Prometheus Labs., Inc. v. Roxane Labs., Inc.

Case Name: Prometheus Labs., Inc. v. Roxane Labs., Inc., 2014-1634, -1635, 2015 U.S. App. LEXIS 19556 (Fed. Cir. Nov. 10, 2015) (Circuit Judges Dyk, Taranto, and Hughes presiding; Opinion by Dyk, J.) (Appeal from D.N.J., Hochberg, J.)

Drug Product and Patent(s)-in-Suit: Lotronex® (alosetron); U.S. Patent No. 6,284,770 (“the ’770 patent)

Nature of the Case and Issue(s) Presented: Irritable bowel syndrome (“IBS”) is a condition defined and diagnosed by its symptoms. Patients may suffer from diarrhea-predominant IBS (“IBS-D”), constipation-predominant IBS (“IBS-C”), or mixed IBS (“IBS-M”). The ’770 patent claims a method of treatment for IBS-D in women showing symptoms for at least six months, including moderate pain. Prometheus also owns U.S. Patent No. 5,360,800 (“the ’800 patent”), which is prior art to the ’770 patent, and also claims a method of treating a condition [such as IBS] which is ameliorated by antagonism of 5-HT[3] receptors which comprises administering to a patient an effective amount of alosetron.

Shortly before the issuance of the ’770 patent, Lotronex was approved by the FDA and launched in 2000. That same year, the drug was taken off the market because of serious side effects, including death. Lotronex was relaunched in 2002 with a new, more-restrictive, label, new warnings about side effects, and a risk-management program. After relaunch, the label specified that Lotronex is indicated only for women with severe IBS-D who have chronic symptoms generally lasting six months or longer.

In 2009, Roxane filed an ANDA with the FDA seeking approval to manufacture and sell generic Lotronex. Prometheus sued. After a bench trial, the district court held that the claims of the ’770 patent were invalid as obvious. Prometheus appealed. The Federal Circuit affirmed.

Why Roxane Prevailed: Everyone agreed that the ’770 patent claims a species of the genus method claimed in the ’800 prior art patent. A narrow species can be non-obvious and patent eligible despite a patent on its genus. But here, the Federal Circuit found that it would have been obvious for a skilled artisan to have separately treated the limited subset claimed in the ’770 patent with alosetron, and that any unexpected results were attributable to factors outside of that patent.

Firstly, it was not disputed that it was well known in the prior art that a majority of IBS patients were women. The record evidence showed that “approximately 75% to 80% of IBS-D patients…have always been[] women.” Secondly, several pre-priority date publications taught that “alosetron and other 5-T[3] antagonists show colonic transit” and “taught that alosetron would be beneficial to prescribe to those with IBS-D and potentially harmful to those with IBS-C.” Thirdly, it was common practice at the time of the ’800 patent to determine whether a patient had suffered symptoms for longer than six months. Prometheus’ own expert testified that the benefit of this timeframe was having “a greater confidence in the diagnosis.” Moreover, the district court found that “most IBS-D patients will have symptoms for more than 6 months” and “it has always been true that waiting a longer period of time to observe a patient’s symptoms decreases the likelihood of a false positive.” Fourthly, it was well known at the time of the ’800 patent to evaluate patients for pain in order to diagnose IBS. Thus, the Federal Circuit concluded, the limitations in the ’770 patent are directed to a known type of IBS, to treating the gender that predominantly experiences IBS, to treating patients with a characteristic that is always or almost always evaluated in establishing IBS, and to assessing symptoms for a duration of time that was common in diagnosing patients with IBS.

The Federal Circuit next addressed the district court’s findings concerning the lack of objective indicia of non-obviousness. The Federal Circuit agreed that the relaunched Lotronex’s commercial success was not due to any nexus with the ’770 patent, but to Prometheus’ actions in marketing, increasing the price of Lotronex, and introducing a series of rebates to stimulate sales of the drug. Moreover, any long-felt need was attributable to the compound itself rather than the ’770 patent’s method of treatment. “[A]ny praise or reduction in the severity of side effects is more likely attributable to elements from the ’800 patent, the new safety precautions, heightened awareness, and warnings issued after Lotronex’s reintroduction.” The Federal Circuit thus found no error in the district court’s findings.