EPHB3-specific antibody and uses thereof

• US 8,586,716 B2
• Filed: 08/03/2007
• Issued: 11/19/2013
• Est. Priority Date: 08/04/2006
• Status: Active Grant

• Current Assignee: Xoma Technology Ltd. (Xoma Corp.)
• Original Assignee: Novartis Ag, Xoma Technology Ltd. (Xoma Corp.)
• Inventors: Hsu, Jeff, Masat, Linda, Abraham, Judy, Handa, Masahisa, Schleyer, Siew
• Primary Examiner(s): Huff, Sheela J
• Assistant Examiner(s): Roark, Jessica H
• Application Number:
  US11/833,726
• Publication Number:
  US 20090142261A1
• Time in Patent Office: 2,300 Days
• Field of Search: None
• US Class Current: 530/388.8
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07K 16/2866 against receptors for cytokines, lymphokines, interferons
• CPC Class Codes: C07K 16/30 from tumour cells
• CPC Class Codes: C07K 2317/56 variable (Fv) region, i.e. VH and/or VL
• CPC Class Codes: C07K 2317/75 Agonist effect on antigen
• CPC Class Codes: C07K 2317/77 Internalization into the cell
• CPC Class Codes: C07K 2317/92 Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value

Abstract

EphB3-specific antibodies are provided, along with pharmaceutical compositions containing such antibody, kits containing a pharmaceutical composition, and methods of preventing and treating cancer.

Claims

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<sup>−

8</sup> or 10<sup>−

9</sup> 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.