Antibodies to alpha synuclein

Patent metadata

Field	Value
Publication number	US-9879071-B2
Application number	US-201213604441-A
Country	US
Kind code	B2
Filing date	Sep 5, 2012
Priority date	May 19, 2003
Publication date	Jan 30, 2018
Grant date	Jan 30, 2018

Abstract

The application identifies novel fragments of alpha-synuclein in patients with Lewy Body Disease (LBD) and transgenic animal models thereof. These diseases are characterized by aggregations of alpha-synuclein. The fragments have a truncated C-terminus relative to full-length alpha-synuclein. Some fragments are characterized by a molecular weight of about 12 kDa as determined by SDS gel electrophoresis in tricine buffer and a truncation of at least ten contiguous amino acids from the C-terminus of natural alpha-synuclein. The site of cleavage preferably occurs after residue 117 and before residue 126 of natural alpha-synuclein. The identification of these novel fragments of alpha-synuclein has a number of application in for example, drug discovery, diagnostics, therapeutics, and transgenic animals.

First claim

What is claimed is:

1. An antibody that specificalIy binds to and is end- specific for the for the free C-terminus of a fragment of alpha-synuclein, wherein the fragment is amino acids 1-119 or 1-122 of SEQ ID NO: 1; and does not specifically bind to full-length alpha-synuclein, wherein specific binding requires an association constant of the antibody for the fragment of at least 10 7 M −1 .

2. An antibody that specifically binds to and is end-specific for the free N-terminus of a fragment of alpha-synuclein, wherein the fragment amino acids 120-140 or 123-140 of SEQ ID NO: 1; and does not specifically bind to full-length alpha-synuclein, wherein specific binding requires an association constant of the antibody for the fragment of at least 10 7 M −1 .

3. The antibody of claim 1 or claim 2 that is a humanized antibody.

4. The antibody of claim 1 or claim 2 that is a monoclonal antibody.

5. The antibody of claim 1 or claim 2 having human isotype IgGI.

Assignees

• Chilcote Tamie J
• Goldstein Jason
• Anderson John P
• Walker Donald
• Prothena Biosciences Ltd

Inventors

• Chilcote Tamie J
• Goldstein Jason
• Anderson John P
• Walker Donald

Classifications

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• G01N33/6896

  Neurological disorders, e.g. Alzheimer's disease · CPC title

• C07K16/18 Primary

  against material from animals or humans · CPC title

• A61K38/00

  Medicinal preparations containing peptides (peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00) · CPC title

• C07K2317/33

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