T 1374/09 (Infections PRRSV/PFIZER) 29-06-2012

Reasons for the Decision

Admissibility of the main request

1. The claims of the main request were filed at the oral proceedings after discussion of the requests previously on file. During this discussion, the board had directed appellant's attention to issues arising under Article 83 EPC. These issues could not be derived from the decision under appeal and had not all been explicitly mentioned in the communication attached to the summons to oral proceedings. In order to address this situation, the appellant requested an opportunity to submit a new main request which consisted of claims 1 to 6, and 8 only of previous auxiliary request III, filed with letter of 23 April 2012.

2. Under Article 13(1) RPBA, any amendment to a party's case after it has filed its grounds of appeal or reply to a communication from the board may be admitted and considered at the board's discretion.

Although the filing of the main request must be regarded as late, the board has decided to admit it in view of the fact that it was filed as a reaction to objections which in their entirety could not have been recognised by the appellant and that the amendment consisted merely of deleting claims from an auxiliary request already on file.

Articles 123(2), 84 and 54 EPC

3. Basis for the feature "85% identical to the sequence of Seq ID NO. 1" can be found in the claims as originally filed in combination with paragraph 36 of the description. Thus the requirements of Article 123(2) are met.

4. The genomic North American PRRSV sequences disclosed in documents D5 and D6 both lack a complete 5' end sequence which is necessary for infectivity (cf. document D4, p. 382, left column, last paragraph; document D11). Thus, despite being more than 85% identical with the sequence of Seq ID No. 1, they do not anticipate the claimed subject matter. The claimed subject matter is novel.

5. The board has no evidence and sees no reason to deviate from the findings of the examining division, and is thus satisfied that the requirements of Articles 123(2), 84 and 54 EPC are met.

Article 83 EPC

6. Claims 1, 2, 5, and 7 are product claims defined by reference to Seq ID No. 1 and are functionally restricted to those sequences which encode an infectious RNA molecule.

In a case where a technical effect is expressed in a claim, in the present case the infectivity of the encoded RNA, the issue whether this effect is achieved across the whole scope of the claim is a question of sufficiency of disclosure (Decision of the Enlarged Board of Appeal, G 001/03, OJ 2004, 413, Reasons 2.5.2).

It remains thus to be established whether the skilled person, taking into account the disclosure of the patent application and its general knowledge, was in a position to perform the claimed invention readily and without undue burden across essentially the entire breadth of the claims.

7. The cloning of a cDNA encoding an infectious RNA of a North American PRRS virus is described in detail in Example I. Cloning of the indispensable 5' and 3' ends is disclosed in [0127] and [0129], respectively. The creation of a full-length infectious cDNA clone included the assembly of overlapping PCR fragments as well as the correction of multiple mutations resulting from the cloning procedures (cf. [0130], line 53; [0132], line 16; [0133], line 20; [0134], line 25; [0135], line 33). A plaque test for assessing infectivity of the assembled full-length clone is disclosed in [0138]. Further tests are described in Examples IV (e.g. [0153]), and V to VII.

8. The present application thus provides a detailed procedure for the cloning of one particular infectious full-length clone, pT7P129A, and the board has no doubts that the skilled person was in a position to readily derive further sequences from Seq ID No. 1 by conventional means such as those mentioned in paragraph [0028] of the description. Any full-length clone derived from Seq ID No. 1 could then readily be tested by one of the tests disclosed in the patent application.

9. The isolated polynucleotide molecule of claim 7 encodes an infectious RNA molecule encoding a North American PRRSV virus that is genetically modified so that it lacks a detectable antigenic epitope.

Example II of the patent application discloses a modified virus with a deletion of ORF 7 and the production of infectious virions in a helper cell. Antibodies to the ORF 7 protein are commonly found in the sera of PRRS virus infected pigs ([0141], last sentence), and although there is no experimental proof on file, it seems plausible that, as also stated in [0141], pigs vaccinated with an ORF7 deleted PRRS virus would lack antibodies to this virus. Moreover, there is no evidence against it and the board has no doubts that the skilled person was in a position to readily produce and test modified virus with deletions of antigenic epitopes on the basis of the disclosed nucleic acid sequence and the above-mentioned test for infectivity.

10. The board is thus satisfied that the requirements of Article 83 EPC are met.

Article 56 EPC

11. The closest prior art document for the assessment of inventive step is document D5, database entry U87392 (Rel. 57 of 19 November 1998) from the EMBL Nucleotide sequence database which discloses 15409 base pairs of nucleotide sequence of the North American PRRSV isolate VR-2332 with 92% sequence identity with Seq ID 1. Due to the absence of a complete 5' sequence, the disclosed cDNA encodes a non-infectious RNA molecule. Document D5 (section "5' UTR", "misc_features") makes reference to primer extension studies suggesting that there are 20 additional nucleotides at the 5' end.

12. Starting from D5, the technical problem is defined as the provision of a cDNA molecule encoding an infectious RNA of a North American PRRS virus.

13. The solution to this problem proposed by claim 1 is an isolated polynucleotide molecule comprising a DNA sequence encoding an infectious RNA molecule having at least 85% sequence identity with Seq ID No. 1.

14. Example 1 of the application describes the assembly of cDNA clone pT7P129A which is capable of infecting MARC-145 cells in vitro and of producing the symptoms of a PRRSV infection in pigs. The cDNA sequence of this clone differs from the consensus sequence of Seq ID 1 derived from viral isolate P129A in two positions.

The board is convinced that the skilled person, based on the teaching of the patent application, was in a position to readily derive further infectious clones having at least 85% sequence identity with Seq ID No. 1 (cf. points 7 and 8 above), and is therefore satisfied that the technical problem, as defined above, has been solved.

15. It remains to be established whether this solution involved an inventive step.

16. In its decision, the Examining Division held in essence that the claimed solution was obvious in view of document D5, explicitly mentioning that "there are 20 nucleotides at the 5' end", and of document D4 disclosing the cloning of an infectious European PRRSV isolate. Document D4 (page 382, left column, last para.) stated that "it is generally admitted that the entire viral sequence, including the 5' and 3' ends, are required to obtain infectious clones". The examining division concluded that the skilled person would have used the method outlined in document D4 in order to obtain the missing 5' end of isolate VR-2332 and would thus have arrived at the claimed solution in an obvious way.

17. The appellant had argued that the sequence disclosed in document D5 contained errors which would most likely abolish infectivity of the clone. The Examining division considered this argument not pertinent because the appellant had not provided sufficient evidence to prove its point.

18. In the grounds for appeal, the appellant further argued that the sequence disclosed in document D5 was the result of assembling multiple short sequences obtained by sequencing small portions of viral strain VR-2332. This could be derived from document D8 which described the work leading to the sequence disclosed in document D5. Assembling small fragments on paper was however not the same as providing a full-length infectious cDNA clone because the cloning process was error prone for multiple reasons.

In response to the board's communication annexed to the summons to oral proceedings, the appellant filed new document D11 to further support this argument.

19. Document D11 is a conference abstract from November 2001, reporting on difficulties when trying to obtain recombinant infectious clones of North American PRRSV strains. The document states that "no infectivity was seen on BHK-21 cell transfection with an in vitro derived RNA representing our full-length cDNA copy of RespPRRS". Sequence comparison showed that the cloning procedure resulted in multiple amino acid substitutions which "may be a reason for the lack of infectivity of the RespPRRS full-length clone", and a deletion "which may also affect infectivity of the cDNA clone". Document D11 further states that "[t]he difficulty in deriving infectious copies of North American PRRSV strains suggests that the genome is unstable in bacteria, even under conditions shown to result in infectious transcripts of the European strain, Lelystad" (note: the cloning of the Lelystad strain is disclosed in document D4). Document D11 concludes that "novel approaches to rapid development and manipulation of PRRSV genomes may need to be established".

20. The board takes from document D11 that even two years after the priority date of the present application, one of the authors of document D5, Kay S. Faaberg, could not obtain cDNA clones encoding infectious RNA molecules of North American PRRSV isolates by simply combining the teaching of document D5 with that of document D4. One of the reasons for these difficulties seems to have been the instability of the cloned DNA sequences. Document D5 is silent in this respect and the solution to this problem was apparently not derivable from document D4 in an obvious way.

21. Thus, as the claimed solution to the technical problem defined in point 12 above was not obvious to an expert in the technical field, such as one of the authors of document D5, even two years after the priority date of the present application, the same must have been all the more true for the average skilled person at the relevant date.

22. Therefore, claim 1 involves an inventive step, and the same applies to claims 2 to 7.