T 0110/11 (Amino acid production/AJINOMOTO) 25-02-2014

Main Request

Admissibility of objections under Article 100(c) EPC

1. The appellant submitted its objections under Article 100(c) EPC only with the statement setting out the grounds of appeal. They concerned features of claim 1 which were already present in claim 1 as granted. Article 100(c) EPC had however not been invoked as a ground of opposition, and during opposition proceedings the opponent had agreed that the claims of the main request were acceptable with regard to Articles 123(2) and 123(3) EPC (cf. minutes of the oral proceedings, page 1).

2. The respondent requested that objections on the ground of 100(c) EPC not be admitted.

3. As stated in decision G 9/91 (OJ EPO 1993,408), "[t]he purpose of the appeal procedure inter partes is mainly to give the losing party a possibility to challenge the decision of the Opposition Division on its merits. It is not in conformity with this purpose to consider grounds for opposition on which the decision of the Opposition Division have not been based. Furthermore, in contrast to the merely administrative character of the opposition procedure, the appeal procedure is to be considered as a judicial procedure, as explained by the Enlarged Board in its recently issued decisions in the cases G 7/91 and G 8/91 (see point 7 of the reasons). Such procedure is by its very nature less investigative than an administrative procedure. Although Article 114(1) EPC formally covers also the appeal procedure, it is therefore justified to apply this provision generally in a more restrictive manner in such procedure than in opposition procedure. In particular with regard to fresh grounds for opposition, for the above reasons the Enlarged Board considers that such grounds may in principle not be introduced at the appeal stage. However, an exception to the above principle is justified in case the patentee agrees that a fresh ground for opposition may be considered".

4. In view of the respondent's request not to admit objections on the ground of Article 100(c) EPC against the main request, this fresh ground of opposition is not considered by the board.

Article 84 EPC

5. Claim 1 of the main request results from the introduction of the features of claim 2 as granted into claim 1 as granted. The appellant did not raise any objections under the provisions of Article 84 EPC and the board has no reason to raise any on its own.

Article 83 EPC

6. The majority of sucrose positive bacteria take up and phosphorylate sucrose via a phosphoenolpyruvate (PEP) dependent phosphotransferase system, known as the PTS system. An alternative, PTS independent, sucrose uptake and phosphorylation system, known as the csc system, comprises a proton symport transport system, an invertase and a fructokinase (cf. document D4, page 22).

7. Claim 1 refers to the use of a bacterium of the genus Escherichia harboring sucrose non-PTS genes coding for a permease, an invertase and a fructokinase for the production of threonine or isoleucine in a medium containing sucrose as its main carbon source. Moreover, the strain has to be capable of growing on sucrose as the sole carbon source.

8. The patent discloses the use of the respective non-PTS genes from E.coli K 12 strain W3350csc (VKPM B-7914) which contains the "csc genes" of E. coli strain EC3132 as described in document D4 (cf. [0047] of the patent specification and Examples 3 and 5).

9. Thus, the patent provides sufficient disclosure only for methods based on the use of the csc genes from E. coli K12 strain VKPM B-7914 and genes derived therefrom.

10. The respondent submitted that the skilled person, at the date of filing was aware of two pathways for sucrose utilization in E. coli, i.e. the sucrose PTS system and the csc system disclosed in document D4. Since the functional properties resulting from the presence of non-PTS genes were readily testable, the disclosure of the patent put the skilled person in a position to readily perform the claimed invention across the full scope of the claim.

11. Claim 1 is however not limited to the use of E. coli strains comprising the csc genes. The claim language merely requires the presence of genes encoding a permease, an invertase and a fructokinase which do not encode the proteins of the PTS system and which render Escherichia capable of growing on sucrose. Also, according to [0018] of the description, "sucrose non-PTS genes are not particularly limited so long as they can function in a bacterium belonging to the genus Escherichia". Thus, the claim encompasses any solution, also not yet known solutions, which is not based on the PTS system.

12. The disclosure of one way of performing an invention is only sufficient if it allows the invention to be performed in the whole range claimed rather than only in some members of the claimed class to be obtained. Sufficiency of disclosure thus presupposes that the skilled person is able to obtain substantially all embodiments falling within the ambit of the claims (Case law of the Boards of Appeal, 7th edition, 2013, II.C.4.4, and decisions cited therein).

13. In the present case, the claimed solution refers to the use of non-PTS genes which are merely defined in functional terms, i.e. the use of a permease, an invertase, and a fructokinase rendering the strain capable of growing on sucrose as the sole carbon source. While the skilled person is in a position to readily make use of the csc genes as disclosed by the patent, it is not in a position to readily perform the invention by using any other alternative set of genes since, as mentioned by the respondent, none is known or readily available.

14. The board therefore decides that claim 1 of the main request does not meet the requirements of Article 83 EPC.

Auxiliary request

Admissibility of the Auxiliary request

15. The respondent filed its auxiliary request during the oral proceedings, in response to the board's decision that the main request was not allowable under Article 83 EPC. Claim 1 of the auxiliary request is the result of the combination of independent claim 1 with dependent claim 2 of the main request. This amendment does not create a fresh case. Moreover, in the communication attached to the summons to oral proceedings, the board had indicated preliminary doubts that objections against the main request under Article 83 EPC were sufficiently substantiated. It was only at the oral proceedings that the board was finally convinced by the appellant's arguments.

Under these circumstances, the board, exercising its discretion under Article 13(1) RPBA, decides to admit the auxiliary request.

Articles 123 and 84 EPC

16. The appellant raised no objections under Article 123 EPC.

17. However, an objection was raised under Article 84 EPC in view of decision T 459/09 of 13 December 2012. The appellant argued that the characterizing feature of previously dependent claim 2 ("genes ... derived from") was unclear and that an objection under Article 84 EPC was admissible because claim 1 of the auxiliary request represents an amended claim, arising from the combination of previously dependent claim 2 with independent claim 1. The appellant requested that the procedure should be stayed and questions of law should be referred to the Enlarged Board of Appeal should the board not admit this objection.

18. The respondent requested that the objection not be admitted.

19. In the light of its decision with regard to the requirements of Article 56 EPC (see points (20) to (36) below), the board refrains from giving a reasoned decision on this issue.

Article 56 EPC

20. Document D8 represents the closest prior art. It discloses a method of producing threonine by E. coli strain BKIIM B-3996. The strain was constructed by transferring into it genetic determinants allowing sucrose (saccharose) assimilation. The strain produced 85 g/l threonine when grown on sucrose at 37 degrees C for 36 hours. According to paragraph [0007] of the patent in suit the strain used in document D8 comprises the PTS genes.

21. The technical problem underlying the invention is seen in the provision of an alternative method of producing threonine or isoleucine by a strain of the genus Escherichia using sucrose as the main carbon source.

22. The respondent submitted that the technical problem should be seen in the provision of an improved method of producing these amino acids. It referred to Tables 2 and 4 of the patent according to which strains VL2055csc and 44-3-15csc yielded more threonine and isoleucine, respectively, when grown on sucrose than when grown on glucose. The figures are 27.9 g/l of threonine and 13.6 g/l of isoleucine when grown on sucrose for 72 hours at 37 degrees C.

23. Claim 1 neither refers to any particular strain of the genus Escherichia nor, apart from growth on sucrose, to any other particular features of the strain to be used. According to established case law, an unexpected or advantageous effect has to be shown by comparison with the closest prior art (Case law of the Boards of Appeal, 7th edition, 2013, I.D.10.9). In the present case, the claimed method has therefore to be compared with the method disclosed in document D8. On this basis, the claimed method does not lead to an improvement over the prior art but constitutes an alternative method.

24. Referring to chapter I.D.9.2.2 of the Case Law of the Boards of Appeal of the EPO (7th Edition, 2013), the appellant argued that the proposed solution was in fact a combination of two independent solutions to two unrelated problems. The first relating to the provision of a microorganism belonging to the genus Escherichia capable of growing on sucrose, and the second relating to the provision of a microorganism belonging to the genus Escherichia and capable of producing threonine or isoleucine. Since the features relating to these two properties were functionally independent, inventive step had to be assessed independently for both of them.

25. This argument is flawed, because sucrose, which is taken up by the microorganism is metabolised to phosphoenol-pyruvate which is one of the major building blocks of several metabolic pathways, inter alia of the threonine and isoleucine biosynthetic pathways (cf. [0005] of the patent in suit). Thus, there is a functional link between the two properties.

26. As a solution of the problem mentioned in point 21, the patent, according to claim 1, proposes the use of a bacterium belonging to the genus Escherichia which comprises non-PTS genes derived from the microorganism having the accession number VKPM B-7914.

27. The results in Tables 2 and 4 of the patent in suit demonstrate that the method as defined in claim 1 indeed solves this technical problem.

28. It remains to be established if the claimed solution involves an inventive step.

29. The appellant argued that the proposed solution was obvious in view of documents D8 and D4.

30. Document D4, entitled "Characterization of a chromosomally encoded, non-PTS metabolic pathway for sucrose utilization in Escherichia coli EC3132", discloses the csc genes. According to [0047] of the patent in suit, the source strain of the csc genes which was used in the Examples, E. coli K12 W3350csc, contains the csc genes of E. coli EC3132. Thus, the genes derived from the microorganism VKPM B-7914 are the genes derived from E. coli strain EC3132 described in document D4.

31. The respondent argued that document D8 made no mention of alternative sucrose uptake systems and that document D4 neither contained a pointer nor any other incentive to the use of the csc system for the production of amino acids. Moreover, document D4 (Table 3, "transport activity" of strain EC3132, and pages 27 to 30) provided data that the sucrose permease encoded by cscB was not sufficiently active and therefore unsuitable for the production of amino acids. Therefore, the skilled person would not have had a reasonable expectation of successfully solving the technical problem by using the csc system.

32. The skilled person in the field of amino acid production by E. coli is aware of the general physiological properties of E. coli, one of the work horses of molecular biology. Therefore, document D4, describing the csc pathway for sucrose utilization represents general knowledge.

In the present situation, where the only known alternative sucrose uptake pathway in E.coli to the PTS-system was the csc pathway disclosed in document D4, the skilled person looking for a solution to the underlying problem could not choose from among several available alternatives. The board is therefore convinced that the skilled person not only could but indeed would have tried to use the csc system.

33. The respondent argued that the experimental data relating to the kinetic properties of the sucrose permease described in document D4 would have kept away the skilled person from trying to solve the technical problem by means of the csc pathway.

34. It is true that document D4 refers to the inefficiency of the cscB encoded sucrose permease expressed by strain EC3132 (Table 3). It is, for instance, stated that transport activity sufficient for a thorough kinetic analysis could not be obtained (page 27, right column) and that the poor expression of cscB seemed to be the result of the inefficient sucrose transport (page 28, right column). On the other hand, document D4 also discloses that strains like ECB1, a spontaneous mutant of strain EC3132, showed a low but reproducible permease activity (Table 3), and that strain HCB101/ R'Csc211, obtained after transformation with a plasmid carrying the csc genes, constitutively expressed all three enzymes of the csc system (Table 3 and page 26, right column). Finally, experiments with E. coli K12 strains carrying all csc genes except for cscB, the sucrose permease, demonstrated an essential role for this permease in sucrose metabolism (page 27, right column, 2nd paragraph). Document D4 also shows that the invertase and fructokinase activities encoded by cscA and cscK are clearly induced by the presence of sucrose in the growth medium (cf. Table 3).

35. In view of the fact that document D4 provided unambiguous evidence for the function of the csc encoded pathway and its three enzymes, the skilled person not only would have been prompted, as set out in point 31 above, to try to solve the problem by using the csc pathway but he would even have done so with the reasonable expectation of successfully obtaining at least some sucrose utilization capacity in a threonine or isoleucine producing strain of the genus Escherichia upon transfer of the csc genes.

36. Since the subject-matter of claim 1 can be derived in an obvious way from the disclosure of document D8 upon combination with that of document D4, it does not involve an inventive step. It follows that the auxiliary request does not meet the requirements of Article 56 EPC.