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 PDFInfo
- 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
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Classifications
-
- 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
Landscapes
- 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.
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)
| 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)
| 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 |
-
2013
- 2013-06-05 RU RU2014153674A patent/RU2014153674A/en not_active Application Discontinuation
- 2013-06-05 HK HK15109745.2A patent/HK1208994A1/en unknown
- 2013-06-05 AU AU2013271737A patent/AU2013271737A1/en not_active Abandoned
- 2013-06-05 CN CN201380030014.1A patent/CN104582476B/en active Active
- 2013-06-05 EP EP13729875.8A patent/EP2854523A1/en not_active Ceased
- 2013-06-05 JP JP2015516160A patent/JP2015525071A/en active Pending
- 2013-06-05 CA CA2874846A patent/CA2874846A1/en not_active Abandoned
- 2013-06-05 SG SG11201407644UA patent/SG11201407644UA/en unknown
- 2013-06-05 WO PCT/US2013/044257 patent/WO2013184761A1/en not_active Ceased
- 2013-06-05 SG SG10201609535TA patent/SG10201609535TA/en unknown
- 2013-06-05 MX MX2014014891A patent/MX2014014891A/en unknown
- 2013-06-05 KR KR20147036869A patent/KR20150023535A/en not_active Withdrawn
-
2014
- 2014-11-18 IL IL235781A patent/IL235781A0/en unknown
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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