Antagonist antibodies against EphB3
View Patent ↗EphB3-specific antibodies are provided, along with pharmaceutical compositions containing such antibody, kits containing a pharmaceutical composition, and methods of preventing and treating an EphB3-related disease or disorder.
1. An isolated antagonist antibody or antigen-binding fragment thereof that comprises the three CDRs of the variable light chain set forth at positions 24 through 35, positions 51 through 57, and positions 90 through 98 of SEQ ID NO 7 and the three CDRs of the variable heavy chain set forth at positions 26 through 35, positions 50 through 67, and positions 99 through 103 of SEQ ID NO: 8, wherein the antibody binds the extracellular domain of EphB3 with an affinity (K D ) of 10 −6 M or less.
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 in which one or two amino acids within either the variable light chain or variable heavy chain have been modified.
4. The antibody of claim 1 that retains 97, 98, or 99% identity over either the variable light chain or variable heavy chain.
5. The antibody of claim 1 comprising a conservative substitution in either the variable light chain or variable heavy chain.
6. The antibody of claim 1 that comprises a constant region of a human antibody sequence and one or more heavy and light chain variable framework regions of a human antibody sequence.
7. The antibody of claim 6 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.
8. The antibody of claim 1 wherein the heavy chain constant region is a modified or unmodified heavy chain constant region of IgG, IgM, IgA, IgD, IgE, a fragment thereof, or combinations thereof.
9. The antibody of claim 1 wherein the light chain constant region is a modified or unmodified lambda light chain constant region, kappa light chain constant region, a fragment thereof, or combinations thereof.
10. The antibody of claim 1 that has a binding affinity of 10 −7 , 10 −8 or 10 −9 M or less to EphB3.
11. The antibody of claim 1 that inhibits EphB3 phosphorylation.
12. The antibody of claim 1 that inhibits EphB3 dimerization.
13. The antibody of claim 1 that inhibits EphB3 ligand-induced receptor activation.
14. The antibody of claim 1 that inhibits EphB3 signaling.
15. The antibody of claim 1 that inhibits the binding of ephrinB2 to EphB3.
16. The antibody of claim 1 that inhibits the binding of ephrinB1 to EphB3.
17. The antibody of claim 1 that inhibits the binding of ephrinB3 to EphB3.
18. The antibody of claim 1 that inhibits proliferation of an intestinal cell.
19. The antibody of claim 1 that inhibits proliferation of a vascular cell.
20. The antibody of claim 1 that promotes proliferation of a neuronal cell.
21. The antibody of claim 1 that is conjugated to a diagnostic agent, therapeutic agent or toxin.
22. The antibody of claim 1 that is purified to at least 95% homogeneity by weight.
23. A pharmaceutical composition comprising the antibody of claim 22 and a pharmaceutically acceptable carrier.
24. A kit comprising a therapeutically effective amount of 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 to treat an EphB3-related disease or disorder.
25. The kit of claim 24 wherein the container is a vial or bottle or prefilled syringe.