Mr Justice Arnold refused Warner Lambert Company LLC’s request for an injunction against Actavis Group PTC EHF’s pregabalin product, which Actavis intended to launch around January 2015 for the treatment of epilepsy and generalised anxiety disorder (“GAD”) after receipt of its marketing authorisation. Although epilepsy and GAD are no longer patented indications for pregabalin, Warner Lambert’s application for interim relief was based on infringement of its second medical use patent for the indication of neuropathic pain. Warner Lambert claimed that in order to avoid infringement, Actavis should take a number of proactive steps to prevent Actavis' pregabalin product being dispensed for treating pain.
Arnold J held that there was no serious issue to be tried as Actavis would not infringe the Patent under s.60(1)(c) by marketing their pregabalin product for epilepsy and GAD. Arnold J held that as the relevant claim is to a process of manufacture and is directed at the manufacturer, therefore, it follows that the relevant intention is that of the person who carries out the process (in this case Actavis or their manufacturer). The word “for” in Swiss form claims 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. While Actavis could foresee that the product might be prescribed for the patented use, they did not have the requisite intention.
Arnold J also considered the position if he was wrong that there was no serious issue to be tried and on application of the American Cyanamid principles, would not have granted the interim injunction because of Warner Lambert’s delay and the potential for irreparable harm to Actavis if it lost first mover advantage.
Warner Lambert's (part of the Pfizer group) patent covering use of pregabalin for the treatment of epilepsy and GAD expired in May 2013, the SPC had been allowed to lapse in 2013 and data exclusivity expired in July 2014. Pfizer Ltd (also part of the Pfizer group) is the owner of the relevant marketing authorisation. Warner Lambert’s pregabalin product is sold as Lyrica® for all three indications in the same doses.
In 1997, Warner Lambert had filed a further second medical use patent for pregabalin for the treatment of neuropathic pain that expires on 16 July 2017 (the "Patent"). Claim 1 of the Patent is framed in the pre-EPC 2000, Swiss form claim and claims "Use of [pregabalin] or a pharmaceutically acceptable salt thereof for the preparation of a pharmaceutical composition for treating pain". Claim 3 is for "Use according to Claim 1 wherein the pain is neuropathic pain".
Following expiry of data exclusivity for pregabalin, a number of companies sought marketing approval for a generic version of pregabalin for the original patented indications. Actavis had launched revocation proceedings and was in correspondence with Warner Lambert about its proposed launch in 2015 but had not launched declaratory proceedings.
As neuropathic pain was a patented indication, Actavis’ Patient Information Leaflet ("PIL") and Summary of Product Characteristics ("SmPC") were approved on a “skinny label” basis. This means that the PIL and SmPC state that the product is for the treatment of the non-patented indications (epilepsy and GAD) and not the patented indication (neuropathic pain).
In the UK the majority of prescriptions identify the drug prescribed by reference to the international non-proprietary name ("INN") (for example, pregabalin) rather than a specific brand name (such as Lyrica®). In addition, prescriptions do not generally identify the condition for which the drug has been prescribed.
Warner Lambert’s concern was that physicians and pharmacists might prescribe and dispense the cheaper generic product for all indications, including the off-label use of the treatment of neuropathic pain. Prescribers are encouraged to prescribe generically by a number of mechanisms, including professional guidance, guidance from NHS England, pressure from Clinical Commissioning Groups ("CCGs") and Health Boards and prescription software. Where a prescription uses the INN, the pharmacist is in principle free to dispense a branded drug or a generic one but if a prescription specifies a particular brand (such as Lyrica®), the pharmacist must dispense that brand.
The Judge and the parties acknowledged that the case was further complicated by the involvement of third parties such as CCGs, Health Boards, the Medicines and Healthcare Products Regulatory Agency and National Institute for Health and Care Excellence not under the parties’ control.
Actavis notified Warner Lambert of its intended launch on 25 September 2014 and on 8 December 2014, Warner Lambert issued infringement proceedings against Actavis seeking an interim injunction to prevent launch of its pregabalin product pending the trial of the revocation action and an Order requiring Actavis to take a number of steps. A proposed Fourth Defendant was NHS Highlands who Warner Lambert alleged had infringed, or threatened to infringe, the Patent by publishing an article that encouraged doctors to prescribe and pharmacists to dispense generic pregabalin for all indications, regardless of the patent position.
In terms of the proactive steps to avoid infringement, Warner Lambert sought unprecedented relief requiring that Actavis:
- Write letters to all CCGs in the UK, the pharmacies to which Actavis' pregabalin product was to be supplied, NICE and the Department of Health stating that Actavis' pregabalin product should not be used for the treatment of pain.
- Include a removable cellophane wrapper on Actavis' pregabalin product packaging stating that the "product is not authorised for the treatment of pain and must not be dispensed for such purposes".
- Make it a condition of any agreement with a pharmacy or intermediary that the pharmacy use reasonable endeavours not to supply or dispense Actavis' pregabalin product to patients who have been prescribed pregabalin for the treatment of pain. WarnerLambert suggested the agreement should request pharmacies make enquiries of a person presenting a prescription for pregabalin to determine whether the prescription is for pain and/or should check pharmacy records for the same information.
- Inform Warner Lambert's solicitors of the name of any intermediary or distributor prior to supply.
At the time of the hearing, Actavis had taken, or offered to take, a series of steps to try to ensure that the Actavis pregabalin product was neither prescribed nor dispensed for pain treatment. They only sought a marketing authorisation for the non-patented indications and agreed that on grant of the authorisation they would write a letter to CCGs, NICE, Health Boards and all superintendent pharmacists. However, Actavis objected to requests (b) to (d).
It was also noted by the Judge that Warner Lambert did not concede that Actavis would not infringe the Patent even if it took all of the steps requested and instead reserved its position on relief should such steps prove to be ineffective.
Warner Lambert and Pfizer also wrote to UK physicians notifying them of the Patent and specifically requesting that physicians prescribe pregabalin by the brand name, Lyrica®, for the treatment of neuropathic pain rather than prescribing by the drug’s INN. The letter stated that "encouraging the usage of generic pregabalin in pain would amount to procurement of patent infringement".
Questions to be decided
The Judge had to resolve two main questions. The first question was whether a generic supplier would infringe the second medical use patent unless the supplier took positive steps to prevent its generic version of the drug being dispensed for patients who had been prescribed the drug for the patented indication. If it was seriously arguable that the generic supplier would infringe the Patent, the second question was whether the generic supplier should be obliged to take certain steps pending the trial of that issue.
Best solution to the problem
Arnold J observed that in his view, the best solution would be for doctors to prescribe pregabalin for the treatment of pain by reference to the brand name Lyrica® rather than by reference to the drug name pregabalin. However, he acknowledged that neither Warner Lambert nor Actavis could ensure that this happened and that the Department of Health was not a position to issue such guidance.
Serious issue to be tried?
Warner Lambert’s primary allegation for infringement of the Patent was under section 60(1)(c) of the Patents Act 1977, i.e., that Actavis' pregabalin was a product obtained directly by means of the process of claims 1 and 3 of the Patent. Actavis did not dispute that this was so accordingly the dispute was centred on the interpretation of "for treating (neuropathic) pain".
Swiss form claims, are process claims formulated as "Use of a substance or composition A for the manufacture of a medicament for therapeutic application B". Therefore, Swiss form claims are aimed at a manufacturer and not infringed by doctors or pharmacists (unless making an extemporaneous preparation). Furthermore, in Hospira UK Ltd v Genentech Inc, Birss J held that the word “for” in such claims meant “suitable and intended for”.
Actavis did not deny that its product was suitable for treating neuropathic pain or that it was foreseeable that pharmacists would be likely to dispense pregabalin for treating pain. Instead they contended that what was required for infringement under s.60(1)(c) was a subjective intention that the pharmaceutical composition should be used for treating pain.
Warner Lambert argued that for intention, it was sufficient that Actavis knew that pharmacists were likely to dispense its product for neuropathic pain if positive steps were not taken to prevent this. Warner Lambert relied on a number of contentions and sought to draw an analogy with the knowledge requirements under s.60(2) of the Act, the tort of procuring breach of contract and an equitable protective duty on an intermediary who knows that goods in his possession will, if disposed of by another, infringe an intellectual property right.
Arnold J held that it was the manufacturer's intention that was relevant for such claims. On this basis, Arnold J did not agree that the tort of procuring a breach of contract assisted Warner Lambert because although it was the case that a conscious decision not to inquire into the existence of a fact had been treated as equivalent to knowledge of that fact, so far as intention was concerned it was not enough that a breach of contract was a foreseeable consequence of the defendant's acts. No equitable protective duty arose either unless it could be shown that others would infringe, which was not the case. Nor did Grimme and the knowledge requirements for s.60(2) assist. While it was sufficient for the purposes of infringement under s.60(2) of the Act that the person supplying the means essential knew or ought to have known that in the circumstances that the end users would infringe, here only Actavis (or its manufacturer) could infringe.
Actavis argued that the only construction which gave effect to the purpose of Swiss form claims and the policies underlying their grant was to interpret "for" as meaning "suitable and (subjectively) intended for". To construe the claim otherwise would mean that an inventor of a first patented use would be prevented from marketing the compound for that use if a subsequent, second use for the same compound was patented. In the circumstances, the first inventor who continued to market the compound for the first use would know it was foreseeable that the product would be dispensed for the second use. If foreseeability was enough, the first inventor (and third parties selling for the same purpose) would infringe the second patent simply by carrying on as before. Arnold J agreed and held that the "for" in Swiss form claims imported a requirement of subjective intention on the part of the manufacturer that the product would be used for treating the specified condition.
On this basis there was no serious issue to be tried and Actavis' product with a skinny label would not infringe the Patent.
Application for Interim relief
In case he was wrong on no serious issue to be tried, the Judge considered whether he would have granted Warner Lambert the interim relief requested. Noting that there was no precedent for the relief sought, Arnold J applied the American Cyanamid principles.
Harm to the parties
In considering the harm to both parties, Arnold J noted that Actavis was lawfully entitled to enter the market for pregabalin for the treatment of epilepsy and GAD. Therefore, Warner Lambert could not complain about the subsequent loss of sales and/or price depression. Warner Lambert's only relevant potential loss related to the pain sector of the market. If the interim relief was awarded, Actavis' launch for its product for epilepsy and GAD would be delayed and there would be considerable expense involved with re-packaging the Actavis product. Further, Actavis had already agreed to take steps to discourage the prescribing of the Actavis product for pain and Warner Lambert would only suffer recoverable loss to the extent that those steps were ineffective.
Arnold J held that because Acatvis could lose a 'first mover' advantage, Actavis would be likely to suffer substantial unquantifiable loss if the order sought by Warner Lambert were wrongly granted. While Warner Lambert's loss would be challenging to quantify (as it would be difficult to ascertain what percentage of Actavis’ sales of the product would have been dispensed for pain), Arnold J was not convinced that this loss would be substantial.
Clearing the path, status quo and delay
Arnold also found that Warner Lambert had delayed in taking steps to prepare for generic entry into the pregabalin market and in launching its application.
Given that Lyrica® was the only pregabalin product available; the status quo would already be due to change once a generic product was launched and the relief sought by Warner Lambert was essentially directed at compelling Actavis to take steps further to change such behaviour (i.e., change the status quo). Therefore, the preservation of the status quo did not favour relief. However, Arnold J did express his view that Actavis should have launched proceedings for a declaration of non-infringement to 'clear the path'.
The Judgment is important as it defines the requirement of the manufacturer's knowledge and intention for infringement under s.60(1)(c) of the Act where there are Swiss form claims.
Although on these facts, Warner Lambert were not successful, Arnold J did consider that there were a number of potential scenarios where Swiss form claims might still be enforced. For example, if a manufacturer put the patented indication on its SmPC or PIL, that would be strong evidence of a subjective intent to carry out the process for that purpose. Likewise, it might also be infringement if a manufacturer or third party promoted the prescribing or dispensing of the product for the patented purpose in another way.
The Judge also expressed a view that a change in practice for prescribing a particular brand for patented indications would be preferable, to balance the interests of incentivising medical research and the policies and practices of the NHS. However, Arnold J did recognise that there were a number of factors such as reimbursement price, overall cost, technology and patient confidentiality that contributed to a resistance to such change on the part of health professionals.
Following the Judgment of Mr Justice Arnold on 21 January 2015 discussed above, there has been a number of further hearings between the parties.
On 6 February 2015, Mr Justice Arnold granted Actavis Summary Judgment on Warner-Lambert’s infringement claim under section 60(2) of the Patents Act 1977 stating that the claim was "simply hopeless". However, Mr Justice Arnold dismissed an application by Actavis to strike out, or alternatively dismiss, Warner-Lambert’s claim for infringement of the Patent under section 60(1)(c) of the Act. Although Arnold J expressed his view that he was not persuaded by Warner-Lambert's amendments to its pleadings, he recognised that he might be wrong about the requisite mental element required for infringement of a Swiss form claim. As this was a developing area of law, he held that it was proper to allow the matter to proceed to trial where the facts could be established before a definitive decision on the law could be made.
On 10 February 2015, at an oral hearing of the renewed application by Warner-Lambert for permission to appeal against Arnold J's refusal of an interim injunction, Floyd LJ granted Warner-Lambert permission to appeal. That appeal has been fixed for the end of April 2015.
During the same period, Warner-Lambert commenced infringement proceedings against Dr Reddy’s and Teva. Both Actavis and Dr Reddy’s received marketing authorisation for their generic pregabalin products on 12 February and 16 February 2015 respectively and subsequently launched their products on a skinny-label basis.
On 16 February 2015, Warner-Lambert’s solicitors wrote to NHS England stating that Warner-Lambert intended to make an application to the Court for an order requiring NHS England to issue guidance to CCGs. This was said to be on the basis that the other steps agreed by Warner-Lambert and Actavis in respect of the CCGs and pharmacists might not be sufficiently effective. In response, NHS England noted that while NHS England was an innocent bystander in the present dispute and was therefore unwilling for various reasons to issue guidance of its own motion, it would not oppose an application by Warner-Lambert for an order requiring it to issue guidance provided certain conditions were met.
On 2 March 2015, Mr Justice Arnold handed down his Judgment, ordering NHS England to issue the guidance. For the purposes of Warner-Lambert's application, NHS England had accepted that the Court had jurisdiction to make the order pursuant to section 37(1) of the Senior Courts Act 1981 and did not oppose the making of the order if the Court was satisfied that it was appropriate to make such an order. For the Court to be satisfied that it was appropriate, the order was required to comply with Article 3 of the Enforcement Directive (2004/48/EC). Specifically, the order should be proportionate, not create barriers to legitimate trade and contain safeguards against abuse. Arnold J held that the Order was proportionate and did not create barriers to trade. The legitimate interests of the generic pregabalin suppliers and pharmacists were protected. The generic pregabalin suppliers' rights were protected by a cross-undertaking as to damages and the pharmacists' lower profit on dispensing a branded product was justified by the existence of the Patent (on the assumption it was valid).
In relation to the generic pharmaceutical suppliers, the scope of the cross-undertaking in damages to be given by Warner-Lambert was contested. Warner-Lambert argued that it was sufficient to give a cross-undertaking in favour of NHS England and the Department of Health. Actavis, Teva and Dr Reddy’s requested an undertaking and that the benefit of the cross-undertaking should be extended to their respective group companies. This was based on the fact that the guidance ordered would mean that the branded product would be likely to be prescribed for pain; should the Patent be held invalid, then generic product sales should not have been prevented. This relief was also extended to Teva's and Actavis' group companies for the reasons given in Actavis Group PTC EHF v Boehringer Ingelheim Pharma GmBH & Co KG which stated the principle that the court must apply its discretion with the aim of doing justice not just to the parties before the court but also to any class that could be identified for which justice demanded a cross-undertaking before an injunction was awarded.