Plausibility at the EPO

Decision T 0488/16 Dasatinib/BRISTOL-MYERS SQUIB

August 2017

An inventive step requiring particular technical effect or solving a particular problem must have a plausible disclosure of having achieved that in the original specification.

EPO case T 0488/16 Dasatinib/BRISTOL-MYERS SQUIB consolidates the existing case law on “plausibility” at the EPO.  It looks at this specifically in the context of small molecule inventions where the extent of original disclosure is about how to synthesise large numbers of compounds and then test them in assays for particular biological activities indicative of medicinal utility, but without revealing any information about which compounds have which activities.  In other words, extensive disclosure of compounds and how to make and test them but no disclosure of any structure-activity relationships.  T1329/04 (Factor-9/JOHN HOPKINS) sets the standard in that an application must make it at least plausible that its teaching indeed solves the technical problem it purports to solve.  

This latest decision on plausibility highlights the hazard of filing a patent application too early; that is before a technical effect critical for inventive step is properly and sufficiently known or understood.  In a highly competitive area of innovation or research there is understandable pressure to file as quickly as possible and what was considered to be a less than adequate extent of disclosure in this case exemplifies how things can go badly wrong.  The decision is also a caution against withholding relevant essential technical information from a patent specification on filing in order to retain confidentiality and try and gain some competitive advantage. 

Plausibility at the EPO - background

Assessment of inventive step using the problem and solution analysis before the EPO is carried out as of the effective date of the patent or application, and in those cases where priority is claimed this is of course the date of filing of the priority application.  Well established EPO jurisprudence for assessment of inventive step is the question as to whether or not the objective technical problem identified in the analysis has been solved; and in instances where the scope of claim may be at issue, whether or not the problem has been solved substantially across the claimed range.

The disclosure of an invention as contained within the entire content of the original specification (and being that of the priority application where priority is claimed) is key for the assessment of the question of whether or not the problem the invention seeks to solve, has indeed been solved.  The content of the original specification, including any examples and data, is considered through the eyes of a skilled person in the field, together with the common general knowledge that person would have.   

All the above is settled law and practice.

In connection with the particular question of whether or not an objective technical problem has been solved, landmark decision T1329/04 (Factor-9/JOHN HOPKINS) sets the standard in that an application must make it at least plausible that its teaching indeed solves the technical problem it purports to solve.  Even if supplementary post-published evidence is available, this cannot serve as the sole basis to establish that the problem was solved.  In that case, the disclosure of the invention in the application was considered to consist of no more than speculation and the asserted post-published evidence of the claimed invention was considered to be the first disclosure going beyond speculation; hence it was not to be taken into consideration.

Dasatinib and the BMS patent

Dasatinib is a small molecule tyrosine kinase inhibitor sold under the trade name Sprycel as an anti-cancer drug for treatment of certain leukaemia’s.  Compounds of the alleged invention were originally disclosed and claimed by way of extremely broad Markush groups.  Within this extremely large number of compounds, 580 preferred compounds were identified from the Markush grouping, including dasatinib which formed the subject of an Example numbered 455. 

Elsewhere in the description was a list of numerous types of protein tyrosine kinase (PTK) which could be the potential targets of the claimed compounds.  Also as part of this description was explanation about how specific PTKs are associated with specific disorders.  This range of disorders included various cancer types but was much more extensive than just cancer.  A key part of the disclosure referred to assays “which can be employed in ascertaining the degree of activity of a compound (“test compound”) as PTK inhibitor”.  Such assays were generically described and referred to “protein kinase of interest” and “test compound” or “compounds of interest”. 

The 580 specific examples all concerned synthesis of the various compounds and there was no disclosure of any experimental data from the various assays described earlier in the description.

The patent claims as granted included a broad Markush grouping for the compounds per se, followed by second medical use for a range of disease states (broader than just cancer) and pharmaceutical composition claims for the compounds.  The granted patent and the fall-back positions attempted in opposition were all rejected by the Opposition Division who decided that there was no plausible demonstration at the filing date that a compound of the invention was a protein tyrosine kinase inhibitor suitable for the claimed use, i.e. the treatment of cancer.  The lack of such plausible disclosure meant there was no possible remedy available in submitting post-published evidence.  In view of the closest prior art documents, the objective problem was seen as the provision of alternative low molecular weight compounds and what was claimed was considered to be mere enrichment of the pool of organic compounds and therefore not inventive.

The sole claim at issue in the Appeal proceedings was to the single compound of dasatanib per se. 

The patentee argued in various ways about how the original specification made it plausible that dasatinib had PTK inhibitory activity, including (a) the EPC does not require experimental proof and so data is not an essential requirement, (b) the disclosure of the various PTK assays was to be understood as teaching that all of the exemplified compounds in the application had been tested, (c) two expert opinions, (d) the opponent actually has the burden of proof of showing that the application does not solve the technical problem it purports to solve.  The patentee also cited extensively from other EPO Boards of Appeal decisions where post-published evidence had been taken into account, as well as various US, Dutch and English court judgments.  No efforts were spared and the patentee also asked for referral of various questions to the Enlarged Board of Appeal.

Regarding the experimental data point, the Board agreed with the patentee that data is not always required but:

“If, as in the present case, the nature of the invention is such that it relies on a technical effect, which is neither self-evident nor predictable or based on a conclusive theoretical concept, at least some technical evidence is required to show that a technical problem has indeed been solved…  …it is not acceptable to draw up a generic formula, which covers millions of compounds, vaguely indicate an “activity” against PTKs and leave it to the imagination of the skilled reader or to future investigations to establish which compound inhibits which kinase and is therefore suitable to treat the respective diseases associated therewith.”

The Board clearly emphasised that the issue was not the absence of any in vivo or clinical data, but an absence of any verifiable data with regards to a technical effect (the PTK inhibitory activity in this case).

Regarding the interpretation of the description that all of the exemplified compounds had been tested, this backfired for the patentee because the post-published evidence showed that some of these compounds did not have the alleged technical effect.

Regarding the expert opinions, the Board neatly summarises what is already known of EP practice as regards expert evidence about what a specification discloses:

“The opinion of highly skilled experts on how a disclosure of a document is to be understood does not reflect the view of the notional skilled addressee, who is a person of ordinary skills aware of what is common general knowledge in the art at the relevant date.  Experts give evidence based on their professional experience and expertise which is not common general [knowledge] and will have an influence on their way of reading the disclosure of a document.  Since the assessment of the disclosure from the point of view of the skilled person does not normally call for special technical knowledge or experience, expert evidence of this matter will not be pertinent.  Such evidence is only necessary when the board does not consider itself in a position to decide a matter without technical assistance.  As the board includes two technically qualified members such cases will be rare and will only occur in special circumstances.”

The burden of proof issue was dismissed, as were the arguments based on the extensive case law and judgments, as was the referral to the Enlarged Board.

Plausibility is a currently a “hot topic” in patent law, with the UK Supreme Court hearing and decision in Warner-Lambert Company LLC (Appellant) v Generics (UK) Ltd t/a Mylan and another (Respondents) awaited; this case will look at plausibility issues under UK patent law, specifically:

  1. Whether (and what) role plausibility should play in the statutory test for sufficiency, and whether a patent should be held insufficient for lack of plausibility even though it is in fact enabled across the full scope of the claim.
  2. If a plausibility test is appropriate, provided there is basis to support the claim across part of its scope, whether later evidence can be used to fill the gap.
  3. The correct approach to (and the use of expert evidence in) the construction of patent claims.
  4. Whether a post-trial application to amend an invalid patent claim to limit it to a part found to be plausible is an abuse of process.

This update was prepared by HGF Partner Dr Richard Williams. If you would like further advise on this or any other matter please contact Richard or your usual HGF representative, alternatively visit our contact page to get in touch with your local HGF office.