CJEU Advocate General in Halozyme C-456/24: An Excipient Cannot Be Treated as an Active Ingredient for SPC Purposes

The Court of Justice of the European Union’s Advocate General has issued an opinion in Halozyme, Case C-456/24, concluding that a substance expressly designated as an excipient in a medicinal product’s marketing authorisation cannot be treated as an active ingredient under the EU’s Supplementary Protection Certificate (SPC) Regulation. If the CJEU follows the opinion, Halozyme’s strategy of layering SPC protection across European markets on top of subcutaneous formulations that combine an active drug with rHuPH20 will lose its legal foundation in most major jurisdictions, with the limited Austrian and German grants standing as outliers. The opinion bears directly on a central commercial question in biopharma: when can a delivery enzyme bundled into a subcutaneous formulation extend the patent monopoly?

The SPC application at the heart of the case combines trastuzumab with rHuPH20 (recombinant human hyaluronidase PH20), relying on European patent EP 2 163 643 and the marketing authorisation for Herceptin SC (also marketed as Herceptin Hylecta). Herceptin SC is a subcutaneous reformulation of Roche/Genentech’s trastuzumab made possible by Halozyme’s ENHANZE platform, in which rHuPH20 transiently degrades hyaluronic acid in the subcutaneous space to allow rapid uptake of co-administered biologics. National IP offices have split on whether rHuPH20 qualifies as an active ingredient: Germany and Austria granted the SPC; France, the Netherlands and Ireland refused it under Article 3(d) of the SPC Regulation.

The reference to the CJEU came from the Czech Republic. After the Czech IP office refused the SPC application under Article 3(d), Halozyme appealed to the Supreme Administrative Court, which then referred six questions on the interpretation of Article 1(b) of Regulation (EC) No 469/2009. Article 1(b) defines the “product” eligible for an SPC as the active ingredient or combination of active ingredients of a medicinal product. The Advocate General’s opinion focuses on the first and most decisive question.

The answer is direct: a substance designated as an excipient in the marketing authorisation cannot be regarded as an active ingredient for SPC purposes. The Advocate General reasons that active-ingredient status must be determined by the classification of the substance in the relevant marketing authorisation, and that scientific findings that emerge after the marketing authorisation—findings not part of the regulator’s underlying assessment—should not be admitted to reclassify a substance for SPC purposes.

The reasoning is consistent with the SPC system’s design. SPCs exist to compensate for time lost to regulatory review. To preserve predictability, the entitlement determination must rest on an authoritative, public document fixed at the time of authorisation. Allowing post-hoc scientific debate to reopen the active-ingredient question would inject uncertainty into the SPC’s gateway test and undermine the regulatory bargain.

The case also turns on Article 3(d) of the SPC Regulation, which conditions SPC grants on a “first marketing authorisation” requirement. If rHuPH20 is not an active ingredient, then Herceptin SC is not a first authorisation for a new product but a later authorisation of trastuzumab in a different formulation. Trastuzumab itself already had a first marketing authorisation as intravenous Herceptin, so Halozyme would not be able to use Herceptin SC as the SPC-eligible “first authorisation.” That structural argument is what closes the door on the Halozyme SPC strategy across the EU if the CJEU adopts the Advocate General’s view.

The CJEU is not bound by the Advocate General’s opinion, but the Court frequently follows it. A judgment along these lines would also raise difficult questions about the previously granted Austrian and German SPCs. As a matter of national procedure, retroactive revocation is not straightforward, but competitors would have stronger arguments in revocation or invalidity proceedings against those national rights.

The implications extend well beyond Halozyme and Roche. Subcutaneous reformulation has become a major lifecycle-management lever in biopharma, combining patient-friendly delivery with effective extension of commercially meaningful exclusivity for biologics whose primary patents are running out. Merck’s subcutaneous Keytruda program and several other co-formulations developed with delivery-enzyme partners such as Alteogen depend on related strategies. If the enzyme used to enable subcutaneous administration is not an “active ingredient” for SPC purposes, the legal value of those reformulations in Europe is materially reduced. Companies will need to reassess how SPC protection layers onto their lifecycle strategies and whether alternative tools—formulation patents, regulatory exclusivities, biosimilar litigation strategy—must do more of the work.

For Halozyme specifically, an adverse CJEU ruling would mark a setback in Europe, even as separate litigation continues in U.S. federal court and at the PTAB over its disputes with Merck on Keytruda SC. Different legal frameworks mean a European loss would not automatically determine global outcomes, but it would significantly narrow the company’s IP runway in the EU. Industry observers are watching for the final judgment, which will also speak more generally to the boundary between regulatory classification and patent law’s “product” concept—an interface that recurs in patent-term-extension regimes around the world.

Sources:
– Opinion of Advocate General, Case C-456/24 Halozyme (non-binding)
– IAM Media, “Halozyme suffers setback in Keytruda patent battle with Merck; receives adverse AG opinion at CJEU,” May 15, 2026
– Mondaq / J A Kemp LLP, “Advocate General Of The CJEU Indicates That An ‘excipient’ Cannot Be Regarded As An Active Ingredient For An SPC,” April 28, 2026
– Regulation (EC) No 469/2009 Articles 1(b), 3(d)