Saturday, 23 October 2010

W 4/09 – Nothing Special


I do not resist the temptation to report what might well be the last W decision to be published. Under the EPC 2000, PCT protests are no longer entrusted to the Boards of appeal, but apparently there still were some residual files awaiting treatment. (It should be noted, however, that the decision, although published recently, was taken on July 1, 2009 already, by a Board chaired by Ms. Kinkeldey.)

The decision concerns the international application published as WO 2008/121132 and having the title “Gene expression profiling for identification, monitoring and treatment of prostate cancer”.

Independent claim 1 read as follows:

“1. A method for evaluating the presence of prostate cancer in a subject based on a sample from the subject, the sample providing a source of RNAs, comprising: a) determining a quantitative measure of the amount of at least one constituent of any constituent of any one table selected from the group consisting of Tables 1, 2, 3, and 4 as a distinct RNA constituent in the subject sample, wherein such measure is obtained under measurement conditions that are substantially repeatable and the constituent is selected so that measurement of the constituent distinguishes between a normal subject and a prostate cancer-diagnosed subject in a reference population with at least 75% accuracy; and b) comparing the quantitative measure of the constituent in the subject sample to a reference value.”

There were four more independent claims and 18 dependent claims. All the independent claims refer to the Tables 1 to 4, each of which contains dozens of genes.

The EPO acting as ISA informed the applicant in an invitation under Article 17(3)(a) PCT and Rule 40.1) PCT that the application did not comply with the requirement of unity of invention (Rule 13.1 PCT) and invited the applicant to pay within a time limit of one month 290 (!) additional search fees.

The applicant paid one additional search fee under protest.

[6] According to Rule 13.3 PCT the determination of whether a group of inventions is so linked as to form a single inventive concept shall be made without regard to whether the inventions are claimed in separate claims or as alternatives within a single claim. […]

[9] The board agrees to the ISA’s finding in the invitation to pay additional fees that the use of “constituents” or marker genes that are differentially expressed in healthy subjects and in subjects suffering from prostate cancer was known in the state of the art.

Indeed, document D1 discloses methods and compositions for gene expression profiling of prostate cancer marker genes based on quantitative RT—PCR, suitable for assessment of the presence of prostate cancer, as well as prognosis, progression and recurrence following therapy […]. The document particularly discloses e.g. ADAMTS1, EGR1, IGFBP3, JUN, MCAM and NRAS as marker genes, suitable for such expression profiling […].

Similarly, document D2 discloses expression profiling of ca. 26.000 genes (amongst them Muc1), allowing sub-typing of prostate cancer, progression prognosis and recurrence prediction […].

Also document D3 discloses expression profiling of 12.625 genes, including FOS (table 1), allowing the prediction or recurrence of prostate cancer with 90% and 75% accurancy (sic), based on a so-called “gene expression—based recurrence predictor algorithm” […].

Document D5 discloses profiling of prostate cancer gene expression (291 genes) by quantitative real—time RT—PCR and reveals 46 genes which are differentially expressed in prostate cancer, and four which are especially suitable for assessment of progression and recurrency […].

Similarly, document D6 discloses gene expression profiling and the identification of 277 genes which are differentially expressed between prostate cancer and normal tissue, as measured by quantitative RT—PCR. This allowed prognosis and recurrence prediction […].

[10] In view of this prior art, the technical problem underlying the two searched inventions was the provision of alternatives to the known “constituents” or marker genes that are differentially expressed in healthy subjects and in subjects suffering from prostate cancer. As solutions to this problem the first searched invention provides the ABCC1 gene and the second searched invention provides the CDH1 gene.

[11] The board cannot recognise structural characteristics or effects common to the two genes provided according to the searched group of inventions common to all claims which go beyond that they are differentially expressed in healthy subjects and in subjects suffering from prostate cancer and could hence represent “special technical features” within the meaning of Rules 13.2 and 13.3 PCT. Therefore the board must conclude that the solutions to the above technical problem as provided by the two searched inventions do not share a technical relationship involving one or more of the same or corresponding special technical features in the sense of Rule 13.2 PCT a posteriori.

[12] The above analysis of prior art cited in the partial search report provided by the ISA, thus establishes that the technical relationship as defined above between the two searched inventions does not involve “special technical features” and can therefore not provide unity of invention in accordance with Rule 13.2 PCT.

[13] The applicant has argued that the ISA had failed to search the invention as defined in the claims and specification and that the restriction of the primary invention to a single gene was improper.

[14] The board notes however, that, as can be taken from the wording of independent claims 1 to 4, the claimed methods concern “determining a quantitative measure of the amount of at least one constituent of any constituent (of any one table selected from the group consisting) of Tables 1, 2, 3, and 4 as a distinct RNA constituent” (claim 1) or similarly “determining a quantitative measure of the amount of at least one constituent of any constituent of Tables 1, 2, 3, and 4 as a distinct RNA constituent” or similarly “at least 1 constituent from Tables 1, 2, 3, and 4 (claims 2 to 4) (emphasis added by the board). The kit of claim 23 is stated to be “comprising at least one reagent for the detection or quantification of any constituent measured according to any one of claims 1 to 22”. The board therefore also concurs with the ISA that both the identified invention relating to gene ABCC1 and the invention defined by the applicant with respect to the CDH1 gene […] are subject-matter of the claimed invention.

[15] In addition the board notes that the wordings of the claims do not mention statistical methods (e.g. stepwise logistic regression analysis) to analyse the expression levels of genes that had been implicated in ovarian cancer in a sample isolated from a subject. Nor do the claims commonly refer to a cut off of 75% classification accuracy for selecting gene models capable of distinguishing between the two subject groups or gene models disclosed in tables 1A-4A of the application as published which recites all of the possible one- and two-gene combinations (i.e. gene models) for the genes shown in tables 1 to 4, capable of distinguishing between healthy, normal subjects and prostate cancer subjects with at least 75% classification accuracy using the claimed methods. Only for this reason therefore the further arguments of the applicants that the search should not have been restricted to one gene must fail.

[16] As a consequence of the above considerations the two groups of inventions searched by the ISA are not so linked as to form a single inventive concept. Consequently, the application is considered not to comply with the requirements of unity of invention under Rule 13.1 PCT, and the invitation to pay additional fees with respect to the invention identified in relation to the DLC1 gene was justified.

The protest under Rule 40.2(c) PCT is dismissed.

Should you wish to download the whole decision, just click here.

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