On January 14, 2021, the Federal Court issued a decision (Janssen Inc. et al v. Apotex Inc. et al, 2021 FC 7) in the consolidated infringement action brought under s. 6(1) of the Patented Medicine (Notice of Compliance) (PM(NOC)) Regulations by Janssen against Apotex, Dr. Reddy’s Laboratory, and Pharmascience. In this decision, the Court invalidated the asserted claims of Janssen’s Canadian Patent 2,661,422 (the 422 Patent), which claimed the combined use of the two active ingredients found in Janssen’s brand name drug ZYTIGA, abiraterone acetate and prednisone, in the treatment of prostate cancer. Concurrently, the Court dealt with Apotex’ counterclaim under s. 6(3) of the PM(NOC) Regulations to invalidate the asserted and non-asserted claims of the 422 Patent. This decision provides important lessons and reminders in drafting and prosecuting patent applications relating to use of therapeutic agents in the treatment of diseases.
Although the 422 Patent had been the focus in earlier proceedings under the previous PM(NOC) Regulations, this action was brought under the current PM(NOC) regime. As such, the parties were able to advance new and more comprehensive evidence and the previous expert witnesses were open to examination. At the same time, the Court was required to approach this infringement action afresh with “a mind willing to understand and be persuaded”.1 As a result, despite prohibiting the Minister of Health from issuing a NOC to Apotex in its 2019 decision (2019 FC 1355), the Court arrived at the opposite conclusion and found the asserted claims of the 422 Patent to be invalid for obviousness. The 2019 NOC decision is currently pending appeal.
A representative asserted claim of the 422 Patent, claim 3, is directed at “[u]se of a therapeutically effectively amount of abiraterone acetate and a therapeutically effective amount of prednisone in the treatment of a prostate cancer in a human”. In construing the asserted claims, there was little contention around the identity of the person of ordinary skill in the art or the citability of the prior art documents.
In following the principles of claim construction laid out in Whirlpool v Camco (2000 SCC 67) and Free World Trust v Électro Santé (2000 SCC 66), the Court looked closely to the definitions provided by the patentee in the description of the 422 Patent. Since the asserted claims of the 422 Patent refer to individual therapeutically effective amounts of abiraterone acetate and prednisone, the Court looked to the definition of each term “therapeutically effective amount of abiraterone acetate” and “therapeutically effective amount of prednisone” as defined in the 422 Patent. The Court found such terms to mean an amount of abiraterone acetate for treating prostate cancer and an amount of prednisone effective for treating prostate cancer respectively. Based on these definitions, the claims were interpreted to mean each of the active ingredients must individually have anti-prostate cancer effect as opposed to the combination of the two having that effect.2
The definitions provided in the patent were also relied upon for the construction of the term “treatment of prostate cancer”, which was explicitly defined in the description to mean “the eradication, removal, modification, management and control of a tumor, or primary, regional, or metastatic cancer cell or tissue and the marginalisation or delay of the spread of cancer” (emphasis added). Consequently, the Court held that this definition only covers effects on the tumour or cancer cells and excludes palliative effects, survival benefits, mitigation of side effects, or reversal of resistance.3
The limiting of the treatment of prostate cancer to the tumour or cancer cell level had consequences in the obviousness analysis. The Plaintiff attempted to argue it would not have been obvious to use the combination of the two drugs in question to overcome resistance to abiraterone acetate since the mechanism for resistance to hormonal therapy was not well understood. Further, it was submitted that the combination led to an improved survival benefit.4 However, the Court denied these lines of reasoning since the claims have already been construed to limit to effects on the cell or tumour level, i.e., reversal of resistance to abiraterone acetate or survival benefit did not fall within the definition of “treatment of prostate cancer”.
Given the limiting interpretation of the asserted claims, the Court then asked what was inventive about combining abiraterone acetate and prednisone to treat prostate cancer. In performing the 4-step Sanofi test5, the Court reviewed numerous prior art documents and concluded that it was known that abiraterone acetate and similar compounds had anti-cancer effects and abiraterone acetate was recognized as more selective than other compounds in its class. It was also disclosed that prednisone has anti-cancer effect in prostate cells and that it has been used in combination with other compounds similar to abiraterone acetate. A skilled person would find motivation in prior art documents to combine abiraterone acetate with a glucocorticoid replacement such as prednisone. Thus, the Court concluded that based on the accepted common general knowledge and the state of the art, the skilled person would have seen the combined use of abiraterone acetate and prednisone as obvious to try with an expectation of success.
There was little dispute to the utility of the combination of abiraterone acetate and prednisone. The Court reminded the parties that the bar for utility in patentability is a “scintilla of utility” and not regulatory approval. Utility is met if some patients respond, even if only those in dire circumstances. No “three arm studies or a significant number of patients’ results” is required.
Although the asserted claims were found invalid, the Court still dealt with the infringement issue. The Court held that the Defendants’ products would have infringed the asserted claims if they had been found valid. Here again, the consequence of limiting “treatment of prostate cancer” to the cellular or tumour level was evident. The Court noted that the asserted claims do not cover any mitigation of side effects by the use of prednisone with abiraterone acetate since the claims were construed to only relate to effects on the tumour or cancer cells. Nevertheless, it was underlined that it would not have been possible to separate the inherent anti-cancer effect of the two drugs from their ability to mitigate side effects. Thus, the Defendant would not have been able to avoid liability by only referring to mitigation of side effects in their product monographs.6
Non-Asserted Claims and Counterclaim
Section 6(1) of the PM(NOC) Regulations provides a patent owner who receives a notice of allegation with a right of action. Section 6(3) provides that the person who sent the notice of allegation “may bring a counterclaim for a declaration … in respect of any patent claim asserted in the action brought under subsection (1)”. The Court observed that s. 6(3) confirms that the right to bring a counterclaim in the s. 6(1) action exists; but that it is “restricted to the claims asserted in the action”. Read in conjunction with another recent decision of the Federal Court, Sunovion Pharmaceuticals Canada Inc. v Taro Pharmaceuticals Inc (2021 FC 37, read our article on the decision here), it seems that while a defendant in a PM(NOC) action may raise issues that extend beyond what is included in a Notice of Allegation, in a counterclaim under s. 6(3) of the PM(NOC) Regulations the defendant is limited to the asserted claims in the corresponding s. 6(1) action.
Patentable Subject Matter
Although the Court did not address the validity of the non-asserted claims, it was noted that the 422 Patent contained several use claims directed to dosage ranges of the two active ingredients that depended from the general use independent claim. The Defendant argued that these dosage range claims amount to methods of medical treatment that are not patentable under s. 2 of the Patent Act. Interestingly, despite the recent revised Patent Examination Notice published by the Canadian Patent Office (read our article here), in which dependent dosage range claims were deemed unpatentable subject matter, the Court in the present decision noted that “the issue of method of medical treatment is not a settled one and therefore a court should be cautious in striking down claims on this basis”. It will be interesting to see how this issue evolve in future litigations.
Patent Drafting Practice Points
This decision should serve as a reminder to patent applicants to be cautious in the use of explicit definitions in a patent description. When definitions are used, they should be drafted carefully to avoid being unduly limiting and to allow for other reasonable interpretations. Moreover, when the invention is directed to a combination of active ingredients, the utility of the combination should be highlighted as opposed to utility of individual elements. As seen here, the recitation of “therapeutically effective amount” of each individual element led the Court to consider individual utility and find invalidity.