Heparanase II, a novel human heparanase paralog
OwnerRobert Leroy Heinrikson, Michael Jerome Bienkowskiinventors
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Abstract
The present invention provides a cDNA encoding a heretofore unknown enzyme termed heparanase II; constructs and recombinant host cells incorporating the cDNA; the heparanase II polypeptide encoded by the gene; antibodies to the polypeptide; and methods of making an using all of the foregoing.
Claims46
An isolated nucleic acid molecule comprising a polynucleotide with a nucleotide sequence selected from the group consisting of:
- (a) a nucleotide sequence encoding a heparanase II polypeptide comprising the amino acid sequence of SEQ ID NO:2
- (b) a nucleotide sequence encoding a heparanase II polypeptide comprising the amino acid sequence at residues 42 through 534 of SEQ ID NO:2
- (c) a nucleotide sequence encoding a heparanase II polypeptide comprising the amino acid sequence at residues 42 through 129 of SEQ ID NO:2
- (d) a nucleotide sequence encoding a heparanase II polypeptide comprising the amino acid sequence at residues 42 through 161 of SEQ ID NO:2
- (e) a nucleotide sequence encoding a heparanase II polypeptide comprising the amino acid sequence at residues 130 through 534 of SEQ ID NO:2
- (f) a nucleotide sequence encoding the heparanase II polypeptide comprising the amino acid sequence at residues 162 through 534 of SEQ ID NO:2 and
- (g) a nucleotide sequence that is complementary to any of the nucleotide sequences of (a), (b), (c), (d), (e) or (f)
16 The vector of claim 15, wherein said nucleic acid molecule is operably linked to a promoter for the expression of a human heparanase polypeptide.
An isolated human heparanase polypeptide comprising an amino acid sequence selected from the group consisting of:
- (a) an amino acid sequence of a heparanase II polypeptide comprising the amino acid sequence of SEQ ID NO:2;
- (b) a heparanase II polypeptide comprising the amino acid sequence at residues 42 through 534 of SEQ ID NO:2;
- (c) a heparanase II polypeptide comprising the amino acid sequence at residues 42 through 129 of SEQ ID NO:2;
- (d) a heparanase II polypeptide comprising the amino acid sequence at residues 42 through 161 of SEQ ID NO:2;
- (e) a heparanase II polypeptide comprising the amino acid sequence at residues 130 through 534 of SEQ ID NO:2 and;
- (f) a heparanase II polypeptide comprising the amino acid sequence at residues 162 through 534 of SEQ ID NO:2.
A heparanase II enzyme comprising
- (a) an isolated heparanase II polypeptide comprising the amino acid sequence at residues 42 through 129 of SEQ ID NO:
- 2;
- and
- (b) and isolated heparanase II polypeptide comprising the amino acid sequence at residues 130 through 534 of SEQ ID NO:2
A heparanase II enzyme comprising
- (a) an isolated human heparanase polypeptide comprising the amino acid sequence at residues 42 through 161 of SEQ ID NO:
- 2;
- and
- (b) and isolated human heparanase polypeptide comprising the amino acid sequence at residues 162 through 534 of SEQ ID NO:2
A heparanase II enzyme comprising
- (a) an isolated human heparanase polypeptide comprising the amino acid sequence at residues 42 through 129 of SEQ ID NO:
- 2;
- and
- (b) and isolated human heparanase polypeptide comprising the amino acid sequence at residues 162 through 534 of SEQ ID NO:2
A composition comprising a polypeptide according to claims 26 through 43 in a pharmaceutically acceptable carrier
A isolated heparanase II polypeptide comprising the amino acid sequence set forth in SEQ ID NO:
- 2, or a fragment thereof comprising an epitope specific to said polypeptide.
An antibody specific for the heparanase II polypeptides of claims 26-43.
A method for the identification of an agent that alters heparanase activity, said method comprising:
- (a) determining the activity of the isolated heparanase II polypeptide
- (i) in the presence of a test agent;
- and
- (ii) in the absence of said test agent;
- and
- (b) comparing the heparanase activity determined in step (a)(i) to the heparanase activity determined in step (a)(ii);
- whereby a change in heparanase activity in sample (a)(i) has compared to sample (a)(ii) indicates that said agent alters the activity of said heparanase II polypeptide.
A method for inhibiting the enzymatic activity of an heparanase II polypeptide comprising the step of contacting said enzyme with an antibody specific for said enzyme, under conditions wherein the antibody binds the enzyme.
A method for treating a disease state comprising the step of administering to a mammal in need of such treatment an amount of an agent sufficient to alter heparanase II enzymatic activity in the tissues of said mammal
Dependencies are inferred from the claim text.