There has been a spattering of case law over the last few years concerned with clinical trial proposals as prior art for patent applications. The status of clinical trial proposals as prior art is particularly relevant to patent applications relating to medical products and medical uses, and this issue has recently been of relevance to one of our clients’ patents.
A clinical trial proposal sets out key details of the purpose of the clinical trial and how it will be conducted. A proposal usually includes details of the background and context for the trial, the primary and secondary outcomes, the design and methodology of the trial, and statistical considerations. Clinical trial proposals are used to monitor the quality of clinical trials, and help to ensure the safety of participants, the integrity of the data and to obtain ethical approval for the clinical trial. A clinical trial proposal is usually published following the relevant approval, although it may be possible to request deferral of publication.
Given that clinical trial proposals are usually published, there is a risk that a clinical trial proposal is cited as prior art against a patent application filed after the date of publication of the proposal. If cited, then a clinical trial proposal can put the novelty and inventive step (i.e. obviousness) of an invention at risk.
The position of the European Patent Office (EPO) in relation to the novelty of an invention over a clinical trial proposal appears to be more straightforward than the EPO’s position in relation to inventive step. In particular, it was held in T 158/96 that the disclosure that a medicament was undergoing a clinical phase evaluation for a specific therapeutic application was not novelty-destroying for a claim directed to the same therapeutic application of the same medicament if it was not possible to conclude from the disclosure that there is actual existence of a therapeutic effect or any pharmacological effect which directly and unambiguously underlies the claimed therapeutic application. Similarly, in T 1859/08, the Board of Appeal held that the mere disclosure that a particular therapy was being explored did not amount to a novelty-destroying disclosure if there was no disclosure of a clinical benefit or the results of any clinical trials. Thus, a disclosure of clinical trial which does not include mention of the results or any clinical benefit (as in a clinical trial proposal) is unlikely to be considered to be novelty-destroying by the EPO.
However, the position of the EPO with respect to inventive step (i.e. obviousness) appears to be more variable, and depends upon the facts of the case. Despite this, the trend appears to be that a clinical trial proposal does make it obvious to the person skilled in the art to provide the claimed invention unless there are ambiguities in the disclosure or there is some evidence which casts doubt on the likely outcome of the clinical trial.
In T 96/20, the Board of Appeal held that the announcement of a detailed safety and efficacy clinical trial protocol for a particular drug and disease did provide the person skilled in the art with a reasonable expectation of success (i.e. a therapeutic benefit) of the particular drug, unless there was known evidence to the contrary.
In T 1806/18, the prior art was three proposed clinical trials, wherein the formulation to be used in the second and third clinical trials depended on the outcome of the first clinical trial. In the first clinical trial, three different formulations of a therapeutic were to be tested. As the result of the first clinical trial was not yet known, the formulation to be used in the second and third clinical trials was also not yet known. The Board of Appeal held that the disclosure of a planned clinical trial does not automatically mean that the outcome of the trial is predictable or that there is a reasonable expectation of success of the clinical trial. In particular, the Board of Appeal held that the outcome of the first clinical trial was not predictable due to known different effects of the different specific components of each formulation, and because unexpected effects had been previously shown in respect of one of the components with another therapeutic. Thus, it could not be predicted which formulation would be used for the second and third clinical trials. Consequently, the Board of Appeal held that the claims had an inventive step because the person skilled in the art was aware of the unpredictability of the components of the formulations and, therefore, would not have had a reasonable expectation that any particular one of the formulations would be successful in having a therapeutic effect. The Board of Appeal also noted that the person skilled in the art would not have used a “try and see” approach in view of the known safety concerns.
The prior art in T 1437/21 was not a clinical trial proposal, but it is still useful to consider the decision of the Board of Appeal in respect of situations when the prior art is a clinical trial proposal. The claims were held to have an inventive step over press releases reporting the results of a phase III clinical trial. Although the results were mentioned in the press releases, they were mentioned in general terms in relation to three sub-groups of patients, and the Board of Appeal held that there was no unambiguous disclosure of a therapeutic effect in respect of the one sub-group claimed in the application. The patentee provided post-published data showing that it was not expected that the treatment would be effective in one of the sub-groups (which was not claimed), and the Board held that the mere inclusion of patients in all three sub-groups in the clinical trial "could not by itself have provided the skilled person with a reasonable expectation of success of the treatment” of all three sub-groups.
In T 0209/22, the prior art was also not a clinical trial proposal, but was a summary of a clinical trial. Importantly, the phase I clinical trial was carried out in healthy subjects, while the claim was directed to a combination of known drugs for use in the treatment of asthma and COPD (i.e. a medical use claim). In addition, there was prior art which suggested each of the two drugs in the claimed combination for the treatment of COPD as a monotherapy (but neither drug had been established as a treatment). The Board of Appeal considered that the claim did have an inventive step because there was nothing in the prior art which would have provided the person skilled in the art with a reasonable expectation that the combination of drugs would succeed in treating asthma and COPD. In particular, the Board held that preclinical data does not necessarily give rise to a well-founded expectation of success, particularly when, as in the present case, neither component of the combination has progressed to the clinical stage of development.
In our own case, the patent was held to lack an inventive step over a clinical trial proposal, which was published before the priority date of the patent. The claims recited a combination therapy for treating cancer, and the stated main aim of the clinical trial proposal was to assess the interference of one component of the combination therapy on the effect of the other component. Ultimately, the Board of Appeal considered that the technical effect of the invention was to provide an effective cancer treatment, rather than an improved cancer treatment, and held that the person skilled in the art would have had a reasonable expectation that the combination therapy would be effective because both components were already known cancer monotherapies. The Board of Appeal also disagreed with the patentee’s arguments that one of the components of the combination could not be identified from the clinical trial proposal, that there was a prejudice in the art against combining the two components of the combination therapy, and that there was no expectation of success in treating cancer in view of the stated purpose of the clinical trial (to assess the interference between the two drugs). Consequently, the Board of Appeal revoked the patent due to a lack of an inventive step.
In summary, a clinical trial proposal, and even the results of a clinical trial, does not necessarily destroy the novelty and inventive step of a claimed medical use. However, the assessment of inventive step, in particular, appears to be very dependent on the specifics of the case, such as the information derivable from the clinical trial proposal, and whether or not there is any prejudice in the art which prevents the reasonable expectation of the alleged technical effect of the invention. It is therefore advisable for patent applicants and their patent attorneys to be aware of the intended date of publication, and the intended content, of clinical trial proposals and the results thereof, as well as preferably filing any relevant patent applications before publication of any clinical trial proposals.
