HUMAN ANTIBODY IMMUNOTHERAPY FOR ALZHEIMER'S DISEASE

DESCRIPTION (provided by the applicant): The plaques characteristic of Alzheimer?s disease result in part from the abnormal deposition of the peptide beta-amyloid (Abeta). Recent work of Schenk et al. (1999) using a transgenic mouse model of Abeta deposition demonstrated the remarkable capacity of antibodies to prevent or clear these deposits. Further studies of Bard et al., (2000) demonstrated that passively administered antibodies could mediate this effect. Based on these studies, the overall goal of this project is to develop human monoclonal antibodies for passive immunotherapy of Alzheimer?s disease. To achieve this goal we have developed a novel proprietary means of generating human antibodies. The method can also be used to select clones with high affinity (affinity maturation). In phase I we will express Beta-amyloid 1-42 in fusion to alpha fragment of Beta-lactamase, express a human scFv library in fusion to beta fragment of Beta-lactamase, select antibody fragments binding to Beta-amyloid 1-42 peptide using Beta-lactamase fragment complementation, prepare selected clones as holo-IgG1 antibodies and demonstrate facilitation of macrophage uptake of Beta-amyloid 1-42. In phase II we will carry out studies in preparation for submission of an IND. PROPOSED COMMERCIAL APPLICATION: At present over 4 million persons suffer from Alzheimer's disease and reliable therapies are non-existent. Thus, a novel, non-toxic therapy for Alzheimer's disease will have considerable commercial potential.