Patent ID: 8211858

Claim:
A modified PAI-1 molecule comprising an active form, said modified PAI-1 molecule comprising a helix D region, an A3 strand, an A4 strand and an A5 strand, said molecule comprising an amino acid sequence which has at least about 90% identity to SEQ ID NO:2, said molecule comprises: (a) one or more pairs of amino acid residues not present in a corresponding wild-type PAI-1 protein wherein such one or more pairs of amino acid residues contain sulfhydryl groups, such that one or more disulfide bridges form between or within said helix D region, A3 strand, A4 strand and/or A5 strand of said modified PAI-1 molecule; and (b) one or more amino acid substitutions relative to the amino acid sequence of SEQ ID NO:2 at positions selected from the group consisting of: 146, 197, 352, 355 and 369, wherein the active form of said modified PAI-1 molecule displays: (i) a longer in vivo half-life; and (ii) one or more decreased of the following characteristics: (1) decreased binding activity to at least one of the following molecules: urokinase plasminogen activator (uPA), tissue plasminogen activator (tPA) and vitronectin (Vn); and (2) decreased specific activity against one of the following molecules: uPA, tPA and Vn, as compared to the active form of a corresponding wild-type PAI-1 protein.