On March 7, 2018, the Federal Court upheld the validity of Kennedy’s patent for a use of infliximab (Janssen’s REMICADE) (Patent No. 2,261,630 [the “630 patent”]), and granted Kennedy’s counterclaim that Hospira’s biosimilar INFLECTRA infringed the 630 patent: Hospira Healthcare Corporation v Kennedy Trust for Rheumatology Research, 2018 FC 259.

Infliximab is an antibody that inhibits binding at TNF-α receptors, a key target in autoimmune diseases. Janssen’s infliximab product, REMICADE, is approved for use in combination with methotrexate (MTX) for the treatment of rheumatoid arthritis (RA). In broad terms the 630 patent claims use of the combination of infliximab with MTX for the treatment of RA in patients whose disease was not controlled by previous MTX treatment alone.

MTX was a commonly used treatment for RA, and studies had been published that established infliximab could provide rapid and significant relief of RA symptoms, though the duration of the effect was limited. The inventors of the 630 patent found that a combination of MTX and infliximab led to a sustained duration of response and enhanced efficacy over MTX or infliximab alone.

Justice Phelan addressed Hospira’s arguments on “an astonishing number and veritable panoply of patent law issues,” including standing, claim construction, various grounds of invalidity and infringement, both direct and induced.

Standing: All of the named plaintiffs were held to have standing to bring the action for infringement. Justice Phelan rejected Hospira’s argument of improper assignment to a different Kennedy entity, holding that any mistake made in filing the patent was later rectified, and Kennedy Trust is the owner of the patent. The standing of the remaining parties (Janssen Canada, Janssen US, and Cilag) was established on the basis that they were licensees/sublicensees of the patent.

Skilled person: The parties disputed the qualifications of the skilled person to whom the 630 patent was addressed. Reasoning that the skilled person must not be imbued with extraordinary levels of skill and experience, nor a cutting edge expert, Justice Phelan held the skilled person was a rheumatologist or team who treated patients, and could also include a post-doctorate level biologist or molecular biochemist with experience with monoclonal antibodies.

Claim Construction: Hospira’s proposed claim construction limited the claimed ‘infliximab’ molecule to the exact molecule described in the patent, and therefore excluded CT-P13 (INFLECTRA) in view of differences in glycosylation. Justice Phelan instead accepted the patentee’s construction, holding that the skilled person would understand that infliximab is defined by its amino acid sequence, as this gives the antibody the defining characteristics of high affinity, neutralization and binding to a TNF-α.

Validity

The Court dismissed Hospira’s validity attacks, including method of medical treatment, overbreadth, double patenting, insufficiency and the unknown attack of “improper priority”. The Court also assessed the following grounds of invalidity:

Novelty: The Court rejected Hospira’s arguments.

  • The asserted prior art documents suggested trying infliximab or anti-TNF‑α antibody in combination with MTX, or referenced clinical trials where that combination was being tried. The Court agreed with Kennedy that the publications were speculative and only suggested avenues for future research without any reason to expect success, or providing any enabling detail (some did not specify infliximab). The Court held that the prior art publications did not disclose the special advantage of the invention, which the Court held was a reduced human anti-chimeric antibodies response and improved pharmacokinetics enabling long-term treatment of infliximab with good efficacy and tolerability.
  • The Court held that clinical trial patient consent forms for one of the trials exemplified in the patent do not anticipate the claims as they are covered under the experimental use exception to anticipation, the forms were confidential, and finding otherwise would be contrary to public policy (may lead to an end to informed consent or the patenting of medication).

Obviousness: As a result of disagreement between the parties on the inventive concept, the Court considered “what is claimed in the patent” and identified the inventive concept as (1) the manufacture of a medicament using and (2) a pharmaceutical composition containing: an anti-human TNF-α antibody that can be used in combination with MTX in the treatment of RA. While the state of the art disclosed the use of each of MTX and infliximab to treat RA, the combination was only suggested in a speculative manner. The Court held it was reasonable to carry out combination trials, but it was not obvious to do so. The mechanism of action of the drugs and treatment of RA were not well-understood, and the prior art contained no indication that the combination was to be preferred or that it would solve the problem of shortened response to treatment that was identified in the prior art. In addition, despite a great deal of motivation to develop a new treatment for RA, others did not try the solution of the patent, instead solutions were being pursued in a number of different ways with other biologics (most of which failed).

Utility/promise: The experts agreed that the 630 patent had a scintilla of utility, including giving a new and useful choice to treat RA, and this was sufficient utility given the Supreme Court of Canada’s decision in AstraZeneca (previously reported). Justice Phelan rejected Hospira’s attempt to import the discarded “promise” doctrine into insufficiency and overbreadth.

Infringement

Justice Phelan concluded Hospira infringed the patent, both directly and by inducing patients:

Direct infringement: The Court found that the essential elements of the asserted claims were infringed. Hospira’s infliximab product was covered by the claims: there was no material difference in glycosylation, and while the infliximab in INFLECTRA has a single additional amino acid at the C-terminal, this was known by the skilled person to have no impact on function.

The Court also rejected Hospira’s argument that it did not produce infliximab in combination with MTX for the treatment of RA, and in relation to the Swiss-type claims, despite manufacture abroad, Hospira was still liable for infringement under the Saccharin doctrine.

Inducing infringement: The Court found that Hospira induced infringement in patients: there was direct infringement by third parties and Hospira’s product monograph amounted to instructions for infringement.

Conclusion

This is the third patent infringement action decision relating to a biologic (after Kirin-Amgen Inc v Hoffmann-La Roche Ltd (1999), 87 CPR (3d) 1, relating to erythropoietin and AbbVie Corporation v Janssen Inc, 2014 FC 55, set aside 2014 FCA 242, relating to ustekinumab/STELARA). It is only the second decision on the merits relating to a biosimilar (the first was in an application under the pre-amended PMNOC Regulations relating to filgrastim, previously reported here). As reported here, there are a number of patent litigation matters relating to biosimilars in progress, including infringement/impeachment actions and applications under the pre-amended PMNOC Regulations and more recently, under the amended PMNOC Regulations. Hospira may appeal as of right.