T 0822/07 (Glucocorticoid receptor antagonist for use in treating MCI / CORCEPT THERAPEUTICS INC.) 15-12-2010

I. European patent application No.00982226.3, was filed as international application WO 01/37840 with nineteen claims.

II. The following documents cited during the proceedings are relevant for the present decision:

(1) WO 99/59596

(2) WO 99/17779

III. The present appeal lies from a decision of the examining division refusing the application (Article 97(1) EPC 1973) for lack of inventive step (Article 56 EPC) of the subject-matter claimed in the main request vis-à-vis document (2), and on grounds pursuant to Article 52(2) EPC 1973.

Claim 1 of the request serving as basis for the examining division's decision read as follows:

FORMULA/TABLE/GRAPHIC

IV. The applicant (appellant) lodged an appeal against said decision and filed grounds thereto. With its grounds of appeal, the appellant maintained the request serving as basis for the examining division's decision as its sole request.

V. On 19 November 2009, the board issued a communication with an invitation to file observations under Rule 100(2) EPC.

In said communication the board recalled that the examining division never gave an opinion during the examination proceedings about Article 84 EPC for the amended claims, although the originally filed claims 1 to 13 (claims directed to a method of treatment in the international application WO 01/37840) were reworded as second medical use claims with the entry into the European regional phase. Moreover, the examining division's decision remained silent about the novelty (Article 54 EPC) of the subject-matter claimed in the use claims 1 to 13 vis-à-vis documents (1) and (2).

Consequently, the board informed the appellant that although the primary purpose of the appeal procedure is to give the losing party the possibility of challenging the decision under appeal as to its merits, the board had to exercise in the present case its discretionary power (Articles 111(1) and 114(1) EPC) and investigate the main request in relation to Articles 84, 83 and 54 EPC.

The Board raised objections within the meaning of Articles 84, 83 EPC, and Article 54(3) EPC vis-à-vis document (1), for the subject-matter claimed in the request serving as basis for the examining division's decision.

VI. The appellant filed a substantive reply to the Board's communication with its letter dated 13 May 2010. It also filed as an annex thereto a "revised set of claims".

Claim 1 of the set of claims filed with the letter of 13 May 2010 read as follows:

FORMULA/TABLE/GRAPHIC

It also filed five additional post-published documents by other authors than the inventors of the application in suit.

VII. On 29 June 2010, the Board sent a communication within the meaning of Article 15(1) RPBA 2007 (which corresponds to Article 14(2) of the previous version of the RPBA) as an annex to the summons for oral proceedings.

In said communication the Board maintained its objections regarding Articles 84 and 83 EPC for the amended set of claims and gave reasons thereto.

VIII. The appellant filed online on 2 November 2010 a reply to the Board's communication sent as an annex to the summons for oral proceedings. It also filed an auxiliary request.

Claim 1 of the auxiliary request read as follows:

FORMULA/TABLE/GRAPHIC

IX. Oral proceedings took place on 15 December 2010. During the oral proceedings the appellant withdrew the main request filed with the letter of 13 May 2010 and filed an amended main request to replace it.

Claim 1 of the main request filed at the oral proceedings before the Board differed from claim 1 of the main request filed with the letter of 13 May 2010 as follows:

The word "specific" was deleted at the beginning of the claim, leaving the expression "glucocorticoid receptor antagonist", which was supplemented by its acronym "(GRA)", and the following definition was introduced at the end of the claim:

"; wherein the GRA preferentially binds to the GR rather than the mineralcorticoid receptor (MR) at a rate of at least 100-fold".

X. The appellant's arguments may be summarised as follows:

The appellant submitted that claim 1 was drafted as purpose-delimited medical use claim. Thus, the claim sought protection for the use of any thinkable (i.e. known and/or unknown substances) glucocorticoid receptor antagonist, which preferentially bound to the glucocorticoid receptor (GR) rather than to the mineralcorticoid receptor (MR) at a rate of at least 100-fold, for the treating mild cognitive impairment (MCI) in a particular group of patients. The specific subgroup of patients defined in the claim was suffering MCI, which was a disease on its own right.

Questioned by the Board, whether the treatment defined in claim 1 encompassed the treatment of MCI independently from its cause, meaning that the treatment claimed also encompassed the treatment of patients who had suffered from a stroke (without diagnostic), or suffering an untreated diabetes condition, hormonal imbalance (brain fog) etc., the appellant answered positively and stated that a functional MCI may have all these different causes. However, MCI was a psychiatric and neurological disease entity since it was a symptomatic established condition with individual and identifiable symptoms. The appellant brought as an analogy the symptomatic treatment of a soared throat. It further stressed that the definitions for the patient subgroup included in the claim had to be fulfilled.

The appellant also submitted that the particular method defined in the claim was especially good in the defined subgroup of patients. Dementia patients were excluded. The appellant argued that only twenty years ago dementia patients were mixed up with patients suffering from MCI. It further argued that the patients to be treated had normal ranges of cortisol and that this prerequisite excluded patients suffering from Cushing's syndrome (independently from its origin) and patients with high levels of cortisol, at the moment of the treatment, caused by stress conditions.

The appellant also submitted that in the purpose-related product claim 1, the product was defined by functional terms. The functional definition "glucocorticoid receptor antagonist" (GRA) was an established definition on its own. At the time of filing of the application underlying the appeal the skilled person in the art had no difficulty in appreciating what a GRA does. The particular structure of the GRA had no immediate relevance. It was the function that was important, i.e. that the substance hinders cortisol binding to the GR. At the time of the effective filing date of the application numerous GRAs were known and well established. The application provided sufficient information in this respect, and included citations to several patent literature about these compounds, which were available before the filing date. The skilled person would take any of these known GRA compounds and would know that it would have the function.

The appellant further contended that the application concerned a "break-through invention" and that claim 1 was not a reach-through claim, since the claim was not a compound "per se" claim looking for absolute product protection. The "invention" lay on the function of the substances for a particular use. There was a certain number of patents granted for medical uses in which the compounds were solely defined by their function. The conclusions reached in decision T 1063/06, OJ EPO, 2009, 516, did not apply to the present case. In the case underlying T 1063/06 the compounds to be used were themselves new compounds and they were defined by a new kind of research tool using a screening method set out in the description. In the present case the GR antagonism was well-established in the field at the effective filing date.

The appellant argued that according to decision T 292/85, OJ EPO, 1989, 275, the definition of the "invention" by functional terms was allowable even if the claim may generically embrace the use of unknown compounds to be provided or invented in the future. It also cited decision T 68/85, OJ EPO, 1987, 228, and submitted that the nature of the "invention" and the contribution to the art were to be considered when assessing the requirements of Articles 84 and 83 EPC.

The appellant further submitted that the "invention" related to a function which was linked to the use claimed and that the function was adequately defined in the claim.

The appellant's additional argumentation was that there were two type of corticoid receptors in the brain the Glucocorticoid (GR) and the Mineralcorticoid (MR). The compounds as defined in claim 1 bound more preferably to GR than to MR, about a 100-fold. The MR was most of the time filled with cortisol, then the ideal was a drug which specifically blocked the GR. If the drug blocked both receptors then one had too many undesirable effects.

The board also asked the appellant to explain in how far there was sufficiency of disclosure and support in the description for the treatment of a patient subgroup which was defined, according to the lowest age limit as 45 years old, without any limitations regarding the causes or origins of the symptoms. The appellant answered that it was only natural that the choice of 45 years as the lowest limit for the age of the patients was arbitrary, but what was meant was to include young patients with diminished cognitive functions or cognitive decrease in earlier ages than the majority of patients suffering from MCI. The MCI in these younger patients was not necessarily the result from stroke or diabetes, but the result from dysfunctional neuronal functions.

As regards the contribution to the art the appellant stated the following. It had been known that people show different responses to stress situations. For instance, two out of ten people from the army may present post-traumatic disorders, and eight out of ten don't and will continue with a normal life after having had similar traumatic experiences to the previous subgroup. This factual situation was also true for the development of depression. The response of people to stress was always different. The claim's wording clearly excluded those patients suffering from Cushing's syndrome and with high levels of cortisol. In analogy to the watering of plants which may reverse the effects of a lack of water in yellowing plants, but which comes too late for the burned out blackish specimens, the effect of the GRA was to prevent or slow further memory impairment in patients having normal levels of cortisol. After the present "invention" all the development in the field went in that sense. In fact, many patients can be helped by means of the "invention".

The appellant also argued that in the extreme case one could get this sort of impairment by giving extra cortisol to people. If one gives the cortisol then the subjects still show MCI four days after its administration. Excess of cortisol may harm cognitive functions (the appellant cited second paragraph on page 2 of the description). Therefore, one had to block cortisol activity reducing the effects of cortisol on the GR at brain level for protecting from cognitive decrease and even for improving it.

The appellant also stated the following: "We know a group of patients with normal levels of cortisol, that for reasons we do not understand are vulnerable to the illness MCI" (it cited first paragraph on page 3). The gist of the "invention" is the fact that the antagonist blocks GR for its natural ligand. The present "invention" was like a "light-bulb invention", it came as a conclusion of observations in a variety of places in relation to the compound mifepristone, which is representative for the GRA group. That is the proof that the principle works.

Asked by the Board which parts of the description were to be considered for the disclosure of the general teaching the appellant referred to page 7, line 2, where it was taught to treat or ameliorate MCI with a GRA by blocking the interaction of cortisol with GR.

The appellant completed its arguments in relation to the main request by arguing that documents (1) and (2) were both applications generated by Dr Belanoff itself. Document (1) was a document within the meaning of Article 54(3) EPC. Both documents explored GR antagonists in the treatment of different psychiatric conditions. The skilled person was aware from document (2) that GR had already some function in this respect but there was no disclosure in document (2) about MCI. This prior art document gave the skilled person a certain level of knowledge but it neither anticipated nor rendered obvious the claimed "invention".

As regards the auxiliary request the appellant stated that the arguments submitted for the main request were valid mutatis mutandis for the auxiliary request. Moreover, the claim specified the TAT assay as the method for identifying the glucocorticoid receptor antagonist according to page 17 of the application. The assay referred to induced TAT activity as compared to a control. The control was normally either cortisol or dexamethasone, which was a well known agonist. One had to measure the TAT activity and see how to reduce it. This specification assisted the definition of the GRA and was a response to the board's objections in relation to the lack of a standard test. The TAT assay was the "universal" test for GR activity used world-wide and it was a standard test (well-established, well-known and generally accepted).

XI. The appellant requested that the decision under appeal be set aside and a patent be granted on the basis of the main request filed during the oral proceedings, or, subsidiarily, on the basis of the auxiliary request filed with the letter of 2 November 2010.