William F. Goure, Franz F. Hefti, Renee C. Gaspar, Paul J. Shughrue, Fubao Wang, Weirong Wang, Ningyan Zhang, and Wei-Qin Zhao
- ACUMEN PHARMACEUTICALS INC., LIvermore, CA (US)
- MERCK SHARP & DOHME CORP., Rahway, NJ (US)
This invention is a method and kit for treating a disease associated with, or resulting from, the accumulation of soluble oligomer amyloid beta 1-42 using an antibody, or antibody fragment thereof, that has a higher affinity for amyloid beta 1-42 oligomers than or amyloid beta 1-42 monomer, amyloid beta 1-40 monomer, plaques and amyloid beta fibrils, wherein the antibody is in combination with a tau therapeutic or an inhibitor of amyloid beta production or aggregation.
CovalX Technology Used
Antibody 19.3 was added to either synthetic ADDLs or ADDLs that had been extracted from Tg2576 mouse brains to create antibody:ADDL complexes. The complexes were cross-linked using the CovalX amine-reactive crosslinker via the photo-induced cross-linking of unmodified proteins (PICUP) method. The cross-linked samples were separated by SEC before being detected by ELISA using a second anti- Aβ antibody, 82E1, and an anti-human kappa antibody. The complexes were extracted at retention times that corresponded to soluble Aβ oligomers. The wild-type mouse brain elutions showed no signal and proved that antibody 19.3 binds to both the synthetic and natural ADDLs with similar size distribution. It was also found that antibody 19.3 had an affinity for a variety of Aβ oligomers that had been separated from Aβ monomers via SEC.