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), such as where 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 method of inhibiting Matrix Metalloproteinase 9 (MMP9) activity in a subject in need thereof, comprising:
 administering to the subject an effective amount of a pharmaceutical composition comprising an isolated antibody or fragment thereof that binds to MMP9, and a pharmaceutically acceptable excipient.   
     
     
         2 . The method of  claim 1 , wherein the subject in need thereof has a disease or condition associated with MMP9 selected from the group consisting of a cancer, an autoimmune disease or condition, an inflammatory disease or condition, and fibrotic disease or condition. 
     
     
         3 . The method of  claim 2 , wherein the cancer is pancreatic cancer, esophagogastric adenocarcinoma, non-small cell lung cancer, lung squamous cell carcinoma, lung adenocarcinoma, gastric adenocarcinoma, colorectal carcinoma, pancreatic adenocarcinoma, head and neck squamous cell carcinoma, hepatocellular carcinomacolorectal cancer, colorectal adenocarcinoma, or hepatocellular carcinoma. 
     
     
         4 . The method of  claim 2 , wherein the autoimmune or inflammatory disease or condition is rheumatoid arthritis, an inflammatory bowel disease (IBD), septicemia, multiple sclerosis, muscular dystrophy, lupus, allergy, or asthma. 
     
     
         5 . The method of  claim 4 , wherein the IBD is ulcerative colitis (UC), Crohn's disease (CD), or indeterminate colitis. 
     
     
         6 . The method of  claim 1 , wherein the isolated antibody or fragment thereof comprises: a heavy chain variable (VH) region comprising a complementary determining region (CDR) with an amino acid sequence selected from the group consisting of SEQ ID NOs: 13, 14, and 15; and a light chain variable (VL) region having a complementary determining region (CDR) with an amino acid sequence selected from the group consisting of SEQ ID NOs: 16, 17, and 18. 
     
     
         7 . The method of  claim 1 , wherein the isolated antibody or fragment thereof comprises the VH region has the amino acid sequence selected from the group consisting of SEQ ID NOs: 3, 5, 6, 7 and 8; and VL region has the amino acid sequence selected from the group consisting of SEQ ID NOs: 4, 9, 10, 11 and 12. 
     
     
         8 . The method of  claim 1 , wherein the isolated antibody or fragment thereof comprises the VH region has a 95% sequence identify to the amino acid sequence of SEQ ID NO: 7 and the VL region has a 95% sequence identify to the amino acid sequence of SEQ ID NO: 12. 
     
     
         9 . The method of  claim 1 , wherein the isolated antibody or fragment thereof comprises the VH region has the amino acid sequence of SEQ ID NO: 7 and the VL region has the amino acid sequence of SEQ ID NO: 12. 
     
     
         10 . The method of any of  claim 1 , wherein the antibody or fragment thereof is administered at a dosage of between at or about 100 and at or about 1800 mg/Kg body weight. 
     
     
         11 . The method of  claim 10 , wherein the dosage is at or about 100, 200, 300, 400, 500, 600, 700, 800, 900, 1000, 1100, 1200, 1300, 1400, 1500, 1600, 1700, or 1800 mg/Kg body weight. 
     
     
         12 . The method of  claim 1 , wherein the antibody or fragment thereof is administered once every week, once every two weeks, or once every three weeks. 
     
     
         13 . The method of  claim 1 , wherein the antibody or fragment thereof is administered intravenously or subcutaneously. 
     
     
         14 . The method of  claim 1 , further comprises one or more therapeutic agent is selected from the group consisting of an anti-inflammatory agent, an immunotherapeutic agent, a chemotherapeutic agent, and an anti-cancer agent, or a combination thereof. 
     
     
         15 . The method of  claim 14 , wherein the one or more therapeutic agent is selected from the group consisting of nab-paclitaxel, mFOLFOX6, FOLFIRI, carboplatin, paclitaxel, pemetrexed, bevacizumab, anti-lysyl oxidase-like 2 (LOXL2) antibody, and an anti-discoidin domain receptor 1 (DDR1) antibody, or a combination thereof. 
     
     
         16 . The method of  claim 14 , wherein the antibody or fragment thereof is administered concurrently or sequentially with the one or more therapeutic agents. 
     
     
         17 . A method of detecting or monitoring MMP9 activity, comprising:
 contacting a sample with MMP9 binding protein,   assessing the presence or absence of MMP9 binding protein-MMP9 complex;   wherein the MMP9 binding protein comprises a VH region comprising a CDR with an amino acid sequence selected from the group consisting of SEQ ID NOs: 13, 14, 15, 34, 35, 36 and 47; and a light chain variable (VL) region having a complementary determining region (CDR) with an amino acid sequence selected from the group consisting of SEQ ID NOs: 16, 17, 18, 37, 38, 39, 42, 43, 44, and 48;   whereby the absence of the MMP9 binding protein-MMP9 complex indicates the sample does not have the MMP9 activity, whereby the presence of the MMP9 binding protein-MMP9 complex indicates the sample has the MMP9 activity.   
     
     
         18 . The method of  claim 17 , wherein the MMP9 binding protein comprises a VH region has the amino acid sequence selected from the group consisting of SEQ ID NOs: 1, 3, 5, 6, 7, 8, 34, 35, 36, and 46; and a VL region has the amino acid sequence selected from the group consisting of SEQ ID NOs: 2, 4, 9, 10, 11, 12, 37, 38, 39, 42, 43, 44, and 45. 
     
     
         19 . A MMP9 binding protein comprises a heavy chain variable (VH) region comprising a complementary determining region (CDR) with an amino acid sequence of SEQ ID NOs: 34, 35, 36 and 47; and a light chain variable (VL) region having a complementary determining region (CDR) with an amino acid sequence selected from the group consisting of SEQ ID NOs: 37, 38, 39, 42, 43, 44, and 48. 
     
     
         20 . The MMP9 binding protein of  claim 19 , wherein the VH region has the amino acid sequence selected from the group consisting of SEQ ID NOs: 30, 32, 46, and 47; and the VL region has the amino acid sequence selected from the group consisting of SEQ ID NOs: 31, 33, 41, 45, and 48.