CN110923256B - 具有人源化程序性细胞死亡1基因的非人动物 - Google Patents

具有人源化程序性细胞死亡1基因的非人动物 Download PDF

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CN110923256B
CN110923256B CN201911291579.0A CN201911291579A CN110923256B CN 110923256 B CN110923256 B CN 110923256B CN 201911291579 A CN201911291579 A CN 201911291579A CN 110923256 B CN110923256 B CN 110923256B
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human
pdcd1
humanized
gene
polypeptide
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CN110923256A (zh
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E·布罗瓦
A·O·穆吉卡
K-M·V·赖
A·J·莫菲
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Regeneron Pharmaceuticals Inc
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Families Citing this family (46)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US8307177B2 (en) 2008-09-05 2012-11-06 Commvault Systems, Inc. Systems and methods for management of virtualization data
TWI605828B (zh) 2008-12-09 2017-11-21 建南德克公司 抗ｐｄ-ｌ１抗體及其於增進ｔ細胞功能之用途
US9461881B2 (en) 2011-09-30 2016-10-04 Commvault Systems, Inc. Migration of existing computing systems to cloud computing sites or virtual machines
US20140181044A1 (en) 2012-12-21 2014-06-26 Commvault Systems, Inc. Systems and methods to identify uncharacterized and unprotected virtual machines
US9378035B2 (en) 2012-12-28 2016-06-28 Commvault Systems, Inc. Systems and methods for repurposing virtual machines
KR102243062B1 (ko) 2013-05-02 2021-04-21 아납티스바이오, 아이엔씨. 예정된 사멸-1에 대한 항체
WO2015196051A1 (en) * 2014-06-19 2015-12-23 Regeneron Pharmaceuticals, Inc. Non-human animals having a humanized programmed cell death 1 gene
RS63410B1 (sr) 2014-11-24 2022-08-31 Regeneron Pharma Ne-humane životinje koje eksprimiraju humanizovani cd3 kompleks
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.
LT3230320T (lt) * 2014-12-09 2021-01-11 Regeneron Pharmaceuticals, Inc. Gyvūnai, išskyrus žmogų, turintys humanizuotą diferenciacijos klasterio 274 geną
US9563514B2 (en) 2015-06-19 2017-02-07 Commvault Systems, Inc. Assignment of proxies for virtual-machine secondary copy operations including streaming backup jobs
US10084873B2 (en) 2015-06-19 2018-09-25 Commvault Systems, Inc. Assignment of data agent proxies for executing virtual-machine secondary copy operations including streaming backup jobs
HK1250033A1 (zh) 2015-07-13 2018-11-23 Cytomx Therapeutics Inc. 抗-pd-1抗体、可活化的抗-pd-1抗体、及其使用方法
LT3376857T (lt) * 2015-11-20 2021-06-25 Regeneron Pharmaceuticals, Inc. Gyvūnai, ne žmonės, turintys humanizuotą limfocitų aktyvavimo geną
CA3012693C (en) * 2016-02-04 2022-08-23 Regeneron Pharmaceuticals, Inc. Non-human animals having an engineered angptl8 gene
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
TWI822521B (zh) 2016-05-13 2023-11-11 美商再生元醫藥公司 藉由投予pd-1抑制劑治療皮膚癌之方法
US11352413B2 (en) 2016-05-17 2022-06-07 Albert Einstein College Of Medicine Engineered PD-1 variants
EP3462853B1 (en) * 2016-06-03 2023-03-01 Regeneron Pharmaceuticals, Inc. Rodents expressing exogenous terminal deoxynucleotidyltransferase
WO2018001241A1 (zh) * 2016-06-28 2018-01-04 北京百奥赛图基因生物技术有限公司 一种pd-1基因修饰人源化动物模型的构建方法及其应用
CN107815466B (zh) 2016-08-31 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
US11317611B2 (en) 2016-08-31 2022-05-03 Biocytogen Pharmaceuticals (Beijing) Co., Ltd. Genetically modified non-human animal with human or chimeric PD-L1
EP3534950A4 (en) 2016-11-01 2020-05-06 AnaptysBio, Inc. Antibodies directed against programmed death- 1 (pd-1)
CN107828722B (zh) * 2016-11-04 2021-07-23 北京泰盛生物科技有限公司 特异性表达pd-1的干细胞、其鉴定和分离方法及用途
JP7105235B2 (ja) * 2016-12-01 2022-07-22 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 免疫ｐｅｔイメージングのための放射性標識された抗ｐｄ－ｌ１抗体
IL267804B2 (en) 2017-01-09 2024-09-01 Tesaro Inc Methods for treating cancer with anti-PD-1 antibodies
CN117442719A (zh) 2017-02-21 2024-01-26 瑞泽恩制药公司 用于治疗肺癌的抗pd-1抗体
US10949308B2 (en) 2017-03-15 2021-03-16 Commvault Systems, Inc. Application aware backup of virtual machines
US10853195B2 (en) 2017-03-31 2020-12-01 Commvault Systems, Inc. Granular restoration of virtual machine application data
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
CN109280674B (zh) * 2017-07-21 2020-12-01 北京百奥赛图基因生物技术有限公司 一种筛选抗体的非人模式动物的构建方法及其应用
WO2019067875A1 (en) * 2017-09-29 2019-04-04 Regeneron Pharmaceuticals, Inc. NON-HUMAN ANIMALS COMPRISING A HUMANIZED TTR LOCUS AND METHODS OF USE
CN109666701B (zh) * 2017-10-13 2021-08-24 百奥赛图(北京)医药科技股份有限公司 一种pd-1基因修饰人源化动物模型的构建方法及其应用
WO2019072241A1 (en) * 2017-10-13 2019-04-18 Beijing Biocytogen Co., Ltd NON-HUMAN ANIMAL GENETICALLY MODIFIED WITH PD-1 HUMAN OR CHIMERIC
AU2018375796B2 (en) 2017-11-30 2024-11-21 Regeneron Pharmaceuticals, Inc. Non-human animals comprising a humanized TRKB locus
AU2019242586B2 (en) 2018-03-26 2025-09-11 Regeneron Pharmaceuticals, Inc. Humanized rodents for testing therapeutic agents
PL3823443T3 (pl) 2018-07-16 2024-09-23 Regeneron Pharmaceuticals, Inc. Modele gryzoni z chorobą ditra i ich zastosowania
CN109266656B (zh) * 2018-10-10 2021-02-19 江苏集萃药康生物科技股份有限公司 一种PD1人源化BALB/c小鼠模型的构建方法及其应用
CN109452229B (zh) * 2018-11-19 2021-10-22 百奥赛图(北京)医药科技股份有限公司 狗源化pd-1基因改造动物模型的制备方法及应用
WO2021018198A1 (en) * 2019-07-29 2021-02-04 Beijing Biocytogen Co., Ltd Genetically modified non-human animal with human or chimeric il33
US12250931B2 (en) * 2020-01-28 2025-03-18 Regeneron Pharmaceuticals, Inc. Genetically modified mouse with a humanized PNPLA3 gene and methods of use
US11656951B2 (en) 2020-10-28 2023-05-23 Commvault Systems, Inc. Data loss vulnerability detection
CN119031932A (zh) 2022-03-16 2024-11-26 第一三共株式会社 多特异性分子和免疫检查点抑制剂的组合
CN119451570A (zh) * 2022-06-29 2025-02-14 百奥赛图(北京)医药科技股份有限公司 一种osm、osmr、il31ra和/或il31基因修饰的非人动物

Family Cites Families (32)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH07291996A (ja) 1994-03-01 1995-11-07 Yuu Honshiyo ヒトにおけるプログラムされた細胞死に関連したポリペプチド、それをコードするｄｎａ、そのｄｎａからなるベクター、そのベクターで形質転換された宿主細胞、そのポリペプチドの抗体、およびそのポリペプチドまたはその抗体を含有する薬学的組成物
US5670356A (en) 1994-12-12 1997-09-23 Promega Corporation Modified luciferase
US5874304A (en) 1996-01-18 1999-02-23 University Of Florida Research Foundation, Inc. Humanized green fluorescent protein genes and methods
NZ522844A (en) 2000-06-28 2005-02-25 Brigham & Womens Hospital PD-L2 molecules: novel PD-1 ligands and methods to identify compounds to modulate T cell activation
US6586251B2 (en) 2000-10-31 2003-07-01 Regeneron Pharmaceuticals, Inc. Methods of modifying eukaryotic cells
KR20030066657A (ko) 2000-11-15 2003-08-09 오노 야꾸힝 고교 가부시키가이샤 Ｐｄ-1 결손 마우스 및 그 용도
US20040033497A1 (en) * 2002-08-13 2004-02-19 Alarcon-Riquelme Marta E. Polymorphisms of PD-1
JP4511943B2 (ja) * 2002-12-23 2010-07-28 ワイス エルエルシー Ｐｄ−１に対する抗体およびその使用
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.
US8071839B2 (en) 2003-12-24 2011-12-06 G2 Inflammation Pty Ltd Transgenic mouse comprising a polynucleotide encoding human or humanized C5aR and methods of production and use
PL1802193T3 (pl) 2004-10-19 2014-09-30 Regeneron Pharma Sposób wytwarzania myszy homozygotycznej pod względem modyfikacji genetycznej
EP3530736A3 (en) * 2005-05-09 2019-11-06 ONO Pharmaceutical Co., Ltd. Human monoclonal antibodies to programmed death 1 (pd-1) and methods for treating cancer using anti-pd-1 antibodies alone or in combination with other immunotherapeutics
US20070054360A1 (en) * 2005-05-12 2007-03-08 Zeren Gao Compositions and methods for modulating immune responses
NZ601439A (en) 2005-06-08 2012-11-30 Brigham & Womens Hospital Methods and compositions for the treatment of persistent infections and cancer by inhibiting the programmed cell death 1 (pd-1) pathway
TWI605828B (zh) 2008-12-09 2017-11-21 建南德克公司 抗ｐｄ-ｌ１抗體及其於增進ｔ細胞功能之用途
RU2425880C2 (ru) * 2009-07-30 2011-08-10 Учреждение Российской академии наук Институт общей генетики им. Н.И. Вавилова РАН Способ получения трансгенных мышей
WO2011020014A1 (en) 2009-08-14 2011-02-17 Regeneron Pharmaceuticals, Inc. Promoter-regulated differentiation-dependent self-deleting cassette
TW201134488A (en) * 2010-03-11 2011-10-16 Ucb Pharma Sa PD-1 antibodies
US8871996B2 (en) * 2010-06-09 2014-10-28 Regeneron Pharmaceuticals, Inc. Mice expressing human voltage-gated sodium channels
LT3262932T (lt) 2011-10-28 2019-08-26 Regeneron Pharmaceuticals, Inc. Pelės su genetiškai modifikuotu pagrindiniu histosuderinamumo kompleksu
IN2014CN03890A (cg-RX-API-DMAC7.html) 2011-10-28 2015-10-16 Regeneron Pharma
LT3590332T (lt) 2011-10-28 2022-08-10 Regeneron Pharmaceuticals, Inc. Genetiškai modifikuotos pelės, ekspresuojančios chimerines pagrindinio audinių dermės komplekso (mhc) ii molekules
WO2013063556A1 (en) * 2011-10-28 2013-05-02 Regeneron Pharmaceuticals, Inc. Humanized il-6 and il-6 receptor
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
SMT201900429T1 (it) 2013-02-20 2019-09-09 Regeneron Pharma Topi esprimenti co-recettori umanizzati linfociti t
EP2958937B1 (en) 2013-02-22 2018-08-15 Regeneron Pharmaceuticals, Inc. Mice expressing humanized major histocompatibility complex
DK4269430T3 (da) 2013-09-23 2025-08-18 Regeneron Pharma Ikke-menneskelige dyr, der har et humaniseret signalregulerende proteingen
MY183188A (en) 2013-11-19 2021-02-18 Regeneron Pharma Non-human animals having a humanized b-cell activating factor gene
ES2794942T3 (es) 2014-04-08 2020-11-19 Regeneron Pharma Animales no humanos que tienen receptores Fc-gamma humanizados
NO2785538T3 (cg-RX-API-DMAC7.html) 2014-05-07 2018-08-04
EP4306648A3 (en) 2014-05-19 2024-04-17 Regeneron Pharmaceuticals, Inc. Genetically modified mice 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

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
Establishment of NOD-Pdcd1-/- mice as an efficient animal model of type I diabetes;Wang J et al.;《Proc Natl Acad Sci U S A》;第第102卷卷(第第102卷期);第11823-11828页 *

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