How to interpret the notion of second medical use with regards to SPCs? This is the question which was asked of the Court of Justice of the European Union (CJEU) by the court of appeal of Paris on behalf of the French industrial property office in the Santen case. On July 9, 2020 the CJEU put an end to ten years of legal uncertainty.

The context: complex law and uncertain case law

As a reminder:

• SPCs extend the duration of patent protection for new drugs to compensate (at least partially) for the time required to obtain marketing authorization. Indeed, the clinical trials which are required prior to applying for marketing authorization delay the launch date of a new drug, thus reducing the effective duration of the monopoly conferred by a patent.

• SPCs, which are granted by most of the patent offices of the EU, take effect at the expiry of the related patent for a maximum period of five years (more precisely, for a period equal to the period elapsed between the date of filing of the patent application and the date of the first marketing authorization in the EU, reduced by a period of five years, without the duration of the SPC being longer than five years).

• The grant of an SPC is subject to four cumulative substantive conditions: (a) the product must be protected by a valid patent; (b) the product, as a drug, must have obtained a valid marketing authorization; (c) the product must not have already been the subject of an SPC; and (d) the marketing authorization referred to in (b) must be the first marketing authorization for the product as a drug.

With regards to condition (d) relating to the first marketing authorization, the CJEU ruled in the Neurim Pharmaceuticals case on July 19, 2012, that a new medical use of an active ingredient may be covered by SPC protection on the basis of the corresponding (second) marketing authorization, even if this active ingredient has already been the subject of a (first) marketing authorization for another medical use. In this case, the SPC is granted solely if the corresponding patent was granted for a second medical use of a known active ingredient (or composition of active ingredients), corresponding to the (second) marketing authorization relied upon. And the SPC will solely cover the second medical use of the active ingredient covered by the corresponding patent, not the active ingredient itself.

In the Neurim case, a first marketing authorization had already been obtained for a drug for veterinary use. A second marketing authorization was obtained for a new medical use of the same active ingredient for a drug for human use. SPC protection was granted on the basis of this second marketing authorization.

The Neurim case was then referred to in the Abraxis case in 2019, where the advocate general at the CJEU suggested to restrict the application of the Neurim case law to the factual circumstances of the Neurim case, i.e. a first drug for veterinary use and a second drug for human use. In its decision of March 21, 2019, the CJEU ruled that the Neurim case law should not apply to a new formulation of a product: a new formulation does not constitute a new medical use.

The CJEU decision in the Santen case: a total reversal of previous case law

In the Santen case, the CJEU was asked to clarify the interpretation of the Neurim case law.

The CJEU’s decision is a total reversal of the Neurim case law which, while it has the merit of clarity and will allow standardizing practices within the EU member states, will also call into question the exploitation of a number of SPCs granted on the basis of the earlier case law as well as economic models built on drug repurposing.

The French company Santen SAS is the owner of a French patent covering an ophthalmic emulsion which the active ingredient is cyclosporine and which is used for the preparation of a composition for the treatment of severe ocular diseases such as keratitis (inflammation of the cornea). Santen obtained a marketing authorization for Ikervis®, which active ingredient is cyclosporine and which treats keratitis. On the grounds of its patent and its marketing authorization, Santen applied for SPC protection for cyclosporine in the form of eye drops for the treatment of keratitis. The French industrial property office rejected this application on the grounds that cyclosporine had already been the subject of a marketing authorization in 1983 for Sandimumm®, an oral solution for the treatment of endogenous uveitis (inflammation of the central part of the ocular globe). According to the French office, cyclosporine in the form of eye drops for the treatment of keratitis was not a new medical use of cyclosporine.

Santen appealed the French office’s decision before the Paris court of appeal, which agreed to refer a preliminary ruling to the CJEU.

The CJEU was asked to clarify the interpretation of condition (d) of article 3 of Regulation No 469/2009, and reformulated the referred questions as follows: may “a marketing authorization be considered to be the first marketing authorization, for the purpose of [article 3(d) of Regulation No 469/2009], where it covers a new therapeutic application of an active ingredient when such active ingredient has already been subject of a marketing authorization for a different therapeutic application”?

The stakes were high within the context of the evolution of pharmaceutical research towards “drug repurposing” (a trend that can be seen in particular in the current context of the fight against COVID-19).

On July 9, 2020, the CJEU answered negatively to this question, adopting a strict interpretation of the European SPC regulation.

First, the CJEU clarified the concept of “product” and adopted a strict definition thereof:

• the term “product” shall be understood, for the purpose of applying the SPC regulation, “as the active ingredient or combination of active ingredients of a medicinal product, without it being necessary to limit its scope only to one of the therapeutic applications to which such an active ingredient or combination of active ingredients may give rise”;

• it follows “that the fact that an active ingredient, or combination of active ingredients, is used for the purposes of a new therapeutic application does not confer on it the status of a distinct product where the same active ingredient, or the same combination of active ingredients, has been used for the purposes of a different, already known, therapeutic application”.

Second, the CJEU determined whether a marketing authorization granted for a new therapeutic application or medical use of an already authorized active ingredient may be regarded as being “the first marketing authorization granted for that product as a medicinal product for the purposes of Article 3(d) of Regulation No 469/2009, in the case where that marketing authorization is the first marketing authorization to fall within the limits of the protection of the basic patent relied on in support of the application for an SPC”:

• the CJEU considers that there is no need to take into account the scope of protection of the basic patent;

• the court also considers that the intent of the EU legislature was to promote not any and all pharmaceutical research leading to the granting of a patent and the marketing of a new drug, but research leading to the first marketing of an active ingredient (or a combination of active ingredients) as a drug;

• the court’s conclusions is that a marketing authorization for a therapeutic application or medical use of a product shall not be considered as the first marketing authorization of such product as a drug (condition (d)) when another marketing authorization has already been granted for a different therapeutic application or medical use of the same product.