CN114302893B - 用于细胞靶向的多特异性抗原结合分子及其用途 - Google Patents

用于细胞靶向的多特异性抗原结合分子及其用途 Download PDF

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CN114302893B
CN114302893B CN202080061412.XA CN202080061412A CN114302893B CN 114302893 B CN114302893 B CN 114302893B CN 202080061412 A CN202080061412 A CN 202080061412A CN 114302893 B CN114302893 B CN 114302893B
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antigen
domain
molecule
binding
cell
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CN114302893A (zh
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L·哈伯
J·A·芬尼
R·麦凯
E·史密斯
C-Y·林
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Regeneron Pharmaceuticals Inc
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    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K16/00Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies
    • C07K16/18Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/28Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
    • C07K16/30Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants from tumour cells
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00Antineoplastic agents
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K14/00Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/705Receptors; Cell surface antigens; Cell surface determinants
    • C07K14/70503Immunoglobulin superfamily
    • C07K14/7051T-cell receptor (TcR)-CD3 complex
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K14/00Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/705Receptors; Cell surface antigens; Cell surface determinants
    • C07K14/70503Immunoglobulin superfamily
    • C07K14/70539MHC-molecules, e.g. HLA-molecules
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K16/00Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies
    • C07K16/18Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/28Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
    • C07K16/2803Immunoglobulins [IG], 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 [IG], 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 [IG], e.g. monoclonal or polyclonal antibodies
    • C07K16/18Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/28Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
    • C07K16/2803Immunoglobulins [IG], 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 [IG], 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 [IG], e.g. monoclonal or polyclonal antibodies
    • C07K16/18Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/28Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
    • C07K16/2863Immunoglobulins [IG], 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 [IG], e.g. monoclonal or polyclonal antibodies
    • C07K16/46Hybrid immunoglobulins
    • C07K16/468Immunoglobulins having two or more different antigen binding sites, e.g. multifunctional antibodies
    • 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
    • C07K2317/50Immunoglobulins 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
    • C07K2317/55Fab or Fab'
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K2317/00Immunoglobulins specific features
    • C07K2317/60Immunoglobulins specific features characterized by non-natural combinations of immunoglobulin fragments
    • C07K2317/62Immunoglobulins specific features characterized by non-natural combinations of immunoglobulin fragments comprising only variable region components
    • C07K2317/622Single chain antibody (scFv)
    • 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
    • C07K2317/90Immunoglobulins 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)
  • Immunology (AREA)
  • Organic Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Biochemistry (AREA)
  • Biophysics (AREA)
  • Genetics & Genomics (AREA)
  • Molecular Biology (AREA)
  • Cell Biology (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Zoology (AREA)
  • Toxicology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Oncology (AREA)
  • Communicable Diseases (AREA)
  • Peptides Or Proteins (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Medicines Containing Material From Animals Or Micro-Organisms (AREA)
CN202080061412.XA 2019-08-15 2020-08-14 用于细胞靶向的多特异性抗原结合分子及其用途 Active CN114302893B (zh)

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CN202510048366.4A CN119954933A (zh) 2019-08-15 2020-08-14 用于细胞靶向的多特异性抗原结合分子及其用途

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US201962887411P 2019-08-15 2019-08-15
US62/887,411 2019-08-15
US201962924435P 2019-10-22 2019-10-22
US62/924,435 2019-10-22
US202062978584P 2020-02-19 2020-02-19
US62/978,584 2020-02-19
US202063057824P 2020-07-28 2020-07-28
US63/057,824 2020-07-28
PCT/US2020/046352 WO2021030680A1 (en) 2019-08-15 2020-08-14 Multispecific antigen-binding molecules for cell targeting and uses thereof

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US (4) US12077603B2 (enExample)
EP (1) EP4013797A1 (enExample)
JP (2) JP7629906B2 (enExample)
KR (1) KR20220044821A (enExample)
CN (2) CN114302893B (enExample)
AU (1) AU2020330063A1 (enExample)
BR (1) BR112022002012A2 (enExample)
CA (1) CA3147791A1 (enExample)
IL (1) IL290299A (enExample)
MX (1) MX2022001942A (enExample)
TW (2) TWI890689B (enExample)
WO (1) WO2021030680A1 (enExample)

Families Citing this family (12)

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WO2016161010A2 (en) 2015-03-30 2016-10-06 Regeneron Pharmaceuticals, Inc. Heavy chain constant regions with reduced binding to fc gamma receptors
AU2016325630B2 (en) * 2015-09-23 2022-11-17 Regeneron Pharmaceuticals, Inc. Optimized anti-CD3 bispecific antibodies and uses thereof
EP4004049A1 (en) 2019-07-24 2022-06-01 Regeneron Pharmaceuticals, Inc. Chimeric antigen receptors with mage-a4 specificity and uses thereof
KR20230121854A (ko) 2020-12-17 2023-08-21 리제너론 파아마슈티컬스, 인크. 단백질-캡슐화 마이크로겔의 제작
MX2023008527A (es) 2021-01-20 2023-07-28 Regeneron Pharma Metodos para mejorar el valor proteico en cultivo celular.
AU2022271212A1 (en) * 2021-05-04 2023-11-30 Regeneron Pharmaceuticals, Inc. Chimeric antigen receptors with mage-a4 specificity and uses thereof
CA3227537A1 (en) * 2021-07-27 2023-02-02 Morphosys Ag Combinations of antigen binding molecules
WO2023183758A2 (en) * 2022-03-19 2023-09-28 Regeneron Pharmaceuticals, Inc. Multispecific molecules targeting cd3 and mage-a4 and uses thereof
JP2025525886A (ja) * 2022-08-02 2025-08-07 オーエスイー・イミュノセラピューティクス Cd28に対する多機能性分子
JP2026507123A (ja) * 2023-02-28 2026-02-27 リジェネロン・ファーマシューティカルズ・インコーポレイテッド T細胞活性化剤およびその使用方法
WO2025199278A2 (en) 2024-03-20 2025-09-25 Regeneron Pharmaceuticals, Inc. Masked multispecific antigen-binding molecules with cleavable linkers
WO2025255480A1 (en) * 2024-06-07 2025-12-11 Regeneron Pharmaceuticals, Inc. Tetravalent multispecific binding molecules and methods of use thereof

Citations (3)

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WO1991003493A1 (en) * 1989-08-29 1991-03-21 The University Of Southampton Bi-or trispecific (fab)3 or (fab)4 conjugates
WO2014022540A1 (en) * 2012-08-02 2014-02-06 Regeneron Pharmaceuticals, Inc. Multivalent antigen-binding proteins
WO2018178074A1 (en) * 2017-03-29 2018-10-04 F. Hoffmann-La Roche Ag Trimeric antigen binding molecules specific for a costimulatory tnf receptor

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US7550143B2 (en) * 2005-04-06 2009-06-23 Ibc Pharmaceuticals, Inc. Methods for generating stably linked complexes composed of homodimers, homotetramers or dimers of dimers and uses
US7850962B2 (en) 2004-04-20 2010-12-14 Genmab A/S Human monoclonal antibodies against CD20
CA2604032C (en) * 2005-04-06 2017-08-22 Ibc Pharmaceuticals, Inc. Methods for generating stably linked complexes composed of homodimers, homotetramers or dimers of dimers and uses
PE20120540A1 (es) * 2009-05-27 2012-05-09 Hoffmann La Roche Anticuerpos triespecificos o tetraespecificos
MY192182A (en) 2009-06-26 2022-08-04 Regeneron Pharma Readily isolated bispecific antibodies with native immunoglobulin format
SMT202600080T1 (it) 2010-02-08 2026-03-09 Regeneron Pharma Topo con catena leggera comune
JOP20200236A1 (ar) 2012-09-21 2017-06-16 Regeneron Pharma الأجسام المضادة لمضاد cd3 وجزيئات ربط الأنتيجين ثنائية التحديد التي تربط cd3 وcd20 واستخداماتها
JP2014124186A (ja) 2012-12-26 2014-07-07 Industrial Technology Research Institute 多価抗体フラグメントおよびその三量体化複合体
TWI635098B (zh) 2013-02-01 2018-09-11 再生元醫藥公司 含嵌合恆定區之抗體
WO2016105450A2 (en) * 2014-12-22 2016-06-30 Xencor, Inc. Trispecific antibodies
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AU2016325630B2 (en) 2015-09-23 2022-11-17 Regeneron Pharmaceuticals, Inc. Optimized anti-CD3 bispecific antibodies and uses thereof
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WO2014022540A1 (en) * 2012-08-02 2014-02-06 Regeneron Pharmaceuticals, Inc. Multivalent antigen-binding proteins
WO2018178074A1 (en) * 2017-03-29 2018-10-04 F. Hoffmann-La Roche Ag Trimeric antigen binding molecules specific for a costimulatory tnf receptor

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JP2025072461A (ja) 2025-05-09
CA3147791A1 (en) 2021-02-18
JP7629906B2 (ja) 2025-02-14
US20230068129A1 (en) 2023-03-02
TWI890689B (zh) 2025-07-21
AU2020330063A1 (en) 2022-03-24
US12077603B2 (en) 2024-09-03
US12065508B2 (en) 2024-08-20
US20240368312A1 (en) 2024-11-07
KR20220044821A (ko) 2022-04-11
US20210047438A1 (en) 2021-02-18
US11952430B2 (en) 2024-04-09
TW202542199A (zh) 2025-11-01
JP2022545647A (ja) 2022-10-28
BR112022002012A2 (pt) 2022-06-07
CN119954933A (zh) 2025-05-09
EP4013797A1 (en) 2022-06-22
IL290299A (en) 2022-04-01
TW202120553A (zh) 2021-06-01
WO2021030680A1 (en) 2021-02-18
US20220251244A1 (en) 2022-08-11
MX2022001942A (es) 2022-07-27
CN114302893A (zh) 2022-04-08

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