CN106995822B - 定制供人类使用的抗体、可变结构域和链 - Google Patents

定制供人类使用的抗体、可变结构域和链 Download PDF

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CN106995822B
CN106995822B CN201610883894.2A CN201610883894A CN106995822B CN 106995822 B CN106995822 B CN 106995822B CN 201610883894 A CN201610883894 A CN 201610883894A CN 106995822 B CN106995822 B CN 106995822B
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human
gene segments
gene
optionally
vertebrate
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Chinese (zh)
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CN106995822A (zh
Inventor
A·布拉德利
G·弗里德里克
E-C·李
M·斯特里文斯
N·英格兰
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Kymab Ltd
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Kymab Ltd
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Priority claimed from GB201116122A external-priority patent/GB201116122D0/en
Priority claimed from GB201116120A external-priority patent/GB201116120D0/en
Priority claimed from GBGB1203257.9A external-priority patent/GB201203257D0/en
Priority claimed from GBGB1204592.8A external-priority patent/GB201204592D0/en
Priority claimed from GBGB1205702.2A external-priority patent/GB201205702D0/en
Priority claimed from GBGB1208749.0A external-priority patent/GB201208749D0/en
Priority claimed from GB201211692A external-priority patent/GB201211692D0/en
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Publication of CN106995822A publication Critical patent/CN106995822A/zh
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies
    • C07K16/18—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
    • A01K67/00—Rearing or breeding animals, not otherwise provided for; New or modified breeds of animals
    • A01K67/027—New or modified breeds of vertebrates
    • A01K67/0275—Genetically modified vertebrates, e.g. transgenic
    • A01K67/0278—Knock-in vertebrates, e.g. humanised vertebrates
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/04—Antibacterial agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
    • A61P31/14—Antivirals for RNA viruses
    • A61P31/16—Antivirals for RNA viruses for influenza or rhinoviruses
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
    • A61P31/14—Antivirals for RNA viruses
    • A61P31/18—Antivirals for RNA viruses for HIV
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P33/00—Antiparasitic agents
    • A61P33/02—Antiprotozoals, e.g. for leishmaniasis, trichomoniasis, toxoplasmosis
    • A61P33/06—Antimalarials
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    • C07K16/00—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies
    • C07K16/08—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from viruses
    • C07K16/081—DNA viruses
    • C07K16/085—Orthoherpesviridae (F), e.g. pseudorabies virus or Epstein-Barr virus
    • C07K16/088—Varicella-zoster virus
    • C—CHEMISTRY; METALLURGY
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    • C07K16/00—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies
    • C07K16/08—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from viruses
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    • C07K16/085—Orthoherpesviridae (F), e.g. pseudorabies virus or Epstein-Barr virus
    • C07K16/089—Cytomegalovirus
    • C—CHEMISTRY; METALLURGY
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    • C07K16/00—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies
    • C07K16/12—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from bacteria
    • C07K16/1203—Gram-negative bacteria
    • C07K16/1217—Neisseriaceae (F)
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    • C07K16/00—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies
    • C07K16/46—Hybrid immunoglobulins
    • C07K16/461—Igs containing Ig-regions, -domains or -residues form different species
    • C07K16/462—Igs containing a variable region (Fv) from one specie and a constant region (Fc) from another
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    • C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09—Recombinant DNA-technology
    • C12N15/63—Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
    • C12N15/79—Vectors or expression systems specially adapted for eukaryotic hosts
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    • C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09—Recombinant DNA-technology
    • C12N15/63—Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
    • C12N15/79—Vectors or expression systems specially adapted for eukaryotic hosts
    • C12N15/85—Vectors or expression systems specially adapted for eukaryotic hosts for animal cells
    • C12N15/8509—Vectors or expression systems specially adapted for eukaryotic hosts for animal cells for producing genetically modified animals, e.g. transgenic
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
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    • A01K2217/00—Genetically modified animals
    • A01K2217/07—Animals genetically altered by homologous recombination
    • A01K2217/072—Animals genetically altered by homologous recombination maintaining or altering function, i.e. knock in
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
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    • A01K2217/00—Genetically modified animals
    • A01K2217/15—Animals comprising multiple alterations of the genome, by transgenesis or homologous recombination, e.g. obtained by cross-breeding
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
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    • A01K2227/00—Animals characterised by species
    • A01K2227/10—Mammal
    • A01K2227/105—Murine
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
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    • C07K16/081—DNA viruses
    • C07K16/085—Orthoherpesviridae (F), e.g. pseudorabies virus or Epstein-Barr virus
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies
    • C07K16/08—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from viruses
    • C07K16/10—RNA viruses
    • C07K16/108—Orthomyxoviridae (F), e.g. influenza virus
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
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    • C07K16/00—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies
    • C07K16/08—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from viruses
    • C07K16/10—RNA viruses
    • C07K16/112—Retroviridae (F), e.g. leukemia viruses
    • C07K16/114—Lentivirus (G), e.g. human immunodeficiency virus [HIV], feline immunodeficiency virus [FIV] or simian immunodeficiency virus [SIV]
    • C—CHEMISTRY; METALLURGY
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    • C07K16/00—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies
    • C07K16/12—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from bacteria
    • C07K16/1203—Gram-negative bacteria
    • C07K16/1228—Enterobacterales (O), e.g. Citrobacter (G), Serratia (G), Proteus (G), Providencia (G), Morganella (G) or Yersinia (G)
    • C07K16/1232—Escherichia (G)
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    • C07K16/1242—Gram-negative bacteria from Pasteurellaceae (F), e.g. Haemophilus influenza
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    • C12N2800/00—Nucleic acids vectors
    • C12N2800/20—Pseudochromosomes, minichrosomosomes
    • C12N2800/204—Pseudochromosomes, minichrosomosomes of bacterial origin, e.g. BAC

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CN201610883894.2A 2011-09-19 2012-09-18 定制供人类使用的抗体、可变结构域和链 Expired - Fee Related CN106995822B (zh)

Applications Claiming Priority (15)

Application Number Priority Date Filing Date Title
GB1116122.1 2011-09-19
GB1116120.5 2011-09-19
GB201116122A GB201116122D0 (en) 2011-09-19 2011-09-19 Synthetically-extended & ethnically diverse superhuman immunoglobulin gene repertoires
GB201116120A GB201116120D0 (en) 2011-09-19 2011-09-19 Manipulation of immunoglobulin gene diversity and multi antibody therapeutics, especially for infectious diseases
GB1203257.9 2012-02-24
GBGB1203257.9A GB201203257D0 (en) 2012-02-24 2012-02-24 Animals, repertoires & methods
GB1204592.8 2012-03-15
GBGB1204592.8A GB201204592D0 (en) 2012-03-15 2012-03-15 Animals, repertoires & methods
GBGB1205702.2A GB201205702D0 (en) 2012-03-29 2012-03-29 Animals,repertoires & methods
GB1205702.2 2012-03-29
GB1208749.0 2012-05-18
GBGB1208749.0A GB201208749D0 (en) 2012-05-18 2012-05-18 Synthetically-extended & ethnically-diverse superhuman immunoglobulin gene repertoires
GB201211692A GB201211692D0 (en) 2012-07-02 2012-07-02 Animals, repertories & methods
GB1211692.7 2012-07-02
CN201280056727.0A CN104080916A (zh) 2011-09-19 2012-09-18 定制供人类使用的抗体、可变结构域和链

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CN201280056727.0A Division CN104080916A (zh) 2011-09-19 2012-09-18 定制供人类使用的抗体、可变结构域和链

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CN106995822A CN106995822A (zh) 2017-08-01
CN106995822B true CN106995822B (zh) 2021-06-29

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CN201610883894.2A Expired - Fee Related CN106995822B (zh) 2011-09-19 2012-09-18 定制供人类使用的抗体、可变结构域和链
CN201280056727.0A Pending CN104080916A (zh) 2011-09-19 2012-09-18 定制供人类使用的抗体、可变结构域和链
CN201610821299.6A Active CN107056936B (zh) 2011-09-19 2012-09-18 免疫球蛋白基因多样性的操纵及多抗体治疗剂
CN201280056528.XA Active CN103945689B (zh) 2011-09-19 2012-09-18 免疫球蛋白基因多样性的操纵及多抗体治疗剂

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CN201610821299.6A Active CN107056936B (zh) 2011-09-19 2012-09-18 免疫球蛋白基因多样性的操纵及多抗体治疗剂
CN201280056528.XA Active CN103945689B (zh) 2011-09-19 2012-09-18 免疫球蛋白基因多样性的操纵及多抗体治疗剂

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US (4) US20140041067A1 (https=)
EP (6) EP2757875B2 (https=)
JP (4) JP2014533930A (https=)
CN (4) CN106995822B (https=)
AU (3) AU2012311288B2 (https=)
BR (2) BR112014006394A2 (https=)
CA (2) CA2846322A1 (https=)
DK (2) DK2757875T3 (https=)
ES (1) ES2612935T3 (https=)
WO (2) WO2013041846A2 (https=)

Families Citing this family (79)

* 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
DK3622815T3 (da) 2009-07-08 2023-06-26 Kymab Ltd Gnavermodeller og terapeutiske molekyler
SMT201700023T1 (it) 2010-08-02 2017-03-08 Regeneron Pharma Topi che producono proteine leganti vl
HUE047278T2 (hu) 2011-08-05 2020-04-28 Regeneron Pharma Humanizált univerzális könnyûláncú egerek
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
SG11201401181YA (en) 2011-10-17 2014-04-28 Regeneron Pharma Restricted immunoglobulin heavy chain mice
US9253965B2 (en) 2012-03-28 2016-02-09 Kymab Limited Animal models and therapeutic molecules
SG10201605675WA (en) 2011-12-20 2016-09-29 Regeneron Pharma Humanized light chain mice
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
ME03551B (me) 2012-06-12 2020-07-20 Regeneron Pharma Humanizovane nehumane živoтinje sa ograničenim lokusima imunoglobulinskog тeškog lanca
MY178882A (en) 2013-02-20 2020-10-21 Regeneron Pharma 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
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
EP3988649B1 (en) * 2013-09-18 2024-11-27 Kymab Limited Methods, cells and organisms
FR3011249A1 (https=) * 2013-10-01 2015-04-03 Kymab Ltd
AU2014330922A1 (en) * 2013-10-01 2016-03-03 Kymab Limited Animal models and therapeutic molecules
US8986691B1 (en) 2014-07-15 2015-03-24 Kymab Limited Method of treating atopic dermatitis or asthma using antibody to IL4RA
US8992927B1 (en) 2014-07-15 2015-03-31 Kymab Limited Targeting human NAV1.7 variants for treatment of pain
US8986694B1 (en) 2014-07-15 2015-03-24 Kymab Limited Targeting human nav1.7 variants for treatment of pain
EP2975058A1 (en) * 2014-07-15 2016-01-20 Kymab Limited Antibodies for use in treating conditions related to specific PCSK9 variants in specific patient populations
US9051378B1 (en) 2014-07-15 2015-06-09 Kymab Limited Targeting rare human PCSK9 variants for cholesterol treatment
US8945560B1 (en) 2014-07-15 2015-02-03 Kymab Limited Method of treating rheumatoid arthritis using antibody to IL6R
DE112014005975T5 (de) * 2013-12-17 2016-09-15 Kymab Limited Menschliche Ziele
US9023359B1 (en) 2014-07-15 2015-05-05 Kymab Limited Targeting rare human PCSK9 variants for cholesterol treatment
DE202014010499U1 (de) 2013-12-17 2015-10-20 Kymab Limited Targeting von humaner PCSK9 zur Cholesterinbehandlung
US9017678B1 (en) 2014-07-15 2015-04-28 Kymab Limited Method of treating rheumatoid arthritis using antibody to IL6R
US9045545B1 (en) 2014-07-15 2015-06-02 Kymab Limited Precision medicine by targeting PD-L1 variants for treatment of cancer
WO2015092393A2 (en) * 2013-12-17 2015-06-25 Kymab Limited Human targets
US9034332B1 (en) 2014-07-15 2015-05-19 Kymab Limited Precision medicine by targeting rare human PCSK9 variants for cholesterol treatment
US9067998B1 (en) 2014-07-15 2015-06-30 Kymab Limited Targeting PD-1 variants for treatment of cancer
US9045548B1 (en) 2014-07-15 2015-06-02 Kymab Limited Precision Medicine by targeting rare human PCSK9 variants for cholesterol treatment
US8883157B1 (en) 2013-12-17 2014-11-11 Kymab Limited Targeting rare human PCSK9 variants for cholesterol treatment
US8980273B1 (en) 2014-07-15 2015-03-17 Kymab Limited Method of treating atopic dermatitis or asthma using antibody to IL4RA
US9914769B2 (en) 2014-07-15 2018-03-13 Kymab Limited Precision medicine for cholesterol treatment
EP2886558A1 (en) * 2013-12-17 2015-06-24 Kymab Limited Antibodies for use in treating conditions related to specific PCSK9 variants in specific patient populations
US10034463B2 (en) 2014-01-24 2018-07-31 Children's Medical Center Corporation High-throughput mouse model for optimizing antibody affinities
GB201403775D0 (en) 2014-03-04 2014-04-16 Kymab Ltd Antibodies, uses & methods
AU2015231025A1 (en) 2014-03-21 2016-09-15 Regeneron Pharmaceuticals, Inc. Vl antigen binding proteins exhibiting distinct binding characteristics
CA3124228C (en) 2014-03-21 2024-05-14 Regeneron Pharmaceuticals, Inc. Non-human animals that make single domain binding proteins
DE202015009006U1 (de) 2014-07-15 2016-08-19 Kymab Limited Targeting von humaner PCSK9 zur Cholesterinbehandlung
US9150660B1 (en) 2014-07-15 2015-10-06 Kymab Limited Precision Medicine by targeting human NAV1.8 variants for treatment of pain
US9139648B1 (en) 2014-07-15 2015-09-22 Kymab Limited Precision medicine by targeting human NAV1.9 variants for treatment of pain
EP2975059A1 (en) 2014-07-15 2016-01-20 Kymab Limited Antibodies for use in treating conditions related to specific pcsk9 variants in specific patients populations
EP4328245A3 (en) 2014-07-15 2024-06-05 Kymab Ltd. Antibodies for use in treating conditions related to specific pcsk9 variants in specific patients populations
WO2016023916A1 (en) 2014-08-12 2016-02-18 Kymab Limited Treatment of disease using ligand binding to targets of interest
US10513711B2 (en) * 2014-08-13 2019-12-24 Dupont Us Holding, Llc Genetic targeting in non-conventional yeast using an RNA-guided endonuclease
WO2016071701A1 (en) 2014-11-07 2016-05-12 Kymab Limited Treatment of disease using ligand binding to targets of interest
CA2979702A1 (en) 2015-03-19 2016-09-22 Regeneron Pharmaceuticals, Inc. Non-human animals that select for light chain variable regions that bind antigen
KR20230006929A (ko) * 2016-01-13 2023-01-11 리제너론 파마슈티칼스 인코포레이티드 조작된 중쇄 다양성 영역을 갖는 설치류
CN113831407B (zh) 2016-05-20 2024-06-11 瑞泽恩制药公司 用于使用多个引导rna来破坏免疫耐受性的方法
KR102483193B1 (ko) 2016-06-03 2023-01-04 리제너론 파마슈티칼스 인코포레이티드 외인성 말단 데옥시뉴클레오타이드 전달효소를 발현하는 비인간 동물
RU2769282C2 (ru) 2016-06-20 2022-03-30 Кимаб Лимитед Анти-PD-L1 и IL-2 цитокины
EP3534947A1 (en) 2016-11-03 2019-09-11 Kymab Limited Antibodies, combinations comprising antibodies, biomarkers, uses & methods
CN107312863A (zh) * 2017-08-08 2017-11-03 深圳华大基因研究院 利用数字PCR鉴定B淋巴细胞的Ig基因分布的方法
WO2019037099A1 (en) * 2017-08-25 2019-02-28 Wenning Qin Large scale modification of eukaryotic genome
CN107557367B (zh) * 2017-09-08 2020-11-03 北京大学人民医院 Ighg1基因突变体及其应用
DK3476942T3 (da) * 2017-10-27 2022-04-19 Trianni Inc Lange kimlinje-dh-gener og antistoffer med lang hcdr3
CN108486126A (zh) * 2018-03-27 2018-09-04 重庆金迈博生物科技有限公司 一种核酸分子及其在人源化抗体中的应用
JP7269963B2 (ja) * 2018-06-08 2023-05-09 クリスタル バイオサイエンス インコーポレイテッド 同じ軽鎖ｉを有する多様な抗体を産生するためのトランスジェニック動物
IL318469A (en) * 2018-06-14 2025-03-01 Regeneron Pharma Non-human animals capable of reorganizing transgenic DH-DH, and their uses
CA3125380A1 (en) * 2019-02-18 2020-08-27 Biocytogen Pharmaceuticals (Beijing) Co., Ltd. Genetically modified non-human animals with humanized immunoglobulin locus
GB201905552D0 (en) * 2019-04-18 2019-06-05 Kymab Ltd Antagonists
JP2023529846A (ja) 2020-06-02 2023-07-12 バイオサイトジェン ファーマシューティカルズ （ベイジン） カンパニー リミテッド 共通軽鎖免疫グロブリン遺伝子座を有する遺伝子改変非ヒト動物
WO2021261620A1 (ko) * 2020-06-25 2021-12-30 주식회사 휴맵 이형접합성 형질전환 동물
US20220090060A1 (en) 2020-09-11 2022-03-24 Regeneron Pharmaceuticals, Inc. Identification and production of antigen-specific antibodies
CN116848254B (zh) 2020-12-16 2026-03-17 瑞泽恩制药公司 表达人源化Fcα受体的小鼠
CA3165366A1 (en) 2020-12-23 2022-06-30 Regeneron Pharmaceuticals, Inc. Nucleic acids encoding anchor modified antibodies and uses thereof
JP7748680B2 (ja) * 2021-11-16 2025-10-03 国立大学法人鳥取大学 改変ｄ領域を含むヒト免疫グロブリン重鎖遺伝子座を有する哺乳動物人工染色体ベクター、及びそのベクターを保持する細胞又は非ヒト動物
JP2025170455A (ja) * 2022-10-05 2025-11-19 株式会社Logomix 細胞ライブラリおよびその製造方法
JP7212982B1 (ja) 2022-10-05 2023-01-26 株式会社Logomix 細胞ライブラリおよびその製造方法
TW202430558A (zh) * 2023-01-18 2024-08-01 美商基利科學股份有限公司 人類免疫球蛋白重鏈長cdr3轉殖基因構築體及其用途
CN119855835A (zh) * 2023-06-13 2025-04-18 南京维立志博生物科技股份有限公司 基于共同轻链产生双特异性抗体的方法
CN117736322B (zh) * 2024-02-21 2024-04-19 吉林大学 抗syce2单分子抗体t2d及其应用
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 (191)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US1014946A (en) 1910-06-16 1912-01-16 Us Sherardizing Company Alloy for coating with metal.
US1006439A (en) 1911-03-11 1911-10-17 Clarence Cosby Can-shearing machine.
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
US6713610B1 (en) 1990-01-12 2004-03-30 Raju Kucherlapati Human antibodies derived from immunized xenomice
US6657103B1 (en) 1990-01-12 2003-12-02 Abgenix, Inc. Human antibodies derived from immunized xenomice
DE69120146T2 (de) 1990-01-12 1996-12-12 Cell Genesys Inc Erzeugung xenogener antikörper
US6673986B1 (en) 1990-01-12 2004-01-06 Abgenix, Inc. Generation of xenogeneic antibodies
US6300129B1 (en) 1990-08-29 2001-10-09 Genpharm International Transgenic non-human animals for producing heterologous antibodies
US5770429A (en) * 1990-08-29 1998-06-23 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
US5633425A (en) * 1990-08-29 1997-05-27 Genpharm International, Inc. Transgenic non-human animals capable of producing heterologous antibodies
ATE158021T1 (de) 1990-08-29 1997-09-15 Genpharm Int Produktion und nützung nicht-menschliche transgentiere zur produktion heterologe antikörper
US5545806A (en) 1990-08-29 1996-08-13 Genpharm International, Inc. Ransgenic non-human animals for producing heterologous antibodies
WO1993012227A1 (en) 1991-12-17 1993-06-24 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
US7084260B1 (en) 1996-10-10 2006-08-01 Genpharm International, Inc. High affinity human antibodies and human antibodies against human antigens
WO1993004169A1 (en) 1991-08-20 1993-03-04 Genpharm International, Inc. Gene targeting in animal cells using isogenic dna constructs
ES2301158T3 (es) 1992-07-24 2008-06-16 Amgen Fremont Inc. Produccion de anticuerpos xenogenicos.
DK1621554T4 (da) 1992-08-21 2012-12-17 Univ Bruxelles Immunoglobuliner blottet for lette kæder
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
JPH08509612A (ja) 1993-04-26 1996-10-15 ジェンファーム インターナショナル インコーポレイテッド 異種抗体を産生することができるトランスジェニック非ヒト動物
DE4331162A1 (de) 1993-09-14 1995-03-16 Bayer Ag Verfahren zur Herstellung von Cyaninfarbstoffen
BE1007904A3 (nl) 1993-12-23 1995-11-14 Dsm Nv Werkwijze voor de bereiding van een alkanol en/of een alkanon.
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.
CA2722378C (en) 1996-12-03 2015-02-03 Amgen Fremont Inc. Human antibodies that bind 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
ATE299938T1 (de) 1997-05-02 2005-08-15 Genentech Inc Ein verfahren zur herstellung multispezifischer antikörper die heteromultimere und gemeinsame komponenten besitzen
US20020088019A1 (en) 1997-09-02 2002-07-04 Oron Yacoby-Zeevi Methods of and pharmaceutical compositions for improving implantation of embryos
WO1999025821A1 (en) 1997-11-18 1999-05-27 Pioneer Hi-Bred International, Inc. Compositions and methods for genetic modification of plants
US6509156B1 (en) 1997-12-05 2003-01-21 Europaisches Laboratorium Fur Molekularoiologie (Embl) DNA cloning method relying on the E. coli recE/recT recombination system
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
WO2000071585A1 (en) 1999-05-03 2000-11-30 Medarex, Inc. 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
US6355412B1 (en) 1999-07-09 2002-03-12 The European Molecular Biology Laboratory Methods and compositions for directed cloning and subcloning using homologous recombination
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
BR0110927A (pt) * 2000-05-19 2003-03-11 Scancell Ltd Anticorpo, ácido nucléico, vetor, célula, método de fabricar um anticorpo, composição farmacêutica, uso de um anticorpo ou de um ácido nucleico, e, método para o tratamento ou profilaxia do câncer
BR0112633A (pt) 2000-07-21 2003-09-16 Us Agriculture Método para substituir, translocar e empilhar dna em genomas eucarióticos
EA013564B1 (ru) * 2000-08-03 2010-06-30 Терапеутик Хьюман Поликлоналз Инк. Гуманизированный иммуноглобулин и содержащая его фармацевтическая композиция
US8165246B1 (en) * 2000-08-28 2012-04-24 Alcatel Lucent Training sequence for low latency LMS implementation
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
AU2001297523B2 (en) 2000-11-17 2007-01-18 Sab, Llc Expression of xenogenous (human) immunoglobulins in cloned, transgenic ungulates
CA2430013C (en) 2000-11-30 2011-11-22 Medarex, Inc. Transgenic transchromosomal rodents for making human antibodies
ES2389251T3 (es) 2000-12-19 2012-10-24 Altor Bioscience Corporation Animales transgénicos que comprenden un sistema inmunitario humanizado
ME00502B (me) * 2001-01-05 2011-10-10 Amgen Fremont Inc Antitjela za insulinu sličan receptor faktora i rasta
GB0115256D0 (en) 2001-06-21 2001-08-15 Babraham Inst Mouse light chain locus
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
US7390885B2 (en) * 2001-11-26 2008-06-24 Cell Matrix, Inc. Humanized collagen antibodies and related methods
EP2319301B1 (en) 2001-11-30 2017-09-06 Amgen Fremont Inc. Transgenic animals bearing human Ig lambda 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
DK2314629T4 (da) 2002-07-18 2023-02-06 Merus Nv Rekombinant produktion af blandinger af antistoffer
EP1539946A4 (en) 2002-09-09 2006-03-15 California Inst Of Techn METHOD AND COMPOSITIONS FOR PRODUCING HUMANIZED MICE
BRPI0315295C1 (pt) * 2002-10-17 2021-05-25 Genmab As anticorpo monoclonal humano isolado, célula hospedeira procariótica, composição farmacêutica, molécula biespecífica, usos de um anticorpo, métodos in vitro de detectar a presença de antígeno de cd20 ou uma célula que expressa cd20 em uma amostra, kit, e, vetor de expressão
DE10251918A1 (de) 2002-11-08 2004-05-19 Horn, Carsten, Dipl.-Biochem. Dr. Systeme zur Erzeugung stabiler genomischer Transgen-Insertionen
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
WO2004041863A2 (en) 2002-11-08 2004-05-21 Ablynx N.V. Single domain antibodies directed against interferon- gamma and uses therefor
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
US20100069614A1 (en) 2008-06-27 2010-03-18 Merus B.V. Antibody producing non-human mammals
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
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
ES2473596T3 (es) * 2003-07-15 2014-07-07 Therapeutic Human Polyclonals, Inc. Loci de inmunoglobulina humanizada
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
PL1691837T3 (pl) 2003-12-10 2012-11-30 Squibb & Sons Llc IP-10 przeciwciała i ich zastosowanie
US20050260679A1 (en) 2004-03-19 2005-11-24 Sirid-Aimee Kellerman Reducing the risk of human 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
AU2005237494B2 (en) * 2004-04-22 2010-06-10 Kyowa Hakko Kirin Co., Ltd Transgenic animals and uses thereof
JP2006029459A (ja) 2004-07-16 2006-02-02 Kayaba Ind Co Ltd 緩衝装置
KR101151957B1 (ko) 2004-07-22 2012-06-01 로저 킹돈 크레이그 결합 분자
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
WO2006029459A1 (en) 2004-09-13 2006-03-23 Evogenix, Inc Antibodies specific for hepatocellular carcinoma and other carcinomas and uses thereof
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
ES2463476T3 (es) 2004-10-19 2014-05-28 Regeneron Pharmaceuticals, Inc. Método para generar un ratón homocigótico para una modificación genética
WO2006055704A2 (en) 2004-11-17 2006-05-26 Curagen Corporation Antibodies directed to ten-m proteins and uses thereof
ZA200705695B (en) 2004-12-21 2009-02-25 Astrazeneca Ab Antibodies directed to angiopoietin-2 and uses thereof
AU2006242854A1 (en) 2005-04-29 2006-11-09 Inserm (Institut National De La Sante Et De La Recherche Medicale) Transgenic animals and methods of making recombinant antibodies
AU2005331864A1 (en) 2005-05-14 2006-11-23 Fudan University Piggybac as a tool for genetic manipulation 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
AU2007219159B8 (en) 2006-01-25 2012-06-28 Roger Kingdon Craig 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
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
JP5307708B2 (ja) 2006-06-02 2013-10-02 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 ヒトｉｌ−６受容体に対する高親和性抗体
EP2409715A1 (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
JP2010501165A (ja) 2006-08-22 2010-01-21 ジーツー インフラメイション プロプライエタリー リミテッド 抗体の作製方法
MY149079A (en) 2006-10-02 2013-07-15 Regeneron Pharma High affinity human antibodies to human il-4 receptor
WO2008070367A2 (en) 2006-11-01 2008-06-12 Facet Biotech Corporation Mammalian cell-based immunoglobulin display libraries
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
US20090075378A1 (en) 2007-02-20 2009-03-19 Anaptysbio, Inc. Somatic hypermutation systems
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
CN101679974B (zh) 2007-03-27 2015-09-30 航道生物技术有限责任公司 包含抗体替代轻链序列的构建体和文库
GB0706628D0 (en) 2007-04-04 2007-05-16 Univ Erasmus Germ-line manipulation 1
PL2602323T3 (pl) * 2007-06-01 2018-06-29 Open Monoclonal Technology, Inc. Kompozycje i sposoby hamowania endogennych genów immunoglobin i wytwarzania transgenicznych ludzkich przeciwciał typu idiotypowego
WO2009013620A2 (en) 2007-06-11 2009-01-29 Erasmus University Medical Center Rotterdam Homologous recombination
MX2010000970A (es) 2007-07-31 2010-03-09 Regeneron Pharma Anticuerpos humanos contra cd20 humano y metodo para utilizarlos.
MX2010001395A (es) 2007-08-10 2010-03-10 Regeneron Pharma Anticuerpos humanos de alta afinidad de factor de crecimiento de nervio humano.
JP5588866B2 (ja) 2007-08-10 2014-09-10 メダレックス エル．エル．シー． Ｈｃｏ３２およびｈｃｏ２７、ならびに関連実施例
PT2592148T (pt) 2007-10-12 2018-11-12 Hoffmann La Roche Expressão proteica de múltiplos ácidos nucleicos
KR20100103810A (ko) 2007-12-10 2010-09-28 알리바 바이오파마수티컬스, 아이엔씨. 동종 재조합에 의한 표적화된 영역의 순차적인 치환 방법
US8227577B2 (en) 2007-12-21 2012-07-24 Hoffman-La Roche Inc. Bivalent, bispecific antibodies
EP2252659A2 (en) 2008-01-25 2010-11-24 Cabot Corporation Method of preparing modified colored pigments
EP2271207A2 (en) 2008-03-26 2011-01-12 ITI Scotland Limited Efficient insertion of dna into embryonic stem cells
US8012714B2 (en) 2008-04-14 2011-09-06 Innovative Targeting Solutions, Inc. Sequence diversity generation in immunoglobulins
EP2669298A3 (en) 2008-05-23 2014-02-26 Ablexis, LLC Single variable immunoglobulin domain comprising VL-DH-JL
EP2147594B1 (en) 2008-06-27 2013-11-13 Merus B.V. Antibody producing non-human mammals
AU2009298458B2 (en) 2008-09-30 2015-10-08 Ablexis, Llc 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).
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
CA2753287A1 (en) 2009-02-24 2010-09-02 Glaxo Group Limited Antigen-binding constructs
GB0905023D0 (en) 2009-03-24 2009-05-06 Univ Erasmus Medical Ct Binding molecules
EP2414507B1 (en) 2009-04-03 2014-07-02 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
DK3622815T3 (da) 2009-07-08 2023-06-26 Kymab Ltd Gnavermodeller og terapeutiske molekyler
US9273118B2 (en) 2009-07-15 2016-03-01 Aimm Therapeutics B.V. Means and methods for producing high affinity antibodies
JO3182B1 (ar) 2009-07-29 2018-03-08 Regeneron Pharma مضادات حيوية بشرية عالية الالفة مع تولد الاوعية البشرية - 2
US8586526B2 (en) 2010-05-17 2013-11-19 Sangamo Biosciences, Inc. DNA-binding proteins and uses thereof
AU2010282508B2 (en) 2009-08-13 2015-05-28 Crystal Bioscience Inc. Transgenic animal for production of antibodies having minimal CDRs
CN102050877B (zh) * 2009-10-30 2014-05-07 上海抗体药物国家工程研究中心有限公司 抗人cd20人源化抗体、其制备方法及用途
US20120251552A1 (en) 2009-11-05 2012-10-04 Anaptysbio, Inc. Methods of generating improved antigen-binding agents using chain shuffling and optionally somatic hypermutation
EP2502993B1 (en) 2009-11-17 2017-07-26 Sanford Applied Biosciences L.L.C. Human artificial chromosome vector
US8961967B2 (en) 2009-11-30 2015-02-24 Janssen Biotech, Inc. Antibody Fc mutants with ablated effector functions
WO2011071957A1 (en) 2009-12-07 2011-06-16 Sea Lane Biotechnologies, Llc Conjugates comprising an antibody surrogate scaffold with improved pharmacokinetic properties
ES2724975T3 (es) 2009-12-10 2019-09-18 Regeneron Pharma Ratones que producen anticuerpos de cadena pesada
JO3274B1 (ar) * 2009-12-24 2018-09-16 Regeneron Pharma أجسام مضادة بشرية للبروتين 4 المشابه لأجيوبيوتين البشري
US20120021409A1 (en) 2010-02-08 2012-01-26 Regeneron Pharmaceuticals, Inc. Common Light Chain Mouse
SMT202600080T1 (it) 2010-02-08 2026-03-09 Regeneron Pharma Topo con catena leggera comune
CN103228130B (zh) 2010-06-17 2016-03-16 科马布有限公司 动物模型及治疗分子
PT3034608T (pt) 2010-06-22 2019-05-28 Regeneron Pharma Ratinhos expressando uma cadeia leve híbrida de imunoglobulina com uma região variável humana
SMT201700023T1 (it) 2010-08-02 2017-03-08 Regeneron Pharma Topi che producono proteine leganti vl
CN103261220B (zh) 2010-08-16 2016-06-15 诺夫免疫股份有限公司 用于生成多特异性和多价抗体的方法
JO3375B1 (ar) 2010-11-08 2019-03-13 Regeneron Pharma أجسام مضادة بشرية للجين a1 الشبيه بعامل النخر الورمي (tl1a)
CN103261230A (zh) 2010-12-22 2013-08-21 霍夫曼-拉罗奇有限公司 抗pcsk9抗体及使用方法
ME02106B (me) 2011-02-25 2015-10-20 Regeneron Pharma Miševi sa adam6
HUE047278T2 (hu) 2011-08-05 2020-04-28 Regeneron Pharma Humanizált univerzális könnyûláncú egerek
BR112014006394A2 (pt) 2011-09-19 2017-03-28 Kymab Ltd manipulação de diversidade genética de imunoglobulina e terapêuticos multi-anticorpos
EP2758534B1 (en) 2011-09-19 2020-04-29 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
SG11201401181YA (en) 2011-10-17 2014-04-28 Regeneron Pharma Restricted immunoglobulin heavy chain mice
KR102024958B1 (ko) 2011-10-20 2019-09-24 쓰리엠 이노베이티브 프로퍼티즈 컴파니 아포다이징된 광대역 부분 반사기
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
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
US20180295821A1 (en) 2011-12-02 2018-10-18 Kymab Limited Transgenic Animals
SG10201605675WA (en) 2011-12-20 2016-09-29 Regeneron Pharma Humanized light chain mice
EP3597038B1 (en) 2012-02-01 2021-04-21 Regeneron Pharmaceuticals, Inc. Humanized rodents that express heavy chains containing vl domains
AR090219A1 (es) 2012-03-02 2014-10-29 Regeneron Pharma Anticuerpos humanos frente a toxinas de clostridium difficile
MX353278B (es) 2012-03-06 2018-01-05 Regeneron Pharma Raton con cadena ligera comun.
WO2013138681A1 (en) 2012-03-16 2013-09-19 Regeneron Pharmaceuticals, Inc. Mice that produce antigen-binding proteins with ph-dependent binding characteristics
SG11201405059XA (en) 2012-03-28 2014-09-26 Kymab Ltd 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
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
AU2013266968B2 (en) 2012-05-25 2017-06-29 Emmanuelle CHARPENTIER Methods and compositions for RNA-directed target DNA modification and for RNA-directed modulation of transcription
ME03551B (me) 2012-06-12 2020-07-20 Regeneron Pharma Humanizovane nehumane živoтinje sa ograničenim lokusima imunoglobulinskog тeškog lanca
US8962913B2 (en) 2012-06-18 2015-02-24 Regeneron Pharmaceuticals, Inc. Humanized IL-7 rodents
EP3031921B1 (en) 2012-12-12 2025-03-12 The Broad Institute, Inc. Delivery, engineering and optimization of systems, methods and compositions for sequence manipulation and therapeutic applications
MY178882A (en) 2013-02-20 2020-10-21 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
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
AU2014330922A1 (en) 2013-10-01 2016-03-03 Kymab Limited Animal models and therapeutic molecules
GB201710984D0 (en) 2017-07-07 2017-08-23 Kymab Ltd Cells, vertebrates, populations & methods

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