Eli Lilly and Company v. Fresenius Kabi Nederland B.V., Preliminary Relief Judge District Court of The Hague, the Netherlands, 24 October 2017, Case number C/09/537158 / KG ZA 17/1072

Eli Lilly and Company v. Teva Nederland B.V., Preliminary Relief Judge District Court of The Hague, the Netherlands, 24 October 2017, Case number C/09/538525 / KG ZA 17/1159

Eli Lilly (”Lilly”) is the holder of the European patent EP 1 313 508 B1 (“EP ‘508”) entitled “Combination containing an antifolate and methylmalonic acid lowering agent”. The patent was filed on 15 June 2001 relying on priority of US 215310 P dated 30 June 2000, US 235859 P dated 27 September 2000 and US 284448 P dated 18 April 2001. Lilly sued Fresenius and Teva in separate preliminary relief proceedings amongst others claiming an injunction. On 24 October 2017 the PI judge (Mr. Brinkman) decided both cases based on similar reasoning.

EP ‘508 primarily claims the use of pemetrexed disodium in the manufacture of a medicament for use in combination therapy for inhibiting tumor growth, wherein said medicament is to be administered in combination with vitamin B12. Lilly markets the medicine Alimta which is protected by EP ‘508. Both Fresenius and Teva offer a generic drug with pemetrexed diacid as the active ingredient, which is prescribed in combination with a vitamin supplement consisting of folic acid and vitamin B12.

Other proceedings in Europe
The PI judge mentions the various (pending) infringement proceedings between Lilly and companies offering generic Alimta in Europe. In the UK the Supreme Court has ruled that the scope of protection of EP ‘508 also covers other salt forms than pemetrexed disodium.

In Germany the Oberlandesgericht Dusseldorf has decided that there was no direct infringement also not by way of equivalence. This decision was later overturned by the Bundesgerichtshof and referred back to the Oberlandesgericht Dusseldorf. This case is still pending. In another case the Oberlandsgericht Munich has decided that pemetrexed diacid is an equivalent of pemetrexed disodium.

In Switzerland, the court found that other pemetrexed salt forms (or diacid) do not infringe. An appeal is still pending. In Italy and Austria courts have also found that there is no infringement. In Sweden, France, Belgium, Denmark, Finland and Portugal infringement proceedings are still pending.

In Dutch proceedings a PI was granted on 1 March 2017 in favour of Lilly against Sandoz. No infringement defense was put forward by Sandoz in those proceedings.

Dutch proceedings Lilly vs Teva and Fresenius
Both Fresenius and Teva argue that they do not infringe EP ‘508, because the claims of EP ‘508 are limited to a specific pemetrexed salt, namely pemetrexed disodium, which Fresenius and Teva do not offer.

The PI judge sets out the relevant legal framework for determining the scope of protection citing article 69 EPC and the Protocol and referring to Dutch Supreme Court case law in which the Supreme Court has ruled that “which is essential for the invention of which protection is sought”, or “the inventive concept underlying the words of the claims”, is to be viewed against the backdrop of the literal text of the claims (the “extremes” as the Protocol states) (cf. the Supreme Court decision of 7 September 2007, ECLI:NL:HR:2007:BA3522 and the Supreme Court decision of 25 May 2012, ECLI:NL:HR:2012:BV3680).

Uncovering the inventive concept behind the words of the claims serves to avoid an interpretation that is solely based on the literal meaning of the wording which for a fair protection of the patent owner may perhaps be overly limited or broad (cf. the Supreme Court decision of 13 January 1995, ECLI:NL:HR:1995:ZC1609, NJ 1995/391). In this respect the description and drawings are an important source.

The PI judge mentions that the knowledge of the skilled person on the priority or application date is relevant for determining the scope of protection. Information from the prosecution file may however also be relevant. For the question of infringement, the knowledge of the skilled person on the date of the infringement is relevant in particular where it concerns equivalent features.

The PI judge considers that the skilled person reading the patent would understand that EP ‘508 is fundamentally about reducing the adverse effects of pemetrexed by adding vitamin B12 and that the invention laid down in EP ‘508 has nothing to do with a way of manufacturing the medicine. Further, the skilled person would understand that it does not matter how the pemetrexed anion enters the bloodstream, because the invention is about adding vitamin B12 to the already existing pemetrexed therapy.

A reasonable protection for the patentee according to the PI judge points in the direction that the difference between disodium and diacid should not matter. A literal reading of the claims would make it easy for third parties to circumvent the patent, while the invention laid down in the patent is actually being used. Fresenius and Teva add B12 to their pemetrexed in order to reduce the toxic effects of the active ingredient, the anion.

The PI judge realizes that the legal certainty for third parties may indicate an interpretation in the opposite direction, as the claims exclusively and explicitly claim pemetrexed disodium. A third party who investigates may therefore at first glance think that pemetrexed diacid does not does infringe. If he would properly study EP ‘508, a skilled person would however also read from the patent that the invention is directed to the beneficial effect of vitamin B12 to the already known therapy with pemetrexed. Further it is not in dispute that the skilled person will know that in the human body only the effect of pemetrexed anion is relevant, which anion forms after dissolving the disodium or the diacid (or another salt form).

The PI judge goes on by stating that due account must be taken of equivalents by determining the extent of protection of the patent. It is undisputed that pemetrexed diacid in the products of Fresenius and Teva is equivalent to the disodium salt. This is logical as it is the pemetrexed anion which is active in the body against the claimed indication.

Fresenius and Teva argued that the prosecution history of EP ‘508 would lead a third party to a literal claim interpretation, as Lilly had limited the claims during prosecution because the examiner was of the opinion that broader claims (only “pemetrexed”) would claim added matter.

The PI judge disagrees and in this regard mentions that the disclosure test or gold standard for assessing added matter should be distinguished from the question of scope of protection and equivalence. Technical equivalents which are not clearly and unambiguously disclosed in the applications would result in added matter. Applying the same test for added matter and equivalence would not do justice article 2 of the Protocol.

For the question of infringement the knowledge of the skilled person on the date of the infringement should also be taken into account while for the question of added matter only the knowledge of the skilled person on the application date is relevant. This conclusion according to the PI judge is supported by Attorney-General Van Peursem (Conclusion A-G to Dutch Supreme Court 5 February 2016, ECLI:NL:PHR:2015:2200), the UK Supreme Court Lilly v Actavis, the Bundesgerichtshof in Lilly v Actavis and the Court of Appeal of The Hague in Medinol/Cordis (ECLI:NL:GHSGR:2003:AH9364).

The PI judge concludes that even if a third party would consult the prosecution file wrapper and take note of the correspondence in relation to added matter he would find no good reason to assume that Lilly intended to waive protection. It is clear from the prosecution history that Lilly wanted a broader protection. From the fact that the examiner forced Lilly to narrow the claims and the fact that Lilly did not appeal or try to formulate the claims differently, a third party would not have understood that Lilly did no longer want protection of different salt forms or the diacid.

Weighing all the relevant factors, the PI judge concludes that EP ‘508 is infringed.

The PI judge mentions that his decision is supported by decisions in some important jurisdictions, but is not in line with decisions in some other jurisdictions. This according to the judge is explained by the fact that the prosecution file wrapper is weighed differently across jurisdictions and the fact that some courts adhere more strictly to the literal wording of the claims. According to the judge the fact that there are diverging decisions shows once more the desirability of a unitary patent and the UPC.

A copy of the judgments (in Dutch) can be read here and here.

Headnote: Mattie de Koning and Rosanne Hoevenaar, Simmons & Simmons LLP