In Cephalon, Inc. v. Watson Pharmaceuticals, Inc., No. 11-1325 (Fed. Cir. Feb. 14, 2013), the Federal Circuit reversed the district court's finding that the asserted patents were invalid for lack of enablement, and affirmed the district court's finding of noninfringement.
Cephalon, Inc. and CIMA Labs, Inc. (collectively "Cephalon") are holders of the NDA for fentanyl buccal tablets, sold under the brand name FENTORA® for the treatment of breakthrough cancer pain. U.S. Patent Nos. 6,200,604 ("the '604 patent") and 6,974,590 ("the '590 patent") (collectively "the Khankari patents") are listed in the FDA's Orange Book for FENTORA® and cover methods of administering a fentanyl tablet containing an effervescent agent and a pH adjusting substance via the mucous membrane lining or mucosa in the oral cavity.
Watson Pharmaceuticals, Inc., Watson Laboratories, Inc., and Watson Pharma, Inc. (collectively "Watson") filed an ANDA seeking approval to market a generic version of FENTORA®. In response, Cephalon sued Watson for patent infringement, first asserting the Khankari patents and later asserting an additional patent in a subsequent suit. The district court consolidated the two actions and after a bench trial concluded that Cephalon did not prove, by a preponderance of the evidence, that Watson's ANDA products infringed either of the Khankari patents. The district court also found that Watson proved, by clear and convincing evidence, that the Khankari patents were invalid for lack of enablement. Further, the district court found that Watson failed to show that the asserted patents were invalid as anticipated or obvious in view of prior art. Cephalon appealed the ruling with respect to the Khankari patents.
On appeal, the Federal Circuit first addressed whether the district court erred in ruling that Watson had carried its burden of proving, by clear and convincing evidence, that the Khankari patents were invalid for lack of enablement. The dispute arose from the district court's construction of the term "effervescent agent" in claim 1 of the Khankari patents to require "at least one compound that evolves gas by means of an effervescent reaction," and its conclusion that "effervescent agent" referred to a single compound. Slip op. at 10 (quoting Cephalon, Inc. v. Watson Pharms., Inc., 769 F. Supp. 2d 729, 744 (D. Del. 2011)). The effervescent reaction, which may play a role in increasing the rate and extent of absorption of an active drug, is most often the result of a soluble acid source, like citric acid, reacting with a source of carbon dioxide that is mostly basic, like an alkaline carbonate or bicarbonate. The district court's "single compound effervescent agent" construction required the soluble acid source to be in a separate tablet or dosage form from the effervescent agent (carbonate source) and required these separate dosage forms to be coadministered to achieve the claimed effervescent reaction.
"Because we must presume a patent enabled, the challenger bears the burden, throughout the litigation, of proving lack of enablement by clear and convincing evidence." Slip op. at 12.
The district court found that formulating and coadministering two separate dosage forms to achieve an effervescent reaction necessitated undue experimentation, and determined that Watson established a prima facie case of lack of enablement, which Cephalon failed to rebut. The Federal Circuit, however, noted that the burden of proof was Watson's alone. "Because we must presume a patent enabled, the challenger bears the burden, throughout the litigation, of proving lack of enablement by clear and convincing evidence." Id. at 12 (citing Morton Int'l, Inc. v. Cardinal Chem. Co., 5 F.3d 1464, 1469-70 (Fed. Cir. 1993)).
In determining that Watson did not meet its burden of proof, the Court noted that Watson relied heavily on its expert's unsubstantiated testimony that coadministration would be difficult and complicated. The Court found such ipse dixit statements insufficient to constitute clear and convincing evidence. The Court noted that the district court's reliance on Cephalon's expert testimony that routine experimentation would be required to create an effervescent reaction by coadministering two dosage forms to support Watson's position of undue experimentation was misplaced. The Court explained that "[t]he question of undue experimentation is a matter of degree, and what is required is that the amount of experimentation not be 'unduly extensive.'" Id. at 13-14 (citing Chiron Corp. v. Genentech, Inc., 363 F.3d 1247, 1253 (Fed. Cir. 2004)). The Court noted that the focus "is not merely quantitative, since a considerable amount of experimentation is permissible, if it is merely routine, or if the specification in question provides a reasonable amount of guidance." Id. at 14 (quoting PPG Indus., Inc. v. Guardian Indus. Corp., 75 F.3d 1558, 1564 (Fed. Cir. 1996)). The Court further noted, however, that "[p]ermissible experimentation is . . . not without bounds." Id. For example, the Court has held that experimentation is unreasonable where (1) eighteen months to two years' work is required to practice the patented invention; (2) the specification lacks guidance by teaching away from the subject matter that is eventually claimed; and (3) there is evidence of the patentee's own failures to make and use the later claimed invention at the time of the application.
Here, the Court found that Watson presented no evidence showing why the formulations for an effervescent "couple"—where the soluble acid source and the effervescent agent are in the same dosage form—described in the Khankari patents did not provide sufficient guidance for a skilled artisan to calculate formulations for single compound effervescent agents without undue experimentation. Nor did Watson show that the resulting experimentation in this case would be excessive. Finding that record evidence did not sufficiently show that the experimentation necessary for coadministration would be unduly extensive, the Court concluded that the district court erred as a matter of law in holding that Watson proved its case on enablement by clear and convincing evidence, and reversed the district court's nonenablement determination.
Next, the Court addressed the district court's ruling that Watson did not infringe the asserted claims. The disputed claim limitation addressed on appeal was "at least one [saliva activated] effervescent agent in an amount sufficient to increase absorption . . . across [the] oral mucosa." Id. at 18 (alterations in original) (quoting Cephalon, 769 F. Supp. 2d at 748). The district court's construction of this limitation required the effervescent agent to be "saliva activated," and the parties' dispute centered on whether potassium bicarbonate and mannitol in the ANDA products reacted to generate an effervescent reaction. The district court found that while Cephalon presented evidence of acidity of mannitol in water, it did not provide any evidence of acidity of mannitol in artificial or human saliva. Agreeing with the district court, the Federal Circuit determined that Cephalon failed to prove that the limitation was practiced by the ANDA products, either literally or under the DOE.
Accordingly, the Federal Circuit reversed the district court's judgment of invalidity and affirmed the district court's judgment of noninfringement.
Judges: Reyna, Bryson, Wallach (author)
[Appealed from D. Del., Judge Robinson]
This article previously appeared in Last Month at the Federal Circuit, March 2013.
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