In a much anticipated judgment, the Supreme Court has issued its decision in Warner-Lambert v Mylan & Actavis, focussing on how concepts of patent sufficiency and plausibility, and infringement, should be assessed in relation to second medical use patents. The decision, that the second medical use patent for Lyrica is invalid, is of extreme importance to the parties – Lyrica is one of the Pfizer Group's most successful drugs in the UK and a number of pharmaceutical companies have launched generic products. However, it also has much broader significance in terms of the potential implications for clinical and prescribing practices, with the Secretary of State for Health making submissions, alongside no fewer than nine other interveners including from a range of interested bodies.
The split in the Lordships' views on a number of central issues clearly demonstrates, as Lord Sumption put it, that "patent protection for second use medical patents is …difficult to accommodate within the traditional scheme of patent law". However, the majority view in relation to plausibility has the potential for imposing a higher hurdle in relation to sufficiency of pharmaceutical patents generally. Meanwhile, the obiter discussion on the proper approach to infringement of second medical use patents, with references to compromises and 'least imperfect' solutions, suggests plenty of scope for further debate, including in relation to infringement of other purpose-limited claims.
The case concerns Warner-Lambert's (now expired) second medical use patent (EP (UK) 0 934 061) for the use of pregabalin for the treatment of pain, including inflammatory and neuropathic pain (the marketing authorisation covers peripheral and central neuropathic pain, epilepsy and generalised anxiety disorder (GAD) but not inflammatory pain). Warner-Lambert argued that the launch of generic products under a skinny label (i.e., limited to non-patented indications of epilepsy and GAD) amounted to both direct and indirect patent infringement. The relevant claims in the Patent are Swiss-form second medical use claims – i.e., "use of substance X for the preparation of a medicament (or pharmaceutical composition) for treating indication Y".
In September 2015, Arnold J decided that the relevant claims, 1 and 3, were invalid for insufficiency. Claims 1 and 3 are in the following form:
Claim 1 "Use of [pregabalin] or a pharmaceutically acceptable salt thereof for the preparation of a pharmaceutical composition for treating pain"
Claim 3 Use according to claim 1, where the pain was neuropathic pain.
Arnold J found there was sufficient disclosure in the specification to support the claim that pregabalin was efficacious in treating inflammatory and peripheral neuropathic pain, but there was not for central neuropathic pain which, according to his construction of the Patent, fell within Claim 3. He subsequently decided that it would be an abuse of process for Warner-Lambert to amend (post trial) Claim 3 to exclude from its scope "central neuropathic pain".
The Court of Appeal rejected Warner-Lambert's appeal on insufficiency and abuse of process. It also considered the important issue of infringement of second medical use patents (by a product being obtained directly by means of the patented process) in the light of the use of the word 'for' in the claim. Disagreeing with Arnold J who had favoured a subjective approach to the question of the generic manufacturer's intention, the Court of Appeal applied a 'qualified objective' test: would the skilled person understand the patentee to be using 'for' to require that a manufacturer knows (including having constructive knowledge) or can reasonably foresee the ultimate intentional use (in this case, for pain), and not that they have that specific intention or desire? The test was qualified because, once intention was made out, it could be negatived if the manufacturer had taken all reasonable steps within its power to prevent the foreseen consequences occurring.
Supreme Court Decision
The Supreme Court's decision focuses on the following key issues.
Construction of the claims (in particular Claim 3)
The Court unanimously agreed with Arnold J and the Court of Appeal that Claim 1 extended to all pain, and Claim 3 to all neuropathic pain, including central neuropathic pain (and was not limited to just peripheral neuropathic pain). In doing so, it preferred Actavis' broad construction of Claim 3, as opposed to Warner-Lambert's narrow construction (i.e., that it only meant peripheral neuropathic pain).
Amendment/abuse of process
It also agreed that Warner-Lambert's application to amend the patent, so as to exclude central neuropathic pain, was an abuse of process. However, given the majority concluded that the patent was insufficient (for want of support in the specification) for treating any neuropathic pain, the proposed amendment would not have saved the claim in any event.
Was the disclosure in the specification sufficient?
This was a split decision. The majority (Lords Sumption, Reed, and Briggs) considered that the disclosure in the specification was not sufficient to support the claims in relation to neuropathic pain, whether peripheral or central (it did support the claims so far as they claimed inflammatory pain). Whilst this was against the approach in France, Germany and Sweden (where Claim 3 has been found sufficient), these decisions did not raise doubts as to the correctness of the majority's decision.
Lord Sumption described plausibility as just one element in the test of sufficiency: "Plausibility is not a distinct condition of validity with a life of its own, but a standard against which that must be demonstrated. Its adoption is a mitigation of the principle in favour of patentability…The test is relatively undemanding. But it cannot be deprived of all meaning or reduced…to little more than a test of good faith".
In particular, he identified a number of principles that will influence the plausibility assessment:
- The proposition that a product is efficacious for the treatment of a given condition must be plausible.
- It is not made plausible by a bare assertion to that effect, and disclosure of a mere possibility that it will work is no better than a bare assertion.
- But, the claimed therapeutic effect may be rendered plausible by a specification showing that something was worth trying for a reason (i.e., reasonable scientific grounds were disclosed for expecting that it might well work).
- Whilst the disclosure does not have to prove definitively that the product works for the designated purpose, there must be something that would cause the skilled person to think there was a reasonable prospect the assertion would prove to be true.
- That reasonable prospect must be based on a 'direct effect on a metabolic mechanism specifically involved in the disease, this mechanism being either known from the prior art or demonstrated in the patent per se' (EPO Decision in SALK).
- However, the effect on the disease process need not necessarily be made in the context of experimental data and can be demonstrated by a priori reasoning. For example, the specification may point to some property of the product which would lead the skilled person to expect that it might well produce the claimed therapeutic effect; or to some unifying principle that relates the product or proposed use to something else which would suggest as much to the skilled person.
- Sufficiency is a characteristic of the disclosure, and these matters must appear from the patent. Whilst the disclosure may be supplemented/explained by the common general knowledge of the skilled person, it is not enough for the patentee to prove that the product can reasonably be expected to work in the designated use (if this could not be derived from the patent's teaching).
Warner-Lambert was wrong, in Lord Sumption's view, to say that plausibility did not have to be demonstrated across the whole scope of the claim and in arguing that the Court should have taken into account later published data. Subsequent data could be admissible in a dispute but not as a substitute for sufficient disclosure in the specification. The question was whether the discovery that it could be expected to work had been sufficiently disclosed in the patent – this is, of course, difficult to demonstrate before clinical trials have taken place but that was reflected, suggested Lord Sumption, in the modest plausibility standard.
On the facts, whilst the experimental data in the specification was predictive of efficacy for treating inflammatory pain, it did not claim that the data made it plausible that it was effective for treating any kind of neuropathic pain. The specification would only have supported Claim 3 if it suggested to the skilled person that there was some unifying principle which made it plausible that pregabalin would also work with any kind of neuropathic pain. However, Warner-Lambert's reliance on central sensitisation as this unifying principle was correctly rejected by the Judge, because it cannot contribute to central neuropathic pain.
Lords Hodge and Mance, in the minority, preferred a lower standard of plausibility which would not require the patentee to demonstrate within its patent a prima facie case of therapeutic efficiency. Lord Mance suggested that Lord Sumption's analysis imposed "too high a threshold, and imposes a burden on a patentee" unsupported and unjustified by the EPO case law. The suggestion that "the specification must disclose some reason for supposing that the implied assertion of the efficacy in the claim is true" amounted to a "requirement that the plausibility of the claim must appear to be established prima facie through scientifically cogent reasoning or experimental evidence set out in the specification". And, whilst Lord Sumption had said that the plausibility test was relatively undemanding, there was a real risk that the majority's test would amount to, or be understood as, involving a requirement to establish a prima facie case on the material contained in the specification. In fact, the EPO cases showed that a tailored claim, which appears scientifically possible, even though it cannot be said to be even prima facie established, without e.g., testing or assays, could be sufficient.
Applying this lower standard of plausibility, the minority concluded that Warner-Lambert had met it in relation to peripheral neuropathic pain. In particular, it was not necessary for the patent to demonstrate by experiment or scientific theory, that pregabalin blocked or reduced central sensitisation. Further, the court could have regard to later evidence as to the efficacy in treating pain to make good the prediction, if there is some basis for it in the patent.
The majority however upheld Actavis' cross-appeal that the specification did not enable plausible prediction to be made that pregabalin would be effective for treating peripheral neuropathic pain. As Lord Sumption put it: "it cannot in my view be enough to justify a monopoly that it is "possible" a priori that a drug which was effective for inflammatory pain would also be effective for neuropathic pain, in the absence of any reason to suppose that the possibility had some scientific basis or that it was more than speculative. Everything is possible that is not impossible, but "not impossible" is very far from being an acceptable test for sufficiency".
Given the findings on sufficiency, the Court's comments in relation to infringement were obiter. However, given the detailed submissions, including on behalf of the Secretary of State and others with an interest in the market for the non-patented use, the Court gave these important and difficult questions full attention, whilst recognising that Swiss-form claims are now a closed class.
The Court agreed that Actavis' Lecaent product would not infringe (directly or indirectly), but for differing reasons in relation to direct infringement. They all rejected the qualified foreseeability approach of the Court of Appeal.
Swiss-form claims are purpose-limited process claims, i.e., of a preparation or manufacture of the product for the designated purpose. The relevant section of the Patents Act, s.60(1)(c), provides that there will be infringement where a product is obtained directly by means of the patented process. As Lord Sumption noted, liability can also attach to anyone in the downstream generic market (i.e., not just the manufacturer), including wholesalers and pharmacists, irrespective of their knowledge.
Whilst the parties all accepted that there was a mental element in assessing infringement, the issue between them was whether the manufacturer must have had a subjective intention to target the patent-protected market (as argued by Actavis) or whether the manufacturer must be taken to intend the foreseeable consequences of its actions including de minimis leaking of generic product into the market for patented uses, i.e., an objective test (as argued by Warner-Lambert). As Lord Briggs put it: "the choice lies between defining infringement so widely that manufacturers will be dissuaded from producing generic drugs even to fulfil the original (no longer patented) use, and defining it so narrowly that patentees are inadequately protected from the invasion of their newly patented second use by generic manufacturers".
Lords Sumption and Reed in fact adopted a position based on neither of the parties' positions (albeit it was one pursued by Actavis as a back-up argument when submissions were sought on it after the hearing). This approach rejects a role for intention entirely. Instead, the sole criterion is an (objective) 'outward presentation' test (a rough paraphrase of the "sinnfällige Herrichtung" approach of the German courts in relation to infringement of purpose-limited patent claims, also called the "only packaging will do" approach by Floyd LJ in the Court of Appeal). Under this test, the assessment is whether the product, as it emerged from the manufacturing process, including its packaging and labelling and patient information leaflet, was presented as suitable for the uses which enjoy patent protection. On the facts, Lecaent was sold with patient information leaflets stating it was for the treatment of seizure disorders and GAD.
Such a test would meet the four policy objectives that had to be considered (or at least, as Lord Sumption put it, it was "less imperfect than any other"):
- Providing reasonable protection to the second medical use patentee so as to reward and incentivise the research and testing processes.
- Allowing the public the benefit of the product for its original therapeutic use, unconstrained by any patent rights once the patent covering that use has expired.
- Providing reasonable legal certainty to all in the generic supply process (manufacturers, marketers and prescribers).
- Protecting the autonomy of clinical judgment.
Lord Sumption did acknowledge the concern that it would give insufficient protection to a patentee if the labelling and patient information leaflet of a generic manufacturer was a 'charade' (e.g., if it manufactured pregabalin with the intention of supplying an unexceptionable label and patient information leaflet but then encouraged dealers and pharmacists to supply it for the treatment of pain). However, he noted that the greater concern was that this scenario could expose to liability not just the manufacturer but any pharmacist who handles the product, even if supplying it only for non-protected use (in the absence of a general defence of good faith for third parties).
Lord Mance (identifying himself as the 'swing voice') agreed that the objective appearance and characteristics of the product as it is prepared, presented and put on the market was relevant. However, he left open the possibility that there may be rare cases where the context makes it obvious that these are not to be taken at face value, or circumstances where the generic manufacturer should positively exclude use for the patent-protected purpose.
Lords Hodge and Briggs, however, agreed with Arnold J that the test is whether the alleged infringer subjectively intended to target the patent-protected market, albeit they also recognised that this 'so-called subjective test' (so-called because intention could be proved objectively by words, conduct and even inactivity) remained a compromise. Lord Hodge identified the risk that it could present serious problems to operators in the downstream market for generic products, or to pharmacists, because they could be exposed to strict liability for infringement due to matters over which they may have neither knowledge nor control, but ultimately this could be addressed by legislation.
All of the Lordships agreed that there was no indirect infringement under s.60(2) i.e., by knowingly supplying to a primary infringer (here, the pharmacist) the means for putting the invention into effect. The invention protected by Claim 3 was the manufacture of pregabalin for the designated use, not the subsequent use of the product for treating patients. The essential features of purpose-limited patents were fatal to any attempt to construe Claim 3 as extending to steps taken by the pharmacist.