RU2656155C2 - Гуманизированные не относящиеся к человеку животные с ограниченными локусами тяжелой цепи иммуноглобулина - Google Patents

Гуманизированные не относящиеся к человеку животные с ограниченными локусами тяжелой цепи иммуноглобулина Download PDF

Info

Publication number
RU2656155C2
RU2656155C2 RU2014153673A RU2014153673A RU2656155C2 RU 2656155 C2 RU2656155 C2 RU 2656155C2 RU 2014153673 A RU2014153673 A RU 2014153673A RU 2014153673 A RU2014153673 A RU 2014153673A RU 2656155 C2 RU2656155 C2 RU 2656155C2
Authority
RU
Russia
Prior art keywords
human
mouse
gene
heavy chain
sequence
Prior art date
Application number
RU2014153673A
Other languages
English (en)
Russian (ru)
Other versions
RU2014153673A (ru
Inventor
Линн МАКДОНАЛД
Джон МКУИРТЕР
Наксин ТУ
Шон СТИВЕНС
Эндрю Джей МЕРФИ
Original Assignee
Регенерон Фармасьютикалз, Инк.
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 Регенерон Фармасьютикалз, Инк. filed Critical Регенерон Фармасьютикалз, Инк.
Publication of RU2014153673A publication Critical patent/RU2014153673A/ru
Application granted granted Critical
Publication of RU2656155C2 publication Critical patent/RU2656155C2/ru

Links

Images

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
    • 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
    • A01K67/0276Knock-out vertebrates
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K16/00Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies
    • C07K16/18Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K16/00Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies
    • C07K16/46Hybrid immunoglobulins
    • C07K16/461Igs containing Ig-regions, -domains or -residues form different species
    • 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
    • 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
    • C12N9/00Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
    • C12N9/14Hydrolases (3)
    • C12N9/48Hydrolases (3) acting on peptide bonds (3.4)
    • C12N9/50Proteinases, e.g. Endopeptidases (3.4.21-3.4.25)
    • C12N9/64Proteinases, e.g. Endopeptidases (3.4.21-3.4.25) derived from animal tissue
    • C12N9/6421Proteinases, e.g. Endopeptidases (3.4.21-3.4.25) derived from animal tissue from mammals
    • C12N9/6489Metalloendopeptidases (3.4.24)
    • 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
    • A01K2217/07Animals genetically altered by homologous recombination
    • A01K2217/075Animals genetically altered by homologous recombination inducing loss of function, i.e. knock out
    • 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
    • A01K2267/03Animal model, e.g. for test or diseases
    • A01K2267/035Animal model for multifactorial diseases
    • A01K2267/0387Animal model for diseases of the immune system
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K2319/00Fusion polypeptide
    • 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
    • C12N2800/00Nucleic acids vectors
    • C12N2800/20Pseudochromosomes, minichrosomosomes
    • C12N2800/204Pseudochromosomes, minichrosomosomes of bacterial origin, e.g. BAC
    • 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
    • C12N2800/00Nucleic acids vectors
    • C12N2800/30Vector systems comprising sequences for excision in presence of a recombinase, e.g. loxP or FRT

Landscapes

  • Life Sciences & Earth Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Environmental Sciences (AREA)
  • Genetics & Genomics (AREA)
  • Zoology (AREA)
  • Biotechnology (AREA)
  • Immunology (AREA)
  • Molecular Biology (AREA)
  • Biochemistry (AREA)
  • Veterinary Medicine (AREA)
  • Animal Husbandry (AREA)
  • Biodiversity & Conservation Biology (AREA)
  • Animal Behavior & Ethology (AREA)
  • Biophysics (AREA)
  • Medicinal Chemistry (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Wood Science & Technology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Biomedical Technology (AREA)
  • General Engineering & Computer Science (AREA)
  • Microbiology (AREA)
  • Plant Pathology (AREA)
  • Physics & Mathematics (AREA)
  • Micro-Organisms Or Cultivation Processes Thereof (AREA)
  • Peptides Or Proteins (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Preparation Of Compounds By Using Micro-Organisms (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
  • Cell Biology (AREA)
  • Toxicology (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
RU2014153673A 2012-06-12 2013-03-07 Гуманизированные не относящиеся к человеку животные с ограниченными локусами тяжелой цепи иммуноглобулина RU2656155C2 (ru)

Applications Claiming Priority (5)

Application Number Priority Date Filing Date Title
US201261658466P 2012-06-12 2012-06-12
US61/658,466 2012-06-12
US201261663131P 2012-06-22 2012-06-22
US61/663,131 2012-06-22
PCT/US2013/029624 WO2013187953A1 (en) 2012-06-12 2013-03-07 Humanized non-human animals with restricted immunoglobulin heavy chain loci

Publications (2)

Publication Number Publication Date
RU2014153673A RU2014153673A (ru) 2016-08-10
RU2656155C2 true RU2656155C2 (ru) 2018-05-31

Family

ID=47892070

Family Applications (1)

Application Number Title Priority Date Filing Date
RU2014153673A RU2656155C2 (ru) 2012-06-12 2013-03-07 Гуманизированные не относящиеся к человеку животные с ограниченными локусами тяжелой цепи иммуноглобулина

Country Status (26)

Country Link
US (5) US10238093B2 (https=)
EP (3) EP3597037B1 (https=)
JP (6) JP2015519076A (https=)
KR (8) KR102650439B1 (https=)
CN (1) CN104540383B (https=)
AU (6) AU2013204582B2 (https=)
BR (1) BR112014030852B1 (https=)
CA (1) CA2876172C (https=)
CY (2) CY1122482T1 (https=)
DK (2) DK3597037T3 (https=)
ES (2) ES2759617T3 (https=)
HR (2) HRP20200093T1 (https=)
HU (2) HUE055617T2 (https=)
IL (1) IL235892A (https=)
LT (2) LT3597037T (https=)
ME (1) ME03551B (https=)
MX (3) MX364449B (https=)
NZ (2) NZ703689A (https=)
PL (2) PL2858487T3 (https=)
PT (2) PT3597037T (https=)
RS (2) RS62121B1 (https=)
RU (1) RU2656155C2 (https=)
SG (3) SG10201913429WA (https=)
SI (2) SI3597037T1 (https=)
SM (2) SMT202000026T1 (https=)
WO (1) WO2013187953A1 (https=)

Families Citing this family (39)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US9445581B2 (en) 2012-03-28 2016-09-20 Kymab Limited Animal models and therapeutic molecules
BR112012000536A2 (pt) 2009-07-08 2020-08-11 Kymab Limited métodos para produção de anticorpo ou cadeia leve ou pesada de anticorpo específico para um antígeno desejado, para produção de anticorpo ou cadeia de anticorpo e seu uso, composição farmacêutica e derivado de anticorpo quimérico
MX2012006616A (es) 2009-12-09 2012-06-21 Procter & Gamble Productos para el cuidado de las telas y el hogar.
US10793829B2 (en) 2010-07-26 2020-10-06 Trianni, Inc. Transgenic mammals and methods of use thereof
JP6482757B2 (ja) 2010-07-26 2019-03-13 トリアンニ インコーポレイテッドTrianni,Inc. トランスジェニック動物および使用方法
US10662256B2 (en) 2010-07-26 2020-05-26 Trianni, Inc. Transgenic mammals and methods of use thereof
RU2722373C2 (ru) 2011-02-25 2020-05-29 Редженерон Фармасьютикалс, Инк. Мыши adam6
RS59728B1 (sr) 2011-08-05 2020-02-28 Regeneron Pharma Humanizovani miševi univerzalnog lakog lanca
BR112014006394A2 (pt) 2011-09-19 2017-03-28 Kymab Ltd manipulação de diversidade genética de imunoglobulina e terapêuticos multi-anticorpos
WO2013045916A1 (en) 2011-09-26 2013-04-04 Kymab Limited Chimaeric surrogate light chains (slc) comprising human vpreb
KR20160098514A (ko) 2011-10-17 2016-08-18 리제너론 파아마슈티컬스, 인크. 제한된 면역글로불린 중쇄 마우스
US9253965B2 (en) 2012-03-28 2016-02-09 Kymab Limited Animal models and therapeutic molecules
RS62023B1 (sr) * 2012-02-01 2021-07-30 Regeneron Pharma Humanizovani glodari koji eksprimiraju teške lance koji sadrže vl domene
GB2502127A (en) 2012-05-17 2013-11-20 Kymab Ltd Multivalent antibodies and in vivo methods for their production
US10251377B2 (en) 2012-03-28 2019-04-09 Kymab Limited Transgenic non-human vertebrate for the expression of class-switched, fully human, antibodies
PT3597037T (pt) 2012-06-12 2021-06-01 Regeneron Pharma Animais não humanos humanizados com lócus de cadeia pesada de imunoglobulina restrito
EP2840892B1 (en) 2013-02-20 2018-04-18 Regeneron Pharmaceuticals, Inc. Non-human animals with modified immunoglobulin heavy chain sequences
US9788534B2 (en) 2013-03-18 2017-10-17 Kymab Limited Animal models and therapeutic molecules
US9783618B2 (en) 2013-05-01 2017-10-10 Kymab Limited Manipulation of immunoglobulin gene diversity and multi-antibody therapeutics
US11707056B2 (en) 2013-05-02 2023-07-25 Kymab Limited Animals, repertoires and methods
US9783593B2 (en) 2013-05-02 2017-10-10 Kymab Limited Antibodies, variable domains and chains tailored for human use
US20140331344A1 (en) * 2013-05-03 2014-11-06 Kymab Ltd. Transgenic Animals
DE112014004537T5 (de) 2013-10-01 2016-07-21 Kymab Limited Tiermodelle und therapeutische Moleküle
US10034463B2 (en) 2014-01-24 2018-07-31 Children's Medical Center Corporation High-throughput mouse model for optimizing antibody affinities
EP3271403A1 (en) 2015-03-19 2018-01-24 Regeneron Pharmaceuticals, Inc. Non-human animals that select for light chain variable regions that bind antigen
EP3384030A4 (en) 2015-12-03 2019-07-03 Trianni, Inc. IMPROVED IMMUNOGLULINIVITY
AU2017213633B2 (en) 2016-02-04 2023-08-03 Trianni, Inc. Enhanced production of immunoglobulins
IL323024A (en) * 2016-05-20 2025-10-01 Regeneron Pharma Methods for breaking immunological tolerance using multiple guide RNAs
DK4140297T3 (da) * 2017-12-05 2025-06-23 Regeneron Pharma Mus med en konstrueret immunglobulin-lambda-letkæde og anvendelser deraf
CN108486125B (zh) * 2018-03-27 2024-01-05 重庆金迈博生物科技有限公司 一种核酸分子及其在制备人源单域抗体中的应用
IL318469A (en) * 2018-06-14 2025-03-01 Regeneron Pharma Non-human animals capable of reorganizing transgenic DH-DH, and their uses
EP3927832A4 (en) 2019-02-18 2022-11-30 Biocytogen Pharmaceuticals (Beijing) Co., Ltd. GENETICALLY MODIFIED NON-HUMAN ANIMALS WITH HUMANIZED IMMUNOGLOBULIN LOCUS
KR20230018439A (ko) 2020-06-02 2023-02-07 바이오사이토젠 파마슈티컬스 (베이징) 컴퍼니 리미티드 공동 경쇄 면역글로불린 좌위를 갖는 유전자 변형 비인간 동물
CA3187680A1 (en) 2020-09-11 2022-03-17 Yashu Liu Identification and production of antigen-specific antibodies
WO2022132943A1 (en) 2020-12-16 2022-06-23 Regeneron Pharmaceuticals, Inc. Mice expressing humanized fc alpha receptors
CA3165366A1 (en) * 2020-12-23 2022-06-30 Regeneron Pharmaceuticals, Inc. Nucleic acids encoding anchor modified antibodies and uses thereof
TW202600011A (zh) * 2023-01-18 2026-01-01 美商基利科學股份有限公司 具有經改變重鏈基因座之嵌合基因轉殖免疫球蛋白小鼠及其製造及使用方法
WO2026030428A2 (en) 2024-08-01 2026-02-05 Regeneron Pharmaceuticals, Inc. Prostate-specific antigen peptides and uses thereof
WO2026035843A2 (en) 2024-08-06 2026-02-12 Regeneron Pharmaceuticals, Inc. Non-human animals having modified immunoglobulin heavy chain constant region locus and uses thereof

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20120021409A1 (en) * 2010-02-08 2012-01-26 Regeneron Pharmaceuticals, Inc. Common Light Chain Mouse

Family Cites Families (91)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB8823869D0 (en) 1988-10-12 1988-11-16 Medical Res Council Production of antibodies
WO1991000906A1 (en) 1989-07-12 1991-01-24 Genetics Institute, Inc. Chimeric and transgenic animals capable of producing human antibodies
US6075181A (en) 1990-01-12 2000-06-13 Abgenix, Inc. Human antibodies derived from immunized xenomice
US6657103B1 (en) * 1990-01-12 2003-12-02 Abgenix, Inc. Human antibodies derived from immunized xenomice
US6150584A (en) 1990-01-12 2000-11-21 Abgenix, Inc. Human antibodies derived from immunized xenomice
US6673986B1 (en) 1990-01-12 2004-01-06 Abgenix, Inc. Generation of xenogeneic antibodies
EP1690934A3 (en) 1990-01-12 2008-07-30 Abgenix, Inc. Generation of xenogeneic antibodies
US5770429A (en) 1990-08-29 1998-06-23 Genpharm International, Inc. Transgenic non-human animals capable of producing heterologous antibodies
US5633425A (en) 1990-08-29 1997-05-27 Genpharm International, Inc. Transgenic non-human animals capable of producing heterologous antibodies
US7041871B1 (en) 1995-10-10 2006-05-09 Genpharm International, Inc. Transgenic non-human animals capable of producing heterologous antibodies
WO1993008210A1 (en) 1991-10-18 1993-04-29 Beth Israel Hospital Association Vascular permeability factor targeted compounds
WO1994012215A1 (en) 1992-12-01 1994-06-09 Protein Design Labs, Inc. Humanized antibodies reactive with l-selectin
CA2161351C (en) 1993-04-26 2010-12-21 Nils Lonberg Transgenic non-human animals capable of producing heterologous antibodies
EP1500329B1 (en) 1996-12-03 2012-03-21 Amgen Fremont Inc. Human antibodies that specifically bind human TNF alpha
CN1203922A (zh) 1997-03-21 1999-01-06 三共株式会社 人源化抗人fas抗体
US20020062010A1 (en) 1997-05-02 2002-05-23 Genentech, Inc. Method for making multispecific antibodies having heteromultimeric and common components
NL1007580C2 (nl) 1997-11-19 1999-05-20 Hoogovens Corporate Services B Vervaardiging van een middel voor de vermindering van de uitwerking van een externe mechanische stoot en het aldus vervaardigde middel.
RU10506U1 (ru) 1999-04-08 1999-08-16 Кривулин Виталий Николаевич Ручной культиватор
WO2000073323A2 (en) 1999-05-27 2000-12-07 Human Genome Sciences, Inc. Adam polynucleotides and polypeptides
GB0001448D0 (en) 2000-01-21 2000-03-08 Novartis Ag Organic compounds
EA013564B1 (ru) 2000-08-03 2010-06-30 Терапеутик Хьюман Поликлоналз Инк. Гуманизированный иммуноглобулин и содержащая его фармацевтическая композиция
US7105348B2 (en) 2000-10-31 2006-09-12 Regeneron Pharmaceuticals, Inc. Methods of modifying eukaryotic cells
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
TWI255272B (en) 2000-12-06 2006-05-21 Guriq Basi Humanized antibodies that recognize beta amyloid peptide
GB0110029D0 (en) 2001-04-24 2001-06-13 Grosveld Frank Transgenic animal
US7034134B2 (en) 2001-04-26 2006-04-25 Bristol-Myers Squibb Company Polynucleotide encoding a novel metalloprotease highly expressed in the testis, MMP-29
US7476536B2 (en) 2001-05-11 2009-01-13 Kirin Pharma Kabushiki Kaisha Artificial human chromosome containing human antibody a light chain gene
US7473557B2 (en) 2001-06-06 2009-01-06 Regeneron Pharmaceuticals, Inc. Method for targeting transcriptionally active loci
WO2003007257A1 (en) * 2001-07-13 2003-01-23 Juan Carlos Cordoba An alarm system for a portable device
US20030108925A1 (en) 2001-10-05 2003-06-12 U.S. Epa Genetic testing for male factor infertility
US20060199204A1 (en) 2001-10-05 2006-09-07 U.S. Epa Genetic testing for male factor infertility
US7435871B2 (en) 2001-11-30 2008-10-14 Amgen Fremont Inc. Transgenic animals bearing human Igλ light chain genes
NZ537277A (en) 2002-07-18 2008-04-30 Crucell Holland Bv Recombinant production of mixtures of antibodies
GB0228210D0 (en) 2002-12-03 2003-01-08 Babraham Inst Single chain antibodies
JP4745242B2 (ja) * 2003-05-20 2011-08-10 アプライド モレキュラー エボリューション,インコーポレイテッド Cd20結合分子
AR044388A1 (es) 2003-05-20 2005-09-07 Applied Molecular Evolution Moleculas de union a cd20
US20100069614A1 (en) 2008-06-27 2010-03-18 Merus B.V. Antibody producing non-human mammals
ES2408582T3 (es) 2003-05-30 2013-06-21 Merus B.V. Biblioteca de Fab para la preparación de una mezcla de anticuerpos
EP1644417B1 (en) 2003-07-15 2014-04-30 Therapeutic Human Polyclonals, Inc. Humanized immunoglobulin loci
WO2005019463A1 (en) 2003-08-11 2005-03-03 Therapeutic Human Polyclonals, Inc. Improved transgenesis with humanized immunoglobulin loci
EP1660186B1 (en) * 2003-08-18 2013-12-25 MedImmune, LLC Humanization of antibodies
RU2251699C1 (ru) 2003-09-25 2005-05-10 Киселев Всеволод Иванович Способ ранней и доклинической диагностики цервикального рака
WO2005038001A2 (en) 2003-10-14 2005-04-28 Therapeutic Human Polyclonals, Inc. Improved transgenesis by sperm-mediated gene transfer
CN101076542A (zh) 2004-09-13 2007-11-21 伊沃詹尼克斯有限公司 特异性针对肝细胞癌和其他癌的抗体及其用途
AU2005295269B2 (en) 2004-10-19 2010-05-13 Regeneron Pharmaceuticals, Inc. Method for generating an animal homozygous for a genetic modification
JP2008538912A (ja) 2005-04-29 2008-11-13 イナート・ファルマ 遺伝子導入動物および組換え抗体の製造方法
PL1739691T3 (pl) 2005-06-30 2009-06-30 Borealis Tech Oy Zewnętrzne osłony dla kabli elektroenergetycznych lub telekomunikacyjnych
TWI404727B (zh) 2006-01-25 2013-08-11 荷蘭鹿特丹Erasmus大學醫學中心 對偶基因排除
AU2007235496B2 (en) 2006-03-31 2013-11-21 E. R. Squibb & Sons, L.L.C. Transgenic animals expressing chimeric antibodies for use in preparing human antibodies
ES2398076T3 (es) 2006-06-02 2013-03-13 Regeneron Pharmaceuticals, Inc. Anticuerpos de alta afinidad contra el receptor de IL-6 humano
DK2602323T3 (en) 2007-06-01 2018-04-16 Open Monoclonal Tech Inc Compositions and Methods for Inhibiting Endogenous Immunoglobin Genes and Producing Transgenic Human Idiotypic Antibodies
WO2009013620A2 (en) 2007-06-11 2009-01-29 Erasmus University Medical Center Rotterdam Homologous recombination
WO2009097006A2 (en) * 2007-08-10 2009-08-06 Medarex, Inc. Hco32 and hco27 and related examples
EP2201040A1 (en) 2007-09-24 2010-06-30 Vanderbilt University Monoclonal antibodies to respiratory syncytial virus and uses thereof
US7659842B2 (en) 2007-10-24 2010-02-09 Infineon Technologies Ag Quantization error reduction in PWM full-MASH converters
CA2708776A1 (en) * 2007-12-10 2009-06-18 Aliva Biopharmaceuticals, Inc. Methods for sequential replacement of targeted region by homologous recombination
KR102057826B1 (ko) 2008-04-11 2019-12-20 추가이 세이야쿠 가부시키가이샤 복수 분자의 항원에 반복 결합하는 항원 결합 분자
WO2009129247A2 (en) 2008-04-14 2009-10-22 Innovative Targeting Solutions Inc. Sequence diversity generation in immunoglobulins
ES2436044T3 (es) 2008-05-23 2013-12-26 Ablexis, Llc Procedimiento de generación de anticuerpos de dominio VL individual en animales transgénicos
EP2346994B1 (en) 2008-09-30 2022-02-16 Ablexis, LLC Knock-in mice for the production of chimeric antibodies
US20110313134A1 (en) * 2008-11-06 2011-12-22 Alexion Pharmaceuticals, Inc. Engineered antibodies with reduced immunogenicity and methods of making
JP5827127B2 (ja) 2008-12-18 2015-12-02 エラスムス・ユニヴァーシティ・メディカル・センター・ロッテルダム ヒト化抗体を発現する非ヒトトランスジェニック動物及びその使用
GB0905023D0 (en) * 2009-03-24 2009-05-06 Univ Erasmus Medical Ct Binding molecules
JP5816170B2 (ja) 2009-06-26 2015-11-18 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. 天然の免疫グロブリン形式を有する容易に単離される二重特異性抗体
BR112012000536A2 (pt) 2009-07-08 2020-08-11 Kymab Limited métodos para produção de anticorpo ou cadeia leve ou pesada de anticorpo específico para um antígeno desejado, para produção de anticorpo ou cadeia de anticorpo e seu uso, composição farmacêutica e derivado de anticorpo quimérico
RU2425880C2 (ru) 2009-07-30 2011-08-10 Учреждение Российской академии наук Институт общей генетики им. Н.И. Вавилова РАН Способ получения трансгенных мышей
US8754287B2 (en) 2009-12-10 2014-06-17 Regeneron Pharmaceuticals, Inc. Mice that make heavy chain antibodies
SI2501817T2 (sl) 2010-02-08 2021-09-30 Regeneron Pharmaceuticals, Inc. Miš z navadno lahko verigo
US9796788B2 (en) 2010-02-08 2017-10-24 Regeneron Pharmaceuticals, Inc. Mice expressing a limited immunoglobulin light chain repertoire
US20130185821A1 (en) 2010-02-08 2013-07-18 Regeneron Pharmaceuticals, Inc. Common Light Chain Mouse
AU2011266843C9 (en) 2010-06-17 2018-03-01 Kymab Limited Animal models and therapeutic molecules
SG10201912639SA (en) 2010-08-02 2020-02-27 Regeneron Pharma Mice that make binding proteins comprising vl domains
WO2012063048A1 (en) 2010-11-08 2012-05-18 Kymab Limited Cells & vertebrates for enhanced somatic hypermutation and class switch recombination
RU2722373C2 (ru) 2011-02-25 2020-05-29 Редженерон Фармасьютикалс, Инк. Мыши adam6
RS59728B1 (sr) * 2011-08-05 2020-02-28 Regeneron Pharma Humanizovani miševi univerzalnog lakog lanca
BR112014006394A2 (pt) 2011-09-19 2017-03-28 Kymab Ltd manipulação de diversidade genética de imunoglobulina e terapêuticos multi-anticorpos
WO2013041845A2 (en) 2011-09-19 2013-03-28 Kymab Limited Animals, repertoires & methods
WO2013045916A1 (en) 2011-09-26 2013-04-04 Kymab Limited Chimaeric surrogate light chains (slc) comprising human vpreb
KR20160098514A (ko) 2011-10-17 2016-08-18 리제너론 파아마슈티컬스, 인크. 제한된 면역글로불린 중쇄 마우스
GB2496375A (en) 2011-10-28 2013-05-15 Kymab Ltd A non-human assay vertebrate comprising human antibody loci and human epitope knock-in, and uses thereof
GB201122047D0 (en) 2011-12-21 2012-02-01 Kymab Ltd Transgenic animals
US9253965B2 (en) 2012-03-28 2016-02-09 Kymab Limited Animal models and therapeutic molecules
RU2664181C2 (ru) * 2011-12-20 2018-08-15 Регенерон Фармасьютикалз, Инк. Мыши с гуманизированной легкой цепью
RS62023B1 (sr) 2012-02-01 2021-07-30 Regeneron Pharma Humanizovani glodari koji eksprimiraju teške lance koji sadrže vl domene
KR102228296B1 (ko) 2012-03-16 2021-03-17 리제너론 파마슈티칼스 인코포레이티드 히스티딘 공학처리된 경쇄 항체 및 그것을 생성하기 위한 유전자 변형된 비-사람 동물
GB2502127A (en) 2012-05-17 2013-11-20 Kymab Ltd Multivalent antibodies and in vivo methods for their production
JP2015512635A (ja) 2012-03-28 2015-04-30 カイマブ・リミテッド クラススイッチした完全ヒト抗体の発現のためのトランスジェニック非−ヒト脊椎動物
PT3597037T (pt) 2012-06-12 2021-06-01 Regeneron Pharma Animais não humanos humanizados com lócus de cadeia pesada de imunoglobulina restrito
EP2840892B1 (en) 2013-02-20 2018-04-18 Regeneron Pharmaceuticals, Inc. Non-human animals with modified immunoglobulin heavy chain sequences
WO2014160202A1 (en) 2013-03-13 2014-10-02 Regeneron Pharmaceuticals, Inc. Mice expressing a limited immunoglobulin light chain repertoire

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20120021409A1 (en) * 2010-02-08 2012-01-26 Regeneron Pharmaceuticals, Inc. Common Light Chain Mouse

Non-Patent Citations (4)

* Cited by examiner, † Cited by third party
Title
BROCKER CHAD N., et al., Evolutionary divergence and functions of the ADAM and ADAMTSgene families, HUMAN GENOMICS, 2009, VOL 4. NO.1, pp. 43 -55. *
WAGNER S. D., et al., The diversity of antigen-specific monoclonal antibodies from transgenic mice bearing human immunoglobulin gene miniloci, European journal of immunology, 1994, Volume 24, Issue 11, pp. 2672-2681. *
WAGNER S. D., et al., The diversity of antigen-specific monoclonal antibodies from transgenic mice bearing human immunoglobulin gene miniloci, European journal of immunology, 1994, Volume 24, Issue 11, pp. 2672-2681. BROCKER CHAD N., et al., Evolutionary divergence and functions of the ADAM and ADAMTSgene families, HUMAN GENOMICS, 2009, VOL 4. NO.1, pp. 43 -55. РЫБЧИН В.Н., Основы генетической инженерии, Учебник дляВУЗов, Санкт-Петербург, Издательство СПбГТУ, 2002, 522 с., с. 410-417. *
РЫБЧИН В.Н., Основы генетической инженерии, Учебник дляВУЗов, Санкт-Петербург, Издательство СПбГТУ, 2002, 522 с., с. 410-417. *

Also Published As

Publication number Publication date
CN104540383A (zh) 2015-04-22
SMT202000026T1 (it) 2020-03-13
RS59890B1 (sr) 2020-03-31
WO2013187953A1 (en) 2013-12-19
NZ717848A (en) 2019-03-29
JP2020110187A (ja) 2020-07-27
EP2858487B1 (en) 2019-10-23
AU2013204582A1 (en) 2014-01-09
PL2858487T3 (pl) 2020-06-01
KR102126217B1 (ko) 2020-06-24
PT2858487T (pt) 2020-01-15
CY1124320T1 (el) 2022-07-22
MX364449B (es) 2019-04-26
US20200281175A1 (en) 2020-09-10
ME03551B (me) 2020-07-20
PT3597037T (pt) 2021-06-01
US11559050B2 (en) 2023-01-24
IL235892A0 (en) 2015-01-29
AU2018201501A1 (en) 2018-03-22
AU2013204582B2 (en) 2016-01-14
SG10201913429WA (en) 2020-03-30
KR20200074271A (ko) 2020-06-24
KR102484480B1 (ko) 2023-01-04
AU2016201612A1 (en) 2016-03-31
US10238093B2 (en) 2019-03-26
NZ703689A (en) 2016-05-27
ES2874515T3 (es) 2021-11-05
CA2876172C (en) 2021-01-19
LT3597037T (lt) 2021-06-10
DK2858487T3 (da) 2020-01-20
AU2026201796A1 (en) 2026-04-02
JP2018029623A (ja) 2018-03-01
EP2858487A1 (en) 2015-04-15
KR20240042174A (ko) 2024-04-01
SI3597037T1 (sl) 2021-07-30
HRP20200093T1 (hr) 2020-04-03
MX379274B (es) 2025-03-10
CN104540383B (zh) 2017-08-29
US20240065238A1 (en) 2024-02-29
ES2759617T3 (es) 2020-05-11
RU2014153673A (ru) 2016-08-10
RS62121B1 (sr) 2021-08-31
CY1122482T1 (el) 2021-01-27
KR20230012073A (ko) 2023-01-25
EP3597037A1 (en) 2020-01-22
KR102381716B1 (ko) 2022-04-01
HRP20211126T1 (hr) 2021-10-15
AU2022291579B2 (en) 2025-12-18
MX2021000829A (es) 2021-03-25
EP3912464A1 (en) 2021-11-24
EP3597037B1 (en) 2021-04-28
KR102650439B1 (ko) 2024-03-26
AU2020202185A1 (en) 2020-04-16
KR20220123322A (ko) 2022-09-06
JP6697430B2 (ja) 2020-05-20
KR20220044871A (ko) 2022-04-11
JP2023165683A (ja) 2023-11-16
AU2018201501B2 (en) 2020-01-02
JP2015519076A (ja) 2015-07-09
SI2858487T1 (sl) 2019-12-31
JP2026040651A (ja) 2026-03-09
KR20150027793A (ko) 2015-03-12
AU2020202185B2 (en) 2022-09-29
IL235892A (en) 2017-04-30
US20200093106A1 (en) 2020-03-26
HK1203762A1 (en) 2015-11-06
KR102436654B1 (ko) 2022-08-26
MX2014015261A (es) 2015-06-23
JP7106596B2 (ja) 2022-07-26
SG11201407789RA (en) 2014-12-30
HUE047266T2 (hu) 2020-04-28
BR112014030852A2 (https=) 2017-08-15
DK3597037T3 (da) 2021-06-28
BR112014030852B1 (pt) 2023-04-11
HUE055617T2 (hu) 2021-12-28
PL3597037T3 (pl) 2021-10-25
JP2022090103A (ja) 2022-06-16
KR20200126439A (ko) 2020-11-06
SMT202100426T1 (it) 2021-09-14
LT2858487T (lt) 2019-12-27
KR102266274B1 (ko) 2021-06-17
KR20190006611A (ko) 2019-01-18
SG10201609277PA (en) 2017-01-27
US11666040B2 (en) 2023-06-06
CA2876172A1 (en) 2013-12-19
US20130333057A1 (en) 2013-12-12
US20190200588A1 (en) 2019-07-04
US10542735B2 (en) 2020-01-28
MX2019004871A (es) 2019-09-04
AU2022291579A1 (en) 2023-03-30

Similar Documents

Publication Publication Date Title
US20240065238A1 (en) Humanized non-human animals with restricted immunoglobulin heavy chain loci
RU2664185C2 (ru) Гуманизированные грызуны, которые экспрессируют тяжелые цепи, содержащие домены vl
HK40064570A (en) Humanized non-human animals with restricted immunoglobulin heavy chain loci
HK40021356A (en) Humanized non-human animals with restricted immunoglobulin heavy chain loci
HK40021356B (en) Humanized non-human animals with restricted immunoglobulin heavy chain loci
HK1203762B (en) Humanized non-human animals with restricted immunoglobulin heavy chain loci
MX2014009300A (es) Roedores humanizados que expresan cadenas pesadas que contienen dominios vl.