Soluble glycosaminoglycanases and methods of preparing and using soluble glycosaminoglycanases
First Claim
1. A method for modulating the immune system in a subject, comprising subcutaneously administering to a subject immune globulin (IG) and a soluble hyaluronidase to enhance the immune system of the subject, wherein:
- the soluble hyaluronidase is a soluble neutral active human hyaluronidase glycoprotein (sHASEGP);
the hyaluronidase is active at neutral pH and contains at least one sugar moiety that is covalently attached to an asparagine (N) residue of the hyaluronidase polypeptide;
the hyaluronidase polypeptide does not comprise the complete sequence of amino acids set forth in SEQ ID NO;
1;
and the hyaluronidase polypeptide consists of;
(i) a contiguous sequence of amino acid residues contained within SEQ ID NO;
1 that includes at least amino acids 36-464 of SEQ ID NO;
1, wherein the polypeptide is truncated within the C-terminus of SEQ ID NO;
1 at a C-terminal amino acid residue selected from among 477, 478, 479, 480, 481, 482, 483 and 494 of SEQ ID NO;
1;
or(ii) a sequence of amino acid residues that has at least 95% amino acid sequence identity with a sequence of amino acids set forth in (i).
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Accused Products
Abstract
The invention relates to the discovery of novel soluble neutral active Hyaluronidase Glycoproteins (sHASEGPs), 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. The invention further comprises sialated and pegylated forms of a recombinant sHASEGP to enhance stability and serum pharmacokinetics over naturally occurring slaughterhouse enzymes. Further described are suitable formulations of a substantially purified recombinant sHASEGP glycoprotein derived from a eukaryotic cell that generate the proper glycosylation required for its optimal activity.
149 Citations
10 Claims
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1. A method for modulating the immune system in a subject, comprising subcutaneously administering to a subject immune globulin (IG) and a soluble hyaluronidase to enhance the immune system of the subject, wherein:
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the soluble hyaluronidase is a soluble neutral active human hyaluronidase glycoprotein (sHASEGP); the hyaluronidase is active at neutral pH and contains at least one sugar moiety that is covalently attached to an asparagine (N) residue of the hyaluronidase polypeptide; the hyaluronidase polypeptide does not comprise the complete sequence of amino acids set forth in SEQ ID NO;
1;and the hyaluronidase polypeptide consists of; (i) a contiguous sequence of amino acid residues contained within SEQ ID NO;
1 that includes at least amino acids 36-464 of SEQ ID NO;
1, wherein the polypeptide is truncated within the C-terminus of SEQ ID NO;
1 at a C-terminal amino acid residue selected from among 477, 478, 479, 480, 481, 482, 483 and 494 of SEQ ID NO;
1;
or(ii) a sequence of amino acid residues that has at least 95% amino acid sequence identity with a sequence of amino acids set forth in (i). - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10)
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Specification