U.S. Pat. No. 8,476,010B2
Final Written Decision (June 5, 2017)
Brief Summary: Board found challenged claims of US 8,476,010B2 relating to formulations of the anesthetic propofol (2,6-diisopropylphenol) stored in containers having nonreactive, inert closures (sold as Diprivan) invalid for obviousness.
Summary: Bass et al. (Petitioner) requested IPR of claims 1, 13-15, 17, 18 and 20 of Fresenius’s US 8,476,010B2 relating to formulations of the anesthetic propofol (2,6-diisopropylphenol) stored in containers having nonreactive, inert closures (sold as Diprivan) on obviousness grounds (see also IPR2015-00715). The FWD explains that “[p]ropofol compositions have been the subject of several patents” (e.g., US 5,714,520 (“a sterile, pyrogen-free emulsion containing 1% (w/v) propofol in 10% (w/v) soybean oil”)). Petitioner cited the Diprivan IPR, “Farinotti” (storage of Diprivan for three years in a glass vial using a bromobutyl stopper) and “van den Heuvel” (bromobutyl rubber does not cause unacceptable deterioration in quality) or “Lundgren” (bromobutyl rubber improves stability of thrombin) as the basis for its obviousness arguments. The Board accepted the Fresenius’s definition of one of ordinary skill in the art as one having at least a master’s degree in a related technical field or equivalent experience but also “experience with propofol and drug product emulsions, emulsion systems and their packaging”, and accepted both parties’ expert declarants. Under the broadest reasonable construction (BRC (Cuozzo, US 2016; In re Translogic, FC 2007; In re Paulson, FC 1994; Wellman, FC 2011), the Board construed “from about 0 to about 10% by weight solvent for propofol” as “from approximately zero to approximately 10% solvent by weight, a range that includes 10%”; “siliconized” as “surface-treated, coated, or manufactured with silicone or one or more siloxane polymers”; and “inert to propofol” as “having no significant reactivity to propofol”. The claims also include a “stability limitation”. The FWD explained that “a patent composed of several elements is not proved obvious merely by demonstrating that each of its elements was, independently, known in the prior art” and “it can be important to identify a reason that would have prompted a person of ordinary skill in the relevant field to combine elements in the way the claimed new inventions does” with “a reasonable expectation of success” (KSR, US 2007; PAR Pharm., FC 2014; In re Gurely, FC 1994 (teaching away suggests path “unlikely to be productive”)). The Board found the stability limitation to be “an inherent property of Diprivan” and statements in the ‘010 specification. And it found the argumetns and evidence provided “a reason to use a siliconized bromobutyl rubber stopper with the claimed propofol formulation” (e.g., van den Heuvel teaches that type of stopper “imparts a stable solution of diazepam”, skilled artisan “would have recognized the advantages” (suggestion “does not have to be found explicitly in the prior art” (In re Kahn, FC 2006), this is not a case “where the art did not appreciate or suggest the existence of a problem” (Novartis Pharms., D. Del. 2004; Leo Pharms., FC 2013; Unwired Planet, FC 2016), KSR (“any need or problem…can provide a reason for combining”)). The Board also disagreed there was a teaching away in other art cited by Fresenius (e.g., “not persuaded that the data are comparable”, “even if” the art “encouraged the use of other stoppers…we are not persuaded that this rises to the level of criticizing, discrediting, or discouraging” (Mieresonne, FC 2017)). The Board also concluded Bass “has a better position” regarding whether it would have been obvious to try using a siliconized rubber stopper since this was “repeatedly identified as a solution” to the known problem of “rubber stoppers sticking to the metallic machinery on automatic filling lines” (KSR (where “finite number of identified, predictable solutions, a person of ordinary skill has good reason to pursue the known options…the product not of innovation but of ordinary skill and common sense”)). It concluded Bass had shown by a preponderance of the evidence that all of the challenged claims are unpatentable as obvious.