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 method for increasing a subject's fertility which comprises administering to the subject a synthetic FSH comprising a β-FSH 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:16) in an amount effective to enhance the subject's fertility.
2. A method for increasing a subject's fertility which comprises administering to the subject 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:16) in an amount effective to enhance the subject's fertility, wherein the β-FSH subunit, α-FSH subunit and polypeptide segment are covalently bound.
3. A method for increasing a subject's egg production which comprises administering to the subject a synthetic FSH comprising a β-FSH 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:16) in an amount effective to enhance the subject's egg production.
4. A method for increasing a subject's egg production which comprises administering to the subject 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:16) in an amount effective to enhance the subject's egg production, wherein the β-FSH subunit, α-FSH subunit and polypeptide segment are covalently bound.
5. A method for increasing the level of inhibin-A in a subject which comprises administering to the subject a synthetic FSH comprising a β-FSH 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:16) in an amount effective to increase the subject's inhibin-A level.
6. A method for increasing the level of inhibin-A in a subject which comprises administering to the subject 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:16) in an amount effective to increase the subject's inhibin A level, wherein the β-FSH subunit, α-FSH subunit and polypeptide segment are covalently bound.
7. A method for increasing the quality of an oocyte which comprises contacting the oocyte with a synthetic FSH comprising a β-FSH 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:16) in an amount effective to increase the quality of an oocyte.
8. A method for increasing the quality of an oocyte which comprises contacting the oocyte with 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:16) in an amount effective to increase the quality of an oocyte, wherein the β-FSH subunit, α-FSH subunit and polypeptide segment are covalently bound.
9. A method for increasing the quality of an oocyte in a subject which comprises administering to the subject a synthetic FSH comprising a β-FSH 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:16) in an amount effective to increase the quality of the oocyte in the subject.
10. A method for increasing the quality of an oocyte in a subject which comprises administering to the subject 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:16) in an amount effective to increase the quality of the oocyte in the subject, wherein the β-FSH subunit, α-FSH subunit and polypeptide segment are covalently bound.
11. The method of claims 1 or 2 wherein the subject is infertile and is to undergo in vitro fertilization.
12. The method of claim 11 , wherein the subject is 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.
13. The method of claim 12 , wherein the subject is a human.
14. The method of claim 11 , wherein the synthetic FSH is administered daily.
15. The method of claim 11 , wherein the synthetic FSH is administered every other day.
16. The method of claim 11 , wherein the synthetic FSH is administered every 6 to 8 days.
17. The method of claim 11 , wherein the synthetic FSH is administered weekly.
18. The method of claim 11 , wherein the synthetic FSH is administered intravenously, subcutaneously, intramuscularly, intraperitoneally, orally or topically.