T 0728/21 - Obscure prior art for sufficiency ?

Key points

• Claim 1 of the patent is directed to a tablet comprising a specific concentration of ivacaftor as the active compound and with certain excipients "for use in combination with one or more other desired therapeutics in treatment of cystic fibrosis in a patient with a DeltaF508 mutation on both alleles".
• It is not entirely clear to me if the tablet composition as such is novel.
• The proprietor filed experimental results in the appeal procedure demonstrating that the specific combination of excipients provided for better dissolution properties.
• "According to G 2/21, a technical effect may be relied upon for inventive step if the skilled person, having the common general knowledge in mind, and based on the application as originally filed, would derive said effect as being encompassed by the technical teaching and embodied by the same originally disclosed invention. The application as originally filed (WO 2011/019413) explicitly addressed the dissolution of tablets comprising a solid dispersion as an aspect of the disclosed invention (see paragraph [0031]) and specifically described the claimed tablet composition as an embodiment of the disclosed invention. The effect of the optimization of the dissolution associated with the specific tablet composition defined in claim 1 of the main request may therefore in accordance with the principles established in G 2/21 be taken into account for the assessment of inventive step. "
• The Board considers claim 1 to be inventive based on the improved dissolution properties.
• The claim, however, also specifies the use of ivacaftor, in combination with a further therapeutic compound, "in treatment of cystic fibrosis in a patient with a DeltaF508 mutation on both alleles". As I understand it, the patent application contained no experimental/clinical results showing this.
• The Board recalls the requirement of G 2/21 r.74 for sufficiency of second medical use claims.
• The Board: "The patent specifically explains that the DeltaF508 mutation leads in patients with cystic fibrosis to impaired trafficking to the membrane and defective channel gating of the mutant CFTR (see paragraphs [0007]-[0008]). The patent also points out that ivacaftor is a potent and selective CFTR potentiator of wild-type and mutant forms of human CFTR, including DeltaF508 (see paragraph [0012]). The patent further teaches that ivacaftor can be effectively combined with other CFTR modulators and lists examples of such agents (see paragraph [0248]). The patent does thereby not describe the activity of ivacaftor as a CFTR potentiator in the form of a simple verbal statement, which might in line with the considerations in T 609/02(see section 9) be considered not to be sufficient, but rather as specific and verifiable technical information supporting the defined therapeutic indication. This information in the patent provides according to the Board a rational basis for the claimed invention, which rendered the utility of the claimed composition in the treatment of homozygous DeltaF508 patients credible at the date of its filing."
• The Board also refers to a prior art document D16A, that provides experimental results of the compound regarding the "activity in cultures of DeltaF508/DeltaF508 human bronchial epithelia". D16A is, however, a poster session abstract. Such documents are usually not evidence of common general knowledge.
• The Board: "In accordance with the jurisprudence exemplified by T 609/02 (see section 9), the suitability of the claimed composition for the defined use needs to be disclosed in the patent, "unless this is already known". This jurisprudence confirms in the Boards view that the disclosed utility of the claimed composition may also derive its credibility from the prior art, even if this prior art does not represent common general knowledge."
• To quote T 609/02 in relevant part: "Where a therapeutic application is claimed [...] in [a second medical use claim], attaining the claimed therapeutic effect is a functional technical feature of the claim []. As a consequence, under Article 83 EPC, unless this is already known to the skilled person at the priority date, the application must disclose the suitability of the product to be manufactured for the claimed therapeutic application. It is a well-known fact that proving the suitability of a given compound as an active ingredient in a pharmaceutical composition might require years and very high developmental costs which will only be borne by the industry if it has some form of protective rights. Nonetheless, variously formulated claims to pharmaceutical products have been granted under the EPC, all through the years. The patent system takes account of the intrinsic difficulties for a compound to be officially certified as a drug by not requiring absolute proof that the compound is approved as a drug before it may be claimed as such."
• As a comment, in the case of T 609/02, the alleged effect was clearly not "known" to the skilled person in any sense on the priority date, so I don't think that T 609/02 intentionally departed from the general principle that sufficiency of disclosure must be based on the application as filed and common general knowledge of the skilled person only. 
• See e.g. G 2/21 r.76 : "T 1599/06, points 6, 7.1, 7.2 and 8 of the Reasons [...]:"[...] if a therapeutic application is to be accepted as sufficiently disclosed, the application or the patent, respectively, and/or the common general knowledge has to provide some information rendering it technically plausible for the skilled person that the claimed compounds can be applied for the claimed therapeutic use (T 219/01 of 15 December 2004; T 609/02 of 27 October 2004)[...]" (emphasis added)
• As a further comment, does the rule proposed in the present decision apply equally to the 'enablement requirement' for prior art to be novelty-destroying? I.e., would the text of the present application have been novelty-destroying for the second medical claim if published a day before?
• As a further comment, G 2/21 does not indicate that the enablement requirement for the medical indication of a second medical use claim can be lower if novelty and inventive step can be based on other features of the claim. 
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T609/02

Where a therapeutic application is claimed in the form allowed by the Enlarged Board of Appeal in its decision G 5/83 (OJ EPO 1985, 64), ie in the form of the use of a substance or composition for the manufacture of a medicament for a defined therapeutic application, attaining the claimed therapeutic effect is a functional technical feature of the claim (see G 2/88 and G 6/88, OJ EPO 1993, 93 and 114, Headnote III. and point 9 of the reasons, for non-medical applications, see also T 158/96 of 28 October 1998, point 3.1 of the reasons). As a consequence, under Article 83 EPC, unless this is already known to the skilled person at the priority date, the application must disclose the suitability of the product to be manufactured for the claimed therapeutic application. It is a well-known fact that proving the suitability of a given compound as an active ingredient in a pharmaceutical composition might require years and very high developmental costs which will only be borne by the industry if it has some form of protective rights. Nonetheless, variously formulated claims to pharmaceutical products have been granted under the EPC, all through the years. The patent system takes account of the intrinsic difficulties for a compound to be officially certified as a drug by not requiring an absolute proof that the compound is approved as a drug before it may be claimed as such. The boards of appeal have accepted that for a sufficient disclosure of a therapeutic application, it is not always necessary that results of applying the claimed composition in clinical trials, or at least to animals are reported. Yet, this does not mean that a simple verbal statement in a patent specification that compound X may be used to treat disease Y is enough to ensure sufficiency of disclosure in relation to a claim to a pharmaceutical. It is required that the patent provides some information in the form of, for example, experimental tests, to the avail that the claimed compound has a direct effect on a metabolic mechanism specifically involved in the disease, this mechanism being either known from the prior art or demonstrated in the patent per se. Showing a pharmaceutical effect in vitro may be sufficient if for the skilled person this observed effect directly and unambiguously reflects such a therapeutic application (T 241/95, OJ EPO 2001, 103, point 4.1.2 of the reasons, see also T 158/96 of 28 October 1998, point 3.5.2 of the reasons) or, as decision T 158/96 also put it, if there is a "clear and accepted established relationship" between the shown physiological activities and the disease (loc. cit.). Once this evidence is available from the patent application, then post-published (so-called) expert evidence (if any) may be taken into account, but only to back-up the findings in the patent application in relation to the use of the ingredient as a pharmaceutical, and not to establish sufficiency of disclosure on their own.

EPO 

The link to the decision is provided after the jump, as well as (an extract of) the decision text.

https://www.epo.org/en/boards-of-appeal/decisions/t210728eu1

3. Sufficiency

3.1 Article 83 EPC requires that the application discloses the invention in a manner sufficiently clear and complete for it to be carried out by a person skilled in the art.

In case a patent defines a new therapeutical utility of a composition in a claim in the format of Article 54(5) EPC it is according to the established jurisprudence for compliance with Article 83 EPC necessary, in order to ensure that a patent is only granted if there is a corresponding contribution to the prior art, that the patent at the date of its filing renders it credible that the claimed composition is indeed suitable for the defined therapeutic use (see G 2/21, section 74). A deficient disclosure cannot be remedied by post-published evidence (see G 2/21, section 77; compare G 1/03, sections 2.5.2-2.5.3).

3.2 The patent specifically explains that the DeltaF508 mutation leads in patients with cystic fibrosis to impaired trafficking to the membrane and defective channel gating of the mutant CFTR (see paragraphs [0007]-[0008]). The patent also points out that ivacaftor is a potent and selective CFTR potentiator of wild-type and mutant forms of human CFTR, including DeltaF508 (see paragraph [0012]). The patent further teaches that ivacaftor can be effectively combined with other CFTR modulators and lists examples of such agents (see paragraph [0248]). The patent does thereby not describe the activity of ivacaftor as a CFTR potentiator in the form of a simple verbal statement, which might in line with the considerations in T 609/02(see section 9) be considered not to be sufficient, but rather as specific and verifiable technical information supporting the defined therapeutic indication.

This information in the patent provides according to the Board a rational basis for the claimed invention, which rendered the utility of the claimed composition in the treatment of homozygous DeltaF508 patients credible at the date of its filing.

3.3 In accordance with the jurisprudence exemplified by T 609/02 (see section 9), the suitability of the claimed composition for the defined use needs to be disclosed in the patent, "unless this is already known". This jurisprudence confirms in the Boards view that the disclosed utility of the claimed composition may also derive its credibility from the prior art, even if this prior art does not represent common general knowledge.

Document D16A describes VX-770 as an orally bioavailable potentiator of CFTR with activity in cultures of DeltaF508/DeltaF508 human bronchial epithelia. The designation VX-770 was known to identify the same compound as the international non-proprietary name ivacaftor (see document D34, paragraph [098]). The information that ivacaftor is a CFTR potentiator of DeltaF508 CFTR was therefore as a matter of fact already part of the prior art. In addition, document D2 already indicated the utility of ivacaftor in treatment of CFTR, including in homozygous DeltaF508 patients (see D2, paragraph [0158]). The Board therefore considers that the prior art confirms the credibility of the disclosed utility of the claimed composition.

3.4 In as far as a patent provides a credible disclosure of the claimed invention a convincing objection of lack of sufficiency of disclosure presupposes according to the established jurisprudence that serious doubts substantiated by verifiable facts have been raised that the skilled person cannot carry out the claimed invention without undue burden on the basis of the teaching in the patent and the common general knowledge (see Case Law of the Boards of Appeal of the EPO, 10th Edition, 2022, sections II.C.7.1.4 and II.C.9).

The appellant argued that the post-published document D15 raises serious doubts regarding the utility of ivacaftor in the treatment of homozygous DeltaF508 patients as defined in claim 1 of the main request, because this document reported a lack of clinical benefit from treatment of homozygous DeltaF508 patients with ivacaftor alone.

However, as pointed out by the respondent, document D15 actually reported that measurable effects from administration of ivacaftor in homozygous DeltaF508 patients had been observed, be it that these effects could not be qualified as a statistically significant clinical benefit (see D15, page 721, under "Efficacy Measures"). According to the Board the mere lack of an observed clinical effect from treatment with ivacaftor alone reported in document D15 (see page 723, under "Conclusions") may well be due to the design of the study reported in document D15. In the Board's view this "lack" of observation does not qualify as verifiable evidence that raises serious doubts regarding the credibly disclosed suitability of the claimed composition comprising ivacaftor for the defined combination treatment of homozygous DeltaF508 patients.

3.5 According to the appellant the patent further failed to provide any information on drug-drug interactions, which in line with the considerations in T 391/18 left the skilled person with the undue burden of identifying the CFTR modulators which are actually compatible for combination with ivacaftor. The Board observes that contrary to the situation in the case decided in T 391/18 (see sections 2.4.2 and 2.5), in the present proceedings no evidence has been submitted which suggests that the treatment involving ivacaftor may not be compatible with the administration of other CFTR modulators. The appellant's objection that the identification of CFTR modulators which are compatible with the administration of ivacaftor required undue burden is therefore considered to lack substantiation.

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