T 0377/18 - Post-published evidence

Key points

Inventive step is at issue in this pharma case. Claim 1 is directed to “ a composition comprising a solid dispersion comprising at least [regorafenib] in substantially amorphous form and a pharmaceutically acceptable matrix”.
D5 is the closest prior art. “The compounds described under entries 42 and 49 [of D5] differ from regorafenib only in a substitution on one of the aryl rings (being hydrogen or chlorine instead of fluorine). ... Concerning the formulation of these actives, some general information is given on page 10, line 10 to page 12, line 29 [of D5]. Solid dispersions are not mentioned.”
“either Formula (I) [a broad Markush formula] or any of the 103 compounds, in particular the closely-related compounds of entries 42 and 49 [of D5], can be taken as the starting point in the present case”

On to the plausibility issue (or closely related issue, in any case, see the G 2/21 referral): “Firstly, it will be discussed whether any surprising effect can be acknowledged to be linked to the difference in [molecule] structure”
“The application as filed does not explicitly identify any surprising effects linked to the structure of the active agent.”
“the respondent [patentee] presented data which according to it demonstrated the superiority in activity of regorafenib as compared with compound 49 (Tables 1 and 2). Having been submitted for the first time in the reply to the grounds of appeal, the data are clearly post-published. As they present data on an effect that cannot be derived from the application as filed, despite document (5) being discussed in the background section, the data are to be disregarded.”

“No information is provided [note: in para. [0004] of the patent, as I understand] as to whether regorafenib is capable of inhibiting raf or any of the other three kinases in a way different from the cited background art (including document (5)) and/or whether such inhibition would lead to any improvement in the treatment. In fact, the application as filed contains no statement relating to and no data confirming the extent of the inhibition or indicating that this inhibition would lead to an improvement in the treatment of any hyper-proliferative disease. The appellant has furthermore pointed to the fact that there was no evidence that regorafenib inhibited these four kinases at all.”
D5 is cited on page 2 at the top of the application as filed, in a section that merely lists a number of prior art references without much discussion or analysis.

“The board thus comes to the conclusion that an improvement over the compounds of document (5) was neither foreshadowed, nor alleged, nor shown in the application as filed. Document (5) is not merely a document that could have been considered by the patent proprietor (or the then applicant) when drafting the application, but a document that actually was considered as can be seen by its being cited in the background section. Since, as a consequence, post-published evidence cannot be taken into account, none of the effects related to improved treatment (different pattern of inhibition, second-line treatment, higher levels of inhibition) can be considered when applying the problem-solution approach.”
The feature of a solid dispersion does not provide for an inventive step either. The Board, as part of a detailed analysis, notes that “Document (6) thus clearly teaches that solid dispersions are a galenic form worth exploring when trying to provide a formulation of a poorly soluble drug.”
The patent is revoked.
The application was filed in 2005, the decision to grant was issued in 2015.
Furthermore, non-anonymous third party observations filed after the summons for oral proceedings in appeal are not admitted: “ In addition, a third party is not an actual party to the proceedings, and as such should not be accorded more favourable treatment than an actual party.”

EPO T 0377/18

Link to the decision after the jump, as well as the text of the decision.

Rent Agreement Format