Filamin A binding proteins and uses thereof
View Patent ↗The present invention encompasses filamin A (FLNA) binding proteins. Specifically, the invention relates to antibodies to FLNA. An antibody of the invention can be a full-length antibody or an antigen-binding portion thereof. Methods of making and methods of using the antibodies of the invention in methods of diagnosis, monitoring and prognosis of prostate cancer are also provided.
1. An antibody, or antigen-binding fragment thereof, capable of binding filamin A (FLNA), comprising
a heavy chain variable region comprising a CDR3 domain comprising the amino acid sequence set forth in SEQ ID NO: 9, a CDR2 domain comprising the amino acid sequence set forth in SEQ ID NO: 8, and a CDR1 domain comprising the amino acid sequence set forth in SEQ ID NO: 7; and
a light chain variable region comprising a CDR3 domain comprising the amino acid sequence set forth in SEQ ID NO: 12, a CDR2 domain comprising the amino acid sequence set forth in SEQ ID NO: 11, and a CDR1 domain comprising the amino acid sequence set forth in SEQ ID NO: 10.
2. The antibody, or antigen-binding fragment thereof, of claim 1 , comprising a heavy chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 1 and a light chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 2.
3. The antibody, or antigen-binding fragment thereof, of claim 1 comprising a heavy chain comprising the amino acid sequence set forth in SEQ ID NO: 25, and a light chain comprising the amino acid sequence set forth in SEQ ID NO: 26.
4. The antibody, or antigen-binding fragment thereof, of claim 1 , wherein said antibody, or antigen-binding fragment thereof has an on rate constant (K on ) to FLNA of at least about 7.90×10 4 M −1 s −1 .
5. The antibody, or antigen-binding fragment thereof, of claim 1 , wherein said antibody, or antigen-binding fragment thereof has a dissociation constant (K D ) to FLNA of 4.82×10 −9 M or less.
6. An antibody construct comprising the antibody, or antigen-binding fragment thereof, of claim 1 , said antibody construct further comprising a linker polypeptide or an immunoglobulin constant domain.
7. An antibody, or antigen-binding fragment thereof, capable of binding FLNA, produced by culturing a host cell comprising a vector comprising an isolated nucleic acid encoding the antibody, or antigen-binding fragment thereof, of claim 1 , in a culture medium under conditions sufficient to produce the antibody, or antigen-binding fragment thereof, capable of binding FLNA.
8. A pharmaceutical composition comprising the antibody, or antigen-binding fragment thereof, of claim 1 , and a pharmaceutically acceptable carrier.
9. A kit for the diagnosis, monitoring, or characterization of prostate cancer, comprising: at least one reagent specific for the detection of a level of FLNA, wherein the reagent is an antibody, or antigen-binding fragment thereof, of claim 1 .
10. The kit of claim 9 , wherein the kit further comprises instructions for the diagnosis, monitoring, or characterization of prostate cancer based on the level of FLNA detected.
11. An antibody, or antigen-binding fragment thereof, capable of binding filamin A (FLNA), comprising
a heavy chain variable region comprising a CDR3 domain comprising the amino acid sequence set forth in SEQ ID NO: 15, a CDR2 domain comprising the amino acid sequence set forth in SEQ ID NO: 14, and a CDR1 domain comprising the amino acid sequence set forth in SEQ ID NO: 13; and
a light chain variable region comprising a CDR3 domain comprising the amino acid sequence set forth in SEQ ID NO: 18, a CDR2 domain comprising the amino acid sequence set forth in SEQ ID NO: 17, and a CDR1 domain comprising the amino acid sequence set forth in SEQ ID NO: 16.
12. The antibody, or antigen-binding fragment thereof, of claim 11 comprising a heavy chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 3 and a light chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 4.
13. The antibody, or antigen-binding fragment thereof, of claim 11 comprising a heavy chain comprising the amino acid sequence set forth in SEQ ID NO: 27, and a light chain comprising the amino acid sequence set forth in SEQ ID NO: 28.
14. The antibody, or antigen-binding fragment thereof, of claim 11 , wherein said antibody, or antigen-binding fragment thereof has an on rate constant (K on ) to FLNA of at least about 8.05×10 5 M −1 s −1 .
15. The antibody, or antigen-binding fragment thereof, of claim 11 , wherein said antibody, or antigen-binding fragment thereof has a dissociation constant (K D ) to FLNA of 9.99×10 −10 M or less.
16. An antibody construct comprising the antibody, or antigen-binding fragment thereof, of claim 11 , said antibody construct further comprising a linker polypeptide or an immunoglobulin constant domain.
17. An antibody, or antigen-binding fragment thereof, capable of binding FLNA, produced by culturing a host cell comprising a vector comprising an isolated nucleic acid encoding the antibody, or antigen-binding fragment thereof, of claim 11 , in a culture medium under conditions sufficient to produce the antibody, or antigen-binding fragment thereof, capable of binding FLNA.
18. A pharmaceutical composition comprising the antibody, or antigen-binding fragment thereof, of claim 11 , and a pharmaceutically acceptable carrier.
19. A kit for the diagnosis, monitoring, or characterization of prostate cancer, comprising: at least one reagent specific for the detection of a level of FLNA, wherein the reagent is an antibody, or antigen-binding fragment thereof, of claim 11 .
20. The kit of claim 19 , wherein the kit further comprises instructions for the diagnosis, monitoring, or characterization of prostate cancer based on the level of FLNA detected.
21. An antibody, or antigen-binding fragment thereof, capable of binding filamin A (FLNA), comprising
a heavy chain variable region comprising a CDR3 domain comprising the amino acid sequence set forth in SEQ ID NO: 21, a CDR2 domain comprising the amino acid sequence set forth in SEQ ID NO: 20, and a CDR1 domain comprising the amino acid sequence set forth in SEQ ID NO: 19; and
a light chain variable region comprising a CDR3 domain comprising the amino acid sequence set forth in SEQ ID NO: 24, a CDR2 domain comprising the amino acid sequence set forth in SEQ ID NO: 23, and a CDR1 domain comprising the amino acid sequence set forth in SEQ ID NO: 22.
22. The antibody, or antigen-binding fragment thereof, of claim 21 comprising a heavy chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 5 and a light chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 6.
23. The antibody, or antigen-binding fragment thereof, of claim 21 comprising a heavy chain comprising the amino acid sequence set forth in SEQ ID NO: 29, and a light chain comprising the amino acid sequence set forth in SEQ ID NO: 30.
24. The antibody, or antigen-binding fragment thereof, of claim 21 , wherein said antibody, or antigen-binding fragment thereof has an on rate constant (K on ) to FLNA of at least about 1.95×10 5 M −1 s −1 .
25. The antibody, or antigen-binding fragment thereof, of claim 21 , wherein said antibody, or antigen-binding fragment thereof has a dissociation constant (K D ) to FLNA of 4.02×10 −9 M or less.
26. An antibody construct comprising the antibody, or antigen-binding fragment thereof, of claim 21 , said antibody construct further comprising a linker polypeptide or an immunoglobulin constant domain.
27. An antibody, or antigen-binding fragment thereof, capable of binding FLNA, produced by culturing a host cell comprising a vector comprising an isolated nucleic acid encoding the antibody, or antigen-binding fragment thereof, of claim 21 , in a culture medium under conditions sufficient to produce the antibody, or antigen-binding fragment thereof, capable of binding FLNA.
28. A pharmaceutical composition comprising the antibody, or antigen-binding fragment thereof, of claim 21 , and a pharmaceutically acceptable carrier.
29. A kit for the diagnosis, monitoring, or characterization of prostate cancer, comprising: at least one reagent specific for the detection of a level of FLNA, wherein the reagent is an antibody, or antigen-binding fragment thereof, of claim 21 .
30. The kit of claim 29 , wherein the kit further comprises instructions for the diagnosis, monitoring, or characterization of prostate cancer based on the level of FLNA detected.