US 12264345

US Patent 12264345B1, titled "PH20 polypeptide variants, formulations and uses thereof," was filed on July 19, 2024, and issued on April 1, 2025. The current assignees are Halozyme Inc and Halozyme Therapeutics Inc, with the original assignee being Halozyme Inc. The inventors are Ge Wei, H. Michael Shepard, Qiping Zhao, and Robert James Connor.

Abstract:
Modified PH20 hyaluronidase polypeptides, including modified polypeptides that exhibit increased stability and/or increased activity, are provided. Also provided are compositions and formulations and uses thereof.

Independent Claims Overview:

• Claim 1: This claim describes a modified PH20 polypeptide that shows increased stability compared to its unmodified counterpart. This increased stability is evident as greater resistance to denaturation under conditions like elevated temperature (above 30°C), agitation, low or no salt, or the presence of denaturing excipients (such as preservatives). The unmodified PH20 polypeptide can be human PH20 (SEQ ID NO: 7) or a soluble C-terminal truncated fragment that retains at least 85% sequence identity to it.
• Claim 17: This claim focuses on a modified PH20 polypeptide that exhibits increased stability specifically in the presence of a phenolic preservative. The stability is increased compared to the unmodified polypeptide without the amino acid replacement. The unmodified PH20 polypeptide is defined as having the amino acid sequence of SEQ ID NO: 7 or being a soluble C-terminal truncated fragment with at least 85% sequence identity thereto.
• Claim 20: This claim covers a method for identifying or selecting a modified hyaluronan-degrading enzyme that demonstrates enhanced stability under denaturing conditions. The method involves comparing the activity of a modified enzyme in a denaturing composition/condition against the activity of a corresponding unmodified enzyme under the same conditions. An enzyme is selected if the modified version shows greater activity, indicating increased stability.
• Claim 35: This claim describes a pharmaceutical composition that includes a modified PH20 polypeptide (as defined in Claim 1) and at least one additional therapeutic agent, along with a pharmaceutically acceptable excipient.
• Claim 36: This claim outlines a method for delivering a therapeutic agent to a subject by co-administering the therapeutic agent with a modified PH20 polypeptide (as defined in Claim 1).
• Claim 37: This claim pertains to a method for treating a hyaluronan-associated disease or condition in a subject. It involves administering a therapeutically effective amount of a modified PH20 polypeptide (as defined in Claim 1) to the subject.

Litigation Status:
The patent family is involved in litigation. A US case has been filed in the New Jersey District Court (Case: 2:25-cv-03179). Additionally, a PTAB case, PGR2025-00052, has been filed and is currently pending and instituted. While these indicate ongoing legal challenges, no specific dockets were found for the U.S. Court of Appeals for the Federal Circuit (CAFC) in 2026 directly related to patent US12264345B1.