公开(公告)号：EP4389764A2

公开(公告)日：2024-06-26

申请号：EP24161280.3

申请日：2013-11-05

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

发明人： FLAVELL, Richard ,  STROWIG, Till ,  MANZ, Markus G. ,  BORSOTTI, Chiara ,  DHODAPKAR, Madhav ,  MURPHY, Andrew J. ,  STEVENS, Sean ,  YANCOPOULOS, George D.

IPC分类号： C07K14/535

CPC分类号： C07K14/535 ,  C07K14/5403 ,  C07K14/5412 ,  A01K2217/05220130101 ,  A01K2217/07220130101 ,  A01K2217/1520130101 ,  A01K2227/10520130101 ,  C07K14/524 ,  A01K2267/0120130101 ,  A01K67/0278 ,  A61K49/0008

摘要： Genetically modified non-human animals are provided that may be used to model human hematopoietic cell development, function, or disease. The genetically modified non-human animals comprise a nucleic acid encoding human IL-6 operably linked to an IL-6 promoter. In some instances, the genetically modified non-human animal expressing human IL-6 also expresses at least one of human M-CSF, human IL-3, human GM-CSF, human SIRPa or human TPO. In some instances, the genetically modified non-human animal is immunodeficient. In some such instances, the genetically modified non-human animal is engrafted with healthy or diseased human hematopoietic cells. Also provided are methods for using the subject genetically modified non-human animals in modeling human hematopoietic cell development, function, and/or disease, as well as reagents and kits thereof that find use in making the subject genetically modified non-human animals and/or practicing the subject methods.

公开(公告)号：EP4248740A3

公开(公告)日：2023-12-27

申请号：EP23175415.1

申请日：2016-04-12

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

发明人： HERNDLER-BRANDSTETTER, Dietmar ,  FLAVELL, Richard A. ,  FRLETA, Davor ,  GURER, Cagan ,  MANZ, Markus, Gabriel ,  MURPHY, Andrew, J. ,  PALM, Noah, W. ,  SHAN, Liang ,  STEVENS, Sean ,  STROWIG, Till ,  YANCOPOULOS, George, D. ,  DE ZOETE, Marcel

IPC分类号： A01K67/027 ,  A01K39/00 ,  A61P35/00 ,  C07K14/47 ,  C07K14/54

摘要： Genetically modified non-human animals expressing human SIRPα and human IL-15 from the non-human animal genome are provided. Also provided are methods for making non-human animals expressing human SIRPα and human IL-15 from the non-human animal genome, and methods for using non-human animals expressing human SIRPα and human IL-15 from the non-human animal genome. These animals and methods find many uses in the art, including, for example, in modeling human T cell and/or natural killer (NK) cell development and function, in modeling human pathogen infection of human T cells and/or NK cells, and in various in vivo screens.

公开(公告)号：EP3308641B1

公开(公告)日：2019-07-03

申请号：EP17184813.8

申请日：2013-11-05

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

发明人： FLAVELL, Richard ,  STROWIG, Till ,  MANZ, Markus G. ,  BORSOTTI, Chiara ,  DHODAPKAR, Madhav ,  MURPHY, Andrew J. ,  STEVENS, Sean ,  YANCOPOULOS, George D.

IPC分类号： A01K67/027 ,  C07K14/54 ,  C07K14/535

公开(公告)号：EP4389764A3

公开(公告)日：2024-08-14

申请号：EP24161280.3

申请日：2013-11-05

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

发明人： FLAVELL, Richard ,  STROWIG, Till ,  MANZ, Markus G. ,  BORSOTTI, Chiara ,  DHODAPKAR, Madhav ,  MURPHY, Andrew J. ,  STEVENS, Sean ,  YANCOPOULOS, George D.

IPC分类号： A01K67/027 ,  C07K14/54 ,  C07K14/535 ,  C12N5/10

CPC分类号： C07K14/535 ,  C07K14/5403 ,  C07K14/5412 ,  A01K2217/05220130101 ,  A01K2217/07220130101 ,  A01K2217/1520130101 ,  A01K2227/10520130101 ,  C07K14/524 ,  A01K2267/0120130101 ,  A01K67/0278 ,  A61K49/0008 ,  C12N5/10

摘要： Genetically modified non-human animals are provided that may be used to model human hematopoietic cell development, function, or disease. The genetically modified non-human animals comprise a nucleic acid encoding human IL-6 operably linked to an IL-6 promoter. In some instances, the genetically modified non-human animal expressing human IL-6 also expresses at least one of human M-CSF, human IL-3, human GM-CSF, human SIRPa or human TPO. In some instances, the genetically modified non-human animal is immunodeficient. In some such instances, the genetically modified non-human animal is engrafted with healthy or diseased human hematopoietic cells. Also provided are methods for using the subject genetically modified non-human animals in modeling human hematopoietic cell development, function, and/or disease, as well as reagents and kits thereof that find use in making the subject genetically modified non-human animals and/or practicing the subject methods.

公开(公告)号：EP4248740A2

公开(公告)日：2023-09-27

申请号：EP23175415.1

申请日：2016-04-12

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

发明人： HERNDLER-BRANDSTETTER, Dietmar ,  FLAVELL, Richard A. ,  FRLETA, Davor ,  GURER, Cagan ,  MANZ, Markus, Gabriel ,  MURPHY, Andrew, J. ,  PALM, Noah, W. ,  SHAN, Liang ,  STEVENS, Sean ,  STROWIG, Till ,  YANCOPOULOS, George, D. ,  DE ZOETE, Marcel

IPC分类号： A01K39/00

摘要： Genetically modified non-human animals expressing human SIRPα and human IL-15 from the non-human animal genome are provided. Also provided are methods for making non-human animals expressing human SIRPα and human IL-15 from the non-human animal genome, and methods for using non-human animals expressing human SIRPα and human IL-15 from the non-human animal genome. These animals and methods find many uses in the art, including, for example, in modeling human T cell and/or natural killer (NK) cell development and function, in modeling human pathogen infection of human T cells and/or NK cells, and in various in vivo screens.

公开(公告)号：EP3308641A1

公开(公告)日：2018-04-18

申请号：EP17184813.8

申请日：2013-11-05

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

发明人： FLAVELL, Richard ,  STROWIG, Till ,  MANZ, Markus G. ,  BORSOTTI, Chiara ,  DHODAPKAR, Madhav ,  MURPHY, Andrew J. ,  STEVENS, Sean ,  YANCOPOULOS, George D.

IPC分类号： A01K67/027 ,  C07K14/54 ,  C07K14/535

CPC分类号： A01K67/0278 ,  A01K67/0276 ,  A01K2207/15 ,  A01K2217/052 ,  A01K2217/072 ,  A01K2217/075 ,  A01K2217/15 ,  A01K2227/105 ,  A01K2267/01 ,  A61K49/0008 ,  C07K14/535 ,  C07K14/5403 ,  C07K14/5412

摘要： Genetically modified non-human animals are provided that may be used to model human hematopoietic cell development, function, or disease. The genetically modified non-human animals comprise a nucleic acid encoding human IL-6 operably linked to an IL-6 promoter. In some instances, the genetically modified non-human animal expressing human IL-6 also expresses at least one of human M-CSF, human IL-3, human GM-CSF, human SIRPa or human TPO. In some instances, the genetically modified non-human animal is immunodeficient. In some such instances, the genetically modified non-human animal is engrafted with healthy or diseased human hematopoietic cells. Also provided are methods for using the subject genetically modified non-human animals in modeling human hematopoietic cell development, function, and/or disease, as well as reagents and kits thereof that find use in making the subject genetically modified non-human animals and/or practicing the subject methods.

摘要翻译： 提供了可用于模拟人造血细胞发育，功能或疾病的基因修饰的非人动物。 经基因修饰的非人动物包含编码与IL-6启动子可操作连接的人IL-6的核酸。 在一些情况下，表达人IL-6的基因修饰的非人动物还表达人M-CSF，人IL-3，人GM-CSF，人SIRPa或人TPO中的至少一种。 在一些情况下，基因修饰的非人动物是免疫缺陷的。 在一些这样的情况下，基因修饰的非人类动物被移植健康或患病的人类造血细胞。 还提供了使用本发明的基因修饰的非人动物模拟人造血细胞发育，功能和/或疾病的方法，以及用于制备本发明的基因修饰的非人动物和/ 或实践主题方法。

公开(公告)号：EP3282835A1

公开(公告)日：2018-02-21

申请号：EP16720234.0

申请日：2016-04-12

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

发明人： HERNDLER-BRANDSTETTER, Dietmar ,  FLAVELL, Richard A. ,  FRLETA, Davor ,  GURER, Cagan ,  MANZ, Markus Gabriel ,  MURPHY, Andrew J. ,  PALM, Noah W. ,  SHAN, Liang ,  STEVENS, Sean ,  STROWIG, Till ,  YANCOPOULOS, George D. ,  DE ZOETE, Marcel

IPC分类号： A01K67/027 ,  A01K39/00

CPC分类号： A01K67/0278 ,  A01K67/0271 ,  A01K2207/12 ,  A01K2217/072 ,  A01K2217/15 ,  A01K2227/105 ,  A01K2267/0331 ,  A01K2267/0337 ,  A61K49/0008

摘要： Genetically modified non-human animals expressing human SIRPα and human IL-15 from the non-human animal genome are provided. Also provided are methods for making non-human animals expressing human SIRPα and human IL-15 from the non-human animal genome, and methods for using non-human animals expressing human SIRPα and human IL-15 from the non-human animal genome. These animals and methods find many uses in the art, including, for example, in modeling human T cell and/or natural killer (NK) cell development and function, in modeling human pathogen infection of human T cells and/or NK cells, and in various in vivo screens.

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：EP3939423A1

公开(公告)日：2022-01-19

申请号：EP21176673.8

申请日：2013-11-05

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

发明人： FLAVELL, Richard ,  STROWIG, Till ,  MANZ, Markus G. ,  BORSOTTI, Chiara ,  DHODAPKAR, Madhav ,  MURPHY, Andrew J. ,  STEVENS, Sean ,  YANCOPOULOS, George D.

IPC分类号： A01K67/027 ,  C07K14/54 ,  C07K14/535

摘要： Genetically modified non-human animals are provided that may be used to model human hematopoietic cell development, function, or disease. The genetically modified non-human animals comprise a nucleic acid encoding human IL-6 operably linked to an IL-6 promoter. In some instances, the genetically modified non-human animal expressing human IL-6 also expresses at least one of human M-CSF, human IL-3, human GM-CSF, human SIRPa or human TPO. In some instances, the genetically modified non-human animal is immunodeficient. In some such instances, the genetically modified non-human animal is engrafted with healthy or diseased human hematopoietic cells. Also provided are methods for using the subject genetically modified non-human animals in modeling human hematopoietic cell development, function, and/or disease, as well as reagents and kits thereof that find use in making the subject genetically modified non-human animals and/or practicing the subject methods.

公开(公告)号：EP2914102B1

公开(公告)日：2017-10-18

申请号：EP13811637.1

申请日：2013-11-05

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

发明人： FLAVELL, Richard ,  STROWIG, Till ,  MANZ, Markus G. ,  BORSOTTI, Chiara ,  DHODAPKAR, Madhav ,  MURPHY, Andrew J. ,  STEVENS, Sean ,  YANCOPOULOS, George D.

IPC分类号： A01K67/027 ,  C07K14/54 ,  C07K14/535

CPC分类号： A01K67/0278 ,  A01K67/0276 ,  A01K2207/15 ,  A01K2217/052 ,  A01K2217/072 ,  A01K2217/075 ,  A01K2217/15 ,  A01K2227/105 ,  A01K2267/01 ,  A61K49/0008 ,  C07K14/535 ,  C07K14/5403 ,  C07K14/5412

摘要： Genetically modified non-human animals are provided that may be used to model human hematopoietic cell development, function, or disease. The genetically modified non-human animals comprise a nucleic acid encoding human IL-6 operably linked to an IL-6 promoter. In some instances, the genetically modified non-human animal expressing human IL-6 also expresses at least one of human M-CSF, human IL-3, human GM-CSF, human SIRPa or human TPO. In some instances, the genetically modified non-human animal is immunodeficient. In some such instances, the genetically modified non-human animal is engrafted with healthy or diseased human hematopoietic cells. Also provided are methods for using the subject genetically modified non-human animals in modeling human hematopoietic cell development, function, and/or disease, as well as reagents and kits thereof that find use in making the subject genetically modified non-human animals and/or practicing the subject methods.