7.2.3 Evidence of therapeutic effect
While the Enlarged Board in G 2/21 (OJ 2023, A85) was predominantly concerned with inventive step, it addressed many different points of law, stating in particular that the term "plausibility" that is found in the case law of the boards does not amount to a distinctive legal concept or a specific patent law requirement under the EPC (point 92 of the Reasons). And evidence submitted by a patent applicant or proprietor to prove a technical effect relied upon for acknowledgement of inventive step of the claimed subject-matter may not be disregarded solely on the ground that such evidence, on which the effect rests, had not been public before the filing date of the patent in suit and was filed after that date (points 56 and 91 of the Reasons, concerning more specifically inventive step; see also the more general conclusion in point 90). See also in this chapter II.C.6.8. This decision does not fundamentally negate the earlier case law (see also points 72, 75 and 76 of the Reasons); it provides a framework but essentially leaves it to the boards to decide on a case-by-case basis (see also point 43 of the Reasons) concerning here post-published evidence lacking prima facie relevance, remarks from the Enlarged Board formulated in relation to inventive step.
The case law since G 2/21 generally no longer refers to the notion of plausibility, making reference instead to G 2/21, which lays down the criteria for taking post-published evidence of a therapeutic effect into account.
Among the later case law referring to G 2/21 in relation to the assessment of sufficiency of disclosure, see for example (key points stated in brackets): T 209/22 (the credibility was further corroborated by a post-published document), T 1057/22 (post-published evidence D27 merely supplemented the information provided in the application as filed – D27 was not necessary in order to consider credible the claimed therapeutic effects but only supported that conclusion) ; T 2735/19 (credibility was acknowledged, post-published evidence D11 considered and the credible therapeutic use confirmed) ; T 1796/22 (D1 contained experimental evidence that allowed the consideration of post-published D41, which confirmed the effect).
The board in T 2037/22 (proof of a claimed technical effect which is not a therapeutic effect) stressed that G 2/21 exclusively concerned the case law relative to claimed therapeutic effects.
Reiteration of the principles set out in the case law prior to G 2/21 – reference to plausibility – consequences of plausibility for whether post-published documents considered.
In T 184/16 the board recalled that a precondition for taking into account post-published evidence to demonstrate a certain effect was that it was already plausible at the filing date that said effect was obtained (seworking every day e T 488/16, T 1329/04 and T 433/05). Plausibility was acknowledged, and post-published evidence was taken into account, for example in cases where there were no "prima facie serious doubts" about plausibility (T 108/09, T 1760/11 of 13 November 2012 date: 2012-11-13, T 919/15; by contrast, in T 1329/04 there were prima facie serious doubts). In the case in hand, the application as filed did not contain any experimental evidence as regards the disputed plausibility, i.e. the plausibility of the claimed compounds being SGLT2 inhibitors. It was thus necessary to determine whether plausibility could be acknowledged in view of the common general knowledge and the prior art. The board considered it plausible that the therapeutic effect was indeed obtained. Post-published evidence D4 (comparative examples filed by the respondent/patent proprietor) could be taken into account. The fact that SGLT1 inhibition might contribute to this effect as well and was not tested in D4 was not relevant. Furthermore, the appellant (opponent) bearing the burden of proof for its assertion, the board could not conclude, in the absence of any such evidence, that compounds with large substituents were not suitable to obtain the therapeutic effect defined in claim 12. Sufficiency of disclosure was considered to be satisfied.
In T 391/18 Claim 1 of the main request was directed to a combination of active ingredients (TMC278 and a NRTI (nucleoside or nucleotide reverse transcriptase inhibitor)) for treating HIV infection in a regime of once-daily administration. The patent did not contain any evidence on combinations of TMC278 with NRTIs. The initial plausibility – in view of the common general knowledge – could not be equated with meeting the requirement of Art. 83 EPC, but nevertheless allowed the board to consider post-published evidence. Post-published document D26 (report with clinical trials for authorisation) was thenconsidered but appeared insufficient to make credible that every possible combination of TMC278 with NRTIs that were therapeutically effective by once-daily administration would be suitable for treating HIV in a once-daily dosage regime. To find suitable combinations and their corresponding doses among all the possibilities covered by claim 1, carrying out an undue amount of research was needed. In the field of pharmaceutical combinations, drug-drug interactions need to be assessed for each drug combination to find whether and at which dose the combination is therapeutically effective. Such an assessment involves clinical studies which cannot be considered routine tests. Even if, as argued by the respondent (patent proprietor), the number of NRTIs suitable for once-daily administration were not particularly high, the research required would go far beyond what may be seen as routine testing. Therefore, there existed serious doubts substantiated by verifiable facts. But claim 1 of auxiliary request 24, limited to encompass the combination tested in D26 met Art. 83 EPC.
In ex parte case T 2015/20 the examining division found that it was not plausible that aclidinium bromide was suitable for treatment of asthma. The application only presented experimental results concerning treatment of COPD (chronic obstructive pulmonary disease), whereas it was part of the common knowledge, as presented by D5, that COPD and asthma were distinct diseases with different mechanisms involved. The board observed that the information in D5 did not cast doubt on the statement in the application about the effectiveness of treatment. Concerning the post-published document D6, it merely warned that the use of "Duakllir Genuair" in asthma had not been officially authorised, which was per se not a ground for any serious doubts regarding the claimed utility of aclidinium in the treatment of asthma. In conclusion, no serious doubts could support the objection of lack of sufficient disclosure. Neither T 609/02 nor the later jurisprudence signalled a deviation from the established jurisprudence, in particular with respect to the precondition of serious doubts for a convincing argument of lack of sufficiency. The board took the view that in the present case the defined utility of aclidinium in treatment of asthma did not go against any prevailing opinion in the prior art. In this context the board considered the statement in the application, that the treatment of respiratory disorders, particularly asthma and COPD, with aclidinium was most effective upon administration by inhalation in a dosage of about 400 µg metered nominal dose to represent a significant technical teaching, which was far from an invitation to perform a research programme and which did not prima facie lack plausibility. This teaching was as such falsifiable, in the sense that it was open to challenge, and was therefore considered to represent information in the form of a specific technical contribution which went beyond some insufficient verbal statement. The board held that sufficiency was therefore not to be denied following its assessment that no serious doubts had come about with respect to the defined utility. The board turned to the examination of inventive step itself, considering in this respect also the question of plausibility.
In T 966/18, which includes detailed technical reasoning, the board was convinced that the medical use of claim 1 was plausible on the basis of several cited documents illustrating the knowledge of the skilled person, taken together with the relevant disclosure of the patent. It concluded that the body of knowledge evidenced had made the skilled person aware of a link between the reduction of α-synuclein aggregation and the treatment of Lewy body disease. Later published evidence was also taken into account and confirmed this conclusion.
On post-published documents, see also chapter II.C.6.8.
- T 0867/23
In T 0867/23 the board decided on the basis of the patent as granted (main request). Claim 1 was worded as a purpose-limited product claim in accordance with Art. 54(5) EPC. The treatment of "primary negative symptoms of schizophrenia" was a functional feature of claim 1.
The parties were in dispute regarding whether the application as filed made the claimed therapeutic effect plausible, and whether post-published evidence could be taken into account. The question was whether, on the basis of the evidence contained in the application as filed, cariprazine was demonstrated to have the claimed therapeutic effect on primary negative symptoms of schizophrenia.
In support of its reasoning, the board cited G 2/21 (point 77 of the Reasons), in which the Enlarged Board had explained that, in order to meet the requirement of sufficiency of disclosure, "[…] 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..
In the board's view, this statement of the Enlarged Board did not set a new standard for reliance on post-published evidence in the context of sufficiency of disclosure, i.e. a standard which would depart from the previously cited case law summarised in G 2/21 (as noted in T 979/23). Following G 2/21, a reliance on post-published evidence was not ruled out generally in the context of sufficiency of disclosure for second medical use claims. The reliance on post-published evidence could also not be limited to situations in which it served no useful purpose, i.e. cases in which the effect was already convincingly proven in the application to such an extent that the use of post-published evidence, as a superfluous confirmation of the already proven effect, would be of no relevance. The board explained that, in other words, the scope of reliance on post-published evidence was not zero.
In the case in hand, the board considered that the application as filed contained experimental data reflecting an effect on primary negative symptoms of schizophrenia, and thus disclosed the suitability of cariprazine for the claimed therapeutic indication (see T 609/02). Under these circumstances, the board established that post-published evidence D13 could be taken into account to back up the findings in the application as filed.
The board found that D13 confirmed the findings of the patent, and showed improvements in negative symptoms while excluding indirect effects related to positive, depressive, or EPS (extrapyramidal) symptoms as causal factor. Accordingly, D13 supported the conclusion that cariprazine was effective on primary negative symptoms and refuted the appellants' objection that the improvement could relate to secondary negative symptoms. Therefore, the criteria of sufficiency of disclosure were satisfied.