The effect of post-published clinical trial outcome on plausibility

The Board in T 0816/22 assessed whether post-published phase III clinical trial data can render the claims insufficiently disclosed, even though the therapeutic effect of a second medical use claim was deemed plausible based on the application as filed.

Background

The decision under appeal T 0816/22 related to the Opposition Division’s [OD] decision to maintain EP3071219 in amended form based on Auxiliary request 4. Claim 1 as maintained contained a specific dosage regimen and read as follows:

‘’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 a dosage regimen consisting of 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."

Both the patent proprietor (P) and the opponent (O) appealed this decision. The appeal centered on whether the patent made the therapeutic effect of C1-INH in treating AMR sufficiently plausible at the time of filing, and whether later clinical data invalidated this premise.

The patent application contained data from a Phase II clinical trial involving kidney transplant recipients treated with Cinryze. According to the patent application, the results demonstrated a reduction in chronic glomerulopathy (CG), with one out of seven patients in the Cinryze group showing signs of CG compared to three out of seven in the placebo group. This finding, combined with known anti-inflammatory properties of C1-INH and its mechanistic rationale, was used by P in support of plausibility of the claimed therapeutic effect.

However, O introduced post-published Phase III clinical trial data. Said trial followed the same dosage and administration regimen as described in the patent but failed to show any statistically significant therapeutic benefit. After six months, transplant glomerulopathy rates were comparable between the experimental and placebo groups. The trial was terminated because it was unlikely to meet its predefined efficacy endpoints.

P argued that regulatory standards, which are designed for clinical trial endpoints, do not necessarily translate to technical insufficiency under Art 83 EPC. They maintained that patents do not require full clinical trials to demonstrate therapeutic effect and meet the requirements of Art 83 EPC. Early data and mechanistic insights should suffice to support plausibility. P further speculated that the short six-month observation period in the Phase III trial may not have been adequate to observe the full therapeutic potential of C1-INH, suggesting a longer-term benefit might yet be revealed.

O emphasized that sufficiency of disclosure must cover the entire scope of the claim and that the Phase III data cast serious doubt on whether the invention works across that scope. 

The Board of Appeal [the Board] agreed with the opponent’s position. It acknowledged that 

Since this new evidence directly contradicted the original claim and the patent proprietor could not dispel these doubts—relying instead on hypothetical outcomes and speculative interpretation—the Board concluded that the patent failed the sufficiency test.

Decision of the Board

The requirements of Art 83 EPC were considered not met and the Board decided to revoke the patent. 

For the footer: Summary written by the NLO EPO Case Law Team