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公开(公告)号:US20120021409A1
公开(公告)日:2012-01-26
申请号:US13093156
申请日:2011-04-25
申请人: John McWhirter , Lynn MacDonald , Sean Stevens , Samuel Davis , David R. Buckler , Karolina A. Hosiawa , Andrew J. Murphy
发明人: John McWhirter , Lynn MacDonald , Sean Stevens , Samuel Davis , David R. Buckler , Karolina A. Hosiawa , Andrew J. Murphy
IPC分类号: C12Q1/68 , G01N33/566 , A01K67/027
摘要: A genetically modified mouse is provided, wherein the mouse expresses an immunoglobulin light chain repertoire characterized by a limited number of light chain variable domains. Mice are provided that express just one or a few immunoglobulin light chain variable domains from a limited repertoire in their germline. Methods for making light chain variable regions in mice, including human light chain variable regions, are provided. Methods for making human variable regions suitable for use in multispecific binding proteins, e.g., bispecific antibodies, are provided.
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公开(公告)号:US20110154512A1
公开(公告)日:2011-06-23
申请号:US12971080
申请日:2010-12-17
申请人: Lynn MACDONALD , Naxin Tu , Cagan Gurer , Sean Stevens , Andrew J. Murphy
发明人: Lynn MACDONALD , Naxin Tu , Cagan Gurer , Sean Stevens , Andrew J. Murphy
IPC分类号: A01K67/027 , G01N33/00 , C12Q1/18 , G01N33/53
CPC分类号: A61K49/0008 , A01K67/0276 , A01K67/0278 , A01K2207/15 , A01K2217/072 , A01K2217/075 , A01K2217/15 , A01K2227/105 , A01K2267/03 , A01K2267/0387 , C07K14/70535 , G01N33/5014
摘要: Genetically modified non-human animals and methods and compositions for making and using them are provided, wherein the genetic modification comprises a deletion of the endogenous low affinity FcγR locus, and wherein the mouse is capable of expressing a functional FcRγ-chain. Genetically modified mice are described, including mice that express low affinity human FcγR genes from the endogenous FcγR locus, and wherein the mice comprise a functional FcRγ-chain. Genetically modified mice that express up to five low affinity human FcγR genes on accessory cells of the host immune system are provided.
摘要翻译: 提供了遗传修饰的非人动物以及用于制备和使用它们的方法和组合物,其中所述遗传修饰包括内源性低亲和力FcγR基因座的缺失,并且其中所述小鼠能够表达功能性FcRγ-链。 描述了转基因小鼠,包括从内源性FcγR基因座表达低亲和性人FcγR基因的小鼠,其中小鼠包含功能性FcRγ-链。 提供了在宿主免疫系统的辅助细胞上表达多达五个低亲和力的人FcγR基因的转基因小鼠。
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公开(公告)号:US20210368751A1
公开(公告)日:2021-12-02
申请号:US17224524
申请日:2021-04-07
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.
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公开(公告)号:US09035128B2
公开(公告)日:2015-05-19
申请号:US13166200
申请日:2011-06-22
IPC分类号: A01K67/027 , C12N5/07 , C12N5/0781 , C07K16/00 , C07K16/46 , C12N15/85 , C07K16/18
CPC分类号: C12N5/0606 , A01K67/0275 , A01K67/0278 , A01K2207/15 , A01K2217/05 , A01K2217/052 , A01K2217/072 , A01K2217/15 , A01K2227/105 , A01K2267/01 , A01K2267/02 , A01K2267/0381 , C07K16/00 , C07K16/18 , C07K16/461 , C07K16/462 , C07K2317/10 , C07K2317/14 , C07K2317/21 , C07K2317/24 , C07K2317/50 , C07K2317/515 , C07K2317/56 , C07K2317/64 , C12N15/10 , C12N15/8509
摘要: Genetically modified mice are provided that express human λ variable (hVλ) sequences, including mice that express hVλ sequences from an endogenous mouse λ light chain locus, mice that express hVλ sequences from an endogenous mouse κ light chain locus, and mice that express hVλ sequences from a transgene or an episome wherein the hVλ sequence is linked to a mouse constant sequence. Mice are provided that are a source of somatically mutated human λ variable sequences useful for making antigen-binding proteins. Compositions and methods for making antigen-binding proteins that comprise human λ variable sequences, including human antibodies, are provided.
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公开(公告)号:US08883496B2
公开(公告)日:2014-11-11
申请号:US13113677
申请日:2011-05-23
申请人: Lynn MacDonald , Naxin Tu , Cagan Gurer , Li-Hsien Wang , Sean Stevens , Andrew J. Murphy
发明人: Lynn MacDonald , Naxin Tu , Cagan Gurer , Li-Hsien Wang , Sean Stevens , Andrew J. Murphy
IPC分类号: C12N5/00 , A01K67/027
CPC分类号: C07K14/70535 , A01K67/0276 , A01K67/0278 , A01K2207/15 , A01K2217/072 , A01K2217/075 , A01K2217/15 , A01K2227/105 , A01K2267/0387 , G01N33/56977 , G01N2333/70535
摘要: Genetically modified non-human animals and methods and compositions for making and using them are provided, wherein the genetic modification comprises a deletion of the endogenous low affinity FcγR locus, and wherein the mouse is capable of expressing a functional FcRγ-chain. Genetically modified mice are described, including mice that express low affinity human FcγR genes from the endogenous FcγR locus, and wherein the mice comprise a functional FcRγ-chain. Genetically modified mice that express up to five low affinity human FcγR genes on accessory cells of the host immune system are provided.
摘要翻译: 提供了遗传修饰的非人动物以及用于制备和使用它们的方法和组合物,其中所述遗传修饰包括内源性低亲和性FcγR基因座的缺失,并且其中所述小鼠能够表达功能性FcRγ-链。 描述了转基因小鼠,包括从内源性FcγR基因座表达低亲和性人FcγR基因的小鼠,其中小鼠包含功能性FcRγ-链。 提供了在宿主免疫系统的辅助细胞上表达多达五个低亲和力的人FcγR基因的转基因小鼠。
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公开(公告)号:US08658853B2
公开(公告)日:2014-02-25
申请号:US13466225
申请日:2012-05-08
申请人: Lynn Macdonald , Naxin Tu , Cagan Gurer , Sean Stevens , Andrew J Murphy
发明人: Lynn Macdonald , Naxin Tu , Cagan Gurer , Sean Stevens , Andrew J Murphy
IPC分类号: A01K67/027 , C12N5/00 , C12N5/02
CPC分类号: A61K49/0008 , A01K67/0276 , A01K67/0278 , A01K2207/15 , A01K2217/072 , A01K2217/075 , A01K2217/15 , A01K2227/105 , A01K2267/03 , A01K2267/0387 , C07K14/70535 , G01N33/5014
摘要: Genetically modified non-human animals and methods and compositions for making and using them are provided, wherein the genetic modification comprises a deletion of the endogenous low affinity FcγR locus, and wherein the mouse is capable of expressing a functional FcRγ-chain. Genetically modified mice are described, including mice that express low affinity human FcγR genes from the endogenous FcγR locus, and wherein the mice comprise a functional FcRγ-chain. Genetically modified mice that express up to five low affinity human FcγR genes on accessory cells of the host immune system are provided.
摘要翻译: 提供了遗传修饰的非人动物,以及用于制备和使用它们的方法和组合物,其中所述遗传修饰包括内源性低亲和力FcγAMR基因座的缺失,并且其中所述小鼠能够表达功能性Fcγγ链。 描述了转基因小鼠,包括从内源性FcgammaR基因座表达低亲和力的人FcγRR基因的小鼠,其中所述小鼠包含功能性Fcγγ链。 提供了在宿主免疫系统的辅助细胞上表达多达五个低亲和力的人FcgammaR基因的转基因小鼠。
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公开(公告)号:US20110145937A1
公开(公告)日:2011-06-16
申请号:US12965050
申请日:2010-12-10
申请人: Lynn MacDonald , Sean Stevens , Andrew J. Murphy
发明人: Lynn MacDonald , Sean Stevens , Andrew J. Murphy
IPC分类号: A01K67/027 , C12P21/00
CPC分类号: A01K67/0278 , A01K67/0275 , A01K67/0276 , A01K2217/072 , A01K2217/075 , A01K2227/105 , A01K2267/01 , C07K16/00 , C07K16/462 , C07K2317/14 , C07K2317/20 , C07K2317/21 , C07K2317/50 , C07K2317/52 , C12N15/8509
摘要: Genetically modified non-human animals and methods and compositions for making and using them are provided, wherein the genetic modification comprises a deletion in an immunoglobulin constant region CH1 gene (optionally a deletion in a hinge region) of an IgG, IgA, IgD, and/or IgE, and wherein the mouse is capable of expressing a functional IgM. Genetically modified mice are described, including mice having a functional IgM gene and modified to have a deletion of a CH1 domain and a hinge region in a heavy chain constant domain that is not an IgM, e.g., in an IgG heavy chain constant domain. Genetically modified mice that make human variable/mouse constant chimeric heavy chain antibodies (antibodies that lack a light chain), fully mouse heavy chain antibodies, or fully human heavy chain antibodies are provided.
摘要翻译: 提供了遗传修饰的非人动物以及用于制备和使用它们的方法和组合物,其中遗传修饰包括IgG,IgA,IgD和/或IgG的免疫球蛋白恒定区CH1基因(任选地在铰链区的缺失)中的缺失 /或IgE,并且其中所述小鼠能够表达功能性IgM。 描述了遗传修饰的小鼠,包括具有功能性IgM基因的小鼠,并且被修饰为具有不是IgM的重链恒定结构域中的CH1结构域和铰链区的缺失,例如在IgG重链恒定结构域中。 提供了使人可变/小鼠恒定的嵌合重链抗体(缺乏轻链的抗体),完全小鼠重链抗体或完全人重链抗体的转基因小鼠。
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公开(公告)号:US09516868B2
公开(公告)日:2016-12-13
申请号:US13195951
申请日:2011-08-02
IPC分类号: A01K67/027 , A01K67/033 , C12P21/00 , C07K16/00 , C12N15/85 , C07K16/46 , C07K16/08
CPC分类号: A01K67/0278 , A01K67/0275 , A01K2217/072 , A01K2227/105 , A01K2267/01 , C07K16/00 , C07K16/082 , C07K16/461 , C07K2317/21 , C12N15/8509
摘要: Genetically modified mice and methods for making an using them are provided, wherein the mice comprise a replacement of all or substantially all immunoglobulin heavy chain V gene segments, D gene segments, and J gene segments with at least one light chain V gene segment and at least one light chain J gene segment. Mice that make binding proteins that comprise a light chain variable domain operably linked to a heavy chain constant region are provided. Binding proteins that contain an immunoglobulin light chain variable domain, including a somatically hypermutated light chain variable domain, fused with a heavy chain constant region, are provided. Modified cells, embryos, and mice that encode sequences for making the binding proteins are provided.
摘要翻译: 提供遗传修饰的小鼠和使用它们的方法,其中小鼠包含用至少一个轻链V基因区段替换全部或基本上所有的免疫球蛋白重链V基因区段,D基因区段和J基因区段, 至少一条轻链J基因片段。 提供了产生结合蛋白质的小鼠,其包含可操作地连接到重链恒定区的轻链可变结构域。 提供了与重链恒定区融合的含有免疫球蛋白轻链可变结构域的结合蛋白,包括体细胞超突变的轻链可变结构域。 提供编码用于制备结合蛋白的序列的修饰的细胞,胚胎和小鼠。
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公开(公告)号:US09012717B2
公开(公告)日:2015-04-21
申请号:US13166171
申请日:2011-06-22
IPC分类号: A01K67/027 , C07K16/00 , C07K16/46 , C12N15/85 , C07K16/18
CPC分类号: C12N5/0606 , A01K67/0275 , A01K67/0278 , A01K2207/15 , A01K2217/05 , A01K2217/052 , A01K2217/072 , A01K2217/15 , A01K2227/105 , A01K2267/01 , A01K2267/02 , A01K2267/0381 , C07K16/00 , C07K16/18 , C07K16/461 , C07K16/462 , C07K2317/10 , C07K2317/14 , C07K2317/21 , C07K2317/24 , C07K2317/50 , C07K2317/515 , C07K2317/56 , C07K2317/64 , C12N15/10 , C12N15/8509
摘要: Genetically modified mice are provided that express human λ variable (hVλ) sequences, including mice that express hVλ sequences from an endogenous mouse λ light chain locus, mice that express hVλ sequences from an endogenous mouse κ light chain locus, and mice that express hVλ sequences from a transgene or an episome wherein the hVλ sequence is linked to a mouse constant sequence. Mice are provided that are a source of somatically mutated human λ variable sequences useful for making antigen-binding proteins. Compositions and methods for making antigen-binding proteins that comprise human λ variable sequences, including human antibodies, are provided.
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公开(公告)号:US08658154B2
公开(公告)日:2014-02-25
申请号:US12971080
申请日:2010-12-17
申请人: Lynn MacDonald , Naxin Tu , Cagan Gurer , Sean Stevens , Andrew J. Murphy
发明人: Lynn MacDonald , Naxin Tu , Cagan Gurer , Sean Stevens , Andrew J. Murphy
CPC分类号: A61K49/0008 , A01K67/0276 , A01K67/0278 , A01K2207/15 , A01K2217/072 , A01K2217/075 , A01K2217/15 , A01K2227/105 , A01K2267/03 , A01K2267/0387 , C07K14/70535 , G01N33/5014
摘要: Genetically modified non-human animals and methods and compositions for making and using them are provided, wherein the genetic modification comprises a deletion of the endogenous low affinity FcγR locus, and wherein the mouse is capable of expressing a functional FcRγ-chain. Genetically modified mice are described, including mice that express low affinity human FcγR genes from the endogenous FcγR locus, and wherein the mice comprise a functional FcRγ-chain. Genetically modified mice that express up to five low affinity human FcγR genes on accessory cells of the host immune system are provided.
摘要翻译: 提供了遗传修饰的非人动物,以及用于制备和使用它们的方法和组合物,其中所述遗传修饰包括内源性低亲和力FcγAMR基因座的缺失,并且其中所述小鼠能够表达功能性Fcγγ链。 描述了转基因小鼠,包括从内源性FcgammaR基因座表达低亲和力的人FcγRR基因的小鼠,其中所述小鼠包含功能性Fcγγ链。 提供了在宿主免疫系统的辅助细胞上表达多达五个低亲和力的人FcgammaR基因的转基因小鼠。
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