WO2014160179A4 - Souris à chaine légère classique - Google Patents

Souris à chaine légère classique Download PDF

Info

Publication number
WO2014160179A4
WO2014160179A4 PCT/US2014/025982 US2014025982W WO2014160179A4 WO 2014160179 A4 WO2014160179 A4 WO 2014160179A4 US 2014025982 W US2014025982 W US 2014025982W WO 2014160179 A4 WO2014160179 A4 WO 2014160179A4
Authority
WO
WIPO (PCT)
Prior art keywords
human
gene
mouse
gene segments
heavy chain
Prior art date
Application number
PCT/US2014/025982
Other languages
English (en)
Other versions
WO2014160179A1 (fr
Inventor
Robert Babb
John Mcwhirter
Lynn Macdonald
Sean Stevens
Samuel Davis
David R. Buckler
Karolina A. Meagher
Andrew J. Murphy
Natasha Levenkova
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 US13/798,310 external-priority patent/US20130185821A1/en
Priority to CN201480013861.1A priority Critical patent/CN105189545A/zh
Priority to AU2014244079A priority patent/AU2014244079A1/en
Priority to KR1020157025655A priority patent/KR20150126863A/ko
Priority to SG11201506294TA priority patent/SG11201506294TA/en
Priority to EP14722432.3A priority patent/EP2970437A1/fr
Application filed by Regeneron Pharmaceuticals, Inc. filed Critical Regeneron Pharmaceuticals, Inc.
Priority to MX2015012540A priority patent/MX2015012540A/es
Priority to CA2903696A priority patent/CA2903696A1/fr
Priority to JP2016502014A priority patent/JP2016519568A/ja
Priority to RU2015143108A priority patent/RU2015143108A/ru
Publication of WO2014160179A1 publication Critical patent/WO2014160179A1/fr
Publication of WO2014160179A4 publication Critical patent/WO2014160179A4/fr
Priority to IL240562A priority patent/IL240562A0/en
Priority to HK16106452.0A priority patent/HK1218550A1/zh

Links

Classifications

    • AHUMAN NECESSITIES
    • A01AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01KANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
    • A01K67/00Rearing or breeding animals, not otherwise provided for; New or modified breeds of animals
    • A01K67/027New or modified breeds of vertebrates
    • A01K67/0275Genetically modified vertebrates, e.g. transgenic
    • A01K67/0278Knock-in vertebrates, e.g. humanised vertebrates
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K16/00Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K16/00Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/18Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/28Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N15/00Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09Recombinant DNA-technology
    • C12N15/63Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
    • C12N15/79Vectors or expression systems specially adapted for eukaryotic hosts
    • C12N15/85Vectors or expression systems specially adapted for eukaryotic hosts for animal cells
    • C12N15/8509Vectors or expression systems specially adapted for eukaryotic hosts for animal cells for producing genetically modified animals, e.g. transgenic
    • AHUMAN NECESSITIES
    • A01AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01KANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
    • A01K2207/00Modified animals
    • A01K2207/15Humanized animals
    • AHUMAN NECESSITIES
    • A01AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01KANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
    • A01K2217/00Genetically modified animals
    • A01K2217/07Animals genetically altered by homologous recombination
    • A01K2217/072Animals genetically altered by homologous recombination maintaining or altering function, i.e. knock in
    • AHUMAN NECESSITIES
    • A01AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01KANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
    • A01K2217/00Genetically modified animals
    • A01K2217/15Animals comprising multiple alterations of the genome, by transgenesis or homologous recombination, e.g. obtained by cross-breeding
    • AHUMAN NECESSITIES
    • A01AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01KANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
    • A01K2227/00Animals characterised by species
    • A01K2227/10Mammal
    • A01K2227/105Murine
    • AHUMAN NECESSITIES
    • A01AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01KANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
    • A01K2267/00Animals characterised by purpose
    • A01K2267/01Animal expressing industrially exogenous proteins
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K2317/00Immunoglobulins specific features
    • C07K2317/10Immunoglobulins specific features characterized by their source of isolation or production
    • C07K2317/14Specific host cells or culture conditions, e.g. components, pH or temperature
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K2317/00Immunoglobulins specific features
    • C07K2317/20Immunoglobulins specific features characterized by taxonomic origin
    • C07K2317/21Immunoglobulins specific features characterized by taxonomic origin from primates, e.g. man
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K2317/00Immunoglobulins specific features
    • C07K2317/30Immunoglobulins specific features characterized by aspects of specificity or valency
    • C07K2317/31Immunoglobulins specific features characterized by aspects of specificity or valency multispecific
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K2317/00Immunoglobulins specific features
    • C07K2317/50Immunoglobulins specific features characterized by immunoglobulin fragments
    • C07K2317/515Complete light chain, i.e. VL + CL
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K2317/00Immunoglobulins specific features
    • C07K2317/70Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
    • C07K2317/76Antagonist effect on antigen, e.g. neutralization or inhibition of binding
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K2317/00Immunoglobulins specific features
    • C07K2317/90Immunoglobulins specific features characterized by (pharmaco)kinetic aspects or by stability of the immunoglobulin
    • C07K2317/92Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value

Landscapes

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

Abstract

L'invention concerne une souris génétiquement modifiée, la souris exprimant un répertoire de chaîne légère d'immunoglobuline caractérisé par un nombre limité de domaines variables de chaîne légère. L'invention concerne des souris qui expriment juste un domaine variable de chaîne légère d'immunoglobuline ou peu de domaines variables de chaîne légère d'immunoglobuline à partir d'un répertoire limité dans leur lignée germinale. L'invention concerne des procédés de fabrication d'anticorps bispécifiques ayant des chaînes légères universelles à l'aide de souris telles que décrites ici, comprenant des régions variables de chaîne légère humaine. L'invention concerne des procédés de fabrication de régions variables humaines appropriés pour l'utilisation dans des protéines de liaison multi-spécifiques, par exemple des anticorps bispécifiques, et des cellules hôtes. L'invention concerne des anticorps bispécifiques capables de se lier à des premier et second antigènes, les premier et second antigènes étant des épitopes séparés d'une protéine unique ou des épitopes séparés sur deux protéines différentes.
PCT/US2014/025982 2013-03-13 2014-03-13 Souris à chaine légère classique WO2014160179A1 (fr)

Priority Applications (11)

Application Number Priority Date Filing Date Title
RU2015143108A RU2015143108A (ru) 2013-03-13 2014-03-13 Мышь с общей легкой цепью
CA2903696A CA2903696A1 (fr) 2013-03-13 2014-03-13 Souris a chaine legere classique
KR1020157025655A KR20150126863A (ko) 2013-03-13 2014-03-13 공통 경쇄 마우스
SG11201506294TA SG11201506294TA (en) 2013-03-13 2014-03-13 Common light chain mouse
EP14722432.3A EP2970437A1 (fr) 2013-03-13 2014-03-13 Souris à chaine légère classique
CN201480013861.1A CN105189545A (zh) 2013-03-13 2014-03-13 常见轻链小鼠
MX2015012540A MX2015012540A (es) 2013-03-13 2014-03-13 Ratón de cadena ligera común.
AU2014244079A AU2014244079A1 (en) 2013-03-13 2014-03-13 Common light chain mouse
JP2016502014A JP2016519568A (ja) 2013-03-13 2014-03-13 共通軽鎖のマウス
IL240562A IL240562A0 (en) 2013-03-13 2015-08-13 A mouse with a common light chain
HK16106452.0A HK1218550A1 (zh) 2013-03-13 2016-06-06 常見輕鏈小鼠

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US13/798,310 2013-03-13
US13/798,310 US20130185821A1 (en) 2010-02-08 2013-03-13 Common Light Chain Mouse

Publications (2)

Publication Number Publication Date
WO2014160179A1 WO2014160179A1 (fr) 2014-10-02
WO2014160179A4 true WO2014160179A4 (fr) 2014-11-20

Family

ID=50555217

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US2014/025982 WO2014160179A1 (fr) 2013-03-13 2014-03-13 Souris à chaine légère classique

Country Status (13)

Country Link
EP (1) EP2970437A1 (fr)
JP (1) JP2016519568A (fr)
KR (1) KR20150126863A (fr)
CN (1) CN105189545A (fr)
AU (1) AU2014244079A1 (fr)
CA (1) CA2903696A1 (fr)
HK (1) HK1218550A1 (fr)
IL (1) IL240562A0 (fr)
MX (1) MX2015012540A (fr)
NL (4) NL2012424C2 (fr)
RU (1) RU2015143108A (fr)
SG (1) SG11201506294TA (fr)
WO (1) WO2014160179A1 (fr)

Families Citing this family (19)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20130045492A1 (en) 2010-02-08 2013-02-21 Regeneron Pharmaceuticals, Inc. Methods For Making Fully Human Bispecific Antibodies Using A Common Light Chain
ES2547142T5 (es) 2010-02-08 2021-12-09 Regeneron Pharma Cadena ligera común de ratón
US9796788B2 (en) 2010-02-08 2017-10-24 Regeneron Pharmaceuticals, Inc. Mice expressing a limited immunoglobulin light chain repertoire
PL3572517T3 (pl) 2011-08-05 2021-10-04 Regeneron Pharmaceuticals, Inc. Myszy z humanizowanym uniwersalnym łańcuchem lekkim
KR20210088756A (ko) 2014-03-21 2021-07-14 리제너론 파마슈티칼스 인코포레이티드 단일 도메인 결합 단백질을 생산하는 비-인간 동물
CN107438622A (zh) 2015-03-19 2017-12-05 瑞泽恩制药公司 选择结合抗原的轻链可变区的非人动物
KR102482103B1 (ko) 2016-01-13 2022-12-28 리제너론 파마슈티칼스 인코포레이티드 조작된 중쇄 다양성 영역을 갖는 설치류
GB201710984D0 (en) 2017-07-07 2017-08-23 Kymab Ltd Cells, vertebrates, populations & methods
KR102617284B1 (ko) 2018-06-14 2023-12-27 리제너론 파마슈티칼스 인코포레이티드 면역글로불린 중쇄 암호화 서열에서 dh-dh 재배열 가능한 비인간 동물
EP3927153A1 (fr) 2019-02-22 2021-12-29 Regeneron Pharmaceuticals, Inc. Rongeurs ayant des canaux sodiques génétiquement modifiés et leurs procédés d'utilisation
AU2020289554A1 (en) * 2019-06-05 2021-11-18 Regeneron Pharmaceuticals, Inc. Non-human animals having a limited lambda light chain repertoire expressed from the kappa locus and uses 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
CA3187680A1 (fr) 2020-09-11 2022-03-17 Yashu Liu Identification et production d'anticorps specifiques a un antigene
KR20230147048A (ko) 2020-12-16 2023-10-20 리제너론 파마슈티칼스 인코포레이티드 인간화 Fc 알파 수용체를 발현하는 마우스
TW202242114A (zh) 2020-12-23 2022-11-01 美商再生元醫藥公司 用於獲得結合至跨膜蛋白之抗體以及抗體生成細胞的方法
US20220195014A1 (en) 2020-12-23 2022-06-23 Regeneron Pharmaceuticals, Inc. Nucleic acids encoding anchor modified antibodies and uses thereof
GB202107372D0 (en) 2021-05-24 2021-07-07 Petmedix Ltd Animal models and therapeutics molecules
GB202209247D0 (en) 2022-06-23 2022-08-10 Petmedix Ltd Animal models and therapeutic molecules
GB202216503D0 (en) 2022-11-05 2022-12-21 Quadrucept Bio Ltd Non-human vertebrates & cells

Family Cites Families (16)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6774279B2 (en) 1997-05-30 2004-08-10 Carnegie Institution Of Washington Use of FLP recombinase in mice
US6737056B1 (en) 1999-01-15 2004-05-18 Genentech, Inc. Polypeptide variants with altered effector function
US6596541B2 (en) 2000-10-31 2003-07-22 Regeneron Pharmaceuticals, Inc. Methods of modifying eukaryotic cells
US6586251B2 (en) 2000-10-31 2003-07-01 Regeneron Pharmaceuticals, Inc. Methods of modifying eukaryotic cells
US7105348B2 (en) 2000-10-31 2006-09-12 Regeneron Pharmaceuticals, Inc. Methods of modifying eukaryotic cells
JP4836451B2 (ja) * 2002-07-18 2011-12-14 メルス ベー ヴェー 抗体混合物の組換え生産
US7217797B2 (en) 2002-10-15 2007-05-15 Pdl Biopharma, Inc. Alteration of FcRn binding affinities or serum half-lives of antibodies by mutagenesis
CN1852925A (zh) * 2003-07-15 2006-10-25 人类多克隆治疗公司 人源化免疫球蛋白基因座
PT1802193E (pt) 2004-10-19 2014-06-23 Regeneron Pharma Método para gerar um murganho homozigótico para uma modificação genética
ES2398076T3 (es) 2006-06-02 2013-03-13 Regeneron Pharmaceuticals, Inc. Anticuerpos de alta afinidad contra el receptor de IL-6 humano
MX2011014008A (es) 2009-06-26 2012-06-01 Regeneron Pharma Anticuerpos biespecificos facilmente aislados con formato de inmunoglobulina original.
ES2547142T5 (es) * 2010-02-08 2021-12-09 Regeneron Pharma Cadena ligera común de ratón
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
JP2015509380A (ja) * 2012-03-06 2015-03-30 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Regeneron Pharmaceuticals, Inc. 共通の軽鎖のマウス
CN104582476B (zh) * 2012-06-05 2017-03-08 瑞泽恩制药公司 使用共同轻链制备完全人双特异性抗体的方法

Also Published As

Publication number Publication date
NL2015603B1 (en) 2016-09-23
NL2014775B1 (en) 2016-03-16
WO2014160179A1 (fr) 2014-10-02
NL2013851C2 (en) 2015-06-08
NL2015603A (en) 2016-03-16
KR20150126863A (ko) 2015-11-13
NL2013851A (en) 2015-01-12
AU2014244079A1 (en) 2015-09-24
JP2016519568A (ja) 2016-07-07
NL2012424A (en) 2014-09-16
EP2970437A1 (fr) 2016-01-20
CA2903696A1 (fr) 2014-10-02
NL2014775A (en) 2015-06-09
IL240562A0 (en) 2015-09-24
CN105189545A (zh) 2015-12-23
MX2015012540A (es) 2016-04-19
HK1218550A1 (zh) 2017-02-24
NL2012424C2 (en) 2014-12-08
SG11201506294TA (en) 2015-09-29
RU2015143108A (ru) 2017-04-20

Similar Documents

Publication Publication Date Title
WO2014160179A4 (fr) Souris à chaine légère classique
AU2013204581B2 (en) Non-human animals expressing pH-sensitive immunoglobulin sequences
US20170367308A1 (en) Non-Human Animals Expressing pH-Sensitive Immunoglobulin Sequences
JP5993102B2 (ja) 修飾された免疫グロブリン重鎖配列を有する非ヒト動物
KR102116296B1 (ko) 일반적인 경쇄 마우스
CN102711449B (zh) 生产重链抗体的小鼠
CA2874846A1 (fr) Procedes pour preparer des anticorps bispecifiques entierement humains en utilisant une chaine legere commune
RU2016139418A (ru) Мыши с ограниченной тяжелой цепью иммуноглобулина
CA2865029A1 (fr) Souris a chaine legere commune
RU2016114306A (ru) Антитела со встроенным в лёгкие цепи гистидином и генетически модифицированные отличные от человека животные для их получения
AU2014244020A1 (en) Mice expressing a limited immunoglobulin light chain repertoire
AU2019280049C1 (en) Non-human animals expressing ph-sensitive immunoglobulin sequences
RU2020116981A (ru) Мыши adam6
RU2021131650A (ru) Отличные от человека животные, имеющие ограниченный репертуар легких лямбда-цепей, экспрессируемый из локуса капли, и их применение

Legal Events

Date Code Title Description
WWE Wipo information: entry into national phase

Ref document number: 201480013861.1

Country of ref document: CN

121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 14722432

Country of ref document: EP

Kind code of ref document: A1

WWE Wipo information: entry into national phase

Ref document number: 240562

Country of ref document: IL

ENP Entry into the national phase

Ref document number: 2903696

Country of ref document: CA

ENP Entry into the national phase

Ref document number: 2016502014

Country of ref document: JP

Kind code of ref document: A

WWE Wipo information: entry into national phase

Ref document number: MX/A/2015/012540

Country of ref document: MX

NENP Non-entry into the national phase

Ref country code: DE

ENP Entry into the national phase

Ref document number: 20157025655

Country of ref document: KR

Kind code of ref document: A

ENP Entry into the national phase

Ref document number: 2014244079

Country of ref document: AU

Date of ref document: 20140313

Kind code of ref document: A

WWE Wipo information: entry into national phase

Ref document number: 2014722432

Country of ref document: EP

ENP Entry into the national phase

Ref document number: 2015143108

Country of ref document: RU

Kind code of ref document: A

REG Reference to national code

Ref country code: BR

Ref legal event code: B01A

Ref document number: 112015022151

Country of ref document: BR

ENP Entry into the national phase

Ref document number: 112015022151

Country of ref document: BR

Kind code of ref document: A2

Effective date: 20150909