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

Patent metadata

Field	Value
Publication number	US-10759837-B2
Application number	US-201615774778-A
Country	US
Kind code	B2
Filing date	Nov 9, 2016
Priority date	Nov 9, 2015
Publication date	Sep 1, 2020
Grant date	Sep 1, 2020

Abstract

The disclosure pertains to epitopes identified in A-beta including conformational epitopes, antibodies thereto and methods of making and using immunogens and antibodies specific thereto.

First claim

The invention claimed is:

1. An isolated antibody or antigen-binding fragment thereof that specifically binds to a cyclic A-beta peptide comprising the amino acid sequence of SEQ ID NO: 3, the antibody or antigen-binding fragment thereof comprising a light chain variable region and a heavy chain variable region, 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 the sequences of either:
A. CDR-H1 GYTFTDYE (SEQ ID NO: 11)
CDR-H2 IDPETGDT (SEQ ID NO: 12)
CDR-H3 TSPIYYDYDWFAY (SEQ ID NO: 13)
CDR-L1 QSLLNNRTRKNY (SEQ ID NO: 14)
CDR-L2 WAS (SEQ ID NO: 15) and
DR-L3 KQSYNLRT (SEQ ID NO: 16); or

B. CDR-H1 GFSLSTSGMG (SEQ ID NO: 21)
CDR-H2 IWWDDDK (SEQ ID NO: 22)
CDR-H3 ARSITTVVATPFDY (SEQ ID NO: 23)
CDR-L1 QNVRSA (SEQ ID NO: 24)
CDR-L2 LAS (SEQ ID NO: 25) and
CDR-L3 LQHWNSPFT (SEQ ID NO: 26).

2. The isolated antibody or antigen-binding fragment thereof of claim 1 , wherein the heavy chain variable region of the antibody A according to claim 1 comprises the amino acid sequence of SEQ ID NO: 18 and the light chain variable region of the antibody A according to claim 1 comprises the amino acid sequence of SEQ ID NO: 20.

3. The isolated antibody or antigen-binding fragment thereof of claim 1 , wherein the heavy chain variable region of the antibody B according to claim 1 comprises the amino acid sequence of SEQ ID NO: 28 and the light chain variable region of the antibody B according to claim 1 comprises the amino acid sequence of SEQ ID NO:30.

4. The antibody or antigen-binding fragment thereof of claim 1 , wherein the light chain variable region and the heavy chain variable region of the antibody A or B according to claim 1 are fused.

5. The antibody or antigen-binding fragment thereof of claim 1 , wherein the antibody is monoclonal or humanized.

6. The antibody or antigen-binding fragment thereof of claim 1 , wherein the antigen-binding fragment is a Fab, Fab′, F(ab′)2, scFv, dsFv, ds-scFv, nanobody, minibody, diabody of the antibody according to claim 1 or a dimer or multimer thereof.

7. An immunoconjugate comprising the antibody or antigen-binding fragment thereof of claim 1 and a detectable label or cytotoxic agent.

8. The immunoconjugate of claim 7 , wherein the detectable label comprises a positron emitting radionuclide.

9. A composition comprising the antibody or antigen-binding fragment thereof of claim 1 , or the immunoconjugate of claim 7 , optionally with a diluent.

Assignees

• Univ British Columbia

Inventors

• Cashman Neil R
• Plotkin Steven S

Classifications

• A61K39/00

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

• C07K14/4711 Primary

  Alzheimer's disease; Amyloid plaque core protein · CPC title

• A61K47/6921

  the form being a particulate, a powder, an adsorbate, a bead or a sphere · CPC title

• A61K47/646

  the entire peptide or protein drug conjugate elicits an immune response, e.g. conjugate vaccines · CPC title

• A61L31/10

  Macromolecular materials · CPC title