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22 Dec 2017

Eli Lilly and Company and Eli Lilly Danmark A/S (“Lilly”) v. Fresenius Kabi AB v/Fresenius Kabi and Fresenius Kabi Oncology Plc. (“Fresenius Kabi”), the Danish Maritime and Commercial High Court, Case number A-19-17, 8 December 2017

The case concerns the infringement of Lilly’s patent DK/EP 1 313 508 (“DK/EP ‘508”) which relates to the use of the active ingredient pemetrexed in combination therapy with vitamin B12 and optionally folic acid (formulated as a so-called Swiss-type claim).

On 22 July 2016, Fresenius Kabi obtained a marketing authorisation for its medicinal product “Pemetrexed Fresenius Kabi”. The medicinal product is approved as a generic product pursuant to Article 8(3) of EU Directive 2001/83/EC (“the Medicines Directive”) with Lilly’s medicinal product Alimta® as the reference medicinal product.

The medicinal product “Pemetrexed Fresenius Kabi” contains the active ingredient pemetrexed (described by Fresenius Kabi as pemetrexed diacid). Instead of disodium (which is used in Alimta®), “Pemetrexed Fresenius Kabi” contains ditromethamine. The question on whether Fresenius Kabi’s medicinal product would be reconstituted at the hospitals by using sodium chloride solution for injection (as stated in the SmPC for Eli Lilly’s product Alimta®) instead of glucose solution for infusion (as stated in the SmPC for Fresenius Kabi’s product) was not a part of the proceedings.

Fresenius Kabi won the tender for pemetrexed in Denmark which entered into effect on 1 July 2017. Consequently, Lilly filed for a preliminary injunction in June 2017, and on 8 December 2017, the Danish Maritime and Commercial High Court handed down its decision granting a preliminary injunction against Fresenius Kabi’s medicinal product “Pemetrexed Fresenius Kabi” in Denmark.

In essence, Lilly argued that Fresenius Kabi’s medicinal product infringed Lilly’s DK/EP ‘508 patent, principally on the basis of a direct/literal infringement based on a purposive interpretation of the patent claims, in the alternative on the basis of equivalence. In this connection, Lilly argued, inter alia, that the selection of the specific salt is irrelevant to the invention.

Fresenius Kabi argued, inter alia, that “Pemetrexed Fresenius Kabi” did not infringe Lilly’s DK/EP ‘508 patent, as “Pemetrexed Fresenius Kabi” does not contain the disodium salt of Pemetrexed, which is the specific salt mentioned in the claims of the DK/EP ‘508 patent. Fresenius Kabi argued in this connection that Lilly had limited the scope of the patent during the prosecution of the patent application in order to obtain grant of the patent, and therefore Lilly could not claim infringement under the doctrine of equivalence. In this context, it should be noted that Lilly had amended the wording of the patent claims due to an objection under Article 123(2) EPC from “pemetrexed” to “pemetrexed disodium”. The validity of the DK/EP ‘508 was uncontested.

The Danish Maritime and Commercial High Court found that there is no literal infringement of the DK/EP ‘508 patent.

In relation to the question of infringement by equivalence, the Danish Maritime and Commercial High Court found that the decisive questions in this regard are:
(1) whether the essential or significant part of the invention can be found in the alleged infringing product;
(2) whether deviations only are less significant; and
(3) whether the scope of the claims has been limited during the prosecution history against the prior art.

The Danish Maritime and Commercial High Court then went on to assess whether the prosecution file history eliminated a possible infringement by equivalence. The Danish Maritime and Commercial High Court stated that the change from “pemetrexed” to “pemetrexed disodium” was due to the EPO’s formality objection to added matter in accordance with Article 123(2) EPC, and that the objection did not relate to lack of novelty or inventive step.

Therefore, in the Danish Maritime and Commercial High Court’s view the prosecution file history in itself could not prevent infringement by equivalence.

The Danish Maritime and Commercial High Court further found that the invention relates to a novel use of the known active ingredient pemetrexed used in combination with vitamin B12 and optionally folic acid in order to reduce the toxic effect of pemetrexed without adversely affecting therapeutic efficacy. “Pemetrexed Fresenius Kabi” solves the same problem.

Finally, the Danish Maritime and Commercial High Court concluded that Lilly has rendered it probable that it would be obvious for a person skilled in the art that the invention could be carried out by using other pemetrexed salts than the specific salt pemetrexed disodium.

The Danish Maritime and Commercial High Court further concluded that the person skilled in the art, by using its common general knowledge of potential and often used counter ions, would expect to find another counter ion to pemetrexed starting with the most commonly used salt formations, including tromethamine. In this connection, the Danish Maritime and Commercial High Court noted that for its approval of “Pemetrexed Fresenius Kabi” Fresenius Kabi had referred to the data already submitted for Alimta® having regard to the products being therapeutically identical and therefore did not need to submit its own clinical data.

Other proceedings across Europe
There are several infringement proceedings against other generic companies (some are final, some are still pending) across Europe. It is noted with interest that the decision from the Danish Maritime and Commercial High Court granting a preliminary injunction is consistent with the majority of the decisions made throughout Europe, including the UK Supreme Court of Justice’s decision of 12 July 2017; the German Supreme Court’s decision of 19 July 2016 (which set aside Oberlandesgericht Düsseldorf’s approach in relation to direct and indirect infringement); Oberlandesgericht München’s decision of 18 May 2017; the Swiss Supreme Court’s decision of 20 October 2017; as well as the Court of Hague’s decisions of 24 October 2017 in the cases Eli Lilly v Teva and Eli Lilly v. Fresenius Kabi.

A copy of the decision (in Danish) can be read here.
A copy of the Maritime and Commercial High Court’s reasoning (in English) can be read here.

Reported by: Mikkel Vittrup, Peter-Ulrik Plesner and Emilie Lerstrøm, Plesner Advokatpartnerselskab, and Ejvind Christiansen, Zacco, who advised Lilly during the PI proceedings in Denmark