公开(公告)号：US20070071764A1

公开(公告)日：2007-03-29

申请号：US11406454

申请日：2006-04-17

申请人： John Sullivan ,  Joseph McGivern ,  Leslie Miranda ,  Hung Nguyen ,  Kenneth Walker ,  Shaw-Fen Hu ,  Colin Gegg ,  Stefan McDonough

发明人： John Sullivan ,  Joseph McGivern ,  Leslie Miranda ,  Hung Nguyen ,  Kenneth Walker ,  Shaw-Fen Hu ,  Colin Gegg ,  Stefan McDonough

IPC分类号： A61K39/395 ,  C07K16/46

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.