Antibodies to EphA3
View Patent ↗The current invention relates to high-affinity antibodies to EphA3 that have reduced immunogenicity when administered to a human to treat diseases and method of using such antibodies.
1. A method of treating a patient that has a myeloproliferative disorder in which the myeloproliferative disorder cells express EphA3, the method comprising administering an anti-EphA3 antibody to the patient in a therapeutically effective amount, wherein the antibody comprises:
(i) a V H region that comprises a CDR1 having the amino acid sequence GYWMN (SEQ ID NO:48), a CDR2 having the amino acid sequence DIYPGSGNTNYDEKFQG (SEQ ID NO:49); and a CDR3 having the amino acid sequence GGYYEDFDS (SEQ ID NO:43); and
(ii) a V L region that comprises a CDR1 having the amino acid sequence RASQGIISYLA (SEQ ID NO:66); a CDR2 having the amino acid sequence AASSLQS (SEQ ID NO:68); and a CDR3 having a sequence GQYANYPYT (SEQ ID NO:57).
2. The method of claim 1 , wherein the V H region comprises a FR4 that has the amino acid sequence WGQGTTVTVSS (SEQ ID NO:47).
3. The method of claim 1 , wherein the V H region comprises a V-segment having the V-segment amino acid sequence of SED ID NO:5.
4. The method of claim 1 , wherein the V H region comprises the amino acid sequence of SED ID NO:5.
5. The method of claim 1 , wherein the V L region comprises a FR4 having the FR4 amino acid sequence FGQGTKLEIK (SEQ ID NO:69).
6. The method of claim 1 , wherein the V L region comprises a V-segment that has the V-segment amino acid sequence of SEQ ID NO:13.
7. The method of claim 1 , wherein the V L region comprise the amino acid sequence of SEQ ID NO:13.
8. The method of claim 1 , wherein the V H region comprises the amino acid sequence of SEQ ID NO:5 and the V L region comprises the amino acid sequence of SEQ ID NO:13.
9. The method of claim 1 , wherein the anti-EphA3 antibody is an IgG.
10. The method of claim 1 , wherein the anti-EphA3 antibody is an IgG1.
11. The method of claim 1 , wherein the anti-EphA3 antibody comprises a heavy chain constant region having the amino acid sequence set forth in SEQ ID NO:24.
12. The method of claim 1 , wherein the anti-EphA3 antibody comprises a kappa light chain constant region having the amino acid sequence set forth in SEQ ID NO:25.
13. The method of claim 1 , wherein the anti-EphA3 antibody comprises a heavy chain constant region having the amino acid sequence set forth in SEQ ID NO:24 and a kappa light chain constant region having the amino acid sequence set forth in SEQ ID NO:25.
14. The method of claim 1 , wherein the anti-EphA3 antibody has a heavy chain amino acid sequence that comprises the amino acid sequence of SEQ ID NO:30 and a light chain amino acid sequence that comprises the amino acid sequence of SEQ ID NO:31.
15. The method of claim 14 , wherein the anti-EpA3 antibody is afucosylated.
16. The method of claim 1 , wherein the anti-EphA3 antibody is afucosylated.
17. The method of claim 14 , wherein the anti-EphA3 antibody is administered in an antibody preparation, wherein the antibody preparation is hypofucosylated.
18. The method of claim 1 , wherein the antibody is administered in an antibody preparation, wherein the antibody preparation is hypofucosylated.
19. The method of claim 1 , wherein the myeloproliferative disorder is idiopathic myelofibrosis.
20. The method of claim 1 , wherein the myeloproliferative disorder is myelodysplatic syndrome.