Opinion ID: 4425850
Heading Depth: 1
Heading Rank: 1

Heading: facts

Text: Appellee Nalpropion Pharmaceuticals, Inc. (“Nalpropion”) 1 holds New Drug Application No. 200063 for and markets Contrave® for weight management in overweight or obese adults. Relevant here are the three Orange Booklisted patents for Contrave® that Nalpropion asserted against Actavis: the ’626, ’195, and ’111 patents. The ’626 patent is drawn to a method for treating overweight or obesity comprising (1) diagnosing an individual as suffering from overweight or obesity by body mass index, (2) administering bupropion in an amount effective to induce weight loss, and (3) administering naltrexone in an 1 Takeda Pharmaceutical Company Limited (“Takeda Ltd.”), Takeda Pharmaceuticals International GmbH, Takeda Pharmaceuticals USA, Inc. (“Takeda USA”), and Takeda Pharmaceuticals, America, Inc. (collectively, “Takeda”) and Orexigen Therapeutics, Inc. (“Orexigen”) filed this suit in the District of Delaware. At the time of filing, Orexigen owned all three patents in suit, Takeda Ltd. was the exclusive licensee of the patents, and Takeda USA held approved New Drug Application No. 200063 for extended-release tablets containing 8 mg of naltrexone hydrochloride and 90 mg of bupropion hydrochloride. During the litigation, Orexigen acquired all of Takeda’s rights to Contrave®, including ownership of the NDA. Stipulation and Order at 1, Orexigen Therapeutics, Inc. v. Actavis Labs. FL, Inc., No. 1:15-cv-451 (D. Del. Oct. 5, 2017), ECF No. 92. After this appeal was taken, however, Orexigen commenced bankruptcy proceedings under Chapter 11 of Title 11 of the United States Code in the U.S. Bankruptcy Court for the District of Delaware and transferred ownership of the patents-in-suit to Nalpropion. Unopposed Motion for Substitution of Nalpropion Pharms. Inc. for Orexigen Therapeutics, Inc. at 1, Nalpropion Pharm. Inc. v. Actavis Labs. FL, Inc., No. 18-1221 (Fed. Cir. Aug. 28, 2018), ECF No. 30. 4 NALPROPION PHARMACEUTICALS v. ACTAVIS LABORATORIES FL, INC. amount effective to enhance the weight loss activity of bupropion. ’626 patent col. 38 l. 60–col. 39 l. 4. Nalpropion asserted claims 26 and 31. Claim 26 depends from claim 25, which recites: A method of treating overweight or obesity, com- prising administering a weight loss effective amount of a first and second compound to an indi- vidual who has been diagnosed as suffering from overweight or obesity in order to treat said over- weight or obesity, wherein said first compound is bupropion, or a pharmaceutically acceptable salt thereof, and said second compound is naltrexone, or a pharmaceutically acceptable salt thereof, and wherein the weight loss activity of said first and second compounds is enhanced compared to the ad- ministration of the same amount of either com- pound alone. Id. col. 40 ll. 16–26. Claim 26 adds the additional limitation that naltrexone and bupropion “are administered together.” Id. col. 40. ll. 27–30. Claim 30 depends from claim 25 and requires that at least one of the drugs be in a “sustained-release formulation,” id. col. 40 ll. 41–44, while claim 31, which depends from claim 30, requires that the drugs be “administered in a single oral dosage form,” id. col. 40 ll. 45–49. The ’195 patent is also directed to methods of treating overweight or obesity, but the claims are drawn to specific dosages of sustained-release naltrexone and bupropion that achieve a specific dissolution profile. At issue here is claim 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 NALPROPION PHARMACEUTICALS v. ACTAVIS LABORATORIES 5 FL, INC. acceptable salt thereof is administered as a sus- tained 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 wa- ter at 37° C. of: a) between 39% and 70% of naltrexone re- leased in one hour; b) between 62% and 90% of naltrexone re- leased in two hours; and c) at least 99% in 8 hours; wherein about 16 mg of said sustained re- lease formulation of naltrexone or a phar- maceutically acceptable salt thereof is administered twice daily, and about 180 mg of said sustained release formulation of bupropion or a pharmaceutically accepta- ble salt thereof is administered twice daily. ’195 patent col. 31 l. 5–col. 32 l. 3. Finally, the ’111 patent is directed to a composition of sustained-release bupropion and naltrexone for affecting weight loss. Asserted here is claim 1: A composition for affecting weight loss comprising: (a) a sustained release formulation of bu- propion or a pharmaceutically acceptable salt thereof in an amount effective to in- duce weight loss in an individual; and (b) a sustained release formulation of nal- trexone or a pharmaceutically acceptable salt thereof in an amount effective to 6 NALPROPION PHARMACEUTICALS v. ACTAVIS LABORATORIES FL, INC. enhance the weight loss effect of the bu- propion or salt thereof; wherein said composition is in a single oral dosage form fixed combination. ’111 patent col. 41 ll. 26–35. Actavis filed an ANDA seeking to enter the market with a generic version of Contrave® prior to the expiration of the patents in suit, and Nalpropion responded by bringing an action for patent infringement, alleging that Actavis’s ANDA product would infringe the ’111, ’626, and ’195 patents. Actavis in turn brought invalidity counterclaims, challenging claim 11 of the ’195 patent as invalid for lack of adequate written description and challenging claim 1 of the ’111 patent and claims 26 and 31 of the ’626 patents as invalid as obvious. The district court held a bench trial on all of these issues and held each claim not invalid and infringed. Decision, 282 F. Supp. 3d at 797. First, the district court considered Actavis’s written description argument. Actavis argued that claim 11 of the ’195 patent lacked adequate written description support because its claimed dissolution profile was achieved using the USP Apparatus 2 Paddle Method (“USP 2”), but the specification discloses data obtained using the different USP Apparatus 1 Basket Method (“USP 1”). The court was not persuaded that the use of a different method from what is prescribed in the claim presented a written description problem, holding that “whether the dissolution data reported in the specification was obtained using the basket method or the paddle method is not relevant to whether the inventors had possession of the invention.” Id. at 802. Instead, the court credited Nalpropion’s expert who opined that a person of ordinary skill would recognize that the inventors possessed an embodiment of the invention as described in Table 10, regardless whether USP 2 or a “‘substantially equivalent’ method” was used. Id. at 801 (citation omitted). NALPROPION PHARMACEUTICALS v. ACTAVIS LABORATORIES 7 FL, INC. Next, the district court addressed the question of obviousness of claim 1 of the ’111 patent and claims 26 and 31 of the ’626 patent. Actavis argued that it would have been obvious for a person of skill to combine bupropion and naltrexone for treating overweight and obesity because both drugs were known to cause weight loss, but the court disagreed, finding Actavis’s argument to be “a classic case of hindsight bias.” Id. at 809. Actavis appealed from the district court judgment, and we have jurisdiction under 28 U.S.C. § 1295(a)(1).