Key decisions in EU patent disputes from the EPO and UPC: June edition

Part 1 – T 1639/21 - Obviousness of a synergistic effect at the EPO

Relevance of these decisions
Both in the field of pharmaceuticals and herbicides, inventions directed to combinations of two (or more) active agents play an important role. Specifically in the field of pharmaceuticals with typically long clinical development phases, combination inventions represent an important element of a successful patent life cycle management for the active agents. Also, in many clinical indication fields, such as oncology, combination therapies represent important, clinically approved treatment regimens.
In a significant number of cases relating to combination inventions at the EPO, the aspect of a “synergistic effect” provided by the combination of two or more active agents plays a role when assessing inventive step at the EPO.

In view of both the medical and commercial importance of combination inventions in the field of combination inventions, decisions of the Board of Appeal providing new insights on the assessment of inventive step in case of a synergistic effect are of interest. The present decision T 1639/21 of March 13, 2024 provides such new insights.

General Principles
A synergistic effect of a combination of two (or more) active agents, is acknowledged by the EPO if the functional interaction between the agents achieves a combined technical effect which is different from, and typically greater than, the sum of the technical effects of the individual agents (see Guidelines for Examination at the EPO, Part G – Chapter VII-21, section 7, for combination of features in general). If no such synergistic effect exists, there is, according to the EPO Guidelines, “no more than a mere aggregation of features”.

Demonstrating a synergistic effect for a combination of active agents is often a promising approach for arguing in favour of inventive step at the EPO, by referring to the synergistic effect as technical effect which would not have been expected by the skilled person. In this context, Case Law of the Boards of Appeal book, which represents the assembly of decisions considered most important by the Boards of Appeal, discusses a single decision in a specific subsection D-9.9.6 on synergistic effects in the context of inventive step (T 1814/11) where it was found that “[s]ynergy was not in principle foreseeable and therefore could not be attributed to a specific mechanism of action and/or structure”.

The Decision and Reasons
In the opposition case underlying the present invention, a combination of an antagonistic anti-PD1 antibody and an mRNA vaccine was claimed. Such antagonistic anti-PD1 antibody is also known as so-called checkpoint inhibitor. Checkpoint inhibitors are generally known to counteract an inhibition of the immune response, i.e. the immune system checkpoint blockade. An mRNA vaccine, in turn, aims at eliciting an immune response in the treated persons.

When assessing inventive step, the closest prior art document, as most promising springboard, was also concerned improving the effectiveness of an mRNA vaccine by combining it with a different checkpoint inhibitor: an anti-CTLA-4 antibody instead of an anti-PD1 antibody.

After concluding that the data on file did not convincingly show a significantly increased therapeutic effectiveness of the claimed vaccine/inhibitor combination over the closest prior art combination with a different checkpoint inhibitor, the Board assessed the patent proprietor’s further argument that there was a synergistic interaction between the mRNA vaccine and the PD-1 inhibitor in terms of a more than additive increase in therapeutic effectiveness (Reasons 15).

Notably, the Board stresses in this context that the mechanisms of action of the single agents of the combination have to be assessed for evaluating the synergistic effect (Reasons 15).

Considering the above-mentioned mechanisms of action of the single agents, the Board finds that an anti-immune checkpoint antibody, such as the anti-PD1 antibody in the claim, “on its own, does not have a direct effect on the tumour; it only counteracts the immune system checkpoint blockade”. According to the Board, “releasing this blockade can only have a therapeutic effect in combination with an existing immune response, which can either come from the immune system itself which recognises the tumour as “non-self” or be stimulated by a vaccine”. The Board makes the analogy of “releasing a break” by administering the checkpoint inhibitor (Reasons 16).

Taking into account these mechanistic actions, the Board found a synergistic effect to be supported by the data in the patent (which show that the combined effect of an anti-PD-1 antibody and a tumour antigen mRNA vaccine is greater than the sum of the individual effects).

However, the objective technical problem, formulated as providing a further synergistic mRNA vaccine/immune checkpoint inhibitor combination, was found to lack an inventive step in view of the closest prior art document. The Board argued that the “synergistic effect of the components of the claimed vaccine/inhibitor combination does not arise by a direct molecular interaction but by an indirect interaction, namely the release of an immune checkpoint block which allows an effective immune response to the vaccination” (Reasons 45).

The Board also discussed mechanistic differences between the checkpoint inhibitors in question, i.e. the anti-PD1 antibody on the one hand, and the anti-CTLA-4 antibody on the other hand (the former acting more limited and the latter acting more broadly on signalling cascades). However, in view of prior art documents showing synergisms for combinations of an anti-PD1 antibody with other type of cancer vaccines, the Board concluded that “the skilled person had a reasonable expectation that anti-PD-1 antibodies achieve a synergistic effect when combined with an mRNA vaccine” (Reasons 49).

In this context, the Board expressly denied an “automatic inventiveness” approach provided by a synergistic effect due to a “synergistic effect [being] per se unpredictable” as found in decision T 1814/11 and several further decisions (Reasons 62, 63).

As set out in Reasons 68 and 69, “as for any other [technical] effect, it has to be established whether, having regard to the state of the art, obtaining a synergistic effect was obvious”. The board states that “the finding that the synergistic effect could be reasonably expected to occur depended on the skilled person's fundamental understanding of the mechanistic relationship between the mRNA vaccine and the antibody targeting an immune checkpoint […] and not on any structural elements of the compounds under consideration.”

Take Home Messages
In the above decision, the Board found that a synergistic effect of a combination does not automatically lead to the acknowledgement of inventive step. Rather, the Board finds that inventive step is to be denied in case a synergistic effect - as in case of any other technical effect relied on by Patentees when arguing in favour of inventive step – could have been reasonably expected in view of the prior art. In this context, mechanisms of actions are to be taken into consideration.

The present decision raises the bar for applicants at the EPO for inventive step based on a synergistic effect.

When drafting patent applications in the field of combinations of active agents, care should be taken to include suitable fall-back positions to ensure that more limited combinations may be considered inventive, even if the broader claims should be considered obvious. In prosecution and opposition proceedings, Patentees should be prepared to present consistent and convincing argumentations as to why the mechanisms of actions of the single agents would not provide bases for a reasonable expectation of success for the synergistic effect. For Opponents, in turn, the present Decision may offer a good corroborating attack to combination claims.

Part 2 – UPC Court of Appeal confirms strict approach to stays versus pending EPO oppositions

Relevance of decision
How UPC and EPO oppositions proceedings interact and impact each other has been a closely watched issue during the UPC’s first year. However, not many cases have arisen, nor (thus far) have any seriously challenged the progression of UPC proceedings.

This was so in one of the cases, Carrier v BITZER, a revocation action before the Paris Central Division. After the denial of the stay at first instance, the Court of Appeal has recently upheld that outcome.

As a ‘non-technical’ appeal, the UPC Court of Appeal has also continued its precedent of hearing this sort of appeal with a panel of 3 legally qualified judges only (despite claims by the appellant that the issue of appointing 2 further technically qualified judges should be referred to the CJEU for clarification).

The Decision and Reasons
These proceedings concern UPC and EPO proceedings closely in parallel – with BITZER filing its UPC revocation the day after its EPO opposition at the end of June 2023.

The Appellant (and patentee), Carrier, requested a stay of the UPC revocation proceedings commenced by BITZER pending the outcome of parallel EPO opposition proceedings. In particular, Carrier did so shortly after filing a request to accelerate the EPO proceedings.

Carrier’s main argument was that it was “procedurally inefficient” for it to have to litigate in parallel when the EPO opposition entirely addressed and subsumed the subject matter of the UPC revocation action.

BITZER countered by pointing to the slow speed of EPO proceedings, and succeeded in convincing the Paris Central Division to reject the stay.

In its appeal, Carrier raised procedural and substantive points, complaining that it did not have the opportunity to reply to BITZER’s comments. It also argued that the acceleration of the EPO proceedings was not fairly taken into account and that the timeframes relied on by BITZER to suggest EPO proceedings were slow were skewed by the delays during the COVID-19 pandemic.

Ultimately, the decision came down to whether the EPO proceedings were sufficiently “rapid” according to Article 33(10) UPCA (or expected “rapidly” under RoP 295). The Court of Appeal swiftly dismissed arguments that either the overlapping duality of EPO and UPC proceedings or that they might come to different outcomes was significant such to lead to any exception.

When it came to assessing the parallel proceedings, the EPO proceedings (including due to the availability of the parties) had been settled in October 2024, compared to a July 2024 date for UPC trial. This in particular seemed fatal to the appellant’s position, and the rejection of their application for a stay was, in the end, firmly upheld.

Given the progression of the UPC proceedings in the meantime and with trial so close, this also weighed heavily against the appellant. In this respect, there is a sense in the UPC Court of Appeal’s decision that the UPC action was so close to trial that it should naturally go ahead, without significant further costs or burden. This highlights that the momentum built by UPC proceedings is significant, including as in this case, when it continues without suspension or pause pending interim appeals. In this case, it made the UPC’s momentum all but unstoppable and an outcome in favour of progression almost self-fulfilling.

Take Home Messages
The decision emphasises that the UPC has discretion when it comes to granting stays versus EPO proceedings. And first instance EPO oppositions proceedings commenced in close parallel with a UPC action, even if accelerated, seem to stand little chance of staying the UPC action. There is no question that a UPC action has significant momentum, which is a principle seen in a number of the UPC’s case management decisions.

Of course, by proceeding with parallel revocation actions in the fora, the opponent hedges their bets. And in closely running parallel actions such as this, it now remains to be seen how quickly the UPC’s decision will be delivered following the July 2024 trial, and how influential and/or consistent it will be with the approach and decision of the Opposition Decision (due simultaneously at the October 2024 hearing).