Sandoz AG v Biogen Ma Inc.

Hearing dates: 22 nd, 24 th, 27 th–30 th November, 5 th & 6 th December 2023

APPROVED JUDGMENT

This judgment was handed down remotely by circulation to the parties' representatives by email. It will also be released for publication on the National Archives and other websites. The date and time for hand-down is deemed to be Friday 11 October 2024 at 10.30am.

THE HON Mr Justice Mellor

INTRODUCTION

This trial was principally concerned with EP (UK) 3 575 792 (‘EP792’ or ‘the Patent’). The action was commenced by the Claimants (‘Sandoz’) seeking revocation of the Patent and certain declaratory relief in view of the existence of further divisional(s) still in the process of prosecution. The Defendant (‘Biogen’) counterclaimed for infringement, as the registered proprietor of the Patent. Since both infringement and validity remained in issue, Biogen opened the trial.

The Patent is entitled ‘ Method of assessing risk of PML’. The parties agreed the priority date was 20 ^th April 2012 (the ‘ Priority Date’). PML stands for Progressive Multifocal Leukoencephalopathy, which is a rare but very serious neurological condition with a high fatality rate.

Biogen has, since 2006, marketed a treatment for relapsing-remitting multiple sclerosis (‘RRMS’) called Tysabri, in which the active ingredient is the monoclonal antibody natalizumab. Natalizumab was protected by a patent and by an SPC which expired in July 2020. Sandoz has been developing a biosimilar natalizumab product for treatment of RRMS called Tyruko, for which marketing authorisation was granted by the MHRA on 9 October 2023. Biogen does not assert that it has any UK rights which would be infringed by Sandoz's Tyruko product.

Natalizumab is generally an effective and well tolerated treatment for RRMS. However, in 2005, during the course of phase III trials, three cases of PML were detected in patients being treated with natalizumab. PML was known to be caused by the John Cunningham virus (‘JCV’). JCV infection is widespread in the population and is generally benign, but occasionally the virus can reactivate and lead to PML, particularly in individuals with suppressed immune systems. By the priority date it was well established that treatment with natalizumab could in some individuals lead to reactivation of JCV and the development of PML, and that prior infection with JCV was a pre-requisite for this occurring. It was also well established that MS patients who tested positive for anti-JCV antibodies were at a higher risk of developing PML than patients who tested negative for anti-JCV antibodies.

By 2012 it was understood that, in addition to JCV infection (as measured by the detection of JCV antibodies in a patient's sample), the risk factors associated with developing PML were: (1) whether or not the patient had been on immunosuppressive drugs; and (2) the length of time the patient had been treated with natalizumab. The following estimates of risk had been published in a review article by Kappos et al in 2011:

Figure 3: Estimated risk of PML based on anti-JCV antibody status, previous immunosuppressant use, and duration of natalizumab treatment

As can be seen from these data, a patient who had been treated with natalizumab for up to 4 years, and was JCV antibody negative, had a ≤0.11 in 1,000 chance of developing PML. For a patient who was JCV antibody positive, the incidence was, for the first 2 years of treatment, three-fold higher at 0.35 in 1,000, rising to 2.5 in 1,000, if treatment was for 2–4 years. Patients were counselled in relation to these risks and based on this information would choose whether or not they wanted to be treated, or continue to be treated, with natalizumab. Many patients were faced with the agonising dilemma of having to face recurrence of episodes of RRMS, which were otherwise being kept at bay by natalizumab, balanced against the alarming potential complication of proceeding with natalizumab therapy and developing PML.

Notwithstanding the issues over construction and validity which I outline below, there is no doubt that the work summarised in the Patent...