Anti-TIGIT antibodies
AssigneeMerck Sharp & Dohme Corp.
InventorsSybil M. G. Williams, Wolfgang Seghezzi, Laurence Fayadat-Dilman, Linda Liang, Veronica Juan
Life of this patent
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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.
Claims22
An antibody or antigen binding fragment thereof that binds to human T cell immunoreceptor with Ig and ITIM domains (TIGIT), wherein the antibody or antigen binding fragment thereof comprises a heavy chain variable region and a light chain variable region, wherein the heavy chain variable region comprises a heavy chain variable region CDR1, a heavy chain variable region CDR2, and a heavy chain variable region CDR3, and the light chain variable region comprises a light chain variable region CDR1, a light chain variable region CDR2, and a light chain variable region CDR3;
- and wherein the antibody or antigen binding fragment thereof is selected from the group consisting of:
- a. an antibody or antigen binding fragment thereof 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, 45, 46, or 47, 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, 57, 58, 59, 60, 61, or 62;
- and
- b. an antibody or antigen binding fragment thereof comprising:
- a heavy chain variable region CDR1 comprising the amino acid sequence of SEQ ID NO:17, a heavy chain variable region CDR2 comprising the amino acid sequence of SEQ ID NO:18, 81, 82, 83, 84, 85, 86, 87, or 88, a heavy chain variable region CDR3 comprising the amino acid sequence of SEQ ID NO:19, a light chain variable region CDR1 comprising the amino acid sequence of SEQ ID NO:20, a light chain variable region CDR2 comprising the amino acid sequence of SEQ ID NO:21, and a light chain variable region CDR3 comprising the amino acid sequence of SEQ ID NO:22.
An antibody or antigen binding fragment thereof that binds to human T cell immunoreceptor with Ig and ITIM domains (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 heavy chain variable region comprising the amino acid sequence of SEQ ID NO:7 and a light chain variable region comprising the amino acid sequence of SEQ ID NO:8;
- b. an antibody or antigen binding fragment thereof comprising a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:9 and a light chain variable region comprising the amino acid sequence of SEQ ID NO:13;
- c. an antibody or antigen binding fragment thereof comprising a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:
- 23 and a light chain variable region comprising the amino acid sequence of SEQ ID NO:24;
- d. an antibody or antigen binding fragment thereof comprising a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:
- 25 and a light chain variable region comprising the amino acid sequence of SEQ ID NO:29;
- e. an antibody or antigen binding fragment thereof comprising a heavy chain variable region selected from the group consisting of SEQ ID NOs:
- 10, 11, 12, 48, 49, 50, 51, 52, 53, 54, 55, and 56 and a light chain variable region selected from the group consisting of SEQ ID NOs:
- 14, 15, 16, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, and 80;
- f. an antibody or antigen binding fragment thereof comprising a heavy chain variable region selected from the group consisting of SEQ ID NOs:
- 26, 27, 28, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, and 112 and a light chain variable region selected from the group consisting of SEQ ID NOs:
- 30, 31, and 32;
- g. an antibody or antigen binding fragment thereof comprising a heavy chain variable region comprising at least 90%, 95%, 96%, 97%, 98% or 99% identity to any one of SEQ ID NOs:
- 10, 11, 12, 48, 49, 50, 51, 52, 53, 54, 55, or 56 and a light chain variable region comprising at least 90%, 95%, 96%, 97%, 98% or 99% identity to any one of SEQ ID NOs:
- 14, 15, 16, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, or 80;
- h. an antibody or antigen binding fragment thereof comprising a heavy chain variable region comprising at least 90%, 95%, 96%, 97%, 98% or 99% identity to any one of SEQ ID NOs:
- 26, 27, 28, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, or 112 and a light chain variable region comprising at least 90%, 95%, 96%, 97%, 98% or 99% identity to any one of SEQ ID NOs:
- 30, 31, or 32;
- i. an antibody or antigen binding fragment thereof comprising a heavy chain variable region comprising at least 90%, 95%, 96%, 97%, 98% or 99% identity to any one of SEQ ID NOs:
- 10, 11, 12, 48, 49, 50, 51, 52, 53, 54, 55, or 56 and a light chain variable region comprising at least 90%, 95%, 95%, 96%, 97%, 98% or 99% identity to any one of SEQ ID NOs:
- 14, 15, 16, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, or 80, wherein any sequence variations occur in the framework regions of the antibody;
- and
- j. an antibody or antigen binding fragment thereof comprising a heavy chain variable region comprising at least 90%, 95%, 96%, 97%, 98% or 99% identity to any one of SEQ ID NOs:
- 26, 27, 28, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, or 112 and a light chain variable region comprising at least 90%, 95%, 95%, 96%, 97%, 98% or 99% identity to any one of SEQ ID NOs:
- 30, 32, or 32, wherein any sequence variations occur in the framework regions of the antibody.
A humanized antibody that binds to human T cell immunoreceptor with Ig and ITIM domains (TIGIT), wherein the antibody wherein the humanized antibody comprises two heavy chains and two light chains, wherein the heavy chain variable region comprises the amino acid sequence of SEQ ID NO:
- 27, and wherein the light chain variable region comprises the amino acid sequence of SEQ ID NO:
- 31.
A humanized antibody that binds to human T cell immunoreceptor with Ig and ITIM domains (TIGIT), wherein the humanized antibody comprises a heavy chain variable region CDR1 comprising the amino acid sequence of SEQ ID NO:17, a heavy chain variable region CDR2 comprising the amino acid sequence of SEQ ID NO:
- 18, a heavy chain variable region CDR3 comprising the amino acid sequence of SEQ ID NO:19, a light chain variable region CDR1 comprising the amino acid sequence of SEQ ID NO:20, a light chain variable region CDR2 comprising the amino acid sequence of SEQ ID NO:21, and a light chain variable region CDR3 comprising the amino acid sequence of SEQ ID NO:22, wherein the humanized antibody comprises two heavy chains and two light chains.
A humanized antibody that binds to human T cell immunoreceptor with Ig and ITIM domains (TIGIT), wherein the antibody comprises two heavy chains and two light chains, wherein each heavy chain comprises a heavy chain variable region and each light chain comprises a light chain variable region, wherein the heavy chain variable region comprises the amino acid sequence the amino acid sequence of SEQ ID NO:
- 27, wherein the light chain variable region comprises the amino acid sequence the amino acid sequence of SEQ ID NO:
- 31, wherein the antibody comprises a human IgG1 constant domain comprising the amino acid sequence of SEQ ID NO:
- 44 and a human kappa constant domain comprising the amino acid sequence of SEQ ID NO:
- 43.
A humanized antibody that binds to human T cell immunoreceptor with Ig and ITIM domains (TIGIT), wherein the antibody comprises two heavy chains and two light chains, wherein each heavy chain comprises a heavy chain variable region and each light chain comprises a light chain variable region, wherein the heavy chain variable region comprises the amino acid sequence the amino acid sequence of SEQ ID NO:
- 27, wherein the light chain variable region comprises the amino acid sequence the amino acid sequence of SEQ ID NO:
- 31, wherein the antibody comprises a human IgG4 constant domain comprising the amino acid sequence of SEQ ID NO:
- 42 and a human kappa constant domain comprising the amino acid sequence of SEQ ID NO:
- 43.
Dependencies are inferred from the claim text.