Halozyme announced on October 7 that the specialized patent court in The Hague had found EP622 valid and infringed by Merck’s subcutaneous Keytruda. MSD BV, Merck’s central European marketing authorization holder, can no longer manufacture, offer, import or stock Keytruda SC in Belgium, Denmark, France, Ireland, Italy, Sweden, Switzerland or the Netherlands. Germany has been blocked since a preliminary injunction in December 2025. Intravenous Keytruda isn’t touched by the patent or the order. Merck told FirstWord it strongly disagrees and is evaluating next steps.
What the court actually ordered #
According to Halozyme’s release, the order also bars MSD from helping affiliates infringe, including through use of its European marketing authorization. The court rejected Merck’s arguments that EP622 is invalid.
The Dutch case has a short history. In July, the same court turned down a separate Halozyme request for a preliminary injunction covering Denmark and Sweden, reasoning that Halozyme had less far-reaching options, such as seeking an injunction on the merits. Merck’s 10-Q shows that Halozyme had added the other seven countries by counterclaim in February 2026. The October ruling is the merits decision that followed.
Why the timing matters to Merck #
Keytruda earned about $29.5 billion in 2024, close to half of Merck’s revenue. The core US compound patent expires in 2028, and European market exclusivity is expected to run to about 2031, according to Fierce Pharma and Labiotech.
The subcutaneous version is Merck’s way of moving patients to a new presentation before biosimilars arrive. The FDA approved it in September 2025 as Keytruda Qlex, and the European Commission has approved Keytruda SC across all 33 adult indications. A blocked launch in Europe doesn’t threaten the 2028 US date, but it does shorten the runway Merck has to convert European clinics before 2031.
The formulation problem #
Subcutaneous tissue is packed with hyaluronan, a gel-like polymer that resists bulk flow and limits conventional injections to a few millilitres. Co-formulating an antibody with a hyaluronidase temporarily breaks the hyaluronan down, so a larger volume can disperse and absorb. The effect fades as the matrix regenerates.
The US prescribing information lists 395 mg in 2.4 mL over one minute every three weeks, or 790 mg in 4.8 mL over two minutes every six weeks. The IV regimen is 200 mg every three weeks or 400 mg every six weeks, given over about 30 minutes.
Two enzymes, one dispute #
Halozyme’s ENHANZE platform (rHuPH20) sits behind Darzalex Faspro, Ocrevus Zunovo, Phesgo and Vyvgart Hytrulo. Merck went another way and licensed Alteogen’s berahyaluronidase alfa (ALT-B4). Korean press reports that Alteogen could receive up to $1 billion in sales milestones plus royalties.
Halozyme’s MDASE patents come from a separate research program. The company says it involved nearly 7,000 modifications to human hyaluronidases, and it says it does not expect the Merck litigation to affect ENHANZE licensing. Merck’s position, stated when the suit began, is that its enzyme was developed independently and that Halozyme’s patents are invalid.
A split scoreboard #
| Party | Europe | United States |
|---|---|---|
| Halozyme | Preliminary injunction in Germany (Dec 2025); merits injunction in the Netherlands (Oct 2026), with validity upheld | Suing in New Jersey over 15 MDASE patents |
| Merck | Invalidity actions pending in Germany, the UK and France | PTAB invalidated US 11,952,600 on May 12, 2026; 15 PGRs and 3 IPRs filed in total |
Keytruda Qlex remains on sale in the US. US courts don’t order injunctions automatically after an infringement finding, so a Halozyme win there could well end in damages or royalties rather than a market block. European patent courts tend to move faster toward an injunction once a patent is held valid and infringed. That difference helps explain why the same enzyme dispute looks so different on either side of the Atlantic. This is our reading, not a point from the sources.
What to watch #
One PTAB win is not a pattern. Merck needs more of its challenges to land, and it needs a Dutch appeal or a German Federal Patent Court ruling that goes its way. Halozyme, for its part, has shown it will pursue the same patent country by country, so the real question is whether the pressure ends in a license.
Takeaway for formulation teams #
If your high-volume subcutaneous antibody depends on a hyaluronidase, freedom-to-operate around enzyme sequence variants now deserves the same attention as viscosity and protein stability.
Sources #
- Halozyme press release, October 7, 2026: PR Newswire — Halozyme Wins Injunction Stopping Manufacture and Sale of Merck's Keytruda SC in Multiple European Markets
- FirstWord Pharma: FirstWord Pharma Coverage (Story #8173641)
- Pearce IP on the July Hague decision: MSD Defeats Halozyme's Preliminary Injunction Application in Denmark & Sweden (July 14, 2026)
- Pearce IP on the PTAB decision: MSD Invalidates US Halozyme Patent in SC Pembrolizumab Dispute (May 12, 2026)
- Merck Form 10-Q, Q2 2026: SEC EDGAR Filing (mrk-20260630.htm)
- Fierce Pharma on Keytruda patent timing: Merck Expects Keytruda to Fall to IRA Price Cuts & 2028 Exclusivity
- Merck’s FDA approval release for Keytruda Qlex: BusinessWire — FDA Approves Merck's KEYTRUDA QLEX (Sept 19, 2025)
