MODIFIED PLASMINOGEN ACTIVATOR INHIBITOR TYPE-1 MOLECULE AND METHODS BASED THEREON

摘要

The present invention relates to a modified plasminogen activator inhibitor type- 1 (PAI-1) molecule that displays an increased in vivo half-life of the active form of PAI- 1, but is deficient in one or more functional activities as compared to the wild-type PAI- 1 protein. The modified PAI-1 molecule that displays an increased half-life further displays at least one of the following funtional characteristics: (i) decreased binding activity to at least one of the following molecules: urokinase plasminogen activator (uPA), tissue plasminogen activator (tPA) and vitronectin (Vn); and (ii) decreased specific activity against at least one of the following molecules: uPA, tPA and Vn. The invention further relates to pharmaceutical compositions comprising modified PAI-I molecules and methods of using these pharmaceutical compositions for treatment.