CO2021014076A2 - Anticuerpos multiespecíficos egfr x cd28 - Google Patents

Anticuerpos multiespecíficos egfr x cd28

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Publication number
CO2021014076A2
CO2021014076A2 CONC2021/0014076A CO2021014076A CO2021014076A2 CO 2021014076 A2 CO2021014076 A2 CO 2021014076A2 CO 2021014076 A CO2021014076 A CO 2021014076A CO 2021014076 A2 CO2021014076 A2 CO 2021014076A2
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Colombia
Prior art keywords
antibodies
egfr
egfrxcd28
lymphocytes
arm
Prior art date
Application number
CONC2021/0014076A
Other languages
English (en)
Inventor
Andrew J Murphy
Dimitris Skokos
Lauric Haber
George D Yancopoulos
Chia-Yang Lin
Original Assignee
Regeneron Pharma
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Regeneron Pharma filed Critical Regeneron Pharma
Publication of CO2021014076A2 publication Critical patent/CO2021014076A2/es

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    • 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
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00Medicinal preparations containing antigens or antibodies
    • A61K39/395Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
    • A61K39/39533Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals
    • A61K39/3955Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals against proteinaceous materials, e.g. enzymes, hormones, lymphokines
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/0012Galenical forms characterised by the site of application
    • A61K9/0019Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00Antineoplastic agents
    • 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
    • C07K16/2803Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the immunoglobulin superfamily
    • C07K16/2809Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the immunoglobulin superfamily against the T-cell receptor (TcR)-CD3 complex
    • 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
    • C07K16/2803Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the immunoglobulin superfamily
    • C07K16/2818Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the immunoglobulin superfamily against CD28 or CD152
    • 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
    • C07K16/30Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants from tumour cells
    • C07K16/3069Reproductive system, e.g. ovaria, uterus, testes, prostate
    • 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
    • C07K16/30Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants from tumour cells
    • C07K16/3076Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants from tumour cells against structure-related tumour-associated moieties
    • C07K16/3092Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants from tumour cells against structure-related tumour-associated moieties against tumour-associated mucins
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K16/00Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/40Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against enzymes
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N5/00Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
    • C12N5/06Animal cells or tissues; Human cells or tissues
    • C12N5/0602Vertebrate cells
    • C12N5/0681Cells of the genital tract; Non-germinal cells from gonads
    • C12N5/0682Cells of the female genital tract, e.g. endometrium; Non-germinal cells from ovaries, e.g. ovarian follicle cells
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00Medicinal preparations containing antigens or antibodies
    • A61K2039/505Medicinal preparations containing antigens or antibodies comprising antibodies
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00Medicinal preparations containing antigens or antibodies
    • A61K2039/505Medicinal preparations containing antigens or antibodies comprising antibodies
    • A61K2039/507Comprising a combination of two or more separate antibodies
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00Medicinal preparations containing antigens or antibodies
    • A61K2039/57Medicinal preparations containing antigens or antibodies characterised by the type of response, e.g. Th1, Th2
    • A61K2039/572Medicinal preparations containing antigens or antibodies characterised by the type of response, e.g. Th1, Th2 cytotoxic response
    • 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
    • C07K2317/30Immunoglobulins specific features characterized by aspects of specificity or valency
    • C07K2317/31Immunoglobulins specific features characterized by aspects of specificity or valency multispecific
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K2317/00Immunoglobulins specific features
    • C07K2317/30Immunoglobulins specific features characterized by aspects of specificity or valency
    • C07K2317/33Crossreactivity, e.g. for species or epitope, or lack of said crossreactivity
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K2317/00Immunoglobulins specific features
    • C07K2317/30Immunoglobulins specific features characterized by aspects of specificity or valency
    • C07K2317/34Identification of a linear epitope shorter than 20 amino acid residues or of a conformational epitope defined by amino acid residues
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K2317/00Immunoglobulins specific features
    • C07K2317/30Immunoglobulins specific features characterized by aspects of specificity or valency
    • C07K2317/35Valency
    • 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
    • C07K2317/50Immunoglobulins specific features characterized by immunoglobulin fragments
    • C07K2317/56Immunoglobulins specific features characterized by immunoglobulin fragments variable (Fv) region, i.e. VH and/or VL
    • C07K2317/565Complementarity determining region [CDR]
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K2317/00Immunoglobulins specific features
    • C07K2317/70Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
    • C07K2317/73Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K2317/00Immunoglobulins specific features
    • C07K2317/70Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
    • C07K2317/75Agonist effect on antigen
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K2317/00Immunoglobulins specific features
    • C07K2317/70Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
    • C07K2317/76Antagonist effect on antigen, e.g. neutralization or inhibition of binding
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K2317/00Immunoglobulins specific features
    • C07K2317/90Immunoglobulins specific features characterized by (pharmaco)kinetic aspects or by stability of the immunoglobulin
    • C07K2317/92Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Immunology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Genetics & Genomics (AREA)
  • Biochemistry (AREA)
  • Molecular Biology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Biophysics (AREA)
  • Engineering & Computer Science (AREA)
  • Animal Behavior & Ethology (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Biomedical Technology (AREA)
  • Epidemiology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
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  • Microbiology (AREA)
  • Wood Science & Technology (AREA)
  • Biotechnology (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Reproductive Health (AREA)
  • Dermatology (AREA)
  • Mycology (AREA)
  • Endocrinology (AREA)
  • General Engineering & Computer Science (AREA)
  • Pregnancy & Childbirth (AREA)
  • Gynecology & Obstetrics (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
  • Peptides Or Proteins (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Micro-Organisms Or Cultivation Processes Thereof (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

La presente invención proporciona anticuerpos multiespecíficos que se unen a EGFR y CD28 (EGFRxCD28) así como anticuerpos anti-EGFR. Tales anticuerpos pueden combinarse con un agente terapéutico adicional tal como un anticuerpo anti-PD1. También se proporcionan métodos para tratar cánceres (por ejemplo, cáncer que expresa EGFR) mediante la administración de los anticuerpos (por ejemplo, y combinaciones de estos con anti-PD1). Los anticuerpos EGFRxCD28 de la presente invención representan una modalidad inmunoterapéutica dirigida al tumor combinada con inhibición de PD-1. Estos anticuerpos biespecíficos se unen a un antígeno específico de tumor (TSA) (EGFR) con un brazo y al receptor coestimulante, CD28, en los linfocitos T, con el otro brazo. La terapia de combinación con inhibidores de PD-1 potenció específicamente la activación de linfocitos T intratumorales, y promovió un fenotipo de linfocitos T de tipo memoria efectora sin secreción sistémica de citocinas en una variedad de modelos de xenoinjerto tumoral singénicos y humanos. Combinar esta clase de anticuerpos biespecíficos coestimulantes CD28 con el tratamiento anti-PD-1 validado clínicamente proporciona una terapia con anticuerpos bien tolerada con eficacia antitumoral marcadamente potenciada.
CONC2021/0014076A 2019-03-22 2021-10-21 Anticuerpos multiespecíficos egfr x cd28 CO2021014076A2 (es)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US201962822124P 2019-03-22 2019-03-22
PCT/US2020/023857 WO2020198009A1 (en) 2019-03-22 2020-03-20 EGFR x CD28 MULTISPECIFIC ANTIBODIES

Publications (1)

Publication Number Publication Date
CO2021014076A2 true CO2021014076A2 (es) 2021-10-29

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US (2) US11912767B2 (es)
EP (1) EP3941941A1 (es)
JP (1) JP2022526764A (es)
KR (1) KR20210142659A (es)
CN (1) CN113661177B (es)
AU (1) AU2020247803A1 (es)
BR (1) BR112021018442A2 (es)
CA (1) CA3134335A1 (es)
CL (2) CL2021002446A1 (es)
CO (1) CO2021014076A2 (es)
EA (1) EA202192566A1 (es)
IL (1) IL286536A (es)
MA (1) MA55363A (es)
MX (1) MX2021011500A (es)
SG (1) SG11202110341WA (es)
WO (1) WO2020198009A1 (es)

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MA52970A (fr) * 2018-06-21 2021-04-28 Regeneron Pharma Anticorps anti-psma x anti-cd28 bispécifiques et leurs utilisations
IL300666A (en) 2020-08-19 2023-04-01 Xencor Inc ANTI–CD28 COMPOSITIONS
JP2023548443A (ja) * 2020-10-30 2023-11-16 ジャナックス セラピューティクス,インク. Cd28およびpd-l1を標的とする多特異性抗体ならびにその使用方法
CA3173151A1 (en) * 2020-11-03 2022-05-12 Deutsches Krebsforschungszentrum Stiftung Des Offentlichen Rechts Target-cell restricted, costimulatory, bispecific and bivalent anti-cd28 antibodies
EP4274901A1 (en) 2021-01-11 2023-11-15 Sana Biotechnology, Inc. Use of cd8-targeted viral vectors
WO2022214652A1 (en) 2021-04-09 2022-10-13 Ose Immunotherapeutics Scaffold for bifunctioanl molecules comprising pd-1 or cd28 and sirp binding domains
TW202321457A (zh) 2021-08-04 2023-06-01 美商薩那生物科技公司 靶向cd4之病毒載體之用途
WO2023150518A1 (en) 2022-02-01 2023-08-10 Sana Biotechnology, Inc. Cd3-targeted lentiviral vectors and uses thereof
WO2023170474A1 (en) 2022-03-07 2023-09-14 Novimmune Sa Cd28 bispecific antibodies for targeted t cell activation
WO2023174925A1 (en) 2022-03-14 2023-09-21 Novimmune Sa Bispecific gpc3xcd28 and gpc3xcd3 antibodies and their combination for targeted killing of gpc3 positive malignant cells
WO2023193015A1 (en) 2022-04-01 2023-10-05 Sana Biotechnology, Inc. Cytokine receptor agonist and viral vector combination therapies
WO2023198042A1 (zh) * 2022-04-11 2023-10-19 江苏恒瑞医药股份有限公司 特异性结合egfr和cd28的抗原结合分子及其医药用途
WO2023198015A1 (zh) * 2022-04-11 2023-10-19 江苏恒瑞医药股份有限公司 特异性结合psma和cd28的抗原结合分子及其医药用途
WO2024015418A1 (en) 2022-07-13 2024-01-18 Regeneron Pharmaceuticals, Inc. Mild acid immunoassays for detection of analytes
WO2024026377A1 (en) 2022-07-27 2024-02-01 Sana Biotechnology, Inc. Methods of transduction using a viral vector and inhibitors of antiviral restriction factors
WO2024076926A1 (en) * 2022-10-03 2024-04-11 Regeneron Pharmaceuticals, Inc. Methods of treating cancer with bispecific egfr x cd28 antibodies alone or in combination with anti-pd-1 antibodies
WO2024084052A1 (en) 2022-10-21 2024-04-25 Novimmune Sa Pd-l1xcd28 bispecific antibodies for immune checkpoint-dependent t cell activation

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Publication number Publication date
EP3941941A1 (en) 2022-01-26
AU2020247803A1 (en) 2021-11-11
WO2020198009A8 (en) 2020-11-19
US11912767B2 (en) 2024-02-27
CN113661177A (zh) 2021-11-16
KR20210142659A (ko) 2021-11-25
MX2021011500A (es) 2021-10-22
IL286536A (en) 2021-10-31
WO2020198009A1 (en) 2020-10-01
CL2023002805A1 (es) 2024-03-15
US20200299388A1 (en) 2020-09-24
JP2022526764A (ja) 2022-05-26
MA55363A (fr) 2022-01-26
CN113661177B (zh) 2024-04-16
BR112021018442A2 (pt) 2022-01-11
SG11202110341WA (en) 2021-10-28
US20230322927A1 (en) 2023-10-12
CL2021002446A1 (es) 2022-05-06
CA3134335A1 (en) 2020-10-01
EA202192566A1 (ru) 2021-12-27

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