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 45-105 mg/ml,
(b) a polyol,
(c) a polysorbate, and
(d) a buffer system comprising succinate 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 pH is from 4.5 to 6.0.
3. The formulation of claim 1 , wherein the pH is from 5.0 to about 6.5.
4. The formulation of claim 1 , wherein the polysorbate is polysorbate 20 or polysorbate 80.
5. The formulation of claim 4 , wherein the polysorbate is polysorbate 20.
6. The formulation of claim 4 , wherein the polysorbate is polysorbate 80.
7. The formulation of claim 6 , wherein the polyol is a sugar.
8. The formulation of claim 7 , wherein the polyol is trehalose.
9. The formulation of claim 8 , wherein the polysorbate 80 concentration is between 0.1 and 10 mg/ml.
10. The formulation of claim 8 , wherein the pH is from 4.5 to 6.0, and the antibody is at a concentration of 50 mg/ml.
11. The formulation of claim 10 , wherein the pH is 5.2.
12. The formulation of claim 10 , wherein the polysorbate 80 concentration is between 0.1 and 10 mg/ml.
13. The formulation of claim 7 , wherein the polyol is sucrose.
14. The formulation of claim 13 , wherein the polysorbate 80 concentration is between 0.1 and 10 mg/ml.
15. The formulation of claim 13 , wherein the pH is from 4.5 to 6.0, and the antibody is at a concentration of 50 mg/ml.
16. The formulation of claim 15 , wherein the pH is 5.2.
17. The formulation of claim 15 , wherein the polysorbate 80 concentration is between 0.1 and 10 mg/ml.
18. The formulation of claim 6 , wherein the polyol is a sugar alcohol.
19. The formulation of claim 18 , wherein the polyol is mannitol.
20. The formulation of claim 19 , wherein the polysorbate 80 concentration is between 0.1 and 10 mg/ml.
21. The formulation of claim 19 , wherein the pH is from 4.5 to 6.0, and the antibody is at a concentration of 50 mg/ml.
22. The formulation of claim 21 , wherein the pH is 5.2.
23. The formulation of claim 21 , wherein the polysorbate 80 concentration is between 0.1 and 10 mg/ml.
24. The formulation of claim 18 , wherein the polyol is sorbitol.
25. The formulation of claim 24 , wherein the polysorbate 80 concentration is between 0.1 and 10 mg/ml.
26. The formulation of claim 24 , wherein the pH is from 4.5 to 6.0, and the antibody is at a concentration of 50 mg/ml.
27. The formulation of claim 26 , wherein the pH is 5.2.
28. The formulation of claim 26 , wherein the polysorbate 80 concentration is between 0.1 and 10 mg/ml.
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.