Low acidic species compositions

Patent metadata

Field	Value
Publication number	US-9334319-B2
Application number	US-201313829989-A
Country	US
Kind code	B2
Filing date	Mar 14, 2013
Priority date	Apr 20, 2012
Publication date	May 10, 2016
Grant date	May 10, 2016

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.

First claim

What is claimed is:

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.

Assignees

• Abbvie Inc

Inventors

• Ramasubramanyan Natarajan
• Yang Lihua
• Herigstad Matthew Omon
• Yang Hong
• Chumsae Christopher

Classifications

• C07K2317/21

  from primates, e.g. man · CPC title

• C07K1/18

  Ion-exchange chromatography · CPC title

• C07K16/241 Primary

  Tumor Necrosis Factors · CPC title

• A61K39/39591

  Stabilisation, fragmentation · CPC title

• C07K2317/14

  Specific host cells or culture conditions, e.g. components, pH or temperature · CPC title