Claims for Patent: 12,102,619

Summary for Patent: 12,102,619

Title:	Methods of treating tuberous sclerosis complex with cannabidiol and everolimus
Abstract:	The present disclosure provides methods of treating tuberous sclerosis complex comprising administering cannabidiol and everolimus.
Inventor(s):	Geoffrey Guy, Volker Knappertz, Eduardo Dunayevich, David CRITCHLEY
Assignee:	Jazz Pharmaceuticals Research Uk Ltd
Application Number:	US17/841,167
Patent Claims:	1. A method of initiating everolimus treatment in a human who is suffering from tuberous sclerosis complex and has seizures and who is currently being treated with a therapeutically effective amount of cannabidiol, the method comprising: (a) co-administering a reduced starting dose of everolimus and the therapeutically effective amount of cannabidiol to the human, wherein the reduced starting dose of everolimus ranges from about 2.25 mg/m2 to about 4.5 mg/m2 once daily; (b) monitoring the human's blood plasma concentration of everolimus; and (c) increasing the starting dose of everolimus administered in step (a) to a dose that achieves a blood plasma trough concentration of everolimus ranging from 5-15 ng/ml, Cmax of everolimus that is less than or equal to 50 ng/mL, or AUC0-24 of everolimus that is less than or equal to 500 h*ng/ml; wherein said monitoring in step (b) occurs one to two weeks after the human begins receiving everolimus; wherein cannabidiol is synthetic or purified. 2. The method of claim 1, wherein the therapeutically effective amount of cannabidiol ranges from about 5 mg/kg/day to about 25 mg/kg/day. 3. The method of claim 1, wherein the therapeutically effective amount of cannabidiol is 25 mg/kg/day. 4. The method of claim 1, wherein the human has normal hepatic status or mild hepatic impairment, and the amount of cannabidiol administered in step (a) is about 25 mg/kg/day. 5. The method of claim 1, wherein the human has moderate hepatic impairment, and the amount of cannabidiol administered in step (a) is about 12.5 mg/kg/day. 6. The method of claim 1, wherein the human has severe hepatic impairment, and the amount of cannabidiol administered in step (a) is about 5 mg/kg/day. 7. The method of claim 1, wherein the cannabidiol is purified. 8. The method of claim 7, wherein the cannabidiol has a purity of at least 95% (w/w) cannabidiol. 9. The method of claim 8, wherein the cannabidiol has a purity of at least 98% (w/w) cannabidiol. 10. The method of claim 1, wherein the reduced starting dose of everolimus administered in step (a) ranges from about 2.5 mg/m2 to about 4.5 mg/m2 once daily of everolimus. 11. The method of claim 1, wherein the reduced starting dose of everolimus administered in step (a) is about 2.5 mg/m2 once daily of everolimus. 12. The method of claim 1, wherein the everolimus is administered to treat Tuberous Sclerosis Complex associated partial onset seizures. 13. The method of claim 1, wherein the reduced starting dose of everolimus administered in step (a) ranges from about 2.25 mg/m2 to about 4.1 mg/m2 once daily of everolimus. 14. The method of claim 1, wherein the reduced starting dose of everolimus administered in step (a) is about 2.25 mg/m2 once daily of everolimus. 15. The method of claim 1, wherein the everolimus is administered to treat Tuberous Sclerosis Complex associated subependylam giant cell astrocytoma. 16. The method of claim 1, wherein the everolimus is administered to treat Tuberous Sclerosis Complex associated renal angiomyolipoma. 17. The method of claim 1, comprising treating generalized seizures. 18. The method of claim 17, wherein the generalized seizures are tonic-clonic, tonic, clonic or atonic seizures. 19. The method of claim 1, comprising treating focal seizures. 20. The method of claim 19, wherein the focal seizures are focal motor seizures without impairment of consciousness or awareness; focal seizures with impairment of consciousness or awareness; or focal seizures evolving to bilateral generalized convulsive seizures and generalized seizures. 21. The method of claim 1, comprising reducing the total number of seizures compared to the number of seizures experienced during a baseline period before cannabidiol was administered. 22. The method of claim 21, wherein the total number of seizures is reduced by at least 50% compared to the number of seizures experienced during a baseline period before cannabidiol was administered. 23. The method of claim 1, wherein step (c) comprises increasing the starting dose of everolimus administered in step (a) to a dose that achieves a blood plasma trough concentration of everolimus ranging from 5-15 ng/mL. 24. The method of claim 1, wherein the reduced starting dose of everolimus administered in step (a) comprises administering 4.5 mg/m2 once daily of everolimus every other day.