Factor ix polypeptide mutant, its uses and a method for its production

Abstract

Disclosed are a modified FIX (Factor IX) polypeptide comprising a leucine, cysteine, aspartic acid, glutamic acid, histidine, lysine, asparagine, glutamine or tyrosine in position 338; pharmaceutical preparations containing said modified FIX polypeptide; a nucleotide sequence coding for the modified FIX polypeptide; and a method for producing the modified FIX polypeptide.

What is claimed is: 
     
         1 . An adeno-associated virus vector comprising:
 a nucleic acid encoding a modified FIX polypeptide, the modified FIX polypeptide comprising SEQ ID NO:2 having a leucine at position 338 of SEQ ID NO:2 and an alanine or threonine at position 148 of SEQ ID NO:2.   
     
     
         2 . The adeno-associated virus vector of  claim 1 , wherein said nucleic acid encoding a modified FIX polypeptide further comprises a sequence encoding a hydrophobic signal peptide consisting of amino acids 1-28 of SEQ ID NO:1. 
     
     
         3 . The adeno-associated virus vector of  claim 1 , wherein said nucleic acid encoding a modified FIX polypeptide further comprises a sequence encoding a propeptide consisting of amino acids 29-46 of SEQ ID NO: 1. 
     
     
         4 . A pharmaceutical composition comprising the adeno-associated virus vector of  claim 1 . 
     
     
         5 . A pharmaceutical composition comprising the adeno-associated virus vector of  claim 2 . 
     
     
         6 . A pharmaceutical composition comprising the adeno-associated virus vector of  claim 3 . 
     
     
         7 . A method of treatment of at least one coagulopathy in a patient in need thereof comprising administering the adeno-associated virus vector of  claim 1  to the patient. 
     
     
         8 . The method of  claim 7 , wherein the at least one coagulopathy is haemophilia B.