IP Verse

Ph20 Polypeptide Variants, Formulations And Uses Thereof

Patent No. US12123035 (titled "Ph20 Polypeptide Variants, Formulations And Uses Thereof") was filed by Halozyme Therapeutics Inc on Dec 19, 2022.

What is this patent about?

’035 is related to the field of hyaluronidase enzymes , specifically modified forms of the PH20 hyaluronidase. Hyaluronidases are enzymes that degrade hyaluronan, a major component of the extracellular matrix. This degradation can be used to treat diseases associated with hyaluronan accumulation or to increase tissue permeability for drug delivery. Current hyaluronidase therapies often use ovine or bovine forms, which can be immunogenic in humans, creating a need for improved hyaluronidase enzymes.

The underlying idea behind ’035 is to engineer modified PH20 polypeptides with improved properties, particularly increased stability and activity . This is achieved by introducing amino acid replacements, deletions, or insertions into the PH20 polypeptide sequence. The modifications are designed to make the enzyme more resistant to denaturation under various conditions, such as elevated temperature, agitation, low salt concentrations, or the presence of denaturing excipients.

The claims of ’035 focus on a modified PH20 polypeptide derived from an unmodified PH20 polypeptide consisting of the amino acid sequence selected from the group consisting of SEQ ID NOs: 3, 7 and 32-66, wherein the modified PH20 polypeptide comprises an amino acid replacement at a position corresponding to residue 312, with reference to amino acid positions set forth in SEQ ID NO:3, wherein the replacement at the position corresponding to residue 312 is selected from the group consisting of G, K, L, N, and T, and wherein the modified PH20 polypeptide has at least 91% sequence identity to a polypeptide having the amino acid sequence selected from the group consisting of SEQ ID NOs: 3, 7 and 32-66.

The modified PH20 polypeptides are implemented by introducing specific amino acid changes at key positions in the PH20 sequence. These changes are identified through screening and selection processes that evaluate the enzyme's activity and stability under various stress conditions. The goal is to create more robust enzymes that maintain their activity even when exposed to conditions that would typically denature or inactivate wild-type PH20.

This approach differentiates from prior art by creating PH20 variants that are more stable and active, particularly in the presence of preservatives or under other denaturing conditions. This increased stability allows for the development of more effective and longer-lasting therapeutic formulations, especially for multi-dose applications where preservatives are necessary. The resulting modified PH20 polypeptides offer improved performance and reduced immunogenicity compared to existing hyaluronidase therapies.

How does this patent fit in bigger picture?

Technical landscape at the time

In the early 2010s when ’035 was filed, protein engineering at a time when directed evolution was typically implemented using iterative cycles of mutagenesis and screening. At that time, protein stability was commonly addressed through empirical optimization of formulation conditions, when hardware or software constraints made computational modeling of protein-protein interactions non-trivial. Systems commonly relied on sequence homology and structural information to guide rational design of protein variants, at a time when high-throughput screening technologies were becoming more accessible for assessing variant libraries.

Novelty and Inventive Step

Claims were objected to and rejected during prosecution. Claims were rejected under 35 U.S.C. 112(b) as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor regards as the invention. It is NOT clear from the prosecution record the technical reasoning or specific claim changes that led to allowance.

Claims

This patent contains 34 claims, with claim 1 being the sole independent claim. Independent claim 1 focuses on a modified PH20 polypeptide with specific amino acid modifications. The dependent claims generally elaborate on the characteristics, modifications, and uses of the modified PH20 polypeptide described in the independent claim.

Key Claim Terms New

Definitions of key terms used in the patent claims.

Term (Source)Support for SpecificationInterpretation
Amino acid modifications
(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. 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.”Changes to the amino acid sequence of a PH20 polypeptide, including amino acid replacements, deletions, and/or insertions.
Corresponding amino acid positions
(Claim 1)		“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.”Amino acid positions in a PH20 polypeptide that align with specific residue numbers in SEQ ID NO:3, as determined by sequence alignment.
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. The modified PH20 polypeptide can be one in which the unmodified form thereof has at least about 68% sequence identity to SEQ ID NO: 3 and further contains modifications that alter stability and/or can be a PH20 polypeptide that includes as many as about up to 100, 110, 120, 130, 150 amino acid differences from PH20 but retains enzymatic activity, particularly, at least about 40% of the activity of the unmodified PH20 polypeptide and exhibits increased stability, such as stability under denaturing conditions.”A PH20 polypeptide that has been altered by at least one amino acid replacement, deletion, or insertion, compared to an unmodified PH20 polypeptide. The unmodified PH20 polypeptide has the amino acid sequence of SEQ ID NOs: 3, 7 or 32-66. The modified PH20 polypeptide has at least 91% sequence identity to a polypeptide having the amino acid sequence selected from the group consisting of SEQ ID NOs: 3, 7 and 32-66.

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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US12123035

HALOZYME THERAPEUTICS INC
Application Number
US18068327
Filing Date
Dec 19, 2022
Status
Granted
Expiry Date
Dec 28, 2032
External Links
Slate, USPTO, Google Patents