Claims for Patent: 9,226,961

Summary for Patent: 9,226,961

Title:	Antibody formulation
Abstract:	The invention provides a stable aqueous pharmaceutical formulation comprising a therapeutically effective amount of an antibody, optionally, not subjected to prior lyophilization, a buffer maintaining the pH in the range from about 4.0 to about 6.0, and an optional surfactant, methods for making such a formulation, and methods of using such a formulation.
Inventor(s):	Gokarn; Yatin R. (Thane, IN), Kamerzell; Timothy J. (Overland Park, KS), Li; Megan (San Francisco, CA), Cromwell; Mary (Redwood City, CA), Liu; Hong (Foster City, CA)
Assignee:	Genentech, Inc. (South San Francisco, CA)
Application Number:	14/046,909
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 9,226,961
Patent Claims:	1. A pharmaceutical formulation comprising: (a) a full length IgG1 antibody susceptible to deamidation or aggregation in an amount from about 10 mg/mL to about 250 mg/mL; (b) arginine acetate buffer, pH 4.5 to 6.0; and (c) polysorbate 20 in an amount from about 0.01% to about 0.1%, wherein the antibody is bevacizumab. 2. A method for reducing aggregation of a therapeutic monoclonal antibody, comprising formulating the antibody in an arginine acetate buffer, pH 4.5 to 6.0, wherein the antibody is bevacizumab. 3. The method of claim 2, wherein the buffer is an arginine acetate buffer, pH 4.5 to 5.5. 4. The method of claim 2, wherein the buffer is an arginine acetate buffer, pH 4.8 to 5.4. 5. The method of claim 2, wherein the buffer is an arginine acetate buffer, pH 5.2. 6. The method of claim 3, wherein the arginine actetate concentration in the buffer is from about 25 mM to about 250 mM. 7. The method of claim 3, wherein the arginine actetate concentration in the buffer is from about 50 mM to about 250 mM. 8. The method of claim 3, wherein the arginine actetate concentration in the buffer is from about 75 mM to about 250 mM. 9. The method of claim 3, wherein the arginine actetate concentration in the buffer is from about 100 mM to about 250 mM. 10. The method of claim 3, wherein the arginine acetate concentration in the buffer is from about 120 mM to about 240 mM. 11. The method of claim 3, wherein arginine acetate concentration in the buffer is from about 150 mM to about 225 mM. 12. The method of claim 3, wherein the arginine acetate concentration in the buffer is about 200 mM. 13. The method of claim 2, wherein the formulation further comprises a surfactant. 14. The method of claim 13, wherein the surfactant is polysorbate. 15. The method of claim 14, wherein the polysorbate is polysorbate 20. 16. The method of claim 13, wherein the surfactant concentration is from 0.0001% to about 1.0%. 17. The method of claim 13, wherein the surfactant concentration is from about 0.01% to about 0.05%. 18. The method of claim 13, wherein the surfactant concentration is 0.04%. 19. The method of claim 2, wherein the antibody concentration is from about 10 mg/ml to about 250 mg/ml. 20. The method of claim 2, wherein the antibody concentration is from about 25 mg/ml to 200 mg/ml. 21. The method of claim 2, wherein the antibody concentration is from about 50 mg/ml to about 150 mg/ml. 22. The method of claim 2, wherein the antibody concentration is from about 75 mg/ml to about 125 mg/ml. 23. The method of claim 2, wherein the antibody is not subject to prior lyophilization. 24. A pharmaceutical formulation comprising an antibody that binds to VEGF in an arginine acetate buffer at a pH from about 4.5 to about 6.0, and a surfactant, wherein the antibody is bevacizumab. 25. The pharmaceutical formulation of claim 24, wherein the arginine acetate buffer is pH 4.5 to 5.5. 26. The pharmaceutical formulation of claim 24, wherein the arginine acetate buffer is pH 4.8 to 5.4. 27. The pharmaceutical formulation of claim 24, wherein the arginine acetate buffer is pH 5.2. 28. The pharmaceutical formulation of claim 25, wherein the arginine actetate concentration in the buffer is from about 25 mm to about 250 mm. 29. The pharmaceutical formulation of claim 25, wherein the arginine actetate concentration in the buffer is from about 50 mm to about 250 mm. 30. The pharmaceutical formulation of claim 25, wherein the arginine actetate concentration in the buffer is from about 75 mm to about 250 mm. 31. The pharmaceutical formulation of claim 25, wherein the arginine actetate concentration in the buffer is from about 100 mm to about 250 mm. 32. The pharmaceutical formulation of claim 25, wherein the arginine acetate concentration in the buffer is from about 120 mm to about 240 mm. 33. The pharmaceutical formulation of claim 25, wherein arginine acetate concentration in the buffer is from about 150 mm to about 225 mm. 34. The pharmaceutical formulation of claim 25, wherein the arginine acetate concentration in the buffer is about 200 mm. 35. The pharmaceutical formulation of claim 24, wherein the surfactant is polysorbate. 36. The pharmaceutical formulation of claim 35, wherein the polysorbate is polysorbate 20. 37. The pharmaceutical formulation of claim 24, wherein the surfactant concentration is from about 0.0001% to about 1.0%. 38. The pharmaceutical formulation of claim 24, wherein the surfactant concentration is from about 0.01% to about 0.05%. 39. The pharmaceutical formulation of claim 24, wherein the surfactant concentration is 0.04%. 40. The pharmaceutical formulation of claim 24, wherein the antibody concentration is from about 10 mg/ml to about 250 mg/ml. 41. The pharmaceutical formulation of claim 24, wherein the antibody concentration is from about 25 mg/ml to about 200 mg/ml. 42. The pharmaceutical formulation of claim 24, wherein the antibody concentration is from about 50 mg/ml to about 150 mg/ml. 43. The pharmaceutical formulation of claim 24, wherein the antibody concentration is from about 75 mg/ml to about 125 mg/ml. 44. The pharmaceutical formulation of claim 36, wherein the antibody concentration is about 75 mg/ml to about 125 mg/ml, the arginine acetate buffer is pH 4.8 to 5.4, the arginine acetate concentration in the buffer is from about 150 mM to about 225 mM, and the polysorbate 20 concentration is from about 0.01% to about 0.05%. 45. The pharmaceutical formulation of claim 44, wherein the antibody concentration is about 100 mg/ml, the arginine acetate buffer is pH 5.2, the arginine acetate concentration in the buffer is about 200 mM, and the polysorbate 20 concentration is 0.04%. 46. The pharmaceutical formulation of claim 24, wherein the antibody is not subject to prior lyophilization. 47. The pharmaceutical formulation of claim 24 which is sterile. 48. The pharmaceutical formulation of claim 24 which is stable upon storage at about 40.degree. C. for at least 28 days. 49. The pharmaceutical formulation of claim 24 which is aqueous and is administered to a subject. 50. The pharmaceutical formulation of claim 49, wherein the pharmaceutical formulation is for intravenous (IV), subcutaneous (SQ) or intramuscular (IM) administration. 51. The pharmaceutical formulation of claim 49, which is for IV administration and the antibody concentration is from about 10 mg/ml to about 250 mg/ml. 52. The pharmaceutical formulation of claim 49, which is for IV administration and the antibody concentration is from about 50 mg/ml to about 100 mg/ml. 53. The pharmaceutical formulation of claim 49, which is for SQ administration and the antibody concentration is from about 25 mg/ml to about 250 mg/ml. 54. The pharmaceutical formulation of claim 49, which is for SQ administration and the antibody concentration is from about 50 mg/ml to about 100 mg/ml. 55. A vial with a stopper pierceable by a syringe comprising the pharmaceutical formulation of claim 24 inside the vial. 56. The vial of claim 55 which is stored at about 2-8.degree. C. 57. The vial of claim 55 which is a 3 cc, 20 cc or 50 cc vial. 58. The vial of claim 55, wherein the antibody concentration in the formulation is about 75 mg/ml to about 125 mg/ml, the arginine acetate buffer is pH 4.8 to 5.4, the arginine acetate concentration in the buffer is from about 150 mM to about 225 mM, and the surfactant is polysorbate 20 at a concentration from about 0.01% to about 0.05%. 59. The vial of claim 58, wherein the antibody concentration in the formulation is about 100 mg/ml, the arginine acetate buffer is pH 5.2, the arginine acetate concentration in the buffer is about 200 mM, and the polysorbate 20 concentration is 0.04%. 60. A stainless steel tank comprising the pharmaceutical formulation of claim 24 inside the tank. 61. The tank of claim 56 wherein the pharmaceutical formulation is frozen. 62. The tank of claim 60, wherein the antibody concentration in the formulation is about 75 mg/ml to about 125 mg/ml, the arginine acetate buffer is pH 4.8 to 5.4, the arginine acetate concentration in the buffer is from about 150 mM to about 225 mM, and the surfactant is polysorbate 20 at a concentration from about 0.01% to about 0.05%. 63. The tank of claim 62, wherein the antibody concentration in the formulation is about 100 mg/ml, the arginine acetate buffer is pH 5.2, the arginine acetate concentration in the buffer is about 200 mM, and the polysorbate 20 concentration is 0.04%.

Details for Patent 9,226,961

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Genentech, Inc.	AVASTIN	bevacizumab	Injection	125085	02/26/2004		2029-12-21