Long-acting follicle stimulating hormone analogues and uses thereof
View Patent ↗This invention provides FSH analogues having increased serum half-life relative to FSH. This invention also provides related compositions and methods for increasing fertility, egg production and spermatogenesis in a subject.
1. A synthetic FSH comprising a β-FSR subunit covalently bound to a polypeptide segment comprising the amino acid sequence ser-gly-ser-asn-ala-thr-gly-ser-gly-ser-asn-ala-thr-ser-gly-ser (SEQ ID NO:9).
2. A synthetic FSH comprising a β-FSH subunit, an α-FSH subunit and a polypeptide segment comprising the amino acid sequence ser-gly-ser-asn-ala-thr-gly-ser-gly-ser-asn-ala-thr-ser-gly-ser (SEQ ID NO:9), wherein the β-FSH subunit, α-FSH subunit and polypeptide segment are covalently bound.
3. A method for producing a synthetic FSH, which method comprises:
(a) co-expressing (i) a nucleic acid which encodes an α-FSH subunit, and (ii) a nucleic acid which encodes a polypeptide comprising a β-FSH subunit and a polypeptide segment comprising the amino acid sequence ser-gly-ser-asn-ala-thr-gly-ser-gly-ser-asn-ala-thr-ser-gly-ser (SEQ ID NO:9), under conditions permitting such co-expression; and
(b) recovering the synthetic FSH so produced.
4. The synthetic FSH of claim 1 wherein the β-FSH subunit is from an animal selected from the group consisting of a primate, a horse, a sheep, a bird, a bovine, a pig, a dog, a cat and a rodent.
5. The synthetic FSH of claim 4 , wherein the β-FSH subunit is a human β-FSH subunit.
6. The synthetic FSH of claim 1 , wherein the β-FSH subunit and the polypeptide segment exist within a single polypeptide chain.
7. The synthetic FSH of claim 1 , wherein the polypeptide segment contains one copy of the amino acid sequence set forth in SEQ ID NO:9.
8. The synthetic FSH of claim 1 , wherein the polypeptide segment comprises a plurality of the amino acid sequence set forth in SEQ ID NO:9.
9. The synthetic FSH of claim 1 , wherein the β-FSH subunit is bound at its C-terminal end to the N-terminal end of the peptide segment.
10. The synthetic FSH of claim 1 , wherein the β-FHS subunit is bound at its N-terminal end to the C-terminal end of the polypeptide segment.
11. The synthetic FSH of claim 2 , wherein the α-FSH and β-FSH subunits are from an animal selected from the group consisting of a primate, a horse, a sheep, a bird, a bovine, a pig, a dog, a cat and a rodent.
12. The synthetic FSH of claim 11 , wherein the α-FSR and β-FHS subunits are human α-FSH and β-FSH subunits.
13. The synthetic FSH of claim 2 , wherein the β-FSH subunit, α-FSH subunit and polypeptide segment exist within a single polypeptide chain.
14. The synthetic FSH of claim 2 , wherein the polypeptide segment contains one copy of the amino acid sequence set forth in SEQ ID NO:9.
15. The synthetic FSH of claim 2 , wherein the polypeptide segment comprises a plurality of the amino acid sequence set forth in SEQ ID NO:9.
16. The synthetic FSH of claim 2 , wherein the β-FSH subunit is bound at its C-terminal end to the N-terminal end of the α-FSH subunit.
17. The synthetic FSH of claim 2 , wherein the α-FSH subunit is bound at its C-terminal end to the N-terminal end of the polypeptide segment.
18. The synthetic FSH of claim 2 , wherein the β-FSH subunit is bound at its N-terminal end to the C-terminal end of the polypeptide segment.
19. The synthetic FSH of claim 2 , wherein the β-FHS subunit is bound at its C-terminal end to the N-terminal end of the polypeptide segment, which polypeptide segment is bound at its C-terminal end to the N-terminal end of the α-FSH subunit.
20. The synthetic FSH of claim 2 , wherein the α-FSH subunit is bound at its C-terminal end to the N-terminal end of the β-FSH subunit.
21. The synthetic FSH of claim 2 , wherein the β-FSH subunit is bound at its C-terminal end to the N-terminal end of the polypeptide segment.
22. The synthetic FSH of claim 2 , wherein the α-FSR subunit is bound at its N-terminal end to the C-terminal end of the polypeptide segment.
23. The synthetic FSH of claim 2 , wherein the α-FSH subunit is bound at its C-terminal end to the N-terminal end of the polypeptide segment, which polypeptide segment is bound at its C-terminal end to the N-terminal end of the β-FHS subunit.
24. The method of claim 3 , wherein the α-FSH and β-FSH subunits are from an animal selected from the group consisting of a primate, a horse, a sheep, a bird, a bovine, a pig, a dog, a cat and a rodent.
25. The method of claim 24 , wherein the α-FSH and β-FSH subunits are human α-FSH and β-FSH subunits.
26. The method of claim 3 , wherein the polypeptide segment contains one copy of the amino acid sequence set forth in SEQ ID NO:9.
27. The method of claim 3 , wherein the polypeptide segment comprises a plurality of the amino acid sequence set forth in SEQ ID NO:9.
28. The method of claim 3 , wherein the β-FSH subunit is bound at its C-terminal end to the N-terminal end of the polypeptide segment.
29. The method of claim 3 , wherein the β-FHS subunit is bound at its N-terminal end to the C-terminal end of the polypeptide segment.