IP Verse

Ph20 Polypeptide Variants, Formulations And Uses Thereof

Patent No. US12152262 (titled "Ph20 Polypeptide Variants, Formulations And Uses Thereof") was filed by Halozyme Inc on Jun 23, 2023.

What is this patent about?

’262 is related to the field of modified hyaluronidase enzymes, specifically focusing on improving the stability and activity of PH20 hyaluronidase . Hyaluronidases are enzymes that degrade hyaluronan, a major component of the extracellular matrix. These enzymes are used to treat diseases associated with hyaluronan accumulation and to enhance the delivery of therapeutic agents by increasing tissue permeability. Existing hyaluronidases, often derived from ovine or bovine sources, can be immunogenic in humans, highlighting the need for improved enzymes.

The underlying idea behind ’262 is to engineer PH20 hyaluronidase variants with enhanced properties, particularly increased stability and activity . This is achieved through specific amino acid modifications, including replacements, deletions, and insertions, at key locations within the PH20 polypeptide sequence. The goal is to create a hyaluronidase that is more robust under various conditions, such as elevated temperatures, low salt concentrations, and in the presence of preservatives, while maintaining its enzymatic function.

The claims of ’262 focus on a modified PH20 polypeptide with at least 95% sequence identity to SEQ ID NO: 3 or 32-66, featuring an amino acid replacement at position 317 (relative to SEQ ID NO: 3). The replacement amino acid must be selected from the group consisting of H, I, K, M, Q, R, and S. This claim specifically covers PH20 variants with a modification at position 317 that retain hyaluronidase activity.

In practice, the invention involves identifying specific amino acid residues within the PH20 polypeptide that, when modified, lead to improved stability or activity. This can be done through directed mutagenesis and high-throughput screening. The modified PH20 polypeptide is then produced using recombinant DNA technology in a suitable host cell, such as CHO cells, ensuring proper glycosylation for optimal activity. The resulting enzyme can then be formulated into pharmaceutical compositions.

’262 differentiates itself from prior approaches by providing specific amino acid modifications that enhance PH20 stability and activity. Unlike previous hyaluronidases that may be prone to denaturation under certain conditions, the modified PH20 polypeptides of this invention are designed to withstand these challenges. This is particularly important for multi-dose formulations where preservatives are necessary, as the modified enzymes exhibit increased resistance to denaturation caused by these preservatives, leading to a longer shelf life and improved efficacy.

How does this patent fit in bigger picture?

Technical landscape at the time

In the early 2010s when ’262 was filed, hyaluronan was typically implemented using hyaluronan-degrading enzymes, such as hyaluronidases, to treat diseases or disorders associated with accumulation of HA or other glycosaminoglycans. At a time when therapeutic hyaluronidases commonly relied on ovine or bovine forms, hardware or software constraints made the reduction of immunogenicity non-trivial.

Novelty and Inventive Step

The examiner approved the application because the prior art does not disclose the modified PH20 polypeptide comprising the amino acid sequence claimed with a modification at position 317 with reference to SEQ ID NO: 3 and with the modifications recited. The examiner considered the closest prior art to be the applicant's own work for which terminal disclaimers have been filed in the application.

Claims

US12,152,262 has 13 claims, with claim 1 being independent. The independent claim focuses on a modified PH20 polypeptide with specific amino acid sequence identity and a modification at position 317. The dependent claims generally specify particular characteristics, activities, modifications, or uses of the modified PH20 polypeptide defined in the independent claim.

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 317 with reference to amino acid positions set forth in SEQ ID NO: 3, wherein the replacement is selected from the group consisting of H, I, K, M, Q, R, and S.
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. Hence, provided are modified PH20 polypeptides that contain one or more amino acid replacements that result in a PH20 polypeptide that retains activity and/or exhibits increased or altered stability under a variety of conditions.”A PH20 polypeptide that has been altered by at least one amino acid modification, such as a replacement, insertion, or deletion, compared to a reference PH20 polypeptide.
Positions corresponding to position 317
(Claim 1)		“These include modified PH20 polypeptides that contain one or more amino acid replacements, where at least one replacement is at an amino acid position corresponding (i.e., by alignment) to a position selected from among 10, 12, 20, 22, 26, 34, 36, 46, 50, 52, 58, 68, 70, 74, 82, 83, 84, 86, 97, 127, 131, 138, 142, 143, 144, 166, 169, 174, 193, 195, 196, 204, 205, 206, 213, 219, 234, 237, 238, 240, 249, 261, 267, 277, 279, 291, 309, 310, 314, 315, 317, 318, 347, 367, 375, 376, 399, 401, 407, 416, 419, 421, 431, 433, 439, 440, 443 or 445 with reference to amino acid positions set forth in SEQ ID NO:3, wherein corresponding amino acid positions are identified by alignment of the PH20 polypeptide with the polypeptide set forth in SEQ ID NO:3.”The amino acid position in a PH20 polypeptide that aligns with position 317 in SEQ ID NO:3 when the sequences are aligned to maximize identical residues.

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

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US12152262

HALOZYME INC
Application Number
US18340802
Filing Date
Jun 23, 2023
Status
Granted
Expiry Date
Dec 28, 2032
External Links
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