METHODS FOR TREATMENT OF RHEUMATIC DISEASES BY USING SOLUBLE CTLA4 Russian patent published in 2006 - IPC A61K38/16 A61P19/04 A61P37/02 

FIELD: medicine, immunology, pharmacy.

SUBSTANCE: invention relates to methods for treatment of autoimmune, rheumatic diseases, immune disorders associated with rejection of transplant and involves administration to patient mutant molecules of a soluble CTLA4. These molecules can be administrated in common or successively with the second agent that is chosen from the group consisting of corticosteroid, nonsteroid anti-inflammatory agent, azathioprine, methotrexate, blocker or antagonist of TNFα, hydroxychlorokin, sulfasalazin, gold salt, anakinra, cyclophosphamide and leflunomide. CTLA4 molecule represented in Fig. 23 given in the invention description comprises mutation in position +104 CTLA4 wherein leucine is substituted with glutamic acid, and mutation in position +29 CTLA4 wherein alanine is substituted with tyrosine. CTLA4 molecule can comprise an extracellular domain and involves a sequence shown in Fig. 19 given in the invention description beginning from methionine in position +1 or from alanine in position -1 and terminating by aspartic acid in position +124. CTLA4 molecule can represent L104EA29YIg beginning from methionine in position +1 or from alanine in position -1 and terminating by lysine in position +357 as shown in Fig. 19. Invention provides blocking the immune interaction between T- and B-cells and prevention of activation of B-cells based on binding B7 molecule by using indicated CTLA4 molecule wherein mutations in its molecule result to positive changes in avidity binding with B7.

EFFECT: improved method of treatment.

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