Establishing the Plausibility of Second Medical Use Patents: Neurim Pharmaceuticals v. Mylan (2022)

Introduction

The legal dispute between Neurim Pharmaceuticals (1991) Ltd & Anor and Generics (UK) Ltd & Anor, popularly known as Mylan, centers around the alleged infringement of European Patent (UK) No. 3 103 443 ("EP443"). Neurim, the proprietor of EP443, claims that Mylan infringed upon their patent by marketing a generic version of Circadin, a prolonged release formulation of melatonin used to improve the restorative quality of sleep in elderly patients suffering from primary insomnia characterized by non-restorative sleep ("NRS"). Mylan contends that EP443 is invalid due to insufficiency, specifically a lack of plausibility in the patent's claims. The case proceeded through various judicial levels, culminating in the Court of Appeal's decision in May 2022.

Summary of the Judgment

The England and Wales Court of Appeal upheld the original decision by Marcus Smith J, who dismissed Mylan's challenges against the validity of EP443. The court affirmed that the patent plausibly disclosed the claimed effect, thereby upholding Neurim's infringement claim. Mylan's appeal, which sought to invalidate EP443 on the grounds of insufficiency, was rejected. The Court of Appeal agreed with the lower court's assessment that the patent met the requisite standard of plausibility as outlined in relevant legal precedents.

Analysis

Precedents Cited

The judgment extensively referenced established legal standards for assessing the plausibility of patent claims, particularly in the context of second medical use patents. A pivotal precedent cited was Warner-Lambert Co LLC v Generics (UK) Ltd [2018] UKSC 56, which articulated the criteria for plausibility, emphasizing that the specification must provide a reasonable basis for expecting the claimed therapeutic effect. Lord Sumption’s elucidation in this case underscored that plausibility is not merely a test of good faith but requires a substantiated expectation based on the disclosure.

Additionally, the judgment referenced Conor Medsystems Inc v Angiotech Pharmaceuticals Inc [2008] 4 All ER 621, para 28, reinforcing that a mere possibility of effect does not satisfy the plausibility requirement. The principles from the Technical Board of Appeal in Salk (T-609/02) were also invoked to delineate the necessity of a direct effect on a metabolic mechanism or a priori reasoning to establish plausibility.

Legal Reasoning

The court's legal reasoning hinged on the interpretation of the term "quality of sleep" within the patent's claims and the associated experimental data. The judge determined that the "quality of sleep" referred to in the Leeds Sleep Evaluation Questionnaire (LSEQ) was intended in its technical sense, aligned with the ICD-10 definition of NRS, rather than the layperson's interpretation. This interpretation was crucial in establishing that the patent plausibly disclosed the claimed therapeutic effect of melatonin.

Mylan's contention that the questionnaire could be interpreted in a non-technical sense was systematically dismantled by the court. The judge emphasized that the skilled person would assume that the trials were conducted competently and that the questionnaire was administered in a manner consistent with technical standards. Expert testimony, particularly from Professor Thomas Roth, supported this interpretation by affirming that the questions were suitable measures of restorative sleep quality within the context of sleep medicine.

Furthermore, the court addressed Mylan's "lay-patient argument," concluding that the skilled person would not disregard the technical intent behind the questionnaire's design. The judge reasoned that, in the absence of evidence to the contrary, it is reasonable to assume that the experimental protocols were aligned with the technical definitions pertinent to NRS.

Impact

This judgment reinforces the stringent requirements for plausibility in second medical use patents. It underscores the necessity for patent specifications to provide a credible and substantiated basis for claimed therapeutic effects. By upholding the patent's validity despite challenges, the court sets a precedent that emphasizes the importance of technical definitions and the competent administration of clinical trials in establishing patent plausibility.

For the pharmaceutical industry, this case highlights the critical importance of meticulous trial design and clear, technically sound patent claims. It may influence how future patents are drafted, particularly in ensuring that experimental evidence directly supports the claimed use.

Moreover, the judgment affirms the viability of second medical use patents, offering a pathway for companies to protect new therapeutic applications of known compounds, provided that the claims meet the established standards of plausibility.

Complex Concepts Simplified

Second Medical Use Patent

A second medical use patent refers to the protection of a known substance or compound when it is used for a new therapeutic purpose. In this case, melatonin, previously recognized for circadian rhythm disorders, is patented for improving the restorative quality of sleep in elderly patients with NRS.

Plausibility in Patent Law

Plausibility is a legal standard that requires a patent to provide a reasonable basis for believing that the claimed invention will achieve the intended effect. It prevents patents from being granted for speculative or unsubstantiated claims.

Non-Restorative Sleep (NRS)

NRS is a condition where individuals feel that their sleep is restless, light, or of poor quality, leading to insufficient restorative benefits. It is a key diagnostic criterion in certain types of primary insomnia.

Lay-Patient Argument

This argument posits that the responses from patients in clinical trials (who are laypersons) do not reliably reflect the technical claims of the patent. Mylan suggested that the patients' interpretation of "quality of sleep" might not align with the technical meaning intended in the patent.

Leeds Sleep Evaluation Questionnaire (LSEQ)

The LSEQ is a standardized tool used to assess various aspects of sleep quality through patient responses. It comprises questions grouped into categories such as ease of getting to sleep, quality of sleep, ease of awakening, and behavior upon wakefulness.

Conclusion

The Court of Appeal's decision in Neurim Pharmaceuticals v. Mylan reaffirms the robustness of second medical use patents when supported by plausible and technically substantiated claims. By meticulously analyzing the interpretation of key terms and the administration of clinical trials, the court ensured that the patent's validity was upheld against challenges of insufficiency.

This judgment serves as a critical reference point for future patent litigations, emphasizing the importance of clear technical definitions and robust experimental evidence. It highlights the judiciary's role in safeguarding genuine innovations while preventing the issuance of patents based on speculative assertions. For stakeholders in the pharmaceutical sector, the case underscores the imperative of aligning clinical trial designs and patent claims to meet established legal standards of plausibility.