Formulation for anti-α4β7 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 an anti-α4β7 antibody at a concentration of about 150 mg/ml to about 180 mg/ml, citrate, at least one free amino acid, a buffering agent, and a surfactant, wherein the anti-α4β7 antibody is an IgG1 isotype comprising a light chain variable region comprising a CDR1 comprising SEQ ID NO: 11, a CDR2 comprising SEQ ID NO: 12, and a CDR3 comprising SEQ ID NO: 13, and comprising a heavy chain variable region comprising a CDR1 comprising SEQ ID NO:8, a CDR2 comprising SEQ ID NO: 9, and a CDR3 comprising SEQ ID NO: 10, and wherein the formulation has a pH of 6 to 7, and wherein the formulation has greater than or equal to 96% monomeric anti-α4β7 antibody as determined by size exclusion chromatography (SEC) after storage at 40° C. for 4 weeks.
2. The stable liquid pharmaceutical formulation of claim 1 , wherein the molar ratio of the anti-α4β7 antibody to citrate is about 1:4 to about 1:100.
3. The stable liquid pharmaceutical formulation of claim 1 , wherein said free amino acid is selected from the group consisting of histidine, alanine, arginine, glycine, and glutamic acid.
4. The stable liquid pharmaceutical formulation of claim 1 , wherein the molar ratio of citrate to the surfactant is about 3:1 to about 156:1.
5. The stable liquid pharmaceutical formulation of claim 1 , wherein said surfactant is polysorbate 80.
6. A stable liquid pharmaceutical formulation comprising an anti-α4β7 antibody at a concentration of about 150 mg/ml to about 180 mg/ml, citrate, histidine, arginine, and polysorbate 80, wherein the anti-α4β7 antibody comprises a light chain variable region comprising a CDR1 comprising SEQ ID NO: 11, a CDR2 comprising SEQ ID NO: 12, and a CDR3 comprising SEQ ID NO: 13, and comprises a heavy chain variable region comprising a CDR1 comprising SEQ ID NO:8, a CDR2 comprising SEQ ID NO: 9, and a CDR3 comprising SEQ ID NO: 10, and wherein the formulation has greater than or equal to 96% monomeric anti-α4β7 antibody as determined by size exclusion chromatography (SEC) after storage at 40° C. for 4 weeks.
7. The stable liquid pharmaceutical formulation of claim 1 , wherein said antibody is vedolizumab.
8. The stable liquid pharmaceutical formulation of claim 6 , wherein said antibody is vedolizumab.
9. The stable liquid pharmaceutical formulation of claim 1 , wherein the concentration of citrate is 20 mM to 30 mM.
10. The stable liquid pharmaceutical formulation of claim 1 , wherein said free amino acid is arginine at a concentration of 50 mM to 150 mM.
11. The stable liquid pharmaceutical formulation of claim 1 , wherein the buffering agent is histidine.
12. The stable liquid pharmaceutical formulation of claim 11 , wherein the concentration of histidine is 25 mM to 65 mM.
13. The stable liquid pharmaceutical formulation of claim 1 , wherein the heavy chain variable region comprises amino acids 20-140 of SEQ ID NO:2 and the light chain variable region comprises amino acids 20-131 of SEQ ID NO:4.
14. The stable liquid pharmaceutical formulation of claim 1 , wherein said formulation has a pH between 6.2 and 6.8.
15. The stable liquid pharmaceutical formulation of claim 1 , wherein there is ≤2.5% aggregate antibody.
16. A stable liquid pharmaceutical formulation comprising about 140 mg/ml to about 170 mg/ml of an anti-α4β7 antibody, about 20 mM to about 30 mM citrate, about 10 mM to about 75 mM histidine, about 0.01% to about 0.5% (w/v) polysorbate 80, and about 50 mM to about 150 mM arginine, wherein the anti-α4β7 antibody is an IgG1 isotype comprising a light chain variable region comprising a CDR1 comprising SEQ ID NO:11, a CDR2 comprising SEQ ID NO: 12, and a CDR3 comprising SEQ ID NO: 13, and comprising a heavy chain variable region comprising a CDR1 comprising SEQ ID NO:8, a CDR2 comprising SEQ ID NO: 9, and a CDR3 comprising SEQ ID NO: 10, and wherein the formulation has greater than or equal to 96% monomeric anti-α4β7 antibody as determined by size exclusion chromatography (SEC) after storage at 40° C. for 4 weeks.
17. The stable liquid pharmaceutical formulation of claim 16 , wherein the heavy chain variable region comprises amino acids 20-140 of SEQ ID NO:2 and the light chain variable region comprises amino acids 20-131 of SEQ ID NO:4.
18. The stable liquid pharmaceutical formulation of claim 16 , wherein said antibody is vedolizumab.
19. The stable liquid pharmaceutical formulation of claim 1 , wherein after 12 months at 5° C. the stable liquid pharmaceutical formulation has less than about 1.0% antibody aggregate formation.
20. The stable liquid pharmaceutical formulation of claim 6 , wherein the heavy chain variable region comprises amino acids 20-140 of SEQ ID NO:2 and the light chain variable region comprises amino acids 20-131 of SEQ ID NO:4.
21. The stable liquid pharmaceutical formulation of claim 6 , comprising a dose of 108 mg of the anti-α4β7 antibody.
22. The stable liquid pharmaceutical formulation of claim 1 , comprising a dose of 108 mg of the anti-α4β7 antibody.
23. The stable liquid pharmaceutical formulation of claim 1 , wherein the molar ratio of the surfactant to the anti-α4β7 antibody is 0.7:1 to 2.0:1.
24. The stable liquid pharmaceutical formulation of claim 16 , comprising a dose of 108 mg of the anti-α4β7 antibody.
25. The stable liquid pharmaceutical formulation of claim 6 , comprising 150 mg/ml to 170 mg/ml of the anti-α4β7 antibody, wherein the antibody is an IgG1 isotype.
26. The stable liquid pharmaceutical formulation of claim 6 , wherein the concentration of histidine is about 25 mM to about 50 mM.
27. The stable liquid pharmaceutical formulation of claim 26 , wherein the concentration of arginine is 50 mM to 150 mM.
28. The stable liquid pharmaceutical formulation of claim 26 , wherein the concentration of citrate is about 5 mM to about 50 mM.
29. The stable liquid pharmaceutical formulation of claim 5 , comprising 0.1% to 0.3% (w/v) polysorbate 80.