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公开(公告)号：US20110195454A1
公开(公告)日：2011-08-11
申请号：US13022759
申请日：2011-02-08
申请人： JOHN MCWHIRTER , LYNN MACDONALD , SEAN STEVENS , SAMUEL DAVIS , DAVID R. BUCKLER , ANDREW J. MURPHY
发明人： JOHN MCWHIRTER , LYNN MACDONALD , SEAN STEVENS , SAMUEL DAVIS , DAVID R. BUCKLER , ANDREW J. MURPHY
IPC分类号： C12P21/02 , A01K67/027
CPC分类号： C07K16/22 , A01K67/0278 , A01K2207/15 , A01K2217/072 , A01K2217/15 , A01K2227/105 , A01K2267/01 , C07K16/00 , C07K2317/21 , C07K2317/24 , C07K2317/515 , C07K2317/565 , C07K2317/567 , C07K2317/76 , C07K2317/92 , C07K2319/30 , C12N15/8509 , C12N2800/204
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.
摘要翻译： 提供遗传修饰的小鼠，其中小鼠不能重新排列并表达内源性小鼠免疫球蛋白轻链可变序列，其中小鼠仅表达由人免疫球蛋白序列编码的一个或两个可操作地连接到小鼠κ的人轻链可变结构域（ ＆kgr;）内源性小鼠的恒定基因 基因座，其中小鼠表达具有仅来自两个人轻链可变区基因片段之一的轻链可变结构域和小鼠kgr的逆嵌合抗体; 恒定结构域，以及来自内源小鼠重链基因座的人重链可变结构域和小鼠重链恒定结构域。 提供了完全人的双特异性表位结合蛋白，其包含两个不同的重链，所述重链与相同的轻链相关，其包含衍生自两个不同人轻链可变区基因片段之一的可变结构域。
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公开(公告)号：US20140033336A1
公开(公告)日：2014-01-30
申请号：US14046285
申请日：2013-10-04
IPC分类号： A01K67/027
摘要： A method for engineering and utilizing large DNA vectors to target, via homologous recombination, and modify, in any desirable fashion, endogenous genes and chromosomal loci in eukaryotic cells. These large DNA targeting vectors for eukaryotic cells, termed LTVECs, are derived from fragments of cloned genomic DNA larger than those typically used by other approaches intended to perform homologous targeting in eukaryotic cells. Also provided is a rapid and convenient method of detecting eukaryotic cells in which the LTVEC has correctly targeted and modified the desired endogenous gene(s) or chromosomal locus (loci) as well as the use of these cells to generate organisms bearing the genetic modification.
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公开(公告)号：US20140017229A1
公开(公告)日：2014-01-16
申请号：US14036530
申请日：2013-09-25
IPC分类号： C07K16/00
CPC分类号： C12P21/00 , A01K67/0275 , A01K67/0278 , A01K2207/15 , A01K2217/05 , A01K2227/105 , A01K2267/01 , C07K16/00 , C07K16/28 , C07K16/462 , C07K2317/10 , C07K2317/21 , C07K2317/24 , C07K2317/51 , C07K2317/515 , C07K2317/56 , C12N15/67 , C12N15/85 , C12N15/8509 , C12N15/902 , C12N15/907 , C12N2800/204
摘要： A method for engineering and utilizing large DNA vectors to target, via homologous recombination, and modify, in any desirable fashion, endogenous genes and chromosomal loci in eukaryotic cells. These large DNA targeting vectors for eukaryotic cells, termed LTVECs, are derived from fragments of cloned genomic DNA larger than those typically used by other approaches intended to perform homologous targeting in eukaryotic cells. Also provided is a rapid and convenient method of detecting eukaryotic cells in which the LTVEC has correctly targeted and modified the desired endogenous gene(s) or chromosomal locus (loci) as well as the use of these cells to generate organisms bearing the genetic modification.
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公开(公告)号：US20140073010A1
公开(公告)日：2014-03-13
申请号：US14080114
申请日：2013-11-14
IPC分类号： C12P21/00
CPC分类号： C12P21/00 , A01K67/0275 , A01K67/0278 , A01K2207/15 , A01K2217/05 , A01K2227/105 , A01K2267/01 , C07K16/00 , C07K16/28 , C07K16/462 , C07K2317/10 , C07K2317/21 , C07K2317/24 , C07K2317/51 , C07K2317/515 , C07K2317/56 , C12N15/67 , C12N15/85 , C12N15/8509 , C12N15/902 , C12N15/907 , C12N2800/204
摘要： A method for engineering and utilizing large DNA vectors to target, via homologous recombination, and modify, in any desirable fashion, endogenous genes and chromosomal loci in eukaryotic cells. These large DNA targeting vectors for eukaryotic cells, termed LTVECs, are derived from fragments of cloned genomic DNA larger than those typically used by other approaches intended to perform homologous targeting in eukaryotic cells. Also provided is a rapid and convenient method of detecting eukaryotic cells in which the LTVEC has correctly targeted and modified the desired endogenous gene(s) or chromosomal locus (loci) as well as the use of these cells to generate organisms bearing the genetic modification.
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公开(公告)号：US20140041068A1
公开(公告)日：2014-02-06
申请号：US14046291
申请日：2013-10-04
IPC分类号： A01K67/027
摘要： A method for engineering and utilizing large DNA vectors to target, via homologous recombination, and modify, in any desirable fashion, endogenous genes and chromosomal loci in eukaryotic cells. These large DNA targeting vectors for eukaryotic cells, termed LTVECs, are derived from fragments of cloned genomic DNA larger than those typically used by other approaches intended to perform homologous targeting in eukaryotic cells. Also provided is a rapid and convenient method of detecting eukaryotic cells in which the LTVEC has correctly targeted and modified the desired endogenous gene(s) or chromosomal locus (loci) as well as the use of these cells to generate organisms bearing the genetic modification.
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公开(公告)号：US20140018522A1
公开(公告)日：2014-01-16
申请号：US14036892
申请日：2013-09-25
IPC分类号： C07K16/28
CPC分类号： C12P21/00 , A01K67/0275 , A01K67/0278 , A01K2207/15 , A01K2217/05 , A01K2227/105 , A01K2267/01 , C07K16/00 , C07K16/28 , C07K16/462 , C07K2317/10 , C07K2317/21 , C07K2317/24 , C07K2317/51 , C07K2317/515 , C07K2317/56 , C12N15/67 , C12N15/85 , C12N15/8509 , C12N15/902 , C12N15/907 , C12N2800/204
摘要： A method for engineering and utilizing large DNA vectors to target, via homologous recombination, and modify, in any desirable fashion, endogenous genes and chromosomal loci in eukaryotic cells. These large DNA targeting vectors for eukaryotic cells, termed LTVECs, are derived from fragments of cloned genomic DNA larger than those typically used by other approaches intended to perform homologous targeting in eukaryotic cells. Also provided is a rapid and convenient method of detecting eukaryotic cells in which the LTVEC has correctly targeted and modified the desired endogenous gene(s) or chromosomal locus (loci) as well as the use of these cells to generate organisms bearing the genetic modification.
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公开(公告)号：US20130024957A1
公开(公告)日：2013-01-24
申请号：US13617448
申请日：2012-09-14
申请人： SEAN STEVENS , Andrew J. Murphy , Richard Flavell , Elizabeth Eynon , Jorge Galan , Tim Willinger , Markus Manz , Anthony Rongvaux
发明人： SEAN STEVENS , Andrew J. Murphy , Richard Flavell , Elizabeth Eynon , Jorge Galan , Tim Willinger , Markus Manz , Anthony Rongvaux
IPC分类号： A01K67/027 , A61K35/14 , A61K35/407 , A61K35/12
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 myeloproliferative neoplasia.
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公开(公告)号：US20130022996A1
公开(公告)日：2013-01-24
申请号：US13617472
申请日：2012-09-14
申请人： SEAN STEVENS , Andrew J. Murphy , Richard Flavell , Elizabeth Eynon , Jorge Galan , Tim Willinger , Markus Manz , Anthony Rongvaux
发明人： SEAN STEVENS , Andrew J. Murphy , Richard Flavell , Elizabeth Eynon , Jorge Galan , Tim Willinger , Markus Manz , Anthony Rongvaux
IPC分类号： A01K67/027 , G01N33/566 , C12Q1/06
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 myeloproliferative neoplasia.
摘要翻译： 具有mIL-3基因和mGM-CSF基因的人源化的小鼠，mRAG基因的敲除和mII2rg亚基基因的敲除; 并且可选地描述了TPO基因的人源化。 描述了RAG / II2rg KO / hTPO敲入小鼠。 描述了维持人类免疫细胞（HIC）群体的人类造血干细胞（HSCs）的小鼠，所述人类免疫细胞（HIC）群体来自HSC并且可被人类病原体例如伤寒沙门氏菌或结核分枝杆菌感染。 描述了模拟在小鼠中模拟不良的人类病原体感染的小鼠，例如模拟人类分枝杆菌感染的小鼠，其中小鼠产生包含人免疫细胞的一种或多种肉芽肿。 描述了包含源于早期人类造血细胞的人类造血恶性肿瘤的小鼠，例如骨髓性白血病或骨髓增生性肿瘤。
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公开(公告)号：US20110269187A1
公开(公告)日：2011-11-03
申请号：US13184603
申请日：2011-07-18
申请人： TAMMY H. HUANG , SEAN STEVENS , JOEL H. MARTIN , JEANETTE L. FAIRHURST , KEVIN J. POBURSKY , MARGARET KAROW , JOAN A. WINDSOR , WARREN R. MIKLUKA
发明人： TAMMY H. HUANG , SEAN STEVENS , JOEL H. MARTIN , JEANETTE L. FAIRHURST , KEVIN J. POBURSKY , MARGARET KAROW , JOAN A. WINDSOR , WARREN R. MIKLUKA
CPC分类号： C07K16/2866 , C07K2317/21 , C07K2317/24 , C07K2317/56 , C07K2317/565 , C07K2317/76
摘要： An isolated antibody or antibody fragment that binds human interleukin-18 receptor alpha (hIL-18Rα), comprising a light chain variable region (LCVR) selected from the group consisting of SEQ ID NO: 5, 9, 13, 17, 21, 25, 29, 33, 37, 41, 45, 49, 53, 61, 65, 69, 73, 77, and 81 and/or a heavy chain variable region (HCVR) selected from the group consisting of SEQ ID NO: 3, 7, 11, 15, 19, 23, 27, 31, 35, 39, 43, 47, 51, 55, 59, 63, 67, 71, 75, and 79, or a fragment or sequence modified by an amino acid substitution, deletion or addition thereof.
摘要翻译： 一种结合人白细胞介素-18受体α（hIL-18Rα）的分离抗体或抗体片段，其包含选自SEQ ID NO：5,9,13,17,21,25的轻链可变区（LCVR） ，29,33,37,41,45,49,53,61,65,69,73,77和81和/或选自SEQ ID NO：3，SEQ ID NO：3的重链可变区（HCVR） 7,11,15,19,23,27,31,35,39,43,47,51,55,59,63,67,71,75和79，或由氨基酸取代修饰的片段或序列 ，删除或添加。
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