An appeal was lodged against the decision of the OD to revoke the European patent No. 2 173 379. The claims of the patent concerned a monoclonal antibody that was functionally defined as capable of disrupting binding of a protein called RSPO to a receptor called LGR5, which had the effect of disrupting of LGR5 signaling, thus leading to growth inhibition of a tumor type.
The OD decided that the subject matter of the concerned claims failed to meet the requirements of Art. 83 EPC (sufficiency of disclosure). In particular, based on a publication cited by the Opponent, the OD considered that the cells used in the examples of the patent (known as HEK293 cells) did not express the receptor LGR5. Hence, the OD concluded that the application's experiments could not show an interaction between RSPO and LGR5 and that, therefore, it was not plausible that the antibodies were functional as defined in the claims in inhibiting tumour growth.
In Appeal, the P argued that the impugned decision solely relied on a single research article (with supplementary information) D14/D15, and was contradicted by another document D25, which showed that LGR5 mRNA was present in the HEK293 cells but was dismissed by the OD. According to the P, the OD incorrectly dismissed D25 and “no convincing evidence had been provided to doubt that an […] antibody as claimed could be used to inhibit solid tumor growth”.
To assess the issue of sufficiency of disclosure, the Board of Appeal (BoA) decided that it was crucial to consider whether it could be accepted that all HEK293 cells did not express a functional LGR5 protein. Following the established case law of the boards (CLBA, sections II.C.5.3., II.C.7.1.4 and II.C.9), the BoA concluded that the objection of lack of sufficient disclosure would only hold if the invention gave rise to serious doubts that were substantiated by verifiable facts.
Hence, the BoA re-evaluated the text and examples of the application as filed, and the evidence provided in documents D14/15 and D25. In view of the experimental data of the application as filed and the reports in D25, the BoA concluded that D14/D15 did not summarise the state of the art with respect to LGR5 expression in all HEK293 cells, and that it did not report that LGR5 had never been detected in HEK293 cells. Thus, they concluded, D14/15 did not qualify as an account of the common general knowledge in the art as regards LGR5 expression in HEK293 cells, but rather presented an isolated finding, especially in view of contradictory reports in document D25. The cause underlying this discrepancy between both research articles was deemed irrelevant for the issue at stake in this decision.
Next, the BoA expressed that they did not agree with the OD that the negative data of document D14/D15 should be given a “much higher weight” over the positive data in document D25, merely because document D14/D15 also studied the expression of similar other LGR proteins in HEK293 cells.
The BoA acknowledged that D25 talked merely about detection of LGR5 mRNA in the HEK293T cells and was silent about LGR5 protein expression, but they also pointed that the skilled person would be aware that proteins are synthesised using the information in mRNA as a template. Consequently, the BoA agreed with the P that the reasonable conclusion was that LGR5 protein had likely been present in the HEK293 cells of D25.
For these reasons, the BoA concluded that it could not be established that all HEK293 cells do not express functional LGR5 protein. Accordingly, no serious doubts existed as to whether these cells expressed functional LGR5 protein. Therefore, the BoA concluded that OD’s reasoning that was solely based on the assumption that HEK293 cells do not express LGR5, could not hold.
Based on the evidence on file and the arguments presented to it, the BoA concluded that the invention as claimed was sufficiently disclosed and, hence, fulfilled the requirements of Article 83 EPC. The decision under appeal was, consequently, set aside and the case was remitted to the OD for further prosecution.