Subjective intention required to infringe swiss form claims

27 January 2015

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.[1]  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[2] 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,[3] 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. 

Background

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[4] 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:

a) 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.

b) 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".

c) 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.  Warner Lambert 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.

d) 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.[5]  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".[6]     

Judgment

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".[7]  Therefore, Swiss form claims are aimed at a manufacturer and not infringed by doctors or pharmacists (unless making an extemporaneous preparation).[8]  Furthermore, in Hospira UK Ltd v Genentech Inc,[9] 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[10] 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'.

Implications

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.


[1] Warner Lambert Company LLC v Actavis Group PTC EHF & anors, [2015] EWHC 72 (Pat), 21.01.2015.

[2] European Patent (UK) No. 0 934 061.

[3] American Cyanamid v National Commercial Bank Jamaica Ltd v Olint Corp Ltd [2009] UKPC 16.

[4] Mylan has also initiated revocation proceedings and the two actions are fixed to be heard from 29 June 2015 (Generics (UK) Ltd v Warner Lambert Company LLC & anr HP14D02524).  If successful, both Mylan and Actavis intend to obtain marketing authorisation to sell pregabalin for all three indications.  

[5] The text was almost agreed by the hearing and the Judge directed that Actavis did not have to include wording indicated that Lyrica should be prescribed for neuropathic pain.

[7] Swiss claims differ from second medical use claims post-EPC 2000 as under Article 54(5) of the EPC 2000, which enables the grant of claims in the form “product X for treating indication Y” (a purpose-limited product claim).  Arnold J caveated that his Judgment did not address such claims.

[8] See, Actavis UK Ltd v Merck & Co Inc [2008] EWCA Civ 444 at [75].

[9] [2014] EWHC 1094 (Pat).

[10] Grimme Maschinenfabrik GmbH & Co KG v Scott, [2010] EWCA Civ 1110, [2011] FSR 7.