Claims for Patent: 11,944,602

Summary for Patent: 11,944,602

Title:	Treatment of autoimmune disease in a patient receiving additionally a beta-blocker
Abstract:	The present invention relates to methods of treating autoimmune diseases with siponimod in patients receiving additionally a beta-blocker.
Inventor(s):	Eric Legangneux, Alexandros Sagkriotis, Pierre Jordaan, Florine Polus, Alan John Camm, Shibadas Biswal, Parasar Pal, Uday Kiran Veldandi, Atul Keshav Pawar, Vassilios Aslanis, Kasra Shakeri-Nejad
Assignee:	Novartis AG
Application Number:	US17/209,940
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 11,944,602
Patent Claims:	1. A method of treating an autoimmune disease in a patient comprising a) administering to said patient an initial titration regimen of siponimod; b) administering to said patient 1-15 mg siponimod daily as a maintenance regimen; and c) introducing in said patient a beta-blocker treatment the earliest at the first day when said patient is receiving the dosage of the maintenance regimen; wherein said initial titration regimen comprises administering siponimod at a dosage lower than the dosage of the maintenance regimen and then increasing the dosage stepwise up to the dosage of the maintenance regimen. 2. The method according to claim 1, wherein said autoimmune disease is selected from inflammatory myopathy and multiple sclerosis. 3. The method according to claim 1, wherein said autoimmune disease is selected from polymyositis, dermatomyositis, inclusion-body myositis and secondary progressive multiple sclerosis. 4. The method according to claim 1, wherein said autoimmune disease is secondary progressive multiple sclerosis. 5. The method according to claim 1, wherein the maintenance regimen administered in step b) of said method comprises 2-10 mg siponimod. 6. The method according to claim 5, wherein said maintenance regimen comprises 2-5 mg siponimod. 7. The method according to claim 1, wherein the maintenance regimen administered in step b) of said method is administered once daily. 8. The method according to claim 1, wherein in the maintenance regimen administered in step b) of said method an immediate release dosage form is used. 9. The method according to claim 1, wherein said initial titration regimen comprises administering siponimod such that the dosage administered on a specific day of the initial titration regimen is the sum of the dosages administered on the previous two days within a range of ±40%. 10. The method according to claim 1, wherein said initial titration regimen is conducted over 3-10 days. 11. The method according to claim 1, wherein the dosage of the maintenance regimen is 2 mg siponimod and wherein said initial titration regimen comprises administering 0.25 mg siponimod at day 1, 0.25 mg of siponimod at day 2, 0.5 mg siponimod at day 3, 0.75 mg siponimod at day 4, 1.25 mg siponimod at day 5 and 2 mg siponimod at day 6. 12. The method according to claim 11, wherein said initial titration regimen comprises one administration of 0.25 mg siponimod at day 1, one administration of 0.25 mg siponimod at day 2, one administration of 0.5 mg siponimod at day 3, one administration of 0.75 mg siponimod at day 4, one administration of 1.25 mg siponimod at day 5 and one administration of 2 mg siponimod at day 6. 13. The method according to claim 12, wherein, in said initial titration regimen, immediate release dosage forms comprising 0.25 mg, 0.5 mg, 1 mg and 2 mg siponimod are used. 14. The method according to claim 1, wherein said autoimmune disease is secondary progressive multiple sclerosis; wherein the maintenance regimen administered in step b) of said method is an immediate release dosage form comprising 2 mg siponimod; wherein the maintenance regimen administered in step b) of said method is administered once daily; wherein the initial titration regimen administered in step a) of said method comprises one administration of 0.25 mg siponimod at day 1, one administration of 0.25 mg siponimod at day 2, one administration of 0.5 mg siponimod at day 3, one administration of 0.75 mg siponimod at day 4, one administration of 1.25 mg siponimod at day 5 and one administration of 2 mg siponimod at day 6; and wherein in the initial titration regimen administered in step a) of said method immediate release dosage forms comprising 0.25 mg, 0.5 mg, 1 mg and 2 mg siponimod are used. 15. A method of treating an autoimmune disease in a patient receiving a chronic beta-blocker treatment and having a resting heart rate of >50 bpm under said chronic beta-blocker treatment comprising introducing in said patient a siponimod treatment by a) administering to said patient an initial titration regimen of siponimod; and b) administering to said patient 1-15 mg siponimod daily as a maintenance regimen; wherein said initial titration regimen comprises administering siponimod at a dosage lower than the dosage of the maintenance regimen and then increasing the dosage stepwise up to the dosage of the maintenance regimen. 16. The method according to claim 15, wherein said autoimmune disease is selected from inflammatory myopathy and multiple sclerosis. 17. The method according to claim 15, wherein said autoimmune disease is selected from polymyositis, dermatomyositis, inclusion-body myositis and secondary progressive multiple sclerosis. 18. The method according to claim 15, wherein said autoimmune disease is secondary progressive multiple sclerosis. 19. The method according to claim 15, wherein the maintenance regimen administered in step b) of said method comprises 2-10 mg siponimod. 20. The method according to claim 19, wherein said maintenance regimen comprises 2-5 mg siponimod. 21. The method according to claim 15, wherein the maintenance regimen administered in step b) of said method is administered once daily. 22. The method according to claim 15, wherein the maintenance regimen administered in step b) of said method is administered as an immediate release dosage form. 23. The method according to claim 15, wherein said initial titration regimen comprises administering siponimod such that the dosage administered on a specific day of the initial titration regimen is the sum of the dosages administered on the previous two days within a range of ±40%. 24. The method according to claim 15, wherein said initial titration regimen is conducted over 3-10 days. 25. The method according to claim 15, wherein the dosage of the maintenance regimen is 2 mg siponimod and wherein said initial titration regimen comprises administering 0.25 mg siponimod at day 1, 0.25 mg of siponimod at day 2, 0.5 mg siponimod at day 3, 0.75 mg siponimod at day 4, 1.25 mg siponimod at day 5 and 2 mg siponimod at day 6. 26. The method according to claim 25, wherein said initial titration regimen comprises one administration of 0.25 mg siponimod at day 1, one administration of 0.25 mg siponimod at day 2, one administration of 0.5 mg siponimod at day 3, one administration of 0.75 mg siponimod at day 4, one administration of 1.25 mg siponimod at day 5 and one administration of 2 mg siponimod at day 6. 27. The method according to claim 26, wherein, in said initial titration regimen, immediate release dosage forms comprising 0.25 mg, 0.5 mg, 1 mg and 2 mg siponimod are used. 28. The method according to claim 15, wherein said autoimmune disease is secondary progressive multiple sclerosis; wherein the maintenance regimen administered in step b) of said method is an immediate release dosage form comprising 2 mg siponimod; wherein the maintenance regimen administered in step b) of said method is administered once daily; wherein the initial titration regimen administered in step a) of said method comprises one administration of 0.25 mg siponimod at day 1, one administration of 0.25 mg siponimod at day 2, one administration of 0.5 mg siponimod at day 3, one administration of 0.75 mg siponimod at day 4, one administration of 1.25 mg siponimod at day 5 and; and one administration of 2 mg siponimod at day 6; wherein in the initial titration regimen administered in step a) of said method immediate release dosage forms comprising 0.25 mg, 0.5 mg, 1 mg and 2 mg siponimod are used. 29. A method of treating an autoimmune disease in a patient receiving a chronic beta-blocker treatment and having a resting heart rate of ≤50 bpm under said chronic beta-blocker treatment comprising a) interrupting said chronic beta-blocker treatment in said patient until the baseline heart-rate is >50 bpm; b) initiating in said patient a siponimod treatment by b1) administering to said patient an initial titration regimen of siponimod; and b2) administering to said patient 1-15 mg siponimod daily as a maintenance regimen; and c) re-initiating in said patient a beta-blocker treatment the earliest at the first day when said patient is receiving the dosage of the maintenance regimen; wherein said initial titration regimen comprises administering siponimod at a dosage lower than the dosage of the maintenance regimen and then increasing the dosage stepwise up to the dosage of the maintenance regimen. 30. The method according to claim 29, wherein said autoimmune disease is selected from inflammatory myopathy and multiple sclerosis. 31. The method according to claim 29, wherein said autoimmune disease is selected from polymyositis, dermatomyositis, inclusion-body myositis and secondary progressive multiple sclerosis. 32. The method according to claim 29, wherein said autoimmune disease is secondary progressive multiple sclerosis. 33. The method according to claim 29, wherein the maintenance regimen administered in step b2) of said method comprises 2-10 mg siponimod. 34. The method according to claim 33, wherein said maintenance regimen comprises 2-5 mg siponimod. 35. The method according to claim 29, wherein the maintenance regimen administered in step b2) of said method is administered once daily. 36. The method according to claim 29, wherein the maintenance regimen administered in step b2) of said method is administered as an immediate release dosage form. 37. The method according to claim 29, wherein said initial titration regimen comprises administering siponimod such that the dosage administered on a specific day of the initial titration regimen is the sum of the dosages administered on the previous two days within a range of ±40%. 38. The method according to claim 29 wherein said initial titration regimen is conducted over 3-10 days. 39. The method according to claim 29, wherein the dosage of the maintenance regimen is 2 mg siponimod and wherein said initial titration regimen comprises administering 0.25 mg siponimod at day 1, 0.25 mg of siponimod at day 2, 0.5 mg siponimod at day 3, 0.75 mg siponimod at day 4, 1.25 mg siponimod at day 5 and 2 mg siponimod at day 6. 40. The method according to claim 39, wherein said initial titration regimen comprises one administration of 0.25 mg siponimod at day 1, one administration of 0.25 mg siponimod at day 2, one administration of 0.5 mg siponimod at day 3, one administration of 0.75 mg siponimod at day 4, one administration of 1.25 mg siponimod at day 5 and one administration of 2 mg siponimod at day 6. 41. The method according to claim 40, wherein, in said initial titration regimen, immediate release dosage forms comprising 0.25 mg, 0.5 mg, 1 mg and 2 mg siponimod are used. 42. The method according to claim 29, wherein the beta-blocker treatment re-initiated in step c) of said method is re-initiated after 2-3 weeks of treatment with siponimod. 43. The method according to claim 29, wherein said autoimmune disease is secondary progressive multiple sclerosis; wherein the maintenance regimen administered in step b2) of said method is an immediate release dosage form comprising 2 mg siponimod; wherein the maintenance regimen administered in step b2) of said method is administered once daily; wherein the initial titration regimen administered in step b1) of said method comprises one administration of 0.25 mg siponimod at day 1, one administration of 0.25 mg siponimod at day 2, one administration of 0.5 mg siponimod at day 3, one administration of 0.75 mg siponimod at day 4, one administration of 1.25 mg siponimod at day 5 and one administration of 2 mg siponimod at day 6; wherein in the initial titration regimen administered in step b1) of said method immediate release dosage forms comprising 0.25 mg, 0.5 mg, 1 mg and 2 mg siponimod are used; and wherein the beta-blocker treatment re-initiated in step c) of said method is re-initiated after 2 weeks of treatment with siponimod.