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) a human IgG1 anti-human Tumor Necrosis Factor alpha (TNFα) antibody, or an antigen-binding portion thereof, at a concentration of 20 to 150 mg/ml,
(b) a polyol,
(c) a surfactant, and
(d) a buffer system having a pH of 4 to 8,
wherein the antibody comprises the light chain variable region and the heavy chain variable region of D2E7.
2. The formulation of claim 1 , wherein the concentration of the antibody or antigen-binding portion is 45 to 105 mg/ml.
3. The formulation of claim 2 , wherein the concentration of the antibody or antigen-binding portion is 50 mg/ml.
4. The formulation of claim 1 , wherein the polyol is a sugar alcohol.
5. The formulation of claim 4 , wherein the sugar alcohol is mannitol.
6. The formulation of claim 5 , wherein the mannitol concentration is between 5 to 20 mg/ml.
7. The formulation of claim 6 , wherein the mannitol concentration is between 10 to 14 mg/ml.
8. The formulation of claim 7 , wherein the mannitol concentration is 12 mg/ml.
9. The formulation of claim 1 , wherein the surfactant is a polysorbate.
10. The formulation of claim 9 , wherein the polysorbate is polysorbate 80.
11. The formulation of claim 10 , wherein the polysorbate 80 concentration is between 0.1 to 10 mg/ml.
12. The formulation of claim 11 , wherein the polysorbate 80 concentration is between 0.5 to 5 mg/ml.
13. The formulation of claim 12 , wherein the polysorbate 80 concentration is 1 mg/ml.
14. The formulation of claim 1 , wherein the pH is from 4.5 to 6.0.
15. The formulation of claim 14 , wherein the pH is from 4.8 to 5.5.
16. The formulation of claim 1 , which is suitable for single use subcutaneous injection.
17. The formulation of claim 1 , wherein the antibody is D2E7.
18. The formulation of claim 17 , wherein the polyol is a sugar alcohol.
19. The formulation of claim 18 , wherein the sugar alcohol is mannitol.
20. The formulation of claim 17 , wherein the surfactant is a polysorbate.
21. The formulation of claim 20 , wherein the polysorbate is polysorbate 80.
22. The formulation of claim 21 , wherein the polysorbate 80 concentration is 1 mg/ml.
23. The formulation of claim 17 , wherein the pH is from 4.5 to 6.0.
24. The formulation of claim 23 , wherein the pH is from 4.8 to 5.5.
25. The formulation of claim 17 , which is suitable for single use subcutaneous injection.
26. The formulation of claim 17 , wherein the concentration of the antibody or antigen-binding portion is 50 mg/ml.
27. The formulation of claim 1 , wherein the buffer system comprises histidine.
28. The formulation of claim 1 , wherein the buffer system comprises succinate.
29. The formulation of claim 1 , wherein the buffer system comprises acetate.
30. The formulation of claim 1 , wherein the buffer system comprises phosphate or gluconate.