IP Verse

Ph20 Polypeptide Variants, Formulations And Uses Thereof

Patent No. US12104185 (titled "Ph20 Polypeptide Variants, Formulations And Uses Thereof") was filed by Halozyme Therapeutics Inc on Mar 8, 2024.

What is this patent about?

’185 is related to the field of hyaluronidase enzymes and their use in enhancing drug delivery. Specifically, it addresses the need for modified hyaluronidases with improved stability and activity, particularly in pharmaceutical formulations. Hyaluronidases like PH20 degrade hyaluronan, a major component of the extracellular matrix, thereby increasing tissue permeability and improving the dispersion of co-administered therapeutic agents. Existing hyaluronidase products, often derived from ovine or bovine sources, can be immunogenic, highlighting the need for improved human-compatible versions.

The underlying idea behind ’185 is to engineer PH20 hyaluronidase variants with enhanced properties through amino acid modifications. The key inventive insight is that specific amino acid replacements in the PH20 polypeptide sequence can lead to increased stability and/or activity. This is achieved by identifying residues and loci that contribute to alteration of a property, such as stability in particular conditions. The resulting modified PH20 polypeptides are designed to retain hyaluronidase activity while exhibiting improved characteristics.

The claims of ’185 focus on a method for enhancing the delivery of a therapeutic agent by co-administering it with a modified PH20 polypeptide. The modified PH20 polypeptide must have at least 95% sequence identity to SEQ ID NO:3 or 32-66 (C-terminal truncations of SEQ ID NO:7) when aligned, and it must also contain an amino acid replacement at a position corresponding to position 320 in SEQ ID NO:3. The replacement at position 320 is limited to histidine, lysine, arginine, or serine.

In practice, the invention involves creating a modified PH20 polypeptide with the specified sequence characteristics and co-administering it with a therapeutic agent. The modified PH20 facilitates the dispersion and absorption of the therapeutic agent in the subject's tissues. This is particularly useful for therapeutic agents that have limited bioavailability or require enhanced tissue penetration to be effective. The modified PH20 polypeptide can be produced recombinantly in cells capable of glycosylation, ensuring proper folding and activity.

The invention differentiates itself from prior approaches by providing specific amino acid modifications that enhance the stability and activity of PH20 hyaluronidases. This addresses the limitations of existing hyaluronidase products, such as their potential immunogenicity and instability in pharmaceutical formulations. By focusing on human-compatible PH20 variants with tailored properties, the invention offers a more effective and reliable means of enhancing drug delivery and treating hyaluronan-associated conditions.

How does this patent fit in bigger picture?

Technical landscape at the time

In the early 2010s when ’185 was filed, at a time when protein engineering commonly relied on site-directed mutagenesis and expression in mammalian cell lines. At that time, characterizing protein stability often involved measuring activity after exposure to various stress conditions, such as elevated temperatures or the presence of denaturing agents. Systems commonly relied on well-established cell culture techniques and analytical methods like SDS-PAGE and enzyme activity assays rather than more advanced high-throughput screening or computational modeling.

Novelty and Inventive Step

The examiner approved the application because the prior art does not teach a modified PH20 polypeptide with at least 95% sequence identity to SEQ ID NO: 3 or 32-66, where the modified PH20 polypeptide has an amino acid modification at a position corresponding to position 320 of SEQ ID NO: 3, and the modification is a replacement with H, K, R, or S.

Claims

This patent contains 11 claims, with claim 1 being the only independent claim. Independent claim 1 is directed to a method for increasing delivery of a therapeutic agent to a subject using a pharmaceutical composition containing the agent and a modified PH20 polypeptide. The dependent claims elaborate on the specifics of the independent claim, such as particular amino acid modifications, sequence identities, hyaluronidase activity levels, types of therapeutic agents, and routes of administration.

Key Claim Terms New

Definitions of key terms used in the patent claims.

Term (Source)Support for SpecificationInterpretation
amino acid modification
(Claim 1)		“The modifications include amino acid replacement, deletion and/or insertions. For purposes herein, amino acid replacements are denoted by the single amino acid letter followed by the corresponding amino acid position in SEQ ID NO:3 in which the replacement occurs. For example, replacement with P at a position corresponding to position 204 in a PH20 polypeptide with reference to amino acid residue positions set forth in SEQ ID NO:3 means that the replacement encompasses F204P in a PH20 polypeptide set forth in SEQ ID NO:3, or the same replacement at the corresponding position in another PH20 polypeptide.”An alteration to the amino acid sequence of a PH20 polypeptide, specifically a replacement at a position corresponding to position 320 with reference to amino acid positions set forth in SEQ ID NO: 3.
modified PH20 polypeptide
(Claim 1)		“Provided are modified PH20 polypeptides that have an altered property or properties compared to the PH20 polypeptide that do not have the modification(s). The modifications include amino acid replacement, deletion and/or insertions. Detailed structure/function of virtually each amino acid in a PH20 polypeptide is provided herein, as well as the identification of residues and loci that contribute to alteration of a property, such as stability in particular conditions, is provided.”A PH20 polypeptide with an amino acid sequence that is at least 95% identical to SEQ ID NO: 3 or 32-66, aligned to maximize identical residues, and contains a specific amino acid replacement at position 320.
therapeutic agent
(Claim 1)		“Also, since HA is a major component of the interstitial barrier, hyaluronan-degrading enzymes (e.g., hyaluronidase) increase tissue permeability and therefore can be used to increase the dispersion and delivery of therapeutic agents. Various hyaluronidases have been used therapeutically (e.g., hyaluronidase sold under the trademarks Hydase® (bovine testicular hyaluronidase), Vitrase® (ovine hyaluronidase), and Wydase® (bovine hyaluronidase)), typically as dispersing and spreading agents in combination with other therapeutic agents.”An agent that provides a therapeutic effect when administered to a subject, co-administered with the modified PH20 polypeptide.

Litigation Cases New

US Latest litigation cases involving this patent.

Case NumberFiling DateTitle
2:25-cv-03179Apr 10, 2025People Co. Ltd. V. Lakeshore Learning Materials, Llc

Patent Family

Patent Family

File Wrapper

The dossier documents provide a comprehensive record of the patent's prosecution history - including filings, correspondence, and decisions made by patent offices - and are crucial for understanding the patent's legal journey and any challenges it may have faced during examination.

  • Date

    Description

  • Get instant alerts for new documents

US12104185

HALOZYME THERAPEUTICS INC
Application Number
US18599428
Filing Date
Mar 8, 2024
Status
Granted
Expiry Date
Dec 28, 2032
External Links
Slate, USPTO, Google Patents