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 . A gene therapy method for the prophylaxis and therapy of hemophilia B, the method comprising:
 administering to a human individual in need thereof an adeno-associated virus (AAV) viral vector, wherein the AAV viral vector comprises a nucleotide sequence encoding a modified Factor IX (FIX) polypeptide,   wherein the modified FIX polypeptide comprises the amino acid sequence of SEQ ID NO:14, and   wherein the amino acid at position 148 of SEQ ID NO:14 is either an alanine or a threonine.   
     
     
         2 . The gene therapy method of  claim 1 , wherein the modified FIX polypeptide shows a specific functional activity of 5 fold or above as compared to FIX wild type. 
     
     
         3 . The gene therapy method of  claim 2 , wherein the modified FIX polypeptide shows a specific functional activity of 8 to 9 fold or above as compared to FIX wild type.