Neptune Generics v. Eli Lilly & Company, Case No. 2018-1257, 2018-1258 (Fed. Cir. April, 2019), concerns an Eli Lilly & Co. patent protecting method of administering folic acid and a methylmalonic acid (MMA) lowering agent, e.g., vitamin B12. Specifically, the method concerns the administration of these products before administering pemetrexed disodium, an anti-folate chemotherapeutic, to reduce toxic effects of the anti-folate. Pemetrexed disrupts metabolic pathways for vital enzymes for making components of DNA and RNA, thereby resulting in cell growth inhibition and cell death. The patent survived IPRs and this appeal ensued.

The IPR petitioners, Neptune Generics, LLC, Fresenius Kabi USA, and Mylan Laboratories Ltd., argued on appeal that (1) the Board erred in conducting its obviousness analyses of three petitions for IPR and (2) Lilly’s claims were invalid because they are directed to an unpatentable law of nature under 35 U.S.C. § 101.  The court said that it would review arguments by the Petitioners with respect to the Board’s determination of non-obviousness, but would not entertain arguments with respect to subject matter eligibility because Section 101 was out of bounds in appeals arising from IPRs as Congress did not include that among the grounds that can be raised in an IPR.

Petitioners’ appeal focused on three references and their teachings with respect to folic acid and vitamin B12 and how these compounds correlated to homocysteine and MMA levels.  The Board found that the prior art taught pretreatment with folic acid to reduce toxicity of the anti-folate, but did not teach pretreatment with vitamin B12 along with folic acid before administering pemetrexed.  The court reviewed the Board’s legal determinations de novo and reviewed the underlying factual findings for substantial evidence.  Belden Inc. v. Berk-Tek LLC, 805 F.3d 1064, 1073 (Fed. Cir. 2015).  Petitioners attempted, according to the court, to evade the substantial evidence standard of review by manufacturing legal error. But the court found no error in the Board’s analyses. In determining that the Board did not err, the court concluded that substantial evidence supported the Board’s analyses.

Petitioners also argued that the Board legally erred in holding that evidence of FDA communications concerning clinical trials supported a finding of skepticism by the FDA to administer a combination of folic acid and vitamin B12, which the Board relied on in support of its conclusion of non-obviousness.  During clinical trials of pemetrexed, Lilly had suggested the combination, but the FDA questioned the idea, asserting that “addition of vitamins … is risky.”  The court determined the FDA’s concern—regarding adding vitamins, i.e., vitamin B12, to the ongoing clinical trial—was sufficient to establish skepticism.  The court held that the FDA’s questioning or concern could constitute skepticism, and that skepticism did not require more stringent premises of being “technically infeasible,” “unworkable,” or “impossible.”  Thus, the court held that the Board did not err in finding that the FDA’s skepticism supported a conclusion of non-obviousness.

Neptune confirms that arguments regarding subject matter eligibility are not appropriate for an appeal of an IPR decision.  Further, Neptune offers an example of where a concern expressed by a third party is enough to establish skepticism in support of non-obviousness.