The patent relates to a “Tablet formulation of N-[2,4-bis(1,1-dimethylethyl)-5-hydroxyphenyl]-1,4-dihydro-4-oxoquinoline-3-carboxamide for use in the treatment of cystic fibrosis”.
Brief outline of the case
The OD decided maintenance according to AR 16 as the claims as granted and AR 1-15 where lacking sufficiency.
The opponent appealed the decision of the OD.
The appeal was dismissed.
The OD’s position
The late filed ground of opposition under Art 100(b) EPC and document D15 filed in support of this ground were admitted in view of their prima facie relevance with respect to the claims as granted.
The MR did not meet the requirement of sufficient disclosure having regard to the information in document D15, which indicated that ivacaftor was not effective in treatment of homozygous DeltaF508 patients.
The objection of lack of sufficient disclosure against claim 1 of the MR also applied with respect to AR 1-15.
AR 16 incorporated in claim 1 the feature of claim 5 as granted that the other desired therapeutic agent is a CFTR modulator other than ivacaftor.
The opponent’s position
The patent merely presented the statement that ivacaftor acts as CFTR potentiator together with a list of intended further CFTR modulators, but failed to provide any experimental data supporting the therapeutic efficacy of ivacaftor or any other CFTR modulator in homozygous DeltaF508 patients.
According to the established jurisprudence, exemplified by T 609/02 and T 2059/13, the patent did not sufficiently disclose the suitability of the claimed composition for the defined therapeutic with such mere verbal statements.
The post-published document D15 reported the lack of clinical benefit from treatment of homozygous DeltaF508 patients with the CFTR potentiator ivacaftor alone.
These serious doubts could not be overcome by reference to the post-published evidence in document D20 regarding the efficacy of combinations of the CFTR potentiator ivacaftor with certain specific CFTR correctors, because sufficiency of disclosure was to be assessed on the basis of the content of the patent and the common knowledge.
The patent further failed to provide any information on relevant drug-drug interactions, which in line with the considerations in T 391/18 gave rise to the undue burden of identifying the other CFTR modulators which are compatible with administration of ivacaftor.
The proprietor’s position
Post-published experimental evidence indicated optimized dissolution from tablets prepared with lactose and microcrystalline cellulose in a 1:1 weight ratio and with 3% sodium croscarmellose.
The defined amounts of the solid dispersion comprising the high loading of 80 wt% ivacaftor together with the defined amounts of the further excipients was thus associated with advantageous properties of the tablets, which was not obvious in view of the prior art.
Sufficiency of disclosure
The patent credibly disclosed the suitability of the defined composition for the described therapeutic indication by explaining that
– the DeltaF508 mutation leads in patients with cystic fibrosis to impaired trafficking to the membrane and defective channel gating of the mutant CFTR,
– ivacaftor was known to potentiate the activity of CFTR with a DeltaF508 mutation and
– ivacaftor can be effectively combined with other CFTR modulators, such as lumacaftor.
The patent could rely on the known activity of ivacaftor as a potentiator of the mutant CFTR, even if the knowledge of this activity was not demonstrated to be part of the common general knowledge.
The board’s decision
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 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 MR = as maintained may therefore in accordance with the principles established in G 2/21 be taken into account for the assessment of inventive step.
The objective technical problem may be seen in the provision of a tablet formulation comprising a solid dispersion of amorphous ivacaftor which exhibits optimized dissolution.
For the board, the subject-matter of claim 1 of the MR = as maintained was not obvious as solution to the identified objective technical problem.
Sufficiency of disclosure
In case a patent defines a new therapeutical utility of a composition in a claim in the format of Art 54(5) it is according to the established jurisprudence for compliance with Art 83 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.
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. 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. The patent further teaches that ivacaftor can be effectively combined with other CFTR modulators and lists examples of such agents.
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.
In accordance with the jurisprudence exemplified by T 609/02 (see section 9), the suitability of the claimed composition for the defined therapeutic 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.
In G 2/21, the EBA restricted its decision to the assessment of IS.
It turns out in the present decision that G 2/21 is also applied when it comes to sufficiency.
This does not come as a surprise as it goes back to G 1/03 and T 2001/12, see the catchword.
It was held that, when a technical effect is not claimed, but cannot be achieved, the objection is lack of IS.
When a technical effect is claimed but cannot be achieved, the objection is lack of sufficiency.
In a claim according to Art 54(5), for a second or further medical use, the medical use is a functional feature of the claim which cannot be ignored when it comes to sufficiency or IS.
It is interesting to also note that, following G 2/21, “plausible” as been replaced by “credible“.