Patent Dispute Escalates as Merck and Halozyme Clash Over Injectable Keytruda

Merck & Co. and Halozyme Therapeutics are locked in an intensifying patent battle over the subcutaneous formulation of Keytruda, Merck's blockbuster cancer drug. The dispute centers on the use of hyaluronidase enzymes, which enable the conversion of intravenous drugs into injectable versions.

Legal Challenges and Patent Claims

Merck has filed petitions with the U.S. Patent and Trademark Office (USPTO) seeking to invalidate seven of Halozyme's patents related to its Mdase enzyme technology. The pharmaceutical giant argues that these patents are overly broad and should not have been granted. Halozyme, in turn, alleges that Merck's new formulation of Keytruda infringes on its patent portfolio, which includes approximately 100 patents with protection extending into 2032 in Europe and 2034 in the U.S.

Helen Torley, CEO of Halozyme, expressed confidence in the company's position during the TD Cowen 45th Annual Healthcare Conference. "We can come at this from a very strong [position of] strength," Torley stated, citing Halozyme's two decades of experience in developing hyaluronidases.

Merck, however, maintains that its subcutaneous Keytruda formulation does not infringe on Halozyme's patents. A Merck spokesperson asserted, "We strongly believe any Halozyme patents that attempt to cover this variant are invalid," adding that the company has "confidence in our legal position."

Strategic Importance of Subcutaneous Keytruda

The development of an injectable version of Keytruda is crucial for Merck as it seeks to extend the drug's market dominance beyond the expiration of its intravenous formulation's patent protection in 2028. Keytruda was the highest-selling drug worldwide last year, generating nearly $30 billion in sales.

Merck CEO Rob Davis announced plans to launch the subcutaneous formulation in 2025, following positive Phase III trial results in November 2024. The company projects that up to 40% of Keytruda patients could switch to the injectable version within two years of its approval.

The new formulation is particularly targeted at patients with early-stage cancers and indications where Keytruda is combined with oral therapies. Merck estimates these uses will represent about 50% of the total Keytruda patient population by 2028.

Potential Resolutions and Industry Implications

Halozyme is currently seeking a licensing agreement with Merck, proposing a milestone-royalties structure with royalty rates ranging from 3% to 7%. However, if negotiations fail, Halozyme's general counsel Mark Snyder indicated the company is prepared to seek an injunction to prevent Merck from selling subcutaneous Keytruda.

The dispute highlights the increasing importance of drug delivery technologies in the pharmaceutical industry. Halozyme's Enhanze platform has already been successfully incorporated into products from other major pharmaceutical companies, including Bristol Myers Squibb's subcutaneous version of Opdivo, which received FDA approval in late 2024.

As the legal battle unfolds, the outcome could have significant implications for both companies and the broader pharmaceutical landscape, potentially influencing future collaborations and patent strategies in drug formulation development.