Factor VII glycoforms

1. A preparation comprising a plurality of Factor VII polpeptides or Factor VII-related polypeptides produced in Chinese Hamster Ovary-K1 (CHO-K1) cells in the absence of serum, wherein said cells are adapted to grow in the absence of serum and are cultured in the absence of serum both in the growth phase and in the production phase.

2. A preparation as defined in claim 1 , wherein the Factor VII polypeptides are selected from the group consisting of: human S52A-Factor VII, human S60A-Factor VII, human Factor VII that has been proteolytically cleaved between residues 290 and 291; human Factor VII that has been proteolytically cleaved between residues 315 and 316; and Factor VII that has been oxidized, wherein wild-type human Factor VII has the sequence of SEQ ID NO:3.

3. A preparation as defined in claim 1 , wherein the human Factor VII-related polypeptides are selected from the group consisting of: R152E-Factor VII, S344A-Factor VII, FFR-Factor VII, and Factor VIIa lacking the Gla domain, wherein wild-type human Factor VII has the sequence of SEQ ID NO:3.

4. A preparation as define in claim 1 , wherein the preparation exhibits a bioavailability that is at least 110% of the bioavailability of a reference preparation, wherein the oligosaccharides of the reference preparation lack fucose linked α1→3 to an antennary N-acetylglucosamine.

5. A preparation as defined in claim 4 , wherein the preparation exhibits a bioavailability that is at least 120% of the bioavailability of a reference preparation.

6. A preparation as defined in claim 4 , wherein the preparation exhibits a bioavailability that is at least 130% of the bioavailability of a reference preparation.

7. A preparation as defined in claim 4 , wherein the preparation exhibits a bloavailability that is at least 140% of the bioavailability of a reference preparation.

8. A preparation as defined in claim 1 , wherein the preparation exhibits tissue factor-independent thrombin generating activity that is at least 110% that of a reference preparation, wherein the oligosaccharides of the reference preparation lack fucose linked α1→3 to an antennary N-acetylglucosamine.

9. A preparation as defined in claim 1 , wherein the preparation exhibits a bioavailability that is at least 110% of the bioavailability of a reference preparation, wherein less than about 93% of the oligosaccharide chains in the reference preparation comprise at least one sialic acid moiety.

10. A pharmaceutical formulation comprising a preparation as defined in claim 1 and pharmaceutically acceptable carrier or adjuvant.

11. A method for treating a Factor VII-responsive syndrome, the method comprising administering a pharmaceutical formulation as defined in claim 10 to a patient in need of such treatment, under conditions that result in a decrease in bleeding and/or an increase in blood clotting.

12. A method as defined in claim 11 , wherein the syndrome is selected from the group consisting of haemophilia A, haemophilia B, Factor XI deficiency, Factor VII deficiency, thrombocytopenia, von Willebrand's disease, presence of clotting factor inhibitor, surgery, trauma, and anticoagulant therapy.

13. A method for decreasing bleeding and/or increasing clotting, the method comprising administering a pharmaceutical formulation as defined in claim 10 to a patient in need of such treatment, under conditions that result in a decrease in bleeding and/or an increase in blood clotting.

14. A method for producing a prepararation comprising Factor VII polypeptides or Factor VII-related polypeptides having a predetermined pattern of N-linked glycosylation, said method comprising culturing a Chinese Hamster Ovary-K1 (CHO-K1) cell that has been adapted to grow in the absence of serum in a medium lacking serum for both growth and production phases.

15. A preparation comprising a plurality of Factor VII polypeptides or Factor VII-related polypeptides produced in Chinese Hamster Ovary-K1 (CHO-K1) cells in the absence of animal-derived components, wherein said cells are adapted to grow in the absence of animal-derived components and are cultured in the absence of animal-derived components both in the growth phase and in the production phase.

16. A preparation as defined in claim 15 , wherein the human Factor VII-related polypeptides are selected from the group consisting of: R152E-Factor VII, S344A-Factor VII, FFR-Factor VII, and Factor VIIa lacking the Gla domain, wherein wild-type human Factor VII has the sequence of SEQ ID NO:3.

17. A preparation as defined in claim 15 , wherein the preparation exhibits a bioavailabiity that is at least 110% of the bioavailabity of a reference preparation, wherein the oligosaccharides of the reference preparbtion lack fucose linked α1→3 to an antennary N-acetylglucosamine.

18. A preparation as defined in claim 17 , wherein the preparation exhibits bioavailability that least 120% of bioavailability of a reference preparation.

19. A preparation as defined in claim 18 , wherein the preparation exhibits a bioavailability that is at least 130% of the bioavailability of a reference preparation.

20. A preparation as defined in claim 19 , wherein the preparation exhibits a bioavailability that is at least 140% of the bioavailability of a reference preparation.

21. A preparation as defined in claim 15 , wherein the preparation exhibits tissue factor-independent thrombin generating activity that is at least 110% that of a reference preparation, wherein the oligosaccharides of the reference preparation lack fucose linked α1→3 to an antennary N-acetylglucosamine.

22. A preparation as defined in claim 15 , wherein the preparation exhibits a bioavailability that is at least 110% of the bioavailability of a reference preparation, wherein less than about 93% of the oligosaccharide chains in the reference preparation comprise at least one slalic acid moiety.

23. A pharmaceutical formulation comprising a preparation as defined in claim 15 and a parmaceutically acceptable carrier or adjuvant.

24. A method for treating a Factor VII-responsive syndrome, the method comprising administering a pharmaceutical formulation as defined in claim 23 to a patient in need of such treatment, under conditions that result in a decrease in bleeding and/or an increase in blood clotting.

25. A method as defined in claim 24 , wherein the syndrome is selected from the group consisting of haemophilia A, haemophilia B, Factor XI deficiency, Factor VII deficiency, thrombocytopenia, von Willebrand's disease, presence of clotting factor inhibitor, surgery, trauma, and anticoagulant therapy.

26. A method for decreasing bleeding and/or increasing clotting, the method comprising administering a pharmaceutical formulation as defined in claim 23 to a patient in need of such treatment, under conditions that result in a decrease in bleeding and/or an increase in blood clotting, wherein the formulation comprises Factor VII polypeptides.

27. A method for producing a preparation comprising Factor VII polypeptides or Factor VII-related polypeptides having a predetermined pattern of N-linked glycosylation, said method comprising culturing a Chinese Hamster Ovary-K1 (CHO-K1) cell that has been adapted to grow in the absence of animal-derived components in a medium lacking animal-derived components for both growth and production phases.