Ph20 Polypeptide Variants, Formulations And Uses Thereof
Patent No. US10865400 (titled "Ph20 Polypeptide Variants, Formulations And Uses Thereof") was filed by Halozyme Inc on Aug 2, 2016.
What is this patent about?
’400 is related to the field of hyaluronidase enzymes, specifically modified versions of the PH20 hyaluronidase. Hyaluronidases are enzymes that degrade hyaluronan, a major component of the extracellular matrix. This degradation can be useful for increasing tissue permeability and improving the delivery of therapeutic agents. Current hyaluronidase products are often derived from ovine or bovine sources, which can be immunogenic in humans, creating a need for improved hyaluronidases with better properties.
The underlying idea behind ’400 is to engineer modified PH20 polypeptides with altered properties, particularly increased stability and/or activity. This is achieved by introducing amino acid replacements, deletions, or insertions into the PH20 polypeptide sequence. The modifications are designed to enhance the enzyme's resistance to denaturation under various conditions, such as elevated temperature, agitation, low salt concentrations, or the presence of denaturing excipients. The goal is to create a more robust and effective hyaluronidase for therapeutic applications.
The claims of ’400 focus on modified PH20 polypeptides that exhibit increased hyaluronidase activity compared to the unmodified PH20 polypeptide. The independent claims specify that the modified PH20 polypeptide must have at least 120% of the hyaluronidase activity of the unmodified form, measured under identical conditions. The claims also specify that the amino acid replacement(s) responsible for the increased activity must be located at specific positions within the PH20 polypeptide sequence, as defined by reference to SEQ ID NO:3.
In practice, the invention involves identifying specific amino acid residues within the PH20 polypeptide that, when replaced, lead to increased enzyme activity and/or stability. This can be done through directed mutagenesis and high-throughput screening. The modified PH20 polypeptides are then produced using recombinant DNA technology in suitable host cells, such as CHO cells, which are capable of glycosylation. The resulting modified enzymes can be purified and formulated into pharmaceutical compositions for therapeutic use.
The invention differentiates itself from prior approaches by providing specific amino acid modifications that enhance the stability and activity of PH20 hyaluronidases. Unlike previous hyaluronidase products derived from animal sources, the modified PH20 polypeptides described in ’400 can be engineered to be more stable under various conditions, including in the presence of preservatives commonly used in pharmaceutical formulations. This increased stability allows for the development of more effective and convenient multi-dose formulations, as well as improved performance in therapeutic applications where the enzyme may be exposed to harsh conditions.
How does this patent fit in bigger picture?
Technical landscape at the time
In the early 2010s when ’400 was filed, hyaluronan-degrading enzymes were already used therapeutically to treat diseases associated with hyaluronan accumulation and to increase tissue permeability for drug delivery. At a time when many hyaluronidases used were ovine or bovine forms, which could be immunogenic in humans, improving hyaluronan-degrading enzymes for human treatment was needed. When protein engineering techniques were becoming more accessible, modifying existing polypeptides to improve their properties, such as stability and activity, was a common approach.
Novelty and Inventive Step
The examiner allowed the claims because the amended claims now recite that the modified PH20 polypeptide has at least 95% sequence identity to SEQ ID NO: 7 or any of SEQ ID NOs: 3 and 32-66, and the examiner determined that no prior art teaches a naturally-occurring PH20 polypeptide with this level of sequence identity that also exhibits increased hyaluronidase activity compared to the unmodified polypeptide. The examiner also stated that the claims are not directed to a judicial exception.
Claims
This patent contains 18 claims, with independent claims 1 and 4 directed to a modified PH20 polypeptide with increased hyaluronidase activity achieved through specific amino acid replacements. The dependent claims elaborate on the specific amino acid replacements, sequence identities, modifications, and formulations of the modified PH20 polypeptide.
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Date
Description
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US10865400
- Application Number
- US15226489
- Filing Date
- Aug 2, 2016
- Status
- Granted
- Expiry Date
- Dec 20, 2034
- External Links
- Slate, USPTO, Google Patents