Pharma update: injunction against generic combination of ezetimibe and simvastatin denied

In the interim relief decision of 11 June 2018 (ECLI:NL:RBDHA:2018:6802) in the matter Merck Sharp & Dohme Corp. / Teva Nederland B.V, Pharmachemie B.V. and Centrafarm B.V. the Provisions Judge of the District Court of The Hague rejected the claim of Merck Sharp & Dohme Corp. for an injunction against the distribution of the generic combination product of ezetimibe and simvastatin. The preliminary ruling of the Provisions Judge was that the Supplementary Protection Certificate (‘’SPC’’) of MSD protecting this combination product is invalid.

Azetidinone compounds

Merck Sharp & Dohme Corp (‘’MSD’’) was the owner of EP 0 720 599 (‘’EP 599’’), relating to a specific group of hydroxyl-substituted azetidinone compounds, useful as hypocholesterolemic agents. One of the substances in this group is ezetimibe. Based on EP 599, MSD obtained the SPC no. 300132 for the combination product consisting of ezetimibe and simvastatin (“Combination-SPC”). This Combination-SPC is valid until 1 April 2019. MSD distributes the combination product under the brand ‘’Inegy’’. Previously, MSD had obtained an SPC for ezetimibe as a monoproduct, which SPC expired on 16 April 2018.

MSD summoned Teva, Pharmachemie and Centrafarm in interim relief proceedings, as they had listed their generic combination product of ezetimibe and simvastatin in the “G-standaard” of April 2018 for distribution as from May onwards, thus infringing the Combination-SPC. Teva et al. and Centrafarm argued that there was a non-negligible chance that MSD’s combination-SPC would be held invalid in final relief proceedings, because MSD had already obtained an SPC for the monoproduct ezetimibe.

Grant of an SPC?

Teva et al. and Centrafarm referred to two judgments by the Court of Justice of the European Union (CJEU) with regard to irbesartan (Actavis/Sanofi) and telmisartan (Actavis/Boehringer) and to the application of these judgments by the District Court of The Hague in the administrative appeal proceedings, in which the decision was handed down on 10 April 2018. These appeal proceedings related to a similar case in which the Dutch Patent Office refused to grant an SPC based on EP 599 to MSD for a combination product consisting of ezetimibe and rosuvastatin.

The Court decided that, since an SPC for ezetimibe as a monoproduct had already been granted, the combination of ezetimibe and rosuvastatin would not be eligible for yet another SPC. The Court considered that the SPC-application consisted of a combination of active substances of which ezetimibe was protected by the basic patent as such, and therefore was considered to be a new active substance. After all, ezetimibe belonged to a new group of azetidinone compounds, which had been described as the invention in the basic patent EP 599. Rosuvastatin, on the other hand, was not “as such” protected by the basic patent, as the cholesterol biosynthesis inhibitors, to which group rosuvastatin belongs, are named in the basic patent, but cannot be considered as new active substances. According to the Court ezetimibe could, contrary to rosuvastatin, be identified as the ‘’subject matter’’ of the basic patent. Since an SPC had already been granted for ezetimibe as a monoproduct, it was not possible to grant a new SPC for the combination.

The case against Teva et al. and Centrafarm differed in two ways from the case described in the Court decision of 10 April 2018: it concerned:

  1. a different cholesterol biosynthesis inhibitor (simvastatin), which;
  2. was specifically mentioned in the basic patent EP 599.

Combination-SPC is invalid

Nevertheless, the Provisions Judge found that this could not result in a different outcome regarding the validity of the current Combination-SPC. After all, in the rosuvastatin decision, it had been decided that the cholesterol biosynthesis inhibitors as a group could not be considered new active substances and could therefore not be identified as the subject matter of the invention of the basic patent. This applies to both cases and leads to the preliminary conclusion that the Combination-SPC is invalid. The Provisions Judge furthermore takes into account that in parallel French interim relief proceedings MSD’s claim for an injunction was also denied. The fact that an ex parte injunction in Germany had been granted was deemed of less importance due to the different test applied in Germany.

Attorneys-at-law Marleen van den Horst and Claudia Zeri represented defendants Teva Nederland B.V, Pharmachemie B.V. and Centrafarm B.V. in the proceedings.