In Neptune Generics, LLC v. Eli Lilly & Co. the Federal Circuit upheld the Patent Trial and Appeals Board’s inter partes review decisions that claims 1-22 of Eli Lilly’s patent U.S. 7,772,209 (‘209 Patent) were not invalid as obvious. It is an interesting case because it illustrates a finding of nonobviousness in a matter having solid arguments on the other side.
The ‘209 Patent includes method claims where folic acid and a methylmalonic acid lowering agent (e.g., vitamin B12) are administered prior to treatment with the antifolate pemetrexed disodium, a chemotherapy agent. The folic acid and methylmalonic acid are used to ameliorate the toxic effects of the pemetrexed. The heart of the Board’s conclusion was that although it was known to use folic acid to reduce the toxicity of antifolates such as pemetrexed, there was no reason to pretreat with vitamin B12 and folic acid prior to treatment with pemetrexed for cancer. On appeal, the Petitioner’s obviousness arguments related to the EP005 reference, which taught use of folic acid in conjunction with vitamin B12 to reduce homocysteine levels for all purposes. Homocysteine is an amino acid, and when present in high levels is predictive of pemetrexed toxicity. On its face this appears to be a solid case for obviousness. Indeed, those arguing against motivation to combine during patent prosecution have almost certainly encountered an Examiner’s response referencing MPEP 2144IV at one time or the other:
The reason for motivation to modify the reference may often suggest what the inventor has done, but for a different purpose or to solve a different problem. It is not necessary that the prior art suggest the combination to achieve the same advantage or result discovered by applicant. (MPEP 2144IV)
However, the Board also found that deficiencies in vitamin B12 and folate lead to higher levels of homocysteine, that higher levels of methylmalonic acid (“MMA”) correlate with B12 deficiencies but not folate deficiencies, and that while higher levels of homocysteine were predictive of pemetrexed toxicity, elevated levels of MMA were not. Finally, the Board concluded that there was no correlation between vitamin B12 deficiency and pemetrexed-induced toxicity because higher MMA levels correlate with vitamin B12 deficiency but are not predictive of toxicity. The Federal Circuit found that substantial evidence supported the Board’s findings.
The reason for the possible disconnect between the holding in this case and what patent practitioners often encounter during prosecution is that here the matter turned on the factual findings underlying the legal conclusions. However, the motivation to combine question is a factual issue, and the standard of review of such fact finding by the Federal Circuit is one of substantial evidence. Substantial evidence requires more than a “scintilla of evidence,” but less than the weight of the evidence, so that it is possible for two reasonable minds to look at the same evidence and arrive at two inconsistent conclusions. Such is the case here.