Long-acting polypeptides and methods of producing and administering same
A polypeptide and polynucleotides comprising at least two carboxy-terminal peptides (CTP) of chorionic gonadotrophin attached to a non-human peptide-of-interest are disclosed. Pharmaceutical compositions comprising the non-human polypeptides and polynucleotides of the invention and methods of using both human and non-human polypeptides and polynucleotides are also disclosed.
1. A method of treating a subject suffering from a fatigue syndrome following cancer chemotherapy or a chronic infection, wherein said subject is anemic, said method comprising administering to a subject a therapeutically effective amount of a polypeptide consisting of a chorionic gonadotropin carboxy terminal peptide (CTP) modified erythropoietin (EPO), said CTP-modified EPO consisting of one chorionic gonadotropin carboxy terminal peptide (CTP) attached to the amino terminus of said EPO, and two chorionic gonadotropin CTPs attached to the carboxy terminus of said EPO, wherein said polypeptide consists of a precursor or a mature polypeptide and optionally a signal peptide attached to the amino terminus of said one CTP, wherein said administration treats the anemic subject suffering from fatigue syndrome following cancer chemotherapy or a chronic infection, or any combination thereof.
2. The method of claim 1 , wherein the sequence of at least one chorionic gonadotropin carboxy terminal peptide consists of an amino acid sequence selected from the group consisting of SEQ ID NO: 17 and SEQ ID NO: 18.
3. The method of claim 1 , wherein at least one chorionic gonadotropin carboxy terminal peptide is truncated.
4. The method of claim 1 , wherein said EPO is glycosylated.
5. The method of claim 1 , wherein said EPO is non-glycosylated.
6. The method of claim 1 , wherein at least one chorionic gonadotropin carbon terminal peptide is glycosylated.
7. The method of claim 1 , wherein the amino acid sequence of said mature CTP-modified EPO polypeptide is set forth in SEQ ID NO: 51.
8. The method of claim 1 , wherein the amino acid sequence of said precursor CTP-modified EPO polypeptide is set forth in SEQ ID NO: 3.
9. The method of claim 8 , wherein said precursor CTP-modified EPO polypeptide comprises a signal peptide attached to the amino terminus of said one CTP, wherein the amino acid sequence of said signal peptide is set forth in SEQ ID NO: 19.
10. The method of claim 1 , wherein said chronic infection comprises HIV, inflammatory bowel disease, or septic episodes, or any combination thereof.