Long-acting veterinary 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 polynucleotide consisting of a nucleic acid encoding a polypeptide, said polypeptide consisting of a non-human growth hormone, one chorionic gonadotrophin carboxy terminal peptide (CTP) attached to the amino terminus of said non-human growth hormone, and two chorionic gonadotrophin CTPs attached to the carboxy terminus of said non-human growth hormone, wherein said polypeptide optionally comprises a signal peptide attached to the amino terminus of said one CTP, and wherein at least one CTP is optionally attached to said non-human growth hormone via a linker.
2. The polynucleotide of claim 1 , wherein at least one CTP is glycosylated.
3. The polynucleotide of claim 1 , wherein at least one CTP is truncated.
4. The polynucleotide of claim 1 , wherein at least one CTP is attached to said non-human growth hormone via a linker.
5. The polynucleotide of claim 4 , wherein said linker is a peptide bond.
6. The polynucleotide of claim 1 , wherein the sequence of at least one CTP consists of an amino acid sequence selected from the group consisting of: SEQ ID NO: 17 and SEQ ID NO: 18.
7. The polynucleotide of claim 1 , wherein said polypeptide further comprises a signal peptide attached to the amino terminus of said one CTP.
8. An expression vector comprising the polynucleotide of claim 1 .
9. An isolated cell comprising the expression vector of claim 8 .
10. A composition comprising the expression vector of claim 8 and a pharmaceutically acceptable carrier.
11. A method of producing a non-human growth hormone with an improved biological half life in an isolated cell, comprising the step of transfecting said cell with an expression vector comprising a polynucleotide consisting of a nucleic acid encoding a polypeptide, said polypeptide consisting of a non-human growth hormone, one chorionic gonadotrophin carboxy terminal peptide (CTP) attached to the amino terminus of said non-human growth hormone, and two chorionic gonadotrophin CTPs attached to the carboxy terminus of said non-human growth hormone, wherein said polypeptide optionally comprises a signal peptide attached to the amino terminus of said one CTP, and wherein at least one CTP is optionally attached to said non-human growth hormone via a linker, thereby producing a non-human growth hormone with an improved biological half life in an isolated cell.
12. The method of claim 11 , wherein the sequence of at least one CTP consists of an amino acid sequence selected from the group consisting of: SEQ ID NO: 17 and SEQ ID NO: 18.
13. The method of claim 11 , wherein said polypeptide further comprises a signal peptide attached to the amino terminus of said one CTP.
14. The method of claim 11 , wherein at least one CTP is glycosylated.
15. The method of claim 11 , wherein at least one CTP is truncated.
16. The method of claim 11 , wherein at least one CTP is attached to said non-human growth hormone via a linker.
17. The method of claim 16 , wherein said linker is a peptide bond.