In Prometheus Laboratories, Inc. v. Roxane Laboratories, Inc., the Federal Circuit affirmed the district court’s finding that Prometheus’ claims were invalid as obvious, but in so doing it cited its own precedent regarding obviousness-type double patenting. Is the court blurring the line between these doctrines? 

The Product At Issue

The product at issue was Roxane’s generic version of Prometheus’ Lotronex® (alosetron HCl) product, which was approved by the FDA for the treatment of irritable bowel syndrome (IBS). As explained by the Federal Circuit, IBS is a condition defined and diagnosed by its collection of symptoms. These symptoms may contribute to diarrhea-predominant IBS (“IBS-D”), constipation-predominant IBS (“IBS-C”), or some combination. Lotronex® first was launched in 2000, but was removed from the market after being linked with severe side effects. It was re-launched in 2002 with a more restrictive label, i.e., indicated only for women with severe IBS-D who have, inter alia, chronic symptoms generally lasting six months or longer, and not for use in patients with constipation.

In 2009, Roxane filed an ANDA seeking approval of its generic version of Lotronex® which included a paragraph IV certification against the Orange Book listed patent, U.S. Patent No. 6,284,770.

The Patent at Issue

The ’770 patent is directed to “[m]edicaments for the treatment of non-constipated female irritable bowel syndrome,” and includes claims that correspond to the approved use of Lotronex®. The patent issued in 2001, and Prometheus sought reexamination of the patent in 2009. A reexamination certificate issued on October 19, 2010, with the following claims amended or added during reexamination:

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.

10. The method for treating according to claim 5, further comprising assessing whether said female IBS patient has experienced at least moderate pain prior to administration of alosetron.

13. 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;
assessing whether said nonconstipated female IBS patient experiences at least moderate baseline pain from IBS; 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 and who experiences at least moderate baseline pain from IBS, wherein said effective amount is dependent on the condition of the patient and is at the discretion of the attendant physician.

The District Court Decision

Roxane challenged the validity of the claims as obvious or invalid for obviousness-type double patenting (OTDP) over a now-expired Prometheus patent—U.S. Patent No. 5,360,800. The ’800 patent included claims directed to treating IBS generally, i.e., the claims were directed to a genus of the claims in the ’770 patent, which recite methods of treating a subpopulations of IBS patients: those who (1) are women, (2) have IBS-D, (3) have experienced symptoms for at least six months, and (4) have had moderate pain.

Despite Prometheus’ evidence of secondary considerations of non-obviousness with respect to commercial success, long-felt need, and unexpected results associated with the patient subpopulations 24claimed in the ’770 patent, the district court found that the claims would have been obvious or, in the alternative, invalid for OTDP, over the ’800 patent.

In terms of commercial success, the court held that Prometheus did not prove a nexus with the claims at issue. The court similarly was not persuaded by Prometheus’ arguments that the claimed methods satisfied a long-felt need. With regard to unexpected results, the court found them unconvincing in view of various prior art teachings and expert testimony to the effect that the results were not in fact unexpected.

The Federal Circuit Decision

The Federal Circuit decision was authored by Judge Dyk, and joined by Judges Taranto and Hughes, and affirmed the district court’s obviousness determination.

Judge Dyk began the analysis by highlighting the distinction between the genus disclosed and claimed in the ’800 patent and the species-type claims at issue in the ’770 patent. Judge Dyk emphasized that “[i]t is well-settled that a narrow species can be non-obvious and patent eligible despite a patent on its genus [and an] earlier disclosure of a genus does not necessarily prevent patenting of a species member of the genus.” He emphasized that, especially in the personalized medicine space “a rejection likely would not be appropriate where the new patient subset displayed unexpected results.”

Yet, the Federal Circuit agreed with the district court that in this case unexpected results were not sufficient to outweigh the evidence of obviousness. The Federal Circuit reviewed the prior art and expert testimony and agreed with the district court’s conclusion that Prometheus’ evidence of improved efficacy in the recited subpopulations were not unexpected. Citing its recent OTDP decision in AbbVie v. Kennedy Inst. of Rheumatology Trust, the Federal Circuit noted that “[t]he record contains abundant evidence that there was a limited number of known parameters [involved in the treatment of IBS] and it would have been obvious to combine the teachings as to each parameter.”

Here, it would have been obvious for a person having ordinary skill in the art reading the ’800 patent to treat female patients with IBS-D who had symptoms for at least six months and who had experienced at least moderate pain. As discussed above, these limitations 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.

As to commercial success, the Federal Circuit agreed with the district court’s decision that this success was not due to the ’770 patent claims, but instead was attributable to Prometheus’ marketing efforts, pricing schemes, and sales tactics. That is, the Federal Circuit agreed that Prometheus had not meet its burden of producing sufficient evidence to show a nexus between the claimed methods and commercial success. The Federal Circuit likewise found no clear error in the district court’s conclusion regarding long-felt need, because it was the recited drug itself (alosetron), and not the claimed methods, that satisfied any long-felt need.

Obviousness Versus Obviousness-Type Double Patenting

While the district court held the ’770 patent claims invalid under alternative theories of obviousness and OTDP, the Federal Circuit decision discusses only obviousness. Indeed, the discussion section of the opinion does not mention double patenting, and the opinion concludes: “We affirm the district court’s holding that the challenged claims of the ’770 patent would have been obvious over the ’800 patent and other prior art.”

Yet, the crux of the Federal Circuit’s affirmance rests on its OTDP jurisprudence, i.e., its decision in AbbVie. While the use of OTDP case law to support a finding of obviousness may seem trivial given the similarity of the doctrines, other decisions have highlighted important distinctions. For instance, Geneva Pharmaceuticals, Inc. v. Glaxosmithkline PLC, 349 F.3d 1373 (2003), included a footnote highlighting “distinctions between obviousness under 35 U.S.C. § 103 and nonstatutory double patenting,” including that the objects of comparison are very different, and that obviousness requires inquiry into a motivation to modify the prior art while OTDP does not. (The footnote also opined that obviousness requires inquiry into objective criteria of non-obviousness while OTDP does not, but the Federal Circuit held in Eli Lilly vTeva Parenteral Medicines, Inc.(Fed. Cir. 2012) that such criteria–including unexpected results–should be considered in an OTDP context.) Parties facing circumstances where such distinctions may impact the outcome should consider reminding the court that obviousness and OTDP are not one and the same.