Antibody formulation

Abstract

Anti-BAFFR antibodies are formulated as lyophilisate or liquid formulation. The lyophilisates can be reconstituted to give a solution with a high concentration of the antibody active ingredient for delivery to a patient without high levels of antibody aggregation. The lyophilisate can be reconstituted with an aqueous reconstituent to provide an aqueous composition in which the antibody has a concentration of at least 50 mg/ml. The lyophilisate or aqueous pharmaceutical composition may include one or more of a sugar, a buffering agent, a surfactant, and/or a free amino acid.

1 . A method of treating a disease or disorder that is mediated by BAFF receptor or that can be treated by killing or depleting B cells, comprising administering to a subject, a lyophilized formulation comprising
 (i) an anti-BAFFR antibody wherein the antibody has a concentration of 20-120 mg/ml, and wherein said anti-BAFFR antibody includes heavy chain CDR1, CDR2 and CDR3 of SEQ ID NOs 3, 4 and 5 respectively, and light chain CDR1, CDR2 and CDR3 of SEQ ID NOs: 6, 7 and 8,   (ii) a stabilizer,   (iii) a buffering agent,   (iv) a surfactant, and optionally   (v) an amino acid.   
     
     
         2 . The method of  claim 1 , wherein said disease or disorder that is mediated by BAFF receptor or that can be treated by killing or depleting B cells is selected from the group consisting of autoimmune disease, B cell neoplasm, lymphoma, leukemia, myeloma, rheumatoid arthritis, systemic lupus erythematosus, and Pemphigus vulgaris. 
     
     
         3 . A method for treating a disease or disorder that is mediated by BAFF receptor or that can be treated by killing or depleting B cells, comprising administering to a subject the aqueous pharmaceutical composition of  claim 1 . 
     
     
         4 . The method of  claim 3 , wherein said disease or disorder that is mediated by BAFF receptor or that can be treated by killing or depleting B cells is selected from the group consisting of autoimmune disease, B cell neoplasm, lymphoma, leukemia, myeloma, rheumatoid arthritis, systemic lupus erythematosus, and Pemphigus vulgaris. 
     
     
         5 . The method of  claim 1 , wherein said formulation is prepared from an aqueous formulation having a pH of 5.0-7.0 and comprising
 (i) an anti-BAFFR antibody wherein the antibody has a concentration of 20-120 mg/ml, and wherein said anti-BAFFR antibody includes heavy chain CDR1, CDR2 and CDR3 of SEQ ID NOs 3, 4 and 5 respectively, and light chain CDR1, CDR2 and CDR3 of SEQ ID NOs: 6, 7 and 8,   (ii) sucrose or trehalose as a stabilizer,   (iii) histidine as a buffering agent,   (iv) polysorbate 80 as a surfactant, and optionally   (v) an amino acid selected from arginine and glycine.   
     
     
         6 . The method of  claim 1 , wherein said formulation is prepared from an aqueous formulation having a pH of 5.0-7.0 and comprising
 (i) an anti-BAFFR antibody wherein the antibody has a concentration of 20-120 mg/ml, and wherein said anti-BAFFR antibody includes heavy chain CDR1, CDR2 and CDR3 of SEQ ID NOs 3, 4 and 5 respectively, and light chain CDR1, CDR2 and CDR3 of SEQ ID NOs: 6, 7 and 8,   (ii) 3-300 mM sucrose or trehalose as a stabilizer,   (iii) 1-60 mM histidine as a buffering agent,   (iv) up to 0.2% polysorbate 80 as a surfactant, and optionally   (v) 2-80 mM arginine or glycine.   
     
     
         7 . The method of  claim 1 , wherein said formulation is prepared from an aqueous formulation having a pH of 6.5 and comprising
 (i) an anti-BAFFR antibody wherein the antibody has a concentration of 50 mg/ml, and wherein said anti-BAFFR antibody includes heavy chain CDR1, CDR2 and CDR3 of SEQ ID NOs 3, 4 and 5 respectively, and light chain CDR1, CDR2 and CDR3 of SEQ ID NOs: 6, 7 and 8,   (ii) 90 mM sucrose as a stabilizer,   (iii) 7 mM histidine as a buffering agent, and   (iv) 0.02% polysorbate 80 as a surfactant.   
     
     
         8 . The method of  claim 1 , wherein said formulation is prepared from an aqueous formulation having a pH of 6.5 and comprising
 (i) an anti-BAFFR antibody wherein the antibody has a concentration of 50 mg/ml, and wherein said anti-BAFFR antibody includes heavy chain CDR1, CDR2 and CDR3 of SEQ ID NOs 3, 4 and 5 respectively, and light chain CDR1, CDR2 and CDR3 of SEQ ID NOs: 6, 7 and 8,   (ii) 90 mM sucrose as a stabilizer,   (iii) 7 mM histidine as a buffering agent,   (iv) 0.02% polysorbate 80 as a surfactant, and   (v) 20 mM glycine-HCl.   
     
     
         9 . The method of  claim 1 , wherein said formulation is prepared from an aqueous formulation having a pH of 6.5 and comprising
 (i) an anti-BAFFR antibody wherein the antibody has a concentration of 50 mg/ml, and wherein said anti-BAFFR antibody includes heavy chain CDR1, CDR2 and CDR3 of SEQ ID NOs 3, 4 and 5 respectively, and light chain CDR1, CDR2 and CDR3 of SEQ ID NOs: 6, 7 and 8,   (ii) 90 mM sucrose as a stabilizer,   (iii) 7 mM histidine as a buffering agent,   (iv) 0.02% polysorbate 80 as a surfactant, and   (v) 17 mM arginine-HCl.   
     
     
         10 . The method of  claim 1 , wherein said formulation is prepared from an aqueous formulation having a pH of 6.5 and comprising
 (i) an anti-BAFFR antibody wherein the antibody has a concentration of 66.6 mg/ml, and wherein said anti-BAFFR antibody includes heavy chain CDR1, CDR2 and CDR3 of SEQ ID NOs 3, 4 and 5 respectively, and light chain CDR1, CDR2 and CDR3 of SEQ ID NOs: 6, 7 and 8,   (ii) 90 mM sucrose as a stabilizer,   (iii) 7 mM histidine as a buffering agent,   (iv) 0.02% polysorbate 80 as a surfactant, and   (v) 17 mM arginine-HCl.