Antibodies to matrix metalloproteinase 9

Abstract

The present disclosure provides compositions and methods of use involving binding proteins, e.g., antibodies and antigen-binding fragments thereof, that bind to the matrix metalloproteinase-9 (MMP9) protein (MMP9 is also known as gelatinase-B), wherein the binding proteins comprise an immunoglobulin (Ig) heavy chain (or functional fragment thereof) and an Ig light chain (or functional fragment thereof).

What is claimed is: 
     
         1 . A MMP9 binding protein comprising
 an immunoglobulin heavy chain polypeptide, or functional fragment thereof, and   an immunoglobulin light chain polypeptide, or functional fragment thereof,   wherein the MMP9 binding protein specifically binds MMP9.   
     
     
         2 . The MMP9 binding protein of  claim 1 , wherein the MMP9 binding protein binds an epitope of human MMP9 comprising amino acid residues R162, E111, D113, and 1198. 
     
     
         3 . The MMP9 binding protein of  claim 1 , wherein the MMP9 binding protein competes for binding to human MMP9 with an antibody comprising a heavy chain polypeptide of   
     
     
         4 . The MMP9 binding protein of  claim 1 , wherein the MMP9 binding protein competes for binding to human MMP9 with an antibody comprising a heavy chain polypeptide comprising an amino acid sequence of SEQ ID NOS: 3 or 5-8. 
     
     
         5 . The MMP9 binding protein of  claim 1 , wherein the MMP9 binding protein competes for binding to human MMP9 with an antibody comprising a light chain polypeptide comprising an amino acid sequence of SEQ ID NOS: 4 or 9-12. 
     
     
         6 . The MMP9 binding protein of  claim 1 , wherein the MMP9 binding protein competes for binding to human MMP9 with an antibody comprising a heavy chain polypeptide comprising complementarity-determining regions (CDRs) of SEQ ID NOs: 13-15 and a light chain polypeptide comprising CDRs of SEQ ID NOs: 16-18. 
     
     
         7 . The MMP9 binding protein of  claim 6 , wherein the heavy chain polypeptide comprises complementarity-determining regions (CDRs) of SEQ ID NOs: 13-15, and the light chain polypeptide comprises CDRs of SEQ ID NOs: 16-18. 
     
     
         8 . The MMP9 binding protein of  claim 1 , wherein the MMP9 binding protein competes for binding to human MMP9 with an antibody comprising a heavy chain polypeptide comprising a variable region selected from the group consisting of SEQ ID NOs: 3 or 5-8, and a light chain polypeptide comprising a variable region selected from the group consisting of SEQ ID NOs: 4 or 9-12. 
     
     
         9 . The MMP9 binding protein of  claim 1 , wherein the heavy chain polypeptide is an IgG. 
     
     
         10 . The MMP9 binding protein of  claim 1 , wherein the binding of the MMP9 binding protein to MMP9 inhibits the enzymatic activity of MMP9. 
     
     
         12 . The MMP9 binding protein of claim  11 , wherein the inhibition is non-competitive. 
     
     
         13 . The MMP9 binding protein of  claim 1 , wherein the wherein the MMP9 binding protein competes for binding to human MMP9 with an antibody comprising a heavy chain polypeptide encoded by a polynucleotide having a nucleotide sequence selected from the group consisting of SEQ ID NOs: 19-22 and a light chain polypeptide encoded by a polynucleotide having a nucleotide sequence selected from the group consisting of SEQ ID NOs: 23-26. 
     
     
         14 . An isolated nucleic acid comprising a nucleotide sequence encoding:
 a heavy chain polypeptide comprising complementarity-determining regions (CDRs) of SEQ ID NOs: 13-15; and/or   a light chain polypeptide comprising CDRs of SEQ ID NOs: 16-18.   
     
     
         15 . The isolated nucleic acid of  claim 14 , wherein the heavy chain polypeptide comprises an amino acid sequence selected from the group consisting of SEQ ID NOS:1, 3, and 5-8. 
     
     
         16 . The isolated nucleic acid of  claim 14 , wherein the light chain polypeptide comprises an amino acid sequence selected from the group consisting of SEQ ID NOS:2, 4, and 9-12. 
     
     
         17 . The isolated nucleic acid of  claim 14  comprising a sequence selected from the group consisting of SEQ ID NOs: 19-26. 
     
     
         18 . A vector comprising the isolated nucleic acid of  claim 14 . 
     
     
         19 . A cell comprising the vector of  claim 18 . 
     
     
         20 . A pharmaceutical composition comprising the MMP9 binding protein of  claim 1 . 
     
     
         21 . A pharmaceutical composition comprising the vector of  claim 18 . 
     
     
         22 . A pharmaceutical composition comprising the cell of  claim 19 . 
     
     
         23 . A method of inhibiting MMP9 activity in a subject having a tumor or tumor-associated tissue having MMP9 activity, the method comprising:
 administering to the subject the pharmaceutical composition of  claim 20  in an amount effective to inhibit MMP9 activity;   wherein MMP9 activity in inhibited in the subject.   
     
     
         24 . A method of detecting MMP9 expression in tissue of a patient, the method comprising:
 contacting a tissue sample from the patient with an MMP9 binding protein of  claim 1 ; and   detecting the presence or absence of MMP9;   wherein the presence of MMP9 in the tissue sample indicates the MMP9 is expressed in tissue.