LOX and LOXL2 inhibitors and uses thereof
The present application relates to anti-LOX and anti-LOXL2 antibodies and their use in purification, diagnostic and therapeutic methods. Antibodies include monoclonal antibodies, humanized antibodies and functional fragments thereof. Anti-LOX and anti-LOXL2 antibodies can be used to identify and treat conditions such as a fibrotic condition, angiogenesis, or to prevent a transition from an epithelial cell state to a mesenchymal cell state.
1. An isolated antibody or antigen binding fragment thereof, comprising a heavy chain variable region comprising the amino acid sequence set forth as SEQ ID NO: 25, 26, 27, or 28, and a light chain variable region comprising the amino acid sequence set forth as SEQ ID NO: 30, 31, or 32, wherein the isolated antibody or antigen binding fragment thereof specifically binds a lysyl oxidase-like 2 (LOXL2) protein.
2. An isolated antibody or antigen binding fragment thereof, comprising a heavy chain variable region comprising the amino acid sequence set forth as SEQ ID NO: 25, 26, 27, or 28, wherein the isolated antibody or antigen binding fragment thereof specifically binds a lysyl oxidase-like 2(LOXL2) protein.
3. An isolated antibody or antigen binding fragment thereof, comprising a light chain variable region comprising the amino acid sequence set forth as SEQ ID NO: 30, 31, or 32, wherein the isolated antibody or antigen binding fragment thereof specifically binds a lysyl oxidase-like 2 (LOXL2) protein.
4. An isolated antibody or antigen binding fragment thereof, comprising the complementarity determining regions (CDRs), CDR1, CDR2, and CDR3, of a heavy chain variable region comprising the amino acid sequence set forth as SEQ ID NO: 25, 26, 27, or 28, and the CDRs, CDR1, CDR2, and CDR3, of a light chain variable region comprising the amino acid sequence set forth as SEQ ID NO: 30, 31, or 32, wherein the isolated antibody or antigen binding fragment thereof specifically binds a lysyl oxidase-like 2(LOXL2) protein.
5. The isolated antibody or antigen binding fragment thereof of claim 1 , wherein the heavy chain variable region comprises the amino acid sequence set forth as SEQ ID NO: 25.
6. The isolated antibody or antigen binding fragment thereof of claim 1 , wherein the heavy chain variable region comprises the amino acid sequence set forth as SEQ ID NO: 26.
7. The isolated antibody or antigen binding fragment thereof of claim 1 , wherein the heavy chain variable region comprises the amino acid sequence set forth as SEQ ID NO: 27.
8. The isolated antibody or antigen binding fragment thereof of claim 1 , wherein the heavy chain variable region comprises the amino acid sequence set forth as SEQ ID NO: 28.
9. The isolated antibody or antigen binding fragment thereof of claim 1 , wherein the light chain variable region comprises the amino acid sequence set forth as SEQ ID NO: 30.
10. The isolated antibody or antigen binding fragment thereof of claim 1 , wherein the light chain variable region comprises the amino acid sequence set forth as SEQ ID NO: 31.
11. The isolated antibody or antigen binding fragment thereof of claim 1 , wherein the light chain variable region comprises the amino acid sequence set forth as SEQ ID NO: 32.
12. The isolated antibody or antigen binding fragment thereof of claim 1 , wherein the heavy chain variable region comprises the amino acid sequence set forth as SEQ ID NO:27 and the light chain variable region comprises the amino acid sequence set forth as SEQ ID NO:31.
13. The isolated antibody or antigen binding fragment thereof of claim 2 , wherein, the heavy chain variable region comprises the amino acid sequence set forth as SEQ ID NO: 25.
14. The isolated antibody or antigen binding fragment thereof of claim 2 , wherein, the heavy chain variable region comprises the amino acid sequence set forth as SEQ ID NO: 26.
15. The isolated antibody or antigen binding fragment thereof of claim 2 , wherein, the heavy chain variable region comprises the amino acid sequence set forth as SEQ ID NO: 27.
16. The isolated antibody or antigen binding fragment thereof of claim 2 , wherein, the heavy chain variable region comprises the amino acid sequence set forth as SEQ ID NO: 28.
17. The isolated antibody or antigen binding fragment thereof of claim 3 , wherein, the light chain variable region comprises the amino acid sequence set forth as SEQ ID NO: 30.
18. The isolated antibody or antigen binding fragment thereof of claim 3 , wherein, the light chain variable region comprises the amino acid sequence set forth as SEQ ID NO: 31.
19. The isolated antibody or antigen binding fragment thereof of claim 3 , wherein, the light chain variable region comprises the amino acid sequence set forth as SEQ ID NO: 32.
20. The isolated antibody or antigen binding fragment thereof of claim 1 , wherein the antibody or fragment is labeled with a detectable label, a therapeutic agent or both.
21. The isolated antibody or antigen binding fragment thereof of claim 1 , wherein the antibody or fragment is a Fv, a scFv, a Fab, a F(ab') 2 , or monoclonal.
22. The isolated antibody or antigen binding fragment thereof of claim 4 , wherein the CDR1, CDR2, and CDR3 of the heavy chain variable region comprise the amino acid sequences set forth as SEQ ID NOs: 41, 42, and 70, respectively, and the CDR1, CDR2, and CDR3of the light chain variable region comprise the amino acid sequences set forth as SEQ ID NOs: 57, 58, and 59, respectively.
23. The isolated antibody or antigen binding fragment thereof of claim 1 , wherein the antibody or fragment is labeled with a therapeutic agent.
24. The isolated antibody or antigen binding fragment thereof of claim 2 , wherein the antibody or fragment is labeled with a detectable label, a therapeutic agent or both.
25. The isolated antibody or antigen binding fragment thereof of claim 2 , wherein the antibody or fragment is labeled with a therapeutic agent.
26. The isolated antibody or antigen binding fragment thereof of claim 2 , wherein the antibody or fragment is a Fv, a scFv, a Fab, a F(ab') 2 , or monoclonal.
27. The isolated antibody or antigen binding fragment thereof of claim 3 , wherein the antibody or fragment is labeled with a detectable label, a therapeutic agent or both.
28. The isolated antibody or antigen binding fragment thereof of claim 3 , wherein the antibody or fragment is labeled with a therapeutic agent.
29. The isolated antibody or antigen binding fragment thereof of claim 3 , wherein the antibody or fragment is a Fv, a scFv, a Fab, a F(ab') 2 , or monoclonal.
30. The isolated antibody or antigen binding fragment thereof of claim 4 , wherein the antibody or fragment is humanized.