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US 9,447,401 B2Granted
PH20 polypeptide variants, formulations and uses thereof
AssigneeHalozyme, Inc.
InventorsGe Wei, H. Michael Shepard, Qiping Zhao, Robert James Connor
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Abstract
Modified PH20 hyaluronidase polypeptides, including modified polypeptides that exhibit increased stability and/or increased activity, are provided. Also provided are compositions and formulations and uses thereof.
Claims49
A modified PH20 polypeptide that exhibits increased stability in the presence of a phenolic preservative, comprising an amino acid replacement in an unmodified PH20 polypeptide, wherein:
- the amino acid replacement confers the increased stability;
- the amino acid replacement is replacement with proline 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;
- corresponding amino acid positions are identified by alignment of the modified PH20 polypeptide with the polypeptide whose sequence is set forth in SEQ ID NO:3;
- the modified PH20 polypeptide has at least 85% sequence identity to the sequence of amino acids set forth in SEQ ID NO:
- 3 or 7;
- and
- stability is increased compared to the unmodified polypeptide without the amino acid replacement, wherein stability is measured by resistance to denaturation in the presence of a phenolic preservative.
4 more elements
Dependencies are inferred from the claim text.