Excipients ineligible for EU supplementary protection certificates, says court adviser

Excipients are inactive substances formulated alongside active pharmaceutical ingredients to aid in drug delivery, stability, and manufacturing. The Court of Justice of the EU (CJEU) has been asked to determine whether excipients can themselves be classed as active ingredients – a question that goes to the heart of their eligibility for EU SPCs.SPCs enable pharmaceutical patent holders to effectively extend the period for which they can exercise monopoly rights over the sale of medicinal products they have invested a lot of time and money into developing. They are specifically provided in EU – and UK – law to reflect the fact that some of the period during which patents might be relied upon to realise value from the monopoly they confer can be lost owing to delays pharmaceutical companies face in first clearing the regulatory process.

SPCs are only available for ‘products’ that fall within the scope of, and meet eligibility criteria set out in, the SPC Regulation. To be eligible for an SPC, certain criteria set out in Article 3 of the SPC Regulation must be satisfied, namely the product must be “protected by a basic patent in force” (Article 3(a)); a marketing authorisation must have been issued to place that product on the market as a medicinal product  (Article 3(b)); the product must not already have been the subject of an SPC  (Article 3(c)); and the marketing authorisation relied on must be the first to place the product on the market as a medicinal product  (Article 3(d)). For the purposes of SPC law, a product is defined as the active ingredient or combination of active ingredients of a medicinal product (Article 1(b)).

In a referral from the Czech Supreme Administrative Court, the CJEU has been asked to determine whether a substance described as an excipient in the marketing authorisation a pharmaceutical company seeks to rely on in an SPC application can qualify as an ‘active ingredient’ and therefore form part of a ‘product’ for the purpose of SPC protection, and whether the classification of a substance in the marketing authorisation is determinative in that regard.

The questions have arisen in the context of a dispute between US biotech company Halozyme, Inc. and the Industrial Property Office in Czechia.

Halozyme has combined recombinant human hyaluronidase PH20 (rHuPH20) – an enzyme found to have properties helpful to the administration of drugs in patients – with trastuzumab, a monoclonal antibody manufactured by Roche that is used as an active substance in cancer treatment and that is sold under the brand name Herceptin.

In 2013, Roche was granted an extension of its marketing authorisation for trastuzumab to cover its combination with rHuPH20. In the marketing authorisation documentation, rHuPH20 is classified as an excipient and described as a ‘novel excipient’.

However, in filing for an SPC to extend the term of its patent protecting rHuPH20, Halozyme described rHuPH20 as an active ingredient. The Czech Industrial Property Office rejected the application, partly because rHuPH20 had been classified as an excipient in the Roche marketing authorisation that Halozyme relied on.

The CJEU has previously considered what constitutes an active ingredient. It has determined that a substance is only an active ingredient if it exerts a therapeutic effect of its own on the human or animal body. Both the Industrial Property Office in Czechia and the Prague City Court on appeal considered that Halozyme had failed to demonstrate that rHuPH20 has an anti-cancer effect of its own.

However, Halozyme has lodged an appeal against the Prague court’s ruling before the Supreme Administrative Court in Czechia, which in turn has asked the CJEU to help it interpret EU law so it can determine the outcome of the dispute before it.

Before the CJEU formally rules on the case, an adviser to the court, advocate general Nicholas Emiliou, has considered the questions the case raises and issued his non-binding opinion on them.

The advocate general said that a substance expressly designated as an excipient in the marketing authorisation relied upon for an SPC application cannot be regarded as an ‘active ingredient’ for the purposes of Article 1(b) of the SPC Regulation. He rejected an approach that would permit reclassification of an excipient as an active ingredient by reference to studies outside the marketing authorisation dossier.

In reaching this view, the AG emphasised that the SPC system is intrinsically linked to the regulatory framework for medicinal products and, in particular, the Medicinal Products Directive. Since SPCs extend patent protection to compensate for regulatory delays, the regulatory assessment in the marketing authorisation, he considered, must be decisive in determining what constitutes the active ingredient.

In this respect, the advocate general highlighted that excipients are not subject to the same level of scrutiny or regulatory burden as compared with new active ingredients. This, he considered, distinguishes them from the products that the SPC regime is designed to protect because the type of the delay the SPC regime seeks to compensate does not arise.

Charlotte Weekes and Catherine Drew of Pinsent Masons said the opinion highlights the importance of a coordinated IP and regulatory strategy for pharmaceutical companies.

Drew, an expert in medicines regulation, said: “There is a lack of clear guidance on how the concept of ‘product’ in the SPC Regulation is to be interpreted. This has led to divergence across the EU. Decisions favourable to Halozyme have been adopted in Belgium, Bulgaria, Spain, Italy, Cyprus, Luxembourg, Poland and Slovenia, whereas the French, Dutch and Swedish competent authorities have rejected its SPC applications. The High Court in England and Wales also upheld the UK Intellectual Property Office’s decision to refuse Halozyme’s SPC applications.”

“With that in mind, the advocate general emphasised the need for the SPC regime to provide a simple and transparent system which can be applied uniformly across member states. Requiring national patent offices to look behind the marketing authorisation and effectively undertake a new substantive assessment of the substance would be at odds with this aim and would continue to lead to different outcomes across Europe,” she said.

Weekes, who specialises in resolving disputes over pharmaceutical patents and SPCs, said: “The advocate general is proposing a strict, marketing authorisation-centric approach, and suggests that external scientific publications and studies undertaken after the granting of the marketing authorisation would not justify disregarding the classification in the marketing authorisation even if they demonstrate the excipient functions comparably to an active ingredient.  He said that SPCs are intended to protect investment into research leading to the granting of the marketing authorisation in the first place, so scientific findings that emerge after grant, and which did not form part of its assessment, should not be taken into account for the purposes of granting an SPC.”

“While the CJEU is not bound to follow the advocate general’s proposals, in this case there is a strong possibility that it may do so, particularly as the European Commission and all national governments submitted observations which supported this approach.”

“This would provide certainty and promote harmonisation but may be criticised for limiting the availability of SPCs where novel excipients have been identified following extensive R&D,” Weekes said. 

The CJEU’s ruling is expected later in 2026. If the advocate general’s reasoning is followed, because rHuPH20 cannot be treated as an active ingredient, the “product” for the purposes of SPC protection is only the antibody, and as that was subject to an earlier marketing authorisation, Halozyme’s SPC application would fail the “first authorisation” requirement under Article 3(d) of the SPC Regulation.

What constitutes a ‘product’ for the purposes of the SPC Regulation is set to be further considered by the CJEU in a case referred to it from Denmark (16-page / 474KB PDF). In that case, the main issue the CJEU is expected to address is whether a derivative of a known active ingredient can constitute a new product and, if so, in what circumstances.