Modified factor x polypeptides and uses thereof

An isolated modified Factor X (FX) polypeptide, wherein the modified FX polypeptide is selected from among:

• a) a modified FX polypeptide comprising an amino acid replacement at a position corresponding to position 196 in an unmodified FX polypeptide based on mature numbering with reference to amino acid positions set forth in SEQ ID NO:134, wherein:
• the amino acid replacement is with a neutral polar amino acid;
• the unmodified FX polypeptide has the sequence of amino acids set forth in SEQ ID NO:134, or is the zymogen, active or catalytically active form thereof, or has a sequence of amino acids that has at least 80% sequence identity to SEQ ID NO:134 or the zymogen, active or catalytically active form thereof, respectively;
• and
• the FX polypeptide does not comprise a modified activation peptide;
• and
• b) a modified FX polypeptide comprising at least two amino acid replacement(s) in an unmodified FX polypeptide, wherein:
• the unmodified FX polypeptide has the sequence of amino acids set forth in SEQ ID NO:134, or is the zymogen, active or catalytically active form thereof, or has a sequence of amino acids that has at least 80% sequence identity to SEQ ID NO:134 or the zymogen, active or catalytically active form thereof, respectively;
• and
• the modified FX polypeptide comprises:
• an amino acid replacement at a position corresponding to position 196 in an unmodified FX polypeptide based on mature numbering with reference to amino acid positions set forth in SEQ ID NO:134, wherein the amino acid replacement is with a neutral polar amino acid;
• and
• a further amino acid replacement that confers one or more of increased co-factor dependence, increased resistance to inhibitors, altered glycosylation, increased half-life or increased catalytic activity, wherein the further amino acid replacement is not replacement with Isoleucine (I), Alanine (A), Serine (S) or Threonine (T) at a position corresponding to position 195 with reference to amino acid positions set forth in SEQ ID NO:134, or the same replacement at a corresponding amino acid residue in the unmodified FX polypeptide.