Pernix Ir. Pain DAC v. Alvogen Malta Operations, Ltd.

Case Name: Pernix Ir. Pain DAC v. Alvogen Malta Operations, Ltd., No. 16-139, 2018 U.S. Dist. LEXIS 144226 (D. Del. Aug. 24, 2018) (Bryson, J.) 

Drug Product and Patent(s)-in-Suit: Zohydro® (hydrocodone bitartrate); U.S Patents Nos. 9,265,760 (“the ’760 patent”) and 9,339,499 (“the ’499 patent”)

Nature of Case and Issue(s) Presented: At issue were two patents claiming methods of treating pain in patients with hepatic impairment (i.e., compromised liver function). Because the liver is primarily responsible for metabolizing opioids, patients with hepatic impairment are often prescribed reduced dosages of opioids in order to avoid the build-up of unsafe levels in the bloodstream. The patented inventions encompass formulations of extended release hydrocodone that have release profiles that are similar for both healthy and hepatically impaired patients. Although Alvogen was found to infringe the patents-in-suit, the asserted claims were also found invalid on the basis of obviousness and a lack of adequate written description.

Why Alvogen Prevailed: Pernix asserted two categories of hydrocodone method-of-treatment claims: the one-step claims were directed to an extended-release, oral dosage unit that resulted in no increased PK response in patients suffering from mild to moderate hepatic impairment relative to subjects not suffering from such impairment; and the two-step claims were directed to an extended-release, oral dosage unit wherein the starting dose was not downwardly adjusted for patients with hepatic impairment. As to the one-step claim, the court found that Alvogen’s proposed label would induce physicians to prescribe the ANDA product to patients with mild to moderate hepatic impairment and would further induce those patients to self-administer the product as prescribed. As to the two-step claims, the court found that Alvogen’s proposed label provided both data and instructions on how to prescribe a starting dose in patients with mild or moderate hepatic impairment and that a physician would not adjust relative to the starting dose prescribed to a patient without hepatic impairment.

Next, Alvogen argued that a published patent application entitled “Multiparticulate Modified Release Composition” (“Devane”) anticipated the patents-in-suit. The court found that the Devane formulation was identical to the formulation disclosed in the asserted claims, and thus taught an extended-release hydrocodone formulation with the specified PK parameters. But the court explained that Alvogen failed to demonstrate that Devane inherently disclosed the treatment of hepatically-impaired patients.

Relatedly, Pernix did not dispute the fact that the PK parameters recited in the asserted claims were necessarily present in the Devane prior-art reference. Further, a different prior-art reference, Jain, explained that the PK profile of hydrocodone in normal subjects and in patients with mild or moderate hepatic impairment was “similar.” In combination with Jain, a person of ordinary skill in the art would have been motivated and had a reasonable expectation that Devane’s formulation would not require dose adjustment for patients suffering from mild or moderate hepatic impairment. Thus, the court found that the asserted claims were obvious.

Finally, according to the Court, all that the inventors contributed, based on the PK results of a routine hepatic impairment study, was a recognition that a single prior-art formulation did not require a dose adjustment for patients with mild to moderate hepatic impairment. The inventors, however, sought, and obtained, much broader claims—any composition having any particular ratio of extended-release to immediate-release components—that were not supported by the common specification. The inventors claimed “expansively” so as to capture a potentially huge number of compounds that satisfied the functional limitations (i.e., specified PK parameters). The common specification, however, disclosed only one formulation that was found to satisfy the functional limitations. This resulted in a finding of inadequate written description and thus yet another finding of invalidity.