Oxymorphone - USA

On May 03, 2019, Federal Circuit affirmed district court’s decision that claims of pure Opana® patent are not obvious.

Actavis appealed the decision of Delaware court which found that Actavis failed to prove by clear & convincing evidence that claims of US 8,871,779 are obvious. Malilnckrodt/Endo owns US’779 patent which is related to compounds “morphinan alkaloid” such as oxymorphone & its process of preparation with low levels of α,β Unsaturated Ketones (low ABUK). Specifically patent relates to lowering of ABUK to level of 10ppm or 0.001%. Claim 1 of US’779 patent reads:

1.    A hydrochloride salt of oxymorphone comprising less than 0.001% of 14-hydroxymorphinone.

Actavis during appeal contended that district court erred by i) misconstruing the claim term “14-hydroxymorphinone” and ii) determining that asserted claims were not obvious in light of the prior arts.

Federal Circuit with respect to claim construction said that district court properly construed the term “14-hydroxymorphinone” mean to “14-hydroxymorphinone hydrochloride”.  Actavis argued that this term requires no construction because of the plain language of the claims & chemical differences between two compounds. But district court said that asserted claims requires “14-hydroxymorphinone” as part of salt or hydrochloride salt of the compound. Also intrinsic evidences along with extrinsic evidences support the district court’s construction.

Next, Federal Circuit with respect to obviousness said that district court did not clearly err in concluding that PHOSITA would lack reasonable expectation of success in combining prior arts, Weiss, Chapman & Rapoport. It said that although Weiss discloses method of purifying oxymorphone ABUK through catalytic hydrogenation, it does not provide key reaction conditions. Moreover, it also does not disclose degree of purification required by claims.  Chaperon in turn discloses process involving catalytic hydrogenation of oxycodone ABUK. Endo’s expert explained that this would likely be ineffective in achieving same purity with oxymorphoen as both are different moieties & requires different process conditions. PHOSITA would not have reasonable expectation of success in combining these two arts because there was material difficulty with using catalytic hydrogenation to purify oxymorphone to the FDA mandated level (FDA through communication asked to Malilnckrod/Endo to bring down impurity to 10 ppm level).

With respect to FDA communications in providing motivation to combine these prior arts, Federal Circuit sided with district court & held that the FDA communications recited a goal without teaching how the goal is attained. Therefore, these communications would not have been enough to overcome disclosures of Weiss, Chapman & Rapoport which indicate that PHOSITA would not reasonably believe their disclosed methods were fruitful to achieve FDA mandated oxymorphone purity level. This conclusion is further substantiated by the fact that inventors of US’779 patent engaged in extensive experimentation, involving much failure, to ultimately produce the oxymorphone of asserted claims. Thus, Federal Circuit affirmed that claims are not obvious.

Circuit Judge, STOLL dissenting:

Stoll said that district court erred by conflating the requirements of reasonable expectation of success and motivation to combine.  Specifically, district court required that the FDA communations to teach how to achieve the claimed invention in order to provide motivation to combine. But present case laws do not require this. If FDA communications also taught “how the goal is attained”, they would anticipate the asserted claims & then there is no need to address the obviousness. Moreover, patent specification is directed to specific process for achieving FDA’s objective. Patentee does not however, claims that process, instead it claimed FDA mandate itself. Therefore, Judge Stoll asked to remand to allow the district court to apply correct obviousness test & properly consider the role of FDA mandate which is the sole reason of US’779 patent’s existence.