ANTI-TIGIT ANTIBODIES, ANTI-PVRIG ANTIBODIES AND COMBINATIONS THEREOF
Anti-PVRIG and anti-TIGIT antibodies are provided.
1 .- 81 . (canceled)
82 . A composition comprising an anti-TIGIT antigen-binding domain, wherein the anti-TIGIT antigen-binding domain binds to human TIGIT (SEQ ID NO:97), wherein the anti-TIGIT antigen-binding domain comprises:
a) a variable heavy domain comprising vhCDR1, vhCDR2, and vhCDR3 from SEQ ID NO:160; and
b) a variable light domain comprising vlCDR1, vlCDR2, and vlCDR3 from SEQ ID NO:165;
wherein the CDRs comprise from 0 to 4 substitutions and wherein no individual CDR comprises more than 1 substitution, and wherein the vhCDR3 and vlCDR3 comprise no substitutions.
83 . The composition according to claim 82 , wherein the variable heavy domain comprises a sequence having at least 90% or 95% identity to SEQ ID NO:160 and the variable light domain comprises a sequence having at least 90% or 95% identity to SEQ ID NO:165.
84 . The composition according to claim 82 , wherein the substitutions comprise one or more conservative substitutions.
85 . The composition according to claim 82 , wherein the composition comprises an antibody comprising:
a) a heavy chain comprising VH-CH1-hinge-CH2-CH3; and
b) a light chain comprising VL-VC, and the VC is either kappa or lambda.
86 . The composition according to claim 85 , wherein the sequence of the CH1-hinge-CH2-CH3 is selected from human IgG1, IgG2 and IgG4, and variants thereof.
87 . The composition according to claim 85 , wherein the hinge optionally comprises one or more mutations.
88 . A composition comprising an anti-TIGIT antigen-binding domain, wherein the anti-TIGIT antigen-binding domain binds to human TIGIT (SEQ ID NO:97), wherein the anti-TIGIT antigen-binding domain comprises:
a. a variable heavy domain comprising vhCDR1, vhCDR2, and vhCDR3 from SEQ ID NO:150; and
b. a variable light domain comprising vlCDR1, vlCDR2, and vlCDR3 from SEQ ID NO:155;
wherein the CDRs comprise from 0 to 4 substitutions and wherein no individual CDR comprises more than 1 substitution, and wherein the vhCDR3 and vlCDR3 comprise no substitutions.
89 . The composition according to claim 88 , wherein the variable heavy domain comprises a sequence having at least 90% or 95% identity to SEQ ID NO:150 and the variable light domain comprises a sequence having at least 90% or 95% identity to SEQ ID NO:155.
90 . The composition according to claim 89 , wherein the substitutions comprise one or more conservative substitutions.
91 . The composition according to claim 89 , wherein the composition comprises an antibody comprising:
a. a heavy chain comprising VH-CH1-hinge-CH2-CH3; and
b. a light chain comprising VL-VC, and the VC is either kappa or lambda.
92 . The composition according to claim 91 , wherein the sequence of the CH1-hinge-CH2-CH3 is selected from human IgG1, IgG2 and IgG4, and variants thereof.
93 . The composition according to claim 91 , wherein the hinge optionally comprises one or more mutations.
94 . A composition comprising an anti-TIGIT antigen-binding domain, wherein the anti-TIGIT antigen-binding domain binds to human TIGIT (SEQ ID NO:97), wherein the anti-TIGIT antigen-binding domain comprises:
i) vhCDR1 comprising SEQ ID NO:161 or a SEQ ID NO:161 variant comprising 1 amino acid substitution;
ii) vhCDR2 comprising SEQ ID NO: 162;
iii) vhCDR3 comprising SEQ ID NO: 163;
iv) vlCDR1 comprising SEQ ID NO:166;
v) vlCDR2 comprising SEQ ID NO: 167; and
vi) vlCDR3 comprising SEQ ID NO:168.
95 . A composition comprising an anti-TIGIT antigen-binding domain, wherein the anti-TIGIT antigen-binding domain binds to human TIGIT (SEQ ID NO:97), wherein the anti-TIGIT antigen-binding domain comprises:
i) vhCDR1 comprising SEQ ID NO:161;
ii) vhCDR2 comprising SEQ ID NO: 162 or a SEQ ID NO:162 variant comprising 1 amino acid substitution;
iii) vhCDR3 comprising SEQ ID NO: 163;
iv) vlCDR1 comprising SEQ ID NO: 166;
v) vlCDR2 comprising SEQ ID NO: 167; and
vi) vlCDR3 comprising SEQ ID NO: 168.
96 . A composition comprising an anti-TIGIT antigen-binding domain, wherein the anti-TIGIT antigen-binding domain binds to human TIGIT (SEQ ID NO:97), wherein the anti-TIGIT antigen-binding domain comprises:
i) vhCDR1 comprising SEQ ID NO:161;
ii) vhCDR2 comprising SEQ ID NO: 162;
iii) vhCDR3 comprising SEQ ID NO: 163;
iv) vlCDR1 comprising SEQ ID NO: 166 or a SEQ ID NO:166 variant comprising 1 amino acid substitution;
v) vlCDR2 comprising SEQ ID NO: 167; and
vi) vlCDR3 comprising SEQ ID NO:168.
97 . A composition comprising an anti-TIGIT antigen-binding domain, wherein the anti-TIGIT antigen-binding domain binds to human TIGIT (SEQ ID NO:97), wherein the anti-TIGIT antigen-binding domain comprises:
i) vhCDR1 comprising SEQ ID NO:161;
ii) vhCDR2 comprising SEQ ID NO: 162;
iii) vhCDR3 comprising SEQ ID NO: 163;
iv) vlCDR1 comprising SEQ ID NO: 166;
v) vlCDR2 comprising SEQ ID NO:167 or a SEQ ID NO:167 variant comprising 1 amino acid substitution; and
vi) vlCDR3 comprising SEQ ID NO:168.
98 . A composition comprising an anti-TIGIT antigen-binding domain, wherein the anti-TIGIT antigen-binding domain binds to human TIGIT (SEQ ID NO:97), wherein the anti-TIGIT antigen-binding domain comprises:
i) vhCDR1 comprising SEQ ID NO:151 or a SEQ ID NO:151 variant comprising 1 amino acid substitution;
ii) vhCDR2 comprising SEQ ID NO: 152;
iii) vhCDR3 comprising SEQ ID NO: 153;
iv) vlCDR1 comprising SEQ ID NO: 156
v) vlCDR2 comprising SEQ ID NO: 157; and
vi) vlCDR3 comprising SEQ ID NO:158.
99 . A composition comprising an anti-TIGIT antigen-binding domain, wherein the anti-TIGIT antigen-binding domain binds to human TIGIT (SEQ ID NO:97), wherein the anti-TIGIT antigen-binding domain comprises:
i) vhCDR1 comprising SEQ ID NO:151;
ii) vhCDR2 comprising SEQ ID NO: 152 or a SEQ ID NO:152 variant comprising 1 amino acid substitution;
iii) vhCDR3 comprising SEQ ID NO:153;
iv) vlCDR1 comprising SEQ ID NO: 156;
v) vlCDR2 comprising SEQ ID NO: 157; and
vi) vlCDR3 comprising SEQ ID NO:158.
100 . A composition comprising an anti-TIGIT antigen-binding domain, wherein the anti-TIGIT antigen-binding domain binds to human TIGIT (SEQ ID NO:97), wherein the anti-TIGIT antigen-binding domain comprises:
i) vhCDR1 comprising SEQ ID NO:151;
ii) vhCDR2 comprising SEQ ID NO: 152;
iii) vhCDR3 comprising SEQ ID NO: 153;
iv) vlCDR1 comprising SEQ ID NO:156 or a SEQ ID NO:156 variant comprising 1 amino acid substitution;
v) vlCDR2 comprising SEQ ID NO: 157; and
vi) vlCDR3 comprising SEQ ID NO:158.
101 . A composition comprising an anti-TIGIT antigen-binding domain, wherein the anti-TIGIT antigen-binding domain binds to human TIGIT (SEQ ID NO:97), wherein the anti-TIGIT antigen-binding domain comprises:
i) vhCDR1 comprising SEQ ID NO:151;
ii) vhCDR2 comprising SEQ ID NO: 152;
iii) vhCDR3 comprising SEQ ID NO: 153;
iv) vlCDR1 comprising SEQ ID NO: 156;
v) vlCDR2 comprising SEQ ID NO: 157 or a SEQ ID NO:157 variant comprising 1 amino acid substitution; and
vi) vlCDR3 comprising SEQ ID NO:158.