IPR2015-01775 (U.S. Pat. No. 8,865,190B2)
February 28, 2017
Brief Summary: Pozen’s claims found not obvious as Lupin did not show by a preponderance of the evidence the limitation requiring that “release of at least a portion of said naproxen is inhibited unless the pH of said medium is 3.5 or higher” would have been reasonably expected from the prior art.
Summary: The Board concluded Lupin did not show by a preponderance of the evidence that claims 1, 2 and 4-8 of the ‘190 patent relating to a process for preparing formulations of the proton pump inhibitor (PPI) esomeprazole (the S- or (-)-enantiomer of omeprazole) and naproxen (Vimovo(TM)) are unpatentable for obviousness based on the combination of US 5,698,225; “Chandramouli”; and WO 00/26185 (“the burden never shifts to Patent Owner” (Dynamic Drinkware, FC 2015; In re Magnum Oil, FC 2016)). Sole independent claim 1 requires the process to include layering a “second layer compris[ing]…esomeprazole” on a “first layer comprising naproxen” “wherein…at least a portion of said esomeprazole is released regardless of the pH of the medium [i.e., immediate release] and release of at least a portion of said naproxen is inhibited unless the pH of said medium is 3.5 or higher.” The Decision first explained that “[t]he person of ordinary skill in the art is a hypothetical person who is presumed to have known the relevant art at the time of the invention”, considering, e.g., “the types of problems encountered in the art, the sophistication of the technology, and the educational level of active workers in the field” (In re GPAC, FC 1995). It adopted Lupin’s proposed definition, “as modified by the Patent Owner’s addition”, as a person with a Ph.D. “in the field of pharmaceutical sciences or equivalent training or degree with at least two years of experience with pharmaceutical formulations” with or without “a graduate degree in chemistry or chemical engineering, because…the interactions between chemical compounds inform our obviousness analysis.” The Decision explained that it was known that NSAIDs such as naproxen cause GI damage, that taking concomitant doses of a PPI “suppresses gastic acid secretion” and “improved NSAID tolerability”, and that PPIs are “highly acid labile” and should “be protected from gastric acid by…e.g., an enteric coating” that are “well known in the art” for, e.g., “coating commercially available NSAIDs.” The Board concluded that Lupin’s expert correctly found that the skilled artisan would have understood from Chandramouli and WO ‘185 that esomeprazole had a similar therapeutic effect” and safety profile as omeprazole (“obviousness does not require the prior art to reach expressly each limitation exactly” (Beckson Marine, FC 2002)). The ‘225 patent was found to disclose “a tablet containing an NSAID core…surrounded by an enteric coating…that protects the NSAID from the acidic environment of the stomach” and an “outer layer…made up of a prostaglandin acid inhibitor (i.e., misoprostol).” The Board concluded Lupin showed by a preponderance of the evidence that the skilled artisan would have been motivated to substitute immediate release esomeprazole for misoprostol (“we again reject Patent Owner’s argument against substitution due to the fact that ‘none of the [prior art] even mention esomeprazole”). However, the Board also concluded that Lupin did not show a reasonable expectation of success (“we cannot demand absolute certainty”, citing Intell. Biosys., FC 2016) regarding the delayed pH-dependent release of naproxen because, e.g., as argued by the Pozen, immediate release of omeprazole is taught by WO ‘185 using a sodium bicarbonate buffer, which protects [it] from acid degradation in the stomach” but “also dissolves enteric coatings in a solution” (leaving “no portion of naproxen…to release only after pH reached 3.5”) and Lupin did not “adequately rebut” that argument (e.g,. “Petitioner provides no reference…to testimony from [its expert] about the ‘fundamental characteristics of enteric coatings’” (Johnston, FC 1989 (“attorney argument” and “common sense” cannot suffice), and “Petitioner provides us with no evidence that succinctly explains the relationship between the time at which the enteric coating will dissolve and the status of the surrounding medium’s pH.”)