Warner-Lambert refused interim relief based on Swiss form claim: no serious issue to be tried regarding carved-out indication

The English Patents Court has refused an application by Warner-Lambert Company (WL) for interim relief, mandatory in nature, regarding conditions to be attached to the launch of generic pregabalin by Actavis. Arnold J found that (among other things) there was no serious issue to be tried on infringement, which of itself makes this decision noteworthy as this is normally a straightforward hurdle to overcome.

Arnold J's decision in Warner-Lambert Company LLC v Actavis Group PTC EHF & Ors [2015] EWHC 72 (Pat) was handed down on 21 January 2015, following a hearing the week before.

The decision is likely to have implications well beyond the parties involved, for the construction and infringement of patent claims in Swiss form. It also appears to indicate that the courts will be reluctant to issue interim injunctions restraining launch of generic medicines authorised with a 'skinny-label', based on patent claims in Swiss form directed to a 'carved-out' therapeutic indication.

Factual background

The Warner Lambert (WL)/Pfizer group of companies market Lyrica (pregabalin), which is approved for epilepsy, generalised anxiety disorder (GAD) and neuropathic pain. Sales of Lyrica in the UK in 2013 were about $310million, of which approx. 44% is thought to be for neuropathic pain. WL's patent protection for the pregabalin compound has expired (through failure to pay SPC renewal fees!) but it continues to have patent protection in Swiss form directed to pregabalin for treating neuropathic pain.

Actavis has applied for, and is close to obtaining, marketing authorisation for generic pregabalin, limited to epilepsy and GAD. (In other words, the list of medical indications for which Actavis' generic pregabalin medicine is stated to be authorised excludes the neuropathic pain indication which remains protected by WL's patent. A marketing authorisation for which a patented indication has been excluded or 'carved-out' is often referred to as having a 'skinny-label'). Once Actavis has obtained marketing authorisation, it plans to launch its 'skinny label' pregabalin medicine in the UK under the trademark Lecaent.

WL alleges that Actavis will infringe the patent. Actavis and Mylan have brought proceedings to revoke the patent.

In the UK, where a doctor's prescription specifies a particular brand of medicine, the pharmacist must dispense that brand. However the overwhelming majority of prescriptions are written by reference to the international non-proprietary name (INN) of the active ingredient. At present, prescriptions very rarely specify, and the dispensing pharmacist very rarely knows, the indication for which a drug has been prescribed.

In these circumstances, and in view of the pricing mechanisms governing pharmaceutical products in the UK, WL contended that without taking appropriate steps to ensure that Lecaent was not dispensed for neuropathic pain, Actavis' launch of its skinny-label Lecaent medicine would infringe the patent and cause irreparable harm to WL before trial of the main action. Actavis disagreed. Actavis had taken, or offered to take, some steps to try to ensure that generic pregabalin would be neither prescribed nor dispensed for pain treatment but WL did not consider these sufficient, and sought an order to place further positive obligations on Actavis.

The relief sought

Agreed by Actavis:

1. Letter in agreed form to be sent to all Clinical Commissioning Groups (CCGs) in the UK on or before the first supply of Lecaent to a pharmacy in the UK.
2. Letter in agreed form to be sent to the chief pharmacist of any pharmacy on or before the first supply of Lecaent to that pharmacy.

WL wanted wording included in the letters instructing that instead of Lecaent, Lyrica should be prescribed (by brand) for pain. Arnold J agreed with Actavis that such wording should not be included in view of "reasonable" concerns from a regulatory perspective.

Not agreed by Actavis (and subsequently refused by Arnold J):

3. Letters to be sent by Actavis to the Department of Health and NICE (National Institute for Clinical Excellence) informing them that Lecaent should not be prescribed or dispensed for the treatment of pain.

Arnold J. held that (in view of past correspondence) there was no point in such letters being sent. Both the Department of Health and NICE were well aware of the position.

4. The inclusion by the defendants of a contractual term in any agreement for the supply of Lecaent requiring (i) reasonable endeavours not to supply or dispense for the pain indication and (ii) that such a term be included in onward supply agreements.
5. Requirement that the defendants inform WL of the names of intermediaries (such as distributors) to whom they supply Lecaent.
6. Application of a removable notification or cling-wrap notifying pharmacists that "This product is not authorised for the treatment of pain and must not be dispensed for such purposes".

Arnold J noted that the Medicines and Healthcare Products Regulatory Authority (MHRA) had stated that it considered that a sticker (neither permanent nor removable) bearing the wording in paragraph 6 above would not comply with Directive 2001/83/EC (which regulates, in part, the marketing of pharmaceutical products). The use of a removable cellophane wrapper might also breach the Directive (no view expressed), infringe the UK pharmaceutical industry practice code and not be effective anyway, since the pharmacist would usually not know the indication for which a prescription written for "pregabalin" (the INN name) was prescribed.

The principles governing award of interim injunctions with a 'mandatory' effect

Arnold J referred ([90]) to Lord Hoffmann's judgment in National Commercial Bank Jamaica Ltd v Olint Corp Ltd [2009] UKPC16, in which Lord Hoffmann referred to the House of Lord's judgment in American Cyanamid v Ethicon [2975] AC 396. Lord Hoffmann commented:

"There is however no reason to suppose that, in stating these principles, Lord Diplock was intending to confine them to injunctions which could be described as prohibitory rather than mandatory. In both cases the underlying principle is the same, namely, that the court should take whichever course seems likely to cause the least irremediable prejudice to one party or the other…What is true is that the features which ordinarily justify describing an injunction as mandatory are often more likely to cause irremediable prejudice than in cases in which a defendant is merely prevented from taking or continuing with some course of action…But this is no more than a generalisation…What matters is what the practical consequences of the actual injunction are likely to be."

Arnold J noted that since the relief sought by WL was intended to affect the conduct of third parties, who were not before the court, the principles had to be applied with particular care.

Serious issue to be tried

It was common ground between the parties that Swiss form claims are process claims. On this Arnold J cited Wyeth's and Scherings' Applications [1985] RPC 545 at 563 and University of Texas Board of Regents/Cancer treatment [2014] EPOR 28 at [16].

WL's primary claim was infringement under s.60(1)(c) - keeping, disposing etc of "any product obtained directly by means of the [claimed] process".

Arnold J then turned to the construction of WL's Swiss form claim. He said:

"As Jacob LJ explained in Actavis v Merck [[2008] EWCA Civ 444, [2009] 1 WLR 1186] at [75], such a claim "is not aimed at and does not touch the doctor - it is directed at the manufacturer." Nor does such a claim touch the pharmacist (except in the case of extemporaneous preparation by the pharmacist). Thus the process will be carried out by Actavis (or their manufacturer), not by the prescriber or the pharmacist."

Arnold J also referred to Birss J's 2014 decision in Hospira v Genentech [2014] EWHC 1094 (Pat). In that case it was common ground between the parties that the word "for" in such claims means "suitable and intended for". This was common ground between WL and Actavis also, although WL reserved the right to contend otherwise at trial. The parties disagreed, though, on what "intended" meant.

WL contended that the relevant intention was not that of the manufacturer, but of the person who disposes or offers to dispose of pregabalin. Arnold J disagreed. He held that the claim is not directed at a person who disposes of the pharmaceutical composition, nor to the composition. The claim "is to a process of manufacture and it is directed at the manufacturer…it follows that the relevant intention is that of the person who carries out the process, here Actavis (or their manufacturer)".

WL also contended that "intended" was satisfied if Actavis intended to sell pregabalin and knew that pharmacists were likely to dispense it for treating neuropathic pain if positive steps were not taken to prevent this. Again, Arnold J. disagreed. Addressing WL's supporting arguments, he held:

1. A requirement that the intention be subjective on the part of the infringer would not mean that a second medical use patent could never be enforced. For example, if a manufacturer puts the patented indication on the SmPC or PIL, that will be strong evidence of subjective intent. Likewise if the manufacturer promotes prescribing or dispensing for the patented purpose in another way. Policy (i.e. grant of patent protection for second medical use inventions) therefore did not support WL's position.
2. Analogy with the interpretation of s.60(2) (infringement by supplying means essential to the invention) adopted by the Court of Appeal in Grimme Maschinenfabrik GmbH & Co KG v Scott [2010] EWCA Civ 1110, as summarised by Jacob LJ in KCI Licensing Inc v Smith & Nephew plc [2010] EWCA Civ 1260, [2011] FSR 8 at [53], did not support WL's position because (a) s.60(2) was a specific statutory provision which makes a particular conduct an infringement and (b) s.60(2) distinguishes between the knowledge of the supplier of the essential means and the intention of the user. That did not assist WL in establishing that the knowledge on the part of the supplier equated to intent.
3. Analogy to the tort of procuring breach of contract also did not support WL's position. Arnold J. referred to OBG v Allan [2007] UKHL 21, where Lord Hoffmann stated "if the breach of contract is neither an end in itself nor a means to an end, but merely a foreseeable consequence, then in my opinion it cannot for this purpose be said to have been intended".
4. There might be analogy with the equitable protective duty described by Buckley LJ in Norwich Pharmacal v Customs & Excise Commissioners [1974] AC 133, and with the duty imposed on intermediaries by Directive 2001/29/EC. However, such duties arise in circumstances where the person in question knows of infringement by another. This did not assist WL to establish that Actavis will infringe unless it was shown that others would infringe; but that was not the case.

In addition to Actavis UK Ltd v Merck & Co Inc [2008] EWCA Civ 444, [2009] 1 WLR 1186, Actavis cited decisions from a number of European jurisdictions as supporting the proposition that subjective intent is required. Although Actavis accepted that "none of them established that this was settled law", Arnold J noted that "Counsel for Warner-Lambert had no cogent answer to this argument", and so Arnold J accepted it:

"Accordingly, I hold that 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."

Since WL did not rely upon any allegation of subjective intention on the part of Actavis for the purposes of its application, there was no serious question to be tried based on s.60(1)(c). This is a significant decision for the court to reach.

WL also asserted infringement of s.60(2) through the supply of essential means. Arnold J held that this also did not raise a serious question to be tried:

"There can only be infringement under section 60(2) if there can be infringement by the person supplied or by a user further down the chain of supply (although it is not necessary for there actually to be an infringing act). This is not the case here, since no wholesaler or pharmacist will use Lecaent to prepare a pharmaceutical composition."

Finally, Arnold J noted that WL "cannot succeed under section 60(1)(a) if it fails under section 60(1)(c) and 60(2)" because the Swiss form claims relied upon "are not product claims".

Balance of harm

Arnold J also analysed the balance of harm, finding this to favour not granting the relief sought. Factors in the balance were:

• WL could not complain about price depression across the whole pregabalin market, only losses specifically related to the pain sector.
• The best solution was for doctors to prescribe Lyrica for pain. "If the NHS issues appropriate guidance, that is likely to happen and Warner-Lambert is unlikely to suffer recoverable loss".
• In the absence of such guidance, Actavis had agreed to take steps to try to discourage prescribing/dispensing of Lecaent for pain. WL would only suffer recoverable loss if and to the extent those steps were ineffective.
• If WL succeeded at trial, it would be very unlikely to obtain relief against Actavis which made it absolutely certain that pregabalin would not be dispensed for pain in the future.
• Losses due to pregabalin being moved to a different category under the pricing mechanism were unlikely to happen until May 2015 at the earliest.
• Actavis would be harmed by the delay to launch that would be caused by the requested relief (involving repackaging) and might find pharmacists less willing to stock their repackaged product.

Other noteworthy points

1. The Health Board for the Scottish Highland, "NHS Highland" published an article in its The One Pink publication, in October/November 2014, which is alleged to encourage doctors to prescribe, and pharmacists to dispense, generic pregabalin for all indications, regardless of the patent position. WL has sued NHS Highland for infringement/threat to infringe/procuring infringement of the Patent.
2. WL's solicitors, acting in accordance with the guidance given by Jacob LJ in SmithKline Beecham plc v Apotex Europe Ltd [2005] EWCA Civ 658, [2007] FSR 6 at [77], notified the Department of Health of Warner-Lambert's application, and served copies of Warner-Lambert's (and subsequently Actavis') evidence on the Department of Health. Although the Department initially declined the opportunity to be represented before Arnold J, it later appeared and requested that, if relief was granted, Warner-Lambert's cross-undertaking in damages should extend to the Department and the NHS. Warner-Lambert agreed to this.
3. WL contended that prescribers should be given clear guidance that, in this situation and other future situations like it, the proper course is to prescribe by reference to the brand name for the patented indication and by reference to the generic name for non-patented indications. Arnold J observed that it was a matter for NHS England and NHS Wales to decide whether or not to issue such guidance, "but for my part I would encourage them to consider doing so as a matter of urgency".

Conclusion and comment

Except where there is strong evidence of subjective intent (for example including the patented indication as an approved indication in the marketing authorisation, or overt promotion for the patented indication), it now seems highly unlikely that the English Patent Court would mandate terms for, let alone prohibit, the launch of a skinny-label generic medicine on the basis of Swiss form claims.

First, the court would hold that there would be no serious issue to be tried i.e. hurdle 1 of the American Cyanamid test would not be cleared, as was the case here. Second, Arnold J's assessment of the balance of convenience (balance of harm) in this case suggests that the court would not, save in truly exceptional cases, favour the grant of an injunction restraining launch.

However, Arnold J's decision on the facts before him was clearly influenced by the steps that Actavis had agreed to take to try to discourage infringing use, and this is important. Where appropriate, generic manufacturers might be well-advised to communicate with pharmacists and health authorities to make clear the indications for which a skinny-label product is approved. Aside from this, it seems that manufacturers of generic medicines can rely upon the regulatory carve-out to get their product on the market for off-patent use without being held to account for subsequent use for the indication which continues to be protected by the patent. The risk of the generic product eventually being dispensed to a patient for the treatment of the patented indication is of course significantly increased by the presence of the generic medicine on the market and the prescribing and reimbursement practices and mechanisms present in the UK.

Once a 'skinny-label' medicine is on the market in the UK (without overt promotion by the manufacturer for an indication protected by a patent claimed in Swiss form), ensuring that it is not in practice used for the patented indication is, in Arnold J's view, a matter of risk-management which is beyond the scope of patent law. He noted that deciding whether or not to issue guidance that for pregabalin, and other future situations like it, the proper course is to prescribe by reference to the brand name for the patented indication and by reference to the INN name for the non-patented indication, was "a matter for NHS England and NHS Wales". But Arnold J said "for my part, I would encourage them to do so". Indeed, he considered "the best solution to the problem is for doctors to prescribe Lyrica for pain" and "[i]f the NHS issues appropriate guidance, that is likely to happen and Warner-Lambert is unlikely to suffer recoverable loss".

Guidance for doctors of this sort, from the NHS, would indeed be a welcome practical step towards holistic compliance with the policy of rewarding second (and later) medical use inventions with patent protection. Arnold J has given a clear indication that it is for the medical authorities to get the necessary safeguards in place. In future cases, the likelihood of such guidance being issued might well be an important factor in the assessment of the balance of convenience.

However, it must be queried whether it is in keeping with the statutory grant of a patent (being the disclosure to the world of an invention in exchange for the grant of a time-restricted monopoly for its exploitation) that the enforcement of a patent essentially becomes a matter within the gift of individual doctors. It must also be queried whether, despite Arnold J's urgings, there is, technically, any incentive for the NHS to issue such guidance, or indeed to respect patents with claims granted in Swiss form. On Arnold J's reasoning, Swiss form claims are directed at the manufacturer and are not infringed by the activities of later parties in the chain, where they merely deal in the packaged medicine until its eventual use by the patient. This is inherent in his reasoning for finding no serious issue to be tried under section 60(2) (supply of essential means).

Finally, on (purpose limited product) claims permissible under Article 54(5) EPC, Arnold J stated:

"It should not be assumed that anything I say in this judgment about Swiss form claims necessarily applies to EPC 2000 claims."

Whereas Swiss form claims are process claims, and on the basis of Arnold J's decision it is only the manufacturer who would infringe them, Article 54(5) claims (also known as EPC 2000 claims) are product claims. For Article 54(5) claims, it might be that the actions (and/or intent) of parties further down the supply chain regarding the patented use could lead to infringement, where the product becomes "for" the protected process. This will undoubtedly fall to be determined on another day.