CA2925723A1 - Animal models and therapeutic molecules - Google Patents

Animal models and therapeutic molecules Download PDF

Info

Publication number
CA2925723A1
CA2925723A1 CA2925723A CA2925723A CA2925723A1 CA 2925723 A1 CA2925723 A1 CA 2925723A1 CA 2925723 A CA2925723 A CA 2925723A CA 2925723 A CA2925723 A CA 2925723A CA 2925723 A1 CA2925723 A1 CA 2925723A1
Authority
CA
Canada
Prior art keywords
human
gene segments
vertebrate
cell
antibody
Prior art date
Legal status (The legal status 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 status listed.)
Abandoned
Application number
CA2925723A
Other languages
English (en)
French (fr)
Inventor
E-Chiang Lee
Jasper Clube
Allan Bradley
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Kymab Ltd
Original Assignee
Kymab Ltd
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 FR1359518A external-priority patent/FR3011249A1/fr
Priority claimed from GBGB1317410.7A external-priority patent/GB201317410D0/en
Application filed by Kymab Ltd filed Critical Kymab Ltd
Publication of CA2925723A1 publication Critical patent/CA2925723A1/en
Abandoned legal-status Critical Current

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 [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
    • 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
    • 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

Landscapes

  • 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)
  • Molecular Biology (AREA)
  • Biochemistry (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)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (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)
CA2925723A 2013-10-01 2014-10-01 Animal models and therapeutic molecules Abandoned CA2925723A1 (en)

Applications Claiming Priority (5)

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

Publications (1)

Publication Number Publication Date
CA2925723A1 true CA2925723A1 (en) 2015-04-09

Family

ID=51663220

Family Applications (1)

Application Number Title Priority Date Filing Date
CA2925723A Abandoned CA2925723A1 (en) 2013-10-01 2014-10-01 Animal models and therapeutic molecules

Country Status (12)

Country Link
US (4) US10149462B2 (enExample)
EP (2) EP3051942B1 (enExample)
JP (3) JP7133902B2 (enExample)
CN (1) CN105683365A (enExample)
AU (1) AU2014330922A1 (enExample)
CA (1) CA2925723A1 (enExample)
DE (1) DE112014004537T5 (enExample)
ES (2) ES2859373T3 (enExample)
NL (2) NL2013554B1 (enExample)
SG (2) SG11201602236SA (enExample)
TW (1) TW201546284A (enExample)
WO (1) WO2015049517A2 (enExample)

Families Citing this family (25)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN102638971B (zh) 2009-07-08 2015-10-07 科马布有限公司 动物模型及治疗分子
AU2012311286B2 (en) 2011-09-19 2018-07-26 Kymab Limited Antibodies, variable domains and chains tailored for human use
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
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
CA2925723A1 (en) 2013-10-01 2015-04-09 Kymab Limited Animal models and therapeutic molecules
WO2017214089A1 (en) * 2016-06-06 2017-12-14 Regeneron Pharmaceuticals, Inc. Non-human animals expressing antibodies with human lambda light chains
PT4082334T (pt) * 2016-11-04 2025-05-21 Regeneron Pharma Animais não humanos possuindo um lócus da cadeia leve lambda de immunoglobulina geneticamente modificada
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
TW202438676A (zh) * 2017-12-05 2024-10-01 美商再生元醫藥公司 具有經改造免疫球蛋白λ輕鏈的非人類動物及其用途
CA3125380A1 (en) 2019-02-18 2020-08-27 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
WO2023091920A1 (en) * 2021-11-16 2023-05-25 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
IL325993A (en) 2023-08-11 2026-03-01 Paragon Therapeutics Inc TL1A binding proteins and methods of use
WO2026030428A2 (en) 2024-08-01 2026-02-05 Regeneron Pharmaceuticals, Inc. Prostate-specific antigen peptides and uses thereof
US20260123608A1 (en) 2024-08-06 2026-05-07 Regeneron Pharmaceuticals, Inc. Non-human animals having modified immunoglobulin heavy chain constant region locus and uses thereof
WO2026096736A1 (en) 2024-10-31 2026-05-07 Regeneron Pharmaceuticals, Inc. Rodents expressing humanized polymeric immunoglobulin receptor

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
US6657103B1 (en) 1990-01-12 2003-12-02 Abgenix, Inc. Human antibodies derived from immunized xenomice
ES2284161T3 (es) 1990-01-12 2007-11-01 Amgen Fremont Inc. Generacion de anticuerpos xenogenicos.
US6713610B1 (en) 1990-01-12 2004-03-30 Raju Kucherlapati Human antibodies derived from immunized xenomice
US5633425A (en) 1990-08-29 1997-05-27 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
US6255458B1 (en) 1990-08-29 2001-07-03 Genpharm International High affinity human antibodies and human antibodies against digoxin
US5545806A (en) 1990-08-29 1996-08-13 Genpharm International, Inc. Ransgenic non-human animals for producing heterologous antibodies
US6300129B1 (en) 1990-08-29 2001-10-09 Genpharm International Transgenic non-human animals for producing heterologous antibodies
US7041871B1 (en) 1995-10-10 2006-05-09 Genpharm International, Inc. Transgenic non-human animals capable of producing heterologous antibodies
US7084260B1 (en) 1996-10-10 2006-08-01 Genpharm International, Inc. High affinity human antibodies and human antibodies against human antigens
AU8507191A (en) 1990-08-29 1992-03-30 Genpharm International, Inc. Transgenic non-human animals capable of producing heterologous antibodies
WO1993004169A1 (en) 1991-08-20 1993-03-04 Genpharm International, Inc. Gene targeting in animal cells using isogenic dna constructs
AU3328493A (en) 1991-12-17 1993-07-19 Genpharm International, Inc. Transgenic non-human animals capable of producing heterologous antibodies
ES2301158T3 (es) 1992-07-24 2008-06-16 Amgen Fremont Inc. Produccion de anticuerpos xenogenicos.
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
AU6819494A (en) 1993-04-26 1994-11-21 Genpharm International, Inc. 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
EP0907726A4 (en) 1996-06-26 2001-11-07 Baylor College Medicine CHROMOSOMAL REORDERING BY INSERTING TWO RECOMBINATION SUBSTRATES
JP2000515002A (ja) 1996-06-27 2000-11-14 フラームス・インテルウニフェルジテール・インスティテュート・フォール・ビオテヒノロジー・ヴェーゼットウェー 標的分子の活性部位またはクレフトと特異的に相互作用する認識分子
ATE549918T1 (de) 1996-12-03 2012-04-15 Amgen Fremont Inc Menschliche antikörper, die ausdrücklich menschliches tnf alpha binden
US6319906B1 (en) 1996-12-31 2001-11-20 Isis Pharmaceuticals Oligonucleotide compositions and methods for the modulation of the expression of B7 protein
DK0979281T3 (da) 1997-05-02 2005-11-21 Genentech Inc Fremgangsmåde til fremstilling af multispecifikke antistoffer med heteromultimere og fælles bestanddele
US20020088019A1 (en) 1997-09-02 2002-07-04 Oron Yacoby-Zeevi Methods of and pharmaceutical compositions for improving implantation of embryos
NZ503859A (en) 1997-11-18 2003-02-28 Pioneer Hi Bred Int Non-identical minimal recombination sites (FRT) which are non-identical for targeted integration of nucleotide sequences into transformed 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
CA2373221A1 (en) 1999-05-03 2000-11-30 Yashwant M. Deo Human antibodies to staphylococcus aureus
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
CN1455817A (zh) 2000-07-21 2003-11-12 (由农业部部长代表的)美利坚合众国 用于在真核基因组中置换、转移和富积dna的方法
US7105348B2 (en) 2000-10-31 2006-09-12 Regeneron Pharmaceuticals, Inc. Methods of modifying eukaryotic cells
US6586251B2 (en) 2000-10-31 2003-07-01 Regeneron Pharmaceuticals, Inc. Methods of modifying eukaryotic cells
US6596541B2 (en) 2000-10-31 2003-07-22 Regeneron Pharmaceuticals, Inc. Methods of modifying eukaryotic cells
MXPA03004313A (es) 2000-11-17 2007-02-27 Hematech Llc Expresion de inmunoglobulinas xenogenas (humanas) en ungulados transgenicos, clonados.
IL155977A0 (en) 2000-11-30 2003-12-23 Medarex Inc Transgenic transchromosomal rodents for making human antibodies
DK1409646T3 (da) 2000-12-19 2012-08-06 Altor Bioscience Corp Transgene dyr omfattende et humaniseret immunsystem
PA8535501A1 (es) 2001-01-05 2003-07-28 Pfizer Anticuerpos contra el receptor del factor de crecimiento similar a 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
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
EP3698626A1 (en) * 2001-11-30 2020-08-26 Amgen Fremont Inc. Transgenic animals bearing human ig lambda light chain genes
AU2003214842A1 (en) 2002-01-17 2003-09-02 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
AU2002304965A1 (en) * 2002-05-24 2003-12-12 Zensun (Shanghai) Sci-Tech.Ltd Neuregulin based methods and compositions for treating viral myocarditis and dilated cardiomyopathy
EP2314629B2 (en) 2002-07-18 2022-11-16 Merus N.V. Recombinant production of mixtures of antibodies
AU2003278790A1 (en) 2002-09-09 2004-03-29 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
WO2004106375A1 (en) 2003-05-30 2004-12-09 Merus Biopharmaceuticals B.V. I.O. Fab library for the preparation of anti vegf and anti rabies virus fabs
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
US20050153392A1 (en) 2003-08-11 2005-07-14 Roland Buelow 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
CA2445602C (en) 2003-10-20 2014-01-14 Campusgen Gmbh Nucleotide sequence for creatinine deiminase and method of use
KR101374514B1 (ko) 2003-12-10 2014-03-13 메다렉스, 인코포레이티드 Ip―10 항체 및 그의 용도
US7625549B2 (en) 2004-03-19 2009-12-01 Amgen Fremont Inc. Determining the risk of human anti-human antibodies in transgenic mice
AU2005227313A1 (en) 2004-03-19 2005-10-06 Amgen Inc. Reducing the risk of human and anti-human antibodies through V gene manipulation
EP1978032A3 (en) 2004-07-22 2009-02-18 Erasmus University Medical Center Rotterdam Binding molecules
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
WO2006044962A1 (en) 2004-10-19 2006-04-27 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
ES2371083T3 (es) 2004-12-21 2011-12-27 Medimmune Limited Anticuerpos dirigidos contra la angiopoyetina-2 y usos de los mismos.
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
EP1896578A4 (en) 2005-05-14 2008-11-05 Univ Fudan PIGGYBAC AS A TOOL FOR GENETIC HANDLING AND ANALYSIS IN VERTEBRATES
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
SG169348A1 (en) 2006-01-25 2011-03-30 Univ Erasmus Medical Ct Generation of heavy-chain only antibodies in transgenic animals
US7462759B2 (en) 2006-02-03 2008-12-09 Pioneer Hi-Bred International, Inc. Brittle stalk 2 gene family and related methods and uses
JP5514539B2 (ja) 2006-03-31 2014-06-04 メダレックス・リミテッド・ライアビリティ・カンパニー ヒト抗体の調製に用いるためのキメラ抗体を発現するトランスジェニック動物
NZ587107A (en) 2006-06-02 2012-05-25 Regeneron Pharma High affinity antibodies to human il-6 receptor
EP2409714A1 (en) 2006-06-27 2012-01-25 Sanofi Pasteur VaxDesign Corporation 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
WO2008022391A1 (en) 2006-08-22 2008-02-28 G2 Inflammation Pty Ltd Method for producing antibodies
LT2769992T (lt) 2006-10-02 2021-04-12 Regeneron Pharmaceuticals, Inc. Didelio afiniškumo žmogaus antikūnai, atpažįstantys žmogaus il-4 receptorių
US7732195B2 (en) 2006-11-01 2010-06-08 Facet Biotech Corporation Tethered vectors for cell surface immunoglobulin display
RU2448979C2 (ru) 2006-12-14 2012-04-27 Ридженерон Фармасьютикалз, Инк. Антитела человека к дельта-подобному лиганду-4 человека
GB0700194D0 (en) 2007-01-05 2007-02-14 Univ Edinburgh Humanisation of animals
NZ579010A (en) 2007-02-20 2012-03-30 Anaptysbio Inc Somatic hypermutation systems
US8551484B2 (en) 2007-02-21 2013-10-08 University Of Massachusetts Human antibodies against hepatitis C virus (HCV) and uses thereof
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
CA2688834C (en) 2007-06-01 2020-01-07 Ronald Buelow Compositions and methods for inhibiting endogenous immunoglobulin genes and producing transgenic human idiotype antibodies
WO2009013620A2 (en) 2007-06-11 2009-01-29 Erasmus University Medical Center Rotterdam Homologous recombination
BRPI0813985B1 (pt) 2007-07-31 2022-05-10 Regeneron Pharmaceuticals, Inc Anticorpos humanos ou fragmentos de ligação a antígenos, composição farmacêutica dos mesmos e método para produzir um anticorpo anti-cd20 humana ou fragmento de ligação a antígeno de um anticorpo
WO2009097006A2 (en) 2007-08-10 2009-08-06 Medarex, Inc. Hco32 and hco27 and related examples
MY161564A (en) 2007-08-10 2017-04-28 Regeneron Pharma High affinity human antibodies to human nerve growth factor
ES2695999T3 (es) 2007-10-12 2019-01-11 Hoffmann La Roche Expresión de proteínas a partir de múltiples ácidos nucleicos
AU2008335178A1 (en) 2007-12-10 2009-06-18 Ablexis Llc 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
EP2271207A2 (en) 2008-03-26 2011-01-12 ITI Scotland Limited Efficient insertion of dna into embryonic stem cells
EP2271758B1 (en) 2008-04-14 2018-09-12 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
RU2731084C2 (ru) 2008-06-27 2020-08-28 Мерюс Н.В. Продуцирующие антитела млекопитающие, не являющиеся человеком
WO2010039900A2 (en) 2008-09-30 2010-04-08 Aliva Biopharmaceuticals, Inc. Non-human mammals 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).
CA2747534C (en) 2008-12-18 2020-08-18 Erasmus University Medical Center Rotterdam Non-human transgenic animals expressing humanised antibodies and use therof
US9085795B2 (en) 2009-02-04 2015-07-21 Molecular Innovations, Inc. Methods for screening candidate agents for modulating prorenin and renin, assays for detecting prorenin and antibodies
US20110305692A1 (en) 2009-02-24 2011-12-15 Glaxo Group Limited Antigen-binding contructs
GB0905023D0 (en) 2009-03-24 2009-05-06 Univ Erasmus Medical Ct Binding molecules
WO2010113039A1 (en) 2009-04-03 2010-10-07 Medical Research Council Mutants of activation-induced cytidine deaminase (aid) and methods of use
CA2764729C (en) 2009-06-26 2019-04-02 Sea Lane Biotechnologies, Llc Expression of surrogate light chains
US9445581B2 (en) 2012-03-28 2016-09-20 Kymab Limited Animal models and therapeutic molecules
CN102638971B (zh) 2009-07-08 2015-10-07 科马布有限公司 动物模型及治疗分子
DK2454283T3 (en) 2009-07-15 2018-05-07 Aimm Therapeutics Bv METHODS AND PROCEDURES FOR MANUFACTURING HIGH EFFICIENCY ANTIBODIES
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
US8580714B2 (en) * 2009-10-14 2013-11-12 Janssen Biotech, Inc. Methods of affinity maturing antibodies
US20120251552A1 (en) 2009-11-05 2012-10-04 Anaptysbio, Inc. Methods of generating improved antigen-binding agents using chain shuffling and optionally somatic hypermutation
EP2502992A4 (en) 2009-11-17 2013-06-12 CHROMOSOME ARTIFICIAL HUMAN VECTOR
EP2509997B1 (en) 2009-12-07 2017-08-30 i2 Pharmaceuticals, Inc. Conjugates comprising an antibody surrogate scaffold with improved pharmacokinetic properties
DK2509409T3 (en) 2009-12-10 2016-11-14 Regeneron Pharma MICE, WHICH PRODUCES HEAVY CHAIN ANTIBODIES
HRP20151188T4 (hr) 2010-02-08 2021-10-01 Regeneron Pharmaceuticals, Inc. Miš sa zajedničkim lakim lancem
US20120021409A1 (en) 2010-02-08 2012-01-26 Regeneron Pharmaceuticals, Inc. Common Light Chain Mouse
EP3156062A1 (en) 2010-05-17 2017-04-19 Sangamo BioSciences, Inc. Novel dna-binding proteins and uses thereof
CN103228130B (zh) * 2010-06-17 2016-03-16 科马布有限公司 动物模型及治疗分子
SI2480675T1 (sl) 2010-06-22 2016-08-31 Regeneron Pharmaceuticals, Inc. Miši, ki izražajo lahko verigo s spremenljivo regijo humanega lambda in konstantno mišjo regijo
KR102024922B1 (ko) * 2010-07-16 2019-09-25 아디맵 엘엘씨 항체 라이브러리
KR102306967B1 (ko) 2010-08-02 2021-10-01 리제너론 파아마슈티컬스, 인크. Vl 도메인을 포함하는 결합 단백질을 생성하는 마우스
AU2011290480B2 (en) 2010-08-16 2015-07-30 Novimmune S.A. Methods for the generation of multispecific and multivalent antibodies
JO3375B1 (ar) 2010-11-08 2019-03-13 Regeneron Pharma أجسام مضادة بشرية للجين a1 الشبيه بعامل النخر الورمي (tl1a)
BR112013015687A2 (pt) 2010-12-22 2016-10-11 Genentech Inc anticorpo anti-pcsk9 ou um fragmento de anticorpo que se liga a pcsk9, ácido nucleico isolado, vetor, célula hospedeira, método para fabricar um anticorpo anti-pcsk9, composição farmacêutica, método de redução do nível de colesterol ldl em um sujeito e método de tratamento de hipercolesterolemia em um sujeito
LT2738259T (lt) 2011-02-25 2020-03-10 Regeneron Pharmaceuticals, Inc. Adam6 pelės
PT3865581T (pt) 2011-08-05 2024-10-04 Regeneron Pharma Murganhos da cadeia leve universal humanizada
AU2012311286B2 (en) 2011-09-19 2018-07-26 Kymab Limited Antibodies, variable domains and chains tailored for human use
EP3741862A1 (en) 2011-09-19 2020-11-25 Kymab Limited Animals, repertoires & methods for the production of human antibodies
WO2013045916A1 (en) 2011-09-26 2013-04-04 Kymab Limited Chimaeric surrogate light chains (slc) comprising human vpreb
KR20140082824A (ko) 2011-10-17 2014-07-02 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
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
PT3527070T (pt) 2011-12-20 2025-12-19 Regeneron Pharma Murganhos de cadeia leve humanizada
NZ810648A (en) 2012-02-01 2025-11-28 Regeneron Pharma Humanized rodents that express heavy chains containing vl domains
NZ714516A (en) 2012-03-02 2017-06-30 Regeneron Pharma Human antibodies to clostridium difficile toxins
MX353278B (es) * 2012-03-06 2018-01-05 Regeneron Pharma Raton con cadena ligera comun.
HK1200271A1 (en) 2012-03-16 2015-08-07 瑞泽恩制药公司 Mice that produce antigen-binding proteins with ph-dependent binding characteristics
GB2502127A (en) 2012-05-17 2013-11-20 Kymab Ltd Multivalent antibodies and in vivo methods for their production
EP2831245A1 (en) 2012-03-28 2015-02-04 Kymab Limited Transgenic non-human vertebrate for the expression of class - switched, fully human, antibodies
US10251377B2 (en) 2012-03-28 2019-04-09 Kymab Limited Transgenic non-human vertebrate for the expression of class-switched, fully human, antibodies
JO3820B1 (ar) 2012-05-03 2021-01-31 Regeneron Pharma أجسام مضادة بشرية لـ fel d1وطرق لاستخدامها
LT3401400T (lt) 2012-05-25 2019-06-10 The Regents Of The University Of California Būdai ir kompozicijos, skirtos rnr molekulės nukreipiamai tikslinės dnr modifikacijai ir rnr molekulės nukreipiamam transkripcijos moduliavimui
EP3912464A1 (en) 2012-06-12 2021-11-24 Regeneron Pharmaceuticals, Inc. Humanized non-human animals with restricted immunoglobulin heavy chain loci
US8962913B2 (en) 2012-06-18 2015-02-24 Regeneron Pharmaceuticals, Inc. Humanized IL-7 rodents
IL239317B (en) 2012-12-12 2022-07-01 Broad Inst Inc Providing, engineering and optimizing systems, methods and compositions for sequence manipulation and therapeutic applications
MY185881A (en) 2013-02-20 2021-06-14 Regeneron Pharma Non-human animals with modified immunoglobulin heavy chain sequences
WO2014141192A1 (en) 2013-03-15 2014-09-18 Erasmus University Medical Center Generation of heavy chain-only antibodies
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
US20150033372A1 (en) 2013-05-01 2015-01-29 Kymab Limited Human VpreB & Chimaeric Surrogate Light Chains in Transgenic Non-Human Vertebrates
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
US20140331339A1 (en) 2013-05-03 2014-11-06 Kymab Limited Transgenic Non-Human Assay Vertebrates, Assays and Kits
CA2925723A1 (en) * 2013-10-01 2015-04-09 Kymab Limited Animal models and therapeutic molecules
GB201710984D0 (en) 2017-07-07 2017-08-23 Kymab Ltd Cells, vertebrates, populations & methods

Also Published As

Publication number Publication date
US10966412B2 (en) 2021-04-06
SG11201602236SA (en) 2016-04-28
US20190174729A1 (en) 2019-06-13
SG10201802295XA (en) 2018-04-27
EP3051942A2 (en) 2016-08-10
JP6843953B2 (ja) 2021-03-17
ES2859373T3 (es) 2021-10-01
DE112014004537T5 (de) 2016-07-21
EP3794941C0 (en) 2024-09-25
NL2015773B1 (en) 2017-05-24
US11399522B2 (en) 2022-08-02
EP3794941B1 (en) 2024-09-25
TW201546284A (zh) 2015-12-16
WO2015049517A3 (en) 2015-08-06
JP2021087442A (ja) 2021-06-10
JP7179106B2 (ja) 2022-11-28
NL2013554A (en) 2015-04-07
AU2014330922A1 (en) 2016-03-03
CN105683365A (zh) 2016-06-15
EP3794941A1 (en) 2021-03-24
JP2016534751A (ja) 2016-11-10
EP3051942B1 (en) 2020-09-02
US20230157264A1 (en) 2023-05-25
US20210204530A1 (en) 2021-07-08
JP7133902B2 (ja) 2022-09-09
ES2993142T3 (en) 2024-12-23
WO2015049517A2 (en) 2015-04-09
NL2013554B1 (en) 2016-01-08
JP2020036618A (ja) 2020-03-12
US10149462B2 (en) 2018-12-11
US20170135327A1 (en) 2017-05-18
NL2015773A (en) 2016-09-22

Similar Documents

Publication Publication Date Title
US11399522B2 (en) Animal models and therapeutic molecules
JP7010902B2 (ja) 限られた免疫グロブリン軽鎖レパートリーを発現するマウス
JP6636498B2 (ja) 単一ドメイン結合タンパク質を作る非ヒト動物
JP2025032218A (ja) Adam6マウス
EP2831244B1 (en) Transgenic mice expressing human lambda and kappa immunoglobulin light chain variable domains
JP6621750B2 (ja) ヒスチジン操作軽鎖抗体およびそれを生成するための遺伝子改変非ヒト動物
JP2019047806A (ja) ヒト化軽鎖マウス
CN105189545A (zh) 常见轻链小鼠
KR20200116547A (ko) Vl 도메인을 포함하는 결합 단백질을 생성하는 마우스
JP2018508224A (ja) 抗原を結合する軽鎖可変領域を選択する非ヒト動物
HK40047239A (en) Animal models and therapeutic molecules
HK40047239B (en) Animal models and therapeutic molecules
HK1200872B (en) Transgenic mice expressing human lambda and kappa immunoglobulin light chain variable domains

Legal Events

Date Code Title Description
FZDE Discontinued

Effective date: 20201001