Anti-oxidized LDL antibody formulation
A formulation comprising a therapeutically effective amount of an antibody, optionally, not subjected to prior lyophilization, a buffer maintaining the pH in the range from about 4.5 to about 6.5, and an optional surfactant is described, along with uses for such a formulation.
1. A formulation comprising a therapeutically effective amount of an anti-oxLDL antibody in a histidine-arginine buffer, pH 4.5 to 6.5, wherein the buffer is a histidine acetate-arginine acetate buffer or a histidine succinate-arginine succinate buffer, and wherein the anti-oxLDL antibody comprises a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:3, and a light chain variable region comprising the amino acid sequence of SEQ ID NO:4.
2. The formulation of claim 1 , wherein the buffer is a histidine acetate-arginine acetate buffer, pH 5.0 to 6.0 or wherein the buffer is a histidine succinate-arginine succinate buffer, pH is 5.0 to 6.0.
3. The formulation of claims 2 , wherein histidine acetate or histidine succinate concentration in the buffer is from 5 mM to 100 mM.
4. The formulation of claims 2 , wherein the histidine acetate or histidine succinate concentration is 20 mM.
5. The formulation of claims 2 , wherein arginine acetate or arginine succinate concentration in the buffer is from 50 mM to 500 mM.
6. The formulation of claims 2 , wherein the arginine acetate or arginine succinate concentration is 150 mM.
7. The formulation of claim 1 , further comprising a surfactant.
8. The formulation of claim 7 , wherein the surfactant is polysorbate.
9. The formulation of claim 8 , wherein the polysorbate is polysorbate 20.
10. The formulation of claim 9 , wherein the surfactant concentration is from 0.0001% to 1.0%.
11. The formulation of claim 10 , wherein the surfactant concentration is from 0.01% to 0.1%.
12. The formulation of claim 11 , wherein the surfactant concentration is 0.02%.
13. The formulation of claim 1 , wherein the antibody concentration is from 10 mg/ml to 250 mg/ml.
14. The formulation of claim 1 , wherein the antibody concentration is from 100 mg/ml to 250 mg/ml.
15. The formulation of claim 1 , wherein the antibody concentration is from 150 mg/ml to 200 mg/ml.
16. The formulation of claim 1 , wherein the antibody concentration is from 25 mg/ml to 200 mg/ml.
17. The formulation of claim 1 , wherein the antibody is not subject to prior lyophilization.
18. The formulation of claim 1 further comprising methionine.
19. The formulation of claim 18 , wherein the methionine concentration is 5 mg/ml.
20. The formulation of claim 1 , further comprising EDTA.
21. The formulation of claim 20 , wherein the EDTA concentration is 1 mM EDTA.
22. The formulation of claim 7 , wherein the buffer is 20 mM histidine acetate and 150 mM arginine acetate pH 5.5, the surfactant is polysorbate in an amount of 0.01-0.1% v/v, wherein the formulation is stable at a temperature of 2-8° C. for at least 12 months or wherein the buffer is 20 mM histidine succinate and 150 mM arginine succinate pH 5.5, the surfactant is polysorbate in an amount of 0.01-0.1% v/v, wherein the formulation is stable at a temperature of 2-8° C. for at least 12 months.
23. The formulation of claim 1 , wherein the formulation is a pharmaceutical formulation.
24. The formulation of claim 1 , wherein the formulation is stable upon storage at 25° C. for at least 12 months or wherein the formulation is stable upon storage at 5° C. for at least 12 months or wherein the formulation is stable upon storage at −20° C. for at least 12 months.
25. An article of manufacture comprising a container holding an aqueous pharmaceutical formulation comprising a therapeutically effective amount of an anti-oxLDL antibody, a histidine acetate-arginine acetate buffer from pH 5.0 to 6.0, and a surfactant, or comprising a container holding an aqueous pharmaceutical formulation comprising a therapeutically effective amount of an anti-oxLDL antibody, a histidine succinate-arginine succinate buffer from pH 5.0 to 6.0, and a surfactant; wherein the anti-oxLDL antibody comprises a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:3, and a light chain variable region comprising the amino acid sequence of SEQ ID NO:4.
26. A method for stabilizing an anti-oxLDL antibody in an aqueous pharmaceutical formulation comprising combining a therapeutically effective amount of the antibody, a histidine acetate-arginine acetate buffer from pH 5.0 to 6.0, and a surfactant, or comprising combining a therapeutically effective amount of the antibody, a histidine succinate-arginine succinate buffer from pH 5.0 to 6.0, and a surfactant; wherein the anti-oxLDL antibody comprises a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:3, and a light chain variable region comprising the amino acid sequence of SEQ ID NO:4.
27. A pharmaceutical formulation comprising: (a) a full length anti-oxLDL IgG1 antibody susceptible to deamidation or aggregation in an amount from 10 mg/mL to 250 mg/mL; wherein the anti-oxLDL antibody comprises a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:3, and a light chain variable region comprising the amino acid sequence of SEQ ID NO:4; (b) histidine acetate-arginine acetate buffer, pH 5.0 to 6.0; and (c) polysorbate 20 in an amount from 0.01% to 0.1%.
28. A pharmaceutical formulation comprising: (a) a full length anti-oxLDL IgG1 antibody susceptible to deamidation or aggregation in an amount from 10 mg/mL to 250 mg/mL; wherein the anti-oxLDL antibody comprises a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:3, and a light chain variable region comprising the amino acid sequence of SEQ ID NO:4; (b) histidine succinate-arginine succinate buffer, pH 5.0 to 6.0; and (c) polysorbate 20 in an amount from 0.01% to 0.1%.
29. The formulation of claim 1 , wherein the anti-oxLDL antibody is a human IgG1 antibody.
30. The formulation of claim 1 , wherein the anti-oxLDL antibody is a chimeric anti-oxLDL antibody.
31. The method of claim 1 , wherein the anti-oxLDL antibody is a human anti-oxLDL antibody.
32. The formulation of claim 1 , wherein the anti-oxLDL antibody is an antibody fragment selected from the group consisting of a Fab, Fab′, F(ab′) 2 and Fv fragment.
33. The formulation of claim 7 , wherein the buffer is 20 mM histidine acetate and 150 mM arginine acetate pH 5.5, and the surfactant is polysorbate 20 in an amount of 0.01-0.1% v/v.
34. The formulation of claim 7 , wherein the buffer is 20 mM histidine succinate and 150 mM arginine succinate pH 5.5, the surfactant is polysorbate 20 in an amount of 0.01-0.1% v/v.
35. The article of manufacture of claim 25 , wherein the anti-oxLDL antibody is a human IgG1 antibody.
36. The article of manufacture of claim 25 , wherein the anti-oxLDL antibody is a human anti-oxLDL antibody.
37. The article of manufacture of claim 25 , wherein the anti-oxLDL antibody is an antibody fragment selected from the group consisting of a Fab, Fab′, F(ab′) 2 and Fv fragment.
38. The method of claim 26 , wherein the anti-oxLDL antibody is a human IgG1 antibody.
39. The method of claim 26 , wherein the anti-oxLDL antibody is a human anti-oxLDL antibody.
40. The method of claim 26 , wherein the anti-oxLDL antibody is an antibody fragment selected from the group consisting of a Fab, Fab′, F(ab′) 2 and Fv fragment.
41. The pharmaceutical formulation of claim 27 , wherein the anti-oxLDL antibody is a human IgG1 antibody.
42. The pharmaceutical formulation of claim 27 , wherein the anti-oxLDL antibody is a human anti-oxLDL antibody.
43. The pharmaceutical formulation of claim 28 , wherein the anti-oxLDL antibody is a human IgG1 antibody.
44. The pharmaceutical formulation of claim 28 , wherein the anti-oxLDL antibody is a human anti-oxLDL antibody.