公开(公告)号：EP2485583A2

公开(公告)日：2012-08-15

申请号：EP10822486.6

申请日：2010-10-04

申请人： REGENERON PHARMACEUTICALS, INC. ,  Yale University ,  Institute for Research in Biomedicine (IRB)

发明人： STEVENS, Sean ,  MURPHY, Andrew J. ,  FLAVELL, Richard ,  EYNON, Elizabeth ,  GALAN, Jorge ,  WILLINGER, Tim ,  MANZ, Markus ,  RONGVAUX, Anthony

IPC分类号： A01K67/027 ,  A01K49/00

CPC分类号： A01K67/0278 ,  A01K67/0271 ,  A01K67/0275 ,  A01K2207/12 ,  A01K2207/15 ,  A01K2217/072 ,  A01K2217/075 ,  A01K2217/15 ,  A01K2227/105 ,  A01K2267/03 ,  A01K2267/0331 ,  A01K2267/0337 ,  A01K2267/0381 ,  A01K2267/0387 ,  A61K49/00 ,  C07K14/524 ,  C07K14/535 ,  C07K14/5403 ,  C07K14/7155 ,  C12N9/00

摘要： A mouse with a humanization of the mIL-3 gene and the mGM-CSF gene, a knockout of a mRAG gene, and a knockout of a mII2rg subunit gene; and optionally a humanization of the TPO gene is described. A RAG/II2rg KO/hTPO knock-in mouse is described. A mouse engrafted with human hematopoietic stem cells (HSCs) that maintains a human immune cell (HIC) population derived from the HSCs and that is infectable by a human pathogen, e.g., S. typhi or M. tuberculosis is described. A mouse that models a human pathogen infection that is poorly modeled in mice is described, e.g., a mouse that models a human mycobacterial infection, wherein the mouse develops one or more granulomas comprising human immune cells. A mouse that comprises a human hematopoietic malignancy that originates from an early human hematopoietic cells is described, e.g., a myeloid leukemia or a yeloproliferative neoplasia.

公开(公告)号：EP3145307B1

公开(公告)日：2019-02-06

申请号：EP15756500.3

申请日：2015-05-18

申请人： Regeneron Pharmaceuticals, Inc. ,  Yale University ,  Institute for Research in Biomedicine (IRB)

发明人： MURPHY, Andrew J. ,  STEVENS, Sean ,  FLAVELL, Richard ,  MANZ, Markus ,  SHAN, Liang

IPC分类号： A01K67/027 ,  C07K14/535 ,  C07K14/715 ,  C07K14/54 ,  C07K14/52 ,  C07K14/505 ,  C12N9/00 ,  A61K49/00 ,  G01N33/50 ,  C07K14/47

公开(公告)号：EP4306648A3

公开(公告)日：2024-04-17

申请号：EP23195231.8

申请日：2015-05-18

申请人： Regeneron Pharmaceuticals, Inc. ,  Yale University ,  Institute for Research in Biomedicine (IRB)

发明人： MURPHY, Andrew J. ,  STEVENS, Sean ,  FLAVELL, Richard ,  MANZ, Markus ,  SHAN, Liang

IPC分类号： A01K67/027 ,  C07K14/535 ,  C07K14/715 ,  C07K14/54 ,  C07K14/52 ,  C07K14/505 ,  C12N9/00 ,  A61K49/00 ,  G01N33/50 ,  C07K14/47

CPC分类号： A01K67/0271 ,  A01K67/0276 ,  A01K67/0278 ,  A61K49/0008 ,  C07K14/505 ,  C07K14/524 ,  C07K14/535 ,  C07K14/5437 ,  C07K14/7155 ,  C07K14/4703 ,  C12N9/00 ,  G01N33/5088 ,  A01K2207/1220130101 ,  A01K2207/1520130101 ,  A01K2217/07220130101 ,  A01K2217/07520130101 ,  A01K2217/1520130101 ,  A01K2227/10520130101 ,  A01K2267/033720130101 ,  A01K2267/038120130101 ,  C12Q1/18 ,  C12N9/14 ,  C12Y301/03048 ,  Y02A50/30

摘要： Genetically modified non-human animals expressing human EPO from the animal genome are provided. Also provided are methods for making non-human animals expressing human EPO from the non-human animal genome, and methods for using non-human animals expressing human EPO from the non-human animal genome. These animals and methods find many uses in the art, including, for example, in modelling human erythropoiesis and erythrocyte function; in modelling human pathogen infection of erythrocytes; in in vivo screens for agents that modulate erythropoiesis and/or erythrocyte function, e.g. in a healthy or a diseased state; in screens for agents that are toxic to erythrocytes or erythrocyte progenitors; in in vivo screens for agents that prevent against, mitigate, or reverse the toxic effects of toxic agents on erythrocytes or erythrocyte progenitors; in in vivo screens of erythrocytes or erythrocyte progenitors from an individual to predict the responsiveness of an individual to a disease therapy.

公开(公告)号：EP4306648A2

公开(公告)日：2024-01-17

申请号：EP23195231.8

申请日：2015-05-18

申请人： Regeneron Pharmaceuticals, Inc. ,  Yale University ,  Institute for Research in Biomedicine (IRB)

发明人： MURPHY, Andrew J. ,  STEVENS, Sean ,  FLAVELL, Richard ,  MANZ, Markus ,  SHAN, Liang

IPC分类号： C12Q1/18

摘要： Genetically modified non-human animals expressing human EPO from the animal genome are provided. Also provided are methods for making non-human animals expressing human EPO from the non-human animal genome, and methods for using non-human animals expressing human EPO from the non-human animal genome. These animals and methods find many uses in the art, including, for example, in modelling human erythropoiesis and erythrocyte function; in modelling human pathogen infection of erythrocytes; in in vivo screens for agents that modulate erythropoiesis and/or erythrocyte function, e.g. in a healthy or a diseased state; in screens for agents that are toxic to erythrocytes or erythrocyte progenitors; in in vivo screens for agents that prevent against, mitigate, or reverse the toxic effects of toxic agents on erythrocytes or erythrocyte progenitors; in in vivo screens of erythrocytes or erythrocyte progenitors from an individual to predict the responsiveness of an individual to a disease therapy.

公开(公告)号：EP4193834A1

公开(公告)日：2023-06-14

申请号：EP22208636.5

申请日：2013-09-06

申请人： Yale University ,  Institute for Research in Biomedicine (IRB) ,  Regeneron Pharmaceuticals, Inc.

发明人： FLAVELL, Richard, A/ ,  MANZ, Markus ,  RONGVAUX, Anthony ,  STROWIG, Till ,  WILLINGER, Tim ,  YANCOPOULOS, George ,  STEVENS, Sean ,  MURPHY, Andrew, J.

IPC分类号： A01K67/027 ,  A01K39/00

摘要： The invention relates generally to genetically modified non-human animals expressing human polypeptides and their methods of use.

公开(公告)号：EP3482629B1

公开(公告)日：2020-11-25

申请号：EP18214077.2

申请日：2015-05-18

申请人： Regeneron Pharmaceuticals, Inc. ,  Yale University ,  Institute for Research in Biomedicine (IRB)

发明人： MURPHY, Andrew J. ,  STEVENS, Sean ,  FLAVELL, Richard ,  MANZ, Markus ,  SHAN, Liang

IPC分类号： A01K67/027 ,  C07K14/535 ,  C07K14/715 ,  C07K14/54 ,  C07K14/52 ,  C07K14/505 ,  C12N9/00 ,  A61K49/00 ,  G01N33/50 ,  C07K14/47

公开(公告)号：EP3482629A1

公开(公告)日：2019-05-15

申请号：EP18214077.2

申请日：2015-05-18

申请人： Regeneron Pharmaceuticals, Inc. ,  Yale University ,  Institute for Research in Biomedicine (IRB)

发明人： MURPHY, Andrew J. ,  STEVENS, Sean ,  FLAVELL, Richard ,  MANZ, Markus ,  SHAN, Liang

IPC分类号： A01K67/027 ,  C07K14/535 ,  C07K14/715 ,  C07K14/54 ,  C07K14/52 ,  C07K14/505 ,  C12N9/00 ,  A61K49/00 ,  G01N33/50 ,  C07K14/47

摘要： Genetically modified non-human animals expressing human EPO from the animal genome are provided. Also provided are methods for making non-human animals expressing human EPO from the non-human animal genome, and methods for using non-human animals expressing human EPO from the non-human animal genome. These animals and methods find many uses in the art, including, for example, in modelling human erythropoiesis and erythrocyte function; in modelling human pathogen infection of erythrocytes; in in vivo screens for agents that modulate erythropoiesis and/or erythrocyte function, e.g. in a healthy or a diseased state; in screens for agents that are toxic to erythrocytes or erythrocyte progenitors; in in vivo screens for agents that prevent against, mitigate, or reverse the toxic effects of toxic agents on erythrocytes or erythrocyte progenitors; in in vivo screens of erythrocytes or erythrocyte progenitors from an individual to predict the responsiveness of an individual to a disease therapy.

公开(公告)号：EP3145307A2

公开(公告)日：2017-03-29

申请号：EP15756500.3

申请日：2015-05-18

申请人： Regeneron Pharmaceuticals, Inc. ,  Yale University ,  Institute for Research in Biomedicine (IRB)

发明人： MURPHY, Andrew J. ,  STEVENS, Sean ,  FLAVELL, Richard ,  MANZ, Markus ,  SHAN, Liang

IPC分类号： A01K67/027 ,  C07K14/535 ,  C07K14/715 ,  C07K14/54 ,  C07K14/52 ,  C07K14/505 ,  C12N9/00 ,  A61K49/00 ,  G01N33/50 ,  C07K14/47

CPC分类号： A01K67/0271 ,  A01K67/0276 ,  A01K67/0278 ,  A01K2207/12 ,  A01K2207/15 ,  A01K2217/05 ,  A01K2217/072 ,  A01K2217/075 ,  A01K2217/15 ,  A01K2227/105 ,  A01K2267/01 ,  A01K2267/0337 ,  A01K2267/0381 ,  A61K49/0008 ,  C07K14/4703 ,  C07K14/475 ,  C07K14/505 ,  C07K14/524 ,  C07K14/535 ,  C07K14/5403 ,  C07K14/5437 ,  C07K14/7155 ,  C12N9/00 ,  C12N9/14 ,  C12Q1/18 ,  C12Y301/03048 ,  G01N33/5088

摘要： Genetically modified non-human animals expressing human EPO from the animal genome are provided. Also provided are methods for making non-human animals expressing human EPO from the non-human animal genome, and methods for using non-human animals expressing human EPO from the non-human animal genome. These animals and methods find many uses in the art, including, for example, in modeling human erythropoiesis and erythrocyte function; in modeling human pathogen infection of erythrocytes; in in vivo screens for agents that modulate erythropoiesis and/or erythrocyte function, e.g. in a healthy or a diseased state; in in vivo screens for agents that are toxic to erythrocytes or erythrocyte progenitors; in in vivo screens for agents that prevent against, mitigate, or reverse the toxic effects of toxic agents on erythrocytes or erythrocyte progenitors; in in vivo screens of erythrocytes or erythrocyte progenitors from an individual to predict the responsiveness of an individual to a disease therapy.

摘要翻译： 提供了从动物基因组表达人EPO的转基因非人动物。 还提供了从非人动物基因组制备表达人EPO的非人动物的方法，以及从非人动物基因组中使用表达人EPO的非人动物的方法。 这些动物和方法在本领域中发现许多用途，包括例如模拟人类红细胞生成和红细胞功能; 在模拟人类病原体感染红细胞; 在用于调节红细胞生成和/或红细胞功能的药剂的体内筛选中。 处于健康或疾病状态; 在体内筛选对红细胞或红细胞祖细胞有毒的药剂; 在体内筛选防止，减轻或逆转毒性剂对红细胞或红细胞祖细胞的毒性作用的药剂; 在体内筛选来自个体的红细胞或红细胞祖细胞以预测个体对疾病治疗的反应性。

公开(公告)号：EP2892330A2

公开(公告)日：2015-07-15

申请号：EP13834735.6

申请日：2013-09-06

申请人： Yale University ,  Institute for Research in Biomedicine (IRB) ,  Regeneron Pharmaceuticals, Inc.

发明人： FLAVELL, Richard, A. ,  MANZ, Markus ,  RONGVAUX, Anthony ,  STROWIG, Till ,  WILLINGER, Tim ,  YANCOPOULOS, George ,  STEVENS, Sean ,  MURPHY, Andrew, J.

IPC分类号： A01K67/027

CPC分类号： A01K67/0278 ,  A01K67/0271 ,  A01K2207/12 ,  A01K2207/15 ,  A01K2217/072 ,  A01K2217/15 ,  A01K2227/105 ,  A01K2267/0331 ,  A01K2267/0381 ,  A01K2267/0387 ,  C12N15/87

摘要： The invention relates generally to genetically modified non-human animals expressing human polypeptides and their methods of use.

公开(公告)号：EP2618656A2

公开(公告)日：2013-07-31

申请号：EP11827353.1

申请日：2011-09-20

申请人： Yale University, Inc.

发明人： FLAVELL, Richard, A. ,  STROWIG, Till ,  EYNON, Elizabeth ,  PHILBRICK, William ,  MANZ, Markus

IPC分类号： A01K67/027

CPC分类号： A01K67/0278 ,  A01K67/0271 ,  A01K2207/12 ,  A01K2207/15 ,  A01K2217/052 ,  A01K2217/072 ,  A01K2227/105 ,  A01K2267/01 ,  A01K2267/0381 ,  C07K14/70503 ,  C07K16/00 ,  C07K16/2803 ,  C07K2317/14 ,  C07K2317/21

摘要： The invention relates generally to compositions and methods of using transgenic non-human animals expressing human SIRPα that are engrafted with a human hematopoietic system. In various embodiments, the human hematopoietic system engrafted, human SIRPα transgenic non-human animals of the invention are useful as systems for the in vivo evaluation of the growth and differentiation of hematopoietic and immune cells, for the in vivo assessment of an immune response, for the in vivo evaluation of vaccines and vaccination regimens, for in vivo production and collection of immune mediators, including human antibodies, and for use in testing the effect of agents that modulate hematopoietic and immune cell function.