Updates

EPO Raises the Plausibility Threshold when Assessing Inventive Step

28 July 2017

In a decision which has significant implications for the pharmaceutical and biotechnology industries, a Board of Appeal at the European Patent Office has issued decision T 488/16 revoking Bristol-Myers Squibb’s (BMS) European patent no. EP1 169 038 relating to anti-cancer therapies.  The key compound covered by this patent was dasatinib (sold as Sprycel®), which is an anti-cancer drug with an annual turnover in excess of US$ 1 billion.  Such was the interest in this case, the European Federation of Pharmaceutical Industries and Associations (EFPIA) submitted observations to the Board of Appeal in favour of BMS’s position.

The claims under appeal were found to lack an inventive step in a decision which hinged on the existence of very limited experimental evidence provided in the application as filed, and whether this was sufficient to render it plausible that the claimed compounds could be effective in treating cancer.
 
The patent application as filed was directed to new chemical compounds defined by a broad generic formula.  580 individual compounds were exemplified in the application, including dasatinib, which was the sole compound recited in the claim under appeal.  The disclosed compounds were stated to be inhibitors of various protein tyrosine kinases (PTKs), and therefore potential anti-cancer agents.
 
No numerical data were present in the application to confirm that any of the exemplified compounds had been tested, or that they possessed the asserted PTK inhibitory activity.  The only information present in the application as filed regarding the efficacy of the compounds was the following statement:
 
Compounds described in the following Examples have been tested in one or more of these assays, and have shown activity”.
 
The Board focused on the absence in the application of any quantitative results, or of any specification of the particular assay or test conditions that had been used to determine the stated activity.  They concluded that, in the absence of verifiable technical evidence, the above statement was not sufficient to render it credible that the technical problem which the application purports to solve, namely providing PTK inhibitors to treat diseases such as cancer, is indeed solved. 
 
When appealing the Opposition Division’s earlier revocation decision, BMS sought to maintain the patent as amended to contain a single claim directed solely to dasatinib (and salts thereof). The novelty of the claim was never in doubt.  Moreover, the cited prior art did not disclose any compounds that were structurally similar to dasatinib.  Nevertheless, dasatinib was not singled out in the application as being of particular interest, nor were any relevant data provided for this compound.  This narrow claim was therefore found to lack an inventive step on the grounds that the mere provision of a new chemical compound without showing any technical effect was considered an arbitrary choice which does not require inventive ingenuity.
 
During prosecution of the application, BMS had sought to remedy the issue of the lack of data in the application by filing post-published evidence of the claimed compound’s biological activity.  However, during opposition and subsequent appeal proceedings, both the Opposition Division and the Board of Appeal indicated that, in line with established case law, they could not take this evidence into consideration as it was not plausible from the application as originally filed that the technical problem that the application purported to solve was indeed solved.  
 
As a contributing factor, the Board also highlighted the fact that the post-published evidence indicated that several compounds of the examples were inactive at certain concentrations, thus further weakening the value of the statement regarding activity in the application as filed.
 
BMS filed declarations from two expert witnesses, and an inventor declaration, in part to demonstrate that a useful pharmacophore could be identified from the compounds exemplified in the application.  Nevertheless, the Board dismissed these submissions based on the facts of the case stating that no structure-activity relationships could be drawn in view of the complete absence of any data.
 
Following established case law, the Board confirmed that it was necessary to establish whether or not it was sufficiently plausible for dasatinib to possess the asserted activity at the effective filing date of the application.  This assessment must be based upon the information in the application as filed and the common general knowledge available to the skilled person at the time of filing.  
 
The Board considered the inventor’s declaration to be irrelevant as it concerned information that was only available to BMS.  Although it referred to results which had been obtained before the filing date, these results were neither present in the application as filed nor had they been provided to the EPO during the examination proceedings.
 
The Boards accept that plausibility is a threshold test which must be satisfied by a credible disclosure, and this decision gives further insight into where that threshold lies in the eyes of the EPO.  Importantly, the Board reiterated that it is not essential that the application contains experimental data or results, provided the nature of the invention is such that it relies on a technical effect which is either self-evident or predictable or based on a conclusive theoretical concept.  Nevertheless, they indicated that it is not sufficient to merely assert that the technical problem the application purports to solve is indeed solved, but “verifiable evidence” should be present in the application as filed.  Patentees should also avoid relying solely on post-filed evidence to rebut inventive step objections of this type, but should consider carefully what evidence should be provided in an application upon filing.
 
It may also be worthwhile considering filing parallel national applications for particularly important technologies where only sparse data is available at the filing date.  National applications may be subject to a different level of scrutiny and so may be granted with a broader claim scope.
 
For opponents, this decision adds another valuable tool for attacking patents, particularly in the pharmaceutical and biotechnology fields. 
 
For more information, please contact your normal Potter Clarkson representative.

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