Halozyme sues Merck over subcutaneous Keytruda

Halozyme is not holding back against Merck & Co. in the companies' injectable Keytruda patent dispute, having now escalated a verbal warning into a lawsuit.

In a lawsuit filed Thursday in a New Jersey federal court, Halozyme alleges that a proposed subcutaneous formulation of Merck’s popular cancer drug Keytruda infringes 15 of its patents.

Those intellectual properties belong to a Halozyme patent family called Mdase, which covers a large group of modified human hyaluronidases. A hyaluronidase protein may allow for under-the-skin administration of otherwise intravenously infused drugs.

Halozyme is seeking an injunction to block Merck’s planned commercialization of subcutaneous (SC) Keytruda, which is under FDA review with a decision expected by Sept. 23. The San Diego drug delivery expert is also asking for monetary relief and “an enhancement of damages,” because the alleged infringement is said to be willful, according to its complaint.

Even though SC Keytruda has not reached the market, Merck opened itself to patent litigation after publicly laying out its intention to launch the product this year pending FDA approval.

The lawsuit comes after Halozyme reached out to Merck for a potential licensing deal and publicly warned that a lawsuit may follow if the two sides couldn’t reach an agreement. That pathway has apparently hit a dead end, as Halozyme now accuses Merck of planning to launch SC Keytruda while “knowingly infringing” on Halozyme’s Mdase patents.

“We believe this suit is meritless, and we are confident in our legal position,” Merck said in a statement to Fierce Pharma.

To make its SC Keytruda, Merck is using a hyaluronidase called berahyaluronidase alfa, or ATL-B4, from South Korean company Alteogen. The platform has become increasingly popular among pharma companies, as AstraZeneca and Daiichi Sankyo have also signed up to develop subcutaneous versions of their cancer drugs.

Merck has argued that ALT-B4 was independently developed by Alteogen and that its sequence is not disclosed in any Halozyme patent.

The New Jersey pharma is challenging seven of the Mdase patents with the U.S. Patent and Trademark Office. However, the outcome of that proceeding won’t affect Halozyme's lawsuit, which claims infringement of a broader range of patents.

Halozyme is best known for its Enhanze subcutaneous delivery technology based on the recombinant human hyaluronidase PH20 enzyme. As the company studied PH20, its scientists created a library of more than 6,700 additional proteins with modified amino acid chains. That library and further research led to the Mdase portfolio of patents starting in 2016.

Although ATL-B4 itself is not in Halozyme’s library, the company claims that many amino acid modifications used in the Alteogen product are actually covered by those 15 Mdase patents.

Merck has been aware of Halozyme’s work on PH20s since at least 2009, when the two first had collaboration discussions, according to the complaint. In 2015, Halozyme shared with Merck its ability to subcutaneously deliver Keytruda. During those negotiations, Merck became aware of Halozyme’s patent plans covering modified PH20s.

“Merck has refused to find a resolution to its infringement with Halozyme, such that a definite and concrete controversy now exists” between the two companies, Halozyme said in the complaint.

Merck developed SC Keytruda to help bolster the top-selling cancer immunotherapy when the original intravenous infusion formulation falls off the patent cliff in 2028. The company hopes to convert about 30% to 40% of patients to the protected SC version within the first two years of launch.

Halozyme filed the lawsuit as Merck reported its first-quarter 2025 financial results Thursday. Keytruda sales during the three months grew 4% year over year to $7.2 billion.

The lawsuit doesn’t affect Halozyme’s Enhanze program or Merck’s original Keytruda.