Human plasma hyaluronidase
AssigneeThe Regents of the University of California
InventorsRobert Stern, Gregory I. Frost, Anthony Csoka, Tim M. Wong
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AssigneeThe Regents of the University of California
InventorsRobert Stern, Gregory I. Frost, Anthony Csoka, Tim M. Wong
Estimating the term…
The invention is based on the discovery of methods for purification of an acid active hyaluronidase found in human plasma (hpHAse), including both biochemical and immunoaffinity purification methods. The method of immunoaffinity purification of the invention is based on the discovery of a method for identifying antibodies that specifically bind native hpHAse (anti-native hpHAse antibodies), and anti-native hpHAse antibodies identified by this screening method. The invention also features an assay for sensitive detection of HAse activity using biotinylated hyaluronic acid (bHA). Purification and characterization of hpHAse lead to the inventors' additional discovery that hpHAse is encoded by the LuCa-1 gene, which gene is present in the human chromosome at 3p21.3, a region associated with tumor suppression. The invention additionally features methods of treating tumor-bearing patients by administration of hpHAse and/or transformation of cells with hpHAse-encoding DNA.
A composition comprising a substantially pure, enzymatically active naturally occuring human plasma hyaluronidase (hpHAse) polypeptide, wherein said polypeptide is at least 60%, by weight, free from the proteins and naturally-occurring organicmolecules with which it is naturally associated and wherein said polypeptide is glysolated, and wherein said hpHAse polypeptide partitions into a non-ionic detergent-rich phase at a temperature above about 25° C.
A composition comprising a recombinant, substantially pure, naturally occuring human plasma hyaluronidase wherein said polypeptide is at least 60%, by weight, free from the proteins and naturally-occurring organic molecules with which it is naturally associated and wherein said polypeptide is glycosylated, and wherein said hpHAse polypeptide partitions into a non-iomc detergent-rich phase at a temperature above 25° C.
A formulation comprising
A formulation comprising
A composition comprising a substantially pure, enzymatically active naturally occurring human plasma hyaluronidase (hpHAse) polypeptide, wherein said polypeptide is at least 60%, by weight, free from the proteins and naturally-occurring organic molecules with which it is naturally associated and wherein said polypeptide is glysolated, and wherein said hpHAse polypeptide exhibits β-1,4-endoglycosidase activity and a pH optimum below pH 4.5.
A composition comprising a recombinant, substantially pure, enzymatically active naturally occuring human plasma hyaluronidase (hpHAse) polypeptide, is at least 60%, by weight, free from the proteins and naturally-occurring organicmolecules with which it is naturally associated and wherein said polypeptide is glycosylated, and wherein said hpHAse polypeptide exhibits β-1,4-endoglycosidase activity and a pH optimum below pH 4.5.
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