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公开(公告)号:US10143186B2
公开(公告)日:2018-12-04
申请号:US13022759
申请日:2011-02-08
摘要: A genetically modified mouse is provided, wherein the mouse is incapable of rearranging and expressing an endogenous mouse immunoglobulin light chain variable sequence, wherein the mouse expresses only one or two human light chain variable domains encoded by human immunoglobulin sequences operably linked to the mouse kappa (κ) constant gene at the endogenous mouse κ locus, wherein the mouse expresses a reverse chimeric antibody having a light chain variable domain derived from one of only two human light chain variable region gene segments and a mouse κ constant domain, and a human heavy chain variable domain and a mouse heavy chain constant domain, from an endogenous mouse heavy chain locus. Bispecific epitope-binding proteins that are fully human are provided, comprising two different heavy chains that associate with an identical light chain that comprises a variable domain derived from one of two different human light chain variable region gene segments.
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公开(公告)号:US20120260357A1
公开(公告)日:2012-10-11
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 , C12N5/10
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:US20120322108A1
公开(公告)日:2012-12-20
申请号:US13404075
申请日:2012-02-24
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 , C12N5/10
CPC分类号: C07K16/40 , A01K67/0275 , A01K67/0278 , A01K2207/15 , A01K2217/072 , A01K2217/15 , A01K2227/105 , A01K2267/01 , C07K16/22 , C07K16/28 , C07K16/2866 , C07K16/461 , C07K16/462 , C07K2317/21 , C07K2317/92 , C12N9/6489 , C12N15/8509 , C12N2800/204 , C12N2800/30
摘要: Mice are provided that comprise a reduction or deletion of ADAM6 activity from an endogenous ADAM6 locus, or that lack an endogenous locus encoding a mouse ADAM6 protein, wherein the mice comprise a sequence encoding an ADAM6 or ortholog or homolog or fragment thereof that is functional in a male mouse. In one embodiment, the sequence is an ectopic ADAM6 sequence or a sequence that confers upon a male mouse the ability to generate offspring by mating. Mice and cells with genetically modified immunoglobulin heavy chain loci that comprise an ectopic nucleotide sequence encoding a mouse ADAM6 or functional fragment or homolog or ortholog thereof are also provided.
摘要翻译: 提供了包含来自内源性ADAM6基因座的ADAM6活性的减少或缺失或缺少编码小鼠ADAM6蛋白的内源性基因座的小鼠,其中所述小鼠包含编码ADAM6或直系同源物或其同源物或其片段的序列,其功能在 一只雄性老鼠 在一个实施方案中,序列是异位ADAM6序列或赋予雄性小鼠通过交配产生后代的能力的序列。 还提供了具有遗传修饰的免疫球蛋白重链基因座的小鼠和细胞,其包含编码小鼠ADAM6或其功能片段或同源物或直系同源物的异位核苷酸序列。
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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: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: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:US20110256556A1
公开(公告)日:2011-10-20
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: G01N33/574 , G01N33/567 , C12N5/00
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:US20120096572A1
公开(公告)日:2012-04-19
申请号:US13195951
申请日:2011-08-02
IPC分类号: A01K67/027
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:US20120070861A1
公开(公告)日:2012-03-22
申请号:US13166171
申请日:2011-06-22
IPC分类号: C12P19/34 , A01K67/027
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.
摘要翻译: 提供基因修饰的小鼠,其表达人λ变量(hVλ)序列,包括从内源小鼠λ轻链基因座表达hVλ序列的小鼠,从内源小鼠和kgr表达hVλ序列的小鼠; 轻链基因座和表达hVλ序列的小鼠,其中hVλ序列与小鼠恒定序列连接。 提供了可用于制备抗原结合蛋白的体细胞突变的人λ可变序列的来源的小鼠。 提供了包含人λ可变序列(包括人抗体)的抗原结合蛋白的组合物和方法。
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