KR102768101B1 - 유전자 변형된 비-인간 동물 및 그것의 사용 방법 - Google Patents
유전자 변형된 비-인간 동물 및 그것의 사용 방법 Download PDFInfo
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Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
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| US201261722437P | 2012-11-05 | 2012-11-05 | |
| US61/722,437 | 2012-11-05 | ||
| PCT/US2013/068569 WO2014071397A2 (en) | 2012-11-05 | 2013-11-05 | Genetically modified non-human animals and methods of use thereof |
| KR1020227036338A KR102649893B1 (ko) | 2012-11-05 | 2013-11-05 | 유전자 변형된 비-인간 동물 및 그것의 사용 방법 |
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| KR1020227036338A Active KR102649893B1 (ko) | 2012-11-05 | 2013-11-05 | 유전자 변형된 비-인간 동물 및 그것의 사용 방법 |
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| KR1020217020816A Active KR102402806B1 (ko) | 2012-11-05 | 2013-11-05 | 유전자 변형된 비-인간 동물 및 그것의 사용 방법 |
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| US6596541B2 (en) | 2000-10-31 | 2003-07-22 | Regeneron Pharmaceuticals, Inc. | Methods of modifying eukaryotic cells |
| US20050144655A1 (en) | 2000-10-31 | 2005-06-30 | Economides Aris N. | Methods of modifying eukaryotic cells |
| EP4502152A3 (en) | 2009-10-06 | 2025-04-30 | 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 |
| KR102241962B1 (ko) * | 2012-09-07 | 2021-04-20 | 예일 유니버시티 | 유전적으로 변형된 비-인간 동물 및 이것들의 사용 방법 |
| DK4389764T3 (da) | 2012-11-05 | 2026-04-13 | Regeneron Pharma | Genetisk modificerede gnavere og fremgangsmåder til anvendelse heraf |
| 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 |
| HRP20231121T1 (hr) | 2013-09-23 | 2023-12-22 | Regeneron Pharmaceuticals, Inc. | Životinje koje nisu ljudi, koje imaju gen za humanizirani protein koji regulira signale |
| JP6492095B2 (ja) | 2013-10-15 | 2019-03-27 | 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il−15動物 |
| 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 |
| RS60398B1 (sr) | 2014-04-08 | 2020-07-31 | Regeneron Pharma | Ne-humane životinje sa humanizovanim fc-gama receptorima |
| BR122023023211A2 (pt) | 2014-04-28 | 2024-01-23 | Recombinetics, Inc. | Método de fazer edições de genes multiplex em uma célula de vertebrado ou de embrião primário não-humano |
| MX2016014504A (es) | 2014-05-05 | 2017-05-23 | Regeneron Pharma | Animales c5 y c3 humanizados. |
| NO2785538T3 (enExample) | 2014-05-07 | 2018-08-04 | ||
| EP3482629B1 (en) * | 2014-05-19 | 2020-11-25 | Regeneron Pharmaceuticals, Inc. | Genetically modified non-human animals expressing human epo |
| WO2015196051A1 (en) | 2014-06-19 | 2015-12-23 | Regeneron Pharmaceuticals, Inc. | Non-human animals having a humanized programmed cell death 1 gene |
| 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 |
| WO2016137841A1 (en) * | 2015-02-26 | 2016-09-01 | William Paterson University Of New Jersey | Transgenic mice |
| 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 |
| 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 |
| 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 |
| US20190183101A1 (en) * | 2016-08-11 | 2019-06-20 | The Jackson Laboratory | Methods and compositions relating to improved human red blood cell survival in genetically modified immunodeficient non-human animals |
| JOP20190009A1 (ar) | 2016-09-21 | 2019-01-27 | Alx Oncology Inc | أجسام مضادة ضد بروتين ألفا منظم للإشارات وطرق استخدامها |
| WO2018102546A1 (en) * | 2016-11-30 | 2018-06-07 | The Jackson Laboratory | Humanized mouse model with improved human innate immune cell development |
| SG11201907490XA (en) * | 2017-02-27 | 2019-09-27 | Regeneron Pharma | Non-human animal models of retinoschisis |
| CN107115424B (zh) * | 2017-05-09 | 2018-05-29 | 江西樟树市正康医药生物科技有限公司 | 改变酸性体质保钙及清热解毒的中药组合物及制备方法 |
| US11778994B2 (en) | 2017-05-12 | 2023-10-10 | The Jackson Laboratory | NSG mice lacking MHC class I and class II |
| WO2019067875A1 (en) | 2017-09-29 | 2019-04-04 | Regeneron Pharmaceuticals, Inc. | NON-HUMAN ANIMALS COMPRISING A HUMANIZED TTR LOCUS AND METHODS OF USE |
| US11712026B2 (en) | 2017-10-18 | 2023-08-01 | The Jackson Laboratory | Murine-MHC-deficient HLA-transgenic nod-mouse models for T1D therapy development |
| 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 |
| WO2019183266A1 (en) | 2018-03-21 | 2019-09-26 | ALX Oncology Inc. | Antibodies against signal-regulatory protein alpha and methods of use |
| IL277355B2 (en) | 2018-03-26 | 2025-01-01 | Regeneron Pharma | Humanized rodents for testing therapeutic agents |
| CA3098040A1 (en) | 2018-07-16 | 2020-01-23 | Regeneron Pharmaceuticals, Inc. | Non-human animal models of ditra disease and uses thereof |
| US12331320B2 (en) | 2018-10-10 | 2025-06-17 | The Research Foundation For The State University Of New York | Genome edited cancer cell vaccines |
| CN111057721B (zh) * | 2018-10-12 | 2021-03-16 | 百奥赛图(北京)医药科技股份有限公司 | 人源化IL-4和/或IL-4Rα改造动物模型的制备方法及应用 |
| CN111172190B (zh) * | 2018-12-25 | 2021-07-30 | 百奥赛图江苏基因生物技术有限公司 | 人源化细胞因子csf2基因改造非人动物的构建方法及应用 |
| 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 |
| 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 |
| 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 |
| WO2021011853A2 (en) * | 2019-07-17 | 2021-01-21 | Yale University | Genetically modified non-human animals and methods of use thereof |
| CN111304246B (zh) * | 2019-12-17 | 2021-05-04 | 百奥赛图江苏基因生物技术有限公司 | 一种人源化细胞因子动物模型、制备方法及应用 |
| EP4087392A4 (en) * | 2020-01-10 | 2024-02-21 | Biocytogen Pharmaceuticals (Beijing) Co., Ltd. | GENETICALLY MODIFIED NON-HUMAN ANIMAL WITH HUMAN OR CHIMERIC MHC PROTEIN COMPLEX |
| US10973908B1 (en) | 2020-05-14 | 2021-04-13 | David Gordon Bermudes | Expression of SARS-CoV-2 spike protein receptor binding domain in attenuated salmonella as a vaccine |
| US12537071B1 (en) | 2020-07-22 | 2026-01-27 | David Gordon Bermudes | Bacteria having boolean control pathways expressing therapeutic proteins including immunotherapeutic cytotoxins |
| AU2021347320A1 (en) | 2020-09-24 | 2023-05-11 | The Jackson Laboratory | Humanized mouse models for assessing immune cell therapy |
| 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 |
| CN116918766A (zh) * | 2022-04-07 | 2023-10-24 | 上海立迪生物技术股份有限公司 | 一种人aml小鼠原位pdox模型的建立方法及应用 |
| CN116918767A (zh) * | 2022-04-07 | 2023-10-24 | 上海立迪生物技术股份有限公司 | 一种人all小鼠原位pdox模型的建立方法及应用 |
| US20240102045A1 (en) | 2022-07-19 | 2024-03-28 | Regeneron Pharmaceuticals, Inc. | Vectors, genetically modified cells, and genetically modified non-human animals comprising the same |
| 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 |
| 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 (1)
| 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 |
Family Cites Families (71)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4870009A (en) | 1982-11-22 | 1989-09-26 | The Salk Institute For Biological Studies | Method of obtaining gene product through the generation of transgenic animals |
| US4736866B1 (en) | 1984-06-22 | 1988-04-12 | Transgenic non-human mammals | |
| US5573930A (en) | 1985-02-05 | 1996-11-12 | Cetus Oncology Corporation | DNA encoding various forms of colony stimulating factor-1 |
| JP2644794B2 (ja) | 1986-10-24 | 1997-08-25 | カイロン コーポレイション | 新規な型のコロニー刺激因子―1 |
| DE3853201T2 (de) | 1987-12-23 | 1995-09-14 | Univ Leland Stanford Junior | Schimäre immunkompromittierende Säugetiere und ihre Verwendung. |
| JP2981486B2 (ja) | 1988-06-14 | 1999-11-22 | メディカル・バイオロジー・インスティチュート | 哺乳動物の免疫系研究方法 |
| JP2935511B2 (ja) * | 1989-10-20 | 1999-08-16 | 忠三 岸本 | ヒトil―6レセプターの製造方法 |
| US5652373A (en) | 1990-01-15 | 1997-07-29 | Yeda Research And Development Co. Ltd. | Engraftment and development of xenogeneic cells in normal mammals having reconstituted hematopoetic deficient immune systems |
| US5849288A (en) | 1990-01-15 | 1998-12-15 | Yeda Research And Development Co. Ltd. | Method for production of monoclonal antibodies in chimeric mice or rats having xenogeneic antibody-producing cells |
| DK0438053T3 (da) | 1990-01-15 | 1999-11-22 | Yeda Res & Dev | Varig transplantation og udvikling af humane hæmopoietiske cellelinjer i normale pattedyr |
| JPH04507109A (ja) | 1990-05-03 | 1992-12-10 | システミックス インコーポレイテッド | 免疫無防備状態宿主中におけるヒトリンパ球組織 |
| WO1991018615A1 (en) | 1990-05-25 | 1991-12-12 | Systemix, Inc. | Human peripheral blood cells in an immunocompromised host |
| US5633426A (en) | 1990-05-25 | 1997-05-27 | Systemix, Inc. | In vivo use of human bone marrow for investigation and production |
| EP0571525A1 (en) | 1991-02-11 | 1993-12-01 | OMMAYA, Ayub K. | Spinal fluid driven artificial organ |
| US5222982A (en) | 1991-02-11 | 1993-06-29 | Ommaya Ayub K | Spinal fluid driven artificial organ |
| EP0517199A1 (en) | 1991-06-04 | 1992-12-09 | Yeda Research And Development Company, Ltd. | Durable engraftment of human tissue and cells in normal mammals |
| WO1993005796A1 (en) | 1991-09-19 | 1993-04-01 | The Scripps Research Institute | Method for producing human antibodies in a non-human animal, and animals therefor |
| EP0539970B1 (en) | 1991-10-30 | 1999-05-26 | Idemitsu Kosan Company Limited | Methods for producing human lymphocytes and human monoclonal antibodies, and human monoclonal antibodies produced thereby |
| US6353150B1 (en) | 1991-11-22 | 2002-03-05 | Hsc Research And Development Limited Partnership | Chimeric mammals with human hematopoietic cells |
| WO1993018144A1 (en) | 1992-03-05 | 1993-09-16 | The Trustees Of Columbia University Of The City Of New York | Recombination activating gene deficient animal |
| US5866757A (en) | 1992-06-02 | 1999-02-02 | Yeda Research And Development Co. Ltd. | Engraftment and development of xenogeneic cells in normal mammals having reconstituted hematopoetic deficient immune systems |
| US6018096A (en) | 1993-05-03 | 2000-01-25 | Surrogen, Inc. | Animal model for engraftment, proliferation and differentiation of human hematopoietic stem cells |
| US5663481A (en) | 1993-08-06 | 1997-09-02 | Mount Sinai Hospital Corporation | Animal model of the human immune system |
| CA2195678A1 (en) | 1994-07-27 | 1996-02-08 | Joseph A. Borkowski | Bradykinin b2 receptor modified transgenic non-human animals |
| US6455756B1 (en) | 1994-08-12 | 2002-09-24 | Novartis Ag | Long term xenogeneic myeloid and lymphoid cell production in chimeric immunocompromised mice |
| US7273753B2 (en) | 1996-08-02 | 2007-09-25 | Center Of Blood Research | Purification and uses of dendritic cells and monocytes |
| US6248721B1 (en) | 1997-04-09 | 2001-06-19 | Lung-Ji Chang | Method of using mouse model for evaluation of HIV vaccines |
| IL132164A0 (en) | 1997-04-09 | 2001-03-19 | Chang Lung Ji | Animal model for evaluation of vaccines |
| GB2337755B (en) * | 1998-05-29 | 2003-10-29 | Secr Defence | Virus vaccine |
| US20030028911A1 (en) | 1999-08-31 | 2003-02-06 | Manley Huang | Transgenic mammal capable of facilitating production of donor-specific functional immunity |
| EP1209968A1 (en) | 1999-08-31 | 2002-06-05 | Genencor International, Inc. | Transgenic mammal capable of facilitating production of donor-specific functional immunity |
| AU2066301A (en) * | 1999-12-09 | 2001-06-18 | Human Genome Sciences, Inc. | Il-6 like polynucleotide |
| AU2001290855A1 (en) | 2000-09-14 | 2002-03-26 | Genetrol Biotherapeutics, Inc. | Method and cell composition for screening compounds for anti-inflammatory activity |
| 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 |
| BR0211079A (pt) * | 2001-07-10 | 2005-08-30 | Johnson & Johnson Res Pty Ltd | Processos para a modificação genética de células hematopoiéticas progenitoras e empregos das células modificadas |
| AU2002363322A1 (en) * | 2001-10-26 | 2003-05-19 | Large Scale Biology Corporation | Endothelial cell derived hemotopoietic growth factor |
| JP4087338B2 (ja) | 2001-11-15 | 2008-05-21 | キリンファーマ株式会社 | キメラ非ヒト動物 |
| JPWO2004005496A1 (ja) | 2002-07-05 | 2005-11-04 | 麒麟麦酒株式会社 | 臍帯血、骨髄、末梢血等に含まれる新規な未分化幹細胞集団 |
| CN101250553A (zh) | 2002-07-13 | 2008-08-27 | 上海医学遗传研究所 | 一种促人血小板生成素表达载体及其构建方法 |
| CA2496233A1 (en) | 2002-09-09 | 2004-03-18 | California Institute Of Technology | Methods and compositions for the generation of humanized mice |
| EP1418185A1 (en) | 2002-11-11 | 2004-05-12 | Aventis Pharma Deutschland GmbH | Use of EDG2 receptor in an animal model of heart failure |
| WO2004060053A2 (en) | 2002-12-16 | 2004-07-22 | Genentech, Inc. | Transgenic mice expressing human cd20 |
| CN102225194B (zh) * | 2003-03-12 | 2014-07-16 | 健泰科生物技术公司 | Bv8和/或EG-VEGF促进造血的用途 |
| US20080311095A1 (en) | 2007-05-23 | 2008-12-18 | Sangamo Biosciences, Inc. | Methods and compositions for increased transgene expression |
| EP1598364A1 (en) * | 2004-05-21 | 2005-11-23 | AGIRx Limited | Chimerical soluble hyper IL-11 receptor and use thereof |
| EP1802193B1 (en) | 2004-10-19 | 2014-04-30 | Regeneron Pharmaceuticals, Inc. | Method for generating a mouse homozygous for a genetic modification |
| GB2434578A (en) | 2006-01-26 | 2007-08-01 | Univ Basel | Transgenic animals |
| SI2019683T2 (sl) | 2006-04-25 | 2022-10-28 | The Regents Of The University Of California | Dajanje rastnih faktorjev za zdravljenje motenj CŽS |
| 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 |
| US20080081064A1 (en) | 2006-09-28 | 2008-04-03 | Surmodics, Inc. | Implantable Medical Device with Apertures for Delivery of Bioactive Agents |
| EP2088854A1 (en) | 2006-12-05 | 2009-08-19 | Academisch Ziekenhuis Bij De Universiteit Van Amsterdam | Improved xenogenic immune system in a non-human mammal |
| GB0718029D0 (en) | 2007-09-14 | 2007-10-24 | Iti Scotland Ltd | Two step cluster deletion and humanisation |
| US20110118446A1 (en) | 2007-09-28 | 2011-05-19 | The General Hospital Corporation | Methods and compositions for antibody production |
| WO2009097468A2 (en) | 2008-01-29 | 2009-08-06 | Kliman Gilbert H | Drug delivery devices, kits and methods therefor |
| JP5727458B2 (ja) * | 2009-04-13 | 2015-06-03 | アプセト ゲゼルシャフト ミット ベシュレンクテル ハフツング ウント コンパニー コマンディトゲゼルシャフトApceth Gmbh & Co. Kg | 改変間葉系幹細胞及びそれを使用した腫瘍の治療方法 |
| SG10201403707QA (en) | 2009-06-29 | 2014-10-30 | Ilya B Leskov | Non-human mammal model of human hematopoietic cancer |
| SG10201403703XA (en) | 2009-06-29 | 2014-10-30 | Qingfeng Chen | Methods of producing humanized non-human mammals |
| RU2425880C2 (ru) | 2009-07-30 | 2011-08-10 | Учреждение Российской академии наук Институт общей генетики им. Н.И. Вавилова РАН | Способ получения трансгенных мышей |
| EP4502152A3 (en) * | 2009-10-06 | 2025-04-30 | Regeneron Pharmaceuticals, Inc. | Genetically modified mice and engraftment |
| EP3498730B1 (en) * | 2009-12-21 | 2026-01-28 | Regeneron Pharmaceuticals, Inc. | Humanized fc gamma r mice |
| WO2012040207A2 (en) * | 2010-09-20 | 2012-03-29 | Yale University | HUMAM SIRPAα TRANSGENIC ANIMALS AND THEIR METHODS OF USE |
| WO2012051572A1 (en) | 2010-10-15 | 2012-04-19 | Massachusetts Institute Of Technology | A humanized non-human mammal model of malaria and uses thereof |
| PT4233537T (pt) | 2011-02-15 | 2025-09-08 | Regeneron Pharma | Ratinhos humanizados para m-csf e utilizações dos mesmos |
| SI2818478T1 (sl) * | 2011-10-28 | 2017-07-31 | Regeneron Pharmaceuticals, Inc. | Humanizirani il-6 in receptor il-6 |
| KR102241962B1 (ko) | 2012-09-07 | 2021-04-20 | 예일 유니버시티 | 유전적으로 변형된 비-인간 동물 및 이것들의 사용 방법 |
| DK4389764T3 (da) | 2012-11-05 | 2026-04-13 | Regeneron Pharma | Genetisk modificerede gnavere og fremgangsmåder til anvendelse heraf |
| HRP20231121T1 (hr) | 2013-09-23 | 2023-12-22 | Regeneron Pharmaceuticals, Inc. | Životinje koje nisu ljudi, koje imaju gen za humanizirani protein koji regulira signale |
| JP6492095B2 (ja) | 2013-10-15 | 2019-03-27 | 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il−15動物 |
| EP3482629B1 (en) | 2014-05-19 | 2020-11-25 | Regeneron Pharmaceuticals, Inc. | Genetically modified non-human animals expressing human epo |
| ES2950399T3 (es) | 2015-04-13 | 2023-10-09 | Regeneron Pharma | Ratones humanizados Sirpa-IL15 insertados y métodos de uso de los mismos |
-
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| 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 |
Non-Patent Citations (4)
| Title |
|---|
| American j. Pathology vol.157 no.5 pp.1485-1493(2000.11.30) |
| J. Exper. Med. vol.185 no.4 pp.755-766(1997.02.17) |
| Proc. Natl. Acad. Sci. USA vol.86 no.19 pp.7547-7551(1989.10.31) |
| Proc. Natl. Acad. Sci. USA vol.92 pp.4862-4866(1995.05.31) |
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