Tissue plasminogen activator having zymogenic or fibrin specific

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

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424 9463, 435 23, 435226, 4352402, 4352523, 4353201, 536 235, 536 2351, C12N 964, C12N 1558, A61K 37547

Patent

active

052621707

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.

REFERENCES:
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Tate, et al., Biochemistry 26:338 (1987).
Peterson, et al., Biochimica Et Biophysica Acta 952:245 (1988).
Rijken, et al., J. Biol. Chem. 257:2920 (1982).
Ross, et al., Annual Reports in Medicinal Chemistry 23:111-1988), Academic Press, Richard C. Alten, Ed.
Pannekoek, et al., Fibrinolysis 2:123 (1988).
Huber and Bode, Accounts of Chemical Research 11:114 (1978).

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