Soluble hyaluronidase glycoprotein (sHASEGP), process for preparing the same, uses and pharmaceutical compositions comprising thereof
First Claim
1. A nucleic acid molecule, comprising a sequence of nucleotides encoding a hyaluronidase polypeptide, wherein:
- the nucleic acid molecule includes a stop codon, whereby the encoded hyaluronidase polypeptide is produced upon expression; and
the encoded hyaluronidase polypeptide is selected from among;
a polypeptide that consists of a sequence of amino acids selected from among amino acid residues 1-477, 1-478, 1-479, 1-480, 1-481, 1-482, 1-483, 36-477, 36-478, 36-479, 36-480, 36-481, 36-482 or 36-483 of SEQ ID NO;
1; and
a polypeptide that consists of a sequence of amino acids that contains amino acid substitutions in the sequence of amino acids set forth as 1-477, 1-478, 1-479, 1-480, 1-481, 1-482, 1-483, 36-477, 36-478, 36-479, 36-480, 36-481, 36-482 or 36-483 of SEQ ID NO;
1, whereby the amino acid-substituted hyaluronidase glycoprotein consists of a sequence of amino acids that has at least 95% amino acid sequence identity to a sequence of amino acids set forth as amino acid residues 1-477, 1-478, 1-479, 1-480, 1-481, 1-482, 1-483, 36-477, 36-478, 36-479, 36-480, 36-481, 36-482 or 36-483 of SEQ ID NO;
1.
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Accused Products
Abstract
Provided are soluble neutral active Hyaluronidase Glycoproteins (sHASEGP'"'"'s), methods of manufacture, and their use to facilitate administration of other molecules or to alleviate glycosaminoglycan associated pathologies. Minimally active polypeptide domains of the soluble, neutral active sHASEGP domains are described that include asparagine-linked sugar moieties required for a functional neutral active hyaluronidase domain. Included are modified amino-terminal leader peptides that enhance secretion of sHASEGP. Sialated and pegylated forms of the sHASEGPs also are provided. Methods of treatment by administering sHASEGPs and modified forms thereof also are provided.
190 Citations
30 Claims
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1. A nucleic acid molecule, comprising a sequence of nucleotides encoding a hyaluronidase polypeptide, wherein:
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the nucleic acid molecule includes a stop codon, whereby the encoded hyaluronidase polypeptide is produced upon expression; and the encoded hyaluronidase polypeptide is selected from among; a polypeptide that consists of a sequence of amino acids selected from among amino acid residues 1-477, 1-478, 1-479, 1-480, 1-481, 1-482, 1-483, 36-477, 36-478, 36-479, 36-480, 36-481, 36-482 or 36-483 of SEQ ID NO;
1; anda polypeptide that consists of a sequence of amino acids that contains amino acid substitutions in the sequence of amino acids set forth as 1-477, 1-478, 1-479, 1-480, 1-481, 1-482, 1-483, 36-477, 36-478, 36-479, 36-480, 36-481, 36-482 or 36-483 of SEQ ID NO;
1, whereby the amino acid-substituted hyaluronidase glycoprotein consists of a sequence of amino acids that has at least 95% amino acid sequence identity to a sequence of amino acids set forth as amino acid residues 1-477, 1-478, 1-479, 1-480, 1-481, 1-482, 1-483, 36-477, 36-478, 36-479, 36-480, 36-481, 36-482 or 36-483 of SEQ ID NO;
1. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26)
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27. A nucleic acid molecule, comprising a sequence of nucleotides encoding a hyaluronidase polypeptide, wherein:
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the nucleic acid molecule includes a stop codon, whereby the encoded hyaluronidase polypeptide is produced upon expression; and the encoded hyaluronidase polypeptide consists of a sequence of amino acids that has at least 98% amino acid sequence identity to the sequence of amino acids set forth as amino acid residues 36-483 of SEQ ID NO;
1. - View Dependent Claims (28, 29, 30)
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Specification