EU Parliament Adopts SPC Reform Proposals: Clarifying the Protection Scope for Biologics

Introduction 

The SPC is a pivotal instrument in the European intellectual property landscape. It serves to extend the protection of patented products, particularly those which, due to the lengthy regulatory approval processes, encounter truncated commercial life.

The previous reform of the SPC regime introduced a manufacturing waiver for generics and biosimilars. Coupled with the UPC's comprehensive oversight of SPC issues, this has amplified the intricacy and diversity of the EU's existing SPC framework. The 2023 proposals stem from lengthy consultations, with a notable reference to a 2018 study by the Max-Planck-Institut für Innovation und Wettbewerb ("MPI"). The study proactively highlighted legal uncertainties surrounding the SPC scope for biologics in the current system. Moreover, there's a discernible lack of case law evolution on this subject, creating challenges for stakeholders in this field. The latest proposals attempt to address the aforementioned concern.

For chemical substances, it is clear that the SPC covers all variants of the active part such as salts or enantiomers falling within the scope of the basic patents, irrespective of the particular form which is the subject of the marketing authorization. However, holders of SPCs for biologics face two legitimate concerns: (i) the SPC does not adequately identify the biological active substance or its variations that can be put on the market under the marketing authorization; (ii) the active ingredient of a biosimilar could be sufficiently similar to that of the reference medicine to permit its marketing, while sufficiently different to lie outside of the scope of the SPC, which would be contrary to the purpose of SPC to delay competition. The recent changes to the EU SPC regulatory framework and pertinent case law have instigated discussions about the scope of SPCs, particularly concerning biological medicinal products and their biosimilars. Here, we recapitulate the comprehensive overview of these developments.

Key Considerations Behind the Scenes

Partly due to the limited number of active substances that have been subjected to biosimilar production, at the time of writing, there's very few case law regarding the scope of an SPC for biologics, especially in the context of biosimilars. In most cases, biosimilars were launched in markets without SPC protection, or after SPC expiry. This very preliminary experience, according to MPI, could be interpreted as indicating that "biological SPCs are achieving their intended effect of delaying generic/biosimilar entry until after SPC expiry". It is clear that there are at least minor differences, particularly in glycosylation patterns, between the active substance of the reference product and that of the biosimilar. According to MPI's observation, irrespective of these minor differences, the biosimilar in each case identifies the same active substance in terms of INN as the reference medicinal product.

Structural differences between the active substances and their relevant reference products (Grampp and Ramanan, Amgen)

However, using the same INN for the active substance of both biosimilars and reference products could mask potential clinical differences. It is argued that biosimilars shouldn't be considered as having the "same" active substance as their reference products or other biosimilar counterparts due to varied quality attributes. Addressing this, the World Health Organization suggests a "Biological Qualifier," or BQ, alongside INNs to uniquely identify biological substances, aiding medicine prescription, dispensing, and transfer. Yet, its efficacy in solving SPC-related issues for biologicals is uncertain. The core issue remains unresolved: How different must a biological active substance be to fall outside an SPC's scope based on the first authorization with the same INN?

Defining the scope of an SPC for biological substances is challenging due to their inherent variability. The MPI study used different epoetin glycoforms and sequence variants to illustrate this issue: alfa (reference), theta (stand-alone, no biosimilarity established), zeta (biosimilar), and darbepoetin (a biobetter with a different amino acid sequence and improved properties).

Scope of the SPC: Biological Substance, Biobetters and Biosimilars

An SPC for epoetin alfa clearly cannot cover darbepoetin due to its distinct sequence and properties. Some argue the SPC should cover only the biosimilar, given that its authorization was secured through comparison with the reference product under Art. 10(4) Dir. 2001/83. But there is provision within Art. 4 of the SPC Regulation suggesting that the scope of an SPC should be limited by the regulatory pathway through which the potential infringing product entered the market.

In the given example, a strict interpretation of Article 4, in conjunction with Recital 10—which mandates that the protection granted be "strictly confined to the product which obtained authorization to be placed on the market"—would appear to exclude epoetin zeta and theta from the scope of an SPC for epoetin alfa (or beta). Such an interpretation would significantly diminish the relevance of SPCs for biologicals, which clearly is not the intent of Article 4 of the SPC Regulation. The MPI study accordingly proposed a practical solution to interpret the scope of SPC protection as covering products with the same INN, and ignoring the glycoform, which aligns with the effect of the approach for chemical substances in the early Court of Justice of the European Union ("CJEU") decision in Farmitalia (CJEU, 16 Sep 1999, C-392/97, ECLI:EU:C:1999:416).

The Resolution

The initial proposal suggested in its new Recital 11 that the scope of an SPC should encompass "therapeutically equivalent derivatives of that product, such as salts, esters, ethers, isomers, mixtures of isomers or complexes, as well as biosimilars, even where such derivatives are not explicitly mentioned in the product description on the certificate." However, JURI removed this recital in its report to the plenary, citing that it was confusing due to its implicit reference to the doctrine of equivalents—a principle that varies from country to country and is challenging to standardize. This amendment likely dampened the enthusiasm of patent proprietors who favored a broader SPC scope, as they saw the potential expansion curtailed.

Additionally, the legislative resolution, in line with the initially proposed Recital 13, emphasizes again the significance of International Nonproprietary Names (INN) in determining the SPC's protective scope: "Where the marketing authorization submitted in support of the application for a certificate for a biological medicinal product identifies that product by means of its International Nonproprietary Name (INN), the protection conferred by the certificate should extend to all biosimilars having the same International Nonproprietary Name as the product referred to in the marketing authorization, irrespective of possible minor differences between a subsequent biosimilar and the product authorized, which are usually unavoidable given the nature of biological products." This new recital appears to encapsulate recent CJEU rulings with respect to the interpretation of Article 3 of the current SPC regulation.

The resolution heralds a future with a more transparent and structured SPC regime for the EU. By addressing the gray areas around the SPC scope for biologics and advocating a standardized approach through the INN nomenclature, the Commission aims to alleviate challenges faced by stakeholders. Furthermore, the impact of these new recitals could undoubtedly have a substantive and far-reaching impact which may extend beyond the EU's boundaries, as other EPC member states will closely monitor the developments given their indispensable roles on the SPCs.