T 2261/15 (Modifying gene expression unpolyadenylated RNA/COMMONWEALTH SCIENTIFIC INDUSTRIAL RESEARCH ORGANISATION) 07-04-2022

Summary of Facts and Submissions

I. European patent no. 1 650 306 is based on the European patent application no. 05 016 726.1 (hereinafter "the patent application"), a divisional application of the earlier European patent application no. 00 953 352.2 (EP 1 208 211), published under the PCT as International patent application WO 01/12824 (hereinafter "the earlier patent application"; for passages common to both, the patent application and the earlier patent application, reference will be made hereinafter to "the (earlier) patent application"). The patent was granted with 52 claims.

II. Two oppositions were filed on the grounds as set forth in Articles 100(a), 100(b) and 100(c) EPC. The opposition division considered the main request to contravene Articles 76(1) and 123(2) EPC and auxiliary request I to fulfil the requirements of the EPC. The patent was thus maintained in amended form on the basis of auxiliary request I.

III. Appeals were lodged by both opponents and, in the statements setting out their grounds of appeal, they maintained the objections raised under Articles 76(1), 123(2), 84, 83, 54 and 56 EPC against auxiliary request I upheld by the opposition. In reply thereto, the patent proprietor ("respondent") filed new documentary evidence, auxiliary requests II and III, and, as a main request, maintained auxiliary request I upheld by the opposition division (i.e. to dismiss the appeals). As an auxiliary measure, oral proceedings were requested by all parties.

IV. Opponent 01 withdrew their opposition and appeal and is thus no longer a party to these proceedings. Opponent 02 is the sole remaining appellant.

V. The parties were summoned to oral proceedings. In a communication issued in preparation of these oral proceedings, the parties were informed of the board's provisional opinion on the issues of the case.

VI. Both parties replied in substance to the board's communication. With submissions dated 2 March 2020, the respondent withdrew the former main request, filed a new auxiliary request II to replace former auxiliary request II, and made this new auxiliary request II their main request; auxiliary request III being thus the respondent's sole auxiliary request.

VII. After several postponements due to, inter alia, the COVID-19 pandemic, oral proceedings were rescheduled for 7 April 2022. With submissions dated 22 March 2022, the respondent withdrew their request for oral proceedings.

VIII. In a communication issued on 28 March 2022, the parties were informed that the oral proceedings were to take place as scheduled on 7 April 2022.

IX. Oral proceedings were held on 7 April 2022 in the absence of the respondent.

X. Claims 1 and 16 of the main request ("new auxiliary request II") read as follows:

"1. A method for reducing the phenotypic expression of a nucleic acid of interest, which is normally capable of being expressed in a eukaryotic cell, said method comprising the step of providing to the nucleus of said eukaryotic cell an unpolyadenylated RNA molecule comprising

- one target-specific sense nucleotide sequence essentially similar to part of an RNA molecule transcribed or produced from the nucleic acid of interest, wherein said target-specific sense nucleotide sequence includes a sequence of about 20 consecutive nucleotides with 100% sequence identity to the corresponding part of the target nucleic acid, and

- one target-specific antisense nucleotide sequence essentially similar to the complement of part of an RNA molecule transcribed or produced from said nucleic acid of interest,

wherein said target-specific sense and antisense nucleotide sequences are essentially complementary to each other and are capable of forming a hairpin structure with each other,

wherein said unpolyadenylated RNA is produced by transcription of a chimeric gene comprised within said eukaryotic cell, said chimeric gene comprising a promoter functional in said eukaryotic cell operably linked to a target specific DNA region encoding said RNA, and

wherein said method is not a method of treatment of the human or animal body by surgery or therapy, or a diagnostic method practised on the human or animal body."

"16. A chimeric gene encoding an unpolyadenylated RNA molecule, said unpolyadenylated RNA molecule comprising one target specific sense nucleotide sequence essentially similar to part of an RNA molecule produced from a nucleic acid of interest, said target specific sense nucleotide sequence being essentially similar to part of an RNA molecule produced from a nucleic acid of interest and including a sequence of about 20 consecutive nucleotides with 100% sequence identity to the sequence of a corresponding part of said nucleic acid of interest,

and one target-specific antisense nucleotide sequence essentially similar to the complement of part of an RNA molecule transcribed or produced from said nucleic acid of interest,

wherein said target-specific sense and antisense nucleotide sequences are essentially complementary to each other and are capable of forming a hairpin structure with each other,

wherein said nucleic acid of interest is normally present in a eukaryotic cell and wherein said unpolyadenylated RNA produced by transcription of the chimeric gene reduces expression of said nucleic acid of interest when provided to the nucleus of said cell,

said chimeric gene comprising a promoter functional in said eukaryotic cell operably linked to a target specific DNA region encoding said RNA."

Claims 2 to 15 are directed to particular embodiments of claim 1; claims 2 to 7 and claims 10 to 15 read as granted claims 8 to 13 and granted claims 20 to 25, respectively; claims 8 and 9 read as granted claims 17 and 18, respectively, the latter with the additional feature "provided said eukaryotic cell comprises the corresponding RNA polymerase in active form". The dependencies of these dependent claims being correctly adapted.

Claims 17 to 24 are directed to particular embodiments of claim 16 and read as granted claims 33 to 40. Claims 25 to 31 and claim 32 read as granted claims 42 to 48 and granted claim 52, respectively. The dependencies of these claims being also correctly adapted.

XI. Claims 1 and 16 of the auxiliary request ("auxiliary request III") read as follows:

"1. A method for reducing the phenotypic expression of a nucleic acid of interest, which is normally capable of being expressed in a eukaryotic cell, said method comprising the step of providing to the nucleus of said eukaryotic cell an unpolyadenylated RNA molecule comprising

- one target-specific sense nucleotide sequence of 20 consecutive nucleotides with 100% sequence identity to part of an RNA molecule transcribed or produced from the nucleic acid of interest, and

- one target-specific antisense nucleotide sequence,

wherein said target-specific sense and antisense nucleotide sequences are complementary to each other and are capable of forming a hairpin structure with each other,

wherein said unpolyadenylated RNA is provided to the nucleus by transcription of a chimeric gene comprised within said eukaryotic cell, said chimeric gene comprising a promoter functional in said eukaryotic cell operably linked to a target specific DNA region encoding said RNA, and

wherein said method is not a method of treatment of the human or animal body by surgery or therapy, or a diagnostic method practised on the human or animal body."

"16. A chimeric gene encoding an unpolyadenylated RNA molecule, said unpolyadenylated RNA molecule comprising one target specific sense nucleotide sequence of 20 consecutive nucleotides with 100% sequence identity to part of an RNA molecule produced from a nucleic acid of interest,

and one target-specific antisense nucleotide sequence

wherein said target-specific sense and antisense nucleotide sequences are complementary to each other and are capable of forming a hairpin structure with each other,

wherein said nucleic acid of interest is normally present in a eukaryotic cell and wherein said unpolyadenylated RNA produced by transcription of the chimeric gene reduces expression of said nucleic acid of interest when provided to the nucleus of said cell,

said chimeric gene comprising a promoter functional in said eukaryotic cell operably linked to a target specific DNA region encoding said RNA."

Claims 2 to 15 and claims 17 to 32 read as the corresponding claims 2 to 15 and claims 17 to 32 of the main request.

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

Consideration/admission of the main request and of the auxiliary request into the appeal proceedings

The main request was filed three months after the issuance of the board's communication and one month before the originally scheduled date of the oral proceedings. It was thus a late-filed request which did not even address, let alone overcome, all the objections raised against the former main request; the late-filed main request addressed only one of the objections raised under Articles 76(1) and 123(2) EPC but none of the others raised under these articles. No exceptional circumstances had been put forward, and none was present, to justify the filing of this claim request at this late stage of the proceedings.

Although the auxiliary request was filed in reply to the appeal, the respondent failed to indicate in this reply a basis for this auxiliary request in the (earlier) patent application. Thus, as regards this auxiliary request, the respondent failed to provide a complete case as required by Article 12 RPBA. Moreover, this auxiliary request neither addressed nor overcame, prima facie, all the objections raised against the former main request. The amendments introduced into independent claims 1 and 16 were the same as those introduced into the corresponding claims of an auxiliary request II filed shortly before the oral proceedings at first instance and renumbered auxiliary request III during these oral proceedings. Neither the admission of this auxiliary request into the proceedings at first instance nor any of these amendments were considered by the department of first instance and there was thus neither a reference thereto in the decision under appeal nor a decision was taken thereupon at first instance.

Auxiliary request ("auxiliary request III")

Articles 76(1) and 123(2) EPC

The sole disclosure of a sequence of 20 consecutive nucleotides was at page 17, line 21 of the (earlier) patent application. However, this disclosure related to a fragment or a subsequence of the total target-specific sense nucleotide sequence which was itself defined at page 17, lines 14 to 19 by a specific length and percentage of sequence identity to the corresponding part of the target nucleic acid. The disclosures on pages 16 and 18 of the (earlier) patent application related to the total target-specific sense nucleotide sequence and required this sequence to be "essentially similar" to the target nucleic acid (page 16) and further defined the meaning of the term "essentially similar" (page 18). However, these requirements relating to the total target-specific sense nucleotide sequence were omitted from claim 1 of the auxiliary request and thus, the scope of the claim was broader than the disclosure of the (earlier) patent application and comprised embodiments that were not envisaged in the (earlier) patent application.

Moreover, the disclosure in the paragraph bridging pages 18 and 19 of the (earlier) patent application defined the target-specific sense and antisense nucleotide sequences to be essentially complementary to each other and capable of forming an artificial hairpin structure. The omission of the terms "essentially" and "artificial" in claim 1 of the auxiliary request contravened Articles 76(1) and 123(2) EPC. The latter term imposed an intended limitation on the hairpin that was no more present in claim 1.

XIII. The arguments of the respondent in writing, insofar as relevant to the present decision, may be summarised as follows:

Consideration/admission of the main request and of the auxiliary request into the appeal proceedings

The main request was derived from the auxiliary request upheld by the opposition division and from the former auxiliary request II by cancellation of several dependent claims that had been objected under Articles 76(1) and 123(2) EPC in the board's communication. The main request was thus a direct response to these objections; it neither changed the respondent's case nor diverged from the subject-matter of the former requests on file, in particular of auxiliary request I upheld by the opposition division. The main request simplified the subject-matter and the number of objections at issue, reducing solely the number of claims.

The auxiliary request was derived from auxiliary request I upheld by the opposition division by cancellation of several dependent claims and by amendment of features in the independent claims to address, inter alia, the objections raised by the appellant in their statement setting out the grounds of appeal. The auxiliary request did not change the respondent's case and was convergent with the subject-matter of the former requests on file; it simplified the subject-matter and reduced the number of claims.

In total, only a small number of claim sets had been filed in these proceedings and their order had never been changed. This approach respected the principle of convergence and contributed to procedural efficiency.

Auxiliary request ("auxiliary request III")

Articles 76(1) and 123(2) EPC

The disclosure of the paragraph bridging pages 18 and 19 of the (earlier) patent application provided a basis for the unpolyadenylated RNA comprising target-specific sense and antisense nucleotide sequences capable of forming a hairpin structure. The disclosure at page 17, lines 19 to 21 of the (earlier) patent application provided the basis for the length of the target-specific sense nucleotide sequence (20 consecutive nucleotides) and its degree of identity (100%) with the target nucleic acid of interest. Page 16, lines 10 to 12 of the (earlier) patent application disclosed that the target nucleic acid of interest, to which the target-specific sense nucleotide sequence was "essentially similar", was part of an RNA molecule transcribed or produced from the nucleic acid of interest. In addition, page 18, lines 6 to 10 disclosed that "essentially similar" meant a sequence identity between two sequences of at least about 75% to 100%. Since this part of the teaching explicitly mentioned 100% identity, it was clearly intended to be combined with the disclosure of the target-specific sense nucleotide sequence having 100% identity to the target nucleic acid of interest as present at page 17, lines 19 to 21 of the (earlier) patent application. These combined passages provided the basis for the target-specific sense nucleotide sequence of 20 consecutive nucleotides with 100% sequence identity to part of an RNA molecule transcribed or produced from the nucleic acid of interest. Claims 33 to 35 of the earlier patent application and page 9, lines 18 to 19 and 22 of the (earlier) patent application provided a basis for the provision of the unpolyadenylated RNA molecule to the nucleus by transcription of the chimeric gene.

XIV. The appellant requests that the decision under appeal be set aside and the patent be revoked.

XV. The respondent requests that the decision under appeal be set aside and the patent be maintained on the basis of the main request (new auxiliary request II filed with submission dated 2 March 2020) or, in the alternative, on the basis of the auxiliary request (auxiliary request III filed with submission dated 25 July 2016).