Federal Court upholds patent validity and grants prohibition order against generic lisdexamfetamine in pre-CETA PM(NOC) application

The Federal Court dismissed Apotex’s action to invalidate the claims of Canadian Patent No. 2,527,646 (the 646 Patent), which was consolidated with Shire’s application to prohibit the Minister of Health from issuing a Notice of Compliance for Apotex’s generic version of VYVANSE® (lisdexamfetamine). Shire’s counterclaim for infringement in the action was dismissed but the Court granted the prohibition order against the Minister.

Patent found to be valid

Amphetamines are used to treat attention deficit and hyperactivity disorder (ADHD), but are controlled substances because they can be abused for their euphoric effect. Abuse typically occurs when tablets are crushed into a powder that is snorted or dissolved and injected. Sustained-release formulations improve convenience for patients but are more susceptible to abuse because they contained greater amounts of amphetamines.

Invention of the 646 Patent

The 646 Patent claimed prodrugs of amphetamines and derivatives or analogs formed by covalent attachments of chemical moieties to the amphetamine. These prodrugs are converted in the body to the active amphetamine over time, providing sustained release of amphetamine while reducing abuse potential. The asserted claims of the 646 Patent covered lisdexamfetamine (LDX), consisting of d-amphetamine conjugated to the amino acid L-lysine. The claims at issue also cover certain salts of LDX, pharmaceutical compositions containing LDX, and use of LDX to treat ADHD.

Not a selection patent

Shire argued that LDX is selected from the class of amphetamine amino acid conjugates encompassed by Australian Patent No. 54168/65 (the AU 168 Patent). Apotex disagreed. Justice Fothergill doubted that the 646 Patent may be properly characterized as a selection patent. However, he found that nothing turned on this point because the outcome of his anticipation and obviousness analyses were not affected by it. In coming to his conclusion, he distinguished and rejected Apotex’s reliance on Hoffmann-La Roche Ltd. v Apotex Inc., 2013 FC 718, noting that there may be reason to approach this decision with caution.

Not anticipated

The Court held that the 646 Patent was not anticipated. Justice Fothergill found that the expert evidence raised many unanswered questions regarding the prior art, which did not clearly relate to prodrugs, did not disclose the process of making LDX, and did not teach that the compounds it disclosed provide a sustained release treatment for ADHD with, or even without, a reduced potential for abuse.

Not obvious

The Court held that the inventive concept for all the claims of the 646 Patent was a sustained-release formulation of a therapeutically useful dose of amphetamine that is resistant to abuse. Justice Fothergill found that the difference between the state of the art and the inventive concept was the compound LDX and its advantageous properties. He also found that the prior art did not indicate or suggest that LDX would provide sustained release of amphetamine with reduced abuse potential, and that the prior art did not suggest prodrugs would render a drug less susceptible to abuse.

The Court held that LDX was not obvious to try. There was no way to know the properties of LDX without testing, even if the testing was routine, and it was not more or less self-evident that the contemplated tests would overcome the differences between the starting point and the ending point

Not overbroad

Justice Fothergill found that the claims were not overbroad, as he construed  the term “L-lysine-d-amphetamine” as only LDX and a group of compounds.

Specification is not insufficient

Justice Fothergill held that the specification of the 646 Patent is not insufficient because LDX’s advantageous properties exist regardless of whether it is in a particular salt form, or as a free base. He also held that the invention of the 646 Patent does not relate to scale-up synthesis or to a particular crystal form, and that the skilled person was capable of making the claimed compounds by following the 646 Patent.

No reliance on foreign decisions

In reaching the foregoing conclusions, Fothergill J. rejected Shire’s position that the Court should regard foreign judgments involving comparable patents, which consistently affirmed the validity of the patents, as being instructive.

No infringement because of experimental or regulatory use exception

The Court found that Apotex obtained LDX for experimental or regulatory use, and that it was a sufficient defence for Apotex to have an internal policy that the approximately 900,000 capsules containing LDX dimesylate in its inventory would be used entirely for future research or making demonstration batches. As a result, the Court dismissed Shire’s infringement action.

Minister prohibited from granting Notice of Compliance

Having decided that the patent was valid, Justice Fothergill also granted a prohibition order against Apotex’s Apo-lisdexafetamine product as the proceeding under the Regulations was confined to the validity issues in the case.


Apotex Inc v Shire LLC, 2018 FC 637

Pan-Canadian Pharmaceutical Alliance (pCPA) releases draft brand process guidelines

On June 13, 2018, the pan-Canadian Pharmaceutical Alliance (pCPA) released its draft Brand Process Guidelines (Guidelines) for stakeholder feedback. As part of the consultation process, pCPA is planning a webinar for innovative manufacturers on June 22, 2018. The pCPA also released a Frequently Asked Questions (FAQ) document, and a Letter of Intent (LOI) template with the Brand Process Guidelines.

Brand Process Guidelines. The Guidelines are intended to promote a common understanding of the pCPA process, and provide an overview of the pCPA process broken down into the following phases: pre-pCPA, initiation, consideration, negotiation, completion, and post-pCPA. The Guidelines provide details on: (i)  initiation of the pCPA process for new drugs, existing drugs and line extensions, (ii) the content expectations for manufacturer proposals, (iii) negotiation format and negotiator expectations, as well as (iv) communication, confidentiality and disclosure requirements during negotiation. The Guidelines also include target completion timelines for the pCPA process, which sets out an estimated timeline of ≤ 140 days from initiation to completion.

Frequently Asked Questions (FAQ). The FAQ document provides an overview of some commonly asked questions such as: (i) factors that can impact negotiation timelines, (ii) whether a manufacturer can negotiate with individual jurisdictions after receiving a Close Letter (a letter indicating that the pCPA is not opening negotiation for a particular drug) from the pCPA, and (iii) whether a decision to close negotiations without an LOI can be reconsidered.

Letter of Intent (LOI) Template. The LOI template is a standard form document that will detail the agreed upon terms and conditions for funding reached between the lead province(s) and the manufacturer. Of note for manufacturers, the template sets out sample provisions for first dollar and incremental rebates. The template also states that participating jurisdictions may renegotiate the terms of the agreement through the pCPA where there are significant market changes or if expenditures for the drug product significantly exceed the participating jurisdictions’ budget impact. Finally, the template includes standard provisions for continued enrolment of patients in a manufacturer’s patient support program (PSP) for a specified period of time after listing or indefinitely where the patient does not meet the reimbursement criteria in the jurisdiction.

Interested stakeholders should consider attending the pCPA’s webinar for innovative manufacturers on June 22, 2018 as well as submitting additional comments on the Guidelines to the pCPA.


Brand Process Guidelines, FAQ Document, LOI Template

CETA Tracker: Update on section 6 actions under the Patented Medicines (Notice of Compliance) Regulations

As we reported, Canada implemented a single-track pharmaceutical patent litigation regime through amendments to the Patented Medicines (Notice of Compliance) Regulations (the Regulations) on September 21, 2017. Below, we provide an update on new actions and decisions under the amended Regulations.

New actions under the amended Regulations

Nearly seven months after the amended Regulations came into force, litigation is gathering steam. As we reported, the first action under the new regime was commenced by Norton Rose Fulbright Canada LLP on behalf of Genentech, Inc. and Hoffmann-La Roche Limited (collectively, Genentech) in respect of trastuzumab biosimilars on December 11, 2017. This was followed by three more trastuzumab-related actions in late December 2017.

Since the beginning of 2018, ten more actions have been commenced, for a total of fourteen actions currently ongoing:

  • Genentech, Inc. et al. v Amgen Canada Inc., Court File No. T-1921-17 (trastuzumab)
  • Genentech, Inc. et al. v Celltrion Healthcare Co., Ltd., Court Files No. T-1969-17, T-1970-17, and T-1971-17 (trastuzumab)
  • Bristol-Myers Squibb Canada Co. et al. v Apotex Inc., Court Files No. T-350-18 and T-351-18 (apixaban)
  • Janssen Inc. et al. v Teva Canada Limited, Court File No. T-353-18 (paliperidone)
  • Hoffmann-La Roche Limited et al. v Pfizer Canada Inc., Court Files No. T-401-18 and T-402-18 (trastuzumab)
  • Allergan et al. v Tillots Pharma AG, Court File No. T-503-18 (mesalamine)
  • Shire LLC et al. v Apotex Inc., Court File No. T-641-18 (lisdexamfetamine)
  • Bayer Inc. v. Jamp Pharma Corp., Court File No. T-666-18 (vardenafil)
  • Eli Lilly et al v Apotex Inc., Court File No. T-724-18 (teriparatide)
  • Amgen Inc. et al v. Pfizer Canada Inc., T-741-18 (filgrastim)

In order to manage the significantly increased number of deadlines in actions under the amended Regulations compared to applications under the former regime, the Court has applied its “Guidelines for Actions under the Amended PMNOC Regulations”, reported here. This includes early scheduling of the steps leading up to trial using a checklist developed by the Court, early assignment of trial judges, and early booking of trial dates to occur within 21 months of the statement of claim being filed.

Two motions have been decided under the amended Regulations. The court dismissed a motion to vary unilaterally imposed confidentiality rules as premature. The court also dismissed a motion to stay a 6.08 motion until after discovery.


Standing Committee on Health releases report and recommendations on National Pharmacare

On April 18, 2018 the Standing Committee on Health tabled its report on national pharmacare entitled Pharmacare Now: Prescription Medicine Coverage for All Canadians.

The Committee believes that the best way to move forward in establishing a universal single payer public prescription drug coverage program is by expanding the Canada Health Act to include prescription drugs dispensed outside of hospitals as an insured service.  The Act establishes criteria and conditions for insured health services that must be met by provinces to receive payments from the federal government.  Federal government funding will be increased, although the Committee believes that the program should be cost-shared between federal, provincial and territorial governments.

In addition to amending the Act, the recommendations include:

  • Expanding the mandate of the Canadian Agency for Drugs and Technologies in Health (“CADTH”) to include maintaining the national formulary, as well as increasing its capacity to undertake therapeutic reviews of high cost specialty drugs, oncology drugs and drugs for rare diseases.
  • Developing a transparent decision-making framework for price negotiations for pharmaceutical drugs undertaken by the pan-Canadian Pharmaceutical Alliance and designating it as the common agent for the bulk buying of pharmaceuticals.
  • Amending the Patent Act to require manufacturers to reduce prices after 15 years if no generic substitute is available.
  • Investigating the market practices of the pharmaceutical sector, including those of patented and generic drug manufacturers, wholesalers and retail pharmacies, to identify opportunities to reduce prices.

As we reported, the government has also created an Advisory Council on the Implementation of National Pharmacare, which is expected to provide a report in 2019.


Pharmacare Now: Prescription Medicine Coverage for All Canadians


Apotex request to re-open validity of esomeprazole patent denied

The Federal Court dismissed Apotex’s motion to re-open the validity phase of the patent infringement action relating to esomeprazole (AstraZeneca’s NEXIUM®). Apotex had moved to re-open validity to allow the Court to adjudicate the issue of “overpromising” in light of the Supreme Court of Canada’s decision in AstraZeneca Canada Inc v Apotex Inc, 2017 SCC 36 , which related to the same patent.

As we reported, the only issue before the SCC was utility. The court allowed AstraZeneca’s appeal and struck down the Promise Doctrine as an error of law. After the SCC released its decision, Apotex brought a motion to the SCC to have the issue of “overpromising” remanded to the Federal Court and the issues of anticipation and obviousness remanded to the Federal Court of Appeal (reported here). Apotex’s motion was dismissed by the SCC without reasons.

In this decision, Justice Locke found that the validity of the patent in issue had been finally decided by the SCC, and there were no other validity issues to debate, including any question of “overpromising.” He reasoned that any confusion as to the SCC’s intent concerning the patent’s validity was resolved when Apotex’s motion to the SCC was dismissed. While the SCC decision does refer to the Patent Act treating “the mischief of overpromising in multiple ways,” Justice Locke was unwilling to infer that this meant this patent could be invalid on other grounds without the SCC having expressly said so. As we reported, he followed a similar line of reasoning in his decision to deny Apotex’s section 8 claim relating to esomeprazole.

Justice Locke also granted AstraZeneca’s motion for a declaration that Apotex infringed the patent, and directed that quantification be by way of reference. He left the decision of whether AstraZeneca was entitled to elect an accounting of Apotex’s profits to be decided in the reference.

Apotex has appealed the decision.

Link: AstraZeneca Aktiebolag et al v Apotex Inc, 2018 FC 185


ONCA upholds dismissal of summary judgment in lansoprazole s. 8 case

As we reported, Abbott Laboratories Limited, Takeda Pharmaceuticals Company Limited and Takeda Pharmaceuticals America Inc. sought dismissal of Apotex’s action for s. 8 damages in the Ontario Superior Court by summary judgment. The Ontario Court of Appeal (ONCA) affirmed the lower court’s finding that a real-world notice of non-compliance – withdrawal (NON-W) issued by Health Canada did not operate to void the patent hold letter ab initio. The ONCA held it was open to the motions judge to accept “essentially unrefuted” expert evidence that in the hypothetical but-for world Health Canada would have issued Apotex its Notice of Compliance as of its patent hold date and that Health Canada would not have suspended or revoked the Notice of Compliance in the absence of exceptional circumstances.

The Court of Appeal found no palpable and overriding error in the judge’s decision, as there was evidence that supported the judge’s conclusions.

NON-W Could Impact Quantum of Damages

The motions judge invited evidence at trial on whether the NON-W would interrupt Apotex’s sales in the but-for world, and the ONCA agreed it will be open to the trial judge to consider the relevance of Apotex’s real-world NON-W on the quantum of damages.


Apotex Inc v Abbott Laboratories Limited, 2018 ONCA 332


Coulda, woulda, shoulda – Federal Court finds Apotex would not have used non-infringing alternatives in perindopril case

On redetermination of an accounting of profits, the Federal Court (FC) rejected Apotex’s claim that the profits awarded to Servier due to Apotex’s manufacture and sale of infringing perindopril should be reduced based on alleged non-infringing alternatives (NIAs).


In 2008, the FC found that Servier’s patent claiming perindopril was valid and infringed by Apotex, and subsequently ordered Apotex to pay a combined total of $CAD 61 million plus interest, representing Apotex’s profits from its Canadian and export sales. Among other things, the trial judge rejected Apotex’s defence that it could and would have sold non-infringing perindopril (sourced from jurisdictions where there were no patents for perindopril) to its foreign affiliates in the UK and Australia.

As we reported, on appeal the Federal Court of Appeal (FCA) held that the trial judge erred by rejecting the relevance of an existing NIA at law.  However, the FCA found no errors in the trial judge’s conclusion that Apotex failed, on the evidence, to establish it could and would have obtained the required quantity of non-infringing perindopril at the relevant time from all but three of its proposed foreign suppliers: Ipca, Intas and Signa.

The FCA held that the trial judge erred by not explaining why she rejected the evidence related to those three foreign suppliers, and remitted the following issues back to the judge: (1) whether Apotex could and would have obtained sufficient quantities of non-infringing perindopril from those three suppliers, and if so, (2) whether Apotex could have and would have used non-infringing perindopril to replace the sales it made in the real world to its affiliates in the UK and Australia.

Legal test for NIA defence

When considering the effect of a defendant marketing a non-infringing alternative in the hypothetical world, courts must answer two questions:

(1) could the infringer have sold the non-infringing alternative?

(2) would the infringer actually have sold the non-infringing alternative?


The trial judge rejected Apotex’s contention that three proposed unaffiliated third-party suppliers (located in India and Mexico) could have made sufficient quantities of non-infringing perindopril during the infringement period (2006-2008).

The judge found that, as the proposed suppliers did not make commercial quantities of perindopril prior to or during the infringement period in the real world, the complexity of effecting the required technology transfers and obtaining the necessary regulatory approvals would have contributed to a delay in Apotex coming to market. As a result, Apotex could not have started to replace its real-world sales to its UK and Australia affiliates until a year after its real-world sales actually began.


The trial judge noted that the intentions, motivations and preferences of the infringing party in the real world are instructive in drawing inferences as to what it would have done in the hypothetical world.

The trial judge found that, although Apotex could have used non-infringing perindopril sourced from its proposed third-party suppliers one year into the infringement period, the evidence suggested it would not have done so.    Rather, drawing inferences from Apotex’s conduct and motivations in the real world, including its admitted preference to manufacture products at its “own sites,” the trial judge held that Apotex would not likely have used the proposed unaffiliated third parties to manufacture perindopril for its foreign markets.  The court held that Apotex would likely have done in the hypothetical world exactly what it did in the real world, which was to wait until its Indian affiliates were ready and then transfer the technology and commercial production to them.

Norton Rose Fulbright Canada LLP represented Servier at both the liability and quantification stages and on appeal.


Redetermination – Les Laboratoires Servier et al v Apotex inc et al, 2018 FC 346

Accounting of profits – 2015 FC 721; 2017 FCA 23

Validity and infringement – 2008 FC 825; 2009 FCA 222

Top 10 Updates on Canadian Market Access, Exclusivity and Pricing Issues

Norton Rose Fulbright Canada LLP recently published an article on the “Top 10 Updates on Canadian Market Access, Exclusivity and Pricing Issues” for the Food and Drug Law Institute’s March/April 2018 issue of Update Magazine. The article contains an overview of some of the most pertinent changes in market access, exclusivity and pricing that have occurred over the past year that will impact stakeholders operating in the Canadian pharmaceutical industry.

A link to the article can be found here. The article is reproduced with permission of the Food and Drug Law Institute’s Update Magazine.

Ontario delays implementation of regulations under the Health Sector Payment Transparency Act

Although there has been no public announcement, we understand that the Ontario government has indicated it will not be proceeding with the final approval of regulations developed under the Health Sector Payment Transparency Act (“HSPTA”) before the upcoming election.  Rather, these regulations will be revisited in the fall of 2018.

As we reported, Ontario passed the HSPTA as part of Bill 160 in December 2017.  It will require reporting certain financial relationships in Ontario’s healthcare system to the government. As we also reported, draft regulations were published for consultation in February 2018.  The deadline for consultation was April 6, 2018, and this deadline has not been extended.

The draft regulations contained an implementation timeline that would require reporting of transactions that occurred in the 2019 calendar year.  It is expected that when the regulations are revisited this timeline will be delayed.

Change in utility law not a factor in s. 8 damages

The Federal Court of Appeal (FCA) has refused to apply the “special circumstances” exception to issue estoppel in view of a change in law arising from the rejection of the “promise doctrine” in AstraZeneca Canada Inc v Apotex Inc, 2017 SCC 36 (NEXIUM, reported here). Noting any injustice to Lilly is “entirely commercial in nature” as well as a concern of Teva being ‟twice vexed,” the court rejected Lilly’s argument that the NEXIUM decision should be considered as a factor in determining damages pursuant to section 8 of the Regulations.


Teva sought damages from Eli Lilly Canada Inc. pursuant to section 8 of the Regulations, as compensation for having been prevented from coming to market in 2006-2007 with a generic version of ZYPREXA® (olanzapine). As we reported, the Federal Court considered the established parameters to calculate Teva’s damages for being delayed from entering the olanzapine market, clarified evidentiary issues on fact witnesses and hearsay, and rejected Teva’s argument that its damages should include a pipefill adjustment.

The FCA upheld the Federal Court on the evidentiary issues but overturned on the issues of pipefill.

Issue Estoppel

On appeal, Lilly argued the FCA ought to consider the Supreme Court’s decision in NEXIUM, which changed the state of the law for patent utility. Lilly argued the sole basis on which Teva succeeded in the prohibition proceedings that gave rise to section 8 liability was a finding of inutility, and in light of the subsequent NEXIUM decision the court should consider the change in law as a factor in assessing section 8 damages.

The FCA applied the doctrine of issue estoppel, finding it would not be appropriate to allow a collateral attack on the findings of invalidity of the patent given that the issue had already been decided. The court noted a change in the law did not trigger the “special circumstance” exception to issue estoppel, and found there was no basis to exercise its discretion to bar the application of issue estoppel in this case.  Given the real-world impact of “entirely commercial” high-stakes litigation, the special circumstance exception warrants further clarity from the courts.

The Court of Appeal refused to follow the Supreme Court of the United Kingdom’s reasoning in Virgin Atlantic Airways Limited v Zodiac Seats UK Limited, [2013] UKSC 46, [2014] 1 A.C. 160, which did consider a change in law in its assessment of damages, and noted its reasoning is consistent with a recent Ontario Superior Court  decision in litigation relating to ramipril, reported here.

Fact Witnesses Speaking to the Construction of the But-For World

In the underlying decision, the Federal Court addressed the admissibility of evidence on actions fact witnesses would have taken in the but-for world. It held that fact witnesses could be asked about what they did in the real world, and whether they knew of any reason why they would have acted differently in the but-for world. However, opinion evidence from a fact witness about what it would have done in the hypothetical but-for world was inadmissible.

The FCA found it was an error for the Federal Court not to consider factual testimony about what would have happened in the but-for world. It clarified that appropriately positioned fact witnesses can testify not only about their conduct in the real world, but about their own conduct and that of their businesses in the but-for world.

Pipefill Sales Recoverable

In quantifying Teva’s damages, the Federal Court found that pipefill sales do not represent lost sales incurred during the liability period because those units would not be sold to end consumers until after the end of the liability period.

The Court of Appeal found this to be an error, noting section 8 damages are intended  to compensate the generic manufacturer for sales it actually would have made during the period. Since the manufacturer would have made sales into its distribution pipeline during the relevant period, it is immaterial that the units might not be sold to end-users until after the end of the liability period.


Eli Lilly Canada Inc v Teva Canada Limited, 2018 FCA 53