Claims for Patent: 8,916,195

Summary for Patent: 8,916,195

Title:	Sustained release formulation of naltrexone
Abstract:	A sustained-release oral dosage form of naltrexone or a pharmaceutically acceptable salt thereof is provided. The oral dosage form may be administered with another compound. Administration of the oral dosage form may reduce a side effect, which may be a side effect at least partially attributable to a weight-loss treatment. The oral dosage form may be administered to treat a weight-loss condition.
Inventor(s):	McKinney; Anthony A. (San Diego, CA), Tollefson; Gary D. (Indianapolis, IN), Soltero; Richard (Holly Springs, NC), Dunzo; Thea Elise (Durham, NC)
Assignee:	Orexigen Therapeutics, Inc. (La Jolla, CA)
Application Number:	11/757,773
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 8,916,195
Patent Claims:	1. A method of treating overweight or obesity having reduced adverse effects comprising: identifying a subject in need of a treatment for obesity or overweight; and orally administering at least daily about 4 mg to about 32 mg of naltrexone and about 90 mg to about 360 mg of bupropion, or pharmaceutically acceptable salts thereof to said subject, wherein the bupropion or pharmaceutically acceptable salt thereof is administered as a sustained-release formulation, wherein the naltrexone or pharmaceutically acceptable salt thereof is administered as a sustained-release formulation having an in vitro naltrexone dissolution profile in a dissolution test of USP Apparatus 2 Paddle Method at 100 rpm in a dissolution medium of water at 37.degree. C. of: a) between 39% and 70% of naltrexone released in one hour; and b) between 62% and 90% of naltrexone released in two hours, whereby at least one adverse effect associated with administration of the same amount of an immediate-release naltrexone formulation and said sustained-release formulation of bupropion or a pharmaceutically acceptable salt thereof is reduced. 2. The method of claim 1, wherein the amount of bupropion or pharmaceutically acceptable salt thereof administered per day is selected from the group consisting of about 90 mg, about 180 mg, about 270 mg, and about 360 mg, and the amount of naltrexone or pharmaceutically acceptable salt thereof administered per day is selected from the group consisting of about 4 mg, about 8 mg, about 12 mg, about 16 mg, about 24 mg and about 36 mg. 3. The method of claim 2, wherein said naltrexone and bupropion, or pharmaceutically acceptable salts thereof, are administered in a single oral unit dosage form. 4. The method of claim 2, wherein said sustained-release formulation of naltrexone provides an in vivo plasma concentration profile of: a) a naltrexone C.sub.max that is less than 80% of the naltrexone C.sub.max of an equal amount of immediate-release naltrexone hydrochloride; and b) a naltrexone AUC.sub.last that is between 80% and 125% of the naltrexone AUC.sub.last of an equal amount of immediate-release naltrexone hydrochloride. 5. The method of claim 4, wherein said naltrexone and bupropion, or pharmaceutically acceptable salts thereof, are administered in a single oral unit dosage form. 6. The method of claim 1, wherein said sustained-release formulation of naltrexone or a pharmaceutically acceptable salt thereof provides an in vitro release rate of naltrexone in the dissolution test of at least 99% in 8 hours. 7. The method of claim 1, wherein said sustained-release formulation of naltrexone or a pharmaceutically acceptable salt thereof is administered twice daily. 8. The method of claim 1, wherein said sustained-release formulation of naltrexone or a pharmaceutically acceptable salt thereof provides an in vitro release rate of naltrexone in the dissolution test of between 23% to 48% in 0.5 hour, between 51% and 67% in 1 hour, and between 74% and 90% in 2 hours. 9. The method of claim 8, wherein said in vitro release rate of naltrexone is about 85% in 2 hours. 10. The method of claim 9, wherein said sustained-release formulation of naltrexone or a pharmaceutically acceptable salt thereof provides an in vitro release rate of naltrexone in the dissolution test of at least 99% in 8 hours. 11. A method of treating overweight or obesity having reduced adverse effects comprising orally administering daily about 32 mg of naltrexone and about 360 mg of bupropion, or pharmaceutically acceptable salts thereof, to a person in need thereof, wherein the bupropion or pharmaceutically acceptable salt thereof is administered as a sustained-release formulation, wherein the naltrexone or pharmaceutically acceptable salt thereof is administered as a sustained-release formulation, and wherein said sustained-release formulation of naltrexone has an in vitro naltrexone dissolution profile in a dissolution test of USP Apparatus 2 Paddle Method at 100 rpm in a dissolution medium of water at 37.degree. C. of: a) between 39% and 70% of naltrexone released in one hour; b) between 62% and 90% of naltrexone released in two hours; and c) at least 99% in 8 hours; wherein about 16 mg of said sustained-release formulation of naltrexone or a pharmaceutically acceptable salt thereof is administered twice daily, and about 180 mg of said sustained-release formulation of bupropion or a pharmaceutically acceptable salt thereof is administered twice daily. 12. The method of claim 1, wherein said at least one adverse effect comprises at least one adverse effect selected from the group consisting of nausea, headache and dizziness. 13. The method of claim 12, wherein said at least one adverse effect comprises nausea. 14. The method of claim 1, wherein said sustained-release naltrexone formulation or pharmaceutically acceptable salt thereof and said sustained-release bupropion or pharmaceutically acceptable salt thereof are administered in separate oral dosage forms. 15. The method of claim 4, wherein said sustained-release formulation of naltrexone further provides an in vivo plasma concentration profile of: c) a 6-beta naltrexol C.sub.max that is less than 80% of the 6-beta naltrexol C.sub.max of an equal amount of immediate-release naltrexone hydrochloride; and d) a 6-beta naltrexol AUC.sub.last that is between 80% and 125% of the 6-beta naltrexol AUC.sub.last of an equal amount of immediate-release naltrexone hydrochloride.