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Applications to prohibit Mylan-tadalafil dismissed

Authored byLynn Ing

As reported last month, in January, Lilly succeeded in obtaining an order of prohibition against Mylan in respect of Canadian Patent 2,226,784 (the 784 Patent) relating to tadalafil (Eli Lilly’s CIALIS). That prohibition application was heard consecutively with two other prohibition applications by Lilly against Mylan relating to the same drug. In February, the Court dismissed the two further applications.

Tadalafil unit dosage form patent, 2015 FC 125

The Court’s decision in 2015 FC 125, issued February 2, relates to Canadian Patent 2,371,684 (the 684 Patent) having claims directed to a unit dosage form of tadalafil specifying different dosages or dosage ranges, and claims specifying the use of that unit dosage form for the treatment of erectile dysfunction (ED). Mylan alleged lack of utility and, in the alternative, anticipation and obviousness. The Court found all of the allegations to be justified.

With respect to utility, Lilly argued that the patent promised that the claimed doses will have a better side effect profile than sildenafil (VIAGRA) when administered to patients for the treatment of ED, while Mylan alleged that the patent promised the claimed unit doses reduced three specific side effects of sildenafil (flushing, vision abnormalities, and the negative effects associated with co-administration with nitrates) to clinically insignificant levels. The Court agreed with Mylan that the patent promised more than marginal improvement over sildenafil. First, the Court found that the experts agreed that the patent focusses on the three side effects associated with sildenafil. Second, the Court found “ambitious and explicit statements throughout” the patent of elimination or minimization of adverse side effects, including that “contraindication [with nitrates]… is unnecessary.”

Mylan also argued that the patent is a selection patent because that is the only way for Lilly to avoid anticipation by the 784 Patent (relating to the use of tadalafil), and accordingly the improvement of tadalafil over sildenafil must be peculiar to the claimed dose range. The Court rejected this argument on the basis that a selection patent is like any other patent and whether or not the patent is a selection is irrelevant to the utility analysis; and in any event, the patent is not a selection patent as there is nothing in the specification to the effect that the promised advantage is peculiar to the claimed dosage range, to the exclusion of unselected doses.

The Court found the patent failed to meet the promise of minimizing significantly or eliminating the negative side effects associated with co-administration with nitrates, and the promise of an improvement over sildenafil in nitrate interaction. Neither was demonstrated or soundly predicted based on the one head to head study performed before the filing date. The Court also found that regardless of what could be predicted at the filing date, as of today (relevant to utility in fact), there is a contraindication against use with nitrates and no improvement in nitrate interaction.

With respect to anticipation, the Court found the claimed dosages were disclosed and enabled by the 784 Patent. In arriving at this conclusion, the Court considered that when a second patent is not interpreted as a selection patent, its advantages do not factor into the inquiry of anticipation. The Court also considered the patent file history as containing objective facts on which inferences may be drawn. Specifically, while Lilly argued that a certain maximum daily dosage was an essential element of the claims, the Court referred to claim amendments removing prior references to such maximum daily dose.

On obviousness, the Court found it was more or less self-evident that the lower and narrower doses of tadalafil (compared to sildenafil and the tadalafil dosages disclosed in the 784 Patent), would be effective in treating ED and would result in a reduced side effect profile. The Court found that, while the taladafil development team did not follow the ordinary course of drug development, there was clearly a motive for the skilled person to look for a minimal effective dose and maximum tolerated dose, and a finite number of predictable solutions.

Eli Lilly has appealed.

Tadalafil tablet formulation patent, 2015 FC 178

The decision in 2015 FC 178, released February 23, relates to Canadian Patent 2,379,948 (the 948 Patent) having claims directed to a pharmaceutical formulation of reduced particle size of tadalafil with particular excipients for the treatment of ED. The Court found Mylan’s allegations of non-infringement and obviousness to be justified.

With respect to non-infringement, Mylan alleged that its formulation of tadalafil will not contain the claimed amount of hydrophilic binder. Lilly asserted that, although Mylan’s (redacted) component exceeded the claimed amount, the component was acting as both a binder and solubilizer such that the amount of binder fell within the claim. The Court rejected Lilly’s hypothesis as speculative and irrelevant.

Mylan also alleged that its formulation will not employ the claimed particle size distribution. The critical issue dividing the parties was whether the particle size should be construed to be measured prior to, or after, formulation. As an initial matter, the Court dismissed Lilly’s argument that Mylan had not alleged in its Notice of Allegation that the particle size should be determined prior to formulation: it would be too onerous to require a second person to make arguments and lead evidence addressing every possible construction, and in an event, Lilly had sufficient notice of Mylan’s allegation. The Court then agreed with Mylan’s (pre-formulation particle size) construction as the only construction compatible with the wording of the patent.

Turning to the parties’ evidence of particle size, the Court accepted Mylan’s evidence of pre-formulation particle size testing in its Abbreviated New Drug Submission as sufficiently reliable and accurate, with values considerably higher than those claimed. The Court also found that even if the claims were construed to pertain to particle size measured post-formulation, Lilly’s testing evidence relating to post-formulation particle size was insufficient to establish infringement.

On obviousness, the Court found the choice of the excipients and their specific amounts was well within the common general knowledge of the skilled person. Since the skilled person would have had a high expectation of success using the excipients and the surfactant of the patent in obtaining a tadalafil formulation with the desired bioavailability, the invention was obvious to try. In addition, the Court found that reduction of particle size was an obvious strategy for which there was a fair expectation of success.

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