Anti-Aβ antibodies and antigen-binding fragments thereof

Patent metadata

Field	Value
Publication number	US-12325741-B2
Application number	US-201917259425-A
Country	US
Kind code	B2
Filing date	Jul 16, 2019
Priority date	Jul 17, 2018
Publication date	Jun 10, 2025
Grant date	Jun 10, 2025

Abstract

Murine, chimeric or humanized anti-Abeta antibody having a specific CDR region, an antigen-binding fragment thereof, a pharmaceutical composition thereof, and usage thereof. Use of a humanized anti-Abeta antibody for the preparation of drugs for the treatment of a disease or disorder (such as Alzheimer's disease) caused by amyloid beta protein.

First claim

The invention claimed is:

1. An anti-Abeta antibody or antigen-binding fragment thereof, wherein the anti-Abeta antibody specifically binds to human Abeta and comprises a heavy chain variable region comprising antibody heavy chain HCDR1, HCDR2 and HCDR3 regions and a light chain variable region comprising antibody light chain LCDR1, LCDR2 and LCDR3 regions, wherein the HCDR1 in comprises the amino acid sequence of SEQ ID NO: 17, the HCDR2 comprises the amino acid sequence of SEQ ID NO: 18 or 52, and the HCDR3 comprises the amino acid sequence of SEQ ID NO: 27, and the LCDR1 comprises the amino acid sequence of SEQ ID NO: 20, the LCDR2 comprises the amino acid sequence of SEQ ID NO: 21, and the LCDR3 comprises the amino acid sequence of SEQ IDNO: 22.

2. The anti-Abeta antibody or antigen-binding fragment thereof according to claim 1 , wherein the antibody is a murine, chimeric or humanized antibody.

3. The anti-Abeta antibody or antigen-binding fragment thereof according to claim 2 , wherein the antibody is a murine antibody, and comprises a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 9, or having at least 95% sequence identity to the amino acid sequence SEQ ID NO: 9 and comprising HCDRs 1-3 of SEQ ID NOs: 17, 18 and 27 respectively; and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 10, or having at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 10 and comprising LCDRs 1-3 of SEQ ID NOs: 20-22 respectively.

4. The anti-Abeta antibody or antigen binding fragment thereof according to claim 3 , wherein the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 9 and the light chain variable region comprises the amino acid sequence of SEQ ID NO: 10.

5. The anti-Abeta antibody or antigen-binding fragment thereof according to claim 2 , wherein the antibody comprises a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 50, or having at least 90% sequence identity to the amino acid sequence of SEQ ID NO: 50 and comprising HCDRs 1-3 of SEQ ID NOs: 17, 18 and 27 respectively, or HCDRs1-3 of SEQ ID NOs: 17, 52 and 27 respectively; and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 51, or having at least 90% sequence identity to the amino acid sequence of SEQ ID NO: 51 and comprising LCDRs 1-3 of SEQ ID NOs: 20-22 respectively.

6. The anti-Abeta antibody or antigen-binding fragment thereof according to claim 2 , wherein the antibody is a humanized antibody and comprises an antibody heavy chain variable region comprising HCDR1 having the amino acid sequence of SEQ ID NO: 17, HCDR2 having the amino acid sequence of SEQ ID NO: 18 or 52 and HCDR3having the amino acid sequence of SEQ ID NO: 27; and an antibody light chain variable region comprising LCDR1 having the amino acid sequence of SEQ ID NO: 20, LCDR2 having the amino acid sequence of SEQ ID NO: 21 and LCDR3 having the amino acid sequence of SEQ ID NO: 22.

7. The anti-Abeta antibody or antigen-binding fragment thereof according to claim 1 , wherein the antibody comprises constant region(s); and
wherein the antibody heavy chain constant region is the amino acid sequence of SEQ ID NO: 42, and the antibody light chain constant region is the amino acid sequence of SEQ ID NO: 43.

8. The anti-Abeta antibody or antigen-binding fragment thereof according to claim 7 , wherein the antibody comprises a heavy chain having the amino acid sequence of SEQ ID NO: 40, and a light chain having the amino acid sequence of SEQ ID NO: 41.

9. The anti-Abeta antibody or antigen-binding fragment thereof according to claim 1 , wherein the antigen-binding fragment is selected from the group consisting of Fab, Fab′, F(ab′)2, scFv, and dsFv.

10. A pharmaceutical composition comprising:
the anti-Abeta antibody or antigen-binding fragment thereof according to claim 1 , and one or more pharmaceutically acceptable carrier(s), excipient(s) or diluent(s).

Assignees

• Jiangsu Hengrui Medicine Co
• Shanghai hengrui pharmaceutical co ltd

Inventors

• Ying Hua
• Zhang Ling
• Shi Jinping
• Zhang Xiaomin
• Sun Jiakang
• Hu Qiyue
• Tao Weikang

Classifications

• C07K2317/92

  Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value · CPC title

• C07K2317/567

  Framework region [FR] · CPC title

• C07K2317/565

  Complementarity determining region [CDR] · CPC title

• C07K2317/24

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

• A61K2039/505

  comprising antibodies · CPC title