The High Court has refused to grant an interim injunction that Warner-Lambert had requested against Actavis. The order sought to prevent alleged infringement by Actavis of Warner-Lambert’s second medical use patent for pregabalin in the treatment of neuropathic pain, by marketing Lecaent, a generic version of the drug. The decision is significant because it is the first time a UK court has dealt comprehensively with second medical use claims and it provides guidance on some of the key issues faced by both patentees and generic competitors.
The claimant, Warner-Lambert, holds a marketing authorisation for pregabalin, which is marketed under the trade mark Lyrica for the treatment of epilepsy, generalised anxiety disorder (GAD) and neuropathic pain. Patent protection for the drug substance itself expired on 17 May 2013.
Warner-Lambert holds a second medical use patent (European Patent (UK) No. 0 934 091) (“the Patent”) which has claims in Swiss form directed to pregabalin for treating pain, in particular neuropathic pain. Actavis will shortly obtain a marketing authorisation for Lecaent, generic pregabalin, for the treatment of epilepsy and GAD only. Lecaent will be marketed under a so-called “skinny label”, which allows Actavis to carve out neuropathic pain from the patient information leaflets associated with the drug.
Statistics show that a high proportion of prescriptions are written generically and also that most prescriptions do not state the indication for which the drug has been prescribed. In the absence of further information, and for commercial reasons, a pharmacist will therefore often dispense the generic version of the drug. As a result, the generic product is likely to be supplied to patients who have in fact been prescribed the drug for treating the patented indication, unless positive steps are taken to prevent this.
Warner-Lambert alleges that Actavis will infringe the Patent by marketing Lecaent, while Actavis and another generic supplier, Mylan, brought revocation proceedings against the Patent. Pending the trial of these issues, Warner-Lambert applied for an interim injunction requiring Actavis to take a number of steps to prevent Lecaent from being dispensed for treating neuropathic pain. These steps would require Actavis to:
- make it a condition of any agreement entered into with a pharmacy for the supply of Lecaent that the pharmacy shall use reasonable endeavours not to supply or dispense Lecaent to patients who have been prescribed pregabalin for neuropathic pain;
- inform Warner-Lambert’s solicitors of the name of any intermediary supplied, prior to supply;
- write a letter, in the form prescribed by Warner-Lambert, to the superintendent pharmacist responsible for the pharmacy to which Lecaent is to be supplied;
- ensure that each pack of Lecaent supplied to a pharmacist is accompanied by a removable notification stating that the product is not authorised for treating pain;
- write to NICE informing it that Lecaent should not be prescribed or dispensed for treating pain; and
- write a letter, in prescribed form, to all Clinical Commissioning Groups in the UK.
Actavis pleaded that Warner Lambert’s infringement claim had no real prospect of success and should therefore be refused, and alternatively that the risk of injustice to Actavis outweighed the risk of injustice to Warner-Lambert, thereby favouring refusal of the injunction.
Arnold J. refused the injunction, holding that there was no serious issue to be tried. In marketing generic pregabalin in the manner proposed, Actavis did not infringe a Swiss-form claim in the Patent.
In the alternative, Arnold J. stated that, even if he was wrong about there not being a serious issue to be tried, applying the legal test set-out in American Cyanamid v Ethicon, the balance of the risk of injustice favoured refusal of the relief sought.
In order to decide whether the relief sought by Warner-Lambert should be granted, Arnold J. applied the general principles set out in American Cyanamid v Ethicon. However, since the relief sought was intended to affect the conduct of third parties, namely prescribers, physicians and the like, none of whom were present at the hearing, these principles should be applied with care.
Was there a serious issue to be tried?
Warner-Lambert’s primary claim for infringement of the Patent was under section 60(1)(c) Patents Act 1977 (the “Act”), which makes it an infringement to keep, dispose of, or offer to dispose of, any product obtained directly by means of the claimed process. The relevant Swiss form claims of the Patent are as follows:
“1. Use of [pregabalin] or a pharmaceutically acceptable salt thereof for the preparation of a pharmaceutical composition for treating pain.
3. Use according to Claim 1 wherein the pain is neuropathic pain.”
If Actavis or their manufacturer were to carry out the process of claims 1 and 3, Lecaent would be a product obtained directly by means of that process. However, the question that needed to be answered was whether the manufacture of pregabalin by Actavis or their manufacturer would fall within the claims upon their proper interpretation. According to Arnold J., citing Birss J. in Hospira UK Ltd v Genentech Inc, this meant determining whether Lecaent was a product obtained by the use of pregabalin for the preparation of a pharmaceutical composition which was intended for treating neuropathic pain.
Following the judgment of Jacob L.J. in Actavis v Merck, Arnold J. held that the relevant intention was that of the person who carried out the process i.e. Actavis or their manufacturer, and not the person dispensing or prescribing the medicine. Moreover, subjective intent was required in order for there to be an infringement. Since Warner-Lambert had not relied upon any allegation of subjective intent on the part of Actavis for the purposes of the application, Arnold J. concluded that Warner Lambert’s claim under section 60(1)(c) of the Act did not raise a serious question to be tried and therefore that the interim injunction should be refused.
Did the risk of injustice favour granting or refusing the injunction?
Warner Lambert argued that if Lecaent entered the market pending trial, and was then subsequently excluded by a final injunction, calculating the profits it had lost would be very difficult and generic competition would result in price depression during this period. This would be difficult to reverse even if a final injunction was granted and so irreparable harm would have been caused.
However, although Arnold J. agreed that any loss suffered by Warner-Lambert by failing to grant the interim injunction would be difficult to quantify, he rejected the argument that such harm would be irreparable and should favour granting the relief sought for a number of reasons.
Many of the cases relied upon by Warner-Lambert related to the entry of generic products which competed with all of the prescribed indications of the medicines subject to a disputed patent. In this case, however, since Actavis and other competitors were lawfully entitled to enter the market for pregabalin for epilepsy and GAD, Warner-Lambert could not complain about any price depression and loss of profits in respect of these indications; they could only complain about any losses specifically related to the pain sector of the market. In the absence of a change in the Drug Tariff Category for pregbalin for treating pain, it was also unlikely that the price of pregabalin for treating pain would drop significantly between the time of the present application and the trial.
Additionally, since Actavis had already agreed to take a number of the steps requested by Warner-Lambert to discourage prescribing or dispensing of Lecaent for the treatment of pain, any loss suffered by Warner-Lambert would only be to the extent that such steps were ineffective. It was also likely that one of the measures requested by Warner-Lambert which was in dispute, namely putting a notice on Lecaent packaging, would not make a significant difference.
Moreover, it was common ground between the parties that the best way of ensuring that Lecaent was not dispensed for pain was for the NHS to issue appropriate guidance to doctors to ensure that, when prescribing pregabalin for pain, the prescription should be for Lyrica, rather than generic pregabalin. If such guidance was issued, Warner-Lambert would not suffer irrecoverable loss and the relief sought would be unnecessary.
When considering the likely harm that Actavis would suffer if the injunction was granted, Arnold J. held that Actavis would suffer unquantifiable loss in two ways.
First, requiring Actavis to put a notice on their packaging would certainly delay their entry into the market. They would have to find a contractor to make the necessary changes to the packaging and would also have to make the necessary regulatory submissions, both of which would cause several weeks’ delay.
Secondly, Actavis had provided evidence that both the requirement to put a removable cellophane notice on the packaging, and the imposition of contractual terms, would deter pharmacists from stocking Lecaent. An additional burden would be placed on them to remove such wrappers before dispensing to patients and, more importantly, they would be concerned that they may not be able to comply with any contractual terms imposed on them through no fault of their own if a prescription for pregabalin was presented which did not state the indication. To the extent that pharmacists were deterred from stocking Lecaent, Actavis would suffer loss which could not easily be quantified.
Taking all of these factors into account, Arnold J. concluded that granting the relief sought by Warner-Lambert would create a greater risk of injustice than refusing it, and therefore that the interim injunction should be refused.
The decision in this case gives a very useful overview of the issues surrounding infringement of second medical use claims; guidance which will be welcomed by both patentees and generic manufacturers. Guidance is also provided on the requirements for infringement of Swiss form claims, a subject with little previous existing jurisprudence.
A number of healthcare policies and practices were discussed in the judgment which affect the rights of patentees of second medical use claims. Although Arnold J. refused the relief sought by Warner-Lambert in this case, he specifically urged the NHS to issue guidance that in situations such as the one considered in this case, a drug should be prescribed by reference to the brand name for the patented indication, and by reference to the generic name for non-patented indications. Such guidance would ensure that the rights of patentees were properly respected without the need to resort to litigation.
The full text of the decision can be found here.