Formulation of human antibodies for treating TNF-α associated disorders
A liquid aqueous pharmaceutical formulation is described which has a high protein concentration, a pH of between about 4 and about 8, and enhanced stability.
1. A stable liquid aqueous pharmaceutical formulation comprising
(a) 50 mg/ml of a human IgG1 anti-human Tumor Necrosis Factor alpha (TNFα) antibody, wherein the antibody comprises a light chain variable region comprising the amino acid sequence of SEQ ID NO:1
and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 2;
(b) a polyol;
(c) a polysorbate; and
(d) a buffer system comprising an organic acid;
wherein the formulation has a pH of 4 to 8, and wherein the formulation is suitable for subcutaneous injection.
2. The formulation of claim 1 , wherein the polysorbate is polysorbate 20 or polysorbate 80.
3. The formulation of claim 2 , wherein the polysorbate concentration is between 0.1 and 10 mg/ml.
4. The formulation of claim 2 , wherein the pH is from 4.5 to 6.0.
5. The formulation of claim 4 , wherein the pH is from 4.8 to 5.5.
6. The formulation of claim 4 , wherein the polyol is a sugar alcohol.
7. The formulation of claim 6 , wherein the sugar alcohol is mannitol.
8. The formulation of claim 6 , wherein the sugar alcohol is sorbitol.
9. The formulation of claim 6 , wherein the formulation is packaged for use in a pre-filled syringe.
10. The formulation of claim 6 , wherein the formulation has a shelf life of at least 18 months in the liquid state.
11. The formulation of claim 6 , wherein the formulation is stable following freezing to −70° C. and thawing of the formulation three times.
12. The formulation of claim 6 , wherein the formulation is stable at 2-8° C. for 1 year.
13. The formulation of claim 4 , wherein the polyol is a sugar.
14. The formulation of claim 13 , wherein the sugar is a non-reducing sugar.
15. The formulation of claim 13 , wherein the sugar is trehalose or sucrose.
16. The formulation of claim 4 , wherein the formulation is packaged for use in a pre-filled syringe.
17. The formulation of claim 4 , wherein the formulation has a shelf life of at least 18 months in the liquid state.
18. The formulation of claim 4 , wherein the formulation is stable at 30° C. for 1 month.
19. The formulation of claim 4 , wherein the formulation is stable at 40° C. for 1 month.
20. The formulation of claim 4 , wherein the formulation is stable at 2-8° C. for 1 year.
21. The formulation of claim 4 , wherein the formulation is stable following freezing to −70° C. and thawing of the formulation three times.
22. The formulation of claim 1 , wherein the buffer system comprises histidine.
23. The formulation of claim 1 , wherein the buffer system comprises succinate.
24. The formulation of claim 1 , wherein the buffer system comprises acetate.
25. The formulation of claim 1 , wherein the formulation is packaged for use in a pre-filled syringe.
26. The formulation of claim 1 , wherein the formulation has a shelf life of at least 18 months in the liquid state.
27. The formulation of claim 1 , wherein the formulation is stable at 30° C. for 1 month.
28. The formulation of claim 1 , wherein the formulation is stable at 40° C. for 1 month.
29. The formulation of claim 1 , wherein the formulation is stable at 2-8° C. for 1 year.
30. The formulation of claim 1 , wherein the formulation is stable following freezing to −70° C. and thawing of the formulation three times.