T 0395/18 (Oligosaccharides for preventing allergic reactions in infants) 11-09-2020

Reasons for the Decision

1. Admissibility of requests

1.1 The respondent requested that the main request and auxiliary requests 1 to 4, 6 and 7 not be admitted into the appeal proceedings. These requests were filed as auxiliary requests 1 to 5, 7 and 8 with the appellant's letter dated 18 March 2019, thus subsequent to the filing of the grounds of appeal. The filing of these requests therefore constitutes an amendment of the party's case, so that their admittance is at the discretion of the board under Article 13(1) of the revised Rules of Procedure of the Boards of Appeal (RPBA 2020, applicable according to the transitional provisions of Article 25 RPBA 2020).

1.2 The board notes that:

- Each of the requests is based on a corresponding request filed with the statement setting out the grounds of appeal and on a further corresponding request which was admitted and examined by the opposition division.

- The new requests differ from the previous ones in that the claimed subject-matter has been limited to the treatment of an allergic reaction, a condition already specified in claim 1 of each of auxiliary requests 1 to 3 and 8 filed during the opposition proceedings, and in the corresponding requests filed with the statement of grounds of appeal.

- The amendments are simple and clearly address the objection that the therapeutic use specified in the previously filed claims (enhancement of an immune system disorder and/or prevention of an immune system disorder) was too broadly defined. Thus, this limitation simplifies the issues to be discussed without giving rise to new ones, which is beneficial for procedural economy. Simplification of the proceedings and prevention of further discussions were indeed the appellant's justification for filing the requests.

1.3 For these reasons, the main request and auxiliary requests 1 to 4, 6 and 7 are admitted into the appeal proceedings.

2. Admissibility of submissions by the respondent

2.1 The appellant requested that certain submissions presented by the respondent after notification of the communication issued by the board in preparation for the oral proceedings be disregarded. These submissions relate to the:

- teaching of paragraphs 4.4.4 and 4.6 of D13

- results presented in paragraph [102] of the opposed patent

- interpretation of the results in Table 3 of D14

2.2 Since the submissions were made after the notification of the summons to oral proceedings dated 27 January 2020, they constitute an amendment of the party's case and their admittance is at the discretion of the board under Article 13(2) of the revised Rules of Procedure of the Boards of Appeal (RPBA 2020, applicable pursuant to Article 25(1) and (3) RPBA 2020).

2.3 The respondent argued that there were compelling reasons to dispute the assumptions and preliminary conclusions presented in paragraph 6 of the communication issued by the board in preparation for the oral proceedings. In particular, it was important to discharge the burden of proof that the board had shifted to it, contrary to the findings in the contested decision. This should justify the late filing of the arguments concerned.

2.4 The preliminary opinion given by the board in its communication is based essentially on facts and arguments presented by the parties in writing. Nonetheless, the communication crystallised for the first time what the board itself had deduced to be the essential elements of the lengthy arguments presented by the parties when discussing sufficiency of disclosure. In particular, the communication drew attention to some paragraphs of the opposed patent discussing the principle underlying the claimed invention which convey the impression that, at the filing date, the skilled person would have assumed any galacto-, fructo- or acidic oligosaccharide to be suitable, individually, to induce the alleged therapeutic effect (paragraphs [0032], [0033], [0092] and [0102]). Furthermore, the communication drew attention to the results of the tests described in paragraph [0102] of the patent. It also clearly put the burden of proof regarding sufficiency on the respondent, thus contradicting the position taken by the opposition division.

2.5 It is thus accepted that the respondent's first opportunity to address these specific points highlighted by the board was after receiving the board's preliminary opinion.

2.6 Concerning D13, it is noted that this is a document filed by the appellant itself as evidence of common general knowledge relating to the use of oligosaccharides as prebiotics. Furthermore, the parts cited by the respondent are contained in the same sections of D13 (4.4 and 4.6) mentioned by the appellant in the statement of grounds of appeal. The relevance of these parts, which raises serious doubts as to the assumptions made in the patent, had already been highlighted by the respondent one month before the scheduled oral proceedings, thus, sufficiently in advance for the appellant to discuss their relevance. In this context, it also needs to be noted that at no stage did the appellant request extra time or even a postponement of the oral proceedings in order to deal with those submissions.

2.7 Concerning paragraph [0102] of the patent, it is pointed out that, in its communication, the board underscored the relevance of and drew preliminary conclusions from the results of the tests described in this paragraph. Thus, the respondent had good reasons to re-examine the results in detail and to comment on the board's conclusions. The discussion certainly involved technical considerations. However, the appellant had to be ready to discuss the results described in its own patent at any stage of the proceedings, including in the course of the oral proceedings before the board.

2.8 Thus, in the context of the particular circumstances of the present case, it can be concluded that the respondent had cogent reasons for filing further submissions referring to D13 and to paragraph [0102] of the patent at a late stage of the appeal proceedings. Furthermore, the respondent had to be prepared to address them during the oral proceedings before the board. Thus, these submissions are admitted into the appeal proceedings.

2.9 As far as the late-filed submissions relating to D14 are concerned, the following is to be considered. D14 was filed by the appellant with the statement setting out the grounds of appeal. However, only the relevance of the results described in Table 2 on page 26 was discussed by the appellant. The results shown in Table 3 on page 27 were mentioned by the respondent for the first time during the oral proceedings before the board. The ensuing discussion involved complex considerations as to the experimental setting used and the interpretation of the results. Since neither the appellant nor the board could be expected to address these entirely new issues during the oral proceedings, the new submissions relating to D14 are not admitted.

3. Objection under Rule 106 EPC

3.1 The board decided to dismiss the objection raised by the appellant under Rule 106 EPC against the admittance of the respondent's latest submissions based on D13 and D14 for the following reasons, complementary to those mentioned above underlying the decision to admit the respondent's arguments based on D13.

3.2 The appellant was made aware of the relevance of two specific passages in D13 one month before the scheduled oral proceedings, namely by the respondent's letter dated 11 August 2020. D13 is an excerpt of a textbook reflecting - according to the appellant, which submitted the document with the statement setting out the grounds of appeal - common general knowledge in the field of prebiotics. The passages highlighted in the respondent's letter are contained in the two sections (4.4 and 4.6) initially cited by the appellant. Thus, the appellant could reasonably be expected to be prepared to discuss the content of those sections and the relevance of the cited passages in detail. Furthermore, should it have needed more time to revise the studies cited in the relevant sections, as argued in the objection, it should have reacted promptly, i.e. immediately after receiving the respondent's letter, rather than waiting for the board to announce its conclusions concerning sufficiency of disclosure regarding the main request.

3.3 Even if it were to be considered that the appellant's complaint about the violation of its right to be heard referred to the board not having properly considered its objections and arguments in the discussion of the contested issue, the board notes that, as is also apparent from the minutes of these oral proceedings, the relevant discussion was exhaustive. The complaint rather appears to stem from the board not deciding in the appellant's favour. This ought to be, however, an acceptable outcome to any and all participants to a contentious procedure such as opposition-appeal proceedings before the EPO Boards of Appeal.

The board cannot recognise any violation of the appellant's right to be heard. The arguments of the appellant were duly considered but were not found convincing. Therefore, the objection is dismissed.

3.4 Concerning the relevance of D14, it is noted that, since the new submissions based on this document (Table 3 in particular) presented by the respondent have not been admitted, the objection is moot.

Main request

4. Sufficiency of disclosure

4.1 The claimed invention relates to the use of a composition comprising a non-digestible oligosaccharide for decreasing or preventing an allergic reaction in a mammalian subject. The composition is administered to a lactating post-partum female who is breastfeeding the mammalian subject.

4.2 As explained in the description of the patent in suit, the idea underlying the invention is to administer the composition to a mother who is breastfeeding her infant, in order to induce a beneficial programming effect on the immune response of the infant. This results in a beneficial decrease or prevention of allergic reactions in the infant (see paragraphs [0001], [0004], [0005] and [0006] of the patent and the corresponding parts of the patent application as filed).

4.3 Claim 1 is drafted in the format foreseen by Article 54(5) EPC. Accordingly, attaining the claimed therapeutic effect is a functional technical feature characterising the claim. Thus, the issue of whether the claimed therapeutic method can be carried out, and the purported effect achieved, is relevant in the context of the assessment of sufficiency of disclosure (G 1/03, see point 2.5.2). According to numerous decisions of the boards of appeal, unless this effect is already known to the skilled person at the relevant date, the patent application must disclose the suitability of the claimed product for the specified therapeutic application (see Case Law of the Boards of Appeal, 9th edition 2019, II.C.7.2).

4.4 Relying on this case law the respondent argued that the application does not make it plausible that the claimed agent is suitable to induce the alleged therapeutic effect.

4.5 Whether the suitability of a product for a new therapeutic application is plausibly disclosed has to be established by relying on the disclosure in the patent application, taking into account the common general knowledge available at the filing date, as well as any available relevant prior art (see T 184/16, point 2.3). In this context, account must be taken, for example, of the results of in vivo or appropriately designed in vitro tests described in the application (see T 241/95, point 4.1.2 and T 609/02, point 9), whether the claimed agent shares structural characteristics or properties with known ones (see T 184/16, points 2.5 to 2.8; T 694/16, points 4.8 to 4.9; T 1329/04, points 6 to 11), and whether known facts throw serious doubts that the claimed therapeutic treatment can be carried out (T 491/08, points 1 to 12, citing T 19/90; T 1150/09, points 15 to 22).

4.6 The objection of lack of sufficiency brought forward by the respondent is based essentially on the following arguments:

- that the results of the tests shown in the patent do not provide any evidence that the tested composition is suitable to induce the alleged therapeutic effect,

- that the results, obtained using a mixture of three specific oligosaccharides, do not make the suitability of a composition comprising only a galacto-oligosaccharide plausible, and

- that verifiable facts throw serious doubts as to that suitability.

4.7 The respondent observed in the first place that there is an inconsistency between the description and the figures in the patent: the numbering of the tests in example 1 does not correspond to that of the results shown in the figures.

4.8 The board agrees with the respondent that, due to this inconsistency, a skilled person would not be able to attribute the data shown in the figures to those mentioned in example 1. However, the information given in paragraphs [0102] to [0107] of the patent (and in the corresponding parts of the patent application), which describe the tests and the results in qualitative terms, is in itself coherent and sufficiently clear for the skilled person to take into account the results at face value. The respondent's argument that the skilled person could consider the figures correct and the description erroneous is not convincing.

4.9 Example 1 describes different tests in which a composition comprising a mixture of galacto-oligosaccharides (GOS), fructo-oligosaccharides (FOS) and acidic oligosaccharides (in a ratio 9:1:2) was administered to female mice during pregnancy or during lactation. The effects of the treatment on the immune responses triggered by an antigen in the dams' offspring were then observed. The tests involved the treatment of dams sensitised with antigen, non-sensitised dams, a placebo group and a sham group.

4.10 The respondent observed that according to paragraph [0102] of the patent, an acute allergic skin response was significantly reduced in the offspring of sensitised dams treated with oligosaccharides during lactation, but not in the offspring of non-sensitised dams. In its opinion, since the claims were not limited to the offspring of sensitised dams, serious doubts existed as to whether the invention could be carried out across the scope of the claims.

4.11 The board does not agree, because the results of the entire set of tests shown in example 1 have to be taken into account. These show that:

- OVA-challenges caused a lower decrease in temperature (indicative of shock) in the offspring of dams treated according to the invention, compared to the control groups; this occurred in the offspring of both sensitised and non-sensitised dams (see paragraph [0103] and compare groups 7 and 9 (sensitised) and groups 4 and 6 (non-sensitised)).

- After challenge with OVA-allergen, the levels of OVA-specific IgE antibodies in the offspring of dams treated according to the invention were lower than in the control group; this again in the offspring of both sensitised and non-sensitised dams (see paragraph [0104] and compare groups 9 and 7 and groups 4 and 6).

- The OVA-specific IgG1 antibody levels also differed significantly between groups 4 and 6 and groups 7 and 9, indicating that the supplementation of oligosaccharides to the dams during lactation is effective in the offspring, regardless of whether the dams are sensitised (see paragraph [0105]).

4.12 These results indicate that the offspring benefits from the treatment, irrespective of whether the dams were sensitised or not.

4.13 The respondent argued that, since claim 1 is directed to the treatment or prevention of allergic reactions, the negative result shown in paragraph [0102], which relates to an acute allergic reaction, outweighed the positive ones shown in following paragraphs.

4.14 This argument is not convincing either. In the test described in paragraph [0102], the ear thickness of mice was measured after challenge with OVA-challenge. An improvement in this parameter was considered to be an indication that the treatment is beneficial in subjects affected by an acute allergic skin response. However, it can be reasonably expected that subjects affected by this condition will benefit from the effects observed in the other tests, irrespectively of the dams being sensitised or not. A change in ear thickness is only one of the criteria for establishing whether the treatment of these subjects is effective.

4.15 Thus, the results shown in the patent and in the corresponding parts of the patent application provide convincing evidence that the tested composition is suitable for carrying out the treatment defined in claim 1.

4.16 What has to be established next is whether these results, obtained using a mixture of a galacto-, a fructo- and an acidic oligosaccharide, are apt to show the suitability of a composition comprising a galacto-oligosaccharide only, and furthermore, if verifiable and substantiated doubts exist that the claimed effect can be achieved.

4.17 According to the patent and the patent application, the invention is based on the discovery that the maternal administration of non-digestible oligosaccharides has a beneficial programming effect on the immune response of the offspring. Prebiotic oligosaccharides, and in particular, galacto-, fructo- and acidic oligosaccharides are proposed to induce this effect (see the passage from page 6, line 34 to page 7, line 11 of the patent application). This means that the assumption is made that these oligosaccharides share the same pharmacological properties and can be used interchangeably, alone or in combination, to carry out the invention. Referring to D13 the appellant explained that the prebiotic properties of these compounds, and the anti-allergic properties of prebiotics, were part of the common general knowledge. Thus, it could be assumed that the effects induced by the tested mixture could be achieved by administering the individual oligosaccharides present in the mixture.

4.18 However, these assumptions are contradicted by the very document D13 that the appellant has referred to as representative of the skilled person's common general knowledge. D13 is a textbook on prebiotics published before the date of filing. Paragraphs 4.4.4 and 4.6, which focus specifically on the use of galacto-oligosaccharides as prebiotics in humans and, in particular in infants, state that:

"GOS have repeatedly shown prebiotic properties in vitro. The bifidogenic effect is often greater than that seen with fructans. This is offset to some degree, however, by the rather mixed data obtained in human studies. There have been several, well-designed, human trials in which GOS has not shown a prebiotic effect" (emphasis by the board; see page 107, section 4.6 conclusions and page 104, paragraph 4.4.3 conveying the same teaching).

and that:

"GOS have also been studied in the context of infant nutrition. Some studies, however, have used mixtures of GOS and FOS, making reliable conclusion about the efficacy of the GOS impossible" (emphasis by the board; see page 105, section 4.4.4, paragraph 1).

4.19 These statements indicate, in the first place, that the skilled person's common general knowledge would have told them that GOS do not always exhibit prebiotic activity. Furthermore, the skilled person would have known that a study conducted using a mixture of GOS and FOS, and even less of GOS, FOS and acidic oligosaccharides, cannot be relied upon to establish whether a composition comprising GOS alone is suitable to achieve the purported therapeutic effect.

4.20 The appellant argued that no evidence had been provided that GOS were not suitable to carry out the invention. To the contrary, D14, Table 2 confirmed that GOS (together with FOS) were beneficial to the immune system. Furthermore, a detailed review of the studies cited in D13 would have confirmed that, at the filing date, the skilled person was well aware of the prebiotic effect of GOS, irrespectively of the presence of other oligosaccharides.

4.21 These arguments are not persuasive. The fact remains that D13 clearly states that a number of well-designed clinical trials, in which oligosaccharides were administered directly to human subjects, have failed to show the desired effects. The mixed results throw serious doubts as to whether the claimed therapeutic treatment can be carried out, all the more so when considering that the principle underlying the invention - to administer oligosaccharides to a lactating mother in order to achieve a pharmacological effect in a child - departs considerably and constitutes a radical development from the teachings in the common general knowledge reflected in D13, which teaches administering the oligosaccharides directly to the child.

4.22 The appellant contended that, since the GOS was the major component of the tested mixture, it was likely to be the agent responsible for the observed effects.

4.23 This argument is not convincing either. Substantial amounts (35%) of FOS and acidic oligosaccharides are also present in the tested mixture. Since it is well known that the biological activity of similar compounds can vary considerably, no assumptions can be drawn relying on the relative amounts of oligosaccharides present in that mixture. Furthermore, and even more relevant, page 20, lines 20 to 24 of the application as filed, corresponding to paragraph [0092] of the granted patent, states that:

"The invention is based on the discovery that the administration of a composition comprising a non-digestible acidic-oligosaccharide as described herein to a female breast-feeding an infant has a long term impact on the development and enhancement of the immune system in the infant".

4.24 The other oligosaccharides mentioned in the application, GOS and FOS in particular, are not mentioned here. It is thus apparent that acidic oligosaccharides have a crucial role for carrying out the invention. This fact throws additional doubts as to whether the claimed composition, which does not contain an acidic oligosaccharide, is suitable to induce the claimed effect.

4.25 For these reasons, it is concluded that there are serious doubts based on verifiable facts which have not been overcome and that the invention claimed in the main request is not sufficiently disclosed (Article 83 EPC).

Auxiliary request 1

5. Sufficiency of disclosure

5.1 Claim 1 of auxiliary request 1 differs from that of the main request in that it relates to a composition comprising galacto- and fructo-oligosaccharides (GOS and FOS).

5.2 According to the appellant, the limitation of the claimed subject-matter to this combination overcame the objection of lack of sufficiency. D14 provided evidence that a composition comprising GOS and FOS was beneficial on the immune system, and D13 did not throw doubts but rather confirmed that the claimed combination had prebiotic properties.

5.3 These arguments are not persuasive. D13 underscores the fact that mixed results are obtained when testing the activity of oligosaccharides (GOS), and that the effects induced by a combination of oligosaccharides of the same class (GOS and FOS, i.e. neutral oligosaccharides) cannot be relied upon to draw any conclusion as to the activity of its individual components. In view of this teaching, the skilled person would be even more reluctant to draw any conclusion as to the activity of the claimed composition, since this does not comprise, like the tested one, an oligosaccharide belonging to a different class (an acidic oligosaccharide). This is all the more so because, as already mentioned above, the patent and the patent application teach that acidic oligosaccharides play a crucial role for carrying out the invention, and the principle underlying the invention departs considerably from the teaching of the prior art (see points 4.18 to 4.24). Thus, the results in D13, D14 and example 1 of the patent are not apt to show the suitability of a GOS/FOS combination in the claimed method, and serious doubts exist that the claimed therapeutic effect can be achieved.

5.4 Accordingly, the invention claimed in auxiliary request 1 is insufficiently disclosed (Article 83 EPC).

Auxiliary requests 2 to 6

6. Sufficiency of disclosure

6.1 Claim 1 of auxiliary request 2 differs from that of the main request in that the non-digestible oligosaccharide "comprises galacto-oligosaccharide and fructo-oligosaccharide, wherein the fructo-oligosaccharide has a degree of polymerisation between 7 and 100".

Claim 1 of each of auxiliary requests 3 to 6 differs from that of the main request, inter alia, in that the non-digestible oligosaccharide is "selected from the group consisting of galacto-oligosaccharide and fructo-oligosaccharide, wherein the fructo-oligosaccharide has a degree of polymerisation between 7 and 100".

6.2 Despite some differences in how the FOS are characterised (their degree of polymerisation) and in how the treatment, the lactating mother and the allergic reaction are defined, the invention claimed does not differ substantially from that claimed in the previous requests. In particular, the compositions defined in the claims of auxiliary requests 2 to 6 do not comprise an acidic oligosaccharide, and the disease to be treated is an allergic reaction.

6.3 The appellant has not provided any argument as to how the amendments of the claims of these requests could overcome the negative conclusions arrived at when examining the previous requests. Therefore, for the same arguments already discussed above, the invention claimed in auxiliary requests 2 to 6 is insufficiently disclosed (Article 83 EPC).

Auxiliary request 7

7. Added subject-matter

7.1 According to the respondent, the replacement of the wording used in claim 1 of the application as filed, "the composition is for administration", with the wording "the composition is administered", adds originally undisclosed subject-matter.

However, this amendment does not lead to any change in the technical teaching. Claim 1 of auxiliary request 7, as well as claim 1 as filed, are drafted as foreseen by Article 54(5) EPC. Despite the different wording, they relate to the same method of treatment, which involves the administration of the relevant composition for the specified use. Therefore, the amendment does not create new subject-matter (Article 123(2) EPC).

8. Sufficiency of disclosure

8.1 Claim 1 of auxiliary request 7 differs from that of the main request in that the non-digestible oligosaccharide "comprises galacto-oligosaccharide, fructo-oligosaccharide and acidic oligosaccharide".

Since acidic oligosaccharides are present in the composition, the negative conclusions arrived at when dealing with the previous requests no longer apply.

8.2 The respondent contended that, in view of the paucity of data recited in the patent, it was unreasonable to extrapolate the claims to cover a significantly broader composition as defined in claim 1. The tested composition comprised a very specific mixture containing short-chain-galacto-oligosaccharides (GOS), long-chain-fructo-oligosaccharides (FOS) and pectin-derived acidic oligosaccharides in a ratio 9:1:2. In its opinion, any suggestion gleaned from the limited data presented in the patent application was undermined by significant errors and far exceeded a reasonable interpretation that might have been drawn, had no errors been present. The respondent also drew attention to paragraph 4.5 of D13, "Further developments", which hypothesised that GOS mixtures might have different properties.

8.3 These arguments are not persuasive. In the first place, as already explained above when discussing the main request, despite the errors and inconsistencies between the figures and the description, the information shown in the patent and the patent application is in itself coherent and sufficiently clear for the skilled person to establish that the tested composition is effective for the claimed use.

8.4 In the second place, no facts have been presented throwing serious doubts that a mixture comprising at least one member of each of the three oligosaccharide classes indicated in claim 1 is not suitable to induce the claimed therapeutic effect. None of the documents on file, let alone the aforementioned paragraph 4.5 of D13, provides evidence, and no concrete technical reason has been presented by the respondent as to why a composition comprising at least one member of each of the three oligosaccharides classes specified in claim 1 should not be suitable for the claimed use.

8.5 For these reasons, it is concluded that the invention claimed in auxiliary request 7 is sufficiently disclosed (Article 83 EPC).

9. Remittal

Both parties have requested remittal of the case to the opposition division for discussion of novelty and inventive step if a request were found to comply with Articles 83 and 123(2) EPC. The board notes that those last-mentioned patentability requirements were not even broached in the opposition proceedings and would thus be discussed for the first time. As set out in Article 12(2) RPBA 2020, the primary object of the appeal proceedings is to review the decision under appeal in a judicial manner. This principle would not be respected if the board were to conduct a complete examination of issues which were not dealt with by the opposition division. Thus, special reasons are present for remitting the case (Article 11 RPBA 2020 and decisions T 1966/16 and T 731/17). Accordingly, in exercise of its discretion under Article 111(1), second sentence EPC, the board decides to remit the case to the opposition division for further prosecution.