Long-acting coagulation factors and methods of producing same
AssigneeProlor Biotech Ltd.
InventorsUdi Eyal FIMA, Gili Hart
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Abstract
Polypeptides comprising at least one carboxy-terminal peptide (CTP) of chorionic gonadotrophin attached to the carboxy terminus but not to the amino terminus of a coagulation factor and polynucleotides encoding the same are disclosed. Pharmaceutical compositions comprising the polypeptides and polynucleotides of the invention and methods of using and producing same are also disclosed.
Claims49
A CTP-modified Factor VII (FVII) polypeptide consisting of a FVII polypeptide and three to five gonadotropin carboxy terminal peptides (CTPs) attached to the carboxy terminus of said CTP-modified FVII polypeptide.
A method of extending the biological half-life, improving the area under the curve (AUC), reducing the dosing frequency, or reducing the clearance rate of a Factor VII (FVII) polypeptide, comprising the step of attaching three to five chorionic gonadotrophin carboxy terminal peptides (CTPs) to the carboxy terminus of said FVII polypeptide, thereby extending the biological half-life of said FVII polypeptide.
A method of producing a CTP-modified Factor VII (FVII) polypeptide, comprising the step of attaching three to five chorionic gonatodrophin carboxy terminal peptides (CTPs) to the carboxy terminus of said FVII polypeptide, thereby producing a CTP-modified FVII polypeptide.
A method of preventing a blood clotting or coagulation disorder in a subject, the method comprising the step of administering to the subject a CTP-modified coagulation factor polypeptide, comprising three to five chorionic gonadotrophin carboxy terminal peptides (CTPs) attached to the carboxy terminus of said coagulation factor, thereby preventing hemophilia in said subject.
A method of treating a bloodclotting or coagulation disorder in a subject, the method comprising the step of administering to the subject a CTP-modified coagulation factor polypeptide, comprising three to five chorionic gonadotrophin carboxy terminal peptides (CTPs) attached to the carboxy terminus of said coagulation factor, thereby preventing hemophilia in said subject.
The method of claim 40, wherein the sequence of said CTP-modified coagulation factor polypeptide is selected from the group consisting of SEQ ID NO:
- 25, 27, 29 or 31.
The method of claim 40, wherein at least one CTP is encoded by an amino acid sequence selected from the group consisting of:
- SEQ ID NO:
- 1 and SEQ ID NO:
- 2.
The method of claim 47, wherein said FVII is activated FVII (FVIIa).
Dependencies are inferred from the claim text.