IP Verse

Ph20 Polypeptide Variants, Formulations And Uses Thereof

Patent No. US12195773 (titled "Ph20 Polypeptide Variants, Formulations And Uses Thereof") was filed by Halozyme Inc on May 9, 2024.

What is this patent about?

’773 is related to the field of hyaluronidase enzymes , specifically modified forms of the PH20 hyaluronidase. Hyaluronan (HA) is a key component of the extracellular matrix and interstitial barrier, playing roles in tissue permeability and various physiological processes. Existing hyaluronidases, often derived from ovine or bovine sources, can be immunogenic in humans, creating a need for improved enzymes with enhanced properties.

The underlying idea behind ’773 is to engineer PH20 hyaluronidase variants with improved characteristics, particularly increased stability under conditions that typically denature proteins. This is achieved by introducing specific amino acid modifications, such as replacements, deletions, or insertions, into the PH20 polypeptide sequence. The goal is to create modified PH20 enzymes that retain or enhance their hyaluronidase activity while exhibiting greater resistance to factors like elevated temperature, agitation, low salt concentrations, and the presence of preservatives.

The claims of ’773 focus on a soluble human PH20 polypeptide that includes a modification at a position aligned to position 320 with reference to the amino acid positions set forth in SEQ ID NO: 3, and 19 or less additional amino acid modifications, after alignment with SEQ ID NO: 3 to maximize the number of identical residues, wherein the modifications comprise insertions, deletions, and replacements, and the modification at position 320 is a replacement selected from the group consisting of H, K, and R.

In practice, the invention involves creating a library of PH20 variants with different amino acid substitutions and then screening these variants for desirable properties. For example, variants can be screened for increased stability in the presence of phenolic preservatives, which are commonly used in pharmaceutical formulations. The screening process involves testing the activity of the modified enzymes under denaturing conditions and comparing it to their activity under normal conditions, as well as comparing it to the activity of the unmodified enzyme under the same denaturing conditions. This allows for the identification of variants that are more resistant to denaturation and retain higher levels of hyaluronidase activity.

This approach differs from prior art by focusing on specific amino acid modifications to enhance the inherent stability of the PH20 enzyme. By identifying and incorporating these stabilizing modifications, the invention aims to overcome the limitations of existing hyaluronidases, such as their immunogenicity and susceptibility to denaturation. The resulting modified PH20 polypeptides can be used in a variety of therapeutic applications, including enhancing drug delivery and treating hyaluronan-associated diseases, with improved efficacy and reduced side effects. The site-directed mutagenesis approach allows for a rational design of improved enzymes, rather than relying on random mutations and selection.

How does this patent fit in bigger picture?

Technical landscape at the time

In the early 2010s when ’773 was filed, protein engineering at a time when X was typically implemented using Y. Specifically, at a time when protein variants were commonly generated and screened to improve stability or activity, when systems commonly relied on Z rather than A. Also, when hardware or software constraints made B non-trivial.

Novelty and Inventive Step

Claims were amended during prosecution. The specification was objected to by the examiner. Certain claims were allowed, while others were rejected for indefiniteness and improper dependent form. The prosecution record does NOT describe the technical reasoning or specific claim changes that led to allowance.

Claims

This patent contains 15 claims, with claim 1 being the only independent claim. Independent claim 1 focuses on a soluble human PH20 polypeptide with specific modifications. The dependent claims generally elaborate on the characteristics, production, and uses of the soluble human PH20 polypeptide described in the independent claim, including nucleic acids, vectors, host cells, pharmaceutical compositions, and methods of administration and manufacture.

Key Claim Terms New

Definitions of key terms used in the patent claims.

Term (Source)Support for SpecificationInterpretation
Amino acid modifications
(Claim 1)		“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. 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.”Changes to the amino acid sequence of the polypeptide, including insertions, deletions, and replacements of amino acids.
Insertions, deletions, and replacements
(Claim 1)		“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. 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.”The types of amino acid changes that can be made to the PH20 polypeptide sequence.
Maximize the number of identical residues
(Claim 1)		“Particular and exemplary modified PH20 polypeptides that exhibit increased stability, such as increased stability to a phenolic preservative, include those that contain a single amino acid modification, such as a replacement, and combinations of modifications, such as at least or 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 30, 40, 50, 60, 70, 80, 90, 100 and more modifications. 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.”Performing an alignment of the modified PH20 polypeptide sequence with SEQ ID NO:3 in a way that results in the greatest number of matching amino acids between the two sequences.
Modification at a position aligned to position 320
(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. Single amino acid abbreviations for amino acid residues are well known to a skilled artisan (see e.g. Table 1), and are used herein throughout the description and examples. 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 amino acid change (insertion, deletion, or replacement) at the amino acid position that corresponds to position 320 in SEQ ID NO:3 after performing an alignment to maximize identical residues.
Soluble human PH20 polypeptide
(Claim 1)		“Provided are modified PH20 polypeptides that exhibit increased stability in low salt conditions, such as, for example, concentrations of NaCl of less than 100 mM, such as, but not limited to concentrations of NaCl less than 90 mM, 80 mM, 70 mM, 60 mM, 50 mM, 40 mM, 30 mM, 25 mM, 20 mM, 15 mM, 10 mM, 5 mM or less.”A human PH20 polypeptide that is soluble, meaning it can be dissolved in an aqueous solution.

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

US12195773

HALOZYME INC
Application Number
US18659215
Filing Date
May 9, 2024
Status
Granted
Expiry Date
Dec 28, 2032
External Links
Slate, USPTO, Google Patents