Case Name: Arius Two, Inc. v. Alvogen PB Rsch. & Dev. LLC, No. 2022-1394, 2022 WL 17828352 (Fed. Cir. Dec. 21, 2022) (Circuit Judges Chen, Clevenger, and Cunningham presiding; Opinion by Chen, J.) (Appeal from D. Del., Connolly, J.)

Drug Product and Patent(s)-in-Suit: Belbuca® (buprenorphine); U.S. Patents Nos. 8,147,866 (“the ’866 patent”), 9,655,843 (“the ’843 patent”), and 9,901,539 (“the ’539 patent”)

Nature of the Case and Issue(s) Presented: BDSI sued Alvogen after Alvogen filed its ANDA to market a generic version of BDSI’s Belbuca film product. BDSI’s asserted patents claimed methods and devices for administering buprenorphine using a bi-layer film placed inside a patient’s cheek (buccal). More specifically, BDSI asserted claims reciting pharmacokinetic properties, claims reciting pH limitations related to the film’s backing layer, and claims reciting pH limitations related to the film’s active (BEMA) layer.

After a bench trial, the district court determined that the pharmacokinetic claims were not invalid, that the pH backing layer claims were not invalid, and that the pH BEMA layer claims were invalid as obvious. In particular, to find obviousness, the district court determined that a skilled artisan would have known that buprenorphine exhibits a high first-pass effect (i.e., when ingested, the liver breaks down the drug into less effective chemicals, decreasing the drug’s bioavailability). The district court also determined that the prior art taught an adhesive bi-layer film to administer drugs for increased bioavailability. Finally, the district court determined that a skilled artisan would have recognized buffering a buprenorphine solution to a pH range between about 4 and 6 would likely maximize bioavailability by providing good solubility and absorption. Critically, the district court also determined that BDSI had not “clearly and convincingly” shown evidence of a long-felt need or unexpected results sufficient to overcome obviousness.

Alvogen’s remaining invalidity defenses failed because: (i) as to the pharmacokinetic claims, the district court determined that Alvogen had not shown a motivation to combine its references, and it waived an inherency argument; and (2) as to the pH backing layer claims, the district court determined that Alvogen had failed to show that the claimed pH was inherently present in the prior art, and secondary indicia supported a finding of non-obviousness. The parties cross-appealed and the Federal Circuit found all claims valid and infringed.

Why BDSI Prevailed: The court determined that Alvogen did not show that the district court erred in making certain evidentiary and procedural findings against Alvogen. But the court determined that BDSI did show that the district court applied an incorrect burden of proof when considering the long-felt need and unexpected results of the asserted claims found invalid for obviousness.

With respect to the pharmacokinetic claims, Alvogen conceded that it did not clearly articulate that a skilled artisan would have been motivated to combine the asserted references in post-trial briefing. Thus, the Federal Circuit determined that the district court did not clearly err with respect to that issue. Nor did the district court clearly err when it determined that Alvogen waived its inherency argument.

With respect to the pH backing layer claims, the district court considered an inventor declaration identifying that the pH of the backing layer in the asserted prior art fell outside of the claimed range. Alvogen had placed the inventor declaration in evidence, without limitation, and the Federal Circuit determined that the district court did not err in considering the declaration for all it disclosed. The district court weighed the evidence, and the Federal Circuit found no clear error in the district court’s reasoning.

Finally, with respect to the pH BEMA layer claims, the Federal Circuit determined that the district court applied the wrong standard in considering secondary indicia of non-obviousness. Secondary indicia evidence is subject to a preponderance of the evidence standard, not a clear and convincing standard. The Federal Circuit determined that “the fairest reading of the Opinion is that it incorrectly required BDSI to prove long-felt need by clear and convincing evidence.” The court vacated and remanded the district court’s obviousness finding.