Human coagulation factor VII variants
AssigneeNovo Nordisk HealthCare A/G
InventorsEgon Persson, Ole Hvilsted Olsen
Life of this patent
Estimating the term…
Loading patent…
AssigneeNovo Nordisk HealthCare A/G
InventorsEgon Persson, Ole Hvilsted Olsen
Estimating the term…
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factor VII variants, wherein the Leu residue in position 305 or the Phe residue in position 374 of SEQ ID NO 1 has been replaced by another amino acid residue which can be encoded by nucleic acid constructs and, optionally, wherein at least one other amino acid residue in the remaining positions in the protease domain has been replaced by another amino acid residue which can be encoded by nucleic acid constructs; with the proviso that the variant is not FVII(Ala305).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a Factor VII variant wherein the Leu residue in position 305 or the Phe residue in position 374 of SEQ ID NO 1 has been replaced by another amino acid residue which can be encoded by nucleic acid constructs and, optionally, wherein at least one other amino acid residue in the remaining positions in the protease domain has been replaced by another amino acid residue which can be encoded by nucleic acid constructs; use of the variants for producing a medicament for treatment or prophylaxis of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.
A human coagulation Factor VII variant comprising a subsitution of the Leu in position 305 of SEQ ID NO 1 with an amino acid residue selected from the group consisting of Val, Ile, Met, Phe, Trp, Pro, Gly, Ser, Thr, Cys, Tyr, Asn, Glu, Lys, Arg, His, Asp and Gln.
A human coagulation Factor Vii variant, comprising a substitution of the Leu in position 305 of SEQ ID NO 1 with Val.
A human coagulation Factor VII variant, comprising a first substitution of the Leu in position 305 of SEQ ID NO 1 with Val and a second substitution selected from the group consisting of:
A human coagulation Factor VII variant comprising a substitution of the Leu in position 305 of SEQ ID NO 1 with an amino acid residue selected from the group consisting of Val, Tyr, and Ile, wherein the ratio between the activity of the variant and the activity of native Factor VII polypeptide having a sequence shown in SEQ ID NO 1 is at least about 1.25 when tested in an in vitro hydrolysis assay.
18 A recombinant host cell as defined in claim 17, wherein the cell is selected from the group consisting of CHO cells and BHK cells.
Dependencies are inferred from the claim text.