April 26, 2019

FDA Skepticism Supported Non-obviousness

In Neptune Generics, LLC v. Eli Lilly & Company, [2018-1257, 2018-1258](April 26, 2019), the Federal Circuit affirmed the PTAB’s Final Written Decisions in multiple Inter Partes Reviews holding Petitioners did not establish that claims 1–22 of U.S. Patent No. 7,772,209 are unpatentable for obviousness.

The Board found that it was known in the prior art that pretreatment with folic acid reduces the toxicity associated with administration of an antifolate, like pemetrexed, but there was no reason to pretreat with vitamin B12 along with folic acid. The Board further found that skepticism of others, particularly the FDA, supported a conclusion of nonobviousness.

Although there was a reference that taught administration of folic acid and B12, it was not for the purpose of reducing toxicity of premetrexed, and the record — including expert testimony — persuasively established that one of skill in the art would not have understood that there was no observed correlation between vitamin B12 deficiency and pemetrexed-induced toxicity.

Petitioners argued that Lilly told the FDA that the prior art suggested that pretreating with folic acid and B12 was a no-risk, predictable way to lower pemetrexed-induced fatalities by lowering pretreatment homocysteine levels. However, since these statements were all made post-critical date, the views Lilly expressed about the prior art references in its communications are made through the lens of what they had invented.

As to secondary considerations, the Board found that evidence of skepticism of others, particularly the FDA, supported a conclusion of nonobviousness. When, during FDA trials, Lilly recommended supplementation with folic acid and vitamin B12, the FDA responded that the “medical officer does not sup-port adding vitamins to the ongoing … trial.” In other communications with Lilly, the FDA stated that the information provided to it “does not appear to support the addition of vitamins,” and that “the addition of vitamins … is risky.” Petitioners argued that skepticism must be premised on whether it is “technically infeasible,” “unworkable,” or “impossible” that the claimed subject matter would work for its intended purpose, but the Federal Circuit disagreed, pointing out that its case law recognizes a range of third-party opinions that can constitute skepticism. The Federal Circuit noted that while evidence that third parties thought the invention was impossible might be entitled to more weight, that does not mean the Board erred in giving weight to the skepticism evidence here.


While evidence of teaching away must specifically discourage the inventive course, the Federal Circuit reminds us in Neptune Generics that evidence that third parties were “worried” or “surprised” is sufficient to establish skepticism.