Claims for Patent: 5,496,801

Summary for Patent: 5,496,801

Title:	Parathyroid hormone formulation
Abstract:	Described herein are preparations containing parathyroid hormone that has been stablized with an excipient and buffering agent. Preferred preparations incorporate human PTH(1-84), mannitol as excipient and citrate as buffering agent, and are incorporated in vials as a freeze-dried powder for reconstitution to treat osteoporosis.
Inventor(s):	Holthuis; Josephus J. M. (AJ Leiden, NL), Mekking; Albert (CR Woerden, NL), Voetman; Alwinus A. (DT Zwanenburg, NL)
Assignee:	Allelix BioPharmaceuticals Inc. (Ontario, CA)
Application Number:	08/172,206
Patent Claims:	1. A parathyroid hormone preparation, comprising: a medically useful amount of parathyroid hormone (1-84); a polyol excipient that co-lyophilizes with said hormone to yield an amorphous cake; a non-volatile buffering agent in an amount sufficient to adjust the pH of the preparation to within a physiologically acceptable pH range; and water. 2. A parathyroid hormone preparation according to claim 1, wherein said excipient is mannitol. 3. A parathyroid hormone formulation according to claim 1, wherein the buffering agent is a citrate source. 4. A parathyroid hormone formulation according to claim 3, wherein said excipient is mannitol. 5. A parathyroid hormone preparation according to claim 1, in the form of a freeze-dried powder containing not more than 2% water by weight. 6. A parathyroid hormone preparation according to claim 5, wherein the hormone is human PTH(1-84). 7. A parathyroid hormone preparation according to claim 6, wherein said excipient is mannitol. 8. A parathyroid hormone preparation according to claim 7, wherein the buffering agent is a citrate source. 9. A parathyroid hormone preparation according to claim 8, wherein said excipient is mannitol. 10. A parathyroid hormone preparation comprising parathyroid hormone (1-84) in a concentration within the range from 25 to 250 .mu.g/mL; mannitol in a concentration in the range from 3 to 7% (w/v); citrate buffer in an amount sufficient to adjust the pH of the preparation to within the range from pH 3.5 to pH 6.5; and water. 11. A parathyroid hormone preparation according to claim 10, wherein the parathyroid hormone is human PTH(1-84). 12. A parathyroid hormone preparation according to claim 11, in the form of a freeze-dried powder containing not more than 2% water by weight. 13. A parathyroid hormone preparation according to claim 12, wherein mannitol is present in a concentration within the range from 4 to 6%. 14. A parathyroid hormone preparation according to claim 13, wherein the citrate buffer is present in an amount sufficient to adjust the pH of the preparation to pH 6.+-.0.4. 15. A vial containing a parathyroid hormone preparation according to claim 1. 16. A vial containing a parathyroid hormone preparation according to claim 5. 17. A vial containing a parathyroid hormone preparation according to claim 9. 18. A vial containing a parathyroid hormone preparation according to claim 12. 19. A kit useful to formulate an injectable PTH solution, comprising at least one first vial containing a parathyroid hormone preparation as defined in claim 5, at least one second vial containing sterile water for reconstituting said preparation, and a sheet instructing preparation of a formulation therefrom. 20. The kit according to claim 19, further comprising a device for injection of the reconstituted PTH solution. 21. A parathyroid hormone preparation as claimed in claim 1, consisting of: a medically useful amount of parathyroid hormone (1-84); an excipient that co-lyophilizes with said hormone to yield an amorphous cake; a non-volatile buffering agent in an amount sufficient to adjust the pH of the preparation to within a physiologically acceptable pH range; and water. 22. A parathyroid hormone preparation as claimed in claim 1, consisting of: parathyroid hormone (1-84) in a concentration within the range from 25 to 250 .mu.g/mL; mannitol in a concentration in the range from 3 to 7% (w/v); citrate buffer in an amount sufficient to adjust the pH of the preparation to within the range from pH 3.5 to pH 6.5; and water. 23. A parathyroid hormone preparation as claimed in claim 1, wherein the polyol excipient and the non-volatile buffering agent are the only substances added to render the composition stable during storage. 24. A parathyroid hormone preparation as claimed in claim 10, wherein D-mannitol and citrate buffer are the only substances added to render the composition stable during storage.

Details for Patent 5,496,801

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Merck Sharp & Dohme Llc	ZOSTAVAX	zoster vaccine live	For Injection	125123	May 25, 2006	5,496,801	2039-03-29
Takeda Pharmaceuticals U.s.a., Inc.	NATPARA	parathyroid hormone	For Injection	125511	January 23, 2015	5,496,801	2039-03-29

International Patent Family for US Patent 5,496,801

Country	Patent Number	Estimated Expiration
Australia	1269895
Australia	681737
Austria	E374621
Brazil	9408398
Canada	2179207