EPHB3-specific antibody and uses thereof

1. An isolated antibody that binds the extracellular domain of EphB3, wherein the antibody comprises six CDR regions selected from the group consisting of:

(a) CDR-L1, CDR-L2, CDR-L3, CDR-H1, CDR-H2 and CDR-H3 of antibody XPA.04.001, wherein the light chain variable region sequence of XPA.04.001 is set out in SEQ ID NO: 3 and the heavy chain variable sequence of XPA.04.001 is set out in SEQ ID NO: 4;

(b) CDR-L1, CDR-L2, CDR-L3, CDR-H1, CDR-H2 and CDR-H3 of antibody XPA.04.013, wherein the light chain variable region sequence of XPA.04.013 is set out in SEQ ID NO: 5 and the heavy chain variable sequence of XPA.04.013 is set out in SEQ ID NO: 6;

(c) CDR-L1, CDR-L2, CDR-L3, CDR-H1, CDR-H2 and CDR-H3 of antibody XPA.04.018, wherein the light chain variable region sequence of XPA.04.018 is set out in SEQ ID NO: 7 and the heavy chain variable sequence of XPA.04.018 is set out in SEQ ID NO: 8; and

(d) CDR-L1, CDR-L2, CDR-L3, CDR-H1, CDR-H2 and CDR-H3 of antibody XPA.04.048, wherein the light chain variable region sequence of XPA.04.048 is set out in SEQ ID NO: 9 and the heavy chain variable sequence of XPA.04.048 is set out in SEQ ID NO: 10.

2. The antibody of claim 1 wherein the antibody is a chimeric antibody, a humanized antibody, a human engineered antibody, a human antibody, a single chain antibody or an antibody fragment.

3. The antibody of claim 1 that retains at least 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identity over either the variable light or heavy region to the antibodies of XPA.04.001, XPA.04.013, XPA.04.018, or XPA.04.048.

4. The antibody of claim 1 that comprises a light chain constant region of a human antibody sequence, a heavy chain constant region of a human antibody sequence, and one or more heavy and light chain variable framework regions of a human antibody sequence.

5. The antibody of claim 4 wherein the human antibody sequence is an individual human sequence, a human consensus sequence, an individual human germline sequence, or a human consensus germline sequence.

6. The antibody of claim 4 wherein the heavy chain constant region is a modified or unmodified IgG, IgM, IgA, IgD, IgE, a fragment thereof, or combinations thereof.

7. The antibody of claim 1 that has a binding affinity of 10 −7 , 10 −8 or 10 −9 M or less to EphB3.

8. The antibody of claim 4 wherein the light chain constant region is a modified or unmodified lambda light chain constant region, a kappa light chain constant region, a fragment thereof, or combinations thereof.

9. The antibody of claim 1 that induces EphB3 phosphorylation.

10. The antibody of claim 1 that induces EphB3 oligomerization.

11. The antibody of claim 1 that induces EphB3 internalization.

12. The antibody of claim 1 that induces EphB3 degradation.

13. The antibody of claim 1 that induces EphB3 signaling.

14. The antibody of claim 1 that inhibits the binding of an ephrinB to EphB3.

15. The antibody of claim 1 that is conjugated to another diagnostic or therapeutic agent.

16. The antibody of claim 1 that is purified to at least 95% homogeneity by weight.

17. A pharmaceutical composition comprising the antibody of claim 16 and a pharmaceutically acceptable carrier.

18. A kit comprising an antibody of claim 1 , packaged in a container, said kit optionally containing a second therapeutic agent, and further comprising a label attached to or packaged with the container, the label describing the contents of the container and providing indications and/or instructions regarding use of the contents of the container.

19. The kit of claim 18 wherein the container is a vial or bottle or prefilled syringe.

20. The antibody of claim 2 wherein said antibody induces an activity selected from the group consisting of: (a) Eph3 phosphorylation; (b) EphB3 oligomerization; (c) EphB3 internalization; (d) EphB3 degradation; and (e) EphB3 signaling.