RU2674910C2 - Животные с гуманизированным геном il-15 - Google Patents
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| ES3040596T3 (en) | 2011-02-15 | 2025-11-03 | Regeneron Pharma | Humanized m-csf mice and uses thereof |
| KR102287541B1 (ko) | 2012-09-07 | 2021-08-10 | 예일 유니버시티 | 유전적으로 변형된 비-인간 동물 및 이것들의 사용 방법 |
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| KR102617691B1 (ko) | 2014-12-05 | 2023-12-27 | 리제너론 파마슈티칼스 인코포레이티드 | 인간화 분화 클러스터 47 유전자를 가진 비인간 동물 |
| JP6752221B2 (ja) | 2015-04-13 | 2020-09-09 | リジェネロン・ファーマシューティカルズ・インコーポレイテッド | ヒト化ｓｉｒｐａ−ｉｌ１５ノックインマウス及びその使用方法 |
| CN108779159B (zh) | 2016-02-04 | 2022-12-30 | 瑞泽恩制药公司 | 具有经改造的angptl8基因的非人动物 |
| JP6980674B2 (ja) | 2016-02-29 | 2021-12-15 | 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. | ヒト化ｔｍｐｒｓｓ遺伝子を有する齧歯類 |
| DK3476865T5 (da) | 2016-06-28 | 2024-09-09 | Biocytogen Pharmaceuticals Beijing Co Ltd | Fremgangsmåde til konstruktion af pd-1-gen-modificeret humaniseret dyremodel og anvendelse deraf |
| CN107815467B (zh) | 2016-08-31 | 2021-03-16 | 百奥赛图(北京)医药科技股份有限公司 | 人源化基因改造动物模型的制备方法及应用 |
| WO2018041121A1 (en) | 2016-08-31 | 2018-03-08 | Beijing Biocytogen Co., Ltd | Genetically modified non-human animal with human or chimeric ctla-4 |
| WO2018041119A1 (en) | 2016-08-31 | 2018-03-08 | Beijing Biocytogen Co., Ltd | Genetically modified non-human animal with human or chimeric ox40 |
| DK3507373T5 (da) | 2016-08-31 | 2024-09-02 | Biocytogen Pharmaceuticals Beijing Co Ltd | Genetisk modificeret ikke-menneskeligt dyr med human eller kimær pd-l1 |
| WO2018041120A1 (en) | 2016-08-31 | 2018-03-08 | Beijing Biocytogen Co., Ltd | Genetically modified non-human animal with human or chimeric tigit |
| CN107815468B (zh) | 2016-08-31 | 2021-03-16 | 百奥赛图(北京)医药科技股份有限公司 | 人源化基因改造动物模型的制备方法及应用 |
| CN108070613B (zh) | 2016-11-11 | 2020-03-13 | 百奥赛图江苏基因生物技术有限公司 | 人源化基因改造动物模型的制备方法及应用 |
| WO2018086594A1 (en) | 2016-11-11 | 2018-05-17 | Beijing Biocytogen Co., Ltd | Genetically modified non-human animal with human or chimeric tim-3 |
| EP3547831A1 (en) | 2016-11-30 | 2019-10-09 | The Jackson Laboratory | Humanized mouse model with improved human innate immune cell development |
| CN108239659B (zh) | 2016-12-23 | 2020-03-03 | 百奥赛图江苏基因生物技术有限公司 | 人源化基因改造动物模型的制备方法及应用 |
| CN108424928B (zh) | 2016-12-30 | 2021-03-16 | 百奥赛图(北京)医药科技股份有限公司 | 人源化基因改造动物模型的制备方法及应用 |
| US11629340B2 (en) | 2017-03-03 | 2023-04-18 | Obsidian Therapeutics, Inc. | DHFR tunable protein regulation |
| 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 |
| CN109136275B (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gitr基因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 |
| CN109136274B (zh) | 2017-06-19 | 2021-04-23 | 百奥赛图江苏基因生物技术有限公司 | 人源化cd40基因改造动物模型的制备方法及应用 |
| WO2019032836A1 (en) * | 2017-08-09 | 2019-02-14 | The Jackson Laboratory | IMMUNODEFICIENT MOUSE EXPRESSING THE HUMAN INTERLEUKINE 15 |
| ES2962277T3 (es) | 2017-09-29 | 2024-03-18 | Regeneron Pharma | Roedores que comprenden un locus Ttr humanizado y métodos de uso |
| WO2019072241A1 (en) | 2017-10-13 | 2019-04-18 | Beijing Biocytogen Co., Ltd | NON-HUMAN ANIMAL GENETICALLY MODIFIED WITH PD-1 HUMAN OR CHIMERIC |
| CN109913493B (zh) | 2017-12-12 | 2021-03-16 | 百奥赛图江苏基因生物技术有限公司 | 人源化cd3基因改造动物模型的制备方法及应用 |
| HRP20240999T1 (hr) | 2018-07-16 | 2024-10-25 | Regeneron Pharmaceuticals, Inc. | Glodavački modeli bolesti ditra i njihova upotreba |
| WO2020074005A1 (en) | 2018-10-12 | 2020-04-16 | Beijing Biocytogen Co., Ltd | Genetically modified non-human animal with human or chimeric genes |
| WO2020125763A1 (en) | 2018-12-20 | 2020-06-25 | Biocytogen Jiangsu Co., Ltd. | Genetically modified non-human animal with human or chimeric lag3 |
| WO2020135518A1 (en) * | 2018-12-25 | 2020-07-02 | Biocytogen Jiangsu Co., Ltd. | Genetically modified non-human animal with human or chimeric il15 |
| CN114164177A (zh) * | 2019-01-17 | 2022-03-11 | 百奥赛图(北京)医药科技股份有限公司 | 人源化转基因动物 |
| WO2020206139A1 (en) | 2019-04-04 | 2020-10-08 | Regeneron Pharmaceuticals, Inc. | Non-human animals comprising a humanized coagulation factor 12 locus |
| EP3801011A1 (en) | 2019-06-04 | 2021-04-14 | Regeneron Pharmaceuticals, Inc. | Non-human animals comprising a humanized ttr locus with a beta-slip mutation and methods of use |
| AU2020289581B2 (en) | 2019-06-07 | 2024-11-21 | Regeneron Pharmaceuticals, Inc. | Non-human animals comprising a humanized albumin locus |
| CN114786479B (zh) * | 2019-12-25 | 2023-12-15 | 江苏集萃药康生物科技股份有限公司 | 一种il-15人源化小鼠模型及其用途 |
| US12250931B2 (en) * | 2020-01-28 | 2025-03-18 | Regeneron Pharmaceuticals, Inc. | Genetically modified mouse with a humanized PNPLA3 gene and methods of use |
| CN111485001A (zh) * | 2020-04-14 | 2020-08-04 | 澎立生物医药技术（上海）有限公司 | 具有nk细胞及adcc能力的人源化免疫系统小鼠的构建方法 |
| CN112481303B (zh) * | 2021-02-09 | 2021-05-25 | 百奥赛图(北京)医药科技股份有限公司 | Il15ra基因人源化非人动物及其构建方法和应用 |
| WO2025212991A1 (en) | 2024-04-05 | 2025-10-09 | Regeneron Pharmaceuticals, Inc. | Rodent models of disease |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2001058914A2 (en) * | 2000-02-08 | 2001-08-16 | Genaissance Pharmaceuticals, Inc. | Haplotypes of the interleukin 15 gene |
| RU2425880C2 (ru) * | 2009-07-30 | 2011-08-10 | Учреждение Российской академии наук Институт общей генетики им. Н.И. Вавилова РАН | Способ получения трансгенных мышей |
| WO2012112544A2 (en) * | 2011-02-15 | 2012-08-23 | Regeneron Pharmaceuticals, Inc. | Humanized m-csf mice |
Family Cites Families (15)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7759541B2 (en) * | 2004-12-13 | 2010-07-20 | Iti Life Sciences | Transgenic animals for assessing drug metabolism and toxicity |
| EP3263581B2 (en) * | 2005-05-17 | 2025-07-09 | University of Connecticut | Compositions and methods for immunomodulation in an organism |
| PT3456190T (pt) * | 2008-06-27 | 2022-02-15 | Merus Nv | Animal murino transgénico produtor de anticorpo |
| CA3040377C (en) | 2009-10-06 | 2025-12-30 | Yale University | Genetically modified mice and engraftment comprising the knock-in of a human thrombopoietin (tpo) gene |
| MY156743A (en) * | 2009-12-21 | 2016-03-31 | Regeneron Pharma | Humanized fc?r mice |
| RS56330B1 (sr) * | 2011-10-28 | 2017-12-29 | Regeneron Pharma | Genetski modifikovani miševi sa ekspresijom himernih molekula klase ii glavnog kompleksa histokompatibilnosti (mhc) |
| MY186903A (en) | 2011-10-28 | 2021-08-26 | Regeneron Pharma | Humanized il-6 and il-6 receptor |
| RS56656B1 (sr) | 2011-10-28 | 2018-03-30 | Regeneron Pharma | Miševi sa genetski modifikovanim glavnim kompleksom gena tkivne podudarnosti |
| US9043996B2 (en) * | 2011-10-28 | 2015-06-02 | Regeneron Pharmaceuticals, Inc. | Genetically modified major histocompatibility complex animals |
| US8962913B2 (en) | 2012-06-18 | 2015-02-24 | Regeneron Pharmaceuticals, Inc. | Humanized IL-7 rodents |
| KR102287541B1 (ko) | 2012-09-07 | 2021-08-10 | 예일 유니버시티 | 유전적으로 변형된 비-인간 동물 및 이것들의 사용 방법 |
| EP4389764B1 (en) | 2012-11-05 | 2026-03-18 | Regeneron Pharmaceuticals, Inc. | Genetically modified rodents and methods of use thereof |
| CN110192541B (zh) | 2013-02-22 | 2022-02-18 | 瑞泽恩制药公司 | 表达人源化主要组织相容性复合物的小鼠 |
| DK3175706T3 (en) | 2013-09-23 | 2019-03-04 | Regeneron Pharma | Non-human animals with a humanized signal regulatory protein gene |
| SMT201900177T1 (it) | 2013-10-15 | 2019-05-10 | Regeneron Pharma | Animali con il-15 umanizzata |
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2014
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Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2001058914A2 (en) * | 2000-02-08 | 2001-08-16 | Genaissance Pharmaceuticals, Inc. | Haplotypes of the interleukin 15 gene |
| RU2425880C2 (ru) * | 2009-07-30 | 2011-08-10 | Учреждение Российской академии наук Институт общей генетики им. Н.И. Вавилова РАН | Способ получения трансгенных мышей |
| WO2012112544A2 (en) * | 2011-02-15 | 2012-08-23 | Regeneron Pharmaceuticals, Inc. | Humanized m-csf mice |
Non-Patent Citations (1)
| Title |
|---|
| OHTA N. et al., IL-15-dependent activation-induced cell death-resistant Th1 type CD8 alpha beta+NK1.1+ T cells for the development of small intestinal inflammation, J Immunol, 2002, Vol.169, N.1, pp.460-468. MARKS-KONCZALIK et al., IL-2-induced activation-induced cell death is inhibited in IL-15 transgenic mice, Proc Natl Acad Sci U S A, 2000, Vol.97, n.21, pp.11445-11450. * |
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