Nucleic acid molecules encoding transmembrane serine proteases, the encoded proteins and methods based thereon

Abstract

Provided herein are antibodies, fragments and derivatives of an antibody containing a binding domain thereof, where the antibody, fragment or derivative specifically binds to a single chain protease domain of a type II transmembrane serine protease (MTSP). Methods using the antibodies to modulate the protease activity of an MTSP are provided. Also provided are antibodies that bind to MTSPs designated MTSP3 and MTSP4 and to a form of an MTSP designated MTSP6.

1 . An antibody, or an antigen binding fragment of the antibody that specifically binds to a single chain protease domain of a type-II membrane-type serine protease (MTSP). 
     
     
         2 . The antibody or fragment thereof of  claim 1  that is a monoclonal or a single chain antibody. 
     
     
         3 . The antibody or fragment thereof of  claim 1  that is humanized or human. 
     
     
         4 . The antibody or fragment thereof of  claim 1 , selected from among a Fab, F(ab′) 2 , Fab′, Fv, scFV, and a Fd fragment. 
     
     
         5 . The antibody or fragment thereof of  claim 1 , wherein the MTSP is selected from among corin, MTSP1, enteropeptidase, human airway trypsin-like protease (HAT), MTSP3, MTSP4, MTSP6, TMPRSS2 and TMPRSS4. 
     
     
         6 . The antibody or fragment thereof of  claim 1 , wherein a free Cys in the protease domain, which is normally disulfide bonded to a Cys in the pro-sequence of the full length MTSP, is replaced with another amino acid. 
     
     
         7 . The antibody or fragment thereof of  claim 1 , wherein the MTSP protease domain consists of a sequence of amino acid residues selected from among amino acids 615-855 of SEQ ID NO: 2, amino acids 205-437 of SEQ ID NO: 4, the amino acids set forth as SEQ ID NO: 5, the amino acids set forth as SEQ ID NO: 6 or as amino acids 217-443 in SEQ ID NO: 12. 
     
     
         8 . The antibody or fragment thereof of  claim 1 , wherein the MTSP protease domain is encoded by a sequence of nucleic acid residues selected from among nucleotides 1865-2585 of SEQ ID NO: 1, nucleotides 873-1571 of SEQ ID NO: 3, the nucleotides set forth as SEQ ID NO: 5 and nucleotides 916-1596 of SEQ ID NO: 11. 
     
     
         9 . An antibody, or an antigen binding fragment of the antibody that specifically binds to an MTSP3 or an MTSP4. 
     
     
         10 . The antibody or fragment thereof of  claim 9  that is a monoclonal or a single chain antibody. 
     
     
         11 . The antibody or fragment thereof of  claim 9  that is humanized or human. 
     
     
         12 . The antibody or fragment thereof of  claim 9 , selected from among a Fab, F(ab′) 2 , Fab′, Fv, scFV, and a Fd fragment.