Posted: December 11th, 2017
LEO Pharma v. Sandoz, Court of Appeal The Hague, 7 November 2017, 200.195.459/01, with thanks to Daan de Lange and Rien Broekstra, Brinkhof, for providing the decision as well as an English translation thereof
LEO Pharma A/S (‘LEO Pharma’) is holder of EP 2 455 083 (EP 083), which claims a ‘pharmaceutical composition for dermal use comprising calcipotriol and betamethasone for treating psoriasis’. In first instance, the District Court in The Hague had rejected an injunction claimed by LEO Pharma against Sandoz B.V. (‘Sandoz’), as it concluded that there was a serious chance that the patent would be considered invalid for lack of inventive step in final relief proceedings.
In EPO opposition proceedings, the OD had decided on 6 October 2016 to uphold the patent in unamended form. Nevertheless, on 7 November 2017, the Court of Appeal rejected the appeal lodged by LEO Pharma, holding that there was a serious chance that the TBA would nevertheless revoke the patent.
Applying the problem-solution-approach, the Court of Appeal identified two differences between the closest prior art (Ortonne) and the claimed subject matter. First, the active substances calcipotriol and betamethasone (dipropionate) are administered as a combination product instead of alternatingly as disclosed in Ortonne, i.e. an ointment with only one active substance in the morning and another ointment with exclusively the other active substance in the evening. Secondly, this combination product is non-aqueous.
The Court of Appeal defined the objective technical problem as the improvement of patient compliance whilst preserving stability in the short term. The person skilled in the art was defined as a team consisting of a dermatologist and a formulation expert. This skilled person faced with the objective problem, departing from the alternating regimen disclosed in Ortonne, would, according to the Court of Appeal, arrive at the matter claimed taking into account the common general knowledge that a combination product increases patient compliance.
The Court of Appeal dismissed LEO Pharma’s argument that, there were reservations to combine calcipotriol and betamethasone (dipropionate) into one medicinal product, due to the fact that this combination would cause stability problem in the long term. Also, LEO Pharma argued that the formulation of a combination product is complex because both active substances must be soluble in the excipients such that the active substance is released in a sufficient manner to the skin. However, neither of these problems were solved by EP 083, so they may not be taken into account when assessing inventive step, according to the Court of Appeal.
LEO Pharma had, additionally, asserted that the combination therapy caused a synergetic effect of an improved treatment of psoriasis. According to Sandoz, however, this synergetic effect was not made plausible in the patent and therefore such effect was not taken into account in the assessment of inventive step.
The Court of Appeal addressed how the plausibility requirement is to be applied. Referring to TBA’s decision in Agrevo, the Court held that the required degree of plausibility of the effect cannot be indicated in general terms. On the one hand it is of importance that it cannot be expected from the inventor that he already furnishes full evidence of an effect on the application date. For this reason, it is referred to as a low threshold. On the other hand, the threshold must be sufficiently high to prevent that inventive step is assessed on the basis of an invention that was only made or disclosed after the application date, e.g. when the patent’s inventive step is derived from assertions about effects that the average skilled person would have found speculative on the application date.
The Court of Appeal furthermore held that the burden of proving (and in preliminary relief proceedings to preliminary demonstrate) that the synergetic effect was not plausible, was on Sandoz. The Court of Appeal ruled that Sandoz had demonstrated that the synergetic effect of the improved treatment of psoriasis had not been made plausible in the patent specification nor was it plausible based on the common general knowledge, and therefore the Court found that EP 083 lacked inventive step.