Case Name: Cadence Pharms., Inc. v. Exela Pharms. Sciences, LLC, Civ. No. 11-733-LPS, 2013 U.S. Dist. LEXIS 166097 (D. Del. Nov. 14, 2013) (Stark, J.) (Finding the asserted patents-in-suit infringed and not invalid.)
Drug Product and Patent(s)-in-Suit: Ofirmev® (intravenous acetaminophen); U.S. Pat. Nos.6,028,222 (“the ’222 patent”) and 6,992,218 (“the ’218 patent”)
Nature of the Case and Issue(s) Presented: Exela filed an ANDA for generic Ofirmev. Exela’s ANDA product formulation is different from the branded product in that it contains sodium ascorbate, which is not present in Ofirmev. The patents-in-suit relate to formulas and methods for making liquid acetaminophen. The ’222 patent is a composition patent. The ’218 patent relates to a deoxygenation process, which reduces the oxygen content during manufacturing. For the ’222 patent, Exela argued that it did not infringe because its formulation did not contain the claimed buffering agent and the claimed antioxidant. Exela also argued that the ’222 patent was anticipated or obvious in view of three prior art references. For the ’218 patent, Exela argued that it did not infringe because its process did not deoxygenate the solution by “bubbling,” it adds an antioxidant in the order required, and its product is below 2.0 ppm prior to the addition of acetaminophen. Exela also argued that the ’218 patent is obvious in view of the ‘222 patent in combination with another prior art reference. The court found that Cadence proved by a preponderance of the evidence that the ‘222 patent and the ‘218 patent are infringed. It also found that Exela failed to demonstrate by clear and convincing evidence that the patents-in-suit are invalid.
Why Cadence Prevailed: The court was not persuaded by Exela’s non-infringement arguments. For the ’222 patent, the dispute focused on whether in Exela’s ANDA product sodium ascorbate functions as a “buffering agent,” and whether mannitol functions as an antioxidant. The court construed the term “buffering agent” as “[a]n agent that helps the formulation resist change in pH.” Exela argued that sodium ascorbate is not a buffering agent because it does not sufficiently “help.” The court disagreed. Relying on experiments that Cadence’s expert conducted, and unpersuaded by Exela’s criticism of those experiments, the court found that formulations with sodium ascorbate resist pH change while formulations without sodium ascorbate do not. The ’222 patent also requires a “free radical scavenger” which the court construed as a “[s]ubstance that functions in the formulation as an antioxidant.” Cadence asserted that the mannitol in Exela’s ANDA product meets this limitation and that Exela never disputed that assertion before trial. The court agreed that Exela waived any responsive argument. In addition, the court determined that Cadence proved that mannitol functions as an antioxidant and noted that the patent identifies mannitol as a preferred free radical scavenger.
For the ’218 patent, the disputes focused on the patent term “bubbling” and the steps of the claimed process. Exela argued that it does not deoxygenate its solution by “bubbling.” The court viewed this as a claim construction dispute that was raised during trial. Cadence contended that any process that creates bubbles of an inert gas in solution satisfied the limitation. Exela contended that “bubbling” referred to the specific process of using pressure to force the inert gas into the liquid. Exela’s process blanketed the solution with argon gas. The court sided with Cadence’s construction and found that Cadence’s expert testimony supported a finding that “argon blanketing” met the claim limitation literally and under the doctrine of equivalents. The ’218 patent also includes the optional step of completing the deoxygenation by adding an antioxidant. Exela argued that it did not infringe the patent since it added the antioxidant prior to the addition of acetaminophen and prior to the dissolved oxygen content being reduced below the level required by the claims. The court disagreed, finding that the claim did not require that this step take place in a specific order since it was optional. Exela’s final non-infringement argument was that it does not form “the solution” before reducing the dissolved oxygen content below 2.0 ppm. The court construed the term “aqueous solution” to mean “[a] composition contain water as solvent and an active ingredient susceptible to oxidation.” Exela argued that an “aqueous solution” is formed only after the addition of acetaminophen and that Exela’s processes reduced the oxygen content prior to adding acetaminophen. The court agreed that Exela did not literally infringe the claim. But the court found infringement under the doctrine of equivalents. The Court found that the specification and the prior art did not require that acetaminophen be added in any specific order. As such the court determined that the differences were insubstantial.
The court also found that Exela failed to prove by clear and convincing evidence that the patents were invalid and that secondary considerations supported a finding of non-obviousness.
