Nalpropion Pharms., Inc. v. Actavis Labs. FL, Inc.

Case Name: Nalpropion Pharms., Inc. v. Actavis Labs. FL, Inc., 934 F.3d 1344 (Fed. Cir. Aug. 15, 2019) (Circuit Judges Prost, Lourie, and Wallach presiding; Opinion by Lourie, J.; Dissent-in-part by Prost, C.J.) (Appeal from D. Del., Andrews, J.)

Drug Product and Patent(s)-in-Suit: Contrave® (bupropion and naltrexone); U.S. Patents Nos. 8,916,195 (“the ’195 patent”), 7,462,626 (“the ’626 patent”), and 7,375,111 (“the ’111 patent”)

Nature of Case and Issue(s) Presented: Contrave is a weight management drug comprised of extended-release bupropion and naltrexone tablets. The ’626 patent claims a method of treating obesity using an effective amount of bupropion and naltrexone. The ’195 patent is also directed to methods of treating obesity using specific dosages of sustained-release naltrexone and bupropion. The ’111 patent is directed to a pharmaceutical composition of sustained-release bupropion and naltrexone.

Nalpropion sued Actavis for infringement of the patents-in-suit after the filing of Actavis’s ANDA. Actavis counterclaimed, alleging a lack of written description in regards to the ’195 patent and obviousness in regards to the ’111 and ’626 patents. The district court found each patent valid and infringed. Actavis appealed and the Federal Circuit held the district court did not clearly err in finding the written description of the ’195 patent adequate. But the Federal Circuit reversed the district court’s holding that the ’111 and ’626 patents were not invalid based on obviousness. Chief Judge Prost dissented in part as to the majority’s written description finding.

Why Nalpropion Prevailed on the ’195 patent: Claim 11 of the ’195 patent claims a dissolution profile achieved using the USP Apparatus 2 Paddle Method, whereas the specification disclosed a profile achieved using the different USP Apparatus 1 Basket Method. Actavis argued the claim lacked written description support based on the differing methodology. The district court found that the difference in methods was irrelevant to whether the inventors possessed the invention. The Federal Circuit found no clear error in the district court’s finding that the specification showed the inventors possessed the invention of treating overweight or obesity with naltrexone and bupropion in particular amounts and adequately described it. The Federal Circuit noted the district court’s fact-finding allowed for the written description to be satisfied by an equivalent disclosure relating to dissolution parameters rather than operative claim steps.

Chief Judge Prost dissented on this issue. She read the USP Apparatus 2 Paddle Method language as limiting and would have found that the ’195 patent disclosure failed to disclose it. Chief Judge Prost declined to follow the substantially equivalent rule adopted by the majority for the written description requirement.

Why Actavis Prevailed on the ’111 and ’626 patents: The asserted claims require the administration of naltrexone and bupropion together or in a single dosage. Actavis argued it would have been obvious for a POSA to combine naltrexone and bupropion given the drugs’ ability to cause weight loss. The district court disagreed, finding that a POSA would not understand bupropion’s mechanism of action and that bupropion’s weight loss effects were modest at best. Further, the district court found a POSA would similarly not have understood naltrexone to have weight loss effects. The district court concluded a POSA would not have known that combination of bupropion and naltrexone would lead to weight loss.

On appeal, the Federal Circuit agreed with Actavis that the claims at issue would have been obvious to a POSA in view of two prior art references, O’Malley and Jain. The Court found that O’Malley disclosed that use of opioid antagonists including naltrexone, alone or with other attenuating agents including bupropion, may minimize weight gain. And it found that Jain, a research paper, taught that studies support the use of bupropion for weight loss. Jain described a double-blind study involving sustained-release bupropion administration for weight reduction. Thus, according to the Federal Circuit, a POSA would have been motivated to combine naltrexone and bupropion to produce the claimed composition in the ’111 patent and the method of the ’626 patent after reading the O’Malley and Jain references. Moreover, according to the Federal Circuit, the prior art showed POSAs already combined the two drugs, understanding bupropion to be safe and well tolerated without an understanding of the mechanism of action.

The Federal Circuit next considered objective indicia of non-obviousness. Nalproprion argued that others tried and failed to find a combination effective for weight loss and that the claimed combination exhibited unexpected results. The Federal Circuit found that the inventors only combined two drugs known to affect weight loss, and that their combined effect of affecting weight loss was not unpredictable.