T 0541/13 (PCR detection system/LGC GENOMICS) of 6.2.2019

Summary of Facts and Submissions

I. European patent No. 1 726 664 with the title "Detection system for PCR assay" was granted from the European patent application No. 06252796.5.

II. The patent was opposed on the grounds for opposition of Article 100(a) in conjunction with Articles 54 and 56, Article 100(b) and Article 100(c) EPC.

III. In a decision posted on 2 January 2013, an opposition division found that the subject-matter of the amended claims according to each of the main request and the auxiliary requests 1 to 5 filed during the oral proceedings, extended beyond the content of the application as filed and, thus, contravened Article 123(2) EPC. The auxiliary requests 6 and 7 were not admitted into the proceedings. Consequently, the opposition division revoked the patent.

IV. The patent proprietor (appellant) filed an appeal. Together with its statement of grounds of appeal, the appellant re-submitted the set of claims according to the main request underlying the decision under appeal, and submitted six sets of claims as new auxiliary requests 1 to 6 which replaced the auxiliary requests previously on file. As a further auxiliary request, oral proceedings were requested.

V. Claims 1, 2 and 5 of the main request read as follows:

"1. An assay detection method for a PCR process using FRET, the method comprising the steps of providing a first single-labelled Oligonucleotide sequence and at least a second single-labelled Oligonucleotide sequence, the first and second Oligonucleotide sequences being of differing Tm, in which the first and second Oligonucleotide sequences hybridise to one another in free solution to form a fluorescent quenched pair, providing at least one primer and initiating PCR thereby generating a complementary sequence to the first Oligonucleotide sequence, wherein the first Oligonucleotides[sic] has a Tm that is above the Ta of the PCR process and the second Oligonucleotide sequence being of a Tm that is below the Ta of the PCR process, characterised in that

the first single-labelled Oligonucleotide sequence consists of an Oligonucleotide sequence having a single 5' fluorescent label and the second single-labelled Oligonucleotide sequence consists of a quencher-labelled Oligonucleotide sequence, the at least one primer comprising at least one unlabelled 5' tailed primer, the unlabelled 5' tailed primer having a tail region, the tail region comprising an Oligonucleotide sequence identical to an Oligonucleotide sequence of the first single-labelled Oligonucleotide sequence, the first single-labelled Oligonucleotide sequence being a primer from which DNA synthesis is initiated once a complementary sequence to the first single-labelled Oligonucleotide sequence has been generated during the PCR process, such that the second single-labelled Oligonucleotide sequence is no longer able to hybridise to the first single-labelled Oligonucleotide sequence, whereby a measurable signal is generated.

2. A detection method as claimed in Claim 1, incorporated in a PCR system to detect a specific sequence, wherein said first single-labelled Oligonucleotide sequence and second single-labelled Oligonucleotide sequence differ by more than 10 bases in length.

5. A detection method as claimed in Claim 1, wherein the PCR process is monitored via the use of hybridisation only."

Dependent claims 3, 4 and 6 to 14 are directed to various embodiments of the detection method of claim 1.

VI. Claim 1 of the auxiliary request 1 differs from claim 1 of the main request in that the wording "... providing at least one primer ..." has been replaced by "... providing an unlabelled 5' tailed primer ...", and the wording "... the at least one primer comprising at least one unlabelled 5' tailed primer, ..." has been deleted. The remaining claims have not been amended.

VII. The set of claims of the auxiliary request 2 differs from that of the auxiliary request 1 in that in claim 1 the second single-labelled oligonucleotide sequence is defined as consisting of a 3' quencher-labelled oligonucleotide sequence. Additionally, claim 14 has been deleted.

VIII. Claim 1 of the auxiliary request 3 differs from claim 1 of the auxiliary request 2 in that the 3' quencher-labelled oligonucleotide sequence is further characterized as being antisense to the first single-labelled oligonucleotide sequence.

IX. In addition to the amendments introduced into the auxiliary request 2 (see section VII above), in claim 1 of auxiliary request 4 the wording "... the tail region comprising an Oligonucleotide sequence identical to an Oligonucleotide sequence of the first single-labelled Oligonucleotide sequence ..." is replaced by "... the tail region being an Oligonucleotide sequence identical to the Oligonucleotide sequence of the first single-labelled Oligonucleotide sequence ..." (emphasis added by the board).

X. Claim 1 of the auxiliary request 5 includes two additional amendments. The unlabelled 5' tailed primer is further characterised as being "... an unlabelled 5' DNA sequence tailed primer ...", and the wording "... the unlabelled 5' tailed primer having a tail region, the tail region being ..." is replaced by "... the unlabelled 5' DNA sequence tailed primer having a 5' DNA sequence tail region that is not directed to the amplicon region of interest and the 3' portion of the primer being directed to the amplicon region of interest, the DNA sequence tail region being ..." (emphasis added by the board).

XI. The amendments introduced into the auxiliary request 6 are the same as those introduced into the auxiliary requests 3 and 5 (see sections VIII and X above).

Claims 2 to 13 of the auxiliary requests 2 to 6 are identical to the corresponding claims of the main request.

XII. Although the respondent (opponent) was given the opportunity to submit observations on the statement of grounds of appeal, none were received.

XIII. The parties were summoned to oral proceedings before the board.

XIV. By letter dated 1 October 2018, the respondent informed the board that it would not be attending the oral proceedings.

XV. In a communication sent in preparation of the oral proceedings, the board made observations on various procedural and substantive issues relevant to the case, and expressed a provisional opinion concerning some of the findings on Article 123(2) EPC in the decision under appeal.

XVI. By letter dated 9 January 2019, the appellant informed the board that it would not be represented at the scheduled oral proceedings, and requested a decision based on the file.

XVII. Oral proceedings were held on 6 February 2019 in the absence of the parties.

XVIII. The submissions made by the appellant in writing, as far as relevant to this decision, were essentially as follows:

Main request - Article 123(2) EPC

The opposition division was wrong in deciding that the subject-matter of the claims extended beyond the content of the application as filed. There was ample basis in the application as filed for the feature "quencher-labelled" without further limitation. Reference to the second single-labelled oligonucleotide being quencher-labelled was found in original claims 6 and 15, dependent on claim 1. Further basis could be found on page 5, lines 16 to 19 and page 6, line 33 to page 7, line 2. The application did not teach that it was essential for the quencher label to be at the 3' end of the oligonucleotide. Moreover, the position of the quencher was not critical in realising the technical effect of the invention. The omission of the position did not require modification of other features. Thus, all three criteria of the essentiality test were fulfilled. For this reason too, the absence of reference to 3' labelling in the claims could not be regarded as an inadmissible addition of new matter.

Admission of the auxiliary requests 1 to 6 into the proceedings

The new auxiliary requests addressed the opposition division's objections. Each of the requests satisfied the requirements of Article 123(2) EPC.

XIX. The respondent did not make any submissions in substance.

XX. The appellant (patent proprietor) requested that the decision under appeal be set aside and the case be remitted to the opposition division for consideration of the outstanding grounds for opposition, based on the main request or any of the auxiliary requests 1 to 6 filed together with the statement of grounds of appeal.

XXI. The respondent (opponent) did not put forward any requests.

Reasons for the Decision

Main request - Article 123(2) EPC

1. Claim 1 is directed to an assay detection method for a PCR process using FRET (fluorescence resonance energy transfer), in which method at least one unlabelled 5' tailed primer and two kinds of single-labelled oligonucleotides are used, a first oligonucleotide having a single 5' fluorescent label and at least one second oligonucleotide which is quencher-labelled at an unspecified position.

2. In the decision under appeal, the opposition division found that the subject-matter of claim 1 of the main request extended beyond the content of the application as filed, inter alia because there was no basis in the application for a method using a quencher-labelled oligonucleotide without any further limitation, in particular as regards the location of the label (see section 6.2 of the decision under appeal).

3. This finding is correct. The assay detection method of claim 1 is based on a FRET system in which the first and second single-labelled oligonucleotide sequences hybridize to one another to form a fluorescent quenched pair. Upon introduction of a complementary sequence to one or both sequences the quenched pair is separated, whereby a measurable light signal is generated (see page 5, lines 29 to 33 of the application as filed). In order to undergo FRET, the fluorophore and the quencher in a quenched pair must be in close proximity (see page 7, lines 5 to 7).

4. The assay detection method disclosed in the application as filed requires the use of a first single-labelled oligonucleotide having a single 5' fluorescent label together with a second single-labelled oligonucleotide having a 3' quencher label, so that, when they hybridize to each other, the quencher label is brought in very close proximity to the fluorophore (see the paragraph bridging pages 6 and 7 and the first paragraph on page 7, as well as each of Figures 1.1, 2.1, 3.1 and 4.1). Accordingly, the quencher-labelled oligonucleotides used in the (sole) Example 1 of the application are labelled at their respective 3' ends (see page 9, lines 35 and 36, and page 11, lines 29 and 30).

5. There is however no clear and unambiguous disclosure in the application as filed of a method using a 5' fluorescent-labelled oligonucleotide together with an oligonucleotide labelled with a quencher at a position other than the 3' end.

6. In its statement of grounds of appeal, the appellant pointed to the passage on page 5, lines 16 to 19 as basis for such a method. The passage reads:

"Furthermore, by use of oligo sequence pairs of which one sequence, suitably the quencher sequence, has a Tm (melting temperature) below the Ta (annealing temperature) of the PCR process, the effectiveness of the technique is dramatically improved."

This passage does not relate to the label of the quencher sequence, but rather to a feature (the melting temperature) associated with the nucleotide sequence of the oligonucleotide as such. In this context, the mere reference to the quencher sequence cannot be regarded as a clear and unambiguous disclosure that the quencher label could be attached to any position of the oligonucleotide.

7. The appellant pointed also to claims 6 and 15 of the application as filed, which specify, respectively, that one of the oligonucleotide sequences used in the detection system has the quencher label of the fluorescent quenched pair, and that the fluorescent oligo pairs are labelled one of the pair with a fluorophore and the other with a non-fluorescent quenching molecule. Neither claims 6 and 15 nor claim 1 of the application as filed, on which they depend, specify that the first single-labelled oligonucleotide has a 5' fluorescent label, as required by the present claim 1. Nor do they specify further features characterizing the method of the present claim 1, e.g. the use of a 5' tailed oligonucleotide primer. Hence, claims 6 and 15 of the application as filed cannot be accepted as a basis for the specific embodiment defined in claim 1.

8. Finally, it should be noted that the passage from page 6, line 33 to page 7, line 2, to which the appellant pointed as basis for a quencher-labelled oligo without any further limitation, includes an express reference to a 3' quencher labelled oligo (see the sentence bridging pages 6 and 7).

9. For these reasons, the board shares the opposition division's view that the method defined in claim 1 represents an unallowable generalization of specific embodiments disclosed in the description and the drawings. Since this finding alone justifies the rejection of the main request for lack of compliance with Article 123(2) EPC, there is no need for the board to decide whether the further adverse findings in sections 6.1, 6.3 and 6.4 of the decision under appeal are correct.

Admission of auxiliary requests 1 to 6 into the proceedings

10. In the communication sent in preparation of the oral proceedings, the board observed that the objections under Article 123(2) EPC addressed by the new auxiliary requests 1 to 4 seemed to have been raised already in the notice of opposition, and that the appellant had not put forward any reasons why the new requests could not have been filed during the proceedings before the opposition division. Since the appellant neither made any submissions in substance in reply to the board's communication, nor attended the oral proceedings, the board, exercising the discretion conferred by Article 12(4) of the Rules of Procedure of the Boards of Appeal, decides not to admit the auxiliary requests 1 to 4 into the appeal proceedings.

11. In its communication, the board also observed that claim 10 of the application as filed, on which the appellant relied as a basis for the subject-matter of claim 5 of the main request, depended on claim 2 which specified that one of the single-labelled oligonucleotides is more than 10 bases shorter than the other. However, this limitation did not apply to the method of claim 5 of the main request because the present claim 5 depended on claim 1. Hence, in the absence of a basis for the subject-matter of claim 5 in the application as filed, Article 123(2) EPC was contravened.

12. This issue, which had been raised already by the opposition division in the decision under appeal (see section 12.5), is prejudicial to the maintenance of the patent on the basis of the auxiliary requests 5 and 6 because both include a claim 5 with the same wording and dependency as claim 5 of the main request. The appellant was made aware of this issue both by the decision under appeal and the board's communication, but nevertheless decided not to remedy the deficiency. Under these circumstances, the board sees no reason to admit the auxiliary requests 5 and 6 into the proceedings.

Article 113(1) - right to be heard

13. The grounds on which the present decision is based are known to the appellant from the decision under appeal and the board's communication sent in preparation of the oral proceedings. Despite the board's provisional conclusion that none of the sets of claims on file met the requirements of Article 123(2) EPC (see points 13 and 20 of the board's communication), the appellant neither replied to the communication nor attended the oral proceedings.

Conclusion

14. There is no request on file that fulfils the requirements of Article 123(2) EPC. Consequently, the board cannot grant the appellant's request that the opposition division's decision to revoke the patent be set aside.

Order

For these reasons it is decided that:

The appeal is dismissed.