The EPO Board of Appeal and UK High Court have recently issued conflicting decisions on the validity of Regeneron Pharmaceuticals' European Patent for the VelocImmune therapeutic antibody development platform.
The Regeneron patent ( EP 1360287) relates to methods of producing transgenic mice possessing human antibody genes that produce complete human antibodies and respond naturally to antigenic challenge. Preserving these natural responses enables concurrent production of a large number of diverse human antibodies within the same mouse against the same target. Therapeutic antibody development previously required cloning of a specific human antibody gene into the mouse, or relied on chimeric antibodies containing both mouse and human components. The Regeneron approach therefore significantly increases the efficiency of therapeutic antibody development and reduces the potential toxicity of the resultant antibodies. The VelocImmune platform has proved to be one of the most effective strategies available for the development of novel antibody therapeutics.
During Opposition proceedings before the EPO brought by Kymab and Merus, the Regeneron VelocImmune patent was revoked for lacking novelty and inventive step. However, in a subsequent appeal against the decision, the patent was maintained in view of claim amendments submitted by Regeneron, whilst arguments submitted by Kymab and Merus that the claims were not sufficiently disclosed were dismissed ( T 2220/14).
By contrast, during infringement proceedings in the UK brought by Regeneron against Kymab and Novo Nordisk, it was found that Kymab was infringing the patent but that the patent was invalid for lack of sufficiency ([2016] EWHC 87 (Pat)). Regeneron still has the opportunity to appeal the High Court decision.
The High Court and EPO decisions are interesting from two perspectives. Firstly, they highlight a difference of interpretation between the EPO and UK High Court regarding the legal concept of sufficiency, and more particularly, the legal interpretation of what expertise may be afforded to the person skilled in the art. Secondly, Regeneron's loss of protection in the UK for its VelocImmune platform is likely to have a significant impact on the direction of research into novel therapeutics by Regeneron and its competitors.
The contradictory conclusions of the UK High Court and the EPO regarding the sufficiency of the patent initially appear to stem from expert testimony submitted to the UK High Court that was not available to the EPO. The UK judge concluded that this testimony proved that a skilled person would not have been able to perform the invention at the time the application was filed. However, it is unclear whether the Board of Appealwould have reached a different decision in view of this evidence. The difference between the decisions may, in fact, lie in differing interpretations of the person skilled in the art by the UK High Court and EPO. In the UK, a more strict interpretation was used, with the judge dismissing the claimed method as impossible for a skilled person at the time of the application in view of the multiple optimisations required. The Appeal Board afforded the skilled person a higher level of competence, arguing that they would have eventually overcome the challenges they faced by using routine methods of optimisation.
As both decisions commented, the field of the patent is complex for anyone not experienced in multiple and highly technical areas of molecular biology and genetics. The opposing views of the EPO and the UK High Court highlight the difficulty in objectively determining the level of discretion and technical expertise that can be afforded to a skilled person. In highly specialised technical fields, what counts as "routine experimentation" may be months, or even years, of technical effort and optimisation.
The VelocImmune platform has proved exceedingly commercially valuable to Regeneron over the past few decades. Using the platform, Regeneron has brought a number of successful therapeutic antibodies to market and have many others currently undergoing clinical trial. In 2007, Regeneron agreed a six-year US$120 million non-exclusive licence with AstraZenca for use of the technology, under which Regeneron would receive royalties on the sale of any products produced using the platform. Astellas Pharma, one of the largest pharmaceutical companies in Japan, also agreed a non-exclusive license for use of the VelocImmune technology up until 2023.
Following the UK High Court decision, Regeneron can no longer prevent the commercial use of mouse models equivalent to the VelocImmune platform (such as Kymab's Kymouse) in the UK. However, before the UK High Court decision was issued, Regeneron had already taken steps to mitigate the potential loss of its VelocImmune patent by branching out into other therapeutic platforms.
The EPO Board of Appeal and UK High Court decisions make for a complex read for anyone lacking a technical background in the field. The complexity of the subject matter underlies the difference between the UK High Court and EPO decisions and the resulting opposing interpretations of the level of skill that can be afforded to a team of experts in the field. Whilst Regeneron's loss in the High Court has received considerable attention in view of the historical commercial success of the VelocImmune platform, its significance may diminish with the emergence of new therapeutic strategies.
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