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AR106491A1 - Conjugados de anticuerpo que comprenden un agonista del receptor tipo toll - Google Patents

Conjugados de anticuerpo que comprenden un agonista del receptor tipo toll

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Publication number
AR106491A1
AR106491A1 ARP160103298A ARP160103298A AR106491A1 AR 106491 A1 AR106491 A1 AR 106491A1 AR P160103298 A ARP160103298 A AR P160103298A AR P160103298 A ARP160103298 A AR P160103298A AR 106491 A1 AR106491 A1 AR 106491A1
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Argentina
Prior art keywords
nnhc
alkyl
independently selected
formulas
group
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ARP160103298A
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English (en)
Inventor
Cortez Alex
Yao Wu Tom
Hsiang Wnag Xing
Uno Tetsuo
Kasibhatla Shailaja
Z Hoffman Timothy
Hubert Geierstanger Bernhard
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Novartis Ag
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Publication of AR106491A1 publication Critical patent/AR106491A1/es

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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/519Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
    • A61K31/52Purines, e.g. adenine
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/51Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
    • A61K47/68Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
    • A61K47/6835Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment the modifying agent being an antibody or an immunoglobulin bearing at least one antigen-binding site
    • A61K47/6849Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment the modifying agent being an antibody or an immunoglobulin bearing at least one antigen-binding site the antibody targeting a receptor, a cell surface antigen or a cell surface determinant
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00Antineoplastic agents
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D487/00Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
    • C07D487/02Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
    • C07D487/04Ortho-condensed systems
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07HSUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
    • C07H15/00Compounds containing hydrocarbon or substituted hydrocarbon radicals directly attached to hetero atoms of saccharide radicals
    • C07H15/26Acyclic or carbocyclic radicals, substituted by hetero rings
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K16/00Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/18Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/28Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
    • C07K16/2863Immunoglobulins [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 growth factors, growth regulators
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K16/00Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/18Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/32Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against translation products of oncogenes
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K2317/00Immunoglobulins specific features
    • C07K2317/20Immunoglobulins specific features characterized by taxonomic origin
    • C07K2317/24Immunoglobulins specific features characterized by taxonomic origin containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K2317/00Immunoglobulins specific features
    • C07K2317/50Immunoglobulins specific features characterized by immunoglobulin fragments
    • C07K2317/51Complete heavy chain or Fd fragment, i.e. VH + CH1
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K2317/00Immunoglobulins specific features
    • C07K2317/50Immunoglobulins specific features characterized by immunoglobulin fragments
    • C07K2317/515Complete light chain, i.e. VL + CL
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K2317/00Immunoglobulins specific features
    • C07K2317/50Immunoglobulins specific features characterized by immunoglobulin fragments
    • C07K2317/52Constant or Fc region; Isotype
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K2317/00Immunoglobulins specific features
    • C07K2317/90Immunoglobulins specific features characterized by (pharmaco)kinetic aspects or by stability of the immunoglobulin
    • C07K2317/94Stability, e.g. half-life, pH, temperature or enzyme-resistance

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Immunology (AREA)
  • Genetics & Genomics (AREA)
  • Biochemistry (AREA)
  • Molecular Biology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Engineering & Computer Science (AREA)
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  • Biophysics (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Biotechnology (AREA)
  • Cell Biology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Oncology (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Peptides Or Proteins (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicinal Preparation (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Saccharide Compounds (AREA)
  • Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

Abstract

Se proporcionan en la presente, conjugados de anticuerpos que comprenden agonistas del receptor tipo toll y el uso de tales conjugados para el tratamiento de cáncer. En algunas modalidades, los conjugados comprenden anticuerpos anti-HER2. Reivindicación 1: Un conjugado de la fórmula (1), o sal farmacéuticamente aceptable del mismo, en donde R⁵⁰ es un compuesto de fórmula (2) ó (3), donde el * indica el punto de unión a Ab; Ab es un anticuerpo o fragmento de unión a antígeno del mismo que específicamente se une a HER2 humano; R¹ es -NHR² o -NHCHR²R³; R² es -alquilo C₃₋₆ o -alquilo C₄₋₆; R³ es L¹OH; L¹ es -(CH₂)ₘ-; L² es -(CH₂)ₙ-, -((CH₂)ₙO)ₜ(CH₂)ₙ-, -(CH₂)ₙX¹(CH₂)ₙ-, -(CH₂)ₙNHC(=O)(CH₂)ₙ-, -(CH₂)ₙNHC(=O)(CH₂)ₙC(=O)NH(CH₂)ₙ-, -((CH₂)ₙO)ₜ(CH₂)ₙNHC(=O)(CH₂)ₙ, -C(=O)(CH₂)ₙ-, -C(=O)((CH₂)ₙO)ₜ(CH₂)ₙ-, -C(=O)((CH₂)ₙO)ₜ(CH₂)ₙX¹(CH₂)ₙ-, -C(=O)((CH₂)ₙO)ₜ(CH₂)ₙNHC(=O)(CH₂)ₙ-, -C(=O)((CH₂)ₙO)ₜ(CH₂)ₙC(=O)NH(CH₂)ₙ-, -C(=O)NH((CH₂)ₙO)ₜ(CH₂)ₙX¹(CH₂)ₙ-, -C(=O)X²X³C(=O)((CH₂)ₙO)ₜ(CH₂)ₙ-, C(=O)X²X³C(=O)(CH₂)ₙ-, -C(=O)X²C(=O)(CH₂)ₙNHC(=O)(CH₂)ₙ-, -C(=O)X²C(=O)(CH₂)ₙNHC(=O)((CH₂)ₙO)ₜ(CH₂)ₙ-, -C(=O)(CH₂)ₙC(R⁷)₂-, -C(=O)(CH₂)ₙC(R⁷)₂S(CH₂)ₙNHC(=O)(CH₂)ₙ-, -(CH₂)ₙX²C(=O)(CH₂)ₙNHC(=O)((CH₂)ₙO)ₜ(CH₂)ₙ- o -C(=O)(CH₂)ₙC(=O)NH(CH₂)ₙ; R⁴⁰ es -S-, NHC(=O)CH₂-, -S(=O)₂CH₂CH₂-, -(CH₂)₂S(=O)₂CH₂CH₂-, -NHS (=O)₂CH₂CH₂, -NHC(=O)CH₂CH₂-, -CH₂NHCH₂CH₂-, -NHCH₂CH₂-, o un compuesto seleccionado del grupo de fórmulas (4); X¹ es un resto del grupo de fórmulas (5); X² es un resto del grupo de fórmulas (6); X³ es un resto del grupo de fórmulas (7); cada R⁷ se selecciona independientemente a partir de H y alquilo C₁₋₆; cada R⁸ se selecciona independientemente a partir de H, alquilo C₁₋₆, F, Cₗ, ʸ ₋OH; ᶜₐᵈₐ R⁹ se selecciona independientemente a partir de H, alquilo C₁₋₆, F, Cₗ, ₋NH₂, -OCH₃, -OCH₂CH₃, -N(CH₃)₂, -CN, -NO₂ y -OH; cada R¹⁰ se selecciona independientemente a partir de H, alquilo C₁₋₆, fluoro, benciloxilo sustituido por -C(=O)OH, bencilo sustituido por -C(=O)OH, C₁₋₄ alcoxilo sustituido por -C(=O)OH y alquilo C₁₋₄ sustituido por -C(=O)OH; R¹² es H, metilo o fenilo; cada m se selecciona independientemente a partir de 1, 2, 3, y 4; cada n se selecciona independientemente a partir de 1, 2, 3, y 4; cada t se selecciona independientemente a partir de 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17 y 18, e y es un entero de 1 a 16.
ARP160103298A 2015-10-29 2016-10-28 Conjugados de anticuerpo que comprenden un agonista del receptor tipo toll AR106491A1 (es)

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US201562247896P 2015-10-29 2015-10-29

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AR106491A1 true AR106491A1 (es) 2018-01-17

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US (2) US10973826B2 (es)
EP (2) EP3368092B9 (es)
JP (2) JP6877420B2 (es)
KR (1) KR20180068989A (es)
CN (1) CN108430515B (es)
AR (1) AR106491A1 (es)
AU (1) AU2016347385B2 (es)
BR (1) BR112018007296A2 (es)
CA (1) CA3001482A1 (es)
CL (1) CL2018000920A1 (es)
CO (1) CO2018004315A2 (es)
CR (1) CR20180229A (es)
CU (1) CU24502B1 (es)
EA (1) EA201891040A1 (es)
EC (1) ECSP18038868A (es)
ES (1) ES2798649T3 (es)
HK (1) HK1257776A1 (es)
IL (1) IL258483A (es)
MA (1) MA44334A (es)
MX (1) MX2018005289A (es)
PE (1) PE20181347A1 (es)
PH (1) PH12018500815A1 (es)
PL (1) PL3368092T3 (es)
PT (1) PT3368092T (es)
RU (1) RU2018119296A (es)
SG (1) SG11201802769RA (es)
TN (1) TN2018000112A1 (es)
TW (1) TW201722482A (es)
UY (1) UY36968A (es)
WO (1) WO2017072662A1 (es)

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