The Federal Court has allowed a second infringement action concerning a macitentan product under the Patented Medicines (Notice of Compliance) Regulations (the Regulations). The Court found that the defendant would induce infringement of claims relating to combination treatment if it were allowed to market its macitentan product.
Janssen Inc. markets OPSUMIT® (macitentan) to treat patients afflicted with pulmonary arterial hypertension (PAH). Canadian Patent No. 2,659,770 (770 Patent) covers the use of macitentan in combination with a phosphodiesterase type-5 inhibitor (PDE5-I), to treat diseases where vasoconstriction is involved, including PAH.
Janssen Inc. and Actelion Pharmaceuticals Ltd. (collectively, the Plaintiffs) have now obtained judgment in their favour concerning two generic challengers to OPSUMIT® and the 770 Patent. The two actions proceeded in parallel, but involved different issues and claim sets:
- As we reported, the first action was brought against Sandoz Canada Inc. Sandoz conceded that it would infringe the asserted claims (claims 21–31), but argued (unsuccessfully) that the claims were invalid.
- The second action was brought against Apotex Inc. In this case, the Plaintiffs asserted claims 1–5 and 10–20, as well as claims 21–31. Apotex did not argue that any of the claims were invalid, instead defending solely on the basis of non-infringement.
Preliminary Issue – Admissibility & Relevance of Regulatory Expert Evidence
The Court relied primarily on the evidence of treating physicians when deciding the construction and infringement issues in the case. The Plaintiffs successfully challenged Apotex’s reliance on the evidence of a pharmaceutical regulatory expert as part of its defence:
- First, the expert addressed whether Apotex would be permitted to market or promote that APO-MACITENTAN can be used in combination therapy based on its product monograph (PM), and provided a generalized opinion about the information that is typically required to be included in a generic PM. The Court allowed the evidence but gave it little weight, as it was of marginal relevance to the issue of whether the PM would actually induce infringement.
- Second, the expert critiqued the Plaintiffs’ physician expert evidence on whether the PM would support the use of Apotex’s product as a monotherapy or in combination. The Court found this evidence to be inadmissible, as treatment was outside the witness’s expertise.
Claims 1–5 of the 770 Patent are directed to a product for therapeutic use and claims 10–20 are Swiss-style claims for the manufacture of a medicament, while claims 21–31 are framed as use claims. However, Apotex took the position that the 770 Patent is a “use patent” and that “all of the Asserted Claims are effectively use claims”.
Apotex’s position related to the fact that macitentan itself was a known compound—so the focus of the patent was on its use in combination with a PDE5-I. The Court rejected Apotex’s argument, opting instead for a construction focussed on the language of the claims.
The 770 Patent is Infringed
No direct infringement. The Court held that Apotex would not directly infringe any of the Asserted Claims. Claims 1–5 and 10–20 require that macitentan be “in combination” with at least one PDE5-I, an element which would not be performed by Apotex. It was not sufficient that the product containing macitentan (claims 1–5) or medicament containing macitentan (claims 10–20) was “for use in combination” with a PDE5-I. There was no dispute that Apotex would not infringe the use claims (claims 21–31).
Induced infringement. Applying the three-prong test for inducement, the Court held that Apotex would infringe claims 1–5 and 21–31:
- The first prong requires that acts of infringement must be committed by a direct infringer. The evidence established that the majority of macitentan is already prescribed for use with a PDE5-I. The Court held that physicians and patients would use APO-MACITENTAN in combination therapy as well, directly infringing claims 1–5 and 21–31. The Court reaffirmed that the first prong of the test does not require direct contact between the inducer and the direct infringer, nor for the inducer to supply all of the elements of the claimed invention.
- The second prong requires that the direct infringement must be influenced by the alleged inducer such that, but for this influence, direct infringement would not take place. The Court focussed on references in theAPO-MACITENTAN PM to a well-known “landmark” clinical study that demonstrated the efficacy of the claimed combination therapy, as well as certain information that was redacted from the Court’s reasons. Apotex argued that it had “scrubbed” its PM of references to the combination, including in its description of the clinical study. However, Apotex’s expert agreed that physicians would not have performed a side-by-side comparison with the OPSUMIT® PM. The Court found that prescribers would review and rely on the PM, and that the information that remained in it was sufficient to induce infringement.
- The third prong requires that the inducer must knowingly exercise its influence. The Court held that Apotex knows or ought to know that the content of its PM would influence physicians to complete the acts of infringement. The Court again rejected Apotex’s assertion that it had “scrubbed” its PM of references to the combination, noting that Apotex did not lead any factual evidence on its efforts to remove information from the PM or any communications with Health Canada in this regard.