On September 10, 2020, the Federal Court released its public Judgement and Reasons holding that all asserted asserted claims of Canadian Patent No. 2,371,684 to be invalid.
Tadalafil is the active ingredient in CIALIS a popular treatment for erectile dysfunction. The 684 Patent generally claims a dosage form containing between 2 to 20 mg of tadalafil for the treatment of erectile dysfunction.
Allegations that the 684 Patent was invalid were previously found to be justified in an application under the Patented Medicines (Notice of Compliance) Regulations largely on the basis of the 784 patent application teaching that a dosage form containing between 0.2 to 400 mg of tadalafil was effective in treating erectile dysfunction (see our previous post here). As a result, generic tadalafil became available in Canada in July 2016. Shortly thereafter, Lilly commenced actions against a number of generic manufacturers of tadalafil alleging infringement of the 684 Patent and two other patents. A common trial involving several generic tadalafil manufacturers was held regarding the 684 Patent.
Lilly argued that the 684 Patent was a selection patent and sought to construe the inventive concept of the asserted claims as including an improved side effect profile as compared to sildenafil or to the broader dosage range of tadalafil claimed in the prior art 784 Application.
Justice St-Louis reviewed the jurisprudence regarding selection patents and noted that the 684 Patent did not mention the 784 Application. She concluded that the 684 Patent did not satisfy the criteria to be considered a selection patent because the 684 Patent does not disclose that the claimed doses of tadalafil were better than any other dose. As a result, Justice St-Louis concluded that the 684 Patent did not satisfy the criteria for a selection patent set out in IG Farbenindustrie and was not a selection patent.
Justice St-Louis noted that the effect of this finding was that the purported advantage of an improved side effect profile was not relevant to the anticipation or obviousness analyses.
Following on her construction of the asserted claims, Justice St-Louis concluded that the 784 Application disclosed all of the essential elements of the asserted claims of the 684 Patent. Turning to the enablement requirement, Justice St-Louis concluded that it would have been routine work for the skilled team to select the dose range claimed in the 684 Patent when starting from the broader dose range of the 784 Application:
Dose selection is a routine pharmaceutical work performed without undue burden, and forming part of Phase II clinical studies at the end of which, typically, a dose response curve is drawn for the final selection of doses for large scale studies. The skilled team, in Phase II, has to ascertain the minimum effective dose as well as the maximum. Although the determination of endpoints in studies involve a judgment call by the urologist, he or she will have no problem identifying what would be minimally effective in treating male ED. The efficacy plateau is identified in Phase II, and using a host of factors from previous work in preclinicals and Phase I, including, for example, what experts have summarized as absorption, distribution, metabolism, and excretion (ADME), as well as the side effect profile, the final doses, which offer the best balance between safety-tolerability and effectiveness, are selected for large scale Phase III studies. Even if the skilled team fails to draw up a dose response curve following a single Phase II trial because the doses studied are too high and all are effective, or because the doses studied are too low and none is effective, a second Phase II trial can be performed (transcript of December 18, 2019 at page 44). Nothing inventive is required for the routine trials.
The asserted claims of the 684 Patent were therefore found to be anticipated by the 784 Application.
Justice St-Louis applied the framework for the obviousness analysis as set out by the Supreme Court in Sanofi. Noting the different approaches that the Courts have taken to the identification of a patent’s inventive concept, Justice St-Louis confirmed that the correct approach is to consider the essential elements of the claims as they have been construed. The efficacy of the claimed doses of tadalafil, administered orally, for the treatment of male erectile dysfunction was determined to be the inventive concept of the 684 Patent.
Justice St-Louis determined that the difference between the inventive concept and the prior art was the lower and narrower dose range in the 684 Patent. Justice St-Louis concluded that this difference would have been obvious to the skilled person:
As outlined by the experts, drug dosing is typically done during Phase II clinical trials. It is routine work, and there are even expert pharmacologists such as Dr. Baughman who are specialised in dose selection (or dosing) of drugs. The skilled team, in attempting to dose tadalafil, would use available information from the 784 Application and the 377 Patent, including information on tadalafil bioavailability, potency and selectivity for PDE5, as well as information from sildenafil. As Dr. Baughman wrote in her Expert Report at paras 68-75, the relative molecular weight of tadalafil versus that of sildenafil, and the relative potency of tadalafil versus that of sildenafil will allow the skilled team to make a rough prediction of the dose, within the range disclosed in the 784 Application. Working from there, and using all available information in the prior art, the skilled team can design a Phase II dose ranging study, graph the dose response curve from data gathered during the study, identify the side effects, and select the dose range that provides the best balance between efficacy, and safety and tolerability … The skilled team, using known and routine trial design techniques, shall be able to design trials to appropriately select the doses for tadalafil and proceed to Phase III large scale studies.
The asserted claims of the 684 Patent were therefore found to be obvious.
A copy of the decision, which may be found here, was placed on the court file for each of the actions.
Scott Beeser and Jon Stainsby of Aitken Klee successfully represented Teva Canada Limited. Marcus Klee, Aleem Abdulla, and Yaseen Manan of Aitken Klee successfully represented Pharmascience Inc. and Laboratoire Riva Inc.