Claims for Patent: 12,370,163

Summary for Patent: 12,370,163

Title:	Levodopa dosing regimen
Abstract:	The invention is a method for treating levodopa naïve patients with Parkinson's disease by orally administering a controlled release levodopa formulation twice a day to the levodopa naïve patient and the method provides an improvement of a patient's motor state as determined by patient's Parkinson's disease diary, provides a reduction of from about 10%-40% in the patient's tremor, dyskinesia, and/or mobility and/or provides a reduction in the patient's Movement Disorders Society version of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS) scores by at least 3 points.
Inventor(s):	Richard D'Souza, Hester Visser, Suneel Gupta
Assignee:	Amneal Pharmaceuticals LLC
Application Number:	US19/022,531
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 12,370,163
Patent Claims:	1. A method for treating a levodopa naïve patient with Parkinson's disease comprising an oral administration of a multiparticulate controlled release levodopa dosage form comprising: a) a controlled release component comprising a plurality of beads that pass through a 12 mesh screen but are retained on a 24 mesh screen wherein the beads are substantially free of carbidopa, free of a catechol-O-methyl transferase inhibitor and comprise: (i) a core comprising levodopa, (ii) a controlled release coating surrounding the core, (iii) a coating comprising a muco-adhesive polymer surrounding the controlled release coating and (iv) a coating comprising an enteric coating polymer surrounding the coating comprising the muco-adhesive polymer; and (b) an immediate release component comprising levodopa and carbidopa; wherein the controlled release dosage form is administered twice a day with each dose administered each time comprising 140 mg of levodopa and a total daily administered levodopa dose of 280 mg; wherein the patient is not being treated with a catechol-O-methyl transferase inhibitor and the patient has not been previously treated with levodopa; and wherein twice a day dosing improves the patient's motor state by about 10% to 50% as determined by patient's Parkinson's disease diary. 2. The method of claim 1, wherein the immediate release component comprises from about 80% to about 100% of the total amount of carbidopa in the multiparticulate controlled release formulation. 3. The method of claim 2, wherein the multiparticulate controlled release dosage form when tested using a USP Apparatus I at 75 rpms and 37°±0.5° C. with 500-900 ml of simulated gastric fluid for 2 hours and pH 6.8 phosphate buffer thereafter exhibits the following levodopa release profile: 20% to 60% of levodopa is released after 2 hours; 40% to 80% of levodopa is released after 3 hours; 60% to 100% of levodopa is released after 4 hours; and not less than 80% is released after 7 hours, wherein the simulated gastric fluid has a pH of about 1 to about 4. 4. The method of claim 2, wherein the controlled release coating comprises a controlled release material selected from the group consisting of ethyl cellulose, cellulose acetate, and mixtures thereof. 5. The method of claim 2, wherein the mucoadhesive polymer is capable of forming a positive ionic charge at pHs present in the human gastrointestinal tract. 6. The method of claim 5, wherein the mucoadhesive polymer is an amino methacrylate copolymer. 7. The method of claim 6, wherein the amino methacrylate copolymer is poly(butyl methacrylate-co-(2-dimethylaminoethyl)methacrylate-co-methylmethacrylate). 8. The method of claim 2, wherein after administration the controlled release dosage form provides a levodopa plasma level of at least about 300 ng/mL within about 1 hour after administration and after twice a day administration of the controlled release dosage form for at least 7 days provides a minimum levodopa plasma level at least about 250 ng/mL at about six hours after dosing. 9. The method of claim 2, wherein after administration of the controlled release dosage form twice a day for at least 7 days, the minimum carbidopa plasma level is at least about 40 ng/mL seven to eight hours after dosing. 10. The method of claim 2, wherein the patient is newly diagnosed with Parkinson's disease. 11. The method of claim 2, wherein the Parkinson's disease is primary parkinsonism, postencephalitic parkinsonism, parkinsonism following carbon monoxide intoxication, or parkinsonism following manganese intoxication. 12. A method for treating a levodopa naïve patient with Parkinson's disease comprising an oral administration of a multiparticulate controlled release levodopa dosage form comprising: a) a controlled release component comprising a plurality of beads that pass through a 12 mesh screen but are retained on a 24 mesh screen wherein the beads are substantially free of carbidopa, free of a catechol-O-methyl transferase inhibitor and comprise: (i) a core comprising levodopa, (ii) a controlled release coating surrounding the core, (iii) a coating comprising a muco-adhesive polymer surrounding the controlled release coating, and (iv) a coating comprising an enteric coating polymer surrounding the coating comprising the muco-adhesive polymer; and (b) an immediate release component comprising levodopa and carbidopa; wherein the controlled release dosage form is administered twice a day with each dose administered each time comprising 140 mg of levodopa and a total daily administered levodopa dose of 280 mg; wherein the patient is not being treated with a catechol-O-methyl transferase inhibitor and the patient has not been previously treated with levodopa; and wherein the twice a day dosing provides a reduction of from about 10%-40% in the patient's tremor, dyskinesia, and/or mobility. 13. The method of claim 12, wherein the immediate release component comprises from about 80% to about 100% of the total amount of carbidopa in the multiparticulate controlled release formulation. 14. The method of claim 13, wherein the multiparticulate controlled release dosage form when tested using a USP Apparatus I at 75 rpms and 37°±0.5° C. with 500-900 ml of simulated gastric fluid for 2 hours and pH 6.8 phosphate buffer thereafter exhibits the following levodopa release profile: 20% to 60% of levodopa is released after 2 hours; 40% to 80% of levodopa is released after 3 hours; 60% to 100% of levodopa is released after 4 hours; and not less than 80% is released after 7 hours, wherein the simulated gastric fluid has a pH of about 1 to about 4. 15. The method of claim 13, wherein the controlled release coating comprises a controlled release material selected from the group consisting of ethyl cellulose, cellulose acetate, and mixtures thereof. 16. The method of claim 13, wherein the mucoadhesive polymer is capable of forming a positive ionic charge at pHs present in the human gastrointestinal tract. 17. The method of claim 16, wherein the mucoadhesive polymer is an amino methacrylate copolymer. 18. The method of claim 17, wherein the amino methacrylate copolymer is poly(butyl methacrylate-co-(2-dimethylaminoethyl)methacrylate-co-methylmethacrylate). 19. The method of claim 13, wherein after administration the controlled release dosage form provides a levodopa plasma level of at least about 300 ng/mL within about 1 hour after administration and after twice a day administration of the controlled release dosage form for at least 7 days provides a minimum levodopa plasma level at least about 250 ng/mL at about six hours after dosing. 20. The method of claim 13, wherein after administration of the controlled release dosage form twice a day for at least 7 days, the minimum carbidopa plasma level is at least about 40 ng/mL seven to eight hours after dosing. 21. The method of claim 13, wherein the patient is newly diagnosed with Parkinson's disease. 22. The method of claim 13, wherein the Parkinson's disease is primary parkinsonism, postencephalitic parkinsonism, parkinsonism following carbon monoxide intoxication, or parkinsonism following manganese intoxication. 23. A method for treating a levodopa naïve patient with Parkinson's disease comprising an oral administration of a multiparticulate controlled release levodopa dosage form comprising: a) a controlled release component comprising a plurality of beads that pass through a 12 mesh screen but are retained on a 24 mesh screen wherein the beads are substantially free of carbidopa, free of a catechol-O-methyl transferase inhibitor and comprise: (i) a core comprising levodopa, (ii) a controlled release coating surrounding the core, (iii) a coating comprising a muco-adhesive polymer surrounding the controlled release coating, and (iv) a coating comprising an enteric coating polymer surrounding the coating comprising the muco-adhesive polymer; and (b) an immediate release component comprising levodopa and carbidopa; wherein the controlled release dosage form is administered twice a day with each dose administered each time comprising 140 mg of levodopa and a total daily administered levodopa dose of 280 mg; wherein the patient is not being treated with a catechol-O-methyl transferase inhibitor and the patient has not been previously treated with levodopa; and wherein the twice a day dosing reduces the patient's Movement Disorders Society version of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS) scores by at least 3 points. 24. The method of claim 23, wherein the twice a day dosing reduces the patient's MDS-UPDRS scores from about 3 points to about 15 points. 25. The method of claim 23, wherein the immediate release component comprises from about 80% to about 100% of the total amount of carbidopa in the multiparticulate controlled release formulation. 26. The method of claim 25, wherein the multiparticulate controlled release dosage form when tested using a USP Apparatus I at 75 rpms and 37°±0.5° C. with 500-900 ml of simulated gastric fluid for 2 hours and pH 6.8 phosphate buffer thereafter exhibits the following levodopa release profile: 20% to 60% of levodopa is released after 2 hours; 40% to 80% of levodopa is released after 3 hours; 60% to 100% of levodopa is released after 4 hours; and not less than 80% is released after 7 hours, wherein the simulated gastric fluid has a pH of about 1 to about 4. 27. The method of claim 25, wherein the controlled release coating comprises a controlled release material selected from the group consisting of ethyl cellulose, cellulose acetate, and mixtures thereof. 28. The method of claim 25, wherein the mucoadhesive polymer is capable of forming a positive ionic charge at pHs present in the human gastrointestinal tract. 29. The method of claim 28, wherein the mucoadhesive polymer is an amino methacrylate copolymer. 30. The method of claim 29, wherein the amino methacrylate copolymer is poly(butyl methacrylate-co-(2-dimethylaminoethyl)methacrylate-co-methylmethacrylate). 31. The method of claim 25, wherein the patient is newly diagnosed with Parkinson's disease. 32. The method of claim 25, wherein the Parkinson's disease is primary parkinsonism, postencephalitic parkinsonism, parkinsonism following carbon monoxide intoxication, or parkinsonism following manganese intoxication.