A healthy balance between novelty and sufficiency for a claimed therapeutic use in view of a clinical trial disclosure in healthy volunteers (T 209/22)

The question of novelty and sufficiency of second medical use claims in light of clinical trial prior art has been addressed by the EPO Boards of Appeal on a number of occasions. In recent decision T 209/22, the Appeal Board considers the impact of a disclosure relating to a clinical trial in healthy volunteers. The Appeal Board also comments on the different standards that apply for novelty and sufficiency of disclosure. The decision highlights that an attack based on novelty-sufficiency squeeze may not always be effective.

Background

The present decision relates to European patent 2506844 which claimed a once daily combination therapy for the treatment of chronic obstructive pulmonary disease (COPD) and/or asthma. The patent provided data for each of the claimed drugs as monotherapies in COPD patients. The patent also provided data for the claimed combination in healthy volunteers. However, no data was provided for the claimed combination in patients having COPD or asthma.

A clinical trial protocol disclosing a phase I clinical study in healthy volunteers corresponding to the experimental set-up on healthy volunteers described in the patent was full prior art against the claims of the patent. Whether the disclosure and the alleged conduct of the study prejudiced the novelty of the claims was argued between the parties. The assessment of sufficiency of disclosure and the alleged squeeze with novelty as argued by the appellants (opponents) was also discussed.

At first instance the Opposition Division (OD) rejected the oppositions and maintained the patent as granted.

The Appeal Board Decision

Novelty

At appeal, one of the appellants argued that “the clinical study described in [the clinical trial protocol], which took place before the priority date of the patent in suit, constituted public prior use” of the claimed combination therapy. The appellant also alleged that the written disclosure of the clinical trial protocol anticipated the claimed subject matter (section 4.1 of the Reasons).

The Appeal Board rejected these lines of argumentation on the basis that “the study [described in the clinical trial protocol] was a phase I study performed on healthy volunteers” (section 4.2 of the Reasons, emphasis added). The Appeal Board noted that according to well-established case law of the Boards of Appeal, “where a therapeutic application is claimed in the format provided in Article 54(5) EPC (as is the case for present claim 1), attaining the claimed therapeutic effect is regarded as a functional technical feature of the claim that may establish novelty or inventive step” (section 2.2 of the Reasons, emphasis added). Therefore, the Board considered that the clinical trial in healthy volunteers could not have anticipated the claimed therapeutic effect “simply because the study subjects did not suffer from COPD or asthma” (section 4.2 of the Reasons, emphasis added).

As such, the Appeal Board found that the clinical trial protocol and the alleged clinical prior use did not prejudice the novelty of the claimed combination therapy for use in the treatment of COPD and/or asthma.

Sufficiency of disclosure

To meet the requirements of sufficiency of disclosure, it needs to be assessed whether the claimed combination therapy for the treatment of COPD and/or asthma by once-daily administration was credible at the effective date, on the basis of the information provided in the patent application together with the common general knowledge then available to the skilled person.

As noted above, whilst the patent application did not provide any data for the claimed combination in patients having COPD or asthma, the application provided data for each of the claimed drugs making the combination as monotherapies in COPD patients, as well as for the claimed combination in healthy volunteers. The Board considered that based on these data, there was “a strong presumption” that the claimed combination therapy “would be effective in the treatment of asthma or COPD, and that a dosage regimen of once-daily administration would be feasible” (section 5.4.5 of the Reasons).

Novelty vs Sufficiency

The appellants argued that if the clinical trial prior art in healthy volunteers “did not take away the novelty of the claimed subject-matter, then it followed that the combination study as described in the application as filed could not be regarded as enabling in support of the claimed therapeutic use” (section 5.5 of the Reasons).

The Board did not agree, indicating that different standards apply for novelty and sufficiency of disclosure.

Specifically, “[t]o be novelty-destroying, a prior-art disclosure must meet the standard of direct and unambiguous disclosure of the claimed subject-matter. This criterion was not met by [the clinical trial prior art] with regard to attaining the claimed therapeutic effect, because the study was performed with healthy subjects” (section 5.6.1 of the Reasons, emphasis added).

In contrast, the assessment as to whether the claimed therapeutic effect was credible at the effective date and thus sufficiently disclosed “is by no means restricted to the description of the combination study [in healthy volunteers in the application] but can be based on any pertinent content in the application as filed, in view of common general knowledge at the effective date” (section 5.6.3 of the Reasons, emphasis added).

Inventive step

Having confirmed the novelty of the claimed subject-matter, the Board further found the claimed subject-matter to be inventive. Interestingly, inventive step in view of the phase I clinical trial protocol is not discussed in the decision and the Board found that the claimed combination therapy was not obvious in view of different prior art disclosing favourable preclinical data for the individual drugs of the combination as monotherapies.

The closest prior art was a published patent application disclosing in vitro data relating to the treatment of diseases including COPD and asthma for one of the compounds of the claimed combination. This publication did not disclose the second claimed compound, but envisaged combination with a compound of the same class (sections 6.4 and 6.5 of the Reasons). Preclinical data (in vitro and animal studies) for the second claimed compound of the combination was disclosed in another prior art document.

The Board considered that at “the relevant date, both [compounds] were still in early stages of their pharmaceutical development. While the basis for proceeding with the pharmaceutical development of a compound is favourable preclinical data, this does not necessarily give rise to a well-founded expectation of success, even less in the case of a combination product when neither combination partner has, as yet, progressed to the clinical stage of development” (section 6.21.2 of the Reasons, emphasis added). In particular, the Board noted that efficacy and safety of the compounds in actual patients had not yet been confirmed. The Board found that the prior art disclosures “at best, have provided the person skilled in the art with the hope to succeed, but that this does not amount to a reasonable expectation of success” (section 6.21.5 of the Reasons, emphasis added).

The Board dismissed the appeals and maintained the patent as granted.

Commentary

This decision might be useful for Patentees attempting to defend against a novelty-sufficiency squeeze attack from an opponent on a medical use claim.

To be novelty-destroying, a prior-art disclosure must meet the standard of direct and unambiguous disclosure of the claimed subject-matter. The discussion of novelty in the present decision confirms the finding in earlier decisions (e.g. T 158/96 and T 1437/21 (discussed in our article here)) that, for  assessing the novelty of a medical use claim, it “has to be examined whether or not the same therapeutic effect has been shown in the prior art documents” (T 158/96; section 3.1 of the Reasons, emphasis added).

Conversely, the assessment of sufficiency for a medical use claim requires a different (and arguably lower standard in this circumstance) to determine whether the claimed therapeutic effect was “credible” at the effective date, based on the content in the application as filed, in view of common general knowledge at the effective date.

In the set of facts for this decision, not only did the Board find there was there no novelty-sufficiency squeeze, there also was apparently no inventive step-sufficiency squeeze. The alleged novelty destroying disclosure was not advanced by the appellants as the closest prior art under inventive step. This is interesting since in other decisions, a clinical trial protocol with no data has been considered as a valid closest prior art in the EPO problem-solution approach. However, whilst a lack of inventive step due to reasonable expectation of success has been previously argued in earlier decisions where the clinical trial related to a study in patients (e.g. T 239/16 and T 1255/21), a similar argument didn’t succeed in T 1732/18 where the clinical trial disclosure related to a study in healthy volunteers. In T 1732/18, the Board considered that the results in healthy volunteers could not be extrapolated to patients with pathology (section 9.22.2 of the Reasons).

In the present decision, in relation to inventive step, the Board found that there was no reasonable expectation of success for a combination therapy in view of prior art disclosing favourable preclinical data for the individual drugs of the combination as monotherapies. This contrasted with the clinical data in the Patent for the monotherapies in COPD patients which was found to make the therapeutic effect credible for sufficiency purposes.

This decision confirms that the outcome of each case depends on the specific facts, particularly the nature of the drug, the condition to be treated, and the data already available to the skilled person at the effective date of the patent. For example, in earlier decisions where preclinical data for the claimed drug or combination was disclosed in the prior art, the Board found that a reasonable expectation of success to take the step from pre-clinical animal studies to clinical studies involving human patients was sufficient to render a claimed medical use obvious (e.g. T 237/15 and T 1853/16).