DK2908626T3 - Humanized IL-15 animals - Google Patents
Humanized IL-15 animals Download PDFInfo
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- DK2908626T3 DK2908626T3 DK14790452.8T DK14790452T DK2908626T3 DK 2908626 T3 DK2908626 T3 DK 2908626T3 DK 14790452 T DK14790452 T DK 14790452T DK 2908626 T3 DK2908626 T3 DK 2908626T3
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- A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
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- A—HUMAN NECESSITIES
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- A—HUMAN NECESSITIES
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| RU2577978C2 (ru) | 2011-02-15 | 2016-03-20 | Ридженерон Фармасьютикалз, Инк. | Гуманизированные m-csf мыши |
| NZ746089A (en) | 2012-09-07 | 2020-05-29 | Institute For Res In Biomedicine Irb | Genetically modified non-human animals and methods of use thereof |
| ES2748662T3 (es) | 2012-11-05 | 2020-03-17 | Institute For Res In Biomedicine Irb | Roedores inmunodeficientes modificados genéticamente y métodos de uso de los mismos |
| TR201904342T4 (tr) | 2013-10-15 | 2019-05-21 | Regeneron Pharma | Hümani̇ze il-15 hayvanlar |
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| SG10202103445QA (en) * | 2015-04-13 | 2021-05-28 | Regeneron Pharma | Humanized sirpa-il15 knockin mice and methods of use thereof |
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| CA3014645C (en) | 2016-02-29 | 2022-10-25 | Regeneron Pharmaceuticals, Inc. | Rodents having a humanized tmprss gene |
| US10912287B2 (en) | 2016-06-28 | 2021-02-09 | Biocytogen Pharmaceuticals (Beijing) Co., Ltd | Genetically modified mice expressing humanized PD-1 |
| 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 |
| WO2018041121A1 (en) | 2016-08-31 | 2018-03-08 | Beijing Biocytogen Co., Ltd | Genetically modified non-human animal with human or chimeric ctla-4 |
| 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 |
| US11317611B2 (en) | 2016-08-31 | 2022-05-03 | Biocytogen Pharmaceuticals (Beijing) Co., Ltd. | Genetically modified non-human animal with human or chimeric PD-L1 |
| WO2018041120A1 (en) | 2016-08-31 | 2018-03-08 | Beijing Biocytogen Co., Ltd | Genetically modified non-human animal with human or chimeric tigit |
| US11279948B2 (en) | 2016-08-31 | 2022-03-22 | Biocytogen Pharmaceuticals (Beijing) Co., Ltd. | Genetically modified non-human animal with human or chimeric OX40 |
| 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 |
| JP7458185B2 (ja) | 2016-11-30 | 2024-03-29 | ザ ジャクソン ラボラトリー | 改善されたヒト自然免疫細胞の発生を有するヒト化マウスモデル |
| 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 |
| 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 |
| WO2018177441A1 (en) | 2017-03-31 | 2018-10-04 | Beijing Biocytogen Co., Ltd | GENETICALLY MODIFIED NON-HUMAN ANIMAL WITH HUMAN OR CHIMERIC SIRPα |
| 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 |
| 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 |
| 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 |
| IL272475B2 (en) * | 2017-08-09 | 2025-05-01 | Jackson Lab | Immunodeficient mice expressing interleukin 15 |
| EP3585162B1 (en) | 2017-09-29 | 2023-08-30 | Regeneron Pharmaceuticals, Inc. | Rodents 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 |
| WO2019114768A1 (en) | 2017-12-12 | 2019-06-20 | Biocytogen Jiangsu Co., Ltd. | GENETICALLY MODIFIED NON-HUMAN ANIMAL WITH HUMAN OR CHIMERIC CD3e |
| HUE067361T2 (hu) | 2018-07-16 | 2024-10-28 | Regeneron Pharma | Ditra betegség rágcsáló modelljei és alkalmazásaik |
| 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 |
| CN111304248B (zh) * | 2018-12-25 | 2021-08-24 | 百奥赛图江苏基因生物技术有限公司 | 人源化细胞因子il15基因改造非人动物的构建方法及应用 |
| CN111218425B (zh) * | 2019-01-17 | 2022-02-08 | 百奥赛图(北京)医药科技股份有限公司 | 人源化转基因动物 |
| AU2020253532B2 (en) | 2019-04-04 | 2024-06-20 | Regeneron Pharmaceuticals, Inc. | Non-human animals comprising a humanized coagulation factor 12 locus |
| 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 |
| SG11202111256XA (en) | 2019-06-07 | 2021-11-29 | Regeneron Pharma | Non-human animals comprising a humanized albumin locus |
| WO2021129766A1 (zh) * | 2019-12-25 | 2021-07-01 | 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 |
| JP2023511626A (ja) * | 2020-01-28 | 2023-03-20 | 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ｐｎｐｌａ３遺伝子座を含む非ヒト動物および使用方法 |
| 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 |
Family Cites Families (18)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU2001239750A1 (en) | 2000-02-08 | 2001-08-20 | Genaissance Pharmaceuticals, Inc. | Haplotypes of the interleukin 15 gene |
| US7759541B2 (en) * | 2004-12-13 | 2010-07-20 | Iti Life Sciences | Transgenic animals for assessing drug metabolism and toxicity |
| PL1899364T5 (pl) * | 2005-05-17 | 2024-12-09 | University Of Connecticut | Kompozycje i sposoby immunomodulacji w organizmie |
| RU2559524C2 (ru) * | 2008-06-27 | 2015-08-10 | Мерюс Б.В. | Продуцирующие антитела млекопитающие, не являющиеся человеком |
| RU2425880C2 (ru) * | 2009-07-30 | 2011-08-10 | Учреждение Российской академии наук Институт общей генетики им. Н.И. Вавилова РАН | Способ получения трансгенных мышей |
| EP3417701B1 (en) | 2009-10-06 | 2021-12-15 | Regeneron Pharmaceuticals, Inc. | Genetically modified mice and engraftment |
| EP3336102A3 (en) * | 2009-12-21 | 2018-08-01 | Regeneron Pharmaceuticals, Inc. | Humanized fc gamma r mice |
| RU2577978C2 (ru) | 2011-02-15 | 2016-03-20 | Ридженерон Фармасьютикалз, Инк. | Гуманизированные m-csf мыши |
| US9043996B2 (en) * | 2011-10-28 | 2015-06-02 | Regeneron Pharmaceuticals, Inc. | Genetically modified major histocompatibility complex animals |
| SG10201510056SA (en) * | 2011-10-28 | 2016-01-28 | Regeneron Pharma | Genetically modified mice expressing chimeric major histocompatibility complex (mhc) ii molecules |
| RU2751240C2 (ru) | 2011-10-28 | 2021-07-12 | Регенерон Фармасьютикалс, Инк. | Гуманизированные il-6 и рецептор il-6 |
| KR102295746B1 (ko) | 2011-10-28 | 2021-09-01 | 리제너론 파아마슈티컬스, 인크. | 유전자 변형된 주요 조직적합성 복합체 마우스 |
| US8962913B2 (en) | 2012-06-18 | 2015-02-24 | Regeneron Pharmaceuticals, Inc. | Humanized IL-7 rodents |
| NZ746089A (en) | 2012-09-07 | 2020-05-29 | Institute For Res In Biomedicine Irb | Genetically modified non-human animals and methods of use thereof |
| ES2748662T3 (es) | 2012-11-05 | 2020-03-17 | Institute For Res In Biomedicine Irb | Roedores inmunodeficientes modificados genéticamente y métodos de uso de los mismos |
| JP6444321B2 (ja) | 2013-02-22 | 2018-12-26 | 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Ｒｅｇｅｎｅｒｏｎ Ｐｈａｒｍａｃｅｕｔｉｃａｌｓ， Ｉｎｃ． | ヒト化主要組織適合性遺伝子複合体を発現するマウス |
| SMT202500280T1 (it) | 2013-09-23 | 2025-09-12 | Regeneron Pharma | Animali non umani aventi un gene umanizzato della proteina regolatrice del segnale |
| TR201904342T4 (tr) | 2013-10-15 | 2019-05-21 | Regeneron Pharma | Hümani̇ze il-15 hayvanlar |
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