PTK7 modulators and methods of use
US-9914784-B2 · Mar 13, 2018 · US
US10836831B2 · US · B2
| Field | Value |
|---|---|
| Publication number | US-10836831-B2 |
| Application number | US-201815882391-A |
| Country | US |
| Kind code | B2 |
| Filing date | Jan 29, 2018 |
| Priority date | Feb 18, 2011 |
| Publication date | Nov 17, 2020 |
| Grant date | Nov 17, 2020 |
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Anti-PTK7 modulators, including antibodies and derivatives thereof, and methods of using such modulators to treat hyperproliferative disorders are provided.
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The invention claimed is: 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.
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