Targeted binding agents against B7-H1
Human monoclonal antibodies directed against B7-H1 and uses of these antibodies in diagnostics and for the treatment of diseases associated with the activity and/or expression of B7-H1 are disclosed. Additionally, hybridomas or other cell lines expressing such antibodies are disclosed.
1 . A purified antibody or an antigen-binding fragment thereof, wherein the antibody or antigen-specific fragment thereof is specific for B7-H1 and comprises:
a) a heavy chain variable domain, wherein the heavy chain variable domain comprises an amino acid sequence having at least about 85% identity to the amino acid sequence of SEQ ID NO: 52; and
b) a light chain variable domain, wherein the light chain variable domain comprises an amino acid sequence having at least about 90% identity to the amino acid sequence of SEQ ID NO: 57.
2 . The purified antibody or antigen-binding fragment thereof of claim 1 , wherein the heavy chain variable domain comprises an amino acid sequence having greater than 85% identity to the amino acid sequence of SEQ ID NO: 52.
3 . The purified antibody or antigen-binding fragment thereof of claim 1 , wherein the light chain variable domain comprises an amino acid sequence having greater than 90% identity to the amino acid sequence of SEQ ID NO: 57.
4 . The purified antibody or antigen-binding fragment thereof of claim 3 , wherein the light chain variable domain comprises an amino acid sequence having greater than 95% identity to the amino acid sequence of SEQ ID NO: 57.
5 . The purified antibody or antigen-binding fragment thereof of claim 1 , wherein the antibody or antigen-binding fragment thereof cross-reacts with cynomolgus monkey B7-H1.
6 . The purified antibody or antigen-binding fragment thereof of claim 1 , wherein the antibody or antigen-binding fragment thereof inhibits binding of human B7-H1 to PD-1 expressed on ES-2 cells with an IC50 of less than 0.2 nM.
7 . The purified antibody or antigen-binding fragment thereof of claim 1 , wherein the antibody or antigen-binding fragment thereof activates CD4+ T cells in dendritic cell-T-cell mixed lymphocyte assay.
8 . The purified antibody or antigen-binding fragment thereof of claim 1 , wherein the antibody or antigen-binding fragment thereof enhances T-cell proliferation in DCMLR assay.
9 . The purified antibody or antigen-binding fragment thereof of claim 1 , wherein the antibody or antigen-binding fragment thereof enhances IFN-γ release in DCMLR assay.
10 . A purified antibody or an antigen-binding fragment thereof, wherein the antibody or antigen-specific fragment thereof is specific for B7-H1 and comprises:
a) a heavy chain variable domain, wherein the heavy chain variable domain comprises an amino acid sequence having at least about 85% identity to the amino acid sequence of SEQ ID NO: 52 and comprises a CDR1 having the amino acid sequence of SEQ ID NO: 101; and
b) a light chain variable domain, wherein the light chain variable domain comprises an amino acid sequence having at least about 99% identity to the amino acid sequence of SEQ ID NO: 57.