High concentration antibody-containing liquid formulation

Abstract

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 antibody molecules in a liquid formulation comprising 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 preparing a stable liquid formulation suitable for subcutaneous administration comprising a humanized anti-IL-6 receptor IgG1 antibody, wherein the method comprises combining 150 to 200 mg/mL of the antibody with 50 to 300 mM arginine and 10 to 50 mM methionine. 
     
     
         17 . The method of  claim 16  wherein the formulation further comprises 0.005 to 3% surfactant, and histidine buffer, pH 5.5 to 6.5. 
     
     
         18 . A stable liquid formulation comprising 150 to 200 mg/mL humanized anti-IL-6 receptor IgG1 antibody, 50 to 100 mM arginine, 10 to 50 mM methionine, 0.005 to 3% surfactant, and histidine buffer, pH 5.5 to 6.5. 
     
     
         19 . The formulation of  claim 18  wherein the antibody comprises the humanized anti-IL-6 receptor IgG1 antibody MRA.