Merck Sharp + Dohme Corp.

Acumen Pharmaceuticals, Inc.

Merk & Co., Inc.

Min Xu

Ningyan Zhang

Paul J Shughrue

Weirong Wang

Fubao Wang

Wei-Qin Zhao

Alexander McCampbell

Renee C Gaspar

William F Goure

Daria Hazuda

Yueming Li

Ming-Tain Lai

Adam J Simon

Abigail L Wolfe

Mary J Savage

Franz F Hefti

Elizabeth Chen Dodson

Xiao-Ping Shi

Guoxin Wu

Bruce Register

Alexander Mccampbell

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 for amyloid beta 1-42 monomer, amyloid beta 1-40 monomer, plaques and amyloid beta fibrils and, optionally, a tau therapeutic or an inhibitor of amyloid beta production or aggregation.

Method for treating a disease associated with soluble, oligomeric species of amyloid beta 1-42

The present invention relates to antibodies that bind amyloid &#x3b2;-derived diffusible ligands, also known as ADDLs. The antibodies of the invention are selective for ADDLs, can penetrate the brain, and are useful in methods of detecting ADDLs and diagnosing Alzheimer's disease. The present antibodies also block binding of ADDLs to neurons, assembly of ADDLS, and tau phosphorylation and are there useful in methods for the preventing and treating diseases associated with ADDLs.

Anti-ADDL monoclonal antibody and uses thereof

This invention is a selective A&#x3b2; oligomer kit and immunoassay method capable of reliably and sensitively detecting A&#x3b2; oligomers in a biological sample of a patient. In one embodiment the inventive assay uses a pair of anti-A&#x3b2; oligomer antibodies, as capture and detection antibodies, to detect and quantify A&#x3b2; oligomers. The method can be used to differentiate Alzheimer's disease (AD) patients from non-AD patients and/or to stratify AD patients according to the severity of their disease.

Antibodies, kit and method for detecting amyloid beta oligomers

Provided are methods of identifying inhibitors of &#x3b2;-secretase that employ modified &#x3b2;-secretase substrates. The modified &#x3b2;-secretase substrates have &#x3b2;-secretase cleavage sites that are altered from wild type. The amino acid sequences of the altered &#x3b2;-secretase cleavage sites contain different amino acids in at least one of the positions P2-P1-P1'-P2&#x2032; of the &#x3b2;-secretase cleavage site. Many of the modified &#x3b2;-secretase substrates are more efficient substrates for &#x3b2;-secretase than are corresponding substrates having wild-type sequences, that is, these modified substrates are more susceptible to enzymatic breakdown by &#x3b2;-secretase. Recombinant polynucleotide molecules encoding the modified &#x3b2;-secretase substrates are provided. Antibodies that recognize cleavage products of the modified &#x3b2;-secretase substrates are provided. Stable cell lines expressing the modified &#x3b2;-secretase substrates are provided. Transgenic animals expressing the modified &#x3b2;-secretase substrates are provided.

Assays using amyloid precursor proteins with modified &#x3b2;-secretase cleavage sites to monitor &#x3b2;-secretase activity

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Ambler, PA, United States of America

Min Xu