IP Library › Granted Patent US 9,334,319
Granted Patent B2
US 9,334,319 · App. 13/829,989 · Granted May 10, 2016

Low acidic species compositions

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Quick Facts
Patent No.
US 9,334,319
App. No.
13/829,989
Granted
May 10, 2016
Kind
B2
Abstract

The instant invention relates to the field of protein production and purification, and in particular to compositions and processes for controlling the amount of charge variants, aggregates, and fragments of a protein of interest, as well as host cell proteins, present in purified preparations by applying particular chromatography conditions during such protein purification.

Claims (62)

1. A composition comprising adalimumab, wherein the composition comprises less than 10% total acidic species of adalimumab, wherein the acidic species of adalimumab correspond to the peaks that elute earlier than the main peak in a WCX-10 HPLC chromatogram of adalimumab, wherein the WCX-10 HPLC chromatogram is generated using a first mobile phase of 10 mM Sodium Phosphate dibasic (pH 7.5) and a second mobile phase of 10 mM Sodium Phosphate dibasic, 500 mM Sodium Chloride (pH 5.5), and wherein the WCX-10 HPLC chromatogram is generated using detection at 280 nm.

2. The composition of claim 1 , wherein the acidic species of adalimumab comprise a first acidic region (AR1) and a second acidic region (AR2).

3. The composition of claim 1 , wherein the composition comprises less than 3.8% total acidic species of adalimumab.

4. The composition of claim 2 , wherein the composition comprises 0.8% AR1 and 3.0% AR2.

5. The composition of claim 1 , wherein the composition comprises less than 2.4% total acidic species of adalimumab.

6. The composition of claim 2 , wherein the composition comprises 0.2% AR1 and 2.2% AR2.

7. The composition of claim 1 , wherein the composition comprises 4.7%-8.3% total acidic species of adalimumab.

8. The composition of claim 7 , wherein the composition comprises 4.7% total acidic species of adalimumab.

9. The composition of claim 7 , wherein the composition comprises 5.0% total acidic species of adalimumab.

10. The composition of claim 7 , wherein the composition comprises 5.8% total acidic species of adalimumab.

11. The composition of claim 7 , wherein the composition comprises 6.1% total acidic species of adalimumab.

12. The composition of claim 7 , wherein the composition comprises 6.4% total acidic species of adalimumab.

13. The composition of claim 7 , wherein the composition comprises 8.1% total acidic species of adalimumab.

14. The composition of claim 7 , wherein the composition comprises 8.3% total acidic species of adalimumab.

15. The composition of claim 2 , wherein the composition comprises 0.8%-1.4% AR1.

16. The composition of claim 2 , wherein the composition comprises 3%-9% AR2.

17. The composition of claim 2 , wherein the composition comprises 0.8% AR1 and 6.4% AR2.

18. The composition of claim 2 , wherein the composition comprises 0.9% AR1 and 9% AR2.

19. The composition of claim 2 , wherein the composition comprises 1.2% AR1 and 7.7% AR2.

20. The composition of claim 2 , wherein the composition comprises 1.2% AR1 and 8.2% AR2.

21. The composition of claim 2 , wherein the composition comprises 1.4% AR1 and 8.4% AR2.

22. The composition of claim 2 , wherein the composition comprises 1.4% AR1 and 8.6% AR2.

23. The composition of claim 1 , wherein the composition further comprises a pharmaceutically acceptable carrier.

24. A pharmaceutical composition suitable for administration to a human subject, comprising a composition comprising adalimumab, wherein the composition comprises less than 10% total acidic species of adalimumab, wherein the acidic species of adalimumab correspond to the peaks that elute earlier than the main peak in a WCX-10 HPLC chromatogram of adalimumab, wherein the WCX-10 HPLC chromatogram is generated using a first mobile phase of 10 mM Sodium Phosphate dibasic (pH 7.5) and a second mobile phase of 10 mM Sodium Phosphate dibasic, 500 mM Sodium Chloride (pH 5.5), and wherein the WCX-10 HPLC chromatogram is generated using detection at 280 nm;

and a pharmaceutically acceptable carrier.

25. The pharmaceutical composition of claim 24 , wherein the acidic species of adalimumab comprise a first acidic region (AR1) and a second acidic region (AR2).

26. The pharmaceutical composition of claim 24 , wherein the composition comprises less than 3.8% total acidic species of adalimumab.

27. The pharmaceutical composition of claim 25 , wherein the composition comprises 0.8% AR1 and 3.0% AR2.

28. The pharmaceutical composition of claim 24 , wherein the composition comprises less than 2.4% total acidic species of adalimumab.

29. The pharmaceutical composition of claim 25 , wherein the composition comprises 0.2% AR1 and 2.2% AR2.

30. The pharmaceutical composition of claim 24 , wherein the composition comprises 4.7%-8.3% total acidic species of adalimumab.

31. The pharmaceutical composition of claim 30 , wherein the composition comprises 4.7% total acidic species of adalimumab.

32. The pharmaceutical composition of claim 30 , wherein the composition comprises 5.0% total acidic species of adalimumab.

33. The pharmaceutical composition of claim 30 , wherein the composition comprises 5.8% total acidic species of adalimumab.

34. The pharmaceutical composition of claim 30 , wherein the composition comprises 6.1% total acidic species of adalimumab.

35. The pharmaceutical composition of claim 30 , wherein the composition comprises 6.4% total acidic species of adalimumab.

36. The pharmaceutical composition of claim 30 , wherein the composition comprises 8.1% total acidic species of adalimumab.

37. The pharmaceutical composition of claim 30 , wherein the composition comprises 8.3% total acidic species of adalimumab.

38. The pharmaceutical composition of claim 25 , wherein the composition comprises 0.8%-1.4% AR1.

39. The pharmaceutical composition of claim 25 , wherein the composition comprises 3%-9% AR2.

40. The pharmaceutical composition of claim 25 , wherein the composition comprises 0.8% AR1 and 6.4% AR2.

41. The pharmaceutical composition of claim 25 , wherein the composition comprises 0.9% AR1 and 9% AR2.

42. The pharmaceutical composition of claim 25 , wherein the composition comprises 1.2% AR1 and 7.7% AR2.

43. The pharmaceutical composition of claim 25 , wherein the composition comprises 1.2% AR1 and 8.2% AR2.

44. The pharmaceutical composition of claim 25 , wherein the composition comprises 1.4% AR1 and 8.4% AR2.

45. The pharmaceutical composition of claim 25 , wherein the composition comprises 1.4% AR1 and 8.6% AR2.

46. The composition of any one of claims 1 - 23 , wherein the composition is a lyophilized composition.

47. The pharmaceutical composition of any one of claims 24 - 45 , wherein the composition is a lyophilized composition.

48. The composition of any one of claims 1 - 23 , wherein the adalimumab is produced in a mammalian host cell grown in cell culture.

49. The composition of claim 48 , wherein the mammalian host cell is selected from the group consisting of a CHO cell, an NSO cell, a COS cell, and an SP2 cell.

50. The composition of claim 49 , wherein the mammalian host cell is a CHO cell.

51. The pharmaceutical composition of any one of claims 24 - 45 , wherein the adalimumab is produced in a mammalian host cell grown in cell culture.

52. The pharmaceutical composition of claim 51 , wherein the mammalian host cell is selected from the group consisting of a CHO cell, an NSO cell, a COS cell, and an SP2 cell.

53. The pharmaceutical composition of claim 52 , wherein the mammalian host cell is a CHO cell.

54. The pharmaceutical composition of any one of claims 24 - 45 , wherein adalimumab is present in the pharmaceutical composition at a concentration of 0.1-250 mg/mL.

55. The pharmaceutical composition of any one of claims 24 - 45 , wherein the pharmaceutically acceptable carrier comprises mannitol.

56. The pharmaceutical composition of any one of claims 24 - 45 , wherein the pharmaceutically acceptable carrier comprises sodium chloride.

57. The pharmaceutical composition of any one of claims 24 - 45 , wherein the pharmaceutically acceptable carrier comprises polysorbate 80.

58. The pharmaceutical composition of any one of claims 24 - 45 , wherein the pharmaceutically acceptable carrier comprises a buffer.

59. The pharmaceutical composition of claim 58 , wherein the buffer is sodium citrate.

60. The pharmaceutical composition of claim 58 , wherein the buffer is histidine.

61. A pre-filled syringe which contains the pharmaceutical composition of any one of claims 24 - 45 .

Assignments (2)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Oct 1, 2014
From: CHUMSAE, CHRISTOPHER
To: ABBVIE INC.
Reel/Frame 033865/0402 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Apr 24, 2014
From: RAMASUBRAMANYAN, NATARAJAN; YANG, LIHUA; HERIGSTAD, MATTHEW OMON; YANG, HONG
To: ABBVIE INC.
Reel/Frame 032750/0956 →