Cadence Pharmaceuticals Inc. v. Exela Pharmsci Inc., No. 2014-1184, 2015 U.S. App. LEXIS 4700 (Fed. Cir. Mar. 23, 2015) (Linn, J.). Click Here for a copy of the opinion.
Cadence sued Exela for infringement of U.S. Patent Nos. 6,028,222 and 6,992,218 after Exela filed an ANDA with a Paragraph IV certification, seeking approval for a generic equivalent of Ofirmev, an injectable acetaminophen product. Claim 1 of the '222 patent recites, inter alia, "[a] stable, liquid formulation consisting essentially of acetaminophen dispersed in an aqueous medium containing a buffering agent..." The district court construed "buffering agent" to mean "an agent that helps the formulation resist change in pH." The Federal Circuit affirmed, concluding that "nothing in the intrinsic record warrants adding requirements of effective concentration or resistance to material change" to the plain and ordinary meaning of "buffering agent." The statement in the specification that the concentration of buffer "may be" between 0.1 and 10 mg/ml was not limiting since "it would not be proper to import from the patent's written description limitations that are not found in the claims themselves." Furthermore, an amendment showed that "a buffering agent is necessary" did not alter the scope and meaning of the term. Because the district court's claim construction was correct, the Federal Circuit affirmed that Exela infringed the '222 patent.
The '218 patent disclosed a method for obtaining stable acetaminophen formulations by deoxygenating solutions with an inert gas. The district court found that Exela's process of deoxygenating the solvent before adding the active ingredient did not literally infringe because the claim covered "only the method of first dissolving an active ingredient to form a solution and then deoxygenating the solution." However, Exela infringed under the doctrine of equivalents because the timing for adding the active ingredient did not matter.
The Federal Circuit affirmed, citing Cadence's expert: "adding acetaminophen before or after the deoxygenation step would have no impact on the stability of the final product." Exela likewise had acknowledged that its formulation is stable. Exela argued that deoxygenating after adding the active ingredient is the "antithesis" of deoxygenating before adding the active ingredient, and such a reversal would "vitiate" the claimed limitation. The Court disagreed and held that "[t]he determination of equivalence depends not on labels like 'vitiation' and 'antithesis' but on the proper assessment of the language of the claimed limitation and the substantiality of whatever relevant differences may exist in the accused structure." In this case the difference was found to be insubstantial.
Claim 1 of the '218 patent recites "[a] method for preparing an aqueous solution . . . comprising deoxygenation of the solution..., and optionally the aqueous solution . . . is topped with an inert gas atmosphere heavier than air and placed in a closed container . . . ." The Federal Circuit affirmed that "optionally" applies to both the "topped with an inert gas" step and the vacuum stoppering step ("placed in a closed container"). The specification contained "examples that exhibit prolonged stability even without vacuum stoppering." The prosecution history did not provide "clear and unmistakable disavowal of the unambiguous recitation of the vacuum stoppering step as being optional." While the applicants mentioned vacuum stoppering in arguing over a reference during prosecution, the applicants were comparing "the degree to which the level of oxygen was reduced" in the reference to the claims. There was "no clear indication that the vacuum stoppering step was the 'contrast' that applicants were trying to make over the cited reference." In other words, the claim could not be read as requiring the "optional" vacuum stoppering step.
Finally, the Court affirmed the ruling of non-obviousness. Acetaminophen degrades primarily by hydrolysis and not oxidation, which was the mechanism described in the disputed prior art. Secondary considerations also supported a finding of non-obviousness. The claimed process achieved unexpected stability and was licensed to third parties, which was probative of non-obviousness.
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