DK2517556T3 - Fremgangsmåde til punkt-specifik rekombination, gnavere og gnaverceller i stand til at udtrykke kimære antistoffer eller kæder - Google Patents

Fremgangsmåde til punkt-specifik rekombination, gnavere og gnaverceller i stand til at udtrykke kimære antistoffer eller kæder Download PDF

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DK2517556T3
DK2517556T3 DK12171791.2T DK12171791T DK2517556T3 DK 2517556 T3 DK2517556 T3 DK 2517556T3 DK 12171791 T DK12171791 T DK 12171791T DK 2517556 T3 DK2517556 T3 DK 2517556T3
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human
region
rodent
dna
cell
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Allan Bradley
E-Chiang Lee
Qi Liang
Wei Wang
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Kymab Ltd
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Claims (30)

1. Fremgangsmåde til fremstilling af en gnaver i stand til at fremstille et repertoire af kimære antistoffer eller tunge antistofkæder, fremgangsmåden omfattende: at indsætte i et gnavercellegenom; (a) en flerhed af human IgH-V -regioner, en eller flere human D regioner og en eller flere human J-regioner opstrøms af en konstant region af værtsgnaveren; og (b) eventuelt en eller flere human Ig-letkæde-kappa-V-regioner og en eller flere human Ig-letkæde-kappa-J-regioner opstrøms af den konstante værtsgnaver-pattedyrs-kappa-region og/eller en eller flere human Ig-letkæde-lambda-V-regioner og en eller flere human Ig-letkæde-lambda-J-regioner opstrøms af den konstante værtsgnaver-pattedyrs-lambda-region; henholdsvis, hvor indsættelsen er således at gnaveren er i stand til at fremstille et repertoire af kimære antistoffer eller tunge antistofkæder med en konstant gnaverregion og en variabel humanregion, hvor trinnene (a) og (b), når begge er til stede, kan udføres i hvilken som helst rækkefølge, hvor, en eller flere indsættelseshændelser anvender punkt-specifik rekombination, hvor indsættelsesfremgangsmåden begynder ved et punkt, hvor en startkassette er blevet indsat i genomet af gnavercellen, såsom en ES-celle, og hvor indsættelsen af et første DNA-fragment i startkassetten efterfølges af indsættelse af et andet DNA-fragment i en del af det første DNA-fragment, og hvor indsættelsen af human-DNA'et foretages mellem den konstante gnaverregion og den sidste, 3', J-gnaverregion.
2. Fremgangsmåde til fremstilling af en gnaver i stand til at fremstille et repertoire af kimære antistoffer eller lette antistofkæder, fremgangsmåden omfattende at indsætte i et gnavercellegenom; (a) en flerhed af human Ig-letkæde-kappa-V-regioner og en eller flere human Ig-letkæde-kappa-J-regioner opstrøms af den konstante værtsgnaver-kappa-region og/eller en flerhed af human Ig-letkæde- lambda-V-regioner og en eller flere human Ig-letkæde-lambda-J-regioner opstrøms af den konstante værtsgnaver-lambda-region; og (b) eventuelt en eller flere human IgH-V-regioner, en eller flere human D-regioner og en eller flere human J-regioner opstrøms af den konstante værtsgnaver-region; hvor indsættelsen er således at gnaveren er i stand til at fremstille et repertoire af kimære antistoffer eller lette antistofkæder med en konstant gnaverregion og en variabel humanregion, hvor trinnene (a) og (b), når begge er til stede, kan udføres i hvilken som helst rækkefølge, hvor en eller flere indsættelseshændelser anvender punkt-specifik rekombination hvor indsættelsesfremgangsmåden begynder ved et punkt, hvor en startkassette er blevet indsat i genomet af gnavercellen, såsom en ES-celle; og hvor indsættelsen af et første DNA-fragment i startkassetten efterfølges af indsættelse af et andet DNA-fragment i en del af det første DNA-fragment, og hvor indsættelsen af human-DNA'et foretages mellem den konstante gnaverregion og den sidste, 3', J-gnaverregion.
3. Fremgangsmåde til fremstilling afen gnavercelle, fremgangsmåden omfattende at indsætte i et gnavercellegenom; (a) en flerhed af human IgH-V-regioner, en eller flere human D-regioner og en eller flere human J-regioner opstrøms af en konstant region af værtsgnaveren; og (b) eventuelt en eller flere human Ig-letkæde-kappa-V-regioner og en eller flere human Ig-letkæde-kappa-J-regioner opstrøms af den konstante værtsgnaver-pattedyrs-kappa-region og/eller en eller flere human Ig-letkæde-lambda-V-regioner og en eller flere human Ig-letkæde-lambda-J-regioner opstrøms af den konstante værtsgnaver-pattedyrs-lambda-region; henholdsvis, hvor trinnene (a) og (b), når begge er til stede, kan udføres i hvilken som helst rækkefølge, hvor, en eller flere indsættelseshændelser anvender punkt-specifik rekombination, hvor indsættelsesfremgangsmåden begynder ved et punkt, hvor en startkassette er blevet indsat i genomet af gnavercellen, såsom en ES-celle, og hvor indsættelsen af et første DNA-fragment i startkassetten efterfølges af indsættelse af et andet DNA-fragment i en del af det første DNA-fragment, og hvor indsættelsen af human-DNA'et foretages mellem den konstante gnaverregion og den sidste, 3', J-gnaverregion.
4. Fremgangsmåde til fremstilling afen gnavercelle fremgangsmåden omfattende at indsætte i et gnavercellegenom; (a) en flerhed af human Ig-letkæde-kappa-V-regioner og en eller flere human Ig-letkæde-kappa-J-regioner opstrøms af den konstante værtsgnaver-kappa -region og/eller en flerhed af human Ig-letkæde-lambda-V-regioner og en eller flere human Ig-letkæde-lambda-J-regioner opstrøms af den konstante værtsgnaver-lambda-region; og (b) eventuelt en eller flere human IgH-V-regioner, en eller flere human D-regioner og en eller flere human J-regioner opstrøms af den konstante værtsgnaver-region; hvor trinnene (a) og (b), når begge er til stede, kan udføres i hvilken som helst rækkefølge, hvor en eller flere indsættelseshændelser anvender punkt-specifik rekombination hvor indsættelsesfremgangsmåden begynder ved et punkt, hvor en startkassette er blevet indsat i genomet af gnavercellen, såsom en ES-celle; og hvor indsættelsen af et første DNA-fragment i startkassetten efterfølges af indsættelse af et andet DNA-fragment i en del af det første DNA-fragment, og hvor indsættelsen af human-DNA'et foretages mellem den konstante gnaverregion og den sidste, 3', J-gnaverregion.
5. Fremgangsmåde ifølge krav 1 -4, hvor den punkt-specifikke rekombination er RMCE.
6. Fremgangsmåde ifølge krav 5, hvor RMCE er sekventiel RMCE (SRMCE).
7. Fremgangsmåde ifølge et hvilket som helst foregående krav omfattende trinnene: i. indsættelse af DNA danner en startkassette i genomet af en celle; ii. indsættelse af et første DNA-fragment i indsættelsespunktet, det første DNA-fragment omfattende en første del af en human VDJ- eller VJ-DNA-region og en første vektordel indeholdende en første valgbar markør eller generende en valgbar markør ved indsættelse; iii. eventuelt fjernelse af en del af vektor-DNA'et; iv. indsættelse af et andet DNA-fragment i vektordelen af det første DNA-fragment, det andet DNA-fragment indeholdende en anden del af human VDJ- eller VJ-DNA og en anden vektordel, den anden vektordel indeholdende en anden valgbar markør, eller generende en anden valgbar markør ved indsættelse; v. fjernelse af et hvilket som helst vektor-DNA for at tillade det første og andet human DNA-fragment at danne en nabosekvens; og vi. iteration af trinnene af indsættelse af en del af human V(D)J-DNA'et og vektor-DNA-fjernelse, efter behov, for at fremstille en celle med hele eller en del af human VDJ- eller VJ-regionen tilstrækkelig til at være i stand til at generere et kimært antistof i forbindelse med en konstant værtsregion.
8. Fremgangsmåde ifølge krav 7 hvor tre heterospecifikke og inkompatible loxP-punkter anvendes.
9. Fremgangsmåde ifølge et hvilket som helst foregående krav hvor de punktspecifikke rekombinationspunkter er ΙοχΡ-punkter, eller variationer deraf, eller FRT-punkter, eller variationer deraf.
10. Fremgangsmåde ifølge et hvilket som helst foregående krav, hvor de punktspecifikke rekombinasesystemer vælges fra Cre-lox, og FLP/FRT, eller kombinationer deraf.
11. Fremgangsmåde ifølge et hvilket som helst foregående krav anvendende en vektor, vektoren omfattende en indsats omfattende en region af human DNA fra nogle af de humane VDJ- eller VJ-locus flankeret af DNA som ikke er fra den locus, og hvor det flankerende DNA omfatter en eller flere valgbare markører eller et eller flere punkt-specifikke rekombinationspunkter.
12. Fremgangsmåde ifølge krav 11, hvor vektoren omfatter 2 eller flere, såsom 3, heterospecifikke og inkompatible punkt-specifikke rekombinationspunkter.
13. Fremgangsmåde ifølge krav 11 eller 12, hvor vektoren omfatter en eller flere transposon ITR (inverteret terminal gentagelse) -sekvenser.
14. Fremgangsmåde ifølge et hvilket som helst foregående krav, hvor startkassetten indsættes i tung kæde gnaverlocussen, til anvendelse i indsættelse af tung kæde human-DNA.
15. Fremgangsmåde ifølge et hvilket som helst foregående krav, hvor en startkassette indsættes i letkæde gnaverlocussen, til anvendelse i indsættelse af letkæde human-VJ-DNA.
16. Fremgangsmåde ifølge et hvilket som helst foregående krav hvor startkassetten indsættes mellem position 114,667,090 og 114,665,190 af mussekromosom 12 (NCBI m37, april 2007 ENSEMBL Release 55.37h for mussestammen C57BL/6J.
17. Fremgangsmåde ifølge et hvilket som helst foregående krav hvor det første humane variable regionfragment indsættes med homolog rekombination ved startkassetteskeletsekvensen og derefter DNA'et af en hvilken som helst negativ valgmarkør og startkassette i vektoren efterfølgende fjernes ved rekombination mellem rekombinasemålsekvenser.
18. Fremgangsmåde ifølge et hvilket som helst foregående krav, hvor 5' enden af human-indsatsen øges i længden.
19. Fremgangsmåde ifølge et hvilket som helst foregående krav, hvor cellen er en ES-celle.
20. Fremgangsmåde ifølge et hvilket som helst foregående krav hvor: en eller flere gnaverkontrolsekvenser såsom enhancer-sekvensen opretholdes opstrøms af den konstante Mu-gnaverregion, passende i sin egen position i forhold til afstanden fra den konstante region; eller en eller flere gnaverkontrolsekvenser såsom en eller flere enhancer-sekvenser opretholdes nedstrøms af den konstante Mu-gnaverregion, passende i sin egen position i forhold til afstanden fra den konstante region; eller en gnaverskiftersekvens, passende den endogene skiftersekvens, opretholdes opstrøms af den konstante Mu-gnaverregion, passende i sin egen position i forhold til afstanden fra den konstante region.
21. Fremgangsmåde ifølge krav 19, hvor ES-cellen omfatter en fuldkommen human VDJ- eller VJ-sekvens, eller en del deraf.
22. Fremgangsmåde til fremstilling af et antistof specifikt til et ønsket antigen, fremgangsmåden omfattende immunisering af en gnaver fremstillet ifølge kravene 1, 2 eller 5-21 med det ønskede antigen og genvinding af antistoffet.
23. Fremgangsmåden ifølge krav 22, yderligere omfattende genvinding af antistoffet eller celler udtrykkende antistoffet, og derefter erstatning af den konstante ikke-human-pattedyrs-region med en konstant human-region for at fremstille et fuldt humaniseret antistof.
24. Fremgangsmåden ifølge krav 22 eller krav 23 yderligere omfattende generering af et kimært antistofderivat af det kimære antistof ifølge krav 22 eller 23.
25. Fremgangsmåden ifølge krav 24, hvor de kimære antistoffer ifølge krav 22 eller 23 manipuleres, eventuelt på DNA-niveauet, til at generere molkyler med antistofagtige egenskaber eller struktur valgt fra: et domæneantistof; eller en variabel humanregion med en hvilken som helst konstant region fra enten tung eller let kæde fra den samme eller forskellige arter; eller en variabel humanregion sammen med en hvilket som helst anden fusionspartner.
26. Fremgangsmåden ifølge et hvilket som helst af kravene 22 til 25 yderligere omfattende fremstilling af en farmaceutisk sammensætning omfattende at kombinere antistoffet, med en farmaceutisk acceptabel bærer eller anden excipiens for at fremstille sammensætningen.
27. Fremgangsmåde ifølge krav 22, yderligere omfattende at dyrke eller aflede en antistof-producerende celle eller cellelinje fra gnavercellen, eventuelt hvor antistofcellen eller cellelinjen immortaliseres enten ved fusion til en tumorcelle for at tilvejebringe en antistof-producerende celle og cellelinje, eller ved direkte cellulær immortalisering.
28. Gnaver genereret med fremgangsmåderne ifølge et hvilket som helst af kravene 1, 2 eller 5-21.
29. Gnaver ifølge krav 28 omfattende en fuldkommen human VDJ- eller VJ-sekvens eller en del deraf.
30. Gnavercelle isoleret fra gnaveren ifølge krav 28 eller 29, cellen omfattende en fuldkommen human VDJ- eller VJ-sekvens eller en del deraf.
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Families Citing this family (122)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6596541B2 (en) 2000-10-31 2003-07-22 Regeneron Pharmaceuticals, Inc. Methods of modifying eukaryotic cells
LT2346994T (lt) 2008-09-30 2022-03-10 Ablexis, Llc Knock-in pelė, skirta chimerinių antikūnų gamybai
PT2564695E (pt) 2009-07-08 2015-06-03 Kymab Ltd Modelos animais e moléculas terapêuticas
US9445581B2 (en) 2012-03-28 2016-09-20 Kymab Limited Animal models and therapeutic molecules
US9796788B2 (en) 2010-02-08 2017-10-24 Regeneron Pharmaceuticals, Inc. Mice expressing a limited immunoglobulin light chain repertoire
US20130045492A1 (en) 2010-02-08 2013-02-21 Regeneron Pharmaceuticals, Inc. Methods For Making Fully Human Bispecific Antibodies Using A Common Light Chain
RS55315B2 (sr) 2010-02-08 2020-08-31 Regeneron Pharma Miš sa zajedničkim lakim lancem
LT3248462T (lt) 2010-03-31 2024-05-27 Ablexis, Llc Pelių genų inžinerija, skirta chimerinių antikūnų gamybai
CN103228130B (zh) * 2010-06-17 2016-03-16 科马布有限公司 动物模型及治疗分子
BR112012032991B1 (pt) * 2010-06-22 2021-08-10 Regeneron Pharmaceuticals, Inc Método para preparar um anticorpo que se liga a um antígeno de interesse
US10793829B2 (en) 2010-07-26 2020-10-06 Trianni, Inc. Transgenic mammals and methods of use thereof
US10881084B2 (en) 2010-07-26 2021-01-05 Trianni, Inc Transgenic animals and methods of use
US10662256B2 (en) 2010-07-26 2020-05-26 Trianni, Inc. Transgenic mammals and methods of use thereof
KR102434557B1 (ko) * 2010-08-02 2022-08-23 리제너론 파아마슈티컬스, 인크. Ｖｌ 도메인을 포함하는 결합 단백질을 생성하는 마우스
PL2738259T3 (pl) * 2011-02-25 2020-08-24 Regeneron Pharmaceuticals, Inc. Myszy adam6
US9920110B2 (en) 2011-03-09 2018-03-20 Cell Signaling Technology, Inc. Methods and reagents for creating monoclonal antibodies
EP2739300B1 (en) 2011-07-05 2019-06-19 Duke University N-terminal deleted gp120 immunogens
PT2739740T (pt) * 2011-08-05 2020-01-09 Regeneron Pharma Cadeia leve universal humanizada de murganhos
GB2501753A (en) * 2012-05-04 2013-11-06 Kymab Ltd Human antibodies
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
JP2014533930A (ja) * 2011-09-19 2014-12-18 カイマブ・リミテッド 免疫グロブリン遺伝子多様性の操作およびマルチ抗体治療薬
GB2495083A (en) * 2011-09-26 2013-04-03 Kymab Ltd Human VpreB and chimaeric surrogate light chains in transgenic non-human vertebrates
EP2761008A1 (en) 2011-09-26 2014-08-06 Kymab Limited Chimaeric surrogate light chains (slc) comprising human vpreb
EP2763699A4 (en) 2011-10-03 2015-05-20 Univ Duke VACCINE
US10246509B2 (en) 2011-10-17 2019-04-02 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
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
MY164836A (en) 2011-10-28 2018-01-30 Regeneron Pharma Genetically modified major histocompatibility complex mice
PT2770822T (pt) 2011-10-28 2017-09-18 Regeneron Pharma Ratinhos geneticamente modificados que expressam moléculas quiméricas de complexo principal de histocompatibilidade (mhc) ii
US9043996B2 (en) 2011-10-28 2015-06-02 Regeneron Pharmaceuticals, Inc. Genetically modified major histocompatibility complex animals
CN114891797A (zh) 2011-10-28 2022-08-12 瑞泽恩制药公司 T细胞受体基因修饰小鼠
US20180295821A1 (en) * 2011-12-02 2018-10-18 Kymab Limited Transgenic Animals
GB201122047D0 (en) * 2011-12-21 2012-02-01 Kymab Ltd Transgenic animals
US9253965B2 (en) 2012-03-28 2016-02-09 Kymab Limited Animal models and therapeutic molecules
MX356429B (es) * 2011-12-20 2018-05-29 Regeneron Pharma Ratones con cadena ligera humanizada.
LT2809150T (lt) * 2012-02-01 2019-10-25 Regeneron Pharma Humanizuota pelė, kuri ekspresuoja sunkiąsias grandines, kurių sudėtyje yar vl domenai
KR20140136462A (ko) * 2012-03-06 2014-11-28 리제너론 파마슈티칼스 인코포레이티드 공통 경쇄 마우스
MX2014011047A (es) 2012-03-16 2015-04-08 Regeneron Pharma Ratones que producen proteinas de union a un antigeno con caracteristicas de union dependientes del ph.
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
RU2644684C2 (ru) 2012-03-16 2018-02-13 Регенерон Фармасьютикалз, Инк. Антитела со встроенным в легкие цепи гистидином и генетически модифицированные отличные от человека животные для их получения
BR112014022855A2 (pt) 2012-03-16 2017-07-18 Regeneron Pharma animal não humano geneticamente modificado, mamífero geneticamente modificado, e, método para fabricar um animal não humano
GB2502127A (en) 2012-05-17 2013-11-20 Kymab Ltd Multivalent antibodies and in vivo methods for their production
SG11201405059XA (en) 2012-03-28 2014-09-26 Kymab Ltd Transgenic non-human vertebrate for the expression of class - switched, fully human, antibodies
US10251377B2 (en) 2012-03-28 2019-04-09 Kymab Limited Transgenic non-human vertebrate for the expression of class-switched, fully human, antibodies
SG10201609277PA (en) 2012-06-12 2017-01-27 Regeneron Pharma Humanized non-human animals with restricted immunoglobulin heavy chain loci
IN2015DN01700A (da) 2012-08-03 2015-05-22 Sab Llc
WO2014093908A2 (en) * 2012-12-14 2014-06-19 Omt, Inc. Polynucleotides encoding rodent antibodies with human idiotypes and animals comprising same
SG10201706190PA (en) 2013-02-06 2017-09-28 Regeneron Pharma B cell lineage based immunogen design with humanized animals
MY185881A (en) 2013-02-20 2021-06-14 Regeneron Pharma Non-human animals with modified immunoglobulin heavy chain sequences
SI2958938T1 (sl) 2013-02-20 2019-08-30 Regeneron Pharmaceuticals, Inc. Miši, ki izražajo humanizirane koreceptorje za celice T
US20150342163A1 (en) 2013-02-22 2015-12-03 Regeneron Pharmaceuticals, Inc. Genetically modified major histocompatibility complex mice
US10154658B2 (en) 2013-02-22 2018-12-18 Regeneron Pharmaceuticals, Inc. Genetically modified major histocompatibility complex mice
US9788534B2 (en) 2013-03-18 2017-10-17 Kymab Limited Animal models and therapeutic molecules
US9783618B2 (en) 2013-05-01 2017-10-10 Kymab Limited Manipulation of immunoglobulin gene diversity and multi-antibody therapeutics
US9783593B2 (en) 2013-05-02 2017-10-10 Kymab Limited Antibodies, variable domains and chains tailored for human use
US11707056B2 (en) 2013-05-02 2023-07-25 Kymab Limited Animals, repertoires and methods
DE202014010413U1 (de) 2013-09-18 2015-12-08 Kymab Limited Zellen und Organismen
CA2925723A1 (en) 2013-10-01 2015-04-09 Kymab Limited Animal models and therapeutic molecules
RU2725520C2 (ru) 2013-12-11 2020-07-02 Регенерон Фармасьютикалс, Инк. Способы и композиции для направленной модификации генома
GB201403775D0 (en) 2014-03-04 2014-04-16 Kymab Ltd Antibodies, uses & methods
US20150266976A1 (en) 2014-03-21 2015-09-24 Regeneron Pharmaceuticals, Inc. Vl antigen binding proteins exhibiting distinct binding characteristics
KR20210088756A (ko) 2014-03-21 2021-07-14 리제너론 파마슈티칼스 인코포레이티드 단일 도메인 결합 단백질을 생산하는 비-인간 동물
KR102374379B1 (ko) * 2014-06-06 2022-03-17 리제너론 파마슈티칼스 인코포레이티드 표적화된 좌를 변형시키는 방법 및 조성물
US20170142942A1 (en) * 2014-07-14 2017-05-25 Washington State University Nanos knock-out that ablates germline cells
CN107072184A (zh) 2014-09-19 2017-08-18 瑞泽恩制药公司 嵌合抗原受体
GB201418713D0 (en) 2014-10-21 2014-12-03 Kymab Ltd Bindings Proteins
WO2016080399A1 (ja) * 2014-11-20 2016-05-26 国立大学法人京都大学 哺乳動物の標的ゲノム領域にｄｎａをノックインする方法及び細胞
BR112017015880A2 (pt) 2015-03-03 2018-07-31 Kymab Ltd anticorpos, usos e métodos
JP2018508224A (ja) 2015-03-19 2018-03-29 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． 抗原を結合する軽鎖可変領域を選択する非ヒト動物
EP4248744A3 (en) 2015-04-06 2023-12-27 Regeneron Pharmaceuticals, Inc. Humanized t cell mediated immune responses in non-human animals
WO2017095939A1 (en) 2015-12-03 2017-06-08 Trianni, Inc. Enhanced immunoglobulin diversity
AU2017213633B2 (en) 2016-02-04 2023-08-03 Trianni, Inc. Enhanced production of immunoglobulins
US11497781B2 (en) 2016-03-10 2022-11-15 Cg Oncology, Inc. Methods of treating bladder cancer by combination therapy comprising the oncolytic adenovirus CG0070 and an immune checkpoint inhibitor
US11066464B2 (en) 2016-03-21 2021-07-20 Kymab Limited Anti-malarial antibodies that bind circumsporozoite protein
WO2017163049A1 (en) 2016-03-21 2017-09-28 Kymab Limited Anti-malarial antibodies that bind circumsporozoite protein
GB2550114A (en) 2016-05-03 2017-11-15 Kymab Ltd Methods, regimens, combinations & antagonists
KR102598120B1 (ko) 2016-06-03 2023-11-07 리제너론 파마슈티칼스 인코포레이티드 외인성 말단 데옥시뉴클레오타이드 전달효소를 발현하는 비인간 동물
WO2017220990A1 (en) 2016-06-20 2017-12-28 Kymab Limited Anti-pd-l1 antibodies
US9567399B1 (en) 2016-06-20 2017-02-14 Kymab Limited Antibodies and immunocytokines
WO2018029474A2 (en) 2016-08-09 2018-02-15 Kymab Limited Anti-icos antibodies
EP3497128A2 (en) 2016-08-09 2019-06-19 Kymab Limited Anti-icos antibodies
WO2018065552A1 (en) 2016-10-06 2018-04-12 Innate Pharma Anti-cd39 antibodies
EP3534947A1 (en) 2016-11-03 2019-09-11 Kymab Limited Antibodies, combinations comprising antibodies, biomarkers, uses & methods
RU2021129958A (ru) * 2016-11-04 2021-11-02 Регенерон Фармасьютикалс, Инк. Отличные от человека животные со сконструированным локусом легкой лямбда-цепи иммуноглобулина
EA201991514A1 (ru) * 2016-12-21 2019-12-30 Сефалон, Инк. Антитела, которые специфически связываются с ил-15, и их применение
SG11201906540WA (en) 2017-01-19 2019-08-27 Open Monoclonal Tech Inc Human antibodies from transgenic rodents with multiple heavy chain immunoglobulin loci
US11680101B2 (en) 2017-01-27 2023-06-20 Kymab Limited Anti-OPG antibodies
US10143187B2 (en) 2017-02-17 2018-12-04 Denali Therapeutics Inc. Transferrin receptor transgenic models
JP2020508049A (ja) 2017-02-17 2020-03-19 デナリ セラピューティクス インコーポレイテッドＤｅｎａｌｉ Ｔｈｅｒａｐｅｕｔｉｃｓ Ｉｎｃ． 操作されたトランスフェリン受容体結合ポリペプチド
US10457717B2 (en) 2017-02-17 2019-10-29 Denali Therapeutics Inc. Engineered polypeptides
CN110382526B (zh) 2017-02-17 2023-12-26 戴纳立制药公司 转铁蛋白受体转基因模型
GB2561352B (en) * 2017-04-10 2023-01-18 Genome Res Ltd Animal models and therapeutic molecules
AU2018251987A1 (en) 2017-04-14 2019-12-05 Cg Oncology, Inc. Methods of treating bladder cancer
GB201709808D0 (en) 2017-06-20 2017-08-02 Kymab Ltd Antibodies
GB201709970D0 (en) 2017-06-22 2017-08-09 Kymab Ltd Bispecific antigen-binding molecules
CN111246882A (zh) 2017-08-01 2020-06-05 希望之城 抗il1rap抗体
WO2019079772A1 (en) * 2017-10-20 2019-04-25 Fred Hutchinson Cancer Research Center SYSTEMS AND METHODS FOR GENETICALLY MODIFIED B-LYMPHOCYTES FOR EXPRESSING SELECTED ANTIBODIES
BR112020011184A2 (pt) 2017-12-05 2020-11-17 Regeneron Pharmaceuticals, Inc. roedor geneticamente modificado, células de roedor isolada, célula imortalizada, embrião de roedor, uso de um roedor, célula b isolada, anticorpo preparado por um método, métodos para produzir um roedor geneticamente modificado, um anticorpo, uma cadeia pesada totalmente humana ou uma cadeia leve totalmente humana, uma sequência nucleotídica, para gerar uma ¿ sequência de domínio variável de cadeia pesada ou leve humana e gerar uma ¿ sequência da região variável de cadeia pesada ou leve humana, célula-tronco embrionária, célula es de roedor, e, célula es isolada de roedor.
GB201721338D0 (en) 2017-12-19 2018-01-31 Kymab Ltd Anti-icos Antibodies
US11629189B2 (en) 2017-12-19 2023-04-18 Kymab Limited Bispecific antibody for ICOS and PD-L1
CN116874591A (zh) 2018-03-24 2023-10-13 瑞泽恩制药公司 用于产生针对肽-mhc复合物的治疗性抗体的经过基因修饰的非人动物、其制造方法和用途
IL314733A (en) 2018-03-26 2024-10-01 Regeneron Pharma Humanized rodents for testing therapeutic agents
CN108486125B (zh) * 2018-03-27 2024-01-05 重庆金迈博生物科技有限公司 一种核酸分子及其在制备人源单域抗体中的应用
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
SG11202012084WA (en) 2018-06-14 2021-01-28 Regeneron Pharma Non-human animals capable of dh-dh rearrangement in the immunoglobulin heavy chain coding sequences
GB2576914A (en) * 2018-09-06 2020-03-11 Kymab Ltd Antigen-binding molecules comprising unpaired variable domains produced in mammals
GB201815629D0 (en) 2018-09-25 2018-11-07 Kymab Ltd Antagonists
GB201820687D0 (en) 2018-12-19 2019-01-30 Kymab Ltd Antagonists
CN117099741A (zh) * 2019-02-18 2023-11-24 百奥赛图(北京)医药科技股份有限公司 具有人源化免疫球蛋白基因座的经遗传修饰的非人动物
EP3952999A4 (en) 2019-04-09 2023-01-25 Abcuro, Inc. ANTIBODIES WITH DEPLETIVE ACTION ON THE KLRG1 RECEPTOR (KILLER CELL LECTIN-LIKE RECEPTOR SUBFAMILY G MEMBER 1)
CN115380049A (zh) 2019-11-29 2022-11-22 凯玛布有限公司 对生理性铁过载的治疗
CA3163549A1 (en) 2019-12-02 2021-06-10 Regeneron Pharmaceuticals, Inc. Peptide-mhc ii protein constructs and uses thereof
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
WO2021261620A1 (ko) 2020-06-25 2021-12-30 주식회사 휴맵 이형접합성 형질전환 동물
TW202229328A (zh) 2020-09-11 2022-08-01 美商再生元醫藥公司 抗原特異性抗體之鑑定及產生
KR20230084157A (ko) 2020-10-08 2023-06-12 주식회사 휴맵 인간화 면역글로불린 유전자좌를 포함하는 게놈을 가지는 형질전환 비인간-동물 제조방법
KR20230147048A (ko) 2020-12-16 2023-10-20 리제너론 파마슈티칼스 인코포레이티드 인간화 Fc 알파 수용체를 발현하는 마우스
US20240317849A1 (en) 2020-12-23 2024-09-26 Regeneron Pharmaceuticals, Inc. Nucleic acids encoding anchor modified antibodies and uses thereof
EP4377346A1 (en) 2021-07-26 2024-06-05 Abcuro, Inc. Killer cell lectin-like receptor subfamily g member 1 (klrg1) depleting antibodies
WO2023097236A1 (en) * 2021-11-24 2023-06-01 The Rockefeller University Compositions and methods for generating immunoglobulin knock-in mice
GB202216503D0 (en) 2022-11-05 2022-12-21 Quadrucept Bio Ltd Non-human vertebrates & cells
US20240294651A1 (en) 2023-01-30 2024-09-05 Kymab Limited Antibodies

Family Cites Families (192)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US114985A (en) * 1871-05-16 Improvement in apparatus for cooling and preserving milk and other liquids
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
DE69120146T2 (de) 1990-01-12 1996-12-12 Cell Genesys Inc Erzeugung xenogener antikörper
US6713610B1 (en) 1990-01-12 2004-03-30 Raju Kucherlapati Human antibodies derived from immunized xenomice
US6657103B1 (en) 1990-01-12 2003-12-02 Abgenix, Inc. Human antibodies derived from immunized xenomice
US6673986B1 (en) 1990-01-12 2004-01-06 Abgenix, Inc. Generation of xenogeneic antibodies
US6255458B1 (en) * 1990-08-29 2001-07-03 Genpharm International High affinity human antibodies and human antibodies against digoxin
US7084260B1 (en) 1996-10-10 2006-08-01 Genpharm International, Inc. High affinity human antibodies and human antibodies against human antigens
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
US6300129B1 (en) 1990-08-29 2001-10-09 Genpharm International Transgenic 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
DK0814159T3 (da) 1990-08-29 2005-10-24 Genpharm Int Transgene, ikke-humane dyr, der er i stand til at danne heterologe antistoffer
US5545806A (en) 1990-08-29 1996-08-13 Genpharm International, Inc. Ransgenic non-human animals for 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
US5859307A (en) 1992-02-04 1999-01-12 Massachusetts Institute Of Technology Mutant RAG-1 deficient animals having no mature B and T lymphocytes
CA2140638C (en) 1992-07-24 2010-05-04 Raju Kucherlapati 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
US5565321A (en) 1993-01-22 1996-10-15 Immunex Corporation Detection of mutations in a CD40 ligand gene
CA2161351C (en) 1993-04-26 2010-12-21 Nils Lonberg Transgenic non-human animals capable of producing heterologous antibodies
DE4331162A1 (de) 1993-09-14 1995-03-16 Bayer Ag Verfahren zur Herstellung von Cyaninfarbstoffen
US7119248B1 (en) 1994-04-12 2006-10-10 Miltenyi Biotec Gmbh Antibodies against epitopes with homology to self antigens, methods of preparation and applications thereof
US6130364A (en) 1995-03-29 2000-10-10 Abgenix, Inc. Production of antibodies using Cre-mediated site-specific recombination
EP0907726A4 (en) 1996-06-26 2001-11-07 Baylor College Medicine CHROMOSOMAL REORDERING BY INSERTING TWO RECOMBINATION SUBSTRATES
DK0937140T3 (da) 1996-06-27 2008-01-28 Vlaams Interuniv Inst Biotech Antistofmolekyler, som interagerer specifikt med et målmolekyles aktive sted eller klöft
CA2273194C (en) 1996-12-03 2011-02-01 Abgenix, Inc. Transgenic mammals having human ig loci including plural vh and vk regions and antibodies produced therefrom
US6319906B1 (en) 1996-12-31 2001-11-20 Isis Pharmaceuticals Oligonucleotide compositions and methods for the modulation of the expression of B7 protein
DK0979281T3 (da) 1997-05-02 2005-11-21 Genentech Inc Fremgangsmåde til fremstilling af multispecifikke antistoffer med heteromultimere og fælles bestanddele
US20020088019A1 (en) 1997-09-02 2002-07-04 Oron Yacoby-Zeevi Methods of and pharmaceutical compositions for improving implantation of embryos
CA2306184C (en) 1997-11-18 2007-05-15 Pioneer Hi-Bred International, Inc. Compositions and methods for genetic modification of plants
DK1034260T3 (da) 1997-12-05 2003-09-29 Europ Lab Molekularbiolog Hidtil ukendt DNA-kloningsmetode under anvendelse af E.coli-RECE/RECT-rekombinationssystemet
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
NZ525513A (en) 1998-08-07 2004-09-24 Pont Pharmaceuticals Du Succinoylamino lactams as inhibitors of Abeta protein production
GB9823930D0 (en) 1998-11-03 1998-12-30 Babraham Inst Murine expression of human ig\ locus
US6914128B1 (en) 1999-03-25 2005-07-05 Abbott Gmbh & Co. Kg Human antibodies that bind human IL-12 and methods for producing
AU5867100A (en) 1999-05-03 2000-12-12 Medarex, Inc. Human antibodies to staphylococcus aureus
US6833268B1 (en) 1999-06-10 2004-12-21 Abgenix, Inc. Transgenic animals for producing specific isotypes of human antibodies via non-cognate switch regions
US6355412B1 (en) 1999-07-09 2002-03-12 The European Molecular Biology Laboratory Methods and compositions for directed cloning and subcloning using homologous recombination
US7605238B2 (en) 1999-08-24 2009-10-20 Medarex, Inc. Human CTLA-4 antibodies and their uses
CA2307503A1 (en) * 2000-05-02 2001-11-02 Carlos F. Barbas Iii Peptides for use as a vaccine or treatment for hiv infection
BR0112633A (pt) * 2000-07-21 2003-09-16 Us Agriculture Método para substituir, translocar e empilhar dna em genomas eucarióticos
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
WO2002040685A2 (en) * 2000-11-16 2002-05-23 Cornell Research Foundation, Inc. Vectors for conditional gene inactivation
KR100882029B1 (ko) 2000-11-17 2009-02-09 교와 핫꼬 기린 가부시키가이샤 클로닝된 트랜스제닉 유제류에서 이종 (사람)면역글로블린의 발현
EP1916303B1 (en) 2000-11-30 2013-02-27 Medarex, Inc. Nucleic acids encoding rearranged human immunoglobulin sequences from transgenic transchromosomal mice
CA2432133C (en) * 2000-12-19 2012-11-13 Sunol Molecular Corporation Transgenic animals comprising a humanized immune system
BRPI0116728B1 (pt) 2001-01-05 2018-10-30 Abgenix Inc anticorpos para receptor de fator de crescimento i semelhante à insulina
AUPR446701A0 (en) 2001-04-18 2001-05-17 Gene Stream Pty Ltd Transgenic mammals for pharmacological and toxicological studies
JP2003000243A (ja) 2001-06-25 2003-01-07 Takachika Azuma 変異体の製造法
FR2827302B1 (fr) * 2001-07-13 2003-10-10 Genoway Cellule et animal transgenique modelisant la presentation antigenique humaine et leurs utilisations
WO2003017336A2 (en) 2001-08-13 2003-02-27 Amberwave Systems Corporation Dram trench capacitor and method of making the same
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
ES2645698T3 (es) 2001-11-30 2017-12-07 Amgen Fremont Inc. Animales transgénicos que portan genes de cadena ligera de Ig humana
WO2003061363A2 (en) 2002-01-17 2003-07-31 Albert Einstein College Of Medicine Of Yeshiva University Mutations caused by activation-induced cytidine deaminase
US8877901B2 (en) 2002-12-13 2014-11-04 Immunomedics, Inc. Camptothecin-binding moiety conjugates
SI1523496T1 (sl) 2002-07-18 2011-11-30 Merus B V Rekombinantno proizvajanje zmesi protiteles
WO2004022738A1 (en) 2002-09-09 2004-03-18 California Institute Of Technology Methods and compositions for the generation of humanized mice
AU2003277075B2 (en) 2002-10-01 2009-12-17 Mitos Pharmaceuticals, Inc. Nitroxide radioprotector formulations and methods of use
US7700356B2 (en) * 2002-11-08 2010-04-20 The United States Of America As Represented By The Secretary Of Agriculture System for gene targeting and producing stable genomic transgene insertions
DE10251918A1 (de) * 2002-11-08 2004-05-19 Horn, Carsten, Dipl.-Biochem. Dr. Systeme zur Erzeugung stabiler genomischer Transgen-Insertionen
AR042145A1 (es) 2002-11-27 2005-06-08 Dow Agrociences Llc Produccion de inmunoglobulinas en plantas con una fucocilacion reducida
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
CN1326878C (zh) * 2003-04-29 2007-07-18 中国抗体制药有限公司 抗人非何杰金淋巴瘤嵌合抗体及其衍生物与应用
AU2004242614B2 (en) 2003-05-30 2011-09-22 Merus N.V. 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
WO2005001087A2 (en) 2003-06-11 2005-01-06 Regeneron Pharmaceuticals, Inc. Methods of modifying genes in eukaryotic cells
GB2403475B (en) 2003-07-01 2008-02-06 Oxitec Ltd Stable integrands
JP2007537704A (ja) 2003-07-15 2007-12-27 セラピューティック ヒューマン ポリクローナルズ， インコーポレイテッド ヒト化免疫グロブリン遺伝子座
US7663017B2 (en) * 2003-07-30 2010-02-16 Institut Pasteur Transgenic mice having a human major histocompatability complex (MHC) phenotype, experimental uses and applications
WO2005019463A1 (en) 2003-08-11 2005-03-03 Therapeutic Human Polyclonals, Inc. Improved transgenesis with humanized immunoglobulin loci
US7604994B2 (en) 2003-09-03 2009-10-20 Morphotek, Inc. Genetically altered antibody-producing cell lines with improved antibody characteristics
CA2445602C (en) 2003-10-20 2014-01-14 Campusgen Gmbh Nucleotide sequence for creatinine deiminase and method of use
EP2865687A1 (en) 2003-12-10 2015-04-29 E. R. Squibb & Sons, L.L.C. IP-10 antibodies and their uses
US7625549B2 (en) 2004-03-19 2009-12-01 Amgen Fremont Inc. Determining the risk of human anti-human antibodies in transgenic mice
US20050260679A1 (en) 2004-03-19 2005-11-24 Sirid-Aimee Kellerman Reducing the risk of human anti-human antibodies through V gene manipulation
SI2311874T1 (sl) 2004-07-22 2017-12-29 Erasmus University Medical Center Rotterdam Department of Cell Biology and Genetics Vezavne molekule
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
PL1802193T3 (pl) 2004-10-19 2014-09-30 Regeneron Pharma Sposób wytwarzania myszy homozygotycznej pod względem modyfikacji genetycznej
CA2584814A1 (en) 2004-10-22 2006-05-04 Therapeutic Human Polyclonals, Inc. Suppression of endogenous immunoglobulin expression in non-human transgenic animals
WO2006055704A2 (en) 2004-11-17 2006-05-26 Curagen Corporation Antibodies directed to ten-m proteins and uses thereof
CN105085678B (zh) 2004-12-21 2019-05-07 阿斯利康公司 血管生成素-2的抗体及其应用
AU2006242854A1 (en) 2005-04-29 2006-11-09 Inserm (Institut National De La Sante Et De La Recherche Medicale) Transgenic animals and methods of making recombinant antibodies
AU2005331864A1 (en) * 2005-05-14 2006-11-23 Fudan University Piggybac as a tool for genetic manipulation and analysis in vertebrates
EP1780272A1 (en) 2005-10-27 2007-05-02 GSF-Forschungszentrum für Umwelt und Gesundheit GmbH Method for enhancing somatic hypermutation, gene conversion and class switch recombination
GB0601513D0 (en) 2006-01-25 2006-03-08 Univ Erasmus Medical Ct Binding molecules 3
KR101481843B1 (ko) * 2006-01-25 2015-01-12 에라스무스 유니버시티 메디컬 센터 로테르담 형질전환 동물 내에서의 중쇄만의 항체의 생성
US7462759B2 (en) 2006-02-03 2008-12-09 Pioneer Hi-Bred International, Inc. Brittle stalk 2 gene family and related methods and uses
JP5514539B2 (ja) 2006-03-31 2014-06-04 メダレックス・リミテッド・ライアビリティ・カンパニー ヒト抗体の調製に用いるためのキメラ抗体を発現するトランスジェニック動物
US7846724B2 (en) * 2006-04-11 2010-12-07 Hoffmann-La Roche Inc. Method for selecting CHO cell for production of glycosylated antibodies
MY159787A (en) 2006-06-02 2017-01-31 Regeneron Pharma High affinity antibodies to human il-6 receptor
WO2008094178A2 (en) 2006-06-27 2008-08-07 Vaxdesign Corporation Models for vaccine assessment
EP1878342A1 (en) 2006-07-13 2008-01-16 Institut Pasteur Immunodeficient mice transgenic for HLA class I and HLA class II molecules and their uses
EP2061812A4 (en) 2006-08-22 2010-06-09 G2 Inflammation Pty Ltd METHOD FOR THE PRODUCTION OF ANTIBODIES
US7778624B2 (en) * 2006-09-01 2010-08-17 Wanda Ying Li Outdoor umbrella with audio system
CA2664343C (en) 2006-10-02 2016-04-26 Regeneron Pharmaceuticals, Inc. High affinity human antibodies to human il-4 receptor
US7732195B2 (en) * 2006-11-01 2010-06-08 Facet Biotech Corporation Tethered vectors for cell surface immunoglobulin display
RU2448979C2 (ru) * 2006-12-14 2012-04-27 Ридженерон Фармасьютикалз, Инк. Антитела человека к дельта-подобному лиганду-4 человека
GB0700194D0 (en) 2007-01-05 2007-02-14 Univ Edinburgh Humanisation of animals
WO2008103474A1 (en) 2007-02-20 2008-08-28 Anaptysbio, Inc. Methods of generating libraries and uses thereof
PL2125889T3 (pl) 2007-02-21 2014-06-30 Univ Massachusetts Ludzkie przeciwciała przeciwko wirusowi żółtaczki typu C (HCV) i ich zastosowania
KR101540822B1 (ko) 2007-03-27 2015-07-30 씨 레인 바이오테크놀로지스, 엘엘씨 항체 대용물 경쇄 서열을 포함하는 구축물 및 라이브러리
GB0706628D0 (en) 2007-04-04 2007-05-16 Univ Erasmus Germ-line manipulation 1
AU2008259939B2 (en) 2007-06-01 2014-03-13 Open Monoclonal Technology, Inc. Compositions and methods for inhibiting endogenous immunoglobulin genes and producing transgenic human idiotype antibodies
WO2009013620A2 (en) 2007-06-11 2009-01-29 Erasmus University Medical Center Rotterdam Homologous recombination
ES2527297T3 (es) 2007-07-31 2015-01-22 Regeneron Pharmaceuticals, Inc. Anticuerpos humanos para CD20 humano y método para utilizar los mismos
SI2187964T1 (sl) 2007-08-10 2015-01-30 Regeneron Pharmaceuticals, Inc. Visokoafinitetna humana protitelesa proti humanemu živčnemu rastnemu faktorju
US9693539B2 (en) 2007-08-10 2017-07-04 E. R. Squibb & Sons, L.L.C. HCO32 and HCO27 and related examples
BRPI0818165B8 (pt) * 2007-10-12 2021-05-25 Hoffmann La Roche método de produção recombinante de uma imunoglobulina heteróloga em células cho que é secretada para o meio de cultura
NZ586149A (en) 2007-12-10 2012-05-25 Ablexis Llc Methods for sequential replacement of targeted region by homologous recombination
US8227577B2 (en) * 2007-12-21 2012-07-24 Hoffman-La Roche Inc. Bivalent, bispecific antibodies
CN101978000A (zh) 2008-01-25 2011-02-16 卡伯特公司 制备改性有色颜料的方法
KR101409375B1 (ko) 2008-01-31 2014-06-18 삼성전자주식회사 반도체 메모리장치의 블록 디코딩 회로
US20110107445A1 (en) 2008-03-26 2011-05-05 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
CA2725169A1 (en) * 2008-05-23 2009-11-26 Aliva Biopharmaceuticals, Inc. Method of generating single vl domain antibodies in transgenic animals
PT2147594E (pt) 2008-06-27 2014-02-17 Merus B V Mamíferos não humanos que produzem anticorpos
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).
JP5827127B2 (ja) 2008-12-18 2015-12-02 エラスムス・ユニヴァーシティ・メディカル・センター・ロッテルダム ヒト化抗体を発現する非ヒトトランスジェニック動物及びその使用
EP2394159B1 (en) 2009-02-04 2018-09-26 Molecular Innovations Assays for detecting prorenin, and antibodies used therein
WO2010097385A1 (en) 2009-02-24 2010-09-02 Glaxo Group Limited Antigen-binding constructs
GB0905023D0 (en) 2009-03-24 2009-05-06 Univ Erasmus Medical Ct Binding molecules
DK2414507T3 (da) 2009-04-03 2014-08-25 Medical Res Council Mutanter af aktiveringsinduceret cytidin-deaminase (aid) og til anvendelsesfremgangsmåder
TWI560271B (en) 2009-06-26 2016-12-01 Sealane Biotechnologies Llc Expression of surrogate light chains
GB0911846D0 (en) 2009-07-08 2009-08-19 Genome Res Ltd Animal models and therapeutic molecules
US9445581B2 (en) 2012-03-28 2016-09-20 Kymab Limited Animal models and therapeutic molecules
PT2564695E (pt) 2009-07-08 2015-06-03 Kymab Ltd Modelos animais e moléculas terapêuticas
GB0913102D0 (en) 2009-07-28 2009-09-02 Genome Res Ltd Animal models and therapeutic molesules
US9273118B2 (en) 2009-07-15 2016-03-01 Aimm Therapeutics B.V. Means and methods for producing high affinity antibodies
JO3182B1 (ar) 2009-07-29 2018-03-08 Regeneron Pharma مضادات حيوية بشرية عالية الالفة مع تولد الاوعية البشرية - 2
AU2010282508B2 (en) 2009-08-13 2015-05-28 Crystal Bioscience Inc. Transgenic animal for production of antibodies having minimal CDRs
US20120251552A1 (en) 2009-11-05 2012-10-04 Anaptysbio, Inc. Methods of generating improved antigen-binding agents using chain shuffling and optionally somatic hypermutation
US9315824B2 (en) 2009-11-17 2016-04-19 Sab, Llc Human artificial chromosome vector
US20120269830A1 (en) 2009-12-07 2012-10-25 Lawrence Horowitz Conjugates with improved pharmacokinetic properties
ES2595376T3 (es) 2009-12-10 2016-12-29 Regeneron Pharmaceuticals, Inc. Ratones que producen anticuerpos de cadena pesada
RS55315B2 (sr) 2010-02-08 2020-08-31 Regeneron Pharma Miš sa zajedničkim lakim lancem
US20120021409A1 (en) 2010-02-08 2012-01-26 Regeneron Pharmaceuticals, Inc. Common Light Chain Mouse
CA2798988C (en) 2010-05-17 2020-03-10 Sangamo Biosciences, Inc. Tal-effector (tale) dna-binding polypeptides and uses thereof
CN103228130B (zh) 2010-06-17 2016-03-16 科马布有限公司 动物模型及治疗分子
BR112012032991B1 (pt) 2010-06-22 2021-08-10 Regeneron Pharmaceuticals, Inc Método para preparar um anticorpo que se liga a um antígeno de interesse
KR102434557B1 (ko) 2010-08-02 2022-08-23 리제너론 파아마슈티컬스, 인크. Ｖｌ 도메인을 포함하는 결합 단백질을 생성하는 마우스
MX338953B (es) 2010-08-16 2016-05-06 Novimmune Sa Metodos para la generacion de anticuerpos multiespecificos y multivalentes.
JO3375B1 (ar) 2010-11-08 2019-03-13 Regeneron Pharma أجسام مضادة بشرية للجين a1 الشبيه بعامل النخر الورمي (tl1a)
WO2012088313A1 (en) 2010-12-22 2012-06-28 Genentech, Inc. Anti-pcsk9 antibodies and methods of use
PL2738259T3 (pl) 2011-02-25 2020-08-24 Regeneron Pharmaceuticals, Inc. Myszy adam6
PT2739740T (pt) 2011-08-05 2020-01-09 Regeneron Pharma Cadeia leve universal humanizada de murganhos
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
JP2014533930A (ja) 2011-09-19 2014-12-18 カイマブ・リミテッド 免疫グロブリン遺伝子多様性の操作およびマルチ抗体治療薬
EP2761008A1 (en) 2011-09-26 2014-08-06 Kymab Limited Chimaeric surrogate light chains (slc) comprising human vpreb
US10246509B2 (en) 2011-10-17 2019-04-02 Regeneron Pharmaceuticals, Inc. Restricted immunoglobulin heavy chain mice
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
US20180295821A1 (en) 2011-12-02 2018-10-18 Kymab Limited Transgenic Animals
US9253965B2 (en) 2012-03-28 2016-02-09 Kymab Limited Animal models and therapeutic molecules
MX356429B (es) 2011-12-20 2018-05-29 Regeneron Pharma Ratones con cadena ligera humanizada.
LT2809150T (lt) 2012-02-01 2019-10-25 Regeneron Pharma Humanizuota pelė, kuri ekspresuoja sunkiąsias grandines, kurių sudėtyje yar vl domenai
TWI592422B (zh) 2012-03-02 2017-07-21 再生元醫藥公司 抗艱難梭狀芽孢桿菌毒素之人類抗體
KR20140136462A (ko) 2012-03-06 2014-11-28 리제너론 파마슈티칼스 인코포레이티드 공통 경쇄 마우스
MX2014011047A (es) 2012-03-16 2015-04-08 Regeneron Pharma Ratones que producen proteinas de union a un antigeno con caracteristicas de union dependientes del ph.
SG11201405059XA (en) 2012-03-28 2014-09-26 Kymab Ltd Transgenic non-human vertebrate for the expression of class - switched, fully human, antibodies
GB2502127A (en) 2012-05-17 2013-11-20 Kymab Ltd Multivalent antibodies and in vivo methods for their production
US10251377B2 (en) 2012-03-28 2019-04-09 Kymab Limited Transgenic non-human vertebrate for the expression of class-switched, fully human, antibodies
JO3820B1 (ar) 2012-05-03 2021-01-31 Regeneron Pharma أجسام مضادة بشرية لـ fel d1وطرق لاستخدامها
DE202013012241U1 (de) 2012-05-25 2016-01-18 Emmanuelle Charpentier Zusammensetzungen für die durch RNA gesteuerte Modifikation einer Ziel-DNA und für die durch RNA gesteuerte Modulation der Transkription
US8518765B1 (en) 2012-06-05 2013-08-27 Intermolecular, Inc. Aqua regia and hydrogen peroxide HCl combination to remove Ni and NiPt residues
SG10201609277PA (en) 2012-06-12 2017-01-27 Regeneron Pharma Humanized non-human animals with restricted immunoglobulin heavy chain loci
US8962913B2 (en) * 2012-06-18 2015-02-24 Regeneron Pharmaceuticals, Inc. Humanized IL-7 rodents
US9938538B2 (en) 2012-11-09 2018-04-10 Shenzhen Institute Of Molecular Crop Design Fertility gene and use thereof
BR112015013784A2 (pt) 2012-12-12 2017-07-11 Massachusetts Inst Technology aplicação, manipulação e otimização de sistemas, métodos e composições para manipulação de sequência e aplicações terapêuticas
MY185881A (en) 2013-02-20 2021-06-14 Regeneron Pharma Non-human animals with modified immunoglobulin heavy chain sequences
US10993420B2 (en) 2013-03-15 2021-05-04 Erasmus University Medical Center Production of heavy chain only antibodies in transgenic mammals
US9788534B2 (en) 2013-03-18 2017-10-17 Kymab Limited Animal models and therapeutic molecules
US9783618B2 (en) * 2013-05-01 2017-10-10 Kymab Limited Manipulation of immunoglobulin gene diversity and multi-antibody therapeutics
US20150033372A1 (en) 2013-05-01 2015-01-29 Kymab Limited Human VpreB & Chimaeric Surrogate Light Chains in Transgenic Non-Human Vertebrates
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
US20140331344A1 (en) 2013-05-03 2014-11-06 Kymab Ltd. Transgenic Animals
US20140331339A1 (en) 2013-05-03 2014-11-06 Kymab Limited Transgenic Non-Human Assay Vertebrates, Assays and Kits
CA2925723A1 (en) 2013-10-01 2015-04-09 Kymab Limited Animal models and therapeutic molecules
GB201710984D0 (en) 2017-07-07 2017-08-23 Kymab Ltd Cells, vertebrates, populations & methods
JP7087648B2 (ja) * 2018-05-08 2022-06-21 トヨタ自動車株式会社 電池パック

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