Anti-EphA4 antibody

Patent metadata

Field	Value
Publication number	US-10947313-B2
Application number	US-202016915412-A
Country	US
Kind code	B2
Filing date	Jun 29, 2020
Priority date	Jul 1, 2019
Publication date	Mar 16, 2021
Grant date	Mar 16, 2021

Abstract

A mouse anti-EphA4 antibody that has binding affinity towards EphA4 and can enhance the cleavage of EphA4 was obtained, and the sequence of the complementarity-determining region (CDR) of the mouse anti-EphA4 antibody was identified. Subsequently, the anti-EphA4 antibody of interest was obtained by producing a humanized antibody of the mouse anti-EphA4 antibody.

First claim

The invention claimed is:

1. An anti-EphA4 antibody, wherein
the anti-EphA4 antibody comprises heavy and light chains, and comprises:
(a) a heavy chain CDR1 consisting of the amino acid sequence shown in SEQ ID NO. 44;
(b) a heavy chain CDR2 consisting of the amino acid sequence shown in SEQ ID NO. 27;
(c) a heavy chain CDR3 consisting of the amino acid sequence shown in SEQ ID NO. 28;
(d) a light chain CDR1 consisting of the amino acid sequence shown in SEQ ID NO. 29;
(e) a light chain CDR2 consisting of the amino acid sequence shown in SEQ ID NO. 30; and
(f) a light chain CDR3 consisting of the amino acid sequence shown in SEQ ID NO. 31.

2. The anti-EphA4 antibody according to claim 1 , wherein the anti-EphA4 antibody is humanized.

3. The anti-EphA4 antibody according to claim 1 , wherein the heavy chain comprises a variable region consisting of the amino acid sequence shown in SEQ ID NO. 45, and the light chain comprises a variable region consisting of the amino acid sequence shown in SEQ ID NO. 46.

4. The anti-EphA4 antibody according to claim 1 , wherein the heavy chain and the light chain comprise constant regions comprising amino acid sequences from a human antibody.

5. The anti-EphA4 antibody according to claim 4 , wherein the constant region of the heavy chain is the constant region of human IgG.

6. The anti-EphA4 antibody according to claim 5 , wherein the constant region of human IgG is the constant region of human IgG 2 .

7. The anti-EphA4 antibody according to claim 6 , wherein the constant region of human IgG 2 comprises the amino acid sequence shown in SEQ ID NO. 47.

8. The anti-EphA4 antibody according to claim 4 , wherein the constant region of the light chain is the constant region of human Igκ.

9. The anti-EphA4 antibody according to claim 8 , wherein the constant region of human Igκ comprises the amino acid sequence shown in SEQ ID NO. 48.

10. An anti-EphA4 antibody, wherein the anti-EphA4 antibody comprises heavy and light chains, the heavy chain comprises the amino acid sequence shown in SEQ ID NO. 59, and the light chain comprises the amino acid sequence shown in SEQ ID NO. 60.

11. A pharmaceutical composition comprising the anti-EphA4 antibody according to claim 1 and at least one pharmaceutically acceptable carrier.

12. An anti-EphA4 antibody, wherein the anti-EphA4 antibody comprises heavy and light chains, the heavy chain comprises the amino acid sequence shown in SEQ ID NO. 59, the light chain comprises the amino acid sequence shown in SEQ ID NO. 60, and the C-terminal lysine of the heavy chain is deleted.

13. A pharmaceutical composition comprising the anti-EphA4 antibody according to claim 10 and at least one pharmaceutically acceptable carrier.

14. A method for inhibiting tau phosphorylation in a subject having Alzheimer's disease, comprising administering to the subject an effective amount of the anti-EphA4 antibody according to claim 1 .

15. A method for inhibiting tau phosphorylation in a subject having Alzheimer's disease, comprising administering to the subject an effective amount of the anti-EphA4 antibody according to claim 10 .

Assignees

• Eisai R&D Man Co Ltd

Inventors

• Inoue Eiji
• Yamada Akio
• Kawakatsu Tomomi
• Imai Toshio
• Deguchi Maki
• Nakatani Aki

Classifications

• C07K2317/76

  Antagonist effect on antigen, e.g. neutralization or inhibition of binding · CPC title

• C07K2317/70

  characterized by effect upon binding to a cell or to an antigen · CPC title

• C07K2317/33

  Crossreactivity, e.g. for species or epitope, or lack of said crossreactivity · CPC title

• C07K2317/24

  containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered · CPC title

• C07K16/2866 Primary

  against receptors for cytokines, lymphokines, interferons · CPC title