T 3109/19 (Crosslinked gel/TEOXANE) 25-03-2022

Reasons for the Decision

1. Admission of evidence

The appellant did not contest the admission of document D18 during the proceedings before the opposition division. The Board finds therefore no ground to overturn the discretionary admission of document D18 by the opposition division.

In the decision under appeal an inventive step was denied taking account of the results in the late-filed document D18. Document D19 presents experimental evidence intended to explain the results reported in document D18. The filing of document D19 with the statement of grounds of appeal by the appellant therefore represents a legitimate reaction to the decision under appeal. Documents D18a and D20 present further experimental evidence contrasting the results reported in document D19. The filing of documents D18a and D20 with the reply to the appeal by the respondent therefore represents a legitimate response to the statement of grounds of appeal. Documents 18a, D19 and D20 are therefore not disregarded under Article 12(4) RPBA 2007 and thus part of the appeal proceedings.

The respondents have not objected to the admission of the data regarding the variation of the elastic modulus of different batches of commercially available products from FILORGA reported in the appellant's letter of 15 October 2020. The respondents have actually taken up these data to argue that the experimental results relied upon by the appellant are not reproducible. This evidence is therefore admitted into the appeal proceedings under Article 13(1) RPBA 2020.

2. Right to be heard / Request for remittal

2.1 Rather than requiring a repeat of the experiments of document D18 from the appellant, the opposition division considered in the reasons for its decision (see page 24, first paragraph) that in view of the available evidence, including document D18, it had not been convincingly demonstrated that the claimed method leads to the advantageous effects mentioned in the patent. As the appellant did not contest the admission of document D18 during the proceedings before the opposition division, the Board does not recognize any violation of the appellant's right to be heard in this matter.

2.2 The Board observes that in requesting remittal for a renewed debate on inventive step before the opposition division the appellant relies on an argument presented for the first time during the appeal proceedings with the letter of 15 October 2020, namely that the opposition division failed to take a further difference with respect to the prior art into account. Such an amendment to the appellant's appeal case is not considered to represent a special reason within the meaning of Article 11 RPBA 2020 that justifies a remittal.

Main request

3. Admission of the main request

The respondents have contested the main request filed with the statement of grounds of appeal as an inadmissible amendment of the appellant's appeal case under 12(4) RPBA 2020. The Board observes that Article 12(4) RPBA 2020 is not applicable in view of the transitional provision of Article 25(2) RPBA 2020.

The amendment of the main request merely concerns the definition in claim 1 of hyaluronic acid or one of its salts as the polysaccharide to be used. As a result, claim 1 of the main request corresponds to claim 1 of auxiliary request 3 on which the decision under appeal was based. The Board considers this amendment, which does not present the respondents with any new aspects of the case, a legitimate response to the finding in the decision under appeal that the presented results obtained with hyaluronic acid could not be extrapolated to polysaccharides in general. Accordingly, the Board finds no reason not to admit the main request under Article 12(4) RPBA 2007.

4. Added subject-matter

4.1 The respondents objected that claim 1 of the main request comprised subject-matter extending beyond the original disclosure due to the introduction in claim 1 as originally filed of the features of the cavity being made within a deformable pouch and the homogenization in step b) as carried out by mechanical deformations of the outer face of the deformable wall or of the pouch (see section IX(e) above).

Dependent claim 6 of the application as originally filed defines:

"Process according to any of the preceding claims, wherein the cavity is made within a deformable pouch.[highlighting by the Board]

Furthermore, the application as originally filed describes on page 9, lines 23-26:

"According to one particular embodiment, the deformable wall, or even the pouch has a degree of deformability such that the homogenization, considered in step b ), may be carried out by optionally successive, mechanical deformations of the outer face of the deformable wall, or even of the pouch."[highlighting by the Board]

The contested features of claim 1 (see sections I and VI above) are thus practically word by word based on the disclosure in the application as filed. In this context the Board agrees with the finding in the decision under appeal, that the remaining reference to a delimitation at least partially by a deformable wall represents at most an ambiguity in the patent as granted and that the degree of deformability mentioned in the cited passage on page 9 is implicit in the requirement of claim 1 of the main request that the homogenization is carried out by the mechanical deformations.

The contested amendments in claim 1 of the main request do therefore not introduce any subject-matter extending beyond the content of the application as filed.

4.2 The respondents further contested the definition of the feature concerning manual palpation in claim 13 in view of its dependence on claim 1 defining homogenization by mechanical deformations (see section IX(e) above).

The application as originally filed describes on page 10, lines 29-31:

"According to one particular embodiment, the homogenization may be carried out firstly by palpation, then using a mechanical device.

According to yet another embodiment, these various homogenization means may be used alternately."[highlighting by the Board]

The Board agrees with the decision under appeal that mechanical deformations of the pouch as described on page 9 lines 23-26 of the application as filed and defined in claim 1 of the main request do not exclude manual palpitations as described in the cited passage of page 10. The definition of the deformation involving such palpation in claim 13 (see section VI above) does therefore not define subject-matter extending beyond the content of the application as filed.

4.3 The respondents further maintained that the definition of the system for homogenization in claim 12 of the main request introduced subject-matter that was not originally disclosed (see section IX(e) above).

The application as originally filed describes on page 9 line 31 to page 10 line 5:

"According to another alternative, the deformations may be carried out mechanically, for example using a device of "paddle mill" type, commonly used for the preparation of biological samples.

According to one such embodiment, the receptacle is placed in the device, then the homogenization is carried out by virtue of a system of two blades side-by-side which alternately press the deformable wall or at least one of the deformable walls following a back and forth motion." [highlighting by the Board]

The Board observes that the additionally defined feature of claim 12 (see section VI above) is described practically word by word in the cited passage of pages 9-10. The Board considers that the defined two blade system requires no further specification in terms of a "paddle mill" type device in order to comply with Article 123(2) EPC, because such a device is mentioned in the cited passage as a mere example of a device for performing the mechanical deformations.

4.4 Accordingly, the Board concludes that the main request meets the requirement of Article 123(2) EPC.

5. Sufficiency

5.1 The Board notes that the ground of lack of sufficient disclosure had been raised in the notice of opposition, but that the requirement of sufficiency of disclosure was not addressed in the decision under appeal following the revocation of the patent on other grounds. The respondents' line of argument in the reply to the appeal, namely that the patent does not teach how the mechanical homogenization in a partially deformable pouch can be realized, is considered to represent a mere further development of the argument in the notice of opposition that the claimed invention cannot be carried out over the whole scope of the claims. The Board does therefore not recognize any ground for disregarding the respondents' line of argument (Article 14(2) RPBA 2007).

5.2 The claims define a process involving homogenization in a deformable pouch by mechanical deformation. The patent demonstrates in its examples how this homogenization may be carried out. The Board does not recognize why, with the examples in the patent at hand, the skilled person would not be able to choose deformable pouches that are suitable for the defined homogenization.

5.3 Accordingly, the Board concludes that the main request meets the requirement of sufficiency of disclosure.

6. Novelty

The Board observes that claim 1 requires the formation of a hyaluronic acid gel in step b) with subsequent addition of a crosslinking agent in step c). In contrast, according to document D1 (see paragraphs [0039] and [0062]) the hyaluronic acid starting material is brought into contact with the dissolved crosslinking agent directly without prior gel formation.

Accordingly, the Board concludes that the main request meets the requirement of novelty.

7. Inventive step

7.1 The Board recalls that the problem solution approach implies that in case an inventive step can be recognized starting from a particular item of prior art which is convincingly identified as most promising starting point and thus represents the closest prior art, attempts to argue a lack of inventive step starting from less promising starting points are bound to fail. However, in case an inventive step is apparently convincingly denied starting from a promising particular item of prior art, the mere argument that the claimed subject-matter nevertheless involves an inventive step in view of an allegedly closer prior art, may not be persuasive, because in such case the allegedly closest prior art is likely to represent a starting point that is in fact not more promising.

In the present case two types of known processes for preparing injectable gels of crosslinked hyaluronic acid have been proposed as starting points in the prior art, namely

(a) the process for preparing a crosslinked hyaluronic acid gel described in examples 4-1/4-2 of document D1 in which a deformable pouch is used as defined in the claims, but in which the crosslinking agent is combined with the hyaluronic acid prior to gel formation

(b) the "conventional" process for preparing a crosslinked hyaluronic acid gel as described in documents D2-D5 in which the crosslinking agent is added after gel formation with the hyaluronic acid as defined in the claims, but in which the process is carried out in a conventional receptacle instead of a deformable pouch.

In view of the common objective of preparing injectable gels of crosslinked hyaluronic acid and the complementary nature of the differences of the two types of processes with the claimed process the Board considers it purposeful to assess the requirement of inventive step starting from each one of the two types of processes rather than to attempt to determine which of the two starting points is actually the more promising.

7.2 Assessment starting from document D1

7.2.1 Document D1 describes the preparation of crosslinked hyaluronic acid gels suitable for injection (see D1 paragraph [0041]) in which physical cutting of the hyaluronic acid polymer chain during stirring and mixing steps is avoided (see paragraphs [0010] and [0024]-[0025]). In examples 4-1/4-2 document D1 discloses the preparation of such a gel in which hyaluronic acid is added to a crosslinking agent in a deformable pouch with subsequent mixing by kneading for 5 minutes (see D1 paragraphs [0062]-[0063]). As explained in section 6 above, the process of claim 1 of the main request differs from this process of document D1 in the formation of a hyaluronic acid gel prior to the addition of a crosslinking agent.

7.2.2 The patent indicates (see paragraph [0122] with reference to Figures 5-7) that the claimed process allows for providing gels with an improved injectability profile with respect to gels which are conventionally prepared in a rigid receptacle. The injection profile in Figure 5, which was obtained with a gel prepared according to the claims, indeed shows a more regular pattern compared to Figures 6 and 7, which were obtained with a gel prepared in a rigid receptacle. Whilst the patent does not present a comparison with the process of document D1 involving the use of a pouch without gel formation prior to crosslinking, the Board acknowledges that the mentioned experimental results reported in the patent substantiate that the claimed process allows for the alternative preparation of injectable gels of crosslinked hyaluronic acid with respect to document D1.

Documents D16, D18 and D20 relied upon by the respondent present apparently less favourable injection profiles for gels prepared in accordance with the claims (see D16, pages 8-9, samples 2 and B; D18, pages 5/7, samples A/A'; D20, pages 5/6, samples A/C) than the profiles reported in the patent. The Board observes that variations in the results from separate experiments are to be expected in view of the possible influence of differences in manual handling and homogenisation times as well as variations that may exist between different batches of hyaluronic acid as indicated by the data presented in the appellant's letter of 15 October 2020. In fact, document D16 presents for a gel prepared in line with examples 4-1/4-2 of document D1 also a rather uneven injection profile (see D16, page 9, sample A). The Board therefore considers that whilst documents D16, D18 and D20 seem to indicate suboptimal conditions for carrying out the claimed process, this process involving gel formation prior to crosslinking performed in a deformable pouch may still be considered to represent a suitable alternative process with respect to the process of examples 4-1/4-2 of document D1.

The problem to be solved starting from document D1 may therefore be seen in the provision of an alternative process allowing the preparation of injectable gels of crosslinked hyaluronic acid.

7.2.3 As mentioned in section 7.2.1 above, document D1 itself discloses the kneading of the pouch as a gentle form of mixing aimed at avoiding physical cutting of the hyaluronic acid polymer. Whilst document D1 suggests that this method of mixing the crosslinking agent with the hyaluronic acid is suitable for a mixture in the solid powder state or in a highly viscous gel state (see D1, paragraph [0039]), the process of examples 4-1/4-2 involves a procedure in which the crosslinking agent and the hyaluronic acid are combined and directly mixed to subsequently obtain a gel-like mixture. In this context the skilled person would expect that the efficient initial blending of the components is favoured by starting the mixing before the actual gel formation and that the initial blending is less efficient if started after the gel formation, because the increased viscosity of a gel opposes such blending. This expectation finds confirmation in document D2, which indicates flake formation and local overcrosslinking from mixing a gel with a crosslinking agent. Accordingly, it would not be evident from document D1 itself that the modification of the process of examples 4-1/4-2 by performing initial gel formation prior to the addition of the crosslinking agent represents a suitable alternative.

Documents D2-D5 describe the preparation of injectable crosslinked hyaluronic acid gels involving initial gel formation and subsequent combination with a crosslinking agent in a conventional receptacle (see D2, reference Example 2, paragraphs [0075]-[0084]; D3 e.g. example 1, paragraph [0070]; D4, example 1, paragraph [0028]; D5, page 11, lines 5-11 and page 15, lines 19-27). These documents do not indicate the exchangeability of a process involving gel formation before the addition of a crosslinking agent and a process involving combination of the hyaluronic acid with the crosslinking agent before gel formation. To the contrary, document D2 specifically indicates that the conventional preparation involving gel formation before addition of the crosslinking agent is associated with the risk of formation of "flakes" and local overcrosslinking and that this risk is effectively avoided by a process in which the crosslinking is carried out during gel formation (see D2, paragraphs [0007]-[0010]). Moreover, documents D3-D5 do not mention any process involving crosslinking during the gel formation, let alone that such process could be exchanged with the conventional type of process involving gel formation prior to crosslinking.

The Board therefore concludes that the process of claim 1 of the main request would not be obvious to the skilled person starting from document D1 as closest prior art.

7.3 Assessment starting from documents D2-D5

7.3.1 As mentioned in section 7.2.3, documents D2-D5 describe the preparation of injectable crosslinked hyaluronic acid gels involving initial gel formation and subsequent combination with a crosslinking agent in a conventional receptacle.

The process of claim 1 of the main request differs from the conventional type of process as described in documents D2-D5 in the use of a deformable pouch for the gel formation and crosslinking instead of a conventional rigid receptacle.

7.3.2 As mentioned in section 7.2.2 above, the patent indicates in paragraph [0122] with reference to Figures 5-7 that the claimed process allows for providing gels with an improved injectability profile with respect to gels which are conventionally prepared in a rigid receptacle. The profile obtained with a gel prepared according to the claims (see Figure 5) indeed shows a more regular pattern compared to the profile obtained with gels prepared in a rigid receptacle (see Figures 6 and 7). The Board therefore considers that the mentioned experimental results reported in the patent substantiate that the claimed process allows for the improved preparation of injectable gels of crosslinked hyaluronic acid with respect to the conventional type of process of documents D2-D5.

The respondents' argument, that the differences in the injection profiles reported in the patent cannot be attributed to the mere use of a pouch as defined in the claims due to the further differences in homogenisation time and temperature profiles in the compared processes, is not considered convincing. According to the description of the experiments in the patent the different homogenisation times and temperature profiles already result themselves from the difference in the receptacle used (see patent, paragraphs [0158] and [0166]-[0169] with reference to Table 1 and Figures 2-4). Document D12, which has been relied upon by the respondents, does not present evidence that casts doubt on the relevance of the use of the pouch for obtaining the injection profiles reported in the patent. The numerical differences in the dissolution time, yield and injectability forces reported in document D12 (see D12, tables 1, 2 and 4) with respect to the results reported in the patent (see tables 1-3) indicate that depending on the set up of the experiments more or less fluid gels are prepared, but do not invalidate the evidence in the patent regarding the injection profiles. On the basis of the available evidence the Board therefore concludes that the use of the deformable pouch indeed allows for obtaining the improved injection profile as reported in the patent.

The problem to be solved starting from the conventional type of process as described in documents D2-D5 may therefore be seen in the provision of a process allowing the preparation of gels of crosslinked hyaluronic acid with an improved injection profile.

7.3.3 Documents D2, D4 and D5 do not make any reference to the use of a deformable pouch. Document D3 only refers to the use of a deformable pouch for preparing a diluted sodium hyaluronate solution without mention of subsequent crosslinking. Documents D2-D5 do therefore not themselves suggest the use of a pouch as defined in claim 1 of the main request.

As mentioned in section 7.2.1 above, document D1 describes the utility of a pouch for gently mixing hyaluronic acid and a crosslinking agent to produce a gel-like mixture. However, document D1 does thereby not suggest that the conventional type of process described in documents D2-D5 involving gel formation prior to crosslinking could be improved in terms of injectability of the crosslinked hyaluronic acid product by performing the process in a deformable pouch.

Documents D6-D11 describe the use of a deformable pouch as a convenient method for mixing a variety of components, but do not refer to any use of a deformable pouch for gel formation and crosslinking. These documents provide therefore no suggestion as to the utility of a deformable pouch for improving the conventional type of process of documents D2-D5 with regard to the injection profile of the resulting crosslinked gels.

The Board therefore concludes that the process of claim 1 of the main request would not be obvious to the skilled person starting from the conventional type of process as described in documents D2-D5 as closest prior art.

7.4 Accordingly, the Board concludes that the main request meets the requirement of inventive step.

Request for suspension of the proceedings pending G 2/21

8. In T 116/18 the following questions were referred to the Enlarged Board of Appeal:

If for acknowledgement of inventive step the patent proprietor relies on a technical effect and has submitted evidence, such as experimental data, to prove such an effect, this evidence not having been public before the filing date of the patent in suit and having been filed after that date (post-published evidence):

- Should an exception to the principle of free evaluation of evidence be accepted in that post-published evidence must be disregarded on the ground that the proof of the effect rests exclusively on the post-published evidence?

- If the answer is yes (the post-published evidence must be disregarded if the proof of the effect rests exclusively on this evidence), can the post-published evidence be taken into consideration if, based on the information in the patent application in suit or the common general knowledge, the skilled person at the filing date of the patent application in suit would have considered the effect plausible (ab initio plausibility)?

- If the answer to the first question is yes (the post-published evidence must be disregarded if the proof of the effect rests exclusively on this evidence), can the post-published evidence be taken into consideration if, based on the information in the patent application in suit or the common general knowledge, the skilled person at the filing date of the patent application in suit would have seen no reason to consider the effect implausible (ab initio implausibility)?

The referral is pending as G 2/21.

As explained in section 7 above (see in particular paragraphs 7.2.2 and 7.3.2), the Board concludes that the subject-matter of claim 1 of the main request involves an inventive step in view of a technical effect which is derivable from the patent and supported by experimental results disclosed in the patent. The referred questions are therefore not considered determinative to the outcome of the present appeal proceedings.

Moreover, the respondents denied a priori that in the absence of any mention of an effect with respect to the teaching of document D1 in the application as filed the appellant could rely for the reformulation of the technical problem on any alleged effect over the teaching of document D1, irrespective of the status of the post-published documents as evidence for such an effect (see section IX(h) above). In contrast, the referred questions address the status of post-published documents as evidence of an effect relied upon to support an inventive step.

Taking account of the interest of procedural economy as well as the interest of legal certainty the Board has therefore rejected the respondents' request for a suspension of the proceedings pending G 2/21.