Humanized antibodies against the beta-amyloid peptide

Patent metadata

Field	Value
Publication number	US-9273126-B2
Application number	US-201213667723-A
Country	US
Kind code	B2
Filing date	Nov 2, 2012
Priority date	Sep 13, 2007
Publication date	Mar 1, 2016
Grant date	Mar 1, 2016

Abstract

The invention discloses an isolated antibody that selectively binds to the C-terminal part of Abeta and is humanized or fully human. The antibody of the invention is capable of preventing oligomerization of Abeta. Furthermore, a method of diagnosis comprising the steps of: (i) Labelling an antibody; (ii) Administering an effective dose of said antibody intranasally or systemically to a subject; and (iii) Detecting the concentration and/or presence of the labelled antibody in body parts of the subject is disclosed.

First claim

The invention claimed is:

1. A nucleic acid sequence encoding an antibody comprising the variable light fragment (VL) sequence set forth in SEQ ID NO: 7 and the variable heavy chain fragment (VH) sequence set forth in SEQ ID NO: 17.

2. A nucleic acid sequence encoding an antibody that selectively binds to the C-terminal part of beta-amyloid, the antibody comprising a variable light chain fragment (VL) sequence comprising the variable light chain CDR1, CDR2 and CDR3 sequences set forth in SEQ ID Nos: 1, 2 and 3, respectively, and a variable heavy chain fragment (VH) sequence comprising the variable heavy chain CDR1, CDR2 and CDR3 sequences set forth in SEQ ID Nos: 4, 5, and 6, respectively, wherein
a) position 1 of the light chain is an aspartate residue;
b) position 43 of the light chain is a proline residue;
c) position 46 of the light chain is an alanine residue;
d) position 61 of the light chain is an arginine residue;
e) position 104 of the light chain is leucine residue;
f) position 105 of the light chain is a glutamate residue; and
g) position 106 of the light chain is a valine residue, according to Kabat numbering.

3. The nucleic acid sequence of claim 2 , wherein:
a) position 9 of the heavy chain is a proline residue;
b) position 28 of the heavy chain is a threonine residue;
c) position 71 of the heavy chain is a valine residue;
d) position 73 of the heavy chain is a arginine residue;
e) position 75 of the heavy chain is a serine residue;
f) position 76 of the heavy chain is a serine residue; and
g) position 78 of the heavy chain is an alanine residue.

4. The nucleic acid sequence of claim 2 , wherein the antibody comprises the variable light fragment (VL) sequence set forth in SEQ ID NO: 7.

5. The nucleic acid sequence of claim 3 , wherein the antibody comprises the variable heavy chain fragment (VH) sequence set forth in SEQ ID NO: 17.

6. The nucleic acid sequence of claim 1 or 2 encoding an antibody comprising SEQ ID No: 24.

7. A vector comprising the nucleic acid sequence of claim 1 or 2 .

8. A host cell comprising the nucleic acid sequence of claim 1 or 2 .

9. A host cell comprising the vector of claim 7 .

Assignees

• Ewert Stefan
• Auf Der Maur Adrian
• Cattepoel Susann
• Nitsch Roger
• Delenex Therapeutics Ag
• Univ Zuerich

Inventors

• Ewert Stefan
• Auf Der Maur Adrian
• Cattepoel Susann
• Nitsch Roger

Classifications

• A61P37/02

  Immunomodulators · CPC title

• C07K2317/56

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

• A61P25/00

  Drugs for disorders of the nervous system · 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