FVII or FVIIa Gla domain variants

Abstract

Gla domain variants of human Factor VII or human Factor VIIa, comprising 1-15 amino acid modifications relative to human Factor VII or human Factor VIIa, wherein a hydrophobic amino acid residue has been introduced by substitution in position 34; or having an amino acid substitution in position 36; and use of the variants for the treatment of intracerebral haemorrhage (ICH) or trauma.

1 - 20 . (canceled)  
     
     
         21 . A nucleotide sequence encoding a Factor VII (FVII) or Factor VIIa (FVIIa) polypeptide variant having an amino acid sequence comprising 1-15 amino acid modifications relative to human Factor VII (hFVII) or human Factor VIIa (hFVIIa) with the amino acid sequence shown in SEQ ID NO:1, wherein the variant comprises substitution of the arginine residue at position 36 with a negatively charged amino acid residue.  
     
     
         22 . An expression vector comprising the nucleotide sequence of  claim 21 .  
     
     
         23 . A host cell comprising the nucleotide sequence of  claim 21  or an expression vector comprising said nucleotide sequence.  
     
     
         24 . A method for producing a Factor VII (FVII) or Factor VIIa (FVIIa) polypeptide variant having an amino acid sequence comprising 1-15 amino acid modifications relative to human Factor VII (hFVII) or human Factor VIIa (hFVIIa) with the amino acid sequence shown in SEQ ID NO:1, wherein the variant comprises substitution of the arginine residue at position 36 with a negatively charged amino acid residue, the method comprising culturing a eukaryotic host cell capable of in vivo N-glycosylation under conditions conducive for the expression of the polypeptide variant, and recovering the polypeptide variant.  
     
     
         25 - 30 . (canceled)