O-linked glycoforms of polypeptides and method to manufacture them
The present invention relates to compositions comprising glycoproteins having altered patterns of O-linked glycosylation, in particular Factor VII, Factor IX, and methods for making these.
1. A method of treating a bleeding disorder in a patient in need thereof, comprising administering to said patient a therapeutically effective amount of a pharmaceutical composition comprising:
a recombinant Factor VII polypeptide comprising the amino acid sequence of SEQ ID NO: 1, wherein at least 80% of the Factor VII polypeptides of said composition contain a Xyl-Xyl-Glc sugar chain linked, via O-linkage, to the serine residue at position 52 of SEQ ID NO:1, and a pharmaceutically acceptable carrier,
wherein said bleeding disorder is haemophilia A.
2. The method of claim 1 , wherein at least 85% of the Factor VII polypeptides of said composition contain a Xyl-Xyl-Glc sugar chain linked, via O-linkage, to the serine residue at position 52 of SEQ ID NO: 1.
3. The method of claim 2 , wherein said bleeding disorder is haemophilia A with inhibitors.
4. The method of claim 1 , wherein at least 90% of the Factor VII polypeptides of said composition contain a Xyl-Xyl-Glc sugar chain linked, via O-linkage, to the serine residue at position 52 of SEQ ID NO: 1.
5. The method of claim 4 , wherein said bleeding disorder is haemophilia A with inhibitors.
6. The method of claim 1 , wherein at least 95% of the Factor VII polypeptides of said composition contain a Xyl-Xyl-Glc sugar chain linked, via O-linkage, to the serine residue at position 52 of SEQ ID NO: 1.
7. The method of claim 6 , wherein said bleeding disorder is haemophilia A with inhibitors.
8. The method of claim 1 , wherein at least 98% of the Factor VII polypeptides of said composition contain a Xyl-Xyl-Glc sugar chain linked, via O-linkage, to the serine residue at position 52 of SEQ ID NO: 1.
9. The method of claim 8 , wherein said bleeding disorder is haemophilia A with inhibitors.
10. The method of claim 1 , wherein said bleeding disorder is haemophilia A with inhibitors.