The Federal Court dismissed an application by Eli Lilly Canada Inc., Ube Industries, Ltd., and Daiichi Sankyo Company, Limited (the Applicants) seeking a prohibition order regarding Apotex’s generic version of Lilly’s EFFIENT® (prasugrel hydrochloride). While the Court rejected Apotex’s allegations of overbreadth, insufficiency, and non-patentable subject matter, it held that the claims were obvious.
The claims of Canadian Patent No. 2,432,644 (the 644 Patent) relate to pharmaceutical compositions comprising prasugrel and aspirin. Prasugrel is a member of the thienopyridine family of compounds. The asserted claims of the patent claimed the use of prasugrel for simultaneous or sequential, separate administration with aspirin and the compound prasugrel for use in combination with aspirin, in preventing or treating a disease caused by thrombus or embolus.
In its obviousness analysis, the Court accepted the Applicants’ construction of the inventive concept: the combination of prasugrel plus aspirin with an antithrombotic effect that is greater than the sum of the effects of each agent alone. The Court also found that this inventive concept had not previously been disclosed and therefore differed from the state of the art.
However, in applying the “obvious-to-try” test, the Court held that the claims were obvious finding that there was a motivation in the art to try the combination of prasugrel with aspirin and that there was a “reasonable expectation” that combining prasugrel, a thienopyridine, simultaneously or sequentially with aspirin would produce a beneficial, complementary mechanism of action.
The Court acknowledged that:
- The test for obviousness is a difficult test to meet and had not been changed by the recent Federal Court of Appeal decisions in Ciba Specialty Chemicals Water Treatments Ltd. v. SNF Inc., 2017 FCA 225, and Bristol-Myers Squibb Canada Co. v. Teva Canada Limited, 2017 FCA 76;
- The specific combined use of prasugrel and aspirin, as claimed in the 644 Patent, could not be predicted with exact certainty;
- There was a lack of knowledge of metabolic pathways of thienopyridines as well as of the potential mechanisms of synergy; and
- The prior art did not consistently show that the use of ticlopidine with aspirin produced synergistic effects.
Central to the Court’s analysis was evidence that the prior art had shown that the substitution of one thienopyridine (ticlopidine) for another (clopidogrel) to use in combination with aspirin had been positive.
Despite finding that one of only two thienopyridines approved for sale did not consistently demonstrate synergy with aspirin and that there was no information in the state of the art regarding the mechanism by which clopidogrel and aspirin had developed a synergy, the Court nevertheless concluded that there was a reasonable expectation that the combined use of prasugrel and aspirin could reasonably be expected to achieve a synergy similar to the combination of clopidogrel with aspirin.
This analysis minimizes the well-known unpredictability of structural changes on biological effect. In combination with the “obvious to try” test, this may create a low bar to obviousness that disproportionately impacts pharmaceutical inventions.
Patentable Subject Matter
The Court held that the patent disclosed that the use of prasugrel combined with aspirin results in an effect on platelet aggregation that is new, useful, and more than the mere sum of the effects of the two agents taken alone. The Court accepted as sufficient, data showing that the combination produced a numerically greater inhibition rate than prasugrel or aspirin alone and did not require a more formal statistical analysis.
Insufficiency & overbreadth
The Court rejected Apotex’s argument that the patent failed to disclose how to administer prasugrel and aspirin sequentially. Although time intervals were not specified in the patent, the experts were able to determine an appropriate interval using the patent and common general knowledge. The Court similarly rejected the argument that claim 29 of the 644 Patent was overly broad for failing to include a maximum time interval.
Link to Decision:
Eli Lilly Canada Inc., Ube Industries, Ltd. and Daiichi Sankyo Company, Limited v. Apotex Inc., 2018 FC 736