Glycopegylated Follicle Stimulating Hormone

• US 20080015142A1
• Filed: 12/03/2004
• Published: 01/17/2008
• Est. Priority Date: 12/03/2003
• Status: Abandoned Application

• Current Assignee: Novo Nordisk A/S
• Original Assignee: Novo Nordisk A/S
• Inventors: DeFrees, Shawn, Bayer, Robert J., Bowe, Caryn
• Application Number:
  US10/581,538
• Publication Number:
  US 20080015142A1
• Time in Patent Office: Days
• US Class Current: 514/8
• CPC Class Codes: A61K 38/17 from animals; from humans enzyme inhibitors A61K38/005
• CPC Class Codes: A61P 15/08 for gonadal disorders or for enhancing fertility, e.g. inducers of ovulation or of spermatogenesis
• CPC Class Codes: C07K 14/59 Follicle-stimulating hormone [FSH]; Chorionic gonadotropins, e.g.hCG [human chorionic gonadotropin]; Luteinising hormone [LH]; Thyroid-stimulating hormone [TSH]
• CPC Class Codes: Y02A 50/30 Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Abstract

The present invention provides conjugates between follicle stimulating hormone and PEG moieties. The conjugates are linked via an intact glycosyl linking group that is interposed between and covalently attached to the peptide and the modifying group. The conjugates are formed from both glycosylated and unglycosylated peptides by the action of a glycosyltransferase. The glycosyltransferase ligates a modified sugar moiety onto either an amino acid or glycosyl residue on the peptide. Also provided are pharmaceutical formulations including the conjugates. Methods for preparing the conjugates are also within the scope of the invention.

Claims

1. A follicle stimulating hormone peptide comprising the moiety:

2. The peptide according to claim 1, wherein L—

R¹ has the formula;

3. The peptide according to claim 1, wherein R¹ has a structure that is a member selected from:

4. The peptide according to claim 1, wherein R¹ has a structure that is a member selected from:

5. The peptide according to claim 1, wherein R¹ has a structure that is a member selected from:

6. The peptide according to claim 1, wherein R¹ has a structure that is a member selected from:

7. The FSH peptide according to claim 1, wherein said moiety has the formula:

8. The peptide according to claim 1, wherein said peptide has an amino acid sequence selected from SEQ. ID. NO:

1 and SEQ ID NO;

2.

9. The FSH peptide according to claim 1, wherein said moiety has the formula:

10. The peptide according to claim 9, wherein said amino acid residue is an asparagine residue.

11. The peptide according to claim 10, wherein said said amino acid residue is an asparagine residue which is a member selected from N7 of SEQ ID NO:

2, N24 of SEQ ID NO;

2, N52 of SEQ ID NO;

1, and N78 of SEQ ID NO;

1, and combinations thereof.

12. The peptide according to claim 1, wherein said peptide is a bioactive follicle stimulating hormone peptide.

21. A method of stimulating ovarian follicles in a mammal, said method comprising administering to said mammal a peptide according to claim 1.

22. A method of treating a condition in a subject in need thereof, said condition characterized by reproductive infertility said method comprising the step of administering to the subject an amount of a peptide according to claim 1, effective to ameliorate said condition in said subject.

23. A pharmaceutical formulation comprising the follicle stimulating hormone peptide according to claim 1, and a pharmaceutically acceptable carrier.

13. A method of making a FSH peptide conjugate comprising the moiety:

14. The method according to claim 13, wherein L—

R¹ has the formula;

15. The method according to claim 13, wherein R¹ has a structure that is a member selected from:

16. The method according to claim 13, wherein R¹ has a structure that is a member selected from:

17. The method according to claim 13, wherein R¹ has a structure that is a member selected from:

18. The method according to claim 13, wherein R¹ has a structure that is a member selected from:

19. The method of claim 13, further comprising, prior to step (a):

(b) expressing said substrate follicle stimulating hormone peptide in a suitable host.

20. The method of claim 13, wherein said host is selected from an insect cell and a mammalian cell.