The UK Supreme Court recently handed down a decision regarding generic manufacturer Actavis and Eli Lilly ([2019] UKSC 15) which essentially agreed with the previous UK Court of Appeal decision. This decision will be welcomed by both pharmaceutical innovators and generics, as it reinforces that dosage regimes may be considered as patentable in the UK.
The patent in question in this decision is EP1173181, owned by ICOS and exclusively licensed to Eli Lilly. The claims refer to the use of Tadalafil, brand name Cialis, which is a phosphodiesterase type 5 inhibitor for use in the treatment of erectile dysfunction. The original patent (EP0839040) disclosing the use of Tadalafil for the use of erectile dysfunction was first published in 1997. In this document it was suggested that doses of 0.5mg to 800mg of Tadalafil would be appropriate for daily use in humans, and a specific example was provided which demonstrated that 50mg of Tadalafil was administered to a human subject.
Subsequently, ownership of the EP0839040 patent passed to ICOS Corporation who conducted further clinical trials using Tadalafil for the treatment of erectile dysfunction. European patent EP1173181 was published in 1999 as a result of these studies, whereby the claims were focused on using a dose of 1 to 5mg of Tadalafil per day in humans to treat erectile dysfunction. Once granted, the validity of EP1173181 was attacked by a number of generic drug manufacturers. At first instance, the patent was found to be valid and infringed by competitors, based on the fact that the surprisingly low dose compared to that disclosed in EP0839040 exerted a therapeutic effect and was therefore novel and inventive. However, on appeal, the UK Court of Appeal issued a decision that the patent lacked inventive step and was therefore invalid.
The reasoning behind this decision was that a 5mg dose of Tadalafil would have been attempted by the skilled team as part of dose-escalation studies in clinical trials, and therefore it would have been obvious to the skilled person to try this dose of Tadalafil. Eli Lilly, who were also party to proceedings, submitted that the discovery of the lower dosage regime was the result of largely unpredictable and costly clinical research and that there was absolutely no motivation to investigate if efficacy was maintained as such low doses. In response, the UK Court of Appeal stated that “routine testing is unlikely to result in innovation”, citing the “obvious to try” test. This decision was appealed by ICOS Corporation to the UK Supreme Court. Surprisingly, the appeal was dismissed by the UK Supreme Court in that the decision of the UK Court of Appeal was justified. This was bolstered by expert witnesses who confirmed that if a dose of 50mg was originally found to be effective, a dose of 5mg would certainly have been tested and included in the Phase II clinical studies.
A number of pharmaceutical bodies launched an intervention regarding the decision to dismiss the appeal by the UK Supreme Court, which resulted in a non-specific statement within the UK Supreme Court decision that “there is no policy reason why a novel and inventive dosage regime should not be rewarded by a patent”. This may not have been the ideal outcome for ICOS Corporation and Eli Lilly, however it does offer a silver lining within the pharmaceutical industry that novel and inventive dosage regimes may be acknowledged and rewarded with patent protection within the UK.