Methylphenidate Dosage Form Patent Valid and Infringed on the Facts

Janssen Inc v Actavis Pharma Company 2016 FC 1361 O’Reilly J
            2,264,852 / methylphenidate dosage form / CONCERTA / NOC

In this brief decision O’Reilly J granted Janssen’s application for an order prohibiting the Minister of Health from issuing an NOC to Actavis in respect of its generic version of CONCERTA, a drug used to threat ADHD [1]. Actavis’ invalidity and non-infringement arguments failed on the facts and on claim construction.

The active ingredient in CONCERTA is methylphenidate (“MP”), but the ‘852 patent does not cover MP itself, which was long used in the treatment of ADHD, particularly in the well-known drug Ritalin [7]. Rather, it covers a formulation which provides a “sustained-ascending dose over time,” for regulation of tolerance to MP. While Ritalin was widely prescribed, the original immediate release formulation had to be taken either two or three times a day, which led to compliance problems with school age children [8]. A subsequent slow-release formulation was puzzlingly ineffective, as it too worked only for a few hours. The insight which was the basis of the ‘852 patent is that the reason for the short duration of effectiveness, even for the slow release formulation, might be “acute tolerance,” where a patient becomes tolerant to a drug within a single dosing period [14]. This would explain the failure of the slow-release formulation; while the plasma concentration was stable over the dosing period, it became less effective because the patient developed tolerance over the same period. This hypothesis turned out to be correct [18]-[19]. This discovery led to the development of the ‘852 formulation, which provides a dosage that increases over time, so as to provide a stable response once balanced against the tolerance that would develop over the same period.

Actavis’ main invalidity attack was based on obviousness. Actavis argued that all the inventors had done was to confirm the hypothesis that the problem with slow-release Ritalin was acute tolerance to MP [44]. However, on the facts, while acute tolerance was one of the conceivable reasons for the problem, is was not at all obvious that it was actually the cause; indeed, most researchers at the time doubted that acute tolerance was the reason for the problems with slow-release Ritalin [47]. In light of this, the fact that it was easy to actually make a sustained-ascending dosage form is beside the point [48]. As was said long ago, in Canadian Gypsum [1931] Ex CR 180, 187, “[T]he inventive ingenuity necessary to support a valid patent may be found in the underlying idea, or in the practical application of that idea, or in both. It may happen that the idea or conception is a meritorious one, but that once suggested, its application is very simple,” but that is no bar to obtaining a patent.

On claim construction, Actavis argued that the phrase “sustained-ascending dose over time” meant “over an entire dosing period”. This was rejected by O’Reilly J, in favour of an interpretation that the dosage would have to rise for a sufficient duration to provide effective treatment over the dosage period [33]. This is different, given that the drug continues to be effective for at least a couple of hours after it stops releasing into the plasma [34].

While Actavis lost on claim construction, it had another non-infringement argument, namely that the release profile of its product was not good enough to make it effective at compensating for acute tolerance [57]. O’Reilly J rejected this argument on the facts, including the fact that Actavis’ product monograph confirmed both that the tablets will release MP at an ascending rate for 6 to 10 hours, and that the Actavis product was essentially equivalent to CONCERTA.