Thrombus-targeted complexes of plasminogen activator and...

Details Thrombus-targeted complexes of plasminogen activator and... Thrombus-targeted complexes of plasminogen activator and...

C - Chemistry, Metallurgy

12

N

195/33.1, 167/10

C12N 9/50 (2006.01) A61K 38/49 (2006.01) C07K 14/75 (2006.01) C12N 9/70 (2006.01) C12N 9/72 (2006.01) A61K 38/00 (2006.01)

Patent

CA 1335361

Thrombolytic hybrids are formed as covalent or non- covalent complexes of fibrin fragments and plasminogen activator molecules. Native plasmin degradation fragments of fibrin or non-native fibrin fragments are covalently or non-covalently linked to plasminogen activators such as t- PA, scu-PA, urokinase, streptokinase, and the like. Useful native fibrin fragments which may be utilized to form complexes with plasminogen activators include fragments E1, E2, E3, D and DD, and (DD)E complex. The fibrin fragment component targets the hybrid to vascular thrombi, immobi- lizing the plasminogen activator molecule onto the fibrin surface of the thrombus. Once localized on a thrombus surface, the plasminogen activator component of the hybrid activates only the clot-surface bound plasminogen trans- ported by the fibrin fragment vehicle, without significant systemic activation of plasminogen. The hybrids are strong potentiators of plasminogen activator activity, generating more plasmin from fibrin-surface bound plasminogen than the plasminogen activator molecule alone. The hybrids have a longer half-life in circulation than the corresponding unprotected plasminogen activator molecules.

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