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US 7,812,135 B2Granted
GITR-binding antibodies
AssigneeTolerRx, Inc.
InventorsL. Mary Smith, Grazyna Szymanska, Paul Ponath, Michael Rosenzweig, Jose F. Ponte
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AssigneeTolerRx, Inc.
InventorsL. Mary Smith, Grazyna Szymanska, Paul Ponath, Michael Rosenzweig, Jose F. Ponte
Estimating the term…
The present invention provides binding molecules that specifically bind to GITR, e.g., human GITR (hGITR), on T cells and dendritic cells. Binding molecules of the invention are characterized by binding to hGITR with high affinity, in the presence of a stimulating agent, e.g., CD3, are agonistic, and abrogate the suppression of Teff cells by Treg cells. Various aspects of the invention relate to binding molecules, and pharmaceutical compositions thereof, as well as nucleic acids, recombinant expression vectors and host cells for making such binding molecules. Methods of using a binding molecule of the invention to detect human GITR or to modulate human GITR activity, either in vitro or in vivo, are also encompassed by the invention.
An isolated monoclonal antibody comprising a light chain and a heavy chain, or an antigen-binding fragment thereof, which antibody or antigen-binding fragment specifically binds glucocorticoid-induced TNFR family-related receptor (GITR), wherein said antibody or antigen-binding fragment thereof comprises (a) the heavy chain variable region set forth in amino acid residues 20-138 of SEQ ID NO:1 or amino acid residues 20-138 of SEQ ID NO:66 and (b) the light chain variable region set forth in amino acid residues 21-127 of SEQ ID NO:2.
An isolated monoclonal antibody comprising a light-chain and a heavy chain, or an antigen-binding fragment thereof, which antibody or antigen-binding fragment specifically binds glucocorticoid-induced TNFR family-related receptor (GITR), wherein said antibody or antigen-binding fragment thereof comprises (a) the heavy chain complementarity determining region (CDR) amino acid sequences in SEQ ID NO:1 and (b) the light chain CDR amino acid sequences in SEQ ID NO:2.
An isolated monoclonal antibody comprising a light chain and a heavy chain, or an antigen-binding fragment thereof, which antibody or antigen-binding fragment specifically binds glucocorticoid-induced TNFR family-related receptor (GITR), wherein said antibody or antigen-binding fragment thereof comprises the light chain complementarity determining region (CDR) amino acid sequences shown in amino acid residues 44-54 of SEQ ID NO:2, amino acid residues 70-76 of SEQ ID NO:2, and amino acid residues 109-117 of SEQ ID NO:2, and heavy chain CDR amino acid sequences shown in amino acid residues 45-56 of SEQ ID NO:1, amino acid residues 119-127 of SEQ ID NO:1, and one of amino acid residues 71-86 of SEQ ID NO:1 and amino acid residues 71-86 of SEQ ID NO:66.
An isolated monoclonal antibody, or antigen-binding fragment thereof, which antibody or antigen-binding fragment specifically binds glucocorticoid-induced-TNFR family-related receptor (GITR) on human T cells and human dendritic cells and has a binding constant (Kd) of 1×10−9 or less;
An isolated monoclonal antibody comprising a light-chain and a heavy chain, or an antigen-binding fragment thereof, which antibody or antigen-binding fragment specifically binds glucocorticoid-induced TNFR family-related receptor (GITR), wherein said antibody or antigen-binding fragment thereof comprises one of:
Dependencies are inferred from the claim text.