FORMULATION FOR ANTI-ALPHA4BETA7 ANTIBODY
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.
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.