T 1018/06 (Ischemia detection/ISCHEMIA) 03-12-2007

Summary of Facts and Submissions

I. European patent application No. 03 027 486.4, published under No. 1 411 356 (referred to in the present decision as "the application as filed"), was filed on 10 July 1992 as a divisional application to the European patent application No. 92 915 563.8, published as International application under No. WO 93/03346 (referred to in the present decision as "the earlier application"). In a decision dated 9 December 2005, the examining division refused the application for failing to fulfil the requirements of Articles 84 and 56 EPC.

II. Claim 1 of the set of thirteen claims refused by the examining division read as follows:

"1. A method of detecting the occurrence of ischemia in a patient, comprising the steps of:

(a) contacting a blood, blood-derived body fluid sample including a serum or plasma sample or tissue sample of said patient with metal ions capable of binding to protein metal ion-binding sites selected from the group consisting of thiol, hydroxyl, carbonyl, amino, imidazole, hydroxymethionyl and guanidinium groups in said sample, to form a mixture containing protein bound metal ions and non-protein bound metal ions, and

(b) detecting the amount of non-protein bound metal ions using a method that detects free metal ions, whereby the amount of free metal ions is a measure of the amount of available metal ion-binding sites of the protein and amount of oxidatively damaged metal ion binding sites, thereby indicating the occurrence or non-occurrence of an ischemic state in said sample."

Claim 1 differed from claim 1 as filed by the addition of the wording "or tissue sample" in part (a) of the claim and the deletion of the term "respectively" at the end of part (b) of the claim. Claims 2 to 13 were as originally filed and were directed to preferred embodiments of claim 1.

III. As for the reasons for the refusal, the decision under appeal referred to the communications of the examining division dated 27 July 2004 and 20 July 2005.

In these communications, the applicant had been informed that the subject-matter of claim 1 was considered not to be supported by the description over the whole range of the claim because the application as filed only taught that protein thiol groups were decreased in ischemic events. However, claim 1 included a list of other non-thiol groups for which there was neither a teaching nor information on their possible use in the disclosed method (Article 84 and Rule 29 EPC). Moreover, in the absence of this information, these non-thiol groups did not provide a working solution to the technical problem underlying the application, i.e. the provision of an alternative method to detect ischemic events in a patient. Therefore, the requirements of Article 56 EPC were considered not to be fulfilled.

Since the applicant had not filed any comments or amendments in reply to the second communication of the examining division and had requested, with letter dated 21 September 2005, a decision according to the state of the file, the application was refused by the examining division making reference only to its previous communications.

IV. With letter dated 16 February 2006, the applicant (appellant) filed a notice of appeal and paid the appeal fee on the same day. The statement setting out the grounds of appeal was filed with letter dated 18 April 2006, together with a main request and a first, second and third auxiliary requests.

V. The decision under appeal was not rectified by the examining division and the case was remitted to the board of appeal (Article 109(2) EPC).

VI. On 25 October 2006, the board sent a communication pursuant to Article 110(2) EPC stating its preliminary, non-binding opinion. The appellant's attention was also drawn to the pending cases under Ref. Nos. G 1/05 of 16 September 2005 and G 1/06 of 4 April 2006 (consolidated with G 3/06 of 15 May 2006) before the Enlarged Board of Appeal, which were considered of relevance for the question whether the present divisional application met the requirements of Articles 76(1) and 123(2) EPC.

VII. With letter dated 28 December 2006, the appellant replied to the board's communication and filed a fourth auxiliary request. The appellant requested the board to stay the further appeal proceedings until the Enlarged Board of Appeal had decided on the pending cases, unless the board could positively decide on Article 76(1) EPC based on said latter request.

VIII. With a communication dated 26 January 2007, the appellant was informed that the board did not intend to proceed with the case before the decisions of the Enlarged Board of Appeal were issued.

IX. After the decisions of the Enlarged Board of Appeal G 1/05 and G 1/06 (both to be published in the OJ EPO) were issued on 28 June 2007, the appellant was summoned to oral proceedings.

X. With letter dated 2 November 2007, the appellant made further submissions together with a document describing details of the commercial product ACB (Albumin Cobalt Binding) Test Reagent Pack as well as the test and the colorimetric detection method based on this product. The appellant further filed a new main request and new first and second auxiliary requests. Claim 1 of the main request read as follows:

"1. An in vitro method of detecting the occurrence of ischemia in a patient, comprising the steps of:

(a) contacting a serum, plasma, fluid or tissue sample from said patient with an excess amount of metal ions capable of binding to protein metal ion-binding sites in said sample, to form a mixture containing protein bound metal ions, including thiol group-bound metal ions, and non-protein bound metal ions, and

(b) detecting the amount of non-protein bound metal ions using a method that detects free metal ions, whereby the amount of free metal ions is a measure of the amount of available metal ion-binding sites of the protein and amount of oxidatively damaged metal ion binding sites, thereby indicating the occurrence or non-occurrence of an ischemic state in said sample."

Claims 2 to 11 and 13 were as filed and were directed to preferred embodiments of claim 1. Claim 12 was also dependent on claim 1 and was identical to claim 12 as filed except for defining the metal ion used as cobalt ion.

XI. Oral proceedings took place on 3 December 2007.

XII. The appellant's arguments, insofar as relevant to the present decision, may be summarised as follows:

Main request

Article 123(2) EPC

The characterization of the claimed method as an "in vitro" method was supported by the whole content of the application as filed. Paragraphs [0017] and [0018] of the application as filed referred to general protein metal ion-binding sites, including thiol groups, and provided a formal support for part (a) of claim 1. Whereas the reference to "an excess amount of metal ions" in claim 1 was supported by paragraph [0019], a formal basis for the type of sample from the patient, including "fluid or tissue", was found in paragraphs [0014] and [0023]. The features of claim 1 were thus supported by the application as filed.

Article 84 EPC

The application disclosed a simple method for detecting the occurrence of an ischemic event in a patient, which comprised only two steps, namely (a) contacting a sample from the patient with metal ions capable of binding to protein metal ion-binding sites, and (b) detecting the quantity of non-protein bound (unbound) metal ions. The introduction of thiol groups into claim 1 ("including thiol group-bound metal ions") reflected the technical feature that was described in the application as essential to the disclosed method. The objection for lack of clarity raised by the examining division was thereby overcome. The references to "an in vitro method" and to "an excess amount of metal ions" did not introduce any ambiguity in claim 1. The meaning of "an excess amount" was clearly defined in paragraph [0019] of the application. The introduction of cobalt as the metal ion in claim 12 reflected the fact that the pH range indicated in this claim was the pH range given in paragraph [0030] for the specific binding of cobalt ion to the protein.

Articles 54 and 56 EPC

The examining division did not raise any objection for lack of novelty and, in the decision under appeal, identified both the closest prior art (document D3, US 4 492 753) and the technical problem to be solved. The solution proposed in the application was acknowledged to be neither disclosed nor hinted at in any of the cited prior art documents and thus, not to be obvious. Subject-matter regarding to thiol groups was explicitly recognized to be inventive in the decision under appeal. The claimed subject-matter was however considered to comprise embodiments that did not solve the technical problem and therefore, inventive step was not acknowledged. The main request necessarily required now the presence of thiol groups and, for this reason, the objection for lack of inventive step was moot.

XIII. The appellant (applicant) requested that the decision under appeal be set aside and that a patent be granted on the basis of the main request or, in the alternative, of the auxiliary request 1 or 2, all filed with a letter of 2 November 2007.