Humanized antibodies binding to amyloid-beta (A-beta)

Patent metadata

Field	Value
Publication number	US-12286469-B2
Application number	US-201816631676-A
Country	US
Kind code	B2
Filing date	Jul 18, 2018
Priority date	Jul 18, 2017
Publication date	Apr 29, 2025
Grant date	Apr 29, 2025

Abstract

The disclosure pertains to antibodies that bind A-beta oligomers and methods of making and using said antibodies. Also provided are chimeric or humanized antibodies, including antibodies having CDRs in Table 2 and/or having a sequence as set forth in Table 4B or a sequence with at least 50% sequence identity thereto optionally wherein the CDR amino acid sequences are as set for forth in SEQ ID Nos: 74-79. Also provided are methods and uses thereof as well as kits comprising said antibodies.

First claim

The invention claimed is:

1. A humanized antibody or antigen binding fragment thereof that binds amyloid-beta (A-beta) comprising:
a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 44 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 64;
a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 44 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 66;
a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 44 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 68;
a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 46 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 64;
a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 46 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 66;
a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 46 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 68;
a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 48 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 64;
a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 48 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 66;
a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 48 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 68;
a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 50 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 68; or
a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 52 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 68.

2. The humanized antibody or antigen binding fragment thereof of claim 1 , wherein
the heavy chain variable region is encoded by a nucleotide sequence that encodes the amino acid sequence of SEQ ID NO: 44 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 64;
the heavy chain variable region is encoded by a nucleotide sequence that encodes the amino acid sequence of SEQ ID NO: 44 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 66;
the heavy chain variable region is encoded by a nucleotide sequence that encodes the amino acid sequence of SEQ ID NO: 44 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 68;
the heavy chain variable region is encoded by a nucleotide sequence that encodes the amino acid sequence of SEQ ID NO: 46 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 64;
the heavy chain variable region is encoded by a nucleotide sequence that encodes the amino acid sequence of SEQ ID NO: 46 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 66;
the heavy chain variable region is encoded by a nucleotide sequence that encodes the amino acid sequence of SEQ ID NO: 46 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 68;
the heavy chain variable region is encoded by a nucleotide sequence that encodes the amino acid sequence of SEQ ID NO: 48 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 64;
the heavy chain variable region is encoded by a nucleotide sequence that encodes the amino acid sequence of SEQ ID NO: 48 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 66;
the heavy chain variable region is encoded by nucleotide sequence that encodes the amino acid sequence of SEQ ID NO: 48 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 68;
the heavy chain variable region is encoded by nucleotide sequence that encodes the amino acid sequence of SEQ ID NO: 50 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 68; or
the heavy chain variable region is encoded by nucleotide sequence that encodes the amino acid sequence of SEQ ID NO: 52 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 68.

3. The humanized antibody or antigen binding fragment thereof of claim 1 , wherein the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 44 and the light chain variable region comprises the amino acid sequence of SEQ ID NO: 64.

4. The humanized antibody or antigen binding fragment thereof of claim 1 , wherein the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 44 and the light chain variable region comprises the amino acid sequence of SEQ ID NO: 66.

5. The humanized antibody or antigen binding fragment thereof of claim 1 , wherein the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 44 and the light chain variable region comprises the amino acid sequence of SEQ ID NO: 68.

6. The humanized antibody or antigen binding fragment thereof of claim 1 , wherein the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 46 and the light chain variable region comprises the amino acid sequence of SEQ ID NO: 64.

7. The humanized antibody or antigen binding fragment thereof of claim 1 , wherein the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 46 and the light chain variable region comprises the amino acid sequence of SEQ ID NO: 66.

8. The humanized antibody or antigen binding fragment thereof of claim 1 , wherein the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 46 and the light chain variable region comprises the amino acid sequence of SEQ ID NO: 68.

9. The humanized antibody or antigen binding fragment thereof of claim 1 , wherein the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 48 and the light chain variable region comprises the amino acid sequence of SEQ ID NO: 64.

10. The humanized antibody or antigen binding fragment thereof of claim 1 , wherein the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 48 and the light chain variable region comprises the amino acid sequence of SEQ ID NO: 66.

11. The humanized antibody or antigen binding fragment thereof of claim 1 , wherein the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 48 and the light chain variable region comprises the amino acid sequence of SEQ ID NO: 68.

12. The humanized antibody or antigen binding fragment thereof of claim 1 , wherein the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 50 and the light chain variable region comprises the amino acid sequence of SEQ ID NO: 68.

13. The humanized antibody or antigen binding fragment thereof of claim 1 , wherein the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 52 and the light chain variable region comprises the amino acid sequence of SEQ ID NO: 68.

14. The humanized antigen binding fragment of claim 1 , wherein the antigen binding fragment is selected from Fab, Fab′, F(ab′)2, dimers, and multimers thereof.

15. The humanized antigen binding fragment of claim 14 , wherein the antigen binding fragment is the Fab fragment.

16. The humanized antibody of claim 1 , wherein the antibody is an IgG1 or IgG4 isotype of the antibody.

17. The humanized antibody of claim 1 , wherein the a

Assignees

• Univ British Columbia
• Promis Neurosciences Inc

Inventors

• Cashman Neil R
• Plotkin Steven S
• Kaplan Johanne
• Silverman Judith Maxwell
• Gibbs Ebrima

Classifications

• C07K2317/64

  comprising a combination of variable region and constant region components · CPC title

• C07K2317/56

  variable (Fv) region, i.e. VH and/or VL · CPC title

• C07K2317/50

  characterized by immunoglobulin fragments · CPC title

• C07K2317/62

  comprising only variable region components · CPC title

• C07K2317/00

  Immunoglobulins specific features · CPC title