T 1528/06 (Concentré de fibrinogène/CAF-DCF) 16-05-2008

Reasons for the Decision

Language of the proceedings

1. The parties used the English language in all their submissions in the appeal procedure and during the oral proceedings (with exception of the claim requests which were submitted in French as the language of the proceedings). They also agreed that the written reasons of the decision be provided in English. This way to proceed is in keeping with decision J 18/90 (OJ EPO 1992, 511; see also decision T 788/91 of 25 November 1994), according to which the board may use in decisions an official language (here: English) other than the language of the proceedings (here: French), provided all the parties to the proceedings give their agreement.

Admissibility of late-filed claims

2. The new main request (claims 1 to 7) has been submitted by the respondent during the oral proceedings. Such a late-filed claim request is according to the established jurisprudence of the Boards of Appeal only admitted if it is clearly allowable having regard to all relevant provisions of the EPC and provided that the circumstances are such that the opponents are not disadvantaged in their right to give proper consideration to the new amendments.

3. In the present case, the claims filed at the oral proceedings correspond to the claims of the 8th auxiliary request filed on 16 April 2008, with only minor amendments. These claims no longer comprise former claim 11 to an installation for the preparation of a fibrinogen concentrate and former claims 1 to 3 to the fibrinogen concentrate itself. In view of these deletions, an amendment was necessary to enter the definition of the fibrinogen concentrate given in former claim 1 into the present process claim 1 and into claim 7. Since the 8th auxiliary request (of which the present claims represent a simpler version) had been filed one month before the oral proceedings before the board and did not give rise to surprising new legal or factual issues, the conclusion cannot be drawn that the appellant is disadvantaged in its right to give proper consideration to the amendments of the respondent's case. Therefore, the board considers this request to be admissible under Article 114(2) EPC and Article 13(1) RPBA.

Article 123(2)(3) EPC

4. The appellant does not raise any objection under this Article against the claims of the main request filed at the oral proceedings and the board also sees none.

Article 83 EPC

5. In the context of the novelty issue, when it comes to the discussion of whether or not the feature "purity higher than 98%" in the claims is able to distinguish over document D5, the respondent notes a contradiction between the statement made in col. 12, lines 62-64 of document D5 ("SDS-polyacrylamide gel electrophoresis showed that it consisted solely of fibrinogen fraction 1") on the one hand, and the clottability of 92-96% referred to in the Examples of document D5, on the other hand (according to col. 2, lines 37-38, clottability is the percentage of thrombin-clottable proteins based on total proteins), suggesting a fibrinogen purity lower than 92-96%. In the light of this inconsistency, the respondent argues that SDS-polyacrylamide gel electrophoresis, as carried out in Example 1 of document D5, is not appropriate for measuring the purity of the fibrinogen concentrate.

6. In response to the above argument, the appellant maintains that, by the same token, the patent in suit is insufficient, since it also relies on SDS-polyacrylamide gel electrophoresis for measuring the purity of the fibrinogen concentrates.

7. The board first observes that the two methods (SDS-polyacrylamide gel electrophoresis versus clottability assay) may lead to divergent results in view of the fact that the clottability measures the quantity of biologically active molecules, whereas SDS-polyacrylamide gel measures denaturated molecules. Therefore, this expected discrepancy does not mean that SDS-polyacrylamide gel electrophoresis is not appropriate for measuring the purity of the fibrinogen concentrates.

Secondly, Table 1 and note "(e)" to this table on page 5 of the patent provide instructions to the skilled person as to how to measure the fibrinogen purity via densitometric analysis of the SDS-PAGE polyacrylamide gels (i.e., the area under the curve relating to the fibrinogen band should represent more than 98% of the total area).

Since there is no evidence before the board showing that the skilled person would be prevented from putting into practice the above instructions, it must be concluded that the patent is not insufficient under Article 83 EPC.

Novelty of claim 7

8. The fibrinogen composition according to claim 7 exhibits a purity higher than 98%, is free from viral contaminants and is free from proteases.

9. The appellant relies on Example 1 of document D5 for questioning the novelty of the claimed composition, arguing that this Example discloses a fibrinogen preparation which i) consists solely of fibrinogen fraction 1 as shown by SDS-polyacrylamide gel electrophoresis (see column 12, lines 62-64); ii) is devoid of protease activity owing to the addition of the protease inhibitor AMCHA and iii) is virus-free.

10. For the sake of argument, the board assumes in the appellant's favour that the composition of Example 1 of document D5 satisfies the requirement "purity higher than 98%" ("pureté supérieure à 98%") in present claim 7.

11. As regards feature (iii) above ("virus-free"), the appellant maintains that the patent relates to cases where the chemical viral inactivation does not allow to completely eliminate the viral contaminants (see in particular paragraph [0079]). However, claim 7 only covers the situation where all the viruses have been completely inactivated, e.g., by an additional UVC irradiation step, in view of the intended pharmaceutical or cosmetical use (see paragraph [0003] of the patent).

12. In the board's judgement, feature (iii) ("virus-free") in present claim 7 cannot be unambiguously derived from document D5. In fact, the appellant himself acknowledged in the Opposition Statement (see page 10) that "D5, however, does not disclose a product which is viral free".

13. Since document D5 already fails on feature (iii) above, the board needs not to decide whether or not the presence of AMCHA in the composition described in Example 1 of document D5 would interfere with the fibrinogen's use as a pharmaceutical/cosmetical composition or as a biological glue.

14. In conclusion, the novelty of the subject-matter of present claim 7 is acknowledged.

Inventive step

Claim 1

Closest prior art

15. The closest prior art is represented by document D5 because it aims at producing high purity fibrinogen by removing non-clottable proteins (see column 1, lines 5 to 10). Example 1 of this document discloses on column 12, lines 38 to 64 the use of two precipitation steps using an acidic solution of an amino acid (glycine) to produce a high purity fibrinogen concentrate. However, this concentrate is not free from proteases since it is explicitly stated in this example that the protease inhibitor AMCHA is added when dialysing the fibrinogen solution for 24h.

Problem to be solved

16. The problem to be solved is the provision of a process for producing a highly purified fibrinogen concentrate, which is free from proteases (and which thus no longer requires the addition of AMCHA) and wherein viral contaminants have been inactivated (see paragraphs [0021] and [0024] of the patent). As regards the feature "free from proteases", it is the board's understanding that the meaning of this expression ("dépourvu de proteases") does not encompass the mere absence of protease activity but it rather means the absence of the corresponding protein bands on the gel (see note "(h)" to Table 1 of the patent and compare with paragraph [0070]).

Has the problem been solved?

17. The appellant argues that the patent does not show that the above problem has actually been solved since it cannot be derived from the examples that a concentrate according to the invention (purity higher than 98%; free from proteases and virus-free) could indeed be obtained. This is because (i) there is a "lack of synergy" in the essential steps of present claim 1; (ii) there are mistakes in Example 1; (iii) it is stated in Example 3 that the solution could be "treated with UVC rays"; and (iv) Examples 1 and 3 comprise far more steps than the essential purifications steps indicated in claim 1.

18. As for the mistakes noted by the appellant (on page 4, glycine is mentioned twice on lines 49 and 51 and on page 5, line 1, there is a filtration on AKS-4-AKS-7 filter which does not make sense), the board is of the opinion that the skilled person will not be misled by the incriminated passages, in view of note (a) to Table 1, summarizing the method described in Example 1.

19. As regards the feature virus-free, a solvent/detergent step is already present as an essential step in the method of claim 1 so that possible virus contaminants may be eliminated. However, additional virus inactivation steps such as heat treatment or UVC irradiation should be seen as an optional step for the method of claim 1.

20. As for the "lack of synergy" in the essential steps of present claim 1 argued by the appellant, a comparison between "Methode I(a)" on the one hand, and "Methode II(b)", "Methode III(c)" or "Methode IV(d)", on the other hand (see Table 1 on page 5 of the patent) shows that it is the performance of at least two amino acid precipitations combined with one or more filtration steps, that renders possible the preparation of a fibrinogen concentrate of more than 98% purity, which is also protease-free. In fact, comparative examples "II(b)" to "IV(d)" demonstrate that amino acid precipitations alone are not able to remove proteases. Therefore, the board disagrees to the appellant's view that there is a "lack of synergy" in the essential steps of present claim 1. This conclusion is in keeping with the board's finding that the process described in Example 1 of document D5, which lacks the final filtration step(s) recited in claim 1, fails to yield a protease-free fibrinogen concentrate (see point 15 supra and point 24 infra).

21. The above comparison also suggests that other steps described in the examples but not listed in claim 1 are optional steps which are not critical for achieving this goal.

22. In conclusion, the board is satisfied that the above problem has been solved.

Is the proposed solution obvious over a combination of D5 with D1, D2, D4, D6 or D7?

23. The appellant maintains that the only difference between the technique described in Example 1 of document D5 and the claimed method lies in the additional solvent/detergent chemical viral inactivation step and that hence it would be obvious for the skilled person to use the known purification process of document D5 in combination with the known solvent/detergent viral inactivation step of D1 (or of any of documents D2, D4, D6 or D7) in order to solve the problem set out above.

24. However, when comparing the process described in Example 1 of document D5 (col. 12, lines 43-44: first precipitation with glycine --> line 44: first recovery by filtration of the precipitate --> lines 44-52: second precipitation with glycine --> line 53: second recovery by filtration of the precipitate --> line 53: "final dissolution") with that described in the patent (see paragraphs [0055] to [0060] and note (a) to Table 1), it becomes apparent that the method according to the invention includes an additional step of filtration performed on the result of the "final dissolution" (see paragraph [0060]), which is, in the understanding of the board, one of the essential features of claim 1 and meant by the term "...et une [ou plusieurs] étape[(s)] de filtration du fibrinogène purifié" (emphasis added). This necessary additional step of filtration is distinct from and should not be confused with any of the "first and second recovery by filtration of the precipitate". As emphasized under point 20 supra, the inclusion of final filtration step(s) is critical for obtaining a protease-free fibrinogen concentrate.

25. Therefore, combining the process described in Example 1 of document D5 with the known solvent/detergent viral inactivation step of D1 (or of documents D2, D4, D6 or D7) would not yield the claimed process, and hence a protease-free fibrinogen concentrate. Therefore, the appellant's line of argument based on the combination of the teaching of document D5 with that of any of documents D1, D2, D4, D6 or D7 for arriving at the method of claim 1 is not convincing.

26. It must be concluded that the method of claim 1 and dependent claims 2 to 6 does not follow from the prior art in an obvious way.

Inventive step of claim 7

27. The appellant argues that documents D4, D5 and D6 disclose the preparation of a fibrinogen concentrate and thus make it available in all grades of purity (see decision T 990/96, supra).

28. The board does not accept that the only possible distinctive feature of the fibrinogen concentrate of claim 7 vis-à-vis the fibrinogen concentrate preparation disclosed in these documents lies in the achievement of a higher degree of purity. The product covered by present claim 7 is indeed a fibrinogen concentrate meeting certain criteria, inter alia that of being devoid of proteases (i.e., absence of protease bands on the SDS gel: see point 16 supra). Therefore, the decisive issue to be answered by the board is whether or not applying the conventional methods for purifying fibrinogen (see documents D4, D5 and D6) pointed out by the appellant would result in fibrinogen concentrate according to present claim 7, being inter alia devoid of proteases. There is no evidence before the board that this is the case.

29. In a different line of argument the appellant maintains that the method of claim 1 which could be used to prepare the fibrinogen concentrate, is the obvious combination of known purification steps without any unexpected benefit and that hence the fibrinogen concentrate resulting from said method lacks an inventive step.

However, this argument must fail in view of the board's conclusion that the method of claim 1 does not follow from the prior art in an obvious way (see point 26 supra).

30. It must be concluded that the subject-matter of claim 7 satisfies the requirements of Article 56 EPC.