DE112014004537T5 - Tiermodelle und therapeutische Moleküle - Google Patents

Tiermodelle und therapeutische Moleküle Download PDF

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Publication number
DE112014004537T5
DE112014004537T5 DE112014004537.3T DE112014004537T DE112014004537T5 DE 112014004537 T5 DE112014004537 T5 DE 112014004537T5 DE 112014004537 T DE112014004537 T DE 112014004537T DE 112014004537 T5 DE112014004537 T5 DE 112014004537T5
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Germany
Prior art keywords
human
gene segments
vertebrate
cell
antibody
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Withdrawn
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DE112014004537.3T
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German (de)
English (en)
Inventor
E-Chiang Lee
Jasper Clube
Allan Bradley
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Kymab Ltd
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Kymab Ltd
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Priority claimed from GBGB1317410.7A external-priority patent/GB201317410D0/en
Priority claimed from FR1359518A external-priority patent/FR3011249A1/fr
Application filed by Kymab Ltd filed Critical Kymab Ltd
Publication of DE112014004537T5 publication Critical patent/DE112014004537T5/de
Withdrawn legal-status Critical Current

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    • 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
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K16/00Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies
    • 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
    • C07K16/462Igs containing a variable region (Fv) from one specie and a constant region (Fc) from another
    • 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
    • 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
    • C12PFERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE
    • C12P21/00Preparation of peptides or proteins
    • C12P21/02Preparation of peptides or proteins having a known sequence of two or more amino acids, e.g. glutathione
    • 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
    • A01K2267/01Animal 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
    • C07K2317/20Immunoglobulins specific features characterized by taxonomic origin
    • C07K2317/24Immunoglobulins specific features characterized by taxonomic origin containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
    • 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
    • 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

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Genetics & Genomics (AREA)
  • Organic Chemistry (AREA)
  • Engineering & Computer Science (AREA)
  • Zoology (AREA)
  • General Health & Medical Sciences (AREA)
  • Biotechnology (AREA)
  • Wood Science & Technology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Biochemistry (AREA)
  • Molecular Biology (AREA)
  • General Engineering & Computer Science (AREA)
  • Biophysics (AREA)
  • Biomedical Technology (AREA)
  • Immunology (AREA)
  • Veterinary Medicine (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Microbiology (AREA)
  • Medicinal Chemistry (AREA)
  • Environmental Sciences (AREA)
  • Plant Pathology (AREA)
  • Physics & Mathematics (AREA)
  • Animal Behavior & Ethology (AREA)
  • Animal Husbandry (AREA)
  • Biodiversity & Conservation Biology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Public Health (AREA)
  • Micro-Organisms Or Cultivation Processes Thereof (AREA)
  • Peptides Or Proteins (AREA)
  • Preparation Of Compounds By Using Micro-Organisms (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
DE112014004537.3T 2013-10-01 2014-10-01 Tiermodelle und therapeutische Moleküle Withdrawn DE112014004537T5 (de)

Applications Claiming Priority (5)

Application Number Priority Date Filing Date Title
GBGB1317410.7A GB201317410D0 (en) 2013-10-01 2013-10-01 Animal models and therapeutic molecules
GB1317410.7 2013-10-01
FRFR1359518 2013-10-01
FR1359518A FR3011249A1 (https=) 2013-10-01 2013-10-01
PCT/GB2014/052971 WO2015049517A2 (en) 2013-10-01 2014-10-01 Animal models and therapeutic molecules

Publications (1)

Publication Number Publication Date
DE112014004537T5 true DE112014004537T5 (de) 2016-07-21

Family

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Family Applications (1)

Application Number Title Priority Date Filing Date
DE112014004537.3T Withdrawn DE112014004537T5 (de) 2013-10-01 2014-10-01 Tiermodelle und therapeutische Moleküle

Country Status (12)

Country Link
US (4) US10149462B2 (https=)
EP (2) EP3794941B1 (https=)
JP (3) JP7133902B2 (https=)
CN (1) CN105683365A (https=)
AU (1) AU2014330922A1 (https=)
CA (1) CA2925723A1 (https=)
DE (1) DE112014004537T5 (https=)
ES (2) ES2993142T3 (https=)
NL (2) NL2013554B1 (https=)
SG (2) SG10201802295XA (https=)
TW (1) TW201546284A (https=)
WO (1) WO2015049517A2 (https=)

Families Citing this family (24)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
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
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
US9253965B2 (en) 2012-03-28 2016-02-09 Kymab Limited Animal models and therapeutic molecules
US10251377B2 (en) 2012-03-28 2019-04-09 Kymab Limited Transgenic non-human vertebrate for the expression of class-switched, fully human, antibodies
GB2502127A (en) 2012-05-17 2013-11-20 Kymab Ltd Multivalent antibodies and in vivo methods for their production
US9788534B2 (en) 2013-03-18 2017-10-17 Kymab Limited Animal models and therapeutic molecules
US9783593B2 (en) 2013-05-02 2017-10-10 Kymab Limited Antibodies, variable domains and chains tailored for human use
US11707056B2 (en) 2013-05-02 2023-07-25 Kymab Limited Animals, repertoires and methods
DE112014004537T5 (de) * 2013-10-01 2016-07-21 Kymab Limited Tiermodelle und therapeutische Moleküle
WO2017214089A1 (en) * 2016-06-06 2017-12-14 Regeneron Pharmaceuticals, Inc. Non-human animals expressing antibodies with human lambda light chains
WO2018128691A1 (en) * 2016-11-04 2018-07-12 Regeneron Pharmaceuticals, Inc. Non-human animals having an engineered immunoglobulin lambda light chain locus
CN109136261B (zh) 2017-06-19 2021-03-16 百奥赛图(北京)医药科技股份有限公司 人源化cd28基因改造动物模型的制备方法及应用
WO2018233608A1 (en) * 2017-06-19 2018-12-27 Beijing Biocytogen Co., Ltd Genetically modified non-human animal with human or chimeric cd28
DK4140297T3 (da) * 2017-12-05 2025-06-23 Regeneron Pharma Mus med en konstrueret immunglobulin-lambda-letkæde og anvendelser deraf
EP3927832A4 (en) 2019-02-18 2022-11-30 Biocytogen Pharmaceuticals (Beijing) Co., Ltd. GENETICALLY MODIFIED NON-HUMAN ANIMALS WITH HUMANIZED IMMUNOGLOBULIN LOCUS
SG11202111258TA (en) * 2019-06-05 2021-11-29 Regeneron Pharma Non-human animals having a limited lambda light chain repertoire expressed from the kappa locus and uses thereof
KR20230018439A (ko) 2020-06-02 2023-02-07 바이오사이토젠 파마슈티컬스 (베이징) 컴퍼니 리미티드 공동 경쇄 면역글로불린 좌위를 갖는 유전자 변형 비인간 동물
GB202107372D0 (en) * 2021-05-24 2021-07-07 Petmedix Ltd Animal models and therapeutics molecules
US20250026814A1 (en) * 2021-11-16 2025-01-23 The University Of Chicago Polypeptides for detection and treatment of coronavirus infection
CN115976196B (zh) * 2022-12-16 2024-12-06 深圳市人民医院 ErbB3作为肺动脉高压生物标志物和治疗靶点的应用
CN121843714A (zh) 2023-08-11 2026-04-10 派拉冈医疗公司 Tl1a结合抗体及使用方法
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

Family Cites Families (174)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5807715A (en) 1984-08-27 1998-09-15 The Board Of Trustees Of The Leland Stanford Junior University Methods and transformed mammalian lymphocyte cells for producing functional antigen-binding protein including chimeric immunoglobulin
US5169939A (en) 1985-05-21 1992-12-08 Massachusetts Institute Of Technology & Pres. & Fellows Of Harvard College Chimeric antibodies
US4720449A (en) 1985-06-03 1988-01-19 Polaroid Corporation Thermal imaging method
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
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
US6657103B1 (en) 1990-01-12 2003-12-02 Abgenix, Inc. Human antibodies derived from immunized xenomice
US6713610B1 (en) 1990-01-12 2004-03-30 Raju Kucherlapati Human antibodies derived from immunized xenomice
US5545806A (en) 1990-08-29 1996-08-13 Genpharm International, Inc. Ransgenic non-human animals for producing heterologous antibodies
US7084260B1 (en) 1996-10-10 2006-08-01 Genpharm International, Inc. High affinity human antibodies and human antibodies against human antigens
US7041871B1 (en) 1995-10-10 2006-05-09 Genpharm International, Inc. Transgenic non-human animals capable of producing heterologous antibodies
US5770429A (en) 1990-08-29 1998-06-23 Genpharm International, Inc. Transgenic non-human animals capable of producing heterologous antibodies
ATE300615T1 (de) 1990-08-29 2005-08-15 Genpharm Int Transgene mäuse fähig zur produktion heterologer antikörper
US6300129B1 (en) 1990-08-29 2001-10-09 Genpharm International Transgenic non-human animals for producing heterologous antibodies
US5633425A (en) 1990-08-29 1997-05-27 Genpharm International, Inc. Transgenic non-human animals capable of producing heterologous antibodies
US6255458B1 (en) 1990-08-29 2001-07-03 Genpharm International High affinity human antibodies and human antibodies against digoxin
WO1993004169A1 (en) 1991-08-20 1993-03-04 Genpharm International, Inc. Gene targeting in animal cells using isogenic dna constructs
CA2124967C (en) 1991-12-17 2008-04-08 Nils Lonberg Transgenic non-human animals capable of producing heterologous antibodies
NZ255101A (en) 1992-07-24 1997-08-22 Cell Genesys Inc A yeast artificial chromosome (yac) vector containing an hprt minigene expressible in murine stem cells and genetically modified rodent therefor
DE4228162C1 (de) 1992-08-25 1994-01-13 Rajewsky Klaus Dr Verfahren zum Ersetzen homologer Genabschnitte aus Säugern in der Keimbahn von nicht-menschlichen Säugern
US5565321A (en) 1993-01-22 1996-10-15 Immunex Corporation Detection of mutations in a CD40 ligand gene
CA2161351C (en) 1993-04-26 2010-12-21 Nils Lonberg Transgenic non-human animals capable of producing heterologous antibodies
DE4331162A1 (de) 1993-09-14 1995-03-16 Bayer Ag Verfahren zur Herstellung von Cyaninfarbstoffen
US7119248B1 (en) 1994-04-12 2006-10-10 Miltenyi Biotec Gmbh Antibodies against epitopes with homology to self antigens, methods of preparation and applications thereof
US6130364A (en) 1995-03-29 2000-10-10 Abgenix, Inc. Production of antibodies using Cre-mediated site-specific recombination
AU3507297A (en) 1996-06-26 1998-01-14 Baylor College Of Medicine Chromosomal rearrangement by insertion of two recombination substrates
ES2294799T3 (es) 1996-06-27 2008-04-01 Vlaams Interuniversitair Instituut Voor Biotechnologie Vzw. Moleculas de anticuerpos que interactuan especificamente con el sitio activo o hendidura de una molecula diana.
EP1500329B1 (en) 1996-12-03 2012-03-21 Amgen Fremont Inc. Human antibodies that specifically bind human TNF alpha
US6319906B1 (en) 1996-12-31 2001-11-20 Isis Pharmaceuticals Oligonucleotide compositions and methods for the modulation of the expression of B7 protein
JP4213224B2 (ja) 1997-05-02 2009-01-21 ジェネンテック,インコーポレーテッド ヘテロマルチマー及び共通成分を有する多重特異性抗体の製造方法
US20020088019A1 (en) 1997-09-02 2002-07-04 Oron Yacoby-Zeevi Methods of and pharmaceutical compositions for improving implantation of embryos
US6187994B1 (en) 1997-11-18 2001-02-13 Pioneer Hi-Bred International, Inc. Compositions and methods for genetic modification of plants
EP0939120A1 (en) 1998-02-27 1999-09-01 Gesellschaft für biotechnologische Forschung mbH (GBF) Method for marker-free repetitive DNA expression cassette exchange in the genome of cells or parts of cells
GB9823930D0 (en) 1998-11-03 1998-12-30 Babraham Inst Murine expression of human ig\ locus
US6914128B1 (en) 1999-03-25 2005-07-05 Abbott Gmbh & Co. Kg Human antibodies that bind human IL-12 and methods for producing
JP2003503015A (ja) 1999-05-03 2003-01-28 メダレツクス・インコーポレーテツド スタフィロコッカス・アウレウスに対するヒト抗体
US6833268B1 (en) 1999-06-10 2004-12-21 Abgenix, Inc. Transgenic animals for producing specific isotypes of human antibodies via non-cognate switch regions
US7605238B2 (en) 1999-08-24 2009-10-20 Medarex, Inc. Human CTLA-4 antibodies and their uses
CA2307503A1 (en) 2000-05-02 2001-11-02 Carlos F. Barbas Iii Peptides for use as a vaccine or treatment for hiv infection
CA2416701A1 (en) 2000-07-21 2002-01-31 The United States Of America, As Represented By The Secretary Of Agricul Ture Methods for the replacement, translocation and stacking of dna in eukaryotic genomes
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
DE60144305D1 (de) 2000-11-17 2011-05-05 Kyowa Hakko Kirin Co Ltd Expression von xenogenen (humanen) Immunglobulinen in klonierten, transgenen Huftieren
CN1487996B (zh) 2000-11-30 2010-06-16 米德列斯公司 用于生产人类抗体的转基因转染色体啮齿动物
EP1409646B1 (en) 2000-12-19 2012-06-13 Altor BioScience Corporation Transgenic animals comprising a humanized immune system
BRPI0116728B1 (pt) 2001-01-05 2018-10-30 Pfizer Inc. anticorpos para receptor de fator de crescimento i semelhante à insulina
JP2003000243A (ja) 2001-06-25 2003-01-07 Takachika Azuma 変異体の製造法
FR2827302B1 (fr) 2001-07-13 2003-10-10 Genoway Cellule et animal transgenique modelisant la presentation antigenique humaine et leurs utilisations
US20060199204A1 (en) 2001-10-05 2006-09-07 U.S. Epa Genetic testing for male factor infertility
US20030108925A1 (en) 2001-10-05 2003-06-12 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
WO2003061363A2 (en) 2002-01-17 2003-07-31 Albert Einstein College Of Medicine Of Yeshiva University Mutations caused by activation-induced cytidine deaminase
US8877901B2 (en) 2002-12-13 2014-11-04 Immunomedics, Inc. Camptothecin-binding moiety conjugates
WO2003099320A1 (en) * 2002-05-24 2003-12-04 Zensun (Shanghai) Sci-Tech.Ltd Neuregulin based methods and compositions for treating viral myocarditis and dilated cardiomyopathy
NZ537277A (en) 2002-07-18 2008-04-30 Crucell Holland Bv Recombinant production of mixtures of antibodies
CA2496233A1 (en) 2002-09-09 2004-03-18 California Institute Of Technology Methods and compositions for the generation of humanized mice
US7700356B2 (en) 2002-11-08 2010-04-20 The United States Of America As Represented By The Secretary Of Agriculture System for gene targeting and producing stable genomic transgene insertions
DE10251918A1 (de) 2002-11-08 2004-05-19 Horn, Carsten, Dipl.-Biochem. Dr. Systeme zur Erzeugung stabiler genomischer Transgen-Insertionen
CL2003002461A1 (es) 2002-11-27 2005-01-07 Dow Chemical Company Agroscien Inmunoglobulina que comprende al menos un glicano afucosilado, composicion que la contiene, secuencia nucleotidica y vector que la comprende, procedimiento para producir dicha inmunoglobulina en plantas.
GB2398784B (en) 2003-02-26 2005-07-27 Babraham Inst Removal and modification of the immunoglobulin constant region gene cluster of a non-human mammal
ES2408582T3 (es) 2003-05-30 2013-06-21 Merus B.V. Biblioteca de Fab para la preparación de una mezcla de anticuerpos
US20100069614A1 (en) 2008-06-27 2010-03-18 Merus B.V. Antibody producing non-human mammals
US7205148B2 (en) 2003-06-11 2007-04-17 Regeneron Pharmaceuticals, Inc. Genome mutation by intron insertion into an embryonic stem cell genome
GB2403475B (en) 2003-07-01 2008-02-06 Oxitec Ltd Stable integrands
US7663017B2 (en) 2003-07-30 2010-02-16 Institut Pasteur Transgenic mice having a human major histocompatability complex (MHC) phenotype, experimental uses and applications
WO2005019463A1 (en) 2003-08-11 2005-03-03 Therapeutic Human Polyclonals, Inc. Improved transgenesis with humanized immunoglobulin loci
US7604994B2 (en) 2003-09-03 2009-10-20 Morphotek, Inc. Genetically altered antibody-producing cell lines with improved antibody characteristics
US7205140B2 (en) 2003-10-20 2007-04-17 Campusgen Gmbh Nucleotide sequence for creatinine deiminase and method of use
RS53984B1 (sr) 2003-12-10 2015-10-30 E. R. Squibb & Sons L.L.C. Ip-10 antitela i njihove upotrebe
WO2005092926A2 (en) 2004-03-19 2005-10-06 Amgen Inc. Reducing the risk of human and anti-human antibodies through v gene manipulation
US7625549B2 (en) 2004-03-19 2009-12-01 Amgen Fremont Inc. Determining the risk of human anti-human antibodies in transgenic mice
SI2311874T1 (sl) 2004-07-22 2017-12-29 Erasmus University Medical Center Rotterdam Department of Cell Biology and Genetics Vezavne molekule
FR2875239B1 (fr) 2004-09-10 2007-07-20 Inst Necker Ass Loi De 1901 Procede pour l'acceleration des mutations somatiques et son application en proteomique
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
WO2006044492A2 (en) 2004-10-14 2006-04-27 Ingenious Targeting Laboratory, Inc. Methods for generating rat embryo-derived cell lines and genetic modification of rat genome
AU2005295269B2 (en) 2004-10-19 2010-05-13 Regeneron Pharmaceuticals, Inc. Method for generating an animal homozygous for a genetic modification
WO2006055704A2 (en) 2004-11-17 2006-05-26 Curagen Corporation Antibodies directed to ten-m proteins and uses thereof
BRPI0519596B1 (pt) 2004-12-21 2022-01-18 Astrazeneca Ab Agente de ligação alvejado, anticorpo monoclonal que se liga a angiopoietina-2, molécula de ácido nucleico, vetor, e, uso do agente de ligação alvejado
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
CN101297031B (zh) 2005-05-14 2013-06-05 复旦大学 在脊椎动物中作为遗传操作和分析工具的piggyBac
EP1780272A1 (en) 2005-10-27 2007-05-02 GSF-Forschungszentrum für Umwelt und Gesundheit GmbH Method for enhancing somatic hypermutation, gene conversion and class switch recombination
GB0601513D0 (en) 2006-01-25 2006-03-08 Univ Erasmus Medical Ct Binding molecules 3
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
US7462759B2 (en) 2006-02-03 2008-12-09 Pioneer Hi-Bred International, Inc. Brittle stalk 2 gene family and related methods and uses
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
US7709257B2 (en) 2006-06-27 2010-05-04 Vax Design Corp. Models for vaccine assessment
EP1878342A1 (en) 2006-07-13 2008-01-16 Institut Pasteur Immunodeficient mice transgenic for HLA class I and HLA class II molecules and their uses
EP2061812A4 (en) 2006-08-22 2010-06-09 G2 Inflammation Pty Ltd METHOD FOR THE PRODUCTION OF ANTIBODIES
CN101522716B (zh) 2006-10-02 2013-03-20 瑞泽恩制药公司 抗人il-4受体的高亲和力人抗体
WO2008070367A2 (en) 2006-11-01 2008-06-12 Facet Biotech Corporation Mammalian cell-based immunoglobulin display libraries
NO347649B1 (no) 2006-12-14 2024-02-12 Regeneron Pharma Humant antistoff eller antistoff fragment som spesifikt binder human deltaliknende ligand 4 (hDII4), nukleinsyremolekyl som koder for slike og vektor og vert-vektorsystemer, samt fremgangsmåte for fremstilling, sammensetning og anvendelse.
GB0700194D0 (en) 2007-01-05 2007-02-14 Univ Edinburgh Humanisation of animals
BRPI0807952A2 (pt) 2007-02-20 2014-06-10 Anaptysbio Inc Sistemas de hipermutação somática
JP5642972B2 (ja) 2007-02-21 2014-12-17 ユニバーシティー オブ マサチューセッツUniversity of Massachusetts C型肝炎ウイルス(hcv)に対するヒト抗体およびその使用
BRPI0809435A2 (pt) 2007-03-27 2014-09-09 Sea Lane Biotechnologies, Llc Constructos e bibliotecas que compreendem sequências de cadeia leve substituida de anticorpos
GB0706628D0 (en) 2007-04-04 2007-05-16 Univ Erasmus Germ-line manipulation 1
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
NZ583019A (en) 2007-07-31 2011-05-27 Regeneron Pharma Human antibodies to human cd20 and method of using thereof
WO2009097006A2 (en) 2007-08-10 2009-08-06 Medarex, Inc. Hco32 and hco27 and related examples
BRPI0815370B8 (pt) 2007-08-10 2021-05-25 Regeneron Pharma anticorpos humanos de alta afinidade contra o fator de crescimento neural humano e seu uso, molécula de ácido nucleico, vetor de expressão, método para produção de um anticorpo anti-ngf humano e composiçao farmacêutica
JP5642549B2 (ja) 2007-10-12 2014-12-17 エフ.ホフマン−ラ ロシュ アーゲーF. Hoffmann−La Roche Aktiengesellschaft 複数の核酸からのタンパク質発現
CA2708776A1 (en) 2007-12-10 2009-06-18 Aliva Biopharmaceuticals, Inc. Methods for sequential replacement of targeted region by homologous recombination
US8227577B2 (en) 2007-12-21 2012-07-24 Hoffman-La Roche Inc. Bivalent, bispecific antibodies
US20110107445A1 (en) 2008-03-26 2011-05-05 Iti Scotland Limited Efficient Insertion of DNA Into Embryonic Stem Cells
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
PL3456190T3 (pl) 2008-06-27 2022-06-06 Merus N.V. Wytwarzające przeciwciała transgeniczne zwierzę z gatunku myszy
EP2346994B1 (en) 2008-09-30 2022-02-16 Ablexis, LLC Knock-in mice for the production of chimeric antibodies
JO3672B1 (ar) 2008-12-15 2020-08-27 Regeneron Pharma أجسام مضادة بشرية عالية التفاعل الكيماوي بالنسبة لإنزيم سبتيليسين كنفرتيز بروبروتين / كيكسين نوع 9 (pcsk9).
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
WO2010091182A2 (en) 2009-02-04 2010-08-12 Molecular Innovations Methods for screening candidate agents for modulating prorenin and renin, assays for detecting prorenin, and antibodies used therein
JP2012518398A (ja) 2009-02-24 2012-08-16 グラクソ グループ リミテッド 抗原結合性構築物
GB0905023D0 (en) 2009-03-24 2009-05-06 Univ Erasmus Medical Ct Binding molecules
CN102482639B (zh) 2009-04-03 2016-01-06 医学研究会 活化诱导胞苷脱氨酶(aid)突变体及使用方法
KR101829073B1 (ko) 2009-06-26 2018-02-13 아이2 파마슈티컬스, 인크. 대리 경쇄의 발현
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
US9445581B2 (en) 2012-03-28 2016-09-20 Kymab Limited Animal models and therapeutic molecules
JP5781508B2 (ja) 2009-07-15 2015-09-24 アイム・セラピューティクス・べー・フェー 高親和性抗体を産生させるための手段および方法
JO3182B1 (ar) 2009-07-29 2018-03-08 Regeneron Pharma مضادات حيوية بشرية عالية الالفة مع تولد الاوعية البشرية - 2
US8592644B2 (en) 2009-08-13 2013-11-26 Crystal Bioscience Inc. Transgenic animal for production of antibodies having minimal CDRS
ES2826883T3 (es) * 2009-10-14 2021-05-19 Janssen Biotech Inc Métodos de maduración por afinidad de anticuerpos
WO2011056864A1 (en) 2009-11-05 2011-05-12 Anaptysbio, Inc. Methods of generating improved antigen-binding agents using chain shuffling and optionally somatic hypermutation
US20120233715A1 (en) 2009-11-17 2012-09-13 Kyowa Hakko Kirin Co., Ltd Human artificial chromosome vector
EP2509997B1 (en) 2009-12-07 2017-08-30 i2 Pharmaceuticals, Inc. Conjugates comprising an antibody surrogate scaffold with improved pharmacokinetic properties
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
US20120021409A1 (en) 2010-02-08 2012-01-26 Regeneron Pharmaceuticals, Inc. Common Light Chain Mouse
JP6208580B2 (ja) 2010-05-17 2017-10-04 サンガモ セラピューティクス, インコーポレイテッド 新規のdna結合タンパク質及びその使用
AU2011266843C9 (en) * 2010-06-17 2018-03-01 Kymab Limited Animal models and therapeutic molecules
US9012717B2 (en) 2010-06-22 2015-04-21 Regeneron Pharmaceuticals, Inc. Human lambda light chain mice
DK2593594T3 (en) * 2010-07-16 2017-12-11 Adimab Llc ANTIBODY LIBRARIES
SG10201912639SA (en) 2010-08-02 2020-02-27 Regeneron Pharma Mice that make binding proteins comprising vl domains
PL2606064T3 (pl) 2010-08-16 2015-07-31 Novimmune Sa Sposoby wytwarzania wieloswoistych i wielowartościowych przeciwciał
JO3375B1 (ar) 2010-11-08 2019-03-13 Regeneron Pharma أجسام مضادة بشرية للجين a1 الشبيه بعامل النخر الورمي (tl1a)
KR20130118925A (ko) 2010-12-22 2013-10-30 제넨테크, 인크. 항-pcsk9 항체 및 사용 방법
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
WO2013041845A2 (en) * 2011-09-19 2013-03-28 Kymab Limited Animals, repertoires & methods
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
US20130102031A1 (en) 2011-10-25 2013-04-25 Anaptysbio, Inc. Use of somatic hypermutation to create insertion and deletion mutations in vitro
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
US20180295821A1 (en) 2011-12-02 2018-10-18 Kymab Limited Transgenic Animals
US9253965B2 (en) 2012-03-28 2016-02-09 Kymab Limited Animal models and therapeutic molecules
GB201122047D0 (en) 2011-12-21 2012-02-01 Kymab Ltd Transgenic animals
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
HK1200463A1 (en) 2012-03-02 2015-08-07 瑞泽恩制药公司 Human antibodies to clostridium difficile toxins
IN2014DN08163A (https=) * 2012-03-06 2015-05-01 Regeneron Pharma
MX2014011047A (es) 2012-03-16 2015-04-08 Regeneron Pharma Ratones que producen proteinas de union a un antigeno con caracteristicas de union dependientes del ph.
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
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
JO3820B1 (ar) 2012-05-03 2021-01-31 Regeneron Pharma أجسام مضادة بشرية لـ fel d1وطرق لاستخدامها
EP3241902B1 (en) 2012-05-25 2018-02-28 The Regents of The University of California Methods and compositions for rna-directed target dna modification and for rna-directed modulation of transcription
PT3597037T (pt) 2012-06-12 2021-06-01 Regeneron Pharma Animais não humanos humanizados com lócus de cadeia pesada de imunoglobulina restrito
US8962913B2 (en) 2012-06-18 2015-02-24 Regeneron Pharmaceuticals, Inc. Humanized IL-7 rodents
DK2931897T3 (en) 2012-12-12 2018-02-05 Broad Inst Inc CONSTRUCTION, MODIFICATION AND OPTIMIZATION OF SYSTEMS, PROCEDURES AND COMPOSITIONS FOR SEQUENCE MANIPULATION AND THERAPEUTICAL APPLICATIONS
EP2840892B1 (en) 2013-02-20 2018-04-18 Regeneron Pharmaceuticals, Inc. Non-human animals with modified immunoglobulin heavy chain sequences
US10993420B2 (en) 2013-03-15 2021-05-04 Erasmus University Medical Center Production of heavy chain only antibodies in transgenic mammals
US9788534B2 (en) 2013-03-18 2017-10-17 Kymab Limited Animal models and therapeutic molecules
US20150033372A1 (en) 2013-05-01 2015-01-29 Kymab Limited Human VpreB & Chimaeric Surrogate Light Chains in Transgenic Non-Human Vertebrates
US9783618B2 (en) 2013-05-01 2017-10-10 Kymab Limited Manipulation of immunoglobulin gene diversity and multi-antibody therapeutics
US9783593B2 (en) 2013-05-02 2017-10-10 Kymab Limited Antibodies, variable domains and chains tailored for human use
US11707056B2 (en) 2013-05-02 2023-07-25 Kymab Limited Animals, repertoires and methods
US20140331339A1 (en) 2013-05-03 2014-11-06 Kymab Limited Transgenic Non-Human Assay Vertebrates, Assays and Kits
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
GB201710984D0 (en) 2017-07-07 2017-08-23 Kymab Ltd Cells, vertebrates, populations & methods

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