T 0985/11 (Delta-4 desaturase/ABBOTT) 09-09-2015

1. The duly summoned respondent did not attend the oral proceedings, as announced in its letter of 5 August 2015. In accordance with Rule 115(2) EPC and

Article 15(3) and (6) RPBA, the oral proceedings therefore took place in its absence.

2. The patent under consideration relates to nucleic acid molecules that encode delta-4 (Delta4)-desaturases from the fungus Thraustochytrium aureum (T. aureum), the fungus Schizochytrium aggregatum (S. aggregatum) and the algae Isochrysis galbana (I. galbana). Desaturases are involved in the production of long-chain polyunsaturated fatty acids (LCPUFAs). Delta4-desaturases catalyse the conversion of, for example, adrenic acid (22:4n-6) to omega6-docosapentaenoic acid (DPA, 22:5n-6) and of

omega3-docosapentaenoic acid (22:5n-3) to docosahexaenoic acid (DHA, 22:6n-3).

Main request

Inventive step (Article 56 EPC)

3. The appellant raised objections under Article 56 EPC against subject-matter relating to the Delta4-desaturase from S. aggregatum. This protein has the amino acid sequence depicted in SEQ ID NO: 37 which is encoded by a nucleic acid molecule having the nucleic acid sequence depicted in SEQ ID NO: 36. It was undisputed that these sequences are not entitled to the first priority date claimed (see section II above) and that therefore document D1 is prior art under Article 54(2) EPC for subject-matter relating to the Delta4-desaturase from

S. aggregatum.

Closest prior art

4. Document D1 relates to the discovery of novel fatty acid desaturase family members termed Fad4 (Delta4-desaturase), Fad5 and Fad5-2 (Delta5-desaturase), and Fad6

(Delta6-desaturase). These are involved in the biosynthesis of LCPUFAs, such as DHA and DPA, in LCPUFA- producing organisms such as Thraustochytrium, Pythium irregulare, Schizochytrium, and Crythecodinium. Document D1 reports that DHA has beneficial effects on human health and that biotechnology has long been considered an efficient way to manipulate the process of producing fatty acids in plants and microorganisms. In particular, document D1 discloses the Delta4-desaturase from Thraustochytrium sp. (see D1, page 7, Figure 1, SEQ ID NO: 1, SEQ ID NO: 2). It was undisputed that document D1 is the closest prior art and the board sees no reason to differ.

Technical problem to be solved and its solution

5. Starting from document D1, the technical problem to be solved consists in the provision of alternative

Delta4-desaturases. In view of the data provided by the patent the board is satisfied that the subject-matter of claim 1, insofar as it relates to the Delta4-desaturase from S. aggregatum, provides a solution to this problem.

Obviousness

6. Document D1 discloses not only the nucleotide sequence that encodes the Delta4-desaturase and corresponding amino acid sequence from Thraustochytrium sp. (see Figure 1, SEQ ID NO: 1, SEQ ID NO: 2), but also the generation of probes and primers for use in identifying and/or cloning other desaturases (see page 15, lines 4 to 14). The identification of orthologues, i.e. of homologous gene sequences encoding desaturases in different species, is disclosed on page 17, line 27 to page 18, line 35 of document D1. Specifically, it is proposed to identify orthologues using methods known in the art, e.g. by hybridisation to an isolated nucleic acid molecule of document D1 under stringent hybridisation conditions.

7. The genus Schizochytrium is explicitly mentioned in document D1 as a possible source for Delta4-desaturases (see page 18, lines 10 to 12). Therefore, in the board's view, the use of any specific species within the genus Schizochytrium, e.g. S. aggregatum, for the provision of an alternative Delta4-desaturase would be obvious for the skilled person who would have isolated the nucleotide sequence encoding a Delta4-desaturase from the organism and confirmed the enzymatic properties of the encoded protein by routine methodology (see document D1, page 18, lines 3 to 12, Examples 6, 7, 8, SEQ ID NO: 1, SEQ ID NO: 2). There is no evidence on file that the

Delta4-desaturase of S. aggregatum differs from the

Delta4-desaturases from the other Schizochytrium species. The specific nucleotide sequence claimed thus can not impart any inventive step because no unexpected property that would go beyond encoding a Delta4-desaturase is linked to it (see also decision T 111/00, point 9 of the reasons). The nucleic acid sequence encoding the Thraustochytrium sp. Delta4-desaturase shows 77.5% identity in 1229 nucleotides' overlap with the nucleic acid sequence encoding the S. aggregatum Delta4-desaturase

(SEQ ID NO: 36). The skilled person thus also had a reasonable expectation of cloning the S. aggregatum sequence using the Thraustochytrium sp. Delta4-desaturase sequence as a probe.

8. The respondent argued that the provision of the

Delta4-desaturase from S. aggregatum was not straightforward. Relying on declaration D11 it submitted that there was nothing in document D1 that would have led the skilled person to consider aligning solely

Delta6-desaturase sequences in order to design primers for cloning a Delta4-desaturase enzyme.

Inventive step is to be assessed on the basis of the skilled person's knowledge before the effective date of the claimed subject-matter. This knowledge may differ from that of the inventors of a patent. In the present case, the skilled person was aware of document D1 which discloses the nucleic acid sequence encoding the

Delta4-desaturase from Thraustochytrium sp. and provides clear teaching to use this sequence and fragments thereof as probes for cloning further desaturases (see D1, page 18, lines 3 to 35). The respondent's argument thus fails.

9. The respondent further submitted that the skilled person taking the route indicated in the prior art would have failed to isolate the nucleotide molecule encoding the Delta4-desaturase of S. aggregatum, as demonstrated by the unsuccessful experiments carried out by the present inventors. Therefore, in line with decision T 18/09, inventive step should be acknowledged.

9.1 However, as set out above (see point 7), the skilled person aware of the teaching of document D1 would not have followed the approach taken by the inventors and would thus not have encountered the problems they faced in taking that approach, based on primers designed on the basis of known Delta5- and Delta6-desaturases. In the absence of any evidence showing that the approach taught in document D1 would have failed, the board sees no reason to assume that the skilled person would not have been able, as a matter of routine, to isolate the nucleic acid sequence encoding Delta4-desaturase from S. aggregatum.

10. In summary, the board concludes from the above that the skilled person would have arrived in an obvious manner at the subject-matter of claim 1, insofar as it relates to the Delta4-desaturase of S. aggregatum. Therefore, the main request fails to meet the requirements of Article 56 EPC.

Auxiliary requests 1 and 2

Article 56 EPC

11. Claim 1 of auxiliary requests 1 and 2 relates inter alia to an isolated nucleotide sequence comprising a nucleotide sequence encoding a polypeptide having Delta4-desaturase activity, wherein the amino acid sequence of said polypeptide comprises the amino acid sequence of SEQ ID NO: 37, i.e. the Delta4-desaturase of S. aggregatum. Thus, the arguments set out above for the main request (see points 3 to 10) apply mutatis mutandis to these requests. Therefore, auxiliary requests 1 and 2 likewise fail to meet the requirements of Article 56 EPC.

Auxiliary request 3

Article 56 EPC

12. Auxiliary request 3 relates to Delta4-desaturases from I. galbana and T. aureum. The appellant raised objections under Article 56 EPC against the subject-matter relating to the Delta4-desaturase from I. galbana. This protein has the amino acid sequence depicted in SEQ ID NO: 55 which is encoded by a nucleic acid molecule having the nucleic acid sequence depicted in SEQ ID NO: 54. It was undisputed that these sequences are not entitled to the first priority date claimed (see section II above) and that therefore document D1 is prior art under Article 54(2) EPC for subject-matter relating to the Delta4-desaturase from I. galbana.

Closest prior art

13. It was undisputed that document D1 is the closest prior art and the board sees no reason to differ.

Technical problem to be solved and its solution

14. Starting from document D1, the technical problem to be solved consists in the provision of alternative Delta4-desaturases. As a solution, claim 1 provides a nucleotide sequence encoding a polypeptide having Delta4-desaturase activity, wherein the amino acid sequence of said polypeptide has at least 70% identity to the amino acid sequence depicted in SEQ ID NO: 55.

15. The appellant submitted that it had not been shown to be plausible that each and every sequence that was at least 70% identical to SEQ ID NO: 55 would also exhibit Delta4-desaturase activity or that Delta4-desaturases existed within said sequence range. Therefore the problem had not been solved.

15.1 As regards the appellant's first argument, the board notes that the claimed subject-matter is restricted to nucleotide sequences "encoding a polypeptide having Delta4-desaturase activity". Accordingly, only functional sequences are encompassed by the claim. The appellant's first argument thus fails.

15.2 As regards its second argument, the board has no reason to doubt that the skilled person would (i) know how to create variants within the claimed range, and also (ii) know both from the teaching of the prior art and the patent itself how to test such variants for Delta4-desaturase activity. The appellant's second argument thus also fails.

16. In view of the data provided by the patent, the board is satisfied that the subject-matter of claim 1 solves the technical problem.

Obviousness

17. The question is whether starting from document D1 it was obvious to provide the Delta4-desaturase from I. galbana. Document D1 suggests looking for further Delta4-desaturases in LCPUFA-producing organisms, and mentions in this context the organisms Thraustochytrium, Pythium irregulare, Schizochytrium, and Crythecodinium (see point 4 above). However, it does not mention any algal species, let alone I. galbana. At the effective date of the claimed subject-matter the species I. galbana was poorly characterised. There is no evidence on file that identifies I. galbana as an LCPUFA-producing organism. Thus, neither document D1 nor any other prior art document provides any motivation for the skilled person to look specifically at I. galbana when faced with the technical problem formulated above (see point 14).

17.1 Even if the skilled person identified I. galbana as a possible source for a Delta4-desaturase, the board has doubts whether the cloning strategy proposed in document D1 would have led to the isolation of the Delta4-desaturase of I. galbana.

17.2 Document D1 proposes using hybridisation to e.g. an isolated nucleic acid molecule "under stringent hybridisation conditions", for the identification of orthologues (see page 18, lines 18 to 26). Document D1 defines "stringent hybridisation conditions" to mean conditions under which sequences which are at least about 70% identical remain hybridised to each other (lines 27 to 32). However, the Delta4-desaturase of I. galbana shares only very limited sequence identity with the Delta4-desaturase from Thraustochytrium sp., namely 30.8% at the amino acid level (see Figure 22 of the patent). It therefore seems unlikely that the nucleic acid encoding the Delta4-desaturase of I. galbana would have been isolated using the route suggested in document D1.

18. The appellant further submitted that the skilled person would have considered an approach based on PCR using degenerate primers.

18.1 However, document D1 does not disclose any degenerate primers that would have been suitable for the isolation of the Delta4-desaturase of I. galbana. Moreover, the required information regarding codon bias was not available for I. galbana to permit the design of degenerate primers based on conserved motifs found in other desaturase enzymes.

19. Lastly, the appellant submitted that the skilled person would have followed the approach taken by the inventors, namely to generate a cDNA library from I. galbana and randomly sequence all of the clones.

19.1 In the board's view this argument involves hindsight, as neither the organism I. galbana nor the approach chosen by the inventors is mentioned in document D1. This argument thus also fails.

20. In summary, the board concludes from the above that the skilled person would not have arrived in an obvious manner at the subject-matter of claim 1, insofar as it relates to the Delta4-desaturase of I. galbana. The considerations in respect of claim 1 of auxiliary request 3 apply also to the subject-matter of independent claims 6, 7, 8, 9, 10, 11, 13, 14 and 18 and of dependent claims 2 to 5, 12, 15 to 17 and 19 to 23. Therefore auxiliary request 3 fulfils the requirements of Article 56 EPC.

Adaptation of the description (Article 84, second sentence, EPC) / Remittal (Article 111(1) EPC)

21. At the oral proceedings, the appellant submitted in relation to auxiliary request 3 that the respondent had failed to provide a description that was adapted to the claims of this request. Therefore, auxiliary request 3 contravened the requirements of Article 84, second sentence, EPC. Since the description could not be adapted at the oral proceedings because the respondent was absent, the patent had to be revoked.

22. The board notes that the claims of auxiliary request 3 held allowable by the board no longer encompass subject-matter relating to the Delta4-desaturase of S. aggregatum. Accordingly, the description as adapted before the opposition division relates to subject-matter which is no longer claimed and therefore needs to be further adapted.

2.3 The board does not share the appellant's view that the board must revoke the patent for this reason because of the respondent's inability, due to its absence, to provide an adapted description at the oral proceedings. Instead, the board takes the view, for the reasons set out below, that under Article 111(1), second sentence, EPC it still has discretion to decide how to proceed in this situation, and in particular whether to (1) remit the case to the opposition division for adaptation of the description or (2) exercise the powers of the opposition division and either (2a) continue the proceedings in writing or (2b) revoke the patent.

24. Rule 115(2) EPC and Article 15(3) RPBA address the situation that a duly summoned party is absent from the oral proceedings. Rule 115(2) EPC provides that the proceedings may continue without that party, and Article 15(3) RPBA confirms that the board is not obliged to delay any step in the proceedings, including its decision, by reason only of the absence of such party who may then be treated as relying only on its written case.

25. These provisions indicate that, by absenting itself from the oral proceedings, a duly summoned party cannot expect that the appeal proceedings will necessarily be conducted differently from if the party had been present, and in particular that they will be continued. The provisions do not however restrict the board's discretion when deciding which of the available options to pursue.

26. In the case of an allowable appeal, whether and to which extent a board deals itself with any issues arising, i.e. exercises the powers of the department whose decision was appealed, or remits the case to that department for further prosecution, is decided by the board on the merits of the case in point. When taking such decisions, the boards consider various aspects, such as the parties' requests, procedural economy, the parties' interest in having the matter examined by two instances, and the right to fair proceedings (see Case Law of the Boards of Appeal, 7th edition 2013, IV.E.7).

27. Considering the available options mentioned in point 23 above, the board decided against continuing the appeal proceedings in writing, for reasons of procedural economy. Furthermore, Article 15(6) RPBA requires boards to ensure that cases are ready for decision at the conclusion of the oral proceedings unless there are special circumstances to the contrary. In the present case, the board could not identify any special circumstances preventing it from taking a decision terminating the appeal proceedings.

28. In support of its request for non-remittal, the appellant argued that the avoidance of further delays, procedural economy, its interest in obtaining a final decision and its need for legal certainty required immediate revocation of the patent.

29. The board is not persuaded by these arguments. From the file history it is apparent that the appellant did not take any steps prior to the oral proceedings to accelerate the opposition or appeal proceedings. The additional delay caused by a remittal seems likely to be fairly short, since the wording of the claims is finalised by the present decision, and the proceedings after remittal will thus be confined to adapting the description. As the board is taking a decision on the allowable version of the claims, procedural economy and legal certainty are also served.

30. As the claims of auxiliary request 3 were found allowable, the board regarded revocation of the patent as inappropriate in the present case. Moreover, it considers that it is required to act in a predictable manner, to ensure fair proceedings for the parties. It has therefore looked at how it has dealt with cases similar to the present one, in which adaptation of the description needs thorough examination because of the extent to which the claims have been amended during the appeal proceedings. It found that in fact it more often than not remitted such cases for adaptation of the description - even if the patentee was present at the oral proceedings and could have filed an adapted description.

31. In support of its case, the appellant further relied on the following five decisions: T 109/02, T 181/02, T 776/05, T 651/08 and T 2294/08. What all these cases have in common is that the appellant-patentee was absent from the oral proceedings, no description adapted to the amended claim requests was on file, and the patent was ultimately revoked.

32. In all five decisions, the board concerned emphasised that a patent proprietor who prior to oral proceedings files amended claims but no description adapted thereto, and who is not represented at the oral proceedings, cannot "rely on" the proceedings being continued in writing or the case being remitted to the department of first instance for adaptation of the description (see T 181/02, point 4 of the reasons; T 109/02, point 4.2 of the reasons, T 651/08, point 3 of the reasons, T 776/05, point 3.3 of the reasons, and T 2294/08, point 3 of the reasons).

33. The board agrees: a patentee who acts in that way cannot be sure of getting a possibility to adapt the description to the amended claims, and - as shown by the decisions cited by the appellant - does indeed run the risk of losing its patent due to a non-adapted description.

34. However, the board notes that the outcome in T 181/02 and T 776/05 could only have been revocation of the patent, because the deciding board came to the conclusion that, irrespective of the absence of an adapted description, the claims as amended did not meet the requirements of the EPC (see T 181/02, point 3.4 of the reasons and T 776/05, points 2.10 and 3.1 of the reasons), whilst in the three other decisions the board did not elaborate on its reasons for opting for revocation. Be that as it may, this board cannot identify anything in any of the five decisions relied on by the appellant to suggest that the deciding board took the view that it was obliged to revoke the patent for lack of an adapted description, or in other words could not have ordered remittal for adaptation of the description had the circumstances of the case so required. That these boards too - like the present one - regarded themselves as having discretion to remit the case is in fact shown by the statements in their decisions that a patent proprietor cannot "rely on" a postponement of the board's final decision or on a remittal of the case for adaptation of the description.

35. For the reasons set out above (see points 29 and 30), the board decided, exercising its discretion under Article 111(1) EPC, to remit the case to the opposition division for adaptation of the description and the drawings to the claims of auxiliary request 3. By doing so the board did not delay any step in the appeal proceedings and was able to reach a final decision at the conclusion of the oral proceedings, in accordance with Article 15(3) and (6) RPBA.

Referral to the Enlarged Board of Appeal (Article 112(1) EPC)

36. The appellant submitted that uniform application of the law required that the board refer the question filed during the oral proceedings (see section VII above) to the Enlarged Board of Appeal if it intended to deviate from decisions T 109/02, T 181/02, T 651/08, T 776/05 or T 2294/08.

37. Pursuant to Article 112(1)(a) EPC, the boards of appeal refer questions to the Enlarged Board, either of their own motion or upon request from a party, in order to ensure uniform application of the law or if a point of law of fundamental importance arises, if they consider that a decision is required for the above purposes.

38. As set out above, none of the five decisions relied on by the appellant called into question the continued existence of the boards' discretion to decide whether - if the duly summoned patentee is absent from the oral proceedings and no description adapted to the amended claims is on file - to exercise the powers of the opposition division or to remit the case. Accordingly, the present decision does not deviate from those cited.

39. Moreover, based on the analysis set out above, the board found a clear answer in the provisions of the EPC and the RPBA. It therefore did not consider a referral to be required.

40. Accordingly, the appellant's request for a referral to the Enlarged Board of Appeal was refused.