FSH mutants with increased glycosylation and longer half-lives are described. The use of FSH mutants for inducing folliculogenesis in human patients is also described.
1. An isolated mutant follicle stimulating hormone (FSH) comprising a β-subunit and an α-subunit, wherein the β-subunit comprises SEQ ID NO: 3 and the α-subunit comprises SEQ ID NO: 4 or 5.
2. The mutant FSH of claim 1 , wherein from 0 to 6 asparagine residues are glycosylated.
3. The mutant FSH of claim 1 , wherein the α-subunit comprises the sequence of SEQ ID NO: 5 and wherein N5 of this sequence is glycosylated.
4. The mutant FSH of claim 1 , wherein the α-subunit comprises SEQ ID NO: 4.
5. A composition comprising a pharmaceutically acceptable carrier or excipient and a mutant (FSH) comprising a β-subunit and an α-subunit, wherein the β-subunit comprises SEQ ID NO: 3 and the α-subunit comprises SEQ ID NO: 4 or 5.
6. The composition of claim 5 , wherein from 0 to 6 asparagine residues are glycosylated.
7. The composition of claim 5 , wherein the α-subunit comprises the sequence of SEQ ID NO: 5 and wherein N5 of this sequence is glycosylated.
8. The composition of claim 5 , wherein the α-subunit comprises SEQ ID NO: 4.
9. A method of stimulating folliculogenesis in a mammal comprising administering to a mammal in need thereof a composition of claim 5 in an amount sufficient to stimulate folliculogenesis.
10. A method of inducing ovarian hyperstimulation in a mammal comprising administering to a mammal in need thereof a composition of claim 5 in an amount sufficient to induce ovarian hyperstimulation.