Anti-VISTA Antibodies And Fragments
3 Assignments
0 Petitions
Accused Products
Abstract
The present invention relates to novel antibodies and fragments that bind to a V-domain Ig Suppressor of T cell Activation (VISTA), and methods of making and using same. Methods of use include methods of treatment of cancer, including leukemias, lymphomas, solid tumors and melanomas.
26 Citations
105 Claims
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1-17. -17. (canceled)
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18. An isolated antibody or antibody fragment thereof comprising an antigen binding region that binds to a V-domain Ig Suppressor of T cell Activation (VISTA), wherein the antibody or antibody fragment comprises at least one heavy chain and at least one light chain, wherein at least one heavy chain comprises the heavy chain variable region sequence as shown in SEQ ID NOs:
- 37-40, and wherein at least one light chain comprises the light chain variable region sequence as shown in SEQ ID NOs;
41-45. - View Dependent Claims (19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 31, 32, 46, 47, 48, 49, 51, 52, 53, 54, 55, 56, 57, 58, 96, 97, 98, 99)
- 37-40, and wherein at least one light chain comprises the light chain variable region sequence as shown in SEQ ID NOs;
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29-30. -30. (canceled)
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33-35. -35. (canceled)
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36. A method of treating a lung cancer in an individual in need thereof comprising administering to the individual a therapeutically effective amount of a V-domain Ig Suppressor of T cell Activation (VISTA) antagonist comprising an antibody or antibody fragment thereof comprising an antigen binding region that binds to VISTA;
- wherein the antibody or antibody fragment binds to VISTA, thereby modulating or enhancing an immune response to the lung cancer.
- View Dependent Claims (72)
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37-45. -45. (canceled)
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50. An antibody or fragment thereof that binds VISTA and which comprises an antibody VH domain comprising a VH CDR1 having an amino acid sequence that is substantially similar to SEQ ID NO:
- 1, a VH CDR2 having an amino acid sequence that is substantially similar to SEQ ID NO;
2 and a VH CDR3 having an amino acid sequence that is substantially similar to SEQ ID NO;
3, and which further comprises an antibody VL domain comprising a VL CDR1 having an amino acid sequence that is substantially similar to SEQ ID NO;
4, a VL CDR2 having an amino acid sequence that is substantially similar to SEQ ID NO;
5 and a VL CDR3 having an amino acid sequence that is identical to SEQ ID NO;
6.
- 1, a VH CDR2 having an amino acid sequence that is substantially similar to SEQ ID NO;
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59. An antibody or antibody fragment thereof, wherein the antibody is selected from the group consisting of:
- VSTB112 (S2), VSTB116 (S5), VSTB95 (S16), VSTB50 (S41), VSTB53 (S43) and VSTB60 (S47).
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60. An antibody or fragment thereof that binds VISTA and which comprises one or more heavy chain complementary determining regions (CDRs) and one or more light chain CDRs of an antibody selected from the group consisting of:
- VSTB112 (S2), VSTB116 (S5), VSTB95 (S16), VSTB50 (S41), VSTB53 (S43) and VSTB60 (S47).
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61. An antibody or fragment thereof that binds VISTA and which comprises at least one heavy chain and at least one light chain of an antibody selected from the group consisting of:
- VSTB112 (S2), VSTB116 (S5), VSTB95 (S16), VSTB50 (S41), VSTB53 (S43) and VSTB60 (S47).
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62. An antibody or antibody fragment that binds VISTA and which comprises at least one heavy chain and at least one light chain, wherein the at least one heavy chain comprises all three heavy chain CDRs of an antibody selected from the group consisting of:
- VSTB112 (S2), VSTB116 (S5), VSTB95 (S16), VSTB50 (S41), VSTB53 (S43) and VSTB60 (S47).
- View Dependent Claims (63, 65, 66, 67)
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64. (canceled)
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68-71. -71. (canceled)
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73. An isolated antibody or antibody fragment thereof comprising an antigen binding region that binds to a V-domain Ig Suppressor of T cell Activation (VISTA), wherein the antibody comprises an antibody VH domain comprising a VH CDR1 having the amino acid sequence of SEQ ID NO:
- 25, a VH CDR2 having the amino acid sequence of SEQ ID NO;
26 and a VH CDR3 having the amino acid sequence of SEQ ID NO;
27, and which further comprises an antibody VL domain comprising a VL CDR1 having the amino acid sequence of SEQ ID NO;
28, a VL CDR2 having the amino acid sequence of SEQ ID NO;
29 and a VL CDR3 having the amino acid sequence of SEQ ID NO;
30. - View Dependent Claims (74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 103, 104, 105)
- 25, a VH CDR2 having the amino acid sequence of SEQ ID NO;
- 100. A method of enhancing an immune response in an individual in need thereof, comprising administering to the individual a therapeutically effective amount of an antibody that binds V-domain Ig Suppressor of T cell Activation (VISTA), or an antibody fragment thereof, comprising an antigen binding region that binds to VISTA, thereby enhancing an immune response to the cancer.
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102. A method of eliciting a biological response in an individual in need thereof, comprising administering to the individual a therapeutically effective amount of an antibody that binds V-domain Ig Suppressor of T cell Activation (VISTA), or an antibody fragment thereof, comprising an antigen binding region that binds to VISTA, thereby enhancing an immune response to the cancer, wherein the biological response is selected from the group consisting of:
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a. activation of monocytes; b. induction of T-cell proliferation and cytokine secretion; c. increased survival of monocytes; d. induction of antibody-dependent cell-mediated cytotoxicity (ADCC) in cells-expressing VISTA; and e. induction of antibody-dependent cellular phagocytosis (ADCP) in cells-expressing VISTA.
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Specification