Docket No. 2017-1115
NEWMAN, LOURIE, HUGES
October 26, 2017
Brief Summary: DC conclusion that the asserted claims of its US 6,486,150 “directed to a stable process for preparing a stable formulation” of the antibiotic ertapenem (marketed by Merck as Invanz®) are invalid for obviousness affirmed.
Summary: Merck appealed DC conclusion that the asserted claims of its US 6,486,150 “directed to a stable process for preparing a stable formulation” of the antibiotic ertapenem are invalid for obviousness. Ertapenem is marketed as Invanz® (NDA 021337; injectable, intramuscular, or intravenous infusion), for which only US 5,952,323 is listed on the Orange Book (PED expires Nov. 15, 2017). The DC found the asserted ‘323 claims to be infringed and not invalid. The ‘150 patent was found to be obvious over the ‘323 patent and a PCT application (WO 98/18800), and is described as addressing both degradation processes known to make the drug unstable (“hydrolysis of the lactam nitrogen…and dimerization via the pyrrolidine nitrogen”). The DC “found that, while none of the three steps of [representative] claim 21…was individually taught by the prior art, the ‘recipe’ for the final formulation was disclosed and the three steps leading to that formulation were nothing more than conventional manufacturing steps that would have been obvious from the disclosures and thus were the product of routein experimentation” (e.g., “while the claimed temperature range” (“about -3oC. to about 15oC.”) “was not explicitly taught in the prior art, it was understood that degradation is minimized at low temperatures, so one of ordinary skill would have wanted to keep the temperature as low as possible without freezing”). The DC did not address the dependent claims since “Merck ‘focused entirely on the validity of claim 21’”. And the DC concluded Merck had shown objective evidence of commercial success and copying “could not overcome the ‘strong prima facie case of obviousness’” (e.g., commercial success arguments “‘weak[ened]’ by the ‘blocking effect’ of” US 5,478,820 “directed to ertapenem itself”).
The FC panel explained that a DC’s conclusions of law are reviewed de novo and findings of fact for clear error (Golden Blount, FC 2004; Gypsum, US 1948). And obviousness is a question of law based on underlying factual findings regarding what is taught by the prior art, the motivation to combine the references, and any relevant objective indicia of nonobviousness (Apple, FC 2016 (en banc)). The FC panel acknowledged Merck’s argument that “degradation by hydrolysis…while operating in the pH range of 6.0-9.0” (as claimed) is “a problem not addressed by the prior art”, but found Merck’s “solution” to be “nothing more than conventional manufacturing steps that implement principles disclosed in the prior art” and therefore agreed with the DC (“[T]he order and detail of the steps, if not already known, would have been discovered by routine experimentation while implementing known principles.”)
Regarding Merck’s objective evidence, the FC panel disagreed with the DC’s “blocking” reasoning since “multiple patents do not necessarily detract from evidence of commercial success of a product or process, which speaks to the mertis of the invention, not to how many patents are owned by a patentee”. Instead, it “may be relevant” to consideration of commercial success, “a fact-specific inquiry” (Merck, FC 2005). The FC panel agreed with the DC that the evidence of copying did not overcome the evidence of obviousness. But it also explained its disagreement with Hospira’s argument “that ‘evidence of copying is not compelling in the context of ANDA cases because the [Hatch-Waxman Act] requires generic drug manufacturers to copy the approved drug” because “[t]he Act does not…require the generic manufacturer to copy the NDA holder’s process of manufacturing the drug.”
Judge Newman’s dissent argued the obviousness analysis procedure has eroded such that some FC “decisions appear to have sought a shortcut” (from the Graham factor analysis), “and converted three of the four Graham factors into a self-standing ‘prima facie’ case, whereby the objective considerations must achieve rebuttal weight”, also criticizing the Cubist (FC 2015), Novo Nordisk (FC 2013), Wm. Wrigley (FC 2012), Otsuka (FC 2012), and several other decisions decided on similar grounds.