Anti-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 monoclonal antibody that specifically binds to human DLL3, wherein the antibody comprises three complementarity determining regions (CDRs) of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 96 and three CDRs of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 97.
2. The monoclonal antibody of claim 1 , comprising residues 24-34 of SEQ ID NO: 96 for CDR-L1, residues 50-56 of SEQ ID NO: 96 for CDR-L2, residues 89-97 of SEQ ID NO: 96 for CDR-L3, residues 31-35 of SEQ ID NO: 97 for CDR-H1, residues 50-65 of SEQ ID NO: 97 for CDR-H2 and residues 95-102 of SEQ ID NO: 97 for CDR-H3, wherein the CDR residues are numbered according to Kabat.
3. The monoclonal antibody of claim 1 comprising a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 96 or a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 97.
4. The monoclonal antibody of claim 3 comprising a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 96 and a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 97.
5. The monoclonal antibody of claim 1 selected from the group consisting of a murine antibody, chimeric antibody, CDR-grafted antibody, humanized antibody, human antibody, primatized antibody, multispecific antibody, bispecific antibody, monovalent antibody, multivalent antibody, anti-idiotypic antibody, diabody, Fab fragment, F(ab′) 2 fragment, Fv fragment, and ScFv fragment; or an immunoreactive fragment thereof.
6. The monoclonal antibody of claim 5 , wherein the antibody is a murine antibody.
7. The monoclonal antibody of claim 1 , wherein the antibody is conjugated to or associated with a reporter molecule.
8. The monoclonal antibody of claim 7 , wherein the reporter molecule is detectable with immunohistochemistry.
9. The monoclonal antibody of claim 1 , wherein the antibody is detectable by immunohistochemistry.
10. The monoclonal antibody of claim 1 , wherein the antibody binds to cancer cells.
11. The monoclonal antibody of claim 10 , wherein the antibody specifically binds to circulating cancer cells.
12. The monoclonal antibody of claim 10 , wherein the antibody binds to cancer stem cells.
13. The monoclonal antibody of claim 10 , wherein the cancer is lung cancer, small cell lung cancer, large cell neuroendocrine carcinoma, thyroid cancer, or prostate cancer.
14. The monoclonal antibody of claim 10 , wherein the cancer cells are obtained from a patient sample.
15. The monoclonal antibody of claim 14 , wherein the patient sample is a tissue sample.
16. The monoclonal antibody of claim 15 , wherein the tissue sample is chemically fixed.
17. The monoclonal antibody of claim 16 , wherein the tissue sample is chemically fixed using formalin.
18. The monoclonal antibody of claim 17 , wherein the tissue sample is paraffin embedded.
19. The monoclonal antibody of claim 14 , wherein the patient sample is a blood sample.
20. A monoclonal antibody that specifically binds to human DLL3, wherein the antibody comprises three complementarity determining regions (CDRs) of a light chain variable region set forth as SEQ ID NO: 96 and three CDRs of a heavy chain variable region set forth as SEQ ID NO: 97, and wherein the antibody is conjugated to or associated with a reporter molecule that is detectable by immunohistochemistry.
21. A monoclonal murine antibody that specifically binds to human DLL3, wherein the antibody comprises three complementarity determining regions (CDRs) of a light chain variable region set forth as SEQ ID NO: 96 and three CDRs of a heavy chain variable region set forth as SEQ ID NO: 97, wherein the antibody binds to human DLL3 in a formalin fixed, paraffin embedded tissue sample, and wherein the monoclonal murine antibody is detectable by immunohistochemistry.