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 45 to 105 mg/ml,
(b) a polyol,
(c) a polysorbate at a concentration of 0.1 to 10 mg/ml, and
(d) a buffer system comprising acetate and having a pH of 4.5 to 7.0,
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 50 to 100 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 formulation has a shelf life of at least 18 months.
5. The formulation of claim 1 , wherein the antibody is D2E7.
6. The formulation of claim 5 , comprising:
(a) 50 to 100 mg/ml of the antibody or antigen-binding portion,
(b) trehalose, and
(c) 0.5-5 mg/ml of polysorbate 80,
wherein said buffer system has a pH of 5.0 to 6.5.
7. The formulation of claim 5 , comprising
(a) 50 mg/ml of D2E7,
(b) 7.5-15 mg/ml mannitol, and
(c) 0.5-5 mg/ml of polysorbate 80,
wherein said buffer system has a pH of 4.5 to 6.0.
8. The formulation of claim 1 , wherein the polyol is a sugar alcohol.
9. The formulation of claim 8 , wherein the sugar alcohol is mannitol.
10. The formulation of claim 1 , 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 polysorbate is polysorbate 20.
14. The formulation of claim 1 , wherein the polysorbate is polysorbate 80.
15. The formulation of claim 14 , wherein the polysorbate 80 concentration is from 0.5 to 5 mg/ml.
16. The formulation of claim 15 , wherein the polysorbate 80 concentration is 1 mg/ml.
17. The formulation of claim 1 , wherein the pH is from 4.5 to 6.0.
18. The formulation of claim 17 , wherein the pH is from 4.8 to 5.5.
19. The formulation of claim 1 , which is suitable for single use subcutaneous injection.
20. The formulation of claim 1 , comprising:
(a) 50 to 100 mg/ml of the antibody or antigen-binding portion,
(b) trehalose, and
(c) 0.5-5 mg/ml of polysorbate 80,
wherein said buffer system has a pH of 5.0 to 6.5.
21. A stable liquid aqueous pharmaceutical formulation comprising
(a) 45 to 105 mg/ml of a human IgG1 anti-human Tumor Necrosis Factor alpha (hTNFα) antibody,
(b) trehalose,
(c) 0.1-10 mg/ml of polysorbate 80, and
(d) a buffer system comprising acetate and having a pH of 4.5 to 7.0,
wherein the antibody comprises the light chain variable region and the heavy chain variable region of D2E7.
22. The formulation of claim 21 , wherein the concentration of the antibody is from 50 to 100 mg/ml.
23. The formulation of claim 21 , wherein the concentration of the antibody is 50 mg/ml.
24. The formulation of claim 21 , wherein the formulation has a shelf life of at least 18 months.
25. The formulation of claim 21 , wherein the antibody is D2E7.
26. The formulation of claim 21 , comprising
(a) 50 to 100 mg/ml of the antibody,
(b) trehalose, and
(c) 0.5-5 mg/ml of polysorbate 80.
27. The formulation of claim 21 , wherein the pH is from 4.5 to 6.0.
28. The formulation of claim 21 , wherein the pH is from 4.8 to 5.5.
29. The formulation of claim 21 , which is suitable for single use subcutaneous injection.