CN109476756B - 一种多特异性Fab融合蛋白及其用途 - Google Patents

一种多特异性Fab融合蛋白及其用途 Download PDF

Info

Publication number
CN109476756B
CN109476756B CN201780029960.2A CN201780029960A CN109476756B CN 109476756 B CN109476756 B CN 109476756B CN 201780029960 A CN201780029960 A CN 201780029960A CN 109476756 B CN109476756 B CN 109476756B
Authority
CN
China
Prior art keywords
seq
cancer
epcam
amino acid
acid sequence
Prior art date
Legal status (The legal status 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 status listed.)
Active
Application number
CN201780029960.2A
Other languages
English (en)
Chinese (zh)
Other versions
CN109476756A (zh
Inventor
崔玉敏
黄智华
陈汉阳
张新峰
戚波
严孝强
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.)
Aetna Virtue Hong Kong Ltd
Original Assignee
Aetna Virtue Hong Kong Ltd
Generon Shanghai Corp Ltd
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 Aetna Virtue Hong Kong Ltd, Generon Shanghai Corp Ltd filed Critical Aetna Virtue Hong Kong Ltd
Publication of CN109476756A publication Critical patent/CN109476756A/zh
Application granted granted Critical
Publication of CN109476756B publication Critical patent/CN109476756B/zh
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Images

Classifications

    • 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
    • C07K16/2803—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the immunoglobulin superfamily
    • C07K16/2809—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the immunoglobulin superfamily against the T-cell receptor (TcR)-CD3 complex
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
    • A61K31/57—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone
    • A61K31/573—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone substituted in position 21, e.g. cortisone, dexamethasone, prednisone or aldosterone
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • 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
    • C07K16/2803—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the immunoglobulin superfamily
    • C07K16/2821—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the immunoglobulin superfamily against ICAM molecules, e.g. CD50, CD54, CD102
    • 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
    • C07K16/30—Immunoglobulins [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
    • 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
    • C07K16/30—Immunoglobulins [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
    • C07K16/3023—Lung
    • 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
    • C07K16/30—Immunoglobulins [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
    • C07K16/3046—Stomach, Intestines
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09—Recombinant DNA-technology
    • C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
    • C12N15/62—DNA sequences coding for fusion proteins
    • 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
    • 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
    • C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
    • C07K2317/55—Fab or Fab'
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/60—Immunoglobulins specific features characterized by non-natural combinations of immunoglobulin fragments
    • C07K2317/62—Immunoglobulins specific features characterized by non-natural combinations of immunoglobulin fragments comprising only variable region components
    • 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
    • C07K2317/73—Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation
    • 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

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Organic Chemistry (AREA)
  • Immunology (AREA)
  • Genetics & Genomics (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Molecular Biology (AREA)
  • Biochemistry (AREA)
  • Biophysics (AREA)
  • Engineering & Computer Science (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Biomedical Technology (AREA)
  • Cell Biology (AREA)
  • General Engineering & Computer Science (AREA)
  • Veterinary Medicine (AREA)
  • Wood Science & Technology (AREA)
  • Biotechnology (AREA)
  • Zoology (AREA)
  • Public Health (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Epidemiology (AREA)
  • Plant Pathology (AREA)
  • Microbiology (AREA)
  • Physics & Mathematics (AREA)
  • Peptides Or Proteins (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
  • Preparation Of Compounds By Using Micro-Organisms (AREA)
  • Medicinal Preparation (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
CN201780029960.2A 2016-03-15 2017-03-15 一种多特异性Fab融合蛋白及其用途 Active CN109476756B (zh)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
CN2016101472278 2016-03-15
CN201610147227 2016-03-15
PCT/CN2017/076816 WO2017157305A1 (en) 2016-03-15 2017-03-15 Multispecific fab fusion proteins and use thereof

Publications (2)

Publication Number Publication Date
CN109476756A CN109476756A (zh) 2019-03-15
CN109476756B true CN109476756B (zh) 2022-05-31

Family

ID=59850975

Family Applications (1)

Application Number Title Priority Date Filing Date
CN201780029960.2A Active CN109476756B (zh) 2016-03-15 2017-03-15 一种多特异性Fab融合蛋白及其用途

Country Status (7)

Country Link
US (1) US10870701B2 (enExample)
EP (1) EP3430058A4 (enExample)
JP (1) JP7034489B2 (enExample)
CN (1) CN109476756B (enExample)
AU (1) AU2017233121B2 (enExample)
CA (1) CA3017776A1 (enExample)
WO (1) WO2017157305A1 (enExample)

Families Citing this family (33)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN107903325B (zh) 2011-05-16 2021-10-29 埃泰美德(香港)有限公司 多特异性fab融合蛋白及其使用方法
EP3024851B1 (en) 2013-07-25 2018-05-09 CytomX Therapeutics, Inc. Multispecific antibodies, multispecific activatable antibodies and methods of using the same
US10669337B2 (en) 2014-07-25 2020-06-02 Cytomx Therapeutics, Inc. Bispecific anti-CD3 antibodies, bispecific activatable anti-CD3 antibodies, and methods of using the same
CA2986575A1 (en) 2015-05-21 2016-11-24 Harpoon Therapeutics, Inc. Trispecific binding proteins and methods of use
AU2017233121B2 (en) 2016-03-15 2023-12-21 Itabmed (Hk) Limited Multispecific Fab fusion proteins and use thereof
US11623958B2 (en) 2016-05-20 2023-04-11 Harpoon Therapeutics, Inc. Single chain variable fragment CD3 binding proteins
SG11201810327XA (en) 2016-05-20 2018-12-28 Harpoon Therapeutics Inc Single domain serum albumin binding protein
KR20190087539A (ko) 2016-11-23 2019-07-24 하푼 테라퓨틱스, 인크. Psma 표적화 삼중특이성 단백질 및 사용 방법
US11535668B2 (en) 2017-02-28 2022-12-27 Harpoon Therapeutics, Inc. Inducible monovalent antigen binding protein
EP3621994A4 (en) 2017-05-12 2020-12-30 Harpoon Therapeutics, Inc. MESOTHELIN BINDING PROTEINS
IL315737A (en) 2017-10-13 2024-11-01 Harpoon Therapeutics Inc B-cell maturation antigen-binding proteins
CN111630070B (zh) 2017-10-13 2024-07-30 哈普恩治疗公司 三特异性蛋白质及使用方法
BR112020007309A2 (pt) * 2017-10-14 2020-09-29 Cytomx Therapeutics, Inc. anticorpos, anticorpos ativáveis, anticorpos biespecíficos e anticorpos ativáveis biespecíficos e métodos de uso dos mesmos
CN119192397A (zh) 2018-05-14 2024-12-27 哈普恩治疗公司 用于条件性激活免疫球蛋白分子的结合部分
US20210214424A1 (en) * 2018-05-16 2021-07-15 Chang Gung Memorial Hospital, Linkou Novel leucine-rich repeat neuronal protein 1 (lrrn1) antibodies and uses thereof
JP2021532135A (ja) * 2018-07-23 2021-11-25 中外製薬株式会社 標的細胞特異的な細胞質侵入抗原結合分子
JP7548587B2 (ja) * 2018-09-07 2024-09-10 アイタブメッド （エイチケイ） リミテッド 二重特異性抗原結合タンパク質及びその使用
WO2020061482A1 (en) 2018-09-21 2020-03-26 Harpoon Therapeutics, Inc. Egfr binding proteins and methods of use
EP3856771A4 (en) 2018-09-25 2022-06-29 Harpoon Therapeutics, Inc. Dll3 binding proteins and methods of use
WO2020132810A1 (en) * 2018-12-24 2020-07-02 Generon (Shanghai) Corporation Ltd. Multispecific antigen binding proteins capable of binding cd19 and cd3, and use thereof
KR20210142638A (ko) * 2019-02-22 2021-11-25 우한 이지 바이오파마 씨오., 엘티디. Cd3 항원 결합 단편 및 이의 응용
EP3969479B1 (en) * 2019-05-14 2025-07-30 Harpoon Therapeutics, Inc. Epcam binding proteins and methods of use
EP3972998A1 (en) 2019-05-21 2022-03-30 Novartis AG Cd19 binding molecules and uses thereof
KR20220071263A (ko) * 2019-09-30 2022-05-31 하버 바이오메드 (쑤저우) 컴퍼니 리미티드 Cd3을 표적으로 하는 항체, 이중 특이성 항체 및 이의 용도
KR20210095781A (ko) * 2020-01-24 2021-08-03 주식회사 에이프릴바이오 항원결합 단편 및 생리활성 이펙터 모이어티로 구성된 융합 컨스트럭트를 포함하는 다중결합항체 및 이를 포함하는 약학조성물
KR20220144841A (ko) 2020-02-21 2022-10-27 하푼 테라퓨틱스, 인크. Flt3 결합 단백질 및 사용 방법
IL300256A (en) 2020-08-25 2023-03-01 Gilead Sciences Inc Multispecific Antigen Binding Molecules Targeting HIV and Methods of Use
WO2022098909A1 (en) * 2020-11-06 2022-05-12 Harpoon Therapeutics, Inc. Epcam targeting trispecific protein for treatment of cancer
JP2025087939A (ja) * 2022-04-13 2025-06-11 アステラス製薬株式会社 がん治療におけるｐｄ－１シグナル阻害剤との組み合わせによる抗ｔｓｐａｎ８－抗ｃｄ３二重特異性抗体の使用
WO2023222024A1 (en) * 2022-05-18 2023-11-23 Bj Bioscience Inc. Bispecific antibodies targeting epcam and cd3
CN120917052A (zh) * 2023-01-04 2025-11-07 普洛迈博生物技术公司 EPCAM-CD3ε双特异性抗体
AU2024234589A1 (en) 2023-03-16 2025-08-28 Itabmed Co., Ltd. Multispecific antigen binding proteins and uses thereof
WO2025188920A1 (en) 2024-03-06 2025-09-12 Mdx Management Llc Local application of agents inhibiting tyrosine kinase or shp-1 signaling

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN103842383A (zh) * 2011-05-16 2014-06-04 法比翁医药有限公司 多特异性fab融合蛋白及其使用方法

Family Cites Families (166)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US191A (en) 1837-05-08 Machine for facing and dressing stone
US7446A (en) 1850-06-18 Apparatus for party-coloring yarn
US4237224A (en) 1974-11-04 1980-12-02 Board Of Trustees Of The Leland Stanford Jr. University Process for producing biologically functional molecular chimeras
FR2413974A1 (fr) 1978-01-06 1979-08-03 David Bernard Sechoir pour feuilles imprimees par serigraphie
US4485045A (en) 1981-07-06 1984-11-27 Research Corporation Synthetic phosphatidyl cholines useful in forming liposomes
US4816567A (en) 1983-04-08 1989-03-28 Genentech, Inc. Recombinant immunoglobin preparations
US4544545A (en) 1983-06-20 1985-10-01 Trustees University Of Massachusetts Liposomes containing modified cholesterol for organ targeting
US4879231A (en) 1984-10-30 1989-11-07 Phillips Petroleum Company Transformation of yeasts of the genus pichia
US4683202A (en) 1985-03-28 1987-07-28 Cetus Corporation Process for amplifying nucleic acid sequences
US4751180A (en) 1985-03-28 1988-06-14 Chiron Corporation Expression using fused genes providing for protein product
US4683195A (en) 1986-01-30 1987-07-28 Cetus Corporation Process for amplifying, detecting, and/or-cloning nucleic acid sequences
US4676980A (en) 1985-09-23 1987-06-30 The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services Target specific cross-linked heteroantibodies
US4935233A (en) 1985-12-02 1990-06-19 G. D. Searle And Company Covalently linked polypeptide cell modulators
US6548640B1 (en) 1986-03-27 2003-04-15 Btg International Limited Altered antibodies
GB8610600D0 (en) 1986-04-30 1986-06-04 Novo Industri As Transformation of trichoderma
EP0279862B1 (en) 1986-08-28 1993-11-03 Teijin Limited Cytocidal antibody complex and process for its preparation
US4946778A (en) 1987-09-21 1990-08-07 Genex Corporation Single polypeptide chain binding molecules
GB8823869D0 (en) 1988-10-12 1988-11-16 Medical Res Council Production of antibodies
US5175384A (en) 1988-12-05 1992-12-29 Genpharm International Transgenic mice depleted in mature t-cells and methods for making transgenic mice
US5530101A (en) 1988-12-28 1996-06-25 Protein Design Labs, Inc. Humanized immunoglobulins
US6291158B1 (en) 1989-05-16 2001-09-18 Scripps Research Institute Method for tapping the immunological repertoire
US6291161B1 (en) 1989-05-16 2001-09-18 Scripps Research Institute Method for tapping the immunological repertiore
EP0402226A1 (en) 1989-06-06 1990-12-12 Institut National De La Recherche Agronomique Transformation vectors for yeast yarrowia
DK0479909T3 (da) 1989-06-29 1997-04-07 Medarex Inc Bispecifikke reagenser til AIDS-behandling
US5013556A (en) 1989-10-20 1991-05-07 Liposome Technology, Inc. Liposomes with enhanced circulation time
SG48759A1 (en) 1990-01-12 2002-07-23 Abgenix Inc Generation of xenogenic antibodies
US6673986B1 (en) 1990-01-12 2004-01-06 Abgenix, Inc. Generation of xenogeneic antibodies
US6075181A (en) 1990-01-12 2000-06-13 Abgenix, Inc. Human antibodies derived from immunized xenomice
US6150584A (en) 1990-01-12 2000-11-21 Abgenix, Inc. Human antibodies derived from immunized xenomice
US5283173A (en) 1990-01-24 1994-02-01 The Research Foundation Of State University Of New York System to detect protein-protein interactions
US5151510A (en) 1990-04-20 1992-09-29 Applied Biosystems, Inc. Method of synethesizing sulfurized oligonucleotide analogs
GB9015198D0 (en) 1990-07-10 1990-08-29 Brien Caroline J O Binding substance
EP0546091B1 (en) 1990-08-29 2007-01-24 Pharming Intellectual Property BV Homologous recombination in mammalian cells
US5874299A (en) 1990-08-29 1999-02-23 Genpharm International, Inc. Transgenic non-human animals capable of producing heterologous antibodies
US5661016A (en) 1990-08-29 1997-08-26 Genpharm International Inc. Transgenic non-human animals capable of producing heterologous antibodies of various isotypes
US5625126A (en) 1990-08-29 1997-04-29 Genpharm International, Inc. Transgenic non-human animals for producing heterologous antibodies
US5877397A (en) 1990-08-29 1999-03-02 Genpharm International Inc. Transgenic non-human animals capable of producing heterologous antibodies of various isotypes
US5789650A (en) 1990-08-29 1998-08-04 Genpharm International, Inc. Transgenic non-human animals for producing heterologous antibodies
US6300129B1 (en) 1990-08-29 2001-10-09 Genpharm International Transgenic non-human animals for producing heterologous antibodies
US6255458B1 (en) 1990-08-29 2001-07-03 Genpharm International High affinity human antibodies and human antibodies against digoxin
US5770429A (en) 1990-08-29 1998-06-23 Genpharm International, Inc. Transgenic non-human animals capable of producing heterologous antibodies
ES2246502T3 (es) 1990-08-29 2006-02-16 Genpharm International, Inc. Animales no humanos transgenicos capaces de producir anticuerpos heterologos.
US5633425A (en) 1990-08-29 1997-05-27 Genpharm International, Inc. Transgenic non-human animals capable of producing heterologous antibodies
US5814318A (en) 1990-08-29 1998-09-29 Genpharm International Inc. Transgenic non-human animals for producing heterologous antibodies
US5545806A (en) 1990-08-29 1996-08-13 Genpharm International, Inc. Ransgenic non-human animals for producing heterologous antibodies
DE4118120A1 (de) 1991-06-03 1992-12-10 Behringwerke Ag Tetravalente bispezifische rezeptoren, ihre herstellung und verwendung
WO1992022670A1 (en) 1991-06-12 1992-12-23 Genpharm International, Inc. Early detection of transgenic embryos
AU2235992A (en) 1991-06-14 1993-01-12 Genpharm International, Inc. Transgenic immunodeficient non-human animals
WO1993004169A1 (en) 1991-08-20 1993-03-04 Genpharm International, Inc. Gene targeting in animal cells using isogenic dna constructs
WO1993008829A1 (en) 1991-11-04 1993-05-13 The Regents Of The University Of California Compositions that mediate killing of hiv-infected cells
DK1024191T3 (da) 1991-12-02 2008-12-08 Medical Res Council Fremstilling af autoantistoffer fremvist på fag-overflader ud fra antistofsegmentbiblioteker
CA2124967C (en) 1991-12-17 2008-04-08 Nils Lonberg Transgenic non-human animals capable of producing heterologous antibodies
US5777085A (en) 1991-12-20 1998-07-07 Protein Design Labs, Inc. Humanized antibodies reactive with GPIIB/IIIA
WO1993016043A1 (en) 1992-02-18 1993-08-19 Otsuka Kagaku Kabushiki Kaisha β-LACTAM COMPOUND AND CEPHEM COMPOUND, AND PRODUCTION THEREOF
US5714350A (en) 1992-03-09 1998-02-03 Protein Design Labs, Inc. Increasing antibody affinity by altering glycosylation in the immunoglobulin variable region
US5733743A (en) 1992-03-24 1998-03-31 Cambridge Antibody Technology Limited Methods for producing members of specific binding pairs
JPH07508410A (ja) 1992-06-18 1995-09-21 ジェンファーム　インターナショナル　インコーポレイテッド 酵母人工染色体を有するトランスジェニック非ヒト動物の製造方法
CA2140638C (en) 1992-07-24 2010-05-04 Raju Kucherlapati Generation of xenogeneic antibodies
DE69330523T4 (de) 1992-08-21 2012-08-23 Vrije Universiteit Brussel Immunoglobuline ohne leichte ketten
US6005079A (en) 1992-08-21 1999-12-21 Vrije Universiteit Brussels Immunoglobulins devoid of light chains
GB9221657D0 (en) 1992-10-15 1992-11-25 Scotgen Ltd Recombinant bispecific antibodies
US5736137A (en) 1992-11-13 1998-04-07 Idec Pharmaceuticals Corporation Therapeutic application of chimeric and radiolabeled antibodies to human B lymphocyte restricted differentiation antigen for treatment of B cell lymphoma
EP0669836B1 (en) 1992-11-13 1996-07-03 Idec Pharmaceuticals Corporation Therapeutic application of chimeric and radiolabeled antibodies to human b lymphocyte restricted differentiation antigen for treatment of b cell lymphoma
EP0754225A4 (en) 1993-04-26 2001-01-31 Genpharm Int HETEROLOGIC ANTIBODY-PRODUCING TRANSGENIC NON-HUMAN ANIMALS
DK0698097T3 (da) 1993-04-29 2001-10-08 Unilever Nv Produktion af antistoffer eller (funktionaliserede) fragmenter deraf afledt af Camelidae-immunoglobuliner med tung kæde
US5625825A (en) 1993-10-21 1997-04-29 Lsi Logic Corporation Random number generating apparatus for an interface unit of a carrier sense with multiple access and collision detect (CSMA/CD) ethernet data network
JP4137997B2 (ja) 1994-01-11 2008-08-20 ダイアックス コープ． クニッツドメインから誘導されたヒトプラスミンの阻害剤
US5837458A (en) 1994-02-17 1998-11-17 Maxygen, Inc. Methods and compositions for cellular and metabolic engineering
JPH10501681A (ja) 1994-02-22 1998-02-17 ダナ−ファーバー キャンサー インスティチュート 核酸送達システムならびにその合成および使用方法
US5643763A (en) 1994-11-04 1997-07-01 Genpharm International, Inc. Method for making recombinant yeast artificial chromosomes by minimizing diploid doubling during mating
US5731168A (en) 1995-03-01 1998-03-24 Genentech, Inc. Method for making heteromultimeric polypeptides
US5703057A (en) 1995-04-07 1997-12-30 Board Of Regents The University Of Texas System Expression library immunization
EP0739981A1 (en) 1995-04-25 1996-10-30 Vrije Universiteit Brussel Variable fragments of immunoglobulins - use for therapeutic or veterinary purposes
KR20050085971A (ko) 1995-04-27 2005-08-29 아브게닉스, 인크. 면역화된 제노마우스 유래의 인간 항체
EP0823941A4 (en) 1995-04-28 2001-09-19 Abgenix Inc HUMAN ANTIBODIES DERIVED FROM IMMUNIZED XENO MOUSES
WO1997007671A1 (en) 1995-08-29 1997-03-06 Kirin Beer Kabushiki Kaisha Chimeric animal and method for constructing the same
ES2279539T3 (es) 1996-05-04 2007-08-16 Astrazeneca Ab Anticuerpo monoclonal anti-cea, conjugados que comprenden dicho anticuerpo, y su uso terapeutico en un sistema adept.
WO1998024893A2 (en) 1996-12-03 1998-06-11 Abgenix, Inc. TRANSGENIC MAMMALS HAVING HUMAN IG LOCI INCLUDING PLURAL VH AND Vλ REGIONS AND ANTIBODIES PRODUCED THEREFROM
PT1034298E (pt) 1997-12-05 2012-02-03 Scripps Research Inst Humanização de anticorpo murino
ES2234241T3 (es) 1998-01-23 2005-06-16 Vlaams Interuniversitair Instituut Voor Biotechnologie Derivados de anticuerpo de multiples fines.
AUPP221098A0 (en) 1998-03-06 1998-04-02 Diatech Pty Ltd V-like domain binding molecules
AU2472400A (en) 1998-10-20 2000-05-08 City Of Hope CD20-specific redirected T cells and their use in cellular immunotherapy of CD20+ malignancies
US7109003B2 (en) 1998-12-23 2006-09-19 Abgenix, Inc. Methods for expressing and recovering human monoclonal antibodies to CTLA-4
US7534866B2 (en) 2005-10-19 2009-05-19 Ibc Pharmaceuticals, Inc. Methods and compositions for generating bioactive assemblies of increased complexity and uses
US6833268B1 (en) 1999-06-10 2004-12-21 Abgenix, Inc. Transgenic animals for producing specific isotypes of human antibodies via non-cognate switch regions
US6949245B1 (en) 1999-06-25 2005-09-27 Genentech, Inc. Humanized anti-ErbB2 antibodies and treatment with anti-ErbB2 antibodies
US7605238B2 (en) 1999-08-24 2009-10-20 Medarex, Inc. Human CTLA-4 antibodies and their uses
JP2004532608A (ja) 2000-10-13 2004-10-28 バイオジェン・アイデック・エムエイ・インコーポレイテッド ヒト化抗ＬＴ−β−Ｒ抗体
ATE338124T1 (de) 2000-11-07 2006-09-15 Hope City Cd19-spezifische umgezielte immunzellen
WO2002051871A2 (fr) 2000-12-26 2002-07-04 Institut National De La Sante Et De La Recherche Medicale (Inserm) Anticorps anti-cd28
US7070995B2 (en) 2001-04-11 2006-07-04 City Of Hope CE7-specific redirected immune cells
US7514537B2 (en) 2001-04-30 2009-04-07 City Of Hope Chimeric immunoreceptor useful in treating human gliomas
EP1396500A4 (en) 2001-05-18 2005-02-02 Kirin Brewery ANTI-TRAIL-R ANTIBODIES
AR039067A1 (es) 2001-11-09 2005-02-09 Pfizer Prod Inc Anticuerpos para cd40
CA2471702C (en) 2002-01-09 2013-03-19 Medarex, Inc. Human monoclonal antibodies against cd30
JP2005522514A (ja) 2002-04-10 2005-07-28 ジェネンテック・インコーポレーテッド 抗ｈｅｒ２抗体改変体
AU2003285878B2 (en) 2002-11-07 2011-04-28 Immunogen, Inc. Anti-CD33 antibodies and method for treatment of acute myeloid leukemia using the same
US20100003253A1 (en) 2002-11-08 2010-01-07 Ablynx N.V. Single domain antibodies directed against epidermal growth factor receptor and uses therefor
ATE455127T1 (de) 2003-05-31 2010-01-15 Micromet Ag Humane anti-humane cd3-bindungsmoleküle
JP4733635B2 (ja) 2003-07-31 2011-07-27 イミューノメディクス、インコーポレイテッド 抗ｃｄ１９抗体
WO2005037235A2 (en) 2003-10-16 2005-04-28 Imclone Systems Incorporated Fibroblast growth factor receptor-1 inhibitors and methods of treatment thereof
ES2237732T3 (es) 2003-11-03 2005-08-01 Peter-Hansen Volkmann Composicion para el cuidado vaginal.
BRPI0416603A (pt) 2003-11-07 2007-01-30 Immunex Corp anticorpo que se liga ao receptor interleucina-4 (il-4) humano
EP1716179A2 (en) 2004-02-12 2006-11-02 Morphotek, Inc. Monoclonal antibodies that specifically bind to folate receptor alpha
AU2005250499B2 (en) 2004-06-03 2011-12-08 Novimmune S.A. Anti-CD3 antibodies and methods of use thereof
PT1830881E (pt) 2004-12-10 2010-08-30 Novimmune Sa Terapias de combinação visando múltiplos receptores do tipo toll e a sua utilização
ATE414718T1 (de) 2005-01-05 2008-12-15 F Star Biotech Forsch & Entw Synthetische immunoglobulindomänen mit in regionen des moleküls, die sich von den die komplementarität bestimmenden bereichen unterscheiden, modifizierten bindeeigenschaften
CA2598454C (en) 2005-02-18 2013-04-09 Medarex, Inc. Monoclonal antibodies against prostate specific membrane antigen (psma) lacking in fucosyl residues
GB0504767D0 (en) 2005-03-08 2005-04-13 Ares Trading Sa Lipocalin protein
BRPI0609543B1 (pt) 2005-03-31 2021-11-09 Biomedics Inc Anticorpo monoclonal anti-cd20, hibridoma, anticorpo monoclonal anti-cd20 quimérico, anticorpo monoclonal anti-cd20 humanizado, agente de diagnóstico, e, agente terapêutico
JP5129122B2 (ja) * 2005-04-26 2013-01-23 トリオン ファーマ ゲーエムベーハー 癌治療のための抗体およびグルココルチコイドの組み合わせ
AU2006268227A1 (en) 2005-07-08 2007-01-18 Xencor, Inc Optimized anti-Ep-CAM antibodies
US8663634B2 (en) 2005-07-11 2014-03-04 Macrogenics, Inc. Methods for the treatment of autoimmune disorders using immunosuppressive monoclonal antibodies with reduced toxicity
US8247188B2 (en) 2005-08-17 2012-08-21 Fasgen Diagnostics, Llc FAS binding antibodies
US7612181B2 (en) 2005-08-19 2009-11-03 Abbott Laboratories Dual variable domain immunoglobulin and uses thereof
EP1940881B1 (en) 2005-10-11 2016-11-30 Amgen Research (Munich) GmbH Compositions comprising cross-species-specific antibodies and uses thereof
CA2629095A1 (en) 2005-11-12 2007-05-24 Eli Lily And Company Anti-egfr antibodies
CA2632094C (en) 2005-12-02 2015-01-27 Wayne A. Marasco Carbonic anhydrase ix (g250) antibodies and methods of use thereof
EP1829895A1 (en) 2006-03-03 2007-09-05 f-star Biotechnologische Forschungs- und Entwicklungsges.m.b.H. Bispecific molecule binding TLR9 and CD32 and comprising a T cell epitope for treatment of allergies
US8871912B2 (en) 2006-03-24 2014-10-28 Merck Patent Gmbh Engineered heterodimeric protein domains
ES2599319T3 (es) 2006-06-26 2017-02-01 Macrogenics, Inc. Anticuerpos específicos de Fc RIIB y métodos de uso de éstos
EP1914242A1 (en) 2006-10-19 2008-04-23 Sanofi-Aventis Novel anti-CD38 antibodies for the treatment of cancer
SI2129396T1 (sl) 2007-02-16 2013-12-31 Merrimack Pharmaceuticals, Inc. Protitelesa proti ErbB3 in njihove uporabe
AU2008226905C1 (en) 2007-03-08 2014-11-06 Humanigen, Inc. EphA3 antibodies for the treatment of solid tumors
HRP20120759T1 (hr) 2007-04-03 2012-10-31 Amgen Research (Munich) Gmbh Bispecifična veziva specifična između vrsta
EP4059964A1 (en) 2007-04-03 2022-09-21 Amgen Research (Munich) GmbH Cross-species-specific binding domain
NZ580746A (en) 2007-04-03 2012-05-25 Micromet Ag Cross-species-specific bispecific binders
SI2520590T1 (sl) 2007-04-03 2018-12-31 Amgen Research (Munich) Gmbh Posebna vezna domena za križanje vrst
CA2694488A1 (en) 2007-07-31 2009-02-05 Medimmune, Llc Multispecific epitope binding proteins and uses thereof
PE20090499A1 (es) 2007-08-09 2009-05-18 Boehringer Ingelheim Int Anticuerpos anti-cd37
WO2009040562A1 (en) 2007-09-26 2009-04-02 Ucb Pharma S.A. Dual specificity antibody fusions
EP2050764A1 (en) 2007-10-15 2009-04-22 sanofi-aventis Novel polyvalent bispecific antibody format and uses thereof
WO2009068631A1 (en) 2007-11-27 2009-06-04 Ablynx N.V. Method for obtaining polypeptide constructs comprising two or more single domain antibodies
KR20100097753A (ko) 2007-12-26 2010-09-03 바이오테스트 아게 Ｃｄ138 표적성 면역접합체 및 이의 용도
KR101319499B1 (ko) 2008-02-22 2013-10-17 엘지디스플레이 주식회사 화학적 자기조립 방법을 이용한 나노선 혹은탄소나노튜브의 적층 및 패턴형성 방법과, 이를 적용한액정표시장치의 제조방법
NZ589436A (en) 2008-06-03 2012-12-21 Abbott Lab Dual variable domain immunoglobulins and uses thereof
EP2313435A4 (en) 2008-07-01 2012-08-08 Aveo Pharmaceuticals Inc FIBROBLAST GROWTH FACTOR RECEPTOR 3 (FGFR3) BINDING PROTEINS
JP2010031968A (ja) 2008-07-29 2010-02-12 Aisin Seiki Co Ltd 流体継手装置
WO2010037838A2 (en) 2008-10-01 2010-04-08 Micromet Ag Cross-species-specific single domain bispecific single chain antibody
WO2010037836A2 (en) 2008-10-01 2010-04-08 Micromet Ag Cross-species-specific psmaxcd3 bispecific single chain antibody
PT3290052T (pt) 2008-11-07 2020-02-06 Galaxy Biotech Llc Anticorpos monoclonais para o recetor 2 do fator de crescimento de fibroblastos
WO2010052014A1 (en) 2008-11-07 2010-05-14 Micromet Ag Treatment of acute lymphoblastic leukemia
AR074439A1 (es) 2008-12-02 2011-01-19 Pf Medicament Anticuerpo anti-cmet (receptor c-met)
MX2011009430A (es) 2009-03-10 2011-11-18 Biogen Idec Inc Anticuerpos anti-bcma.
GB0909904D0 (en) 2009-06-09 2009-07-22 Affitech As Product
US9676845B2 (en) 2009-06-16 2017-06-13 Hoffmann-La Roche, Inc. Bispecific antigen binding proteins
JP5593641B2 (ja) 2009-06-26 2014-09-24 味の素株式会社 減塩飲食品用組成物
WO2011028952A1 (en) 2009-09-02 2011-03-10 Xencor, Inc. Compositions and methods for simultaneous bivalent and monovalent co-engagement of antigens
RU2646139C1 (ru) 2009-09-03 2018-03-01 Мерк Шарп И Доум Корп. Анти-gitr-антитела
EP2478110B1 (en) 2009-09-16 2016-01-06 Immunomedics, Inc. Class i anti-cea antibodies and uses thereof
MX2012003175A (es) 2009-09-18 2012-04-11 Micromet Ag Regimen de dosificacion para administrar un anticuerpo bi-especifico epcamxcd3.
US20110165161A1 (en) * 2009-12-23 2011-07-07 Shih-Yao Lin Anti-epcam antibodies that induce apoptosis of cancer cells and methods using same
JP5967987B2 (ja) 2012-03-13 2016-08-10 エスアイアイ・セミコンダクタ株式会社 基準電圧回路
BR112015000798A2 (pt) 2012-07-13 2017-06-27 Zymeworks Inc heterodímeros assimétricos biespecíficos compreendendo construtos anti-cd3
US9111624B2 (en) 2013-03-22 2015-08-18 Katsuyuki Fujita Semiconductor memory device
EP2789630A1 (en) 2013-04-09 2014-10-15 EngMab AG Bispecific antibodies against CD3e and ROR1
JP2017536341A (ja) 2014-10-09 2017-12-07 エンクマフ アーゲー 卵巣がんの処置における使用のためのＣＤ３εおよびＲＯＲ１に対する二特異性抗体
CN104788567B (zh) 2015-01-21 2019-03-26 武汉友芝友生物制药有限公司 一种靶向鼠T淋巴细胞CD3和人肿瘤抗原EpCAM的双特异性抗体制备方法及应用
CN104592391B (zh) * 2015-01-21 2020-08-21 武汉友芝友生物制药有限公司 一种双特异性抗体EpCAM×CD3的构建及应用
EP3064507A1 (en) 2015-03-06 2016-09-07 Deutsches Krebsforschungszentrum Stiftung des öffentlichen Rechts Fusion proteins comprising a binding protein and an interleukin-15 polypeptide having a reduced affinity for IL15ra and therapeutic uses thereof
WO2016189014A1 (en) 2015-05-26 2016-12-01 Morphosys Ag Combination of an anti-cd19 antibody and a bruton's tyrosine kinase inhibitor and uses thereof
JP6937746B2 (ja) 2015-10-02 2021-09-22 エフ・ホフマン−ラ・ロシュ・アクチェンゲゼルシャフト 二重特異性抗ｃｄ１９×ｃｄ３ｔ細胞活性化抗原結合分子
AU2017233121B2 (en) 2016-03-15 2023-12-21 Itabmed (Hk) Limited Multispecific Fab fusion proteins and use thereof
CN108690138A (zh) 2017-04-12 2018-10-23 鸿运华宁（杭州）生物医药有限公司 一种能与人cd19或cd20和人cd3结合的双特异性抗体及其应用
CN107903324B (zh) 2017-11-15 2021-01-29 北京绿竹生物技术股份有限公司 一种结合人cd19和cd3的双特异性抗体
JP7548587B2 (ja) 2018-09-07 2024-09-10 アイタブメッド （エイチケイ） リミテッド 二重特異性抗原結合タンパク質及びその使用

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN103842383A (zh) * 2011-05-16 2014-06-04 法比翁医药有限公司 多特异性fab融合蛋白及其使用方法

Also Published As

Publication number Publication date
US20190092862A1 (en) 2019-03-28
EP3430058A4 (en) 2019-10-23
AU2017233121A1 (en) 2018-09-13
JP7034489B2 (ja) 2022-03-14
WO2017157305A1 (en) 2017-09-21
US10870701B2 (en) 2020-12-22
EP3430058A1 (en) 2019-01-23
JP2019513701A (ja) 2019-05-30
CA3017776A1 (en) 2017-09-21
CN109476756A (zh) 2019-03-15
AU2017233121B2 (en) 2023-12-21

Similar Documents

Publication Publication Date Title
CN109476756B (zh) 一种多特异性Fab融合蛋白及其用途
US11673954B2 (en) Single-domain antibodies and variants thereof against PD-L1
AU2019207276B2 (en) Single-domain antibodies and variants thereof against PD-1
JP7548587B2 (ja) 二重特異性抗原結合タンパク質及びその使用
US11958903B2 (en) Single-domain antibodies against LAG-3 and uses thereof
JP2019533719A (ja) Ｃｔｌａ−４に対する単一ドメイン抗体及びその変異体
CN113906054B (zh) 能够结合cd19和cd3的多特异性抗原结合蛋白及其用途
WO2020168555A1 (zh) Cd3抗原结合片段及其应用
US12060416B2 (en) Humanized anti-VEGF monoclonal antibody
CN114008077B (zh) 抗体和使用方法
TWI875812B (zh) 抗-幹細胞因子抗體及其使用方法
JP7430137B2 (ja) 抗体および使用方法
JP2022538374A (ja) Ｐｄｇｆ－ｂおよびｐｄｇｆ－ｄに結合する抗原結合分子ならびにその使用
HK1263052B (en) Multispecific fab fusion proteins and use thereof
HK1263052A1 (en) Multispecific fab fusion proteins and use thereof
TW202340246A (zh) D3結合分子及其用途

Legal Events

Date Code Title Description
PB01 Publication
PB01 Publication
SE01 Entry into force of request for substantive examination
SE01 Entry into force of request for substantive examination
REG Reference to a national code

Ref country code: HK

Ref legal event code: DE

Ref document number: 1263052

Country of ref document: HK

CB02 Change of applicant information
CB02 Change of applicant information

Address after: 201207 Shanghai Pudong New Area free trade trial area, 1 spring 3, 400 Fang Chun road.

Applicant after: Yiyi biomedical development (Shanghai) Co.,Ltd.

Address before: Room 307, 1011 Halley Road, Shanghai pilot Free Trade Zone, 201203

Applicant before: GENERON (SHANGHAI) Corp.,Ltd.

TA01 Transfer of patent application right
TA01 Transfer of patent application right

Effective date of registration: 20210317

Address after: Greater Cayman Islands, British Cayman Islands

Applicant after: Yiyi Biotechnology Co.,Ltd.

Address before: 201207 Shanghai Pudong New Area free trade trial area, 1 spring 3, 400 Fang Chun road.

Applicant before: Yiyi biomedical development (Shanghai) Co.,Ltd.

TA01 Transfer of patent application right
TA01 Transfer of patent application right

Effective date of registration: 20210601

Address after: Hongkong, Tongluowan, China

Applicant after: Aetna virtue (Hong Kong) Ltd.

Address before: Greater Cayman Islands, British Cayman Islands

Applicant before: Yiyi Biotechnology Co.,Ltd.

GR01 Patent grant
GR01 Patent grant