SPC for darunavir considered invalid in Dutch preliminary relief proceedings

On 8 January 2019, the District Court of The Hague dismissed a request for a preliminary injunction based on the Dutch supplementary protection certificate for darunavir because it considered the certificate to be invalid. This is the second case in the Netherlands where a court has applied the rule of law from the decision CJEU Teva/Gilead (C-121/17) of 25 July 2018.

Facts

Prezista is a medicine used to treat HIV infection. The active ingredient in Prezista is darunavir.

Searle was the holder of patent EP 0 810 209 B1 (EP 209) titled Alpha - and beta-amino acid hydroxyethylamino sulfonamides useful as retroviral protease inhibitors, which expired on 23 August 2013. EP 209 claimed a so-called Markush formula.

This is a generic formula that covers a large class of chemical compounds, without reciting them individually. So, darunavir was not specified or identified in any of the claims of the patent, by specific name or structure, or anywhere in the specification.

Based on EP 209, Searle obtained a supplementary protection certificate for "Darunavir, or the pharmaceutically acceptable salt, ester, in particular darunavir ethanolate" (the SPC), which was in force until 23 February 2019.

Sandoz obtained a marketing authorization in the Netherlands for a generic version of Prezista, which is within the scope of protection of the SPC. Sandoz included its generic version in the G-standard (a Dutch medicine database that contains all the products that are dispensed by or used in the pharmacy) that was published on 18 October 2018 and declared to put its product on the market as of 1 November 2018.

Searle requested for a preliminary injunction against Sandoz based on the SPC. Sandoz argued that a preliminary injunction must be denied because there is a serious chance that the SPC will be invalidated in proceedings on the merits. According to Sandoz, the SPC does not meet the requirement of Article 3(a) of Regulation (EC) No 469/2009 (SPC Regulation) because darunavir is not protected by EP 209.

Article 3(a) SPC Regulation states that a SPC shall be granted if the active ingredient is protected by a basic patent.

On 25 January 2018, the UK Court of Appeal referred a preliminary question to the CJEU concerning the interpretation of Article 3(a) SPC Regulation and a Markush formula (EP 209 as well). The German Federal Patents Court also referred a preliminary question to the CJEU concerning the interpretation of Article 3(a) SPC Regulation on 17 October 2017.

Assessment of the court

The court holds, referring to CJEU 12 December 2013, C‑493/12 (Eli Lilly), that the rules for determining what is protected by a basic patent are those relating to the extent of the invention covered by such a patent, such as Article 69 of the European Patent Convention and Article 1 of the Protocol, and not the rules governing infringement proceedings.

It follows from CJEU Eli Lilly that Article 3(a) SPC Regulation does not, in principle, preclude an active ingredient which is given a functional definition in the claims of a basic patent, being regarded as protected by the patent, on the condition that it can be concluded that the claims relate implicitly but necessarily and specifically to the active ingredient in question.

The court holds that it is not unlikely that the same applies to an active ingredient that falls within structural formula that is claimed in a basic patent, such as the Markush formula in EP 209, that covers a very large number of compounds.

However, considering the CJEU case law and, in particular, Eli Lilly and Teva/Gilead it is to be expected that the CJEU will rule in the pending referrals of the English and German courts that this will only be possible when the aforementioned condition is satisfied and consequently the active ingredient is made available to the person skilled in the art.

This condition has been further explained in CJEU Teva/Gilead. The CJEU ruled that an active ingredient is protected by a basic patent if:

• the active ingredient embodies the invention
• the active ingredient is "specifically identifiable" for the person skilled in the art in the light of all the information disclosed of the basic patent and on the basis of his/her common general knowledge on the priority date.

According to the court the first requirement is fulfilled. Darunavir embodies the invention since it is undisputed that the structural formula of darunavir falls under the Markush formula of claim 1 and claim 5 and that this compound has a HIV-inhibiting effect.

According to the court, the second requirement is not fulfilled. An enormous number of compounds fall under the claimed Markush formulae of EP 209. Darunavir is not disclosed in the claims nor in the description of EP 209, unlike the approximately one hundred preferred compounds that are specified.

Moreover, darunavir was an unusual compound on the priority date, that was not general knowledge for a person skilled in the field of HIV-medication. Darunavir did not exist on the priority date, and was developed and synthesized only six years later. Therefore, on the priority date, darunavir was not "specifically identifiable" for a person skilled in the art, in light of all the information disclosed about EP 209. Therefore, EP 209 does not necessarily and specifically relate to darunavir.

The court did not accept Searle's argument that the decision Teva/Gilead only has relevance for combination products and not, as in this case, for mono-products. The court holds that the CJEU intended to formulate general rules, in view of:

• the fact that the decision was pronounced by the Grand Chamber of the CJEU
• the wording of the decision.

Additionally, after pronouncing Teva/Gilead, the CJEU asked the UK and German courts whether they wished to maintain the preliminary questions. It is not disputed that the CJEU only sends such a letter when it thinks that the preliminary questions are identical or analogous to questions that have already been answered.

The court concluded that there was a serious chance that the SPC would be invalidated in proceedings on these merits, and dismissed the preliminary injunction.

Note

Searle and Sandoz are involved in pan-European litigation concerning the darunavir SPCs. In France, the Paris First Instance Court ruled on 11 January 2019 that the French equivalent of the SPC was valid. Accordingly, the preliminary injunction was granted, as well as the seizure of the infringing drugs and a product recall.

The UK Court of Appeal preliminary question relates to the UK equivalent of the SPC. At first instance, the UK High Court ruled that the English equivalent of the SPC was valid. The CJEU will now bring clarification in the diverged European legal landscape of Article 3(a) SPC Regulation and Markush formulae.