Prometheus Laboratories, Inc. v. Roxane Laboratories, Inc. and Cipla, Ltd., (Fed. Cir. November 10, 2015)

The U.S. Court of Appeals for the Federal Circuit upheld the U.S. District Court for the District of New Jersey’s finding of patent invalidity on the basis of obviousness, but did not reach the issue of invalidity due to double patenting, in this Hatch-Waxman patent infringement action. Prometheus Laboratories, Inc. v. Roxane Laboratories, Inc. and Cipla, Ltd., 805 F.3d 1092 (Fed. Cir. 2015).

The patent at issue, U.S. Patent No. 6,284,770, relates to Prometheus’ medication used to treat irritable bowel syndrome (IBS), Lotronex® (alosetron). Prometheus filed suit against Roxane alleging infringement of select claims of the ’770 patent. In relevant part, claim 5 of the ‘770 patent is directed to: “A method for treating a diarrhea-predominant female IBS patient . . . administering an effective amount of alosetron . . . to said patient who has experienced symptoms for at least six months. . .” Claim 13 also added the limitation that the female patient, “experiences at least moderate baseline pain.” 

Roxane challenged the validity of the ‘770 patent under theories of obviousness (and obviousness-type double patenting) in view of the ‘800 patent (owned by Prometheus) and the state of the art of treating IBS. The parties agreed on the level of one of skill in the art of the ‘770 patent (gastroenterologist with three years of experience), and the parties agreed that the ‘770 patent claims species of the genus methods claimed in the prior art ‘800 patent.

Finding this case analogous to AbbVie Inc. v. Mathilda & Terence Kennedy Inst. of Rheumatology Tr., 764 F.3d 1366 (Fed.Cir.2014), the court held 1) that the ‘770 patent was obvious; 2) secondary considerations did not support a conclusion that the patent was not obvious; and 3) the district court did not improperly shift the burden of proof to Prometheus to demonstrate a nexus between its secondary consideration evidence and the ‘770 patent claims—even if the district court opinion may have included “imperfect language” on the burden to produce evidence of secondary indicia of non-obviousness. Prometheus Labs at 1101-1102.

The court commented that, [t]he genus species distinction may have particular relevance in the field of personalized medicine, where for example, a particular treatment may be effective with respect to one subset of patients and ineffective (and even harmful) to another subset of patients.” Id. at 1098. While a narrow species can be non-obvious despite prior art disclosing a genus (such as “where the new patient subset displayed unexpected results”), the court did not find that situation in this case. Id. at 1098.

Here, the court found insubstantial differences between the prior art and the limitations set forth in claim 5 of the ‘770 patent drawn to 1) a known type of IBS (diarrhea-predominant or IBS-D); 2) the gender most commonly effected by IBS (female); 3) treatment of a patient only after a duration of time  commonly used when evaluating patients for treatment (six months); and 4) treatment after a physician evaluates a patient for at least moderate pain (claim 13). Id. at 1098-1101.

With regard secondary indicia of non-obviousness, the court found that it was not unexpected that alosetron was more effective for patients with IBS-D, rather than IBS predominated by constipation (IBS-C), because prior art disclosed that “alosetron and other 5-HT3 antagonists slow colonic transit” and “taught that alosetron would be beneficial to prescribe with those with IBS-D and potentially harmful to those with IBS-C.” Id. at 1099. The court also found product praise and allegedly long-felt, unexpected improvements in safety and risk profiles more attributable to the alosetron compound and the precautions issued after the product’s relaunch due to safety concerns, rather than the asserted method claims. Id. at 1101.

Additionally, the court found that Prometheus had not advanced sufficient evidence of commercial success where there was only a modest increase in Lotronex sales following its relaunch with prescribing information mirroring the ‘770 patent claims. Finally, the court found the incremental increase in Lotronex revenue was attributable to marketing activity, increases in sales price and rebates provided to patients to stimulate sales. Id. at 1101-1102. Notably, the court criticized Prometheus’ failure to control for these marketing variables when assessing increases in Lotronex’s sales and revenue. Id. at 1101.

The ‘770 patent was Orange Book-listed for Lotronex with a patent expiry on October 5, 2018. Roxane is the only company with the U.S. Food and Drug Administration’s final approval to sell AB-rated, generic alosetron products.