ANTI-TIGIT ANTIBODIES
First Claim
Patent Images
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.
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Abstract
The present invention relates to anti-TIGIT antibodies, as well as use of these antibodies in the treatment of diseases such as cancer and infectious disease.
48 Citations
34 Claims
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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:
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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; andc. 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. - View Dependent Claims (2, 3, 4, 6, 10, 11, 14, 15, 16, 18, 19, 20, 22, 23, 24)
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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:
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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; andh. 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; andp. 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.
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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:
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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, andc. 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. - View Dependent Claims (8, 9)
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12. (canceled)
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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.
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17. (canceled)
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21. (canceled)
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25. (canceled)
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26. (canceled)
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27. (canceled)
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28. (canceled)
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29. (canceled)
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30. (canceled)
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31. (canceled)
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32. (canceled)
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33. (canceled)
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34. (canceled)
Specification