EP 2 493 466 B1 relates to the antitumoral use of cabazitaxel in the treatment of prostate cancer, especially for patients who are not catered for by a taxane-based treatment.
Brief outline of the case
The patent was originally opposed by 12 opponents under Art 100(a), (b) and (c). Opponents 3 and 4 and withdrew their oppositions.
The oppositions were rejected.
During appeal, opponent 6 withdrew its opposition and appeal.
Opponents 1, 2, 5 and 7 to 12 remained in appeal.
The board confirmed the rejection of the oppositions.
The present decision centres on the issue of reasonable expectation of success in view of announcements of clinical studies in the prior art.
The opponents’ point of view
The opponents essentially argued that, for a second medical use claim, where the prior art disclosed that a clinical study with the same active agent(s) for the same therapeutic indication had been proposed or was underway, it was established jurisprudence of the boards that a reasonable expectation of success was generally implied by the mere fact that the study had been authorised, unless there was some evidence of a dissuading teaching in the prior art.
In other words, the announcement of a clinical study established a legal presumption of reasonable expectation of success, with the consequence that a proprietor had the burden of rebutting such a legal presumption by showing that the skilled person would have been dissuaded by the prior art from following the study protocol with a reasonable expectation of success and so achieve its inevitable outcome.
In addition to the announcement of the TROPIC study, the available evidence on cabazitaxel would have further incentivised the skilled person skilled to follow the phase III TROPIC study protocol with a reasonable expectation of success.
The proprietor’s point of view
The proprietor referred to T 1437/21, Reasons 4.3.1, and T 3165/19, Reasons 22, that the presumption of success is not absolute in case of a phase III study, but must be understood in the context of the circumstances of the individual cases underlying those particular decisions.
The board’s decision
The board was of the view that the skilled person’s expectation of success had to be considered in particular in relation to the TROPIC study’s primary endpoint, which was overall survival. Success in the context of a clinical study means meeting the primary endpoint.
To lead to a finding of lack of IS, the board held that an expectation of success for improved overall survival must have been present.
The present board considered that the boards have developed a large body of decisions dealing with reasonable expectation of success, including in cases of second medical use where clinical studies were announced in the prior art.
This case law mainly focuses on balancing positive and negative pointers. As such pointers are necessarily always linked with the individual circumstances of the case at issue, it cannot be concluded, without taking the circumstances of each case into account, whether there would have been a reasonable expectation of success. Thus the probative value of a clinical study announcement always depends on the particular circumstances of the case.
Thus, and contrary to the opponents’ argument, the analysis of the cited jurisprudence of the boards does not lead to the conclusion that ongoing clinical studies automatically establish a legal presumption of success.
A legal presumption, especially if it would override established facts, must be explicitly stated in the law.
In principle, the board agreed with the statement in T 1437/21 that a prior disclosure that an investigational product, i.e. active agent, for use in the treatment of a particular condition is undergoing a clinical study may preclude that a subsequently claimed invention involving this product for use in the treatment of that specific condition is considered to involve an IS, even where the results of the study have not been made available to the public. The board also referred to T 2963/19, Reasons 4.3.1), and confirmed in T 1437/21, Reasons 4.3.1., to decide that the approval of a clinical study does not necessarily imply an expected positive outcome.
In this regard, the present board concurred also with T 1941/21, Reasons 1.7.1 to 1.7.4, in which the board held that IS over clinical studies has to be assessed on a case-by-case basis and further that the reasonable expectation of success which “may arise” from the announcement of a clinical study would have to be denied in the presence of negative pointers dissuading the skilled person from pursuing such a study
The board in T 1941/21, Reasons 1.5.1 to 1.5.3, went on to investigate also the possible existence of positive pointers, which is in agreement with the approach that all the facts, i.e. negative as well as positive pointers, must be taken into account.
The lack of a general presumption of an expectation of success had already been emphasised in T 1806/18, Reasons 7.21.
In T 239/16, Reasons 6.5 and 5.2, the board undertook a detailed analysis of what was known in the art for the agent under consideration and for related actives. It was due to the particular circumstances of the case that the board concluded that the skilled person would have entertained an expectation of success, and that negative pointers would have been required to dissuade the skilled person from this expectation.
The board held the factual situation in T 239/16 was different from that in the present case in that the data available for the active under consideration was rather solid. In contrast, the case in hand relates to a new cancer drug used in a new indication, and the situation is complicated by the further issue of resistance to taxanes.
For the same reason, namely the individual aspects relevant for the assessment of the presence of a reasonable expectation of success, the present case differs from the situation underlying the decision in T 2506/12, Reasons 3.10 to 3.12 and 3.15. The relevant question was thus merely to confirm the usefulness of the drug combination and for this reason the board concluded that, in the absence of contrary information on file, there was no reason for the skilled person to expect the combination to fail.
In T 96/20, Reasons 9, the board held differently that the announcement of a detailed safety and efficacy clinical study protocol for a particular therapeutic and disease alone provided the skilled person with a reasonable expectation of success of this particular therapeutic, unless there was evidence to the contrary in the state of the art.
The crucial issue in the assessment of IS starting from the experimental arm of the TROPIC study remains whether, in view of the available information in the prior art, the skilled person had a reasonable expectation that cabazitazel in combination with prednisone would be effective to improve overall survival.
Under usual circumstances, the fact that a Phase III clinical trial is carried out might provide a pointer indicating a successful development path of a new drug/new drug application.
Irrespective of the starting point for assessing IS, the board concluded that there was no expectation of success.
The oppositions were thus rejected.
Comments
The present decision illustrates the fact that a Phase III study does not necessarily mean that the skilled person has an expectation of success.
That this might not be the case in Phase I studies, it is however doubtful that this is valid when Phase III studies are carried out.
In the present case, after the Phase I study, no Phase II study was carried out in prostate cancer, and, for unknown reasons, cabazitaxel was not taken forward in breast cancer after a Phase II study in breast cancer.
A Phase III study for cabazitaxel-based treatment in mCRPC had been approved but the results were not yet known.
However the purpose of a Phase III study is to determine a drug’s therapeutic effect and at this point, the drug is presumed to have some effect.
In view of the definition of Phase III studies, the position of the board is not absolutely convincing.
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