The CJEU’s decision in Santen confirms a restrictive interpretation of ‘product’ under article 1(b) and 3(d) of the SPC Regulation, and rejects the possibility of an SPC based on a Marketing Authorisation for a new use of a previously authorised product

On 9 July 2020, the Grand Chamber of the Court of Justice of the European Union (“CJEU”) handed down its decision in Santen SAS v Directeur général de l’Institut national de la propriété industrielle (C-673/18), a reference from the Paris Court of Appeal concerning the interpretation of Articles 1(b) and 3(d) of Regulation (EC) No 469/2009 of the European Parliament and of the Council of 6 May 2009 concerning the supplementary protection certificate (“SPC”) for medicinal products (“SPC Regulation“).

The CJEU considered whether the definition of ‘product’ in Article 1(b) of the SPC Regulation is tied to the therapeutic application of the active ingredient, and in particular if a new therapeutic application of a previously authorised active ingredient can be considered a distinct ‘product’, such that a further marketing authorisation (“MA”) covering that new therapeutic application would constitute the “first authorisation” under Article 3(d) of the SPC Regulation.

The CJEU held that an MA cannot be considered as the first MA within the meaning of Article 3(d) when it concerns a new therapeutic application of a known active ingredient (or combination of active ingredients) which has already been the subject matter of an MA for another therapeutic application.

This decision severely limits the availability of SPCs for second medical uses of known products and removes the ability to obtain an SPC based on a later MA for a subsequent therapeutic use of a known and previously authorised medicinal product. It will no doubt be disappointing to R&D based pharmaceutical companies that are investigating such new uses and which would wish to rely on the additional protection afforded by an SPC based on that later MA to compensate them for the loss of exclusivity caused due to regulatory delays in getting a product authorised for that new therapeutic use to the market.

Legal Background

Article 3(d) of the SPC Regulation provides that an SPC cannot be granted if there has been an earlier MA for the same ‘product’ (ie, the active ingredient or active ingredients of the medicinal product under Article 1(b) of the SPC Regulation). Despite the seemingly straightforward wording of this Article of the SPC Regulation, the issue of what constitutes a ‘product’ for the purposes of Article 3(d) has been the subject of significant debate in recent years.

The CJEU traditionally afforded a narrow interpretation to ‘product’ under Articles 3(d) and 1(b) of the SPC Regulation. In Yissum (C-202/05), which concerned a patent for a composition containing the compound ‘calcitrol’ for use in topical treatment of skin disorders, the CJEU interpreted Article 1(b) of the SPC Regulation as meaning that in a case where a basic patent protects a second medical use of an active ingredient, that use does not form an integral part of the definition of the ‘product’. As a consequence of which an SPC could not be granted on the basis of the MA for the new use if the same active ingredient had been subject to a previous MA authorised for a different use.

Similarly, in Pharmacia Italia (C-31/03), which concerned a patent covering the compound ‘cabergoline’, the CJEU held that the grant of an SPC based on an authorisation of a medicinal product for human use was precluded by a prior MA for that same product as a veterinary medicinal product. In that case, the later human medicinal product, DOSTINEX® containing the active ingredient ‘cabergoline’ was authorised in Germany, after an earlier veterinary medicinal product with that active ingredient, GALASTOP®, had been authorised in Italy.

However, in its decision in Neurim (C‑130/11), the CJEU departed from its previous case law, and instead indicated that SPCs would be available for second medical uses of known active ingredients. The Neurim case concerned a patent covering a formulation of melatonin, which was subsequently authorised and marketed as CIRCADIN® by Neurim. Neurim applied for an SPC on the basis of the CIRCADIN® MA despite there being an earlier authorisation for a veterinary product, REGULIN®, which used melatonin in regulating the seasonal breeding activity of sheep.

In considering this reference from the UK Court of Appeal, the CJEU held that the mere existence of an earlier MA obtained for a veterinary medicinal product does not preclude the grant of an SPC for a different application of the same product for which an MA has been granted, provided that the application is within the limits of the protection conferred by the basic patent relied upon for the SPC. (the “Neurim exception”). In short, the Neurim exception permits the grant of an SPC on the basis of a subsequent MA for a new therapeutic use of a known active ingredient, where the earlier MA covering the known active ingredient falls outside the scope of protection of the basic patent relied upon for that SPC.

In reaching this conclusion the Grand Chamber noted that the fundamental objective of the SPC Regulation is to ensure sufficient protection to encourage pharmaceutical research. Therefore, if a patent protects a new therapeutic application of a known active ingredient, this should enable its proprietor to obtain an SPC for the new use of that active ingredient, even if it has already been marketed as a medicinal product (for veterinary or human use) for other therapeutic indications previously.

This Neurim exception was also subsequently suggested to cover a patent relating to any new therapeutic application of a previously known active ingredient, notably in paragraph 27 of the CJEU’s decision in Actavis v. Sanofi (C-443/12), and was seen as an encouraging development for the pharmaceutical industry as it incentivised investment in researching and developing new indications for known products that improve treatments and save lives.

However, in  Abraxis Bioscience LLC v the Comptroller General of Patents (C-443/17), the CJEU returned to its old strict approach, and confirmed that SPCs cannot be obtained on the basis of MAs for new formulations of previously authorised active ingredients (see our summary here). This case concerned “nab-paclitaxel” (ABRAXANE®) which contains the previously authorised active ingredient paclitaxel, but formulated as albumin bound nanoparticles. When considering this reference form the UK High Court, the CJEU held that Article 1(b) of the SPC Regulation must be interpreted narrowly, and that adjuvants (such as albumin) are excluded from the meaning of ‘product’ even if they allow the active ingredient with which they are associated to exercise its therapeutic effect more effectively. Having made its finding that Article 1(b) must be interpreted narrowly, the CJEU recognised that the objective of the SPC Regulation would not be fulfilled by allowing an SPC based on an MA for a new formulation of a previously authorised product. The CJEU therefore expressly rejected an extension of the Neurim exception to SPCs based on MAs for new formulations of a previously authorised product, but in doing so it did not provide any further clarity on the scope of this Neurim exception insofar as it related to new therapeutic uses.

In the above context, it was hoped that such scope would finally be clarified by the CJEU when it considered the current reference in Santen.

Factual background to Santen (C-673/18)

A reference was made to the CJEU by the Paris Court of Appeal concerning Santen’s French SPC application based on European Patent No. 1 809 237 (entitled ‘Ophthalmic oil-in-water type emulsion with stable positive zeta potential’), and a centralised MA for the medicinal product IKERVIS®, containing as its active ingredient 1 mg/ml cyclosporine in the form of an emulsion, administered as an eye drop for the treatment of severe keratitis in adult patients.

Prior to the grant of the centralised MA for IKERVIS®, an MA had been granted for the medicinal product SANDIMMUN®, which contained as its active ingredient 100 mg/ml of cyclosporine in the form of an oral solution for the prevention of rejection of solid organ and bone marrow grafts, and for the treatment of endogenous uveitis (an inflammation of some or all of the uvea, which is the middle layer of the eye).

In light of the earlier authorisation for SANDIMMUN®, the French Parent office rejected Santen’s SPC application, and this rejection was appealed to the Paris Court of Appeal, which in turn referred the two questions below to the CJEU on the scope of the Neurim exception (the full procedural background to the case is available here in our previous update). The two questions referred to the CJEU were:

“Must the concept of a ‘different application’ within the meaning of the judgment of 19 July 2012, Neurim (C-130/11, EU:C:2012:489), be interpreted strictly, that is to say:

–    as limited only to the situation where an application for human use follows a veterinary application;

–    or as relating to an indication within a new therapeutic scope, in the sense of a new proprietary medical product, compared with the earlier marketing authorisation, or a medicinal product in which the active ingredient acts differently from how it acts in the medicinal product to which the first marketing authorisation related;

–    or more generally, in the light of the objectives of Regulation (EC) No 469/2009 of establishing a balanced system taking into account all the interests at stake, including those of public health, must the concept of a “new therapeutic use” be assessed according to stricter criteria than those for assessing the patentability of the invention;

–    or must it on the other hand be interpreted broadly, that is to say, as including not only different therapeutic indications and diseases, but also different formulations, posologies and/or means of administration?

Does the expression “[application] within the limits of the protection conferred by the basic patent” within the meaning of the judgment [of the Court of Justice] of 19 July 2012, Neurim (C-130/11, [EU:C:2012:489]), mean that the scope of the basic patent must be the same as that of the marketing authorisation relied upon and, therefore, be limited to the new medical use corresponding to the therapeutic indication of that marketing authorisation?” 

AG’s opinion in Santen

On 23 January 2020, AG Giovanni Pitruzzella provided his Opinion on the referred questions. A full analysis of this Opinion is available here in our previous post.

Briefly, AG Pitruzzella made two proposals to the CJEU. His favoured proposal was for the CJEU to reverse its decision in Neurim and strictly interpret the meaning of ‘product’ under Article 1(b).

His alternative proposal permits SPCs for second medical uses of known and previously authorised products in some instances by interpreting the Neurim exception as allowing an SPC if the new MA “covers a new therapeutic indication of said active ingredient or relates to a use of it in which this active ingredient exerts a new pharmacological, immunological or metabolic action of its own”.

Analysis of the Santen decision of the Grand Chamber of the CJEU

In its decision, the Grand Chamber states that in order to respond to the Paris Court of Appeal in a useful way, the question that needs to be addressed is whether Article 3(d) can be interpreted as meaning that an MA can be the first MA within the meaning of this article if it concerns a new therapeutic application of a known active ingredient (or combination of active ingredients), which has already been the subject of an MA for another therapeutic application.

In responding to this question, the Grand Chamber notes that the MA in Article 3(d) is for a given ‘product’ as defined in Article 1(b), and that the first issue was whether a ‘product’ is dependent on or tied to a therapeutic application, in particular if a new therapeutic application of a known active ingredient can be considered as a product distinct from another therapeutic application of the same active ingredient.

In this respect, the Grand Chamber concludes that, as a result of a joint reading of Article 1(b) and 4 of the SPC Regulation, ‘product’ means the active ingredient or combination of active ingredients of a medicinal product, and it is not limited to any particular therapeutic application. This is supported by the Explanatory Memorandum for the SPC Regulation, which states that the term ‘product’ is to be understood strictly as the active ingredient, and that minor changes (such as a new dosage, the use of a different salt or ester or even the form of the pharmaceutical product), are not likely to give rise to a new SPC. Consequently, the fact that an active ingredient or a combination of active ingredients can be used for a new therapeutic indication does not make it a distinct ‘product’ because of this new therapeutic use.

The second issue considered by the Grand Chamber is whether an MA granted for a new therapeutic application of a known active ingredient or combination of active ingredients can be considered as the ‘first’ MA within the meaning of Article 3(d), where this MA is the first one to fall within the scope of protection of the basic patent relied upon in the SPC application.

The Grand Chamber notes that Article 3(d) does not refer to the scope of protection of the basic patent. In this respect, the Grand Chamber restates its decision in Abraxis that the first MA for a medicinal product is simply the one incorporating the active ingredient or the combination of active ingredients, whatever the therapeutic application for this active ingredient or combination of active ingredients might be. If one were to consider the scope of protection of the basic patent in assessing Article 3(d), then this would go against this definition of ‘product’ in Article 1(b), and it would then become possible for an SPC to be granted for a new therapeutic application of a known active ingredient, when the same active ingredient is already covered by a previous MA for another therapeutic use. The Grand Chamber then stresses that the Neurim decision, which allows for this possibility, is inconsistent with the SPC Regulation in this regard, as the scope of protection of the basic patent is irrelevant when assessing Article 3(d).

The Grand Chamber goes on to state that, on the basis of its ruling in Abraxis and the Explanatory memorandum to the SPC Regulation, the SPC regulation is not intended to reward any and all research, but is rather aimed at only rewarding research leading to the first placing on the market of an active ingredient or combination of active ingredients as a medicinal product. This objective would not be achieved if Article 3(d) were interpreted as meaning that the ‘first’ MA to fall under the scope of protection of the basic patent would entitle the proprietor to an SPC based on the later authorisation. Difficulties would also result from a different interpretation of Article 3(d) that relied on concepts such as a new “therapeutic indication”. As mentioned in the Opinion of Advocate General Pitruzzella, the notion of “therapeutic indication” is not even defined by the SPC Regulation and this might lead to National Patent Offices adopting inconsistent interpretations of such an Article 3(d) test.

The decision of the Grand Chamber therefore only leaves a (small) door open for SPCs for new therapeutic uses for “known” products, namely where the “known” product has not been previously authorised.

The ruling of the Grand Chamber of the CJEU is thus as follows:

“60. […] The premiss on which the referring court relies, mentioned in paragraph 34 above, must be disregarded and that an MA for a therapeutic application of a product cannot be regarded as the first MA for that product as a medicinal product, for the purpose of Article 3(d) of Regulation No 469/2009, where another MA was granted previously for a different therapeutic application of the same product. The fact that the most recent MA is the first MA to fall within the limits of the protection of the basic patent relied on in support of the SPC application cannot call that interpretation into question.

61.[…] An MA cannot be considered to be the first MA, for the purpose of [Article 3(d)], where it covers a new therapeutic application of an active ingredient, or of a combination of active ingredients, and that active ingredient or combination has already been the subject of an MA for a different therapeutic application."

The Grand Chamber considers this to be a balanced approach between, on the one hand, ensuring that the objective of the SPC Regulation to incentivise research and compensate for the insufficient protection offered by the basic patent is met, and on the other hand taking into account all interests at stake.

This is as close to a “reversal” of the Neurim decision as we are likely to get from the CJEU. It is clear from the language adopted by the Grand Chamber, ie, that the Neurim decision is “contrary” to the SPC Regulation (paragraph 53), and that the premise arising from the Neurim decision “must be rejected” (paragraphs 34 and 60), that there is likely to be little scope to argue for the grant of an SPC based on an subsequent MA for a new therapeutic use of known and previously authorised active ingredient.

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