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1. 发明申请

WO2018209344A1 NSG MICE LACKING MHC CLASS I AND CLASS II 审中-公开
公开(公告)号：WO2018209344A1
公开(公告)日：2018-11-15
申请号：PCT/US2018/032548
申请日：2018-05-14
申请人： THE JACKSON LABORATORY , UNIVERSITY OF MASSACHUSETTS
发明人： BREHM, Michael, A. , WILES, Michael, V. , GREINER, Dale, L. , SHULTZ, Leonard, D.
IPC分类号： A01K67/027
摘要： A NOD.Cg- Prkdc scid H2rg tm1 Wjl /SzJ .(NOD- scid -IL2rϒ null , NSG) mouse which is genetically modified such that the NSG mouse lacks functional major histocompatibility complex I (MHC I) and lacks functional major histocompatibility complex II (MHC II) is provided according to aspects of the present, invention. According to specific aspects the genetically modified NSG mouse, is a NOD.Cg- Prkdc scid H2-K1 tml Bpe H2-Ab1 eml Mvw H2-D1 tml Bpe H2rg tm Wjl /SzJ (NSG -K b D b ) null ( IA null )) mouse, NSG - RIP-DTR ( K b D b ) null ( IA null ) mouse, or a NOD.Cg- B 2 m tml Une PrKdc scid H2 dlAb1-E α H2rg tm1 Wjl /SzJ (NSG- B2M null (IA IE null )) mouse. Human, immune cells and/or human: tumor cells are administered to a genetically modified immunodeficient mouse according to aspects described herein and assays of one or more test substances can be performed using the provided mice.

2. 发明申请

WO2018102546A1 HUMANIZED MOUSE MODEL WITH IMPROVED HUMAN INNATE IMMUNE CELL DEVELOPMENT 审中-公开
公开(公告)号：WO2018102546A1
公开(公告)日：2018-06-07
申请号：PCT/US2017/063948
申请日：2017-11-30
申请人： THE JACKSON LABORATORY , UNIVERSITY OF MASSACHUSETTS
发明人： SHULTZ, Leonard, D. , KECK, James, G. , GREINER, Dale, L. , BREHM, Michael, A.
IPC分类号： A01K67/027
摘要： A genetically-modified, immunodeficient mouse is provided along with methods of use, wherein the mouse includes (a) a nucleotide sequence encoding human stem cell factor (hSCF); (b) a nucleotide sequence encoding human granulocyte-macrophage colony-stimulating factor (hGM-CSF); (c) a nucleotide sequence encoding human interleukin-3 (hIL-3); and (d) a nucleotide sequence encoding human colony-stimulating factor 1 (hCSFl), wherein each of the nucleotide sequences is operably linked to a promoter, and wherein the genetically-modified, immunodeficient mouse expresses hSCF, hGM-CSF, hIL-3, and hCSFl, wherein the genetically-modified, immunodeficient mouse allows engraftment of human hematopoietic stem cells along with engraftment of human-patient derived tumor xenografts and/or human tumor cell lines to enable in vivo investigation of the interactions between the human immune system and human cancer.

3. 发明申请

WO2016205523A1 GENETICALLY MODIFIED NON-HUMAN ANIMALS AND METHODS RELATING TO COMPLEMENT DEPENDENT CYTOTOXICITY 审中-公开
标题翻译：遗传修饰的非人动物及相关依赖性细胞毒性相关方法
公开(公告)号：WO2016205523A1
公开(公告)日：2016-12-22
申请号：PCT/US2016/037882
申请日：2016-06-16
申请人： THE JACKSON LABORATORY , UNIVERSITY OF MASSACHUSETTS
发明人： SHULTZ, Leonard, D. , VERMA, Mohit, Kumar , GREINER, Dale, L. , BREHM, Michael, A.
IPC分类号： A01K67/027 , C07K14/705 , G01N33/15
CPC分类号： A01K67/0275 , A01K2217/07 , A01K2227/105 , A01K2267/0387 , A61K49/0008 , C07K14/472 , C12N15/907
摘要： The present invention relates generally to genetically modified non-human animals and immunodeficient non-human animals characterized by restored complement-dependent cytotoxicity, as well as methods and compositions for assessment of therapeutic antibodies in the genetically modified immunodeficient non- human animals. In specific aspects, the present invention relates to immunodeficient non-obese diabetic (NOD), A/J, A/He, AKR, DBA/2, NZB/BIN, B10.D2/oSn and other mouse strains genetically modified to restore complement-dependent cytotoxicity which is lacking in the unmodified immunodeficient mice. In further specific aspects, the present invention relates to NOD.Cg- Prkdc scid IL2rg tm1Wjl /SzJ (NSG), NOD. Cg- Rag1 tm1Mom IL 2rg tmlWjl /SzJ (NRG) and NOD.Cg- Prkdc scid IL2rg tm1Sug /JicTAc (NOG) mice genetically modified to restore complement-dependent cytotoxicity which is lacking in unmodified NSG, NRG and NOG mice. Methods for assessment of therapeutic antibodies or putative therapeutic antibodies in the genetically modified immunodeficient mice characterized by an intact complement system are provided according to specific aspects of the present invention.
摘要翻译：本发明一般涉及以遗传修饰的免疫缺陷型非人类动物评估治疗性抗体为基础的遗传修饰的非人类动物和以恢复的补体依赖性细胞毒性为特征的免疫缺陷型非人类动物，以及用于评估治疗性抗体的方法和组合物。在具体方面，本发明涉及免疫缺陷型非肥胖性糖尿病（NOD），A / J，A / He，AKR，DBA / 2，NZB / BIN，B10D2 / oSn和其他经遗传修饰以恢复补体的小鼠在未修饰的免疫缺陷小鼠中缺乏依赖性细胞毒性。在其它具体方面，本发明涉及NOD.Cg-Prkdc scid IL2rg tm1Wj1 / SzJ（NSG），NOD。 Cg-Rag1 tm1Mom IL2rg tmlWj1 / SzJ（NRG）和NOD.Cg-Prkdc scid IL2rg tm1Sug / JicTAc（NOG）小鼠遗传修饰以恢复未修饰的NSG，NRG和NOG小鼠缺乏的补体依赖性细胞毒性。根据本发明的具体方面提供了用完整的补体系统表征的遗传修饰的免疫缺陷小鼠中治疗性抗体或推定的治疗性抗体的评估方法。

4. 发明申请

WO2019032836A1 IMMUNODEFICIENT MICE EXPRESSING HUMAN INTERLEUKIN 15 审中-公开
公开(公告)号：WO2019032836A1
公开(公告)日：2019-02-14
申请号：PCT/US2018/046021
申请日：2018-08-09
申请人： THE JACKSON LABORATORY , UNIVERSITY OF MASSACHUSETTS MEDICAL SCHOOL
发明人： SHULTZ, Leonard, D. , BREHM, Michael, A. , GREINER, Dale, L.
IPC分类号： A01K67/027 , C07K14/54 , C12N5/078
摘要： An immunodeficient mouse is provided which is useful as a model of functions and regulation of human natural killer (NK) cells and other interleukin 15 (IL-15)-dependent cell populations and processes in studies of human immunity, cancer, infectious diseases, and other areas. According to specific aspects, an immunodeficient mouse is provided which is genetically modified to express human interleukin 15, wherein the mouse does not have or produce functional mouse natural killer cells, and wherein the mouse is modified to include human natural killer cells. Methods of identifying anti-tumor activity of a test substance using a mouse of the present invention are described along with methods of making the mouse.

5. 发明申请

WO2018209344A8 NSG MICE LACKING MHC CLASS I AND CLASS II 审中-公开
公开(公告)号：WO2018209344A8
公开(公告)日：2018-11-15
申请号：PCT/US2018/032548
申请日：2018-05-14
申请人： THE JACKSON LABORATORY , UNIVERSITY OF MASSACHUSETTS
发明人： BREHM, Michael, A. , WILES, Michael, V. , GREINER, Dale, L. , SHULTZ, Leonard, D.
IPC分类号： A01K67/027
摘要： A NOD.Cg- Prkdc scid H2rg tm1 Wjl /SzJ .(NOD- scid -IL2rϒ null , NSG) mouse which is genetically modified such that the NSG mouse lacks functional major histocompatibility complex I (MHC I) and lacks functional major histocompatibility complex II (MHC II) is provided according to aspects of the present, invention. According to specific aspects the genetically modified NSG mouse, is a NOD.Cg- Prkdc scid H2-K1 tml Bpe H2-Ab1 eml Mvw H2-D1 tml Bpe H2rg tm Wjl /SzJ (NSG -K b D b ) null ( IA null )) mouse, NSG - RIP-DTR ( K b D b ) null ( IA null ) mouse, or a NOD.Cg- B 2 m tml Une PrKdc scid H2 dlAb1-E α H2rg tm1 Wjl /SzJ (NSG- B2M null (IA IE null )) mouse. Human, immune cells and/or human: tumor cells are administered to a genetically modified immunodeficient mouse according to aspects described herein and assays of one or more test substances can be performed using the provided mice.

6. 发明公开

EP3621433A1 NSG MICE LACKING MHC CLASS I AND CLASS II 有权
公开(公告)号：EP3621433A1
公开(公告)日：2020-03-18
申请号：EP18730891.1
申请日：2018-05-14
申请人： The Jackson Laboratory , University Of Massachusetts
发明人： BREHM, Michael, A. , WILES, Michael, V. , GREINER, Dale, L. , SHULTZ, Leonard, D.
IPC分类号： A01K67/027

7. 发明公开

EP4144213A1 NSG MICE LACKING MHC CLASS I AND CLASS II 无效
公开(公告)号：EP4144213A1
公开(公告)日：2023-03-08
申请号：EP22179461.3
申请日：2018-05-14
申请人： The Jackson Laboratory , University Of Massachusetts
发明人： BREHM, Michael, A. , WILES, Michael, V. , GREINER, Dale, L. , SHULTZ, Leonard, D.
IPC分类号： A01K67/027
摘要： A NOD.Cg- Prkdc scid Il2rg tm1Wjl / SzJ (NOD- scid -IL2rγ null , NSG) mouse which is genetically modified such that the NSG mouse lacks functional major histocompatibility complex I (MHC I) and lacks functional major histocompatibility complex II (MHC II) is provided according to aspects of the present invention. According to specific aspects the genetically modified NSG mouse is a NOD.Cg- Prkdc scid H2-K1 tm1Bpe H2-Ab1 em1Mvw H2-D1 tm1Bpe Il2rg tm1Wjl /SzJ (NSG- (K b D b ) null ( IA null )) mouse, NSG-RIP-DTR (K b D b ) null ( IA null ) mouse, or a NOD.Cg- B2m tm1Unc Prkdc scid H2 dlAb1-Ea Il2rg tm1Wjl /SzJ (NSG -B2M null (IA IE null )) mouse. Human immune cells and/or human tumor cells are administered to a genetically modified immunodeficient mouse according to aspects described herein and assays of one or more test substances can be performed using the provided mice.

8. 发明公开

EP3547831A1 HUMANIZED MOUSE MODEL WITH IMPROVED HUMAN INNATE IMMUNE CELL DEVELOPMENT 审中-公开
公开(公告)号：EP3547831A1
公开(公告)日：2019-10-09
申请号：EP17825653.3
申请日：2017-11-30
申请人： The Jackson Laboratory , University of Massachusetts
发明人： SHULTZ, Leonard, D. , KECK, James, G. , GREINER, Dale, L. , BREHM, Michael, A.
IPC分类号： A01K67/027

9. 发明公开

EP3310159A1 GENETICALLY MODIFIED NON-HUMAN ANIMALS AND METHODS RELATING TO COMPLEMENT DEPENDENT CYTOTOXICITY 有权
标题翻译：遗传修饰的非人类动物和与补充相关细胞毒性有关的方法
公开(公告)号：EP3310159A1
公开(公告)日：2018-04-25
申请号：EP16812441.0
申请日：2016-06-16
申请人： The Jackson Laboratory , University of Massachusetts
发明人： SHULTZ, Leonard, D. , VERMA, Mohit, Kumar , GREINER, Dale, L. , BREHM, Michael, A.
IPC分类号： A01K67/027 , C07K14/705 , G01N33/15
CPC分类号： A01K67/0275 , A01K2217/07 , A01K2227/105 , A01K2267/0387 , A61K49/0008 , C07K14/472 , C12N15/907
摘要： The present invention relates generally to genetically modified non-human animals and immunodeficient non-human animals characterized by restored complement-dependent cytotoxicity, as well as methods and compositions for assessment of therapeutic antibodies in the genetically modified immunodeficient non-human animals. In specific aspects, the present invention relates to immunodeficient non-obese diabetic (NOD), A/J, A/He, AKR, DBA/2, NZB/BIN, B10.D2/oSn and other mouse strains genetically modified to restore complement-dependent cytotoxicity which is lacking in the unmodified immunodeficient mice. In further specific aspects, the present invention relates to NOD.Cg-Prkdcscid IL2rgtm1Wj1/SzJ (NSG), NOD. Cg-Rag1tm1Mom IL2rgtm1Wj1/SzJ (NRG) and NOD.Cg-Prkdcscid IL2rgtm1Wj1/JicTAc (NOG) mice genetically modified to restore complement-dependent cytotoxicity which is lacking in unmodified NSG, NRG and NOG mice. Methods for assessment of therapeutic antibodies or putative therapeutic antibodies in the genetically modified immunodeficient mice characterized by an intact complement system are provided according to specific aspects of the present invention.

10. 发明申请

WO2017075585A1 COMPOSITIONS AND METHODS RELATING TO TUMOR ANALYSIS 审中-公开
标题翻译：与肿瘤分析相关的组合物和方法
公开(公告)号：WO2017075585A1
公开(公告)日：2017-05-04
申请号：PCT/US2016/059711
申请日：2016-10-31
申请人： THE JACKSON LABORATORY
发明人： WILES, Michael, V. , HOSUR, Vishnu , SHULTZ, Leonard, D.
IPC分类号： A01K67/027 , C12N9/64 , G01N33/50 , A61K49/00
CPC分类号： A01K67/0275 , A01K67/0278 , A01K2207/12 , A01K2217/072 , A01K2217/15 , A01K2227/105 , A01K2267/0331 , A61K49/0008 , C12N9/6424 , G01N33/5011 , G01N33/5088
摘要： A genetically modified NOD.Cg -Prkdc scid Il2rg tm1Wjl /Sz J mouse is provided by the present invention wherein the genome of the mouse includes a mutated Rhbdf2 gene such that the mouse expresses a mutant iRhom2 protein, wherein the mutant iRhom2 protein differs from wild-type iRhom2 protein due to one or more mutations selected from p.I156T, p.D158N and p.P159L, and wherein the mouse is characterized by hairless phenotype and increased growth of an exogenous tumor compared to a mouse of the same genetic background which express wild-type iRhom2 protein.
摘要翻译：基因修饰的NOD.Cg -Prkdc ^{scid Il2rg ^{本发明提供了一种小鼠基因组，其中小鼠的基因组包含突变的Rhbdf2基因，使得小鼠表达突变iRhom2蛋白，其中突变iRhom2蛋白由于选自p.I156T，p.D158N和p.P159L的一个或多个突变而与野生型iRhom2蛋白不同，并且其中小鼠的特征在于无毛表型和增长的生长的外源性肿瘤与表达野生型iRhom2蛋白的相同遗传背景的小鼠相比较。}}

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