This is another decision in the long-running series of patent cases regarding the anti-cancer drug pemetrexed (Alimta®). By interim decision issued on 12 September 2017 in the case Fresenius Kabi Oncology Plc and other v Eli Lilly and Company and other, the Court of Milan ruled in stark contrast with the judgment of United Kingdom Supreme Court handed down on 12 July 2017 , declaring that Fresenius Kabi's generic product – based on pemetrexed diacid in combination with tromethamine – does not infringe the Italian designation of Eli Lilly's European patent EP 1 313 508.

Background

Eli Lilly is proprietor of the patent EP 1 313 508 ("EP '508") claiming the use of pemetrexed disodium in combination with vitamin B12 and optionally a folic binding protein agent for inhibiting tumour growth.

Fresenius initiated proceedings in the Court of Milan seeking a declaration of non-infringement of the Italian designation of Eli Lilly's patent for its product containing pemetrexed diacid in combination with tromethamine to be reconstituted in glucose.

Eli Lilly counterclaimed seeking a preliminary injunction. In particular Eli Lilly argued that the Italian Court had to apply the judgment of United Kingdom Supreme Court ("UKSC") of 12 July 2017, which declared that Actavis' generic product – based on pemetrexed diacid – came within the scope of the Italian designation of Eli Lilly's patent under the "doctrine of equivalents".

In contrast to the UKSC, the Italian Court held that Fresenius' generic product does not directly or indirectly infringe the patent and dismissed the preliminary injunction claim of Eli Lilly.

It appears that an appeal was filed by Eli Lilly against this precautionary decision.

Reasoning of the decision

Effects of the UKSC judgment in Italy

First, the Court of Milan acknowledged that the UKSC judgment was issued against a party – Actavis – who is not part of the Italian proceedings and who has no contractual relationship with Fresenius. As a consequence the Judge held that the UKSC judgment, even if it has effect in Italy because it ruled on the Italian designation of EP '508, is not binding in proceedings involving Fresenius.

Moreover, according to the Judge, the case decided by the UKSC relates to different products to those of Fresenius (for example different excipients and dosage ratios are used)which are used for different indications.

Direct infringement

In order to assess whether or not there was infringement, the Judge first identified the scope of protection of Eli Lilly's patent.

The Court stated that EP '508 is limited to pemetrexed disodium because of the wording of claims 1 and 12 and the entire specification of the patent.

Furthermore the Judge – in line with the previous case law of the Court of Milan - stressed the relevance of the prosecution history to construe the scope of protection of a patent, pointing out that during prosecution Eli Lilly had voluntarily limited EP '508 to pemetrexed disodium. In fact Eli Lilly had amended the claims of the patent from “antifolate” to "pemetrexed" and finally to “pemetrexed disodium” in order to overcome objections made by the EPO Examiner.

Accordingly, the Court held that it would be illogical, as well as contrary to the legitimate expectations of third parties and good faith, for Eli Lilly to be able to claim a scope of protection through infringement by equivalence which would have led to the patent being declared invalid if the same scope had been pursued in the EPO (i.e. in the absence of the voluntary limitation proposed before the EPO) -.

In particular the Judge stressed that "The proprietor of the patent is therefore bound to the limitations, regardless of the subjective reasons that led him to carry out them, since he cannot, in violation of the principles of consistency and good faith, then claim, by means of equivalence, a broader scope of protection, contrary to the said limitation. Such conduct, which would constitute an abuse by the patent proprietor, would undermine the legitimate expectations of third parties, whose interests must always be balanced with the monopolistic interest of the patent proprietor".

In light of the above the Court of Milan concluded that "the interpretation of the claim, the description, the entire patent text, the examination of the amendments made during the patent grant procedure, univocally, and even autonomously, give evidence in favor of the clear limitation of patent protection to pemetrexed disodium, excluding that it may also be extended to other compounds, such as the pemetrexed diacid contained in the [Fresenius]'s product".

As a consequence, the Judge declared that Fresenius' product containing pemetrexed diacid/ ditromethamine does not constitute either a literal infringement or infringement by equivalence of Eli Lilly's patent.

Moreover, the Judge acknowledged that that the Court Expert appointed in the proceedings stated in her report that it was not obvious for the skilled person to use pemetrexed diacid in combination with tromethamine instead of pemetrexed disodium. According to the Judge, this circumstance - even if it is not a crucial point - strengthens the finding of non-infringement.

Indirect infringement

Eli Lilly argued that the commercialization of Fresenius' product also amounts to indirect infringement since:

  • Fresenius would provide the means relating to an essential element for the invention and necessary for its implementation, i.e. pemetrexed anions, obtained by dissolution in the glucose solution; and, in any event,
  • the leaflet and summary product characteristics of Fresenius' product providing the dilution in glucose (instead of saline provided by Eli Lilly's product Alimta®) would not be followed by the healthcare professionals who would have used saline for Fresenius' product in the same way as they did for Alimta®.

The Judge rejected Eli Lilly's arguments highlighting that:

  • Fresenius does not supply an "essential element" of the invention because this element can not be held to be the pemetrexed anion, but instead is pemetrexed disodium;
  • Fresenius' product has to be reconstituted in glucose as provided by the leaflet and summary product characteristics and it cannot be expected that healthcare professionals would depart from the leaflet by using saline.