claims, wherein the antibody, or antigen binding fragment thereof, that binds OX40L and/or the antibody, or antigen binding fragment thereof, that binds IL-4Rα comprises a human Fc region, and wherein the human Fc region comprises a human heavy chain constant region of the class IgG and a subclass selected from IgG1, IgG2, IgG3, and IgG4. 47. The isolated antibodies of claim 46, wherein the human Fc region of the antibody, or antigen binding fragment thereof, that binds OX40L and/or the antibody, or antigen binding fragment thereof, that binds IL-4Rα comprises a human IgG1 Fc region. 48. The isolated antibodies of claim 46, wherein the human Fc region of the antibody, or antigen binding fragment thereof, that binds OX40L and/or the antibody, or antigen binding fragment thereof, that binds IL-4Rα comprises a human IgG4 Fc region. 49. The isolated antibodies of claim 46, wherein the human Fc region of the antibody, or antigen binding fragment thereof, that binds OX40L and/or the antibody, or antigen binding fragment thereof, that binds IL-4Rα comprises a human IgG2 Fc region. 50. The isolated antibodies of any one of the preceding claims, wherein the antibody, or antigen binding fragment thereof, that binds OX40L and/or the antibody, or antigen binding fragment thereof, that binds IL-4Rα comprises a heavy chain comprising a constant heavy chain sequence selected from the amino acid sequences set forth in any one of SEQ ID NOs: 637-737 and 847-1070. 51. The isolated antibodies of any one of the preceding claims, wherein the antibody, or antigen binding fragment thereof, that binds OX40L and/or the antibody, or antigen binding fragment thereof, that binds IL-4Rα comprises a light chain comprising a constant light chain sequence selected from the sequences set forth in SEQ ID NOs: 738 and 1071. 52. The isolated antibodies of any one of the preceding claims, wherein the antibody, or antigen binding fragment thereof, that binds OX40L and/or the antibody, or antigen binding fragment thereof, that binds IL-4Rα comprises an Fc region comprising one or more amino acid substitutions, wherein the one or more substitutions result in an increase in one or more of antibody half-life, ADCC activity, ADCP activity, or CDC activity compared with the Fc without the one or more substitutions. 53. The isolated antibodies of any one of the preceding claims, wherein the antibody, or antigen binding fragment thereof, that binds OX40L and/or the antibody, or antigen binding fragment thereof, that binds IL-4Rα comprises an Fc region comprising one or more amino acid substitutions, wherein the one or more substitutions result in a decrease in one or more of, ADCC activity, ADCP activity or CDC activity compared to an antibody comprising a wild-type Fc region. 54. The isolated antibodies of claim 52 or 53, wherein the one or more amino acid substitutions is selected from the group consisting of S228P, M252Y, S254T, T256E, T256D, T250Q, H285D, T307A, T307Q, T307R, T307W, L309D, Q411H, Q311V, A378V, E380A, M428L, N434A, N434S, N297A, D265A, L234A, L235A, and N434W; optionally, wherein the one or more amino acid substitutions comprises a plurality of amino acid substitutions selected from the group consisting of M428L/N434S (LS), M252Y/S254T/T256E (YTE), T250Q/M428L, T307A/E380A/N434A, T256D/T307Q (DQ), T256D/T307W (DW), M252Y/T256D (YD), T307Q/Q311V/A378V (QVV), T256D/H285D/T307R/Q311V/A378V (DDRVV), L309D/Q311H/N434S (DHS), S228P/L235E (SPLE), L234A/L235A (LALA), M428L/N434A (LA), L235A/G237A (LAGA), L234A/L235A/G237A (LALAGA), L234A/L235A/P329G (LALAPG), D265A/YTE, LALA/YTE, LAGA/YTE, LALAGA/YTE, LALAPG/YTE, N297A/LS, D265A/LS, LALA/LS, LALAGA/LS, LALAPG/LS, N297A/DHS, D265A/DHS, LALA/DHS, LAGA/DHS, LALAGA/DHS, LALAPG/DHS, SP/YTE, SPLE/YTE, SP/LS, SPLE/LS, SP/DHS, SPLE/DHS, N297A/LA, D265A/LA, LALA/LA, LAGA/LA, LALAGA/LA, LALAPG/LA, N297A/N434A, D265A/N434A, LALA/N434A, LAGA/N434A, LALAGA/N434A, LALAPG/N434A, N297A/N434W, D265A/N434W, LALA/N434W, LAGA/N434W, LALAGA/N434W, LALAPG/N434W, N297A/DQ, D265A/DQ, LALA/DQ, LAGA/DQ, LALAGA/DQ, LALAPG/DQ, N297A/DW, D265A/DW, LALA/DW, LAGA/DW, LALAGA/DW, LALAPG/DW, N297A/YD, D265A/YD, LALA/YD, LAGA/YD, LALAGA/YD, LALAPG/YD, T307Q/Q311V/A378V (QVV), N297A/QVV, D265A/QVV, LALA/QVV, LAGA/QVV, LALAGA/QVV, LALAPG/QVV, DDRVV, N297A/DDRVV, D265A/DDRVV, LALA/DDRVV, LAGA/DDRVV, LALAGA/DDRVV, and LALAPG/DDRVV. 55. The isolated antibodies of any one of the preceding claims, wherein the antibody, or antigen binding fragment thereof, that binds OX40L comprises a VH domain comprising the amino acid sequence set forth in SEQ ID NO: 1, a VL domain comprising the amino acid sequence set forth in SEQ ID NO: 11, a constant heavy chain sequence set forth in any one of SEQ ID NOs: 651 and 973, and a constant light chain sequence set forth in SEQ ID NO: 738. 56. The isolated antibodies of any one of the preceding claims, wherein the antibody, or antigen binding fragment thereof, that binds IL-4Rα comprises a VH domain comprising the amino acid sequence set forth in SEQ ID NO: 297, a VL domain comprising the amino acid sequence set forth in SEQ ID NO: 300, a constant heavy chain sequence set forth in any one of SEQ ID NOs: 651 and 973, and a constant light chain sequence set forth in SEQ ID NO: 738. 57. The isolated antibodies of any one of the preceding claims, wherein the Fc region of the antibody, or antigen binding fragment thereof, that binds OX40L and/or the antibody, or antigen binding fragment thereof, that binds IL-4Rα binds to Neonatal Fc receptor (FcRn). 58. The isolated antibodies of claim 57, wherein the Fc region of the antibody, or antigen binding fragment thereof, that binds OX40L and/or the antibody, or antigen binding fragment thereof, that binds IL-4Rα binds an FcRn with higher affinity at pH 6.0 compared to an antibody comprising a wild-type Fc region. 59. The isolated antibodies of claim 57 or 58, wherein the Fc region of the antibody, or antigen binding fragment thereof, that binds OX40L and/or the antibody, or antigen binding fragment thereof, that binds IL-4Rα binds to FcRn with a KD of <1 x 10-7 M at pH 6.0. 60. The isolated antibodies of any one of the preceding claims, wherein the antibody, or antigen binding fragment thereof, that binds OX40L and/or the antibody, or antigen binding fragment thereof, that binds IL-4Rα is a monoclonal antibody. 61. The isolated antibodies of any one of the preceding claims, wherein the antibody, or antigen binding fragment thereof, that binds OX40L binds an OX40L sequence set forth in the amino acid sequence of SEQ ID NO: 739. 62. The isolated antibodies of any one of the preceding claims, wherein the antibody, or antigen binding fragment thereof, that binds IL-4Rα binds an IL-4Rα sequence set forth in any one of the amino acid sequences of SEQ ID NOs: 301-303. 63. The isolated antibodies of any one of the preceding claims for use in the treatment of an inflammatory disorder or disease. 64. The isolated antibodies of claim 63 for use in the treatment of atopic dermatitis (AD). 65. The isolated antibodies of claim 64, wherein the treatment reduces disease severity in a patient and wherein disease severity is assessed by an atopic dermatitis disease severity outcome measure. 66. The isolated antibodies of claim 63, for use in the treatment of asthma; chronic sinusitis with nasal polyps; Chronic Rhinosinusitis without Nasal Polyps (CRSsNP); eosinophilic esophagitis (EoE); an Eosinophilic gastrointestinal disorder or disease (EGID) selected from the group consisting of Eosinophilic Gastritis (EoG), Eosinophilic Enteritis (EoN), Eosinophilic Colitis (EoC), and Eosinophilic Gastroenteritis (EGE); Churg-Strauss syndrome/Eosinophilic granulomatosis with polyangiitis (EGPA); Prurigo Nodularis (PN); Chronic Spontaneous Urticaria (CSU); Chronic Pruritis of Unknown Origin (CPUO); Bullous Pemphigoid (BP); Cold Inducible Urticaria (ColdU); Allergic Fungal Rhinosinusitis (AFRS); Allergic Bronchopulmonary Aspergillosis (ABPA); Chronic Obstructive Pulmonary Disease (COPD); Crohn’s disease; lupus; rheumatoid arthritis (RA); psoriasis; ulcerative colitis; hidradenitis suppurativa; celiac disease; systemic sclerosis; idiopathic pulmonary fibrosis; alopecia areata, allergic rhinitis; eosinophilic fasciitis; scleromyxedema; scleredema; or nephrogenic systemic fibrosis. 67. A multi-specific antibody comprising: a first antigen binding region that binds OX40L and comprises: a) a variable heavy (VH) chain sequence having three heavy chain CDR sequences, CDR-H1, CDR-H2, and CDR-H3; and b) a variable light (VL) chain sequence having three light chain CDR sequences, CDR-L1, CDR-L2, and CDR-L3; wherein the antigen binding region that binds OX40L comprises: (i) a CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 2-4; a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 5-7; a CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 8-10; a CDR-L1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 12-14; a CDR-L2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 15-16; and a CDR-L3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 17-18; (ii) a CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 20-22; a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 23-25; a CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 26-28; a CDR-L1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 30-32; a CDR-L2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 33-34; and a CDR-L3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 35-36; (iii) a CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 38-40; a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NO: s 41-43; a CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 44-46; a CDR-L1 comprising the amino acid sequence set forth in any one of SEQ ID NO: s 48-50; a CDR-L2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 51-52; and a CDR-L3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 53-54; or (iv) a CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 56-58; a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 59-61; a CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 62-64; a CDR-L1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 66-68; a CDR-L2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 69-70; and a CDR-L3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 71-72; and a second antigen binding region that binds IL-4Rα. 68. The multi-specific antibody of claim 67, wherein the antigen binding region that binds IL- 4Rα comprises a CDR-H1, CDR-H2, CDR-H3, CDR-L1, CDR-L2, and CDR-L3 of an antibody selected from dupilumab, stapokibart, and 611. 69. The multi-specific antibody of claim 67, wherein the antigen binding region that binds IL- 4Rα comprises: a) a VH chain sequence having three heavy chain CDR sequences, CDR-H1, CDR-H2, and CDR-H3; and b) a VL chain sequence having three light chain CDR sequences, CDR-L1, CDR-L2, and CDR-L3, wherein the antigen binding region that binds IL-4Rα comprises: (i) a CDR-H1 comprising the sequence set forth in any one of SEQ ID NOs: 273, 274, and 275; a CDR-H2 comprising the sequence set forth in any one of SEQ ID NOs: 276, 277, and 278; a CDR-H3 comprising the sequence set forth in any one of SEQ ID NOs: 281 and 282; a CDR-L1 comprising the sequence set forth in any one of SEQ ID NOs: 285 and 286; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 292 or the amino acid sequence LG; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 293; (ii) a CDR-H1 comprising the sequence set forth in any one of SEQ ID NOs: 273, 274, and 275; a CDR-H2 comprising the sequence set forth in any one of SEQ ID NOs: 279, 277, and 280; a CDR-H3 comprising the sequence set forth in any one of SEQ ID NOs: 283 and 284; a CDR-L1 comprising the sequence set forth in any one of SEQ ID NOs: 287 and 288; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 291 or the amino acid sequence LG; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 293; or (iii) a CDR-H1 comprising the sequence set forth in any one of SEQ ID NOs: 273, 274, and 275; a CDR-H2 comprising the sequence set forth in any one of SEQ ID NOs: 279, 277, and 280; a CDR-H3 comprising the sequence set forth in any one of SEQ ID NOs: 281 and 282; a CDR-L1 comprising the sequence set forth in any one of SEQ ID NOs: 289 and 288; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 290 or the amino acid sequence EG; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 293. 70. A multi-specific antibody comprising: a first antigen binding region that binds OX40L; and a second antigen binding region that binds IL-4Rα and comprises: a) a variable heavy (VH) chain sequence having three heavy chain CDR sequences, CDR-H1, CDR-H2, and CDR- H3; and b) a variable light (VL) chain sequence having three light chain CDR sequences, CDR- L1, CDR-L2, and CDR-L3; wherein the antigen binding region that binds IL-4Rα comprises: (i) a CDR-H1 comprising the sequence set forth in any one of SEQ ID NOs: 273, 274, and 275; a CDR-H2 comprising the sequence set forth in any one of SEQ ID NOs: 276, 277, and 278; a CDR-H3 comprising the sequence set forth in any one of SEQ ID NOs: 281 and 282; a CDR-L1 comprising the sequence set forth in any one of SEQ ID NOs: 285 and 286; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 292 or the amino acid sequence LG; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 293; (ii) a CDR-H1 comprising the sequence set forth in any one of SEQ ID NOs: 273, 274, and 275; a CDR-H2 comprising the sequence set forth in any one of SEQ ID NOs: 279, 277, and 280; a CDR-H3 comprising the sequence set forth in any one of SEQ ID NOs: 283 and 284; a CDR-L1 comprising the sequence set forth in any one of SEQ ID NOs: 287 and 288; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 291 or the amino acid sequence LG; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 293; or (iii) a CDR-H1 comprising the sequence set forth in any one of SEQ ID NOs: 273, 274, and 275; a CDR-H2 comprising the sequence set forth in any one of SEQ ID NOs: 279, 277, and 280; a CDR-H3 comprising the sequence set forth in any one of SEQ ID NOs: 281 and 282; a CDR-L1 comprising the sequence set forth in any one of SEQ ID NOs: 289 and 288; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 290 or the amino acid sequence EG; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 293. 71. The multi-specific antibody of claim 70, wherein the antigen binding region that binds OX40L comprises a CDR-H1, CDR-H2, CDR-H3, CDR-L1, CDR-L2, and CDR-L3 of an antibody selected from amlitelimab and oxelumab. 72. The multi-specific antibody of claim 70, wherein the antigen binding region that binds OX40L comprises: a) a VH chain sequence having three heavy chain CDR sequences, CDR-H1, CDR-H2, and CDR-H3; and b) a VL chain sequence having three light chain CDR sequences, CDR-L1, CDR-L2, and CDR-L3, wherein the antigen binding region that binds OX40L comprises: (i) a CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 2-4; a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 5-7; a CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 8-10; a CDR-L1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 12-14; a CDR-L2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 15-16; and a CDR-L3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 17-18; (ii) a CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 20-22; a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 23-25; a CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 26-28; a CDR-L1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 30-32; a CDR-L2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 33-34; and a CDR-L3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 35-36; (iii) a CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 38-40; a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 41-43; a CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 44-46; a CDR-L1 comprising the amino acid sequence set forth in any one of SEQ ID NO: s 48-50; a CDR-L2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 51-52; and a CDR-L3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 53-54; or (iv) a CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 56-58; a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 59-61; a CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 62-64; a CDR-L1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 66-68; a CDR-L2 comprising the amino acid sequence set forth in any one of SEQ ID NO: 69-70s; and a CDR-L3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 71-72. 73. The multi-specific antibody of claim 69 or 72, wherein: (a) the antigen binding region that binds OX40L comprises: (i) a CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 2-4; a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 5-7; a CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 8-10; a CDR-L1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 12-14; a CDR-L2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 15-16; and a CDR-L3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 17-18; and (b) the antigen binding region that binds IL-4Rα comprises: (i) a CDR-H1 comprising the sequence set forth in any one of SEQ ID NOs: 273, 274, and 275; a CDR-H2 comprising the sequence set forth in any one of SEQ ID NOs: 276, 277, and 278; a CDR-H3 comprising the sequence set forth in any one of SEQ ID NOs: 281 and 282; a CDR-L1 comprising the sequence set forth in any one of SEQ ID NOs: 285 and 286; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 292 or the amino acid sequence LG; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 293. 74. The multi-specific antibody of claim 69 or 72, wherein: (a) the antigen binding region that binds OX40L comprises: (ii) a CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 20-22; a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 23-25; a CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 26-28; a CDR-L1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 30-32; a CDR-L2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 33-34; and a CDR-L3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 35-36; and (b) the antigen binding region that binds IL-4Rα comprises: (i) a CDR-H1 comprising the sequence set forth in any one of SEQ ID NOs: 273, 274, and 275; a CDR-H2 comprising the sequence set forth in any one of SEQ ID NOs: 276, 277, and 278; a CDR-H3 comprising the sequence set forth in any one of SEQ ID NOs: 281 and 282; a CDR-L1 comprising the sequence set forth in any one of SEQ ID NOs: 285 and 286; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 292 or the amino acid sequence LG; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 293. 75. The multi-specific antibody of claim v, wherein: (a) the antigen binding region that binds OX40L comprises: (iii) a CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 38-40; a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 41-43; a CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 44-46; a CDR-L1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 48-50; a CDR-L2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 51-52; and a CDR-L3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 53-54; and (b) the antigen binding region that binds IL-4Rα comprises: (i) a CDR-H1 comprising the sequence set forth in any one of SEQ ID NOs: 273, 274, and 275; a CDR-H2 comprising the sequence set forth in any one of SEQ ID NOs: 276, 277, and 278; a CDR-H3 comprising the sequence set forth in any one of SEQ ID NOs: 281 and 282; a CDR-L1 comprising the sequence set forth in any one of SEQ ID NOs: 285 and 286; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 292 or the amino acid sequence LG; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 293. 76. The multi-specific antibody of claim 69 or 72, wherein: (a) the antigen binding region that binds OX40L comprises: (iv) a CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 56-58; a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 59-61; a CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 62-64; a CDR-L1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 66-68; a CDR-L2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 69-70; and a CDR-L3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 71-72; and (b) the antigen binding region that binds IL-4Rα comprises: (i) a CDR-H1 comprising the sequence set forth in any one of SEQ ID NOs: 273, 274, and 275; a CDR-H2 comprising the sequence set forth in any one of SEQ ID NOs: 276, 277, and 278; a CDR-H3 comprising the sequence set forth in any one of SEQ ID NOs: 281 and 282; a CDR-L1 comprising the sequence set forth in any one of SEQ ID NOs: 285 and 286; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 292 or the amino acid sequence LG; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 293. 77. The multi-specific antibody of claim 69 or 72, wherein: (a) the antigen binding region that binds OX40L comprises: (i) a CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 2-4; a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 5-7; a CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 8-10; a CDR-L1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 12-14; a CDR-L2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 15-16; and a CDR-L3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 17-18; and (b) the antigen binding region that binds IL-4Rα comprises: (ii) a CDR-H1 comprising the sequence set forth in any one of SEQ ID NOs: 273, 274, and 275; a CDR-H2 comprising the sequence set forth in any one of SEQ ID NOs: 279, 277, and 280; a CDR-H3 comprising the sequence set forth in any one of SEQ ID NOs: 283 and 284; a CDR-L1 comprising the sequence set forth in any one of SEQ ID NOs: 287 and 288; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 291 or the amino acid sequence LG; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 293. 78. The multi-specific antibody of claim 69 or 72, wherein: (a) the antigen binding region that binds OX40L comprises: (ii) a CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 20-22; a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 23-25; a CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 26-28; a CDR-L1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 30-32; a CDR-L2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 33-34; and a CDR-L3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 35-36; and (b) the antigen binding region that binds IL-4Rα comprises: (ii) a CDR-H1 comprising the sequence set forth in any one of SEQ ID NOs: 273, 274, and 275; a CDR-H2 comprising the sequence set forth in any one of SEQ ID NOs: 279, 277, and 280; a CDR-H3 comprising the sequence set forth in any one of SEQ ID NOs: 283 and 284; a CDR-L1 comprising the sequence set forth in any one of SEQ ID NOs: 287 and 288; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 291 or the amino acid sequence LG; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 293. 79. The multi-specific antibody of claim 69 or 72, wherein: (a) the antigen binding region that binds OX40L comprises: (iii) a CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 38-40; a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 41-43; a CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 44-46; a CDR-L1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 48-50; a CDR-L2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 51-52; and a CDR-L3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 53-54; and (b) the antigen binding region that binds IL-4Rα comprises: (ii) a CDR-H1 comprising the sequence set forth in any one of SEQ ID NOs: 273, 274, and 275; a CDR-H2 comprising the sequence set forth in any one of SEQ ID NOs: 279, 277, and 280; a CDR-H3 comprising the sequence set forth in any one of SEQ ID NOs: 283 and 284; a CDR-L1 comprising the sequence set forth in any one of SEQ ID NOs: 287 and 288; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 291 or the amino acid sequence LG; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 293. 80. The multi-specific antibody of claim 69 or 72, wherein: (a) the antigen binding region that binds OX40L comprises: (iv) a CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 56-58; a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 59-61; a CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 62-64; a CDR-L1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 66-68; a CDR-L2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 69-70; and a CDR-L3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 71-72; and (b) the antigen binding region that binds IL-4Rα comprises: (ii) a CDR-H1 comprising the sequence set forth in any one of SEQ ID NOs: 273, 274, and 275; a CDR-H2 comprising the sequence set forth in any one of SEQ ID NOs: 279, 277, and 280; a CDR-H3 comprising the sequence set forth in any one of SEQ ID NOs: 283 and 284; a CDR-L1 comprising the sequence set forth in any one of SEQ ID NOs: 287 and 288; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 291 or the amino acid sequence LG; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 293. 81. The multi-specific antibody of claim 69 or 72, wherein: (a) the antigen binding region that binds OX40L comprises: (i) a CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 2-4; a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 5-7; a CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 8-10; a CDR-L1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 12-14; a CDR-L2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 15-16; and a CDR-L3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 17-18; and (b) the antigen binding region that binds IL-4Rα comprises: (iii) a CDR-H1 comprising the sequence set forth in any one of SEQ ID NOs: 273, 274, and 275; a CDR-H2 comprising the sequence set forth in any one of SEQ ID NOs: 279, 277, and 280; a CDR-H3 comprising the sequence set forth in any one of SEQ ID NOs: 281 and 282; a CDR-L1 comprising the sequence set forth in any one of SEQ ID NOs: 289 and 288; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 290 or the amino acid sequence EG; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 293. 82. The multi-specific antibody of claim 69 or 72, wherein: (a) the antigen binding region that binds OX40L comprises: (ii) a CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 20-22; a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 23-25; a CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 26-28; a CDR-L1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 30-32; a CDR-L2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 33-34; and a CDR-L3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 35-36; and (b) the antigen binding region that binds IL-4Rα comprises: (iii) a CDR-H1 comprising the sequence set forth in any one of SEQ ID NOs: 273, 274, and 275; a CDR-H2 comprising the sequence set forth in any one of SEQ ID NOs: 279, 277, and 280; a CDR-H3 comprising the sequence set forth in any one of SEQ ID NOs: 281 and 282; a CDR-L1 comprising the sequence set forth in any one of SEQ ID NOs: 289 and 288; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 290 or the amino acid sequence EG; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 293. 83. The multi-specific antibody of claim 69 or 72, wherein: (a) the antigen binding region that binds OX40L comprises: (iii) a CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 38-40; a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 41-43; a CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 44-46; a CDR-L1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 48-50; a CDR-L2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 51-52; and a CDR-L3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 53-54; and (b) the antigen binding region that binds IL-4Rα comprises: (iii) a CDR-H1 comprising the sequence set forth in any one of SEQ ID NOs: 273, 274, and 275; a CDR-H2 comprising the sequence set forth in any one of SEQ ID NOs: 279, 277, and 280; a CDR-H3 comprising the sequence set forth in any one of SEQ ID NOs: 281 and 282; a CDR-L1 comprising the sequence set forth in any one of SEQ ID NOs: 289 and 288; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 290 or the amino acid sequence EG; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 293. 84. The multi-specific antibody of claim 69 or 72, wherein: (a) the antigen binding region that binds OX40L comprises: (iv) a CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 56-58; a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 59-61; a CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 62-64; a CDR-L1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 66-68; a CDR-L2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 69-70; and a CDR-L3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 71-72; and (b) the antigen binding region that binds IL-4Rα comprises: (iii) a CDR-H1 comprising the sequence set forth in any one of SEQ ID NOs: 273, 274, and 275; a CDR-H2 comprising the sequence set forth in any one of SEQ ID NOs: 279, 277, and 280; a CDR-H3 comprising the sequence set forth in any one of SEQ ID NOs: 281 and 282; a CDR-L1 comprising the sequence set forth in any one of SEQ ID NOs: 289 and 288; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 290 or the amino acid sequence EG; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 293. 85. The multi-specific antibody of any one of claims 67-84, wherein the antigen binding region that binds OX40L comprises a heavy chain variable domain (VH) sequence comprising the amino acid sequence set forth in any one of SEQ ID NOs: 1, 19, 37, and 55. 86. The multi-specific antibody of any one of claims 67-85, wherein the antigen binding region that binds IL-4Rα comprises a VH sequence comprising the amino acid sequence set forth in any one of SEQ ID NOs: 295-297. 87. The multi-specific antibody of any one of claims 67-86, wherein the antigen binding region that binds OX40L comprises a light chain variable domain (VL) sequence comprising the amino acid sequence set forth in any one of SEQ ID NOs: 11, 29, 47, and 65. 88. The multi-specific antibody of any one of claims 67-87, wherein the antigen binding region that binds IL-4Rα comprises a VL sequence comprising the amino acid sequence set forth in any one of SEQ ID NOs: 298-300. 89. The multi-specific antibody of any one of claims 85-88, wherein: (a) the antigen binding region that binds OX40L comprises: (i) a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 1; (ii) a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 19; (iii) a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 37; or (iv) a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 55; and/or (v) a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 11; (vi) a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 29; (vii) a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 47; or (viii) a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 65; and/or (b) the antigen binding region that binds IL-4Rα comprises: (i) a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 295; (ii) a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 296; or (iii) a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 297; and/or (iv) a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 298; (v) a VL sequence comprising the amino acid sequence set forth in SEQ ID NO:299; or (vi) a VL sequence comprising the amino acid sequence set forth in SEQ ID NO:300. 90. The multi-specific antibody of claim 89, wherein the antigen binding region that binds OX40L comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 1; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 11. 91. The multi-specific antibody of claim 89, wherein the antigen binding region that binds OX40L comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 19; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 29. 92. The multi-specific antibody of claim 89, wherein the antigen binding region that binds OX40L comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 37; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 47. 93. The multi-specific antibody of claim 89, wherein the antigen binding region that binds OX40L comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 55; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 65. 94. The multi-specific antibody of claim 89, wherein the antigen binding region that binds IL-4Rα comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 295; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 298. 95. The multi-specific antibody of claim 89, wherein the antigen binding region that binds IL-4Rα comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 296; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 299. 96. The multi-specific antibody of claim 89, wherein the antigen binding region that binds IL-4Rα comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 297; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 300. 97. The multi-specific antibody of claim 89, wherein the antigen binding region that binds OX40L comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 1; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 11; and wherein the antigen binding region that binds IL-4Rα comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 295; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 298. 98. The multi-specific antibody of claim 89, wherein the antigen binding region that binds OX40L comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 1; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 11; and wherein the antigen binding region that binds IL-4Rα comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 296; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 299. 99. The multi-specific antibody of claim 89, wherein the antigen binding region that binds OX40L comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 1; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 11; and wherein the antigen binding region that binds IL-4Rα comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 297; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 300. 100. The multi-specific antibody of claim 89, wherein the antigen binding region that binds OX40L comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 19; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 29; and wherein the antigen binding region that binds IL-4Rα comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 295; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 298. 101. The multi-specific antibody of claim 89, wherein the antigen binding region that binds OX40L comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 19; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 29; and wherein the antigen binding region that binds IL-4Rα comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 296; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 299. 102. The multi-specific antibody of claim 89, wherein the antigen binding region that binds OX40L comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 19; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 29; and wherein the antigen binding region that binds IL-4Rα comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 297; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 300. 103. The multi-specific antibody of claim 89, wherein the antigen binding region that binds OX40L comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 37; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 47; and wherein the antigen binding region that binds IL-4Rα comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 295; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 298. 104. The multi-specific antibody of claim 89, wherein the antigen binding region that binds OX40L comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 37; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 47; and wherein the antigen binding region that binds IL-4Rα comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 296; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 299. 105. The multi-specific antibody of claim 89, wherein the antigen binding region that binds OX40L comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 37; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 47; and wherein the antigen binding region that binds IL-4Rα comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 297; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 300. 106. The multi-specific antibody of claim 89, wherein the antigen binding region that binds OX40L comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 55; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 65; and wherein the antigen binding region that binds IL-4Rα comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 295; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 298. 107. The multi-specific antibody of claim 89, wherein the antigen binding region that binds OX40L comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 55; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 65; and wherein the antigen binding region that binds IL-4Rα comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 296; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 299. 108. The multi-specific antibody of claim 89, wherein the antigen binding region that binds OX40L comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 55; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 65; and wherein the antigen binding region that binds IL-4Rα comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 297; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 300. 109. The multi-specific antibody of any one of claims 67-108, wherein the antigen binding region that binds OX40L and/or the antigen binding region that binds IL-4Rα is humanized, human, or chimeric. 110. The multi-specific antibody of any one of claims 67-109, wherein the antigen binding region that binds OX40L and/or the antigen binding region that binds IL-4Rα is humanized. 111. The multi-specific antibody of any one of claims 67-110, wherein the multi-specific antibody comprises a heavy chain human constant region of a class selected from IgG, IgA, IgD, IgE, and IgM. 112. The multi-specific antibody of any one of claims 67-111, wherein the multi-specific antibody comprises a human Fc region, and wherein the human Fc region comprises a human heavy chain constant region of the class IgG and a subclass selected from IgG1, IgG2, IgG3, and IgG4. 113. The multi-specific antibody of claim 112, wherein the human Fc region comprises a human IgG1 Fc region. 114. The multi-specific antibody of claim 112, wherein the human Fc region comprises a human IgG4 Fc region. 115. The multi-specific antibody of claim 112, wherein the human Fc region comprises a human IgG2 Fc region. 116. The multi-specific antibody of any one of claims 67-115, wherein the multi-specific antibody comprises a heavy chain comprising a constant heavy chain sequence selected from the amino acid sequences set forth in any one of SEQ ID NOs: 637-737 and 847-1070. 117. The multi-specific antibody of any one of claims 67-116, wherein the multi-specific antibody comprises a light chain comprising a constant light chain sequence selected from the sequences set forth in SEQ ID NOs: 738 and 1071. 118. The multi-specific antibody of any one of claims 67-117, wherein the multi-specific antibody comprises an Fc region comprising one or more amino acid substitutions, wherein the one or more substitutions result in an increase in one or more of antibody half-life, ADCC activity, ADCP activity, or CDC activity compared with the Fc without the one or more substitutions. 119. The multi-specific antibody of any one of claims 67-118, wherein the multi-specific antibody comprises an Fc region comprising one or more amino acid substitutions, wherein the one or more substitutions result in a decrease in one or more of, ADCC activity, ADCP activity or CDC activity compared to an antibody comprising a wild-type Fc region. 120. The multi-specific antibody of claim 118 or 119, wherein the one or more amino acid substitutions is selected from the group consisting of S228P, M252Y, S254T, T256E, T256D, T250Q, H285D, T307A, T307Q, T307R, T307W, L309D, Q411H, Q311V, A378V, E380A, M428L, N434A, N434S, N297A, D265A, L234A, L235A, and N434W; optionally, wherein the one or more amino acid substitutions comprises a plurality of amino acid substitutions selected from the group consisting of M428L/N434S (LS), M252Y/S254T/T256E (YTE), T250Q/M428L, T307A/E380A/N434A, T256D/T307Q (DQ), T256D/T307W (DW), M252Y/T256D (YD), T307Q/Q311V/A378V (QVV), T256D/H285D/T307R/Q311V/A378V (DDRVV), L309D/Q311H/N434S (DHS), S228P/L235E (SPLE), L234A/L235A (LALA), M428L/N434A (LA), L235A/G237A (LAGA), L234A/L235A/G237A (LALAGA), L234A/L235A/P329G (LALAPG), D265A/YTE, LALA/YTE, LAGA/YTE, LALAGA/YTE, LALAPG/YTE, N297A/LS, D265A/LS, LALA/LS, LALAGA/LS, LALAPG/LS, N297A/DHS, D265A/DHS, LALA/DHS, LAGA/DHS, LALAGA/DHS, LALAPG/DHS, SP/YTE, SPLE/YTE, SP/LS, SPLE/LS, SP/DHS, SPLE/DHS, N297A/LA, D265A/LA, LALA/LA, LAGA/LA, LALAGA/LA, LALAPG/LA, N297A/N434A, D265A/N434A, LALA/N434A, LAGA/N434A, LALAGA/N434A, LALAPG/N434A, N297A/N434W, D265A/N434W, LALA/N434W, LAGA/N434W, LALAGA/N434W, LALAPG/N434W, N297A/DQ, D265A/DQ, LALA/DQ, LAGA/DQ, LALAGA/DQ, LALAPG/DQ, N297A/DW, D265A/DW, LALA/DW, LAGA/DW, LALAGA/DW, LALAPG/DW, N297A/YD, D265A/YD, LALA/YD, LAGA/YD, LALAGA/YD, LALAPG/YD, T307Q/Q311V/A378V (QVV), N297A/QVV, D265A/QVV, LALA/QVV, LAGA/QVV, LALAGA/QVV, LALAPG/QVV, DDRVV, N297A/DDRVV, D265A/DDRVV, LALA/DDRVV, LAGA/DDRVV, LALAGA/DDRVV, and LALAPG/DDRVV. 121. The multi-specific antibody of any one of claims 67-120, wherein the antigen binding region that binds OX40L comprises a VH domain comprising the amino acid sequence set forth in SEQ ID NO: 1, a VL domain comprising the amino acid sequence set forth in SEQ ID NO: 11, a constant heavy chain sequence set forth in any one of SEQ ID NOs: 651 and 973, and a constant light chain sequence set forth in SEQ ID NO: 738. 122. The multi-specific antibody of any one of claims 67-121, wherein the antigen binding region that binds IL-4Rα comprises a VH domain comprising the amino acid sequence set forth in SEQ ID NO: 297, a VL domain comprising the amino acid sequence set forth in SEQ ID NO: 300, a constant heavy chain sequence set forth in any one of SEQ ID NOs: 651 and 973, and a constant light chain sequence set forth in SEQ ID NO: 738. 123. The multi-specific antibody of any one of claims 67-122, wherein the Fc region binds to Neonatal Fc receptor (FcRn). 124. The multi-specific antibody of claim 123, wherein the Fc region binds an FcRn with higher affinity at pH 6.0 compared to an antibody comprising a wild-type Fc region. 125. The multi-specific antibody of claim 123 or 124, wherein the Fc region binds IL-4Rα binds to FcRn with a KD of <1 x 10-7 M at pH 6.0. 126. The multi-specific antibody of any one of claims 67-125, wherein the antigen binding region that binds OX40L and/or the antigen binding region that binds IL-4Rα is a monoclonal antigen binding region. 127. The multi-specific antibody of any one of claims 67-126, wherein the antigen binding region that binds OX40L binds an OX40L sequence set forth in the amino acid sequence of SEQ ID NO: 739. 128. The multi-specific antibody of any one of claims 67-127, wherein the antigen binding region that binds IL-4Rα binds an IL-4Rα sequence set forth in any one of the amino acid sequences of SEQ ID NOs: 301-303. 129. The multi-specific antibody of any one of claims 67-128 for use in the treatment of an inflammatory disorder or disease. 130. The multi-specific antibody of claim 129 for use in the treatment of atopic dermatitis (AD). 131. The multi-specific antibody of claim 130, wherein the treatment reduces disease severity in a patient and wherein disease severity is assessed by an atopic dermatitis disease severity outcome measure. 132. The multi-specific antibody of claim 129, , for use in the treatment of asthma; chronic sinusitis with nasal polyps; Chronic Rhinosinusitis without Nasal Polyps (CRSsNP); eosinophilic esophagitis (EoE); an Eosinophilic gastrointestinal disorder or disease (EGID) selected from the group consisting of Eosinophilic Gastritis (EoG), Eosinophilic Enteritis (EoN), Eosinophilic Colitis (EoC), and Eosinophilic Gastroenteritis (EGE); Churg-Strauss syndrome/Eosinophilic granulomatosis with polyangiitis (EGPA); Prurigo Nodularis (PN); Chronic Spontaneous Urticaria (CSU); Chronic Pruritis of Unknown Origin (CPUO); Bullous Pemphigoid (BP); Cold Inducible Urticaria (ColdU); Allergic Fungal Rhinosinusitis (AFRS); Allergic Bronchopulmonary Aspergillosis (ABPA); Chronic Obstructive Pulmonary Disease (COPD); Crohn’s disease; lupus; rheumatoid arthritis (RA); psoriasis; ulcerative colitis; hidradenitis suppurativa; celiac disease; systemic sclerosis; idiopathic pulmonary fibrosis; alopecia areata, allergic rhinitis; eosinophilic fasciitis; scleromyxedema; scleredema; or nephrogenic systemic fibrosis. 133. An isolated polynucleotide or set of polynucleotides encoding the isolated antibodies or multi-specific antibodies of any one of the preceding claims, a VH thereof, a VL thereof, a light chain thereof, a heavy chain thereof, or an antigen-binding portion thereof, optionally, wherein the polynucleotide or set of polynucleotides comprises cDNA. 134. A vector or set of vectors comprising the polynucleotide or set of polynucleotides of claim 133. 135. A host cell comprising the polynucleotide or set of polynucleotides of claim 133 or the vector or set of vectors of claim 134. 136. A method of producing one or more of the isolated antibodies or multi-specific antibodies of any one of the preceding claims, the method comprising expressing one or more of the isolated antibodies or multi-specific antibodies within the host cell of claim 135 and isolating the one or more expressed antibodies. 137. A pharmaceutical composition comprising the isolated antibodies or multi-specific antibodies of any one of claims 1-62 and 67-128 and a pharmaceutically acceptable excipient. 138. A kit comprising the isolated antibodies or multi-specific antibodies of any one of claims 1-62 and 67-128 or the pharmaceutical composition of claim 137 and instructions for use. 139. A method for treating an inflammatory disorder or disease in a mammalian subject in need thereof, the method comprising administering to the mammalian subject a therapeutically effective amount of the isolated antibodies or multi-specific antibodies of any one of claims 1-62 and 67-128; a therapeutically effective amount of the pharmaceutical composition of claim 137; or a therapeutically effective amount of a pharmaceutical composition comprising an isolated antibody, or antigen binding fragment thereof, that binds OX40L and a pharmaceutically acceptable excipient and a therapeutically effective amount of a pharmaceutical composition comprising an antibody, or antigen binding fragment thereof, that binds IL-4Rα and a pharmaceutically acceptable excipient137. 140. The method of claim 139, wherein the mammalian subject is a human. 141. The method of claim 139 or 140, wherein the inflammatory disorder or disease is atopic dermatitis. 142. The method of claim 139 or 140, wherein the inflammatory disorder or disease is asthma. 143. The method of claim 139 or 140, wherein the inflammatory disorder or disease is chronic sinusitis with nasal polyps; Chronic Rhinosinusitis without Nasal Polyps (CRSsNP); eosinophilic esophagitis (EoE); an Eosinophilic gastrointestinal disorder or disease (EGID) selected from the group consisting of Eosinophilic Gastritis (EoG), Eosinophilic Enteritis (EoN), Eosinophilic Colitis (EoC), and Eosinophilic Gastroenteritis (EGE); Churg-Strauss syndrome/Eosinophilic granulomatosis with polyangiitis (EGPA); Prurigo Nodularis (PN); Chronic Spontaneous Urticaria (CSU); Chronic Pruritis of Unknown Origin (CPUO); Bullous Pemphigoid (BP); Cold Inducible Urticaria (ColdU); Allergic Fungal Rhinosinusitis (AFRS); Allergic Bronchopulmonary Aspergillosis (ABPA); Chronic Obstructive Pulmonary Disease (COPD); celiac disease; Crohn’s disease; lupus; rheumatoid arthritis (RA); psoriasis; ulcerative colitis; hidradenitis suppurativa; systemic sclerosis; idiopathic pulmonary fibrosis; alopecia areata, allergic rhinitis; eosinophilic fasciitis; scleromyxedema; scleredema; or nephrogenic systemic fibrosis. 144. A method for treating a pathology associated with elevated levels of OX40L and/or IL-4 in a mammalian subject in need thereof, the method comprising administering to the mammalian subject a therapeutically effective amount the isolated antibodies or multi-specific antibodies of any one of claims 1-62 and 67-128; the pharmaceutical composition of claim 137; or a therapeutically effective amount of a pharmaceutical composition comprising an isolated antibody, or antigen binding fragment thereof, that binds OX40L and a pharmaceutically acceptable excipient and a therapeutically effective amount of a pharmaceutical composition comprising an antibody, or antigen binding fragment thereof, that binds IL-4Rα and a pharmaceutically acceptable excipient. 145. A method of reducing biological activity of OX40L and/or IL-4Rα in a mammalian subject in need thereof, the method comprising administering to the mammalian subject a therapeutically effective amount the isolated antibodies or multi-specific antibodies of any one of claims 1-62 and 67-128; the pharmaceutical composition of claim 137; or a therapeutically effective amount of a pharmaceutical composition comprising an isolated antibody, or antigen binding fragment thereof, that binds OX40L and a pharmaceutically acceptable excipient and a therapeutically effective amount of a pharmaceutical composition comprising an antibody, or antigen binding fragment thereof, that binds IL-4Rα and a pharmaceutically acceptable excipient. 146. The method of any one of claims 139-127, wherein the mammalian subject is a human. 147. A pharmaceutical composition comprising: an isolated antibody, or antigen binding fragment thereof, that binds OX40L comprising a VH domain comprising the amino acid sequence set forth in SEQ ID NO: 1, a VL domain comprising the amino acid sequence set forth in SEQ ID NO: 11, a constant heavy chain sequence set forth in any one of SEQ ID NOs: 651 and 973, and a constant light chain sequence set forth in SEQ ID NO: 738; an isolated antibody, or antigen binding fragment thereof, that binds IL-4Rα comprising a VH domain comprising the amino acid sequence set forth in SEQ ID NO: 297, a VL domain comprising the amino acid sequence set forth in SEQ ID NO: 300, a constant heavy chain sequence set forth in any one of SEQ ID NOs: 651 and 973, and a constant light chain sequence set forth in SEQ ID NO: 738; and a pharmaceutically acceptable excipient. 148. A pharmaceutical composition comprising: a multi-specific antibody comprising: an antigen binding region that binds OX40L comprising a VH domain comprising the amino acid sequence set forth in SEQ ID NO: 1, a VL domain comprising the amino acid sequence set forth in SEQ ID NO: 11, a constant heavy chain sequence set forth in any one of SEQ ID NOs: 651 and 973, and a constant light chain sequence set forth in SEQ ID NO: 738; an antigen binding region that binds IL-4Rα comprising a VH domain comprising the amino acid sequence set forth in SEQ ID NO: 297, a VL domain comprising the amino acid sequence set forth in SEQ ID NO: 300, a constant heavy chain sequence set forth in any one of SEQ ID NOs: 651 and 973, and a constant light chain sequence set forth in SEQ ID NO: 738; and a pharmaceutically acceptable excipient. 149. A composition comprising an isolated antibody, or antigen binding region thereof, that binds OX40L, an isolated antibody, or antigen binding region thereof, that binds Interleukin-4 Receptor Alpha (IL-4Rα), and a hyaluronidase or variant thereof. 150. A composition comprising an isolated antibody, or antigen binding region thereof, that binds OX40L, an isolated antibody, or antigen binding region thereof, that binds Interleukin-4 Receptor Alpha (IL-4Rα), and a hyaluronidase or variant thereof, wherein the antibody, or antigen binding region thereof, that binds OX40L comprises a CDR-H1 comprising the sequence set forth in SEQ ID NO: 2; a CDR-H2 comprising the sequence set forth in SEQ ID NO: 5; a CDR-H3 comprising the sequence set forth in SEQ ID NO: 8; a CDR-L1 comprising the sequence set forth in SEQ ID NO: 12; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 15; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 17. 151. A composition comprising an isolated antibody, or antigen binding region thereof, that binds OX40L, an isolated antibody, or antigen binding region thereof, that binds Interleukin-4 Receptor Alpha (IL-4Rα), and a hyaluronidase or variant thereof, wherein the antibody, or antigen binding region thereof, that binds OX40L comprises a VH sequence set forth in SEQ ID NO: 1 and a VL sequence set forth in SEQ ID NO: 11. 152. A composition comprising an isolated antibody, or antigen binding region thereof, that binds OX40L, an isolated antibody, or antigen binding region thereof, that binds Interleukin-4 Receptor Alpha (IL-4Rα), and a hyaluronidase or variant thereof, wherein the antibody, or antigen binding region thereof, that binds IL-4Rα comprises a CDR-H1 comprising the sequence set forth in SEQ ID NO: 273; a CDR-H2 comprising the sequence set forth in SEQ ID NO: 279; a CDR-H3 comprising the sequence set forth in SEQ ID NO: 281; a CDR-L1 comprising the sequence set forth in SEQ ID NO: 289; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 290; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 293. 153. A composition comprising an isolated antibody, or antigen binding region thereof, that binds OX40L, an isolated antibody, or antigen binding region thereof, that binds Interleukin-4 Receptor Alpha (IL-4Rα), and a hyaluronidase or variant thereof, wherein the antibody, or antigen binding region thereof, that binds IL-4Rα comprises a VH sequence set forth in SEQ ID NO: 297 and a VL sequence set forth in SEQ ID NO: 300. 154. A composition comprising an isolated antibody, or antigen binding region thereof, that binds OX40L, an isolated antibody, or antigen binding region thereof, that binds Interleukin-4 Receptor Alpha (IL-4Rα), and a hyaluronidase or variant thereof, wherein the antibody, or antigen binding region thereof, that binds OX40L comprises a CDR-H1 comprising the sequence set forth in SEQ ID NO: 2; a CDR-H2 comprising the sequence set forth in SEQ ID NO: 5; a CDR-H3 comprising the sequence set forth in SEQ ID NO: 8; a CDR-L1 comprising the sequence set forth in SEQ ID NO: 12; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 15; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 17, and wherein the antibody, or antigen binding region thereof, that binds IL-4Rα comprises a CDR-H1 comprising the sequence set forth in SEQ ID NO: 273; a CDR-H2 comprising the sequence set forth in SEQ ID NO: 279; a CDR-H3 comprising the sequence set forth in SEQ ID NO: 281; a CDR-L1 comprising the sequence set forth in SEQ ID NO: 289; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 290; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 293. 155. A composition comprising an isolated antibody, or antigen binding region thereof, that binds OX40L, an isolated antibody, or antigen binding region thereof, that binds IL-4Rα, and a hyaluronidase or variant thereof, wherein the antibody, or antigen binding region thereof, that binds OX40L comprises a VH sequence set forth in SEQ ID NO: 1 and a VL sequence set forth in SEQ ID NO: 11; and wherein the antibody, or antigen binding region thereof, that binds IL-4Rα comprises a VH sequence set forth in SEQ ID NO: 297 and a VL sequence set forth in SEQ ID NO: 300. 156. A composition comprising hyaluronidase or variant thereof and a multi-specific antibody comprising a first antigen binding region that binds OX40L and a second antigen binding region that binds IL-4Rα, wherein the antigen binding region that binds OX40L comprises a CDR-H1 comprising the sequence set forth in SEQ ID NO: 2; a CDR-H2 comprising the sequence set forth in SEQ ID NO: 5; a CDR-H3 comprising the sequence set forth in SEQ ID NO: 8; a CDR-L1 comprising the sequence set forth in SEQ ID NO: 12; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 15; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 17, and wherein the antigen binding region that binds IL-4Rα comprises a CDR-H1 comprising the sequence set forth in SEQ ID NO: 273; a CDR-H2 comprising the sequence set forth in SEQ ID NO: 279; a CDR-H3 comprising the sequence set forth in SEQ ID NO: 281; a CDR-L1 comprising the sequence set forth in SEQ ID NO: 289; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 290; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 293. 157. A composition comprising hyaluronidase or variant thereof and a multi-specific antibody comprising a first antigen binding region that binds OX40L and a second antigen binding region that binds IL-4Rα, wherein the antigen binding region that binds OX40L comprises a VH sequence set forth in SEQ ID NO: 1 and a VL sequence set forth in SEQ ID NO: 11; and wherein the antigen binding region that binds IL-4Rα comprises a VH sequence set forth in SEQ ID NO: 297 and a VL sequence set forth in SEQ ID NO: 300. 158. A combination comprising an isolated antibody, or antigen binding region thereof, that binds OX40L, an isolated antibody, or antigen binding region thereof, that binds IL-4Rα, and a hyaluronidase or variant thereof, wherein the antibody, or antigen binding region thereof, that binds OX40L comprises a CDR-H1 comprising the sequence set forth in SEQ ID NO: 2; a CDR-H2 comprising the sequence set forth in SEQ ID NO: 5; a CDR-H3 comprising the sequence set forth in SEQ ID NO: 8; a CDR-L1 comprising the sequence set forth in SEQ ID NO: 12; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 15; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 17, and wherein the antibody, or antigen binding region thereof, that binds IL-4Rα comprises a CDR-H1 comprising the sequence set forth in SEQ ID NO: 273; a CDR-H2 comprising the sequence set forth in SEQ ID NO: 279; a CDR-H3 comprising the sequence set forth in SEQ ID NO: 281; a CDR-L1 comprising the sequence set forth in SEQ ID NO: 289; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 290; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 293. 159. A combination comprising an isolated antibody, or antigen binding region thereof, that binds OX40L, an isolated antibody, or antigen binding region thereof, that binds IL-4Rα, and a hyaluronidase or variant thereof, wherein the antibody, or antigen binding region thereof, that binds OX40L comprises a VH sequence set forth in SEQ ID NO: 1 and a VL sequence set forth in SEQ ID NO: 11; and wherein the antibody, or antigen binding region thereof, that binds IL-4Rα comprises a VH sequence set forth in SEQ ID NO: 297 and a VL sequence set forth in SEQ ID NO: 300. 160. A combination comprising hyaluronidase or variant thereof and a multi-specific antibody comprising a first antigen binding region that binds OX40L and a second antigen binding region that binds IL-4RΑ, wherein the antigen binding region that binds OX40L comprises a CDR-H1 comprising the sequence set forth in SEQ ID NO: 2; a CDR-H2 comprising the sequence set forth in SEQ ID NO: 5; a CDR-H3 comprising the sequence set forth in SEQ ID NO: 8; a CDR-L1 comprising the sequence set forth in SEQ ID NO: 12; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 15; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 17, and wherein the antigen binding region that binds IL-4Rα comprises a CDR-H1 comprising the sequence set forth in SEQ ID NO: 273; a CDR-H2 comprising the sequence set forth in SEQ ID NO: 279; a CDR-H3 comprising the sequence set forth in SEQ ID NO: 281; a CDR-L1 comprising the sequence set forth in SEQ ID NO: 289; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 290; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 293. 161. A combination comprising hyaluronidase or variant thereof and a multi-specific antibody comprising a first antigen binding region that binds OX40L and a second antigen binding region that binds IL-4Rα, wherein the antigen binding region that binds OX40L comprises a VH sequence set forth in SEQ ID NO: 1 and a VL sequence set forth in SEQ ID NO: 11; and wherein the antigen binding region that binds IL-4Rα comprises a VH sequence set forth in SEQ ID NO: 297 and a VL sequence set forth in SEQ ID NO: 300. 162. A method of treating an inflammatory disorder or disease in a human patient comprising administering to the patient an isolated antibody, or antigen binding region thereof, that binds OX40L, an isolated antibody, or antigen binding region thereof, that binds IL-4Rα, and a hyaluronidase or variant thereof, wherein the antibody, or antigen binding region thereof, that binds OX40L comprises a CDR-H1 comprising the sequence set forth in SEQ ID NO: 2; a CDR-H2 comprising the sequence set forth in SEQ ID NO: 5; a CDR-H3 comprising the sequence set forth in SEQ ID NO: 8; a CDR-L1 comprising the sequence set forth in SEQ ID NO: 12; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 15; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 17; and wherein the antibody, or antigen binding region thereof, that binds IL-4Rα comprises a CDR-H1 comprising the sequence set forth in SEQ ID NO: 273; a CDR-H2 comprising the sequence set forth in SEQ ID NO: 279; a CDR-H3 comprising the sequence set forth in SEQ ID NO: 281; a CDR-L1 comprising the sequence set forth in SEQ ID NO: 289; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 290; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 293. 163. A method of treating an inflammatory disorder or disease in a human patient comprising administering to the patient an isolated antibody, or antigen binding region thereof, that binds OX40L, an isolated antibody, or antigen binding region thereof, that binds IL-4Rα, and a hyaluronidase or variant thereof, wherein the antibody, or antigen binding region thereof, that binds OX40L comprises a VH sequence set forth in SEQ ID NO: 1 and a VL sequence set forth in SEQ ID NO: 11; and wherein the antibody, or antigen binding region thereof, that binds IL-4Rα comprises a VH sequence set forth in SEQ ID NO: 297 and a VL sequence set forth in SEQ ID NO: 300. 164. A method of treating an inflammatory disorder or disease in a human patient comprising administering to the patient hyaluronidase or variant thereof and a multi-specific antibody comprising a first antigen binding region that binds OX40L and a second antigen binding region that binds IL-4Rα, wherein the antigen binding region that binds OX40L comprises a CDR-H1 comprising the sequence set forth in SEQ ID NO: 2; a CDR-H2 comprising the sequence set forth in SEQ ID NO: 5; a CDR-H3 comprising the sequence set forth in SEQ ID NO: 8; a CDR-L1 comprising the sequence set forth in SEQ ID NO: 12; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 15; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 17, and wherein the antigen binding region that binds IL-4Rα comprises a CDR-H1 comprising the sequence set forth in SEQ ID NO: 273; a CDR-H2 comprising the sequence set forth in SEQ ID NO: 279; a CDR-H3 comprising the sequence set forth in SEQ ID NO: 281; a CDR-L1 comprising the sequence set forth in SEQ ID NO: 289; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 290; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 293. 165. A method of treating an inflammatory disorder or disease in a human patient comprising administering to the patient hyaluronidase or variant thereof and a multi-specific antibody comprising a first antigen binding region that binds OX40L and a second antigen binding region that binds IL-4Rα, wherein the antigen binding region that binds OX40L comprises a VH sequence set forth in SEQ ID NO: 1 and a VL sequence set forth in SEQ ID NO: 11; and wherein the antigen binding region that binds IL-4Rα comprises a VH sequence set forth in SEQ ID NO: 297 and a VL sequence set forth in SEQ ID NO: 300. 166. The composition of any one of claims 149-157, the combination of any one of claims 158-161, or the method of any one of claims 162-165, wherein the antibody or antigen binding region that binds OX40L and/or the antibody or antigen binding region that binds IL-4Rα is a humanized, human, or chimeric antibody. 167. The composition of any one of claims 149-157, the combination of any one of claims 158-161, or the method of any one of claims 162-165, wherein the antibody or antigen binding region that binds OX40L and/or the antibody or antigen binding region that binds IL-4Rα is a humanized antibody. 168. The composition of any one of claims 149-157, the combination of any one of claims 158-161, or the method of any one of claims 162-165, wherein the antibody or antigen binding region that binds OX40L and/or the antibody or antigen binding region that binds IL-4Rα comprises a heavy chain human constant region of a class selected from IgG, IgA, IgD, IgE, and IgM. 169. The composition of any one of claims 149-157, the combination of any one of claims 158-161, or the method of any one of claims 162-165, wherein the antibody or antigen binding region that binds OX40L and/or the antibody or antigen binding region that binds IL-4Rα comprises a human Fc region, and wherein the human Fc region comprises a human heavy chain constant region of the class IgG and a subclass selected from IgG1, IgG2, IgG3, and IgG4. 170. The composition of any one of claims 149-157, the combination of any one of claims 158-161, or the method of any one of claims 162-165, wherein the antibody or antigen binding region that binds OX40L and/or the antibody or antigen binding region that binds IL-4Rα comprises a human Fc region, and wherein the human Fc region comprises a human IgG1 Fc region. 171. The composition of any one of claims 149-157, the combination of any one of claims 158-161, or the method of any one of claims 162-165, wherein the antibody or antigen binding region that binds OX40L and/or the antibody or antigen binding region that binds IL-4Rα comprises a human Fc region, and wherein the human Fc region comprises a human IgG4 Fc region. 172. The composition of any one of claims 149-157, the combination of any one of claims 158-161, or the method of any one of claims 162-165, wherein the antibody or antigen binding region that binds OX40L and/or the antibody or antigen binding region that binds IL-4Rα comprises a human Fc region, and wherein the human Fc region comprises a human IgG2 Fc region. 173. The composition of any one of claims 149-157, the combination of any one of claims 158-161, or the method of any one of claims 162-165, wherein the antibody or antigen binding region that binds OX40L and/or the antibody or antigen binding region that binds IL-4Rα comprises a human IgG1 Fc region with LALA and YTE mutations. 174. The composition of any one of claims 149-157, the combination of any one of claims 158-161, or the method of any one of claims 162-165, wherein the antibody or antigen binding region that binds OX40L and/or the antibody or antigen binding region that binds IL-4Rα comprises a human Fc region, and wherein the human Fc region of the antibody or antigen binding region that binds OX40L comprises a human IgG1 Fc with LALA mutations (L235A/L236A by direct numbering) and YTE mutations (M253Y/S255T/T257E by direct numbering) and/or the human Fc region of the antibody or antigen binding region that binds IL- 4Rα comprises a human IgG1 Fc with LALA mutations (L242A/L243A by direct numbering) and YTE mutations (M260Y/S262T/T264E by direct numbering). 175. The composition of any one of claims 149-157, the combination of any one of claims 158-161, or the method of any one of claims 162-165, wherein the antibody or antigen binding region that binds OX40L and/or the antibody or antigen binding region that binds IL-4Rα comprises an Fc region that binds to Neonatal Fc receptor (FcRn). 176. The composition of any one of claims 149-157, the combination of any one of claims 158-161, or the method of any one of claims 162-165, wherein the antibody or antigen binding region that binds OX40L and/or the antibody or antigen binding region that binds IL-4Rα comprises an Fc region that binds an FcRn with higher affinity at pH 6.0 compared to an antibody comprising a wild-type Fc region. 177. The composition of any one of claims 149-157, the combination of any one of claims 158-161, or the method of any one of claims 162-165, wherein the antibody or antigen binding region that binds OX40L and/or the antibody or antigen binding region that binds I IL-4Rα comprises an Fc region that binds to FcRn with a KD of <1 x 10-7 M at pH 6.0. 178. The composition of any one of claims 149-157, the combination of any one of claims 158-161, or the method of any one of claims 162-165, wherein the antibody or antigen binding region that binds OX40L and/or the antibody or antigen binding region that binds IL-4Rα is a monoclonal antibody. 179. The composition of any one of claims 149-157, the combination of any one of claims 158-161, or the method of any one of claims 162-165, wherein the antibody or antigen binding region that binds OX40L binds an OX40L sequence set forth in the amino acid sequence of SEQ ID NO: 739. 180. The composition of any one of claims 149-157, the combination of any one of claims 158-161, or the method of any one of claims 162-165, wherein the antibody or antigen binding region that binds IL-4Rα binds an IL-4Rα sequence set forth in any one of the amino acid sequences of SEQ ID NOs: 301-303. 181. The composition of any one of claims 149-157, the combination of any one of claims 158-161, or the method of any one of claims 162-165, wherein the antibody or antigen binding region that binds OX40L comprises a heavy chain comprising a constant heavy chain sequence set forth in SEQ ID NO: 651 or SEQ ID NO: 973. 182. The composition of any one of claims 149-157, the combination of any one of claims 158-161, or the method of any one of claims 162-165, wherein the antibody or antigen binding region that binds OX40L comprises a light chain comprising a constant light chain sequence set forth in SEQ ID NO: 738. 183. The composition of any one of claims 149-157, the combination of any one of claims 158-161, or the method of any one of claims 162-165, wherein the antibody or antigen binding region that binds IL-4Rα comprises a heavy chain comprising a constant heavy chain sequence set forth in SEQ ID NO: 651 or SEQ ID NO: 973. 184. The composition of any one of claims 149-157, the combination of any one of claims 158-161, or the method of any one of claims 162-165, wherein the antibody or antigen binding region that binds IL-4Rα comprises a light chain comprising a constant light chain sequence set forth in SEQ ID NO: 738. 185. The composition of any one of claims 149-157, the combination of any one of claims 158-161, or the method of any one of claims 162-165, wherein the hyaluronidase is a recombinant human hyaluronidase. 186. The composition, combination, or method of claim 185, wherein the recombinant human hyaluronidase comprises the amino acid sequence set forth in any one of SEQ ID NOs: 1076- 1085 and 1087-1142. 187. The composition, combination, or method of claim 185, wherein the recombinant human hyaluronidase is rHuPH20. 188. The composition, combination, or method of claim 187, wherein the rHuPH20 formulation is ENHANZE®. 189. The composition of any one of claims 149-157, the combination of any one of claims 158-161, or the method of any one of claims 162-165, wherein the hyaluronidase and antibody or antibodies are administered in separate formulations. 190. The composition of any one of claims 149-157, the combination of any one of claims 158-161, or the method of any one of claims 162-165, wherein the hyaluronidase and antibody or antibodies are administered simultaneously in separate formulations. 191. The composition, combination, or method of claim 189, wherein the hyaluronidase is administered to the patient prior to administration of the antibody or antibodies. 192. The composition, combination, or method of claim 189, wherein the hyaluronidase is administered to the patient after administration of the antibody or antibodies. 193. The composition, combination, or method of claim 189, wherein the hyaluronidase is administered to the patient after administration of one of the antibodies, but before administration of the other antibody. 194. The composition of any one of claims 149-157, the combination of any one of claims 158-161, or the method of any one of claims 162-165, wherein the hyaluronidase and antibody or antibodies are administered in a single formulation. 195. The composition of any one of claims 149-157, the combination of any one of claims 158-161, or the method of any one of claims 162-165, wherein the hyaluronidase and antibody or antibodies are administered by subcutaneous injection. 196. The composition of any one of claims 149-157, the combination of any one of claims 158-161, or the method of any one of claims 162-165, wherein the hyaluronidase and antibody or antibodies are administered by intravenous injection. 197. The composition of any one of claims 149-157, the combination of any one of claims 158-161, or the method of any one of claims 162-165, wherein the hyaluronidase is rHuPH20 (ENHANZE®) administered at a concentration of 5,000, 6,000, 7,000, 8,000, 9,000, 10,000, 11,000, 12,000, 13,000, 14,000, 15,000, 16,000, 17,000, 18,000, 19,000, 20,000, 21,000, 22,000, 23,000, 24,000, 25,000, 26,000, 27,000, 28,000, 29,000, 30,000, 31,000, 32,000, 33,000, 34,000, 35,000, 36,000, 37,000, 38,000, 39,000, or 40,000 units. 198. The method of any one of claims 162-165, wherein the inflammatory disorder or disease is atopic dermatitis. 199. The method of claim 198, wherein the treatment reduces disease severity in the patient and wherein disease severity is assessed by an atopic dermatitis disease severity outcome measure. 200. The method of any one of claims 162-165, wherein the inflammatory disorder or disease is asthma; chronic sinusitis with nasal polyps; Chronic Rhinosinusitis without Nasal Polyps (CRSsNP); eosinophilic esophagitis (EoE); an Eosinophilic gastrointestinal disorder or disease (EGID) selected from the group consisting of Eosinophilic Gastritis (EoG), Eosinophilic Enteritis (EoN), Eosinophilic Colitis (EoC), and Eosinophilic Gastroenteritis (EGE); Churg- Strauss syndrome/Eosinophilic granulomatosis with polyangiitis (EGPA); Prurigo Nodularis (PN); Chronic Spontaneous Urticaria (CSU); Chronic Pruritis of Unknown Origin (CPUO); Bullous Pemphigoid (BP); Cold Inducible Urticaria (ColdU); Allergic Fungal Rhinosinusitis (AFRS); Allergic Bronchopulmonary Aspergillosis (ABPA); Chronic Obstructive Pulmonary Disease (COPD); Crohn’s disease; lupus; rheumatoid arthritis (RA); psoriasis; ulcerative colitis; hidradenitis suppurativa; celiac disease; systemic sclerosis; idiopathic pulmonary fibrosis; alopecia areata, allergic rhinitis; eosinophilic fasciitis; scleromyxedema; scleredema; or nephrogenic systemic fibrosis. 201. A kit for treating an inflammatory disorder or disease in a human patient, the kit comprising: (a) a dose of an antibody, or antigen binding fragment thereof, that binds OX40L, wherein the antibody comprises a VH sequence set forth in SEQ ID NO: 1 and a VL sequence set forth in SEQ ID NO: 11; (b) a dose of an antibody, or antigen binding fragment thereof, that binds IL-4Rα, wherein the antibody comprises a VH sequence set forth in SEQ ID NO: 297 and a VL sequence set forth in SEQ ID NO: 300; (c) a dose of a hyaluronidase or variant thereof; and (d) instructions. 202. The kit of claim 201, wherein the hyaluronidase is a recombinant human hyaluronidase. 203. The kit of claim 202, wherein the recombinant human hyaluronidase comprises the amino acid sequence set forth in any one of SEQ ID NOs: 1076-1085 and 1087-1142. 204. The kit of claim 202, wherein the recombinant human hyaluronidase is rHuPH20. 205. The kit of claim 204, wherein the rHuPH20 formulation is ENHANZE®. 206. The kit of claim 202, for use in treating an inflammatory disorder or disease. 207. The kit of claim 206, wherein the inflammatory disorder or disease is atopic dermatitis. 208. The kit of claim 206, wherein the inflammatory disorder or disease is asthma; chronic sinusitis with nasal polyps; Chronic Rhinosinusitis without Nasal Polyps (CRSsNP); eosinophilic esophagitis (EoE); an Eosinophilic gastrointestinal disorder or disease (EGID) selected from the group consisting of Eosinophilic Gastritis (EoG), Eosinophilic Enteritis (EoN), Eosinophilic Colitis (EoC), and Eosinophilic Gastroenteritis (EGE); Churg-Strauss syndrome/Eosinophilic granulomatosis with polyangiitis (EGPA); Prurigo Nodularis (PN); Chronic Spontaneous Urticaria (CSU); Chronic Pruritis of Unknown Origin (CPUO); Bullous Pemphigoid (BP); Cold Inducible Urticaria (ColdU); Allergic Fungal Rhinosinusitis (AFRS); Allergic Bronchopulmonary Aspergillosis (ABPA); Chronic Obstructive Pulmonary Disease (COPD); Crohn’s disease; lupus; rheumatoid arthritis (RA); psoriasis; ulcerative colitis; hidradenitis suppurativa; celiac disease; systemic sclerosis; idiopathic pulmonary fibrosis; alopecia areata, allergic rhinitis; eosinophilic fasciitis; scleromyxedema; scleredema; or nephrogenic systemic fibrosis. 209. An isolated antibody, or an antigen binding fragment thereof, that binds OX40L, comprising: a) a variable heavy (VH) chain sequence having three heavy chain CDR sequences, CDR-H1, CDR-H2, and CDR-H3; and b) a variable light (VL) chain sequence having three light chain CDR sequences, CDR-L1, CDR-L2, and CDR-L3; wherein the antibody, or antigen binding fragment thereof, that binds OX40L comprises: (i) a CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 2-4; a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 5-7; a CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 8-10; a CDR-L1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 12-14; a CDR-L2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 15-16; and a CDR-L3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 17-18; and an isolated antibody, or an antigen binding fragment thereof, that binds IL-4Rα, wherein the isolated antibody, or antigen binding fragment thereof, that binds IL-4Rα comprises: a) a VH chain sequence having three heavy chain CDR sequences, CDR-H1, CDR-H2, and CDR-H3; and b) a VL chain sequence having three light chain CDR sequences, CDR-L1, CDR-L2, and CDR-L3, wherein the isolated antibody, or antigen binding fragment thereof, that binds IL-4Rα comprises: (iii) a CDR-H1 comprising the sequence set forth in any one of SEQ ID NOs: 273, 274, and 275; a CDR-H2 comprising the sequence set forth in any one of SEQ ID NOs: 279, 277, and 280; a CDR-H3 comprising the sequence set forth in any one of SEQ ID NOs: 281 and 282; a CDR-L1 comprising the sequence set forth in any one of SEQ ID NOs: 289 and 288; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 290 or the amino acid sequence EG; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 293, wherein the isolated antibody, or antigen binding fragment thereof, that binds OX40L and/or the isolated antibody, or antigen binding fragment thereof, that binds IL-4Rα comprises a heavy chain comprising a heavy chain constant region having a means for extending the half-life of the isolated antibody. 210. A multi-specific antibody comprising: a first antigen binding region that binds OX40L, comprising: a) a VH chain sequence having three heavy chain CDR sequences, CDR-H1, CDR- H2, and CDR-H3; and b) a VL chain sequence having three light chain CDR sequences, CDR- L1, CDR-L2, and CDR-L3; wherein the antigen binding region that binds OX40L comprises: (i) a CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 2-4; a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 5-7; a CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 8-10; a CDR-L1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 12-14; a CDR-L2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 15-16; and a CDR-L3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 17-18; and a second antigen binding region that binds IL-4Rα comprising: a) a VH chain sequence having three heavy chain CDR sequences, CDR-H1, CDR-H2, and CDR-H3; and b) a VL chain sequence having three light chain CDR sequences, CDR-L1, CDR-L2, and CDR-L3, wherein the antigen binding region that binds IL-4Rα comprises: (iii) a CDR-H1 comprising the sequence set forth in any one of SEQ ID NOs: 273, 274, and 275; a CDR-H2 comprising the sequence set forth in any one of SEQ ID NOs: 279, 277, and 280; a CDR-H3 comprising the sequence set forth in any one of SEQ ID NOs: 281 and 282; a CDR-L1 comprising the sequence set forth in any one of SEQ ID NOs: 289 and 288; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 290 or the amino acid sequence EG; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 293, wherein the multi-specific antibody comprises a heavy chain constant region having a means for extending the half-life of the multi-specific antibody. 211. A composition comprising an isolated antibody, or antigen binding region thereof, that binds OX40L and an isolated antibody, or antigen binding region thereof, that binds IL-4Rα, wherein the antibody, or antigen binding region thereof, that binds OX40L comprises a CDR-H1 comprising the sequence set forth in SEQ ID NO: 2; a CDR-H2 comprising the sequence set forth in SEQ ID NO: 5; a CDR-H3 comprising the sequence set forth in SEQ ID NO: 8; a CDR-L1 comprising the sequence set forth in SEQ ID NO: 12; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 15; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 17, and wherein the antibody, or antigen binding region thereof, that binds IL-4Rα comprises a CDR-H1 comprising the sequence set forth in SEQ ID NO: 273; a CDR-H2 comprising the sequence set forth in SEQ ID NO: 279; a CDR-H3 comprising the sequence set forth in SEQ ID NO: 281; a CDR-L1 comprising the sequence set forth in SEQ ID NO: 289; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 290; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 293, wherein the composition further comprises a means for increasing the bioavailability of the isolated antibody, or antigen binding region thereof, that binds OX40L and/or the isolated antibody, or antigen binding region thereof, that binds IL-4Rα.
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