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Fresenius Kabi Oncology PLC and Fresenius Kabi Italia S.r.l. (“Fresenius”) sought before the Court of Milan a urgent declaration of non-infringement with respect to their new antitumor drug based on pemetrexed diacid in combination with tromethamine. Fresenius requested the Court to declare that its drug does not infringe – whether directly or indirectly – EP 1313508 (“EP ‘508”) owned by Eli Lilly and Co. (“Lilly”). The patent claims the use of the disodium salt of pemetrexed in the manufacture of a medicament for use in combination with vitamin B12 for the treatment of cancer.

The alleged infringement of the same patent by drugs based on pemetrexed compounds (including pemetrexed diacid in combination with tromethamine) has been the subject matter of some decisions of Courts around Europe, including the recent judgement by the UK Supreme Court in the case Actavis v Eli Lilly & Co which held that Actavis’ products directly infringed by equivalents EP ‘508 and in particular its Italian portion.

The Court of Milan ruled the case in stark contrast with the Supreme Court of Justice decision.

First, the Court noted that the claims of EP ‘508 are limited to pemetrexed disodium only (i.e. ALIMTA), because of the unambiguous wording of the claims combined with the entire text of the patent and in particular with the description, which clearly limits the scope to pemetrexed disodium combined with B12 vitamin and its specified pharmaceutical derivatives.

The Court of Milan also weighed the file history of the patent, deeming that the patentee had voluntarily limited the scope of the application to overcome the EPO examiner’s objections. Indeed, in the original patent application, the claims extended to the entire class of antifolates. Subsequently these claims were limited by the patentee (to overcome the objections of the examiner) to ‘pemetrexed’, and finally to ‘pemetrexed disodium’.

Said changes (along with the consistent amendments to the description) were a “clear delineation of patent protection” to pemetrexed disodium only. Other antifolates and other compounds, including pemetrexed diacid were therefore excluded from the scope of the patent pursuant to such limitations.

Accordingly, the Court held that it would be illogic and contrary to the good faith and legitimate expectations of third parties to widen the scope of protection through the infringement by equivalence when the patentee itself has limited such scope. The Court also recalled several decisions of the Court of Milan and the Court of Turin which excluded infringement on similar basis arguing that it would be illogic to grant protection by equivalents broadening the scope of protection that previously the patentee voluntarily waived to preserve the validity of the patent during the granting procedure or in judicial proceedings.

Moreover, the Court reckoned that while Fresenius’ product has the same therapeutic effect of Eli Lilly’s Alimta, the association of pemetrexed diacid with tromethamine (Fresenius) cannot be considered an obvious substitution of the expression “pemetrexed disodium associated with B12 vitamin” claimed by Lilly’s patent. Thus, the Court of Milan implicitly decided to depart from the new Improver test developed by the UK Supreme Court.

With respect to indirect infringement, the Court of Milan has followed the same arguments previously accepted by the UK High Court of Justice in the Eli Lilly-Actavis’ decision on the reconstitution of pemetrexed diacid in glucose solution: in particular, the Court valued the fact that the SmPC of Fresenius’ product clearly indicated that the reconstitution and dilution shall happen in a glucose solution which means that there is no possibility to form pemetrexed disodium at any stage of the preparation and administration of the drug to the patient. Accordingly, the Court held that medical personnel would never run the risk of liabilities reconstituting and diluting a product in a solution different from that indicated in the SmPC.

This is one of the first implementations of Article 66 paragraph 2 bis of Italian Intellectual Property Code, which was introduced following the Italian ratification of the Agreement on the UPC occurred in November, to codify in the Italian legal framework the indirect infringement.

A copy of the decision can be read here.

Headnote: Luca Giove and Andrea Comelli, Studio Legale Giove