Nucleic acid molecules encoding a transmembrane serine protease 25, the encoded polypeptides and methods based thereon
OwnerEdwin L Madison, Jiunn-Chern Yehinventors
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Abstract
Abstract Provided herein are type I transmembrane serine protease 25 (MTSP25) polypeptides. Activated forms of these polypeptides and single and two chain forms of the protease domain are also provided. Methods using the polypeptides for therapeutic and diagnostic purposes are provided.
Claims87
A substantially purified single or two chain polypeptide, consisting essentially of protease domain of a type-I membrane-type serine protease 25 (MTSP25) or a catalytically active portion thereof;
- and optionally additional sequences of amino acids, wherein the only MTPS25 sequences of amino acids are the protease domain portion.
A substantially purified polypeptide selected from the group consisting of:
- a) a single chain polypeptide that consists essentially of sequence of amino acids set forth as residues 1-237 in SEQ ID No. 6, residues 78-323 in SEQ ID No. 16 or catalytically active portions thereof;
- and optionally additional sequences of amino acids from other than an MTSP25 polypeptide;
- b) an activated two chain polypeptide that comprises the sequence of amino acids set forth as residues 1-237 in SEQ ID No. 6 or the sequence of amino acids set forth as residues 17-313 or residues 78-313 in SEQ ID No. 16 or catalytically active portions thereof;
- c) an activated two chain or single chain polypeptide that consists essentially of residues 17-237 or 1-237 of SEQ ID No. 6 or residues 78-323 or C-terminal truncated variants thereof in SEQ ID No. 16 or residues 17-323 of SEQ ID No. 16, or catalytically active portions of any of these polypeptides;
- and optionally additional sequences of amino acids from other than an MTPS25 polypeptide;
- d) an activated two chain polypeptide that comprises the sequence of amino acids set forth as residues 64-191 of SEQ ID No. 16 or catalytically active portions thereof;
- e) a polypeptide that includes a sequence of amino acids having at least about 60%, 70%, 75%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity with the sequence of amino acids of the MTSP25 portion of any of the polypeptides of a)-d);
- f) a protease domain of a polypeptide encoded by a splice variant of a sequence of nucleotides that encodes an MTSP25 of any of a)-e);
- and g) a polypeptide encoded by a sequence of nucleotides that hybridizes under conditions of low, moderate or high stringency to the sequence of nucleotides encoding the MTPS25 portion of the polypeptides of any of a)-f) where the sequence of nucleotides hybridizes along at least about 70%, 80% or 90% of its full-length under such conditions.
A polypeptide that consists essentially of amino acids 1-17 of SEQ ID No. 6 optionally operatively linked as a signal polypeptide to a polypeptide other than an MTSP25 polypeptide.
A method for treating or preventing a neoplastic disease, in a mammal, comprising administering to a mammal an effective amount of an inhibitor of the protease activity of an MTSP25 polypeptide.
An isolated substantially pure polypeptide that consists essentially of a protease domain of an MTSP25 polypeptide.
A transgenic non-human animal, comprising heterologous nucleic acid encoding an MTSP25 polypeptide.
Dependencies are inferred from the claim text.