PTK7 modulators and methods of use
View Patent ↗PTK modulators, including antibodies and derivatives thereof, and methods of using such modulators to treat hyper-proliferative disorders are provided.
1. An antibody comprising a chimeric, CDR-grafted, or humanized antibody, or fragment thereof, which specifically binds to PTK7, comprising:
(a) CDR-L1, CDR-L2 and CDR-L3 of a light chain variable region set forth as SEQ ID NO: 62 and CDR-H1, CDR-H2 and CDR-H3 of a heavy chain variable region set forth as SEQ ID NO: 63; or
(b) CDR-L1, CDR-L2 and CDR-L3 of a light chain variable region set forth as SEQ ID NO: 64 and CDR-H1, CDR-H2 and CDR-H3 of a heavy chain variable region set forth as SEQ ID NO: 65.
2. The antibody of claim 1 , which is a neutralizing antibody.
3. The antibody of claim 1 , which is an internalizing antibody.
4. The antibody of claim 1 , which specifically binds to a PTK7 isoform selected from the group consisting of isoform a, isoform b, isoform c, and isoform d.
5. The antibody of claim 4 , which specifically binds to PTK7 isoform a.
6. The antibody of claim 1 comprising:
(a) a heavy chain variable region comprising an amino acid sequence TSNMGVG (SEQ ID NO: 170) for CDR1, an amino acid sequence HIWWDDDKYYSPSLKS (SEQ ID NO: 171) for CDR2, and an amino acid sequence SNYGYAWFAY (SEQ ID NO: 172) for CDR3; and
(b) a light chain variable region comprising an amino acid sequence KASQDIYPYLN (SEQ ID NO: 173) for CDR1, an amino acid sequence RTNRLLD (SEQ ID NO: 174) for CDR2, and an amino acid sequence LQYDEFPLT (SEQ ID NO: 175) for CDR3.
7. The antibody of claim 1 comprising a heavy chain variable region having an amino acid sequence that is at least 60% identical to SEQ ID NO: 63 and a light chain variable region having an amino acid sequence that is at least 60% identical to SEQ ID NO: 62.
8. The antibody of claim 7 comprising a heavy chain variable region set forth as SEQ ID NO: 63 and a light chain variable region set forth as SEQ ID NO: 62.
9. The antibody of claim 1 comprising:
(a) a heavy chain variable region comprising an amino acid sequence DYAVH (SEQ ID NO: 176) for CDR1, an amino acid sequence VISTYNDYTYNNQDFKG (SEQ ID NO: 177) for CDR2, and an amino acid sequence GNSYFYALDY (SEQ ID NO: 178) for CDR3; and
(b) a light chain variable region comprising an amino acid sequence RASESVDSYGKSFMH (SEQ ID NO: 179) for CDR1, an amino acid sequence RASNLES (SEQ ID NO: 180) for CDR2, and an amino acid sequence QQSNEDPWT (SEQ ID NO: 181) for CDR3.
10. The antibody of claim 1 comprising a heavy chain variable region having an amino acid sequence that is at least 60% identical to SEQ ID NO: 65 and a light chain variable region having an amino acid sequence that is at least 60% identical to SEQ ID NO: 64.
11. The antibody of claim 10 comprising a heavy chain variable region set forth as SEQ ID NO: 65 and a light chain variable region set forth as SEQ ID NO: 64.
12. The antibody of claim 1 comprising a heavy chain variable region set forth as SEQ ID NO: 63 or 65.
13. The antibody of claim 1 comprising a light chain variable region set forth as SEQ ID NO: 62 or 64.
14. The antibody of claim 1 comprising:
(a) a heavy chain variable region set forth as SEQ ID NO: 63, and a light chain variable region set forth as SEQ ID NO: 62; or
(b) a heavy chain variable region set forth as SEQ ID NO: 65, and a light chain variable region set forth as SEQ ID NO: 64.
15. The antibody of claim 1 , which is conjugated, linked or otherwise associated with a cytotoxic agent.
16. The antibody of claim 8 , which is conjugated, linked or otherwise associated with a cytotoxic agent.
17. The antibody of claim 11 , which is conjugated, linked or otherwise associated with a cytotoxic agent.
18. A pharmaceutical composition comprising the antibody of claim 1 .
19. A pharmaceutical composition comprising the antibody of claim 8 .
20. A pharmaceutical composition comprising the antibody of claim 11 .
21. An antibody conjugate comprising a chimeric, CDR-grafted, or humanized antibody, or a fragment thereof, which specifically binds to PTK7, which antibody is conjugated, linked or otherwise associated with a cytotoxic agent, wherein the antibody conjugate comprises:
(a) a light chain variable region comprising CDR-L1, CDR-L2 and CDR-L3 of SEQ ID NO: 62 and a heavy chain variable region comprising CDR-H1, CDR-H2 and CDR-H3 of SEQ ID NO: 63; or
(b) a light chain variable region comprising CDR-L1, CDR-L2 and CDR-L3_of SEQ ID NO: 64 and a heavy chain variable region comprising CDR-H1, CDR-H2 and CDR-H3 of SEQ ID NO: 65.
22. A pharmaceutical composition comprising the antibody conjugate of claim 21 .
23. A nucleic acid encoding a heavy chain variable region set forth as SEQ ID NO: 63 or 65, or a light chain variable region set forth as SEQ ID NO: 62 or 64.
24. A vector comprising the nucleic acid of claim 23 .
25. A host cell comprising the nucleic acid of claim 23 .
26. The antibody of claim 1 comprising:
(a) a heavy chain variable region comprising an amino acid sequence GFSLSTSNM (SEQ ID NO: 182) for CDR1, an amino acid sequence WWDDD (SEQ ID NO: 183) for CDR2, and an amino acid sequence SNYGYAWFAY (SEQ ID NO: 172) for CDR3; and
(b) a light chain variable region comprising an amino acid sequence KASQDIYPYLN (SEQ ID NO: 173) for CDR1, an amino acid sequence RTNRLLD (SEQ ID NO: 174) for CDR2, and an amino acid sequence LQYDEFPLT (SEQ ID NO: 175) for CDR3.
27. The antibody of claim 1 comprising:
(a) a heavy chain variable region comprising an amino acid sequence GYTFTDY (SEQ ID NO: 184) for CDR1, an amino acid sequence STYNDY (SEQ ID NO: 185) for CDR2, and an amino acid sequence GNSYFYALDY (SEQ ID NO: 178) for CDR3; and
(b) a light chain variable region comprising an amino acid sequence RASESVDSYGKSFMH (SEQ ID NO: 179) for CDR1, an amino acid sequence RASNLES (SEQ ID NO: 180) for CDR2, and an amino acid sequence QQSNEDPWT (SEQ ID NO: 181) for CDR3.
28. The antibody of claim 1 comprising:
(a) a heavy chain variable region comprising an amino acid sequence STSNMGVG (SEQ ID NO: 186) for CDR1, an amino acid sequence WLAHIWWDDDKY (SEQ ID NO: 187) for CDR2, and an amino acid sequence VRSNYGYAWFA (SEQ ID NO: 188) for CDR3; and
(b) a light chain variable region comprising an amino acid sequence YPYLNWF (SEQ ID NO: 189) for CDR1,an amino acid sequence TLIYRTNRLL (SEQ ID NO: 190) for CDR2, and an amino acid sequence LQYDEFPL (SEQ ID NO: 191) for CDR3.
29. The antibody of claim 1 comprising:
(a) a heavy chain variable region comprising an amino acid sequence TDYAVH (SEQ ID NO: 192) for CDR1, an amino acid sequence WIGVISTYNDYTY (SEQ ID NO: 193) for CDR2, and an amino acid sequence ARGNSYFYALD (SEQ ID NO: 194) for CDR3; and
(b) a light chain variable region comprising an amino acid sequence DSYGKSFMHWY (SEQ ID NO: 195) for CDR1, an amino acid sequence LLIYRASNLE (SEQ ID NO: 196) for CDR2, and an amino acid sequence QQSNEDPW (SEQ ID NO: 197) for CDR3.