Reproducibility isn’t enough: European Patent Office demands problem-solving proof over closest prior art

The decision relates to European patent 3 468 568 pertaining to a pharmaceutical preparation comprising a fraction that is enriched for human platelet lysate derived extracellular vesicles for use in medicine, in particular in the treatment and/or prevention of specific diseases.

An opposition was filed against the patent on the grounds that its subject-matter lacked novelty and inventive step and it was not sufficiently disclosed. The opposition division took the decision to revoke the patent for lack of inventive step of auxiliary requests 9 and 10 starting from document D9 as closest prior art in combination with common general knowledge.

The patent proprietor/appellant filed an appeal against the above decision of the opposition division. With their statement setting out the grounds of appeal, the appellant defended their case on the basis of auxiliary request 9 as the main request, and on the basis of auxiliary request 10, both filed during the opposition proceedings and resubmitted with the statement setting out the grounds of appeal. Further auxiliary requests 11 and 12 were newly filed by the appellant during the appeal proceedings.

Claim 1 of auxiliary request 9 read as follows: “Pharmaceutical preparation comprising a fraction that is enriched for human platelet lysate derived extracellular vesicles for use in the prevention and/or treatment of inflammatory driven diseases, immune/autoimmune diseases, transplant rejections, or Graft-versus- Host Disease, wherein the human platelet lysate originates from pooled donor-donated platelets.”

Claim 1 of auxiliary request 10 corresponded to claim 1 of auxiliary request 9 wherein the feature “of at least 15 donors” was added at the end of the claim to further specify the pooled donor-donated platelets.

Claims 1 of auxiliary requests 11 and 12 corresponded to claims 1 of auxiliary requests 9 and 10 respectively wherein the feature “inflammatory driven disease” had been deleted from the list of diseases.

Oral proceedings were held before the Board of Appeal on 24 June 2025. 

On the admissibility of auxiliary requests 9 and 10, the Board decided that the requests form part of the appeal proceedings as these auxiliary requests were admitted in the opposition proceedings and formed part of the decision under appeal.

On the inventive step of auxiliary claim 9, the Board considered in line with the respondent’s arguments that D9 – and not D17 or D19 – represented the closest prior art. The Board found that in line with established case law, the criterium of being directed to the same purpose or effect as the claimed invention is central when determining the closest prior art. In this respect, D9 disclosed the use of microvesicles in the treatment of inter alia inflammation and inflammation driven diseases as well as autoimmune diseases, diseases associated with graft rejection and graft versus host disease, while D17 or D19 did not directly and unambiguously disclose the treatment of such diseases.

The subject-matter of claim 1 of auxiliary request 9 differed from D9 in that the human platelet lysate originates from pooled donor-donated platelets. Furthermore, it also differed in that D9 does not disclose the specific combination of human platelet derived extracellular vesicles with the presently claimed diseases.

The appellant stated that human platelet derived extracellular vesicles had anti-inflammatory and immunosuppressive activity as substantiated in the patent and post-published data. The Board agreed that anti-inflammatory and immunosuppressive effects had been described in the application as filed but no experimental data were provided in the patent. Anti-inflammatory and immunosuppressive effects were experimentally substantiated with the post-published data, however, no particular effect over the microvesicles of the closest prior art D9 had been provided.

The Board further observed that none of the experimental data on file was suitable to substantiate the effect that the pooling of platelets would reduce variability and hence provide more reliable efficacy. No comparison with the absence of pooling was performed. Furthermore, a direct and necessary correlation between reduced variability and more reliable efficacy had not been substantiated.

Starting from D9, the objective technical problem thus resided in the provision of a microvesicles preparation having reduced variability for use in the treatment of inflammatory diseases, autoimmune diseases, diseases associated with graft rejection and graft versus host disease. However, as deemed by the Board, in the absence of any particular effect relative to D9’s alternatives, the choice of human platelet derived extracellular vesicles for use in the present treatments amongst the various equally disclosed options described in D9 represented an arbitrary choice, which did not require any inventive skills.

Finally, the pooling of samples was not interrelated with the choice of human platelet derived extracellular vesicles for the specific claimed diseases and could be assessed separately. This feature was not linked to any particular effect beyond the reduction of variability, which was considered to be established from common general knowledge. Furthermore, the pooling of specifically human platelet derived extracellular vesicles had already been routinely done in the prior art as substantiated by D5. This feature would therefore have appeared obvious to the skilled person.

Accordingly, the Board decided that the subject-matter of claim 1 of auxiliary request 9 did not comply with the requirement of inventive step.

For similar reasons, the board also decided that the claims of auxiliary request 10 did not involve an inventive step. Auxiliary requests 11 and 12 were likewise found to lack an inventive step since the deletion of the feature “inflammatory driven disease” of the claim did not lead to any further distinguishing features in addition to those identified in the case of auxiliary requests 9 and 10.

In view thereof, the appeal was dismissed. 

This decision emphasizes the importance of comparative data in obtaining robust patent protection. Even if a prior art solution has not been clinically advanced or widely used in practice, it appears from the EPO’s decision that patent applications in the field of life-sciences are more likely to succeed when they demonstrate that the invention addresses a specific problem and shows a particular technical effect over existing solutions – whether or not those solutions have been clinically tested or fully realized in the market.

In other words, reproducibility is only part of the story. While demonstrating that your invention works is critical, proving that it offers a technical advance over what is already known is also essential. This is especially relevant in the field of advanced therapies such as extracellular vesicles (EVs), where innovations can be groundbreaking, but comparative efficacy data may not always be available.

If you’re currently in the process of seeking patent protection for an invention in this field, consider revisiting your application to ensure that you are presenting the necessary comparative data. If you’re in the early stages, think about designing experiments that will help demonstrate your invention’s superiority in the context of existing competing technology, even if the latter is not fully developed or clinically tested.

Our experienced team of European patent attorneys at De Clercq & Partners is willing to help you select the most suitable ways to protect your inventions in the field of advanced therapies and broader in the life-sciences field. You can reach out to us at info@dcp-ip.com.