Human tissue inhibitor of metalloproteinase-4
OwnerJohn M. Greene, Craig A. Roseninventors
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Abstract
A human tissue inhibitor of metalloproteinases-4 polypeptide and DNA (RNA) encoding such polypeptide and a procedure for producing such polypeptide by recombinant techniques. Also disclosed are methods for utilizing such polypeptide for the treatment of diseases, including arthritis and cancer. Antagonists against such polypeptides and their use as a therapeutic to resorb scar tissue are also disclosed. Diagnostic assays for detecting levels of human TIMP-4 protein and mutations in human TIMP-4 nucleic acid sequence are also disclosed.
Claims23
An isolated polynucleotide comprising a member selected from the group consisting of:
- (a) a polynucleotide encoding the polypeptide as set forth in SEQ ID NO:2;
- (b) a polynucleotide capable of hybridizing to and which is at least 70% identical to the polynucleotide of (a);
- and
- (c) a polynucleotide fragment of the polynucleotide of (a) or (b).
An isolated polynucleotide comprising a member selected from the group consisting of:
- (a) a polynucleotide which encodes a mature polypeptide encoded by the DNA contained in ATCC Deposit No. 75946;
- (b) a polynucleotide which encodes a polypeptide expressed by the DNA contained in ATCC Deposit No. 75946;
- (c) a polynucleotide capable of hybridizing to and which is at least 70% identical to the polynucleotide of (a) or (b);
- and
- (d) a polynucleotide fragment of the polynucleotide of (a), (b) or (c).
A polypeptide comprising a member selected from the group consisting of (i) a polypeptide having the deduced amino acid sequence of SEQ ID NO:2 and fragments, analogs and derivatives thereof;
- (ii) a polypeptide comprising amino acid 1 to amino acid 195 of SEQ ID NO:2;
- and (iii) a polypeptide encoded by the cDNA of ATCC Deposit No. 75946 and fragments, analogs and derivatives of said polypeptide.
A method of treating restenosis in a patient, comprising administering to the patient an isolated nucleic acid molecule encoding a TIMP-4 polypeptide selected from the group consisting of:
- (a) the amino acid sequence shown as residues −29 to 195 in SEQ ID NO:2;
- (b) the amino acid sequence shown as residues −28 to 195 in SEQ ID NO:2;
- (c) the amino acid sequence shown as residues 1 to 195 in SEQ ID NO:2;
- and
- (d) a fragment of the sequence described in (a) whereing a polypeptide consisting of the fragment retains protease inhibiting activity;
- wherein said nucleic acid molecule is operatively linked to a transcription control sequence;
- and wherein the expression of said nucleic acid molecule results in an increased amount of the TIMP-4 polypeptide in an amount effective to inhibit metalloproteinase activity.
Dependencies are inferred from the claim text.