CN100497642C - 修饰真核细胞的方法 - Google Patents

修饰真核细胞的方法 Download PDF

Info

Publication number
CN100497642C
CN100497642C CNB018216609A CN01821660A CN100497642C CN 100497642 C CN100497642 C CN 100497642C CN B018216609 A CNB018216609 A CN B018216609A CN 01821660 A CN01821660 A CN 01821660A CN 100497642 C CN100497642 C CN 100497642C
Authority
CN
China
Prior art keywords
gene
cells
embryonic stem
chromosomal locus
ltvec
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Expired - Lifetime
Application number
CNB018216609A
Other languages
English (en)
Chinese (zh)
Other versions
CN1484707A (zh
Inventor
A·N·埃科诺米德斯
A·J·默菲
D·M·瓦伦泽拉
D·弗伦德维
G·D·彦科普洛斯
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Regeneron Pharmaceuticals Inc
Original Assignee
Regeneron Pharmaceuticals Inc
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Regeneron Pharmaceuticals Inc filed Critical Regeneron Pharmaceuticals Inc
Publication of CN1484707A publication Critical patent/CN1484707A/zh
Application granted granted Critical
Publication of CN100497642C publication Critical patent/CN100497642C/zh
Anticipated expiration legal-status Critical
Expired - Lifetime legal-status Critical Current

Links

Images

Classifications

    • 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
    • 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
    • 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
    • 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
    • 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
    • C12N15/87—Introduction of foreign genetic material using processes not otherwise provided for, e.g. co-transformation
    • C12N15/90—Stable introduction of foreign DNA into chromosome
    • C12N15/902—Stable introduction of foreign DNA into chromosome using homologous recombination
    • C12N15/907—Stable introduction of foreign DNA into chromosome using homologous recombination in mammalian cells
    • 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
    • A01K2217/05—Animals comprising random inserted nucleic acids (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
    • A01K2227/00—Animals characterised by species
    • A01K2227/10—Mammal
    • A01K2227/105—Murine

Landscapes

  • Life Sciences & Earth Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Genetics & Genomics (AREA)
  • Engineering & Computer Science (AREA)
  • Biotechnology (AREA)
  • Zoology (AREA)
  • Organic Chemistry (AREA)
  • Chemical & Material Sciences (AREA)
  • Wood Science & Technology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Biomedical Technology (AREA)
  • General Engineering & Computer Science (AREA)
  • General Health & Medical Sciences (AREA)
  • Molecular Biology (AREA)
  • Environmental Sciences (AREA)
  • Microbiology (AREA)
  • Physics & Mathematics (AREA)
  • Biophysics (AREA)
  • Plant Pathology (AREA)
  • Biochemistry (AREA)
  • Mycology (AREA)
  • Cell Biology (AREA)
  • Biodiversity & Conservation Biology (AREA)
  • Animal Husbandry (AREA)
  • Animal Behavior & Ethology (AREA)
  • Veterinary Medicine (AREA)
  • Micro-Organisms Or Cultivation Processes Thereof (AREA)
  • Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
CNB018216609A 2000-10-31 2001-10-31 修饰真核细胞的方法 Expired - Lifetime CN100497642C (zh)

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
US24466500P 2000-10-31 2000-10-31
US60/244,665 2000-10-31
US09/732,234 US6586251B2 (en) 2000-10-31 2000-12-07 Methods of modifying eukaryotic cells
US09/732,234 2000-12-07

Publications (2)

Publication Number Publication Date
CN1484707A CN1484707A (zh) 2004-03-24
CN100497642C true CN100497642C (zh) 2009-06-10

Family

ID=26936709

Family Applications (1)

Application Number Title Priority Date Filing Date
CNB018216609A Expired - Lifetime CN100497642C (zh) 2000-10-31 2001-10-31 修饰真核细胞的方法

Country Status (18)

Country Link
US (1) US6586251B2 (enExample)
EP (1) EP1399575B1 (enExample)
JP (7) JP5339566B2 (enExample)
KR (1) KR100833136B1 (enExample)
CN (1) CN100497642C (enExample)
AT (1) ATE332388T1 (enExample)
AU (2) AU2002220048B2 (enExample)
BR (1) BRPI0115096B1 (enExample)
CA (1) CA2426398C (enExample)
CZ (1) CZ304856B6 (enExample)
DE (1) DE60121372T2 (enExample)
HU (1) HU227639B1 (enExample)
MX (1) MXPA03003797A (enExample)
NO (1) NO332300B1 (enExample)
NZ (1) NZ525511A (enExample)
PL (1) PL204759B1 (enExample)
RU (1) RU2290441C2 (enExample)
WO (1) WO2002036789A2 (enExample)

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN105010238A (zh) * 2010-02-08 2015-11-04 瑞泽恩制药公司 共有轻链小鼠
CN107002093A (zh) * 2014-06-26 2017-08-01 瑞泽恩制药公司 用于靶向遗传修饰的方法和组合物，以及这些组合物的使用方法

Families Citing this family (223)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6908744B1 (en) * 2000-03-14 2005-06-21 Regeneron Pharmaceuticals, Inc. Methods of stimulating cartilage formation
ES2394877T3 (es) * 2000-08-14 2013-02-06 The Government Of The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services Recombinación homóloga mejorada mediada por proteínas de recombinación de lambda
US20050144655A1 (en) 2000-10-31 2005-06-30 Economides Aris N. 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
GB0110029D0 (en) 2001-04-24 2001-06-13 Grosveld Frank Transgenic animal
US7763466B2 (en) 2002-05-17 2010-07-27 Mount Sinai School Of Medicine Of New York University Mesoderm and definitive endoderm cell populations
NZ537277A (en) 2002-07-18 2008-04-30 Crucell Holland Bv Recombinant production of mixtures of antibodies
USRE47770E1 (en) 2002-07-18 2019-12-17 Merus N.V. Recombinant production of mixtures of antibodies
CA2496233A1 (en) * 2002-09-09 2004-03-18 California Institute Of Technology Methods and compositions for the generation of humanized mice
WO2004067725A2 (en) * 2003-01-30 2004-08-12 Regeneron Pharmaceuticals, Inc. Methods of identifying modulators of nmur2-mediated activity
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
EP1802193B1 (en) 2004-10-19 2014-04-30 Regeneron Pharmaceuticals, Inc. Method for generating a mouse homozygous for a genetic modification
US20060117396A1 (en) * 2004-11-30 2006-06-01 Murphy Andrew J Assay methods for identifying modulators of OPSDL3 and transgenic knockouts
BRPI0809042B1 (pt) 2007-03-22 2021-08-31 Biogen Ma Inc. Proteína de ligação a cd154 isolada, seu uso, e composição
KR101703299B1 (ko) 2007-06-01 2017-02-06 오픈 모노클로날 테크놀로지, 인코포레이티드 내생적 면역글로불린 유전자를 억제하고 트랜스제닉 인간 이디오타입 항체를 생산하기 위한 방법 및 조성물
KR20100103810A (ko) * 2007-12-10 2010-09-28 알리바 바이오파마수티컬스, 아이엔씨. 동종 재조합에 의한 표적화된 영역의 순차적인 치환 방법
CA2720903C (en) * 2008-04-14 2019-01-15 Sangamo Biosciences, Inc. Linear donor constructs for targeted integration
US20090328240A1 (en) * 2008-06-24 2009-12-31 Sing George L Genetically modified mice as predictors of immune response
DE102008002715A1 (de) * 2008-06-27 2009-12-31 Evonik Röhm Gmbh 2-Hydroxyisobuttersäure produzierende rekombinante Zelle
PL2346994T3 (pl) 2008-09-30 2022-04-19 Ablexis, Llc Myszy knock-in do wytwarzania chimerycznych przeciwciał
DK3241435T3 (da) 2009-07-08 2021-08-23 Kymab Ltd Dyremodeller og terapeutiske molekyler
US9445581B2 (en) 2012-03-28 2016-09-20 Kymab Limited Animal models and therapeutic molecules
EP4502152A3 (en) 2009-10-06 2025-04-30 Regeneron Pharmaceuticals, Inc. Genetically modified mice and engraftment
CN102666854B (zh) 2009-10-29 2016-08-24 瑞泽恩制药公司 多功能等位基因
WO2011072204A1 (en) 2009-12-10 2011-06-16 Regeneron Pharmaceuticals, Inc. Mice that make heavy chain antibodies
EP3498730B1 (en) 2009-12-21 2026-01-28 Regeneron Pharmaceuticals, Inc. Humanized fc gamma r mice
US9796788B2 (en) 2010-02-08 2017-10-24 Regeneron Pharmaceuticals, Inc. Mice expressing a limited immunoglobulin light chain repertoire
US20120021409A1 (en) 2010-02-08 2012-01-26 Regeneron Pharmaceuticals, Inc. Common Light Chain Mouse
US20130045492A1 (en) 2010-02-08 2013-02-21 Regeneron Pharmaceuticals, Inc. Methods For Making Fully Human Bispecific Antibodies Using A Common Light Chain
PL3248462T3 (pl) 2010-03-31 2024-07-08 Ablexis, Llc Modyfikacja myszy metodami inżynierii genetycznej w celu wytworzenia przeciwciał chimerycznych
US9242014B2 (en) 2010-06-15 2016-01-26 The Regents Of The University Of California Receptor tyrosine kinase-like orphan receptor 1 (ROR1) single chain Fv antibody fragment conjugates and methods of use thereof
MY195217A (en) 2010-06-22 2023-01-11 Regeneron Pharma MICE Expressing An Immunoglobulin Hybrid Light Chain
US10793829B2 (en) 2010-07-26 2020-10-06 Trianni, Inc. Transgenic mammals and methods of use thereof
CN103025884B (zh) 2010-07-26 2015-11-25 特里安尼公司 转基因动物和使用方法
US10662256B2 (en) 2010-07-26 2020-05-26 Trianni, Inc. Transgenic mammals and methods of use thereof
EP2601298B1 (en) 2010-08-02 2016-11-30 Regeneron Pharmaceuticals, Inc. Mice that make binding proteins comprising vl domains
WO2012063048A1 (en) 2010-11-08 2012-05-18 Kymab Limited Cells & vertebrates for enhanced somatic hypermutation and class switch recombination
EP3252076B1 (en) 2011-01-14 2019-09-04 The Regents Of The University Of California Diagnostic use of antibodies against ror-1 protein
PT4233537T (pt) 2011-02-15 2025-09-08 Regeneron Pharma Ratinhos humanizados para m-csf e utilizações dos mesmos
CN105861548B (zh) 2011-02-25 2020-01-10 瑞泽恩制药公司 Adam6小鼠
US10920242B2 (en) 2011-02-25 2021-02-16 Recombinetics, Inc. Non-meiotic allele introgression
EP2527842B1 (en) 2011-05-12 2013-06-05 Regeneron Pharmaceuticals, Inc. Neuropeptide release assay for sodium channels
ES2872081T3 (es) 2011-08-05 2021-11-02 Regeneron Pharma Ratones con cadena ligera universal humanizada
WO2013041845A2 (en) 2011-09-19 2013-03-28 Kymab Limited Animals, repertoires & methods
AU2012311286B2 (en) 2011-09-19 2018-07-26 Kymab Limited Antibodies, variable domains and chains tailored for human use
WO2013045916A1 (en) 2011-09-26 2013-04-04 Kymab Limited Chimaeric surrogate light chains (slc) comprising human vpreb
EP4074833A1 (en) 2011-10-17 2022-10-19 Regeneron Pharmaceuticals, Inc. Restricted immunoglobulin heavy chain mice
US9591835B2 (en) 2011-10-28 2017-03-14 Regeneron Pharmaceuticals, Inc. Genetically modified major histocompatibility complex animals
US9043996B2 (en) 2011-10-28 2015-06-02 Regeneron Pharmaceuticals, Inc. Genetically modified major histocompatibility complex animals
KR102295746B1 (ko) 2011-10-28 2021-09-01 리제너론 파아마슈티컬스, 인크. 유전자 변형된 주요 조직적합성 복합체 마우스
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
RS63220B1 (sr) 2011-10-28 2022-06-30 Regeneron Pharma Genetski modifikovani miševi sa ekspresijom himernih molekula klase ii glavnog kompleksa histokompatibilnosti (mhc)
RS61455B1 (sr) 2011-10-28 2021-03-31 Regeneron Pharma Genetski modifikovani miševi t ćelijskog receptora
EP2773323A4 (en) 2011-10-31 2015-04-22 Merck Sharp & Dohme NANO-SUSPENSION METHOD
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
SMT201900296T1 (it) 2011-12-20 2019-07-11 Regeneron Pharma Topi di catena leggera umanizzata
RU2664185C2 (ru) 2012-02-01 2018-08-15 Регенерон Фармасьютикалз, Инк. Гуманизированные грызуны, которые экспрессируют тяжелые цепи, содержащие домены vl
JP2015509380A (ja) 2012-03-06 2015-03-30 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Ｒｅｇｅｎｅｒｏｎ Ｐｈａｒｍａｃｅｕｔｉｃａｌｓ， Ｉｎｃ． 共通の軽鎖のマウス
US20140013456A1 (en) 2012-03-16 2014-01-09 Regeneron Pharmaceuticals, Inc. Histidine Engineered Light Chain Antibodies and Genetically Modified Non-Human Animals for Generating the Same
WO2013138681A1 (en) 2012-03-16 2013-09-19 Regeneron Pharmaceuticals, Inc. Mice that produce antigen-binding proteins with ph-dependent binding characteristics
HUE037659T2 (hu) 2012-03-16 2018-09-28 Regeneron Pharma Hisztidinmódosított könnyûlánc antitestek és genetikailag módosított rágcsálók ennek az elõállítására
US9801362B2 (en) 2012-03-16 2017-10-31 Regeneron Pharmaceuticals, Inc. Non-human animals expressing pH-sensitive immunoglobulin sequences
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
SG11201405059XA (en) 2012-03-28 2014-09-26 Kymab Ltd Transgenic non-human vertebrate for the expression of class - switched, fully human, antibodies
ES2683071T3 (es) 2012-04-25 2018-09-24 Regeneron Pharmaceuticals, Inc. Direccionamiento mediado por nucleasas con grandes vectores de direccionamiento
NZ703689A (en) 2012-06-12 2016-05-27 Regeneron Pharma Humanized non-human animals with restricted immunoglobulin heavy chain loci
AR091482A1 (es) * 2012-06-21 2015-02-04 Recombinetics Inc Celulas modificadas geneticamente y metodos par su obtencion
TR201900694T4 (tr) 2012-08-23 2019-02-21 Agensys Inc 158p1d7 proteinlerine bağlanan antikor ilaç konjugatları (adc).
PL3489261T3 (pl) 2012-08-24 2021-08-16 The Regents Of The University Of California Przeciwciała i szczepionki do stosowania w leczeniu nowotworów z ekspresją ROR1 i w hamowaniu przerzutu
KR102241962B1 (ko) 2012-09-07 2021-04-20 예일 유니버시티 유전적으로 변형된 비-인간 동물 및 이것들의 사용 방법
UA118090C2 (uk) * 2012-09-07 2018-11-26 ДАУ АГРОСАЙЄНСІЗ ЕлЕлСі Спосіб інтегрування послідовності нуклеїнової кислоти, що представляє інтерес, у ген fad2 у клітині сої та специфічний для локусу fad2 білок, що зв'язується, здатний індукувати спрямований розрив
DK4389764T3 (da) 2012-11-05 2026-04-13 Regeneron Pharma Genetisk modificerede gnavere og fremgangsmåder til anvendelse heraf
MX2015010841A (es) 2013-02-20 2016-05-09 Regeneron Pharma Modificacion genetica de ratas.
RS57582B1 (sr) 2013-02-20 2018-11-30 Regeneron Pharma Nehumane životinje sa modifikovanim sekvencama imunoglobulinskog teškog lanca
US9848587B2 (en) 2013-02-20 2017-12-26 Regeneron Pharmaceuticals, Inc. Humanized T cell co-receptor mice
SI2958937T1 (sl) 2013-02-22 2018-12-31 Regeneron Pharmaceuticals, Inc. Miš, ki izraža humanizirani poglavitni histokompatibilnostni kompleks
US20150342163A1 (en) 2013-02-22 2015-12-03 Regeneron Pharmaceuticals, Inc. Genetically modified major histocompatibility complex mice
CA2902543A1 (en) 2013-03-11 2014-10-09 Regeneron Pharmaceuticals, Inc. Transgenic mice expressing chimeric major histocompatibility complex (mhc) class i molecules
AU2014249148B2 (en) 2013-03-11 2020-04-02 Regeneron Pharmaceuticals, Inc. Transgenic mice expressing chimeric major histocompatibility complex (mhc) class ii molecules
HUE061977T2 (hu) 2013-03-13 2023-09-28 Regeneron Pharma Korlátozott immumglobulin könnyûlánc-repertoárt expresszáló egerek
KR20150126863A (ko) 2013-03-13 2015-11-13 리제너론 파마슈티칼스 인코포레이티드 공통 경쇄 마우스
US9788534B2 (en) 2013-03-18 2017-10-17 Kymab Limited Animal models and therapeutic molecules
DK3456831T3 (da) * 2013-04-16 2021-09-06 Regeneron Pharma Målrettet modifikation af rottegenom
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
AR097161A1 (es) 2013-08-01 2016-02-24 Agensys Inc Conjugados de fármacos anticuerpo (adc) que se unen a las proteínas cd37
HK1220990A1 (zh) 2013-08-07 2017-05-19 瑞泽恩制药公司 缺乏lincrna的非人类动物
MY191512A (en) 2013-09-18 2022-06-28 Regeneron Pharma Histidine engineered light chain antibodies and genetically modified non-human animals for generating the same
HRP20231121T1 (hr) 2013-09-23 2023-12-22 Regeneron Pharmaceuticals, Inc. Životinje koje nisu ljudi, koje imaju gen za humanizirani protein koji regulira signale
WO2015049517A2 (en) 2013-10-01 2015-04-09 Kymab Limited Animal models and therapeutic molecules
MY183188A (en) 2013-11-19 2021-02-18 Regeneron Pharma Non-human animals having a humanized b-cell activating factor gene
US20150143559A1 (en) 2013-11-19 2015-05-21 Regeneron Pharmaceuticals, Inc. Non-human animals having a humanized a proliferation-inducing ligand gene
EP3460063B1 (en) 2013-12-11 2024-03-13 Regeneron Pharmaceuticals, Inc. Methods and compositions for the targeted modification of a genome
MX388127B (es) 2013-12-11 2025-03-19 Regeneron Pharma Metodos y composiciones para la modificacion dirigida de un genoma.
US11160879B2 (en) 2014-01-15 2021-11-02 Masamichi Yamamoto Transgenic animal for visualization of ATP and use thereof
AU2015230938C1 (en) 2014-03-21 2021-10-14 Regeneron Pharmaceuticals, Inc. Non-human animals that make single domain binding proteins
SG10201808083VA (en) 2014-03-21 2018-10-30 Regeneron Pharma Vl antigen binding proteins exhibiting distinct binding characteristics
EP3482629B1 (en) 2014-05-19 2020-11-25 Regeneron Pharmaceuticals, Inc. Genetically modified non-human animals expressing human epo
ES2691529T3 (es) 2014-05-30 2018-11-27 Regeneron Pharmaceuticals, Inc. Animales con dipeptidil peptidasa iv (dpp4) humanizada
DK3152312T3 (da) 2014-06-06 2020-04-06 Regeneron Pharma Fremgangsmåder og sammensætninger til modifikation af et mållocus
WO2015196051A1 (en) 2014-06-19 2015-12-23 Regeneron Pharmaceuticals, Inc. Non-human animals having a humanized programmed cell death 1 gene
US9738897B2 (en) 2014-06-23 2017-08-22 Regeneron Pharmaceuticals, Inc. Nuclease-mediated DNA assembly
US20160081314A1 (en) 2014-09-19 2016-03-24 Regeneron Pharmaceuticals, Inc. Chimeric Antigen Receptors
BR112017007770A2 (pt) 2014-10-15 2018-01-16 Regeneron Pharma cultura in vitro, população de hipscs, método para modificar um locus-alvo genômico, e, hipsc.
EP3221457B1 (en) 2014-11-21 2019-03-20 Regeneron Pharmaceuticals, Inc. Methods and compositions for targeted genetic modification using paired guide rnas
BR112017010793A2 (pt) 2014-11-24 2017-12-26 Regeneron Pharma animal não humano geneticamente modificado, camundongo, métodos para produzir um animal não humano geneticamente modificado e de triagem de candidatos a fármaco direcionados a um antígeno de interesse, e, modelo de camundongo.
BR112017010490A2 (pt) 2014-12-05 2018-04-03 Regeneron Pharma roedor, polipeptídeo cd47, célula ou tecido de roedor isolado, célula-tronco emprionária de roedor, embrião de roedor, e, métodos de produzir um roedor, de fornecimento de um roedor, de enxerto de células humanas em um roedor, de avaliação de eficácia terapêutica de uma droga direcionada a células humanas e de avaliar as propriedades farmacocinéticas, de avaliar a toxicidade específica e inespecífica de uma droga direcionada ao cd47 humano.
ES2841353T3 (es) 2014-12-09 2021-07-08 Regeneron Pharma Animales no humanos que tienen un gen del grupo de diferenciación 274 humanizado
MX388784B (es) 2014-12-19 2025-03-20 Regeneron Pharma Métodos y composiciones para la modificación genética dirigida a través de direccionamiento múltiple de una sola etapa.
CA2978631C (en) 2015-03-09 2023-06-27 Agensys, Inc. Antibody drug conjugates (adc) that bind to flt3 proteins
US10285387B2 (en) 2015-03-16 2019-05-14 Regeneron Pharmaceuticals, Inc. Non-human animal exhibiting diminished upper and lower motor neuron function and sensory perception
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
MX2017012829A (es) 2015-04-06 2018-02-23 Regeneron Pharma Respuestas inmunitarias mediadas por células t humanizadas en animales no humanos.
ES2950399T3 (es) 2015-04-13 2023-10-09 Regeneron Pharma Ratones humanizados Sirpa-IL15 insertados y métodos de uso de los mismos
ES3063952T3 (en) 2015-05-18 2026-04-21 Agensys Inc Antibodies that bind to axl proteins
US10395759B2 (en) 2015-05-18 2019-08-27 Regeneron Pharmaceuticals, Inc. Methods and systems for copy number variant detection
WO2016187354A1 (en) 2015-05-18 2016-11-24 Agensys, Inc. Antibodies that bind to axl proteins
AU2016270587B2 (en) 2015-05-29 2020-12-24 Regeneron Pharmaceuticals, Inc. Non-human animals having a disruption in a C9ORF72 locus
JP2018526005A (ja) 2015-09-02 2018-09-13 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Ｒｅｇｅｎｅｒｏｎ Ｐｈａｒｍａｃｅｕｔｉｃａｌｓ， Ｉｎｃ． 前立腺がんのげっ歯類モデル
TWI824372B (zh) 2015-10-12 2023-12-01 美商再生元醫藥公司 活化瘦素受體的抗原結合蛋白
CN108366548B (zh) 2015-11-20 2021-10-08 瑞泽恩制药公司 具有人源化淋巴细胞活化基因3的非人动物
KR102067352B1 (ko) * 2015-11-24 2020-01-16 글락소스미스클라인 인털렉츄얼 프로퍼티 디벨로프먼트 리미티드 레트로바이러스 생산을 위한 일시적인 형질감염 방법
FR3044016A1 (fr) * 2015-11-24 2017-05-26 Glaxosmithkline Ip Dev Ltd Lignees cellulaires stables pour la production retrovirale
EP3384030A4 (en) 2015-12-03 2019-07-03 Trianni, Inc. IMPROVED IMMUNOGLULINIVITY
US20190037816A1 (en) 2016-01-13 2019-02-07 Regeneron Pharmaceuticals, Inc. Rodents having an engineered heavy chain diversity region
US20170218398A1 (en) * 2016-01-30 2017-08-03 Markus Alexander Brown Method to selectively target cancerous cells for genetic manipulation
EP4414484A3 (en) 2016-02-04 2025-01-15 Trianni, Inc. Enhanced production of immunoglobulins
WO2017136712A1 (en) * 2016-02-04 2017-08-10 Regeneron Pharmaceuticals, Inc. Non-human animals having an engineered angptl8 gene
JP6765433B2 (ja) 2016-02-12 2020-10-07 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Ｒｅｇｅｎｅｒｏｎ Ｐｈａｒｍａｃｅｕｔｉｃａｌｓ， Ｉｎｃ． 異常な核型の検出のための方法
JP2019509059A (ja) 2016-02-16 2019-04-04 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Ｒｅｇｅｎｅｒｏｎ Ｐｈａｒｍａｃｅｕｔｉｃａｌｓ， Ｉｎｃ． 変異型キヌレニナーゼ遺伝子を有する非ヒト動物
CN109068621B (zh) 2016-02-29 2021-07-20 再生元制药公司 具有人源化的tmprss基因的啮齿类动物
EP3437001A1 (en) 2016-03-29 2019-02-06 Regeneron Pharmaceuticals, Inc. Genetic variant-phenotype analysis system and methods of use
SG10202102885UA (en) 2016-05-20 2021-05-28 Regeneron Pharma Methods for breaking immunological tolerance using multiple guide rnas
CN109640644B (zh) 2016-06-03 2021-10-26 瑞泽恩制药公司 表达外源末端脱氧核苷酸转移酶的非人动物
KR20230047507A (ko) 2016-06-27 2023-04-07 더 리젠츠 오브 더 유니버시티 오브 캘리포니아 암 치료 조합
US10912287B2 (en) 2016-06-28 2021-02-09 Biocytogen Pharmaceuticals (Beijing) Co., Ltd Genetically modified mice expressing humanized PD-1
CN109803530A (zh) 2016-07-29 2019-05-24 瑞泽恩制药公司 包含引起c-截短的原纤维蛋白-1表达的突变的小鼠
MX381216B (es) 2016-09-30 2025-03-12 Regeneron Pharma Animales no humanos que tienen una expansion de repeticiones de hexanucleotidos en un locus c9orf72.
EP4567119A3 (en) 2016-11-04 2025-09-24 Regeneron Pharmaceuticals, Inc. Non-human animals having an engineered immunoglobulin lambda light chain locus
CA3050715A1 (en) 2017-01-19 2018-07-26 Open Monoclonal Technology, Inc. Human antibodies from transgenic rodents with multiple heavy chain immunoglobulin loci
SG11201907490XA (en) 2017-02-27 2019-09-27 Regeneron Pharma Non-human animal models of retinoschisis
GB201710984D0 (en) 2017-07-07 2017-08-23 Kymab Ltd Cells, vertebrates, populations & methods
CN111182790A (zh) 2017-07-31 2020-05-19 瑞泽恩制药公司 Crispr报告体非人类动物及其用途
KR102712142B1 (ko) 2017-07-31 2024-10-07 리제너론 파마슈티칼스 인코포레이티드 Cas-형질전환 마우스 배아 줄기 세포 및 마우스 및 이것의 용도
DK3687287T5 (da) 2017-09-29 2024-08-26 Regeneron Pharma Gnavere, udtrykkende humaniseret c1q-kompleks
WO2019067875A1 (en) 2017-09-29 2019-04-04 Regeneron Pharmaceuticals, Inc. NON-HUMAN ANIMALS COMPRISING A HUMANIZED TTR LOCUS AND METHODS OF USE
WO2019072241A1 (en) * 2017-10-13 2019-04-18 Beijing Biocytogen Co., Ltd NON-HUMAN ANIMAL GENETICALLY MODIFIED WITH PD-1 HUMAN OR CHIMERIC
CN109666701B (zh) * 2017-10-13 2021-08-24 百奥赛图(北京)医药科技股份有限公司 一种pd-1基因修饰人源化动物模型的构建方法及其应用
JP7361031B2 (ja) 2017-11-30 2023-10-13 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ｔｒｋｂ遺伝子座を含む非ヒト動物
WO2019113065A1 (en) 2017-12-05 2019-06-13 Regeneron Pharmaceuticals, Inc. Non-human animals having an engineered immunoglobulin lambda light chain and uses thereof
EP3592140A1 (en) 2018-03-19 2020-01-15 Regeneron Pharmaceuticals, Inc. Transcription modulation in animals using crispr/cas systems
IL277355B2 (en) 2018-03-26 2025-01-01 Regeneron Pharma Humanized rodents for testing therapeutic agents
SMT202500283T1 (it) 2018-04-06 2025-09-12 Regeneron Pharma Un anticorpo agonista del recettore della leptina da utilizzare per aumentare la massa ossea in un soggetto affetto da disfunzione metabolica o ipoleptinemia
US20190370254A1 (en) 2018-06-01 2019-12-05 Regeneron Pharmaceuticals, Inc. Methods and systems for sparse vector-based matrix transformations
IL318469A (en) 2018-06-14 2025-03-01 Regeneron Pharma Non-human animals capable of reorganizing transgenic DH-DH, and their uses
CA3098040A1 (en) 2018-07-16 2020-01-23 Regeneron Pharmaceuticals, Inc. Non-human animal models of ditra disease and uses thereof
US12653168B2 (en) 2018-09-13 2026-06-16 Regeneron Pharmaceuticals, Inc. Complement factor H gene knockout rat as a model of C3 glomerulopathy
CN109504708A (zh) * 2018-12-03 2019-03-22 江苏集萃药康生物科技有限公司 一种筛选标记自我删除的基因打靶载体及方法
WO2020131632A1 (en) 2018-12-20 2020-06-25 Regeneron Pharmaceuticals, Inc. Nuclease-mediated repeat expansion
US20220104468A1 (en) 2019-01-22 2022-04-07 St. Jude Children's Research Hospital Modulation of lc3-associated endocytosis pathway and genetically modified non-human animals as a model of neuroinflammation and neurodegeneration
WO2020169022A1 (en) 2019-02-18 2020-08-27 Beijing Biocytogen Co., Ltd Genetically modified non-human animals with humanized immunoglobulin locus
BR112021016173A2 (pt) 2019-02-22 2021-11-03 Regeneron Pharma Roedor geneticamente modificado, métodos de produção de um roedor geneticamente modificado e de produção de um anticorpo anti-nav1.7, célula ou tecido isolado de roedor, linhagem celular imortalizada, embrião de roedor, construto de ácido nucleico de direcionamento, e, hibridoma
AU2020253531C1 (en) 2019-04-04 2022-06-16 Regeneron Pharmaceuticals, Inc. Methods for scarless introduction of targeted modifications into targeting vectors
JP7506686B2 (ja) * 2019-04-04 2024-06-26 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 ヒト化凝固因子１２遺伝子座を含む非ヒト動物
CA3136602A1 (en) 2019-04-15 2020-10-22 Qwixel Therapeutics Llc Fusion protein composition(s) comprising targeted masked type i interferons (ifna and ifnb) and an antibody against tumor antigen, for use in the treatment of cancer
WO2020247452A1 (en) 2019-06-04 2020-12-10 Regeneron Pharmaceuticals, Inc. Non-human animals comprising a humanized ttr locus with a beta-slip mutation and methods of use
PT3979790T (pt) 2019-06-05 2026-05-05 Regeneron Pharma Roedores possuindo um reportrio limitado de cadeias leves lambda expressadas a partir do lcus kappa e suas utilizaes
CN113939595A (zh) 2019-06-07 2022-01-14 瑞泽恩制药公司 包括人源化白蛋白基因座的非人动物
CA3139469A1 (en) 2019-06-27 2020-12-30 Aarti Sharma-Kanning Modeling tdp-43 proteinopathy
DK3993876T3 (en) 2019-07-01 2024-12-02 Tonix Pharma Ltd Anti-cd154 antibodies and uses thereof
KR20220079590A (ko) 2019-10-04 2022-06-13 티에이이 라이프 사이언시스 Fc 돌연변이 및 부위-특이적인 접합 성질을 포함하는 항체 조성물
WO2021108363A1 (en) 2019-11-25 2021-06-03 Regeneron Pharmaceuticals, Inc. Crispr/cas-mediated upregulation of humanized ttr allele
WO2021154791A1 (en) 2020-01-28 2021-08-05 Regeneron Pharmaceuticals, Inc. Non-human animals comprising a humanized pnpla3 locus and methods of use
EP4099821A1 (en) 2020-02-07 2022-12-14 Regeneron Pharmaceuticals, Inc. <smallcaps/>? ? ?klkb1? ? ? ? ?non-human animals comprising a humanizedlocus and methods of use
US20230102342A1 (en) 2020-03-23 2023-03-30 Regeneron Pharmaceuticals, Inc. Non-human animals comprising a humanized ttr locus comprising a v30m mutation and methods of use
KR20230004472A (ko) 2020-04-21 2023-01-06 리제너론 파마슈티칼스 인코포레이티드 인간화 cxcl13 유전자를 갖는 비인간 동물
CN115667532A (zh) 2020-06-02 2023-01-31 百奥赛图(北京)医药科技股份有限公司 具有共有轻链免疫球蛋白基因座的经遗传修饰的非人动物
RU2751237C1 (ru) * 2020-06-10 2021-07-12 Регенерон Фармасьютикалс, Инк. Способы и композиции для направленной модификации генома
WO2021261620A1 (ko) 2020-06-25 2021-12-30 주식회사 휴맵 이형접합성 형질전환 동물
EP4171215A2 (en) 2020-06-26 2023-05-03 Regeneron Pharmaceuticals, Inc. Non-human animals comprising a humanized ace2 locus
US20220090060A1 (en) 2020-09-11 2022-03-24 Regeneron Pharmaceuticals, Inc. Identification and production of antigen-specific antibodies
KR20230078677A (ko) 2020-10-01 2023-06-02 리제너론 파마슈티칼스 인코포레이티드 인간 cr1을 발현하는 설치류 동물
US12012441B2 (en) 2020-10-26 2024-06-18 Neptune Biosciences Llc Engineered human IL-21 cytokines and methods for using the same
EP4262373A1 (en) 2020-12-16 2023-10-25 Regeneron Pharmaceuticals, Inc. Mice expressing humanized fc alpha receptors
JP2024500153A (ja) 2020-12-21 2024-01-04 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ｔｓｌｐ遺伝子、ヒト化ｔｓｌｐ受容体遺伝子、及び／又はヒト化ｉｌ７ｒａ遺伝子を有する非ヒト動物
MX2023007401A (es) 2020-12-23 2023-07-06 Regeneron Pharma Acidos nucleicos que codifican anticuerpos modificados por anclaje y usos de los mismos.
AU2022205313A1 (en) 2021-01-06 2023-07-20 Tonix Pharma Limited Methods of inducing immune tolerance with modified anti-cd154 antibodies
CN116981357A (zh) 2021-03-31 2023-10-31 瑞泽恩制药公司 包含具有改善的tcrb组库多样性的人源化细胞免疫系统组分的基因修饰的小鼠
US20240199725A1 (en) 2021-04-16 2024-06-20 Korea University Research And Business Foundation Human antibody targeting covid-19 virus
KR20240021943A (ko) 2021-06-18 2024-02-19 남미 테라퓨틱스, 인크. 암의 치료에 사용하기 위한 마스킹된 유형 I 인터페론 (IFNα 및 IFNβ)을 포함하는 융합 단백질 조성물(들) 및 그의 방법
EP4423271A2 (en) 2021-10-28 2024-09-04 Regeneron Pharmaceuticals, Inc. Crispr/cas-related methods and compositions for knocking out c5
AU2022408167A1 (en) 2021-12-08 2024-06-06 Regeneron Pharmaceuticals, Inc. Mutant myocilin disease model and uses thereof
EP4451863A1 (en) 2021-12-20 2024-10-30 Regeneron Pharmaceuticals, Inc. Non-human animals comprising humanized ace2 and tmprss loci
WO2023150798A1 (en) 2022-02-07 2023-08-10 Regeneron Pharmaceuticals, Inc. Compositions and methods for defining optimal treatment timeframes in lysosomal disease
CN118613498A (zh) 2022-02-11 2024-09-06 瑞泽恩制药公司 用于筛选4R Tau靶向剂的组合物和方法
US20250295096A1 (en) 2022-04-26 2025-09-25 Regeneron Pharmaceuticals, Inc. A rodent model of fibrodysplasia ossificans progressiva
US20250344681A1 (en) 2022-05-31 2025-11-13 Regeneron Pharmaceuticals, Inc. Animal model of tdp-43 proteinopathy
WO2023235725A2 (en) 2022-05-31 2023-12-07 Regeneron Pharmaceuticals, Inc. Crispr-based therapeutics for c9orf72 repeat expansion disease
US20230417899A1 (en) 2022-06-27 2023-12-28 Oshkosh Corporation Position tracking for a lift device
US20240102045A1 (en) 2022-07-19 2024-03-28 Regeneron Pharmaceuticals, Inc. Vectors, genetically modified cells, and genetically modified non-human animals comprising the same
CA3265746A1 (en) 2022-09-22 2024-03-28 Regeneron Pharmaceuticals, Inc. GENETICALLY MODIFIED MICE EXPRESSING COMPONENTS OF A HUMAN CELLULAR IMMUNE SYSTEM
EP4593590A1 (en) 2022-09-29 2025-08-06 Regeneron Pharmaceuticals, Inc. Correction of hepatosteatosis in humanized liver animals through restoration of il6/il6r/gp130 signaling in human hepatocytes
KR20250144399A (ko) 2023-02-01 2025-10-10 리제너론 파마슈티칼스 인코포레이티드 변형된 klhdc7b 유전자좌를 포함하는 동물
AU2024304180A1 (en) 2023-06-13 2026-01-08 Adcentrx Therapeutics, Inc. Methods and compositions related to antibodies and antibody drug conjugates (adcs) that bind nectin-4 proteins
JP2026522329A (ja) 2023-06-16 2026-07-07 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 ベクター、遺伝子改変細胞、およびそれらを含む遺伝子改変非ヒト動物
WO2025122669A1 (en) 2023-12-05 2025-06-12 Regeneron Pharmaceuticals, Inc. Non-human animals having a humanized complement factor b gene
WO2025171307A1 (en) 2024-02-08 2025-08-14 Regeneron Pharmaceuticals, Inc. Vectors, genetically modified cells, and genetically modified non-human animals comprising the same
WO2025212991A1 (en) 2024-04-05 2025-10-09 Regeneron Pharmaceuticals, Inc. Rodent models of disease
WO2025235388A1 (en) 2024-05-06 2025-11-13 Regeneron Pharmaceuticals, Inc. Transgene genomic identification by nuclease-mediated long read sequencing
WO2025250495A1 (en) 2024-05-28 2025-12-04 Regeneron Pharmaceuticals, Inc. Acceleration of human hepatocyte engraftment in humanized liver animals by supplementing paracrine ligands or agonists that activate human liver regeneration signals
WO2025264533A1 (en) 2024-06-17 2025-12-26 Adcentrx Therapeutics Inc. Methods and compositions related to antibody drug conjugates (adcs) that bind steap-1 proteins
WO2026030428A2 (en) 2024-08-01 2026-02-05 Regeneron Pharmaceuticals, Inc. Prostate-specific antigen peptides and uses thereof
US20260123608A1 (en) 2024-08-06 2026-05-07 Regeneron Pharmaceuticals, Inc. Non-human animals having modified immunoglobulin heavy chain constant region locus and uses thereof
WO2026039661A1 (en) 2024-08-15 2026-02-19 Regeneron Pharmaceuticals, Inc. Non-human animals with humanized fc epsilon receptors that lack functional alpha-1, 3-galactosyltransferase (ggta1)
US20260116978A1 (en) 2024-10-28 2026-04-30 Tae Life Sciences Llc Methods of Performing Boron Neutron Capture Therapy (BNCT) in Combination with Immune Checkpoint Inhibitors to Enhance BNCT and the Anti-tumor effects of Immune Check Point Inhibitors as well as the Abscopal Effect Induced by Radiation Therapy and Methods Thereof
WO2026096736A1 (en) 2024-10-31 2026-05-07 Regeneron Pharmaceuticals, Inc. Rodents expressing humanized polymeric immunoglobulin receptor
WO2026102284A1 (en) 2024-11-08 2026-05-15 Regeneron Pharmaceuticals, Inc. Humanized stathmin2 allele to track human tdp-43-dependent splicing changes caused by tdp-43 pathology
WO2026117686A1 (en) 2024-11-27 2026-06-04 Nammi Therapeutics, Inc. FUSION PROTEIN COMPOSITION(S) COMPRISING MASKED TYPE I INTERFERONS (IFNα AND IFNβ) FOR USE IN THE TREATMENT OF CANCER AND METHODS THEREOF

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5789215A (en) * 1991-08-20 1998-08-04 Genpharm International Gene targeting in animal cells using isogenic DNA constructs

Family Cites Families (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5770429A (en) * 1990-08-29 1998-06-23 Genpharm International, Inc. Transgenic non-human animals capable of producing heterologous antibodies
ES2301158T3 (es) * 1992-07-24 2008-06-16 Amgen Fremont Inc. Produccion de anticuerpos xenogenicos.
DE4228162C1 (de) * 1992-08-25 1994-01-13 Rajewsky Klaus Dr Verfahren zum Ersetzen homologer Genabschnitte aus Säugern in der Keimbahn von nicht-menschlichen Säugern
US5436149A (en) 1993-02-19 1995-07-25 Barnes; Wayne M. Thermostable DNA polymerase with enhanced thermostability and enhanced length and efficiency of primer extension
AU6819494A (en) * 1993-04-26 1994-11-21 Genpharm International, Inc. Transgenic non-human animals capable of producing heterologous antibodies
DE60023451T2 (de) * 1999-02-05 2006-07-20 Therapeutic Human Polyclonals, Inc., Mountain View Aus nicht-menschlichen transgenen tieren gewonnene menschliche polyklonale antikörper
US6586251B2 (en) * 2000-10-31 2003-07-01 Regeneron Pharmaceuticals, Inc. Methods of modifying eukaryotic cells

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5789215A (en) * 1991-08-20 1998-08-04 Genpharm International Gene targeting in animal cells using isogenic DNA constructs

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN105010238A (zh) * 2010-02-08 2015-11-04 瑞泽恩制药公司 共有轻链小鼠
CN105010238B (zh) * 2010-02-08 2018-07-20 瑞泽恩制药公司 共有轻链小鼠
CN107002093A (zh) * 2014-06-26 2017-08-01 瑞泽恩制药公司 用于靶向遗传修饰的方法和组合物，以及这些组合物的使用方法

Also Published As

Publication number Publication date
WO2002036789A3 (en) 2003-12-31
NO20031897L (no) 2003-06-24
KR100833136B1 (ko) 2008-05-28
AU2002220048B2 (en) 2006-09-21
NO332300B1 (no) 2012-08-20
MXPA03003797A (es) 2004-04-20
US20020106628A1 (en) 2002-08-08
EP1399575A2 (en) 2004-03-24
CA2426398C (en) 2010-10-26
JP2013162803A (ja) 2013-08-22
HK1059802A1 (en) 2004-07-16
EP1399575B1 (en) 2006-07-05
KR20030074614A (ko) 2003-09-19
CA2426398A1 (en) 2002-05-10
HUP0301575A3 (en) 2010-01-28
JP5892975B2 (ja) 2016-03-23
JP2017123855A (ja) 2017-07-20
HU227639B1 (en) 2011-10-28
CZ304856B6 (cs) 2014-12-10
DE60121372T2 (de) 2007-07-26
NO20031897D0 (no) 2003-04-28
BR0115096A (pt) 2003-10-07
CN1484707A (zh) 2004-03-24
NZ525511A (en) 2006-02-24
JP5339566B2 (ja) 2013-11-13
PL361927A1 (en) 2004-10-04
JP2015062432A (ja) 2015-04-09
ATE332388T1 (de) 2006-07-15
CZ20031197A3 (cs) 2003-11-12
JP5945263B2 (ja) 2016-07-05
BRPI0115096B1 (pt) 2016-03-01
JP2010220628A (ja) 2010-10-07
JP6486979B2 (ja) 2019-03-20
RU2003116125A (ru) 2005-01-20
RU2290441C2 (ru) 2006-12-27
HUP0301575A2 (hu) 2003-09-29
US6586251B2 (en) 2003-07-01
PL204759B1 (pl) 2010-02-26
JP2004536556A (ja) 2004-12-09
WO2002036789A2 (en) 2002-05-10
DE60121372D1 (de) 2006-08-17
JP2017104125A (ja) 2017-06-15
AU2004802A (en) 2002-05-15
JP2014039567A (ja) 2014-03-06

Similar Documents

Publication Publication Date Title
US10344299B2 (en) Compositions and methods for modifying cells
JP6486979B2 (ja) 真核生物細胞を改変する方法
US8791323B2 (en) Hybrid antibodies comprising human variable regions and mouse constant regions produced in a genetically modified mouse
AU2002220048A1 (en) Methods of modifying eukaryotic cells
HK1059802B (en) Methods of modifying eukaryotic cells
IL155580A (en) Ex vivo method for modifying endogenous gene or chromosomal locus in eukaryotic cells

Legal Events

Date Code Title Description
C06 Publication
PB01 Publication
C10 Entry into substantive examination
SE01 Entry into force of request for substantive examination
C14 Grant of patent or utility model
GR01 Patent grant
CX01 Expiry of patent term

Granted publication date: 20090610

CX01 Expiry of patent term