The invention concerns novel
coagulation factor VII variants, wherein the Leu residue in position 305 or the Phe residue in position 374 of SEQ ID NO 1 has been replaced by another
amino acid residue which can be encoded by
nucleic acid constructs and, optionally, wherein at least one other
amino acid residue in the remaining positions in the
protease domain has been replaced by another
amino acid residue which can be encoded by
nucleic acid constructs;with the proviso that the variant is not FVII(Ala305).The invention further concerns nucleic acids encoding the
Factor VII variants; vectors and cells comprising the
nucleic acid; methods for producing the variants; pharmaceutical compositions comprising a
Factor VII variant wherein the Leu residue in position 305 or the Phe residue in position 374 of SEQ ID NO 1 has been replaced by another
amino acid residue which can be encoded by nucleic acid constructs and, optionally, wherein at least one other
amino acid residue in the remaining positions in the
protease domain has been replaced by another
amino acid residue which can be encoded by nucleic acid constructs; use of the variants for producing a medicament for treatment or prophylaxis of bleeding disorders or enhancement of the
coagulation system; and methods of treatment.