Inducing Infringement: is the bar too low? A review of the case of Janssen Inc. v. Apotex Inc.
In the pharmaceutical area, the issue of inducing infringement is an important one. Consider the fact situation: A brand company obtains a basic patent on a new compound A. That patent expires. The brand then obtains a second patent, a use patent for a combination of compound A with another compound B. A generic company applies for approval to sell compound A but does not apply for approval to sell compound A for use in combination with compound B. Should the generic company (or any other company) be prevented from selling compound A?
The Federal Court of Appeal in AB Hassle v. Canada (Minister of National Health and Welfare)[1] considered the mischief that arises when a subsequent use patent becomes a means for extending the life of a compound patent, both to the generic company and to other companies or researchers who discover new uses for the old compound:
Thus Apotex cannot be prevented from obtaining a NOC solely on the basis that it will sell omeprazole. If it were otherwise, then serious policy issues would arise. If there was any likelihood that a patient would consume a generic product for a patented use, then the generic product would not be approved. This would prevent new uses from being approved for existing drugs because there is always the possibility that someone somewhere will use the drug for the prohibited, patented purpose. This would result in a real injustice: since a generic company cannot possibly control how everyone in the world uses its product, the prevention of the generic from marketing the product would further fortify and artificially extend the monopoly held by the patent holders. The patent holder would, therefore, effectively control not just the new uses for the old compound, but the compound itself, even though the compound itself is not protected by the patent in the first place. The patent holders, as a result, would obtain a benefit they were not meant to have. In the end, society would be deprived of the benefit of new methods of using existing pharmaceutical medicines at a lower cost.
The question of inducement was recently considered by the Federal Court and the Federal Court of Appeal in the case of Janssen Inc. v. Apotex Inc.[2] According to the patent disclosure:
“The Applicant has now surprisingly found that the combination of a compound of formula (I) with a compound having PDE5-inhibitory properties results in unexpected synergistic effect in the treatment of diseases wherein vasoconstriction is involved.”[3]
The claims in issue covered the use of macitentan in combination with a PDE5-inhibitor for the treatment of a disease wherein vasoconstriction is involved. The claims included product for use claims, Swiss-type claims (“use…in the manufacture of a medicament intended to treat a disease…”) and use claims.
Claim 1 covered a product containing macitentan in combination with at least one PDE5-inhibitor for therapeutic use in the treatment of a disease wherein vasoconstriction is involved.
Although the patent’s focus was on a new use – the combination of macitentan and a PDE5-inhibitor, the court found that “administration to a patient” was not an essential element of Claim 1 which was a “product claim”. However, the court also found that the product required the two active ingredients in the same dosage form or in a package that contains the two dosage forms (although not limited to such embodiment).
Claim 10 covered the use of macitentan in combination with at least one PDE5-inhibitor compound for the manufacture of a medicament to treat a disease wherein vasoconstriction is involved. The plaintiffs argued that Claim 10, the Swiss-type claim, was a type of product claim. Apotex argued that a purposive claim construction oriented to what was invented meant the claim (and dependent claims) was a use claim consistent with the earlier case of Hoffmann-La Roche v. Sandoz Inc.[4] The Trial Judge found that the claim covered the use of the combination of macitentan and a PDE-5 inhibitor in the manufacture of a medicament. There was no disclosure of manufacturing a medicament nor did the ‘770 Patent state that it had invented a new medicament or method of manufacturing.
Although the Trial Judge did not find that the product claim and the Swiss claims were use claims, the Trial Judge found that Apotex did not infringe the product or the Swiss-style claims since Apotex would not (i) make, use or sell a product that contains macitentan in combination with a PDE5-I; (ii) combine a product that contains macitentan with a PDE5-inhibitor to treat pulmonary arterial hypertension (“PAH”); or (iii) use macitentan in combination with a PDE5- inhibitor to manufacture a medicament. Apotex did not perform the “in combination” element of the claims.
The crux of the case is the analysis of inducement of the use claims. The independent use claim (Claim 21) covered a use of macitentan in combination with at least one PDE5-inhibitor compound for treating a disease wherein vasoconstriction in involved. The key document for purposes of inducement is the proposed Apotex product monograph[5]. No witnesses from Apotex testified at trial. According to the plaintiffs, the product monograph included:[6]
- bioequivalence data;
- results from a clinical trial, SERAPHIN, that established that macitentan is safe and effective as monotherapy and in combination with a PDE5- inhibitor; and
- a reference in the “drug interaction section” which is redacted from the decision
Apotex argued that there was no inducement by the product monograph, as:[7]
- there was no reference to combination therapy in the Indications and Clinical Use section;
- the monograph removed all mentions of combination therapy present in the brand product monograph; and
- the only results from the clinical study, SERAPHIN, were those relating to monotherapy
- there was no information on how to administer macitentan in combination with a PDE5- inhibitor
The Trial Judge considered the three prong test set out in Corlac Inc v Weatherford Canada Ltd:[8]
- The acts of infringement must have been completed by the direct infringer;
- The completion of the acts of infringement must be influenced by the acts of the alleged inducer to the point that, without the influence, direct infringement would not take place; and
- The influence must be knowingly exercised by the inducer; in other words, the inducer knows that this influence will result in the completion of the acts of infringement.
With respect to direct infringement, the Trial Judge noted that the standard of care for most PAH patients was combination therapy.[9] The Trial Judge found that, if approved, the Apotex product would be combined with a PDE5-inhibitor for the treatment of PAH. Thus direct infringement was established.
The second prong of the Corlac test was critical in this case. What was the influence of Apotex without which direct infringement would not take place?
The Trial Judge started with the comment made under direct infringement, namely: “The physician experts agree that the standard of care for PAH patients is combination treatment, and most commonly, the combination is an ERA (e.g., macitentan) and a PDE5-I”[10]. Stopping there, what the Trial Judge is saying is that the doctors will be prescribing the combination because it is standard of care not because of Apotex’s product monograph. That should really be the end of the matter. How can Apotex be inducing when the standard of care has already been established by the medical community?
The Trial Judge went even further quoting the expert for the Plaintiffs: “(i) any physician who is prescribing macitentan would be aware of the SERAPHIN data from its publication in the New England Journal of Medicine; and (ii) SERAPHIN was ground-breaking, as the first landmark study to show combination therapy was effective in PAH patients.” [11] The study showed that macitentan is safe and effective for the treatment of PAH, whether on its own or in combination with PDE5-inhibitors.
When considering the Product Monograph, the Trial Judge referred to the expert for the Plaintiffs: “I accept Dr. Mielniczuk’s evidence that, while the “indications and Clinical Use” section of the APO-MACITENTAN states [redacted – but based on the facts of the case only refers to monotherapy] when read in context of the entire PM, this statement does not suggest to physicians that they should depart from the well-established and evidence-based practice of prescribing macitentan to WHO functional class II and III PAH patients”.[12] This is an interesting comment. The monograph does not tell the doctor to use the combination, but on the other hand it does not tell them NOT to use the combination. Is that really the test for inducement? Is the generic company required to say do NOT use this combination to avoid inducement?
The Trial Judge went on to state that there were additional references in the product monograph to the SERAPHIN study found under “Clinical Trial Adverse Drug Reactions”, “Drug Interactions” and under “Clinical Trials”[13].
There was conflicting evidence on whether or not physicians would read the Apotex product monograph. Apotex’s expert said that physicians would not consult the monograph but would prescribe based on the needs of the patient, their understanding of the drug in the academic literature, information from conferences and from clinical practice. The Plaintiffs’ experts (who were preferred by the Trial Judge) gave evidence that they would read the Apotex product monograph “to be satisfied that a generic medicine will provide the same safety and efficacy profile as the brand name drug”.
It is difficult to see how the Plaintiffs’ evidence showed that the doctors would be influenced by the Apotex product monograph when they said they would not depart from the well-established and evidence based practice of prescribing macitentan and that combination therapy was standard of care.
There is certainly the argument that each case must be decided on its facts but there is also a concern that the test for inducement has been watered down. The influence of the infringer does not appear to be material in this case. The evidence was that the doctors were going to prescribe according to the standard of care – the product monograph of Apotex should have been considered in that context. The use in combination would not be an approved use and the references to the SERAPHIN study under drug reactions is not a direction to use in combination.
This case is unlike the decision of the Federal Court of Appeal in Teva Canada Limited v. Janssen Inc.[14] where the Court found inducement as one of the recommended uses in the product monograph was an infringing use. The reference to the SERAPHIN study under “Clinical Trials” is redacted in the decision. For argument’s sake, assume that it referred to the combination use. If the standard of care was already established and would not be “departed” from, then this reference would not be the influence without which infringement would not take place.
The Trial Judge also found that Apotex would be aware that it would exert influence. There was no evidence on this point from the Plaintiffs who had the burden of proof. Instead, the Trial Judge found that “there is no evidence before this Court about Apotex’s efforts to remove information from the PM, and any communications with Health Canada in this regard.”[15] That is, the Trial Judge required Apotex to prove its knowledge, not the Plaintiffs.
The Federal Court of Appeal upheld this decision again referring to the fact that Apotex had not provided evidence of its knowledge. The FCA also found that the Trial Judge was entitled to draw inferences about Apotex’s knowledge from the evidence before it.[16]
Where do we go from here
What is troubling about this decision is that it makes no reference to the problem of extending a compound patent’s monopoly through a new use patent. It is also incredibly difficult to understand how inducement can be found in the face of evidence that the physicians will be following the standard of care in spite of the product monograph and not because of it. This apparent lowering of the standard for inducement has resulted in the courts have artificially extended a compound monopoly. In this author’s opinion, that is a serious problem that will further burden an already struggling public healthcare system.
Citations
[1] 2002 FCA 421
[2] 2022 FC 996 (Macitentan FC), upheld 2023 FCA 221 (Macitentan FCA)
[3] Canadian Patent No. 2,659,770
[4] 2021 FC 384
[5] A product monograph sets out key information on a drug such as indications, adverse effects, dosing etc.
[6] Macitentan FC at para. 153
[7] Macitentan FC at para. 164
[8] 2011 FCA 228
[9] Macitentan FC at para. 174
[10] Macitentan, FC para. 183
[11] Macitentan, FC para. 185
[12] Macitentan, FC para. 192
[13] Macitentan, FC para. 193
[14] 2023 FCA 68 at para. 110
[15] Macitentan, FC para. 203
[16] Macitentan FCA paras 23-24
The views expressed in this op-ed are those of the author and do not necessarily represent the position of IPIC as an organization. We welcome submissions from members of the IP community that contribute toward further development of IP law
