CJEU's AG again tries to persuade the CJEU to abandon Neurim, this time in Santen
Recently, on January 23, 2020 the Advocate General (AG) issued his opinion in case C-673/18 Santen (the Opinion) on preliminary questions raised by the French Court of Appeal. These questions concern the interpretation of Neurim. The Opinion is currently only available in a limited number of languages including French.
The Opinion was eagerly awaited by those wanting to know whether after Neurim and after Abraxis an SPC can be obtained for a new indication of an old active ingredient.
The AG primarily proposes to essentially abandon Neurim and treat this as an exceptional case (a new human indication following a first veterinary indication): a rare wild animal which should never surface again. Only alternatively, does the AG propose a balanced interpretation of Neurim in response to the questions posed. In that case an SPC can be obtained for a new therapeutic indication for an old active ingredient or relate to a use of that active ingredient, in which it should exert a new pharmacological, immunological or metabolic action of its own.
We will elaborate on this below, share some background on Neurim and Abraxis and conclude what might be next.
The SPC Regulation 469/2009 (the Regulation) provides an extension of exclusivity for new medicinal products in the form of Supplementary Protection Certificates (an SPC). This to make up for the regulatory time it took before new medicinal product can be marketed while the standard patent term already commenced. The rationale of the Regulation being to allow recouping actual years of delay caused by research into a new product. The application for an SPC is done based on a combination of the patent relied on and a marketing authorization (MA) held for the new product. This MA must be the first MA for that product (which is relevant given the time limits to apply for an SPC). The CJEU in previous case law ruled that "product" is defined by the active ingredient and in short that minor changes do not make it a distinct product.
In 2012 in Neurim the CJEU ruled that an SPC can be granted for a product which differs in the indication treated relying on the MA for that distinct product and on a patent only covering the new product and not the old. That way only the exclusivity for the new product would be extended.
Neurim related to a first veterinary use (regulating the reproductive cycle of sheep) and a second human use (insomnia) and a different formulation following full clinical trials; good cases bring good case law. Some considered Neurim to apply only to such cases, while others believed it could also be applied to products with a new human indication following a previous human indication, in particular if this followed a full clinical trial program. The rationale of the SPC Regulation is after all to recoup part of the exclusivity of patent protection that is lost due to the regulatory process for a new product. The conditions of Neurim ensured that exclusivity would be limited to the new product and could not encompass the old product.
It was against this background that in 2018 the Dutch Council of State (the highest court on these topics) held that there was no doubt that Neurim applied broadly and not just to the circumstances in Neurim. The Council noted that no questions to the CJEU were needed because this was clearly the proper application and held that Bayer should be granted an SPC for a new indication product.
Now that the CJEU in Neurim showed that it attached weight to the rationale of the Regulation, some wondered whether an SPC would now be possible for new formulations if that formulation would have certain effects such as increase efficacy and be the result of a full clinical trial program (rather than merely a relatively quick bioequivalence study).
In Abraxis the CJEU about a year ago draw a clear line and ruled that an SPC cannot be obtained for new formulations of old active ingredients (in case the "formulation" does not have any therapeutic effects of its own).
This case is worth mentioning here because also there the AG (different AG from the Santen case) primarily proposed to abandon Neurim and only alternatively proposed that Neurim was limited to a case of a first veterinary use and a second human use (still providing a new medicinal product to humans).
The CJEU in Abraxis suggested that Neurim fitted into existing case law and that there was no reason to consider its application. This since Abraxis would merely relate to a new formulation which could not benefit from the application of Neurim.
Hence, what remained was the question as to the application of Neurim to other less exceptional cases. A topic debated ever since Neurim was rendered. Santen should ultimately provide an answer.
In underlying case, Santen is a pharmaceutical laboratory specializing in ophthalmology and holder of the EP "Ophtalmic oil-in water type emulsion with stable positive zeta potential" and obtained an EU MA on March 19, 2015 for the medicinal product 'Ikervis'. The active ingredient of that medicinal product is ciclosporin which has the form of an emulsion (eye drops) and treats severe keratitis in adult patients with dry eye diseases that has not improved despite treatment with tear substitutes. On June 3, 2015 Santen filed an SPC application with the INPI based on the 2015 MA for Ikervis.
On October 6, 2017, the director of the INPI rejected that application, on the ground that the MA relied on was not the first MA. Already on December 23, 1983 an MA was granted for the medicinal product Sandimmun (an oral solution) with ciclosporin as active ingredient, and several therapeutic indications including inflammation of the middle part of the eye. In its decision, the director considered that Neurim would not apply because i) the patent would be a formulation patent not limited to the new indication, ii) Santen would not have shown that Ikervis related to a new indication compared to Sandimmun.
With aforementioned in mind, the Parisian Court asked the following two preliminary questions to the Court.
The first question relates to the concept of 'different application' within the meaning of Neurim and whether it should be interpreted in a strict manner, where the French Court of Appeal sketches three cases, or interpreted broadly.
The first question is as follows:
- Should the concept of different
application be interpreted in a strict manner, that is,
- 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 medicinal product, compared with the earlier marketing authorization, or a medical product in which the active ingredient acts differently from how it acts in the medicinal product to which the first marketing authorization related; or
- more generally, in the light of the objectives of the Regulation 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 patentability of the invention?
- Or must it be interpreted broadly, that is, as including not only different therapeutic indications and diseases, but also different formulations, posologies and/or means of administrations?
The second question relates to the concept of 'application within the limits of the protection conferred by the basic patent'. Does the expression 'application within the limits of the protection conferred by the basic patent' within the meaning of Neurim, mean that the scope of the basic patent must be the same as that of the MA relied upon and, therefore, be limited to the new medical use corresponding to the therapeutic indication of that MA?
In an elaborate explanation, the AG states that the CJEU should abandon the Neurim approach completely.
In its thorough analysis, the AG discusses Neurim, its implications on the interpretation of the Regulation, the teleological approach of the CJEU in Neurim and the objectives and preparatory work of the Regulation. Although the reasoning by the CJEU is consequent, the AG explains, it leaves multiple questions unanswered which makes its scope difficult to assess. The AG points out that Neurim is not in line with older jurisprudence of the CJEU, namely Pharmacie Italia, MIT and Yissum, on the concept of 'product' as stated in Article 1(b) of the Regulation. Before Neurim, the Court had established a clear jurisprudence of a strict interpretation of the concept product. The CJEU in Abraxis tried to mitigate that contradiction by reaffirming the strict interpretation of the concept of 'product' and re-establishing the link between Article 1(b) and Article 3(d) of the Regulation. The AG concludes that it is not a sufficient option to 'marginalize' Neurim. Firstly, because the judgment cannot be seen as an exception whose application is limited to the factual circumstances of the main proceedings that gave rise to it. Secondly, the marginalization would not eliminate the contradictions that exists in the case law of the Court. The AG underlines a new approach, which is to follow Abraxis and rely on the analysis in paras 24 to 40 since in these paras the CJEU applied a strict interpretation of Article 3(d) of the Regulation which is incompatible with the reasoning in Neurim.
Only subsidiary, if the CJEU ultimately wishes to hold on to the approach in Neurim, the AG formulates an answer to the two preliminary questions. Regarding the first question, the AG concludes that Article 3 of the Regulation should be interpreted as meaning that issuing an SPC for a different application of an active ingredient for which an MA has been granted within Neurim, requires that the MA that serves as a basis for the application of an SPC should cover a new therapeutic indication for that active ingredient or relate to a use of that active ingredient, in which it should exert a new pharmacological, immunological or metabolic action of its own. Thus, in the opinion of the AG, Neurim consists of two different situations of 'different application'. The first situation is in the case there is a new therapeutic application, where the innovation enables treating a new disease. The second situation is that in which the old active ingredient exerts a "pharmacological, immunological or metabolic action" of its own, different from that which is previously known.
The relevant paragraphs are 67-69 (of which we provide an unofficial internal English translation until the official English translation becomes available):
 The scope of the Neurim judgment must therefore be identified between both extremes. Two cases should be considered to be covered by this judgment. The first is in case of a new therapeutic application, for example when an invention protected by the patent on which the SPC application is based makes it possible to treat a new disease. If the Court decides to go with this reading, it would have to go back from the MIT judgment. The second case, which is envisaged by the Commission in its written observations, is that in which the old active ingredient exerts a "pharmacological, immunological or metabolic action" of its own, different from that which is previously known. In the presence of such a new action, the old active ingredient would be assimilated to a new product.
 In the written observations and at the hearing by the French Government, the criteria proposed above could complicate the examination that needs to be conducted by national patent offices on SPC applications. However, I would not overestimate these difficulties. On the one hand, these offices should be equipped to resolve questions relating to the application of the said criteria and, on the other hand, as the Commission correctly pointed out at the hearing, it would be the responsibility of the applicant for an SPC to provide the evidence necessary to establish the new therapeutic indication or the new action of the active ingredient or the known composition, in failing to do so the application would be rejected.
 On the basis of the aforementioned consideration, I propose that alternatively, the Court should answer the first preliminary question that Article 3 of the Regulation must be interpreted as meaning that issuing an SPC for a different application of an active ingredient for which a market authorization has been granted in the Member State concerned, within the meaning of the Neurim-judgement, requires that the marketing authorization that serves as a basis for the application of an SPC should cover a new therapeutic indication for that active ingredient or relate to a use of that active ingredient, in which it should exert a new pharmacological, immunological or metabolic action of its own.
The second question related to the interpretation of the concept of 'application within the limits of the protection conferred by the basic patent' as stated in Neurim. The question implied that the INPI feared that a Neurim SPC could extend exclusivity also of the existing use. The AG clarifies that Neurim clearly limits the scope of an SPC for a new indication to that new indication (and not extending to the active ingredient as such or other indications).
The relevant paragraphs are 71-74 (of which we provide an unofficial internal English translation until the official English translation becomes available):
 As Santen argues, the Neurim-judgement does not contain an element that allows a conclusion to be drawn the way INPI means. The Court states in that judgement that the different application of the known active ingredient must fall within the scope of protection conferred by the basic patent, it merely declines another criterion from as stated in paragraph 26 of that judgement, according to which the market authorization of the first medicine that is authorized for 'a therapeutic use of the product corresponding to that protected by the patent invoked by the SPC application" that constitutes a first market authorization of this product in the meaning of Article 3(d) of the Regulation.
 The underlying concern of the position of the INPI and the French government – to avoid the granting of an SPC for a different application for an old product – might lead to a delay in the moment in which the active ingredient as such falls within the public domain, or that the scope of the SPC should stretch, conforming to article 4 of the Regulation, to other uses of the product as a medicine, protected by the basic patent and authorized before the expiration of the certificate is entirely justified. In that regard, I underline that the Neurim-judgement itself precises that the scope of such an SPC can, in any event, cover the new use of the older active ingredient, which is protected by the basic patent and covered by the market authorization which serves as basis of the SPC application. Under no circumstances, the scope of the SPC may extend to the active ingredient as such or to other uses of that active ingredient. This follows from paragraph 25 of the Neurim-judgement and from the fact that this judgement has interpreted at the same time Article 4 of the Regulation which defines the purpose of the SPC. Consequently, where a SPC relates to a different application of an old active ingredient is granted, the "product" covered by the market authorization of the corresponding medicine, in which the protection of the SPC extends, in accordance to Article 4 of the Regulation, the protection given by the SPC is not the 'active ingredient' itself, but the "different application of that ingredient" which falls within the scope of the basic patent. Assuming that the SPC application of Santen satisfies the criterion indicated the response to the first preliminary question, it is for the referring national court to decide, the SPC would only cover the application "ciclosporin for the treatment of keratitis".
 In the written observations of the Commission, it doubts that the application of the active ingredient 'ciclosporin' is part of the invention that is covered by the basic patent that is at issue in the main proceeding. In that regard, as the Commission itself points out, I (red. the AG) find that the referring national court starts from the premise that the condition laid down in Article 3(a) of the Regulation is satisfied (or, at least, from the finding that such a premise is not in dispute) and the referring court did not pose questions on this topic. The Court is therefore not obliged to adopt a position on that issue. In any event, the question to assess whether the Commission's doubts are justified is a matter of application of the provisions of the Regulation. It is for the national court to assess whether the new application of 'ciclosporin' on which the SPC application of Santen is based falls within the scope of the basic patent, on the base of the indications that are given in the Courts' jurisprudence and, notably, in the Teva-judgement, in which the criteria of the application of the condition of Article 3(a) of the Regulation are summarized.
 On the basis of the aforementioned considerations, I propose, subsidiary, to the Court to respond to the second preliminary question as follows: Article 4 of the Regulation should be interpreted in a way that, where the SPC relates to a different application of the older active ingredient, the concept of "product" within the meaning of that provision refers only to that application and does not extend to the active ingredient as such or other applications thereof.
This of course is "only" the opinion of the AG and not yet the decision of the CJEU. It remains to be seen whether the CJEU will adopt the AG's suggestions. It seems unlikely, given the decision in Abraxis not abandoning Neurim, that the CJEU would opt for the AG's first suggestion to mark Neurim as a rare wild animal. Adopting the second suggestion of a balanced broader application of Neurim is more likely.
If the CJEU would indeed adopt the second suggestion, it would embrace a new formula of "a new therapeutic indication for that active ingredient or relate to a use of that active ingredient, in which it should exert a new pharmacological, immunological or metabolic action of its own". It would be for the national courts to decide whether this is fulfilled based on a burden of proof lying with the applicant, but no doubt spark further questions as to when this formula is met.
The Opinion could already have implications for pending applications for SPCs and the approach taken by national offices. Companies that have not considered SPCs for a new indication or a "new use" should reconsider their SPC filing strategy given the time constraints in filing and the potential that the CJEU could endorse such SPCs.
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