Factor IX polypeptide mutant, its uses and a method for its production

1. A pharmaceutical composition comprising:

a modified recombinant FIX (factor IX) polypeptide comprising at least 70% identity to SEQ ID NO: 2 and a leucine in position 338 of SEQ ID NO: 2; the modified recombinant FIX polypeptide in an amount suitable to provide a daily dosage comprised between 0.1 μg/kg and 400 μg/kg body weight, and

at least one pharmaceutically acceptable excipient.

2. The pharmaceutical composition according to claim 1 , wherein the polypetide comprises at least 90% identity to SEQ ID NO: 2.

3. The pharmaceutical composition according to claim 1 formulated for oral, parenteral or rectal administration or suited to administration by inhalation or insufflation.

4. A method of treatment, the method comprising administering to an individual in need thereof the pharmaceutical composition according to claim 1 .

5. The method according to claim 4 wherein the administering is performed to treat at least one coagulopathy in the individual.

6. A sequence of nucleotides encoding a modified FIX (Factor IX) polypeptide comprising at least 70% identity to SEQ ID NO: 2 and a leucine at position 338 of SEQ ID NO: 2.

7. The sequence of nucleotides according to claim 6 , wherein the nucleotide sequence has at least 90% homology with the sequence having accession number K02402 (GenBank).

8. The nucleotide sequence according to claim 6 , comprising in positions corresponding to positions 34098, 34099 and 34100 of an unmodified mature FIX polypeptide having SEQ ID NO: 2, a triplet selected in a group consisting of: TTA, UUA, TTG, UUG, CTT, CUU, CTC, CUC, CTA, CUA, CTG, CUG, GAT, GAU and GAC.

9. A nucleic acid comprising the nucleotide sequence according to claim 6 .

10. The nucleic acid according to claim 9 , the nucleic acid comprising a promoter in operational linkage with said nucleotide sequence.

11. A vector comprising the nucleic acid according to claim 9 .

12. A pharmaceutical composition comprising the sequence of nucleotide according to claim 6 .

13. A method for producing a modified FIX (Factor IX) polypeptide, the method comprising

expressing the modified FIX polypeptide by means of a nucleic acid according to claim 9 .

14. A method to perform gene therapy, the method comprising

administering to an individual in need thereof the nucleotide sequence according to claim 6 via a vector configured for gene therapy.

15. The method according to claim 14 , wherein the administering is performed to treat at least one coagulopathy in the individual.