KR102407354B1 - 인간화된 신호-조절 단백질 유전자를 가지는 비-인간 동물 - Google Patents

인간화된 신호-조절 단백질 유전자를 가지는 비-인간 동물 Download PDF

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KR102407354B1
KR102407354B1 KR1020227006825A KR20227006825A KR102407354B1 KR 102407354 B1 KR102407354 B1 KR 102407354B1 KR 1020227006825 A KR1020227006825 A KR 1020227006825A KR 20227006825 A KR20227006825 A KR 20227006825A KR 102407354 B1 KR102407354 B1 KR 102407354B1
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sirpα
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mouse
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cells
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앤드류 제이. 머피
오. 게빈 써스톤
빈두 바르게즈
카간 구레어
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리제너론 파마슈티칼스 인코포레이티드
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Families Citing this family (54)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US8541646B2 (en) 2009-10-06 2013-09-24 Regeneron Pharmaceuticals, Inc. Genetically modified mice and engraftment
PT4233537T (pt) 2011-02-15 2025-09-08 Regeneron Pharma Ratinhos humanizados para m-csf e utilizações dos mesmos
IN2015DN02032A (enExample) 2012-09-07 2015-08-14 Univ Yale
ES2884598T3 (es) 2012-11-05 2021-12-10 Regeneron Pharma Animales no humanos modificados genéticamente y métodos de uso de los mismos
MX368931B (es) 2013-09-23 2019-10-22 Regeneron Pharma Animales no humanos que tienen un gen de proteina reguladora de señal humanizado.
AU2014337526B2 (en) 2013-10-15 2020-09-10 Regeneron Pharmaceuticals, Inc. Humanized IL-15 animals
US20150143558A1 (en) 2013-11-19 2015-05-21 Regeneron Pharmaceuticals, Inc. Non-human animals having a humanized b-cell activating factor gene
RU2700484C2 (ru) 2014-04-08 2019-09-17 Регенерон Фармасьютикалз, Инк. Не относящиеся к человеку животные, имеющие гуманизированные fc-гамма-рецепторы
NO2785538T3 (enExample) 2014-05-07 2018-08-04
PT3482629T (pt) 2014-05-19 2021-02-18 Univ Yale Animais não humanos geneticamente modificados que expressam epo humana
EP3683238A1 (en) 2014-06-19 2020-07-22 Regeneron Pharmaceuticals, Inc. Non-human animals having a humanized programmed cell death 1 gene
KR102659123B1 (ko) 2014-11-24 2024-04-22 리제너론 파마슈티칼스 인코포레이티드 인간화 cd3 복합체를 발현하는 비인간 동물
FI3850946T3 (fi) 2014-12-05 2023-12-28 Regeneron Pharma Ei-ihmiseläimiä, joilla on humanisoitu erilaistumisklusterin 47 geeni
EP3808775B1 (en) 2014-12-09 2024-04-17 Regeneron Pharmaceuticals, Inc. Non-human animals having a humanized cluster of differentiation 274 gene
PT3282835T (pt) * 2015-04-13 2023-07-25 Univ Yale Ratinhos knockin de sirpa-il15 humanizadas e métodos de utilização dos mesmos
CN104904661B (zh) * 2015-06-05 2018-07-24 杭州正因生物技术有限公司 一种人源化小鼠
WO2017027422A1 (en) 2015-08-07 2017-02-16 Alexo Therapeutics Inc. Constructs having a sirp-alpha domain or variant thereof
KR102454546B1 (ko) 2015-11-20 2022-10-14 리제너론 파마슈티칼스 인코포레이티드 인간화 림프구 활성화 유전자 3을 갖는 비인간 동물
EP3411392B1 (en) 2016-02-04 2021-12-29 Regeneron Pharmaceuticals, Inc. Non-human animals having an engineered angptl8 gene
EP3895529B1 (en) 2016-02-29 2026-04-29 Regeneron Pharmaceuticals, Inc. Rodents having a humanized tmprss gene
CN108467873B (zh) 2017-03-17 2020-03-13 百奥赛图江苏基因生物技术有限公司 一种cd132基因缺失的免疫缺陷动物模型的制备方法及应用
WO2018177441A1 (en) * 2017-03-31 2018-10-04 Beijing Biocytogen Co., Ltd GENETICALLY MODIFIED NON-HUMAN ANIMAL WITH HUMAN OR CHIMERIC SIRPα
CN108588126B (zh) 2017-03-31 2020-04-10 北京百奥赛图基因生物技术有限公司 Cd47基因人源化改造动物模型的制备方法及应用
CN109136261B (zh) 2017-06-19 2021-03-16 百奥赛图(北京)医药科技股份有限公司 人源化cd28基因改造动物模型的制备方法及应用
WO2018233608A1 (en) * 2017-06-19 2018-12-27 Beijing Biocytogen Co., Ltd Genetically modified non-human animal with human or chimeric cd28
CN110891420B (zh) 2017-07-31 2022-06-03 瑞泽恩制药公司 Cas转基因小鼠胚胎干细胞和小鼠及其应用
CA3068072A1 (en) 2017-07-31 2019-02-07 Regeneron Pharmaceuticals, Inc. Methods and compositions for assessing crispr/cas-mediated disruption or excision and crispr/cas-induced recombination with an exogenous donor nucleic acid in vivo
JP7139419B2 (ja) 2017-09-29 2022-09-20 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ｔｔｒ遺伝子座を含む非ヒト動物および使用方法
IL274740B2 (en) 2017-11-30 2024-06-01 Regeneron Pharma Non-human animals comprising a humanized trkb locus
KR20240038811A (ko) 2018-03-19 2024-03-25 리제너론 파마슈티칼스 인코포레이티드 CRISPR/Cas 시스템을 사용한 동물에서의 전사 조절
WO2019190990A1 (en) 2018-03-26 2019-10-03 Regeneron Pharmaceuticals, Inc. Humanized rodents for testing therapeutic agents
KR102816742B1 (ko) 2018-07-10 2025-06-05 고쿠리츠다이가쿠호진 고베다이가쿠 항 SIRPα 항체
IL315703A (en) 2018-07-16 2024-11-01 Regeneron Pharma Non-human animal models of DITRA disease and their uses
US12331320B2 (en) 2018-10-10 2025-06-17 The Research Foundation For The State University Of New York Genome edited cancer cell vaccines
WO2020160285A1 (en) * 2019-02-01 2020-08-06 The Board Of Trustees Of The Leland Stanford Junior University SIRPα EXPRESSION ON T CELLS IS A BIOMARKER FOR FUNCTIONAL T CELLS DURING EXHAUSTION
ES2966625T3 (es) 2019-04-04 2024-04-23 Regeneron Pharma Roedores que comprenden un locus del factor de coagulación 12 humanizado
KR20220044904A (ko) 2019-05-31 2022-04-12 알렉소 온콜로지 인크. 면역 관문 억제제와 병용하는 sirp 알파 fc 융합으로 암을 치료하는 방법
US11891618B2 (en) 2019-06-04 2024-02-06 Regeneron Pharmaceuticals, Inc. Mouse comprising a humanized TTR locus with a beta-slip mutation and methods of use
CA3137764A1 (en) 2019-06-07 2020-12-10 Regeneron Pharmaceuticals, Inc. Non-human animals comprising a humanized albumin locus
CN114845710A (zh) 2019-11-27 2022-08-02 Alx肿瘤生物技术公司 用于治疗癌症的组合疗法
WO2021136537A1 (en) * 2019-12-31 2021-07-08 Biocytogen Pharmaceuticals (Beijing) Co., Ltd. GENETICALLY MODIFIED IMMUNODEFICIENT NON-HUMAN ANIMAL WITH HUMAN OR CHIMERIC SIRPα/CD47
CN115175559A (zh) 2020-01-28 2022-10-11 瑞泽恩制药公司 包含人源化pnpla3基因座的非人动物及其使用方法
CA3167557A1 (en) 2020-04-21 2021-10-28 Davor Frleta Non-human animals having a humanized cxcl13 gene
CA3171455A1 (en) 2020-12-21 2022-06-30 Yajun Tang Non-human animals having a humanized tslp gene, a humanized tslp receptor gene, and/or a humanized il7ra gene
BR112023022774A2 (pt) 2021-05-13 2024-01-02 Alx Oncology Inc Terapias de combinação para tratamento de câncer
US12582104B2 (en) 2021-12-08 2026-03-24 Regeneron Pharmaceuticals, Inc. Mutant myocilin disease model and uses thereof
WO2023143341A1 (en) * 2022-01-25 2023-08-03 Biocytogen Pharmaceuticals (Beijing) Co., Ltd. Genetically modified non-human animal with human or chimeric nkp46
AU2023310163A1 (en) 2022-07-19 2025-01-16 Regeneron Pharmaceuticals, Inc. Genetically modified animal model and its use to model the human 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
IL325100A (en) 2023-06-16 2026-02-01 Regeneron Pharma Vectors, genetically modified cells and genetically modified non-human animals containing them
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
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
WO2026096736A1 (en) 2024-10-31 2026-05-07 Regeneron Pharmaceuticals, Inc. Rodents expressing humanized polymeric immunoglobulin receptor

Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5149635A (en) 1986-09-12 1992-09-22 Abbott Biotech, Inc. Messenger RNA stabilization in animal cells
WO1999012965A2 (en) 1997-09-12 1999-03-18 Biogen, Inc. April- a novel protein with growth effects
WO2006128163A2 (en) 2005-05-27 2006-11-30 Memory Pharmaceuticals Corp. Transgenic alzheimer's mouse model vectors and uses thereof
US20070028316A1 (en) 2005-06-02 2007-02-01 Xiaoxia Li Transgenic non-human Act1-deficient mammals and uses thereof
WO2012112544A2 (en) 2011-02-15 2012-08-23 Regeneron Pharmaceuticals, Inc. Humanized m-csf mice
US20180295818A1 (en) 2015-04-30 2018-10-18 Institute Of Immunology Co., Ltd. TRANSGENIC NON-HUMAN ANIMAL EXPRESSING HUMAN SPECIFIC MOLECULE AND HUMAN FCy RECEPTOR FAMILY

Family Cites Families (18)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6586251B2 (en) 2000-10-31 2003-07-01 Regeneron Pharmaceuticals, Inc. Methods of modifying eukaryotic cells
ES2364335T3 (es) * 2003-12-24 2011-08-31 G2 Inflammation Pty Ltd Mamífero no humano transgénico que comprende un polinucleótido que codifica el c5ar humano o humanizado.
WO2006044962A1 (en) 2004-10-19 2006-04-27 Regeneron Pharmaceuticals, Inc. Method for generating an animal homozygous for a genetic modification
EP2573112A1 (en) * 2007-10-11 2013-03-27 The Hospital For Sick Children Modulation of sirpa - cd47 interaction for increasing human hematopoietic stem cell engraftment and compounds therefor
TWI476280B (zh) 2008-03-07 2015-03-11 Regeneron Pharma 來自二倍體宿主胚胎注射之ｅｓ－細胞衍生的老鼠
RU2425880C2 (ru) * 2009-07-30 2011-08-10 Учреждение Российской академии наук Институт общей генетики им. Н.И. Вавилова РАН Способ получения трансгенных мышей
US8541646B2 (en) 2009-10-06 2013-09-24 Regeneron Pharmaceuticals, Inc. Genetically modified mice and engraftment
US9402377B2 (en) * 2010-09-20 2016-08-02 Yale University Human SIRPAalpha transgenic animals and their methods of use
CA2827348C (en) * 2011-02-14 2021-02-23 Revivicor, Inc. Genetically modified pigs for xenotransplantation of vascularized xenografts and derivatives thereof
PL2818478T3 (pl) 2011-10-28 2017-09-29 Regeneron Pharmaceuticals, Inc. Humanizowane il-6 i receptor il-6
RS63220B1 (sr) 2011-10-28 2022-06-30 Regeneron Pharma Genetski modifikovani miševi sa ekspresijom himernih molekula klase ii glavnog kompleksa histokompatibilnosti (mhc)
ES2741649T3 (es) 2011-10-28 2020-02-11 Regeneron Pharma Ratones con complejo mayor de histocompatibilidad modificado genéticamente
US8962913B2 (en) 2012-06-18 2015-02-24 Regeneron Pharmaceuticals, Inc. Humanized IL-7 rodents
IN2015DN02032A (enExample) 2012-09-07 2015-08-14 Univ Yale
ES2884598T3 (es) 2012-11-05 2021-12-10 Regeneron Pharma Animales no humanos modificados genéticamente y métodos de uso de los mismos
CA2900832A1 (en) 2013-02-20 2014-08-28 Regeneron Pharmaceuticals, Inc. Mice expressing humanized t-cell co-receptors
CA2900824A1 (en) 2013-02-22 2014-08-28 Regeneron Pharmaceuticals, Inc. Mice expressing humanized major histocompatibility complex
MX368931B (es) 2013-09-23 2019-10-22 Regeneron Pharma Animales no humanos que tienen un gen de proteina reguladora de señal humanizado.

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5149635A (en) 1986-09-12 1992-09-22 Abbott Biotech, Inc. Messenger RNA stabilization in animal cells
WO1999012965A2 (en) 1997-09-12 1999-03-18 Biogen, Inc. April- a novel protein with growth effects
WO2006128163A2 (en) 2005-05-27 2006-11-30 Memory Pharmaceuticals Corp. Transgenic alzheimer's mouse model vectors and uses thereof
US20070028316A1 (en) 2005-06-02 2007-02-01 Xiaoxia Li Transgenic non-human Act1-deficient mammals and uses thereof
WO2012112544A2 (en) 2011-02-15 2012-08-23 Regeneron Pharmaceuticals, Inc. Humanized m-csf mice
US20180295818A1 (en) 2015-04-30 2018-10-18 Institute Of Immunology Co., Ltd. TRANSGENIC NON-HUMAN ANIMAL EXPRESSING HUMAN SPECIFIC MOLECULE AND HUMAN FCy RECEPTOR FAMILY

Non-Patent Citations (8)

* Cited by examiner, † Cited by third party
Title
Improving human hemato-lymphoidsystem mice by cytokine knock-in gene replacement, vol.32 no.7 pp.321-327, 2011
J Clin Invest vol.109 no.12 pp.1587-1598, 2002
J immunol. vol.175 no.1 pp.319-328 2005
mproving human hemato-lymphoidsystem mice by cytokine knock-in gene replacement, vol.32 no.7 pp.321-327 2011
PLoS One vol.3 no.9 pp.e3192 2008
PNAS vol.101 no.11 pp.3903-3908, 2004
Semin Immunol. vol.18 no.5 pp.263-275 2006
Semin Immunol. vol.18 no.5 pp.263-275, 2006

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