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Expert Opinion Does Not Prevent Summary Judgment of Noninfringement

November 07, 2001
Swan, Jennifer S.

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Last Month at the Federal Circuit - December 2001

Judges: Clevenger (author), Friedman, and Schall

In Novartis Corp. v. Ben Venue Laboratories, Inc., No. 01-1122 (Fed. Cir. Nov. 7, 2001), the Federal Circuit affirmed the district court’s grant of SJ to Ben Venue Laboratories, Inc. and Ben Laboratories (collectively “Ben Venue”) for noninfringement, ruling that Novartis Corporation (“Novartis”) had not set forth sufficient facts to entitle it to a trial.

The drug pamidronate disodium is used to treat disorders of bone metabolism. Novartis had obtained a period of new-drug exclusivity for the use of this drug based on a new indication for the treatment of bone metastases in breast cancer. While the substance pamidronate disodium itself is unpatented, U.S. Patent No. 4,711,880 (“the ‘880 patent”) covers crystalline forms of pamidronate disodium containing water of crystallization. Novartis, owner of the ‘880 patent, sells its drug product in the form of a pamidronate disodium pentahydrate.

Ben Venue filed a “paper” New Drug Application (“NDA”) with the FDA seeking approval for its own formulation of pamidronate disodium, which Ben Venue described as a liquid formulation. Ben Venue planned to begin selling its liquid formulation when Novartis’s period of exclusivity expired. Ben Venue filed a Paragraph IV certification asserting that its formulation of pamidronate disodium did not infringe Novartis’s formulation since neither its formulation nor its manufacturing process involved the crystalline form of the drug claimed in Novartis’s ‘880 patent. Ben Venue notified Novartis of its Paragraph IV certification, and Novartis timely filed suit against Ben Venue for infringement of the ‘880 patent. Ben Venue moved for SJ of noninfringement, which was granted by the district court following discovery, submission of expert affidavits, and oral arguments. The infringement dispute centered on whether the crystalline form of pamidronate disodium existed at any point during Ben Venue’s process for manufacturing its liquid pamidronate disodium.

Ben Venue’s process for producing pamidronate disodium consists of starting with pamidronic acid dissolved in water. Pamidronic acid is only slightly soluble in water, so only a small amount is dissolved in solution. Concentrated NaOH is added to the solution, neutralizing the pamidronic acid and yielding pamidronate disodium. This reaction occurs on an equilibrium process, with the dissolved pamidronic acid reacting to form the pamidronate disodium causing more pamidronic acid to dissolve, which then reacts with the concentrated NaOH to form pamidronate disodium and so forth. Provided enough concentrated NaOH is added to the mixture, the reaction will continue until all of the pamidronic acid has been dissolved and converted to dissolved pamidronate disodium. Thus, the reaction is a twopart scheme: the conversion of solid pamidronic acid to dissolved pamidronic acid and the conversion of dissolved pamidronic acid to dissolved pamidronic disodium.

The parties agreed that no crystalline pamidronate disodium was present at the beginning or end of Ben Venue’s process. Novartis, however, contended that crystalline pamidronate disodium was formed during a reaction in Ben Venue’s manufacturing process. Specifically, Novartis contended that during the reaction scheme, solid particles of pamidronic acid remain in contact with the concentrated NaOH for an appreciable length of time and that these areas create zones where crystalline material can form. To prove this, Novartis submitted affidavits of two experts, Drs. McKenna and Nauman. Dr. McKenna performed experiments to measure the lifetime of a pamidronic-acid particle as it dissolved in concentrated NaOH and the time required for infringing crystalline material to precipitate from supersaturated zones. Dr. Nauman created a computer model that simulated the environment around a pamidronic-acid particle in contact with concentrated NaOH and predicted the amount of pamidronate disodium in excess of the solubility limit that would form around the surface of a pamidronic-acid particle in a short time. Based on this computer model, Dr. Nauman predicted that infringing crystalline pamidronate disodium would temporarily precipitate out of solution before the pamidronicacid particles dissolved completely.

On appeal, the Federal Circuit discounted Dr. Nauman’s computer model because the record was devoid of what specifics relating to Ben Venue’s process Dr. Nauman had based his model on. The Court stated that while nothing is inherently unreliable or suspect about computer simulations as evidence, because Dr. Nauman did not submit any explanation as to the parameters of his model or how he had employed them, the simulation offered no support for a finding of infringement. Since Novartis had not provided the theoretical or factual foundation underlying Dr. Nauman’s theory of infringement, Novartis had failed to set forth facts sufficient to entitle it to a trial.