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1. (WO2018042415) DEPOT SYSTEMS COMPRISING GLATIRAMER ACETATE
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CLAIMS

1. A method of alleviating at least one symptom of relapsing -remitting multiple sclerosis (RRMS) in a human patient suffering from RRMS or a human patient who has experienced a first clinical episode and is determined to be at high risk of developing clinically definite multiple sclerosis, comprising administering to the patient a therapeutically effective regimen of a single intramuscular injection of a depot formulation comprising 40 mg dose of glatiramer acetate (GA) every 2 to 6 weeks, the regimen being sufficient to alleviate the at least one symptom of the patient, wherein the symptom is selected from the group consisting of the frequency of relapses, the number of enhancing lesions or the number of new lesions images of brain MRI, and the Expanded Disability Status Scale (EDSS) score of the patient.

2. The method of claim 1, wherein the depot formulation is administered once every 4 weeks.

3. The method of claim 1 or claim 2, wherein alleviating a symptom comprises reducing the frequency of relapses.

4. The method of any one of the preceding claims, wherein alleviating a symptom comprises reducing the number or volume of enhancing lesions or the number of new lesions in the brain.

5. The method of claim 4, wherein alleviating a symptom comprises reducing brain atrophy, reducing the number or volume of Gd-enhancing lesions, reducing the number or volume of Ti-weighted enhancing lesions, or reducing the number of new T2-weighted lesions, in the patient.

6. The method of any one of claims 1 to 4, wherein alleviating a symptom comprises reducing the EDSS score of the patient.

7. The method of any one of the preceding claims, wherein the method alleviates the symptom at least as effectively as daily subcutaneous administrations of 20 mg GA or thrice weekly subcutaneous injections of 40 mg GA.

8. The method of claim 1 or claim 7, wherein the patient has received GA therapy prior to initiation of the regimen.

9. The method of any one of the preceding claims, wherein the depot formulation further comprises a pharmaceutically acceptable biodegradable carrier selected from the group

consisting of poly(lactic-co-glycolic acid) (PLGA), poly(lactic acid) (PLA), poly(glycolic acid) (PGA), and any combination thereof.

10. The method of claim 9, wherein the biodegradable carrier is PLGA.

11. The method of any one of the preceding claims, wherein the depot formulation is in the form of microparticles comprising an internal aqueous phase comprising the GA, a water immiscible polymeric phase comprising a biodegradable or non-biodegradable polymer, and an external aqueous phase.

12. The method of any one of the preceding claims, wherein the depot formulation is in the form of microparticles prepared by a water-in oil-in water (w/o/w) double emulsification process.

13. The method of claim 12, wherein the internal aqueous phase comprises the GA.

14. The method of any one of claims 11 to 13, wherein the water immiscible polymeric phase comprises PLGA.

15. The method of any one of claims 11 to 14, wherein the external water phase comprises a surfactant selected from poly(vinyl alcohol) (PVA), polysorbate, polyethylene oxide-polypropylene oxide block copolymers and cellulose esters.

16. The method of any one of the preceding claims, wherein the depot formulation comprises 20% to 30% solids.

17. The method of any one of claims 9 to 16, wherein the weight ratio between the GA and the pharmaceutically acceptable biodegradable carrier is between 1 : 1 to 1 : 100.

18. The method of claim 17, wherein the weight ratio between the GA and the pharmaceutically acceptable biodegradable carrier is between 1 :5 to 1:25.

19. The method of any one of the preceding claims, wherein the depot formulation provides prolonged release or prolonged action of glatiramer in a subject as compared to a substantially similar dose of an immediate release formulation of glatiramer.

20. The method of claim 19, wherein about 80% of the glatiramer is released from the depot formulation within 22 days in PBS at 37°C under continuous agitation.

21. The method of claim 19 or claim 20, wherein about 20% of the glatiramer is released from the depot formulation within 5 days in PBS at 37°C under continuous agitation.

22. A method of increasing the tolerability of GA treatment in a human patient suffering from relapsing-remitting multiple sclerosis, comprising reducing the frequency of subcutaneous injections from daily subcutaneous injections of a 20 mg dose of GA or three subcutaneous injections of a 40 mg dose of GA over a period of seven days with at least one day between every injection, to a therapeutically effective regimen of a single intramuscular injection of a depot formulation of a 40 mg dose of GA every 2 to 6 weeks, so as to thereby increase the tolerability of GA treatment in the patient.

23. A method of preventing or slowing progression of relapsing-remitting multiple sclerosis (PvRMS) in a human patient suffering from RRMS, comprising administering to the human patient a therapeutically effective regimen of a single intramuscular injection of a depot formulation comprising 40 mg dose of glatiramer acetate (GA) every 2 to 6 weeks.

24. The method of claim 23, wherein the regimen is sufficient to ameliorate (a) the frequency of relapses, (b) the number or volume of enhancing lesions, (c) the number of new lesions, or (d) the Expanded Disability Status Scale (EDSS) score of the patient.

25. The method of claim 24, wherein the regimen is sufficient to ameliorate the frequency of relapses, the number or volume of enhancing lesions, the number of new lesions, and the Expanded Disability Status Scale (EDSS) score of the patient.

26. A method of preventing disease activity in a human patient suffering from relapsing-remitting multiple sclerosis, comprising administering to the patient a therapeutically effective regimen of a single injection of a depot formulation of a 40 mg dose of GA every 2 to 6 weeks, the regimen being sufficient to prevent relapses, 12-week confirmed disability progression (CDP), new lesion formation and enhancement of existing lesions in the patient.

27. A kit, comprising a first container comprising GA encapsulated with a poly(lactic-co-glycolic acid) (PLGA), and a second separate container comprising a pharmaceutically acceptable diluent for injection.

28. The kit of claim 27, wherein the kit comprises 40 mg GA and water for injection (WFI).

29. The kit of claim 27 or claim 28, wherein mixing the content of the first container and the second container provides 40 mg GA per 2 mL of diluent.

30. The kit of any one of claims 27 to 29, for use in a method of alleviating at least one symptom of relapsing-remitting multiple sclerosis (RRMS), increasing the tolerability of GA treatment, preventing or slowing progression of RRMS, or preventing RRMS activity.