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1. 发明授权

US07833979B2 Toxin peptide therapeutic agents 有权
标题翻译：毒素肽治疗剂
公开(公告)号：US07833979B2
公开(公告)日：2010-11-16
申请号：US11406454
申请日：2006-04-17
申请人： John K. Sullivan , Joseph G. McGivern , Leslie P. Miranda , Hung Q. Nguyen , Kenneth W. Walker , Shaw-Fen Sylvia Hu , Colin V. Gegg , Stefan I. McDonough
发明人： John K. Sullivan , Joseph G. McGivern , Leslie P. Miranda , Hung Q. Nguyen , Kenneth W. Walker , Shaw-Fen Sylvia Hu , Colin V. Gegg , Stefan I. McDonough
IPC分类号： A61K38/00 , C07K14/00
CPC分类号： A61K47/48215 , A61K38/00 , A61K47/60 , C07K14/43504 , C07K2319/30 , C07K2319/55
摘要： Disclosed is a composition of matter of the formula (X1)a—(F1)d—(X2)b—(F2)e—(X3)c (I) and multimers thereof, in which F1 and F2 are half-life extending moieties, and d and e are each independently 0 or 1, provided that at least one of d and e is 1; X1, X2, and X3 are each independently -(L)f-P-(L)g-, and f and g are each independently 0 or 1; P is a toxin peptide of no more than about 80 amino acid residues in length, comprising at least two intrapeptide disulfide bonds; L is an optional linker; and a, b, and c are each independently 0 or 1, provided that at least one of a, b and c is 1. Linkage to the half-life extending moiety or moieties increases the in vivo half-life of the toxin peptide, which otherwise would be quickly degraded. A pharmaceutical composition comprises the composition and a pharmaceutically acceptable carrier. Also disclosed are a DNA encoding the inventive composition of matter, an expression vector comprising the DNA, and a host cell comprising the expression vector. Methods of treating an autoimmune disorder, such as, but not limited to, multiple sclerosis, type 1 diabetes, psoriasis, inflammatory bowel disease, contact-mediated dermatitis, rheumatoid arthritis, psoriatic arthritis, asthma, allergy, restinosis, systemic sclerosis, fibrosis, scleroderma, glomerulonephritis, Sjogren syndrome, inflammatory bone resorption, transplant rejection, graft-versus-host disease, and lupus and of preventing or mitigating a relapse of a symptom of multiple sclerosis are also disclosed.
摘要翻译：公开了式（X1）a-（F1）d-（X2）b-（F2）e-（X3）c（Ⅰ）及其多元素的物质组成，其中F1和F2是半衰期延长部分，d和e各自独立地为0或1，条件是d和e中的至少一个为1; X1，X2和X3各自独立地为 - （L）f-P-（L）g-，f和g各自独立地为0或1; P是长度不超过约80个氨基酸残基的毒素肽，其包含至少两个肽内二硫键; L是可选的接头; 并且a，b和c各自独立地为0或1，条件是a，b和c中的至少一个为1.与半衰期延长部分或部分的连接增加毒素肽的体内半衰期，否则会很快退化。药物组合物包含该组合物和药学上可接受的载体。还公开了编码本发明组合物的DNA，包含DNA的表达载体和包含表达载体的宿主细胞。治疗自身免疫性疾病，例如但不限于多发性硬化，1型糖尿病，牛皮癣，炎性肠病，接触介导性皮炎，类风湿性关节炎，银屑病关节炎，哮喘，过敏，再狭窄，系统性硬化，纤维化，还公开了硬皮病，肾小球肾炎，干燥综合征，炎性骨吸收，移植排斥反应，移植物抗宿主病和狼疮以及预防或减轻多发性硬化症状的复发。

2. 发明授权

US08907071B2 Toxin peptide therapeutic agents 有权
标题翻译：毒素肽治疗剂
公开(公告)号：US08907071B2
公开(公告)日：2014-12-09
申请号：US12938294
申请日：2010-11-02
申请人： John K. Sullivan , Joseph G. McGivern , Leslie P. Miranda , Hung Q. Nguyen , Kenneth W. Walker , Shaw-Fen Sylvia Hu , Colin V. Gegg , Stefan I. McDonough
发明人： John K. Sullivan , Joseph G. McGivern , Leslie P. Miranda , Hung Q. Nguyen , Kenneth W. Walker , Shaw-Fen Sylvia Hu , Colin V. Gegg , Stefan I. McDonough
IPC分类号： C07H21/04 , C12N1/20 , C12N15/85 , C12N15/63 , A61K47/48 , C07K14/435 , A61K38/00
CPC分类号： A61K47/48215 , A61K38/00 , A61K47/60 , C07K14/43504 , C07K2319/30 , C07K2319/55
摘要： Disclosed is a DNA encoding a composition of matter of the formula (X1)a—(F1)d—(X2)b—(F2)e—(X3)c (I) and multimers thereof, in which F1 and F2 are half-life extending moieties, and d and e are each independently 0 or 1, provided that at least one of d and e is 1; X1, X2, and X3 are each independently -(L)f-P-(L)g-, and f and g are each independently 0 or 1; P is a ShK peptide analog of no more than about 80 amino acid residues in length; L is an optional linker; and a, b, and c are each independently 0 or 1, provided that at least one of a, b and c is 1. A DNA encoding the ShK peptide analog is disclosed. Also disclosed are an expression vector comprising the DNA, and a host cell comprising the expression vector.
摘要翻译：公开了编码式（X1）a-（F1）d-（X2）b-（F2）e-（X3）c（Ⅰ）及其多聚体的物质组成的DNA，其中F1和F2为一半并且d和e各自独立地为0或1，条件是d和e中的至少一个为1; X1，X2和X3各自独立地为 - （L）f-P-（L）g-，f和g各自独立地为0或1; P是长度不超过约80个氨基酸残基的ShK肽类似物; L是可选的接头; 和a，b和c各自独立地为0或1，条件是a，b和c中的至少一个为1.编码ShK肽类似物的DNA。还公开了包含DNA的表达载体和包含表达载体的宿主细胞。

3. 发明授权

US09340590B2 Potent and selective inhibitors of NaV1.3 and NaV1.7 有权
标题翻译： NaV1.3和NaV1.7的有效和选择性抑制剂
公开(公告)号：US09340590B2
公开(公告)日：2016-05-17
申请号：US14005135
申请日：2012-03-16
申请人： Justin K. Murray , Leslie P. Miranda , Stefan I. McDonough
发明人： Justin K. Murray , Leslie P. Miranda , Stefan I. McDonough
IPC分类号： C07K14/435 , C07K14/00 , A61K47/48 , A61K38/00
CPC分类号： C07K14/43518 , A61K38/00 , A61K47/60 , A61K47/68 , A61K47/6817 , C07K14/00 , C07K16/44 , C07K2317/35 , C07K2317/76 , C07K2319/30
摘要： 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.
摘要翻译：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。

4. 发明申请

US20140073577A1 POTENT AND SELECTIVE INHIBITORS OF NAV1.3 AND NAV1.7 有权
标题翻译： NAV1.3和NAV1.7的POTENT和选择性抑制剂
公开(公告)号：US20140073577A1
公开(公告)日：2014-03-13
申请号：US14005135
申请日：2012-03-16
申请人： Justin K. Murray , Leslie P. Miranda , Stefan I. McDonough
发明人： Justin K. Murray , Leslie P. Miranda , Stefan I. McDonough
IPC分类号： C07K14/435 , A61K47/48
CPC分类号： C07K14/43518 , A61K38/00 , A61K47/60 , A61K47/68 , A61K47/6817 , C07K14/00 , C07K16/44 , C07K2317/35 , C07K2317/76 , C07K2319/30
摘要： 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.
摘要翻译：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。

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