公开(公告)号：WO2012125973A3

公开(公告)日：2013-01-03

申请号：PCT/US2012029537

申请日：2012-03-16

Applicant: MURRAY JUSTIN K ,  MIRANDA LESLIE P ,  MCDONOUGH STEFAN I ,  AMGEN INC

Inventor： MURRAY JUSTIN K ,  MIRANDA LESLIE P ,  MCDONOUGH STEFAN I

IPC: C07K14/435

CPC classification number: C07K14/43518 ,  A61K38/00 ,  A61K47/60 ,  A61K47/68 ,  A61K47/6817 ,  C07K14/00 ,  C07K16/44 ,  C07K2317/35 ,  C07K2317/76 ,  C07K2319/30

Abstract: Disclosed is a composition of matter comprising an isolated polypeptide, which is a peripherally-restricted Nav1.7 inhibitor. In some disclosed embodiments, the isolated polypeptide is an inhibitor of Nav1.7 and/or Nav1.3. Other embodiments are conjugated embodiments of the inventive composition of matter and pharmaceutical compositions containing the inventive composition of matter. Isolated nucleic acids encoding some embodiments of inventive polypeptides and expression vectors, and recombinant host cells containing them are disclosed. A method of treating or preventing pain is also disclosed.

Abstract translation: 公开了包含分离的多肽的物质组合物，其是外周限制的Nav1.7抑制剂。 在一些公开的实施方案中，分离的多肽是Nav1.7和/或Nav1.3的抑制剂。 其它实施方案是本发明组合物和包含本发明组合物的药物组合物的共轭实施方案。 公开了编码本发明多肽和表达载体的一些实施方案的分离的核酸，以及含有它们的重组宿主细胞。 还公开了治疗或预防疼痛的方法。

公开(公告)号：WO2012125973A2

公开(公告)日：2012-09-20

申请号：PCT/US2012/029537

申请日：2012-03-16

Applicant: MURRAY, Justin K. ,  MIRANDA, Leslie P. ,  MCDONOUGH, Stefan I. ,  AMGEN INC.

Inventor： MURRAY, Justin K. ,  MIRANDA, Leslie P. ,  MCDONOUGH, Stefan I.

IPC: C07K14/435

CPC classification number: C07K14/43518 ,  A61K38/00 ,  A61K47/60 ,  A61K47/68 ,  A61K47/6817 ,  C07K14/00 ,  C07K16/44 ,  C07K2317/35 ,  C07K2317/76 ,  C07K2319/30

Abstract: Disclosed is a composition of matter comprising an isolated polypeptide, which is a peripherally-restricted Nav1.7 inhibitor. In some disclosed embodiments, the isolated polypeptide is an inhibitor of Nav1.7 and/or Nav1.3. Other embodiments are conjugated embodiments of the inventive composition of matter and pharmaceutical compositions containing the inventive composition of matter. Isolated nucleic acids encoding some embodiments of inventive polypeptides and expression vectors, and recombinant host cells containing them are disclosed. A method of treating or preventing pain is also disclosed.

Abstract translation: 公开了包含分离的多肽的物质组合物，其是外周限制的Nav1.7抑制剂。 在一些公开的实施方案中，分离的多肽是Nav1.7和/或Nav1.3的抑制剂。 其它实施方案是本发明组合物和包含本发明组合物的药物组合物的共轭实施方案。 公开了编码本发明多肽和表达载体的一些实施方案的分离的核酸，以及含有它们的重组宿主细胞。 还公开了治疗或预防疼痛的方法。

公开(公告)号：WO2012099983A1

公开(公告)日：2012-07-26

申请号：PCT/US2012/021757

申请日：2012-01-18

Applicant: AMGEN INC. ,  GINGRAS, Jacinthe ,  MCDONOUGH, Stefan I.

Inventor： GINGRAS, Jacinthe ,  MCDONOUGH, Stefan I.

IPC: C12N15/85 ,  A01K67/027 ,  C07K16/00 ,  A61K49/00 ,  G01N33/50

CPC classification number: C12N15/8509 ,  A01K67/0276 ,  A01K2217/077 ,  A01K2227/105 ,  A01K2267/03 ,  A61K49/0008 ,  C07K16/00

Abstract: A viable global Na v 1.7 -/- knockout mouse is disclosed, and a breeding colony of global Na v 1.7 -/- knockout mice. Also disclosed are an isolated mouse gamete that does not encode a functional Na v 1.7, produced by the Na v 1.7 -/- knockout mouse; an isolated Na v 1.7 -/- mouse cell, or a progeny cell thereof, isolated from the Na v 1.7 -/- knockout mouse; and a primary cell culture or a secondary cell line and a tissue or organ explant or culture thereof derived from the Na v 1.7 -/- knockout mouse. Disclosed also are a hybridoma, wherein the hybridoma was originally formed from the fusion of the isolated Na v 1.7 -/- mouse cell mouse cell and a myeloma cell, and a method of making an antibody. Also disclosed are assays useful for screening prospective Na v 1.7 inhibitors and dose ranging a test Na v 1.7 inhibitor compound, which were validated using the Na v 1.7 -/- knockout mouse.

Abstract translation: 公开了一种可行的全球Nav1.7 - / - 敲除小鼠，以及全球Nav1.7 - 敲除小鼠的繁殖群。 还公开了不编码由Nav1.7 - / - 敲除小鼠产生的功能性Nav1.7的分离的小鼠配子; 从Nav1.7 - 敲除小鼠分离的分离的Nav1.7 - / - 小鼠细胞或其后代细胞; 和源自Nav1.7 - 敲除小鼠的原代细胞培养物或二次细胞系和组织或器官外植体或培养物。 还公开了杂交瘤，其中杂交瘤最初由分离的Nav1.7 - / - 小鼠细胞小鼠细胞和骨髓瘤细胞的融合形成，以及制备抗体的方法。 还公开了可用于筛选潜在的Nav1.7抑制剂和剂量范围测试Nav1.7抑制剂化合物的测定法，其使用Nav1.7 - 敲除小鼠进行验证。