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 tonicity agent,
(c) a surfactant, and
(d) a buffer system having a pH of 4.0 to 8.0,
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 antibody is D2E7.
5. The formulation of claim 1 , wherein the formulation is isotonic.
6. The formulation of claim 1 , wherein the formulation has an osmotic pressure from 250 to 350 mOsm.
7. The formulation of claim 1 , wherein the tonicity agent is a polyol.
8. The formulation of claim 7 , wherein the polyol is a sugar alcohol.
9. The formulation of claim 8 , wherein the sugar alcohol is mannitol.
10. The formulation of claim 7 , wherein the polyol is a sugar.
11. The formulation of claim 10 , wherein the sugar is a nonreducing sugar.
12. The formulation of claim 11 , wherein the nonreducing sugar is trehalose.
13. The formulation of claim 1 , wherein the tonicity agent is sodium chloride.
14. The formulation of claim 1 , wherein the tonicity agent comprises mannitol and sodium chloride.
15. The formulation of claim 1 , wherein the surfactant is at a concentration of 0.1 to 10 mg/ml.
16. The formulation of claim 1 , wherein the surfactant is a polysorbate.
17. The formulation of claim 16 , wherein the polysorbate is polysorbate 20.
18. The formulation of claim 16 , wherein the polysorbate is polysorbate 80.
19. The formulation of claim 18 , wherein the polysorbate 80 concentration is from 0.5 to 5 mg/ml.
20. The formulation of claim 19 , wherein the polysorbate 80 concentration is 1 mg/ml.
21. The formulation of claim 1 , wherein the pH is from 4.5 to 6.0.
22. The formulation of claim 21 , wherein the pH is from 4.8 to 5.5.
23. The formulation of claim 1 , which is suitable for subcutaneous injection.
24. A stable liquid aqueous pharmaceutical formulation comprising
(a) 20 to 150 mg/ml of a human IgG1 anti-human Tumor Necrosis Factor alpha (TNFα) antibody,
(b) a tonicity agent,
(c) a polysorbate, and
(d) a buffer system having a pH of 4.0 to 8.0,
wherein the antibody comprises the light chain variable region and the heavy chain variable region of D2E7.
25. The formulation of claim 24 , wherein the tonicity agent is a polyol.
26. The formulation of claim 24 , wherein the concentration of the antibody is 50 mg/ml.
27. The formulation of claim 24 , wherein the polysorbate is polysorbate 80.
28. The formulation of claim 24 , wherein the antibody is D2E7.
29. The formulation of claim 24 , wherein the formulation is isotonic.
30. The formulation of claim 24 , wherein the pH is from 4.8 to 5.5.