May 16, 2018

Case Name: Endo Pharms. Inc. v. Teva Pharms. USA, Inc., Fed. Cir. Nos. 2015-2021, -2022, -2023, -2024, -2025, -2026, -2028, -2031, -2033, -2034, -2035, -2041, -2042, -2046, -2047, -2049, -2059, -2060, 2016-1025, -1060, -1117, -1118, 2018 U.S. App. LEXIS 12961 (Fed. Cir. May 16, 2018) (Circuit Judges Moore, Bryson, and Hughes presiding; Opinion by Hughes, J.) (Appeal from S.D.N.Y., Griesa, J.)

Drug Product and Patent(s)-in-Suit: Opana® ER (oxymorphone hydrochloride); U.S. Patents Nos. 8,309,122 (“the ’122 patent”) and 8,329,216 (“the ’216 patent”)

Nature of Case and Issue(s) Presented: Opana ER is a controlled-release formulation of the painkiller oxymorphone. Endo sued multiple generic manufacturers alleging infringement of the ’122 and ’216 patents based on the generic manufacturers’ filing of ANDAs. After a bench trial, the district court found for all asserted claims of the ’122 and ’216 patents that they were not invalid, and that all but two asserted claims were infringed. The generic manufacturers appealed the district court’s findings, arguing: (i) the asserted patents were invalid as obvious; (ii) the asserted patents were invalid for lack of written description; (iii) the asserted patents were invalid for indefiniteness; (iv) Endo failed to prove infringement; and (v) the district court improperly granted a permanent injunction. The Federal Circuit affirmed.

Why Endo Prevailed: The asserted claims of the ’122 and ’216 patents generally recited the following categories of limitations: (i) a dissolution or release-rate limitation, measured by the USP Paddle Method; (ii) a pharmacokinetic limitation, further divided into the following subcategories: (a) an analgesic-effect limitation, (b) a food-effect limitation, (c) a detectable-level limitation, and (d) a multiple-peaks limitation describing when and how often a patient’s blood would exhibit peak concentrations of the drug.

Obviousness: Appellants argued that the district court erred in concluding that the asserted claims were not invalid as obvious. The Federal Circuit disagreed. First, the court pointed to prior-art references that “strongly discouraged a controlled release formulation of opioids with low bioavailability, such as oxymorphone, and more critically, do not suggest the dissolution and pharmacokinetic limitations recited in the asserted claims.” The Federal Circuit found that overwhelming evidence at trial supported the district court’s factual finding that oxymorphone’s low bioavailability taught away from attempting a controlled-release formulation. The court further rejected appellants’ argument that low bioavailability could be addressed by increasing the dosage; crediting the district court’s finding that such an approach risked toxicity. Moreover, the Federal Circuit found that the inclusion of oxymorphone in lists of candidate molecules in two prior-art references was not enough to prove invalidity.

Appellants also argued that the district court erred in finding that no prior-art reference disclosed the dissolution limitations. The Federal Circuit rejected that argument too, holding that the asserted patents expressed dissolution using the USP Paddle Method, but the prior-art references measured dissolution in a different manner. The Federal Circuit held that a POSA would not have expected a correlation between the results obtained using different methods, and therefore a POSA would not have been able to extrapolate the dissolution limitations claimed in the prior art.

Appellants further argued that the district court erred by giving patentable weight to the pharmacokinetic limitations inherent to the formulations disclosed by the prior art. Appellants argued that the claimed pharmacokinetic properties were inherent to controlled-release formulations. The Federal Circuit, however, found that the claims were not directed to any controlled-release oxymorphone formulation that resulted in the claimed pharmacokinetic properties, but instead claimed only specific controlled-release formulations designed to result in the those pharmacokinetic properties upon administration. “Endo does not claim any controlled release configuration of oxymorphone dosage, rather only those which have been specifically calibrated to produce the pharmacokinetic properties recited in the claims – excluding those that do not exhibit such properties.” The Federal Circuit also found that the prior art did not disclose the claimed food-effect limitations.

Finally, the Federal Circuit considered secondary indicia of non-obviousness. The Federal Circuit credited Endo’s commercial-success expert, who established sales growth and nexus. It also credited Endo’s expert on long-felt need, who testified that the available immediate-release opioids had a short duration and were inconvenient to administer.

Written Description: Appellants argued that the district court erred by holding that the dissolution limitations were not invalid for lack of written description. They argued that the dissolution limitations claimed a broader range of release rates than the ranges disclosed by the specification. The Federal Circuit found that the ranges disclosed in the specification were the result of testing one dosage strength, but that the specification contained examples of additional dosage strengths. Thus, it held that Endo was entitled to claim the broad dissolution ranges covering the broader range of disclosed dosage strengths.

Indefiniteness: The district court held that the multiple-peaks limitations were not invalid as indefinite. Appellants argued that the specification contained no explanation of how to measure “peaks,” or what constituted peaks. But the Federal Circuit found that peaks were readily ascertainable and identifiable from a chart, and that Appellants’ argument asked for more precision than reasonable certainty.

Non-infringement: Appellants argued that the district court erred in finding infringement of the food-effect limitations. The Federal Circuit credited the district court’s reliance on the proposed package inserts, which stated that the food-effect limitations were satisfied, and thus found no error.

Permanent Injunction: The Federal Circuit decided that the district court did not abuse its discretion in granting a permanent injunction based on evidence Endo presented of irreparable harm through the introduction of generics into the market such as loss of market share, cutting of sales force, reducing promotional expenses, and intangible reputational, organizational, and administrative harms, etc.