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 a humanized anti-α4β7 antibody, citrate, at least one free amino acid, and a buffering agent, wherein the humanized anti-α4β7 antibody is an IgG1 isotype and 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, wherein the liquid formulation has a pH of 6 to 7, wherein the liquid formulation comprises 100 mg/ml to 180 mg/ml of the humanized anti-α4β7 antibody, and wherein the liquid formulation has less than or equal to 2.5% aggregate determined by size exclusion chromatography (SEC) after storage at 40 degrees Celsius for 4 weeks.
2. The stable liquid pharmaceutical formulation of claim 1 , wherein the molar ratio of the humanized 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, glutamic acid and combinations thereof.
4. The stable liquid pharmaceutical formulation of claim 1 , wherein said formulation further comprises a surfactant.
5. The stable liquid pharmaceutical formulation of claim 4 , wherein the molar ratio of citrate to the surfactant is about 3:1 to about 156:1.
6. The stable liquid pharmaceutical formulation of claim 1 , wherein said humanized anti-α4β7 antibody is vedolizumab.
7. 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.
8. 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 to 131 of SEQ ID NO:4.
9. The stable liquid pharmaceutical formulation of claim 1 , wherein the liquid formulation has less than 2.0% antibody aggregate formation at about 25° C. after 12 months as determined by size exclusion chromatography (SEC).
10. A stable liquid pharmaceutical formulation comprising a humanized anti-α4β7 antibody, citrate, arginine, and a buffering agent, wherein the humanized anti-α4β7 antibody is an IgG1 isotype and 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, wherein the formulation has a pH of 6 to 7, wherein the liquid formulation comprises 100 mg/ml to 180 mg/ml of the humanized anti-α4β7 antibody, and wherein the liquid formulation has less than or equal to 2.5% aggregate determined by size exclusion chromatography (SEC) after storage at 40 degrees Celsius for 4 weeks.
11. The stable liquid pharmaceutical formulation of claim 10 , 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.
12. The stable liquid pharmaceutical formulation of claim 10 , 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 to 131 of SEQ ID NO:4.
13. The stable liquid pharmaceutical formulation of claim 10 , wherein the humanized anti-α4β7 antibody is vedolizumab.
14. The stable liquid pharmaceutical formulation of claim 10 , further comprising a surfactant.
15. The stable liquid pharmaceutical formulation of claim 14 , wherein the molar ratio of surfactant to antibody is form about 0.7:1 to about 1.5:1.
16. The stable liquid pharmaceutical formulation of claim 14 , wherein the surfactant is a polysorbate.
17. The stable liquid pharmaceutical formulation of claim 10 , wherein the buffering agent is histidine.
18. The stable liquid pharmaceutical formulation of claim 17 , comprising 10 mM to 75 mM histidine.
19. The stable liquid pharmaceutical formulation of claim 10 , wherein the liquid formulation has less than 2.0% antibody aggregate formation at about 25° C. after 12 months as determined by size exclusion chromatography (SEC).
20. The stable liquid pharmaceutical formulation of claim 10 , comprising 20 mM to 30 mM citrate.
21. The stable liquid pharmaceutical formulation of claim 10 , comprising 50 to 150 mM arginine.
22. The stable liquid pharmaceutical formulation of claim 1 , comprising a dose of 108 mg of the humanized anti-α4β7 antibody.
23. The stable liquid pharmaceutical formulation of claim 10 , comprising a dose of 108 mg of the humanized anti-α4β7 antibody.
24. The stable liquid pharmaceutical formulation of claim 4 , wherein the molar ratio of surfactant to antibody is form about 0.7:1 to about 1.5:1.
25. The stable liquid pharmaceutical formulation of claim 4 , wherein the surfactant is a polysorbate.
26. A container comprising the stable liquid pharmaceutical formulation of claim 1 , wherein the container is selected from the group consisting of an autoinjector, a preloaded syringe, or a cartridge.
27. A container comprising the stable liquid pharmaceutical formulation of claim 10 , wherein the container is selected from the group consisting of an autoinjector, a preloaded syringe, or a cartridge.
28. The stable liquid pharmaceutical formulation of claim 1 , wherein the formulation is prepared for self-administration by a human subject.
29. The stable liquid pharmaceutical formulation of claim 10 , wherein the formulation is prepared for self-administration by a human subject.
30. The stable liquid pharmaceutical formulation of claim 1 , wherein the liquid formulation has less than about 2.5% aggregate at 25 degrees Celsius as determined by size exclusion chromatography (SEC).
31. The stable liquid pharmaceutical formulation of claim 10 , wherein the liquid formulation has less than about 2.5% aggregate at 25 degrees Celsius as determined by size exclusion chromatography (SEC).
32. The stable liquid pharmaceutical formulation of claim 1 , comprising 5 mM to 50 mM citrate.
33. The stable liquid pharmaceutical formulation of claim 10 , comprising 5 mM to 50 mM citrate.