Could Alteogen Patent Dispute Spread Beyond Keytruda? Dutch Ruling Offers Clues

Court: "Halozyme's Patent Covers the Enzyme Itself"
Lawyer: "Changing a Drug's Ingredients or Formulation May Not Be Enough to Work Around the Patent"
Concerns Over Disputes Spreading to Partners... Need to Review Response Plans

There are concerns that the patent dispute over Alteogen's subcutaneous (SC) formulation technology could spread beyond Merck (MSD)'s Keytruda SC (U.S. brand name: Keytruda Qlex) to products made by other global pharmaceutical companies. The concern stems from a Dutch court's decision to assess patent infringement based on Alteogen's enzyme, ALT-B4, itself rather than the finished drug, potentially exposing other medicines that use the same enzyme to disputes in Europe.

Merck (MSD)'s immunotherapy drug Keytruda in a subcutaneous (SC) formulation. Its U.S. brand name is Keytruda Qlex. MSD

According to the October 7 ruling by the District Court of The Hague in the Netherlands, in the patent infringement lawsuit Halozyme brought against MSD, the court held that Halozyme's patent protects the enzyme itself, not the drug. Accordingly, the court found that Keytruda SC, which contains Alteogen's enzyme ALT-B4, infringes the patent and ordered a ban on its sale.

Halozyme had previously sought a ban on Keytruda SC sales based on its patent for an "enzyme that remains stable even in the presence of preservatives," while MSD countered that Keytruda SC contains no preservatives and therefore is not covered by the patent. In this ruling, however, the court found that regardless of whether preservatives are present, infringement occurs if Alteogen's enzyme ALT-B4 meets the patent's requirements. A lawyer specializing in pharmaceutical and biotech patents in South Korea said, "The key point in this ruling is that the court broadly interpreted the scope of Halozyme's claims, which protect the enzyme itself, while also upholding the patent's validity and finding that ALT-B4 meets the patent's requirements."

The court relied on tests comparing the stability of the enzymes themselves. In tests Halozyme commissioned from a Korean research lab, Alteogen's enzyme product Tergase retained 92.76% of its function after four hours of exposure to preservatives, while Halozyme's product retained just 44.90%. Based on these results, the court found that ALT-B4 had the preservative stability required by the patent.

If this ruling stands, Halozyme's infringement claims could extend to products made by other partners that use ALT-B4. The lawyer, who reviewed the ruling, added, "It would be difficult to avoid this patent simply by changing the antibody used in the formulation or the final formulation," and said, "The need to review provisions in existing agreements on responding to patent disputes, bearing costs and damages, and handling delays to product launches could grow."

Alteogen has licensing agreements for ALT-B4 with 10 global pharmaceutical companies. Its partners are developing products that use ALT-B4, including Enhertu, Dupixent and Jemperli. Most of these products are still in clinical development and are not immediate targets for lawsuits. However, because switching to an SC formulation takes a relatively short time, some analysts say products launched in Europe before Halozyme's patent expires in December 2032 could face the same dispute as Keytruda SC.

The sales ban ordered by the court applies in eight European countries and remains in effect even if an appeal is filed. In the seven countries other than the Netherlands, however, the ban will be lifted if the court in that country rules at first instance that the patent is invalid.

The lawyer said, "The court of first instance rejected the invalidity claim, but given the patent's broad scope, whether the specification sufficiently describes the technology needed to support it will remain an issue in subsequent proceedings." Germany's Federal Patent Court has already issued a preliminary opinion that the patent is valid. MSD is pursuing invalidity lawsuits in France, Denmark, Sweden and Switzerland.

In the United States, MSD has won a series of challenges to invalidate Halozyme's patents. These proceedings are conducted by the Patent Trial and Appeal Board (PTAB), an agency under the U.S. Patent and Trademark Office, and examine only whether a patent was valid in the first place. Courts decide whether infringement occurred and whether to ban sales. The U.S. District Court for the District of New Jersey paused an infringement lawsuit Halozyme filed in April last year in August this year. This is because patents finally invalidated by the PTAB cannot be used in court litigation.

The key factors ahead are the invalidity lawsuits in various European countries and the appeals. The appeal hearing on the German preliminary injunction is scheduled for November 19, while the New Jersey court will discuss whether to resume the lawsuit on November 23. MSD said it is reviewing its response options.

Another key question is whether partner products will be launched in Europe before the patent expires. Alteogen maintains that its ALT-B4 business is not limited to any particular product or region.

This content was produced with the assistance of AI translation services.