Generic Pemetrexed Diacid infringes patent Pemetrexed Disodium

In two judgments of 24 October 2017, the Provisions Judge of the District Court in The Hague held that Teva’s and Fresenius Kabi’s generic pemetrexed diacid products infringe EP 1 313 508 (‘EP ‘508’) of Eli Lilly. EP ‘508 relates to the use of pemetrexed disodium in combination with vitamin B12 for the treatment of certain types of lung cancer.

Pemetrexed

Eli Lilly markets the medicinal product Alimta® containing the active ingredient pemetrexed. In 2016, Fresenius Kabi and Teva obtained market authorisations for pemetrexed Fresenius and Teva’s Armisarte. After listing its generic product on the “G-standaard” price list in February 2017, Fresenius Kabi introduced its product on the Dutch market. Teva’s Armisarte was listed and launched on the Dutch market in June 2017.

In these interim relief proceedings, initiated by Eli Lilly, the question is whether Fresenius Kabi’s and Teva’s pemetrexed diacid products infringe EP ‘508, which relates to pemetrexed disodium.
The Provisions Judge acknowledges that a literal interpretation of the claims of EP ‘508 would mean that pemetrexed diacid would not fall within the scope of protection of this patent. This literal
interpretation would benefit the legal certainty for third parties. However, the Judge also acknowledges that the skilled person, when reading the patent, understands that the essence of the invention is in the reduction of side effects caused by the permetrexed (anion), due to the addition of vitamin B12.

Infringing EP ‘508

The skilled person knows that when pemetrexed disodium respectively diacid is dissolved, the pemetrexed anion is created in free form, which is the active ingredient that is dispersed in the blood
stream. A reasonable protection for the patentee therefore dictates that the (salt- or acid) form in which the product is put on the market (diacid instead of disodium) should not matter. If pemetrexed diacid would not fall within the scope of protection of EP ‘508, this would make it extremely easy – according to the Judge – to circumvent the patent, while still applying the essence of the invention. Pemetrexed diacid of Teva and Fresenius Kabi therefore infringes EP ‘508.

Specific salt form of less importance

The fact that the safety and efficacy of different salts are unpredictable is not considered relevant, as the patent does not contain any information (regarding for instance a salt selection process) which explains to the skilled person why specifically disodium salt was selected. On the contrary: it follows from the description of EP ‘508 that the benefit obtained by adding vitamin B12 is achieved irrespective of the antifolate that is used, and therefore the skilled person would understand that the specific salt form is of much less importance.

Equivalents need to be taken into account

The Judge further emphasises that equivalents need to be taken into account when determining the scope of protection of a patent. The parties had not disputed that the products are technically
equivalent. Furthermore, the Judge makes reference to the European Public Assessment Reports of the generic products of Fresenius Kabi and Teva, in which it was acknowledged that the active moiety of both products is the same.

Scope of protection of the patent

The fact that during the prosecution of the patent, Eli Lily had been forced to explicitly limit its claims to pemetrexed disodium, because “pemetrexed” (without disodium) would be considered
impermissible added matter, did not alter the findings of the Judge. The Judge confirms that the question as to whether a variant would constitute added matter, has to be distinguished from the
question relating to the scope of protection of the patent in which equivalent variants may be included. The Judge finds support in the judgments of Supreme Court in the United Kingdom and the German Bundesgerichtshof.

The Judge mentions obiter dictum that courts in other jurisdictions (such as Switzerland, Italy and Austria), based on the prosecution file, have come to a different conclusion. According to the Judge, this emphasises the desirability of the Unified Patent Court, which would be able to render a uniform decision in a large number of European countries.