Immunological control of β-amyloid levels in vivo
Disclosed are bispecific antibodies comprising a first antibody binding specificity which confers the ability of the bispecific antibody to cross the blood-brain barrier, and a second antibody specificity conferring the ability of the bispecific antibody to bind to a β-amyloid epitope. Also disclosed are methods for inhibiting the formation of β-amyloid plaques in the brain of a human, of promoting the disaggregation of a preformed β-amyloid plaque. Such methods recite the administration of a bispecific antibody.
1. A bispecific antibody comprising:
a) a first antibody binding specificity which confers the ability of the bispecific antibody to cross the blood-brain barrier; and
b) a second antibody specificity conferring the ability of the bispecific antibody to bind to a β-amyloid epitope.
2. The bispecific antibody of claim 1 which is produced by fusing a first and a second hybridoma clone, the first hybridoma clone generating the specificity of step a) and the second hybridoma clone generating the specificity of step b).
3. The bispecific antibody of claim 1 which is produced by recombinant DNA techniques.
4. The bispecific antibody of claim 1 wherein the first and second antibody binding specificities are provided by chemically linking a first antibody, or fragment thereof, to a second antibody, or fragment thereof.
5. The bispecific antibody of claim 4 wherein the first and second antibodies are monoclonal antibodies.
6. The bispecific antibody of claim 4 which is an F(ab′) 2 hybrid.
7. The bispecific antibody of claim 3 which is a single chain Fv heterobispecific dimer.
8. The bispecific antibody of claim 1 wherein the second antibody specificity further confers the ability of the bispecific antibody to inhibit the formation of βamyloid aggregates and plaques.
9. The bispecific antibody of claim 1 wherein the second antibody binding specificity further confers the ability of the bispecific antibody to disaggregate preformed β-amyloid aggregates and plaques.