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1. 发明授权

US10143186B2 Common light chain mouse 有权
公开(公告)号：US10143186B2
公开(公告)日：2018-12-04
申请号：US13022759
申请日：2011-02-08
申请人： John McWhirter , Lynn Macdonald , Sean Stevens , David R. Buckler , Andrew J. Murphy
发明人： John McWhirter , Lynn Macdonald , Sean Stevens , David R. Buckler , Andrew J. Murphy
IPC分类号： A01K67/027 , C07K16/46 , C07K16/00 , C07K16/28 , C12N15/85 , C12N15/90 , C07K16/22
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.

2. 发明申请

US20140013457A1 Methods of Modifying Eukaryotic Cells 审中-公开
公开(公告)号：US20140013457A1
公开(公告)日：2014-01-09
申请号：US14036518
申请日：2013-09-25
申请人： Andrew J. Murphy , George D. Yancopoulos , Margaret Karow , Lynn Macdonald , Sean Stevens
发明人： Andrew J. Murphy , George D. Yancopoulos , Margaret Karow , Lynn Macdonald , Sean Stevens
IPC分类号： C12N15/85
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.

3. 发明授权

US08425907B2 Methods for treating pruritus by administering an antibody that specifically binds human PAR2 有权
标题翻译：通过施用特异性结合人PAR2的抗体来治疗瘙痒的方法
公开(公告)号：US08425907B2
公开(公告)日：2013-04-23
申请号：US13325098
申请日：2011-12-14
申请人： Lynn MacDonald , Andrew J. Murphy , Nicholas J. Papadopoulos , Marc R. Morra , Robert R. Salzler , Michael L. LaCroix-Fralish
发明人： Lynn MacDonald , Andrew J. Murphy , Nicholas J. Papadopoulos , Marc R. Morra , Robert R. Salzler , Michael L. LaCroix-Fralish
IPC分类号： A61K39/00 , A61K39/395
CPC分类号： A61K39/3955 , A61K45/06 , A61K2039/505 , C07K16/28 , C07K2317/21 , C07K2317/24 , C07K2317/34 , C07K2317/76
摘要： The present invention provides methods for treating pruritus by blocking human protease activated receptor-2 (PAR2) activity. The methods of the invention can be used to treat pruritus associated with atopic dermatitis, psoriasis, burn scarring, hypertrophic scarring, keloids, renal failure or hepatic failure. The methods of the invention include administering an antibody or antigen-binding fragment thereof that specifically binds human PAR2.
摘要翻译：本发明提供了通过阻断人蛋白酶活化的受体-2（PAR2）活性来治疗瘙痒的方法。本发明的方法可用于治疗与特应性皮炎，银屑病，烧伤瘢痕，肥大性瘢痕形成，瘢痕疙瘩，肾衰竭或肝衰竭相关的瘙痒。本发明的方法包括施用特异性结合人PAR2的抗体或其抗原结合片段。

4. 发明申请

US20130045492A1 Methods For Making Fully Human Bispecific Antibodies Using A Common Light Chain 审中-公开
标题翻译：使用普通轻链制备全人类双特异性抗体的方法
公开(公告)号：US20130045492A1
公开(公告)日：2013-02-21
申请号：US13488628
申请日：2012-06-05
申请人： Robert Babb , John McWhirter , Lynn MacDonald , Sean Stevens , Samuel Davis , David R. Buckler , Karolina A. Hosiawa , Andrew J. Murphy
发明人： Robert Babb , John McWhirter , Lynn MacDonald , Sean Stevens , Samuel Davis , David R. Buckler , Karolina A. Hosiawa , Andrew J. Murphy
IPC分类号： C12P21/00 , G01N21/64 , G01N33/566
CPC分类号： C07K16/468 , A01K67/0278 , A01K2207/15 , A01K2217/072 , A01K2217/15 , A01K2227/105 , A01K2267/01 , C07K16/00 , C07K16/28 , C07K2317/21 , C07K2317/24 , C07K2317/31 , C07K2317/515 , C07K2317/56 , 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 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 bispecific antibodies having universal light chains using mice as described herein, 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, and host cells are provided. Bispecific antibodies capable of binding first and second antigens are provided, wherein the first and second antigens are separate epitopes of a single protein or separate epitopes on two different proteins are provided.
摘要翻译：提供遗传修饰的小鼠，其中小鼠表达免疫球蛋白轻链总谱，其特征在于有限数量的轻链可变结构域。提供的小鼠在其种系中仅来自有限谱系的一个或几个免疫球蛋白轻链可变结构域。提供了使用如本文所述的小鼠制备具有通用轻链的双特异性抗体的方法，包括人轻链可变区。提供了适合用于多特异性结合蛋白（例如双特异性抗体）和宿主细胞的人可变区的方法。提供了能够结合第一和第二抗原的双特异性抗体，其中第一和第二抗原是单个蛋白质的分离表位或两种不同蛋白质上的分离表位。

5. 发明申请

US20120260357A1 Low Affinity FcgR Deficient Mice 有权
标题翻译：低亲和力FcgR缺陷小鼠
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。

6. 发明申请

US20120021409A1 Common Light Chain Mouse 审中-公开
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.

7. 发明申请

US20110154512A1 Humanized Fc gamma R Mice 有权
标题翻译：人源化FcγR小鼠
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。

8. 发明申请

US20110059095A1 HIGH AFFINITY HUMAN ANTIBODIES TO HUMAN PROTEASE-ACTIVATED RECEPTOR-2 有权
标题翻译：人类抗原激活受体-2的高亲和力人体抗体
公开(公告)号：US20110059095A1
公开(公告)日：2011-03-10
申请号：US12877133
申请日：2010-09-08
申请人： Lynn MacDonald , Andrew J. Murphy , Nicholas J. Papadopoulos , Marc R. Morra , Robert R. Salzler , Michael L. LaCroix-Fralish
发明人： Lynn MacDonald , Andrew J. Murphy , Nicholas J. Papadopoulos , Marc R. Morra , Robert R. Salzler , Michael L. LaCroix-Fralish
IPC分类号： A61K39/395 , C07K16/28 , A61P29/00 , A61P17/04 , A61P11/06 , A61P19/02 , A61P1/00 , A61P1/04 , A61P1/18 , A61P35/00
CPC分类号： A61K39/3955 , A61K45/06 , A61K2039/505 , C07K16/28 , C07K2317/21 , C07K2317/24 , C07K2317/34 , C07K2317/76
摘要： The present invention provides antibodies that bind to protease-activated receptor-2 (PAR-2) and methods of using same. According to certain embodiments of the invention, the antibodies are fully human antibodies that bind to human PAR-2. The antibodies of the invention are useful, inter alia, for the treatment of diseases and disorders associated with one or more PAR-2 biological activities, including the treatment of pain conditions, inflammatory conditions and gastrointestinal conditions.
摘要翻译：本发明提供了结合蛋白酶激活的受体-2（PAR-2）的抗体及其使用方法。根据本发明的某些实施方案，抗体是与人类PAR-2结合的完全人抗体。本发明的抗体尤其用于治疗与一种或多种PAR-2生物活性相关的疾病和病症，包括治疗疼痛病症，炎性病症和胃肠病症。

9. 发明申请

US20100129817A1 IDENTIFYING GERMLINE COMPETENT EMBRYONIC STEM CELLS 审中-公开
标题翻译：鉴定GERMLINE COMPETENT胚胎干细胞
公开(公告)号：US20100129817A1
公开(公告)日：2010-05-27
申请号：US12597694
申请日：2008-05-02
申请人： Yi Wei , Lynn MacDonald , Hsin Chieh Lin
发明人： Yi Wei , Lynn MacDonald , Hsin Chieh Lin
IPC分类号： C12Q1/68 , C40B40/08 , C40B30/00
CPC分类号： G01N33/6842 , C12Q1/6813 , G01N33/56966
摘要： Methods and compositions for selecting ES cells that are germline competent are provided, including gene expression arrays of from one to about 300 or more genes. Selecting ES cells that are competent for germline transmission by comparing the expression of one or more genes between an ES cell that is competent at germline transmission with an ES cell of interest is described. Selecting ES cells likely to be competent at germline transmission, based on their level of expression of gtl2, is also described.
摘要翻译：提供了选择具有种系能力的ES细胞的方法和组合物，包括1至约300个或更多个基因的基因表达阵列。描述通过比较在种系传播下有能力的ES细胞与感兴趣的ES细胞之间的一个或多个基因的表达来选择能够进行种系传播的ES细胞。还描述了基于其gtl2的表达水平选择可能在种系传播方面胜任的ES细胞。

10. 发明授权

US08871996B2 Mice expressing human voltage-gated sodium channels 有权
标题翻译：表达人电压门控钠通道的小鼠
公开(公告)号：US08871996B2
公开(公告)日：2014-10-28
申请号：US13155491
申请日：2011-06-08
申请人： Lynn Macdonald , Andrew J. Murphy , Michael L. LaCroix-Fralish , Nicole M. Alessandri Haber
发明人： Lynn Macdonald , Andrew J. Murphy , Michael L. LaCroix-Fralish , Nicole M. Alessandri Haber
IPC分类号： A01K67/027
CPC分类号： A01K67/0278 , A01K2217/072 , A01K2227/105 , A01K2267/0356
摘要： Genetically modified non-human animals and methods and compositions for making and using them are provided, wherein the genetic modification comprises a humanization of an extracellular loop of an endogenous NaV channel gene, in particular a humanization of the one or more extracellular pore loops of a NaV1.7 channel protein. Genetically modified non-human animals are also provided, wherein the genetic modification comprises replacement of an endogenous NaV channel gene, in particular a replacement of the endogenous NaV1.7 gene with a human NaV1.7 gene, and wherein the genetically modified non-human animals are capable of generating action potentials and communicating through the excitable cells of the genetically modified non-human animals via the expressed human or humanized NaV1.7 protein the surface of the excitable cells. Genetically modified mice are described, including mice that express the human or humanized NaV1.7 gene from the endogenous NaV1.7 locus, and wherein the mice comprise functional β-subunits.
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NaV通道基因的细胞外环的人源化，特别是一种或多种细胞外孔环的人源化 NaV1.7通道蛋白。还提供了遗传修饰的非人动物，其中遗传修饰包括内源性NaV通道基因的替换，特别是用人NaV1.7基因替代内源性NaV1.7基因，并且其中所述遗传修饰的非人动物动物能够通过表达的人或人源化NaV1.7蛋白质产生动力电位并通过基因修饰的非人动物的可兴奋细胞进行通信，所述可激活细胞的表面。描述了转基因小鼠，包括从内源性NaV1.7基因座表达人或人源化NaV1.7基因的小鼠，其中小鼠包含功能性和亚基。

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