Humanized antibodies that sequester abeta peptide

Abstract

A method to treat conditions characterized by formation of amyloid plaques both prophylactically and therapeutically is described. The method employs humanized antibodies which sequester soluble Aβ peptide from human biological fluids or which preferably specifically bind an epitope contained within position 13-28 of the amyloid beta peptide Aβ.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS [0001] This application is a continuation of U.S. patent application Ser. No. 10 / 226,435, filed Aug. 22, 2002, which is a continuation of PCT patent application PCT / US01 / 06191, filed Feb. 26, 2001, which was published in English and designated the United States and which claims the priority of U.S. provisional applications 60 / 184,601, filed Feb. 24, 2000, 60 / 254,465, filed Dec. 8, 2000, and 60 / 254,498, filed Dec. 8, 2000, the contents of which are all incorporated herein by reference.TECHNICAL FIELD [0002] The invention relates to humanized antibodies that bind to an epitope between amino acids 13 and 28 of the Aβ peptide and to preventive and therapeutic treatment of conditions associated with beta amyloid, such as Alzheimer's disease, Down's syndrome, and cerebral amyloid angiopathey. More specifically, it concerns use of humanized monoclonal antibodies to sequester amyloid beta (Aβ) peptide in plasma, brain, and cerebrospinal fluid to preve...

AI Technical Summary

Benefits of technology

[0017] Administration of an appropriate humanized antibody in vivo to sequester Aβ peptide-circulating in biological fluids is useful for preventive and therapeutic treatment of conditions associated with the formation of Aβ-containing diffuse, neuritic, and cerebrovascular plaques in the brain. The humanized antibody, including an immunologically reactive fragment thereof, results in removal of the Aβ peptide from macromolecular complexes which would normally be relevant in transporting it in body fluids to and from sites where plaques can form or where it can be toxic. In addition, sequestering of plasma Aβ peptide with the antibody or fragment thereof behaves as a “sink,” effectively sequestering soluble Aβ peptide in the plasma compartment, and inducing Aβ to enter the plasma from locations in the central nervous system (CNS). By sequestering Aβ in the blood, net efflux from the brain is enhanced and soluble Aβ is prevented from depositing in insoluble plaques and from forming toxic soluble species in the brain. In addition, insoluble Aβ in plaques which is in equilibrium with soluble Aβ can be removed from the brain through a sequestering effect in the blood. Sequestering the Aβ peptide with the antibody also enhances its removal from the body and inhibits toxic effects of soluble Aβ in the brain and the development and further accumulation of insoluble Aβ as amyloid in plaques. The antibodies useful in the invention do not cross the blood-brain barrier in large amounts (≦0.1% plasma levels). In addition, humanized antibodies used in the invention, when administered peripherally, do not need to elicit a cellular immune response in brain when bound to Aβ peptide or when freely circulating to have their beneficial effects. Further, when administered peripherally they do not need to appreciably bind aggregated Aβ peptide in the brain to have their beneficial effects.

Problems solved by technology

Further, the document provides no in vivo evidence that administration of antibodies causes efflux of Aβ from the central nervous system, interferes with plaque formation, reduces plaque burden, forms complexes between the antibodies and Aβ in tissue samples, or affects cognition.

Yet, the antibody does not have the properties that the art teaches are required for an antibody to be effective in treating Alzheimer's disease, Down's syndrome, and other conditions related to the Aβ peptide.

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