T 0342/98 (A. orizae/NOVOZYME) 20-11-2001

Reasons for the Decision

Article 114 EPC

1. The date of filing of the respondent's last submissions (ie 22 October 2001) is in agreement with the period of one month indicated by the Board in its communication under Article 11(2) of the rules of procedure of the boards of appeal, since the 20 and 21 October 2001 fell within a week-end.

2. Documents (39), (40), (41), (44) and (45), which are declarations concerning comparative experiments, are not admitted into the procedure under Article 114(2) EPC. In the Board's view, not only the relevance and the date of submission are important factors for the admissibility of late-filed documents into the procedure, but also their nature in connection with the principle of fair and equal treatment of the parties involved. Comparative data, contrary to scientific publications, are specifically directed to a particular technical aspect having a particular importance in the context of the procedure concerning a specific patent. Their teaching may accordingly be of a particular value. As a consequence, the reaction to such comparative data is for the other party (parties) particularly cumbersome, time-consuming and extends beyond the normal analysis of a scientific publication. The Board considers that to place a party in such a situation at a time so close to the oral proceedings is not in agreement with the principle of fair and equal treatment of the parties.

3. Document (34) submitted with third party observations under Article 115 EPC cannot be identified as a scientific publication, since it mentions neither the name of a scientific journal nor a publication date. Therefore, document (34) is not admitted into the appeal procedure according to Article 114(2) EPC.

4. Document (33) has been cited as a "P"-document in the search report, but has not been used during the opposition procedure. It could only be possibly relevant, if the claims of the patent in suit were not entitled to the priority of document (11). In view of the conclusions reached (cf infra, points 6 to 10 and 31. to 32), document (33) is not taken into consideration.

5. Documents (36) to (39), (42), (43) and (46) are admitted into the proceedings, since they relate to the subject-matter of the appeal, have been introduced in answer to arguments submitted by the appellant or remarks made by the Board in its communication under Article 11(2) of the rules of the procedure of the boards of appeal and are prima facie relevant.

Main request

Articles 87 to 89 EPC

6. The right of priority is governed by Articles 87 to 89 EPC which require that the European patent application and the application, the priority of which is claimed relate to the same invention, ie to the same subject-matter. Decision G 2/98 (cf supra) has decided that a narrow interpretation should be given to the concepts of "the same invention" and "the same subject-matter". The main criterion in this respect is whether the claimed invention is disclosed in the priority document, seen as a whole, with all its essential features. According to decision T 81/87 (cf supra) the disclosure of these essential features "must be either express, or be directly and unambiguously implied in the text". Identical wording is nevertheless not required and the common general knowledge of the skilled person may also be used.

7. Document (11) discloses in Example 10 the transformation of A. orizae with the amds and argB genes of A. nidulans. Since the transformed organisms are able to grow on acetamide or become prototroph toward arginine, a protein or a group of proteins must have been expressed. Thus, document (11), besides the transformation, also discloses the expression in A. orizae. Document (11) further discloses on page 4 the use of a two vector system. From the fact that Example 10 has been written in the present tense the Board cannot conclude with certainty that it has not been reduced to practice. Furthermore, there is no evidence on file that could lead the Board to the conclusion that Example 10 is not enabling.

8. As far as the question of "high level expression" is concerned, no prior art document on file describes the expression of a foreign gene in A. orizae. Therefore, the only A. orizae, which could be considered as a comparison reference, is the non-transformed A. orizae itself. Of course, in this context, even the slightest expression, such as that obtained with the weaker promoters used in documents (22) and (23), is already a "high level expression" as mentioned in the claims of document (11).

9. Furthermore, the Board is of the opinion that the concept of "high level expression" should be understood as defining a range rather than a single point. Indeed, if an expression system allows under certain circumstances a certain level of expression, the physico-chemical conditions of this system (culture medium composition, temperature, pH, etc...) may be so modified using the common general knowledge of the skilled person as to allow a lower level of expression, which could for instance be desired to avoid too high a viscosity of the culture medium due to a high concentration of secreted protein or the formation of insoluble refractile bodies within the cells in the case of non-secreted proteins. In view of this interpretation, document (11) could well confer the priority right to claims directed to both high and low levels of expression. It seems in this context that all the subject-matter covered by the claims of document (11) is enabled, so that decision T 694/92 (cf. supra) does not apply.

10. As a consequence, the patent in suit enjoys the priority right from document (11).

Article 54(3) EPC

11. Document (1) (filing date: 27 August 1986, publication date: 25 March 1987) would only be novelty-destroying as far as it related to the subject-matter disclosed in its priority document (19) (filing date: 29 August 1985). Document (19), contrary to document (1), is silent about A. orizae. Therefore, document (1) cannot enjoy the priority of document (19) as far as A. orizae is concerned and cannot destroy the novelty of the subject-matter of the claims of the main request.

Article 54(2) EPC

12. Since the claims of the main request enjoy the priority right from document (11), document (33), published after the priority date, is no longer prior art in the meaning of Article 54(2) EPC. There is therefore no need to answer the question of its admissibility into the procedure (cf supra, point 4).

Article 56 EPC

13. Since the claims of the main request enjoy the priority right of document (11), document (35) published on 11. June 1986 is under Article 56 EPC (second sentence) no prior art.

14. The closest prior art is represented in the Board's view by either document (8) or document (9), which are very similar in their disclosures and equivalent in their teaching, since they both describe the transformation of A. niger by foreign genes using the transformation method already designed for A. nidulans.

Document (8) describes the transformation of A. niger cells defective in ornithine transcarbamylase function with the A. nidulans argB gene, which results in an arginine prototrophy of the transformed A. niger cells. Further, document (8) indicates that the foreign gene has been integrated into the genome of the host (page 211) and concludes (page 212) that the transformation system described allows foreign genes to be introduced and maintained stably in A. niger.

Document (9) describes the transformation of A. niger with the amdS gene encoding the acetamidase of A. nidulans, which results in the ability of the transformed A. niger cells to grow on acetamide. The transformed gene is stably integrated in the recipient genome. Co-transformation is said to allow manipulation without complex plasmid constructions because selected and unselected genes need not to be on the same plasmid (pages 477 and 478). It is concluded that the introduction of desired genes into industrially important fungal species should be relatively simple and the development of high level expression vectors for filamentous fungi possible (page 478).

15. Since a new function (arginine prototrophy or growth on acetamide) appeared in the transformed A. niger cells of documents (8) and (9), the expression of the foreign gene (amds or argB) must have occurred. Therefore, contrary to the respondent's interpretation (cf supra, paragraph IX), the technical problem to be solved in view of documents (8) or (9) is no longer the expression of a foreign gene in A. niger, but the provision of an alternative expression system to the already existing A. niger system.

16. The solution of this problem as proposed in the claims of the main request is the use of A. orizae as a host organism and the examples disclosed in said patent show that the problem mentioned above has been solved.

17. The question to be answered in view of the assessment of inventive step under Article 56 EPC is whether A. orizae was an obvious choice for the skilled person at the priority date of the patent in suit in view of the cited prior art and/or whether its use was related to a reasonable expectation of success.

18. The Board is of the opinion that this question has to be positively answered in view of the disclosure of document (6), which only recognizes A. niger and A. orizae as "GRAS" organisms among all the fungi cited, so that the skilled person, even if documents (6), (25), (27), (28), (42) or (43) mention other Aspergilli or other fungi, was caught into a "one-way-street" situation and led to give the preference to A. orizae.

19. Furthermore, the Board is of the opinion that it was part of the common general knowledge of the skilled person at the priority date of the patent in suit that A. niger and A. orizae are phylogenically more closely related to each other than any of them to A. nidulans. This can be seen, for instance, from the fact that neither A. niger nor A. orizae, contrary to A. nidulans, exhibit parasexual phenomena. Confirmation of this common general knowledge can be found in document (18), a textbook published for the first time in 1932 and present on file in its edition of 1962 (ie almost 25 years before the priority date of the patent in suit). Therefore, the skilled person, aware from documents (8) and (9) of the fact that the technology transfer took place between A. nidulans and A. niger, would have been confident in the successful transfer of technology between A. niger and A. orizae.

20. In this context, the Board considers document (29), containing some sceptical comments, as irrelevant, since it concerns Basidomycetes, which are not closely related to the Ascomycetes, to which the Aspergillus genus belongs. Furthermore, the author of document (29) was obviously not aware of (or not interested in) the technology transfer, which had occurred between A. nidulans and A. niger, since document (29) only makes reference to scientific publications related to A. nidulans and is silent about said technology transfer.

21. The Board thus considers that the choice of A. orizae for the technology transfer from A. niger was obvious for the skilled person and related to a reasonable expectation of success in view of the combined teaching of either document (8) or document (9) with that of document (6). Therefore, decision T 386/94 (cf supra), which suggests the acknowledgment of inventive step in cases where success could not reasonably be expected, does not apply to the present case.

As a consequence, the claims of the main request do not fulfil the requirements of Article 56 EPC.

Auxiliary request I

Article 107 EPC

22. Claim 1 of auxiliary request I is a combination of claims 1 and 12 of the main request. The claims of the main request are the claims as granted, which have been maintained by the opposition division. In his notice of opposition, the appellant had not explicitly argued against claim 12, although he indicated on the EPO Form 2300 that the opposition was directed to the whole patent.

23. The question is whether an argumentation of the appellant at the appeal stage against claim 1 of auxiliary request I would constitute a "fresh ground" of opposition in the sense of decisions G 9/91 (EPO OJ 1993, 408) and G 10/91 (EPO OJ 1993, 420) and would extend beyond the factual and legal framework defined in the appellant's notice of opposition.

24. Decision T 114/95 (8 April 1997), in a case concerned with the same legal question, came to the conclusion that the appeal is admissible, since it suffices for an opponent to substantiate an attack under Article 100 EPC on only one claim of the patent, and that there is no obligation under the EPC to object to any of the claims at the stage of filing the notice of opposition (cf points 1.1 to 1.5).

Decision T 896/90 (22 April 1994) in a case concerning the extent of opposition under Rule 55(c) EPC, also came to a similar conclusion (points 4 to 5) and decided that it cannot be concluded from an argumentation only directed against claim 1 that this sole claim be attacked. Reference was made to Decision G 9/91 (cf supra) stating that subject-matters of claims depending on an independent claim, which falls in opposition or appeal proceedings, may be examined as their patentability even if they have not been explicitly opposed, if their validity is prima facie in doubt on the basis of already available information.

25. In this context it should be kept in mind that opponent 1. had indicated during the opposition procedure (letter of 1 April 1997) that, although he did not intend to attend the oral proceedings before the opposition division, he still requested the patent in suit to be revoked and his arguments under Articles 54(3) and 56 EPC to be taken into consideration. Opponent 1 had indicated on EPO Form 2300 that the opposition was directed to the whole patent and that, more particularly, the objection of lack of novelty was directed to claims 1 to 6, 12, 16 and 17. Claim 12 was directly objected on page 5 of the notice of opposition under Article 54(3) EPC and on page 16 under Article 56 EPC. Therefore, the legal framework defined by opponent 1. included and still includes Articles 54(3) and 56 EPC objections directly raised against claims 1 and 12 as granted.

26. Decision T 114/95 (cf supra) also dealt with such a situation and concluded that there is no limitation set by the EPC to allowing an opponent whose opposition is considered admissible to support and use grounds, evidence and arguments for revocation of the patent that were submitted by other opponent(s) (point 1.5).

27. Therefore, the appeal of the appellant against auxiliary request I is admissible under Article 107 EPC.

Article 123(2)(3) EPC

28. Claim 1 of auxiliary request I differs from that of the main request by the introduction into claim 1 as granted of the feature "preregion allowing the secretion of the expressed product into the culture medium" and of an additional step (d) of recovery of said secreted product in the culture medium.

29. This amendment does not contravene the requirements of Article 123(2) EPC, since secretion and recovery from the culture medium are disclosed in the application as filed (claims 12 to 15, for instance).

30. This amendment also meets the requirements of Article 123(3) EPC, because prima facie the introduction of the technical feature of a dependent claim into an independent one results in the restriction of the scope of the latter. In the present case, the scope of claim 1 of auxiliary request I has been restricted to proteins excreted from the bacteria by the introduction of the feature "preregion" of claim 12.

Articles 87 to 89 EPC

31. Claim 1 of auxiliary request I now requests the presence of a preregion providing for secretion of the expressed product into the culture medium and the isolation of the expressed product from the culture medium.

32. Priority document (11), seen as a whole, mentions the secretion on pages 2 (line 2) and 3 (lines 4 to 9 line 23), the preregions or signal/leader sequences on page 4 (lines 3 to 21) and indicates on page 4 (line 3) that secretion of the expressed product in the culture medium is a preferred embodiment. This teaching is not brought in relation with a particular Aspergillus species, but refers to all the cited Aspergillus species, ie A. nidulans, A. niger and A. orizae. This gives a basis for claim 1 of auxiliary request I, which is thus entitled to the priority right of document (11).

Article 54(2)(3) EPC

33. Since the right of priority from document (11) can be acknowledged for auxiliary request I, the conclusions reached in view of the main request (cf supra, points 10 and 12) equally apply to auxiliary request I.

Article 56 EPC

34. Therefore, as in the case of the main request (cf supra, point 13), document (35) is according to Article 56 EPC (second sentence) no prior art.

35. The closest prior art is document (10) which discloses the secretion of rennin in A. nidulans under the control of various secretion signals and heterologous promoters.

36. The technical problem to be solved is to find an alternative to the secretion system of document (10), specially in view of the fact that A. nidulans is a "laboratory strain" unsuitable for commercial purpose.

37. The solution given in the patent in suit is the use of A. orizae as a host organism for the secretion.

38. The question to be answered in view of inventive step is whether the extension of the teaching of document (10) to A. orizae would have been considered at the priority date of the patent in suit as obvious and promising by the skilled person.

39. In view of the finding under point 40 (cf infra) the question whether document (10) is an enabling disclosure appears to be of minor importance. It can nevertheless be noted that document (10) does not precisely identify any signal sequences and is silent about modifications which seem to be possibly necessary, since the sentence referring to the signal sequences begins with "Further modifications involved...". Furthermore, document (10) is a descriptive abstract, which merely states the results obtained, but does not provide the skilled person with any technical information on the possibility to reduce this teaching to practice.

40. The key problem in view of document (10) is, however, that it does not point at all to any other Aspergillus than A. nidulans. In that sense the situation is different from that encountered with the main request, for which A. orizae was the only alternative to the already used A. niger, since both Aspergilli were the only obvious choices in view of document (6) considering them as "GRAS" organisms. In the present case, even if document (6) is combined with document (10), the skilled man has still two possibilities for extending the teaching of document (10) to an Aspergillus other than A. nidulans, namely A. niger and A. orizae. This means that the skilled person is not in a "one-way-street" situation as in the case of the main request, but has to make a deliberate choice. Therefore, A. orizae is, as far as the secretion is concerned, no longer an obvious choice, but one of the two possibilities offered to the skilled man by document (6).

41. Furthermore, nothing suggests in document (10) that the technology transfer between A. nidulans and A. orizae concerning the secretion may be possible. It can also not be extrapolated from the positive results obtained with the technology transfer concerning the expression from A. nidulans to A. niger that similar positive results could be obtained for the secretion, since expression and secretion are different phenomena involving different molecular mechanisms.

42. Moreover, contrary to the situation evoked in the case of the main request for the transformation and expression (points 17 to 21) , the technology transfer in the case of the secretion should no longer take place between A. niger and A. orizae, ie two closely related fungi (cf supra, point 19), but between A. nidulans and A. orizae, which are phylogenically much more remote from each other than are A. niger and A. orizae, so that a success could not have been reasonably expected.

43. Document (2) which describes the secretion of A. awamori glucoamylase in yeast under the control of its own signal sequence is of no help as far as secretion in A. orizae is concerned, since it concerns another Aspergillus strain and the secretion does not occur in a filamentous fungus, but in a yeast.

44. As a consequence, the Board is of the opinion that A. orizae was not an obvious choice as a host organism for a secretion system in filamentous fungus and that a success could not have been reasonably expected. Therefore, claim 1 of the auxiliary request I fulfils the requirements of Article 56 EPC. Since claims 2 to 16. directly or indirectly depend on claim 1 they as such meet the requirements of Article 56 EPC.