Thrombin-activatable plasminogen activator

Details Thrombin-activatable plasminogen activator Thrombin-activatable plasminogen activator

1993-04-19

1996-11-05

Wax, Robert A.

Chemistry: molecular biology and microbiology

Enzyme , proenzyme; compositions thereof; process for...

Hydrolase

424 9463, 4241921, 435 71, 4351885, 435212, 435214, 435217, 5303873, 536 221, 536 231, 536 232, 536 234, 536 2353, C12P 2108, A61K 3848, C07K 1600, C07H 1900

Patent

active

055717080

ABSTRACT:
A new chimeric plasminogen activator with high fibrin affinity was designed to bind to a fibrin clot and initiate clot destruction in the presence of thrombin, but not plasmin. The chimeric molecule has an antibody variable region having a fibrin-specific antigen binding site and a single chain urokinase region having a thrombin activation site but not a plasmin activation site. The preferred embodiment, 59D8-ScuPA-T, has an N-terminal fragment of an anti-fibrin antibody (59DB) and a C-terminal thrombin-activatable low molecular weight single-chain urokinase plasminogen activator (scuPA-T). The scuPA-T portion was obtained by deletion of two amino acids (Phe157 and Lys 158) that make up the plasmin activation site from low molecular weight single chain urokinase-type plasminogen activator (scuPA).

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