Antibodies against hmgb1 and fragments thereof

What is claimed is: 
     
         1 . An antibody or antigen-binding fragment thereof that specifically binds to a fragment of HMGB1, wherein said fragment of HMGB1 is selected from the group consisting of Hp-16 (YAFFVQTCREEHKKKHPD; SEQ ID NO:5), Hp-91 (DPNAPKRPPSAFFLFCSE; SEQ ID NO:10), Hp-106 (CSEYRPKIKGEHPGLSIG; SEQ ID NO:11) and an epitope of HMGB1 comprising amino acid residues 106-108 of HMGB1 (Cys-Ser-Glu). 
     
     
         2 . The antibody or antigen-binding fragment of  claim 1 , wherein said antibody or antigen-binding fragment inhibits release of a cytokine from a vertebrate cell treated with HMGB1. 
     
     
         3 . The antibody or antigen-binding fragment of  claim 2 , wherein said cytokine is selected from the group consisting of IL-6, IL-12, TNF-α, IL-18, IL-8, IL-2, IL-1β and IL-5. 
     
     
         4 . The antibody or antigen-binding fragment 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 Fab′ fragment, an F(ab′) 2  fragment and an Fv fragment. 
     
     
         5 . The antibody or antigen-binding fragment of  claim 1 , wherein said antibody or antigen-binding fragment is selected from the group consisting of a monoclonal antibody, a human antibody, a humanized antibody, a chimeric antibody, and an antigen-binding fragment of any of the foregoing. 
     
     
         6 . An isolated cell that produces the antibody or antigen-binding fragment thereof of  claim 1 . 
     
     
         7 . The isolated cell of  claim 6 , wherein said isolated cell is selected from the group consisting of an immortalized B cell, a hybridoma cell, and a recombinant cell comprising one or more exogenous nucleic acid molecules that encode said antibody or antigen-binding fragment thereof. 
     
     
         8 . The isolated cell of  claim 6 , wherein said antibody or antigen-binding fragment is a monoclonal antibody or an antigen-binding fragment thereof. 
     
     
         9 . A composition comprising the antibody or antigen-binding fragment of  claim 1  and a pharmaceutically-acceptable excipient. 
     
     
         10 . A method of treating a condition in a subject characterized by activation of an inflammatory cytokine cascade comprising administering to the subject a therapeutically effective amount of an antibody or antigen-binding fragment thereof that specifically binds to a fragment of HMGB1, wherein said fragment of HMGB1 is selected from the group consisting of Hp-16 (YAFFVQTCREEHKKKHPD; SEQ ID NO:5), Hp-31 (HPDASVNFSEFSKKCSER; SEQ ID NO:6), Hp-91 (DPNAPKRPPSAFFLFCSE; SEQ ID NO:10), Hp-106 (CSEYRPKIKGEHPGLSIG; SEQ ID NO:11) and an epitope of HMGB1 comprising amino acid residues 106-108 of HMGB1 (Cys-Ser-Glu). 
     
     
         11 . The method of  claim 10  wherein said condition is selected from the group consisting of sepsis, allograft rejection, arthritis, asthma, lupus, adult respiratory distress syndrome, chronic obstructive pulmonary disease, psoriasis, pancreatitis, peritonitis, burns, ischemia, Behcet's disease, graft versus host disease, inflammatory bowel disease, multiple sclerosis, and cachexia. 
     
     
         12 . A method of detecting and/or identifying an agent that binds to an HMGB1 polypeptide or a fragment thereof and inhibits release of a cytokine from a vertebrate cell treated with HMGB1, wherein said method comprises combining:
 a) an antibody or antigen-binding fragment thereof that specifically binds to a fragment of HMGB1 wherein said fragment of HMGB1 is selected from the group consisting of Hp-16 (YAFFVQTCREEHKKKHPD; SEQ ID NO:5), Hp-31 (HPDASVNFSEFSKKCSER; SEQ ID NO:6), Hp-91 (DPNAPKRPPSAFFLFCSE; SEQ ID NO:10), Hp-106 (CSEYRPKIKGEHPGLSIG; SEQ ID NO:11), and an epitope of HMGB1 comprising amino acid residues 106-108 of HMGB1 (Cys-Ser-Glu);   b) a test agent; and   c) a composition comprising an HMGB1 polypeptide or a fragment thereof;   and detecting or measuring the formation of a complex between said antibody or antigen-binding fragment and said HMGB1 polypeptide or fragment thereof, wherein a decrease in the formation of said complex relative to a suitable control indicates that said test agent binds to said HMGB1 polypeptide or fragment thereof.   
     
     
         13 . The antibody or antigen-binding fragment of  claim 12 , wherein said cytokine is selected from the group consisting of IL-6, IL-12, TNF-α, IL-18, IL-2, IL-1β and IL-5. 
     
     
         14 . A method of detecting an HMGB1 polypeptide or a fragment thereof in a sample comprising:
 a) contacting a sample with an antibody or antigen-binding fragment thereof that specifically binds to a fragment of HMGB1, wherein said fragment of HMGB1 is selected from the group consisting of Hp-16 (YAFFVQTCREEHKKKHPD; SEQ ID NO:5), Hp-31 (HPDASVNFSEFSKKCSER; SEQ ID NO:6), Hp-91 (DPNAPKRPPSAFFLFCSE; SEQ ID NO:10), Hp-106, (CSEYRPKIKGEHPGLSIG; SEQ ID NO:11), and an epitope of HMGB1 comprising amino acid residues 106-108 of HMGB1 (Cys-Ser-Glu) under conditions suitable for binding of said antibody or antigen-binding fragment to said HMGB1 polypeptide or fragment thereof present in said sample; and   b) detecting antibody-HMGB1 polypeptide complexes, antigen-binding fragment-HMGB1 polypeptide complexes, antibody-HMGB1 fragment complexes or antigen-binding fragment-HMGB1 fragment complexes,   wherein detection of said antibody-HMGB1 polypeptide complexes, antigen-binding fragment-HMGB1 polypeptide complexes, antibody-HMGB1 fragment complexes or antigen-binding fragment-HMGB1 fragment complexes is indicative of the presence of an HMGB1 polypeptide or fragment thereof in said sample.   
     
     
         15 . The method of  claim 14 , wherein said antibody or antigen-binding fragment comprises a detectable label. 
     
     
         16 . The method of  claim 14 , wherein said detecting of antibody-HMGB1 polypeptide complexes, antigen-binding fragment-HMGB1 polypeptide complexes, antibody-HMGB1 fragment complexes or antigen-binding fragment-HMGB1 fragment complexes is by immunoassay. 
     
     
         17 . The method of  claim 16 , wherein said immunoassay is an ELISA. 
     
     
         18 . A test kit for use in detecting the presence of an HMGB1 polypeptide or fragment thereof in a sample comprising:
 a) antibody or antigen-binding fragment thereof of  claim 1 ; and   b) one or more ancillary reagents suitable for detecting the presence of a complex between said antibody or antigen-binding fragment and said HMGB1 polypeptide or fragment thereof.