Multivalent DLL3 antibodies
View Patent ↗Novel modulators, including antibodies and derivatives thereof, and methods of using such modulators to treat proliferative disorders are provided.
1. A multivalent antibody comprising (a) a first target binding site that specifically binds to an epitope within the DSL domain of a DLL3 protein set forth in SEQ ID NO: 3 or 4, and (b) a second target binding site that binds to an epitope on a different molecule.
2. The multivalent antibody of claim 1 , wherein the first target binding site specifically binds to an epitope comprising amino acids G203, R205, and P206 (SEQ ID NO:10).
3. The multivalent antibody of claim 1 , wherein the multivalent antibody competes for binding to a human DLL3 protein with an antibody comprising a light chain variable region set forth as SEQ ID NO: 84 and a heavy chain variable region set forth as SEQ ID NO: 85.
4. The multivalent antibody of claim 1 , wherein the first target binding site comprises three CDRs of a light chain variable region set forth as SEQ ID NO: 84 and three CDRs of a heavy chain variable region set forth as SEQ ID NO: 85.
5. The multivalent antibody of claim 1 , wherein the first target binding site comprises residues 24-34 of SEQ ID NO: 84 for CDR-L1, residues 50-56 of SEQ ID NO: 84 for CDR-L2, residues 89-97 of SEQ ID NO: 84 for CDR-L3, residues 31-35 of SEQ ID NO: 85 for CDR-H1, residues 50-65 of SEQ ID NO: 85 for CDR-H2, and residues 95-102 of SEQ ID NO: 85 for CDR-H3, wherein the residues are numbered according to Kabat.
6. The multivalent antibody of claim 1 , wherein the second target binding site binds to an epitope on a cytotoxic T-cell.
7. The multivalent antibody of claim 6 , wherein the second target binding site binds to an epitope on a CD3 protein.
8. The multivalent antibody of claim 1 , wherein the multivalent antibody is a bispecific antibody.
9. The multivalent antibody of claim 8 , wherein the bispecific antibody is a single chain antibody.
10. A multivalent antibody comprising (a) a first target binding site that specifically binds to an epitope on a DLL3 protein, and (b) a second target binding site that binds to an epitope on a cytotoxic T-cell.
11. The multivalent antibody of claim 10 , wherein the first target binding site specifically binds to an epitope within the DSL domain of a DLL3 protein set forth in SEQ ID NO: 3 or 4.
12. The multivalent antibody of claim 10 , wherein the first target binding site specifically binds to an epitope comprising amino acids G203, R205, and P206 (SEQ ID NO:10).
13. The multivalent antibody of claim 10 , wherein the multivalent antibody competes for binding to a human DLL3 protein with an antibody comprising a light chain variable region set forth as SEQ ID NO: 84 and a heavy chain variable region set forth as SEQ ID NO: 85.
14. The multivalent antibody of claim 10 , wherein the first target binding site comprises three CDRs of a light chain variable region set forth as SEQ ID NO: 84 and three CDRs of a heavy chain variable region set forth as SEQ ID NO: 85.
15. The multivalent antibody of claim 10 , wherein the first target binding site comprises residues 24-34 of SEQ ID NO: 84 for CDR-L1, residues 50-56 of SEQ ID NO: 84 for CDR-L2, residues 89-97 of SEQ ID NO: 84 for CDR-L3, residues 31-35 of SEQ ID NO: 85 for CDR-H1, residues 50-65 of SEQ ID NO: 85 for CDR-H2, and residues 95-102 of SEQ ID NO: 85 for CDR-H3, wherein the residues are numbered according to Kabat.
16. The multivalent antibody of claim 10 , wherein the second target binding site is an epitope on a CD3 protein expressed on a cytotoxic T-cell.
17. The multivalent antibody of claim 10 , wherein the multivalent antibody is a bispecific antibody.
18. The multivalent antibody of claim 17 , wherein the bispecific antibody is a single chain antibody.
19. A bispecific antibody comprising (a) a first target binding site that specifically binds to an epitope on a DLL3 protein, and (b) a second target binding site that binds to an epitope on a CD3 protein expressed on a cytotoxic T-cell.
20. The bispecific antibody of claim 19 , wherein the first target binding site specifically binds to an epitope within the DSL domain of a DLL3 protein set forth in SEQ ID NO: 3 or 4.
21. The bispecific antibody of claim 19 , wherein the first target binding site specifically binds to an epitope comprising amino acids G203, R205, and P206 (SEQ ID NO:10).
22. The bispecific antibody of claim 19 , wherein the bispecific antibody competes for binding to a human DLL3 protein with an antibody comprising a light chain variable region set forth as SEQ ID NO: 84 and a heavy chain variable region set forth as SEQ ID NO: 85.
23. The bispecific antibody of claim 19 , wherein the first target binding site comprises three CDRs of a light chain variable region set forth as SEQ ID NO: 84 and three CDRs of a heavy chain variable region set forth as SEQ ID NO: 85.
24. The bispecific antibody of claim 19 , wherein the first target binding site comprises residues 24-34 of SEQ ID NO: 84 for CDR-L1, residues 50-56 of SEQ ID NO: 84 for CDR-L2, residues 89-97 of SEQ ID NO: 84 for CDR-L3, residues 31-35 of SEQ ID NO: 85 for CDR-H1, residues 50-65 of SEQ ID NO: 85 for CDR-H2, and residues 95-102 of SEQ ID NO: 85 for CDR-H3, wherein the residues are numbered according to Kabat.
25. The bispecific antibody of claim 19 , wherein the bispecific antibody is a single chain antibody.
26. A bispecific antibody comprising (a) a first target binding site that specifically binds to an epitope on a DLL3 protein, wherein the first target binding site comprises three CDRs of a light chain variable region set forth as SEQ ID NO: 84 and three CDRs of a heavy chain variable region set forth as SEQ ID NO: 85; and (b) a second target binding site that binds to an epitope on a CD3 protein.
27. The bispecific antibody of claim 26 , wherein the first target binding site comprises residues 24-34 of SEQ ID NO: 84 for CDR-L1, residues 50-56 of SEQ ID NO: 84 for CDR-L2, residues 89-97 of SEQ ID NO: 84 for CDR-L3, residues 31-35 of SEQ ID NO: 85 for CDR-H1, residues 50-65 of SEQ ID NO: 85 for CDR-H2, and residues 95-102 of SEQ ID NO: 85 for CDR-H3, wherein the residues are numbered according to Kabat.
28. The bispecific antibody of claim 26 , wherein the bispecific antibody is a single chain antibody.