Pemetrexed - Netherlands

On May 08, 2018, Court of Appeal The Hague handed down its decision in ALIMTA case & denied appeal filed by Fresenius & Teva against lower court’s decision of infringement.

Lilly markets the Alimta® for the treatment of certain lung cancers (tumor growth). The active ingredient in Alimta® (after solution) consists of pemetrexed anions. In Alimta® the anions are bound to sodium ions and thus the pemetrexed disodium salt is formed. Lilly is holder of the European patent EP (NL) 1 313 508 for a 'Combination containing an antifolate and methylmalonic acid lowering agent'.

Fresenius and Teva both appealed an interlocutory judgment of 24 October 2017 (the first instance judgments). In the first instance, Lilly has demanded that the relief judge prohibit Fresenius & Teva from infringing the Dutch part of EP 508. Lilly has argued for that “pemetrexed tromethamine” product of both appellants’ falls within the scope of protection of EP 508. The preliminary relief judge awarded the infringement prohibition. Both Fresenius & Teva appealed.

The question that kept the parties divided is whether pemetrexed tromethamine falls within the scope of protection of EP 508. Court said that the person skilled in the art knows that only the anion is responsible for the efficacy (and toxicity) of pemetrexed. He furthermore finds confirmation for the insight that the invention relates more to the active form of pemetrexed after its administration and not to the specific disodium salt form disclosed therein in EP’508. In the opinion of the court, the average person skilled in the art would recognize that the disodium salt form was not mentioned in the description for the technical advantage associated with that salt form or a salt test (for which the description does not contain any indication), but rather because the disodium salt form was available. Precisely because, on the basis of his general professional knowledge, the average person skilled in the art knew that the acid form and other salt forms of pemetrexed were also possible. He understood that the explicit mention of disodium was motivated by the fact that this form already existed and had been used in research into the invention and therefore should rather be seen as illustration. It was clear to him that also for other forms of pemetrexed they were within the inventive concept of EP 508, while the description did not give rise to the assumption that there was a technical reason for the patent holder to limit himself to the disodium salt form.

In the Court's opinion, the description does not give the average person skilled in the art any reason to suppose that there is a technical reason why Lilly intended to limit the scope of protection of  EP 508 to the disodium salt form of pemetrexed. The experts of appellants have also failed to clarify this. The court agreed with Lilly that the pemetrexed diacid with tromethamine in the appellant’s product should be regarded as a technical equivalent to pemetrexed disodium. The cations differ, but do not play a role in the function, mechanism of action and outcome of both drugs. In both cases there is dissociation in aqueous solution, whereby the same active pemetrexed anion becomes available, which performs the same function, namely to work as an antifolate in the body, with the same result: the prevention of tumor growth and toxicity.

Thus, the appeal was dismissed & infringement affirmed.