CABINET CHAILLOT

Opponent 2 (appellant) filed an appeal against the decision of the opposition division that European Patent No. 2 943 507 as amended fulfilled the requirements of the EPC.
Claim 1 of the main request concerns a protein having an Fc region comprising a first polypeptide and a second polypeptide, each comprising regions of a human IgG1 immunoglobulin heavy chain, wherein in both said first and second polypeptide the amino acids at positions L234, L235, D265, N297 and P331 of the human IgG1 heavy chain, are F, E, A, N and P, respectively, and wherein a wild-type protein is identical to said protein except that in both first and second polypeptides the amino acids at positions L234, L235 and D265 of the human IgG1 heavy chain, are L, L, and D, respectively.
The prior art does not disclose IgG1 heavy chain constant regions which comprise the combination of mutations L234F, L235E, D265A in the context of N297 and P331.
The board considers the variant FE disclosed in both D10 and D21 to differ the least from the claimed subject-matter. It therefore represents the most appropriate starting point. The difference between the said FE variant and the claimed variant is that the latter includes an additional modification of D265A.
Applying the principles of G 2/21, the board does not consider that an improvement of an effect, here further reduced effector functions mediated by the Fc region, is encompassed by the technical teaching and embodied by the same originally disclosed invention merely because the effect itself (but not the improvement), was shown to be achieved in the application as filed.
The board therefore must turn to the disclosure in the application as filed to determine if the evidence for a further reduced effector function of the FEA variant compared to the FE variant reported in post-published documents D25 and D26 can be taken into account.
Figure 3A is the only figure representing an example in which the FE and FES variants of the prior art are directly compared to the claimed FEA variant. The application concludes that "incubation with FE and FES induced CD69 to a lesser extent" while "[i]ncubation of PBMCs with FEA antibodies did not induce any expression of CD69 on T-cells". The board notes that a consistent difference between the FE (or FES) and the FEA variant over a large concentration range is apparent from Figure 3A. The board considers that the differences over a large concentration range render it credible that reduced effector function, as reflected by decreased CD69 release, was achieved by the FEA variant compared to FE or FES.
In conclusion, the board considers the improved effect of decreased CD69 release of the FEA variant compared to the FEFE variant to have been credibly disclosed in the application as filed. Thus, while it is not strictly necessary to consult the evidence in documents D25 and D26, it can be noted that their disclosure supports the improved effect shown in the application as filed. 
The board therefore formulates the objective technical problem as the provision of a protein having an improved Fc region that reduces T cell activation as measured by CD69 expression and retains plasma clearance comparable to a protein with the corresponding wild type Fc region. 
While the D265A mutation is disclosed in D10 as advantageous, the FE mutation was not tested. The skilled person would not have had a reasonable expectation of success that the combination of the FE variant with D265A would result in an improvement.
Similar considerations apply if the inventive step is assessed starting from document D21. 
The additional cited documents, D6, D15 and D23, which disclose D265A as an advantageous mutation for reducing the effector function of the Fc region do not provide the skilled person with any guidance how this mutation would behave in combination with other mutations, such as L234F and L235E.
The claimed subject-matter therefore involves an inventive step (Article 56 EPC).
The case is remitted to the opposition division with the order to maintain the patent on the basis of the set of claims of the main request.