T 0331/07 (Negative-strand RNA virus/CONZELMANN) 17-07-2008

Summary of Facts and Submissions

I. European patent No. 0 702 085 with the title "Recombinant infectious non-segmented negative strand RNA virus" and claiming priority from the European patent application 94202089 of 18 July 1994 was granted with 18 claims on the basis of the European patent application No. 95201936.2 filed on 14 July 1995.

Claims 1, 8 and 11 read as follows:

"1. A genetically manipulated infectious replicating non-segmented negative-stranded RNA virus mutant comprising an insertion and/or deletion in an open reading frame, a pseudogene region or an intergenic region of the virus genome.

8. A virus mutant according to claims 1-6, characterized in that the virus mutant belongs to the family of rhabdoviridae.

11. A virus mutant according to claim 8, characterized in that the virus mutant is rabies virus."

II. Five oppositions were filed under Article 100(a) to (c) EPC for lack of novelty and inventive step, insufficiency of disclosure and added subject-matter. The opposition division considered that the subject-matter of the main, first and second auxiliary requests then on file did not enjoy priority as of the filing date of the priority document and, therefore, lacked novelty over the teachings of documents (10) and (11) (see infra) which were published in the priority interval. The patent was maintained on the basis of the third auxiliary request then on file. Claims 1 and 7 of this request read as follows:

"1. A genetically manipulated infectious replicating rabies virus mutant comprising an insertion or deletion in an open reading frame, a pseudogene region or an intergenic region of the virus genome.

7. A genetically manipulated infectious replicating rabies virus mutant comprising an insertion and/or deletion in an open reading frame, a pseudogene region or an intergenic region of the virus genome, characterized in that the virus mutant carries a heterologous nucleic acid sequence encoding an epitope or polypeptide of a pathogenic virus or microorganism."

Claims 2 to 6 and 8 to 13 respectively related to further features of the viruses of claims 1 or 7. Claim 14 was directed to a vaccine comprising a rabies virus mutant according to the preceding claims 1 to 13. Claim 15 related to a process for the preparation of a genetically manipulated infectious replicating rabies virus and claims 16 and 17 related to further features of the process of claim 15.

III. The appellant (patentee) filed an appeal, paid the appeal fee and submitted a statement of grounds of appeal together with a new main and three auxiliary requests. The third auxiliary request was the request accepted by the opposition division.

IV. Respondents I to V (opponents 1 to 5) submitted replies thereto.

V. The board sent a communication pursuant to Article 15(1) of the Rules of Procedure of the Boards of Appeal, indicating its preliminary, non binding-opinion.

VI. The appellant and respondents I to III replied to this communication. The appellant's submissions were accompanied by the same main request as filed with the grounds of appeal and new auxiliary requests I, II and V, the pending auxiliary requests I to III being renumbered auxiliary requests II, IV and VI respectively - the sixth auxiliary request thus being the request accepted by the opposition division, see II, supra.

Claim 1 of the main request and of the first auxiliary request read as follows:

"1. A genetically manipulated infectious replicating non-segmented negative-stranded RNA virus mutant comprising an insertion or deletion in an open reading frame, a pseudogene region or an intergenic region of the virus genome."

Claim 1 of the second and third auxiliary requests read as follows:

"1. A genetically manipulated infectious replicating non-segmented negative-stranded RNA virus mutant comprising an insertion or deletion in an open reading frame, a pseudogene region or an intergenic region of the virus genome, characterized in that the virus mutant belongs to the family of rhabdoviridae."

Claim 1 of the fourth and fifth auxiliary requests read as follows:

"1. A genetically manipulated infectious replicating rabies or vesicular stomatitis virus comprising an insertion or deletion in an open reading frame, a pseudogene region or an intergenic region of the virus genome."

VII. Oral proceedings took place on 17 July 2008. Although duly summoned, respondent IV did not take part in the proceedings. At the end of the oral proceedings, the appellant withdrew auxiliary request VI - the claim request accepted by the opposition division - as it was redundant.

VIII. The documents on file which are mentioned in this decision are the following:

(2): Conzelmann, K-K and Schnell, M., J. of Virology,

Vol.68, No.2, pages 713 to 719, February 1994;

(10): Lawson, N.D. et al., Proc.Natl.Acad.Sci.USA, Vol. 92, pages 4477 to 4481, May 1995;

(11): Schnell, M.J. et al., EMBO J. Vol.13, No.18, pages 4195 to 4203, 1994;

(26): Rose, J.K., Proc.Natl.Acad.Sci.USA, Vol.94, pages 14998 to 15000, December 1996.

IX. The appellant's arguments in writing and during oral proceedings insofar as relevant to the present decision may be summarized as follows:

All requests

Articles 87 and 88 EPC; priority rights

The claimed subject-matter enjoyed priority rights as of the filing date of the priority document because this document taken as a whole left no doubt that the invention was to be carried out with any kind of infectious replicating non-segmented negative-stranded RNA viruses, including rhabdoviridae, vesicular stomatitis virus (VSV) and rabies virus.

- On page 1 of the priority document, the title of the invention, "Recombinant infectious non-segmented negative strand RNA virus" already made it clear that the disclosure was not limited to rabies viruses. In fact, rabies viruses were shortly thereafter identified "as an example of a non-segmented negative-stranded RNA virus of the Rhabdoviridae family." Other species were also identified as belonging to this family such as VSV. From page 6, line 22 to page 7, line 9, it was taught that all non-segmented, negative-stranded RNA virus replicated by the same mechanism which necessarily involved the formation of a ribonucleoprotein complex (RNP). On page 13, the reason was given why earlier attempts at multiplying them in vivo in a recombinant manner had failed: the positive-stranded messenger RNAs encoding the viral proteins hybridized to the negative-stranded genomic RNA and, thus, interfered with the crucial encapsidation step. Then, the priority document gave extensive information as to how to multiply rabies viruses (as an example of non-segmented, negative-stranded RNA virus) by circumventing the above mentioned problem due to RNA/RNA hybridisation using an antigenomic approach. Since the problem with encapsidation was common to all non-segmented negative-stranded RNA virus and its solution was described for one of them, the skilled person would take it as a matter of fact that this solution was equally applicable to all of them.

- Document (2) on file taught that, using earlier techniques, attempts at encapsidating negative-stranded RNA transcripts were only successful when these transcripts were of a relatively short size. On the contrary, the priority document showed that full length rabies genomic RNA such as rabies viral RNA could be made into infectious particles. The skilled person would, thus, be all the more inclined to use the technique therein described with other RNA viruses of the same type.

After the antigenomic approach to non-segmented, negative-stranded RNA virus replication had become known, many groups working with different species of such viruses had made use of it, which was a clear indication that the teaching established with rabies viruses was recognized by the scientific community as generally applicable to all of them.

- There were two declarations on file, namely that of Prof. Baltimore of 2 July 1997 and of Dr. Schnell of 1 July 1997, to the effect that the positive results obtained with rabies viruses would not necessarily be/had not been reproducible with other negative-stranded RNA viruses. However, the first one did not provide any scientific basis for its allegations. As for the second one, it was of limited credibility inasmuch as before its author's reported failure to use the antigenomic approach for the multiplication of VSV, another group had succeeded to do so.

In accordance with the practice of the EPO as reflected in the Guidelines for Examination, the implicit as well as explicit disclosures of the priority document had to be taken into account when assessing priority. Here, there was no doubt that the concept of the "antigenomic approach to negative-stranded RNA viruses recombinant replication" was at least implicitly disclosed in the priority document as being applicable to all these viruses. The priority date was, thus, valid.

Articles 54 and 56 EPC; novelty

As the subject-matter of the main request enjoyed priority rights, documents (10) and (11) published in the priority interval were not relevant to novelty or inventive step and the request fulfilled the requirement of Art.54 and 56 EPC. This was also true of auxiliary requests I to V for the same reason.

X. The respondents' arguments in writing and during oral proceedings insofar as relevant to the present decision may be summarized as follows:

All requests

Articles 87 and 88 EPC; priority rights

- The Enlarged Board of Appeal's decision G 2/98 (OJ EPO 2001, 413) established the principles to be followed when assessing the validity of a priority document. In particular, it was stated in point 6.8 of the decision that a narrow and strict interpretation of the concept of "the same invention" should be applied. Reading the priority document made it absolutely clear that its teaching only related to rabies viruses. Its title, "Recombinant infectious non-segmented negative strand RNA virus", had no legal value and, besides, the word "virus" was used in the singular, which certainly did not convey the information that the invention was meant to be covering more than the rabies virus itself. On page 1, the rabies virus was put in its phylogenetic context (page 1), its clinical effects, its genomic organisation and the problems associated with its use as a vaccine were then described (pages 2 to 5). On pages 6 and 7, a somewhat broader disclosure of the ways to manipulate viral genomes in general was given with a specific passage on page 7 dealing with negative-stranded viruses. From page 8 onwards, only rabies viruses were mentioned. Even in the passage on page 16 which related to future lines of investigation, there was no mention at all of applying the technique to further non-segmented negative-stranded viruses. Neither the generic invention as claimed in claim 1 of the main request and auxiliary requests I to III nor the invention as claimed in auxiliary requests IV and V relating to VSV viruses were even as much as hinted at in the priority document which, therefore, was not suitable for establishing priority rights.

- Post-published document (26) (see page 14998, right-hand column) mentioned that, because of low efficiency, it was not obvious that the antigenomic approach would work with other viruses than rabies virus, eg. with VSV. There was, thus, evidence on file that the scientific community did not regard it as a matter of fact that the teachings of the priority document could be extended. In this respect, it ought to be kept in mind that the examples provided by the priority document all concerned rabies viruses with alterations in the intergenic region and that not all non-segmented, negative-strand viruses had such a region in their genome.

- The appellant's argument as regards scientific groups having immediately understood the antigenomic approach also to be applicable to other non-segmented, negative stranded viruses than rabies virus may have reflected a possible lack of inventive step of further inventions. Yet, it did not amount to evidence that these further inventions were comprised in the priority document, even in an implicit manner.

- There were two declarations on file, namely that of of Prof. Baltimore of 2 July 1997 and of Dr. Schnell of 1 July 1997, expressing the view that, at the priority date, the skilled person would not have expected that the antigenomic approach for the recombinant production of rabies viruses would necessarily work with other non-segmented negative-stranded RNA viruses.

In accordance with G 2/98 (supra), common general knowledge could be taken into account when assessing the content of a priority document and, indeed, it would have been a matter of common general knowledge that rabies viruses were part of the family of non-segmented, negative-stranded viruses and that their replication required the formation of the RNP complex (as indicated in the priority document). Yet, in accordance with the case law, common general knowledge could be used to interpret a disclosure but not to broaden it. Here, there was nothing to interpret, the disclosure of the priority document being, as already explained, strictly limited to rabies viruses. For this reason, neither of the main request and auxiliary requests I to V enjoyed priority.

Articles 54 and 56 EPC; novelty and inventive step

As documents (11) and (10) published in the priority interval respectively disclosed the claimed invention and the antigenomic approach applied to VSV, novelty or inventive step must be denied to claim 1 of the main request and auxiliary requests I to III whereas claim 1 of auxiliary requests IV and V lacked inventive step.

XI. The appellant requested that the decision under appeal be set aside and the patent be maintained on the basis of the main request filed on 16 April 2007 or auxiliary requests I to V filed on 17 June 2008.

The respondents requested that the appeal be dismissed.