Antibodies specific of the β-amyloid peptides and their uses as diagnostic agents or drugs

1. A monoclonal antibody, Antibody Tei A 1.6, comprising:

a light chain variable region: SSLTVTAGEKVTMSCKSSQSLLAGRYQKNYLTWYQQKPGQPPKLLIYWASTRDSGVPDRFTGSGS GTDFTLTISSVQAEDLAVYYCQNDYTYPLTFAG (SEQ ID NO :1), wherein complementarity determining regions of the light chain variable region (CDR-L) comprise the following sequences:

CDR-L1: KSSQSLLAGRYQKNYLT (SEQ ID NO : 11)

CDR-L2: WASTRDSG (SEQ ID NO : 12)

CDR-L3: QNDYTYPLT (SEQ ID NO : 13); and

a heavy chain variable region: GGLVQPGGSLRLSCAISGFTFSDFYMEWVRQPPGKRLEWIAASRNKANDYTTEYSASVKGRFIVS RDTSQSILYLQMNALRAEDTAIYYCATYHDYAMDYWGQGTSVTVSS (SEQ ID NO:2), wherein complementarity determining regions of the heavy chain variable region (CDR-H) comprise the following sequences:

CDR-H1: GFTFSDFYME (SEQ ID NO : 14)

CDR-H2: ASRNKANDYTTEYSASVKG (SEQ ID NO : 15), and

CDR-H3: YHDYAMDY (SEQ ID NO : 16),

wherein said monoclonal antibody specifically binds to the N-terminal region of Aβ 8-x peptide, x being comprised from 15 to 42, and recognises neither Aβ 1-40 nor Aβ 1-42 .

2. The monoclonal antibody according to claim 1 , wherein said antibody presents a high specificity for the free N-terminal end of Aβ 8-x peptide.

3. The monoclonal antibody according to claim 1 , wherein said antibody presents a high affinity with respect to Aβ 8-x peptide.

4. The monoclonal antibody according to claim 1 , wherein said antibody specifically targets parenchymal amyloid deposits of Aβ 8-x peptide in the brain and does not interact with vascular amyloid deposits.

5. The monoclonal antibody according to claim 1 , wherein said antibody is labelled with a compound chosen from the group comprising: a radionuclide, a fluorophore, an enzyme label, an enzyme substrate, an enzyme co-factor, enzyme inhibitor and a hapten.

6. The monoclonal antibody according to claim 1 , which is a humanised antibody.

7. A hybridoma producing a monoclonal antibody according to claim 1 .

8. The hybridoma according to claim 7 , wherein said hybridoma have been deposited on Aug. 23, 2007,

at:

BCCM/LMBP Plasmid Collection under the following Accession No:

TeiA 1.6 or 2.6F4C2(IGH521)-->LMBP 6594CB.

9. A kit comprising at least one buffer, and at least one detection compound, said at least one detection compound being at least one N-truncated Aβ 8-x specific antibody as defined in claim 1 .

10. The kit of claim 9 , further comprising a labelled second antibody which binds to an antibody which specifically binds to the N-terminal region of Aβ 8-x peptide, x being comprised from 15 to 42, and recognises neither Aβ 1-40 nor Aβ 1-42 .

11. A therapeutic composition comprising as an active ingredient a monoclonal antibody of claim 1 in association with a pharmaceutically acceptable vehicle.

12. The therapeutic composition of claim 11 being suitable for the administration to an individual of a dose of a monoclonal antibody from 1 mg/kg/day to 200 mg /kg/day.

13. A vaccine composition comprising as an active ingredient a monoclonal antibody of claim 1 , or epitope binding fragments thereof, in association with a pharmaceutically acceptable vehicle.

14. The vaccine composition of claim 13 being suitable for the administration to an individual of a dose of a monoclonal antibody from 1 mg/kg/day to 200 mg /kg/day.

15. A method for the treatment of Alzheimer's disease in a patient, comprising administering monoclonal antibodies of claim 1 to the patient.

16. A method for the clearance of β-amyloid burden in the brain of a patient comprising administering monoclonal antibodies of claim 1 to the patient.

17. A method for the clearance of b-amyloid burden in the brain of a mammal comprising administering a composition of claim 11 to the mammal.