Formulation for anti-alpha4beta7 antibody

Abstract

Antibody formulations are described comprising a mixture of an anti-α4β7 antibody, an antioxidant or chelator, and at least one free amino acid. The disclosed formulations may have improved stability, reduced aggregate formation, or both. The present invention further provides a safe dosing regimen of these antibody formulations that is easy to follow, and which results in a therapeutically effective amount of the anti-α4β7 antibody in vivo.

What is claimed is: 
     
         1 . A stable liquid pharmaceutical formulation comprising a mixture of an anti-α4β7 antibody, an antioxidant or chelator, and at least one free amino acid, wherein the formulation is in liquid form, and the antigen-binding region comprises the CDRs:
 Light chain: CDR1 SEQ ID NO:11
 CDR2 SEQ ID NO:12 
 CDR3 SEQ ID NO:13 
 
 Heavy chain: CDR1 SEQ ID NO:8
 CDR2 SEQ ID NO:9 
 CDR3 SEQ ID NO:10. 
 
 
     
     
         2 . The stable liquid pharmaceutical formulation of  claim 1 , wherein the molar ratio of the anti-α4β7 antibody to the antioxidant or chelator is about 1:4 to about 1:100. 
     
     
         3 . The stable liquid pharmaceutical formulation of  claim 1 , wherein after 12 months at 5° C. the stable liquid formulation has less than about 1.0% aggregate formation. 
     
     
         4 . The stable liquid pharmaceutical formulation of  claim 3 , wherein said formulation has less than about 0.2% aggregate formation. 
     
     
         5 . The stable liquid pharmaceutical formulation of  claim 1 , wherein said antioxidant or chelator is citrate. 
     
     
         6 . The stable liquid pharmaceutical formulation of  claim 1 , wherein said chelator is EDTA. 
     
     
         7 . The stable liquid pharmaceutical formulation of  claim 1 , wherein said free amino acid is selected from the group consisting of histidine, alanine, arginine, glycine, glutamic acid and combinations thereof. 
     
     
         8 . The stable liquid pharmaceutical formulation of  claim 1 , wherein said formulation further comprises a surfactant. 
     
     
         9 . The stable liquid pharmaceutical formulation of  claim 8 , wherein the molar ratio of the antioxidant or chelator to the surfactant is about 3:1 to about 156:1. 
     
     
         10 . The stable liquid pharmaceutical formulation of  claim 8 , wherein said surfactant is selected from the group consisting of polysorbate 20, polysorbate 80, a poloxamer and combinations thereof. 
     
     
         11 . The stable liquid pharmaceutical formulation of  claim 1 , wherein said formulation has a pH between about 6.1 and about 7.0. 
     
     
         12 . The stable liquid pharmaceutical formulation of  claim 1 , wherein said formulation has a pH between about 6.5 and about 6.8. 
     
     
         13 . The stable liquid pharmaceutical formulation of  claim 1 , wherein said formulation comprises at least about 60 mg/ml to about 160 mg/ml anti-α4β7 antibody. 
     
     
         14 . The stable liquid pharmaceutical formulation of  claim 1 , wherein said formulation comprises at least about 160 mg/ml anti-α4β7 antibody. 
     
     
         15 . A stable liquid pharmaceutical formulation comprising at least about 60 mg/ml to about 160 mg/ml anti-α4β7 antibody, a buffering agent and at least about 5 mM citrate, wherein said formulation is a liquid formulation. 
     
     
         16 . The stable liquid pharmaceutical formulation of  claim 15 , wherein said buffering agent is histidine buffer. 
     
     
         17 . A stable liquid pharmaceutical formulation comprising at least about 160 mg/ml anti-α4β7 antibody and at least about 5 mM citrate. 
     
     
         18 . The stable liquid pharmaceutical formulation of  claim 17 , wherein said formulation further comprises polysorbate 80. 
     
     
         19 . A stable liquid pharmaceutical formulation comprising a mixture of an anti-α4β7 antibody, citrate, histidine, arginine, and polysorbate 80, wherein the formulation is in liquid form. 
     
     
         20 . The stable liquid pharmaceutical formulation of  claim 19 , wherein said formulation is present in a container selected from the group consisting of a vial, cartridge, syringe and autoinjector. 
     
     
         21 . A stable liquid formulation selected from any one of the formulations in Table 2. 
     
     
         22 . The stable liquid pharmaceutical formulation of any one of  claims 1 - 21 , wherein said antibody is vedolizumab. 
     
     
         23 . The stable liquid pharmaceutical formulation of  claim 1 , wherein the humanized anti-α4β7 antibody comprises a heavy chain variable region comprising amino acids that are at least 95% identical to amino acids 20 to 140 of SEQ ID NO:2, and a light chain variable region comprising amino acids that are at least 95% identical to amino acids 20 to 131 of SEQ ID NO:4. 
     
     
         24 . The stable liquid pharmaceutical formulation of  claim 1 , wherein the humanized anti-α4β7 antibody comprises a heavy chain variable region comprising amino acids 20 to 140 of SEQ ID NO:2, and a light chain variable region comprising amino acids to 20 to 131 of SEQ ID NO:4.