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 human anti-human Tumor Necrosis Factor alpha (TNFα) IgG 1 antibody at a concentration of 50 mg/ml, wherein the antibody comprises the light chain variable region and the heavy chain variable region of D2E7, and a buffer system;
wherein the formulation is isotonic, suitable for single-use subcutaneous injection, and has a pH of 4.0 to 8.0.
2. The formulation of claim 1 , wherein the buffer system comprises an organic acid.
3. The formulation of claim 2 , wherein the organic acid is selected from the group consisting of gluconate, citrate, succinate, acetate, and histidine.
4. The formulation of claim 3 , wherein the pH is 4.8 to 5.5.
5. The formulation of claim 1 , wherein the buffer system comprises phosphate.
6. The formulation of claim 1 , wherein the pH is 4.5 to 6.0.
7. The formulation of claim 1 , wherein the pH is 4.8 to 5.5.
8. The formulation of claim 1 , wherein the pH is 5.0 to 5.2.
9. The formulation of claim 1 , wherein the antibody is D2E7.
10. The formulation of claim 9 , wherein the formulation further comprises a tonicity agent.
11. The formulation of claim 10 , wherein the tonicity agent is a polyol.
12. The formulation of claim 11 , wherein the polyol is a sugar, a sugar alcohol or a sugar acid.
13. The formulation of claim 10 , wherein the tonicity agent is sodium chloride.
14. The formulation of claim 9 , wherein the buffer system comprises an organic acid.
15. The formulation of claim 14 , wherein the organic acid is selected from the group consisting of gluconate, citrate, succinate, acetate, and histidine.
16. The formulation of claim 1 , wherein the formulation comprises a tonicity agent.
17. The formulation of claim 16 , wherein the tonicity agent is a polyol.
18. The formulation of claim 17 , wherein the polyol is a sugar, a sugar alcohol or a sugar acid.
19. The formulation of claim 18 , wherein the sugar acid is L-gluconate.
20. The formulation of claim 18 , wherein the sugar is a nonreducing sugar.
21. The formulation of claim 20 , wherein the nonreducing sugar is trehalose.
22. The formulation of claim 18 , wherein the sugar alcohol is mannitol.
23. The formulation of claim 16 , wherein the tonicity agent is sodium chloride.
24. The formulation of claim 1 , wherein the formulation comprises a surfactant.
25. The formulation of claim 24 , wherein the surfactant is a polysorbate.
26. The formulation of claim 25 , wherein the polysorbate is polysorbate-80.
27. The formulation of claim 1 , wherein the formulation comprises a preservative.
28. The formulation of claim 1 , wherein the formulation comprises a chelating agent.
29. The formulation of claim 1 , wherein the formulation comprises an antioxidant.
30. The formulation of claim 29 , wherein the antioxidant is ascorbic acid or methionine.