T 1791/11 - Mutations and plausible effect

Key points

• The Board confirms as established case law that " simply proposing a series of possible mutations [for an enzyme] without showing an effect is not considered to involve any inventive contribution over the prior art wherein a number of other mutations has already been proposed"  (citing T 537/02).

T 1791/11 - link

3.2 Inventive step

3.2.1 The present patent discloses "novel subtilase variants exhibiting alterations relative to the parent subtilase in one or more properties including: Wash performance, thermal stability, storage stability or catalytic activity" (application as filed: page 1, first paragraph; page 16, fourth paragraph). Specific variants of BPN' (BASBPN) and of Savinase (BLSAVI) are set out on page 23 of the application as filed as being "considered interesting". The paragraph immediately following this list of variants then states that "The wash performance of a selected variant of the invention may be tested in the "Model Detergent Wash Performance Test" disclosed in Example 3 herein". No results concerning wash performance (or any other properties) are however provided for any of the listed variants, nor is it apparent why these variants have been selected as "interesting". 

The only information concerning the activity of these variants in the application as filed is found on page 56, first paragraph, where it is stated that "All these variants exhibited proteolytic activity as indicated above" (apparently referring to page 50, where the proteolytic activity is further defined). It can thus be concluded that the patent aims at providing subtilase variants with improved properties, in particular with improved wash performance, and that it discloses a number of selected "interesting" variants which are however still to be tested for their performance. It is not apparent from the patent which of the selected variants - if any - do indeed display improved wash performance as compared to the parent subtilase. In fact, while it may be expected that some of the many variants disclosed by the patent may display improved wash performance, it is not rendered plausible by the patent that this property is present in any one of the specific variants.

3.2.2 The closest prior art is document D1. Like the patent, it discloses subtilisin variants "having a different proteolytic activity, stability, substrate specificity, pH profile and/or performance characteristic as compared to the precursor carbonyl hydrolase from which the amino acid sequence of the variant is derived" (page 23, first paragraph). In particular, D1 discloses protease variants derived from a Bacillus subtilisin, "more preferably" derived from Bacillus lentus subtilisin and/ or subtilisin 309 (D1, page 23, lines 15 to 17). Subtilisin 309 is BLSAVI, as apparent from the patent application (page 4, sixth full paragraph). Example 1 of D1 (starting on page 38), discloses the production of such variants (displayed in Table 3), a large number of which are then tested for their wash performance in Example 2 (starting on page 60). Among the variants tested are also variants that have the substitution V68A and show improved wash performance over wild type Savinase/BLSAVI (further discussed below).

3.2.3 The difference to claim 1 of the main request is that the specific variants claimed, i.e. the variants V68A+S106A and V68A+V139I, are not disclosed. There is however no data in the patent application or elsewhere on file which allows the performance of the claimed variants to be compared with that of the variants of D1. Accordingly, the technical problem in view of D1 has to be formulated as the provision of further variants of BLSAVI. Such problem can be considered plausibly solved by the claimed subject-matter, since the patent discloses that the claimed variants have proteolytic activity (as discussed above, section 3.2.1).

3.2.4 However, the mere provision of further subtilase variants, of which the claimed variants are just two among many possible alternative solutions, would be obvious for the skilled person, because "simply proposing a series of possible mutations without showing an effect is not considered to involve any inventive contribution over the prior art wherein a number of other mutations has already been proposed" (decision T 537/02 of 19 October 2004, Reasons 22). Claim 1 of the main request is thus considered to lack an inventive step.

For the sake of completeness, it is furthermore noted that D1 already discloses the substitution V68A as being one among a number of possible mutations that leads to variants with improved properties, and variants comprising this mutation were shown in D1 to have an improved wash performance: [] It would thus not come as a surprise that mutants comprising this particular mutation (independently of the presence of other mutations) eventually showed better wash performance than the parent Savinase/BLSAVI.

3.2.5 The appellant-patent proprietor formulated the technical problem differently, namely as the provision of further variants with improved wash performance in relation to the parent BLSAVI, and argued that the patent application made plausible that the claimed variants indeed solved such a problem. D10 should be taken into consideration as post-published data confirming what the patent application had already rendered plausible. The solution would furthermore be inventive because there was no pointer in D1 to the claimed mutations and no disclosure at all in the prior art of the claimed mutation combinations.

3.2.6 The board cannot agree with the arguments of the appellant-proprietor. As discussed above, the patent does not provide any experimental data concerning the claimed variants (or any of the many listed variants) and thus no functional characterisation of the variants by an alleged advantage should be taken into account when formulating the technical problem. Otherwise, if the technical problem was formulated to include any such advantage, then it would, in the absence of any experimental data in the patent application, not be possible to conclude that such problem had been plausibly solved: this would thus require reformulating the technical problem in a less ambitious manner, resulting in the problem as formulated by the board.

3.2.7 The post-published experimental data of D10, which indeed shows that the claimed variants have better wash performance than the parent BLSAVI (Table 2), could only be taken into account if it just served to confirm what had been rendered plausible by the patent application.

In fact, according to established case law, "the definition of an invention as being a contribution to the art, i.e. as solving a technical problem and not merely putting forward one, requires that it is at least made plausible by the disclosure in the application that its teaching solves indeed the problem it purports to solve. Therefore, even if supplementary post-published evidence may in the proper circumstances also be taken into consideration, it may not serve as the sole basis to establish that the application solves indeed the problem it purports to solve" (T 1329/04 of 28 June 2005, Catchword).

As discussed above (section 3.2.1), it is apparent from the patent application itself that it was not yet known which variants solved the problem and that a test still had to be performed to confirm the alleged advantage. The board thus comes to the conclusion that the patent does not render it plausible that the claimed subject-matter solves the technical problem as formulated by the appellant-proprietor, and the experimental post-published evidence of D10 is in fact the sole basis allowing to conclude that said problem has been plausibly solved.

4. Auxiliary request 1 - Inventive step

4.1 Claim 1 of auxiliary request 1 is identical to claim 1 of the main request and thus, for the same reasons as given above, also fails to meet the requirements of Article 56 EPC.

5. Auxiliary request 2 - Inventive step

5.1 Claim 1 of this request differs from claim 1 of the main request solely in the addition of an optional feature. Since the optional feature does not restrict the claimed subject-matter, auxiliary request 2 is also considered to lack an inventive step, for the same reasons as for the main request.

6. Auxiliary request 3 - Inventive step

6.1 The board fails to see any difference in the subject-matter covered by claim 1 of this request and claim 1 of auxiliary request 2, and the appellant-proprietor also agreed that in fact they covered the same subject-matter. As such, auxiliary request 3 also contravenes the requirements of Article 56 EPC for the reasons given for the main request.

7. Auxiliary requests 4 and 5 - Inventive step

7.1 Claim 1 of these requests differs from claim 1 of the main request in that the variants are further defined by a functional feature, namely that they have "improved wash performance compared to BLSAVI". The board notes that, since the claim is a product claim covering two specific variants, such functional features are in fact redundant as they refer to intrinsic properties of the product, which the product either possesses or not. The subject-matter claimed, namely the claimed variants, is still the same whether the intrinsic property is recited in the claim or not. As such, claim 1 of auxiliary requests 4 and 5 does not fulfil Article 56 EPC for the same reasons as for the main request.

8. Auxiliary requests 6 and 7 - Inventive step

8.1 Claim 1 of auxiliary request 6 only differs from claim 1 of auxiliary requests 4 and 5 in the addition of an optional feature, which does not further limit the claimed subject-matter. As such, the same considerations as for auxiliary requests 4 and 5 also apply to this request. Claim 1 of auxiliary request 7, on its turn, only differs from claim 1 of auxiliary request 6 in the use of the same language as in auxiliary request 2. As discussed above in relation to auxiliary request 2, the subject-matter covered by claim 1 of auxiliary request 7 is considered to be the same as that covered by claim 1 of auxiliary request 6.

8.2 Hence, auxiliary requests 6 and 7 also fail to meet the requirements of Article 56 EPC.

Order

For these reasons it is decided that:

1. The decision under appeal is set aside.

2. The patent is revoked.