JP6283031B2 - 遺伝学的に修飾された非ヒト動物およびその使用法 - Google Patents

遺伝学的に修飾された非ヒト動物およびその使用法 Download PDF

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JP6283031B2
JP6283031B2 JP2015531224A JP2015531224A JP6283031B2 JP 6283031 B2 JP6283031 B2 JP 6283031B2 JP 2015531224 A JP2015531224 A JP 2015531224A JP 2015531224 A JP2015531224 A JP 2015531224A JP 6283031 B2 JP6283031 B2 JP 6283031B2
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human
cells
genetically modified
mice
animal
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JP2015529083A5 (enExample
JP2015529083A (ja
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リチャード エイ． フラベル
リチャード エイ． フラベル
マルクス マンツ
マルクス マンツ
アンソニー ロンヴォークス
アンソニー ロンヴォークス
ティル ストロウィッグ
ティル ストロウィッグ
ティム ウィリンガー
ティム ウィリンガー
アンドリュー ジェイ． マーフィー
アンドリュー ジェイ． マーフィー
ショーン スティーブンズ
ショーン スティーブンズ
ジョージ ヤンコポーロス
ジョージ ヤンコポーロス
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Yale University
Regeneron Pharmaceuticals Inc
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Yale University
Regeneron Pharmaceuticals Inc
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    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
    • A01K67/00—Rearing or breeding animals, not otherwise provided for; New or modified breeds of animals
    • A01K67/027—New or modified breeds of vertebrates
    • A01K67/0275—Genetically modified vertebrates, e.g. transgenic
    • A01K67/0278—Knock-in vertebrates, e.g. humanised vertebrates
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
    • A01K67/00—Rearing or breeding animals, not otherwise provided for; New or modified breeds of animals
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    • A01K67/00—Rearing or breeding animals, not otherwise provided for; New or modified breeds of animals
    • A01K67/027—New or modified breeds of vertebrates
    • A01K67/0271—Chimeric vertebrates, e.g. comprising exogenous cells
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    • C07K14/46—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
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    • C07K14/4701—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals not used
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    • C07K14/52—Cytokines; Lymphokines; Interferons
    • C07K14/524—Thrombopoietin, i.e. C-MPL ligand
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    • C07K14/52—Cytokines; Lymphokines; Interferons
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    • C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/52—Cytokines; Lymphokines; Interferons
    • C07K14/53—Colony-stimulating factor [CSF]
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    • C07K14/52—Cytokines; Lymphokines; Interferons
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    • C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09—Recombinant DNA-technology
    • C12N15/63—Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
    • C12N15/79—Vectors or expression systems specially adapted for eukaryotic hosts
    • C12N15/85—Vectors or expression systems specially adapted for eukaryotic hosts for animal cells
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    • C12N15/09—Recombinant DNA-technology
    • C12N15/87—Introduction of foreign genetic material using processes not otherwise provided for, e.g. co-transformation
    • A—HUMAN NECESSITIES
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    • A01K2207/00—Modified animals
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    • A01K2207/15—Humanized animals
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    • A01K2217/07—Animals genetically altered by homologous recombination
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    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
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    • A01K2217/00—Genetically modified animals
    • A01K2217/15—Animals comprising multiple alterations of the genome, by transgenesis or homologous recombination, e.g. obtained by cross-breeding
    • A—HUMAN NECESSITIES
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    • A01K2267/0387—Animal model for diseases of the immune system

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JP2015531224A 2012-09-07 2013-09-06 遺伝学的に修飾された非ヒト動物およびその使用法 Active JP6283031B2 (ja)

Applications Claiming Priority (5)

Application Number Priority Date Filing Date Title
US201261698002P 2012-09-07 2012-09-07
US61/698,002 2012-09-07
US201361775171P 2013-03-08 2013-03-08
US61/775,171 2013-03-08
PCT/US2013/058448 WO2014039782A2 (en) 2012-09-07 2013-09-06 Genetically modified non-human animals and methods of use thereof

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JP2015529083A JP2015529083A (ja) 2015-10-05
JP2015529083A5 JP2015529083A5 (enExample) 2017-10-05
JP6283031B2 true JP6283031B2 (ja) 2018-02-21

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JP2015531224A Active JP6283031B2 (ja) 2012-09-07 2013-09-06 遺伝学的に修飾された非ヒト動物およびその使用法
JP2018010192A Active JP6517958B2 (ja) 2012-09-07 2018-01-25 遺伝学的に修飾された非ヒト動物およびその使用法
JP2019079029A Active JP6732998B2 (ja) 2012-09-07 2019-04-18 遺伝学的に修飾された非ヒト動物およびその使用法
JP2020117482A Active JP7066785B2 (ja) 2012-09-07 2020-07-08 遺伝学的に修飾された非ヒト動物およびその使用法
JP2022072893A Active JP7605789B2 (ja) 2012-09-07 2022-04-27 遺伝学的に修飾された非ヒト動物およびその使用法

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JP2019079029A Active JP6732998B2 (ja) 2012-09-07 2019-04-18 遺伝学的に修飾された非ヒト動物およびその使用法
JP2020117482A Active JP7066785B2 (ja) 2012-09-07 2020-07-08 遺伝学的に修飾された非ヒト動物およびその使用法
JP2022072893A Active JP7605789B2 (ja) 2012-09-07 2022-04-27 遺伝学的に修飾された非ヒト動物およびその使用法

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US (6) US9820476B2 (enExample)
EP (3) EP4606818A3 (enExample)
JP (5) JP6283031B2 (enExample)
KR (7) KR102473555B1 (enExample)
CN (4) CN104955326B (enExample)
AU (3) AU2013312359B8 (enExample)
CA (1) CA2881468C (enExample)
DK (1) DK2892330T3 (enExample)
ES (2) ES3034290T3 (enExample)
FI (1) FI2892330T3 (enExample)
IL (4) IL282472B2 (enExample)
IN (1) IN2015DN02032A (enExample)
MX (2) MX364714B (enExample)
NZ (3) NZ746089A (enExample)
PT (1) PT2892330T (enExample)
RU (2) RU2768282C2 (enExample)
SG (2) SG10201701759VA (enExample)
WO (1) WO2014039782A2 (enExample)

Families Citing this family (33)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP4049535B1 (en) 2009-10-06 2024-11-27 Regeneron Pharmaceuticals, Inc. Genetically modified mice and engraftment
RU2730643C2 (ru) 2011-02-15 2020-08-24 Ридженерон Фармасьютикалз, Инк. Гуманизированные m-csf мыши
JP6283031B2 (ja) 2012-09-07 2018-02-21 イエール ユニバーシティ 遺伝学的に修飾された非ヒト動物およびその使用法
EP3308641B1 (en) * 2012-11-05 2019-07-03 Regeneron Pharmaceuticals, Inc. Immunodeficient, genetically modified rodent and methods of use thereof
SMT201900067T1 (it) 2013-09-23 2019-02-28 Regeneron Pharma Animali non umani aventi un gene di proteina regolatoria del segnale umanizzato
HRP20170380T1 (hr) 2013-10-15 2017-05-19 Regeneron Pharmaceuticals, Inc. Životinje s humaniziranim il-5
CA2929774C (en) 2013-11-19 2020-09-15 Regeneron Pharmaceuticals, Inc. Non-human animal cells having a humanized proliferation-inducing ligand gene
MA51519A (fr) 2014-05-05 2020-11-11 Regeneron Pharma Animaux c5 et c3 humanisés
NO2785538T3 (enExample) 2014-05-07 2018-08-04
CA2947309A1 (en) 2014-05-19 2015-11-26 Regeneron Pharmaceuticals, Inc. Genetically modified non-human animals expressing human epo
CN107205368B (zh) 2014-12-05 2020-11-17 瑞泽恩制药公司 具有人源化分化簇47基因的非人动物
SMT202400313T1 (it) 2014-12-09 2024-09-16 Regeneron Pharma Animali non umani aventi un cluster umanizzato di un gene di differenziazione 274
JP6830437B2 (ja) 2014-12-10 2021-02-17 リージェンツ オブ ザ ユニバーシティ オブ ミネソタ 疾患を処置するための遺伝子改変された細胞、組織および臓器
ES2950399T3 (es) 2015-04-13 2023-10-09 Regeneron Pharma Ratones humanizados Sirpa-IL15 insertados y métodos de uso de los mismos
RS61866B1 (sr) 2015-11-20 2021-06-30 Regeneron Pharma Ne-humane životinje koje imaju humanizovani gen za aktivaciju limfocita 3
JP6843872B2 (ja) 2016-02-04 2021-03-17 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． 操作されたａｎｇｐｔｌ８遺伝子を有する非ヒト動物
RU2749715C2 (ru) 2016-02-29 2021-06-16 Регенерон Фармасьютикалз, Инк. Грызуны, характеризующиеся гуманизированным геном tmprss
CN106119284A (zh) * 2016-06-27 2016-11-16 北京维通达生物技术有限公司 一种用于构建免疫缺陷动物模型的产品及其应用
WO2018102546A1 (en) * 2016-11-30 2018-06-07 The Jackson Laboratory Humanized mouse model with improved human innate immune cell development
US11778994B2 (en) * 2017-05-12 2023-10-10 The Jackson Laboratory NSG mice lacking MHC class I and class II
PT3823443T (pt) 2018-07-16 2024-07-29 Regeneron Pharma Modelos de roedores da-doença ditra e as suas utilizações
WO2020068615A1 (en) * 2018-09-24 2020-04-02 Albert Einstein College Of Medicine Interleukin-8 for maintenance of human acute myeloid leukemia and myelodysplastic syndrome 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
CN111073907B (zh) * 2018-12-25 2025-07-29 百奥赛图江苏基因生物技术有限公司 人源化细胞因子csf1基因改造非人动物的构建方法及应用
CN111118019B (zh) * 2018-12-25 2021-03-16 百奥赛图江苏基因生物技术有限公司 人源化细胞因子il3基因改造非人动物的构建方法及应用
US20220354098A1 (en) * 2019-07-17 2022-11-10 Yale University Genetically Modified Non-Human Animals and Methods of Use Thereof
CN112779284B (zh) * 2019-11-01 2022-12-20 百奥赛图(北京)医药科技股份有限公司 Thpo基因人源化的非人动物的构建方法及应用
US11339279B2 (en) * 2020-04-01 2022-05-24 Chevron Phillips Chemical Company Lp Dual catalyst system for producing LLDPE and MDPE copolymers with long chain branching for film applications
CN114853871B (zh) * 2021-04-20 2024-04-05 百奥赛图(北京)医药科技股份有限公司 Csf1和/或csf1r基因人源化的非人动物及其构建方法和应用
WO2024020057A1 (en) 2022-07-19 2024-01-25 Regeneron Pharmaceuticals, Inc. Genetically modified animal model and its use to model the human immune system
CN121335619A (zh) 2023-06-16 2026-01-13 瑞泽恩制药公司 载体、经基因修饰的细胞和包含其的经基因修饰的非人动物
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

Family Cites Families (67)

* Cited by examiner, † Cited by third party
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
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
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
DK0438053T3 (da) 1990-01-15 1999-11-22 Yeda Res & Dev Varig transplantation og udvikling af humane hæmopoietiske cellelinjer i normale pattedyr
DK0481058T3 (da) 1990-05-03 1996-12-02 Systemix Inc Humant, lymfatisk væv i en immunokompromitteret vært
US5633426A (en) 1990-05-25 1997-05-27 Systemix, Inc. In vivo use of human bone marrow for investigation and production
JPH05500617A (ja) 1990-05-25 1993-02-12 システミックス，インコーポレイティド 免疫処理された宿主におけるヒト末梢血液細胞
US5222982A (en) 1991-02-11 1993-06-29 Ommaya Ayub K Spinal fluid driven artificial organ
JPH06505186A (ja) 1991-02-11 1994-06-16 オマーヤ，アユブ　ケー． 脊髄液駆動式人工器官
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
WO1998044788A2 (en) 1997-04-09 1998-10-15 Chang Lung Ji Animal model for evaluation of vaccines
US20030028911A1 (en) 1999-08-31 2003-02-06 Manley Huang Transgenic mammal capable of facilitating production of donor-specific functional immunity
CA2382383A1 (en) 1999-08-31 2001-03-08 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
WO2002022786A1 (en) 2000-09-14 2002-03-21 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
CN1553963A (zh) * 2001-07-10 2004-12-08 ǿ����ǿ���о����޹�˾ 用于遗传修饰造血祖细胞的方法和这些被修饰细胞的应用
WO2003039232A2 (en) 2001-10-26 2003-05-15 Large Scale Biology Corporation Endothelial cell derived hemotopoietic growth factor
US20050177884A1 (en) 2001-11-15 2005-08-11 Kirin Beer Kabushiki Kaisha Chimeric nonhuman animal
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
WO2004022738A1 (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
EP1573313A4 (en) 2002-12-16 2006-05-17 Genentech Inc HUMAN CD20 AND / OR CD16EXPRIMATING TRANSGENIC MICE
PT1802193E (pt) 2004-10-19 2014-06-23 Regeneron Pharma Método para gerar um murganho homozigótico para uma modificação genética
US7759541B2 (en) 2004-12-13 2010-07-20 Iti Life Sciences Transgenic animals for assessing drug metabolism and toxicity
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
EP2155873B1 (en) 2007-05-23 2016-11-09 Sangamo BioSciences, Inc. Methods and compositions for increased transgene expression
GB0718029D0 (en) 2007-09-14 2007-10-24 Iti Scotland Ltd Two step cluster deletion and humanisation
WO2009042917A1 (en) 2007-09-28 2009-04-02 The General Hospital Corporation Methods and compositions for antibody production
JP2011500005A (ja) * 2007-10-11 2011-01-06 ユニバーシティー ヘルス ネットワーク ヒト造血幹細胞の生着を増加させるためのＳＩＲＰα−ＣＤ４７相互作用の調節およびそのための化合物
EP2257250A2 (en) 2008-01-29 2010-12-08 Gilbert H. Kliman Drug delivery devices, kits and methods therefor
CN102725400A (zh) * 2009-06-29 2012-10-10 麻省理工学院 制造人源化的非人类哺乳动物的方法
WO2011002721A1 (en) * 2009-06-29 2011-01-06 Leskov Ilya B Non-human mammal model of human hematopoietic cancer
RU2425880C2 (ru) * 2009-07-30 2011-08-10 Учреждение Российской академии наук Институт общей генетики им. Н.И. Вавилова РАН Способ получения трансгенных мышей
EP4049535B1 (en) 2009-10-06 2024-11-27 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
WO2012051572A1 (en) 2010-10-15 2012-04-19 Massachusetts Institute Of Technology A humanized non-human mammal model of malaria and uses thereof
RU2730643C2 (ru) 2011-02-15 2020-08-24 Ридженерон Фармасьютикалз, Инк. Гуманизированные m-csf мыши
ES2624605T3 (es) 2011-10-28 2017-07-17 Regeneron Pharmaceuticals, Inc. IL-6 y receptor de IL-6 humanizados
JP6283031B2 (ja) 2012-09-07 2018-02-21 イエール ユニバーシティ 遺伝学的に修飾された非ヒト動物およびその使用法
EP3308641B1 (en) 2012-11-05 2019-07-03 Regeneron Pharmaceuticals, Inc. Immunodeficient, genetically modified rodent and methods of use thereof
SMT201900067T1 (it) 2013-09-23 2019-02-28 Regeneron Pharma Animali non umani aventi un gene di proteina regolatoria del segnale umanizzato
HRP20170380T1 (hr) 2013-10-15 2017-05-19 Regeneron Pharmaceuticals, Inc. Životinje s humaniziranim il-5
CA2947309A1 (en) 2014-05-19 2015-11-26 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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