Anti-tigit antibodies and methods of use

Abstract

The invention provides anti-TIGIT (T-cell immunoreceptor with Ig and ITIM domains) antibodies and methods of using the same.

1 . An antibody that specifically binds to human TIGIT, wherein the antibody binds to an epitope on human TIGIT comprising one or more of amino acid residues Ser78, Ser80, and Lys82 of human TIGIT. 
     
     
         2 . The antibody of  claim 1 , wherein the epitope comprises amino acid residues Ser80 and Lys82 of human TIGIT. 
     
     
         3 . The antibody of  claim 1  or  2 , wherein the epitope comprises amino acid residues Ser78, Ser80, and Lys82 of human TIGIT. 
     
     
         4 . The antibody of  claim 1 , wherein the epitope further comprises amino acid residue Ala67 of human TIGIT. 
     
     
         5 . The antibody of  claim 1 , wherein the epitope further comprises one or more additional amino acid residues selected from the group consisting of Glu60, Leu65, and Ile68 of human TIGIT. 
     
     
         6 . The antibody of  claim 1 , wherein the epitope further comprises one or more additional amino acid residues selected from the group consisting of Gln56, Asn70, Leu73, and His111 of human TIGIT. 
     
     
         7 . The antibody of  claim 1 , wherein the epitope further comprises one or more additional amino acid residues selected from the group consisting of Thr55, Asn58, Asp63, Gln64, His76, Ile77, and Pro79 of human TIGIT. 
     
     
         8 . The antibody of  claim 1 , wherein the epitope consists of amino acid residues Thr55, Gln56, Asn58, Glu60, Asp63, Gln64, Leu65, Ala67, Ile68, Asn70, Leu73, His76, Ile77, Ser78, Pro79, Ser80, Lys82, and His111 of human TIGIT. 
     
     
         9 . An antibody that specifically binds to human TIGIT, wherein the antibody binds to an epitope on human TIGIT comprising one or more of amino acid residues Thr55, Ser80, and Lys82 of human TIGIT. 
     
     
         10 . The antibody of  claim 9 , wherein the epitope comprises amino acid residue Lys82 of human TIGIT. 
     
     
         11 . The antibody of  claim 9 , wherein the epitope comprises amino acid residues Thr55, Ser80, and Lys82 of human TIGIT. 
     
     
         12 . The antibody of  claim 9 , wherein the epitope further comprises amino acid residue Gln56 of human TIGIT. 
     
     
         13 . The antibody of  claim 9 , wherein the epitope further comprises amino acid residue Ile77 or Pro79 of human TIGIT. 
     
     
         14 . (canceled) 
     
     
         15 . The antibody of  claim 9 , wherein the epitope further comprises amino acid residue Asn58 or Glu60 of human TIGIT. 
     
     
         16 . (canceled) 
     
     
         17 . The antibody of  claim 9 , wherein the epitope further comprises one or more additional amino acid residues selected from the group consisting of Leu65, Ile68, Leu73, His76, Ser78, and His111 of human TIGIT. 
     
     
         18 . The antibody of  claim 17 , wherein the epitope further comprises amino acid residues Leu65, Ile68, Leu73, His76, Ser78, and His111 of human TIGIT. 
     
     
         19 . The antibody of  claim 9 , wherein the epitope consists of Thr55, Gln56, Asn58, Glu60, Leu65, Ile68, Leu73, His76, Ile77, Ser78, Pro79, Ser80, Lys82, and His111 of human TIGIT. 
     
     
         20 - 40 . (canceled) 
     
     
         41 . The antibody of  claim 1 , wherein the antibody is capable of binding to rabbit TIGIT. 
     
     
         42 . The antibody of  claim 1 , wherein the antibody is capable of binding to both human TIGIT and cynomolgus monkey (cyno) TIGIT, but not murine TIGIT. 
     
     
         43 . The antibody of  claim 42 , wherein the antibody binds human TIGIT with a Kd of about 10 nM or lower and cyno TIGIT with a Kd of about 10 nM or lower. 
     
     
         44 - 45 . (canceled) 
     
     
         46 . The antibody of  claim 1 , wherein the antibody is an antagonist antibody. 
     
     
         47 . The antibody of  claim 46 , wherein the antagonist antibody specifically binds TIGIT and inhibits or blocks TIGIT interaction with poliovirus receptor (PVR). 
     
     
         48 - 53 . (canceled) 
     
     
         54 . The antibody of  claim 1 , wherein the antibody is an agonist antibody. 
     
     
         55 . The antibody of  claim 54 , wherein the agonist antibody specifically binds TIGIT and stimulates the interaction of PVR with CD226 or CD96. 
     
     
         56 - 58 . (canceled) 
     
     
         59 . An isolated antibody that competes for binding to TIGIT with the antibody of  claim 1 . 
     
     
         60 . An isolated antibody that binds to the same epitope as the antibody of  claim 1 . 
     
     
         61 . The antibody of  claim 1 , wherein the antibody is monoclonal. 
     
     
         62 . The antibody of  claim 1 , wherein the antibody is human, humanized, or chimeric. 
     
     
         63 . (canceled) 
     
     
         64 . The antibody of  claim 1 , wherein the antibody is (a) a full-length antibody, (b) is an antibody fragment that binds TIGIT, (c) is an antibody fragment that binds TIGIT selected from the group consisting of Fab, Fab′, Fab′-SH, Fv, single chain variable fragment (scFv), and (Fab′) 2  fragments, (d) is an IgG class antibody, or (e) is an IgG1 subclass antibody. 
     
     
         65 . The antibody of  claim 1 , wherein the antibody has a clearance following intravenous injection of about 3 ml/kg/day to about 10 ml/kg/day. 
     
     
         66 - 178 . (canceled) 
     
     
         179 . A kit comprising the antibody of  claim 1  and a package insert comprising instructions for using the antibody for (a) treating or delaying progression of a cancer, (b) treating or delaying progression of an immune-related disease, or (c) for increasing, enhancing, or stimulating an immune response or function in a subject. 
     
     
         180 - 181 . (canceled) 
     
     
         182 . The kit of  claim 179 , wherein the subject is a human.