Janssen Pharmaceuticals, Inc. et al. v. Teva Pharmaceuticals USA, Inc., Mylan Labs. Ltd.
Docket No. 2022-1258, -1307 (https://cafc.uscourts.gov/opinions-orders/22-1258.OPINION.4-1-2024_2293991.pdf)
DYK, PROST, HUGHES
April 1, 2024
Brief Summary: DC obviousness decision vacated and remanded; no indefiniteness finding affirmed. Summary: Teva appealed DC bench trial decision that it had not proved the obviousness of the asserted claims of Janssens’ Orange Book (OB) US 9,439,906 relating to an extended-release intramuscular injectable paliperidone palmitate (PP) for treating schizophrenia (sold as Invega Sustenna). The ‘906 patent claims “[a] dosing regimen…comprising” intramuscular (im) administration of “about 150 mg-eq sustained release PP “in the deltoid” on day 1 (“first loading dose”), about 100 mg-eq sustained release PP in the deltoid from about days 6-10 (“second loading dose”), and then “about 25 mg-eq. to about 150 mg-eq.” sustained release PP “in the deltoid or gluteal muscle” per month. Dependent claim 2 claims a dosing regimen of “about 25 mg-eq. to about 150 mg-eq.” sustained release PP “in the deltoid or gluteal muscle” at monthly intervals “after administration of the first maintenance dose”. Claims 10 (“aqueous nanoparticle suspension”) and 13 (25-50 mg-eq. for the maintenance dose) depend from independent claim 8 relate to renally impaired patients, while claims 19-21 are “particle-size claims” (“about 1600 nm to about 900 nm”). The ‘906 patent explains that “‘[p]aliperidone is the major active metabolite of risperidone,’ an antipsychotic that was developed in the 1990s” and that a tablet formulation was already on the market but patients are not compliant with daily dosing. The ‘906 patent also explains that “deltoid injections result in a faster rise in initial plasma concentration” and is therefore used for the “initial loading dose[s]”, and preferred subsequent injections are in the gluteal muscle. Teva relied on three prior art references, the ‘548 Phase III PP clinical study protocol that “does not contain any results”, the Invega OB ‘544 patent disclosing 90% PP particles “of less than 2,000 nm” and im administration to beagles, and Janssen’s WO ‘384 publication directed to “‘a process for preparing aseptic crystalline’ paliperidone palmitate” and “matches both the composition elements of claims 20 and 21 and the Invega Sustenna formulation”. Teva argued the DC required it to show that “it would have been obvious to use the recited dosing regimens for the general population of patients—i.e., a generalized dosing regimen” (e.g., “population-wide safety and efficacy”), which Teva argued was improper because the claims are not directed to a population but to “a” patient. The FC panel agreed with Teva (e.g., DC should have “focus[ed] its findings on single patient administration”). Teva also argued the DC “also read a ‘mild’ limitation into the renal-impairment claims, whereas the claims do not specify a level of renal impairment” and the FC panel agreed (e.g., DC improperly concluded that “if a prior art reference does not contain safety and efficacy data, there is no reason to combine it with other prior art references” (United Ther. (FC 2023), Allergan (FC 2013) (cannot import FDA requirements); Alza (FC 2006), Adapt Pharma (FC 2022), Bayer (FC 2017) (motivation to combine, “suitable option”)). The FC panel also instructed the DC to reconsider its secondary consideration determinations, which favored Janssen, that the FC panel wrote “might well be inadequate to support a conclusion of nonobviousness” (Tokai, FC 2011; Bristol-Myers, FC 2014; Henny Penny (FC 2019), Merck (FC 2015) (nexus); Forest Labs., FC 2019 (“surprising or unexpected” results; would the skilled artisan have been aware of side effects?); Kao, FC 2006) (e.g., “unclear how, if at all, the unexpectedness of these [clinical trial] failures relates to the claims”, effect of blocking patents /safe harbor (271(e)(1) (Acorda, FC 2018). Teva also argued the claims are indefinite because there were multiple methods for measuring particle size and one was not specified, but the FC panel disagreed that the differences “would be significant or meaningful.”