Fibrinogen Preparations Enriched In Fibrinogen With An Extended Alpha Chain

Abstract

The present invention relates to fibrinogen preparations enriched in α-extended fibrinogen. Compositions comprising such preparations show improved clotting properties compared to preparations based on HMW Fib which typically contain no or only low amounts of α-extended fibrinogen. In particular, clot formation time and the clot strength of a clot made by α-extended fibrinogen are improved. In addition, plasmin-mediated degradation of α-extended fibrinogen is reduced as compared to plasma derived fibrinogen.

1 . A fibrinogen preparation which has a clot formation time which is less than the clot formation time of a plasma-derived fibrinogen preparation in a ROTEM® thromboelastography test under similar conditions. 
     
     
         2 . a fibrinogen preparation according to  claim 1  containing at least 95% (w/w) fibrinogen and wherein at least 10% (w/w) of the fibrinogen is in the form of Fib420. 
     
     
         3 . A fibrinogen preparation according to  claim 1 , which is free of Factor XIII. 
     
     
         4 . A pharmaceutical composition comprising a fibrinogen preparation according to  claims 1  and a pharmaceutically acceptable carrier, diluents or excipient. 
     
     
         5 . A pharmaceutical composition according to  claim 4 , wherein the composition is suitable for facilitating tissue adherence, improving wound healing or for intravenous administration. 
     
     
         6 . A pharmaceutical composition according to  claim 4 , wherein the pharmaceutical composition is a fibrin sealant or a topical haemostat. 
     
     
         7 . A pharmaceutical composition according to  claims 4  which further comprises thrombin. 
     
     
         8 . A pharmaceutical composition according to  claims 4  in dry form. 
     
     
         9 . A fibrinogen preparation according to  claims 1  for use as a medicament. 
     
     
         10 . A fibrinogen preparation according to  claims 1  for use in a method for treating acute bleeding episodes, hyperfibrinolysis, fibrinogen deficiency or other bleeding disorders. 
     
     
         11 . A method of using a fibrinogen preparation according to  claim 1  for the preparation of a medicament for the treatment of acute bleeding episodes, hyperfibrinolysis, fibrinogen deficiency or other bleeding disorders. 
     
     
         12 . A method for preparing a Fib420 fibrinogen preparation, which method comprises:
 providing an expression vector comprising a nucleotide sequence encoding an alpha extended polypeptide chain of fibrinogen;   transforming a mammalian cell with the expression vector;   maintaining the mammalian cell under such conditions which allow for the expression of the nucleotide sequence encoding the alpha extended polypeptide chain of fibrinogen.   
     
     
         13 . The method according to  claim 12 , wherein the nucleotide sequence encoding an alpha extended polypeptide chain of fibrinogen is an optimized sequence, preferably an optimized sequence according to SEQ ID No. 5. 
     
     
         14 . The method according to  claim 12 , wherein the mammalian cell is a human cell, preferably a PER.C6 cell. 
     
     
         15 . A pharmaceutical composition according to  claim 4  for use in a method for treating acute bleeding episodes, hyperfibrinolysis, fibrinogen deficiency or other bleeding disorders. 
     
     
         16 . A method of using a pharmaceutical composition according to  claim 4  for the preparation of a medicament for the treatment of acute bleeding episodes, hyperfibrinolysis, fibrinogen deficiency or other bleeding disorders.