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1. 发明授权

US08101724B2 High-affinity human antibodies to human protease-activated receptor-2 有权
标题翻译：人类蛋白酶激活受体-2的高亲和力人抗体
公开(公告)号：US08101724B2
公开(公告)日：2012-01-24
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： C12P21/08 , A61K39/00 , A61K39/395 , C07K16/00
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 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。本发明的抗体可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。

2. 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。

3. 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。

4. 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。

5. 发明申请

US20110307966A1 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：US20110307966A1
公开(公告)日：2011-12-15
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 , C12N15/63 , C12N5/10
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。

6. 发明申请

US20120083000A1 Neuropeptide Release Assay For Sodium Channels 有权
标题翻译：钠通道神经肽释放测定
公开(公告)号：US20120083000A1
公开(公告)日：2012-04-05
申请号：US13236117
申请日：2011-09-19
申请人： Nicole M. Alessandri Haber , Lynn Macdonald , Michael L. LaCroix-Fralish , Andrew J. Murphy
发明人： Nicole M. Alessandri Haber , Lynn Macdonald , Michael L. LaCroix-Fralish , Andrew J. Murphy
IPC分类号： G01N33/567
CPC分类号： C07K14/435
摘要： Methods and compositions for using genetically modified non-human animals are provided, wherein the genetic modification comprises a humanization of the one or more extracellular pore loops of a NaV1.7 channel protein or a complete humanization of an endogenous NaV1.7 gene. Methods for using isolated DRG cultures from genetically modified non-human animals are also provided, wherein the isolated DRG express a human or chimeric NaV1.7 protein on the surface, in particular measuring primary nociceptive activation through the release of calcitonin gene-related peptide (CGRP) in isolated DRG in vitro, and wherein the isolated DRG cultures are capable of generating action potentials and communicating through an excitable signal via the expressed human or chimeric NaV1.7 protein the cell surface. In vivo and in vitro methods for characterizing NaV1.7-specific antagonists and evaluation of corresponding therapeutic potential for NaV1.7-mediated disease are also provided.
摘要翻译：提供了使用遗传修饰的非人动物的方法和组合物，其中遗传修饰包括NaV1.7通道蛋白的一个或多个胞外孔环的人源化或内源性NaV1.7基因的完全人源化。还提供了使用来自遗传修饰的非人动物的分离的DRG培养物的方法，其中分离的DRG在表面上表达人或嵌合的NaV1.7蛋白，特别是通过释放降钙素基因相关肽测量初级伤害感受激活（ CGRP），其中分离的DRG培养物能够产生动作电位并通过表达的人或嵌合的NaV1.7蛋白的细胞表面通过可兴奋的信号传递。还提供了用于表征NaV1.7特异性拮抗剂的体内和体外方法以及对NaV1.7介导的疾病的相应治疗潜力的评估。

7. 发明授权

US08486647B2 Neuropeptide release assay for sodium channels 有权
标题翻译：钠通道神经肽释放测定
公开(公告)号：US08486647B2
公开(公告)日：2013-07-16
申请号：US13236117
申请日：2011-09-19
申请人： Nicole M. Alessandri Haber , Lynn Macdonald , Michael L. LaCroix-Fralish , Andrew J. Murphy
发明人： Nicole M. Alessandri Haber , Lynn Macdonald , Michael L. LaCroix-Fralish , Andrew J. Murphy
IPC分类号： C07K14/705 , C07K19/00 , C12N15/62 , G01N33/567
CPC分类号： C07K14/435
摘要： Methods and compositions for using genetically modified non-human animals are provided, wherein the genetic modification comprises a humanization of the one or more extracellular pore loops of a NaV1.7 channel protein or a complete humanization of an endogenous NaV1.7 gene. Methods for using isolated DRG cultures from genetically modified non-human animals are also provided, wherein the isolated DRG express a human or chimeric NaV1.7 protein on the surface, in particular measuring primary nociceptive activation through the release of calcitonin gene-related peptide (CGRP) in isolated DRG in vitro, and wherein the isolated DRG cultures are capable of generating action potentials and communicating through an excitable signal via the expressed human or chimeric NaV1.7 protein the cell surface. In vivo and in vitro methods for characterizing NaV1.7-specific antagonists and evaluation of corresponding therapeutic potential for NaV1.7-mediated disease are also provided.
摘要翻译：提供了使用遗传修饰的非人动物的方法和组合物，其中遗传修饰包括NaV1.7通道蛋白的一个或多个胞外孔环的人源化或内源性NaV1.7基因的完全人源化。还提供了使用来自遗传修饰的非人动物的分离的DRG培养物的方法，其中分离的DRG在表面上表达人或嵌合的NaV1.7蛋白，特别是通过释放降钙素基因相关肽测量初级伤害感受激活（ CGRP），其中分离的DRG培养物能够产生动作电位并通过表达的人或嵌合的NaV1.7蛋白的细胞表面通过可兴奋的信号传递。还提供了用于表征NaV1.7特异性拮抗剂的体内和体外方法以及对NaV1.7介导的疾病的相应治疗潜力的评估。

8. 发明申请

US20170204158A1 IL-33 Antagonists and Uses Thereof 有权
公开(公告)号：US20170204158A1
公开(公告)日：2017-07-20
申请号：US15463910
申请日：2017-03-20
申请人： Andrew J. Murphy , Nicholas J. Papadopoulos , Jamie M Orengo
发明人： Andrew J. Murphy , Nicholas J. Papadopoulos , Jamie M Orengo
IPC分类号： C07K14/715 , A61K39/395 , A61K45/06
CPC分类号： C07K14/7155 , A61K38/00 , A61K39/3955 , A61K45/06 , C07K2319/30 , C07K2319/32 , C07K2319/735
摘要： The present invention provides interleukin-33 (IL-33) antagonists comprising one or more IL-33-binding domains and one or more multimerizing domains and methods of using the same. According to certain embodiments of the invention, the IL-33-binding domains can comprise an IL-33-binding portion of an ST2 protein and/or an extracellular portion of an IL-1RAcP protein. The IL-33 antagonists of the invention are useful for the treatment of diseases and disorders associated with IL-33 signaling and/or IL-33 cellular expression, such as infectious diseases, inflammatory diseases, allergic diseases and fibrotic diseases.

9. 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.

10. 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.

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