Stable liquid antibody formulation
View Patent ↗The present invention relates generally to the field of pharmaceutical formulations of antibodies. Specifically, the present invention relates to a stable liquid antibody formulation and its pharmaceutical preparation and use. This invention is exemplified by a liquid formulation of a humanized anti-NGF antibody.
1. A liquid composition comprising;
about 2.5 mg/ml to about 20 mg/ml of an anti-NGF antibody,
about 80 mg/ml to 85 mg/ml trehalose dihydrate,
about 9.0 mM to 10.0 mM histidine buffer,
about 0.05 mg/ml to 0.1 mg/ml disodium EDTA, and
about 0.01 mg/ml to 0.15 mg/ml polysorbate 20 (PS20),
wherein the pH of said composition is from 5.8 to 6.8, wherein the antibody comprises a heavy chain variable region amino acid sequence shown in SEQ ID NO: 1, and a light chain variable region amino acid sequence shown in SEQ ID NO: 2.
2. The liquid composition according to claim 1 which further comprises an antioxidant agent and/or a preservative agent.
3. The liquid composition according to claim 1 which does not comprise an antioxidant agent, a preservative agent or both.
4. The liquid composition according to claim 1 comprising;
2.5 mg/ml to about 20 mg/ml of said anti-NGF antibody,
9.0 mM to 10.0 mM histidine buffer,
80 mg/ml to 85 mg/ml trehalose dihydrate,
0.01 mg/ml to 0.15 mg/ml PS20, and
0.05 mg/ml to 0.1 mg/ml disodium EDTA,
wherein said composition is of a pH from 5.8 to 6.8, wherein the antibody comprises a heavy chain variable region amino acid sequence shown in SEQ ID NO: 1, and a light chain variable region amino acid sequence shown in SEQ ID NO: 2.
5. The liquid composition according to claim 3 consisting of;
about 2.5 mg/ml to about 20 mg/ml of said anti-NGF antibody,
about 9.0 mM to 10.0 mM histidine buffer,
about 80 mg/ml to 85 mg/ml trehalose dihydrate,
about 0.01 mg/ml to 0.15 mg/ml PS20, and
about 0.05 mg/ml to 0.1 mg/ml disodium EDTA,
wherein said composition is of a pH from 5.8 to 6.8.
6. The liquid composition according to claim 1 comprising;
about 2.5 mg/ml, 5 mg/ml, 10 mg/ml, or 20 mg/ml, of said anti-NGF antibody,
about 10 mM histidine buffer,
about 84 mg/ml trehalose dihydrate,
about 0.1 mg/ml PS20, and
about 0.05 mg/ml disodium EDTA,
wherein said composition is of a pH 6.0+/−0.2.
7. The liquid composition according to claim 1 comprising;
about 2.5 mg/ml, 5 mg/ml, 10 mg/ml, or 20 mg/ml of said anti-NGF antibody,
about 10 mM histidine buffer,
about 84 mg/ml trehalose dihydrate,
about 0.1 mg/ml PS20, and
about 0.05 mg/ml disodium EDTA,
wherein said composition is of a pH from 5.8 to 6.5.
8. The liquid composition according to claim 1 wherein the composition is not lyophilized.
9. The liquid composition according to claim 1 wherein the composition can be stored for a period of at least about 26 weeks at a temperature of about 40° C. and wherein there is less than about 10% increase in aggregation of the antibody of the composition.
10. The liquid composition according to claim 1 wherein the composition can be stored for a period of at least about 26 weeks at a temperature of about 40° C. and wherein there is less than about 10% increase in oxidation of the antibody of the composition.
11. The liquid composition according to claim 1 wherein the composition can be stored for a period of at least about 26 weeks at a temperature of about 40° C. and wherein there is less than about 10% decrease in activity of the antibody of the composition.
12. The liquid composition according to claim 1 wherein the composition can stored for a period of at least about 26 weeks at a temperature of between 2 to 8° C. and wherein there is less than about 10% increase in aggregation of the antibody of the composition.
13. A pharmaceutical composition for treating pain in a mammal comprising an effective amount of the liquid composition of claim 1 .