New patent application published for: ANTIBODIES AGAINST CD24 AND USES THEREOF
ANTIBODIES AGAINST CD24 AND USES THEREOF
Abstract
Described herein are CD24 binding antibodies and fragments thereof.
Inventors:
Liu; Junli (Shanghai, CN), Yuan; Puwei (Beijing, CN), Lei; Ying (Shanghai, CN), Chen; Mingchen (Beijing, CN), Guo; Bingshi (Shanghai, CN), Liu; Fan (Beijing, CN)
Applicant:
Beijing neoX Biotech Limited (Beijing, CN)
Family ID:
1000009493458
Appl. No.:
19/124274
Filed (or PCT Filed):
October 26, 2023
PCT No.:
PCT/CN2023/126795
Claims
1. An antibody, or antigen binding fragment thereof, that binds to CD24, wherein the antibody does not bind to T lymphocytes.
2. The antibody of claim 1, wherein the antibody does not bind to activated T lymphocytes.
3. The antibody of claim 1 or 2, wherein the antibody does not bind to B lymphocytes.
4. The antibody of any one of claims 1 to 3, wherein the antibody binds to CD24 with a K.sub.D of less than 1×10.sup.−8.
5. The antibody of any one of claims 1 to 3, wherein the antibody binds to CD24 with a K.sub.D of less than 1×10.sup.−9.
6. The antibody of any one of claims 1 to 5, wherein the antibody is a humanized or chimeric antibody.
7. The antibody of any one of claims 1 to 6, wherein the antibody is a Fab, F (ab) 2, or a single chain variable fragment (scFv).
8. The antibody of any one of claims 1 to 6, wherein the antibody is a heavy chain antibody or antigen binding fragment thereof.
9. The antibody of any one of claims 1 to 6, wherein the antibody is an IgG antibody.
10. The antibody of claim 9, wherein the antibody is an IgG.sub.1 isotype.
11. The antibody of claim 9, wherein the antibody is an IgG.sub.4 isotype.
12. The antibody of any one of claims 1 to 11, wherein the antibody binds to the serine at residue 18 of SEQ ID NO: 500.
13. The antibody of any one of claims 1 to 11, wherein the antibody requires the presence of a serine at residue 18 of SEQ ID NO: 500 for binding.
14. The antibody of any one of claims 1 to 13, wherein the antibody binds to an epitope consisting of the amino acid sequence of SEQ ID NO 501.
15. An antibody, or antigen binding fragment thereof, that binds to CD24, wherein the antibody or antigen binding fragment thereof comprises: a. a light chain complementarity determining region 1 (LCDR1) comprising the amino acid sequence set forth in SEQ ID NO: 401; b. a light chain complementarity determining region 2 (LCDR2) comprising the amino acid sequence set forth in SEQ ID NO: 403; c. a light chain complementarity determining region 3 (LCDR3) comprising the amino acid sequence set forth in SEQ ID NO: 405; d. a heavy chain complementarity determining region 1 (HCDR1) comprising the amino acid sequence set forth in SEQ ID NO: 407; e. a heavy chain complementarity determining region 2 (HCDR2) comprising the amino acid sequence set forth in SEQ ID NO: 409; and/or f. a heavy chain complementarity determining region 3 (HCDR3) comprising the amino acid sequence set forth in SEQ ID NO: 411.
16. The antibody of any one of claims 1 to 15, wherein the antibody comprises: a. a light chain complementarity determining region 1 (LCDR1) comprising the amino acid sequence set forth in SEQ ID NO: 401; b. a light chain complementarity determining region 2 (LCDR2) comprising the amino acid sequence set forth in SEQ ID NO: 403; c. a light chain complementarity determining region 3 (LCDR3) comprising the amino acid sequence set forth in SEQ ID NO: 405; d. a heavy chain complementarity determining region 1 (HCDR1) comprising the amino acid sequence set forth in SEQ ID NO: 407; e. a heavy chain complementarity determining region 2 (HCDR2) comprising the amino acid sequence set forth in SEQ ID NO: 409; and/or f. a heavy chain complementarity determining region 3 (HCDR3) comprising the amino acid sequence set forth in SEQ ID NO: 411.
17. The antibody of any one of claims 1 to 15, wherein the antibody comprises: a. a light chain complementarity determining region 1 (LCDR1) comprising the amino acid sequence set forth in SEQ ID NO: 402; b. a light chain complementarity determining region 2 (LCDR2) comprising the amino acid sequence set forth in SEQ ID NO: 403; c. a light chain complementarity determining region 3 (LCDR3) comprising the amino acid sequence set forth in SEQ ID NO: 406; d. a heavy chain complementarity determining region 1 (HCDR1) comprising the amino acid sequence set forth in SEQ ID NO: 408; e. a heavy chain complementarity determining region 2 (HCDR2) comprising the amino acid sequence set forth in SEQ ID NO: 409; and/or f. a heavy chain complementarity determining region 3 (HCDR3) comprising the amino acid sequence set forth in SEQ ID NO: 412.
18. The antibody of any one of claims 1 to 15, wherein the antibody comprises: a. a light chain complementarity determining region 1 (LCDR1) as set forth in SEQ ID NO: 402; b. a light chain complementarity determining region 2 (LCDR2) comprising the amino acid sequence set forth in SEQ ID NO: 403; c. a light chain complementarity determining region 3 (LCDR3) comprising the amino acid sequence set forth in SEQ ID NO: 406; d. a heavy chain complementarity determining region 1 (HCDR1) comprising the amino acid sequence set forth in SEQ ID NO: 408; e. a heavy chain complementarity determining region 2 (HCDR2) comprising the amino acid sequence set forth in SEQ ID NO: 409; and/or f. a heavy chain complementarity determining region 3 (HCDR3) comprising the amino acid sequence set forth in SEQ ID NO: 412.
19. The antibody of any one of claims 1 to 15, wherein the antibody comprises: a. a light chain complementarity determining region 1 (LCDR1) comprising an amino acid sequence selected from the group consisting of SEQ ID NO: 13, 23, 33, 43, 53, 63, 73, 83, 703, 713, 723, 733, and 743; b. a light chain complementarity determining region 2 (LCDR2) comprising an amino acid sequence selected from the group consisting of SEQ ID NO: 14, 24, 34, 44, 54, 64, 74, 84, 704, 714, 724, 734, and 744; c. a light chain complementarity determining region 3 (LCDR3) comprising an amino acid sequence selected from the group consisting of SEQ ID NO: 15, 25, 35, 45, 55, 65, 75, 85, 705, 715, 725, 735, and 745; d. a heavy chain complementarity determining region 1 (HCDR1) comprising an amino acid sequence selected from the group consisting of SEQ ID NO: 16, 26, 36, 46, 56, 66, 76, 86, 706, 716, 726, 736, and 746; e. a heavy chain complementarity determining region 2 (HCDR2) comprising an amino acid sequence selected from the group consisting of SEQ ID NO: 17, 27, 37, 47, 57, 67, 77, 87, 707, 717, 727, 737, and 747; and/or f. a heavy chain complementarity determining region 3 (HCDR3) comprising an amino acid sequence selected from the group consisting of SEQ ID NO: 18, 28, 38, 48, 58, 68, 78, 88, 708, 718, 728, 738, and 748.
20. The antibody of any one of claims 1 to 15, wherein the antibody comprises a combination of LCDR1, LCDR2, and LCDR3 and HCDR1, HCDR2, and HCDR3, wherein the combination is selected from the group consisting of: (i) LCDR1 comprising SEQ ID NO: 13, LCDR2 comprising SEQ ID NO: 14, LCDR3 comprising SEQ ID NO: 15, HCDR1 comprising SEQ ID NO: 16, HCDR2 comprising SEQ ID NO: 17, HCDR3 comprising SEQ ID NO: 18; (ii) LCDR1 comprising SEQ ID NO: 23, LCDR2 comprising SEQ ID NO: 24, LCDR3 comprising SEQ ID NO: 25, HCDR1 comprising SEQ ID NO: 26, HCDR2 comprising SEQ ID NO: 27, HCDR3 comprising SEQ ID NO: 28; (iii) LCDR1 comprising SEQ ID NO: 33, LCDR2 comprising SEQ ID NO: 34, LCDR3 comprising SEQ ID NO: 35, HCDR1 comprising SEQ ID NO: 36, HCDR2 comprising SEQ ID NO: 37, HCDR3 comprising SEQ ID NO: 38; (iv) LCDR1 comprising SEQ ID NO: 43, LCDR2 comprising SEQ ID NO: 44, LCDR3 comprising SEQ ID NO: 45, HCDR1 comprising SEQ ID NO: 46, HCDR2 comprising SEQ ID NO: 47, HCDR3 comprising SEQ ID NO: 48; (v) LCDR1 comprising SEQ ID NO: 53, LCDR2 comprising SEQ ID NO: 54, LCDR3 comprising SEQ ID NO: 55, HCDR1 comprising SEQ ID NO: 56, HCDR2 comprising SEQ ID NO: 57, HCDR3 comprising SEQ ID NO: 58; (vi) LCDR1 comprising SEQ ID NO: 63, LCDR2 comprising SEQ ID NO: 64, LCDR3 comprising SEQ ID NO: 65, HCDR1 comprising SEQ ID NO: 66, HCDR2 comprising SEQ ID NO: 67, HCDR3 comprising SEQ ID NO: 68; (vii) LCDR1 comprising SEQ ID NO: 73, LCDR2 comprising SEQ ID NO: 74, LCDR3 comprising SEQ ID NO: 75, HCDR1 comprising SEQ ID NO: 76, HCDR2 comprising SEQ ID NO: 77, HCDR3 comprising SEQ ID NO: 78; (viii) LCDR1 comprising SEQ ID NO: 83, LCDR2 comprising SEQ ID NO: 84, LCDR3 comprising SEQ ID NO: 85, HCDR1 comprising SEQ ID NO: 86, HCDR2 comprising SEQ ID NO: 87, HCDR3 comprising SEQ ID NO: 88; (ix) LCDR1 comprising SEQ ID NO: 703, LCDR2 comprising SEQ ID NO: 704, LCDR3 comprising SEQ ID NO: 705, HCDR1 comprising SEQ ID NO: 706, HCDR2 comprising SEQ ID NO: 707, HCDR3 comprising SEQ ID NO: 708; (x) LCDR1 comprising SEQ ID NO: 713, LCDR2 comprising SEQ ID NO: 714, LCDR3 comprising SEQ ID NO: 715, HCDR1 comprising SEQ ID NO: 716, HCDR2 comprising SEQ ID NO: 717, HCDR3 comprising SEQ ID NO: 718; (xi) LCDR1 comprising SEQ ID NO: 723, LCDR2 comprising SEQ ID NO: 724, LCDR3 comprising SEQ ID NO: 725, HCDR1 comprising SEQ ID NO: 726, HCDR2 comprising SEQ ID NO: 727, HCDR3 comprising SEQ ID NO: 728; (xii) LCDR1 comprising SEQ ID NO: 733, LCDR2 comprising SEQ ID NO: 734, LCDR3 comprising SEQ ID NO: 735, HCDR1 comprising SEQ ID NO: 736, HCDR2 comprising SEQ ID NO: 737, HCDR3 comprising SEQ ID NO: 738; and (xiii) LCDR1 comprising SEQ ID NO: 743, LCDR2 comprising SEQ ID NO: 744, LCDR3 comprising SEQ ID NO: 745, HCDR1 comprising SEQ ID NO: 746, HCDR2 comprising SEQ ID NO: 747, HCDR3 comprising SEQ ID NO: 748.
21. The antibody of any one of claims 1 to 15, wherein the antibody comprises a combination of LCDR1, LCDR2, and LCDR3 and HCDR1, HCDR2, and HCDR3, wherein the combination is selected from the group consisting of: (i) LCDR1 as set forth in SEQ ID NO: 13, LCDR2 as set forth in SEQ ID NO: 14, LCDR3 as set forth in SEQ ID NO: 15, HCDR1 as set forth in SEQ ID NO: 16, HCDR2 as set forth in SEQ ID NO: 17, HCDR3 as set forth in SEQ ID NO: 18; (ii) LCDR1 as set forth in SEQ ID NO: 23, LCDR2 as set forth in SEQ ID NO: 24, LCDR3 as set forth in SEQ ID NO: 25, HCDR1 as set forth in SEQ ID NO: 26, HCDR2 as set forth in SEQ ID NO: 27, HCDR3 as set forth in SEQ ID NO: 28; (iii) LCDR1 as set forth in SEQ ID NO: 33, LCDR2 as set forth in SEQ ID NO: 34, LCDR3 as set forth in SEQ ID NO: 35, HCDR1 as set forth in SEQ ID NO: 36, HCDR2 as set forth in SEQ ID NO: 37, HCDR3 as set forth in SEQ ID NO: 38; (iv) LCDR1 as set forth in SEQ ID NO: 43, LCDR2 as set forth in SEQ ID NO: 44, LCDR3 as set forth in SEQ ID NO: 45, HCDR1 as set forth in SEQ ID NO: 46, HCDR2 as set forth in SEQ ID NO: 47, HCDR3 as set forth in SEQ ID NO: 48; (v) LCDR1 as set forth in SEQ ID NO: 53, LCDR2 as set forth in SEQ ID NO: 54, LCDR3 as set forth in SEQ ID NO: 55, HCDR1 as set forth in SEQ ID NO: 56, HCDR2 as set forth in SEQ ID NO: 57, HCDR3 as set forth in SEQ ID NO: 58; (vi) LCDR1 as set forth in SEQ ID NO: 63, LCDR2 as set forth in SEQ ID NO: 64, LCDR3 as set forth in SEQ ID NO: 65, HCDR1 as set forth in SEQ ID NO: 66, HCDR2 as set forth in SEQ ID NO: 67, HCDR3 as set forth in SEQ ID NO: 68; (vii) LCDR1 as set forth in SEQ ID NO: 73, LCDR2 as set forth in SEQ ID NO: 74, LCDR3 as set forth in SEQ ID NO: 75, HCDR1 as set forth in SEQ ID NO: 76, HCDR2 as set forth in SEQ ID NO: 77, HCDR3 as set forth in SEQ ID NO: 78; (viii) LCDR1 as set forth in SEQ ID NO: 83, LCDR2 as set forth in SEQ ID NO: 84, LCDR3 as set forth in SEQ ID NO: 85, HCDR1 as set forth in SEQ ID NO: 86, HCDR2 as set forth in SEQ ID NO: 87, HCDR3 as set forth in SEQ ID NO: 88; (ix) LCDR1 as set forth in SEQ ID NO: 703, LCDR2 as set forth in SEQ ID NO: 704, LCDR3 as set forth in SEQ ID NO: 705, HCDR1 as set forth in SEQ ID NO: 706, HCDR2 as set forth in SEQ ID NO: 707, HCDR3 as set forth in SEQ ID NO: 708; (x) LCDR1 as set forth in SEQ ID NO: 713, LCDR2 as set forth in SEQ ID NO: 714, LCDR3 as set forth in SEQ ID NO: 715, HCDR1 as set forth in SEQ ID NO: 716, HCDR2 as set forth in SEQ ID NO: 717, HCDR3 as set forth in SEQ ID NO: 718; (xi) LCDR1 as set forth in SEQ ID NO: 723, LCDR2 as set forth in SEQ ID NO: 724, LCDR3 as set forth in SEQ ID NO: 725, HCDR1 as set forth in SEQ ID NO: 726, HCDR2 as set forth in SEQ ID NO: 727, HCDR3 as set forth in SEQ ID NO: 728; (xii) LCDR1 as set forth in SEQ ID NO: 733, LCDR2 as set forth in SEQ ID NO: 734, LCDR3 as set forth in SEQ ID NO: 735, HCDR1 as set forth in SEQ ID NO: 736, HCDR2 as set forth in SEQ ID NO: 737, HCDR3 as set forth in SEQ ID NO: 738; and (xiii) LCDR1 as set forth in SEQ ID NO: 743, LCDR2 as set forth in SEQ ID NO: 744, LCDR3 as set forth in SEQ ID NO: 745, HCDR1 as set forth in SEQ ID NO: 746, HCDR2 as set forth in SEQ ID NO: 747, HCDR3 as set forth in SEQ ID NO: 748.
22. The antibody of any one of claims 1 to 15, wherein the antibody comprises: a. a light chain complementarity determining region 1 (LCDR1) comprising an amino acid sequence set forth in SEQ ID NO: 13; b. a light chain complementarity determining region 2 (LCDR2) comprising an amino acid sequence set forth in SEQ ID NO: 14; c. a light chain complementarity determining region 3 (LCDR3) comprising an amino acid sequence set forth in SEQ ID NO: 15; d. a heavy chain complementarity determining region 1 (HCDR1) comprising an amino acid sequence set forth in SEQ ID NO: 16; e. a heavy chain complementarity determining region 2 (HCDR2) comprising an amino acid sequence set forth in SEQ ID NO: 17; and/or f. a heavy chain complementarity determining region 3 (HCDR3) comprising an amino acid sequence set forth in SEQ ID NO: 18.
23. The antibody of any one of claims 1 to 15, wherein the antibody comprises: a. a light chain complementarity determining region 1 (LCDR1) comprising an amino acid sequence set forth in SEQ ID NO: 23; b. a light chain complementarity determining region 2 (LCDR2) comprising an amino acid sequence set forth in SEQ ID NO: 24; c. a light chain complementarity determining region 3 (LCDR3) comprising an amino acid sequence set forth in SEQ ID NO: 25; d. a heavy chain complementarity determining region 1 (HCDR1) comprising an amino acid sequence set forth in SEQ ID NO: 26; e. a heavy chain complementarity determining region 2 (HCDR2) comprising an amino acid sequence set forth in SEQ ID NO: 27; and/or f. a heavy chain complementarity determining region 3 (HCDR3) comprising an amino acid sequence set forth in SEQ ID NO: 28.
24. The antibody of any one of claims 1 to 15, wherein the antibody comprises: a. a light chain complementarity determining region 1 (LCDR1) comprising an amino acid sequence set forth in SEQ ID NO: 33; b. a light chain complementarity determining region 2 (LCDR2) comprising an amino acid sequence set forth in SEQ ID NO: 34; c. a light chain complementarity determining region 3 (LCDR3) comprising an amino acid sequence set forth in SEQ ID NO: 35; d. a heavy chain complementarity determining region 1 (HCDR1) comprising an amino acid sequence set forth in SEQ ID NO: 36; e. a heavy chain complementarity determining region 2 (HCDR2) comprising an amino acid sequence set forth in SEQ ID NO: 37; and/or f. a heavy chain complementarity determining region 3 (HCDR3) comprising an amino acid sequence set forth in SEQ ID NO: 38.
25. The antibody of any one of claims 1 to 15, wherein the antibody comprises: a. a light chain complementarity determining region 1 (LCDR1) comprising an amino acid sequence set forth in SEQ ID NO: 43; b. a light chain complementarity determining region 2 (LCDR2) comprising an amino acid sequence set forth in SEQ ID NO: 44; c. a light chain complementarity determining region 3 (LCDR3) comprising an amino acid sequence set forth in SEQ ID NO: 45; d. a heavy chain complementarity determining region 1 (HCDR1) comprising an amino acid sequence set forth in SEQ ID NO: 46; e. a heavy chain complementarity determining region 2 (HCDR2) comprising an amino acid sequence set forth in SEQ ID NO: 47; and/or f. a heavy chain complementarity determining region 3 (HCDR3) comprising an amino acid sequence set forth in SEQ ID NO: 48.
26. The antibody of any one of claims 1 to 15, wherein the antibody comprises: a. a light chain complementarity determining region 1 (LCDR1) comprising an amino acid sequence set forth in SEQ ID NO: 53; b. a light chain complementarity determining region 2 (LCDR2) comprising an amino acid sequence set forth in SEQ ID NO: 54; c. a light chain complementarity determining region 3 (LCDR3) comprising an amino acid sequence set forth in SEQ ID NO: 55; d. a heavy chain complementarity determining region 1 (HCDR1) comprising an amino acid sequence set forth in SEQ ID NO: 56; e. a heavy chain complementarity determining region 2 (HCDR2) comprising an amino acid sequence set forth in SEQ ID NO: 57; and/or f. a heavy chain complementarity determining region 3 (HCDR3) comprising an amino acid sequence set forth in SEQ ID NO: 58.
27. The antibody of any one of claims 1 to 15, wherein the antibody comprises: a. a light chain complementarity determining region 1 (LCDR1) comprising an amino acid sequence set forth in SEQ ID NO: 63; b. a light chain complementarity determining region 2 (LCDR2) comprising an amino acid sequence set forth in SEQ ID NO: 64; c. a light chain complementarity determining region 3 (LCDR3) comprising an amino acid sequence set forth in SEQ ID NO: 65; d. a heavy chain complementarity determining region 1 (HCDR1) comprising an amino acid sequence set forth in SEQ ID NO: 66; e. a heavy chain complementarity determining region 2 (HCDR2) comprising an amino acid sequence set forth in SEQ ID NO: 67; and/or f. a heavy chain complementarity determining region 3 (HCDR3) comprising an amino acid sequence set forth in SEQ ID NO: 68.
28. The antibody of any one of claims 1 to 15, wherein the antibody comprises: a. a light chain complementarity determining region 1 (LCDR1) comprising an amino acid sequence set forth in SEQ ID NO: 73; b. a light chain complementarity determining region 2 (LCDR2) comprising an amino acid sequence set forth in SEQ ID NO: 74; c. a light chain complementarity determining region 3 (LCDR3) comprising an amino acid sequence set forth in SEQ ID NO: 75; d. a heavy chain complementarity determining region 1 (HCDR1) comprising an amino acid sequence set forth in SEQ ID NO: 76; e. a heavy chain complementarity determining region 2 (HCDR2) comprising an amino acid sequence set forth in SEQ ID NO: 77; and/or f. a heavy chain complementarity determining region 3 (HCDR3) comprising an amino acid sequence set forth in SEQ ID NO: 78.
29. The antibody of any one of claims 1 to 15, wherein the antibody comprises: a. a light chain complementarity determining region 1 (LCDR1) comprising an amino acid sequence set forth in SEQ ID NO: 83; b. a light chain complementarity determining region 2 (LCDR2) comprising an amino acid sequence set forth in SEQ ID NO: 84; c. a light chain complementarity determining region 3 (LCDR3) comprising an amino acid sequence set forth in SEQ ID NO: 85; d. a heavy chain complementarity determining region 1 (HCDR1) comprising an amino acid sequence set forth in SEQ ID NO: 86; e. a heavy chain complementarity determining region 2 (HCDR2) comprising an amino acid sequence set forth in SEQ ID NO: 87; and/or f. a heavy chain complementarity determining region 3 (HCDR3) comprising an amino acid sequence set forth in SEQ ID NO: 88.
30. The antibody of any one of claims 1 to 29, wherein the antibody comprises an immunoglobulin light chain amino acid variable region sequence at least about 90%, 95%, 96%, 97%, 98%, or 99% identical to any one of SEQ ID NOs: 155, 157, 169, 267, 271, 275, 277, 309, 311, 313, 315, 317, or 319; and an immunoglobulin heavy chain variable region amino acid sequence at least about 90%, 95%, 96%, 97%, 98%, or 99% identical to any one of SEQ ID NOs: 156, 158, 170, 268, 272, 276, 278, 310, 312, 314, 316, 318, or 320.
31. The antibody of any one of claims 1 to 29, wherein the antibody comprises an immunoglobulin light chain amino acid variable region sequence identical to any one of SEQ ID NOs: 155, 157, 169, 267, 271, 275, 277, 309, 311, 313, 315, 317, or 319; and an immunoglobulin heavyl chain variable region amino acid sequence identical to any one of SEQ ID NOs: 156, 158, 170, 268, 272, 276, 278, 310, 312, 314, 316, 318, or 320.
32. The antibody of any one of claims 1 to 15, wherein the antibody comprises: (i) a light chain variable region (VL) having the identical LCDR1, LCDR2, and LCDR3 with any one of SEQ ID NOs: 155, 157, 169, 267, 271, 275, 277, 309, 311, 313, 315, 317, and 319; and (ii) a heavy chain variable region (VH) having the identical HCDR1, HCDR2, and HCDR3 with any one of SEQ ID NOs: 156, 158, 170, 268, 272, 276, 278, 310, 312, 314, 316, 318, and 320; wherein the CDRs are defined according to any one of the Kabat definition, Chothia definition, Aho definition, Abm definition, IMGT definition, Contact definition and North definition.
33. The antibody of any one of claims 1 to 15, wherein the antibody comprises: (i) a light chain variable region (VL) having the identical LCDR1, LCDR2, and LCDR3 with any one of SEQ ID NOs: 155, 157, 169, 267, 271, 275, 277, 309, 311, 313, 315, 317, and 319; and (ii) a heavy chain variable region (VH) having the identical HCDR1, HCDR2, and HCDR3 with any one of SEQ ID NOs: 156, 158, 170, 268, 272, 276, 278, 310, 312, 314, 316, 318, and 320; wherein the CDRs are defined using a hybrid scheme of any two or three of the Kabat definition, Chothia definition, Aho definition, Abm definition, IMGT definition, Contact definition and North definition.
34. The antibody of any one of claims 1 to 15, wherein the antibody comprises: (i) a light chain variable region (VL) having the identical LCDR1, LCDR2, and LCDR3 with any one of SEQ ID NOs: 155, 157, 169, 267, 271, 275, 277, 309, 311, 313, 315, 317, and 319; and (ii) a heavy chain variable region (VH) having the identical HCDR1, HCDR2, and HCDR3 with any one of SEQ ID NOs: 156, 158, 170, 268, 272, 276, 278, 310, 312, 314, 316, 318, and 320; wherein the CDRs are defined according to the Kabat definition.
35. The antibody of any one of claims 1 to 15, wherein the antibody comprises: (i) a light chain variable region (VL) having the identical LCDR1, LCDR2, and LCDR3 with any one of SEQ ID NOs: 155, 157, 169, 267, 271, 275, 277, 309, 311, 313, 315, 317, and 319; and (ii) a heavy chain variable region (VH) having the identical HCDR1, HCDR2, and HCDR3 with any one of SEQ ID NOs: 156, 158, 170, 268, 272, 276, 278, 310, 312, 314, 316, 318, and 320; wherein the CDRs are defined according to the Chothia definition.
36. The antibody of any one of claims 1 to 29, wherein the antibody comprises an immunoglobulin light chain variable region amino acid sequence at least about 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 275; and an immunoglobulin heavy chain variable region amino acid sequence at least about 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 276.
37. The antibody of any one of claims 1 to 29, wherein the antibody comprises an immunoglobulin light chain variable region amino acid sequence identical to SEQ ID NOs: 275; and an immunoglobulin heavy chain variable region amino acid sequence identical to SEQ ID NO: 276.
38. The antibody of any one of claims 1 to 29, wherein the antibody comprises an immunoglobulin light chain variable region amino acid sequence at least about 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 277; and an immunoglobulin heavy chain variable region amino acid sequence at least about 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 278.
39. The antibody of any one of claims 1 to 29, wherein the antibody comprises an immunoglobulin light chain variable region amino acid sequence identical to SEQ ID NOs: 277; and an immunoglobulin heavy chain variable region amino acid sequence identical to SEQ ID NO: 278.
40. The antibody of any one of claims 1 to 29, wherein the antibody comprises an immunoglobulin light chain variable region amino acid sequence at least about 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 309; and an immunoglobulin heavy chain variable region amino acid sequence at least about 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 310.
41. The antibody of any one of claims 1 to 29, wherein the antibody comprises an immunoglobulin light chain variable region amino acid sequence identical to SEQ ID NOs: 309; and an immunoglobulin heavy chain variable region amino acid sequence identical to SEQ ID NO: 310.
42. The antibody of any one of claims 1 to 29, wherein the antibody comprises an immunoglobulin light chain variable region amino acid sequence at least about 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 155; and an immunoglobulin heavy chain variable region amino acid sequence at least about 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 156.
43. The antibody of any one of claims 1 to 29, wherein the antibody comprises an immunoglobulin light chain variable region amino acid sequence identical to SEQ ID NOs: 155; and an immunoglobulin heavy chain variable region amino acid sequence identical to SEQ ID NO: 156.
44. The antibody of any one of claims 1 to 29, wherein the antibody comprises an immunoglobulin light chain variable region amino acid sequence at least about 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 157; and an immunoglobulin heavy chain variable region amino acid sequence at least about 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 158.
45. The antibody of any one of claims 1 to 29, wherein the antibody comprises an immunoglobulin light chain variable region amino acid sequence identical to SEQ ID NOs: 157; and an immunoglobulin heavy chain variable region amino acid sequence identical to SEQ ID NO: 158.
46. The antibody of any one of claims 1 to 29, wherein the antibody comprises an immunoglobulin light chain variable region amino acid sequence at least about 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 169; and an immunoglobulin heavy chain variable region amino acid sequence at least about 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 170.
47. The antibody of any one of claims 1 to 29, wherein the antibody comprises an immunoglobulin light chain variable region amino acid sequence identical to SEQ ID NOs: 169; and an immunoglobulin heavy chain variable region amino acid sequence identical to SEQ ID NO: 170.
48. The antibody of any one of claims 1 to 29, wherein the antibody comprises an immunoglobulin light chain variable region amino acid sequence at least about 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 267; and an immunoglobulin heavy chain variable region amino acid sequence at least about 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 268.
49. The antibody of any one of claims 1 to 29, wherein the antibody comprises an immunoglobulin light chain variable region amino acid sequence identical to SEQ ID NOs: 267; and an immunoglobulin heavy chain variable region amino acid sequence identical to SEQ ID NO: 268.
50. The antibody of any one of claims 1 to 29, wherein the antibody comprises an immunoglobulin light chain variable region amino acid sequence at least about 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 271; and an immunoglobulin heavy chain variable region amino acid sequence at least about 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 272.
51. The antibody of any one of claims 1 to 29, wherein the antibody comprises an immunoglobulin light chain variable region amino acid sequence identical to SEQ ID NOs: 271; and an immunoglobulin heavy chain variable region amino acid sequence identical to SEQ ID NO: 272.
52. The antibody of any one of claims 1 to 29, wherein the antibody comprises an immunoglobulin light chain variable region amino acid sequence at least about 90%, 95%, 96%, 97%, 98%, or 99% identical to any one of the immunoglobulin light chain variable region sequences of Table 1; and an immunoglobulin heavy chain variable region amino acid sequence at least about 90%, 95%, 96%, 97%, 98%, or 99% identical to any one of the immunoglobulin heavy chain variable region sequences of Table 1.
53. The antibody of any one of claims 1 to 29, wherein the antibody comprises an immunoglobulin light chain amino acid sequence identical to any one of the immunoglobulin light chain variable region sequences of Table 1; and an immunoglobulin heavy chain variable region amino acid sequences identical to any one of the immunoglobulin heavy chain variable region sequences of Table 1.
54. The antibody of any one of claims 1 to 53, wherein the antibody comprises an arginine substitution at position number 17 of the immunoglobulin light chain according to Kabat numbering.
55. The antibody of any one of claims 1 to 54, wherein the antibody comprises a tyrosine substitution at position number 12 of the immunoglobulin light chain according to Kabat numbering.
56. The antibody of any one of claims 1 to 55, wherein the antibody does not bind to T lymphocytes.
57. The antibody of any one of claims 1 to 56, wherein the antibody does not bind to activated T lymphocytes.
58. The antibody of any one of claims 1 to 57, wherein the antibody does not bind to B lymphocytes.
59. The antibody of any one of claims 1 to 58, wherein the antibody comprises an Fc region comprising an amino acid alteration selected from the list consisting of D356E, L358M, and combinations thereof.
60. A pharmaceutical composition comprising the antibody of any one of claims 1 to 59 and a pharmaceutically acceptable carrier, diluent, or excipient.
61. The pharmaceutical composition of claim 60 formulated for intravenous administration.
62. A nucleic acid encoding the antibody of any one of claims 1 to 59.
63. An expression vector comprising the nucleic acid of claim 62.
64. A eukaryotic cell comprising the expression vector of claim 63.
65. The eukaryotic cell of claim 64, wherein the eukaryotic cell is a CHO cell line.
66. A method of treating a cancer or tumor comprising administering to an individual afflicted with the cancer or tumor the antibody of any one of claims 1 to 59 or the pharmaceutical composition of claim 60 or 61.
67. The method of claim 66, wherein the cancer or tumor is a solid tissue cancer.
68. The method of claim 66, wherein the cancer or tumor is a blood cancer.
69. The method of claim 66, wherein the cancer or tumor comprises breast cancer, colorectal cancer, or ovarian cancer.
70. The method of claim 69, wherein the breast cancer is triple negative breast cancer.
71. A method of inhibiting CD24 signaling in a cancer cell comprising contacting the cancer cell to the antibody of any one of claims 1 to 59 or the pharmaceutical composition of claim 60 or 61.
72. The method of claim 71, wherein CD24 signaling is not inhibited in non-neoplastic B lymphocytes or non-neoplastic T lymphocytes.
73. The method of claim 71 or 72, wherein the cancer cell is a cancer cell is in vivo in an individual.
- Company
- Beijing neoX Biotech Limited
- Keywords
- C07K16/2896, A61P35/00