T 0713/15 (Vasculitis/CHUGAI) 02-10-2019

1. Any reference in this decision to the RPBA concerns RPBA 2007.

2.

3. The appeal is admissible.

4. Sufficiency of disclosure

4.1 The patent in suit relates to a novel preventive and/or therapeutic agent for vasculitis (paragraph [0001]).

According to paragraph [0005] intensive and extensive research led the inventors to demonstrate that IL-6 was indispensable in the pathology of vasculitis. It was found surprisingly that when the binding of IL-6 to its receptor was inhibited by an IL-6 receptor antibody IL-6 per se was decreased in the blood. Thus, IL-6 inhibition not only had an anti-inflammatory effect on vasculitis but also treated vasculitis per se by acting on the core of vasculitis.

Paragraph [0005] relates to vasculitis in general and does not distinguish between various types of vasculitis.

No further mechanistic explanation is provided in the patent in suit. However, the clinical data of patients having either aortitis syndrome, also called Takayasu's arteritis, or arteritis nodosa show that the treatment of certain types of vasculitis by anti IL-6 receptor antibody which inhibits the binding of IL-6 to the IL-6 receptor leads to a marked improvement in patients' conditions.

4.2 The appellant has provided arguments that the effect, the prevention and/or treatment of vasculitis, would not be achieved for all types of vasculitis. The subject-matter of claim 1 of the main request was thus not sufficiently disclosed over the whole scope of claim 1.

In order to substantiate this argument, the appellant has referred, inter alia, to documents (49) and (50). According to the appellant, these documents showed that certain forms of vasculitis, in particular mucocutaneous Behçet's disease/syndrome, could not be treated by an anti IL-6 receptor antibody.

The respondent has argued that it could not be understood from documents (49) and (50) that the treatments were not effective at all. In fact, the treatments were stopped due to side effects. A lack of efficacy in isolated patients due to toxicity could not lead to a finding of lack of sufficiency of disclosure.

4.3 A detailed analysis of documents (49) and (50) is thus necessary.

Document (49) reports in its abstract that a patient diagnosed with Behçet's disease experienced a paradoxical mucocutaneous flare following tocilizumab (an anti IL-6 receptor antibody inhibiting binding of IL-6 to IL-6 receptor) administration, which worsened after the second infusion. The authors of document (49) considered this to be an acute exacerbation of the disease (page 2, left-hand column, second paragraph). It is said that different cytokine clusters might be involved and that a treatment based on IL-6 antagonism may cause imbalances in the cytokine network (page 3, left-hand column, first paragraph). In their conclusion, the authors of document (49) hypothesise that, although favourable responses can be obtained with tocilizumab in neuro-Behçet's disease (see titles of references [10], [20] and [25]), the attempt to manage mucocutaneous lesions by blocking IL-6 leads to a worsening of the disease (page 3, last paragraph).

Document (50) relates to the "Lack of efficacy of tocilizumab in mucocutaneous Behçet's syndrome: report of two cases" (title). It starts off by describing that Behçet's syndrome is a rare multisystem inflammatory disease that presents clinically with mucocutaneous, ophthalmic, neurological, joint and vascular manifestations (page 1923, left-hand column, first paragraph). Studies on two patients with genital and mouth ulcers showed a deterioration of the mouth and/or genital ulcers. The first patient experienced the worsening of her condition already after the first infusion of tocilizumab. The second patient, after showing a partial response to the treatment, developed painful genital ulcers which had to be treated with high doses of opioid analgesics and corticosteroids (page 1923, paragraph bridging the columns). The authors of document (50) considered that their patients failed to respond to the treatment. They state that their report of the failure of patients to respond to the treatment with tocilizumab is in contrast to others that describe the efficacy of tocilizumab for severe neurological and ocular Behçet's syndrome (page 1923, right-hand column, second paragraph). Document (50) then goes on to speculate that mucocutaneous Behçet's syndrome had a different cytokine profile from other phenotypes of Behçet's syndrome, such as for example neurological and ocular Behçet's syndrome (page 1923, right-hand column, paragraph 3).

From the disclosure of documents (49) and (50) it can be taken that a specific type of Behçet's disease, i.e. Behçet's disease with mucocutaneous manifestations or phenotype, cannot be treated with an anti IL-6 receptor antibody. These two documents also find that not only no treatment but a worsening of the manifestations of the disease occurs. The authors of these documents class the symptoms occurring after administration of tocilizumab as manifestations of mucocutaneous Behçet's disease. They do not identify the occurring symptoms as side effects. Furthermore, these two documents address the question of cytokine profiles and potential differences in these profiles between different types of Behçet's disease. Both documents question whether the mere blocking of IL-6 would address issues relating to the pathogenesis of mucocutaneous Behçet's disease. Document (50) in particular expresses its doubts in an extremely clear manner: "It was hypothesized that there are clusters of disease expression in BS [Behçet's syndrome] with different pathogenic mechanisms and response to treatment with different agents" (page 1923, right-hand column, last paragraph).

The discussion of cytokine profiles by the authors of documents (49) and (50) shows that the patients discussed in these documents are not seen as representing isolated failures.

There is thus evidence on file that inhibiting the binding of IL-6 to IL-6 receptor by an anti IL-6 receptor antibody does not lead to a prevention or treatment of every type of vasculitis.

4.4 In sum, the relevant facts relating to sufficiency of disclosure are the following.

The patent in suit provides indications on a mechanism of action for vasculitis in general and data for patients having two specific forms of vasculitis.

There is however evidence on file, in the form of documents (49) and (50), that the claimed treatment does not work for all types of vasculitis.

It has thus been shown that the general mechanism postulated, which has led to a therapy relying on IL-6 inhibition, does not allow each and every form of vasculitis to be treated. The application as filed does not provide any form of guidance as to which types of vasculitis respond to the administration of an anti IL-6 receptor antibody. There is thus no teaching in the application as filed on how to treat vasculitis in all its forms. As a consequence of these findings, the subject-matter of claim 1 of the main request is not sufficiently disclosed over the whole scope of the claim.

4.5 Having come to this conclusion, it is not necessary to discuss document (47).

4.6 Two further arguments have been brought forward by the respondent:

Firstly, the respondent has referred to the expert declaration (54). There, Professor Pusey comes to the conclusion that based on the clinical data of the patent in suit, and possibly on two further post-published documents (see point 20 of document (54)), it was plausible and scientifically reasonable to predict that different types of vasculitis may be treated with an anti IL-6 receptor antibody. However, Professor Pusey neither mentions nor discusses the data of documents (49) and (50). In the absence of any appraisal of these documents, the expert declaration cannot provide crucial input on the issue of sufficiency of disclosure.

Secondly, the respondent has pointed to the fact that a marketing authorisation had been granted for tocilizumab. However, the marketing authorisation does not concern the treatment of vasculitis in general or the treatment of Behçet's disease. The granting of a marketing authorisation for particular diseases that are distinct from Behçet's disease cannot change the findings of point 2.4 above.

4.7 In view of the finding of lack of sufficiency of disclosure, it is not necessary to provide a reasoning for novelty of the main request.

5. Admission of auxiliary request 1

According to the Rules of Procedure of the Boards of Appeal (RPBA), appeal proceedings in inter partes cases are based on the statement(s) of grounds of appeal and the reply/replies of the other party/parties, subject to further conditions (Article 12(1),(4) RPBA). The admission of subsequent submissions (requests, facts or evidence) representing an amendment to a party's case is at the discretion of the boards (Article 114(2) EPC and Article 13 RPBA). This discretion has to be exercised appropriately, requiring the boards to consider all relevant factors, taking into account the specific circumstances of the case. Examples of criteria to be taken into consideration by the boards when exercising their discretion include the complexity of the new subject-matter submitted, the current state of the proceedings and the need for procedural economy (confer Article 13(1) RPBA). These criteria are not exhaustive, and the boards have also considered aspects such as the reasons for the new submission or the extent of the amendments.

Auxiliary request 1 was filed at a very advanced stage of the appeal proceedings, namely at the oral proceedings before the board and after the discussion of sufficiency of disclosure of the main request. The board does not consider that a new situation had arisen during the oral proceedings which might justify the filing of this request. The fact that a board, on the basis of arguments presented by a party, might take a different view than the department whose decision is appealed, can not be considered a surprising event as it is one of the two possibilities. As the patent proprietor is the party that is solely responsible for determining the text of the patent (see Article 113(2) EPC), it is however obliged to submit amendments or possible fall-back positions. For reasons of procedural economy and fairness to the other party this must be done at the earliest possible opportunity.

In the present case, the respondent waited until after a negative finding of sufficiency of disclosure, a ground of opposition that was an issue throughout the opposition and appeal proceedings, before submitting auxiliary request 1. In view of the fact that sufficiency of disclosure had been a major issue in the appellant's case, the filing of auxiliary request 1 during oral proceedings before the board was contrary to procedural economy.

Consequently, in view of the extremely late state of the proceedings and the need for procedural economy, the board did not admit auxiliary request 1 into the proceedings (Article 13(1) and (3) RPBA).