HIGH CONCENTRATION ANTIBODY-CONTAINING LIQUID FORMULATION
The problem to be solved is to provide an antibody-containing formulation which is stable and suited for subcutaneous administration, wherein dimerization and deamidation is prevented during long-term storage. The present application is directed to a stable antibody-containing liquid formulation characterized by containing arginine and methionine.
1 . A method for inhibiting dimerization of molecules of an antibody in a liquid formulation containing the antibody, comprising adding arginine and methionine to the liquid formulation.
2 . The method of claim 1 wherein the antibody comprises humanized anti-IL-6 receptor IgG1 antibody.
3 . A method for inhibiting dimerization of humanized anti-IL-6 receptor IgG1 antibody in a liquid formulation comprising 100 to 300 mg/mL of the antibody, comprising adding 50 to 300 mM arginine and 10 to 50 mM methionine to the formulation.
4 . The method of claim 3 wherein the antibody comprises the humanized anti-IL-6 receptor IgG1 antibody MRA.
5 . The method of claim 3 comprising adding 100 mM arginine to the formulation.
6 . The method of claim 3 further comprising adding 0.005 to 3% surfactant, and histidine buffer pH 5.0 to 7.5, to the formulation.
7 . The method of claim 6 wherein the surfactant comprises polysorbate 80.
8 . The method of claim 6 wherein the pH of the formulation is 5.5 to 6.5.
9 . The method of claim 6 wherein the pH of the formulation is 6.0.
10 . The method of claim 3 wherein the formulation comprises 150 to 200 mg/mL of the antibody.
11 . The method of claim 10 wherein the formulation comprises 180 mg/mL of the antibody.
12 . The method of claim 3 wherein the formulation is for subcutaneous administration.
13 . The method of claim 3 wherein the formulation has not been subjected to lyophilization during preparation thereof.
14 . The method of claim 3 wherein the formulation has a viscosity of from 2 to 15 mPa.
15 . The method of claim 3 wherein the formulation is stable at 22-28° C. for at least 6 months.
16 . A method for inhibiting dimerization of molecules of an antibody in a liquid formulation containing the antibody, comprising adding arginine and methionine to the liquid formulation wherein the antibody is a humanized anti-IL-6 receptor IgG1 antibody, and 150 to 200 mg/mL of the antibody are combined with 50 to 300 mM arginine and 10 to 50 mM methionine.