Formulation of human antibodies for treating TNF-alpha 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) a human IgG1 anti-human Tumor Necrosis Factor alpha (TNFα) antibody at a concentration of 50 mg/ml,
(b) a polyol,
(c) a polysorbate, and
(d) a buffer system comprising an organic acid and having a pH of 4 to 8,
wherein the antibody is D2E7, 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 is polysorbate 20.
4. The formulation of claim 2 , wherein the polysorbate is polysorbate 80.
5. The formulation of claim 4 , wherein the polysorbate 80 concentration is between 0.1 and 10 mg/ml.
6. The formulation of claim 1 , wherein the pH is from 4.5 to 6.0.
7. The formulation of claim 1 , wherein the polyol is a sugar alcohol.
8. The formulation of claim 7 , wherein the sugar alcohol is mannitol.
9. The formulation of claim 7 , wherein the sugar alcohol is sorbitol.
10. The formulation of claim 7 , wherein the polysorbate is polysorbate 20 or polysorbate 80.
11. The formulation of claim 10 , wherein the polysorbate is polysorbate 20.
12. The formulation of claim 10 , wherein the polysorbate is polysorbate 80.
13. The formulation of claim 10 , wherein the pH is from 4.5 to 6.0.
14. The formulation of claim 10 , wherein the pH is from 4.8 to 5.5.
15. The formulation of claim 1 , wherein the polyol is a sugar.
16. The formulation of claim 15 , wherein the sugar is a non-reducing sugar.
17. The formulation of claim 15 , wherein the sugar is trehalose or sucrose.
18. The formulation of claim 15 , wherein the polysorbate is polysorbate 80 or polysorbate 20.
19. The formulation of claim 18 , wherein the polysorbate is polysorbate 20.
20. The formulation of claim 18 , wherein the polysorbate is polysorbate 80.
21. The formulation of claim 18 , wherein the pH is from 4.5 to 6.0.
22. The formulation of claim 18 , wherein the pH is from 4.8 to 5.5.
23. The formulation of claim 1 , wherein the polyol is a sugar acid.
24. The formulation of claim 23 , wherein the sugar acid is L-gluconate.
25. The formulation of claim 1 , wherein the organic acid comprises histidine.
26. The formulation of claim 1 , wherein the organic acid comprises a succinate.
27. The formulation of claim 1 , wherein the organic acid comprises an acetate.
28. The formulation of claim 1 , wherein the organic acid comprises a phosphate or a gluconate.
29. The formulation of claim 1 , wherein the formulation is packaged for use in a pre-filled syringe.
30. The formulation of claim 1 , wherein the formulation has a shelf life of at least 18 months in the liquid state.