In November and December 2014, the Federal Court dismissed Janssen Inc.’s two applications to prohibit the Minister of Health from issuing a Notice of Compliance (NOC) to Teva Canada Limited for its generic injectable bortezomib product (which was compared to Janssen’s VELCADE). Teva’s NOC issued on December 18, 2014. The public reasons for the decisions were released in February, 2015.
Bortezomib formulation patent: 2015 FC 184
The 146 patent relates to formulations of boronic acids and esters thereof, and the claim at issue claimed the lyophilized mannitol ester of bortezomib. The mannitol ester is the reaction product formed when the bulking agent, mannitol, is lyophilized with bortezomib.
The Court agreed with Teva that the skilled person included both a formulator and medicinal chemist.
Janssen had submitted that the invention was non-obvious because the choices required were complex and the results obtained were unexpected; specifically, it was unexpected that lyophilization of bortezomib and mannitol would result in an ester of bortezomib that was stable and could be easily reconstituted. Indeed, the inventor himself was not aware that he had created a mannitol ester. However, the Court held that if a patentee obtains a workable formulation, the later discovery of one of its inherent characteristics does not add anything inventive to what had already been discovered. The Court therefore instead focussed on the steps that the skilled person would have taken to arrive at a stable formulation.
The Court held that a skilled person would know that since bortezomib is a peptide-based compound, it cannot be administered orally and needs to be formulated for injection. The Court found that a skilled person, faced with the knowledge that bortezomib was unstable in solution would immediately consider solid state formulations, for which there were two options. Given that bortezomib was a small peptide molecule, it was a good candidate for lyophilization. A bulking agent, such as mannitol, was commonly used and was known to be a stabilizer, and there was nothing to teach away from the use of it in this application. Indeed, the prior art had shown that boronate esters were known to have a stabilizing effect and could be made with mannitol, and such esters would have been expected to be reversible.
The Court held that the use of esters for stabilization of boronic acids and the selection of mannitol was routine. Even though the skilled person may have to make a few choices and test the formulation to ensure efficacy, this does not render the formulation exercise non-obvious: “the existence of [a] number of possible routes to solve a problem does not mean that the route taken was not obvious.” The Court characterized the inventor’s course of conduct as routine, and found that it followed the steps that a skilled person would have taken and did not suggest any particular insight. The Court concluded that a skilled person would have had a fair expectation that by lyophilizing bortezomib and mannitol, a successful, stable formulation would result, whether or not the skilled person would have understood that the ester would be formed.
Bortezomib compound patent: 2015 FC 247
On February 26, the Court released its decision in 2015 FC 247 relating to Canadian Patent 2,203,936 (936 patent). The 936 patent relates broadly to dipeptide boronic acid compounds, including bortezomib, which are proteasome inhibitors. The proteasome is a protein complex implicated in cell cycle control, the inhibition of which could be useful to treat proliferative cell diseases like cancer. The three claims at issue related specifically to bortezomib, its use to treat cancer and a unit dosage form.
While Teva had initially alleged invalidity on the bases of anticipation, obviousness, invalid selection and lack of demonstrated or predicted utility, the Court dealt only with obviousness, finding in favour of Teva on this issue.
The Court concluded that the inventive concept was the compound bortezomib and its property as a proteasome inhibitor. However, the Court agreed with Teva that the inventive concept does not “incorporate any enhanced aspects of potency or selectivity nor does the  Patent assert any such relative advantages.”
While Teva relied on three pieces of prior art referred to in the “Description of Related Art” portion of the 936 patent, the Court found it sufficient to consider obviousness with reference to only a genus patent identified as the 904 patent.
The Court agreed with Teva that the 936 patent is a selection from the 904 patent as the 904 patent discloses (1) a genus of peptide boronate compounds that includes bortezomib by a selection of substituents at five positions and (2) the peptide boronate compounds are potent inhibitors of the proteasome.
The Court held that the 904 patent provided a “clear roadmap to bortezomib,” and that a skilled person “is not doing anything inventive when he chooses options provided in a prior patent to build a molecule that he expects will work.” Janssen’s evidence that a skilled person would not know which choices would work best or function in a special way was held not germane as the 936 patent does not assert that the choices made to arrive at bortezomib were ‘best’ or ‘special.’
The Court reasoned that it “does not matter that the 904 [genus] Patent does not specifically describe bortezomib. It is sufficient that bortezomib is included in the genus of previously claimed compounds so that, in the absence of some special or unexpected advantage favouring bortezomib, the compound cannot be reclaimed.”
Janssen had argued that one of the groups in the structure of bortezomib, pyrazinecarbonyl, was not encompassed by the genus in the 904 patent. The Court disagreed, but held that even if it that were true, the choice of that group did not require inventive ingenuity. In doing so, the Court relied on Teva’s expert evidence that the group was a protective group with no role in potency. Additionally, the Court considered the inventors’ actual course of conduct and found that the chemists merely chose one of a group of available choices that was expected to work and that it was a matter of routine bench work.
While Janssen appealed, as Teva had received its NOC, Janssen’s appeal was dismissed as moot (Janssen Inc v Teva Canada Limited, 2015 FCA 36). Janssen had argued that the Court of Appeal should exercise its discretion to hear the appeal in light of the “equivalent and effective rights of appeal” referenced in the Comprehensive Economic and Trade Agreement (CETA) between Canada and the EU. The Court rejected the argument, in part because CETA has not yet been implemented by statute.
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