T 1045/13 - Single patient studies not sufficient

Key points

• In this examination appeal, claim 1 is directed to a compound for use in a method of alleviating symptoms of psychological condistion selected from a group including depression and anxiety disorders.
• The application included some examples, but each with only a single patient (all females, at different ages) These do not make the therapeutic use plausible, according to the Board.
• "Each example relates to a single patient only, contrary to common practice which requires a certain number of patients to be tested under the same conditions in order to allow statistical analysis of the results. Also, in the absence of a control group, placebo effects cannot be excluded. To sum up, the appellant has chosen to rely solely on experimental evidence in support of the therapeutic treatment as claimed in claim 1. The experimental evidence on file fails however to provide evidence for the effects claimed. The examples do not cover the whole scope of the claim and do not provide evidence of therapeutic efficacy that meets scientific standards (statistically significant number of patients, control group). Effective treatment of the medical conditions under consideration has thus not been shown. Consequently, the board comes to the conclusion that the subject-matter of claim 1 is not sufficiently disclosed (Article 83 EPC)."
• The PCT application was drafted in US style. "The application as filed does not provide any indication of the principle underlying the relationship between the activity of the pharmaceutically active agent, i.e. the NGF, and the therapeutic effect, i.e. the alleviation of the symptoms of the psychological conditions claimed. The description does not provide any information on the mechanism of action of NGF. "

EPO T 1045/13 - link

Reasons for the Decision

[] 3. Sufficiency of disclosure

Claim 1 is a second medical use claim worded in accordance with Article 54(5) EPC. Attaining the claimed therapeutic effect is a functional feature of the claim. The application must thus disclose the suitability of the substance or composition for the therapeutic application claimed.

It will now be examined which therapeutic effect is defined by the wording of claim 1, and whether the evidence on file is sufficient to show that the claimed compound is suitable for said therapeutic application.

3.1 Claim construction

Claim 1 defines a nerve growth factor for use in a method of alleviating symptoms of psychological conditions selected from a group consisting of depression, bi-polar disorders, anxiety disorders, panic attacks, agoraphobia, attention deficit syndrome, premenstrual dysphoric disorder and premenstrual syndrome.

Claim 1 thus defines a treatment in the form of alleviation of symptoms. The symptoms themselves are not specified. They therefore include all symptoms that arise in the psychological conditions defined in the claims. A study of the description reveals a plethora of symptoms linked to said conditions (page 1, line 19 to page 12, line 25).

The symptoms range from those - such as anxiety and suicidal thoughts - that are clearly linked to the psychological conditions claimed, to others - such as constipation and headaches - which can also be caused by quite different conditions. There seems to be no link between these symptoms, other than being caused by the various psychological conditions claimed.

The board also notes that claim 1 is not limited to the symptoms specifically mentioned in the description.

The subject-matter of claim 1 is thus extremely broad. To make it plausible that the effect of alleviating all these different symptoms is achieved, support for the treatment of all the psychological conditions defined in claim 1 is necessary.

3.2 Evidence for effective treatment

The application as filed does not provide any indication of the principle underlying the relationship between the activity of the pharmaceutically active agent, i.e. the NGF, and the therapeutic effect, i.e. the alleviation of the symptoms of the psychological conditions claimed. The description does not provide any information on the mechanism of action of NGF. No background references are cited that link NGF to the therapeutic effects to be obtained, and no in vitro assays are provided to illustrate any such effect. In the complete absence of such information, the experimental evidence on file is of decisive importance.

The experimental evidence consists of eleven examples. Each of these examples describes the treatment of a single patient. Various amounts of NGF are administered for various periods of time. The following conditions are treated:

example I: panic attacks and agoraphobia;
example II: anxiety attacks;
example III: anxiety, panic disorder, and hot flashes;
example IV: depression and anxiety;
example V: clinical depression;
example VI: clinical depression and anxiety;
example VII: depression, irritability, frequent headaches, restless sleep, and hot flashes during the patient's one-week premenstrual cycle; chronic month long anxiety;
example VIII: severe situational anxiety and depression;
example IX: depression and anxiety;
example X: constipation, exacerbated by multiple sclerosis;
example XI: hot flashes and mid-cycle dysphoria.

The examples relate to various conditions, but do not cover all the conditions defined in claim 1. There is no data for example on bi-polar disorders and attention deficit syndrome. Also, only a few of the symptoms disclosed in the description are mentioned in these examples. Consequently, the experimental evidence of these examples cannot provide a full disclosure over the whole scope of claim 1.

Nor do the examples give rise to statistically significant data. Each example relates to a single patient only, contrary to common practice which requires a certain number of patients to be tested under the same conditions in order to allow statistical analysis of the results. Also, in the absence of a control group, placebo effects cannot be excluded.

To sum up, the appellant has chosen to rely solely on experimental evidence in support of the therapeutic treatment as claimed in claim 1. The experimental evidence on file fails however to provide evidence for the effects claimed. The examples do not cover the whole scope of the claim and do not provide evidence of therapeutic efficacy that meets scientific standards (statistically significant number of patients, control group). Effective treatment of the medical conditions under consideration has thus not been shown.

3.3 Consequently, the board comes to the conclusion that the subject-matter of claim 1 is not sufficiently disclosed (Article 83 EPC).

3.4 In view of that conclusion, it is not necessary to discuss the physico-chemical properties of NGF and its mode of administration.

3.5 Appellant's further arguments

3.5.1 Documents (8) and (9)

It is established case law that once evidence is available from the patent application as filed, then post-published evidence may be taken into account, but only to back up the findings in the patent application. Post-published evidence cannot establish sufficiency of disclosure on its own.

The board has come to the conclusion that the evidence in the application as filed does not constitute a sufficient disclosure. The contents of post-published documents (8) and (9) cannot change that finding and therefore need not be discussed.

3.5.2 Appellant's references to the case law

The appellant has referred to decisions T 609/02, T 394/06 and T19/90.

The situation leading to T 609/02 differs in several aspects from the case in point. The most important difference is that the description under consideration in T 609/02 provided an explanation - at least a theoretical one - of the mechanism underlying the therapeutic application. T 609/02 is however relevant for the present case in establishing that, where the therapeutic effect is a functional technical feature of the claim, the application must disclose the suitability of the product to be manufactured for the claimed therapeutic application and that evidence filed later cannot be used to remedy a fundamental insufficiency of disclosure.

T 394/06 is also based on a factual situation where there was a theoretical background (the over-expression of CASB7439 transcript in tumours) supported by experimental evidence (example 1 of the description as filed). The present situation differs in that no theoretical explanation of the link between NGF and the symptoms of the psychological conditions claimed has been given. T 394/06 is thus not relevant for the present situation.

The board does not consider T 19/90 to be relevant for the present decision. T 19/90 does not deal with a situation where a therapeutic effect which is a functional technical feature of the claim under consideration has to be established for the first time. This requires (see above) the present application to disclose the suitability of NGF for the claimed therapeutic application. Such suitability has not been convincingly demonstrated.

Order

For these reasons it is decided that:

The appeal is dismissed.