Claims for Patent: 10,040,855

Summary for Patent: 10,040,855

Title:	Formulation for anti-.alpha.4.beta.7 antibody
Abstract:	Antibody formulations are described comprising a mixture of an anti-.alpha.4.beta.7 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-.alpha.4.beta.7 antibody in vivo.
Inventor(s):	Diluzio; Willow (Westford, MA), Nguyen; Phoung M. (Cambridge, MA), Varga; Csanad M. (Newton, MA), Palaniappan; Vaithianathan (Andover, MA), Brown; Jason (Burlington, MA)
Assignee:	Millennium Pharmaceuticals, Inc. (Cambridge, MA)
Application Number:	14/114,835
Patent Claims:	1. A stable liquid pharmaceutical formulation comprising an anti-.alpha.4.beta.7 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-.alpha.4.beta.7 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-.alpha.4.beta.7 antibody as determined by size exclusion chromatography (SEC) after storage at 40.degree. C. for 4 weeks. 2. The stable liquid pharmaceutical formulation of claim 1, wherein the molar ratio of the anti-.alpha.4.beta.7 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-.alpha.4.beta.7 antibody at a concentration of about 150 mg/ml to about 180 mg/ml, citrate, histidine, arginine, and polysorbate 80, wherein the anti-.alpha.4.beta.7 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-.alpha.4.beta.7 antibody as determined by size exclusion chromatography (SEC) after storage at 40.degree. 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 .ltoreq.2.5% aggregate antibody. 16. A stable liquid pharmaceutical formulation comprising about 140 mg/ml to about 170 mg/ml of an anti-.alpha.4.beta.7 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-.alpha.4.beta.7 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-.alpha.4.beta.7 antibody as determined by size exclusion chromatography (SEC) after storage at 40.degree. 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.degree. 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-.alpha.4.beta.7 antibody. 22. The stable liquid pharmaceutical formulation of claim 1, comprising a dose of 108 mg of the anti-.alpha.4.beta.7 antibody. 23. The stable liquid pharmaceutical formulation of claim 1, wherein the molar ratio of the surfactant to the anti-.alpha.4.beta.7 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-.alpha.4.beta.7 antibody. 25. The stable liquid pharmaceutical formulation of claim 6, comprising 150 mg/ml to 170 mg/ml of the anti-.alpha.4.beta.7 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.

Details for Patent 10,040,855

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Takeda Pharmaceuticals U.s.a., Inc.	ENTYVIO	vedolizumab	For Injection	125476	May 20, 2014	10,040,855	2031-05-02
Takeda Pharmaceuticals U.s.a., Inc.	ENTYVIO	vedolizumab	Injection	761133	September 27, 2023	10,040,855	2031-05-02
Takeda Pharmaceuticals U.s.a., Inc.	ENTYVIO PEN	vedolizumab	Injection	761133	September 27, 2023	10,040,855	2031-05-02