Anti-PTK7 antibodies and methods of use
Anti-PTK7 modulators, including antibodies and derivatives thereof, and methods of using such modulators to treat hyperproliferative disorders are provided.
1. An antibody, or antigen-binding fragment thereof, that specifically binds to PTK7 comprising:
(a) three CDRs of a light chain variable region set forth as SEQ ID NO: 66 and three CDRs of a heavy chain variable region set forth as SEQ ID NO: 67; or
(b) three CDRs of a light chain variable region set forth as SEQ ID NO: 68 and three CDRs of a heavy chain variable region set forth as SEQ ID NO: 69.
2. The antibody or antigen-binding fragment thereof of claim 1 , comprising:
(a) a light chain variable region comprising three CDRs set forth as residues 24-34 of SEQ ID NO: 66 for V L CDR1, residues 50-56 of SEQ ID NO: 66 for V L CDR2, and residues 89-97 of SEQ ID NO: 66 for V L CDR3; and
(b) a heavy chain variable region comprising three CDRs set forth as residues 31-35 of SEQ ID NO: 67 for V H CDR1, residues 50-65 of SEQ ID NO: 67 for V H CDR2, and residues 95-102 of SEQ ID NO: 67 for V H CDR3;
wherein the CDR numbering is according to Kabat.
3. The antibody or antigen-binding fragment thereof of claim 1 , comprising:
(a) a light chain variable region comprising three CDRs set forth as residues 24-34 of SEQ ID NO: 68 for V L CDR1, residues 50-56 of SEQ ID NO: 68 for V L CDR2, and residues 89-97 of SEQ ID NO: 68 for V L CDR3; and
(b) a heavy chain variable region comprising three CDRs set forth as residues 31-35 of SEQ ID NO: 69 for V H CDR1, residues 50-65 of SEQ ID NO: 69 for V H CDR2, and residues 95-102 of SEQ ID NO: 69 for V H CDR3;
wherein the CDR numbering is according to Kabat.
4. The antibody or antigen-binding fragment thereof of claim 1 , comprising:
(a) a light chain variable region comprising three CDRs set forth as residues 23-34 of SEQ ID NO: 66 for V L CDR1, residues 50-56 of SEQ ID NO: 66 for V L CDR2, and residues 89-97 of SEQ ID NO: 66 for V L CDR3; and
(b) a heavy chain variable region comprising three CDRs set forth as residues 26-32 of SEQ ID NO: 67 for V H CDR1, residues 50-58 of SEQ ID NO: 67 for V H CDR2, and residues 95-102 of SEQ ID NO: 67 for V H CDR3;
wherein the CDR numbering is according to Chothia.
5. The antibody or antigen-binding fragment thereof of claim 1 , comprising:
(a) a light chain variable region comprising three CDRs set forth as residues 23-34 of SEQ ID NO: 68 for V L CDR1, residues 50-56 of SEQ ID NO: 68 for V L CDR2, and residues 89-97 of SEQ ID NO: 68 for V L CDR3; and
(b) a heavy chain variable region comprising three CDRs set forth as residues 26-32 of SEQ ID NO: 69 for V H CDR1, residues 50-58 of SEQ ID NO: 69 for V H CDR2, and residues 95-102 of SEQ ID NO: 69 for V H CDR3;
wherein the CDR numbering is according to Chothia.
6. The antibody or antigen-binding fragment thereof of claim 1 , comprising:
(a) a light chain variable region comprising three CDRs set forth as residues 30-36 of SEQ ID NO: 66 for V L CDR1, residues 46-55 of SEQ ID NO: 66 for V L CDR2, and residues 89-96 of SEQ ID NO: 66 for V L CDR3; and
(b) a heavy chain variable region comprising three CDRs set forth as residues 30-35 of SEQ ID NO: 67 for V H CDR1, residues 47-58 of SEQ ID NO: 67 for V H CDR2, and residues 93-101 of SEQ ID NO: 67 for V H CDR3;
wherein the CDR numbering is according to MacCallum.
7. The antibody or antigen-binding fragment thereof of claim 1 , comprising:
(a) a light chain variable region comprising three CDRs set forth as residues 30-36 of SEQ ID NO: 68 for V L CDR1, residues 46-55 of SEQ ID NO: 68 for V L CDR2, and residues 89-96 of SEQ ID NO: 68 for V L CDR3; and
(b) a heavy chain variable region comprising three CDRs set forth as residues 30-35 of SEQ ID NO: 69 for V H CDR1, residues 47-58 of SEQ ID NO: 69 for V H CDR2, and residues 93-101 of SEQ ID NO: 69 for V H CDR3;
wherein the CDR numbering is according to MacCallum.
8. The antibody or antigen-binding fragment thereof of claim 1 , comprising a light chain variable region set forth as SEQ ID NO: 66 and a heavy chain variable region set forth as SEQ ID NO: 67.
9. The antibody or antigen-binding fragment thereof of claim 1 , comprising a light chain variable region set forth as SEQ ID NO: 68 and a heavy chain variable region set forth as SEQ ID NO: 69.
10. An antibody conjugate comprising the antibody or antigen-binding fragment thereof of claim 1 , which antibody is conjugated, linked, or otherwise associated with a cytotoxic agent.
11. A pharmaceutical composition comprising the antibody or antigen-binding fragment thereof of claim 1 .
12. A pharmaceutical composition comprising the antibody conjugate of claim 10 .
13. A nucleic acid encoding a light chain variable region set forth as SEQ ID NO: 66 or 68, or a heavy chain variable region set forth as SEQ ID NO: 67 or 69.
14. A vector comprising the nucleic acid of claim 13 .
15. A host cell comprising the nucleic acid of claim 13 .
16. A host cell comprising the vector of claim 14 .
17. A method of treating a PTK7-associated neoplastic disorder comprising administering a therapeutically effective amount of the antibody or antigen-binding fragment thereof of claim 1 to a subject in need thereof, wherein the antibody or antigen-binding fragment thereof is optionally conjugated, linked, or otherwise associated with a cytotoxic agent.
18. The method of claim 17 , wherein the PTK7-associated neoplastic disorder comprises a solid tumor.
19. The method of claim 17 , wherein the PTK7-associated neoplastic disorder is breast cancer, ovarian cancer, colorectal cancer, pancreatic cancer, lung cancer, or melanoma.
20. The method of claim 19 , wherein the PTK7-associated neoplastic disorder is ovarian cancer.
21. The method of claim 19 , wherein the PTK7-associated neoplastic disorder is breast cancer.
22. The method of claim 19 , wherein the PTK7-associated neoplastic disorder is non-small cell lung cancer.
23. A kit comprising one or more containers comprising the antibody or antigen-binding fragment thereof of claim 1 , wherein the antibody or antigen-binding fragment thereof is optionally conjugated, linked, or otherwise associated with a cytotoxic agent.