Genentech, Inc., Intermune, Inc. v. Sandoz Inc., LEK Pharmaceuticals, D.D.
Docket No. 2022-1595 (https://cafc.uscourts.gov/opinions-orders/22-1595.OPINION.12-22-2022_2052253.pdf)
NEWMAN, LOURIE, PROST
December 22, 2022
Brief Summary: DC findings that Genetech’s disputed Esbriet® patents are invalid for obviousness and not infringed by Sandoz’s ANDA affirmed.
Summary: Genentech (“GT”) appealed DC decision holding that: (1) GT’s Liver Function Test (“LFT”) claims are invalid for obviousness (US 7,566,729; 7,635,707; 8,592,462; and 8,609,701) (2) “Sandoz’s” generic product sales would not induce infringement of the LFT patents, and (3) Sandoz’s generic product sales would not directly infringe GT’s Drug-Drug Interaction (“DDI”) patents (US 7,816,383 and 8,013,002 directed to avoiding adverse interactions between pirfenidone and fluvoxamine). Sandoz’s ANDAs sought approval to market a generic version of pirfenidone that is sold by Genentech (as Esbriet® with 17 and 19 patents listed on the Orange Book for the capsule and tablet forms, respectively) to treat about half of all idiopathic pulmonary fibrosis (IPF) patients. The FC panel opinion explains that “[t]he major differences between the [available] drugs center on side effects and metabolism” and that pirfenidone was first studied as an IND in 1973, granted orphan drug status in the US in 2004, and that Esbriet® was approved to treat IPF in 2014. The FC panel opinion also explains that “[t]he LFT patents are directed to methods for administering pirfenidone to a patient who has exhibited abnormal biomarkers of liver function in response to pirfenidone administration” (e.g., “a grade 2 abnormality” indicated by alanine transaminase (ALT) or aspartate transaminase (AST) levels) “by reducing, maintaining, or discontinuing then returning to the full or a reduced dose (e.g., “2400 mg/day for a time period, followed by…2400 mg/day or 2403 mg/day”, “administering…1600…or 1602 mg/day”). Sandoz’s proposed ANDA label includes instructions to modify the dosage if “liver enzyme and bilirubin elevations are exhibited”, including “ALT and/or AST”. The DC agreed with Sandoz’s obviousness arguments regarding the LFT patents based on the Azuma reference (a pirfenidone clinical trial suggesting reduced dosages with “an adverse event of Grade 2 or worse”), the Pirespa® label (suggesting discontinuing pirfenidone administration with increased AST or ALT), “and known, standard medical practices” and its argument that “there was no specific intent for induced infringement” as only “four of the five dose modification options provided in the label were covered by the asserted claims” and “the portion of the label that referred to infringing uses did not recommend any of the infringing uses, but rather, merely described them.” The FC panel agreed with the DC on obviousness (e.g., no clear error in DC’s conclusion that “claiming” “varying doses in response to the occurrence of side effects [is] a well-established, hence obvious, practice” (Adapt, FC 2022); “weak secondary considerations” (W. Union, FC 2010)), and therefore did not review the DC’s infringement findings.
The DC agreed with Sandoz “that there was insufficient evidence of direct infringement” of the DDI patents (e.g., “the language in Sandoz’s label that encourages, recommends, or promotes an infringing use without any additional evidence showing such an infringing use will in fact occur, is insufficient for a finding of direct infringement”). The FC panel also agreed with Sandoz, explaining that while “[i]t is true that although the Hatch-Waxman Act provides that the filing of an ANDA before a patent covering a compound or a use expires meets the technical jurisdictional requirement of infringement, that is not the same as the direct infringement that serves as a predicate for finding induced infringement” (35 USC 271(e)(2)(A); Glaxo, FC 1997). “Here,” the FC panel wrote, “as in Eli Lilly and Takeda, the district court did not clearly err by considering all the relevant evidence, including Sandoz’s proposed label and physician practice” (e.g., “testimony from physicians that, in their decades of treating IPF patients, they had never prescribed pirfenidone to an IPF patient taking fluvoxamine; and were they to find themselves in that position, they would choose a noninfringing response—i.e., prescribing nintedanib instead”; Glaxo, FC 1997; Vanda, FC 2018 (“specific intent to encourage another’s infringement”); Takeda, FC 2015 (label “recommends, encourages, or promotes”; “evidence outside the label” showing direct infringement); Ferring, FC 2014; Lilly, FC 2017 (“product labeling, combined with…physicians’ general practices”)).
Federal Circuit summaries 