Prothena Biosciences Limited

Onclave Therapeutics Limited

Elan Pharmaceuticals, Inc.

Other

The Brigham and Women's Hospital, Inc.

University of Tennessee Research Foundation

Janssen Alzheimer Immunotherapy

Peter Andrew Seubert

Dale Bernard Schenk

Robin McDaid Barbour

Yue Liu

Philip James Dolan, Iii

Jonathan Wall

José W Saldanha

Kate Dora Games

Russell E Rydel

Dennis J Selkoe

Martin Citron

Jose William Saldanha

Lisa Claire McConlogue

Lisa Clair McConlogue

Thierry Bussiere

Kelly Johnson-Wood

The invention provides antibodies to tau. The antibodies inhibit or delay tau-associated pathologies and associated symptomatic deterioration.

Tau immunotherapy

Methods useful for effecting prophylaxis or treatment of amyloidosis, including AA Amyloidosis and AL amyloidosis, by administering peptides comprising neoepitopes, such as AA fragments from a C-terminal region of AA, and antibodies specific for neoepitopes of aggregated amyloid proteins, for example, antibodies specific for the C-terminal region of AA fibrils. Antibodies for inhibition of formation and/or increasing clearance of amyloid deposits in a patient thus effecting prophylaxis or treating amyloid disease.

Treatment and prophylaxis of amyloidosis

Detection of amyloid deposits using anti-amyloid antibodies

Chimeric, humanized, or human antibody 2A4

The application provides novel neuroactive fragments of human amyloid precursor protein (APP). The fragments include sequence from the A&#x3b2; region of APP but also extend upstream. The fragments are soluble in aqueous solution most bands are about 10 kDa and above and do not correspond with the expected molecular weight of a dimer or trimer. The fragments and subfragments thereof can be used as immunogens in methods of immunotherapy to treat Alzheimer's and other amyloidogenic diseases characterized by deposits of A&#x3b2; in the brain. Antibodies to the part of the fragment upstream from APP or the interface between A&#x3b2; and the upstream sequence can also be used in such therapeutic method. The fragments are also useful as markers, which can be detected for diagnosis or prognosis of disease or for screening agents.

Neuroactive fragments of APP

Anti-amyloid antibodies

This invention provides methods of screening compounds for their ability to alter the production of A&#x3b2;(x&#x2267;41) alone or in combination with A&#x3b2;(x&#x2266;40). The methods involve administering compounds to cells, specifically measuring the amounts of A&#x3b2;(x&#x2266;40) and A&#x3b2;(x&#x2267;41) produced by the cells, and comparing these amounts to that produced by the cells without administration of the compounds.

Methods for determining whether a compound alters the amount of at least one &#x3b1;&#x3b2; (X-41) peptide and the amount of either total &#x3b1;&#x3b2; or at least one &#x3b1;&#x3b2; (X-40) peptide produced by a non-human mammal

The construction of transgenic animal models of human Alzheimer's disease, and methods of using the models to screen potential Alzhe## disease therapeutics, are described. The models are characterized by pathologies similar to pathologies observed in Alzheimer's disease, based on expression of all three forms of the &#x3b2;-amyloid precursor protein (APP), APP695, APP751, and APP770, as well as various point mutations based on naturally occurring mutations, such as the London and Indiana familial Alzheimer's disease (FAD) mutations at amino acid 717, predicted mutations in the APP gene, and truncated forms of APP that contain the A&#x3b2; region. Animal cells can be isolated from the transgenic animals or prepared using the same constructs with standard techniques such as lipofection or electroporation. The transgenic animals, or animal cells, are used to screen for compounds altering the pathological course of Alzheimer's disease as measured by their effect on the amount of APP, &#x3b2;-amyloid peptide, and numerous other Alzheimer's disease markers in the animals, the neuropathology of the animals, as well as by behavioral alterations in the animals.

Testing compounds for effects on synaptophysin in transgenic mice expressing an Alzheimer's disease FAD DNA sequence

The construction of transgenic animal models of human Alzheimer's disease, and methods of using the models to screen potential Alzheimer's disease therapeutics, are described. The models are characterized by pathologies similar to pathologies observed in Alzheimer's disease, based on expression of all three forms of the &bgr;-amyloid precursor protein (APP), APP695, APP751, and APP770, as well as various point mutations based on naturally occurring mutations, such as the London and Indiana familial Alzheimer's disease (FAD) mutations at amino acid 717, predicted mutations in the APP gene, and truncated forms of APP that contain the A&bgr; region. Animal cells can be isolated from the transgenic animals or prepared using the same constructs with standard techniques such as lipofection or electroporation. The transgenic animals, or animal cells, are used to screen for compounds altering the pathological course of Alzheimer's disease as measured by their effect on the amount of APP, &bgr;-amyloid peptide, and numerous other Alzheimer's disease markers in the animals, the neuropathology of the animals, as well as by behavioral alterations in the animals.

Method for selecting a transgenic mouse model of alzheimer's disease

This invention provides methods of screening compounds for their ability to alter the production of A&bgr;(x&gE;41) alone or in combination with A&bgr;(x&lE;40). The methods involve administering compounds to cells, specifically measuring the amounts of A&bgr;(x&lE;40) and A&bgr;(x&gE;41) produced by the cells, and comparing these amounts to that produced by the cells without administration of the compounds.

Screening compounds for the ability to alter the production of amyloid-&bgr; peptide

Growing community of inventors

South San Francisco, CA, United States of America

Peter Andrew Seubert