23 Mar 2018

T 1255/11 - Claim for Alzheimer treatment plausible

Key points
  • In this opposition appeal, the Board finds claim 1 to be plausible.
  • Claim 1 is " Use of an effective amount of medium chain triglyceride for the preparation of a pharmaceutical composition for the treatment or prevention of loss of cognitive function caused by reduced neuronal metabolism in Alzheimer's disease,
    wherein said treatment or prevention comprises oral administration of a single dose of medium chain triglyceride to a patient such that the blood level of D-beta-hydroxybutyrate in the patient is raised to 1-10mM [] causing hyperketonemia in the patient resulting in ketone bodies being utilized for energy in the brain in the presence of glucose."
  • The Board: " The application as filed thus provides a complete theoretical explanation, backed up by scientific literature, for the treatment of Alzheimer's disease by MCT. In the present case the presence of the claimed effect is plausible in view of this theoretical explanation.
    Since the effect has been made plausible by the theoretical background explanations provided in the application as filed, the appellant may provide post-published evidence."


EPO T 1255/11 - link

5. Sufficiency of disclosure
5.1 Treatment of disease
The application as filed provides information on various background issues that allow for a theoretical understanding of the biochemical processes that are said to underlie the claimed therapeutic treatment.
[...]

In sum, the description as filed explains that Alzheimer's disease is linked to a problem of glucose metabolism in the brain and that an alternative energy source for neurons are ketone bodies. It establishes that ketone bodies result from the metabolism of MCT and provides some indications that ketone bodies may improve cognitive dysfunction.
The application as filed thus provides a complete theoretical explanation, backed up by scientific literature, for the treatment of Alzheimer's disease by MCT. In the present case the presence of the claimed effect is plausible in view of this theoretical explanation.
Since the effect has been made plausible by the theoretical background explanations provided in the application as filed, the appellant may provide post-published evidence.


5.2 Achievability of ketone levels in blood/urine
It is undisputed that document (15), a review document, discloses that one study found that administration of a single dose of 45-100 g MCT led to blood ketone levels of up to 700 mymol/L. The opposition division came to the conclusion that levels above 1000 mymol/L, as defined by claim 1 of the main request (i.e. 1-10mM D-beta-hydroxybutyrate), could not be achieved without difficulties. The board cannot endorse this view. Document (15) goes on to disclose that the level of ketonemia is directly correlated with the MCT supply. Given this information it seems to be reasonable that an increase in the MCT dose would lead to an increase of ketone levels in the blood. There is no evidence to the contrary.
5.3 Burden to find necessary MCT dose
In view of the information summarised in document (15) regarding the various blood ketone levels achieved in fed healthy subjects, fasting healthy subjects, patients having untreated diabetes or obese women on a low-energy diet, the effective dose of MCT will indeed have to be determined. However, such a determination is well within the skill of the person skilled in the art. The application as filed provides information of a commercially available product that enables determination of ketone bodies in blood and/or urine by routine measurements (page 15, lines 31/32). Thus, by carrying out routine measurements and by giving consideration to the patient to be treated, a skilled person can find the necessary MCT dose without undue burden.
5.4 Ketone levels and the claimed effect
The application as filed does not contain any experimental evidence providing proof of effectiveness for the defined beta-hydroxybutyrate levels. However, the description as filed, on page 13, lines 13 to 16, discloses that the administration of MCT leads to hyperketonemia. In this context "Hasselbalch et al. 1996", which is document (25), is cited. In document (25) hyperketonemia is exemplified by a mean beta-hydroxybutyrate blood concentration of 2.16 mM (abstract), which falls within the range defined in the independent claims of the patent as granted. Document (24), cited on page 13, lines 16 to 17, as "Veneman et al. 1994", then provides a basis for the link between hyperketonemia and reduced cognitive dysfunction. A link between the claimed ketone levels and the therapeutic effect is thus plausible in view of the literature cited in the application as filed. The respondent has not submitted any arguments questioning this conclusion, which is based on the application as filed and the prior art cited therein.
5.5 The subject-matter of the claims of the patent as granted (main request) is sufficiently disclosed.
5.6 The observations by a third party received on 11 January 2017 in accordance with Article 115 EPC do not contribute any further arguments to the discussion of sufficiency of disclosure and are consequently not taken into account.
6. Remittal
The decision under appeal only concerned the grounds of appeal under Articles 100(b) and (c) EPC. Therefore, the patent in suit needs further examination as to the requirements of Article 100(a) in conjunction with Articles 54 and 56 EPC. In these circumstances, and in accordance with the appellant's request, the board finds it appropriate to make use of its power under Article 111(1) EPC and to remit the case to the department of first instance for further prosecution.
Order
For these reasons it is decided that:
1. The decision under appeal is set aside.
2. The case is remitted to the opposition division for further prosecution.

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