T 0795/12 - Closest prior art because not inventive

Key points

• " 7. In the present case, in deciding which of documents D56 or D81 should represent the closest prior art for assessment of inventive step of the claimed subject-matter, the board recognises that both documents are good candidates. However, the board has satisfied itself that the claimed subject-matter was not inventive when starting from the disclosure of document D81 (see point 18. , below). This document may therefore be taken to represent the closest prior art." 

EPO T 0795/12 - link

Reasons for the Decision

1. The appeal of the patent proprietors is admissible.

2. During the oral proceedings before the board, the parties were heard on the requirements of Article 54 EPC of the subject-matter of claim 1 of the main request and the board expressed its opinion on this matter. However, in view of its conclusions on inventive step (Article 56 EPC) in respect of this subject-matter, there is no need to to provide detailed written reasons for this opinion.

Claim construction

3. The board considers that the skilled person would understand that the medicament to be prepared according to the claimed use (see Section VI.) may comprise rituximab (RTX) alone or may comprise both RTX and methotrexate (MTX) and that the claim is for uses involving the deliberate treatment of rheumatoid arthritis (RA) with both of RTX and MTX. Since the claim includes no indication of timing or sequence of the administration of either active component, the RTX containing medicament to be manufactured according to the claimed use may be administered with MTX separately or together, at the same time or at a different time. The RTX and MTX may be administered in either order.

Inventive step - Article 56 EPC

The closest prior art

4. There was a difference in opinion between the parties as to which document represented the closest prior art for the claimed invention. The appellants chose document D56, whereas the respondents selected document D81, as did the opposition division in the decision under appeal.

5. Document D81 is an editorial in a scientific journal concerning combination therapy of RA with MTX with certain biological agents, in particular, monoclonal antibodies. Document D56 is a declaration by Professor Jonathan Edwards, dated 27 February 2008, relating to a five patient open label clinical study aiming to investigate the treatment of RA with RTX. The document includes appendices A to H, where appendix H is a set of record sheets of patients participating in the study. The public availability of the study and the treatments used was not disputed by the appellants.

6. It has been established in the case law of the Boards of Appeal that, where more than one document is cited as the closest prior art, the one which must be deemed the closest is that which provides the skilled person with the most promising springboard to the invention (see Case Law of the Boards of Appeal of the European Patent Office, 7th edition, 2013, I.D. 3.4.).

7. In the present case, in deciding which of documents D56 or D81 should represent the closest prior art for assessment of inventive step of the claimed subject-matter, the board recognises that both documents are good candidates. However, the board has satisfied itself that the claimed subject-matter was not inventive when starting from the disclosure of document D81 (see point 18.18. , below). This document may therefore be taken to represent the closest prior art.

Problem to be solved

8. The difference between the disclosure of document D81 and the claimed invention lies in the choice of RTX as the biological agent to be administered with MTX.

9. The appellants argued that treatment of RA with a combination of MTX and RTX provided an unexpected therapeutic synergy. The evidence for this therapeutic synergy was to be found in document D15. Accordingly, the problem to be solved was the provision of an improved treatment of RA.

10. In accordance with the case law of the boards, reformulation of the problem to take a technical effect into account is only allowable, if the new problem can be deduced from the application as filed. In the same vein, the case law of the boards has consistently held that post-published evidence to support that the claimed subject-matter solves the technical problem underlying the invention, is taken into account only if it is already credible from the disclosure in the patent that the problem is indeed solved (see Case Law of the Boards of Appeal of the European Patent Office, 7th Edition, 2013, I.D. 4.4.1, 4.4.2 and 4.6). In other words, a subsequently invoked technical effect cannot be taken into account when determining the problem underlying the invention if it could not be deduced by the skilled person from the application as filed (see Case Law of the Boards of Appeal of the European Patent Office, 7th Edition, 2013, I.D. 4.4.2).

11. The board notes that document D15 was published after the effective date of the patent in suit. Moreover, the board cannot identify in or deduce from the patent any disclosure of a synergistic effect between the two agents which would amount to a teaching to be backed up by the disclosure of document D15. The disclosure of document D15 is therefore not taken into account in the assessment of the inventive step of the claimed subject-matter.

12. Accordingly, starting from the disclosure in document D81, the technical problem to be solved is the provision of an alternative biological agent (drug) to be used in combination with methotrexate for the treatment of rheumatoid arthritis.

Obviousness

13. The question to be answered by the board is whether the skilled person starting from therapies for RA disclosed in document a document D81 and seeking a solution to the above formulated technical problem, would have considered administration of MTX with RTX for the treatment of RA.

14. Document D81 teaches that methotrexate (MTX) was accepted as "the most efficacious and best-tolerated single agent for the treatment of rheumatoid arthritis (RA)". The treatment of RA with the biological agent RTX was also known to the skilled person, at least from the public prior use represented by document D56. Neither of the above facts is a matter of dispute among the parties.

Document D81 discloses that RA patients would benefit from a lowering of the weekly dose of MTX administered (see document D81, page 1548, column 2, penultimate paragraph). That such a lowering might be achieved through the combination of MTX with a new "biotechnology" agent is also disclosed. On the subject of "[w]hich combination [of biologic agent and MTX] makes the most sense" document D81 concludes that "[b]ecause of these uncertainties about the mechanism of action of MTX and cytokine inhibition, neither TNFalpha or IL-lbeta inhibitors can claim to be inherently better positioned to promote their use with MTX as making the most conceptual sense. Therefore, these and other biotechnology interventions are, quite reasonably, being empirically combined with MTX while hoping for the best. This approach can, and should, be advocated because our patients simply do not have the time to wait until we determine how all of the new and existing drugs work, let alone how MTX works" (page 1550, column 1, paragraph 1). Document D81 furthermore states: "Nevertheless, the current practice of combining virtually all new agents with MTX, the drug of many therapeutic possibilities, makes it likely that the cart will come before the horse. That is, we will empirically determine the combinations which result in the very best clinical efficacy and then investigate the effects on the immune and inflammatory cascade. This has been the scenario which has occurred with MTX as monotherapy as the scientific community began to recognize its clinical value" (page 1550, paragraph 2; emphasis added by the board).

In summary, the board concludes that document D81 suggested to the skilled person that the standard therapy of RA with MTX could be improved by administering it in combination with biological agents, in particular antibodies, newly developed for the treatment of RA. Given the urgency of the need for improved treatments, rather than waiting for a complete understanding of the mechanism of action of such agents or indeed of a complete understanding of the mechanism of action of MTX, an empirical approach to combination therapy was advocated. Following this empirical approach, the skilled person would have considered treating RA in a patient by administering MTX in combination with any new biological agent developed to treat RA. Thus, given that RTX was one such newly developed biological agent, the board takes the view that the skilled person had an incentive to administer MTX in combination with RTX to treat RA.

17. The appellants submitted that the skilled person, starting from document D81 as closest prior art, would not have combined MTX with RTX as a therapy for RA because there was no scientific rationale for combining the two agents and also because the disclosure of document D81 provided a disincentive to the skilled person concerning such combinations (see section XI.XI. ). However, in view of the board's conclusion that document D81, contrary to the appellants' views, provided the skilled person an incentive to empirically combine any new biological agent developed for treating RA, with MTX for the treatment of RA, regardless of the mechanism of either agent, these arguments cannot succeed.

18. Thus, the board concludes that the subject-matter of claim 1 lacks an inventive step.

Order

For these reasons it is decided that:

The appeal is dismissed