ANTIBODIES AND BLOCKING THE INTERACTION OF VISTA AND ITS BINDING PARTNER
Disclosed herein are antibodies that specifically bind to LRIG1 and methods of use thereof. In some embodiments, also described herein are methods of modulating immune system activity or promoting immune cell proliferation with an antibody that specifically binds to LRIG1.
1 . An antigen binding polypeptide, wherein the polypeptide exhibits specific binding to LRIG1 protein (SEQ ID NO: 2), and wherein the polypeptide binds to an epitope present on one or more regions of the LRIG1 protein selected from a group consisting of any amino acid sequence from amino acid residues from position 1 to 564 or position 655 to 1093 from N terminus to C terminus of the LRIG1 protein.
2 .- 13 . (canceled)
14 . The antigen binding polypeptide of claim 1 , wherein the polypeptide disrupts LRIG1-VISTA interaction, and wherein the polypeptide binds to an epitope of LRIG1 in a region from SEQ ID NOs: 69 to 75.
15 . The antigen binding polypeptide of claim 1 , wherein the polypeptide binds to an epitope present within the region of LRIG1 defined by Peptide 65 (SEQ ID NO: 69).
16 . The antigen binding polypeptide of claim 1 , wherein the polypeptide binds to an epitope present within the region of LRIG1 defined by Peptide 66 (SEQ ID NO: 70).
17 . The antigen binding polypeptide of claim 1 , wherein the polypeptide binds to an epitope present within the region of LRIG1 defined by Peptide 67 (SEQ ID NO: 71).
18 . The antigen binding polypeptide of claim 1 , wherein the polypeptide binds to an epitope present within the region of LRIG1 defined by Peptide 68 (SEQ ID NO: 72).
19 . The antigen binding polypeptide of claim 1 , wherein the polypeptide binds to an epitope present within the region of LRIG1 defined by Peptide 69 (SEQ ID NO: 73).
20 . The antigen binding polypeptide of claim 1 , wherein the polypeptide binds to an epitope present within the region of LRIG1 defined by Peptide 70 (SEQ ID NO: 74).
21 . The antigen binding polypeptide of claim 1 , wherein the polypeptide binds to an epitope present within the region of LRIG1 defined by Peptide 71 (SEQ ID NO: 75).
22 . The antigen binding polypeptide of claim 1 , wherein the antigen binding polypeptide comprises a full-length antibody or a fragment thereof.
23 . The antigen binding polypeptide of claim 1 , wherein the antigen binding polypeptide comprises a bispecific antibody or a binding fragment thereof.
24 . The antigen binding polypeptide of claim 1 , wherein the antigen binding polypeptide comprises a monovalent Fab′, a divalent Fab2, a single-chain variable fragment (scFv), a diabody, a minibody, a nanobody, a single-domain antibody (sdAb), or a camelid antibody or binding fragment thereof.
25 . (canceled)
26 . The antigen binding polypeptide of claim 1 , wherein the antigen binding polypeptide comprises an IgG framework, an IgG1 framework, an IgG2 framework, or an IgG4 framework.
27 . (canceled)
28 . The antigen binding polypeptide of claim 1 , wherein the antigen binding polypeptide comprises a k D of less than 30 nM.
29 . The antigen binding polypeptide of claim 1 , wherein the antigen binding polypeptide comprises a humanized antibody.
31 .- 52 . (canceled)
53 . An antigen binding polypeptide, wherein the polypeptide exhibits specific binding to LRIG1 protein such that upon binding said polypeptide reduces an interaction between LRIG1-VISTA by (i) at least 79%, wherein said antibody is not IMT300 or (ii) a greater degree than IMT300.
54 . (canceled)
55 . A method of disrupting an interaction between VISTA and LRIG1, comprising:
contacting a plurality of cells comprising a LRIG1-expressing cell, a VISTA-expressing cell, or a combination thereof with the antigen binding polypeptide of claim 1 .
56 .- 70 . (canceled)
71 . A method of modulating an immune response in a subject, comprising:
administering to the subject an antigen binding polypeptide that specifically binds to an LRIG1 protein (SEQ ID NO: 2).
72 .- 91 . (canceled)
92 . A pharmaceutical composition comprising the antigen binding polypeptide of claim 1 and at least one pharmaceutically acceptable carrier, excipient, diluent, or adjuvant.
93 . The antigen binding polypeptide of claim 1 , wherein the antigen binding polypeptide comprises at least one heavy chain CDR1 selected from the group consisting of SEQ ID NOs: 84, 87, 90, 93, 96, 99, 102, 105, 108, 111, 114, 117, 120, 123, 126, 129, 134, 138, 143, and 242.
94 . The antigen binding polypeptide of claim 1 , wherein the antigen binding polypeptide comprises at least one heavy chain CDR2 selected from the group consisting of SEQ ID NOs: 85, 88, 91, 94, 97, 100, 103, 106, 109, 112, 115, 118, 121, 124, 127, 130, 132, 136, 139, 141, 142, 144, and 243.
95 . The antigen binding polypeptide of claim 1 , wherein the antigen binding polypeptide comprises at least one heavy chain CDR3 selected from the group consisting of SEQ ID NOs: 86, 89, 92, 95, 98, 101, 104, 107, 110, 113, 116, 119, 122, 125, 128, 131, 133, 135, 137, 140, 145, and 244.
96 . The antigen binding polypeptide of claim 1 , wherein the antigen binding polypeptide comprises at least one light chain CDR1 selected from the group consisting of SEQ ID NOs: 149, 152, 154, 157, 163, 166, 168, 171, 172, 173, 175, 178, 181, 183, 187, 246, 251, and 253.
97 . The antigen binding polypeptide of claim 1 , wherein the antigen binding polypeptide comprises at least one light chain CDR2 selected from the group consisting of SEQ ID NOs: 150, 155, 158, 160, 164, 169, 176, 179, 185, 247, and 249.
98 . The antigen binding polypeptide of claim 1 , wherein the antigen binding polypeptide comprises at least one light chain CDR3 selected from the group consisting of SEQ ID NOs: 151, 153, 156, 159, 161, 162, 165, 167, 170, 174, 177, 180, 182, 184, 186, 248, 250, and 252.
99 . The antigen binding polypeptide of claim 1 , wherein the antigen binding polypeptide comprises 3 heavy chain CDRs selected from the group consisting of SEQ ID NOs: 81-145 and 242-245, and 3 light chain CDRs selected from the group consisting of SEQ ID NOs: 146-187 and 246-254.
100 . (canceled)
101 . The antigen binding polypeptide of claim 1 , wherein the antigen binding polypeptide comprises a VH domain having a sequence with at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% homology to SEQ ID NOs: 192-216.
102 . The antigen binding polypeptide of claim 1 , wherein the antigen binding polypeptide comprises a VL domain having a sequence with at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% homology to SEQ ID NOs: 217-241.
103 . (canceled)
104 . (canceled)