T 1372/05 (FIV immunoassay/IDEXX) 28-11-2007

Admission of the amended main request into the proceedings

1. The amended main request (sole request on file) was filed during the oral proceedings. In spite of the fact that this set of claims was clearly late-filed, for the following reasons the board decided to admit the amended main request into the proceedings.

2. Claims 1 to 4 of the amended main request correspond essentially to claims 1, 2, 7 and 6 of the claim request underlying the decision under appeal, except for claim 1 being restricted to an enzyme-linked immunosorbent assay (ELISA) method, and for the language of claims 1 and 3 being partially reformulated. The amended claims do not contain any subject-matter which has not been claimed before, nor do they raise any issues which the board could not reasonably be expected to deal with without adjournment of the oral proceedings (cf. Article 10b(3) RPBA). Furthermore, the introduced amendments are manifestly allowable from a formal point of view, in particular in respect of the issues of added matter (Article 123(2) EPC) and clarity (Article 84 EPC). In fact, the amended claims represent a serious attempt at remedying severe clarity deficiencies present in the previous claim request as well as at establishing an inventive step over the teaching of document D2.

3. The amended main request was thus admitted into the proceedings.

Sufficiency of disclosure (Article 83 EPC)

4. The immunoassay method of claim 1, which is based on the detection of the humoral immune response induced by FIV in infected cats, comprises as a first step contacting a sample from the animal with a purified fragment of at least 5 amino acids of the FIV env gp130 polypeptide, which fragment contains an epitope of the gp130 polypeptide. In a second step of the method, formation of an antibody/polypeptide complex between the polypeptide fragment and antibodies in the sample is allowed under suitable conditions, detection of such complex formation indicating the presence of antibodies in serum in response to FIV infection.

5. Although during oral proceedings the issue of inventive step in respect of the immunoassay of claim 1 was discussed to some extent, the decisive question in the present case is whether or not the claimed subject-matter fulfils the requirements of Article 83 EPC, ie whether a person skilled in the art, taking into account the guidance provided by the application as filed and the common general knowledge at the time the disclosure was made, would have arrived at the invention as claimed, without an undue burden of experimentation and without exercising any inventive skill.

6. In defining whether or not the required experimentation amounts to an undue burden, the boards of appeal have acknowledged that, when it comes to the sufficiency of disclosure in an unexplored or difficult field, a reasonable amount of trial and error is permissible. However, there must be adequate instructions available in the specification or on the basis of common general knowledge which would lead the skilled person necessarily and directly towards success through the evaluation of initial failures or through an acceptable statistical expectation rate in case of random experiments (cf. T 639/95 of 21 January 1998, point 1 of the Reasons; and T 226/85, OJ EPO 1988, 336, point 8 of the Reasons).

7. The assessment whether a European application fulfils the requirements of Article 83 EPC has to be conducted in each case on its own merits (cf. decisions T 158/91 of 30 July 1991, point 2.3 of the Reasons; T 639/95 of 21 January 1998, point 3 of the Reasons; and T 891/02 of 29 October 2003, point 3 of the Reasons). In the present case, for carrying out the immunoassay of claim 1 the skilled person should have had the required means readily available, in particular a fragment of at least 5 amino acids of the FIV env gp130 polypeptide that contains an epitope of this polypeptide.

8. However, as observed by the examining division in the decision under appeal, the application discloses neither the amino acid sequence of the FIV env gp130 polypeptide, nor any fragments derived therefrom that contain an epitope of the gp130 polypeptide.

9. This has not been disputed by the appellant. In its statement setting out the grounds of appeal, the appellant nevertheless argued that, at the filing date of the application, a person skilled in the art was in the position to obtain the amino acid sequence of the FIV env gp130 polypeptide or the nucleotide sequence encoding it, either from document D2 or via a search in the appropriate databases, eg the NCBI database (cf. printout of the record no. NP_040976 filed as Annex B1 to the statement of grounds of appeal). Once the amino acid sequence had been obtained, it was allegedly a matter of routine experimentation to obtain suitable fragments of the FIV env gp130 polypeptide containing an epitope of this polypeptide.

10. The board notes that document D2, a scientific publication authored by, among others, the present inventors, is not mentioned in the present application, and that, not being a textbook or general technical literature, the content of this document cannot be considered to be part of the common general knowledge of the person skilled in the art which he/she may use to supplement the information given in the application (cf. in particular decisions T 206/83, OJ EPO 1987, 5, point 5 and T 234/93 of 15 May 1997, point 4). Moreover, document D2, whilst identifying the gp130 polypeptide as the sole FIV polypeptide which reacts with all serum samples obtained from 14 cats experimentally infected with FIV, does not provide any sequence information for the polypeptide in question.

11. As regards the NCBI database record (cf. Annex B1), which discloses the amino acid sequence of an envelope polypeptide of the feline immunodeficiency virus, nowhere in the application is there a reference to this record. Thus, not being part of the disclosure content of the application itself, the sequence information contained in the record could only be used to supplement the disclosure if it was part of the common general knowledge of the skilled person at the filing date.

12. In its communication sent in preparation for the oral proceedings, the board expressed its doubts concerning the probative value of the Annex B1 in respect of the alleged public availability of the amino acid sequence of the gp130 polypeptide at the filing date of the application, and drew the attention of the appellant to the fact that the sole date indicated in the record was 12 January 2004, ie roughly fourteen years after the filing date. The board also pointed to the reference made in the record to a scientific publication by Olmsted et al. (cf. document B2 supra) published in October 1989, ie prior to the filing date of the application. However, the appellant did not submit any arguments in response to these observations, either in writing or at the oral proceedings.

13. On the basis of the evidence on file, the board is not in the position to acknowledge that the sequence information contained in the record no. NP_040976 of the NCBI database (cf. Annex B1) belongs to the common general knowledge of the skilled person for the purpose of assessing sufficiency of disclosure in respect of the present application.

14. First, there is no conclusive evidence on file in respect of the actual date on which the database record in question was made available to the public. Consequently, the appellant's allegation that, at the filing date of the application, the amino acid sequence contained in the record of the NCBI database was available to a person skilled in the art cannot be accepted.

15. And secondly, even if it is assumed that the database record and the sequence information contained in it were made available to the public shortly before or after the scientific publication to which the record refers (document B2 published in October 1989, ie 7 months before the filing date of the application), the board is not convinced that the required information, ie the amino acid sequence of the gp130 polypeptide, is provided in the record in a straightforward and unambiguous manner so that supplementary searches were not needed (cf. decision T 890/02, OJ EPO 2005, 497, point 9 of the Reasons). The NCBI database record does not identify the amino acid sequence contained in it as corresponding to the env gp130 polypeptide of the feline immunodeficiency virus; rather, one of the CDS features in the record reads "/locus_tag="FIVgp5"", which appears to indicate that the disclosed sequence may correspond to a different FIV envelope polypeptide. This ambiguity cannot be clarified by document B2, to which reference is made in the database record, because in document B2 only three FIV envelope polypeptides are mentioned: a 140 kDa polypeptide, designated gp140 (precursor), a 100 kD polypeptide, designated gp100 (outer mebrane) and a gp36 polypeptide (transmembrane). Prima facie, none of these polypeptides appears to correspond to the gp130 polypeptide mentioned in claim 1.

16. At oral proceedings, the appellant argued further that the skilled person could obtain the information required to clone and sequence the genome of FIV, and in particular the nucleotide sequence encoding the gp130 polypeptide, from document D3. However, as in the case of document D2 discussed above (cf. point 10), no reference is made in the application to document D3. Since this document is a scientific publication, not a textbook or an encyclopaedia, and since no reasons have been put forward why this document should exceptionally be considered to form part of the common general knowledge at the filing date, the appellant's argument cannot be accepted.

17. Furthermore, the board judges that, even if the skilled person could, in principle, have tried to clone and sequence the genome of the feline immunodeficiency virus, with or without the guidance provided in document D3, the whole amount of experimentation required not only for cloning and sequencing the gene encoding the env gp130 polypeptide, but also for finding fragments of this polypeptide containing an epitope, which fragments could be as short as five amino acids, would have amounted to an undue burden.

18. A further line of argument of the appellant relied on the passage on page 5, lines 12ff. of the application, in which the isolation of antigenic glycopeptides of FIV using a Lentil Lectin Sepharose 4B column is described. In the appellant's view, following the instructions given in this passage the skilled person could isolate the gp130 polypeptide and, by partial digestion, obtain polypeptide fragments from which the sequence could be determined using techniques well known in the art. Isolating and testing the polypeptide fragments for antigenicity required only routine experimentation.

19. The board disagrees with this view. It is apparent from the application that, among the FIV polypeptides reacting with sera of all 14 cats experimentally infected with FIV, three are glycoproteins, namely gp40, gp47 and gp130 (cf. page 5, lines 4 and 5). The method disclosed in the application for the isolation of glycopeptides is not specific for any of these three glycoproteins. Consequently, further purification steps would be necessary to isolate the gp130 polypeptide. However, only rather general references to HPLC and affinity chromatography using polyclonal or monoclonal antibodies, but no detailed instructions are provided in the application in this respect. Moreover, there is no specific guidance in the application either with respect to the proteolytic digestion of the isolated gp130 polypeptide or the purification of the polypeptide fragments obtained after digestion. The skilled person is also left to his or her own resources when it comes to the selection of polypeptide fragments of gp130 having an epitope of this polypeptide, as neither specific epitopes of the gp130 polypeptide nor monoclonal antibodies that bind to them have been described.

20. In sum, in order to obtain polypeptide fragments derived from the FIV env gp130 polypeptide that have an epitope of this polypeptide, a person skilled in the art would have to embark on a research program, for which the application provides very little guidance. Even if each individual step per se can be considered to be feasible with a certain amount of trial and error, the total amount of experimental effort necessary to obtain the means for carrying out the invention is regarded as undue for the skilled person (cf. T 639/95 of 21 January 1998, point 15 of the Reasons). Consequently, the disclosure of the application is considered to be insufficient as regards the means for carrying out the invention as claimed.

21. The experimental evidence presented by the appellant (cf. Annex B to the statement of grounds of appeal) cannot change the board's finding. By this evidence, the appellant intended to show that two specific fragments derived from the FIV env gp130 polypeptide and corresponding to amino acids 398-410 and 599-615, could be used in the immunoassay of claim 1 for the detection of FIV seropositive samples, and that using these fragments the claimed assay was at least as reliable as the PetCheck Anti-FIV test kit.

22. The board notes that the two specific gp130 fragments used in the experiments of Annex B are not disclosed in the application as filed, and that the fact that sixteen years after the filing date of the application two fragments of the FIV env gp130 polypeptide suitable for carrying out the claimed invention are described, cannot remedy the insufficient guidance provided in the application for isolating such fragments.

23. The board thus concludes that the sufficiency requirements of Article 83 EPC are not satisfied in respect of the means necessary for carrying out the invention as claimed, in particular in respect of the provision of suitable fragments of the FIV env gp130 polypeptide having an epitope of this polypeptide. Since the findings in the decision under appeal with regard to Article 83 EPC were justified, the appellant's request to set aside this decision cannot be granted.