Immunogens and corresponding antibodies specific for high molecular weight aggregation intermediates common to amyloids formed from proteins of differing sequence
View Patent ↗Compositions of matter that comprise one or more conformational epitopes found on amyloid peptide aggregates, antibodies to such epitopes and methods for making and using the compositions, eptitopes and/or antibodies. The invention includes synthetic or isolated compositions that contain or consist of certain conformational epitopes that are found on peptide aggregates (e.g., toxic peptide aggregates) present in human or veterinary patients who suffer from, or who are likely to develop, amyloid diseases (e.g., Alzheimer's Disease). The invention includes methods for the detection, treatment and prevention of diseases in humans or animals, using such compositions. The invention further includes antibodies which bind to the conformational epitopes as well as methods for making such antibodies and methods for the detection, treatment and prevention of diseases and/or identification of potential therapies (e.g., drug screening) using such antibodies.
1. A composition comprising an isolated conformational epitope of a soluble amyloid aggregate which a) forms in a human or animal and b) contributes to amyloid disease;
said conformational epitope comprising five or more monomers, wherein the epitope is affixed to a curved or flat support surface, wherein affixation to the support surface causes the epitope to assume and be constrained in a three-dimensional conformation, wherein the three-dimensional confirmation causes the epitope to be recognized by an antibody that binds an Aβ peptide aggregate that is not a monomer, dimer, trimer, tetramer or Aβ fibril; and wherein the support surface comprises a material selected from; gold, zinc, cadmium, tin, titanium, silver, selenium, gallium, indium, arsenic, silicon, mixtures thereof and combinations thereof.
2. A composition according to claim 1 wherein the epitope composition is conformationally constrained.
3. A composition according to claim 1 wherein the composition is chemically bound to the surface.
4. A composition according to claim 1 wherein the amyloid aggregate has a molecular weight in a range of about 1 kDa to about 100,000,000 kDa.
5. A composition according to claim 1 wherein the epitope comprises an epitope of a toxic species of an amyloid aggregate.
6. A composition according to claim 1 wherein the epitope is chemically bound to the surface.
7. A composition according to claim 6 wherein the epitope comprises a C terminus, wherein the C terminus is bound to the support surface.
8. A composition according to claim 7 wherein the C terminus is bound to the surface by a carboxy thiol linkage.
9. A composition according to claim 8 wherein the surface comprises a gold surface.
10. A composition according to claim 9 wherein the gold surface comprises colloidal gold.
11. A composition according to claim 1 wherein the epitope comprises an epitope of Aβ.
12. A composition according to claim 1 wherein the epitope is coupled to gold on the support surface.
13. A composition according to claim 12 wherein the epitope comprises a C terminus, wherein the C terminus is coupled to gold on the support surface.
14. A composition according to claim 13 wherein the gold comprises colloidal gold.
15. A composition according to claim 1 wherein the surface comprises a surface of a film.
16. A composition according to claim 1 wherein the surface comprises a surface of a sheet.
17. A composition according to claim 1 wherein the surface comprises a surface of a pleated sheet.
18. A composition according to claim 1 wherein the surface comprises a surface of a protein.
19. A composition according to claim 1 wherein the epitope comprises SEQ ID NO. 2.