Orexo AB et al. v. Actavis Elizabeth LLC

Docket No. 2017-1333

September 10, 2018

Brief summary: DC holding of Orexo’s Orange Book-listed claims related to the opioid dependence drug Zubsolv® invalid for obviousness reversed and remanded.

Summary: Orexo appealed DC holding of claims 1, 3-6 and 8-10 of Orexo’s Orange Book (OB)-listed US 8,940,330 related to the opioid dependence drug Zubsolv® invalid for obviousness. Five other patents are listed on the OB for Zubsolv®, and the FC panel opinion explains that one of these (US 8,454,996) was also challenged by Actavis and held valid (not involved here). Representative ‘330 claims 1 and 6 are directed to “[a] tablet suitable for sublingual administration”, the ingredients of which the DC found were all generally known. The DC “held that although the specific formulation was not shown or suggested in any reference, the new combination would have been obvious to a person of skill.” Orexo argued that “the improvements achieved by the Zubsolv product” (“66% high bioavailablity” as shown in the ‘330 Example 2, but not claimed) as compared to the prior art sublingual product Suboxone® are due to its product’s “microparticles of buprenorphine adhered to the surface of citric acid carrier particles”, and that its higher bioavailability “is not suggested or reasonably predictable from the prior art”. Actavis did “not dispute the improvement, or its value in treatment of addiction”, but argued that the claimed “formulation is obvious based on [the] combination of references, and that improved function and use are irrelevant if the product is obvious.” The FC panel found Actavis’s “theory” to be “flawed, for an unobvious improvement in properties or use is highly relevant to patentability of a new product.” In its Discussion, the FC panel explained that it reviewed the DC’s findings for clear error and its conclusions of law de novo (In re Cyclobenzaprine, FC 2012), that “[j]udicial hindsight must be avoided” (KSR, US 2007), and “[i]t is inappropriate to use the template provided by the inventor, to render the inventor’s contribution obvious” (Interconnect Planning, FC 1985 (“The invention must be evaluated not through the eyes of the inventor, who may have been of exceptional skill, but as by one of ‘ordinary skill’.”)). The DC relied on three prior art references (the ‘832 patent for “the use of citric acid with an interactive mixture would also improve bioavailability”; Orexo’s ‘432 application “for its disclosure of particles of buprenorphine adhered to carrier particles”; and the EP ‘725 application “for its general description of interactive mixtures as pharmaceutical formulations”) and admitted “[t]he product herein is…new”, acknowledging the undisputed testimony of Orexo’s experts supporting that point but favored Actavis’s expert testimony. The DC supported its decision by stating that the evidence showed “a person of ordinary skill in the art would not have excluded citric acid” but the FC panel explained that this “is not a teaching or suggestion to use citric acid” (“no reference or combination of references proposes the path of the ‘330 Patent”, there is no “suggestion of the sublingual tablet…or a teaching of its benefit in deterring use”; In re Gordon, FC 1984 (“The mere fact that the prior art could be so modified would not have made the modification obvious unless the prior art suggested the desirability of the modification.”)) The FC panel also disagreed with the DC’s finding that the improved 66% bioavailability was “‘a difference in degree,’ not a difference in ‘kind’” and the DC’s discounting of “Orexo’s evidence that Zubsolv is less susceptible to abuse than Suboxone” (“Although the weight of this evidence was disputed, the FDA deemed the product worthy of approval for the efficacy that was established in the clinical trials…reduced dosage and enhanced efficacy in substitution therapy products, deterring abuse.”) The DC decision was therefore reversed and remanded.

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