Claims for Patent: 5,929,028

Summary for Patent: 5,929,028

Title:	Liquid gonadotropin containing formulations
Abstract:	The invention concerns a liquid gonadotropin-containing formulation characterised in that the formulation comprises a gonadotropin and stabilising amounts of a polycarboxylic acid or a salt thereof and of a thioether compound. The particular proteins (e.g. LH, TSH, FSH, or HCG) are in admixture with the particular stabilizers in an aqueous solution. The preparations contain a sufficient amount of the polycarboxylic acid or a salt thereof, preferably sodium citrate, and a sufficient amount of the thioether compound, preferably methionine, to stabilize the protein. The preparations preferably also include a nonreducing disaccharide like sucrose, and a non-ionic surfactant.
Inventor(s):	Skrabanja; Arnold Titus Philip (An Nijmegen, NL), van den Oetelaar; Petrus Johannes Maria (Et Heesch, NL)
Assignee:	Akzo Nobel, N.V. (Arnhem, NL)
Application Number:	09/006,812
Patent Claims:	1. A stabilized liquid gonadotropin-containing formulation contained in a closed cartridge suited for storage, said formulation comprising a gonadotropin and stabilizing amounts of a polycarboxylic acid or salt thereof and of a thioether compound. 2. The liquid gonadotropin-containing formulation of claim 1, wherein the thioether compound is the amino acid methionine. 3. The liquid gonadotropin-containing formulation of claim 1 or 2, wherein the polycarboxylic acid is citric acid or the sodium salt thereof. 4. The liquid gonadotropin-containing formulation of claim 3, wherein the concentration of sodium citrate is 25-100 mM and the concentration of methionine is 1-10 mM. 5. The liquid gonadotropin-containing formulation of claim 1, further comprising a non-reducing sugar. 6. The liquid gonadotropin-containing formulation of claim 5, wherein the non-reducing sugar is sucrose in a concentration of 25-300 mM. 7. The liquid gonadotropin-containing formulation of claim 1, further comprising a non-ionic surfactant. 8. The liquid gonadotropin-containing formulation of claim 1, wherein the pH of the formulation is between 6.5 and 7.2. 9. The liquid gonadotropin-containing formulation of claim 1, wherein the gonadotropin is selected from luteinizing hormone (LH), human chorionic gonadotropin (hCG), follicle stimulating hormone (FSH), or derivatives thereof, and mixtures thereof. 10. The liquid gonadotropin-containing formulation of claim 9, wherein the gonadotropin is recombinant human FSH (recFSH) or recombinant FSH-CTP. 11. A method for preparing a stabilized liquid gonadotropin formulation comprising: admixing, in an aqueous solution, at least one gonadotropin with a stabilizing amount of a polycarboxylic acid or a salt thereof, and a stabilizing amount of a thioether compound; optionally dissolving an amount of a nonreducing disaccharide in the resulting admixture and optionally dissolving a nonionic surfactant in said admixture; adjusting the pH of the resulting solution to a value between 6.5 and 7.2; and sealing the pH adjusted solution in a cartridge suited for storage. 12. A method for preparing a stabilized liquid gonadotropin formulation comprising: admixing, in an aqueous solution, at least one gonadotropin with an amount of sodium citrate to a concentration of 25-100 mM, and an amount of methionine to a concentration of 1-10 mM; optionally dissolving an amount of sucrose in the resulting admixture to a concentration of 25-300 mM and optionally dissolving a surfactant in said admixture; adjusting the pH of the resulting solution to a value between 6.5 and 7.2; and sealing the pH adjusted solution in a cartridge suited for storage. 13. A method for treating infertility of a patient, comprising administering to the patient an effective amount of a formulation according to claim 1. 14. The liquid gonadotropin-containing formulation of claim 8, wherein the pH is 7.

Details for Patent 5,929,028

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Ferring Pharmaceuticals Inc.	NOVAREL	chorionic gonadotropin	For Injection	017016	January 15, 1974		2017-01-15
Ferring Pharmaceuticals Inc.	NOVAREL	chorionic gonadotropin	For Injection	017016	December 27, 1984		2017-01-15
Ferring Pharmaceuticals Inc.	NOVAREL	chorionic gonadotropin	For Injection	017016	February 15, 1985		2017-01-15
Ferring Pharmaceuticals Inc.	NOVAREL	chorionic gonadotropin	For Injection	017016	February 16, 1990		2017-01-15
Bel-mar Laboratories, Inc.	CHORIONIC GONADOTROPIN	chorionic gonadotropin	Injection	017054	March 26, 1974		2017-01-15
Fresenius Kabi Usa, Llc	CHORIONIC GONADOTROPIN	chorionic gonadotropin	For Injection	017067	March 05, 1973		2017-01-15
Organon Usa Llc, A Subsidiary Of Organon & Co.	FOLLISTIM AQ CARTRIDGE	follitropin beta	Injection	021211	March 23, 2004		2017-01-15

International Patent Family for US Patent 5,929,028

Country	Patent Number	Estimated Expiration
South Africa	9883
Taiwan	518235
Turkey	199800062
Saudi Arabia	98181124
Russian Federation	2203086
Portugal	853945
Poland	324279