Federal Court prevents Minister of Health from allowing sale of generic version of immunosuppressive drug MMF
Geoffrey North & Lindsay Gwyer -
In an application pursuant to the Patented Medicines (Notice of Compliance) Regulations, Hoffman-La Roche sought an order preventing the Minister of Health from issuing a notice of compliance to Apotex for the drug mycophenolate mofetil (MMF), an immunosuppressive drug used primarily in organ transplants, until after the expiry of Canadian Patent No. 1,333,285. Seeking early market entry, Apotex on the other hand alleged that the ‘285 patent was invalid on the grounds of lack of utility and obviousness.
Construction of the ‘285 Patent
The first consideration of the Court was to construe the ‘285 patent. In this respect, the Honourable Mr. Justice O’Reilly provided useful guidelines:
[T]he task of construing a patent does not simply involve a search for that morsel of utility on which the patent holder hopes to rely. The Court must review the patent’s specification with an eye to the essence of the invention, appreciating how a skilled person would interpret the words the inventor used to describe it.
As Justice Roger Hughes put it, “in construing the specification of a patent, in particular the ‘promise’, the Court is to look at the specification through the eyes of a person skilled in the art, bearing in mind commercial realities, being neither benevolent nor harsh, in order to determine fairly the true intent”.
… In my view, construction of the patent is a preliminary step which precedes the analysis of
the grounds of potential invalidity. It should be carried out without regard for the impact of the construction on utility or obviousness, or whatever other issues arise in the case … As Apotex argued, where advantages form part of the stated invention, it would be unfair to allow the patent holder to rely on those advantages to show that the invention was unobvious and, at the same time, dismiss those advantages as being irrelevant to utility. A patent holder cannot read up the invention for obviousness and read it down for utility.
With these principles in mind, the Court found that the essence of the invention lay in the identification of a useful prodrug (i.e. MMF) of the known immunosuppressant mycophenolic acid (MPA), which itself unfortunately suffered from poor solubility and bioavailability. In particular, as a prodrug with advantageous pharmacokinetic properties, MMF was found to be absorbed and metabolized in the body to yield MPA with greater bioavailability (translating into greater activity) following ingestion, making it useful as an immunosuppressive agent.
The Court noted that the ‘285 patent did not disclose any tests on humans, instead providing in vitro or in vivo studies in rats and monkeys. However, because MMF’s sole mission was to deliver MPA (and MPA was already well-known to be useful in the treatment of a number of conditions in humans), an example in the patent that showed that MMF produced higher concentrations of MPA in the bloodstream than oral dosing with an equal amount of MPA itself, was sufficient for demonstrating MMF’s utility in humans.
The Court found that the evidence merely showed that there was a possibility that an ester derivative of MPA might deliver enhanced bioavailability. Although the measures that were taken to find a solution to the bioavailability problems with MPA may not have been inventive in themselves, the inventors showed persistence in continuing to explore a field of inquiry in which the prior art suggested that success was doubtful. MMF was therefore found to be neither obvious to try, nor was it self-evident that it would work.
Consequently, the validity of the ‘285 patent was upheld and the application was granted, which precludes Apotex from obtaining a notice of compliance at this time to market its generic version of MMF.
For more information, please see: Hoffman-La Roche Limited v. Apotex Inc.