Halozyme patent injunction blocks under-the-skin Keytruda in eight European markets
A Dutch court found that Merck's subcutaneous Keytruda infringes Halozyme's EP622 drug-delivery patent. The order does not cover intravenous Keytruda, and Merck says the patent is invalid and it is evaluating its next steps.
The story
A specialized Dutch patent court has ordered Merck to stop specified activities involving the subcutaneous version of Keytruda in eight European markets after finding infringement of a Halozyme drug-delivery patent. Halozyme announced the October 7 decision, and Reuters independently reported the ruling and Merck's opposition. The order affects Keytruda SC in Belgium, Denmark, France, Ireland, Italy, Sweden, Switzerland and the Netherlands. It does not stop access to the established intravenous version of Keytruda.
The patent at the center of the case is European patent EP 2,797,622, commonly shortened to EP622. Its title covers PH20 polypeptide variants, formulations and uses. PH20 is a form of hyaluronidase, an enzyme that acts on hyaluronan in the tissue beneath the skin. Modified versions can help a comparatively large volume of a biologic medicine disperse after an under-the-skin injection. Halozyme calls the relevant portfolio MDASE and says the inventions resulted from studying thousands of modifications to human hyaluronidases.
According to Halozyme, the court found both that Merck infringed EP622 and that Merck's invalidity arguments failed. The injunction directs MSD BV—Merck's central European marketing-authorization holder and global packaging and distribution hub—to refrain from manufacturing, arranging manufacture, offering, marketing, using, importing or stocking Keytruda SC for the covered purposes. It also bars MSD BV from facilitating infringement by affiliates, including through use of the European marketing authorization.
The scope matters. Keytruda, or pembrolizumab, is an antibody that blocks the PD-1 immune checkpoint, helping T cells recognize and attack certain cancers. The traditional product is given by intravenous infusion. Keytruda SC combines pembrolizumab with berahyaluronidase alfa, an enzyme supplied through Merck's relationship with South Korea's Alteogen, to permit subcutaneous delivery. The European Commission approved the under-the-skin formulation in November 2025. The patent order targets that delivery configuration, not pembrolizumab as a cancer treatment and not the IV product.
Merck rejects the result. A company spokesperson told Reuters that Merck strongly disagrees with the cross-border injunction, considers Halozyme's patent invalid globally and regards the infringement allegation as meritless. Merck said it is evaluating next steps. The public statements do not establish whether an appeal will automatically suspend the order, so the injunction should not be described as the final resolution of the multinational dispute.
The litigation already extends beyond the Netherlands. Halozyme obtained a preliminary injunction in Germany in December 2025 that stopped the German launch of Keytruda SC; Merck's appeal is scheduled for November 19, 2026. Halozyme has also sued in US federal court in New Jersey, alleging infringement of 15 MDASE patents by the product marketed there as Keytruda Qlex. Merck has challenged related US patents at the Patent Trial and Appeal Board and filed revocation actions against EP622 in several European countries.
Those parallel cases make the patent landscape less uniform than the new order may suggest. Merck's latest quarterly filing says Halozyme consented to revocation of the UK part of EP622 in May, while the Dutch court has now rejected Merck's validity arguments for the markets before it. Patent rights are territorial, and claim wording, procedural posture and the evidence considered can produce different outcomes even within the same patent family. A Dutch cross-border injunction is therefore consequential without settling every validity and infringement question worldwide.
INNOVOX analysis: the case is a reminder that lifecycle innovation in biologic drugs creates a second contest over delivery technology. Keytruda's active ingredient is already clinically and commercially established. The new value proposition is convenience: replacing a longer infusion workflow with a rapid injection can reduce chair time and change how hospitals deploy staff and facilities. But that improvement depends on an additional enzyme technology, turning a formulation change into a high-stakes patent boundary.
The commercial stakes also extend beyond immediate sales. Merck is preparing for key patents on intravenous Keytruda to expire later in the decade, and a differentiated subcutaneous formulation is part of its strategy for maintaining the franchise. Halozyme, meanwhile, licenses other hyaluronidase technology to pharmaceutical partners, although it says the MDASE patents in this dispute are distinct from its ENHANZE licensing program. The ruling does not assign a royalty, require a license or disclose settlement terms; it imposes a market restriction unless later proceedings alter it.
What to watch next is whether Merck seeks rapid appellate relief and how the eight markets implement the order across packaging, distribution and local launches. The November German appeal will provide another near-term signal, while the US case and Patent Trial and Appeal Board proceedings will test related rights under a different legal system. For patients and clinicians, the immediate distinction remains simple but important: the injunction concerns the under-the-skin product in named markets, while intravenous Keytruda remains available.
INNOVOX analysis
The decision shows that drug-delivery intellectual property can be as commercially important as the medicine's active antibody. Moving an established biologic from an infusion chair to a rapid under-the-skin injection may create a differentiated product, but it also introduces a separate layer of enzyme and formulation patents that can determine where the new version launches.
What to watch
Watch for an appeal or request to suspend enforcement, country-level implementation of the Dutch order and the November hearing in Merck's German appeal. The larger test is whether courts in different jurisdictions reach consistent conclusions on EP622's validity and whether the US patent proceedings produce a different result.