Specific antibodies to amyloid beta peptide, pharmaceutical compositions and methods of use thereof
The invention relates to methods of treating a subject having Alzheimer's Disease, comprising the step of administering an antibody molecule which is targeted to β amyloid peptide or to fragment thereof. In another embodiment the invention relates to methods of treating a disease or a disorder, characterized by amyloid beta deposition. In another embodiment, the invention relates to an antibody molecule, which is free end-specific for the N-terminus or the C-terminus of an amyloid β peptide and to a pharmaceutical composition thereof. In another embodiment, the invention relates to an antibody molecule, which is targeted to the free C or N-terminus of a N-and/or C-terminus truncated amyloid β peptide fragment.
1. A method for inhibiting accumulation of amyloid β peptide in the brain of a patient suffering from Alzheimer's disease, comprising contacting in vivo soluble amyloid β peptide in the cerebrospinal fluid of said patient with an exogenous free-end specific antibody which is targeted to a free C-terminus of amyloid β peptide Aβ1-40, to inhibit the accumulation of said amyloid β peptide in the brain of said patient.
2. The method of claim 1 , wherein the antibody is a monoclonal antibody, a humanized antibody, a chimeric antibody, a scFv antibody or a F(ab), or fragment thereof.
3. The method of claim 1 wherein said exogenous free-end specific antibody is stably expressed in neuronal cells in the brain.
4. A method for inhibiting the neurotoxicity of amyloid β peptide in a patient suffering from Alzheimer's disease, comprising contacting in vivo soluble amyloid β peptide in the cerebrospinal fluid of said patient with an exogenous free-end specific antibody which is targeted to a free C-terminus of amyloid β peptide Aβ1-40, to inhibit the neurotoxicity of amyloid β peptide in said patient.
5. The method of claim 4 , wherein the antibody is a monoclonal antibody, a humanized antibody, a chimeric antibody, a scFv antibody or a F(ab), or fragment thereof.
6. The method of claim 4 wherein said exogenous free-end specific antibody is stably expressed in neuronal cells in the brain.
7. A method of forming a complex, said method comprising:
providing to the cerebrospinal fluid of an individual, an agent that is a monoclonal antibody, humanized antibody, chimeric antibody, scFv antibody, F(ab) antibody, or a fragment of the foregoing types of antibodies, which agent specifically binds to an epitope within residues 34-40 of an amyloid β-peptide and which binds said amyloid β-peptide but does not significantly bind amyloid precursor protein,
to form in said cerebrospinal fluid a complex comprising said agent and said amyloid β-peptide.
8. The method of claim 7 , wherein said agent is a humanized antibody or fragment thereof.
9. The method of claim 7 , wherein said agent is a chimeric antibody or fragment thereof.
10. The method of claim 7 wherein said individual is an individual suffering from Alzheimer's disease or having a predisposition to develop Alzheimer's disease.
11. The method of claim 10 wherein said complex comprising said agent and said amyloid β-peptide is a soluble complex.
12. The method of claim 7 wherein said complex comprising said agent and said amyloid β-peptide is a soluble complex.
13. The method of claim 7 wherein said agent is stably expressed in neuronal cells in the brain.
14. A method for reducing the quantity of amyloid β-peptide in the cerebrospinal fluid of a patient suffering from Alzheimer's disease which comprises contacting said amyloid β-peptide in said cerebrospinal fluid of said patient with a monoclonal antibody, humanized antibody, chimeric antibody, scFv antibody, F(ab) antibody, or a fragment of the foregoing types of antibodies, that specifically binds to an epitope within residues 34-40 of said amyloid β-peptide and which binds said amyloid β-peptide but does not significantly bind amyloid precursor protein.
15. The method of claim 14 , wherein said antibody is a humanized antibody or fragment thereof.
16. The method of claim 14 , wherein said antibody is a chimeric antibody or fragment thereof.
17. The method of claim 14 wherein said antibody binds amyloid β-peptide that is soluble in the cerebrospinal fluid of said patient.
18. The method of claim 14 wherein said monoclonal antibody, humanized antibody, chimeric antibody, scFv antibody, F(ab) antibody, or fragment of the foregoing types of antibodies is stably expressed in neuronal cells in the brain.
19. A method for inhibiting the accumulation of amyloid β-peptide in a patient suffering from Alzheimer's disease which comprises contacting said amyloid β-peptide in the cerebrospinal fluid of said patient in vivo with a monoclonal antibody, humanized antibody, chimeric antibody, scFv antibody, F(ab) antibody, or a fragment of the foregoing types of antibodies, that specifically binds to an epitope within residues 34-40 of said amyloid β-peptide and which binds said amyloid β-peptide but does not significantly bind amyloid precursor protein.
20. The method of claim 19 , wherein said antibody is a humanized antibody or fragment thereof.
21. The method of claim 19 , wherein said antibody is a chimeric antibody or fragment thereof.
22. The method of claim 19 wherein said antibody binds amyloid β-peptide that is soluble in the cerebrospinal fluid of said patient.
23. The method of claim 19 wherein said monoclonal antibody, humanized antibody, chimeric antibody, scFv antibody, F(ab) antibody, or fragment of the foregoing types of antibodies is stably expressed in neuronal cells in the brain.