CN104508135B - 用于在体内产生双重特异性免疫球蛋白或者仅高变重链免疫球蛋白的转基因非人脊椎动物 - Google Patents

用于在体内产生双重特异性免疫球蛋白或者仅高变重链免疫球蛋白的转基因非人脊椎动物 Download PDF

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CN104508135B
CN104508135B CN201380038167.0A CN201380038167A CN104508135B CN 104508135 B CN104508135 B CN 104508135B CN 201380038167 A CN201380038167 A CN 201380038167A CN 104508135 B CN104508135 B CN 104508135B
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antibody
cell
human
vertebrate
light chain
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CN104508135A (zh
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V·热尔马舍韦斯基
E-C·李
H·阿里
J·克拉贝
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Kymab Ltd
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    • 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
    • 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
    • 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
    • C07K16/468—Immunoglobulins having two or more different antigen binding sites, e.g. multifunctional antibodies
    • C—CHEMISTRY; METALLURGY
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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
    • A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
    • A01K2207/00—Modified animals
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    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
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    • 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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    • A01K2217/00—Genetically modified animals
    • A01K2217/20—Animal model comprising regulated expression system
    • A01K2217/206—Animal model comprising tissue-specific expression system, e.g. tissue specific expression of transgene, of Cre recombinase
    • 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
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    • A01K2267/01—Animal expressing industrially exogenous proteins
    • 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
    • C07K16/462—Igs containing a variable region (Fv) from one specie and a constant region (Fc) from another
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/30—Immunoglobulins specific features characterized by aspects of specificity or valency
    • C07K2317/31—Immunoglobulins specific features characterized by aspects of specificity or valency multispecific
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/30—Immunoglobulins specific features characterized by aspects of specificity or valency
    • C07K2317/35—Valency
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
    • C07K2317/51—Complete heavy chain or Fd fragment, i.e. VH + CH1
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    • 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
    • C12N2015/8518—Vectors or expression systems specially adapted for eukaryotic hosts for animal cells for producing genetically modified animals, e.g. transgenic expressing industrially exogenous proteins, e.g. for pharmaceutical use, human insulin, blood factors, immunoglobulins, pseudoparticles
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CN201380038167.0A 2012-05-17 2013-05-17 用于在体内产生双重特异性免疫球蛋白或者仅高变重链免疫球蛋白的转基因非人脊椎动物 Active CN104508135B (zh)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
GB1208708.6 2012-05-17
GB1208708.6A GB2502127A (en) 2012-05-17 2012-05-17 Multivalent antibodies and in vivo methods for their production
PCT/GB2013/051280 WO2013171505A2 (en) 2012-05-17 2013-05-17 In vivo guided selection & antibodies

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CN104508135A CN104508135A (zh) 2015-04-08
CN104508135B true CN104508135B (zh) 2017-09-22

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US (2) US10667501B2 (enExample)
EP (2) EP4116427A1 (enExample)
JP (1) JP2015519055A (enExample)
CN (1) CN104508135B (enExample)
GB (1) GB2502127A (enExample)
SG (1) SG11201406947RA (enExample)
WO (1) WO2013171505A2 (enExample)

Families Citing this family (50)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2006008548A2 (en) 2004-07-22 2006-01-26 Erasmus University Medical Centre Rotterdam Binding molecules
EP3028565B1 (en) 2009-07-08 2017-09-27 Kymab Limited Animal models and therapeutic molecules
US10662256B2 (en) 2010-07-26 2020-05-26 Trianni, Inc. Transgenic mammals and methods of use thereof
RU2580017C2 (ru) 2010-07-26 2016-04-10 Трианни, Инк. Трансгенные животные и способы применения
US10793829B2 (en) 2010-07-26 2020-10-06 Trianni, Inc. Transgenic mammals and methods of use thereof
RU2612903C2 (ru) 2010-08-02 2017-03-13 Ридженерон Фармасьютикалз, Инк. Мыши, у которых вырабатываются связывающие белки, содержащие vl-домены
EP2757875B2 (en) 2011-09-19 2023-03-22 Kymab Limited Manipulation of immunoglobulin gene diversity and multi-antibody therapeutics
WO2013045916A1 (en) 2011-09-26 2013-04-04 Kymab Limited Chimaeric surrogate light chains (slc) comprising human vpreb
PL3216871T3 (pl) 2011-10-17 2022-03-21 Regeneron Pharmaceuticals, Inc. Ograniczony łańcuch ciężki immonoglobuliny pochodzącej od myszy
US9253965B2 (en) 2012-03-28 2016-02-09 Kymab Limited Animal models and therapeutic molecules
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
EP2858487B1 (en) 2012-06-12 2019-10-23 Regeneron Pharmaceuticals, Inc. Humanized non-human animals with restricted immunoglobulin heavy chain loci
RS57582B1 (sr) 2013-02-20 2018-11-30 Regeneron Pharma Nehumane životinje sa modifikovanim sekvencama imunoglobulinskog teškog lanca
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
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
WO2015049517A2 (en) 2013-10-01 2015-04-09 Kymab Limited Animal models and therapeutic molecules
WO2015143406A2 (en) 2014-03-21 2015-09-24 Regeneron Pharmaceuticals, Inc. Vl antigen binding proteins exhibiting distinct binding characteristics
RU2016141307A (ru) 2014-03-21 2018-04-24 Регенерон Фармасьютикалз, Инк. Отличные от человека животные, которые вырабатывают однодоменные связывающие белки
GB2584219B (en) * 2014-10-22 2021-03-24 Crescendo Biologics Ltd Transgenic Mice
GB2547587B (en) 2014-10-22 2020-12-09 Crescendo Biologics Ltd Transgenic mice
US11111314B2 (en) 2015-03-19 2021-09-07 Regeneron Pharmaceuticals, Inc. Non-human animals that select for light chain variable regions that bind antigen
EP3322735A4 (en) 2015-07-15 2019-03-13 Zymeworks Inc. ACTIVE CONJUGATED BIS-SPECIFIC ANTIGEN-BONDING CONSTRUCTS
KR20180038055A (ko) * 2015-08-24 2018-04-13 트리아니, 인코포레이티드 면역글로불린의 강화된 생산
WO2017095939A1 (en) 2015-12-03 2017-06-08 Trianni, Inc. Enhanced immunoglobulin diversity
WO2017136734A1 (en) 2016-02-04 2017-08-10 Trianni, Inc. Enhanced production of immunoglobulins
AU2017244108B2 (en) * 2016-03-29 2021-03-18 University Of Southern California Chimeric antigen receptors targeting cancer
US10988754B2 (en) 2017-07-04 2021-04-27 Cure Vac AG Nucleic acid molecules
IL321714A (en) 2017-10-19 2025-08-01 CureVac SE Novel artificial nucleic acid molecules
CN109970860A (zh) * 2017-12-27 2019-07-05 信达生物制药(苏州)有限公司 三链抗体、其制备方法及其用途
SMT202500038T1 (it) * 2018-03-24 2025-03-12 Regeneron Pharma Topi o ratti geneticamente modificati per la generazione di anticorpi terapeutici contro complessi peptide-mhc, metodi di produzione e loro utilizzo
KR20250121150A (ko) * 2018-03-26 2025-08-11 리제너론 파마슈티칼스 인코포레이티드 치료제를 시험하기 위한 인간화된 설치류
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
GB2576914A (en) 2018-09-06 2020-03-11 Kymab Ltd Antigen-binding molecules comprising unpaired variable domains produced in mammals
TW202039534A (zh) 2018-12-14 2020-11-01 美商美國禮來大藥廠 KRAS變體mRNA分子
AU2020226445B2 (en) 2019-02-18 2025-05-29 Biocytogen Pharmaceuticals (Beijing) Co., Ltd. Genetically modified non-human animals with humanized immunoglobulin locus
AU2020253023B2 (en) 2019-03-29 2022-07-14 F. Hoffmann-La Roche Ag Method for the generation of an FcRn expressing cell by targeted integration of multiple expression cassettes in a defined organization
KR20220024637A (ko) * 2019-06-19 2022-03-03 에프. 호프만-라 로슈 아게 정의된 조직의 다수 발현 카세트들의 표적화 통합에 의한 3가 항체 발현 세포의 생성 방법
BR112021025806A2 (pt) * 2019-06-28 2022-02-08 Hoffmann La Roche Métodos para produzir um anticorpo da subclasse igg1 humana cultivando uma célula cho e uso da remoção de sítios de splice de doador não pareados em uma parte de uma sequência de ácido nucleico de humano ou hamster
KR20210095781A (ko) 2020-01-24 2021-08-03 주식회사 에이프릴바이오 항원결합 단편 및 생리활성 이펙터 모이어티로 구성된 융합 컨스트럭트를 포함하는 다중결합항체 및 이를 포함하는 약학조성물
MX2022013898A (es) 2020-05-05 2023-02-09 Regeneron Pharma Car que comprende cd28 zeta y cd3 zeta.
AU2021283564B2 (en) 2020-06-02 2025-05-29 Biocytogen Pharmaceuticals (Beijing) Co., Ltd. Genetically modified non-human animals with common light chain immunoglobulin locus
EP4211155A1 (en) 2020-09-11 2023-07-19 Regeneron Pharmaceuticals, Inc. Identification and production of antigen-specific antibodies
EP4262373A1 (en) 2020-12-16 2023-10-25 Regeneron Pharmaceuticals, Inc. Mice expressing humanized fc alpha receptors
CA3218564A1 (en) * 2021-05-05 2022-11-10 Leveragen, Inc. Engineered non-human animals for producing antibodies
CN117057015B (zh) * 2023-08-18 2025-05-02 国家海洋环境监测中心 海上风力发电结构极端荷载计算分析方法
EP4512243A1 (en) 2023-08-21 2025-02-26 Kymab Limited Binding molecules
WO2025088088A1 (en) 2023-10-27 2025-05-01 CureVac SE Rna composition for improving cell therapy

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2007096779A2 (en) * 2006-01-25 2007-08-30 Erasmus University Medical Center Rotterdam Generation of heavy-chain only antibodies in transgenic animals
CN101410412A (zh) * 2006-01-25 2009-04-15 伊拉兹马斯大学鹿特丹医学中心 在转基因动物中产生仅有重链之抗体

Family Cites Families (198)

* 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
US6713610B1 (en) 1990-01-12 2004-03-30 Raju Kucherlapati Human antibodies derived from immunized xenomice
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
DE69133566T2 (de) 1990-01-12 2007-12-06 Amgen Fremont Inc. Bildung von xenogenen Antikörpern
US6300129B1 (en) 1990-08-29 2001-10-09 Genpharm International Transgenic non-human animals for producing heterologous antibodies
US6255458B1 (en) 1990-08-29 2001-07-03 Genpharm International High affinity human antibodies and human antibodies against digoxin
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
US5545806A (en) 1990-08-29 1996-08-13 Genpharm International, Inc. Ransgenic non-human animals for producing heterologous antibodies
US5633425A (en) 1990-08-29 1997-05-27 Genpharm International, Inc. Transgenic non-human animals capable of producing heterologous antibodies
KR100272077B1 (ko) 1990-08-29 2000-11-15 젠팜인터내셔날,인코포레이티드 이종 항체를 생산할 수 있는 전이유전자를 가진 인간이외의 동물
US5770429A (en) * 1990-08-29 1998-06-23 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
CA2124967C (en) 1991-12-17 2008-04-08 Nils Lonberg Transgenic non-human animals capable of producing heterologous antibodies
WO1994002602A1 (en) 1992-07-24 1994-02-03 Cell Genesys, Inc. Generation of xenogeneic antibodies
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
JP4242447B2 (ja) 1993-01-22 2009-03-25 イミュネックス・コーポレーション Ｃｄ４０リガンド遺伝子の突然変異の検出および治療
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
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
US6077667A (en) 1996-06-26 2000-06-20 Bradley; Allan Method for chromosomal rearrangement by consecutive gene targeting of two recombination substrates to the deletion endpoints
CA2258518C (en) 1996-06-27 2011-11-22 Vlaams Interuniversitair Instituut Voor Biotechnologie Vzw Recognition molecules interacting specifically with the active site or cleft of a target molecule
DE69738539T2 (de) 1996-12-03 2009-03-26 Amgen Fremont Inc. Vollkommen humane Antikörper die EGFR binden
US6319906B1 (en) 1996-12-31 2001-11-20 Isis Pharmaceuticals Oligonucleotide compositions and methods for the modulation of the expression of B7 protein
DE19742706B4 (de) 1997-09-26 2013-07-25 Pieris Proteolab Ag Lipocalinmuteine
ATE401410T1 (de) 1997-11-18 2008-08-15 Pioneer Hi Bred Int Zusammensetzungen und verfahren für die genetische modifizierung von pflanzen
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
IL127127A0 (en) 1998-11-18 1999-09-22 Peptor Ltd Small functional units of antibody heavy chain variable regions
US7115396B2 (en) 1998-12-10 2006-10-03 Compound Therapeutics, Inc. Protein scaffolds for antibody mimics and other binding proteins
US6818418B1 (en) 1998-12-10 2004-11-16 Compound Therapeutics, Inc. Protein scaffolds for antibody mimics and other binding proteins
US6914128B1 (en) 1999-03-25 2005-07-05 Abbott Gmbh & Co. Kg Human antibodies that bind human IL-12 and methods for producing
JP2003503015A (ja) 1999-05-03 2003-01-28 メダレツクス・インコーポレーテツド スタフィロコッカス・アウレウスに対するヒト抗体
US6833268B1 (en) 1999-06-10 2004-12-21 Abgenix, Inc. Transgenic animals for producing specific isotypes of human antibodies via non-cognate switch regions
US7605238B2 (en) 1999-08-24 2009-10-20 Medarex, Inc. Human CTLA-4 antibodies and their uses
CA2307503A1 (en) 2000-05-02 2001-11-02 Carlos F. Barbas Iii Peptides for use as a vaccine or treatment for hiv infection
EP2386575A3 (en) 2000-06-29 2011-11-30 Abbott Laboratories Dual specificity antibodies and methods of making and using
AU2001270609A1 (en) * 2000-06-30 2002-01-14 Vlaams Interuniversitair Instituut Voor Biotechnologie Vzw Heterodimeric fusion proteins
AU2001277076A1 (en) 2000-07-21 2002-02-05 The United States Of America As Represented By The Secretary Of Agriculture Methods for the replacement, translocation and stacking of DNA in eukaryotic genomes
EP1332209B1 (en) 2000-09-08 2009-11-11 Universität Zürich Collections of repeat proteins comprising repeat modules
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
WO2002070648A2 (en) 2000-11-17 2002-09-12 Hematech, Llc Expression of xenogenous (human) immunoglobulins in cloned, transgenic ungulates
DK1354034T3 (da) 2000-11-30 2008-03-25 Medarex Inc Transgene transchromosomale gnavere til fremstilling af humane antistoffer
WO2002059263A2 (en) 2000-12-19 2002-08-01 Sunol Molecular Corporation Transgenic animals comprising a humanized immune system
AR032028A1 (es) 2001-01-05 2003-10-22 Pfizer Anticuerpos contra el receptor del factor de crecimiento similar a insulina
GB0110029D0 (en) 2001-04-24 2001-06-13 Grosveld Frank Transgenic animal
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
CA2457636C (en) 2001-08-10 2012-01-03 Aberdeen University Antigen binding domains
WO2003031656A1 (en) 2001-10-05 2003-04-17 United States Environmental Protection Agency Genetic testing for male factor infertility
US20060199204A1 (en) 2001-10-05 2006-09-07 U.S. Epa Genetic testing for male factor infertility
ES2283368T3 (es) 2001-11-14 2007-11-01 Affimed Therapeutics Ag Anticuerpos biespecificos anti-cd19 y anti-cd16 y usos de los mismos.
US7435871B2 (en) 2001-11-30 2008-10-14 Amgen Fremont Inc. Transgenic animals bearing human Igλ 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
SI1523496T1 (sl) 2002-07-18 2011-11-30 Merus B V Rekombinantno proizvajanje zmesi protiteles
AU2003278790A1 (en) 2002-09-09 2004-03-29 California Institute Of Technology Methods and compositions for the generation of humanized mice
ES2559763T3 (es) 2002-09-10 2016-02-15 Affimed Gmbh Anticuerpo humano específico de CD3 con propiedades inmunosupresoras
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
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.
CA2512647C (en) 2003-01-07 2013-10-08 Symphogen A/S Method for manufacturing recombinant polyclonal proteins
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
CA2522586C (en) 2003-05-31 2017-02-21 Micromet Ag Pharmaceutical compositions comprising bispecific anti-cd3, anti-cd19 antibody constructs for the treatment of b-cell related disorders
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
CA2531238C (en) 2003-07-04 2015-02-24 Affibody Ab Polypeptides having binding affinity for her2
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
WO2005019255A1 (en) 2003-08-25 2005-03-03 Pieris Proteolab Ag Muteins of tear lipocalin
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
KR20060129246A (ko) 2003-12-05 2006-12-15 컴파운드 쎄라퓨틱스, 인크. 타입 2 혈관 내피 성장 인자 수용체의 억제제
ZA200604620B (en) 2003-12-10 2007-10-31 Medarex Inc IP-10 antibodies and their uses
US7235641B2 (en) 2003-12-22 2007-06-26 Micromet Ag Bispecific antibodies
WO2005092926A2 (en) 2004-03-19 2005-10-06 Amgen Inc. Reducing the risk of human and anti-human antibodies through v gene manipulation
US7625549B2 (en) 2004-03-19 2009-12-01 Amgen Fremont Inc. Determining the risk of human anti-human antibodies in transgenic mice
WO2006008548A2 (en) * 2004-07-22 2006-01-26 Erasmus University Medical Centre 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
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
EP1802193B1 (en) 2004-10-19 2014-04-30 Regeneron Pharmaceuticals, Inc. Method for generating a mouse homozygous for a genetic modification
WO2006055704A2 (en) 2004-11-17 2006-05-26 Curagen Corporation Antibodies directed to ten-m proteins and uses thereof
HRP20110859T1 (hr) 2004-12-21 2011-12-31 Medimmune Limited Protutijela usmjerena na angiopoietin-2 i njihova upotreba
WO2006117699A2 (en) 2005-04-29 2006-11-09 Innate Pharma Transgenic animals and methods of making recombinant antibodies
US20100154070A1 (en) 2005-05-14 2010-06-17 Tian Xu PiggyBac as a Tool for Genetic Manipulation and Analysis in Vertebrates
GB0510790D0 (en) 2005-05-26 2005-06-29 Syngenta Crop Protection Ag Anti-CD16 binding molecules
TWI323734B (en) * 2005-08-19 2010-04-21 Abbott Lab Dual variable domain immunoglobulin and uses thereof
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
US7462759B2 (en) 2006-02-03 2008-12-09 Pioneer Hi-Bred International, Inc. Brittle stalk 2 gene family and related methods and uses
EP2505058A1 (en) * 2006-03-31 2012-10-03 Medarex, Inc. Transgenic animals expressing chimeric antibodies for use in preparing human antibodies
CA2652976C (en) 2006-06-02 2015-08-11 Regeneron Pharmaceuticals, Inc. High affinity antibodies to human il-6 receptor
ATE525093T1 (de) 2006-06-27 2011-10-15 Sanofi Pasteur Vaxdesign Corp Modelle für die bewertung von impfstoffen
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
WO2008054606A2 (en) 2006-10-02 2008-05-08 Regeneron Pharmaceuticals, Inc. 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
US7556337B2 (en) * 2006-11-02 2009-07-07 Xerox Corporation System and method for evaluating line formation in an ink jet imaging device to normalize print head driving voltages
NO347649B1 (no) 2006-12-14 2024-02-12 Regeneron Pharma Humant antistoff eller antistoff fragment som spesifikt binder human deltaliknende ligand 4 (hDII4), nukleinsyremolekyl som koder for slike og vektor og vert-vektorsystemer, samt fremgangsmåte for fremstilling, sammensetning og anvendelse.
GB0700194D0 (en) 2007-01-05 2007-02-14 Univ Edinburgh Humanisation of animals
EP1958957A1 (en) 2007-02-16 2008-08-20 NascaCell Technologies AG Polypeptide comprising a knottin protein moiety
JP2010520748A (ja) * 2007-02-20 2010-06-17 アナプティスバイオ インコーポレイティッド 体細胞超変異系
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
EP2132312B1 (en) 2007-03-27 2016-01-27 Sea Lane Biotechnologies,llc. Constructs and libraries comprising antibody surrogate light chain sequences
GB0706628D0 (en) * 2007-04-04 2007-05-16 Univ Erasmus Germ-line manipulation 1
NZ581316A (en) 2007-05-25 2012-02-24 Symphogen As Method for manufacturing a recombinant polyclonal protein
EP2602323B1 (en) 2007-06-01 2018-02-28 Open Monoclonal Technology, Inc. Compositions and methods for inhibiting endogenous immunoglobin genes and producing transgenic human idiotype antibodies
WO2009013620A2 (en) 2007-06-11 2009-01-29 Erasmus University Medical Center Rotterdam Homologous recombination
EP2171455A4 (en) * 2007-07-06 2010-11-24 Vaxdesign Corp RAPID GENERATION OF ANTIBODY RESPONSES INDEPENDENT OF T LYMPHOCYTES TO ANTIGENS DEPENDING ON T-CELLS
US20090021474A1 (en) 2007-07-17 2009-01-22 Motorola, Inc. System and method for displaying status information of a multimedia broadcast receiver on an ambient device
WO2009018411A1 (en) 2007-07-31 2009-02-05 Regeneron Pharmaceuticals, Inc. Human antibodies to human cd20 and method of using thereof
EP3293269A1 (en) * 2007-08-03 2018-03-14 MUSC Foundation For Research Development Human monoclonal antibodies and methods for producing the same
US9693539B2 (en) 2007-08-10 2017-07-04 E. R. Squibb & Sons, L.L.C. HCO32 and HCO27 and related examples
RS53661B1 (sr) 2007-08-10 2015-04-30 Regeneron Pharmaceuticals, Inc. Humana antitela visokog afiniteta prema humanom nervnom faktoru rasta
DE112008003232T5 (de) * 2007-11-30 2011-02-24 Glaxo Group Limited, Greenford Antigen-Bindungskonstrukte
WO2009076464A2 (en) 2007-12-10 2009-06-18 Aliva Biopharmaceuticals, Inc. Methods for sequential replacement of targeted region by homologous recombination
US8227577B2 (en) 2007-12-21 2012-07-24 Hoffman-La Roche Inc. Bivalent, bispecific antibodies
WO2009118524A2 (en) 2008-03-26 2009-10-01 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
EP2281845B1 (en) * 2008-04-25 2020-09-02 Kyowa Kirin Co., Ltd. Stable polyvalent antibody
EP2669298A3 (en) * 2008-05-23 2014-02-26 Ablexis, LLC Single variable immunoglobulin domain comprising VL-DH-JL
RU2559524C2 (ru) 2008-06-27 2015-08-10 Мерюс Б.В. Продуцирующие антитела млекопитающие, не являющиеся человеком
LT2346994T (lt) 2008-09-30 2022-03-10 Ablexis, Llc Knock-in pelė, skirta chimerinių antikūnų gamybai
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).
CN112690250B (zh) 2008-12-18 2024-03-08 伊拉兹马斯大学鹿特丹医学中心 表达人源化抗体的非人转基因动物及其用途
CA2750520C (en) 2009-02-04 2017-12-05 Molecular Innovations Methods for screening candidate agents for modulating prorenin and renin, assays for detecting prorenin, and antibodies used therein
EP2401298A1 (en) * 2009-02-24 2012-01-04 Glaxo Group Limited Antigen-binding constructs
GB0905023D0 (en) 2009-03-24 2009-05-06 Univ Erasmus Medical Ct Binding molecules
DK2414507T3 (da) 2009-04-03 2014-08-25 Medical Res Council Mutanter af aktiveringsinduceret cytidin-deaminase (aid) og til anvendelsesfremgangsmåder
WO2010132872A1 (en) 2009-05-15 2010-11-18 Novimmune S.A Combination therapies and methods using anti-cd3 modulating agents and anti-tnf antagonists
EP2435482B1 (en) 2009-05-28 2019-04-03 Glaxo Group Limited Antigen-binding proteins
CA2763493A1 (en) 2009-05-28 2010-12-02 Glaxo Group Ltd. Antigen-binding proteins
TWI560271B (en) 2009-06-26 2016-12-01 Sealane Biotechnologies Llc Expression of surrogate light chains
MX368932B (es) 2009-06-26 2019-10-22 Regeneron Pharma Anticuerpos biespecificos facilmente aislados con formato de inmunoglobulina original.
EP3028565B1 (en) 2009-07-08 2017-09-27 Kymab Limited Animal models and therapeutic molecules
US9445581B2 (en) 2012-03-28 2016-09-20 Kymab Limited Animal models and therapeutic molecules
ES2666584T3 (es) * 2009-07-15 2018-05-07 Aimm Therapeutics B.V. Medios y métodos para producir anticuerpos de alta afinidad
JO3182B1 (ar) 2009-07-29 2018-03-08 Regeneron Pharma مضادات حيوية بشرية عالية الالفة مع تولد الاوعية البشرية - 2
EP2464220A4 (en) 2009-08-13 2014-05-07 Crystal Bioscience Inc Transgenic animal for the production of antibodies with minimal complementarity-determining regions
JP2013509878A (ja) * 2009-11-05 2013-03-21 アナプティスバイオ インコーポレイティッド 鎖シャフリングおよび任意に体細胞超変異を用いる、改善された抗原結合物質の生成方法
AU2010320130B2 (en) 2009-11-17 2015-03-12 Sab, Llc Human artificial chromosome vector
US20120269830A1 (en) 2009-12-07 2012-10-25 Lawrence Horowitz Conjugates with improved pharmacokinetic properties
US8754287B2 (en) 2009-12-10 2014-06-17 Regeneron Pharmaceuticals, Inc. Mice that make heavy chain antibodies
US20120021409A1 (en) 2010-02-08 2012-01-26 Regeneron Pharmaceuticals, Inc. Common Light Chain Mouse
SMT201900372T1 (it) 2010-02-08 2019-09-09 Regeneron Pharma Topo con catena leggera comune
CA2798988C (en) 2010-05-17 2020-03-10 Sangamo Biosciences, Inc. Tal-effector (tale) dna-binding polypeptides and uses thereof
NZ605966A (en) * 2010-06-17 2015-04-24 Kymab Ltd Animal models and therapeutic molecules
SI2480676T1 (sl) 2010-06-22 2016-10-28 Regeneron Pharmaceuticals, Inc. Hibridna mišja lahka veriga
US8890233B2 (en) * 2010-07-06 2014-11-18 Macronix International Co., Ltd. 3D memory array with improved SSL and BL contact layout
EP2407487A1 (en) * 2010-07-14 2012-01-18 F-Star Biotechnologische Forschungs - und Entwicklungsges. M.B.H. Multispecific modular antibody
RU2612903C2 (ru) 2010-08-02 2017-03-13 Ридженерон Фармасьютикалз, Инк. Мыши, у которых вырабатываются связывающие белки, содержащие vl-домены
EP2606064B1 (en) * 2010-08-16 2015-02-25 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)
WO2012063048A1 (en) * 2010-11-08 2012-05-18 Kymab Limited Cells & vertebrates for enhanced somatic hypermutation and class switch recombination
WO2012088313A1 (en) 2010-12-22 2012-06-28 Genentech, Inc. Anti-pcsk9 antibodies and methods of use
DK2813573T1 (da) * 2011-02-25 2015-01-12 Regeneron Pharma ADAM6 mus
HUE068728T2 (hu) 2011-08-05 2025-01-28 Regeneron Pharma Humanizált univerzális könnyûláncú egerek
EP2757875B2 (en) 2011-09-19 2023-03-22 Kymab Limited Manipulation of immunoglobulin gene diversity and multi-antibody therapeutics
JP2014531452A (ja) 2011-09-19 2014-11-27 カイマブ・リミテッド 動物、レパートリーおよび方法
WO2013045916A1 (en) 2011-09-26 2013-04-04 Kymab Limited Chimaeric surrogate light chains (slc) comprising human vpreb
PL3216871T3 (pl) 2011-10-17 2022-03-21 Regeneron Pharmaceuticals, Inc. Ograniczony łańcuch ciężki immonoglobuliny pochodzącej od myszy
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
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
MX378871B (es) 2011-12-20 2025-03-10 Regeneron Pharma Ratones con cadena ligera humanizada.
PL2809150T3 (pl) 2012-02-01 2020-04-30 Regeneron Pharmaceuticals, Inc. Humanizowane myszy wykazujące ekspresję łańcuchów ciężkich zawierających domeny VL
RU2628305C2 (ru) 2012-03-02 2017-08-15 Регенерон Фармасьютиказ, Инк. Человеческие антитела к токсинам clostridium difficile
AU2013204140B2 (en) 2012-03-06 2016-01-28 Regeneron Pharmaceuticals, Inc. Common light chain mouse
CA2865644A1 (en) 2012-03-16 2013-09-19 Regeneron Pharmaceuticals, Inc. 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
US10251377B2 (en) 2012-03-28 2019-04-09 Kymab Limited Transgenic non-human vertebrate for the expression of class-switched, fully human, antibodies
WO2013144567A1 (en) 2012-03-28 2013-10-03 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
FI3597749T3 (fi) 2012-05-25 2023-10-09 Univ California Menetelmiä ja koostumuksia rna-ohjattua kohde-dna-modifikaatiota varten ja rna-ohjattua transkription modulaatiota varten
EP2858487B1 (en) 2012-06-12 2019-10-23 Regeneron Pharmaceuticals, Inc. Humanized non-human animals with restricted immunoglobulin heavy chain loci
KR20150105956A (ko) 2012-12-12 2015-09-18 더 브로드 인스티튜트, 인코퍼레이티드 서열 조작 및 치료적 적용을 위한 시스템, 방법 및 조성물의 전달, 유전자 조작 및 최적화
RS57582B1 (sr) 2013-02-20 2018-11-30 Regeneron Pharma Nehumane životinje sa modifikovanim sekvencama imunoglobulinskog teškog lanca
US9788534B2 (en) 2013-03-18 2017-10-17 Kymab Limited Animal models and therapeutic molecules
US20150033372A1 (en) 2013-05-01 2015-01-29 Kymab Limited Human VpreB & Chimaeric Surrogate Light Chains in Transgenic Non-Human Vertebrates
US9783618B2 (en) 2013-05-01 2017-10-10 Kymab Limited Manipulation of immunoglobulin gene diversity and multi-antibody therapeutics
US9783593B2 (en) 2013-05-02 2017-10-10 Kymab Limited Antibodies, variable domains and chains tailored for human use
US11707056B2 (en) 2013-05-02 2023-07-25 Kymab Limited Animals, repertoires and methods
US20140331339A1 (en) 2013-05-03 2014-11-06 Kymab Limited Transgenic Non-Human Assay Vertebrates, Assays and Kits
US20140331344A1 (en) 2013-05-03 2014-11-06 Kymab Ltd. Transgenic Animals
WO2015049517A2 (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

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2007096779A2 (en) * 2006-01-25 2007-08-30 Erasmus University Medical Center Rotterdam Generation of heavy-chain only antibodies in transgenic animals
CN101410412A (zh) * 2006-01-25 2009-04-15 伊拉兹马斯大学鹿特丹医学中心 在转基因动物中产生仅有重链之抗体

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
Generation of heavy-chain-only antibodies in mice.;JANSSENS RICK. ET AL;《PNAS 》;20061010;第103卷(第41期);15130-15135 *

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CN104508135A (zh) 2015-04-08
WO2013171505A3 (en) 2014-01-03
JP2015519055A (ja) 2015-07-09
US20200267952A1 (en) 2020-08-27
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