T 0816/22 - Even more than plausibility is required

Key points

• With all the attention for G 2/21 r.74 (which requires the application as filed to make the claimed therapeutic use credible), it is easy to overlook that even more is required for second medical use claims. 
• The opponent had filed post-published evidence of failure of clinical trials with the (example) compound of the invention: "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"."
• Why would the opponent oppose if the compound ("Cinryze") failed in the clinical trials? Perhaps because claim 1 is not limited to a specific compound and reads: " Claim 1 of the main request reads as follows: "1. A C1 esterase inhibitor (C1-INH) for use in a method of treating antibody-mediated rejection (AMR) of an organ allograft in a patient in need thereof, wherein the method comprises intravenous administration of the C1-INH at a dose of 5,000 units to 20,000 units given in divided doses over 10 to 20 days, and wherein the organ is kidney.""
• The Board: "The board therefore concludes that the only relevant data in the patent are finding CG [a type of rejection of the organ allograft]  in 1 out of 7 patients in the Cinryze arm [treatment arm] compared with 3 out of 7 patients in the placebo arm"
• "In view of the small number of patients, the opponent considered that a treatment effect had not been demonstrated. The board, however, does not deem it necessary to establish this and instead starts from the assumption that the opposition division was correct in finding that the experimental data provided in the patent (see above), together with the mechanistic explanation provided in paragraphs [0032] to [0039] and Figure 1, 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 is not enough to demonstrate that the invention is sufficiently disclosed if the opponent provides evidence which raises serious doubts that the therapeutic effect can indeed be achieved (see below)."
• "Post-published documents D15, D16 and D54 relate to the phase III clinical trial NCT02547220 (SHP616-302), which was carried out using the same dosage regimen as in the examples of the patent and falling under the terms of the claim"
• " Document D54 shows the complete absence of any therapeutic effect with the claimed dosage regimen. "
• " In conclusion, a phase III clinical trial with the same setup as the examples in the patent and using the dosage regimen which is 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 has not dispelled the serious doubts regarding the presence of a treatment effect in view of these data. Therefore, the invention as claimed is not reproducible."
• "The board therefore considers that the patent does not disclose the claimed invention in a manner sufficiently clear and complete for it to be carried out by a person skilled in the art (Article 83 EPC)."
• Question: can the proprietor file post-published evidence that the invention works? E.g. for another C1 esterase inhibitor than Cinryze?

EPO 

The link to the decision can be found after the jump.

https://www.epo.org/en/boards-of-appeal/decisions/t220816eu1