This is an informal case summary prepared for the purposes of facilitating exchange during the 2025 WIPO IP Judges Forum.
Session 2: Pharmaceutical Patents
Boards of Appeal of the European Patent Office [2023]: Case No. T 1779/21 - Fenfluramine for Use in the Treatment of Dravet Syndrome
Date of judgment: December 19, 2023
Issuing authority: Boards of Appeal of the European Patent Office
Level of the issuing authority: Final Instance
Type of procedure: Judicial (Administrative)
Subject matter: Patents (inventions)
Appellant: Teva Pharmaceutical Industries Ltd.
Respondents: Katholieke Universiteit Leuven, University Hospital Antwerp
Keywords: Pharmaceutical Patents, Sufficiency of Disclosure
Basic facts: The case, T 1779/21, concerns the European patent No. 2991637, titled “Fenfluramine for use in the treatment of Dravet syndrome,” filed by Katholieke Universiteit Leuven and University Hospital Antwerp. The patent was opposed by Teva Pharmaceutical Industries Ltd. on grounds of lack of inventive step (Article 56 European Patent Convention (EPC)), insufficiency of disclosure (Article 100(b) EPC), and added subject matter (Article 100(c) EPC).
The patent claimed a formulation comprising fenfluramine or its pharmaceutically acceptable salt for oral administration as a monotherapy for treating Dravet syndrome. The opposition focused on the insufficiency of disclosure, arguing that the patent lacked experimental data or credible evidence to support the therapeutic effect of fenfluramine as a monotherapy for Dravet syndrome. The patent proprietors argued that the mechanism of action of fenfluramine made its therapeutic effect plausible, supported by prior art and post-published evidence.
Held: The Board referred to point 74 of the Reasons of decision G 2/21 (OJ EPO 2023, A85), which confirmed in obiter the relevant case law, that “a technical effect, which in the case of for example a second medical use claim is usually a therapeutic effect, is a feature of the claim, so that the issue of whether it has been shown that this effect is achieved is a question of sufficiency of disclosure under Article 83 EPC” and that “it is necessary that the patent at the date of its filing renders it credible that the known therapeutic agent, i.e. the product, is suitable for the claimed therapeutic application”.
It therefore had to be decided whether fenfluramine as a monotherapy, i.e. as the sole therapeutic
agent, could be considered suitable for the treatment of Dravet syndrome at the relevant date. As
decision G 2/21 further explains, in point 77 of the Reasons:
“[i]n order to meet the requirement that the disclosure of the invention be sufficiently clear and complete for it to be carried out by the person skilled in the art, the proof of a claimed therapeutic effect has to be provided in the application as filed, in particular if, in the absence of experimental data in the application as filed, it would not be credible to the skilled person that the therapeutic effect is achieved. A lack in this respect cannot be remedied by post-published evidence.”
The present Board noted that the Enlarged Board endorsed the conclusions in T 609/02 (G 2/21, point 75 of the Reasons), and decisions T 754/11 and T 887/14. The expression “proof of a claimed therapeutic effect” in point 77 of the Reasons could therefore not be interpreted as a deviation from the established case law in the context of second medical uses: it did not apply a stricter requirement than the established case law prior to decision G 2/21. Rather, the Enlarged Board confirmed that means other than experimental data in the application as filed could establish proof of a claimed therapeutic effect.
What is required, however, in the absence of experimental evidence, is for the patent or the application as filed to provide some information demonstrating that the claimed compound had a direct effect on a metabolic mechanism specifically involved in the disease, this mechanism being either known from the prior art or demonstrated in the patent itself (see T 609/02, points 5 to 9 of the Reasons). With reference also to G 1/03, the Board thus concluded that a contribution to the state of the art which enabled the skilled person to carry out the invention had to be present in the application as filed.
In the absence of experimental data for fenfluramine monotherapy in the application as filed, the Board considered whether achieving the claimed therapeutic effect was made credible in the application as filed in another way. “Monotherapy” was explicitly mentioned in the application as filed as an alternative to combination therapy. However, this mere statement was not in itself sufficient to provide any “proof” in the sense of decision G 2/21.
Regarding the level of proof required, the Board noted that in view of the serious nature of the disease, additional circumstances have to be borne in mind when deciding whether “proof of the therapeutic effect” is provided in the application as filed. In this particular case, namely a very serious disease for which an established, albeit sub-optimal, therapy exists and where a wrong therapy decision could lead to irreversible damage, the level of proof required has to be at least such that the skilled person has reason to assume that the standard valproate treatment could be discontinued and replaced by fenfluramine without worsening the condition of the patient.
In the absence of experimental or clinical data in the application as filed that would indicate that a fenfluramine monotherapy had a therapeutic effect, the Board further considered whether the application as filed or the prior art established a direct effect by fenfluramine on a metabolic mechanism specifically involved in the disease. It concluded that, at the filing date, it was far from established whether the greater number of seizure-free patients with Dravet syndrome who were treated with fenfluramine as an add-on therapy resulted from increased serotonin levels, and importantly, the skilled person could not derive from the experimental data in the patent or the application as filed whether fenfluramine was able to exert its beneficial effect alone.
Since “proof of the therapeutic effect” is not provided in the application as filed, the Board also considered whether the teaching of the prior art provided the skilled person with any indication of a therapeutic effect of fenfluramine as a monotherapy for Dravet syndrome. In view of the established use of fenfluramine in combination with other anti-convulsive medicaments, and the very different nature and isolated cases of the two epileptic diseases for which monotherapy with fenfluramine was reported, the skilled person could not draw any conclusions as to the effectiveness of fenfluramine as a monotherapy for Dravet syndrome.
From the technical teaching of the application as filed, even taking into account the prior art, it was not credible that fenfluramine achieved a therapeutic effect in Dravet syndrome patients when given as a monotherapy. In line with decision G 2/21, the Board did not take the post-published data into account (see Reasons, point 77).
Relevant holdings in relation to Pharmaceutical Patents:
The Enlarged Board in G2/21 did not apply a stricter requirement than the established case law prior to this decision with regard to sufficiency of disclosure (Article 83 EPC) - means other than experimental data in the application as filed can establish proof of a claimed therapeutic effect.
In the absence of experimental evidence, the patent or the application as filed must provide some information demonstrating that the claimed compound had a direct effect on a metabolic mechanism specifically involved in the disease, either known from the prior art or demonstrated in the patent itself; a contribution to the state of the art which enables the skilled person to carry out the invention has to be present in the application as filed.
A mere statement is not in itself sufficient to provide any "proof" in the sense of decision G 2/21. However, regarding the level of proof required, additional circumstances may be borne in mind when deciding whether "proof of the therapeutic effect" is provided in the application as filed (in the case in hand, the serious nature of the disease).
It can be considered whether the application as filed or the prior art establishes the claimed therapeutic effect, or whether the teaching of the prior art provides the skilled person with any indication of a therapeutic effect.
Post-published evidence was not taken into consideration in the case in hand, in line with G2/21, point 77 of the Reasons.
Relevant legislation: Articles 83,100(b), 100(c) EPC