The patent proprietor and opponents 1-8 and 11-14 filed appeals against an interlocutory decision of the opposition division deciding that European patent 2 962 690 ("the patent") as amended in accordance with auxiliary request 3 met the requirements of the EPC.
Claim 1 is formulated in the "compound for use" format of Articles 54(4) and 54(5) EPC, wherein the utility as a medicament is further specified as the use as a medicament which is administered orally.
The Guidelines for Examination G-VI 6.1.2 suggest that in a claim which only defines the mode of delivery but no specific therapeutic effect, the definition of the mode of delivery is merely illustrative and not a restrictive technical feature capable of establishing novelty.
However, the requirement underlying the specificity of the use within the meaning of Article 54(5) of the EPC 2000 is according to the explicit conclusion in G 2/08 to be construed merely by contrast to the generic broad protection conferred by the first claimed medical application of a substance or composition, and is in principle not confined to a particular medical indication.
In line with the considerations in G 2/08 the Board therefore considers that the oral administration as defined in claim 1 represents, in accordance with Article 54(5) EPC, a characterizing feature of the claimed subject-matter.
The difference of the claimed subject-matter with respect to the teaching in document D1 concerns the feature of the oral administration of the claimed compound, i.e. apremilast comprising greater than 80% by weight of the (+) enantiomer and less than 20% by weight of the (-) enantiomer.
Based on experimental results presented in the patent, the Board concludes that the subject-matter of claim 1 is associated with the potent inhibition of PDE4 with outstanding selectivity over PDE3, an outstanding therapeutic effect following oral administration and favourable aqueous solubility, at least with respect to the racemate.
The opponents maintained that the objective technical problem could only be formulated on the basis of effects arising from the difference with the prior art and thus not on the basis of properties inherent in the starting point in the prior art. The experimental results reported in the patent did in their view not concern effects that could be attributed to the difference with the prior art, namely the oral administration, but were inherent properties of stereomerically pure apremilast as an active anti-inflammatory agent, which represented the starting point in the prior art.
However, as explained in T 970/00, any conclusion going beyond what the skilled person would have objectively inferred from the prior art, without the benefit of hindsight knowledge of the invention, is of necessity at variance with a proper application of the problem-solution approach. The relevant properties of apremilast which had remained unrecognized in the prior art resulted in meaningful technical effects following the oral administration of apremilast as defined in claim 1. The Board therefore considers that these effects are associated with the differentiating feature of claim 1 and cannot be ignored for the formulation of the objective technical problem.
The Board formulates the objective technical problem as the provision of an administration route for stereomerically pure apremilast which allows for the safe and well-tolerated effective treatment for PDE4-mediated diseases.
It was not in dispute that the oral administration of PDE4 inhibitors represented challenges associated with the potential cardiovascular side effects following systemic delivery due to a lack of selectivity for PDE4 and concomitant PDE3 inhibition and the propensity of PDE4 inhibitors to induce emesis.
The Board considers that the reported challenges regarding the oral administration of PDE4 inhibitors reflect the skilled person's compelling motivation to seek the oral administration of PDE4 inhibitors, which represents typically his first choice for systemic delivery of a pharmaceutically active agents because of the ease of administration.
The skilled person may not have predicted the actual level of the PDE4 selectivity, the level of the therapeutic index versus emesis and the level of the solubility of stereomerically pure apremilast as indicated by the experimental results reported in the patent.
According to the established jurisprudence, an effect which may be said to be unexpected can be regarded as an indication of an inventive step, but certain preconditions have to be met. If, having regard to the state of the art, it would already have been obvious for a skilled person to arrive at the subject-matter defined in a claim, because an advantageous effect could be expected to result from the prior art documents, such a claim may lack an inventive step, irrespective of the circumstance that an extra effect (possibly unforeseen) was obtained. As pointed out in T 1356/21 this jurisprudence, which typically concerns cases involving a so-called "one-way-street" situation in which practical alternative solutions are absent, may not apply to any situation of a plurality of technical effects without regard to their respective technical and practical importance.
Taking account of this jurisprudence the Board considers that in the present case the reasonable expectation that orally administered apremilast allows for safe and well-tolerated effective treatment prevails over any unforeseen level of the PDE4 selectivity, the therapeutic index versus emesis or the solubility of stereomerically pure apremilast as reported in the patent having regard to the compelling motivation to administer PDE4 inhibitors by the oral route.
Accordingly, the Board concludes that the subject-matter does not involve an inventive step.
The patent is revoked.