Federal Court declines to grant injunction for infringement of HUMIRA formulation patent | Smart & Biggar

On December 4, 2023, the Federal Court issued its public judgment and reasons in two patent infringement actions pursuant to s. 6(1) of the Patented Medicines (Notice of Compliance) Regulations (“Regulations”) and two patent impeachment actions pursuant to s. 60(1) of the Patent Act (“Act”). The proceedings concerned AbbVie’s patents for dosing regimens and formulations of adalimumab (AbbVie’s HUMIRA) and JAMP’s biosimilar, SIMLANDI: AbbVie Corporation v Jamp Pharma Corporation, 2023 FC 1520.

At issue were Canadian Patent Nos.:

• 2,504,868 (868 patent): adalimumab dosing regimens for treating inflammatory bowel disease (IBD) (including Crohn’s disease and ulcerative colitis);
• 2,801,917 (917 patent): adalimumab dosing regimens for treating hidradenitis suppurativa (HS), a skin disorder; and
• 2,904,458 (458 patent): protein-containing aqueous pharmaceutical formulations (including of adalimumab).

Writing for the Court, McVeigh J found the 868 and 917 patents invalid for obviousness but upheld the validity of the 458 patent.

Though JAMP conceded infringement of the 458 patent, the Court declined to grant the permanent injunction sought by AbbVie (which would have enjoined JAMP from making, using, promoting or selling SIMLANDI in Canada until the 458 patent’s expiry on November 28, 2028). The Court concluded that an injunction would not be in the public interest. There was evidence that increased injection site pain could result from forcing patients taking JAMP’s high concentration, citrate-free SIMLANDI biosimilar (the only adalimumab product marketed in Canada in an 80 mg/0.8 mL presentation) to switch to another biosimilar (which may have higher injection volume and/or contain citrate).

Procedural background

AbbVie commenced the patent infringement actions under the Regulations in March 2021 (in response to JAMP’s notices of allegation). In April 2021, JAMP commenced the patent impeachment actions under the Act, seeking to invalidate the patents at issue.

In January 2022, the Minister of Health issued notices of compliance for SIMLANDI. In response, AbbVie applied for judicial review of:

1. the Minister’s determination that JAMP was not a “second person” under the Regulations because the HUMIRA 40 mg/0.4 mL and 80 mg/0.8 mL reference drugs, while approved, were not marketed when JAMP filed its regulatory submission (and thus that JAMP need not address patents listed against HUMIRA on the Patent Register); and
2. the Minister’s decision to issue notices of compliance for SIMLANDI.

In the meantime, JAMP launched its SIMLANDI products in April 2022 in three presentations: 40 mg/0.4 mL (pre-filled syringe and auto-injector pen) and 80 mg/0.8 mL (pre-filled syringe). 

The Court dismissed AbbVie’s applications in AbbVie Corporation v Canada (Health), 2022 FC 1209 [AbbVie 2022] ( previously reported; appeal ongoing).

In the present matter, the parties agreed that JAMP’s impeachment actions were unaffected by the ongoing appeal of AbbVie 2022. The Court thus released its decision without waiting for determination of the AbbVie 2022 appeal, noting that AbbVie’s infringement actions under the Regulations were “not presently at issue”.

868 patent invalid for obviousness

The 868 patent claims relate to the use of adalimumab for treating IBD according to an every other week dosing regimen of 160 mg, 80 mg and then 40 mg thereafter (i.e., use of 160 mg and 80 mg “loading doses”).

The Court found the 868 patent invalid for obviousness but not as a method of medical treatment:

• Obviousness: The Court held the dosing regimen of the 868 patent was obvious to try. The prior art pointed towards using antibodies against tumor necrosis factor alpha (TNF-α), of which adalimumab was a “most preferred” option, for treating IBD. In view of dosing regimens used for rheumatoid arthritis, the skilled person would envision use of loading doses of 80 mg and 160 mg for IBD.
• Patentable subject matter (method of medical treatment): The Court agreed with AbbVie’s assertion that the relevant question is whether the claimed subject matter requires skill and judgment to practise. Here, the claimed dosing regimen was the only option for physicians implementing adalimumab under the 868 patent. That physicians might deviate from this dosing regimen would simply place their conduct outside the scope of the 868 patent, rather than render the claims invalid.

917 patent invalid for obviousness

The 917 patent claims relate to the use of adalimumab in multiple doses for treating HS, wherein the multiple doses comprise a 160 mg dose at week zero, an 80 mg dose at week two, and a 40 mg weekly maintenance dose starting at week four.

The Court rejected JAMP’s method of medical treatment attack for substantially the same reasons provided in respect of the 868 patent. JAMP’s remaining challenges to the validity of the 917 patent – anticipation, obviousness and “claim term not described” – were addressed as follows:

• Anticipation: The Court rejected JAMP’s allegation that the 917 patent was anticipated by the application for the 868 patent (868 application). While the 868 application disclosed the use of TNF-α inhibitors (including adalimumab) for treating 16 broad categories of disorders (one of which included HS), the skilled person would still have to choose from a range of dose amounts, dose intervals and durations of treatment to create a multiple variable dosing regimen.
• Obviousness: The dosing regimen of the 917 patent was both obvious and obvious to try. It was known from off-label use case reports that the adalimumab dosing regimen used to treat Crohn’s disease (160 mg, 80 mg and 40 mg thereafter biweekly) could be used to treat HS. Safety concerns would not have deterred the skilled person from using a 160/80/40 dosing regimen for HS.
• Claim term not described (s. 38.2(2) of the Act): JAMP’s allegation centered on the claim term “…wherein said multiple doses are not subject to any discretionary adjustment by a physician or medical practitioner”. This term was inserted into claim 1 of the 917 patent during prosecution. JAMP alleged that the added term was not supported by the specification or drawings as filed and that, as a result, the 917 patent was invalid for failing to comply with s. 38.2(2) of the Act.

The Court analyzed this issue in the alternative, given the Court’s obviousness conclusions. The Court agreed with JAMP that amended language that cannot be reasonably inferred from the specification or drawings violates s. 38.2(2) of the Act and can render a patent invalid, noting that “it is fundamentally unfair to allow an applicant to successfully broaden or enlarge the patent through amendments to specifications or drawings.”

Turning to the 917 patent, the Court concluded that, although the added claim term conflicted with the disclosure, the term did not change or broaden claim 1. As a result, AbbVie had “not gained anything more than it originally had.”

Validity of 458 patent upheld

The asserted 458 patent claims relate generally to a 100 mg/mL aqueous pharmaceutical formulation of adalimumab. Some asserted claims further specify particular conductivity or pH; others specify that the formulation does not comprise a buffering system.

The Court rejected JAMP’s overbreadth allegations (for which JAMP did not put forward expert evidence). The Court also rejected JAMP’s remaining validity challenges:

• Anticipation: It was not clear how the skilled person would select adalimumab from the more than 60 “preferred” proteins listed in Patent Cooperation Treaty (PCT) Application No. WO 2006/138181 (181 application). Nor was it clear how the skilled person would select the appropriate adalimumab concentration, pH and salt concentration from the ranges or options in the 181 application.
• Obviousness: JAMP alleged that the 458 patent was obvious in view of the 181 application and a PCT application that claimed buffered antibody solutions ranging from 1-150 mg/mL and contained examples of adalimumab solutions up to 63 mg/mL. These references taken together did not render the 458 patent obvious or obvious to try. While there was motivation to use adalimumab at higher concentrations (to reduce injection volume), a 100 mg/mL formulation was not obvious to try considering that the prior art taught adalimumab formulations only up to 63 mg/mL.
• Double patenting: JAMP alleged double patenting based on a Canadian patent with a laterfiling date (and thus later expiry date) than that of the 458 patent. The Court observed that this did not create an “evergreen problem” – the 458 patent would not extend AbbVie’s monopoly on the subject matter of the later-filed patent (which AbbVie had subsequently dedicated to the public). The Court was open to the possibility that double patenting may lead to an unfair advantage under the Regulations beyond extending the time of the monopoly. However, JAMP had not clearly articulated that any such advantage was conferred on AbbVie.

Court declines to grant injunction for infringement of 458 patent

JAMP conceded infringement of the 458 patent claims if their validity was upheld. Thus, the Court considered AbbVie’s request for relief but ultimately declined to grant a permanent injunction or order delivery-up of infringing JAMP products, stating: “[t]his is one of those rare cases where I will not grant a permanent injunction given the public interest factor.”

The Court observed that SIMLANDI was the only adalimumab biosimilar that is higher concentration, lower volume, and citrate-free at an 80 mg/0.8 mL presentation. While Celltrion’s YUFLYMA was available as a 40 mg/0.4 mL pen, there was no evidence on whether its market entry was conditional on SIMLANDI’s. Other adalimumab biosimilars were lower concentration and higher volume; some contained citrate.

The expert evidence suggested that higher injection volumes and the presence of citrate could each cause increased injection site pain for some patients. Evidence from JAMP’s experts further suggested that non-medical switching could cause a perceived increase in injection site pain (through the “nocebo effect”).

Accordingly, it was not in the public interest to force SIMLANDI patients to switch to another biosimilar. Noting AbbVie’s licensing agreements with seven other pharmaceutical companies in Canada that offer adalimumab biosimilars, the Court found – as argued by JAMP – that AbbVie could be compensated by a reasonable, running royalty on future sales of SIMLANDI. This rate was left to be determined at the bifurcated quantification and specific damages assessment.

AbbVie has appealed.

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