HK1208994A1 - Methods for making fully human bispecific antibodies using a common light chain - Google Patents

Methods for making fully human bispecific antibodies using a common light chain Download PDF

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Publication number
HK1208994A1
HK1208994A1 HK15109745.2A HK15109745A HK1208994A1 HK 1208994 A1 HK1208994 A1 HK 1208994A1 HK 15109745 A HK15109745 A HK 15109745A HK 1208994 A1 HK1208994 A1 HK 1208994A1
Authority
HK
Hong Kong
Prior art keywords
light chain
bispecific antibodies
methods
chain variable
fully human
Prior art date
Application number
HK15109745.2A
Other languages
Chinese (zh)
Inventor
Robert Babb
John Mcwhirter
Lynn Macdonald
Sean Stevens
Davis.Samuel
David R.Buckler David R. Buckler
Karolina A. Hosiawa
Andrew J. Murphy
Original Assignee
Regeneron Pharmaceuticals, Inc.
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
Priority claimed from US13/488,628 external-priority patent/US20130045492A1/en
Application filed by Regeneron Pharmaceuticals, Inc. filed Critical Regeneron Pharmaceuticals, Inc.
Publication of HK1208994A1 publication Critical patent/HK1208994A1/en

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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)
  • Molecular Biology (AREA)
  • Biophysics (AREA)
  • Biochemistry (AREA)
  • Medicinal Chemistry (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Engineering & Computer Science (AREA)
  • Zoology (AREA)
  • Biotechnology (AREA)
  • Environmental Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Biomedical Technology (AREA)
  • Wood Science & Technology (AREA)
  • General Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Animal Behavior & Ethology (AREA)
  • Animal Husbandry (AREA)
  • Biodiversity & Conservation Biology (AREA)
  • Microbiology (AREA)
  • Physics & Mathematics (AREA)
  • Plant Pathology (AREA)
  • Micro-Organisms Or Cultivation Processes Thereof (AREA)
  • Peptides Or Proteins (AREA)
  • Preparation Of Compounds By Using Micro-Organisms (AREA)

Abstract

A genetically modified mouse is provided, wherein the mouse expresses an immunoglobulin light chain repertoire characterized by a limited number of light chain variable domains. Mice are provided that express just one or a few immunoglobulin light chain variable domains from a limited repertoire in their germline. Methods for making bispecific antibodies having universal light chains using mice as described herein, including human light chain variable regions, are provided. Methods for making human variable regions suitable for use in multispecific binding proteins, e.g., bispecific antibodies, and host cells are provided. Bispecific antibodies capable of binding first and second antigens are provided, wherein the first and second antigens are separate epitopes of a single protein or separate epitopes on two different proteins are provided.
HK15109745.2A 2012-06-05 2013-06-05 Methods for making fully human bispecific antibodies using a common light chain HK1208994A1 (en)

Applications Claiming Priority (3)

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

Publications (1)

Publication Number Publication Date
HK1208994A1 true HK1208994A1 (en) 2016-03-24

Family

ID=48652344

Family Applications (1)

Application Number Title Priority Date Filing Date
HK15109745.2A HK1208994A1 (en) 2012-06-05 2013-06-05 Methods for making fully human bispecific antibodies using a common light chain

Country Status (12)

Country Link
EP (1) EP2854523A1 (en)
JP (1) JP2015525071A (en)
KR (1) KR20150023535A (en)
CN (1) CN104582476B (en)
AU (1) AU2013271737A1 (en)
CA (1) CA2874846A1 (en)
HK (1) HK1208994A1 (en)
IL (1) IL235781A0 (en)
MX (1) MX2014014891A (en)
RU (1) RU2014153674A (en)
SG (2) SG11201407644UA (en)
WO (1) WO2013184761A1 (en)

Families Citing this family (32)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20100069614A1 (en) 2008-06-27 2010-03-18 Merus B.V. Antibody producing non-human mammals
US9796788B2 (en) 2010-02-08 2017-10-24 Regeneron Pharmaceuticals, Inc. Mice expressing a limited immunoglobulin light chain repertoire
ES2547142T5 (en) 2010-02-08 2021-12-09 Regeneron Pharma Mouse common light chain
US20120021409A1 (en) 2010-02-08 2012-01-26 Regeneron Pharmaceuticals, Inc. Common Light Chain Mouse
US20130045492A1 (en) 2010-02-08 2013-02-21 Regeneron Pharmaceuticals, Inc. Methods For Making Fully Human Bispecific Antibodies Using A Common Light Chain
AU2013204581B2 (en) 2012-03-16 2015-06-25 Regeneron Pharmaceuticals, Inc. Non-human animals expressing pH-sensitive immunoglobulin sequences
RU2664473C2 (en) 2012-03-16 2018-08-17 Регенерон Фармасьютикалз, Инк. Non-human animals expressing ph-sensitive immunoglobulin sequences
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
EP2825036B1 (en) 2012-03-16 2018-05-02 Regeneron Pharmaceuticals, Inc. Histidine engineered light chain antibodies and genetically modified rodents for generating the same
CN120383672A (en) 2012-04-20 2025-07-29 美勒斯公司 Methods and means for producing immunoglobulin-like molecules
TWI682941B (en) 2013-02-01 2020-01-21 美商再生元醫藥公司 Antibodies comprising chimeric constant domains
CN105189545A (en) * 2013-03-13 2015-12-23 瑞泽恩制药公司 common light chain mouse
TWI754319B (en) 2014-03-19 2022-02-01 美商再生元醫藥公司 Methods and antibody compositions for tumor treatment
EP3699198B1 (en) 2014-11-17 2025-03-26 Regeneron Pharmaceuticals, Inc. Methods for tumor treatment using cd3xcd20 bispecific antibody
RS60615B1 (en) * 2014-11-20 2020-08-31 Hoffmann La Roche Common light chains and methods of use
EP3023437A1 (en) * 2014-11-20 2016-05-25 EngMab AG Bispecific antibodies against CD3epsilon and BCMA
DK3277725T3 (en) 2015-03-30 2021-01-11 Regeneron Pharma Constant heavy chain regions with reduced binding to FC gamma receptors
ES2881359T3 (en) 2015-05-12 2021-11-29 Regeneron Pharma Determination of the purity of multimeric proteins
PT3353212T (en) * 2015-09-23 2022-01-05 Regeneron Pharma Optimized anti-cd3 bispecific antibodies and uses thereof
TWI752920B (en) 2015-10-12 2022-01-21 美商再生元醫藥公司 Antigen-binding proteins that activate the leptin receptor
IL302725A (en) 2016-01-13 2023-07-01 Regeneron Pharma Rodents with an engineered DIVERSITY region of the heavy chain
CA3094400A1 (en) 2018-04-06 2019-10-10 Regeneron Pharmaceuticals, Inc. A leptin receptor agonist antibody for use in treating a metabolic dysfunction or hypoleptinemia
IL318469A (en) 2018-06-14 2025-03-01 Regeneron Pharma Non-human animals capable of engineered dh-dh rearrangement and uses thereof
DK3844189T3 (en) 2018-08-31 2025-02-24 Regeneron Pharma Dosing strategy that reduces cytokine release syndrome for CD3/CD20 bispecific antibodies
CN120399084A (en) * 2018-11-16 2025-08-01 维尔托索宾科公司 CD38 and ICAM1 antibodies and their uses
US11464217B2 (en) 2019-02-22 2022-10-11 Regeneron Pharmaceuticals, Inc. Rodents having genetically modified sodium channels and methods of use thereof
KR20210095781A (en) 2020-01-24 2021-08-03 주식회사 에이프릴바이오 A multi-specific antibody comprising a fusion construct consisting of a Fab and a bioactive effector moiety
TW202229328A (en) 2020-09-11 2022-08-01 美商再生元醫藥公司 Identification and production of antigen-specific antibodies
JP2024500399A (en) 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 Mice expressing humanized Fc alpha receptors
CA3197426A1 (en) 2020-12-23 2022-06-30 Regeneron Pharmaceuticals, Inc. Methods for obtaining antibodies that bind transmembrane proteins and cells that produce the same
IL303868A (en) 2020-12-23 2023-08-01 Regeneron Pharma Nucleic acids encoding anchor modified antibodies and uses thereof
CN118496357A (en) * 2023-02-15 2024-08-16 康源博创生物科技(北京)有限公司 Polypeptide and antibody containing same as light chain

Family Cites Families (12)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE68929167T2 (en) * 1988-09-06 2000-11-16 Xoma Corp., Berkeley Gene expression elements and production of chimeric mouse-human antibodies
US5770429A (en) * 1990-08-29 1998-06-23 Genpharm International, Inc. Transgenic non-human animals capable of producing heterologous antibodies
JPH08509612A (en) * 1993-04-26 1996-10-15 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 Transgenic non-human animal capable of producing heterologous antibody
US6596541B2 (en) * 2000-10-31 2003-07-22 Regeneron Pharmaceuticals, Inc. Methods of modifying eukaryotic cells
US6881557B2 (en) * 2001-07-12 2005-04-19 Arrowsmith Technologies Llp Super humanized antibodies
PT1652920E (en) * 2001-10-01 2010-11-08 Deutsches Krebsforsch Methods of producing protein libraries and selection of proteins from them
AU2003214842A1 (en) * 2002-01-17 2003-09-02 Albert Einstein College Of Medicine Of Yeshiva University Mutations caused by activation-induced cytidine deaminase
MXPA04012656A (en) * 2002-06-14 2005-08-15 Immunomedics Inc Humanized monoclonal antiboby hpam4.
CN101962408A (en) * 2002-07-12 2011-02-02 杰斐逊·富特 superhumanized antibody
ES2445193T3 (en) * 2008-06-27 2014-02-28 Merus B.V. Non-human antibody-producing mammals
ES2547142T5 (en) * 2010-02-08 2021-12-09 Regeneron Pharma Mouse common light chain
IL273982B2 (en) * 2011-08-05 2023-03-01 Regeneron Pharma Humanized universal light chain mice

Also Published As

Publication number Publication date
CN104582476A (en) 2015-04-29
MX2014014891A (en) 2015-06-17
WO2013184761A1 (en) 2013-12-12
SG10201609535TA (en) 2017-01-27
CN104582476B (en) 2017-03-08
KR20150023535A (en) 2015-03-05
IL235781A0 (en) 2015-01-29
EP2854523A1 (en) 2015-04-08
AU2013271737A1 (en) 2015-01-22
CA2874846A1 (en) 2013-12-12
SG11201407644UA (en) 2014-12-30
RU2014153674A (en) 2016-07-27
JP2015525071A (en) 2015-09-03

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