T-pa substitution variants with improved fibrin-specificity

Details T-pa substitution variants with improved fibrin-specificity T-pa substitution variants with improved fibrin-specificity

C - Chemistry, Metallurgy

12

N

C12N 15/58 (2006.01) A61K 38/49 (2006.01) C12N 9/64 (2006.01) C12N 9/72 (2006.01) A61K 38/00 (2006.01)

Patent

CA 2124937

Tissue plasminogen activator (t-PA) variants with substitution of leucine far phenylalanine, histidine for arginine, serine for isoleucine and threonine for lysine at amino acid positions (274, 275, 276 and 277) respectively, of wild-type human t-PA are prepared. DNA sequences can be prepared that encode such variants, as well as expression vectors incorporating the DNA se- quences, and host cells transformed with the expression vectors. The variants exhibit improved fibrin-specificity and can be used in a pharmaceutical preparation to treat a vascular disease or condition or to prevent fibrin deposition or adhesion formation or reformation in mammals.

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