Claims for Patent: 9,901,623

Summary for Patent: 9,901,623

Title:	Rapid-acting insulin compositions
Abstract:	The invention is a pharmaceutical composition of human insulin or insulin analog that includes citrate, treprostinil and stabilizing agents, that has faster pharmacokinetic and/or pharmacodynamic action than commercial formulations of existing insulin analog products and that is stable for commercial use.
Inventor(s):	Akers; Michael Patrick (Indianapolis, IN), Christe; Michael Edward (Pendleton, IN), Hardy; Thomas Andrew (Carmel, IN), Majumdar; Ranajoy (Indianapolis, IN), Nguyen; Chi Arch (Fishers, IN), Paavola; Chad Donald (Carmel, IN), Sarin; Virender Kumar (Carmel, IN), Schulte; Nanette Elizabeth (Indianapolis, IN)
Assignee:	Eli Lilly and Company (Indianapolis, IN)
Application Number:	15/241,412
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 9,901,623
Patent Claims:	1. A pharmaceutical composition comprising: a. an insulin; b. citrate, in a concentration from about 5 to about 25 mM; c. treprostinil, in a concentration from about 0.04 to about 20 .mu.g/mL; d. zinc, in a concentration sufficient to provide at least 2 zinc ions per six molecules of insulin; e. a preservative; and f. one or more additional stabilizing agents, selected from the group consisting of a magnesium-containing compound and sodium chloride; and having a pH of about 7.0 to about 7.8 at room temperature. 2. The pharmaceutical composition of claim 1 wherein the zinc concentration is from about 0.2 to about 2 mM. 3. The pharmaceutical composition of claim 1 wherein the zinc concentration is from about 0.2 to about 1 mM. 4. The pharmaceutical composition of claim 1, wherein the zinc concentration is from about 0.6 to about 0.8 mM. 5. The pharmaceutical composition of claim 1, wherein the one or more additional stabilizing agents comprise a magnesium-containing compound. 6. The pharmaceutical composition of claim 5, wherein the magnesium-containing compound is present in a concentration resulting in a molar ratio of magnesium to citrate from about 1:2 to about 1:10. 7. The pharmaceutical composition of claim 6, wherein the molar ratio of magnesium to citrate is from about 1:3 to about 1:5. 8. The pharmaceutical composition of claim 6 wherein the magnesium-containing compound is magnesium chloride. 9. The pharmaceutical composition of claim 1, wherein the insulin concentration is from about 100 to about 300 U/mL. 10. The pharmaceutical composition of claim 1, wherein the insulin concentration is either about 100 U/mL or about 200 U/mL. 11. The pharmaceutical composition of claim 1, wherein the insulin is insulin lispro. 12. The pharmaceutical composition of claim 1, wherein the concentration of citrate is from about 10 to about 25 mM. 13. The pharmaceutical composition of claim 1, wherein the concentration of treprostinil is from about 0.04 to about 10 .mu.g/mL. 14. The pharmaceutical composition of claim 1, wherein the concentration of treprostinil is from about 0.5 to about 2 .mu.g/mL. 15. The pharmaceutical composition of claim 1, wherein the preservative is m-cresol. 16. The pharmaceutical composition of claim 15, wherein the concentration of m-cresol is from about 2.5 to about 3.8 mg/mL. 17. The pharmaceutical composition claim 1, wherein the one or more additional stabilizing agents comprise sodium chloride. 18. The pharmaceutical composition of claim 17 wherein the sodium chloride is present in a concentration from about 1 to about 50 mM. 19. The pharmaceutical composition of claim 18, wherein the total concentration of chloride is from about 10 to about 50 mM. 20. The pharmaceutical composition of claim 1, further comprising a tonicity agent. 21. The pharmaceutical composition of claim 20, wherein the tonicity agent is glycerol. 22. The pharmaceutical composition of claim 21, wherein the concentration of glycerol is from about 1 to about 15 mg/mL. 23. A pharmaceutical composition comprising: a. insulin lispro, in a concentration from about 100 to about 200 U/mL; b. citrate, in a concentration from about 5 to about 25 mM; c. treprostinil, in a concentration from about 0.5 to about 2 .mu.g/mL; and d. zinc, in a concentration from about 0.2 mM to about 2 mM. 24. The pharmaceutical composition of claim 23, wherein the concentration of citrate is from about 15 to about 25 mM. 25. The pharmaceutical composition of claim 24, wherein the concentration of zinc is from about 0.6 to about 0.9 mM. 26. The pharmaceutical composition of claim 25, further comprising a magnesium-containing compound, in a concentration resulting in a molar ratio of magnesium to citrate from about 1:3 to about 1:5. 27. The pharmaceutical composition of claim 26 having a pH of about 7.4. 28. The pharmaceutical composition of claim 23 wherein: a. insulin lispro is in a concentration of about 100 U/mL; b. citrate is in a concentration of about 15 mM; c. treprostinil is in a concentration of about 1 .mu.g/mL; and d. zinc is in a concentration of about 0.6 mM; and further comprising: e. magnesium chloride in a concentration of about 5 mM; f. m-cresol, in a concentration of about 3.15 mg/mL; and g. glycerol, in a concentration of about 12 mg/mL; and having a pH of about 7.4. 29. The pharmaceutical composition of claim 23 wherein: a. insulin lispro is in a concentration of about 200 U/mL; b. citrate is in a concentration of about 15 mM; c. treprostinil is in a concentration of about 1 .mu.g/mL; and d. zinc is in a concentration of about 0.8 mM; and further comprising: e. magnesium chloride in a concentration of about 5 mM; f. m-cresol, in a concentration of about 3.15 mg/mL; and g. glycerol, in a concentration of about 12 mg/mL; and having a pH of about 7.4. 30. A method of treating diabetes comprising administering to a human in need thereof an effective dose of the pharmaceutical composition of claim 23. 31. A pharmaceutical composition comprising: a. an insulin; b. citrate, in a concentration from about 5 to about 25 mM; c. treprostinil, in a concentration from about 0.04 to about 20 .mu.g/mL; d. a preservative; and e. a stabilizing agent comprising zinc, in a concentration sufficient to provide at least 2 zinc ions per six molecules of insulin; and having a pH of about 7.0 to about 7.8 at room temperature.

Details for Patent 9,901,623

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Eli Lilly And Company	HUMALOG	insulin lispro	Injection	020563	06/14/1996		2040-03-31
Eli Lilly And Company	HUMALOG	insulin lispro	Injection	020563	08/06/1998		2040-03-31
Eli Lilly And Company	HUMALOG	insulin lispro	Injection	020563	09/06/2007		2040-03-31
Eli Lilly And Company	HUMALOG	insulin lispro	Injection	020563	06/06/2017		2040-03-31
Eli Lilly And Company	HUMALOG	insulin lispro	Injection	020563	11/15/2019		2040-03-31
Sanofi-aventis U.s. Llc	ADMELOG	insulin lispro	Injection	209196	12/11/2017		2040-03-31