Nucleic acid molecules encoding transmembrane serine proteases, the encoded proteins and methods based thereon
AssigneeCorvas International, Inc.
InventorsEdwin L. Madison, Edgar O. Ong, Jiunn-Chern Yeh
Life of this patent
Estimating the term…
Abstract
Provided herein is are polypeptides that include the protease domain of a type II transmembrane serine protease (MTSP) as a single chain. Methods using the polypeptides to identify compounds that modulate the protease activity of an MTSP are provided. Also provided are MTSPs designated MTSP3 and MTSP4 and a form of an MTSP designated MTSP6.
Claims136
A substantially purified single chain polypeptide, comprising the protease domain of a type-II membrane-type serine protease (MTSP) or a catalytically active portion thereof, wherein:
- the MTSP portion of the protein consists essentially of the protease domain of the MTSP or a catalytically active portion thereof.
A substantially purified membrane-type serine protease 3 (MTSP3).
A substantially purified membrane-type serine protease 4 (MTSP4).
The substantially purified MTSP4 that is an MTSP4-L or an MTSP4-S.
A substantially purified membrane-type serine protease 6 (MTSP6) selected from the group consisting of:
- a polypeptide encoded by the sequence of nucleotides set forth in SEQ ID No. 11;
- a polypeptide encoded by a sequence of nucleotides that hybridizes along the full length thereof under conditions of high stringency to the sequence of nucleotides set forth in SEQ ID No. 11;
- a polypeptide that comprises the sequence of amino acids set forth as amino acids 217-443 of SEQ ID No. 12;
- a polypeptide encoded by a splice variant of the sequence of nucleotides set forth in SEQ ID No. 11.
A recombinant non-human animal, wherein an endogenous gene of an MTSP has been deleted or inactivated by homologous recombination or insertional mutagenesis of the animal or an ancestor thereof.
An MTSP6 polypeptide, comprising amino acids set forth as amino acids 46-55 in SEQ ID No. 12 and/or amino acids 368-394 of SEQ ID No. 12, and that is encoded by a sequence of nucleic acids that hybridizes under moderate stringency to nucleic acid encoding the polypeptide set forth in SEQ ID No. 12.
A method for treating tumors, comprising administering a prodrug that is specifically cleaved by an MTSP, whereby, upon contact with a cell that expresses MTSP activity, the prodrug is converted into an active drug.
Dependencies are inferred from the claim text.