Humanized antibodies against the beta-amyloid peptide
View Patent ↗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.
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 .