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    Toxin peptide therapeutic agents
    1.
    发明授权
    Toxin peptide therapeutic agents 有权
    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。

    POTENT AND SELECTIVE INHIBITORS OF NAV1.3 AND NAV1.7
    3.
    发明申请
    POTENT AND SELECTIVE INHIBITORS OF NAV1.3 AND NAV1.7 有权
    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。

    NAV1.7-RELATED ASSAYS
    4.
    发明申请
    NAV1.7-RELATED ASSAYS 审中-公开
    NAV1.7相关测定

    公开(公告)号：US20130115171A1

    公开(公告)日：2013-05-09

    申请号：US13353202

    申请日：2012-01-18

    申请人： Stefan I. MCDONOUGH

    发明人： Stefan I. MCDONOUGH

    IPC分类号： A61K49/00

    CPC分类号： A61K49/0008

    摘要： A viable global NaV1.7−/− knockout mouse is disclosed, and a breeding colony of global NaV1.7−/− knockout mice. Also disclosed are an isolated mouse gamete that does not encode a functional NaV1.7, produced by the NaV1.7−/− knockout mouse; an isolated NaV1.7−/− mouse cell, or a progeny cell thereof, isolated from the NaV1.7−/− knockout mouse; and a primary cell culture or a secondary cell line and a tissue or organ explant or culture thereof derived from the NaV1.7−/− knockout mouse. Disclosed also are a hybridoma, wherein the hybridoma was originally formed from the fusion of the isolated NaV1.7−/− mouse cell mouse cell and a myeloma cell, and a method of making an antibody. Also disclosed are assays useful for screening prospective NaV1.7 inhibitors and dose ranging a test NaV1.7 inhibitor compound, which were validated using the NaV1.7−/− knockout mouse.

    摘要翻译： 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前瞻性NaV1.7抑制剂和剂量范围测试的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。

    Potent and selective inhibitors of NaV1.3 and NaV1.7
    5.
    发明授权
    Potent and selective inhibitors of NaV1.3 and NaV1.7 有权
    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。