In Janssen v Sandoz, the Federal Court held that Canadian Patent No. 2,659,770 was valid and would be infringed by Sandoz’s proposed macitentan product.
Sandoz sought to manufacture a generic version of Janssen’s OPSUMIT product, which contains the active ingredient macitentan. Janssen commenced a proceeding in the Federal Court on the basis that Sandoz’s product would infringe some claims of the 770 Patent.
The asserted claims of the 770 Patent relate to the treatment of diseases relating to vasoconstriction, such as pulmonary arterial hypertension, using a combination of macitentan and a PDE5 inhibitor. The claimed combination blocks two of the three pathways that cause these diseases: macitentan is an endothelin receptor antagonist (ERA) that blocks the endothelin pathway; PDE5 inhibitors block nitric oxide pathway.
Sandoz alleged that the patent was invalid.
Patent not obvious
Justice Pallotta identified the inventive concept of the 770 Patent as the use of macitentan in combination with a PDE5 inhibitor to treat a disease involving vasoconstriction.
The prior art disclosed the combination of a different ERA in combination with a PDE5 inhibitor to treat diseases involving vasoconstriction. Sandoz argued that there was a class effect, and that the skilled person would know that any ERA (including macitentan) could be combined with a PDE5 inhibitor. Justice Pallotta held that there was no basis to extrapolate the results to other drugs within the same classes based on their shared mechanisms of action. As a result, the skilled person would not focus on combinations of an ERA and a PDE5 inhibitor and would not expect that a different ERA such as macitentan would be effective when combined with a PDE5 inhibitor.
Sandoz also argued that the asserted claims of the 770 Patent were obvious in light of a prior art patent application which disclosed and provided the structure of several ERAs, including macitentan. Sandoz argued that even if the combination of any ERA with a PDE5 inhibitor was not obvious, the combination of macitentan specifically with a PDE5 inhibitor was obvious or obvious to try.
Justice Pallotta held that the evidence did not establish how the skilled person would select macitentan as the ERA to be used:
I find there were not, as Sandoz argues, limited numbers of possible combinations of drug therapies. The patent references in evidence disclose large numbers of ERAs. In my view, even accepting that the skilled person would be steered toward combining an ERA with a PDE5-I, a fundamental gap in Sandoz’s obviousness argument is that there is no basis, apart from hindsight, that would lead the skilled person to identify a group of candidate ERA compounds that would include macitentan for testing.
The Court therefore found that the asserted claims of the 770 Patent were not obvious.
Other invalidity arguments unsuccessful
Sandoz alleged that the 770 Patent was invalid for lack of utility. The 770 Patent disclosed that macitentan lowered blood pressure in rat models when combined with 2 different PDE5 inhibitors and that the effects observed with the combination were greater than those observed with any single drug.
The Court concluded that the utility of the claims was not demonstrated as of the filing date of the 770 Patent because the animal testing it disclosed did not necessarily translate to benefit in humans. However, Justice Pallotta held that the testing described in the patent combined with the common general knowledge provided a sound line of reasoning to predict the utility of the 770 Patent.
Justice Pallotta also concluded that Sandoz had failed to establish that that the asserted claims were invalid for overbreadth and insufficiency.
Sandoz agreed that if the 770 Patent was valid, its macitentan product would infringe the claims. The Court therefore granted the relief sought by Janssen.
A copy of the decision may be found here.