Anti-trem-1 antibodies and uses thereof
AssigneeBristol-Myers Squibb Company
InventorsAchal PASHINE, Michael L. GOSSELIN, Aaron P. YAMNIUK, Derek A. HOLMES, Guodong CHEN, Priyanka Apurva MADIA, Richard Yu-Cheng HUANG, Stephen Michael CARL
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Abstract
Provided herein are antibodies, or antigen-binding portions thereof, that specifically bind and inhibit TREM-1 signaling, wherein the antibodies do not bind to one or more FeyRs and do not induce the myeloid cells to produce inflammatory cytokines. Also provided are uses of such antibodies, or antigen-binding portions thereof in therapeutic applications, such as treatment of autoimmune diseases.
Claims60
An isolated antibody which specifically binds to a triggering receptor expressed on myeloid cells-1 (TREM-1), comprising a heavy chain variable region (VH), a light chain variable region (VL), and an IgG1 heavy chain constant region, wherein the IgG1 heavy chain constant region comprises one or more amino acid substitutions compared to a wild-type IgG1 heavy chain constant region (SEQ ID NO:
- 9).
An isolated antibody which cross-competes with mAb 0318 for binding to blocking TREM-1, comprising a heavy chain variable region (VH), a light chain variable region (VL), and an IgG1 heavy chain constant region, wherein the IgG1 heavy chain constant region comprises one or more amino acid substitutions compared to a wild-type IgG1 heavy chain constant region (SEQ ID NO:
- 9).
An isolated antibody which specifically binds to TREM-1, comprising a heavy chain CDR1, CDR2, CDR3;
- a light chain CDR1, CDR2, CDR3;
- and an IgG1 heavy chain constant region, wherein the heavy chain CDR1, CDR2, and CDR3 comprises TYAMH (SEQ ID NO:
- 24), RIRTKSSNYATYYAASVKG (SEQ ID NO:
- 25), and DMGIRRQFAY (SEQ ID NO:
- 26), respectively;
- wherein the light chain CDR1, CDR2, and CDR3 comprises RASQSVDTFDYSFLH (SEQ ID NO:
- 27), RASNLES (SEQ ID NO:
- 28), and QQSNQDPYT (SEQ ID NO:
- 29), respectively;
- and
- wherein the IgG1 heavy chain constant region comprises one or more amino acid substitutions selected from the group consisting of L234A, L235E, and G237A, per EU numbering.
An isolated antibody which specifically binds to TREM-1, comprising a heavy chain CDR1, CDR2, CDR3;
- a light chain CDR1, CDR2, CDR3;
- and an IgG1 heavy chain constant region,
- wherein the heavy chain CDR1, CDR2, and CDR3 comprises TYAMH (SEQ ID NO:
- 24), RIRTKSSNYATYYAASVKG (SEQ ID NO:
- 25), and DMGIRRQFAY (SEQ ID NO:
- 26), respectively;
- wherein the light chain CDR1, CDR2, and CDR3 comprises RASQSVDTFDYSFLH (SEQ ID NO:
- 27), RASNLES (SEQ ID NO:
- 28), and QQSNQDPYT (SEQ ID NO:
- 29), respectively;
- and
- wherein the IgG1 heavy chain constant region comprises amino acid substitutions selected from the group consisting of L234A, L235E, G237A, A330S, and P331S, per EU numbering.
An isolated antibody which specifically binds to TREM-1, comprising a heavy chain CDR1, CDR2, CDR3;
- a light chain CDR1, CDR2, CDR3;
- and an IgG1 heavy chain constant region,
- wherein the heavy chain CDR1, CDR2, and CDR3 comprises TYAMH (SEQ ID NO:
- 24), RIRTKSSNYATYYAASVKG (SEQ ID NO:
- 25), and DMGIRRQFAY (SEQ ID NO:
- 26), respectively;
- wherein the light chain CDR1, CDR2, and CDR3 comprises RASQSVDTFDYSFLH (SEQ ID NO:
- 27), RASNLES (SEQ ID NO:
- 28), and QQSNQDPYT (SEQ ID NO:
- 29), respectively;
- and
- wherein the IgG1 heavy chain constant region comprises one or more amino acid substitutions selected from the group consisting of K214R, C226S, C229S, and P238S, per EU numbering.
An isolated antibody which specifically binds to TREM-1, comprising a heavy chain CDR1, CDR2, CDR3;
- a light chain CDR1, CDR2, CDR3;
- and an IgG1 heavy chain constant region,
- wherein the heavy chain CDR1, CDR2, and CDR3 comprises TYAMH (SEQ ID NO:
- 24), RIRTKSSNYATYYAASVKG (SEQ ID NO:
- 25), and DMGIRRQFAY (SEQ ID NO:
- 26), respectively;
- wherein the light chain CDR1, CDR2, and CDR3 comprises RASQSVDTFDYSFLH (SEQ ID NO:
- 27), RASNLES (SEQ ID NO:
- 28), and QQSNQDPYT (SEQ ID NO:
- 29), respectively;
- and
- wherein the IgG1 heavy chain constant region comprises one or more amino acid substitutions selected from the group consisting of S131C, K133R, G137E, G138S, Q196K, I199T, N203D, K214R, C226S, C229S, and P238S, per EU numbering.
Dependencies are inferred from the claim text.