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    • 9. 发明授权
    • Toxin peptide therapeutic agents
    • 毒素肽治疗剂
    • US07833979B2
    • 2010-11-16
    • US11406454
    • 2006-04-17
    • John K. SullivanJoseph G. McGivernLeslie P. MirandaHung Q. NguyenKenneth W. WalkerShaw-Fen Sylvia HuColin V. GeggStefan I. McDonough
    • John K. SullivanJoseph G. McGivernLeslie P. MirandaHung Q. NguyenKenneth W. WalkerShaw-Fen Sylvia HuColin V. GeggStefan I. McDonough
    • A61K38/00C07K14/00
    • A61K47/48215A61K38/00A61K47/60C07K14/43504C07K2319/30C07K2319/55
    • 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.
    • 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。