A phase III clinical trial protocol does not by itself provide a reasonable expectation of success of the investigated treatment (T 122/23)

To date, a number of EPO Board of Appeal decisions support the argument that the publication of a clinical trial protocol can establish a “reasonable expectation of success” when there is no evidence showing that a person skilled in the art was “dissuaded”; in other words, unless there was some sort of “prejudice” in the art.[1] As a result, it can be difficult for a Patentee to convince the EPO that a claim defining the same composition and the same disease indication as a clinical trial protocol is inventive. For example, in T 2506/12, the Board commented that “drug compounds to be used in a clinical trial with human subjects are not selected based on a general ‘try-and-see’ attitude, but based on existing favourable scientific data, for both ethical and economical reasons. Thus, a clinical trial is not a mere screening exercise”. The Board further noted that “[t]he reason why clinical studies are carried out at all is that they have uncertain outcomes. But they are routine tests and the fact that their outcome is uncertain does not in itself turn their results into an invention” (T 2506/12, sections 3.10 and 3.12.2 of the Reasons).

However, as previously seen in T 2963/19 and in  T 1437/21 (discussed in our article here), the disclosure of a clinical trial protocol does not always mean that there is a reasonable expectation of success of achieving treatment: the outcome depends on the specific facts, e.g., evidence relating to the nature of the investigational product and/ or of the condition to be treated. Recent decision T 122/23 from Board 3.3.07 now brings such other evidence into the spotlight not only for demonstrating lack of an expectation of success at the EPO but also as being decisive in supporting a clinical trial protocol to establish an expectation of success. Accordingly, questions arise as to the strength of an objection of lack of inventive step based on a clinical trial protocol when taken alone, and Applicants, Patentees and Opponents should carefully consider other evidence beyond the protocol whichever side they are arguing on so that the conclusion on reasonable expectation of success (or lack thereof) is reached “in view of the prior art”.

Background

Board of Appeal decision T 122/23 relates to European patent 2350096. The claims filed at appeal relate to rifaximin for use in decreasing the risk of hepatic encephalopathy (HE) breakthrough episodes in a subject suffering from HE, wherein rifaximin is administered at a dose of 550mg two times a day or 275mg four times a day and wherein rifaximin is administered concomitantly with lactulose.

The patent provides data supporting the claimed medical use in the form of a randomised controlled trial and the results of an ongoing open-label treatment extension study (section 4.1 of the Reasons).

The closest prior art (D7d) disclosed a phase III clinical trial protocol (referred to herein as “the protocol”) describing the claimed treatment. A second prior art document (D9) disclosed the results from an open-label study indicating clinical efficacy and tolerability of the administration of rifaximin in combination with lactulose during 15 consecutive days in the treatment of hepatic encephalopathy.

At first instance, the Opposition Division revoked the patent for lack of inventive step over the protocol disclosure.

At Appeal, the Board considered the subject-matter of claim 1 to be novel over the protocol because the protocol did not “[reveal] any results from the trial” (section 3 of the Reasons). This was not discussed between the parties during the hearing. However, whether the protocol provided the skilled person with a reasonable expectation of success was argued between the parties (section 4.1 of the Reasons).

The Decision - Inventive Step

The Appeal Board considered that the protocol in D7d “represent[ed] a suitable starting point in the prior art for the assessment of inventive step”. The phase III clinical trial described in the protocol differed from the claimed treatment in that the protocol “does not report the actual effectiveness of the described treatment” (section 4.1 of the Reasons, emphasis added).

The Board formulated the objective technical problem “as the provision of effective long-term treatment for decreasing the risk of hepatic encephalopathy breakthrough episodes in patients who previously suffered from overt hepatic encephalopathy” (section 4.1 of the Reasons).

The Board considered that:

“the mere fact that document D7d reports the protocol for the evaluation of efficacy and safety of rifaximin with optionally lactulose in a phase III clinical trial does not by itself provide the skilled person with a reasonable expectation of success of the trial.

The assessment of inventive step starting from document D7d therefore crucially depends on the question whether the skilled person had in view of the prior art, in particular having regard to the available information on the nature of the products under investigation and the condition to be treated, a reasonable expectation that the use of rifaximin with concomitant lactulose therapy would be effective in decreasing the risk of hepatic encephalopathy breakthrough episodes.

In this context the Board relies on the considerations in T 2963/19 (see reasons 4.2.1) and T 1437/21 (see reasons 4.3.1)” (section 4.2.1 of the Reasons, emphasis added).

In section 4.2.2 of the Reasons, the Board refers to a second prior art document D9 reporting “the results from an open-label study indicating clinical efficacy and tolerability of the administration of rifaximin at a dose of 1200 mg/day in combination with lactulose during 15 consecutive days in the treatment of hepatic encephalopathy”, thus “[confirming] the clinical efficacy of rifaximin in controlling episodes of encephalopathy”. The Board finds that the results in D9 “provided the skilled person with a reasonable expectation of success regarding the prevention of breakthrough episodes of hepatic encephalopathy under investigation in the trial of document D7d” (section 4.2.2 of the Reasons, emphasis added).

Sections 4.2.3 to 4.2.7 of the Reasons set out the Patentee’s arguments and the reasons why the Board found them to not be convincing. For brevity, these arguments are not discussed here.

The appeal was dismissed.

Commentary

The Board’s reasoning on inventive step in this decision is brief, and cross-references two earlier decisions: T 2963/19 (section 4.3.1 of the Reasons) and T 1437/21 (section 4.3.1 of the Reasons). To understand the context of these earlier decisions, we provide a brief overview below.

Interestingly, T 2963/19 has been cited by only four T decisions to date, including the present decision T 122/23 and T 1437/21.[2] The other decisions citing T 2963/19 are G 2/21 (in the context of post-published evidence) and T 1941/21. In T 1941/21, the claims were directed to the use of tauroursodeoxycholic acid (TUDCA) in the treatment of amyotrophic lateral sclerosis (ALS). The difference between a phase II clinical trial protocol disclosure and the patent was that the latter presented evidence that the claimed therapeutic effect was achieved. There was no document indicating the established efficacy of any class of agents in the treatment of ALS, and in addition there was evidence calling the relevance of the preclinical results for TUDCA into question (sections 1.7.1 and 1.7.2 of the Reasons). As a result, the claimed subject matter was found to involve an inventive step.

T 1437/21 has been cited by one T decision only to date, i.e. the present decision.[3]

Thus, in each of the above-mentioned decisions, the prior art provided some sort of “prejudice” against a reasonable expectation of success of the treatment described in the protocol.

As such, in stating that “the mere fact that document D7d reports the protocol for the evaluation of efficacy and safety of rifaximin with optionally lactulose in a phase III clinical trial does not by itself provide the skilled person with a reasonable expectation of success of the trial”, the Board in T 122/23 appears to depart from the approach taken in earlier Boards of Appeal decisions. In those earlier decisions, the Boards held that a clinical trial protocol establishes a reasonable expectation of success even in the absence of results, unless evidence shows that a person skilled in the art was “dissuaded”; in other words, unless there was some sort of “prejudice” in the art. This case law is discussed in detail in a recent article by the present authors published in the April 2025 issue of the CIPA Journal.

However, the Board also emphasizes that the assessment of whether a skilled person would reasonably expect the trial to succeed must be made “in view of the prior art, in particular having regard to the available information on the nature of the products under investigation and the condition to be treated”. This reasoning aligns with previous decisions of the Boards of Appeal. Frances Lowe from CMS Cameron McKenna Nabarro Olswang  who represented Opponent 1 at the Appeal hearing considers that “the outcome of the decision would have been different in the absence of the disclosure of document D9 or another prior art document disclosing the positive effects of rifaximin on HE”. She explains that “the Board made it clear that such supporting prior art was necessary to demonstrate a reasonable expectation of success starting from the clinical trial”. It will be interesting to see how this line of jurisprudence is evolving in future decisions.

[1] See, e.g. T 239/16; T 1255/21; T 2506/12; T 1123/16.

[2] According to a search for cases citing T 2963/19 carried out on the Boards of Appeal database “Decisions of the Boards of Appeal” on 13 August 2025: | epo.org.

[3] According to a search for cases citing T 1437/21 carried out on the Boards of Appeal database “Decisions of the Boards of Appeal” on 13 August 2025: | epo.org.