HRP20171357T1 - Ograničeni teški lanac imunoglobulina u miševa - Google Patents

Ograničeni teški lanac imunoglobulina u miševa Download PDF

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HRP20171357T1
HRP20171357T1 HRP20171357TT HRP20171357T HRP20171357T1 HR P20171357 T1 HRP20171357 T1 HR P20171357T1 HR P20171357T T HRP20171357T T HR P20171357TT HR P20171357 T HRP20171357 T HR P20171357T HR P20171357 T1 HRP20171357 T1 HR P20171357T1
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seq
gene
human
segments
mouse
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HRP20171357TT
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Lynn Macdonald
John Mcwhirter
Cagan Gurer
Karolina A. Meagher
Andrew J. Murphy
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Regeneron Pharmaceuticals, Inc.
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Publication of HRP20171357T1 publication Critical patent/HRP20171357T1/hr

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
    • 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
    • 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
    • A61P31/10—Antimycotics
    • 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/46—Hybrid immunoglobulins
    • C07K16/461—Igs containing Ig-regions, -domains or -residues form different species
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
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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
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N5/00—Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
    • C12N5/10—Cells modified by introduction of foreign genetic material
    • 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
    • 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
    • A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
    • 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
    • A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
    • 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
    • A01K2267/00—Animals characterised by purpose
    • A01K2267/01—Animal expressing industrially exogenous proteins
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/10—Immunoglobulins specific features characterized by their source of isolation or production
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/20—Immunoglobulins specific features characterized by taxonomic origin
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/20—Immunoglobulins specific features characterized by taxonomic origin
    • C07K2317/21—Immunoglobulins specific features characterized by taxonomic origin from primates, e.g. man
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/20—Immunoglobulins specific features characterized by taxonomic origin
    • C07K2317/24—Immunoglobulins specific features characterized by taxonomic origin containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
    • C07K2317/515—Complete light chain, i.e. VL + CL
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
    • C07K2317/52—Constant or Fc region; Isotype
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
    • C07K2317/56—Immunoglobulins specific features characterized by immunoglobulin fragments variable (Fv) region, i.e. VH and/or VL
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
    • C07K2317/56—Immunoglobulins specific features characterized by immunoglobulin fragments variable (Fv) region, i.e. VH and/or VL
    • C07K2317/565—Complementarity determining region [CDR]
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
    • C07K2317/56—Immunoglobulins specific features characterized by immunoglobulin fragments variable (Fv) region, i.e. VH and/or VL
    • C07K2317/567—Framework region [FR]
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2800/00—Nucleic acids vectors
    • C12N2800/20—Pseudochromosomes, minichrosomosomes
    • C12N2800/204—Pseudochromosomes, minichrosomosomes of bacterial origin, e.g. BAC

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  • Health & Medical Sciences (AREA)
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  • Wood Science & Technology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Biomedical Technology (AREA)
  • General Engineering & Computer Science (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Animal Behavior & Ethology (AREA)
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  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Pharmacology & Pharmacy (AREA)
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  • Cell Biology (AREA)
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  • Micro-Organisms Or Cultivation Processes Thereof (AREA)
  • Preparation Of Compounds By Using Micro-Organisms (AREA)
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Claims (14)

1. Miš čiji je lokus teškog lanca endogenog imunoglobulina ograničen tako da se sastoji od jednog segmenta ljudskog VH gena, jednog ili više segmenata ljudskog DH gena i jednog ili više segmenata ljudskog JH gena i koji se ne sastoji od funkcionalnog lokusa varijabilne regije teškog lanca endogenog imunoglobulina; miš se nadalje sastoji od jednog ili više segmenata VL gena ljudskog imunoglobulina operativno povezanih s jednim ili više segmenata JL gena, pri čemu su jedan segment ljudskog VH gena, jedan ili više segmenata ljudskog DH gena, i jedan ili više segmenata ljudskog JH gena operativno povezani s genom konstantne regije teškog lanca neljudskog imunoglobulina, pri čemu je jedan segment ljudskog VH gena VH1-69 ili polimorfna varijanta tog gena.
2. Miš prema patentnom zahtjevu 1, pri čemu miš sadrži brisanje svih endogenih segmenata VH, DH, i JH gena.
3. Miš t prema patentnom zahtjevu 1 ili prema patentnom zahtjevu 2, pri čemu jedan segment ljudskog VH gena, jedan ili više segmenata ljudskog DH gena, i jedan ili više segmenata ljudskog JH gena zamjenjuju sve endogene segmente VH, DH, i JH gena na lokusu teškog lanca endogenog imunoglobulina u zametnoj liniji navedenih miševa.
4. Miš prema patentnom zahtjevu 3 u kojem jedan ili više segmenata ljudskog VL gena i jedan ili više segmenata ljudskog JL gena zamjenjuju sve endogene segmente VL i JL gena na lokusu laganog lanca endogenog imunoglobulina.
5. Miš prema bilo kom od predhodnih patentnih zahtjeva, pri čemu se jedan ili više segmenata ljudskog VL gena i/ili jedan ili više segmenata ljudskog JL gena odabire iz segmenata ljudskog κ i ljudskog λ gena.
6. Miš prema bilo kom od predhodnih patentnih zahtjeva, pri čemu su jedan ili više segmenata VL gena ljudskog imunoglobulina i jedan ili više segmenata JL gena operativno povezani s neljudskim konstantnim genom laganog lanca, na primjer mišjim ili štakorskim κ ili λ genom konstantne regije.
7. Miš prema bilo kom od predhodnih patentnih zahtjeva, pri čemu su jedan segment ljudskog VH gena, jedan ili više segmenata ljudskog DH gena i jedan ili više segmenata JH gena operativno povezani s mišjim ili štakorskim genom konstantne regije imunoglobulina.
8. Miš prema bilo kom od predhodnih patentnih zahtjeva , pri čemu su jedan segment ljudskog VH gena, jedan ili više segmenata ljudskog DH gena i jedan ili više segmenata JH gena operativno povezani s mišjim IgM genom konstantne regije.
9. Stanica ili tkivo izvedeno iz miša prema bilo kom od predhodnih patentnih zahtjeva.
10. Metoda izrade slijeda nukleinske kiseline kojom se kodira ljudska VH domena gena sastoji se od sljedećih koraka: (a) imunizacija miša bilo koje prethodne tvrdnje s antigenom od interesa; (b) dopuštanje da navedeni miš razvije imunosni odgovor na antigen od interesa; i (c) uzimanje slijeda nukleinske kiseline VH regije gena imunoglobulina kojim se kodira ljudska VH domena gena od navedenog miša.
11. Metoda prema patentnom zahtjevu 10, pri čemu slijed nukleinske kiseline regije VH imunoglobulina: (a) čini slijed koji je barem 75 % identičan identifikacijskim brojevima slijeda SEQ ID NO: 34, SEQ ID NO: 36, SEQ ID NO: 38, SEQ ID NO: 40, SEQ ID NO: 42, SEQ ID NO: 44, SEQ ID NO: 46, SEQ ID NO: 48, SEQ ID NO: 50, SEQ ID NO: 52, SEQ ID NO: 54, SEQ ID NO: 56 ili SEQ ID NO: 58; ili (b) čini identifikacijske brojeve slijeda SEQ ID NO: 34, SEQ ID NO: 36, SEQ ID NO: 38, SEQ ID NO: 40, SEQ ID NO: 42, SEQ ID NO: 44, SEQ ID NO: 46, SEQ ID NO: 48, SEQ ID NO: 50, SEQ ID NO: 52, SEQ ID NO: 54, SEQ ID NO: 56, SEQ ID NO: 58 ili polimorfnu varijantu tog slijeda; ili (c) kodira protein koji je barem 75 % identičan identifikacijskim brojevima slijeda SEQ ID NO: 35, SEQ ID NO: 37, SEQ ID NO: 39, SEQ ID NO: 41, SEQ ID NO: 43, SEQ ID NO: 45, SEQ ID NO: 47, SEQ ID NO: 49, SEQ ID NO: 51, SEQ ID NO: 53, SEQ ID NO: 55, SEQ ID NO: 57 ili SEQ ID NO: 59.
12. Upotreba miša prema prema bilo kom od patentnih zahtjeva od 1 do 8 u metodi proizvodnje slijeda nukleinske kiseline kojim se kodira varijabilna domena ljudskog teškog lanca.
13. Upotreba prema prema patentnom zahtjevu 12, pri čemu varijabilna domena ljudskog teškog lanca ima karakteristike ljudskih sljedova FR1-CDR1-FR2-CDR2-FR3 izvedenih iz polimorfnog segmenta ljudskog VH 1-69 gena.
14. Upotreba miša prema prema bilo kom od patentnih zahtjeva od 1 do 8 za izradu ljudskog protutijela, pri čemu se ljudsko protutijelo sastoji od varijabilne domene teškog lanca izvedene iz preuređenog segmenta ljudskog VH1-69 gena ili njegove polimorfne varijante, pri čemu je preuređeni segment ljudskog VH1-69 gena barem 75 % identičan identifikacijskim brojevima sljedova SEQ ID NO: 34, SEQ ID NO: 36, SEQ ID NO: 38, SEQ ID NO: 40, SEQ ID NO: 42, SEQ ID NO: 44, SEQ ID NO: 46, SEQ ID NO: 48, SEQ ID NO: 50, SEQ ID NO: 52, SEQ ID NO: 54, SEQ ID NO: 56 ili SEQ ID NO: 58.
HRP20171357TT 2011-10-17 2017-09-11 Ograničeni teški lanac imunoglobulina u miševa HRP20171357T1 (hr)

Applications Claiming Priority (5)

Application Number Priority Date Filing Date Title
US201161547974P 2011-10-17 2011-10-17
US201261597969P 2012-02-13 2012-02-13
US201261658459P 2012-06-12 2012-06-12
PCT/US2012/060487 WO2013059230A1 (en) 2011-10-17 2012-10-17 Restricted immunoglobulin heavy chain mice
EP12783456.2A EP2627773B1 (en) 2011-10-17 2012-10-17 Restricted immunoglobulin heavy chain mice

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HRP20171357T1 true HRP20171357T1 (hr) 2017-12-15

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HRP20220253TT HRP20220253T1 (hr) 2011-10-17 2012-10-17 Miševi s ograničenim teškim lancem imunoglobulina
HRP20171357TT HRP20171357T1 (hr) 2011-10-17 2017-09-11 Ograničeni teški lanac imunoglobulina u miševa

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US (5) US10246509B2 (hr)
EP (3) EP4074833A1 (hr)
JP (6) JP6271435B2 (hr)
KR (6) KR20160098514A (hr)
CN (3) CN104024418B (hr)
AU (4) AU2012326283C1 (hr)
BR (1) BR112014008775A8 (hr)
CA (1) CA2850534A1 (hr)
CY (2) CY1119335T1 (hr)
DK (2) DK3216871T3 (hr)
ES (2) ES2640139T3 (hr)
HR (2) HRP20220253T1 (hr)
HU (2) HUE057680T2 (hr)
IL (5) IL292030B2 (hr)
IN (1) IN2014CN03572A (hr)
LT (2) LT3216871T (hr)
MX (1) MX355062B (hr)
MY (1) MY172946A (hr)
PL (2) PL3216871T3 (hr)
PT (2) PT3216871T (hr)
RS (2) RS56458B1 (hr)
RU (2) RU2743589C2 (hr)
SG (3) SG11201401181YA (hr)
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Families Citing this family (43)

* 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
EP2792236B2 (en) 2009-07-08 2023-03-22 Kymab Limited Animal models and therapeutic molecules
HUE045591T2 (hu) 2010-02-08 2019-12-30 Regeneron Pharma Közönséges könnyûláncú egér
US20130045492A1 (en) 2010-02-08 2013-02-21 Regeneron Pharmaceuticals, Inc. Methods For Making Fully Human Bispecific Antibodies Using A Common Light Chain
US9796788B2 (en) 2010-02-08 2017-10-24 Regeneron Pharmaceuticals, Inc. Mice expressing a limited immunoglobulin light chain repertoire
RU2750219C2 (ru) 2010-08-02 2021-06-24 Ридженерон Фармасьютикалз, Инк. Мыши, у которых вырабатываются связывающие белки, содержащие vl-домены
RS59661B2 (sr) 2011-02-25 2023-06-30 Regeneron Pharma Adam6 miševi
MY172718A (en) 2011-08-05 2019-12-11 Regeneron Pharma Humanized universal light chain mice
AU2012311288B2 (en) 2011-09-19 2017-08-17 Kymab Limited Manipulation of immunoglobulin gene diversity and multi-antibody therapeutics
EP2761008A1 (en) 2011-09-26 2014-08-06 Kymab Limited Chimaeric surrogate light chains (slc) comprising human vpreb
HUE057680T2 (hu) 2011-10-17 2022-06-28 Regeneron Pharma Korlátozott immunglobulin-nehézlánccal rendelkezõ egerek
US9253965B2 (en) 2012-03-28 2016-02-09 Kymab Limited Animal models and therapeutic molecules
CA2859408C (en) 2011-12-20 2020-06-16 Regeneron Pharmaceuticals, Inc. 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
PL3597037T3 (pl) * 2012-06-12 2021-10-25 Regeneron Pharmaceuticals, Inc. Humanizowane zwierzęta inne niż ludzie z ograniczonymi loci łańcucha ciężkiego immunoglobuliny
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
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
WO2015049517A2 (en) 2013-10-01 2015-04-09 Kymab Limited Animal models and therapeutic molecules
WO2015112790A2 (en) * 2014-01-24 2015-07-30 Children's Medical Center Corporation High-throughput mouse model for optimizing antibody affinities
ES2762640T3 (es) 2014-03-21 2020-05-25 Regeneron Pharma Proteínas VL de unión a antígeno que exhiben diferentes características de unión
WO2015143414A2 (en) 2014-03-21 2015-09-24 Regeneron Pharmaceuticals, Inc. Non-human animals that make single domain binding proteins
US20170121399A1 (en) 2014-05-16 2017-05-04 Ablynx N.V. Improved immunoglobulin variable domains
CN107438622A (zh) 2015-03-19 2017-12-05 瑞泽恩制药公司 选择结合抗原的轻链可变区的非人动物
CN108777951B (zh) 2016-01-13 2021-11-05 瑞泽恩制药公司 具有包括改造的多样性簇的免疫球蛋白重链可变区的非人动物及其用途
RU2018130010A (ru) 2016-02-16 2020-03-17 Регенерон Фармасьютикалз, Инк. Животные, отличные от человека, имеющие мутантный ген кинурениназы
KR102628909B1 (ko) 2016-05-20 2024-01-25 리제너론 파마슈티칼스 인코포레이티드 다중 가이드 RNAs를 이용한 면역학적 내성 파괴 방법
PT3462853T (pt) 2016-06-03 2023-04-21 Regeneron Pharma Animais não humanos que expressam desoxinucleotidiltransferase terminal exógena
AU2017391167B2 (en) 2016-11-04 2024-02-15 Regeneron Pharmaceuticals, Inc. Non-human animals having an engineered immunoglobulin lambda light chain locus
CN108265035A (zh) * 2016-12-30 2018-07-10 深圳先进技术研究院 一种进化噬菌体宿主特异性的方法
US20210345591A1 (en) 2017-12-05 2021-11-11 Regeneron Pharmaceuticals, Inc. Non-human animals having an engineered immunoglobulin lambda light chain and uses thereof
CN112040769B (zh) 2018-03-24 2023-05-16 瑞泽恩制药公司 用于产生针对肽-mhc复合物的治疗抗体的经过基因修饰的非人动物、制造方法和用途
SG11202008620VA (en) 2018-03-26 2020-10-29 Regeneron Pharma Humanized rodents for testing therapeutic agents
CN112312766A (zh) 2018-06-14 2021-02-02 瑞泽恩制药公司 在免疫球蛋白重链编码序列中具有dh-dh重排能力的非人动物
US20220330532A1 (en) 2019-06-05 2022-10-20 Regeneron Pharmaceuticals, Inc. Non-human animals having a limited lambda light chain repertoire expressed from the kappa locus and uses thereof
CN114901678A (zh) 2019-12-02 2022-08-12 瑞泽恩制药公司 肽-mhc ii蛋白构建体及其用途
JP2023540808A (ja) 2020-09-11 2023-09-26 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 抗原特異的抗体の同定及び産生
JP2024500399A (ja) 2020-12-16 2024-01-09 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 ヒト化Ｆｃアルファ受容体を発現するマウス
TW202241934A (zh) * 2020-12-23 2022-11-01 美商再生元醫藥公司 編碼錨定修飾抗體之核酸及其用途
WO2023179620A1 (en) * 2022-03-21 2023-09-28 Biocytogen Pharmaceuticals (Beijing) Co., Ltd. Genetically modified non-human animals with humanized immunoglobulin and mhc loci

Family Cites Families (84)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB8823869D0 (en) 1988-10-12 1988-11-16 Medical Res Council Production of antibodies
WO1991000906A1 (en) 1989-07-12 1991-01-24 Genetics Institute, Inc. Chimeric and transgenic animals capable of producing human antibodies
US6150584A (en) 1990-01-12 2000-11-21 Abgenix, Inc. Human antibodies derived from immunized xenomice
EP0463151B1 (en) 1990-01-12 1996-06-12 Cell Genesys, Inc. Generation of xenogeneic 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
US6075181A (en) 1990-01-12 2000-06-13 Abgenix, Inc. 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
US7041871B1 (en) 1995-10-10 2006-05-09 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
CA2161351C (en) 1993-04-26 2010-12-21 Nils Lonberg Transgenic non-human animals capable of producing heterologous antibodies
EP1978033A3 (en) * 1995-04-27 2008-12-24 Amgen Fremont Inc. Human antibodies derived from immunized xenomice
EP1500329B1 (en) 1996-12-03 2012-03-21 Amgen Fremont Inc. Human antibodies that specifically bind human TNF alpha
CN1203922A (zh) 1997-03-21 1999-01-06 三共株式会社 人源化抗人fas抗体
US20020062010A1 (en) 1997-05-02 2002-05-23 Genentech, Inc. Method for making multispecific antibodies having heteromultimeric and common components
FI105105B (fi) * 1998-02-27 2000-06-15 Finnish Immunotechnology Ltd O Itsereplikoiva DNA-vektori immunisoimiseksi HIV:ta vastaan
AU5043200A (en) 1999-05-27 2000-12-18 Human Genome Sciences, Inc. Adam polynucleotides and polypeptides
CN101498731A (zh) * 2000-05-18 2009-08-05 日本烟草产业株式会社 抗协同刺激信号转导分子ailim的人单克隆抗体及其药物用途
US20020028488A1 (en) * 2000-06-19 2002-03-07 Sujay Singh Transgenic avian species for making human and chimeric antibodies
US7129084B2 (en) 2000-08-03 2006-10-31 Therapeutic Human Polyclonals, Inc. Production of humanized antibodies in transgenic animals
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
TWI255272B (en) 2000-12-06 2006-05-21 Guriq Basi Humanized antibodies that recognize beta amyloid peptide
GB0110029D0 (en) 2001-04-24 2001-06-13 Grosveld Frank Transgenic animal
US7034134B2 (en) 2001-04-26 2006-04-25 Bristol-Myers Squibb Company Polynucleotide encoding a novel metalloprotease highly expressed in the testis, MMP-29
JP4115281B2 (ja) 2001-05-11 2008-07-09 キリンファーマ株式会社 ヒト抗体λ軽鎖遺伝子を含むヒト人工染色体、および子孫伝達可能な該ヒト人工染色体を含む非ヒト動物
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
ATE514717T1 (de) 2002-07-18 2011-07-15 Merus B V Rekombinante produktion von antikörpermischungen
GB0228210D0 (en) 2002-12-03 2003-01-08 Babraham Inst Single chain antibodies
AR044388A1 (es) 2003-05-20 2005-09-07 Applied Molecular Evolution Moleculas de union a cd20
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
AU2004257292A1 (en) 2003-07-15 2005-01-27 Therapeutic Human Polyclonals, Inc. Humanized immunoglobulin loci
US20050153392A1 (en) 2003-08-11 2005-07-14 Roland Buelow Transgenesis with humanized immunoglobulin loci
EP1660186B1 (en) 2003-08-18 2013-12-25 MedImmune, LLC Humanization of antibodies
RU2251699C1 (ru) 2003-09-25 2005-05-10 Киселев Всеволод Иванович Способ ранней и доклинической диагностики цервикального рака
WO2005038001A2 (en) 2003-10-14 2005-04-28 Therapeutic Human Polyclonals, Inc. Improved transgenesis by sperm-mediated gene transfer
CN101076542A (zh) * 2004-09-13 2007-11-21 伊沃詹尼克斯有限公司 特异性针对肝细胞癌和其他癌的抗体及其用途
EP1874817A2 (en) 2005-04-29 2008-01-09 Innate Pharma Transgenic animals and methods of making recombinant antibodies
BRPI0706750A2 (pt) 2006-01-25 2011-04-05 Univ Erasmus Medical Ct geração de anticorpos de cadeia pesada em animais transgênicos
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
DK2374818T3 (da) 2006-06-02 2013-01-21 Regeneron Pharma Højaffinitetsantistoffer mod human IL-6-receptor
LT2602323T (lt) 2007-06-01 2018-04-10 Open Monoclonal Technology, Inc. Kompozicijos ir būdai endogeninių imunoglobulinų genams slopinti ir transgeniniams žmogaus idiotipo antikūnams gaminti
WO2009013620A2 (en) 2007-06-11 2009-01-29 Erasmus University Medical Center Rotterdam Homologous recombination
WO2009097006A2 (en) * 2007-08-10 2009-08-06 Medarex, Inc. Hco32 and hco27 and related examples
WO2009042589A1 (en) * 2007-09-24 2009-04-02 Vanderbilt University Monoclonal antibodies to respiratory syncytial virus and uses thereof
KR20100103810A (ko) 2007-12-10 2010-09-28 알리바 바이오파마수티컬스, 아이엔씨. 동종 재조합에 의한 표적화된 영역의 순차적인 치환 방법
ES2563483T3 (es) 2008-04-11 2016-03-15 Chugai Seiyaku Kabushiki Kaisha Molécula de unión a antígeno capaz de unirse repetidamente a dos o más moléculas de antígeno
EP2271758B1 (en) 2008-04-14 2018-09-12 Innovative Targeting Solutions Inc. Sequence diversity generation in immunoglobulins
CN102099378B (zh) * 2008-05-16 2016-01-20 埃博灵克斯股份有限公司 针对CXCR4和其他GPCRs的氨基酸序列以及包含所述氨基酸序列的多肽
US20110123527A1 (en) 2008-05-23 2011-05-26 Hiroaki Shizuya Method of generating single vl domain antibodies in transgenic animals
WO2010039900A2 (en) 2008-09-30 2010-04-08 Aliva Biopharmaceuticals, Inc. Non-human mammals for the production of chimeric antibodies
ES2613730T3 (es) 2008-12-18 2017-05-25 Erasmus University Medical Center Rotterdam Animales transgénicos no humanos que expresan anticuerpos humanizados y su uso
GB0905023D0 (en) 2009-03-24 2009-05-06 Univ Erasmus Medical Ct Binding molecules
KR20120027055A (ko) * 2009-06-26 2012-03-20 리제네론 파라마큐티칼스 인코포레이티드 천연 면역글로불린 포맷을 가지는 용이하게 분리된 이중특이성 항체
EP2792236B2 (en) 2009-07-08 2023-03-22 Kymab Limited Animal models and therapeutic molecules
RU2425880C2 (ru) * 2009-07-30 2011-08-10 Учреждение Российской академии наук Институт общей генетики им. Н.И. Вавилова РАН Способ получения трансгенных мышей
SG181477A1 (en) 2009-12-10 2012-07-30 Regeneron Pharma Mice that make heavy chain antibodies
US20120021409A1 (en) 2010-02-08 2012-01-26 Regeneron Pharmaceuticals, Inc. Common Light Chain Mouse
HUE045591T2 (hu) 2010-02-08 2019-12-30 Regeneron Pharma Közönséges könnyûláncú egér
US20130185821A1 (en) 2010-02-08 2013-07-18 Regeneron Pharmaceuticals, Inc. Common Light Chain Mouse
US9796788B2 (en) 2010-02-08 2017-10-24 Regeneron Pharmaceuticals, Inc. Mice expressing a limited immunoglobulin light chain repertoire
NZ605966A (en) 2010-06-17 2015-04-24 Kymab Ltd Animal models and therapeutic molecules
RU2750219C2 (ru) 2010-08-02 2021-06-24 Ридженерон Фармасьютикалз, Инк. Мыши, у которых вырабатываются связывающие белки, содержащие vl-домены
EP2638155A1 (en) 2010-11-08 2013-09-18 Kymab Limited Cells & vertebrates for enhanced somatic hypermutation and class switch recombination
RS59661B2 (sr) 2011-02-25 2023-06-30 Regeneron Pharma Adam6 miševi
MY172718A (en) 2011-08-05 2019-12-11 Regeneron Pharma Humanized universal light chain mice
AU2012311288B2 (en) 2011-09-19 2017-08-17 Kymab Limited Manipulation of immunoglobulin gene diversity and multi-antibody therapeutics
WO2013041845A2 (en) 2011-09-19 2013-03-28 Kymab Limited Animals, repertoires & methods
EP2761008A1 (en) 2011-09-26 2014-08-06 Kymab Limited Chimaeric surrogate light chains (slc) comprising human vpreb
HUE057680T2 (hu) 2011-10-17 2022-06-28 Regeneron Pharma Korlátozott immunglobulin-nehézlánccal rendelkezõ egerek
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
CA2859408C (en) * 2011-12-20 2020-06-16 Regeneron Pharmaceuticals, Inc. Humanized light chain mice
MY172730A (en) 2012-03-16 2019-12-11 Regeneron Pharma Histidine engineered light chain antibodies and genetically modified non-human animals for generating the same
WO2013144567A1 (en) 2012-03-28 2013-10-03 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
PL3597037T3 (pl) 2012-06-12 2021-10-25 Regeneron Pharmaceuticals, Inc. Humanizowane zwierzęta inne niż ludzie z ograniczonymi loci łańcucha ciężkiego immunoglobuliny
MY178882A (en) 2013-02-20 2020-10-21 Regeneron Pharma Non-human animals with modified immunoglobulin heavy chain sequences
PL2967013T3 (pl) 2013-03-13 2019-07-31 Regeneron Pharmaceuticals, Inc. Mysz, w której zachodzi ekspresja ograniczonego repertuaru lekkiego łańcucha immunoglobuliny

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