In Merck v Ono  EWHC 2973 (Pat), the High Court has provided guidance on the nature of the experimental data required to support the disclosure of an invention, emphasising that what matters is what is made “plausible” by the data, as distinguished from what was mere “speculation”. In this case, neither the patent nor the prior art contained experimental data relating precisely to the invention claimed; however, the experimental work in the patent was held to make the claimed therapeutic effect plausible to the skilled person, whereas the experimental data in the prior art did not meet this plausibility requirement. The patent was thus found to be valid and infringed. The decision builds on the notion of “plausibility” when considering what is enabled by a document, and details the application of this notion to the sufficiency and novelty of medical use claims.
Patent EP1537878 (owned by Ono Pharmaceutical Co, Ltd and Prof. Tasuku Honjo) claims an anti-PD-1 antibody which inhibits the immunosuppressive signal of PD-1 for use in cancer treatment. No particular cancer or group of cancers to be treated were specified.
The patent (and priority document) contains experimental data from mouse tumour models showing that PD-1 knockout mice exhibit reduced tumour growth. The tumour models used were chosen or engineered to express the ligand of PD-1, PD-L1. No data were provided showing anti-PD-1 antibodies reducing tumour growth, as claimed by the patent.
Merck alleged that the patent claims were unduly broad, arguing that the experimental data in the patent were not produced using an anti-PD-1 antibody, and do not demonstrate that all cancers can be treated by an anti-PD-1 inhibitory antibody. On these grounds, the application was alleged to be insufficient and to lack priority. Merck also alleged that the claims lacked novelty, citing a prior art document disclosing anti-PD-1 inhibitory antibodies and teaching that they could be used for treating tumours. The only in vivo experimental data in the prior art document showed the immunosuppressive effect of PD-1 but in a mouse model of autoimmunity and did not use anti-PD-1 antibodies.
The matters of insufficiency, priority and novelty in this case each turned on enablement – that is, which of the priority document, patent and prior art, if any, enable the skilled person to put into effect anti-PD-1 inhibitory antibodies for cancer treatment. In order to answer this question, the judge (Birss J) considered that what mattered was what was made “plausible” by each document.
In defining what was meant by “plausible”, the judge referred to the UK Supreme Court decision in HGS v Eli Lilly  UKSC 51, distinguishing between “speculation” on one side, and “plausible”, “reasonably credible” or an “educated guess” on the other. From the same judgement, the judge repeated that “plausible conveys…there must be some real reason for supposing that the statement is true…the standard is not any higher than that”.
When applying this concept of “plausibility” in the context of second medical use claims, the judge held that “the material relied upon to establish plausibility [e.g. experimental data] must be both sufficiently specific, and have sufficient breadth of application, to fairly support the claim both in terms of the nature of the agent claimed to have an effect, and in terms of the effect claimed”. In other words, in the language of the present case, the experimental data must be sufficiently specific to plausibly apply to anti-PD-1 inhibitory antibodies, and also sufficiently broad in application to make plausible the use of such antibodies in all cancer treatment.
The experimental data in the patent and the priority document were held to meet these aspects, and the patent was thus found to be sufficient and the claims entitled to priority.
However, the experimental data in the prior art document cited against novelty of the patent were held to fail the plausibility test set out by the judge for medical use claims. It was deemed that the PD-1-L1 fusion protein used in the experiments was not specific enough to an anti-PD-1 agent. In addition it was held that the use of the agent in a mouse model of autoimmunity only was not sufficiently widely applicable to make it plausible that the agent could be used in treating cancer. The patent was therefore held to be novel over the prior art document.
The facts of this case would indicate that the experimental data in a patent claiming a particular medical use of an agent simply has to make the claimed medical use of that agent plausible – exact correspondence between claims and experimental data may not be required. Such factors should be borne in mind by applicants and attorneys, for example when determining when to proceed with filing a patent application. However, many of the findings in this case were highly dependent on the specific facts of the case and the field in question. Moreover, Birss J emphasised that the UK does not have a “law of plausibility” as such, and that the concept and its interpretation may apply differently in a very different context.