RECOMBINANT ANTIBODIES SPECIFIC FOR BETA-AMYLOID ENDS, DNA ENCODING AND METHODS OF USE THEREOF
DNA encoding a recombinant antibody molecule end-specific for an amyloid-beta peptide, pharmaceutical compositions thereof, and a method for preventing or inhibiting progression of Alzheimer's Disease by introducing such a DNA molecule into brain cells to express the recombinant antibody molecule and prevent the accumulation of amyloid-beta peptides in the cerebrospinal fluid.
1 . A method for delaying, inhibiting, or suppressing the accumulation of an amyloid β peptide or fragment thereof in a brain of a mammal, comprising administering to said mammal a composition comprising a recombinant DNA molecule, containing a gene encoding a recombinant antibody molecule free end-specific for the N-terminus or the C-terminus of an amyloid-β peptide, operably-linked to a promoter which is expressed in the central nervous system.
2 . The method according to claim 1 , wherein the composition is administered by injection intravenously, intra-arterially, intracranially, or intracephalically.
3 . The method according to claim 1 , wherein the amyloid-β peptide is selected from the group consisting of amyloid-β peptides having the amino acid sequence of residues 5-44 of SEQ ID NO:1, residues 5-46 of SEQ ID NO:1, residues 5-47 of SEQ ID NO:1, and mixtures thereof.
4 . The method according to claim 1 , wherein the recombinant antibody molecule is free end-specific for the N-terminus of the amyloid-β peptide.
5 . The method according to claim 1 , wherein the recombinant antibody molecule is free end-specific for the C-terminus of the amyloid-β peptide.
6 . The method according to claim 1 , wherein the promoter operably-linked to the gene encoding a recombinant antibody molecule is a βAPP promoter.
7 . The method according to claim 1 , wherein the recombinant DNA molecule is in association with a viral vector.
8 . The method according to claim 7 , wherein the viral vector is adeno-associated vector (AAV).
9 . The method according to claim 7 , wherein said composition further comprises cationic lipids or cationic liposomes.
10 . The method according to claim 1 , wherein said composition further comprises cationic lipids or cationic liposomes.
11 . The method according to claim 1 , wherein the recombinant DNA molecule is in association with comprises a ligand capable of binding to a cell surface receptor.
12 . The method according to claim 11 , wherein the ligand is biotin.
13 . The method according to claim 1 , wherein the recombinant antibody molecule is a single chain variable region fragment.
14 . (canceled)
15 . A recombinant DNA molecule, comprising a gene encoding a recombinant antibody molecule free end-specific for the N-terminus or the C-terminus of an amyloid-β peptide.
16 . The recombinant DNA molecule according to claim 15 , wherein said gene encoding a recombinant antibody molecule free end-specific for the N-terminus or the C-terminus of an amyloid-β peptide is operably linked to a promoter capable of expressing said gene in brain cells.
17 . A vector comprising the recombinant DNA molecule of claim 15 .
18 . A host cell transformed with the vector of claim 17 .
19 . A pharmaceutical composition for delaying, inhibiting, or suppressing the accumulation of an amyloid β peptide or fragment thereof in a brain of a mammal, comprising the recombinant DNA molecule of claim 16 , an agent for delivering the recombinant DNA molecule to a cell in the brain of said mammal, and a pharmaceutically acceptable excipient.
20 . The pharmaceutical composition according to claim 19 , wherein said agent is selected from the group consisting of viral vectors, cationic lipids, cationic liposomes, ligands capable of binding to a cell surface receptor, and combinations thereof.
21 . The pharmaceutical composition according to claim 19 , wherein said gene encodes a recombinant antibody molecule free end-specific for the N-terminus of an amyloid-β peptide.
22 . The pharmaceutical composition according to claim 19 , wherein said gene encodes a recombinant antibody molecule free end-specific for the C-terminus of an amyloid-β peptide.