Docket No. 2018-1257-8, -1288, -1290 (multiple IPRs)
Moore, WALLACH, HUGHES
April 26, 2019
Brief summary: Board IPR decisions finding Lilly’s claims relating to administration of vitamin B12 with pemetrexed were not shown to be obvious affirmed.
Summary: Neptune Genetics (NG) appealed Board holding that claims 1-22 of Lilly’s US 7,772,209 relating to administering pemetrexed disodium with folic acid and a “methylmalonic acid lowering agent” (MMA; e.g., vitamin B12) were not shown to be unpatentable for obviousness. Claim 12 relates to a similar method but as “[a]n improved method for administering pemetrexed disodium to a patient in need of chemotherapeutic treatment”. Three IPRs alleged obviousness over Calver, Niyikiza I (Niyizaka being the sole named ‘209 inventor), EP 0595005A1 (“EP005”), and US 5,217,974 (IPR2016-00318); Niyikaza I, the ‘974 patent, and EP005 (IPR2016-00237); and Rusthoven and EP005 (IPR2016-00240). 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 not a reason to pretreat with vitamin B112 along with folic acid before administering pemetrexed to treat cancer” and that “skepticism of others, particularly the FDA, supported a conclusion of nonobviousness.” The FC panel agreed with the Board’s analysis (e.g., “no observed correlation between vitamin B12 deficiency and pemetrexed-induced toxicity”) that “[e]ach step of the Board’s analysis is supported by substantial evidence” (“supported by additional prior art and are consistent with the testimony of Petitioner’s expert”, “evidence indicates that pemetrexed-induced toxicity correlated with folate deficiencies” (e.g., elevated homocysteine levels) “but not vitamin B12 deficiencies”). “Collectively,” the FC panel wrote, the evidence (e.g., “while elevated levels of homocysteine were known to be predictive of pemetrexed toxicity, elevated levels of MMA were understood not to be predictive of pemetrexed toxicity”) “constitutes substantial evidence…that the art did not provide a motivation for a skilled artisan to administer an MMA lowering agent, such as vitamin B12, in addition to folic acid”. The FC panel acknowledged that “EP005 states that it ‘is applicable to the lowering of total homocysteine blood levels if elevated by any known cause” but “does not discuss antifolates generally, and only generally mentions certain cancers”, and that “the Board found that the levels of homocysteine associated with elevated pemetrexed toxicity risk were not ‘elevated’ as that term is defined in EP005” (also noting that “Niyikiza II explained that pemetrexed did not increase homocysteine levels”). NG also argued that Lilly’s statements to the FDA indicated the prior art suggested pretreating with folic acid and B12, but the FC panel noted that those statements “were made…more than five months after the critical date” and the Board did not err in finding that “the views Lilly expressed about the prior art references…are made through the lens of what they had invented” (In re Copaxone, FC 2018 (“a patent owner’s own disclosures to the FDA may be considered in assessing the state of the prior art”)). The FC panel also found no error with the Board’s in finding the FDA’s skepticism weighed in favor of non-obviousness (WBIP, FC 2016; Circuit Check, FC 2015). The FC also declined to consider NG’s § 101 arguments since IPRs are limited to § 102 and 103 arguments.