Liquid il-1 beta antibody formulation having ph of 5.5 to 7.0

Abstract

The present invention relates to novel pharmaceutical formulations, in particular novel pharmaceutical formulations in which the active ingredient comprises human antibodies to human interleukin I beta (IL-1β), in particular ACZ885 antibody, pharmaceutical formulations which are stable and aggregate-free upon storage and delivery.

1 . A liquid pharmaceutical formulation, comprising 50 to 150 mg/ml of an antibody to IL-1β which comprises amino acids 20 to 137 of SEQ ID NO:1 and amino acids 20 to 126 of SEQ ID NO:2, [about 270 mM mannitol,] about 10 mM to about 50 mM [a] histidine buffer and about [0.04 to 0.06%] 0.01 to 0.1% (m/v) polysorbate [80], wherein
 the pH of the formulation is 5.5 to 7.0[, wherein the pharmaceutical formulation is in liquid form], and 
 [further wherein] the formulation maintains at least about 70% activity following storage for 24 months at 25° C.[.] as determined by a reporter gene assay. 
 
     
     
         2 . The pharmaceutical formulation of  claim 1 , wherein the pH of the formulation is 6.2 to 6.8. 
     
     
         3 . The pharmaceutical formulation of  claim 2 , wherein the pH of the formulation is 6.5. 
     
     
         4 . The pharmaceutical formulation of  claim 1 , wherein the antibody is ACZ885 and the buffer is 20-30 mM histidine. 
     
     
         5 . The pharmaceutical formulation of  claim 2 , wherein the antibody is ACZ885 and the buffer is 20-30 mM histidine. 
     
     
         6 . The pharmaceutical formulation of  claim 3 , wherein the antibody is ACZ885 and the buffer is 20-30 mM histidine. 
     
     
         7 . The pharmaceutical formulation of  claim 4 , wherein the concentration of the antibody is 150 mg/ml[, the concentration of histidine is 20 mM,] and the polysorbate is selected from the group consisting of polysorbate 80 and polysorbate 20 [concentration of polysorbate 80 is 0.04% (m/v)]. 
     
     
         8 . The pharmaceutical formulation of  claim 5 , wherein the concentration of the antibody is 150 mg/ml[, the concentration of histidine is 20 mM,] and the polysorbate is selected from the group consisting of polysorbate 80 and polysorbate 20 [concentration of polysorbate 80 is 0.04% (m/v)]. 
     
     
         9 . The pharmaceutical formulation of  claim 6 , wherein the concentration of the antibody is 150 mg/ml[, the concentration of histidine is 20 mM,] and the polysorbate is selected from the group consisting of polysorbate 80 and polysorbate 20 [concentration of polysorbate 80 is 0.04% (m/v)]. 
     
     
         10 . The pharmaceutical formulation of  claim 1 , comprising about 50 to 300 mM mannitol. 
     
     
         11 . The pharmaceutical formulation of  claim 10 , wherein the mannitol is present in an amount of about 180 to 300 mM. 
     
     
         12 . The pharmaceutical formulation of  claim 11 , wherein the mannitol is present in an amount of about 270 mM. 
     
     
         13 . The pharmaceutical formulation of  claim 1 , wherein the polysorbate is selected from the group consisting of polysorbate 80 and polysorbate 20. 
     
     
         14 . The pharmaceutical formulation of  claim 12 , wherein the polysorbate is present in an amount of about 0.04 to 0.06% (m/v). 
     
     
         15 . The pharmaceutical formulation of  claim 5 , comprising about 270 mM mannitol, and wherein the polysorbate includes polysorbate 80 in an amount of 0.04 to 0.06% (m/v). 
     
     
         16 . A liquid pharmaceutical formulation, comprising 50 to 150 mg/ml of an antibody to IL-10 which comprises amino acids 20 to 137 of SEQ ID NO:1 and amino acids 20 to 126 of SEQ ID NO:2, about 10 mM to about 50 mM histidine buffer and about 0.01 to 0.1% (m/v) polysorbate, wherein
 the pH of the formulation is 5.5 to 7.0, and   the formulation maintains at least between 80% and 125% biological activity following storage for 24 months at 5° C. as determined by a reporter gene assay.   
     
     
         17 . The pharmaceutical formulation of  claim 16 , wherein the pH of the formulation is 6.2 to 6.8. 
     
     
         18 . The pharmaceutical formulation of  claim 17 , wherein the pH of the formulation is 6.5. 
     
     
         19 . The pharmaceutical formulation of  claim 16 , wherein the antibody is ACZ885 and the buffer is 20-30 mM histidine. 
     
     
         20 . The pharmaceutical formulation of  claim 17 , wherein the antibody is ACZ885 and the buffer is 20-30 mM histidine. 
     
     
         21 . The pharmaceutical formulation of  claim 18 , wherein the antibody is ACZ885 and the buffer is 20-30 mM histidine. 
     
     
         22 . The pharmaceutical formulation of  claim 19 , wherein the concentration of the antibody is 150 mg/ml and the polysorbate is selected from the group consisting of polysorbate 80 and polysorbate 20. 
     
     
         23 . The pharmaceutical formulation of  claim 20 , wherein the concentration of the antibody is 150 mg/ml and the polysorbate is selected from the group consisting of polysorbate 80 and polysorbate 20. 
     
     
         24 . The pharmaceutical formulation of  claim 21 , wherein the concentration of the antibody is 150 mg/ml and the polysorbate is selected from the group consisting of polysorbate 80 and polysorbate 20. 
     
     
         25 . The pharmaceutical formulation of  claim 16 , comprising about 50 to 300 mM mannitol. 
     
     
         26 . The pharmaceutical formulation of  claim 25 , wherein the mannitol is present in an amount of about 180 to 300 mM. 
     
     
         27 . The pharmaceutical formulation of  claim 26 , wherein the mannitol is present in an amount of about 270 mM. 
     
     
         28 . The pharmaceutical formulation of  claim 16 , wherein the polysorbate is selected from the group consisting of polysorbate 80 and polysorbate 20. 
     
     
         29 . The pharmaceutical formulation of  claim 28 , wherein the polysorbate is present in an amount of about 0.04 to 0.06% (m/v). 
     
     
         30 . The pharmaceutical formulation of  claim 19 , comprising about 270 mM mannitol, and wherein the polysorbate includes polysorbate 80 in an amount of 0.04 to 0.06% (m/v).