T 1329/11 (Use of BNP-type peptides/ROCHE) 19-11-2015

Reasons for the Decision

1. The appeal is admissible.

2. Admissibility of oral submissions by the accompanying person, Mr Hess, on the statistical information contained in document D23

2.1 According to decision G 4/95 (OJ EPO 1996, 412), oral submissions by an accompanying person in opposition or opposition appeal proceedings cannot be made as a matter of right, but only with the permission of and under the discretion of the board.

When exercising this discretion the main criteria to be considered are:

i) The professional representative should request permission for such oral submissions to be made. The request should state the name and qualifications of the accompanying person, and should specify the subject-matter of the proposed oral submissions.

ii) The request should be made sufficiently in advance of the oral proceedings so that all opposing parties are able to properly prepare themselves in relation to the proposed oral submissions.

iii) A request which is made shortly before or at the oral proceedings should in the absence of exceptional circumstances be refused, unless each opposing party agrees to the making of the oral submissions requested.

iv) The EPO should be satisfied that oral submissions by an accompanying person are made under the control of the professional representative (see G 4/95 (supra), headnote and point 10 of the reasons).

2.2 At the oral proceedings, the respondents requested that Mr Hess, one of the inventors, be permitted to make oral submissions on the statistical information contained in document D23.

Document D23, which is not a published document, had been filed on 12 March 2012 by the respondents with their reply to the grounds of appeal in order to show a statistical correlation between the natriuretic peptides BNP, NT-proBNP and NT-proANP in patients with different extents of heart failure.

In their letter dated 21 September 2015, the respondents requested Mr Hess to be permitted to make oral submissions "relative to technical topics in connection with the invention underlying the patent, prior art and further medical topics which may arise during oral proceedings". Said request did thus not specify the subject-matter of the proposed oral submissions, namely the statistical information contained in document D23, in sufficient detail so as to permit the opposing party to properly prepare itself in relation to the proposed oral submissions.

It follows that criteria (i) and (ii) were not complied with, and the respondents' request that specified the subject-matter of the proposed oral submissions was only made at the oral proceedings.

In view of criterion (iii) and the appellant's request not to allow the oral submissions by Mr Hess on the statistical information contained in document D23, the respondents' request had to be refused. It is, however, also noted that the information contained in document D23 could in any case only supplement but not substitute the information in the patent in suit in the determination of sufficiency of disclosure.

Consequently, the board did not allow Mr Hess to make the requested submissions.

It is pointed out that in view of the fact that the main request now under consideration refers solely to NT-proBNP, the contents of document D23 is of no relevance with respect to the present decision (see point 3 below).

3. Main request - Sufficiency of disclosure

3.1 According to Articles 100(b) and 83 EPC, the claimed invention must be disclosed in the European patent and in the European patent application in a manner sufficiently clear and complete for it to be carried out by a person skilled in the art. According to the established case law of the boards of appeal, this requirement must be complied with at the effective date.

3.2 Claim 1 is directed to a method for diagnosing the risk of a patient, who shows no symptoms of a cardiovascular disease according to the NYHA classification and who has no history of a cardiovascular complication, of suffering from a cardiovascular complication as a consequence of a future increase of intravasal volume, whereby the level of the natriuretic peptide NT-proBNP is measured in vitro and the risk of the patient is diagnosed by comparing the measured level to at least one known level(s) associated with different grades of risk in a patient.

The claimed method thus concerns diagnosing the risk of suffering from a cardiovascular complication as a consequence of a future increase of intravasal volume in a patient of a specified patient group, namely patients who show no symptoms of a cardiovascular disease according to the NYHA classification and who have no history of a cardiovascular complication.

3.3 The classification of cardiovascular diseases into the functional classification system according to the New York Heart Association (NYHA) is referred to in paragraph [0029] of the patent in suit. It is stated in said paragraph that patients of class I have no obvious symptoms of cardiovascular disease; physical activity is not limited, and ordinary physical activity does not cause undue fatigue, palpitation, or dyspnea (shortness of breath). Patients of class II have slight limitation of physical activity; they are comfortable at rest, but ordinary physical activity results in fatigue, palpitation, or dyspnea. Patients of class III show a marked limitation of physical activity; they are comfortable at rest, but less than ordinary activity causes fatigue, palpitation, or dyspnea. Patients of class IV are unable to carry out any physical activity without discomfort; they show symptoms of cardiac insufficiency at rest. If any physical activity is undertaken, discomfort is increased.

Furthermore, paragraph [0040] of the patent in suit states with respect to the term "patient" according to the invention that "the patient has no known history of cardiovascular complication, and no (NYHA class I or II) symptoms of a cardiovascular complication".

In view of these teachings, the board considers that only those patients that do not show any of the symptoms set out in paragraph [0029] of the patent in suit, such as slight limitation of physical activity, or fatigue, palpitation or dyspnea resulting from ordinary physical activity, are patients according to claim 1.

The respondents' submission that because class I and II patients only showed symptoms which were not typical for a cardiac dysfunction, i.e. "non-obvious" symptoms, such patients would fall under claim 1 as long as their cardiac status (i.e. their classification into class I or II) had not been determined, cannot be followed by the board. This is because claim 1 explicitly refers to "symptoms of a cardiovascular disease according to the NYHA classification", and not to "obvious" symptoms or to symptoms typical for a cardiac dysfunction; the respondents' reading of claim 1 would thus be contrary to both the explicit wording of claim 1 and the teaching of the description of the patent in suit, notably paragraphs [0029] and [0040].

3.4 None of the examples of the patent in suit describes that a method according to claim 1 was actually carried out, i.e. that the risk of a patient of the specified patient group of suffering from a cardiovascular complication as a consequence of a future increase of intravasal volume was diagnosed on the basis of measuring the level of NT-proBNP. This was not disputed by the respondents.

In these circumstances, it needs to be assessed whether or not, at the priority date, it would have been plausible for the skilled person on the basis of the disclosure of the patent in suit and/or common general knowledge that the claimed method would work, i.e. that the risk of a patient of the patient group specified in claim 1 of suffering from a cardiovascular complication as a consequence of a future increase of intravasal volume can be diagnosed on the basis of measuring the level of NT-proBNP.

3.5 Example 8 is the only example in the patent in suit which attempts to correlate the diagnosis of a cardiovascular complication occurring after an increase of intravasal volume to the level of NT-proBNP present before the increase of intravasal volume. It is stated that a total of 120 patients in an intensive care unit were diagnosed in regular intervals and NT-proBNP was analysed retrospectively. Five patients with a history of cardio­vascular complication, who obtained infusion therapy and/or termination of treatment with diuretics, had a subsequent clinical diagnosis of cardiac insufficiency. The example provides the data of the NT-proBNP levels of these five patients only, and not those of any of the remaining 115 patients, who did not suffer from a cardiac complication following an increase of intravasal volume. The significance of the data provided with respect to a correlation between the level of NT-proBNP and the risk of suffering from a cardiac complication following a future increase of intravasal volume is therefore rather limited. Notwithstanding this lack of statistical significance, all five patients for whom such correlation is alleged to be present had a history of cardiovascular complication, which means that none of them is a patient according to claim 1. Consequently, the data of Example 8 do not allow any conclusion as to whether or not NT-proBNP may serve as a prognostic marker for the risk of suffering from a cardiovascular complication as a consequence of a future increase of intravasal volume with respect to the patient group of claim 1.

3.6 The respondents have argued that the combination of Examples 2, 3, 4 and 8 showed that the claimed method worked.

3.6.1 Examples 2 and 3 provide data relating to apparently healthy patients who qualify as patients according to claim 1.

Example 2 concerns experiments with healthy volunteers and reports NT-proBNP levels measured after an increase of the intravasal volume had occurred. These data thus do not allow any conclusion with respect to the prognostic value of NT-proBNP in said patient group.

Example 3 concerns the determination of NT-proBNP levels in blood donors that were considered to be clinically healthy. The data obtained were used to define reference values based on the 97.5 percentile for males and females under the age of 50 years. It was observed that a substantial number of individuals had NT-proBNP levels exceeding said reference values, and that the number of such individuals increased with age.

The board cannot follow the respondents' argument that the blood donors of Example 3 with elevated NT-proBNP levels had hidden, asymptomatic cardiovascular diseases, because there is no evidence or information whatsoever to show that this was the case. The respondents' suggestion that said blood donors with elevated NT-proBNP levels had such hidden diseases and consequently had an increased risk of suffering from a cardiovascular complication, like the patients of Example 8, thus amounts to mere speculation. Such speculation cannot provide a basis for a sufficient disclosure under Article 83 EPC.

3.6.2 Example 4 concerns NT-proBNP levels in patients presenting to cardiologists with suspected cardiac disorders. The patients were classified into NYHA classes I to IV. The majority of the patients had elevated NT-proBNP levels.

The board takes the position that said patients with suspected cardiac disorders are not to be regarded as patients according to claim 1. Therefore, the data presented in Example 4, taken alone or in combination with Example 8, do not allow any conclusion with respect to diagnosing the risk of a patient as defined in claim 1 of suffering from a cardiovascular complication as a consequence of a future increase of intravasal volume.

3.6.3 Consequently, Examples 2, 3, 4 and 8, taken alone or in combination, cannot make it plausible that the claimed method works.

3.7 The respondents have furthermore submitted that in order to perform the claimed invention, the skilled person would simply have to carry out the teachings of Example 8, but with samples of patients as defined in claim 1. He/she would then see that the invention worked.

The board cannot follow this line of argument, because in order to establish whether or not the claimed invention could be carried out, the skilled person would have to collect and evaluate additional clinical data, which would represent a research project and hence an undue burden.

3.8 The respondents have referred to post-published documents, in particular to document D8 published more than five years after the priority date, in order to show that the claimed method worked.

It is the established case law of the boards of appeal that post-published evidence may not be used to establish sufficiency of disclosure. Such evidence may only be used to backup a finding of sufficiency of disclosure.

Therefore, the contents of documents which were not available to the skilled person at the priority date cannot help to overcome the major problem of sufficiency of disclosure of the claimed invention at the priority date, as set out in points 3.1 to 3.7 above.

3.9 The board also cannot accept the respondents' argument that the claimed invention was sufficiently disclosed because the appellant did not present verifiable facts that it did not work. Although generally, the burden of proof in the framework of sufficiency of disclosure lies with the appellant, this principle does not apply to cases like the present one, where the application as filed does not provide a single example or other technical information from which it is plausible that the claimed invention can be carried out.

3.10 In view of the above, the requirement of sufficiency of disclosure is not complied with.

Consequently, the main request must be refused pursuant to Article 83 EPC.

4. Auxiliary request IB - Admission (Article 13 RPBA)

4.1 Auxiliary request IB was filed at the oral proceedings. Its claim 1 differs from claim 1 of the main request in that it defines plasma levels of NT-proBNP which are supposed to be associated with an increased risk of suffering from a cardiovascular complication.

4.2 The board had to decide on the admission of this request. According to the established case law of the boards of appeal, claims filed at oral proceedings must prima facie overcome the issues raised, without giving rise to new ones, in order to be admissible.

4.3 The amendments in claim 1 introduce cut-off values for plasma NT-proBNP levels, which prima facie do not overcome the fundamental deficiency under Article 83 EPC set out above for the main request.

4.4 Consequently, the board has decided not to admit the auxiliary request 1B into the proceedings.