PTK7 modulators and methods of use
View Patent ↗PTK7 modulators, including antibodies and derivatives thereof, and methods of using such modulators to treat hyper-proliferative disorders are provided.
1. A method of treating a PTK7-associated neoplastic disorder comprising administering a therapeutically effective amount of a composition comprising an antibody or a fragment thereof that specifically binds to PTK7 to a subject having the PTK7-associated neoplastic disorder, wherein the antibody or fragment thereof comprises:
(a) three CDRs of a light chain variable region set forth as SEQ ID NO: 62 and three CDRs of a heavy chain variable region set forth as SEQ ID NO: 63; or
(b) three CDRs of a light chain variable region set forth as SEQ ID NO: 64 and three CDRs of a heavy chain variable region set forth as SEQ ID NO: 65,
and wherein the antibody or fragment thereof is conjugated or linked to a cytotoxic agent.
2. The method of claim 1 , wherein the PTK7-associated neoplastic disorder comprises a solid tumor.
3. The method of claim 1 , wherein the PTK7-associated neoplastic disorder is breast cancer, ovarian cancer, colorectal cancer, pancreatic cancer, lung cancer, or melanoma.
4. The method of claim 3 , wherein the PTK7-associated neoplastic disorder is ovarian cancer.
5. The method of claim 3 , wherein the breast cancer is triple-negative breast cancer.
6. The method of claim 3 , wherein the lung cancer is non-small cell lung cancer.
7. The method of claim 1 , wherein the antibody or fragment thereof comprises:
(a) a light chain variable region comprising residues 24-34 of SEQ ID NO: 62 for CDR-L1, residues 50-56 of SEQ ID NO: 62 for CDR-L2, and residues 89-97 of SEQ ID NO: 62 for CDR-L3;
(b) a heavy chain variable region comprising residues 31-35 of SEQ ID NO: 63 for CDR-H1, residues 50-65 of SEQ ID NO: 63 for CDR-H2, and residues 95-102 of SEQ ID NO: 63 for CDR-H3; and
wherein the CDR numbering is according to Kabat.
8. The method of claim 1 , wherein the antibody or fragment thereof comprises:
(a) a light chain variable region comprising residues 24-34 of SEQ ID NO: 62 for CDR-L1, residues 50-56 of SEQ ID NO: 62 for CDR-L2, and residues 89-97 of SEQ ID NO: 62 for CDR-L3; and
(b) a heavy chain variable region comprising residues 26-32 of SEQ ID NO: 63 for CDR-H1, residues 50-58 of SEQ ID NO: 63 for CDR-H2, and residues 95-102 of SEQ ID NO: 63 for CDR-H3;
wherein the CDR numbering is according to Chothia.
9. The method of claim 1 , wherein the antibody or fragment thereof comprises:
(a) a light chain variable region comprising residues 30-36 of SEQ ID NO: 62 for CDR-L1, residues 46-55 of SEQ ID NO: 62 for CDR-L2, and residues 89-96 of SEQ ID NO: 62 for CDR-L3; and
(b) a heavy chain variable region comprising residues 30-35 of SEQ ID NO: 63 for CDR-H1, residues 47-58 of SEQ ID NO: 63 for CDR-H2, and residues 93-101 of SEQ ID NO: 63 for CDR-H3; and
wherein the CDR numbering is according to MacCallum.
10. The method of claim 1 , wherein the antibody or fragment thereof comprises a light chain variable region having an amino acid sequence that is at least 60% identical to SEQ ID NO: 62 and a heavy chain variable region having an amino acid sequence that is at least 60% identical to SEQ ID NO: 63.
11. The method of claim 1 , wherein the antibody or fragment thereof comprises a light chain variable region having an amino acid sequence set forth as SEQ ID NO: 62 and a heavy chain variable region having an amino acid sequence set forth as SEQ ID NO: 63.
12. The method of claim 1 , wherein the antibody or fragment thereof comprises:
(a) a light chain variable region comprising residues 24-34 of SEQ ID NO: 64 for CDR-L1, residues 50-56 of SEQ ID NO: 64 for CDR-L2, and residues 89-97 of SEQ ID NO: 64 for CDR-L3;
(b) a heavy chain variable region comprising residues 31-35 of SEQ ID NO: 65 for CDR-H1, residues 50-65 of SEQ ID NO: 65 for CDR-H2, and residues 95-102 of SEQ ID NO: 65 for CDR-H3; and
wherein the CDR numbering is according to Kabat.
13. The method of claim 1 , wherein the antibody or fragment thereof comprises:
(a) a light chain variable region comprising residues 24-34 of SEQ ID NO: 64 for CDR-L1, residues 50-56 of SEQ ID NO: 64 for CDR-L2, and residues 89-97 of SEQ ID NO: 64 for CDR-L3; and
(b) a heavy chain variable region comprising residues 26-32 of SEQ ID NO: 65 for CDR-H1, residues 50-58 of SEQ ID NO: 65 for CDR-H2, and residues 95-102 of SEQ ID NO: 65 for CDR-H3;
wherein the CDR numbering is according to Chothia.
14. The method of claim 1 , wherein the antibody or fragment thereof comprises:
(a) a light chain variable region comprising residues 30-36 of SEQ ID NO: 64 for CDR-L1, residues 46-55 of SEQ ID NO: 64 for CDR-L2, and residues 89-96 of SEQ ID NO: 64 for CDR-L3; and
(b) a heavy chain variable region comprising residues 30-35 of SEQ ID NO: 65 for CDR-H1, residues 47-58 of SEQ ID NO: 65 for CDR-H2, and residues 93-101 of SEQ ID NO: 65 for CDR-H3; and
wherein the CDR numbering is according to MacCallum.
15. The method of claim 1 , wherein the antibody or fragment thereof comprises a light chain variable region having an amino acid sequence that is at least 60% identical to SEQ ID NO: 64 and a heavy chain variable region having an amino acid sequence that is at least 60% identical to SEQ ID NO: 65.
16. The method of claim 1 , wherein the antibody or fragment thereof comprises a light chain variable region having an amino acid sequence set forth as SEQ ID NO: 64 and a heavy chain variable region having an amino acid sequence set forth as SEQ ID NO: 65.
17. A method of treating a PTK7-associated cancer comprising administering a therapeutically effective amount of a composition comprising an antibody or a fragment thereof that specifically binds to PTK7 comprising three CDRs of a light chain variable region set forth as SEQ ID NO: 64 and three CDRs of a heavy chain variable region set forth as SEQ ID NO: 65 to a subject having the PTK7-associated cancer, wherein the antibody or fragment thereof is conjugated or linked to a cytotoxic agent.
18. A method of treating a PTK7-associated ovarian cancer comprising administering a therapeutically effective amount of a composition comprising an antibody or a fragment thereof that specifically binds to PTK7 comprising three CDRs of a light chain variable region set forth as SEQ ID NO: 64 and three CDRs of a heavy chain variable region set forth as SEQ ID NO: 65 to a subject having the PTK7-associated cancer, wherein the antibody or fragment thereof is conjugated or linked to a cytotoxic agent.
19. A method of treating a PTK7-associated non-small cell lung cancer comprising administering a therapeutically effective amount of a composition comprising an antibody or a fragment thereof that specifically binds to PTK7 comprising three CDRs of a light chain variable region set forth as SEQ ID NO: 64 and three CDRs of a heavy chain variable region set forth as SEQ ID NO: 65 to a subject having the PTK7-associated cancer, wherein the antibody or fragment thereof is conjugated or linked to a cytotoxic agent.