The rise of Swiss-form claims
The type of second medical use claim relevant in the pregabalin cases is the so-called Swiss-form claims (“Use of drug X in the manufacture of a medicament for the treatment of disease Y”). Such a claim format is ultimately a legal fiction, introduced by the Enlarged Board of Appeal of the EPO in the Eisai case to allow parties to patent new uses of known drugs, without failing.
The issue of construction and infringement of Swiss-form claims has not substantively come before the UK Courts until fairly recently, and the issue of “cross-label” use (use of a medicament indicated for a non-infringing use being used in an infringing manner) is the novel subject of the recent Warner Lambertcases.
Preliminary relief application
In January 2015, Warner-Lambert made an application to the Patents Court for interim relief in respect of Actavis’ generic pregabalin medicine, known as Lecaent. Warner-Lambert held a patent with Swiss-form claims for the use of pregabalin in the treatment of pain, following expiry of its compound patent in 2013, and alleged direct and indirect infringement of the claims as covering either a product or a process.
Approximately 50% of Warner-Lambert’s sales of its pregabalin medicine, Lyrica, were thought to be for the treatment of pain. While Actavis’ Lecaent is not authorised for pain and has a skinny label (i.e. the label does not identify that the product is for the treatment of pain), Warner-Lambert asserted that some of the product was being prescribed cross-label, dispensed and used for the treatment of pain.
The basis of this assertion was that in the UK, doctors are encouraged to prescribe drugs using the international non-proprietary name (INN), including by the relevant prescribing software. Pharmacists, who often have no knowledge of the indication for which the product is to be used by the patient, are then financially incentivised to dispense the cheapest product available (in this case, Actavis’ Lecaent).
The relief requested by Warner Lambert was unique. It applied for a mandatory injunction forcing Actavis to:
Contractually oblige pharmacists and wholesalers to make reasonable endeavours not to dispense Lecaent for the treatment of pain;
Notify Warner Lambert of any supply to intermediaries;
Label Lecaent as not being authorised for the treatment of pain; and
Send correspondence to NICE, all Clinical Commissioning Groups (“CCGs”) and pharmacists supplied by Actavis noting that Lecaent was not to be used in the treatment of pain.
After three days of argument, the Court applied the American Cyanamid case and refused Warner Lambert’s application. Applying the first limb, Arnold J. held that there was no serious issue to be tried, as the word “for” in the Swiss-form claim imports a requirement of subjective intention on the part of the manufacturer that the medicament or pharmaceutical composition will be used for treating the specified condition, and Warner Lambert had failed to evidence this in support of is claim to direct infringement of the process claim under s60(1)(c).
He also suggested that there could be no claim to indirect infringement under s60(2), as there would be no preparation/manufacture by a downstream wholesaler or pharmacist. It is quite clear that in considering construction, Arnold J. considered that the relevant process element of the claim was the manufacture or preparation of the product, as such a claim “is not aimed at, and does not touch the doctor” in accordance with Actavis v Merck.
Considering the second limb, Arnold J. found that even if there was an arguable case of infringement, the balance of the risk of injustice favoured the refusal of the relief sought, principally because the relief sought could deter pharmacists from dispensing Lecaent for any indication, effectively excluding Actavis from the market for the non-patented indication.
The application for NHS guidance
In his interim relief decision of 21 January, Arnold J. also commented that the “best solution” to the problem encountered by Warner-Lambert was for the NHS to issue guidance recommending that doctors should prescribe pregabalin by brand (i.e. “Lyrica”) for the treatment of pain and to prescribe pregabalin generically for other indications.
Because pharmacists in the UK would be legally obliged to dispense the branded medicine to fulfill prescriptions written for the brand, if doctors adhered to the guidance, this ought to ensure that the generic medicine was not dispensed for the patented indication. The Judge also encouraged software providers to amend their electronic prescription systems to prompt doctors to prescribe branded pregabalin for pain. Arnold J. commented that “I consider that there is a reasonable prospect of NHS England issuing guidance in the near future but a lower prospect of software suppliers modifying their software quickly.”
No doubt spurred on, at least in part by the observations of the Judge, Warner-Lambert immediately engaged in correspondence with NHS England, asking it to issue guidance to CCGs. After some discussion, NHS England indicated that it would not oppose an Order that it must provide guidance, provided that certain conditions were met.
The matter came before Arnold J. on 26 February, at which time he considered that the Court had jurisdiction to make the Order against an “innocent third party who is mixed up in the wrongdoing of others” and that the injunction was appropriate in all the circumstances as “the issuing of guidance by NHS England is the most efficacious, dissuasive and cheapest solution to the problem which confronts Warner-Lambert”. An order was granted requiring the NHS to issue guidance to the CCGs, who were then requested to issue further guidance to practitioners.
A cross-undertaking in damages was provided in favour of NHS England and those generic companies that applied for it and their group companies. Arnold J.’s willingness to order such an undertaking in favour of the generic companies was based on the possibility that the patent was later held invalid, and also, even if the patent was held valid, the possibility that the guidance would have the effect of Lyrica being prescribed and dispensed at the expense of generic pregabalin for non-patented indications (referred to as “a chilling effect”).
Quite how the chilling effect could be quantified in any subsequent enquiry is unclear. Finally, it is worth noting that the Order made by Arnold J. makes provision for additional guidance to be issued when the patent expires (or earlier in the event that the patent is revoked). The essence of the additional guidance is that practitioners should revert to their normal prescribing practices and that any software modifications should be reversed.
Appeal of the PI
The Court of Appeal, (Floyd LJ giving the leading judgment) issued a unanimous decision on 28 May, upholding Arnold J’s decision not to order the measures sought by Warner Lambert. This decision was based on the ground that Arnold J. had properly evaluated the evidence before him and reached a sensible conclusion on the balance of justice.
However, perhaps more significantly, the Court reached an alternative view on the correct approach to be taken to the construction of Swiss-form claims that will have a significant impact on the assessment of the infringement of such claims in the future. The Court of Appeal disagreed with the construction adopted by Arnold J. Instead, the key is what the manufacturer knows (including constructive knowledge) or could reasonably foresee about the ultimate intentional end use of the product for the patented indication. So, in the appeal court’s view, infringement will occur if the manufacturer knows or can reasonably foresee the ultimate intentional use for pain. The manufacturer does not necessarily need to have to have that specific intention or desire itself.
Also of note is the Court of Appeal’s comment during an earlier strike out application that it is arguable that “putting the invention into effect” in s60(2) may occur when one person manufactures and another uses the product for the patented indication. This certainly pointed towards the Court of Appeal considering a quite different approach to construction than that articulated by Arnold J. at first instance.
The main action
The case was heard at the end of last term and a decision was handed down on 10 September. Despite finding that the main claims of the patent were invalid due to insufficiency, Arnold J. considered the infringement position. He held that Actavis did not infringe the claims asserted against them and that Pfizer was liable for making groundless threats of infringement.
In his judgment, Arnold J. clearly disagrees with the Court of Appeal’s preferred test of reasonable foreseeability, due to the potential unexpected consequence that where it is reasonably foreseeable that some of a generics product would be used in an infringing manner, all acts of manufacture would be infringing.
Despite this criticism, Arnold J. applied the test and held that, on a number of dates in question, it was not foreseeable that the medicine would have been “intentionally administered for the treatment of pain”. This was principally on the basis that the doctor would not know which company’s pregabalin would be dispensed, and the pharmacist was unlikely to know the indication for which it was prescribed (and if it did, would dispense Lyrica as a result of the letters written to superintendant pharmacists by Actavis).
This is particularly interesting, given Floyd LJ’s observation during the preliminary relief appeal that “the judge found that in these circumstances, it was foreseeable that a generic version of Lyrica with a skinny label will be dispensed for patients who have in fact been prescribed the drug for pain”.
An appeal is almost certainly inevitable and it is not hard to imagine these issues eventually (or perhaps more quickly as a result of a “leapfrog” appeal) being considered by the Supreme Court, such is their complexity and importance.
Arnold J. also refused to find infringement under s60(2), noting that he was “puzzled”, “baffled” and did not understand the reasoning behind the Court of Appeal’s decision to reverse his strike out decision. Returning to the theme of his decision on preliminary relief, he also stressed that the answer to this problem should not be found in the patent system, but should lie in centralised and authoritative guidance instructing prescribers to prescribe by brand name where patents exist.
Concluding remarks
While Arnold J.’s initial subjective intent approach provides certainty for generic companies, it would be quite difficult without detailed disclosure for patentees to determine whether their patents had been infringed, even where significant sales were taking place for the patented indication.
The more objective approach of the Court of Appeal is consistent with the gradual erosion of strict liability for direct patent infringement, but is, perhaps a sound solution to ensure that the rights of patentees are adequately protected and therefore promotes innovation and research into new uses of known compounds, which is a growing field.
Arnold J.’s application of the Court of Appeal’s decision is a little tortuous but does have the effect of limiting that erosion. Once again, the decision contains proposals straying from the strict application of patent law, comprising a note proposing that the Secretary of State take steps to put a suitable prescribing system in place in England.
This solution may not be forthcoming, considering that the NHS guidelines have not been popular with healthcare professionals, thought by many to be overcomplicated, motivated by financial rather than medical benefit and guidance for which the consequences of non-compliance are unclear. It remains uncertain whether the NHS will provide such guidelines for all second medical use products in the absence of a court order to do so.
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