Claims for Patent: 10,512,689

Summary for Patent: 10,512,689

Title:	Compositions comprising a combination of nivolumab and ipilimumab
Abstract:	This provides pharmaceutical compositions that comprise a combination of an anti-cancer agent which is an first antibody and a second antibody. In some embodiments, the first antibody is an anti-Programmed Death-1 (PD-1) antibody. In certain embodiments, the composition is a fixed dose formulation. In certain embodiments, the composition is administered as a flat-dose. The disclosure also provides a kit for treating a subject afflicted with a disease, the kit comprising a dosage of any composition disclosed herein and instructions for using the composition in any of the disclosed methods for treating a disease.
Inventor(s):	Sadineni; Vikram (Belle Mead, NJ), Quan; Yong (Dublin, CA), Kaserer; Wallace (Lawrence Township, NJ)
Assignee:	Bristol-Myers Squibb Company (Princeton, NJ)
Application Number:	15/365,717
Patent Claims:	1. A pharmaceutical composition comprising about 1.54 mg/ml nivolumab, about 4.62 mg/ml ipilimumab, about 18.46 mM Tris hydrochloride (HCl), about 1.54 mM sodium citrate dihydrate, about 1.15% mannitol, about 96.15 mM NaCl, about 93.85 .mu.M pentetic acid, and about 0.012% PS80. 2. The composition of claim 1, wherein the composition: (i) is stable at about 5.degree. C. for at least about 1 week; (ii) is stable at about 40.degree. C. for at least about 1 week; or (iii) is stable at about 25.degree. C. for at least about 1 week. 3. A kit comprising the composition of claim 1 and instructions to administer the composition to a subject in need thereof. 4. The pharmaceutical composition of claim 1, wherein the pH of the composition is about 6.0, about 6.2, about 6.5, about 6.6, or about 7.0. 5. The pharmaceutical composition of claim 1, wherein the pH is about 6.2. 6. The pharmaceutical composition of claim 1, wherein the pH is about 6.2. 7. The pharmaceutical composition of claim 1, wherein the pH is 6.1. 8. The pharmaceutical composition of claim 1, comprising 1.54 mg/mL nivolumab and 4.62 mg/ml ipilimumab. 9. The pharmaceutical composition of claim 1, comprising about 30 mg nivolumab and about 90 mg ipilimumab. 10. The pharmaceutical composition of claim 1, comprising about 40 mg nivolumab and about 120 mg ipilimumab. 11. The pharmaceutical composition of claim 1, comprising 18.46 mM Tris hydrochloride (HCl). 12. The pharmaceutical composition of claim 1, comprising 1.54 mM sodium citrate dihydrate. 13. The pharmaceutical composition of claim 1, comprising 1.15% mannitol. 14. The pharmaceutical composition of claim 1, comprising 96.15 mM NaCl. 15. The pharmaceutical composition of claim 1, comprising 93.85 .mu.M pentetic acid. 16. The pharmaceutical composition of claim 1, comprising 0.012% PS80. 17. The pharmaceutical composition of claim 1, comprising 18.46 mM Tris hydrochloride (HCl) and 1.54 mM sodium citrate dihydrate. 18. The pharmaceutical composition of claim 1, comprising 1.15% mannitol, 96.15 mM NaCl, and 93.85 .mu.M pentetic acid. 19. The pharmaceutical composition of claim 1, comprising 18.46 mM Tris hydrochloride (HCl), 1.54 mM sodium citrate dihydrate, 1.15% mannitol, 96.15 mM NaCl, and 93.85 .mu.M pentetic acid. 20. The pharmaceutical composition of claim 1, comprising 18.46 mM Tris hydrochloride (HCl), 1.54 mM sodium citrate dihydrate, 1.15% mannitol, 96.15 mM NaCl, 93.85 .mu.M pentetic acid, and 0.012% PS80. 21. The pharmaceutical composition of claim 20, wherein the pH is 6.2 at 25.degree. C. 22. The pharmaceutical composition of claim 1, wherein the pH is between about 6.0 and about 7.0. 23. The pharmaceutical composition of claim 1, wherein the composition: (i) is stable at 5.degree. C. for at least 1 week; (ii) is stable at 40.degree. C. for at least 1 week; or (iii) is stable at 25.degree. C. for at least 1 week. 24. A pharmaceutical composition comprising 1.54 mg/ml nivolumab, 4.62 mg/ml ipilimumab, 18.46 mM Tris hydrochloride (HCl), 1.54 mM sodium citrate dihydrate, 1.15% mannitol, 96.15 mM NaCl, 93.85 .mu.M pentetic acid, and 0.012% PS80. 25. The pharmaceutical composition of claim 24, wherein the pH is between about 6.0 and about 7.0. 26. The pharmaceutical composition of claim 24, wherein the pH is 6.2 at 25.degree. C. 27. The pharmaceutical composition of claim 24, wherein the composition: (i) is stable at 5.degree. C. for at least 1 week; (ii) is stable at 40.degree. C. for at least 1 week; or (iii) is stable at 25.degree. C. for at least 1 week. 28. The pharmaceutical composition of claim 24, comprising about 30 mg nivolumab and about 90 mg ipilimumab. 29. The pharmaceutical composition of claim 24, comprising about 40 mg nivolumab and about 120 mg ipilimumab.

Details for Patent 10,512,689

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Bristol-myers Squibb Company	YERVOY	ipilimumab	Injection	125377	March 25, 2011		2036-11-30
Bristol-myers Squibb Company	OPDIVO	nivolumab	Injection	125554	December 22, 2014		2036-11-30
Bristol-myers Squibb Company	OPDIVO	nivolumab	Injection	125554	October 04, 2017		2036-11-30
Bristol-myers Squibb Company	OPDIVO	nivolumab	Injection	125554	August 27, 2021		2036-11-30

International Patent Family for US Patent 10,512,689

Country	Patent Number	Estimated Expiration
World Intellectual Property Organization (WIPO)	2016168716
United States of America	2024091354
United States of America	2020197518
United States of America	2017143827
United States of America	2016304607
United States of America	11612654