Anti-TIGIT antigen-binding proteins and methods of uses thereof

A method of treating a cancer in a human subject in need thereof, comprising administering to the subject:

• a) an effective amount of an isolated antibody or antigen-binding fragment thereof that specifically binds human TIGIT (hTIGIT) as set forth in SEQ ID NO:
• 1, comprising a heavy chain variable (VH) domain comprising from N-terminus to C-terminus, CDR-H1, CDR-H2, and CDR-H3;
• and a light chain variable (VL) domain comprising from N-terminus to C-terminus CDR-L1, CDR-L2, and CDR-L3, wherein the CDRs of the VH and VL are selected from the group consisting of:
• (1) a CDR-H3 having the sequence A-R-D-A-N-Y-Y-G-X1-A-W-A-F-D-P, wherein X1 is S or G (SEQ ID NO:
• 131), a CDR-H2 having the sequence S-I-Y-Y-S-G-X2-T-F-Y-N-P-S-L-K-X3, wherein X2 is S or A, and X3 is S or G (SEQ ID NO:
• 132), a CDR-H1 having the sequence G-S-I-X4-S-X5-X6-X7-Y-W-G, wherein X4 is S or T, X5 is S or T, X6 is S or K, and X7 is H or Y (SEQ ID NO:
• 133), a CDR-L3 having the sequence QQHFNLPT (SEQ ID NO:
• 63), a CDR-L2 having the sequence DASNRAT (SEQ ID NO:
• 67), and a CDR-L1 having the sequence RASQSVSSYLA (SEQ ID NO:
• 70);
• (2) a CDR-H3 having the sequence A-R-G-G-R-T-T-W-I-C-A-X1-D-I, wherein X1 is F or L (SEQ ID NO:
• 134), a CDR-H2 having the sequence I-I-N-P-S-X2-G-L-T-S-Y-A-X3-K-F-Q-G, wherein X2 is L or I, and X3 is Q or R (SEQ ID NO:
• 135), a CDR-H1 having the sequence Y-T-F-X4-X5-Y-Y-X6-H, wherein X4 is G, P or R, X5 is N, A or E, and X6 is M or I (SEQ ID NO:
• 136), a CDR-L3 having the sequence QQYWWPPLT (SEQ ID NO:65), a CDR-L2 having the sequence GASTRAT (SEQ ID NO:69), and a CDR-L1 having the sequence RASQSVSSNLA (SEQ ID NO:72);
• (3) a CDR-H3 having the sequence ARLHVSGSYYPAYLDY (SEQ ID NO:
• 35), a CDR-H2 having the sequence X1-I-N-P-S-M-G-A-T-S-Y-X2-Q-K-F-X3-G, wherein X1 is V or I, X2 is A or T, and X3 is Q or R (SEQ ID NO:
• 137), a CDR-H1 having the sequence YTFTSHYMG (SEQ ID NO:
• 62), a CDR-L3 having the sequence QQYIVFPWT (SEQ ID NO:
• 66), a CDR-L2 having the sequence GASTRAT (SEQ ID NO:
• 69), and a CDR-L1 having the sequence RASQSVSSNLA, (SEQ ID NO:
• 72);
• and
• (4) a CDR-H3 having the sequence A-R-D-G-V-L-X1-L-N-K-R-S-F-D-I, wherein X1 is A or T (SEQ ID NO:
• 128), a CDR-H2 having the sequence S-I-Y-Y-S-G-X2-T-Y-Y-N-P-S-L-K-S, wherein X2 is S, Q or G (SEQ ID NO:
• 129), a CDR-H1 having the sequence G-S-I-X3-S-G-X4-Y-Y-W-G, wherein X3 is E or A, and X4 is L, V or S (SEQ ID NO:
• 130), a CDR-L3 having the sequence QQHTVRPPLT (SEQ ID NO:
• 64), a CDR-L2 having the sequence GASSRAT (SEQ ID NO:
• 68);
• and a CDR-L1 having the sequence RASQSVSSSYLA (SEQ ID NO:
• 71),
• or a pharmaceutical composition comprising an effective amount of the antibody or antigen-binding fragment thereof and a pharmaceutically acceptable carrier;
• and
• b) at least one additional therapeutic agent selected from an immunomodulatory agent, a chemotherapeutic agent, an immunostimulatory agent, radiation, and combinations thereof.