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 for treating a patient, comprising: a) providing i) a patient having an intravascular catheter defining a lumen therethrough, said lumen having a blood clot, and ii) an infusing solution comprising a pro-UK mutant; b) introducing said solution into the lumen under conditions such that said lumen is cleared. 
     
     
         2 . The method of  claim 1 , wherein said pro-UK mutant is M5. 
     
     
         3 . The method of  claim 1 , wherein after step b) said blood clot is dissolved. 
     
     
         4 . The method of  claim 1 , wherein said UK mutant consists essentially of the catalytic domain of the complete mutant UK molecule. 
     
     
         5 . A UK mutant, consisting essentially of the catalytic domain of the complete mutant UK molecule. 
     
     
         6 . A method, comprising: a) providing i) a device comprising a lumen; and ii) an infusing solution comprising a pro-UK mutant; b) introducing said solution into the lumen to produce a treated device 
     
     
         7 . The method of  claim 6 , wherein said pro-UK mutant is M5. 
     
     
         8 . The method of  claim 6 , wherein said device is a catheter. 
     
     
         9 . The method of  claim 6 , wherein said device is a shunt.