Docket No. 2015-2021(22 others)
MOORE, BRYSON, HUGHES
May 16, 2018
Brief summary: DC findings that the proposed ANDA of Endo’s OPANA®ER infringe the claims, and that those claims are not invalid for obviousness or indefiniteness, affirmed.
Summary: Teva et al. appealed DC finding that all asserted claims of Endo’s US 8,309,122 B2 and 8,329,216 B2 relating to controlled release oxymorphone formulations (as in Endo’s OPANA®ER) and methods for treating pain using the same valid and infringed. The FC panel opinion explains that the asserted claims includes limitations regarding “dissolution” or “release rate” measured “using the ‘USP Paddle Method at 50 rpm in 500 ml media’”; and pharmacokinetic limitations relating to the analgesic effect (e.g, at least about 12 hours), food effects (AUC(0-inf) between fed and fasted conditions is less than 20%”), detectable blood plasma levels (e.g., “of 6-OH oxymorphone and oxymorphone”), and “multiple peaks” (e.g., “two or three” peak concentrations “about 12 hours after administration”). The DC found the asserted claims are not invalid for obviousness, written description (WD), or indefiniteness, and that “Endo carried its burden to show that defendants infringe or will infringe all but two of the asserted claims”. The DC also issued a permanent injunction against Actavis as it was already selling a generic OPANA®ER.
Regarding obviousness, the FC panel found Teva et al. failed to show obviousness because “the prior art references in the record strongly discourage a controlled release formulation of opioids with low bioavailability, such as oxymorphone, and, more critically, do not suggest the dissolution and pharmacokinetic limitations” (KSR, US 2007; Apple, FC 2016 (en banc); § 282; Microsoft, US 2011). The FC panel found no error with the DC’s analysis which was based in part on expert testimony (e.g., “…the Oshlack reference also taught that ‘bioavailability is a significant, even crucial factor, in evaluating a drug’s suitability for placement in a controlled release vehicle”, “Appellants’ own expert maintained the view that active ingredients with poor bioavailability would not be good candidates for controlled release dose forms.”) The FC panel disagreed with Amneal’s argument “that the low bioavailability…could be addressed by increasing the dosage” as the prior art taught away from this as a solution (Allergan, FC 2015 (teaching away where “a person of ordinary skill…would be discouraged…or led in a direction divergent”)). The FC panel also found no error with the DC’s consideration of the dissolution limitations (e.g., the DC “found Endo’s expert testimony more persuasive”, the prior art “measured dissolution in a different manner…at twice the speed, at 100 rpm, and in nearly twice the aqueous buffer (900 ml compared to Endo’s 500 ml of media)”. Amneal also argued the DC erred by ignoring Kao (FC 2011 (PTAB interference appeal involving “a less fulsome record and a different evidentiary burden for showing obviousness” (FN6)) “by giving patentable weight to the pharmacokinetic limitations inherent to” prior art formulations. The FC panel found the DC did not err because, e.g., “Endo does not claim any controlled release configuration” but “only those which have been specifically calibrated to produce the pharmacokinetic properties recited in the claims-excluding those that do not exhibit such properties”, and the prior art did not “give any indication” that the limitations, for oxymorphone, “were neither ‘necessarily…present’ nor ‘the natural result of the combination of elements explicitly disclosed by the prior art” (PAR Pharm., FC 2014). The FC panel also agreed that the prior art does not disclose the claimed food effect limitations, and that the DC properly relied on secondary considerations as “strongly indicating” non-obviousness (e.g., expert testimony on commercial success, clear nexus between the claims and market success, and long-felt need).
The DC concluded the “multiple peaks limitation” was not indefinite “[b]ecause the specification sufficiently describes the meaning and scope” of the limitation based on its reference “to peaks of curves drawn on charts”. The FC panel agreed that “a skilled artisan would recognize a peak as occurring where blood concentration of oxymorphone reaches a high-point before declining” (Nautilus, US 2014 (“reasonable certainty”); Halliburton, FC 2008).
Teva et al. also argued “the ANDA products do not infringe the ‘food effect’ limitations” and the DC therefore erred in finding infringement under § 271(e)(2) (“‘if a particular drug were put on the market…would [it] infringe the relevant patent’ in the usual, non-artificial sense” (Acorda, FC 2016; Warner-Lambert, FC 2003 (compare claims to “ANDA product that is likely to be sold”)). The FC panel agreed with the DC, however, since “the package inserts, which are representations made to the FDA to establish that the proposed generics possess the same characteristics, including the food effect limitations, present in Endo’s approved products.”
The FC panel also found no error with the DC’s grant of a permanent injunction against Actavis under § 283 (“to prevent the violation of any right secured by a patent”) since “Endo presented evidence of irreparable harm as well as other factors” (e.g., Actavis’ generic OPANA infringed the patents, Endo and Actavis are direct competitors, Actavis made no argument it would suffer, public policy favored Endo; eBay, US 2006).