Novel clot-specific steptokinase proteins possessing altered plasminogen activation-characteristics and a process for the preparation of said proteins

Abstract

Clot-specific streptokinase proteins possessing altered plasminogen characteristics, including enhanced fibrin selectivity. The kinetics of plasminogen activation by these proteins are distinct from those of natural streptokinase, in that there is a temporary delay or lag in the initial rate of catalytic conversion of plasminogen to plasmin. Also disclosed are processes for preparing the proteins.

1 .- 32 . (canceled)  
     
     
         33 . A hybrid polypeptide comprising at least one functional fragment of streptokinase (SK) and fibrin binding domains 4 and 5, or fibrin binding domains 1 and 2 of human fibronectin, said functional fragment of SK and said fibrin binding domains being connected via a flexible connecting oligopeptide, said SK fragment lacking plasminogen activation function unless said fibrin binding domains are bound to fibrin.  
     
     
         34 . The hybrid polypeptide of  claim 33 , wherein said fibrin binding domains of human fibronectin are domains 4 and 5.  
     
     
         35 . A pharmaceutical composition comprising the hybrid polypeptide of  claim 34  and a stabilizer.  
     
     
         36 . The pharmaceutical composition of  claim 35 , wherein said stabilizer is human serum albumin or mannitol.  
     
     
         37 . The hybrid polypeptide of  claim 33 , wherein said fibrin binding domains of human fibronectin are domains 1 and 2.  
     
     
         38 . A pharmaceutical composition comprising the hybrid polypeptide of  claim 37  and a stabilizer.  
     
     
         39 . The pharmaceutical composition of  claim 38 , wherein said stabilizer is human serum albumin or mannitol.  
     
     
         40 . A method of treating a thrombus in a subject comprising administering the pharmaceutical composition of  claim 36  or  39 .