Introduction

On March 7 2018 the Federal Court:

  • upheld the validity of Kennedy Trust's Patent 2,261,630 (the 630 patent), which covers a use of infliximab (Janssen's Remicade); and
  • granted Kennedy's counterclaim that Hospira's biosimilar Inflectra had infringed the 630 patent.(1)

Background

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. In broad terms, the 630 patent claims use of the combination of infliximab with MTX for the treatment of rheumatoid arthritis in patients whose disease has not been controlled by previous MTX treatment alone.

MTX was previously a common treatment for rheumatoid arthritis. Further, studies were published which established that infliximab could provide rapid and significant relief of rheumatoid arthritis symptoms, although 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.

Arguments

The court addressed Hospira's arguments concerning "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. The court rejected Hospira's argument of improper assignment to a different Kennedy entity, holding that any mistake made in filing the patent had later been rectified and that Kennedy Trust was the owner of the patent. The standing of the remaining parties (ie, Janssen Canada, Janssen US and Cilag) was established on the basis that they were licensees or sub-licensees 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 or a cutting-edge expert, the court held that 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. The court instead accepted the patentee's claim 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;
  • neutralisation; 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 in this regard.

The court asserted that 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 did not anticipate the claims, as they were covered under the experimental use exception to anticipation and were confidential. According to the court, finding otherwise would be contrary to public policy (ie, may lead to an end to informed consent or the patenting of medication).

Obviousness As a result of the parties' disagreement on the inventive concept, the court considered the patent's claims and identified the inventive concept as both the manufacture of a medicament using, and a pharmaceutical composition containing, an anti-human TNF-α antibody that can be used in combination with MTX in the treatment of rheumatoid arthritis.

While the state of the art disclosed the use of both MTX and infliximab to treat rheumatoid arthritis, the combination was only suggested in a speculative manner. The court held that it was reasonable to carry out combination trials, but not obvious to do so. The mechanism of action of the drugs and treatment of rheumatoid arthritis 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 rheumatoid arthritis, other parties had not tried the solution of the patent. Instead, solutions were being pursued in several different ways with other biologics (most of which were failing).

Utility/promise The experts agreed that the 630 patent had a scintilla of utility, including providing a new and useful choice to treat rheumatoid arthritis, and that this was sufficient utility given the Supreme Court's decision in AstraZeneca (for further details please see "Promise doctrine struck down and AstraZeneca's NEXIUM patent upheld as useful"). The court rejected Hospira's attempt to import the discarded promise doctrine into insufficiency and overbreadth.

Infringement The court concluded that Hospira had infringed the patent, both directly and by inducing patients.

Direct infringement The court found that the essential elements of the asserted claims had been infringed. Hospira's infliximab product was covered by the claims as:

  • there was no material difference in glycosylation; and
  • although 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 rheumatoid arthritis. Further, in relation to the Swiss-type claims, the court held that, despite manufacture abroad, Hospira was still liable for infringement under the Saccharin doctrine.

Inducing infringement The court found that Hospira had induced infringement in patients, as there had been direct infringement by third parties and Hospira's product monograph amounted to instructions for infringement.

Comment

This is the third patent infringement action decision relating to a biologic(2) and the second on the merits relating to a biosimilar.(3) There are a number of patent litigation matters relating to biosimilars in progress, including infringement and impeachment actions and applications under the pre-amended Patented Medicines (Notice of Compliance) Regulations, as well as, more recently, the amended regulations (for further details please see "Biosimilars update"). Hospira may appeal as of right.

For further information on this topic please contact Katie Lee or Urszula Wojtyra at Smart & Biggar/Fetherstonhaugh by telephone (+1 416 593 5514) or email (khlee@smart-biggar.ca or uawojtyra@smart-biggar.ca). The Smart & Biggar/Fetherstonhaugh website can be accessed at www.smart-biggar.ca.

Endnotes

(1) Hospira Healthcare Corporation v Kennedy Trust for Rheumatology Research, 2018 FC 259.

(2) The first two patent infringement actions were 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.

(3) The first biosimilar decision concerned an application under the pre-amended Patented Medicines (Notice of Compliance) Regulations relating to filgrastim. Further details are available here.

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