Urszula Wojtyra Katie Lee October 5 2022 Patented Medicines (Notice of Compliance) Regulations: five-year anniversary of major amendments Smart & Biggar | Healthcare & Life Sciences - Canada Urszula Wojtyra , Katie Lee Healthcare & Life Sciences Status of actions under RegulationsTrial decisions on the meritsFederal Court of Appeal decisions on the meritsProcedural mattersThe fifth anniversary of the significant amendments to the Patented Medicines (Notice of Compliance) Regulations (the Regulations) was marked on 21 September 2022. This article provides an update on activities in the fifth year following the amendments, including new actions and a wave of court decisions, both on the merits and procedural.(1)Status of actions under RegulationsIn the period from 21 September 2021 to 21 September 2022, approximately 29 sets(2) (40 total) of actions were started. A comparison to previous years is provided in Figure 1.(3)Figure 1: sets of actions started since 2017Of the approximately 221 actions started since the amendments, the majority continue to be resolved prior to completion of the trial (155, in grey in Figure 2). 26 actions were pursued to a decision on the merits; the innovator was successful in 12. Since some of the actions were tried and decided in a single set of reasons, there are 15 decisions on the merits, nine of which were in favour of the innovator. Appeals are pending from eight decisions on the merits; four trial decisions were affirmed on appeal.Figure 2: outcome of actions started since 2017The following 19 drugs have at least one action ongoing:adalimumab (AbbVie's Humira);aflibercept (Bayer's Eylea);bimatoprost (Allergan's Lumigan RC);carfilzomib (Amgen's Kyprolis);dexlansoprazole (Takeda's Dexilant);efinaconazole (Bausch's Jublia);empagliflozin (Boehringer's Jardiance);emtricitabine, rilpivirine, tenofovir alafenamide (Gilead's Odefsey);ibrutinib (Janssen's Imbruvica);linagliptin (Boehringer's Trajenta);nintedanib (Boehringer's Ofev);paliperidone palmitate (Janssen's Invega Sustenna);riociguat (Bayer's Adempas);sacubitril/valsartan (Novartis's Entresto);selexipag (Janssen's Uptravi);sitagliptin and metformin hydrochloride (Merck's Janumet);tenofovir alafenamide (Gilead's Vemlidy);tenofovir alafenamide/emtricitabine (Gilead's Descovy); andvortioxetine (Lundbeck's Trintellix).In the past year, Apotex was the most active patent challenger (a defendant in 17 actions relating to seven drugs), followed by a tie for second between JAMP Pharma and Sandoz, each with five actions relating to five drugs.In addition, in the past year, four actions were commenced further to section 8.2 (for a total of 17 commenced since the amendments to the Regulations). Section 8.2 permits a first person/patentee to bring an infringement action asserting a patent not listed on the Patent Register once served with a notice of allegation (NOA). Only the four actions started in the past year are ongoing, relating to:efinaconazole (Bausch's Jublia)sitagliptin and metformin hydrochloride (Merck's Janumet)aflibercept (Bayer's Eylea)In general, trials of section 8.2 proceedings have been scheduled approximately three to four months after the trial of the section 6 proceedings. None have yet proceeded to trial.Three actions pursuant to section 8 of the Regulations were commenced in the past year (for a total of eight started under the amended Regulations, though only five are pending) seeking damages following unsuccessful patent infringement actions:fampridine (commenced by Pharmascience and separately Taro Pharmaceuticals); andabiraterone (commenced by Pharmascience)To date, there have been no decisions on the merits of a section 8 action under the amended Regulations. The first trials are scheduled for June 2023 (Apotex and Dr Reddy's Laboratories' actions against Janssen regarding abiraterone).Trial decisions on the meritsA number of further decisions on the merits were released in the fifth year (for further details, see "2022 mid-year highlights in Canadian life sciences IP and regulatory law"):Janssen v Pharmascience, Janssen v Apotex (paliperidone palmitate, Invega Sustenna) – for further details, see "Federal Court holds summary trial appropriate, Apotex and Pharmascience will induce infringement of paliperidone palmitate patent"). Following the first summary trials under the Regulations, the trial judge concluded Pharmascience and Apotex would induce infringement of claims for a dosing regimen. Appeals by both are pending. Subsequent to the summary trial, Pharmascience's invalidity defence was unsuccessful at trial (for further details see "Federal Court upholds validity of patent relating to paliperidone palmitate");Allergan v Apotex (risedronate sodium, Actonel DR) – for further details, see "Federal Court finds formulation patent relating to Actonel DR valid but not infringed"). Formulation claims "for use with or without food or beverage intake" were held to be valid (not anticipated, not obvious, useful, sufficient, not overbroad), but not infringed (product monograph stated should be taken with food). Allergan's appeal is pending;Merck Sharp & Dohme Corp v Pharmascience (sitagliptin phosphate monohydrate, Januvia) – for further details, see "Merck's Januvia crystalline monohydrate DHP salt patent found valid"). A claim to R-enantiomer of the dihydrogen phosphate salt of sitagliptin in crystalline monohydrate form was held to be valid (not obvious in view of the prior genus, which included sitagliptin and its hydrochloride salt, not insufficient). Pharmascience's appeal is pending; andJanssen v Sandoz, Janssen v Apotex (macitentan, Opsumit) – for further details, see "Federal Court finds Janssen's macitentan combination therapy patent valid" and "Janssen succeeds on infringement against Apotex in macitentan combination patent case". In the Sandoz case, claims to macitentan in combination with a phosphodiesterase type-5 inhibitor to treat diseases where vasoconstriction is involved, including pulmonary arterial hypertension, were held to be valid (not obvious, utility soundly predicted, not overbroad, not insufficient). In the Apotex case, validity was not challenged, and the Court held Apotex would induce infringement. Appeals by both are pending.Federal Court of Appeal decisions on the meritsFederal Court of Appeal decisions on the merits include the following:Pharmascience v Teva (glatiramer acetate, Copaxone, Glatect) – for further details, see "Federal Court of Appeal upholds validity of glatiramer acetate patent". The Federal Court of Appeal upheld the finding that claims to use of 40 milligrams of glatiramer acetate administered by subcutaneous injection three times weekly for treatment of relapsing-remitting multiple sclerosis (the 802 patent) were valid (utility soundly predicted, not obvious). The infringement finding was not challenged on appeal. Pharmascience has sought leave to appeal.Pharmascience Inc v Bristol-Myers Squibb Canada Co (apixaban, Eliquis) – for further details, see "Federal Court of Appeal upholds validity of two patents relating to Eliquis". The Federal Court of Appeal upheld the finding that the two patents were valid:the 202 patent, which claims apixaban, an anticoagulant, and the use of apixaban in the treatment of thromboembolic disorders (novel, not obvious, no double patenting and sufficient); andthe 171 patent, which claims tablet formulations of apixaban (not obvious, not ambiguous/overbroad); andBiogen Canada Inc v Pharmascience Inc, Taro (fampridine, Fampyra) – for further details, see "Federal Court of Appeal upholds invalidity of fampridine patent". The Federal Court of Appeal upheld the finding that the patent relating to uses of fampridine sustained release compositions to treat multiple sclerosis was invalid (obvious).Procedural mattersIn addition, a number of procedural decisions were released, including to provide interpretation on aspects of the Regulations:The Federal Court of Appeal dismissed Merck's appeal and upheld a strict interpretation of the 30-day deadline for listing a patent on the Patent Register (for further details, see "Federal Court of Appeal dismisses appeal and upholds strict interpretation of patent listing deadline for Keytruda formulation patent").The Federal Court found the minister of health was reasonable in his interpretation of section 5(1) of the Regulations as applying only to the drug identification number specific version of the innovator's drug. As a result, JAMP was not a "second person" under the Regulations for its product Simlandi, a biosimilar of AbbVie's Humira (adalimumab) (for further details, see "Federal Court finds minister of health reasonable in concluding JAMP not "second person" for Simlandi biosimilar").The Federal Court permitted Sandoz to add multiple grounds of invalidity six months into the proceeding, even though its notice of allegations only asserted non-infringement and a Gillette defence, but only if the scheduled trial was adjourned to a future date and the 24-month stay was correspondingly extended (for further details, see "Sandoz granted leave to add new allegations on condition of trial adjournment and extension of 24-month stay").For further information on this topic please contact Urszula Wojtyra or Katie Lee at Smart & Biggar by telephone (+1 416 593 5514) or email ([email protected] or [email protected]). The Smart & Biggar website can be accessed at www.smartbiggar.ca.Endnotes(1) See prior updates marking the first, second, third and fourth anniversary of the amendments.(2) Actions between the same parties in respect of the same innovator reference drug are considered one "set". The counts are provided as of the fifth-year anniversary, 21 September 2022.(3) The number for 2020-2021 is lower than reported in the article published to mark the fourth anniversary of the amendments, which included five section 8.2 actions.