The Federal Court has granted an order prohibiting the Minister of Health from issuing a Notice of Compliance to Apotex Inc. for a generic version of ZYTIGA (abiraterone acetate). It held that the use of the combination of abiraterone acetate and prednisone claimed by Janssen Inc.'s patent was patentable subject matter, and that the patent's claims were non-obvious and possessed at least a scintilla of demonstrated utility. The Court also held that Apotex would induce infringement of Janssen's patent with the product monograph for its proposed generic. This will likely be one of the last cases decided under the pre-September 2017 Patented Medicines (Notice of Compliance) Regulations (the PM(NOC) Regulations).
Background
Janssen Inc. markets ZYTIGA in Canada for use in the treatment of prostate cancer. Apotex Inc. (Apotex) sought approval for a generic version of ZYTIGA, APO-ABIRATERONE. Canadian Patent No. 2,662,422 (the 422 Patent) is listed on the patent register in respect of ZYTIGA. Apotex served a Notice of Allegation under the PM(NOC) Regulations, as they read prior to September 21, 2017, alleging that the 422 Patent was invalid and would not be infringed. Janssen Inc., Janssen Oncology, Inc., and BTG International Ltd. (collectively, the Applicants) brought an application for a prohibition order on the basis that Apotex's allegations were not justified. The Applicants argued that Apotex should therefore be denied a Notice of Compliance until the expiry of the 422 Patent.
The invention and Asserted Claims of the 422 Patent
The 422 Patent's invention is described as methods for treating cancer by administering a 17α-hydroxylase/C17,20-lyase (CYP17) enzyme inhibitor, such as abiraterone acetate (AA), in combination with one or more additional therapeutic agents, such as prednisone (PN).
All of the claims at issue in this proceeding (the Asserted Claims) were directed towards the use of therapeutically effective amounts of AA and PN combined to treat prostate cancer. The dispute also turned on the function of PN as an anti-cancer agent (as claimed by the Applicants) and/or as a means to treat AA's side effects (its more commonly known function).
The Applicants argued that the 422 Patent claimed the invention of the combination of AA and PN for the treatment of prostate cancer. Apotex contended that AA and PN did not work synergistically and that the 422 Patent did not claim such an interaction. The Court ultimately held that the 422 Patent claimed the cancer-fighting feature of PN, rather than its palliative effects. In considering the expert evidence, the Court debated the pros and cons of expert "blinding". Ultimately, the Court declined to prefer the opinions of Apotex's experts merely on the basis that they were "blinded".
The 422 Patent claims patentable subject matter
The Applicants argued that the Asserted Claims were to patentable subject matter because AA and PN, when combined, produced an unexpected anti-cancer effect that was not observed when either drug was administered alone. Apotex asserted that the subject matter of the Asserted Claims was unpatentable because they merely claimed the combination of two known anti-cancer agents without suggesting any synergistic results.
The Court rejected Apotex's allegation, holding that if a combination claimed to produce a greater cumulative effect than those produced individually by its components, then that was patentable. Even though the individual anti-cancer effects of AA and PN were not well-established as of the relevant time, the Asserted Claims disclosed an anti-cancer combination that was more effective than the sum of the effects of those agents used alone.
The Asserted Claims are not obvious
With respect to obviousness, the Court found that the inventive concept required not only the combination of AA and PN, but their combination for the purpose of treating prostate cancer, where each drug contributed to an anti-cancer effect (as opposed to treating side-effects). To come to the inventive concept, the skilled person would have had to determine that AA should be further tested for the treatment of prostate cancer and then decide to combine AA and PN to treat prostate cancer.
The O'Donnell 2004 article was an important piece of prior art in this case in that it set out the only reported trial of AA treatment of prostate cancer in humans prior to the relevant time. Based on the article, a skilled person would have found AA promising in terms of secondary hormonal treatment for prostate cancer. However, O'Donnell 2004 did not point to observable AA side effects that would have prompted the introduction of a concurrent prescription of a glucocorticoid replacement, such as PN.
The Court held that the invention was not obvious because no prior art suggested that the effectiveness of AA in treating prostate cancer might be increased if used in tandem with another drug. Further, the prior art did not establish the existence of any observable AA side effects. Therefore, it would not have been obvious to concurrently prescribe AA and PN. The Court also found that the combination of AA and PN to treat prostate cancer was not obvious to try because such an arrangement was neither set out nor predicted in any prior art. Consequently, considerable effort and inventive ingenuity would have been required to discover this treatment method.
The Asserted Claims do not lack utility
Apotex argued that the Asserted Claims lacked demonstrated utility on the basis that the studies relied upon by the Applicants were conducted with a combination of AA and an alternative glucocorticoid to PN, dexamethasone. Apotex also argued that the Applicants could not rely on sound prediction because no factual basis or sound line of reasoning was provided in the 422 Patent.
With respect to sound prediction, the Court applied the "enhanced disclosure" requirement and found in favour of Apotex. It then went on to consider whether utility had nonetheless been demonstrated.
The Court held that the equivalent dosage of dexamethasone and PN was known at the relevant date, and that the hypothesis that the invention would work was relevant to all glucocorticoids — not just PN. The Court also accepted that preliminary findings from one of the Applicants' clinical trials showed that the combination of AA and PN had utility in the treatment of prostate cancer. Although this study did not demonstrate that the combination had any greater effect than AA or PN on its own, the Court was satisfied that there was a scintilla of evidence that this was true when the results were viewed in the light of earlier studies. The Court therefore rejected Apotex's inutility allegations.
Apotex would induce infringement of the 422 Patent
Apotex asserted that the product monograph (PM) for its proposed generic AA drug, which indicated only AA as the anti-cancer treatment, did not recite the same combination use set out in the Asserted Claims. The Court disagreed, holding that Apotex intended the same drugs to be used in the same amounts and for the same overall purposes based on to the PM.
Although the words "therapeutically effective amount" were not included in the PM with respect to PN, the Court noted that Apotex could not argue that it indicated a use of its drug in an amount that was ineffective to treat prostate cancer.
The case is: Janssen Inc. v Apotex Inc., 2019 FC 1355
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