Tissue plasminogen activator having zymogenic or fibrin specific

Drug – bio-affecting and body treating compositions – Enzyme or coenzyme containing – Hydrolases

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435212, 435226, 4353201, 4352523, 435369, 435359, 536 232, 424 9463, A61K 3849, C12N 950, C12N 964, C12N 1555

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active

056141904

ABSTRACT:
Tissue plasminogen activator (t-PA) zymogens and variants are prepared, including a fibrinolytically active variant of t-PA that has an amino acid alteration at a site within the protease domain of t-PA as compared with the corresponding wild-type t-PA, which alteration renders the variant zymogenic in the presence of plasmin-degraded fibrinogen, and/or fibrin (or plasma clot) specific, as compared to the corresponding wild-type t-PA. DNA sequences can be prepared that encode the zymogens and variants, as well as expression vectors incorporating the DNA sequences, and host cells transformed with the expression vectors. The zymogens and variants may 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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