OxyContin® (oxycodone HCl)
Case Name: Purdue Pharma L.P. v. Accord Healthcare, Inc., No. 2023-1953, 2024 WL 5244764 (Fed. Cir. Dec. 30, 2024) (Circuit Judges Prost, Reyna, and Taranto presiding; Opinion by Prost, J.) (Appeal from D. Del., Andrews, J.)
Drug Product and Patent(s)-in-Suit: OxyContin® (oxycodone HCl); U.S. Patents Nos. 9,763,933 (“the Mannion ’933 patent”), 9,775,808 (“the ’808 patent”), and 9,763,886 (“the ’886 patent”) (collectively, “the abuse-deterrent patents”); U.S. Patents Nos. 9,073,933 (“the ’933 patent”) and 9,522,919 (“the ’919 patent”) (collectively, “the low-ABUK patents”)
Nature of the Case and Issue(s) Presented: Oxycodone was first developed in the 1910s. Purdue developed an extended-release formulation, approved by the FDA in 1995. Oxycodone become one of the most frequently abused prescription medications and its creation resulted in 14-hydroxy, an alpha beta unsaturated ketone (“ABUK”), which is “a potentially genotoxic (i.e., carcinogenic) impurity.” The abuse-deterrent patents claim a crush-resistant formulation of oxycodone to minimize some of the more common methods of abusing OxyContin. The curing method claimed in these patents has four general steps: (i) the tablet must be “compression shaped”; (ii) the tablet must be air cured by heated air, without compression; (iii) the heating must be done for about 10 minutes to about 10 hours; and (iv) the heating must be done above the softening temperature of polyethylene oxide (PEO) and at about 70–85° C or 65–90° C. Purdue’s purported points of novelty were that no one had ever cured PEO tablets using heated air without simultaneous compression or at the times and temperatures and that the recited process had the surprising benefit of decreasing tablet density that promoted faster gelling. The low-ABUK patents claim a formulation and process of reducing 14-hydroxy to reduce toxicity concerns. The synthesis process in these patents involves three steps: (i) oxidation of thebaine to form 14-hydroxy; (ii) hydrogenation of 14-hydroxy to form oxycodone; and (iii) addition of hydrochloric acid to form a salt. During the third step of the process, 14-hydroxy would reform in the drug, along with another impurity, known as 8α. The low-ABUK patents explain that 8α is converted to 14-hydroxy under acidic conditions, such as salt formation, which explains why residual 14-hydroxy was reappearing in the third manufacturing step. The low-ABUK patents recite minimizing 14-hydroxy and removing 8α.
In 2010, Purdue developed and the FDA approved a new formulation of OxyContin. Accord filed an ANDA referencing this formulation that included paragraph IV certifications to the patents-in-suit. Purdue sued and Accord stipulated to infringement. The district court held a three-day bench trial in September 2021 on the sole issue of invalidity and found all claims invalid as obvious. Purdue appealed and the Federal Circuit affirmed.
Why Accord Prevailed: The abuse-deterrent patents. Purdue argued that the district court erred in (i) finding a motivation to combine with a reasonable expectation of success and (ii) dismissing Purdue’s arguments related to secondary considerations. The Federal Circuit found that the district court relied on multiple factual findings that all supported its conclusion that it would have been obvious to try ovens for heating tablets. That evidence included Accord’s expert’s testimony, the prior art itself, and the fact that plaintiffs’ witnesses did not provide any testimony to the contrary. The prior art already taught making hardened tablets, including PEO anti-abuse tablets with compression and heating. Therefore, the district court’s reliance on the obvious-to-try rationale—another argument raised by Purdue—was a “natural choice.” Finally, with respect to secondary considerations, the Federal Circuit saw no clear error in the district court’s finding that Purdue failed to prove commercial success due to the claimed features of the invention. Expert testimony confirmed that the new formulation replaced the original formulation, with all sales transferred to the new formulation, and “there was no demonstrated increase in the success of OxyContin relative to other opioids when the patented features were introduced.” In sum, the district court found no nexus between the claimed invention and the commercial success. With respect to industry skepticism, any FDA skepticism at the time of the invention would have been about applying the abuse-deterrent label, not about the creation (even at large scale) and utility of the claimed product. Regarding failure of others, the district court, again, found that Purdue had not established a nexus between the alleged secondary consideration and the claimed invention.
The low-ABUK patents. Purdue argued that the low-ABUK patents were not obvious because Purdue discovered the previously unknown problem that 14-hydroxy reappeared after its removal during the synthesis of oxycodone, and it discovered the source of the problem, the 8α impurity. Purdue’s argument necessarily failed because the problem was known. Specifically, the Federal Circuit credited the district court’s finding “testimony at trial ... indicated that an understanding or suspicion that ABUKs were toxic existed even before September 2002.” Therefore, a skilled artisan would have two clear starting points: “either adding a final hydrogenation step to remove 14-hydroxy hydrochloride or attempting to remove 14-hydroxy at an earlier stage.”
Claim 3 of the ’933 patent required only that 8α be present in the composition.” The district court correctly concluded that claim 3 was obvious because 8α was inherently present in the prior art compositions based, in part, on Purdue’s not disputing that 8α was present in prior art compositions. Other asserted claim limitations requiring a specific ratio of 8α to oxycodone or removing 8α were also found to be obvious based on a sequence of facts showing that a skilled artisan would achieve such results via routine experimentation.
