CN104582476B - 使用共同轻链制备完全人双特异性抗体的方法 - Google Patents

使用共同轻链制备完全人双特异性抗体的方法 Download PDF

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Publication number
CN104582476B
CN104582476B CN201380030014.1A CN201380030014A CN104582476B CN 104582476 B CN104582476 B CN 104582476B CN 201380030014 A CN201380030014 A CN 201380030014A CN 104582476 B CN104582476 B CN 104582476B
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human
light chain
heavy chain
mouse
sequence
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Chinese (zh)
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CN104582476A (zh
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R·巴布
J·麦克维尔特
L·麦克唐纳
S·史蒂文斯
S·戴维斯
D·R·巴克勒
K·A·霍西阿瓦
A·J·墨菲
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Regeneron Pharmaceuticals Inc
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Regeneron Pharmaceuticals Inc
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/46—Hybrid immunoglobulins
    • C07K16/468—Immunoglobulins having two or more different antigen binding sites, e.g. multifunctional antibodies
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
    • A01K67/00—Rearing or breeding animals, not otherwise provided for; New or modified breeds of animals
    • A01K67/027—New or modified breeds of vertebrates
    • A01K67/0275—Genetically modified vertebrates, e.g. transgenic
    • A01K67/0278—Knock-in vertebrates, e.g. humanised vertebrates
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/40—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against enzymes
    • 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
    • C12N15/63—Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
    • C12N15/79—Vectors or expression systems specially adapted for eukaryotic hosts
    • C12N15/85—Vectors or expression systems specially adapted for eukaryotic hosts for animal cells
    • C12N15/8509—Vectors or expression systems specially adapted for eukaryotic hosts for animal cells for producing genetically modified animals, e.g. transgenic
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
    • A01K2207/00—Modified animals
    • A01K2207/15—Humanized animals
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
    • A01K2217/00—Genetically modified animals
    • A01K2217/07—Animals genetically altered by homologous recombination
    • A01K2217/072—Animals genetically altered by homologous recombination maintaining or altering function, i.e. knock in
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
    • A01K2217/00—Genetically modified animals
    • A01K2217/15—Animals comprising multiple alterations of the genome, by transgenesis or homologous recombination, e.g. obtained by cross-breeding
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
    • A01K2227/00—Animals characterised by species
    • A01K2227/10—Mammal
    • A01K2227/105—Murine
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
    • A01K2267/00—Animals characterised by purpose
    • A01K2267/01—Animal expressing industrially exogenous proteins
    • 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
    • C07K2317/51—Complete heavy chain or Fd fragment, i.e. VH + CH1
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
    • C07K2317/56—Immunoglobulins specific features characterized by immunoglobulin fragments variable (Fv) region, i.e. VH and/or VL
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
    • C07K2317/56—Immunoglobulins specific features characterized by immunoglobulin fragments variable (Fv) region, i.e. VH and/or VL
    • C07K2317/565—Complementarity determining region [CDR]
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
    • C07K2317/56—Immunoglobulins specific features characterized by immunoglobulin fragments variable (Fv) region, i.e. VH and/or VL
    • C07K2317/567—Framework region [FR]
    • 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

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Organic Chemistry (AREA)
  • Genetics & Genomics (AREA)
  • General Health & Medical Sciences (AREA)
  • Immunology (AREA)
  • Biochemistry (AREA)
  • Biophysics (AREA)
  • Molecular Biology (AREA)
  • Medicinal Chemistry (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Engineering & Computer Science (AREA)
  • Biotechnology (AREA)
  • Zoology (AREA)
  • Environmental Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Biodiversity & Conservation Biology (AREA)
  • Animal Behavior & Ethology (AREA)
  • Animal Husbandry (AREA)
  • Biomedical Technology (AREA)
  • General Engineering & Computer Science (AREA)
  • Wood Science & Technology (AREA)
  • Physics & Mathematics (AREA)
  • Microbiology (AREA)
  • Plant Pathology (AREA)
  • Micro-Organisms Or Cultivation Processes Thereof (AREA)
  • Peptides Or Proteins (AREA)
  • Preparation Of Compounds By Using Micro-Organisms (AREA)
CN201380030014.1A 2012-06-05 2013-06-05 使用共同轻链制备完全人双特异性抗体的方法 Active CN104582476B (zh)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US13/488,628 2012-06-05
US13/488,628 US20130045492A1 (en) 2010-02-08 2012-06-05 Methods For Making Fully Human Bispecific Antibodies Using A Common Light Chain
PCT/US2013/044257 WO2013184761A1 (en) 2012-06-05 2013-06-05 Methods for making fully human bispecific antibodies using a common light chain

Publications (2)

Publication Number Publication Date
CN104582476A CN104582476A (zh) 2015-04-29
CN104582476B true CN104582476B (zh) 2017-03-08

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Country Link
EP (1) EP2854523A1 (cg-RX-API-DMAC7.html)
JP (1) JP2015525071A (cg-RX-API-DMAC7.html)
KR (1) KR20150023535A (cg-RX-API-DMAC7.html)
CN (1) CN104582476B (cg-RX-API-DMAC7.html)
AU (1) AU2013271737A1 (cg-RX-API-DMAC7.html)
CA (1) CA2874846A1 (cg-RX-API-DMAC7.html)
HK (1) HK1208994A1 (cg-RX-API-DMAC7.html)
IL (1) IL235781A0 (cg-RX-API-DMAC7.html)
MX (1) MX2014014891A (cg-RX-API-DMAC7.html)
RU (1) RU2014153674A (cg-RX-API-DMAC7.html)
SG (2) SG11201407644UA (cg-RX-API-DMAC7.html)
WO (1) WO2013184761A1 (cg-RX-API-DMAC7.html)

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US20100069614A1 (en) 2008-06-27 2010-03-18 Merus B.V. Antibody producing non-human mammals
US20130045492A1 (en) 2010-02-08 2013-02-21 Regeneron Pharmaceuticals, Inc. Methods For Making Fully Human Bispecific Antibodies Using A Common Light Chain
US9796788B2 (en) 2010-02-08 2017-10-24 Regeneron Pharmaceuticals, Inc. Mice expressing a limited immunoglobulin light chain repertoire
US20120021409A1 (en) 2010-02-08 2012-01-26 Regeneron Pharmaceuticals, Inc. Common Light Chain Mouse
PL3095871T3 (pl) 2010-02-08 2019-10-31 Regeneron Pharma Mysz zawierająca wspólny łańcuch lekki
LT2883449T (lt) 2012-03-16 2018-05-10 Regeneron Pharmaceuticals, Inc. Histidinu modifikuoti lengvosios grandinės antikūnai ir juos gaminantys genetiškai modifikuoti graužikai
US20140013456A1 (en) 2012-03-16 2014-01-09 Regeneron Pharmaceuticals, Inc. Histidine Engineered Light Chain Antibodies and Genetically Modified Non-Human Animals for Generating the Same
EP3539374A1 (en) 2012-03-16 2019-09-18 Regeneron Pharmaceuticals, Inc. Non-human animals expressing ph-sensitive immunoglobulin sequences
CN106318951A (zh) 2012-03-16 2017-01-11 瑞泽恩制药公司 生产具有ph依赖性结合特性的抗原结合蛋白的小鼠
ES2740749T3 (es) 2012-04-20 2020-02-06 Merus Nv Métodos y medios para la producción de moléculas heterodiméricas similares a Ig
TWI635098B (zh) 2013-02-01 2018-09-11 再生元醫藥公司 含嵌合恆定區之抗體
EP2970437A1 (en) * 2013-03-13 2016-01-20 Regeneron Pharmaceuticals, Inc. Common light chain mouse
TWI701042B (zh) 2014-03-19 2020-08-11 美商再生元醫藥公司 用於腫瘤治療之方法及抗體組成物
LT3699198T (lt) 2014-11-17 2025-05-12 Regeneron Pharmaceuticals, Inc. Būdai navikams gydyti naudojant cd3×cd20 bispecifinį antikūną
EP3023437A1 (en) * 2014-11-20 2016-05-25 EngMab AG Bispecific antibodies against CD3epsilon and BCMA
LT3221357T (lt) * 2014-11-20 2020-08-25 F. Hoffmann-La Roche Ag Bendros lengvosios grandinės ir naudojimo būdai
EP3277725B1 (en) 2015-03-30 2020-11-25 Regeneron Pharmaceuticals, Inc. Heavy chain constant regions with reduced binding to fc gamma receptors
AU2016261854B2 (en) 2015-05-12 2022-05-26 Regeneron Pharmaceuticals, Inc. Multimeric protein purity determination
SMT202200050T1 (it) * 2015-09-23 2022-03-21 Regeneron Pharma Anticorpi bispecifici anti-cd3 ottimizzati e loro usi
TW202417497A (zh) 2015-10-12 2024-05-01 美商再生元醫藥公司 活化瘦素受體的抗原結合蛋白
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EP4596043A3 (en) 2018-04-06 2025-10-01 Regeneron Pharmaceuticals, Inc. A leptin receptor agonist antibody for use in increasing bone mass in a subject suffering from metabolic dysfunction or hypoleptinemia
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FI3844189T3 (fi) 2018-08-31 2025-03-05 Regeneron Pharma Annostusstrategia, joka lieventää bispesifisten CD3/CD20-vasta-aineiden sytokiinien vapautumisoireyhtymää
EP3883967A4 (en) * 2018-11-16 2023-04-19 Virtuoso Binco, Inc. CD38 AND ICAM1 ANTIBODIES AND USES THEREOF
SG11202107589PA (en) 2019-02-22 2021-08-30 Regeneron Pharma Rodents having genetically modified sodium channels and methods of use thereof
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
TW202229328A (zh) 2020-09-11 2022-08-01 美商再生元醫藥公司 抗原特異性抗體之鑑定及產生
JP2024500399A (ja) 2020-12-16 2024-01-09 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 ヒト化Ｆｃアルファ受容体を発現するマウス
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CN1199422A (zh) * 1995-10-10 1998-11-18 真药物国际公司 能够生产异源抗体的转基因非人动物
EP1298207A1 (de) * 2001-10-01 2003-04-02 Deutsches Krebsforschungszentrum Stiftung des öffentlichen Rechts Verfahren zur Herstellung von Protein-Bibliotheken und zur Selektion von Proteinen daraus
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CN1671416A (zh) * 2001-07-12 2005-09-21 杰斐逊·富特 超人源化抗体
CN1675245A (zh) * 2002-06-14 2005-09-28 免疫医疗公司 人源化单克隆抗体hPAM4
CN101962408A (zh) * 2002-07-12 2011-02-02 杰斐逊·富特 超人源化抗体
CN102123582A (zh) * 2008-06-27 2011-07-13 莫鲁斯有限公司 产生抗体的非人哺乳动物
WO2011097603A1 (en) * 2010-02-08 2011-08-11 Regeneron Pharmaceuticals, Inc. Common light chain mouse

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EP0364096A2 (en) * 1988-09-06 1990-04-18 International Genetic Engineering, Inc. (Ingene) Gene expression elements and the production of chimeric mouse-human antibodies
CN1199422A (zh) * 1995-10-10 1998-11-18 真药物国际公司 能够生产异源抗体的转基因非人动物
CN1671416A (zh) * 2001-07-12 2005-09-21 杰斐逊·富特 超人源化抗体
EP1298207A1 (de) * 2001-10-01 2003-04-02 Deutsches Krebsforschungszentrum Stiftung des öffentlichen Rechts Verfahren zur Herstellung von Protein-Bibliotheken und zur Selektion von Proteinen daraus
WO2003061363A2 (en) * 2002-01-17 2003-07-31 Albert Einstein College Of Medicine Of Yeshiva University Mutations caused by activation-induced cytidine deaminase
CN1675245A (zh) * 2002-06-14 2005-09-28 免疫医疗公司 人源化单克隆抗体hPAM4
CN101962408A (zh) * 2002-07-12 2011-02-02 杰斐逊·富特 超人源化抗体
CN102123582A (zh) * 2008-06-27 2011-07-13 莫鲁斯有限公司 产生抗体的非人哺乳动物
WO2011097603A1 (en) * 2010-02-08 2011-08-11 Regeneron Pharmaceuticals, Inc. Common light chain mouse

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KR20150023535A (ko) 2015-03-05
MX2014014891A (es) 2015-06-17
HK1208994A1 (en) 2016-03-24
AU2013271737A1 (en) 2015-01-22
CN104582476A (zh) 2015-04-29
IL235781A0 (en) 2015-01-29
WO2013184761A1 (en) 2013-12-12
JP2015525071A (ja) 2015-09-03
EP2854523A1 (en) 2015-04-08
SG11201407644UA (en) 2014-12-30
RU2014153674A (ru) 2016-07-27
CA2874846A1 (en) 2013-12-12
SG10201609535TA (en) 2017-01-27

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