Merck Faces Patent Challenge Over Keytruda Qlex as PTAB Institutes Seven Post-Grant Reviews
Key Insights
The USPTO's Patent Trial and Appeal Board has instituted seven post-grant reviews challenging Halozyme's patents related to modified PH20 hyaluronidase (search) polypeptides used in Merck's recently approved Keytruda Qlex (search).
Merck filed 14 patent challenges beginning in November 2024, alleging that Halozyme's patents are invalid due to obviousness, lack of written description, and enablement failures.
The patent dispute centers on modified polypeptides that exhibit increased stability and activity, with concurrent litigation ongoing in New Jersey federal court.
Merck Sharp & Dohme faces a significant patent challenge over its recently approved cancer (search) immunotherapy Keytruda Qlex (search), as the USPTO's Patent Trial and Appeal Board (PTAB) has instituted seven post-grant reviews (PGRs) targeting key patents owned by Halozyme, Inc.
The patent dispute began in November 2024 when Merck requested post-grant review of 14 patents owned by Halozyme, with claims directed to modified PH20 hyaluronidase (search) polypeptides. These modified polypeptides exhibit increased stability and/or increased activity and are likely related to Merck's FDA-approved Keytruda Qlex (search) (pembrolizumab and berahyaluronidase alfa-pmph (search)).
PTAB Institution Decisions
The PTAB has systematically instituted reviews across multiple Halozyme patents. On September 8, 2025, the board instituted PGR2025-00017 against Halozyme's U.S. Patent No. 12,110,520. This was followed by additional institutions on October 1-2, 2025, covering patents 12,049,652 and 12,104,185.
The patent challenges expanded further in October 2025, with the PTAB instituting four additional reviews on October 10 and 16. These targeted patents 12,091,692, 12,264,345, 12,060,590, and 12,054,758, bringing the total number of instituted reviews to seven.
Validity Challenges
Merck's petitions allege that the challenged patent claims are invalid on multiple grounds, including obviousness, lack of written description, and failure to comply with enablement requirements. The PGRs assert that the claims encompass a large genus of modified PH20 polypeptides, with examples that are not representative of the full scope of the claimed genus.
In its institution decisions, the PTAB found that evidence better supported Merck's position regarding both written description and enablement challenges. The board determined that the disclosure fails to enable the genus of modified PH20 polypeptides claimed. However, regarding obviousness, the PTAB found that Merck had not shown it was more likely than not to establish that the patents are obvious in light of prior art.
Patent Claim Disclaimers
Prior to the institution decisions, Halozyme strategically disclaimed multiple claims across several patents. For the '520 patent, Halozyme disclaimed claims 3-5, 16, and 31-35. Similar disclaimers were made for other patents, including claims 3-5 and 30-40 of the '652 patent, and claims 5-6 of the '185 patent.
Concurrent Litigation
The patent dispute extends beyond the PTAB proceedings, with one co-pending litigation between Merck and Halozyme in New Jersey federal court, Case No. 2:25-cv-03179 (D.N.J.).
Regulatory and Commercial Context
Keytruda Qlex (search) received FDA approval in September 2025, representing a significant advancement in cancer (search) immunotherapy delivery. The combination therapy pairs pembrolizumab, Merck's blockbuster PD-1 inhibitor, with berahyaluronidase alfa-pmph (search), a modified hyaluronidase enzyme that facilitates subcutaneous administration.
Sales data for Keytruda Qlex (search) is not yet available, given its recent approval. The outcome of these patent challenges could significantly impact the commercial landscape for this new formulation and similar hyaluronidase-enhanced therapies.
Claim Construction
In the petitions, Merck asserted that the claim terms are either expressly defined in the common disclosure or are used with their common and ordinary meaning. The PTAB agreed with this interpretation, finding that evidence showed the patents recognized a broad understanding of a "modified PH20 polypeptide."