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    • 84. 发明公开
    • 독소 펩티드 치료제
    • 毒素代谢治疗药物
    • KR1020100017942A
    • 2010-02-16
    • KR1020097027223
    • 2006-04-18
    • 암젠 인크
    • 설리반,존케이.맥기번,조세프쥐.미란다,레슬리피.응우옌,훙큐.워커,케네쓰더블유.후,쇼-펜실비아게그주니어,콜린브이.
    • C07K14/435C12N15/62A61K38/17A61K47/48
    • A61K47/48215A61K38/00A61K47/60C07K14/43504C07K2319/30C07K2319/55C07K14/435A61K38/17A61K47/50C12N15/62
    • Disclosed is a composition of matter of the formula (I) (X)-(F)-(X)-(F)-(X)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; X, X, and Xare each independently-(L)-P-(L)-, 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, obesity, psoriasis, inflammatory bowel disease, contact-mediated dermatitis, rheumatoid arthritis, psoriatic arthritis, 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(I)(X) - (F) - (X) - (F) - (X)和多元素的物质组合物,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; X,X和X各自独立地为(L)-P-(L) - ,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的方法,例如但不限于多发性硬化,1型糖尿病,肥胖,牛皮癣,炎性肠病,接触介导性皮炎,类风湿性关节炎,牛皮癣关节炎,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也被公开。