Methods, Devices, And Compositions For Lysis Of Occlusive Blood Clots While Sparing Wound Sealing Clots

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.

1 . A method, comprising: a) providing a UK mutant and C1 inhibitor; and b) mixing said UK mutant with said C1 inhibitor. 
     
     
         2 . The method of  claim 1 , wherein said UK mutant is M5. 
     
     
         3 . The method of  claim 2 , wherein M5 is an active two-chain derivative of M5. 
     
     
         4 . The method of  claim 1 , wherein said C1 inhibitor is in solution. 
     
     
         5 . The method of  claim 4 , wherein said solution is plasma. 
     
     
         6 . The method of  claim 1 , wherein said mixing results in a C1 inhibitor complex. 
     
     
         7 . The method of  claim 6 , further comprising the step of detecting the C1 inhibitor complex. 
     
     
         8 . A mixture comprising a UK mutant and a C1 inhibitor. 
     
     
         9 . The mixture of  claim 7 , wherein at least a portion of said mutant and said inhibitor are in a complex.