Factor ix polypeptide mutant, its uses and 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.

We claim: 
     
         1 . A modified recombinant FIX (factor IX) polypeptide comprising at least 70% identity to SEQ ID NO: 2 or SEQ ID NO: 1 and an aspartic acid at a position corresponding to position 338 of SEQ ID NO: 2. 
     
     
         2 . A polypeptide according to  claim 1 , and having an identity of at least 90% SEQ ID NO: 2 or SEQ ID NO: 1. 
     
     
         3 . A method to perform replacement therapy, the method comprising administering to an individual in need thereof the modified FIX polypeptide according to  claim 1 . 
     
     
         4 . The method according to  claim 3  for the treatment of at least one coagulopathy. 
     
     
         5 . The method according to  claim 3  wherein the modified FIX polypeptide is administered in a daily dosage comprise between 0.1 μg/kg and 400 μg/kg. 
     
     
         6 . A pharmaceutical composition comprising a modified recombinant FIX polypeptide according to  claim 1 , and at least one pharmaceutically acceptable excipient. 
     
     
         7 . The pharmaceutical composition according to  claim 6  comprising the modified FIX polypeptide in an amount suitable to provide a daily dosage comprised between 0.1 μg/kg and 400 μg/kg. 
     
     
         8 . The pharmaceutical composition according to  claim 6  formulated for oral, parenteral or rectal administration or suited to administration by inhalation or insufflation. 
     
     
         9 . A method for producing a modified FIX polypeptide according to  claim 1 , whereby the modified FIX polypeptide is expressed by means of a nucleic acid comprising a nucleotide sequence encoding a modified FIX polypeptide according to  claim 1 . 
     
     
         10 . The method according to  claim 9  wherein the nucleotide sequence has at least 90% identity with the sequence having accession number K02402 (GenBank). 
     
     
         11 . The method according to  claim 10  wherein the nucleotide sequence comprises in positions corresponding to positions 34098, 34099 and 34100 a triplet selected in a group consisting of: GAT, GAU, GAC. 
     
     
         12 . The method according to  claim 9  wherein the nucleic acid comprises a promoter in operational linkage with said nucleotide sequence.