In Prometheus Laboratories., Inc. v. Roxane Laboratories. Inc., Nos. 2014-1634, -1635 (Fed. Cir. Nov. 10, 2015), the Federal Circuit affirmed the district court’s finding of invalidity for obviousness. It did not, however, address the district court’s judgment of invalidity on the ground of obviousness-type double patenting.

The patent-in-suit was U.S. Patent No. 6,284,770 (“the ’770 patent”) owned by Prometheus. The ’770 patent claims a method of treatment for a type of irritable bowel syndrome (IBS), i.e., diarrhea-predominant IBS (IBS-D), using alosetron. In 2009, Roxane submitted an Abbreviated New Drug Application (ANDA) with the Food and Drug Administration (FDA), seeking approval to commercially market a generic version of alosetron before the ’770 patent expired. A reexamination certificate for the ’770 patent was issued on October 19, 2010. Following the Orange Book relisting of the re-examined ’770 patent, Roxane submitted to the FDA a paragraph IV certification that the reexamined patent was noninfringed or invalid. Prometheus subsequently filed suit against Roxane, alleging infringement of reexamined claims 5, 6, 10, 13, and 14 of the ’770 patent based on the filing of the ANDA.

The reexamined claim 5, which is representative of the asserted claims, reads as follows (the underlined portions were added during reexamination of the ’770 patent):

5. A method for treating a diarrhea-predominant female IBS patient, while excluding those with predominant constipation, said method comprising:

assessing whether said diarrhea-predominant female IBS patient has experienced symptoms for at least six months; and

administering an effective amount of alosetron or a pharmaceutically acceptable derivative thereof to said patient who has experienced symptoms for at least six months, wherein said effective amount is dependent on the condition of the patient and is at the discretion of the attendant physician.

Alosetron was initially approved by the FDA in 2000 for treatment of IDS. Due to severe side effects, alosetron was taken off the market in the same year of approval. Alosetron was relaunched in 2002 with indications corresponding to the limitations of the above reexamined claim 5.

The district court, relying on U.S. Patent No. 5,360,800 (“the ’800 patent”) as the primary prior art reference, found that the asserted claims would have been obvious in view of the prior art and secondary considerations of nonobviousness. The district court also held that the asserted claims were invalid over the claims of the ’800 patent on the ground of obviousness-type double patenting.

On appeal, the Federal Circuit affirmed the invalidity of the asserted claims as obvious. Agreeing with the district court and the parties, the Federal Circuit characterized the asserted claims as a species of the genus method claimed in the ’800 patent. The ’800 patent claims treating patients suffering from IBS generally using alosetron. The ’770 patent, as claim 5 illustrates, claims treating a subset of IBS patients: those who (1) are women, (2) with IBS-D, and (3) have experienced symptoms for at least six months, and (4) have had moderate pain.

The Federal Circuit acknowledged that a species claim can be patentable over prior art genus claims or disclosure, referring to opinions given in AbbVie Inc. v. Mathilda & Terence Kennedy Institute of Rheumatology Trust, 764 F.3d 1366, 1379 (Fed. Cir. 2014), and Eli Lilly & Co. v. Board of Regents of University of Washington, 334 F.3d 1264, 1270 (Fed. Cir. 2003). It further emphasized the relevance of genus-species distinction in the field of personalized medicine and opined that “[a]n obviousness rejection likely would not be appropriate where the new patient subset displayed unexpected results.”Prometheus, slip op. at 9.

The Federal Circuit, however, held that was not the situation in this case. Specifically, the Federal Circuit did not find any error in the district court’s factual findings that it would have been obvious for a person skilled in the art to have treated the subset patients recited in the asserted claims of the ’770 patent using alosetron and that any unexpected results were attributable to factors unrelated to the ’770 patent.

In particular, the Federal Circuit reviewed the prior art and expert testimony, and agreed with the district court that each of the four subset limitations recited in the asserted claims was known in the art prior to the filing date of the ’770 patent application. For example, the district court found that scientific publications taught that the 5-HT3 inhibitors, to which alosetron belongs, "slowed colonic transit and would be helpful in treating IBS-D and harmful in treating IBS-C.” Id. at 11 (citation omitted). IBS-C refers to constipation-predominant IBS. Recognizing that those studies were not focused on alosetron, the Federal Circuit, in view of ample testimony, found no clear error in the district court’s conclusions that those studies were applicable to alosetron, a species of 5-HT3 inhibitors. The Federal Circuit further agreed with the district court’s finding that “it would have been obvious to combine the teachings of the prior art in the form of the ’770 patent.” Id. at 14.

With regard to secondary considerations, the Federal Circuit underlined the importance of establishing a nexus between secondary considerations and asserted claims. First, it agreed with the district court that there was no nexus between the commercial success and the asserted claims. Rather, the commercial success resulted from Prometheus’s marketing and sales tactics. The Federal Circuit further emphasized that the burden was on the patentee to prove the nexus between the commercial success and the ’770 patent once the challenger had introduced evidence of a prima facie case of obviousness.

The Federal Circuit also rejected Prometheus’s challenge on the district court’s conclusion regarding unexpected results (improving the safety and risk-benefit profiles of alosetron) and long-felt need. It agreed with the district court that it was alosetron, not the claimed methods, that satisfied any long-felt need, and that the unexpected results were “attributable to elements from the ’800 patent, the new safety precautions, heightened awareness, and warnings issued” after alosetron’s relaunch. Id.at 17 (citation omitted.)

This is another case after AbbVie wherein the Federal Circuit found a species claim obvious over a prior art genus. Unlike the species claims in AbbVie, which were found obvious over genus claims on the ground of nonstatutory obviousness-type double patenting, the species claims in this case were found statutorily obvious over prior art disclosure. Those two doctrines, while sharing similarities, have distinctions. In re Basell PoliolefineItalia S.P.A. 547 F.3d 1371, 1379, 89 U.S.P.Q.2d 1030, 1036 (Fed. Cir. 2008). Yet, the Federal Circuit appeared to analogize this case to AbbVie to support its obviousness affirmance. Prometheus, slip op. at 14.

The distinctions between those two doctrines could have been further clarified at least with respect to the treatment of secondary references, if the Federal Circuit had reached the correctness of the district court’s double-patenting determination. The USPTO allows using reference patent disclosure to construe reference claims during double-patenting analysis. The USPTO apparently also allows the use of secondary references in making double-patenting rejections. But it is not clear whether secondary references can be relied upon during double patenting analysis only for construing claims, or in a manner similar as that applied in statutory obviousness analysis. This case involves a few different variables (i.e., the four subset limitations). In reaching the decision that the subset limitations were statutorily obvious, the district court relied on a number of research publications and expert testimony. Had the court addressed the double-patenting issue, the Federal Court could have at least provided guidance on the extent to which secondary references can be relied upon during double-patenting analysis.