Infringement of second medical use patents in the UK: pregabalin in the Supreme Court

Supreme Court decisions about patent law are relatively rare and usually significant. The latest such decision, Warner-Lambert v Mylan & Actavis [2018] UKSC 56, which was handed down by the court on 14 November 2018, is no exception. The decision concerns a number of issues, the most important of which are the direct infringement of Swiss-form second medical use patent claims and the role of plausibility in assessing validity on the grounds of insufficiency.

This article explains the infringement part of the decision.

How did the Warner-Lambert case arise?

Actavis markets a generic pregabalin product under the brand name Lecaent, which was launched in February 2015. Lecaent was marketed under a "skinny label", which means that some possible indications are carved out of the Summary of Product Characteristics (SmPC) of the product. In this case the SmPC and the Patient Information Leaflet included in the packet state that the conditions for which Lecaent is indicated are epilepsy and generalized anxiety disorder only, for which patent protection has expired.

Warner-Lambert owns a patent, for which the relevant claims in this case are 1 and 3, in the following 'Swiss-form ' (that is, "the use of X in the preparation of a medicament for treating Y"):

• Use of (S)-3-(aminomethyl)-5-methylhexanoic acid [which is to say 'pregabalin '] or a pharmaceutically acceptable salt thereof for the preparation of a pharmaceutical composition for treating pain.

…

• Use according to Claim 1 wherein the pain is neuropathic pain.

Actavis, together with Mylan, claimed the revocation of the Warner-Lambert patent, and – despite the treatment of pain being carved out on the skinny label – claimed against Actavis for infringement of Claims 1 and 3.

The lower instance and Supreme Court decisions in summary

At first instance, Arnold J held that none of the claims of the patent were obvious, but that claims 1 and 3, as well as other claims, were invalid on the ground of insufficiency; the claims were not plausible across their scope. The judge also held that, if claims 1 and 3 were valid, Actavis 's activities with Lecaent would not infringe those claims either directly or indirectly.

The Court of Appeal dismissed appeals by both parties, upholding the first instance decision. That decision was then appealed to the Supreme Court, which heard the case in February 2018. By the time the case reached the Supreme Court, the issues left to be resolved included the test for infringement of a second medical use claim and the test for insufficiency based on lack of plausibility, in particular with regards to claim 3.

On the issue of infringement all the judges of the Supreme Court decided that Lecaent would not infringe the patent, if held valid. Those reasons by which they hold non-infringement are, however, split 2:2:1 around whether the test should be one of subjective intention of the manufacturer (Lords Briggs and Hodge) or whether it is the outward presentation of the product emerging from the manufacturing process that matters (Lords Sumption, Reed and to a qualified extent, Lord Mance).

The Supreme Court also agreed with the first instance judge that there was no indirect infringement (for the same reason the judge gave). However, this article focuses on the issue of direct infringement only.

The underlying challenge with second medical use claims

Aside from the difficulties that have been encountered in how to draft second medical use claims in the past, these patents also raise an issue of enforcement: when patent protection of the underlying active ingredient has expired, how can a second medical use patentee prevent a generic version of the drug finding its way onto the market for the patented indication, either deliberately or accidentally? Conversely, how does a generic company supply the drug for the legitimate – unpatented – use with the confidence that it will not be used for patent infringement?

Closely connected to this issue is prescribing practice at the national level. In England and Wales, a doctor will usually identify a drug on the prescription using its international non-proprietary name. And, when a prescription is written generically, the pharmacist is free to dispense a branded drug or a generic one. So, in this situation, the doctor does not know which will be dispensed. Furthermore, only a small percentage of prescriptions identify the condition being treated and so pharmacists do not usually know the indication for which the drug has been prescribed. As a result, a skinny label in itself may be ineffective in preventing generic drug being used for a patented indication.

How was the Swiss-form claim construed?

The starting point for the judges in Warner-Lambert was to construe the meaning of "neuropathic pain" in claim 3 of the patent. On this, the Supreme Court unanimously agreed with both the first instance judge and the Court of Appeal: it should be broadly construed to cover central neuropathic pain and peripheral neuropathic pain.

As regards the correct statutory provision, English law recognizes Swiss-form claims as a form of process claim (because it is a preparation of a medicament), so there was no dispute that the relevant Section of the Patents Act 1977 is 60(1)(c). This says that where the invention is a process, a person without consent is prohibited from acts including: the disposal of, offer to dispose of, use or import of any product obtained directly by means of that process. The issue before the Supreme Court was not what this section meant, however, but instead what was meant by the word "for" in a Swiss form claim and what, if any, mental element it requires of the manufacturer.

At first instance, Arnold J held that the word "for" requires a subjective intention on the part of the manufacturer. The Court of Appeal held that the word "for" requires the third party manufacturer to know or be able to reasonably foresee the ultimate intentional use for the infringing purpose by an end user – which is an objective test. The Court of Appeal also added a defence for the manufacturer that would apply when all reasonable steps have been taken to prevent the generic product being used to treat the patented indication.

What the court said about the foreseeability test

All the judges of the Supreme Court rejected the foreseeability test favoured by the Court of Appeal. Lords Sumption and Reed give detailed reasons for this. They begin by stating that foreseeability is a way of attributing legal responsibility to the person who should have foreseen the objectionable consequences of their acts, whether or not they actually did so. But when attributing legal responsibility to someone else, such as a pharmacist, who deals downstream with a direct product of the process, it is entirely arbitrary – that party has no knowledge of or control over what the manufacturer should have foreseen.

Another difficulty is that some more than de minimis leakage of generic pregabalin into the market for treating neuropathic pain is always foreseeable, whatever reasonable steps are taken. So, according to the simple foreseeability test, this means that all stocks of generic pregabalin will be manufactured by use of the patented process, and any subsequent dealing with those stocks by importers, distributors or pharmacists will constitute infringements. This is an unjustified de facto extension of the expired patent for the original compound.

The defence set out by the Court of Appeal was also rejected, on the basis that it is not the function of the courts to invent non-statutory defences to statutory torts when Parliament has not provided one.

What the Supreme Court said about the Subjective intention test

In attempting to find the correct test, Lords Sumption and Briggs set out the competing interests that need to be balanced:

• providing reasonable protection to the second medical use patentee, both to reward and to incentivise the complex and expensive processes of research and testing necessary to bring second medical uses to fruition
• protecting the public against the loss of the patent-free use of the relevant drug for treating the indications for which it was originally developed (meaning that the patentee for the new use should not obtain, by a 'side wind ', an effective continuing monopoly in relation to the old use, after the expiry of the patent protection for it), and
• providing reasonable legal certainty for those engaged in the manufacture, marketing and prescribing of the generic drug for the non-patented use, that their conduct is lawful.

The majority of the Supreme Court reject the subjective intention test as the means to achieve this balance. Lord Sumption (and Reed) summarise the reasons for this, which include the following:

• A patent is supposed to define exhaustively what the product or process is that is protected. For the scope of the monopoly to be dependent on the unascertainable state of mind of the manufacturer is not consistent with this.
• Secondly, if subjective intention is relevant, then liability under section 60(1)(c) can extend to a person by virtue not of their own intentions but of the intention of someone else, namely the generic manufacturer.
• Thirdly, subjective intention implies choice – in other words, the manufacturer of the generic product must intend use for the patent-protected purpose downstream. But this is actually outside the manufacturer's control - they can only have a hope rather than an intention.
• Fourthly, there are practical problems of applying a test based on subjective intention. Lord Sumption gives the example where the generic manufacturer makes pregabalin intending it to be used for the treatment of pain, but this does not happen. Does the mere intention therefore taint the entire production run, even if it is all used for conditions such as epilepsy for which patent protection has expired?

Lords Sumption (and Reed agreeing with him) propose to replace the foreseeability and subjective intention tests altogether, as follows:

The new "outward presentation" test

Lords Sumption, with the agreement of Lord Reed, instead proposes an "outward presentation" test. According to the outward presentation test the badge of purpose is the physical characteristics of the product as it emerges from the relevant process, including its formulation and dosage, packaging and labelling (including skinny labelling) and the patient information leaflet in which the conditions for whose treatment the product is intended are identified.

In these judges' view, this has several advantages including:

• First, it is objective, and not dependent on proof of the internal mindset of the manufacturer.
• Secondly, in a purpose-limited claim, the designated purpose is an inherent characteristic of the invention. The outward presentation test is consistent with this notion and a test based on intention is not.
• Thirdly, the outward presentation test properly reflects the critical feature of Swiss-form patents, namely that the patent is for the process of manufacture, not for the subsequent use that may be made of the product. The physical presentation of the product is generally part of the process of manufacture.
• Fourth, it provides legal certainty, in particular for those downstream of the manufacturer who deals in the product.
• Fifthly, and critically, in the judges ' view, it strikes a fair balance between the public interest in rewarding invention by allowing the patentee to exploit his monopoly and the public interest in the free use of the invention for therapeutic uses which do not have, or no longer have, patent protection.

It is not a completely perfect test, though, as Lord Sumption admits: there could be circumstances in which the labelling and the patient information leaflet of a generic manufacturer might be regarded as a charade. This is an issue that the other judges, in particular Lord Mance, seek to deal with. However, Lord Sumption says, if this is a real problem, it would be for the legislature to deal with.

How did Lords Mance, Hodge and Briggs decide?

Giving a minority judgment, Lord Mance agrees that the correct infringement test in the circumstances of this case should depend on the objective appearance and characteristics of the product as it is prepared, presented and put on the market. But recognizing the problem of 'charade' cases, he leaves open the possibility that in rare cases the context may make it obvious that appearances are not to be taken at face value, and also that there may be circumstances in which the generic manufacturer should positively exclude use for the patent-protected purpose.

This leaves Lords Hodge and Briggs. These two judges prefer the view of Arnold J that the test should be whether the alleged infringer subjectively intended to target the patent-protected market. Explaining this conclusion, Lord Briggs also states a number of reasons, including:

• The purpose limitation in a Swiss-form claim necessarily involves a mental element. When someone speaks of making something "for" a particular use, and concludes that "for" means something more than "suitable for", it must point to something in the mind of the manufacturer. However, the judge emphasises that this does not mean that presentation to the market will not often, or indeed usually, be decisive evidence, one way or the other, of the manufacturer 's intended purpose.
• The "outward presentation" test would not strike a fair balance. For example, a generic manufacturer might demonstrate the requisite purpose by flooding the market for pregabalin beyond the non-patented indication, or by covertly encouraging dealers and pharmacists to use it for the treatment of pain, regardless of what appears on the label. Or a smoking-gun internal document might reveal that the manufacturer's packaging for the non-patented use was just a charade. These forms of evidence might prove the requisite intent, even if the packaging did not.

Lord Briggs also accepts that there are limitations on the subjective intention test. In particular, he recognises the concern that section 60(1)(c), in conjunction with Swiss-form patents, imposes draconian strict liability on dealers in generic products, without giving them the ability to find out whether the manufacturer has an intention that taints products in their hands.

In its favour, the subjective intention test would, the judge thinks, allow for all forensic evidential means to establish whether a manufacturer is seeking to serve and profit from the patent protected market. This could include, but not be limited to, the packaging on the product, but extend to targeted disclosure during litigation of documentary records of the manufacturer 's decision-making processes.

What does the decision change?

The Court of Appeal foreseeability test is gone, together with the defence of taking reasonable steps. In its place are two possibilities, each representing the reasoning of two Supreme Court justices: first the "outward presentation" test and second the subjective intention test. This appears confusing – which test is it? They are not actually mutually exclusive. As Lord Briggs states, the outward presentation to the market of a product will often, or indeed usually, be decisive evidence, one way or the other, of the manufacturer's intended purpose. In other words, the subjective intention test incorporates but is not limited to the product 's outward presentation. Lord Briggs would also include evidence of smoking gun documents and marketing activity in his test.

Even though the Supreme Court 's decision on direct infringement is obiter, because the relevant claims of the patent were invalid, it will be very influential on the lower courts. Therefore, those generics wishing to avoid allegations of infringement of second medical use patents to certain indications, would be well advised to note all of the factors relevant to outward presentation and subjective intention. What they do not need to do anymore, it seems, is write letters to doctors ' and pharmacists' organisations to defend themselves against the foreseeability test.

The change also take the UK away from the tests that are being applied elsewhere. For instance, Germany has recently started to move away from an outward presentation test to something closer to the English Court of Appeal foreseeability test. The Netherlands also uses such a test, with possible defences.

One big issue remains unanswered by this decision, however. The case is concerned with Swiss-form claims, but second medical use claims dating from 13 December 2007 and after use the EPC 2000 claim form: "X for use in treating Y". These are product claims, rather than process claims, so would that change the analysis of the Supreme Court? The emphasis of the court 's decision on direct infringement was on the word "for" and the practical implications of tests that use intention as a touchstone of direct infringement. It seems that, for direct infringement, these factors are not altered by the EPC 2000 form of claim, which also uses "for" in the same way, and that the Supreme Court judges would come to the same conclusions. Perhaps the Court will one day return to this issue.