US2005032703A1PendingUtilityA1

Method of preparation of stabilized thrombin-activatable fibrinolysis inhibitor (TAFI) and methods of use thereof

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Assignee: AMERICAN DIAGNOSTIC INCPriority: Apr 4, 2001Filed: Sep 13, 2004Published: Feb 10, 2005
Est. expiryApr 4, 2021(expired)· nominal 20-yr term from priority
Inventors:Robert S. GreenfieldSeong Soo Alexander An
Y10S435/975A61K 38/363C12N 9/48A61P 7/02A61K 38/05A61K 38/49A61P 7/04
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Claims

Abstract

The invention is directed in part to a purified form of stabilized activated thrombin-activatable fibrinolysis inhibitor (TAFIa). The invention is further directed to a method of producing stabilized TAFIa. The invention is also directed to methods for therapeutic use of stabilized TAFIa such as in the treatment, prevention or management of diseases via an anti-coagulant effect. The invention is also directed to methods for therapeutic use of inhibitors of TAFIa such as in the treatment, prevention or management of diseases via a procoagulant effect. The invention is also directed to methods of diagnostic use of stabilized TAFIa such as a standard in a chromogenic or a fluorometric carboxypeptidase activity assay. The present invention is also directed to kits comprising stabilized TAFIa useful in measuring carboxypepetidase activity.

Claims

exact text as granted — not AI-modified
1 . A method of preparing stabilized TAFIa, said method comprising proteolytic cleavage of TAFI with a protease that cleaves TAFI to TAFIa in a substantially calcium-free environment.  
     
     
         2 . The method of  claim 1 , wherein the stabilized TAFIa remains stable for at least one hour at 37° C.  
     
     
         3 . The method of  claim 1 , wherein the stabilized TAFIa remains stable for at least eight hours at 37° C.  
     
     
         4 . The method of  claim 1 , wherein the TAFI is a wild-type TAFI protein.  
     
     
         5 . The method of  claim 4 , wherein the TAFI is recombinantly produced.  
     
     
         6 . The method of  claim 1 , wherein the TAFI is a mutant TAFI protein.  
     
     
         7 . The method of  claim 1 , wherein there is less than 1 mM calcium present.  
     
     
         8 . The method of  claim 1 , wherein the protease is thrombin.  
     
     
         9 . The method of  claim 1 , wherein the protease is a thrombin-thrombomodulin complex.  
     
     
         10 . The method of  claim 1 , wherein the protease is plasmin.

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