Antibodies against HMGB1 and fragments thereof
View Patent ↗In various embodiments, the present invention is drawn to antibodies or antigen-binding fragments thereof that bind to particular fragments of HMGB1, methods of treating a condition in a subject characterized by activation of an inflammatory cytokine cascade, methods of detecting and/or identifying an agent that binds to an HMGB1 polypeptide or fragment thereof, and methods of detecting HMGB1 in a sample.
1. An antibody or antigen-binding fragment thereof that specifically binds to an HMGB1 polypeptide consisting of SEQ ID NO:6, wherein said antibody or antigen-binding fragment binds an epitope comprising the sequence 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 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 test kit for use in detecting the presence of an HMGB1 polypeptide or fragment thereof in a sample comprising:
a) the 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.
11. A monoclonal antibody or antigen-binding fragment thereof that specifically binds to an HMGB1 polypeptide consisting of SEQ ID NO:6, or a fragment thereof, and wherein the antibody or antigen-binding fragment thereof inhibits release of TNF-α from a human dendritic cell treated with HMGB1, and further wherein the antibody or antigen-binding fragment thereof binds an epitope comprising the sequence Cys-Ser-Glu.