T 1514/17 (Apx subunit vaccine with polymyxin/INTERVET) 13-01-2022

1. The appeal complies with Articles 106 to 108 and

Rule 99 EPC and is admissible.

The decision under appeal

2. The decision refusing the application referred to two communications of the examining division, the first dated 21 July 2015 and the second dated dated 30 August 2016. The first communication dealt with the set of claims dated 12 February 2015. In this communication, the examining division raised objections under Articles 83 and 84 EPC. In the reply, dated 7 October 2015, the appellant submitted an amended set of claims and presented arguments concerning Articles 83 and 84 EPC.

3. The communication dated 30 August 2016 was issued together with the summons to oral proceedings. It raised objections under Articles 56, 83 and 84 EPC not mentioned in the previous communication. The objections raised in the communication 21 July 2015 were not mentioned again.

4. Since the communication dated 21 July 2015 raised objections to a set of claims superseded by the set of claims filed 7 October 2015, the board considers that the objections raised in the communication dated 21 July 2015 did not form part of the grounds for the decision to refuse the application, even though this communication was explicitly mentioned on EPO Form 2061.

Main request - claim 1

Inventive step (Article 56 EPC)

5. The claimed subject-matter is a product. The product is a vaccine composition comprising lipopolysaccharide (LPS) that originates from Actinobacillus pleuropneumoniae purified from a bacterial culture complexed with one or more ApxI, ApxII and ApxIII toxins (referred to in the claim as "repeats in toxins"). This vaccine further comprises a polymyxin. The claim specifies that the polymyxin is present "to reduce symptoms of an endotoxic shock arising from the lipopolysaccharide". The board understands this to require that the amount of LPS is sufficient for this purpose.

6. In the decision under appeal, the commercial subunit Actinobacillus pleuropneumoniae vaccine comprising repeats in toxins ApxI, ApxII, ApxIII (Porcilis® App) disclosed in document D16 was said to represent the closest prior art for the claimed invention. The examining division held that the claimed subject-matter was obvious to the skilled person starting from the closest prior art, in the light of the disclosure in any of documents D5, D7 and D18 (see section III., above).

7. The appellant's arguments as to why the examining division was wrong to hold the subject matter of claim 1 as obvious rely entirely on the assumption that it was known to the skilled person at the relevant date, that the repeats in toxins ApxI, ApxII and ApxIII, present in the Porcilis® App vaccine, existed in complex with LPS. They had two main lines of argument which were purported to show that this was the case. The first was that the relevant information was available from the disclosure in document D3 as well as from documents referenced therein and also from the disclosure in document D13, which was a patent application disclosing the manufacture of the Porcilis® App vaccine. The second was based on the commercial availability of the Porcilis® App vaccine mentioned in document D16.

8. The board, having reviewed the available evidence, is not persuaded that the skilled person knew that the repeats in toxins ApxI, ApxII and ApxIII, present in the Porcilis® App vaccine existed in complex with LPS, let alone that the complex formed the major immunogen in the vaccine.

9. Document D16 itself makes no mention of such a complex. It can be taken from the abstract that the authors considered that Porcilis® App was "a subunit multivalent vaccine indicated for piglets and based on 3 Apx toxins (Apx I, Apx II, Apx III) and an OMP protein". Residual LPS is mentioned in the discussion as an explanation for induced cross reactivity seen mainly with ELISA LPS tests: "An explanation could be the presence of residual LPS in the subunit vaccine" (see page 235, right column, "Discussion").

10. In the board's view, this disclosure imparts that the authors were surprised by the cross-reactivity with LPS and sought to explain it. The skilled person reading document D16 would therefore have considered that the Porcilis® App vaccine primarily consisted of three Apx toxins and an OMP protein. They would have considered any LPS present to be "residual", i.e. not as an essential constituent of the vaccine.

11. The appellant submitted that the knowledge that Apx toxins in the Porcilis® App vaccine existed in a complex with LPS was well established in the art, for instance from documents D3 and D13.

12. Document D3 was said to disclose details about the interaction between LPS and the Apx I and Apx II toxins via the core oligosaccharide (see abstract). The association between LPS and the toxin proteins had long been known in the art as was disclosed in the discussion section and the references mentioned therein (see page 228, right column).

13. However, document D3 does not concern or even mention the Porcilis® App vaccine. The board can accept that the skilled person knew from document D3 that LPS and Apx toxins could associate with each other. There is however nothing in this document to the effect that the Apx toxins in the commercially available Porcilis® App vaccine existed in a complex with LPS. Thus, the skilled person could draw no conclusions about the composition of this vaccine from document D3.

14. The board notes that at oral proceedings, the appellant also argued that skilled person would have known that Apx toxins in the Porcilis® App vaccine existed in a complex with LPS from the documents referenced in document D3. However, since none of these documents is on file, the board cannot take their disclosure into consideration, in as far as it goes beyond that reproduced in document D3 itself.

15. Turning to the disclosure in document D13, in the board's view this does the opposite of what was argued for by the appellant. Document D13 reports the molecular weight of the Apx toxin (referred to therein as hemolysin) as being 105 kD, i.e. the molecular weight of the toxin on its own (see page 8, section 2).

16. The only reference to products having a higher molecular weight is found in the passage bridging pages 8 and 9 which reads "Hemolysin purified from serotype 1 and serotype 5b reference strain following the procedure described in the Methods, both showed a band in SDS-PAGE at 105 kD after CBB staining. A gel scan of purified serotype 5b hemolysin is shown in Fig. 4. Although the apparent MW in SDS-PAGE appeared to be approx. 105 kD, native hemolysin was retained during filtration using a filter with a MW cut-off of 300 kD. Furthermore, from the elution profile obtained in gel filtration it was concluded that the native hemolysin or aggregates thereof have a MW of at least 10x10**(6) D (Fig. 5)".

17. From this it is apparent that the authors of document D13 were not of the view that high molecular weight forms were the result of the formation of a complex between Apx toxins and LPS, but rather considered that they were the result of hemolysin (Apx) aggregate formation.

18. Documents D5, D7, D11, D18 were cited to show that the skilled person knew that the LPS-protein complex would be disrupted by the binding of polymyxin to the LPS. The board accepts that the skilled person knew the mechanism by which polymyxin acts on protein/LPS complexes. However, this was not at issue here. Rather, the board is of the view that it has not been established that the skilled person at the relevant date knew that in the commercially available Porcilis® App vaccine, the Apx toxins were in complex with LPS.

19. Documents D25 and D26 were also cited by the appellant in support of the view the the skilled person at the relevant date knew that polymyxin would interfere with the LPS-Apx complex in the Porcilis® App vaccine.

20. However, both documents D25 and D26 concern the effect of polymyxin B on the antigenicity of LPS/outer membrane from S. marcescens. The skilled person reading them would not be able to draw any conclusions about the composition or structure of the Porcilis® App vaccine.

21. In a second line the appellant argued that the commercial availability of the Porcilis® App vaccine meant that all of its characteristics, including the alleged fact that LPS and the Apx toxins were in complex, were available to the skilled person. In their view, the skilled person would have merely needed to analyse the commercially available vaccine using standard techniques. Doing this, they would have found out that the size of the proteins did not correspond to known sizes of the Apx toxins but to the considerably larger Apx/LPS complex.

22. It is likely that the appellant had in mind the case law of the Boards of Appeal, according to which the internal structure of a product in prior use is made available to the public when a skilled person, relying on the normal means of investigation available, would have been able to analyse the product (see for example opinion G 1/92 of the Enlarged Board of Appeal (EBA) and decisions T 0953/90, T 0969/90).

23. In the present case, the board considers that the internal structure of the commercially available Porcilis® App vaccine as far as it concerns its composition, e.g. the fact that it contains Apx toxins and residual LPS was indeed state of the art. However, the board has seen no convincing evidence of the allegation that the Porcilis® App vaccine actually contains Apx toxins in complex with LPS, for instance in the form of an analysis of the relevant Porcilis® App vaccine. The findings of the EBA in Opinion G1/92 are therefore moot.

24. The fact that LPS in complex with Apx toxins is a feature of the claim does not advance the appellant's case on obviousness either, since the claim formulation cannot alter the skilled person's knowledge of the state of the art at the relevant date and therefore cannot alter the board's assessment of obviousness according to the problem and solution approach.

25. In view of the above considerations, the board concludes that it has not been established that the skilled person at the relevant date knew that in the commercially available Porcilis® App vaccine, mentioned in document D16, the Apx toxins were in complex with LPS.

26. All of the appellant's submissions on the inventive step of the claimed subject matter rely on the skilled person at the relevant date knowing that in the commercially available Porcilis® App vaccine, mentioned in document D16, the Apx toxins were in complex with LPS. Since this had not been shown to the board's satisfaction, the appellant's submissions on inventive step must fail.

27. The board has therefore seen no persuasive reasons why the decision of the examining division that the subject matter of claim 1 lacks an inventive step should be overturned.

Auxiliary request - claim 1

Admission of a line of argument on inventive step (Article 13(1) and (3) RPBA 2007)

28. As the summons to oral proceedings was notified before the date of entry into force of the RPBA 2020, Article 13 RPBA 2007 is applicable to the admission of auxiliary request 1 and the associated line of argument on inventive step into the appeal proceedings (Article 25 RPBA 2020).

29. This claim request was filed during the hearing before the board. The board admitted it into the appeal proceedings because the appellant could reasonably have been confident that their auxiliary requests (see section VII.) had been received and would therefore be considered by the board.

30. The appellant argued that the subject-matter of this claim request was inventive because of the particularly low dose of polymyxin used. They submitted that this was not a new line of argument presented for the first time at the hearing but rather had already been developed in the statement of grounds of appeal at page 7, third paragraph. This paragraph reads as follows:

"So D7 even makes a reservation regarding vaccine efficacy for a vaccine where in the LPS is not part of the essential immunogen. This makes even more clear that D7 does not even remotely teach that for a vaccine wherein the LPS is actually part of the essential immunogen of the vaccine that "the powerful endotoxin disruptor polymyxin (as D7 calls it) polymyxin will not negatively interfere with a LPS-protein immunogenic complex, let alone the LPS-Apx complex of the vaccine of D16. Interestingly (cf present claim 2), D7 also discusses the level of polymyxin that would be needed to reduce the endotoxic effect of the LPS naturally present in the outer membrane of the bacteria in the vaccine: it is stated that a "more realistic concentration" would be "5000 myg of polymyxin/ml" (page 380, lines 1-3 of third paragraph), i.a. about 42.000 (42 thousand) IU/ml, i.e. more than 20 times the amount according to the embodiment of claim 2".

31. In the board's view, the above referenced paragraph cannot be taken as containing an argument as to why the subject matter of claim 1 (then pending claim 2), which specifies that the vaccine comprises less than 2000 IU of polymyxin per dose, is inventive. In the paragraph it is merely noted that document D7 "interestingly" discusses the level of polymyxin that would be needed and that these were higher than the amount specified in the claim. The arguments presented at the oral proceedings before the board implying that this additional feature would overcome the inventive step objection against the subject-matter of the main request are therefore a change of the appellant's case.

32. Pursuant to Article 13(1) RPBA 2007, "(1) Any amendment to a party's case after it has filed its grounds of appeal or reply may be admitted and considered at the Board's discretion. The discretion shall be exercised in view of inter alia the complexity of the new subject-matter submitted, the current state of the proceedings and the need for procedural economy". Article 13(3) RPBA 2007 provides that "Amendments sought to be made after oral proceedings have been arranged shall not be admitted if they raise issues which the Board or the other party or parties cannot reasonably be expected to deal with without adjournment of the oral proceedings".

33. In the present case admitting the appellant's argument on inventive step would have meant that the board was faced with a line of argument that had not been developed before and for which it was not prepared. Taking it into account would therefore have required the adjournment of the oral proceedings. Such an action would naturally not be procedurally economic. For this reason alone the change of case could not be admitted into the appeal proceedings.

34. In view of the above, no claim request on file is allowable and the appeal must be dismissed.