ANTI-TIGIT ANTIBODIES

1 . An antibody or antigen binding fragment thereof that binds to human TIGIT, wherein the antibody or antigen binding fragment is selected from the group consisting of:

a. an antibody or antigen binding fragment comprising: a heavy chain variable region CDR1 comprising the amino acid sequence of SEQ ID NO:1, a heavy chain variable region CDR2 comprising the amino acid sequence of SEQ ID NO:2, a heavy chain variable region CDR3 comprising the amino acid sequence of SEQ ID NO:3, 79, 80, 81, 82, 83 or 140, a light chain variable region CDR1 comprising the amino acid sequence of SEQ ID NO:4, a light chain variable region CDR2 comprising the amino acid sequence of SEQ ID NO:5, 65, 66, 67, 68, 69, 70, 71, 72, 73 or 41, and a light chain variable region CDR3 comprising the amino acid sequence of SEQ ID NO:6, 74, 75, 76, 77, 78 or 142;

b. an antibody or antigen binding fragment comprising: a heavy chain variable region CDR1 comprising the amino acid sequence of SEQ ID NO:57, a heavy chain variable region CDR2 comprising the amino acid sequence of SEQ ID NO:58, a heavy chain variable region CDR3 comprising the amino acid sequence of SEQ ID NO:59, a light chain variable region CDR1 comprising the amino acid sequence of SEQ ID NO:60, a light chain variable region CDR2 comprising the amino acid sequence of SEQ ID NO:61, and a light chain variable region CDR3 comprising the amino acid sequence of SEQ ID NO:62; and

c. an antibody or antigen binding fragment comprising: a heavy chain variable region CDR1 comprising the amino acid sequence of SEQ ID NO:88, a heavy chain variable region CDR2 comprising the amino acid sequence of SEQ ID NO:89, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 134, 135 or 147, a heavy chain variable region CDR3 comprising the amino acid sequence of SEQ ID NO:90, 153, 154, 155, 156, 157, 158, 159, 160, 161, 162, 163, 164, 165, 166 or 167, a light chain variable region CDR1 comprising the amino acid sequence of SEQ ID NO:91, a light chain variable region CDR2 comprising the amino acid sequence of SEQ ID NO:92, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122 or 148, and a light chain variable region CDR3 comprising the amino acid sequence of SEQ ID NO:93.

2 . The antibody or antigen binding fragment of claim 1 , wherein the antibody comprises a heavy chain variable region CDR1 comprising the amino acid sequence of SEQ ID NO:1, a heavy chain variable region CDR2 comprising the amino acid sequence of SEQ ID NO:2, a heavy chain variable region CDR3 comprising the amino acid sequence of SEQ ID NO:3, a light chain variable region CDR1 comprising the amino acid sequence of SEQ ID NO:4, a light chain variable region CDR2 comprising the amino acid sequence of SEQ ID NO:5, and a light chain variable region CDR3 comprising the amino acid sequence of SEQ ID NO:6.

3 . The antibody or antigen binding fragment of claim 1 , wherein the antibody comprises a heavy chain variable region CDR1 comprising the amino acid sequence of SEQ ID NO:88, a heavy chain variable region CDR2 comprising the amino acid sequence of SEQ ID NO:89, 134 or 135, a heavy chain variable region CDR3 comprising the amino acid sequence of SEQ ID NO:90, a light chain variable region CDR1 comprising the amino acid sequence of SEQ ID NO:91, a light chain variable region CDR2 comprising the amino acid sequence of SEQ ID NO:92, and a light chain variable region CDR3 comprising the amino acid sequence of SEQ ID NO:93.

4 . The antibody or antigen binding fragment of claim 1 , wherein the antibody comprises a heavy chain variable region CDR1 comprising the amino acid sequence of SEQ ID NO:88, a heavy chain variable region CDR2 comprising the amino acid sequence of SEQ ID NO: 134, a heavy chain variable region CDR3 comprising the amino acid sequence of SEQ ID NO:90, a light chain variable region CDR1 comprising the amino acid sequence of SEQ ID NO:91, a light chain variable region CDR2 comprising the amino acid sequence of SEQ ID NO:92, and a light chain variable region CDR3 comprising the amino acid sequence of SEQ ID NO:93.

5 . An antibody or antigen binding fragment thereof that binds to human TIGIT comprising a light chain immunoglobulin, a heavy chain immunoglobulin or both a light chain and a heavy chain immunoglobulin selected from the group consisting of:

a. an antibody or antigen binding fragment thereof comprising a variable heavy chain comprising the amino acid sequence of SEQ ID NO:7 and/or a variable light chain comprising the amino acid sequence of SEQ ID NO:8;

b. an antibody or antigen binding fragment thereof comprising a variable heavy chain comprising the amino acid sequence of SEQ ID NO:63 and/or a variable light chain comprising the amino acid sequence of SEQ ID NO:64;

c. an antibody or antigen binding fragment thereof comprising a variable heavy chain comprising the amino acid sequence of SEQ ID NO: 94 and/or a variable light chain comprising the amino acid sequence of SEQ ID NO:95;

d. an antibody or antigen binding fragment thereof comprising a variable heavy chain selected from the group consisting of SEQ ID NOs: 9-24, 37-47 and 63 and/or a variable light chain selected from the group consisting of any one of SEQ ID NOs: 25-30, 48-52 and 64;

e. an antibody or antigen binding fragment thereof comprising a variable heavy chain selected from the group consisting of SEQ ID NOs: 124-129 and/or a variable light chain selected from the group consisting of any one of SEQ ID NOs: 130-133;

f. an antibody or antigen binding fragment thereof comprising a variable heavy chain comprising the amino acid sequence of SEQ ID NO:128 and/or a variable light chain comprising the amino acid sequence of SEQ ID NO:132;

g. an antibody or antigen binding fragment thereof comprising a variable heavy chain comprising the amino acid sequence of SEQ ID NO:127 and/or a variable light chain comprising the amino acid sequence of SEQ ID NO:130; and

h. an antibody or antigen binding fragment thereof comprising a variable heavy chain comprising the amino acid sequence of SEQ ID NO:128 and/or a variable light chain comprising the amino acid sequence of SEQ ID NO:133;

i. an antibody or antigen binding fragment thereof comprising a variable heavy chain comprising the amino acid sequence of SEQ ID NO:143 and/or a variable light chain comprising the amino acid sequence of SEQ ID NO:145;

j. an antibody or antigen binding fragment thereof comprising a variable heavy chain comprising the amino acid sequence of SEQ ID NO:149 and/or a variable light chain comprising the amino acid sequence of SEQ ID NO:151;

k. an antibody or antigen binding fragment thereof comprising a variable heavy chain comprising the amino acid sequence of SEQ ID NO:144 and/or a variable light chain comprising the amino acid sequence of SEQ ID NO:146;

l. an antibody or antigen binding fragment thereof comprising a variable heavy chain comprising the amino acid sequence of SEQ ID NO:150 and/or a variable light chain comprising the amino acid sequence of SEQ ID NO:152;

m. an antibody or antigen binding fragment thereof comprising a variable heavy chain comprising at least 90%, 95%, 96%, 97%, 98% or 99% identity any one of SEQ ID NOs: 7, 9-24, 37-47 and 63 and/or a variable light chain comprising at least 90%, 95%, 96%, 97%, 98% or 99% identity to any one of SEQ ID NOs: 8, 25-30, 48-52 and 64;

n. an antibody or antigen binding fragment thereof comprising a variable heavy chain comprising at least 90%, 95%, 96%, 97%, 98% or 99% identity any one of SEQ ID NOs: 7, 9-24, 37-47 and 63 and/or a variable light chain comprising at least 90%, 95%, 95%, 96%, 97%, 98% or 99% identity to any one of SEQ ID NOs: 8, 25-30, 48-52 and 64, wherein any sequence variations occur in the framework regions of the antibody;

o. an antibody or antigen binding fragment thereof comprising a variable heavy chain comprising at least 90%, 95%, 96%, 97%, 98% or 99% identity any one of SEQ ID NOs: 124-129 and/or a variable light chain comprising at least 90%, 95%, 96%, 97%, 98% or 99% identity to any one of SEQ ID NOs: 130-133; and

p. an antibody or antigen binding fragment thereof comprising a variable heavy chain comprising at least 90%, 95%, 96%, 97%, 98% or 99% identity any one of SEQ ID NOs: 124-129 and/or a variable light chain comprising at least 90%, 95%, 95%, 96%, 97%, 98% or 99% identity to any one of SEQ ID NOs: 130-133, wherein any sequence variations occur in the framework regions of the antibody;

q. an antibody or antigen binding fragment thereof comprising a variable heavy chain comprising at least 90%, 95%, 96%, 97%, 98% or 99% identity SEQ ID NO:128 and/or a variable light chain comprising at least 90%, 95%, 96%, 97%, 98% or 99% identity to any one of SEQ ID NOs: 132;

r. an antibody or antigen binding fragment thereof comprising a variable heavy chain comprising at least 90%, 95%, 96%, 97%, 98% or 99% identity SEQ ID NO:128 and/or a variable light chain comprising at least 90%, 95%, 96%, 97%, 98% or 99% identity to any one of SEQ ID NOs: 132, wherein any sequence variations occur in the framework regions of the antibody;

s. an antibody or antigen binding fragment thereof comprising a variable heavy chain comprising at least 90%, 95%, 96%, 97%, 98% or 99% identity SEQ ID NO:127 and/or a variable light chain comprising at least 90%, 95%, 96%, 97%, 98% or 99% identity to any one of SEQ ID NOs: 130;

t. an antibody or antigen binding fragment thereof comprising a variable heavy chain comprising at least 90%, 95%, 96%, 97%, 98% or 99% identity SEQ ID NO:127 and/or a variable light chain comprising at least 90%, 95%, 96%, 97%, 98% or 99% identity to any one of SEQ ID NOs: 130, wherein any sequence variations occur in the framework regions of the antibody;

u. an antibody or antigen binding fragment thereof comprising a variable heavy chain comprising at least 90%, 95%, 96%, 97%, 98% or 99% identity SEQ ID NO:128 and/or a variable light chain comprising at least 90%, 95%, 96%, 97%, 98% or 99% identity to any one of SEQ ID NOs: 133;

v. an antibody or antigen binding fragment thereof comprising a variable heavy chain comprising at least 90%, 95%, 96%, 97%, 98% or 99% identity SEQ ID NO:128 and/or a variable light chain comprising at least 90%, 95%, 96%, 97%, 98% or 99% identity to any one of SEQ ID NOs: 133, wherein any sequence variations occur in the framework regions of the antibody.

6 . The antibody or antigen binding fragment of claim 1 , wherein the antibody or antigen binding fragment thereof binds to human TIGIT with a KD value of about 1×10-9 M to about 1×10-12 M as determined by surface plasmon resonance (e.g., BIACORE) or a similar technique (e.g. KinExa or OCTET).

7 . An antibody or antigen binding fragment thereof that binds to the same epitope of human TIGIT as an antibody selected from the group consisting of:

a. an antibody comprising the variable heavy chain of SEQ ID NO:7 and the variable light chain of SEQ ID NO:8,

b. an antibody comprising the variable heavy chain of SEQ ID NO:63 and the variable light chain of SEQ ID NO:64, and

c. an antibody comprising the variable heavy chain of SEQ ID NO:94 and the variable light chain of SEQ ID NO:95;

wherein the antibody or fragment thereof has at least one of the following characteristics:

i. binds to human TIGIT with a KD value of about 1×10-9 M to about 1×10-12 M as determined by surface plasmon resonance (e.g., BIACORE) or a similar technique (e.g. KinExa or OCTET);

ii. cross-reacts with cynomolgous and rhesus TIGIT;

iii. blocks binding of human TIGIT to human CD155 and human CD112;

iv. increases T cell activation;

v. stimulates antigen-specific T-cell production of IL-2 and IFNγ;

vi. blocks induction of T cell suppression of activation induced by TIGIT ligation with cognate ligands CD155 and CD112.

8 . The antibody or antigen binding fragment of claim 7 , wherein the antibody binds to an epitope comprising the following regions of human TIGIT (SEQ ID NO:31): residues 54-57, 68-70 and 76-81.

9 . The antibody or antigen binding fragment of claim 7 , wherein the antibody binds to an epitope comprising the following regions of human TIGIT (SEQ ID NO:31): residues 53-57, 60-65, 68-70, 72-81, 94-95, and 109-119.

10 . The antibody or antigen binding fragment of claim 1 , which is a humanized antibody comprising two heavy chains and two light chains.

11 . The antibody or antigen binding fragment of claim 1 , which is a humanized antibody, wherein the antibody comprises a human IgG1 constant domain and a human kappa constant domain.

12 . (canceled)

13 . An isolated polypeptide comprising the amino acid sequence of any one of SEQ ID NOs: 7-30, 37-52, 63-64, 94-95 or 124-133, 136-139, 143-146, 149-151.

14 . An isolated nucleic acid encoding: any one of the antibodies or antigen binding fragments of claim 1 .

15 . An expression vector comprising the isolated nucleic acid of claim 14 .

16 . A host cell comprising the expression vector of claim 15 .

17 . (canceled)

18 . A composition comprising the antibody or antigen binding fragment of claim 1 and a pharmaceutically acceptable carrier or diluent.

19 . The composition of claim 18 , further comprising an agent selected from the group consisting of:

a. an anti-PD1 antibody or an antigen binding fragment thereof;

b. an anti-LAG3 antibody or an antigen binding fragment thereof;

c. an anti-VISTA antibody or an antigen binding fragment thereof;

d. an anti-BTLA antibody or an antigen binding fragment thereof;

e. an anti-TIM3 antibody or an antigen binding fragment thereof;

f. an anti-CTLA4 antibody or an antigen binding fragment thereof;

g. an anti-HVEM antibody or an antigen binding fragment thereof;

h. an anti-CD27 antibody or an antigen binding fragment thereof;

i. an anti-CD137 antibody or an antigen binding fragment thereof;

j. an anti-OX40 antibody or an antigen binding fragment thereof;

k. an anti-CD28 antibody or an antigen binding fragment thereof;

l. an anti-PDL1 antibody or an antigen binding fragment thereof;

m. an anti-PDL2 antibody or an antigen binding fragment thereof;

n. an anti-GITR antibody or an antigen binding fragment thereof;

o. an anti-ICOS antibody or an antigen binding fragment thereof;

p. an anti-SIRPα antibody or an antigen binding fragment thereof;

q. an anti-ILT2 antibody or an antigen binding fragment thereof;

r. an anti-ILT3 antibody or an antigen binding fragment thereof;

s. an anti-ILT4 antibody or an antigen binding fragment thereof; and

t. an anti-ILT5 antibody or an antigen binding fragment thereof.

20 . The composition of claim 19 , wherein the anti-PD1 antibody or an antigen binding fragment thereof is selected from the group consisting of: pembrolizumab or an antigen binding fragment thereof and nivolumab or an antigen binding fragment thereof.

21 . (canceled)

22 . A method of treating cancer in a human subject, comprising administering to the subject an effective amount of the antibody or antigen binding fragment of claim 1 , optionally in association with a further therapeutic agent or therapeutic procedure.

23 . A method of treating an infection or infectious disease in a human subject, comprising administering to the subject an effective amount of the antibody or antigen binding fragment of claim 1 , optionally in association with a further therapeutic agent or therapeutic procedure.

24 . A vaccine comprising the antibody or antigen binding fragment of claim 1 and an antigen.

25 . (canceled)

26 . (canceled)

27 . (canceled)

28 . (canceled)

29 . (canceled)

30 . (canceled)

31 . (canceled)

32 . (canceled)

33 . (canceled)

34 . (canceled)