Monoclonal antibodies against HMGB1

1. An isolated antibody produced by murine hybridoma 2G7 HMGB1 mAb, deposited as ATCC Accession Number PTA-5432, or an antigen-binding fragment thereof.

2. An isolated antibody or antigen-binding fragment thereof, wherein the antibody or antigen-binding fragment thereof specifically binds polypeptides consisting of the amino acid sequences of SEQ ID NO: 23 and SEQ ID NO: 47, further wherein the antibody or antigen-binding fragment does not specifically bind a polypeptide consisting of the amino acid sequence of SEQ ID NO: 48.

3. An isolated cell that produces the antibody of claim 1 .

4. An isolated cell that produces the antibody or antigen-binding fragment thereof of claim 2 .

5. An isolated antibody, or antigen-binding fragment thereof, that specifically binds human high mobility group box 1 protein (HMGB1), mouse HMGB1, or rat HMGB1, wherein said antibody or antigen-binding fragment comprises:

i) a variable light chain comprising the light chain CDRs (CDR1, CDR2 and CDR3) of the variable light chain comprising the amino acid sequence of SEQ ID NO: 44 and a variable heavy chain comprising the heavy chain CDRs (CDR1, CDR2 and CDR3) of the variable heavy chain comprising the amino acid sequence of SEQ ID NO: 42;

ii) a variable light chain comprising the amino acid sequence of SEQ ID NO: 44, or a humanized variant thereof, comprising the light chain CDRs (CDR1, CDR2 and CDR3) of the variable light chain comprising the amino acid sequence of SEQ ID NO: 44, and a variable heavy chain;

iii) a variable heavy chain comprising the amino acid sequence of SEQ ID NO: 42, or a humanized variant thereof, comprising the heavy chain CDRs (CDR1, CDR2 and CDR3) of the variable heavy chain comprising the amino acid sequence of SEQ ID NO: 42, and a variable light chain; or

iv) both the variable light chain of ii) and the variable heavy chain of iii).

6. The antibody or antigen-binding fragment of claim 5 , wherein said antibody or antigen-binding fragment further comprises a human framework region.

7. The antibody or antigen-binding fragment of claim 5 , wherein said antibody or antigen-binding fragment is an antigen-binding fragment selected from the group consisting of a Fab fragment, a Fab′ fragment, a F(ab) 2 fragment and a Fv fragment.

8. A composition comprising the antibody or antigen-binding fragment of claim 2 and a pharmaceutically-acceptable excipient.

9. The antibody or antigen-binding fragment of claim 2 , wherein said antibody or antigen-binding fragment is selected from the group consisting of a human antibody, a humanized antibody, a chimeric antibody and an antigen-binding fragment of any of the foregoing.

10. An in vitro method of detecting and/or identifying an agent that binds to a vertebrate high mobility group box 1 (HMGB1) polypeptide, comprising combining:

i) isolated antibody, or antigen-binding fragment thereof, of claim 2 ;

ii) a test agent; and

iii) a composition comprising a vertebrate HMGB1 polypeptide;

and detecting or measuring the formation of a complex between said antibody or antigen-binding fragment and said HMGB1 polypeptide, wherein a decrease in the formation of said complex relative to a suitable control indicates that said test agent binds to said HMGB1 polypeptide.

11. A method of treating a condition in a subject, characterized by activation of an inflammatory cytokine cascade, comprising administering to the subject the antibody, or antigen-binding fragment thereof, of claim 2 , wherein said condition is selected from the group consisting of sepsis and rheumatoid arthritis.

12. A method of treating a subject with sepsis or rheumatoid arthritis, comprising administering to the subject an effective amount of the antibody, or antigen-binding fragment thereof, of claim 2 .

13. An in vitro method of detecting a vertebrate high mobility group box 1 (HMGB1) polypeptide in a sample, comprising:

a) contacting a sample with the antibody, or antigen-binding fragment thereof, of claim 2 , under conditions suitable for binding of said antibody or fragment to said HMGB1 polypeptide present in said sample; and

b) detecting antibody-HMGB1 complexes or antigen-binding fragment-HMGB1 complexes,

wherein detection of said antibody-HMGB1 complexes or antigen-binding fragment-HMGB1 complexes is indicative of the presence of HMGB1 polypeptide in said sample.

14. The method of claim 13 , wherein said antibody or antigen-binding fragment comprises a detectable label.

15. The method of claim 13 , wherein said detecting of antibody-HMGB1 complexes or antigen-binding fragment-HMGB1 complexes is by immunoassay.

16. A test kit for use in detecting the presence of a vertebrate high mobility group box 1 (HMGB1) polypeptide or portion thereof in a sample, comprising:

a) antibody, or antigen-binding fragment thereof, of claim 2 ; 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 portion thereof.