7. The requirement of sufficiency of disclosure in the biotechnology field

In T 883/23 the board had to decide whether claim 1 of the main request was entitled to claim priority from the earliest priority application (P1). P1 disclosed a method for treating pancreatic cancer in a human subject who has not previously received chemotherapy involving the administration of MM-398 liposomal irinotecan, wherein the liposomal irinotecan was administered in combination with oxaliplatin, leucovorin and 5-fluorouracil (claim 3). P1 defined doses of 60 or 80 mg/m2 liposomal irinotecan (claim 5) and 60, 75 or 85 mg/m2 oxaliplatin (claim 8)..

Example 4 of the patent presented the results of a dose escalation/de-escalation study demonstrating the tolerability of the selected dose combination of claim 1 of the main request, as opposed to the intolerable and thus unsuitable alternative dose combinations defined in claims 5 and 8 of P1. The board observed that information concerning the tolerability of the selected dose combination of claim 1 of the main request was not revealed in P1. In particular, this information was not provided by the mere outline for the dose escalation/de-escalation study in P1, which the patent proprietor relied on as a pointer to the subject-matter of claim 1 of the main request with reference to T 1261/21. The board noted that in T 1261/21 the competent board had explained that a "pointer" in an original disclosure was an implicit or explicit indication or hint towards a combination of features, which demonstrated that this combination of features did not represent an arbitrary combination of features only conceptually comprised, but was actually envisaged in the original disclosure. However, the competent board had emphasised that what information a skilled person would directly and unambiguously derive from the original disclosure remained to be assessed on a case-by-case basis.

According to the board, in the present case, P1 provided with the outline for the dose escalation/de-escalation study only a conditional proposal for the use of a combination of 60 mg/m2 liposomal irinotecan and 60 mg/m2 oxaliplatin as part of a study still to be carried out. This proposal could not be considered to provide any pointer to the combination of 60 mg/m2 liposomal irinotecan and 60 mg/m2 oxaliplatin uniquely tolerable in first-line treatment of patients with metastatic pancreatic cancer as defined in claim 1 of the main request.

The board rejected the patent proprietor's argument that P1 described the same subject-matter as defined in claim 1 of the main request, which should in accordance with G 2/98 therefore benefit from the priority of P1, regardless of any additional technical effects, such as the results of the dose escalation/de-escalation study, which may have been described only in the subsequent application from which the patent was derived. The board observed that, according to the established jurisprudence of the Boards of Appeal, attaining the claimed therapeutic effect was regarded as a functional technical feature of claims in the format of Art. 54(5) EPC. Notably, the tolerability of the defined treatment was a prerequisite for the therapeutic efficacy (T 2506/12). The tolerability of the dose combination as defined in claim 1 of the main request, as opposed to the intolerability of the alternative combinations with higher doses of claims 5 and 8 and the dose escalation/de-escalation scheme in P1, was thus a functional technical feature of the subject-matter defined in claim 1 of the main request. This feature concerned information which was not directly and unambiguously derivable from P1.

The board further observed that the Enlarged Board determined in G 2/98 that it is a condition for the compliance with the requirement of "the same invention" that the claimed subject-matter is directly and unambiguously derivable from the earlier application. However, the Enlarged Board did not conclude that the requirement of "the same invention" is necessarily satisfied if this condition is fulfilled, irrespective of any technical information associated with the claimed subject-matter, which is only described in the subsequent patent application. Notably, the established jurisprudence confirmed the need for sufficient disclosure of the claimed invention in the priority document.

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.

In case T 816/22, the patent contained data from a randomised, double-blind, placebo-controlled pilot study to evaluate the safety and efficacy of Cinryze (C1 esterase inhibitor [human]) for the treatment of acute antibody-mediated rejection (AMR) in recipients of donor-sensitised kidney transplants.

The patent proprietor had alleged inter alia that for medical use claims, the patent had to disclose the suitability of the product to be manufactured for the claimed therapeutic application. Clinical trials were not required to establish such suitability.

According to the opponent, D54 (clinical trial results) represented the best available evidence concerning the efficacy of the claimed treatment and it demonstrated a complete failure to provide any therapeutic effect. The opponent alleged also that it could not be expected that an opponent had to conduct even more comprehensive clinical studies than a phase III trial in order to discharge its burden of proof of insufficiency. The disclosure of a patent was insufficient if the invention could not be reproduced across the whole breadth of the claims. Even a plausible disclosure of a therapeutic effect (which was missing in the present case) still had to be subject to refutation by evidence that the therapeutic effect was not in fact attained (which was provided by documents D15, D16 and D54), the standard of proof being "serious doubts, substantiated by verifiable facts".

In view of the small number of patients (clinical trial), the opponent considered that a treatment effect had not been demonstrated. The board, however, did not deem it necessary to establish this and instead started from the assumption that the opposition division was correct in finding that the experimental data provided in the patent, together with the mechanistic explanation provided, made it plausible (or credible) to the skilled person at the time of filing that a therapeutic effect on AMR could be achieved; however, this in itself was not enough to demonstrate that the invention was sufficiently disclosed if the opponent provided evidence which raised serious doubts that the therapeutic effect could indeed be achieved.

Post-published documents D15, D16 and D54 related to the phase III clinical trial. Due to the termination of the trial after 36 months, data was not collected, analysed and reported for any of the secondary endpoints related to efficacy (see D54). The patent proprietor argued that the termination of the trial was a commercial decision which did not mean that there was no therapeutic effect of any kind.

To the board, what was crucial was whether the skilled person, with the teaching of the patent in hand and applying common general knowledge, was able to reproduce the invention, i.e. to achieve a therapeutic effect on kidney transplant AMR when administering C1-INH intravenously using the dosage regimen indicated in the claim and identified in the presently discussed embodiment. The board agreed with the patent proprietor that therapy was not limited to completely curing a disease or condition, but also included alleviating, removing or lessening the symptoms of any disorder or malfunction of the human or animal body.

D54 showed the complete absence of any therapeutic effect with the claimed dosage regimen. For the very parameter that was considered "a clinical marker of AMR in a transplant patient" in the patent, D54 found no effect for a larger patient cohort. The board considered this sufficient to raise serious doubts based on verifiable facts that the claimed treatment achieved a therapeutic effect. In view of this evidence, it was not sufficient for the patent proprietor to refer to potential beneficial effects that might arise when following up with patients for a longer period of time.

In conclusion, a phase III clinical trial with the same setup as the examples in the patent and using the dosage regimen which was an embodiment of the claim could not reproduce the claimed subject-matter as exemplified in the embodiment under discussion as it did not exhibit any efficacy after 36 months. The patent proprietor had not dispelled the serious doubts regarding the presence of a treatment effect in view of these data. Therefore, the invention as claimed was not reproducible.