Antibodies to 46798, a human matrix metalloproteinase and uses thereof

Abstract

The invention provides isolated nucleic acids molecules, designated 46798 nucleic acid molecules, which encode a novel matrix metalloproteinase. The invention also provides antisense nucleic acid molecules, recombinant expression vectors containing 46798 nucleic acid molecules, host cells into which the expression vectors have been introduced, and non-human transgenic animals in which a 46798 gene has been introduced or disrupted. The invention still further provides isolated 46798 proteins, fusion proteins, antigenic peptides and anti-46798 antibodies. Diagnostic methods utilizing compositions of the invention are also provided.

What is claimed is:  
     
         1 . An antibody or antigen-binding fragment thereof which selectively binds to a 46798 polypeptide selected from the group consisting of: 
 a) a polypeptide which is encoded by a nucleic acid molecule comprising a nucleotide sequence which is at least 95% identical to the nucleotide sequence of SEQ ID NO: 11, wherein the nucleic acid molecule encodes a polypeptide having matrix metalloproteinase activity;    b) a polypeptide which does not include residues 128 to 202 of SEQ ID NO: 2, wherein said polypeptide has matrix metalloproteinase activity; and    c) a polypeptide comprising a fragment of the amino acid sequence of SEQ ID NO: 12, wherein the fragment comprises the peptidase_M10 domain (amino acid residues 39 to 150 of SEQ ID NO: 12) and has matrix metalloproteinase activity.    
     
     
         2 . The antibody or antigen-binding fragment thereof of  claim 1 , wherein said antibody or antigen-binding fragment thereof selectively binds a polypeptide having an amino acid sequence of SEQ ID NO: 12.  
     
     
         3 . The antibody or antigen-binding fragment thereof of  claim 1  wherein said antibody or antigen-binding fragment thereof is selected from the group consisting of a fully-human antibody, an antigen-binding fragment of a fully-human antibody, a humanized antibody, an antigen-binding fragment of a humanized antibody, a chimeric antibody, an antigen-binding fragment of a chimeric antibody, a single chain antibody and a dimer or multimer of a single chain antibody.  
     
     
         4 . The antibody or antigen-binding fragment thereof of  claim 1 , wherein said antibody or antigen-binding fragment is an antigen-binding fragment selected from the group consisting of an Fab fragment, an F(ab′) 2  fragment and an Fv fragment.  
     
     
         5 . The antibody or antigen-binding fragment thereof of  claim 1 , wherein said antibody or antigen-binding fragment has reduced or no ability to bind an Fc receptor.  
     
     
         6 . The antibody or antigen-binding fragment thereof of  claim 1 , wherein said antibody is a monoclonal antibody.  
     
     
         7 . An anti-idiotypic antibody reactive to the antibody or antigen-binding fragment of  claim 1 .  
     
     
         8 . The antibody or antigen-binding fragment thereof of  claim 1 , wherein said antibody or antigen-binding fragment is labeled with a detectable substance.  
     
     
         9 . The antibody or antigen-binding fragment thereof of  claim 8 , wherein said detectable substance is selected from the group consisting of an enzyme, a prosthetic group, a fluorescent material, a luminescent material, a bioluminescent material and a radioactive material.  
     
     
         10 . The antibody or antigen-binding fragment thereof of  claim 1 , wherein said antibody or antigen-binding fragment is conjugated to a therapeutic moiety.  
     
     
         11 . The antibody or antigen-binding fragment thereof of  claim 10 , wherein said therapeutic moiety is selected from the group consisting of a cytotoxin, a therapeutic agent, a radioactive metal ion and a drug moiety.  
     
     
         12 . The antibody or antigen-binding fragment thereof of  claim 1 , wherein said antibody or antigen-binding fragment is immobilized on a solid support.  
     
     
         13 . A kit comprising the antibody or antigen-binding fragment of  claim 1  and instructions for use.  
     
     
         14 . The kit of  claim 13 , further comprising a second antibody which is conjugated to a detectable agent.  
     
     
         15 . A pharmaceutical composition comprising the antibody or antigen-binding fragment of  claim 1  and a physiologically acceptable carrier.  
     
     
         16 . A pharmaceutical composition comprising the antibody or antigen-binding fragment of  claim 2  and a physiologically acceptable carrier.  
     
     
         17 . The antibody or antigen-binding fragment thereof of  claim 1 , wherein said antibody or antigen-binding fragment is conjugated to a second antibody in an antibody heteroconjugate.