Advocate General gives opinion on Abraxis SPC and sets sights on Neurim

​In December 2018, the Advocate General handed down its Opinion in Abraxis (C-433/17) on whether the SPC Regulation permits the grant of an SPC where the product is a new formulation of an old active ingredient.

In December 2018, the Advocate General (AG) published its Opinion (available here) in Abraxis (C-443/17) on whether the SPC Regulation permits the grant of an SPC where the product is a new formulation of an old active ingredient. This argument is dependent on the application of the principles set out in Neurim (C-130/11), which permits SPCs for “different applications” of old active ingredients. In the AG’s opinion, the answer should be no and the Abraxis SPC rejected. The AG went as far as to suggest that the practice following Neurim should be curtailed, if not overruled altogether.

We discuss the AG Opinion below, which, should it be followed by the CJEU, could have significant implications for the SPC field.

Background

The Abraxis case concerns the medicinal product Abraxane, which contains nanoparticle albumin-bound paclitaxel (termed nab-paclitaxel) for the treatment of certain breast, pancreatic and lung cancers. According to Abraxane’s Summary of Product Characteristics, albumin is thought to enhance transport of paclitaxel across endothelial cells (lining the interior surface of blood vessels and lymphatic vessels) and enhance accumulation of paclitaxel in the area of a tumour. Thus, nab-paclitaxel has been shown to provide greater efficacy than traditional formulations of paclitaxel for the treatment of certain cancers, as well as some benefits in patient tolerance. As a result, Abraxane required considerable investment and extensive research to develop through years of clinical trials before obtaining its marketing authorisation (MA).

Abraxis then applied for an SPC based on its MA (and patent) for Abraxane, with the product for SPC purposes as "paclitaxel formulated as albumin-bound nanoparticles". By the stage of the CJEU referral, it had already been determined (and neither referred to the CJEU nor further appealed by Abraxis) that nab-paclitaxel was, for SPC purposes, no different to paclitaxel and constituted the same “product” under Article 1(b) of the SPC Regulation. Paclitaxel had already been marketed under previous authorisations (eg Paxene and Taxol), which brought into question whether the Abraxane MA for nab-paclitaxel was the “first authorisation to place [paclitaxel] on the market as a medicinal product”, as required under Article 3(d) of the SPC Regulation.

The UK IPO had held that Article 3(d) was not satisfied on the basis that Neurim should be limited to new therapeutic uses of old active ingredients, not new formulations as in the case of Abraxane. On appeal to the UK Patents Court, Mr Justice Arnold agreed with the UK IPO, but considered the case law sufficiently unclear to merit a referral to the CJEU. For further background and analysis of the UK decision, please see our previous article here

AG’s opinion

The AG (Saugmandsgaard Øe) considered Neurim “difficult to reconcile” with pre-existing case law concerning the concept of a product under the SPC Regulation. Thus, in answering the referred question, the AG believed that the case provided the Court with an “opportunity to resolve the contradictions [in the case law]”. The AG also remarked that the Court would “have to clarify how [previous cases] can coexist harmoniously or, where appropriate, indicate whether certain judgments have been, or should be, reversed”. With that in mind, the AG seems to have set its sights on the interpretation of Neurim and raised the issue whether the existing approaches to its principles should be revisited.

The AG acknowledged four possible interpretations of Neurim put forward by interested parties. In essence, these interpretations propose an increasingly narrowing cascade of possible interpretations for approaching Article 3(d); that Article 3(d) should allow an SPC for:

  1. Any new formulations (or therapies) of known active ingredients, on the condition that the MA is the first to fall within the scope of protection conferred by the basic patent (advanced by Abraxis)
  2. Any new therapeutic uses of known active ingredients, but not formulations, on the condition that the MA is the first to fall within the scope of protection conferred by the basic patent (advanced by the UK Government and European Commission)
  3. The first therapeutic use in human medicine of a known active ingredient, where any previous MA only covered a therapeutic use in veterinary medicine, and the MA for human use is the first to fall within the scope of protection conferred by the basic patent (advanced by the Czech, Dutch and Polish Governments), or
  4. Only the first MA for the active ingredient in all situations, according to a strict literal interpretation of Article 3(d) (advanced by the Hungarian Government). This interpretation would have the effect of overturning the decision in Neurim.

In the AG’s view, the intention of the SPC Regulation is to protect research leading to the placing on the market of an active (or combination of actives) as a medicinal product for the first time. On that basis, it would not apply to all pharmaceutical research, even that which leads to a genuine therapeutic advance. For these reasons, the AG favoured a strict, literal interpretation set out in option 4 above.

The AG also saw “certain advantages” and in the alternative endorsed option 3 - ie limiting Neurim to scenarios more aligned with the same facts and ‘species switch’ from veterinary to human.

Either of the AG’s alternatives under options 3 or 4 would result in Abraxis’ SPC being rejected.

While not favoured by the AG, even option 2 (which had the support of the Commission) did not, in the AG’s opinion, go far enough to save Abraxis’ SPC. Abraxis had argued that Abraxane was authorised for a new therapeutic indication (namely the treatment of certain pancreatic cancers), which were not covered by the prior marketing authorisations for paclitaxel. However, the AG said that this is irrelevant for the purposes of answering the referred question as Abraxis’ basic patent does not contain any particular claim for the use of nab-paclitaxel to treat pancreatic cancer specifically (only eliminating cancer cells generally, which therefore was a known therapeutic use of paclitaxel). This emphasises the significance, even on a broader interpretation of Neurim, of having a specific claim relating to any new therapeutic use if it is to be relied on for SPC purposes. Of course, such requirements will be superseded and moot if the CJEU adopts options 3 or 4.

Comments

In reaching his opinion, it is interesting to note the AG’s reference to the recent legal study on the SPC regime conducted by the Max Planck Institute (MPI), which was similarly critical of the approach taken in and following the Neurim decision. Notwithstanding that the current legislative reforms surrounding the MPI legal study seem to be focussed on the issue of an export waiver, this highlights the impact that this study might have on legal development in the field of SPCs.

Further questions on the interpretation of Article 3(d) have recently been referred to the CJEU by the French Court of Appeal, in Santen (C-673/18). The first question referred, which sought clarification of the criteria for assessing Article 3(d) in light of Neurim, would seem to have been answered by Abraxis and is certainly addressed by the AG’s consideration of options 1-4 above. The second question in Santen is about the need for any new therapeutic use to be matched by a claim in the basic patent, which was also addressed by the AG’s reference to the lack of claims in Abraxis’ basis patent to the particular new (pancreatic) cancer indications (albeit that it will be superseded should either of the narrow interpretations of the AG be adopted by the CJEU).

It will be of considerable significance if the CJEU follow the AG’s opinion to select either of the narrow options 3 or 4. The Neurim decision had been welcomed by SPC applicants as a justified interpretation of the SPC Regulation to ensure incentivisation and reward to pharmaceutical research and development in the field of formulation development. Should such a decision be reached by the CJEU, it could result in Neurim being overturned (ie option 4), or at the very list constrained to a narrow application (ie option 3). Not only would Abraxis’ SPC be rejected, but the validity of a number of other pending and granted SPCs may also be cast into doubt.

As both the Neurim and Abraxis cases were referred from the English Courts, and given they have traditionally been in favour of the principles in Neurim, it is also interesting to consider the timing and effect of the Abraxis referral in the context of the continuing uncertainties surrounding Brexit.

Should the CJEU hand down its decision before 29 March 2019, it may become enshrined in English law as Supreme Court precedent under the European Union (Withdrawal) Act 2018, thereby effectively overriding earlier UK decisions in cases like the Court of Appeal’s referral in Neurim itself, and other earlier decisions such as Draco A.B.’s Application (1996).

This document (and any information accessed through links in this document) is provided for information purposes only and does not constitute legal advice. Professional legal advice should be obtained before taking or refraining from any action as a result of the contents of this document.