Claims for Patent: 12,329,851

Summary for Patent: 12,329,851

Title:	Long acting injectable formulation comprising risperidone and biodegradable polymers
Abstract:	The present invention is directed to methods of treating psychiatric diseases and disorders comprising administering to a subject in need thereof at a frequency of no more than once every 28 days an injectable formulation comprising risperidone, triblock and diblock copolymers wherein the concentration of the risperidone is 250-400 mg/mL and injection volume is 1 mL or less.
Inventor(s):	Avia Merenlender Wagner, Anna Elgart VALITSKY, Eran HARARY
Assignee:	MedinCell SA
Application Number:	US18/585,349
Patent Claims:	1. A method of switching a subject from a daily oral risperidone therapy to a long acting injectable risperidone formulation, said method comprising: i. orally administering to the subject a final dose of the daily oral risperidone therapy, after which no further oral risperidone therapy is administered; and ii. the next day subcutaneously administering to the subject a first injectable dose from a pre-filled syringe of a long acting injectable risperidone formulation comprising: (a) risperidone, or a pharmaceutically acceptable salt thereof, at a concentration of about 300-400 mg/mL, equivalent to risperidone; (b) a biodegradable triblock copolymer having a formula: poly(lactic acid)v-poly(ethylene glycol)w-poly(lactic acid)x, wherein v and x are numbers of repeat units ranging from 24 to 682 and w is a number of repeat units ranging from 4 to 273 and v=x or v≠x; and, (c) a biodegradable diblock copolymer having the formula: methoxy-poly(ethylene glycol)y-poly(lactic acid)z, wherein y and z are numbers of repeat units, wherein y is a number of repeat units ranging from 3 to 50 and z is a number of units ranging from 7 to 327; and wherein a ratio of the biodegradable triblock copolymer of (b) and the biodegradable diblock copolymer of (c) is 1:3 to 1:8 or 1:1 to 1:19 or 3:2 to 1:19, in said formulation, which is insoluble in an aqueous environment; wherein the daily oral risperidone therapy is 2 mg/day and the dose from the pre-filled syringe is 50 mg; or wherein the daily oral risperidone therapy is 2 mg/day and the dose from the pre-filled syringe is 100 mg; or wherein the daily oral risperidone therapy is 3 mg/day and the dose from the pre-filled syringe is 75 mg; or wherein the daily oral risperidone therapy is 3 mg/day and the dose from the pre-filled syringe is 150 mg; or wherein the daily oral risperidone therapy is 4 mg/day and the dose from the pre-filled syringe is 100 mg; or wherein the daily oral risperidone therapy is 4 mg/day and the dose from the pre-filled syringe is 200 mg; or wherein the daily oral risperidone therapy is 5 mg/day and the dose from the pre-filled syringe is 125 mg; or wherein the daily oral risperidone therapy is 5 mg/day and the dose from the pre-filled syringe is 250 mg; thereby switching the subject from the daily oral risperidone therapy to the long acting injectable risperidone formulation. 2. The method of claim 1, further comprising subcutaneously administering after said first injectable dose, once monthly, a subsequent dose, from another pre-filled syringe, of the long acting injectable risperidone formulation; wherein the subsequent dose from the other pre-filled syringe is 50 mg, 75 mg, 100 mg, or 125 mg. 3. The method of claim 1, further comprising subcutaneously administering after said first injectable dose, once every two months, a subsequent dose from another pre-filled syringe of the long acting injectable risperidone formulation; wherein the subsequent dose from the other pre-filled syringe is 100 mg, 150 mg, 200 mg, or 250 mg. 4. The method of claim 1, wherein said dose from the pre-filled syringe comprises from 50 mg to 250 mg risperidone in a volume of from 0.1 mL to 0.7 mL. 5. The method of claim 1, wherein the dose from the pre-filled syringe is subcutaneously administered into the upper arm of the subject or the abdomen of the subject. 6. The method of claim 1, wherein the dose from the pre-filled syringe is subcutaneously administered into the back of the upper arm of the subject. 7. The method or claim 1, wherein the dose from the pre-filled syringe is subcutaneously administered into the abdomen of the subject. 8. The method of claim 1, wherein the pre-filled syringe is fitted with a needle having a gauge number equal to or greater than 21 and/or a length equal to or shorter than ⅝ inch. 9. The method of claim 1, wherein the subject is suffering from a psychiatric disease that is schizophrenia, bipolar disorder, or irritability associated with autism (IAA). 10. The method of claim 1, wherein the subject is suffering from schizophrenia. 11. The method of claim 10, wherein the method results in a post-stabilization decrease in the subject's PANSS total score. 12. The method of claim 1, wherein the subject is an adult from an age of 18 to 65 years old or an adolescent from an age of 13 to 17 years old. 13. The method of claim 1, wherein the dose from the pre-filled syringe results in a mean exposure of TAM (AUC0-tau) that is equivalent to that of the daily oral risperidone therapy administered over an equivalent dosing period. 14. The method of claim 2, wherein: the dose from the pre-filled syringe is subcutaneously administered to the upper arm of the subject and the subsequent dose from the other pre-filled syringe is subcutaneously administered to the subject's abdomen; or the dose from the pre-filled syringe is a subcutaneously administered to the abdomen of the subject and the subsequent dose from the other pre-filled syringe is subcutaneously administered to the subject's upper arm. 15. The method of claim 3, wherein the dose from the pre-filled syringe is subcutaneously administered to the upper arm of the subject and the subsequent dose from the other pre-filled syringe is subcutaneously administered to the subject's abdomen; or the dose from the pre-filled syringe is a subcutaneously administered to the abdomen of the subject and the subsequent dose from the other pre-filled syringe is subcutaneously administered to the subject's upper arm. 16. The method of claim 1, wherein the concentration equivalent to risperidone is about 350 mg/mL. 17. The method of claim 1, wherein the concentration equivalent to risperidone is about 360 mg/mL. 18. The method of claim 1, wherein the daily oral risperidone therapy is 2 mg/day and the dose from the pre-filled syringe is 50 mg; or wherein the daily oral risperidone therapy is 3 mg/day and the dose from the pre-filled syringe is 75 mg; or wherein the daily oral risperidone therapy is 4 mg/day and the dose from the pre-filled syringe is 100 mg; or wherein the daily oral risperidone therapy is 5 mg/day and the dose from the pre-filled syringe is 125 mg. 19. The method of claim 18, wherein the volume of the 50 mg dose from the pre-filled syringe is 0.14 mL; the volume of the 75 mg dose from the pre-filled syringe is 0.21 mL; the volume of the 100 mg dose from the pre-filled syringe is 0.28 mL; or the volume of the 125 mg dose from the pre-filled syringe is 0.35 mL. 20. The method of claim 18, further comprising subcutaneously administering after said first injectable dose, once monthly, a subsequent dose from another pre-filled syringe of the long acting injectable risperidone formulation, wherein the subsequent dose from the other pre-filled syringe is 50 mg or 75 mg or 100 mg or 125 mg. 21. The method of claim 1, wherein wherein the daily oral risperidone therapy is 2 mg/day and the dose from the pre-filled syringe is 100 mg; or wherein the daily oral risperidone therapy is 3 mg/day and the dose from the pre-filled syringe is 150 mg; or wherein the daily oral risperidone therapy is 4 mg/day and the dose from the pre-filled syringe is 200 mg; or wherein the daily oral risperidone therapy is 5 mg/day and the dose from the pre-filled syringe is 250 mg. 22. The method of claim 21, wherein the volume of the 100 mg dose from the pre-filled syringe is 0.28 mL; the volume of the 150 mg dose from the pre-filled syringe is 0.42 mL; the volume of the 200 mg dose from the pre-filled syringe is 0.56 mL; or the volume of the 250 mg dose from the pre-filled syringe is 0.7 mL. 23. The method of claim 21, further comprising subcutaneously administering after said first injectable dose, once every two months, a subsequent dose from another pre-filled syringe of the long acting injectable risperidone formulation, wherein the subsequent dose from the other pre-filled syringe is 100 mg, 150 mg, 200 mg, or 250 mg. 24. A method of switching a subject from a daily oral risperidone therapy to a long acting injectable risperidone formulation, said method comprising: i. orally administering to the subject a final dose of the daily oral risperidone therapy, after which no further oral risperidone therapy is administered; and ii. the next day subcutaneously administering to the subject a first injectable dose from a pre-filled syringe of a long acting injectable risperidone formulation comprising: (a) risperidone, or a pharmaceutically acceptable salt thereof, at a concentration of about 300-400 mg/mL, equivalent to risperidone; (b) a biodegradable triblock copolymer having a formula: poly(lactic acid)v-poly(ethylene glycol)w-poly(lactic acid)x, wherein v and x are numbers of repeat units ranging from 24 to 682 and w is a number of repeat units ranging from 4 to 273 and v=x or vx; and, (c) a biodegradable diblock copolymer having the formula: methoxy-poly(ethylene glycol)y-poly(lactic acid)z, wherein y and z are numbers of repeat units, wherein y is a number of repeat units ranging from 3 to 50 and z is a number of units ranging from 7 to 327; and wherein a ratio of the biodegradable triblock copolymer of (b) and the biodegradable diblock copolymer of (c) is 1:3 to 1:8 or 1:1 to 1:19 or 3:2 to 1:19, in said formulation, which is insoluble in an aqueous environment; wherein the daily oral risperidone therapy is 2 mg/day and the dose from the pre-filled syringe is 50 mg; or wherein the daily oral risperidone therapy is 2 mg/day and the dose from the pre-filled syringe is 100 mg; or wherein the daily oral risperidone therapy is 3 mg/day and the dose from the pre-filled syringe is 75 mg; or wherein the daily oral risperidone therapy is 3 mg/day and the dose from the pre-filled syringe is 150 mg; or wherein the daily oral risperidone therapy is 4 mg/day and the dose from the pre-filled syringe is 100 mg; or wherein the daily oral risperidone therapy is 4 mg/day and the dose from the pre-filled syringe is 200 mg; or wherein the daily oral risperidone therapy is 5 mg/day and the dose from the pre-filled syringe is 125 mg; or wherein the daily oral risperidone therapy is 5 mg/day and the dose from the pre-filled syringe is 250 mg; wherein there is no oral risperidone administration after said first injectable dose thereby switching the subject from the daily oral risperidone therapy to the long acting injectable risperidone formulation.