公开(公告)号：EP2953452A1

公开(公告)日：2015-12-16

申请号：EP14705679.0

申请日：2014-02-06

申请人： Regeneron Pharmaceuticals, Inc. ,  Duke University

发明人： HAYNES, Barton ,  KELSOE, Garnett ,  LOWY, Israel ,  MACDONALD, Lynn ,  BARAS, Aris, I. ,  GURER, Cagan ,  MEAGHER, Karolina, A. ,  MCWHIRTER, John ,  MURPHY, Andrew, J. ,  YANCOPOULOS, George, D.

IPC分类号： A01K67/027 ,  A61K39/00 ,  C07K16/00

CPC分类号： C07K16/1045 ,  A01K67/0278 ,  A01K2217/072 ,  A01K2227/105 ,  A01K2267/01 ,  C07K16/10 ,  C07K16/1018 ,  G01N2500/00

摘要： Non-human animals with humanized immunoglobulin loci and methods of using them in vaccine design are described, as well as methods for making broadly neutralizing antibodies against infectious agents and pathogens are provided. Non-human animals with humanized immunoglobulin loci used in B-cell-lineage immunogen design in vaccine development are provided, as are methods of carrying out such design.

公开(公告)号：EP4374690A3

公开(公告)日：2024-08-21

申请号：EP24155637.2

申请日：2014-02-20

申请人： Regeneron Pharmaceuticals, Inc.

发明人： MACDONALD, Lynn ,  MURPHY, Andrew, J. ,  TU, Naxin ,  VORONINA, Vera ,  GURER, Cagan

IPC分类号： C07K14/73 ,  C07K14/705 ,  C12N15/85 ,  A01K67/027

CPC分类号： C07K14/70514 ,  C07K14/70517 ,  C07K14/70539 ,  C12N15/8509 ,  A01K2207/1520130101 ,  A01K2217/07220130101 ,  A01K2267/0320130101 ,  A01K67/0278

摘要： The invention provides genetically modified non-human animals that express chimeric human/non-human T cell co-receptor polypeptides (e.g. CD4, CD8α, CD8β), as well as embryos, cells, and tissues comprising the same. Also provided are constructs for making said genetically modified animals and methods of making the same.

公开(公告)号：EP4311833A2

公开(公告)日：2024-01-31

申请号：EP23193595.8

申请日：2012-10-26

申请人： Regeneron Pharmaceuticals, Inc.

发明人： MACDONALD, Lynn ,  MURPHY, Andrew J. ,  GURER, Cagan ,  MCWHIRTER, John ,  VORONINA, Vera ,  HARRIS, Faith ,  STEVENS, Sean

IPC分类号： C07K14/705

摘要： The invention provides genetically modified non-human animals that express chimeric human/non-human MHC I polypeptide and/or human or humanized beta2 microglobulin polypeptide, as well as non-human embryos, cells, and tissues comprising the same. Also provided are constructs for making said genetically modified animals and methods of making the same. Methods of using the genetically modified animals to study various aspects of human immune system are provided.

公开(公告)号：EP4248744A3

公开(公告)日：2023-12-27

申请号：EP23175865.7

申请日：2016-04-06

申请人： Regeneron Pharmaceuticals, Inc.

发明人： MACDONALD, Lynn ,  MURPHY, Andrew, J. ,  GURER, Cagan ,  KYRATSOUS, Christos

IPC分类号： A01K67/027

摘要： Disclosed herein are non-human animals (e.g., rodents, e.g., mice or rats) genetically engineered to express a humanized T cell co-receptor (e.g., humanized CD4 and/or CD8 (e.g., CD8α and/or CD8β)), a human or humanized T cell receptor (TCR) comprising a variable domain encoded by at least one human TCR variable region gene segment and/or a human or humanized major histocompatibility complex that binds the humanized T cell co-receptor (e.g., human or humanized MHC II (e.g., MHC II α and/or MHC II β chains) and/or MHC I (e.g., MHC Iα) respectively, and optionally human or humanized β2 microglobulin) . Also provided are embryos, tissues, and cells expressing the same. Methods for making a genetically engineered animal that expresses at least one humanized T cell co-receptor (e.g., humanized CD4 and/or CD8), at least one humanized MHC that associates with the humanized T cell co-receptor (e.g., humanized MHC II and/or MHC I, respectively) and/or the humanized TCR are also provided. Methods for using the genetically engineered animals that mount a substantially humanized T cell immune response for developing human therapeutics are also provided.

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：EP3912465A1

公开(公告)日：2021-11-24

申请号：EP21167681.2

申请日：2013-02-01

申请人： Regeneron Pharmaceuticals, Inc.

发明人： MACDONALD, Lynn ,  GURER, Cagan ,  MEAGHER, Karolina A ,  STEVENS, Sean ,  MURPHY, Andrew J

IPC分类号： A01K67/027 ,  C07K16/46 ,  C12N9/64

摘要： Non-human animals, tissues, cells, and genetic material are provided that comprise a modification of an endogenous non-human heavy chain immunoglobulin sequence and that comprise an ADAM6 activity functional in a rodent (e.g., a mouse), wherein the non-human animals rearrange human immunoglobulin light chain gene segments in the context of heavy chain constant regions and express immunoglobulin-like molecules comprising human immunoglobulin light chain variable domains fused to heavy chain constant domains that are cognate with human immunoglobulin light chain variable domains fused to light chain constant domains.

公开(公告)号：EP3795587A1

公开(公告)日：2021-03-24

申请号：EP20198394.7

申请日：2012-10-26

申请人： Regeneron Pharmaceuticals, Inc.

发明人： MACDONALD, Lynn ,  MURPHY, Andrew, J. ,  MCWHIRTER, John ,  TU, Naxin ,  VORONINA, Vera ,  GURER, Cagan ,  MEAGHER, Karolina ,  STEVENS, Sean

IPC分类号： C07K14/705 ,  A01K67/027

摘要： The invention provides a genetically modified non-human animal that comprises in its genome unrearranged T cell receptor variable gene loci, as well as non-human embryos, cells, and tissues comprising the same. Also provided are constructs for making said genetically modified non-human animal and methods of making the same. Various methods of using the genetically modified non-human animal are also provided.

公开(公告)号：EP3466255A1

公开(公告)日：2019-04-10

申请号：EP18207075.5

申请日：2015-11-25

申请人： REGENERON PHARMACEUTICALS, INC.

发明人： GURER, Cagan ,  IOFFE, Ella ,  MUJICA, Alexander ,  THURSTON, Gavin

IPC分类号： A01K67/027 ,  G01N33/50 ,  C07K14/705 ,  C07K16/28

摘要： Non-human animals, and methods and compositions for making and using the same, are provided, wherein said non-human animals comprise a humanization of an endogenous cluster of differentiation (CD) gene, in particular a humanization of a CD47 gene. Said non-human animals may be described, in some embodiments, as having a genetic modification to an endogenous CD47 gene so that said non-human animals express a CD47 polypeptide that includes a human portion and a non-human portion (e.g., a murine portion).

公开(公告)号：EP3034608B1

公开(公告)日：2019-01-30

申请号：EP16154526.4

申请日：2011-06-22

申请人： REGENERON PHARMACEUTICALS, INC.

发明人： MACDONALD, Lynn ,  STEVENS, Sean ,  GURER, Cagan ,  MURPHY, Andrew J. ,  HOSIAWA, Karolina A.

IPC分类号： C12N15/85 ,  A01K67/027 ,  C07K16/00 ,  C07K16/46 ,  C07K16/18 ,  C12N15/10

公开(公告)号：EP3216871A1

公开(公告)日：2017-09-13

申请号：EP17163115.3

申请日：2012-10-17

申请人： Regeneron Pharmaceuticals, Inc.

发明人： MACDONALD, Lynn ,  MCWHIRTER, John ,  GURER, Cagan ,  MEAGHER, Karolina A. ,  MURPHY, Andrew J.

IPC分类号： C12N15/85 ,  A01K67/027 ,  C07K16/46

CPC分类号： C07K16/28 ,  A01K67/0278 ,  A01K2217/072 ,  A01K2217/15 ,  A01K2227/105 ,  A01K2267/01 ,  C07K16/00 ,  C07K2317/21 ,  C07K2317/56 ,  C07K2317/565 ,  C12N15/8509 ,  C12N2800/204

摘要： Mice having a restricted immunoglobulin heavy chain locus are provided, wherein the locus is characterized by a single polymorphic human V H gene segment, a plurality of human D H gene segments and a plurality of J H gene segments. Methods for making antibody sequences that bind an antigen ( e.g ., a viral antigen) are provided, comprising immunizing a mouse with an antigen of interest, wherein the mouse comprises a single human V H gene segment, a plurality of human D H gene segments and a plurality of J H gene segments, at the endogenous immunoglobulin heavy chain locus.