Claims for Patent: 10,544,200

Summary for Patent: 10,544,200

Title:	Glycoprotein hormone long-acting superagonists
Abstract:	This invention provides long-acting, superactive analogs of glycoprotein hormones demonstrating enhanced bioactivity both in vitro and in vivo as compared to wild type counterparts. The analogs are particularly useful for treating subjects showing low receptor expression or poor receptor responsiveness, and for the treatment of any condition associated with glycoprotein hormone activity.
Inventor(s):	Szkudlinski; Mariusz (Rockville, MD), Weintraub; Bruce D. (Rockville, MD)
Assignee:	TROPHOGEN, INC. (Rockville, MD)
Application Number:	15/034,670
Patent Claims:	1. A modified glycoprotein hormone comprising an amino acid sequence having at least one basic amino acid substitution in the alpha-L1 loop of the alpha subunit and one or more inserts between the amino acids at positions 3 and 8 of the alpha subunit, wherein the inserts introduce NVTINV (SEQ ID NO: 1) glycosylation sites into the alpha subunit compared with a wild type glycoprotein hormone. 2. The modified glycoprotein hormone of claim 1, wherein the inserts are between D3 and Q5 of the wild type glycoprotein hormone alpha subunit, and the wild type glycoprotein has the sequence of SEQ ID NO: 6. 3. The modified glycoprotein hormone of claim 1, comprising at least one basic amino acid substitution at amino acid positions 13, 14, 16, or 20 of a wild type glycoprotein hormone alpha subunit. 4. The modified glycoprotein hormone of claim 1, comprising at least two basic amino acid substitutions at amino acid positions 13, 14, 16, or 20 of a wild type glycoprotein hormone alpha subunit. 5. The modified glycoprotein hormone of claim 1, comprising at least three basic amino acid substitutions at amino acid positions 13, 14, 16, or 20 of a wild type glycoprotein hormone alpha subunit. 6. The modified glycoprotein hormone of claim 1, comprising at least four basic amino acid substitutions at amino acid positions 13, 14, 16, and 20 of a wild type glycoprotein hormone alpha subunit. 7. The modified glycoprotein hormone of claim 1, comprising at least one basic amino acid substitution at amino acid positions 13Q, 14E, 16P, or 20Q of a wild type glycoprotein hormone alpha subunit, wherein the wild type glycoprotein hormone alpha subunit has the amino acid sequence of SEQ ID NO: 6. 8. The modified glycoprotein hormone of claim 1, comprising at least two basic amino acid substitutions at amino acid positions 13Q, 14E, 16P, or 20Q of a wild type glycoprotein hormone alpha subunit, wherein the wild type glycoprotein hormone alpha subunit has the amino acid sequence of SEQ ID NO: 6. 9. The modified glycoprotein hormone of claim 1, comprising at least three basic amino acid substitutions at amino acid positions 13Q, 14E, 16P, or 20Q of a wild type glycoprotein hormone alpha subunit, wherein the wild type glycoprotein hormone alpha subunit has the amino acid sequence of SEQ ID NO: 6. 10. The modified glycoprotein hormone of claim 1, comprising at least four basic amino acid substitutions at amino acid positions 13Q, 14E, 16P, or 20Q of a wild type glycoprotein hormone alpha subunit, wherein the wild type glycoprotein hormone alpha subunit has the amino acid sequence of SEQ ID NO: 6. 11. The modified glycoprotein hormone of claim 1, further comprising the beta subunit of luteinizing hormone (LH). 12. The modified glycoprotein hormone of claim 1, further comprising the beta subunit of chorionic gonadotropin (CG). 13. The modified glycoprotein hormone of claim 1, further comprising the beta subunit of follicle-stimulating hormone (FSH). 14. The modified glycoprotein hormone of claim 1, further comprising the beta subunit of thyroid-stimulating hormone (TSH). 15. The modified glycoprotein hormone of claim 1, wherein the basic amino acid is arginine. 16. The modified glycoprotein hormone of claim 1, wherein the alpha subunit is derived from a mammalian alpha subunit. 17. The modified glycoprotein hormone of claim 16, wherein the alpha subunit is derived from a human alpha subunit. 18. A method for stimulating a glycoprotein hormone receptor in an animal, comprising administering the modified glycoprotein hormone of claim 1 to the animal. 19. The method of claim 18, wherein the animal is a mammal. 20. The method of claim 19, wherein the mammal is a human.

Details for Patent 10,544,200

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Ferring Pharmaceuticals Inc.	NOVAREL	chorionic gonadotropin	For Injection	017016	January 15, 1974	10,544,200	2033-11-05
Ferring Pharmaceuticals Inc.	NOVAREL	chorionic gonadotropin	For Injection	017016	December 27, 1984	10,544,200	2033-11-05
Ferring Pharmaceuticals Inc.	NOVAREL	chorionic gonadotropin	For Injection	017016	February 15, 1985	10,544,200	2033-11-05
Ferring Pharmaceuticals Inc.	NOVAREL	chorionic gonadotropin	For Injection	017016	February 16, 1990	10,544,200	2033-11-05