Antibody formulations

Abstract

The present application describes antibody formulations, including monoclonal antibodies formulated in histidine-acetate buffer, as well as a formulation comprising an antibody that binds to domain II of HER2 (for example, Pertuzumab), and a formulation comprising an antibody that binds to DR5 (for example, Apomab).

1 . A method for reducing deamidation or aggregation of a therapeutic monoclonal antibody, comprising formulating the antibody in a histidine-acetate buffer, pH 5.5 to 6.5. 
     
     
         2 . The method of  claim 1  comprising evaluating any antibody deamidation or aggregation before and after the antibody is formulated. 
     
     
         3 . The method of  claim 1  wherein the antibody binds to domain II of HER2. 
     
     
         4 . The method of  claim 1  further comprising formulating the antibody in a saccharide and a surfactant. 
     
     
         5 . The method of  claim 3  wherein the antibody is formulated at a concentration from 20 mg/mL to 40 mg/mL, the antibody comprises the variable light and variable heavy amino acid sequences in SEQ ID Nos. 3 and 4, respectively, the saccharide is sucrose which is formulated at a concentration from about 60 mM to about 250 mM, and the surfactant is polysorbate 20 which is formulated at a concentration from about 0.01% to about 0.1%. 
     
     
         6 . The method of  claim 3  wherein the HER2 antibody comprises a light chain amino acid sequence selected from SEQ ID No. 15 and 23, and a heavy chain amino acid sequence selected from SEQ ID No. 16 and 24. 
     
     
         7 . The method of  claim 1  wherein the pH of the buffer is from about 5.8 to about 6.2. 
     
     
         8 . The method of  claim 5  wherein the antibody is a full length antibody. 
     
     
         9 . The method of  claim 1  wherein the formulation is aqueous and has not been subjected to prior lyophilization, and is administered to a subject. 
     
     
         10 . The method of  claim 9  wherein the formulation is administered to the subject intravenously. 
     
     
         11 . The method of  claim 1  wherein the antibody comprises Pertuzumab formulated in an amount from 20 mg/mL to 40 mg/mL. 
     
     
         12 . A formulation comprising Pertuzumab in a histidine-acetate buffer, pH 5.5 to 6.5. 
     
     
         13 . The formulation of  claim 12  further comprising saccharide and surfactant. 
     
     
         14 . The formulation of  claim 12  wherein the Pertuzumab concentration in the formulation is from 20 mg/mL to 40 mg/mL. 
     
     
         15 . The formulation of  claim 13  comprising 60 mM to 250 mM sucrose. 
     
     
         16 . The formulation of  claim 13  comprising 0.01% to 0.1% polysorbate. 
     
     
         17 . The formulation of  claim 12  wherein the pH of the buffer is from 5.8 to 6.2. 
     
     
         18 . The formulation of  claim 12  which is aqueous and has not been subjected to prior lyophilization, and is administered to a subject. 
     
     
         19 . The formulation of  claim 18  which is administered to the subject intravenously.