Anti-amyloid beta antibodies binding to a cyclic amyloid beta peptide

Patent metadata

Field	Value
Publication number	US-10751382-B2
Application number	US-201816148601-A
Country	US
Kind code	B2
Filing date	Oct 1, 2018
Priority date	Nov 9, 2016
Publication date	Aug 25, 2020
Grant date	Aug 25, 2020

Abstract

The disclosure pertains to methods of treating or preventing a disease or condition associated with and/or induced by soluble A-beta oligomer such as Alzheimer's disease by administering to a subject in need thereof conformation specific and/or selective antibodies or binding fragments thereof and related products.

First claim

The invention claimed is:

1. Two or more antibodies or antigen-binding fragments thereof selected from the group consisting of:
a) an antibody or antigen-binding fragment thereof comprising a light chain variable region and a heavy chain variable region, optionally fused, the heavy chain variable region comprising complementarity determining regions CDR-H1, CDR-H2 and CDR-H3, the light chain variable region comprising complementarity determining region CDR-L1, CDR-L2 and CDR-L3 and with the amino acid sequences of said CDRs comprising SEQ ID NOs: 20-25 respectively, wherein the antibody or antigen-binding fragment thereof specifically and/or selectively binds a cyclic compound having the amino acid sequence of SEQ ID NO: 2;
b) an antibody or antigen-binding fragment thereof comprising a light chain variable region and a heavy chain variable region, optionally fused, the heavy chain variable region comprising complementarity determining regions CDR-H1, CDR-H2 and CDR-H3, the light chain variable region comprising complementarity determining region CDR-L1, CDR-L2 and CDR-L3 and with the amino acid sequences of said CDRs comprising SEQ ID NOs: 53-58 respectively, wherein the antibody or antigen-binding fragment thereof specifically and/or selectively binds a cyclic compound having the amino acid sequence of SEQ ID NO: 10; and
c) an antibody or antigen-binding fragment thereof comprising a light chain variable region and a heavy chain variable region, optionally fused, the heavy chain variable region comprising complementarity determining regions CDR-H1, CDR-H2 and CDR-H3, the light chain variable region comprising complementarity determining region CDR-L1, CDR-L2 and CDR-L3 and with the amino acid sequences of said CDRs comprising SEQ ID NOs: 41, 42, 43, 44, 45 and 46 respectively, wherein the antibody or antigen-binding fragment thereof specifically and/or selectively binds a cyclic compound having the amino acid sequence of SEQ ID NO: 6;
wherein each of the two or more antibodies or antigen-binding fragments thereof has different CDRs from each other.

2. The two or more antibodies or antigen-binding fragments thereof of claim 1 , wherein each of the two or more antibodies is monoclonal chimeric or humanized.

3. The two or more antibodies or antigen-binding fragments thereof of claim 2 , wherein the antigen-binding fragment is a Fab, Fab′, F(ab′)2, scFv, dsFv 7 or ds-scFv of the antibody or at least one of the two or more antibodies is a nanobody, minibody or diabody of the antibody, or a dimer or multimer thereof.

4. The two or more antibodies of claim 1 , wherein the antibody a) is produced from a hybrdioma cell line deposited under the provisions of the Budapest Treaty with the American Type Culture Collection (ATCC) and given the Accession number PTA-124318.

5. Two or more immunoconjugates each comprising an antibody or antigen-binding fragment thereof selected from the antibodies or antigen-binding fragments of claim 1 and a detectable label or cytotoxic agent.

6. The two or more immunoconjugates of claim 5 , wherein the detectable label comprises a positron emitting radionuclide.

7. A kit comprising the two or more antibodies or antigen-binding fragments of claim 1 , or the two or more immunoconjugates according to claim 2 .

8. A composition comprising the two or more antibodies or antigen-binding fragments thereof of claim 1 , or the two or more immunoconjugates of claim 2 .

9. The composition of claim 8 , wherein the two or more antibodies or antigen binding fragments thereof or the two or more immunoconjugates selectively bind an A-beta oligomer.

10. The composition of claim 8 , wherein each of the two or more antibodies is monoclonal, chimeric or humanized.

11. The composition of claim 8 , wherein at least one of the antigen-binding fragments is a Fab, Fab′, F(ab′)2, scFv, dsFv or ds-scFv of the antibody, or at least one of the two or more antibodies is nanobody, minibody or diabody of the antibody, or a dimer or multimer thereof.

12. The composition of claim 8 , wherein the light chain variable region and the heavy chain variable region of at least one of the two or more antibodies are fused.

13. The composition of claim 8 , wherein the heavy chain variable region and the light chain variable region of the two or more antibodies or antigen-binding fragments thereof recited in a, b) and c) of claim 1 , comprise the amino acid sequences selected from:
a) SEQ ID NOs: 84 and 86;
b) is SEQ ID NOs: 106 and 108; and
c) is SEQ ID NOs: 98 and 100 respectively.

14. The composition of claim 8 , wherein the composition comprises the two or more immunoconjugates of claim 5 .

15. The composition of claim 8 , wherein the composition is formulated for administration directly to the brain or other portion of the CNS.

Assignees

• Univ British Columbia
• Promis Neurosciences Inc

Inventors

• Cashman Neil R

Classifications

• A61K39/00

  Medicinal preparations containing antigens or antibodies (materials for immunoassay G01N33/53) · CPC title

• A61K45/05

  Immunological preparations stimulating the reticulo-endothelial system, e.g. against cancer · CPC title

• C07K2317/56

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

• C07K2317/526

  CH3 domain · CPC title

• C07K7/64

  Cyclic peptides containing only normal peptide links · CPC title