IPR2016-00458 (US 7,625,558)
Final Written Decision
July 13, 2017
Brief summary: PTAB FWD found claims of Penn’s ‘558 patent allegedly relating to Lilly’s Erbitux® (centuximab) to be invalid for obviousness.
Summary: IPR as to claims 1-7, 9-12, 14, 16, 17, and 19-31 of the ‘558 patent was instituted on July 14, 2016 for obviousness over the combination of the “Saleh”, “DeNardo”, and “Balaban” prior art documents. Litigation (ED PA) regarding the ‘558 patent in which Penn alleged infringement by Lilly’s Erbitux® (centuximab) is currently stayed pending any motions for reconsideration or appeals of this FWD. At least one application related to the ‘558 patent (15/442,046 filed Feb. 1, 2017) is currently pending at the USPTO. The challenged claims (for obviousness in view of a combination of the “Saleh”, “DeNardo”, and “Balaban” references) are directed to “[a] method of treating an individual who has an erbB protein mediated tumor” by “administering to said individual an antibody which inhibits formation of erbB protein dimers that produce elevated tyrosine kinase activity in a tumor cells, said inhibition having a cytostatic effect on the tumor cell; and (b) thereafter exposing said individual to a therapeutically effective amount of anti-cancer radiation.” In its Decision to Insitute, the PTAB construed “anti-cancer radiation” and “gamma radiation” (ind. claim 5) to mean “any of the protocols and parameters” described “in the Perez & Brady textbook”. In this FWD, the PTAB agreed with Lilly that under the broadest reasonable construction (Cuozzo, US 2016) “anti-cancer” and “gamma irradiation” are not limited to “conventional external beam radiation” as argued by Penn (“neither standard nor conventional in the art at the time of the invention”, relying on, e.g., the specification’s incorporation by reference (Zenon, FC 2007) and expert witness testimony) and do not exclude radio immunotherapy (“RIT”) (Glaxo, FC 2003 (“When a claim term has an accepted scientific meaning, that meaning is generally not subject to restriction to the specific examples in the specification.”); and “there was no prosecution history disavowel” (SAS Inst., FC 2016)). The PTAB also concluded that “[a] showing in the prior art of an antibody that disrupts tyrosine kinase activity, such as by inhibiting dimer formation, is sufficient to satisfy the claimed inhibition having a ‘cytostatic effect’.” The FWD discussed but did not construe “‘multimeric receptor ensembles’ because both parties agree” it “includes EGFR-p185 heterodimers.” The PTAB found “that the cited prior art is representative of the level of ordinary skill in the art” (Okajima, FC 2001). It also allowed Penn’s motion to amend and its arguments regarding a fourth reference since it was mentioned in Lilly’s Petition, and disagreed with Penn regarding the propriety of Lilly’s expert witnesses.
Regarding the combination of references, the PTAB first concluded that Saleh’s disclosure of the C225 anti-EGFR antibody showed a “cytostatic effect” (as opposed to a cytotoxic effect as argued by Penn) on erbB protein mediated tumor cells. Interestingly, a second Saleh reference, “Saleh II”, having a post-‘558 filing date publication date, was also relied on as evidence to show an inherent property, see FN10 (Schering, FC 2003 (rejecting the contention that inherent anticipation requires recognition in the prior art before the critical date)). The claimed requirement that radiation be administered after antibody was found to be disclosed by the combination of the three references. The PTAB also found the references provided “a reasonable expectation of inhibiting, the formation or of kinase activity mediate by, ‘a heterodimer of p185 and EGFR’”, as in claims 5, 10, 14, 17 and 20. It also found Lilly had shown a skilled artisan would have had reason to combine the references since, e.g., according to Lilly’s expert, “DeNardo indicates that cancer patients will have better outcomes if they receive radiation after the treated with C225” and “it is of no matter that the prior art might not have recognized the mechanism of operation” (In re Litner, CCPA 1972 (reason to combine taught by the references differing from applicant’s reason to combine did not alter the conclusion of prima facie obviousness); Senji, FC 2015 (affirming DC decision that even statistically insignificant data can serve as motivation to combine)). Penn argued the art taught away (Tec Air, FC 1999) from the claimed subject matter since cytotstatic cancer therapies would have been thought to decrease radiation sensitivity, but the PTAB disagreed. The PTAB also disagreed with Penn’s unexpected results argument, finding those to be “unsupported by evidence, such as expert testimony, and amount[ing] to attorney argument.”