August 15, 2022
Neurim Pharmaceuticals (1991) Ltd issued proceedings against Generics (UK) Ltd (trading as Mylan at the time) in relation to the alleged infringement of Neurim’s second medical use Divisional European Patent designating the UK for “Circadin”, which is a prolonged release melatonin product indicated for the short-term treatment of primary insomnia characterised by poor-quality sleep in patients aged 55 or over (the Divisional). Neurim sought relief to stop Mylan from supplying or selling any generic version of Neurim’s Circadin product. The Divisional is due to expire on 12 August 2022.
Mylan contended that the Divisional was invalid on the ground of insufficiency due to lack of plausibility.
Neurim had originally issued proceedings against Mylan for infringement of Neurim’s parent patent (the Parent), whose claims were materially the same as in the Divisional and which had the same expiry date. In December 2020, Mr Justice Marcus Smith dismissed various challenges to the validity of the Parent (the December Judgment). Shortly after, however, the Parent was revoked as a result of Neurim’s withdrawal of an appeal against an order for revocation by the European Patent Office at the conclusion of a hearing before the Board of Appeal.
Neurim then issued proceedings against Mylan for infringement of the Divisional. There was no material difference between the Claims of the Parent and those of the Divisional. Smith J found that the Divisional was valid and infringed for reasons given in the December Judgment, as supplemented by a judgment given in March 2022 (the March Judgment) and granted an injunction against Mylan.
Mylan appealed with permission granted by the Court of Appeal. Neurim offered a cross-undertaking in damages in the event that Mylan’s appeal was dismissed and the Divisional subsequently revoked by the EPO. In the light of that offer, Mylan no longer pursued its application for a stay of the injunction granted by Smith J, pending the decision of the EPO (in practice, until expiry of the Divisional) if the appeal was dismissed.
Giving the lead judgment, Lord Justice Arnold, with whom the other Justices agreed, said that, given that Smith’s J’s reasoning in the December Judgment and the March Judgment concerned the Parent, but was equally applicable to the Divisional, he used the term “the Patent” to refer to both.
Arnold LJ noted that the criterion for plausibility was stated by Lord Sumption in Warner-Lambert Co LLC v Generics (UK) Ltd  UKSC 56.
Mylan contended that the Patent did not plausibly disclose the effect that it claimed because of what it called the “lay-patient argument”. Mylan said that the Claims were second medical use Claims directed to the use of melatonin for the treatment of insomnia characterised by non-restorative sleep. Non-restorative sleep refers to the situation where a patient spends time asleep but does not feel refreshed. It is therefore distinct from not being able to get to sleep, having trouble maintaining sleep, or getting to sleep but waking up too early. Mylan argued that:
- because the invention was a second medical use, the clinical result had to be made plausible by the specification;
- since the Claims specifically addressed non-restorative sleep, they had to render that plausible, not merely some more general improvement in sleep quality;
- there was no objective test or measurement of sleep quality in the Claims; it was assessed by asking patients about their subjective experience; and
- the relevant materials in the Patent related to asking patients about their sleep, but there was no description showing that what they were asked was about restorative sleep, or that that was what they reported on; they might have interpreted the questions as being about improvement in sleep generally and if they reported an improvement, it might only have been an improvement in, for example, getting to sleep.
Mylan accepted that at first instance it had not articulated the lay-patient argument very clearly. Therefore, Smith J had not squarely addressed it in the December Judgment. He did, however, consider it in the March Judgment based on the evidence at trial and his findings in the December Judgment.
In the December Judgment Smith J held that the Patent did plausibly disclose the effect that it claimed because the assessment of sleep quality involved a reasonably large study of 170 elderly individuals, who were “Primary Insomniacs”, at least some of whose sleep was characterised by its non-restorative quality. The study was conducted on established lines (use of placebos and blind testing) and resulted in a statistically significant outcome in that it enabled the conclusion that melatonin enhanced the restorative value of sleep. Further, it was clear that the focus of the study was the effect of melatonin on non-restorative sleep in Primary Insomniacs. Although the results were not statistically significant, obviously a relevant factor, the fact was that the study showed that there was “something in” the invention that went well-beyond mere assertion.
In the March judgment, Smith J rejected Mylan’s argument that the questionnaire used in the study referred only to the “quality of sleep”, which was ambiguous and directed only at quality of sleep in the non-technical sense. Smith J held that the skilled person would attach a technical meaning to the term “quality of sleep” and, further, that such skilled person would expect and presume that the clinicians in charge of the trials, although not skilled persons, would conduct the trials in such a way as to evaluate the quality of sleep in the technical sense, i.e., they would do their job competently.
Arnold LJ found that Smith J’s decision that the Patent plausibly disclosed the effect that it claimed was an evaluative assessment. Therefore, Mylan had to establish that he had erred in principle.
Arnold LJ rejected all Mylan’s submissions as to how Smith J had erred, finding that:
- Smith J had been correct to focus on the purpose for which the “quality of sleep” question was asked, rather than on how the layperson would understand the question as Mylan argued; although it was right that the Claims in question referred to “subjectively assessed sleep quality”, the skilled reader of the Patent would read those statements in the context of the whole specification and it would be clear to such skilled person that the purpose of the questions on “quality of sleep” was to demonstrate that melatonin was effective in enhancing the restorative value of sleep in primary insomnia patients i.e. treating non-restorative sleep;
- Smith J had been correct to find that the skilled person would assume that the study was competently conducted such as to produce meaningful data, unless there was some reason to think otherwise; this was not to reduce plausibility to a mere test of good faith because plausibility depends on the reported results of the trials; nor was it to assume that the results supported the conclusions drawn in the Patent, which was a separate question; even if it was correct that the “quality of sleep” question was not specific to non-restorative sleep, there were two ways in which it could have been administered to produce meaningful data; and
- it was not necessarily correct that, even if administered in isolation and without further instructions, the “quality of sleep” question would not be specific to non-restorative sleep, as identified by the expert evidence at trial, which Smith J was entitled to accept.
Accordingly, the appeal was dismissed. (Neurim Pharmaceuticals (1991) Ltd v Generics (UK) Ltd  EWCA Civ 699 (27 May 2022) — to read the judgment in full, click here).