Abstract: Methods for reducing bleeding during fibrinolysis treatment and for inhibiting the enzymatic activity of a two-chain urokinase mutant are described. Exogenous C1-inactivator is administered during fibrinolysis treatment with the pro-urokinase mutant polypeptide, M5. The C1-inactivator inhibits the formation of two-chain M5 resulting in less hemostatic bleeding.

Abstract: It has now been discovered that certain mutant forms of pro-urokinase (“pro-UK”), such as so-called pro-UK mutant “M5” (Lys.sup.300.fwdarw.His)-, perform in the manner of pro-UK in lysing “bad” blood clots (those clots that occlude blood vessels), while sparing hemostatic fibrin in the so-called “good” blood clots (those clots that seal wounds, e.g., after surgery or other tissue injury). Thus, these pro-UK mutants are excellent and safe thrombolytic agents. These advantages allow them to be used in a variety of new methods, devices, and compositions useful for thrombolysis and treating various cardiovascular disorders in clinical situations where administration of other known thrombolytic agents has been too risky or even contraindicated.

Abstract: It has now been discovered that certain mutant forms of pro-urokinase (“pro-UK”), such as so-called pro-UK mutant “M5” (Lys300?His), perform in the manner of pro-UK in lysing “bad” blood clots (those clots that occlude blood vessels), while sparing hemostatic fibrin in the so-called “good” blood clots (those clots that seal wounds, e.g., after surgery or other tissue injury). Thus, these pro-UK mutants are excellent and safe thrombolytic agents. These advantages allow them to be used in a variety of new methods, devices, and compositions useful for thrombolysis and treating various cardiovascular disorders in clinical situations where administration of other known thrombolytic agents has been too risky or even contraindicated.

Abstract: Methods are provided for producing non-glycosylated, single-chain and two-chain pro-urokinase (pro-UK) mutants. The methods include cultivating a specific E. coli type B strain that has been transformed with specific plasmids carrying a cDNA sequence that encodes pro-UK mutants and carries specific promoter sequences. Products produced by the methods have medical use for thrombolysis performed while sparing hemostatic clots, e.g., for particular applications such as after a stroke or heart attack.