In Abraxis Bioscience LLC v the Comptroller General of Patents (Case C-443/17) the Court of Justice of the European Union (“CJEU”) held that Supplementary Protection Certificates (“SPCs”) cannot be obtained for new formulations of previously approved active ingredients. This limitation on the availability of SPCs will be disappointing to the pharmaceutical industry, which continues to invest significantly in researching and developing new formulations that improve the efficacy of previously authorised active ingredients or combinations of them. The CJEU did not expressly set out the limit of the “exception” provided by its earlier decision in Neurim (Case C‑130/11), which permits an SPC to be obtained for new uses of previously authorised active ingredients. It is hoped that the limits of this exception will be clarified by the CJEU when it considers the pending reference from the Paris Court of Appeal in Santen (Case C-673/18), which is the first ever reference from the French Courts on the SPC Regulation.
On 21 March 2019, the Fourth Chamber of the CJEU handed down its decision following a reference from the Patents Court (Arnold J). In its decision, the CJEU held that the definition of “product” under Article 1(b) of the SPC Regulation (i.e. the active ingredient or combination of active ingredients of a medicinal product) must be interpreted strictly and narrowly. This means that substances forming part of a medicinal product which do not have an effect of their own on the human or animal body are excluded from the meaning of “product”. It therefore excludes excipients (adjuvants or carriers), even if these are linked to, or allied to, the active ingredient of the medicinal product.
The CJEU also adopted a narrow, literal interpretation to Article 3(d) which provides that the SPC must be based on the first marketing authorisation (“MA”) for that product, such that it excludes new formulations of previously approved products. The CJEU describes its decision in Neurim as “the exception to the narrow interpretation of Article 3(d)”, which cannot be relied upon for new formulations of previously approved products. The CJEU summarises its earlier decision in Neurim as holding 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 purposes of the SPC application”. However, the CJEU did not then further elaborate on all the circumstances in which the “Neurim exception” applies to Article 3(d).
The Abaxis case relates to the cancer treatment “nabpaclitaxel” (Abraxane®), which contains the previously authorised active ingredient paclitaxel, but formulated as albumin bound nanoparticles. It was undisputed before Arnold J that Abraxis undertook prolonged and expensive research to develop Abraxane®, and that it took significant time for Abraxis to obtain a marketing authorisation for Abraxane®.
Although Abraxis advanced an argument that nab-paclitaxel was to be considered the active ingredient, this was rejected by Arnold J who held that paclitaxel is the active ingredient and albumin is a carrier. Arnold J reached this conclusion on the basis of the unchallenged facts before him and in light of the existing CJEU case law that the definition of “product” under Article 1(b) of the SPC Regulation must be interpreted narrowly. In light of this Arnold J held:
“In my judgment, it is clear that nab-paclitaxel is not the active ingredient of Abraxane within the meaning of Article 1(b) of the SPC Regulation: paclitaxel is the active ingredient and albumin is a carrier. It is not necessary to seek further guidance from the CJEU as to the interpretation of Article 1(b) since the interpretation of that provision is acte éclairé.”
However, Arnold J recognised that it was unclear how far the reasoning of the CJEU in Neurim extended as, although the reasoning of the CJEU was limited to new therapeutic uses, it was arguable that the same policy considerations apply to new formulations of old active ingredients even if the therapeutic use is the same. As a consequence, Arnold J referred the following question to the CJEU:
“Is Article 3(d) of the SPC Regulation to be interpreted as permitting the grant of an SPC where the marketing authorisation referred to in Article 3(d) is the first authorisation within the scope of the basic patent to place the product on the market as a medicinal product and where the product is a new formulation of an old active ingredient?”
In referring this question, Arnold J opined that in light of the balancing of interests of patentees, generic manufacturers, patients and other relevant stakeholders, and the need for a simple and predictable system of the grant of SPCs, SPCs should be not be granted for new formulations of old active ingredients. Arnold J held that this view was consistent with the strict interpretation of the definition of “product” under Article 1(b) of the SPC Regulation, and consistent with the need for the SPC Regulation to provide “bright-line rules even if they sometimes deprive meritorious inventions of extended protection”.
The subsequent Opinion of Advocate General Saugmandsgaard Øe in the Abraxis case also highlighted that the relationship of the CJEU’s case law on Article 1(b) on the one hand and the CJEU’s decision in Neurim on Article 3(d) on the other required clarification by the CJEU. Similarly to Arnold J, Advocate General Saugmandsgaard Øe reviewed the CJEU’s earlier case law on Article 1(b) and opined that this supported a narrow interpretation of that provision, such that it excluded from the meaning of “product” its therapeutic use or aspects of a medicinal product’s formulation that are not “active ingredients” even those parts of the formulation impact therapeutic efficacy.
Advocate General Saugmandsgaard Øe also recognised that this approach to Article 1(b) was “difficult to reconcile” with the CJEU’s decision in Neurim on Article 3(d). He recognised that Abraxis’s development of Abraxane® constituted a genuine therapeutic advance for which there was a significant loss of patent exclusivity due to the regulatory process (particularly as Abraxis had to make a full application for a marketing authorisation and could not rely on any “hybrid” procedure), but this did “not justify the creation by judicial decision of a test departing from the wording of Article 3(d)… and from the intention of the legislature“. He therefore urged the CJEU to overturn the approach developed by it in Neurim. In the alternative, he opined that if the CJEU was not minded to overturn Neurim, then it should be limited to the “particular, and probably exceptional, kind of situations at issue in Neurim“ so that an SPC can be permitted for a new therapeutic indication in human medicine despite an earlier approval for a different indication for veterinary use that is outside the scope of its basic patent.
The CJEU’s decision
In its decision the CJEU agreed with both Arnold J and Advocate General Saugmandsgaard Øe and confirmed that Article 1(b) of the SPC Regulation must be interpreted narrowly. In doing so, the CJEU drew parallels from its earlier Reasoned Order in GSK (Case C-210/13) that concerned whether an adjuvant of a vaccine could be considered an active ingredient in circumstances where the adjuvant had no therapeutic effect on its own but influenced the therapeutic effect of the active ingredient. The CJEU held that the reasoning to exclude such adjuvants from the meaning of “product” applied equally to excluding carriers, such as albumin, even if it allows the active ingredient with which it is associated to exercise its therapeutic effect more effectively. The CJEU held that this position is not changed by the active ingredient and carrier being linked together in the form of nanoparticles, as the nanoparticles cannot be regarded as being a “product” distinct from the “product” consisting solely of the active ingredient (i.e. paclitaxel).
Having made its finding that Article 1(b) must be interpreted narrowly, the CJEU recognised that a literal interpretation of Article 3(d) would preclude SPCs based on new formulations of known active ingredients or new uses of previously authorised active ingredients. The CJEU agreed with the analysis of Advocate General Saugmandsgaard Øe that the SPC regime was not established to protect “all pharmaceutical research giving rise to the grant of a patent and the marketing of a new medicinal product, but to protect research leading to the first placing on the market of an active ingredient or a combination of active ingredients as a medicinal product”. This resulted in the CJEU concluding that the objective of the SPC Regulation would not be fulfilled by allowing an SPC for a new formulation of a previously authorised product. As part of its reasoning, the CJEU also endorsed Arnold J’s view that, in light of the balancing of interests of patentees, generic manufacturers, patients and other relevant stakeholders, and the need for a simple and predictable system of the grant of SPCs, SPCs should not be granted for new formulations of old active ingredients. The CJEU therefore expressly rejects an application of its decision in Neurim to new formulations.
However, despite Advocate General Saugmandsgaard Øe in his opinion being unable to find any arguments to justify a distinction being taken in the approach to permitting SPCs for new uses of previously approved products and new formulations of previously approved products, the CJEU did not follow his invitation to overturn the CJEU’s decision in Neurim. The CJEU explicitly describes its decision in Neurim as “the exception to the narrow interpretation of Article 3(d)”.
In rationalising its decisions, the CJEU held that Neurim does not cast doubt on the narrow interpretation of Article 1(b) which, when read in light of Article 3(d), precludes SPCs for new formulations of previously authorised products. It describes Neurim as being a finding 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 purposes of the SPC application”. Despite Advocate General Saugmandsgaard Øe’s views in his opinion, the CJEU does not appear to have seen any tension between its express rejection of the application of the “Neurim exception” to new formulations of previously authorised products, but allowing its application for new uses of previously known products.
Although the CJEU’s description of its decision in Neurim could be read as meaning that the “Neurim exception” should be approached in the way suggested by Advocate General Saugmandsgaard Øe, namely that it is limited to the “particular, and probably exceptional, kind of situations at issue in Neurim“ (i.e. where the earlier use was a veterinary use and the subsequent use was in humans), the CJEU again did not expressly state this. It is therefore hoped that the CJEU will provide further guidance on the scope of the “Neurim exception” when it considers the pending reference in Santen.