On June 8, 2026, the Patent Trial and Appeal Board (“PTAB”) issued a Final Written Decision (“FWD”) in PGR2025-00004 finding all remaining challenged claims of Halozyme’s U.S. Patent No. 12,018,298 (“the ’298 patent”) unpatentable. The ’298 patent was challenged by Merck and is part of a broader dispute between Merck and Halozyme relating to Keytruda Qlex™ (pembrolizumab; berahyaluronidase alfa-pmph) and Halozyme’s PH20 hyaluronidase patent portfolio.
The ’298 patent is directed to modified PH20 hyaluronidase polypeptides, including modified polypeptides that exhibit increased stability and/or increased activity. Merck challenged claims 1–22 on written description, enablement, and obviousness grounds. After Halozyme disclaimed claims 5, 6, 20, and 21, claims 1–4, 7–19, and 22 remained at issue. Merck argued that the claims covered very broad genera of modified PH20 proteins defined through sequence identity limitations and amino acid substitutions, including PH20 polypeptides with a modification at position 313.
As in the FWDs in PGR2025-00003 and PGR2025-00006 (previously reported Keytruda Qlex™ Updates: Final Written Decisions Find Two Halozyme PH20 Patents Unpatentable While Institution is Denied for Third Patent), the Board found that the term “modified PH20 polypeptide” required hyaluronidase activity and that the claims covered very broad genera of modified PH20 polypeptides. The Board found that the specification’s single-substitution data and limited disclosure of multiply modified PH20 polypeptides did not adequately describe the full scope of the challenged claims. The Board also found the claims unpatentable for lack of enablement, concluding that the specification provided essentially no examples of multiple mutations and no detailed approach for reliably obtaining multiply modified PH20 polypeptides across the full scope of the challenged claims. The Board concluded that practicing the full scope of the claims would have required undue experimentation.
The Board did not find the challenged claims unpatentable as obvious. Merck argued that the claims were obvious because they encompassed the M313K PH201–447 mutant, a species in the claimed genus, relying on the ’429 patent and Chao reference. The Board found that Merck had not provided any persuasive reason that the prior art would have suggested targeting position 313 for modification, and that evidence that the M313K substitution may have been tolerated, among others, did not provide a sufficient reason to make the specific claimed modification.
There is one co-pending New Jersey litigation between Merck and Halozyme, Case No. 2:25-cv-03179 (D.N.J.) and 11 PGRs that have been instituted and are awaiting FWDs.
Keytruda Qlex™ was approved in September 2025 and generated approximately $40 million in 2025 sales, including approximately $35 million in the fourth quarter of 2025.
For more information about these and other biosimilars, please visit BiologicsHQ.
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The authors would like to thank April Breyer Menon for her contributions to this article.
