Tissue inhibitor of metalloproteinase type three (TIMP-3) composition and methods
AssigneeAmgen Inc.
InventorsScott M. Silbiger, Raymond A. Koski
Life of this patent
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Abstract
The present invention relates in general to metalloproteinase inhibitors and to polynucleotides encoding such inhibitors. In particular, the invention relates to novel mammalian inhibitors of metalloproteinase, which are designated as type three or TIMP-3, to fragments, derivatives, and analogs thereof, and to polynucleotides encoding the same. Novel methods of producing such compositions and novel methods of using such compositions are also provided.
Claims74
Purified and isolated mammalian TIMP-3.
Human TIMP-3 free of association with other human protein.
A purified and isolated polypeptide having part or all of the primary structure of mammalian TIMP-3 as presented in FIG. 1, and at least one of the biological properties of mammalian TIMP-3.
A purified and isolated polypeptide having the amino acid sequence presented in FIG. 1.
A purified and isolated polypeptide having the amino acid sequence of amino acids 1-188 as presented in FIG. 1, optionally having a methionyl residue at position −1.
An isolated DNA sequence for use in securing expression in a procaryotic or eucaryotic host cell of a polypeptide product having an amino acid sequence sufficiently duplicative of that of mammalian TIMP-3 to allow possession of a metalloproteinase inhibition activity of mammalian TIMP-3, said DNA sequence selected from among:
- (a) the DNA sequence set forth in FIG. 1 (and complementary strands);
- (b) a DNA sequence which hybridizes to the DNA in FIG. 1, wherein said hybridization conditions are those allowing detection of human TIMP-3 cDNA using a ChIMP-3 DNA probe or more stringent conditions;
- (c) a DNA sequence of subpart (b) which, but for the degeneracy of the genetic code, would hybridize to the DNA in FIG. 1;
- or
- (d) a fragment of the DNA sequences of subpart (a), (b) or (c) above which is at least long enough to selectively hybridize to human genomic DNA encodings TIMP-3.
A DNA sequence as set forth in FIG. 1 or FIG. 16, said sequence encoding at least amino acids 1-188 as set forth in FIG. 1, and optionally encoding an additional methionyl residue at the −1 position.
The host cell selected from the group consisting of those with ATCC designations (Timp3clone7/pCFM, Timp3clone7/puC19, Timp3clone2/puC19, Timp3HCM3, TimP3PCR29) ______, ______, ______, ______, and ______.
A pharmaceutical composition comprising purified and isolated human TIMP-3 in a pharmaceutically acceptable diluent, adjuvant or carrier.
An article of manufacture comprising a packaging material and a pharmaceutical agent, wherein said pharmaceutical agent contains human TIMP-3 and wherein said packaging material comprises a label which indicates that said pharmaceutical agent may be used for an indication selected from the group consisting of cancer, inflammation, arthritis, dystrophic epidermolysis bullosa, peridontal disease, ulceration, emphysema, bone disorders, scleroderma, wound healing, erythrocyte deficiencies, cosmetic tissue reconstruction, fertilization or embryo implant modulation and nerve cell disorders.
A kit containing a preparation of human TIMP-3 and one or more additional compositions beneficial for the treatment of a disorder involving the degradation of extracellular matrix.
A method of treating a lung disorder characterized by undue extracellular matrix degradation in a mammal comprising administering to the lungs of said mammal an effective amount of a DNA encoding human TIMP-3.
A method of treating emphysema in a mammal comprising administering to the lungs of said mammal an effective amount of a DNA encoding human TIMP-3, said DNA optionally within a vector or associated with a pharmaceutically acceptable carrier.
An article of manufacture comprising a packaging material and a pharmaceutical agent, wherein said pharmaceutical agent contains a DNA encoding human TIMP-3 and wherein said packaging material comprises a label which indicates that said pharmaceutical composition may be used for an indication benefitting from genetic therapy using such DNA.
A kit including a DNA encoding human TIMP-3 and one or more additional factors affecting the ex vivo growth of cells transformed or transfected with said DNA.
Anti-human TIMP-3 antibody.
A kit containing an anti-human TIMP-3 antibody.
A selective binding molecule prepared against the amino acid sequence H E X G H where X is either F or L.
A mature human TIMP-3 polypeptide as set forth in FIG. 1, optionally having a methionyl residue at position −1, lacking one or more of the six C-terminal cysteine residues.
A human TIMP-3 polypeptide as set forth in FIG. 1, optionally having a methionyl residue at position −1, having the amino acid sequence 1-121 and optionally all or part of amino acids 122-188.
Dependencies are inferred from the claim text.