Elan Pharmaceuticals, Inc.

Elan Pharma International Limited

Leland Stanford Junior University

Wyeth

Janssen Sciences Ireland Uc

Guriqbal Basi

Sukanto Sinha

John P Anderson

Lisa Claire McConlogue

Varghese John

Jay S Tung

Gwen Tatsuno

Shuwen Wang

Normand Frigon

Minh Tam Doan

Michael Power

John Logan Anderson

Jason Marc Goldstein

Kelly Banducci

David Chereau

Normand L Frigon, Jr

Dale Bernard Schenk

Tamie Chilcote

Irene Griswold-Prenner

William I Weis

Irene Griswold

Tami J Chilcote

Hadar Hana Feinberg

The present invention provides crystals including amino acids 1-7 of SEQ ID NO:1 and a Fab fragment of 12A11, 12B4, 10D5 or 3D6, as well as of amino acids 1-40 of SEQ ID NO:1 and a Fab fragment of 12A11 or 3D6, as well as methods for preparing the crystals. The present invention also provides a computer implemented method for analyzing binding of a candidate antibody fragment to a peptide including an epitope of amino acids 1-7 of SEQ ID NO:1, a method for identifying an antibody fragment that can mimic the Fab fragment of 12A11, a method for identifying an antibody fragment that can mimic the Fab fragment of 3D6, a method for identifying a candidate antibody fragment that binds to a peptide including an epitope of amino acids 1-7 of SEQ ID NO:1, and a method for designing a humanized antibody that binds to a peptide comprising an epitope of amino acids 1-7 of SEQ ID NO:1.

Hybrid amyloid-beta antibodies

The invention provides agents and methods for treatment of diseases associated with Lewy body diseases (LBDs) in the brain of a patient. Preferred agents include inhibitors of PLK2 kinase.

Alpha-synuclein kinase

Human BACE polypeptides having modifications to the N-linked glycosylation sites including one or more of the following amino acid substitutions: S174I, N223A, N153Q and N354S. DNA sequences, vectors, and host cells for producing the polypeptides. Crystalline protein compositions formed from the purified polypeptides. Methods of screening for compounds that inhibit A&#x3b2; using the polypeptides.

Glycosylation variants of BACE

The invention provides agents and methods for treatment of diseases associated with Lewy body diseases (LBDs) in the brain of a patient. Preferred agents include inhibitors of PLK2 and GRK6 kinases.

Disclosed is an active, isolated &#x3b2;-secretase enzyme in purified and recombinant form. This enzyme is implicated in the production of amyloid plaque components which accumulate in the brains of individuals afflicted with Alzheimer's disease. Recombinant cells that produce this enzyme either alone or in combination with some of its natural substrates (APP and APPsw) are also disclosed. These compositions are useful for use in methods of selecting compounds that modulate &#x3b2;-secretase. Inhibitors of &#x3b2;-secretase are implicated as therapeutics in the treatment of neurodegenerative diseases, such as Alzheimer's disease.

&#x3b2;-secretase enzyme compositions and methods

Disclosed are various forms of an active, isolated &#x3b2;-secretase enzyme in purified and recombinant form. This enzyme is implicated in the production of amyloid plaque components which accumulate in the brains of individuals afflicted with Alzheimer's disease. Recombinant cells that produce this enzyme either alone or in combination with some of its natural substrates (&#x3b2;-APPwt and &#x3b2;-APPsw) are also disclosed, as are antibodies directed to such proteins. These compositions are useful for use in methods of selecting compounds that modulate &#x3b2;-secretase. Inhibitors of &#x3b2;-secretase are implicated as therapeutics in the treatment of neurodegenerative diseases, such as Alzheimer's disease.

Beta-secretase enzyme compositions and methods

Disclosed are various forms of an active, isolated &#x3b2;-secretase enzyme in purified and recombinant form. This enzyme is implicated in the production of amyloid plaque components which accumulate in the brains of individuals afflicted with Alzheimer's disease Recombinant cells that produce this enzyme either alone or in combination with some of its natural substrates (&#x3b2;-APPwt and &#x3b2;-APPsw) are also disclosed, as are antibodies directed to such proteins. These compositions are useful for use in methods of selecting compounds that modulate &#x3b2;-secretase. Inhibitors of &#x3b2;-secretase are implicated as therapeutics in the treatment of neurodegenerative diseases, such as Alzheimer's disease.

Disclosed are various forms of an active, isolated &bgr;-secretase enzyme in purified and recombinant form. This enzyme is implicated in the production of amyloid plaque components which accumulate in the brains of individuals afflicted with Alzheimer's disease. Recombinant cells that produce this enzyme either alone or in combination with some of its natural substrates (&bgr;-APPwt and &bgr;-APPsw) are also disclosed, as are antibodies directed to such proteins. These compositions are useful for use in methods of selecting compounds that modulate &bgr;-secretase. Inhibitors of &bgr;-secretase are implicated as therapeutics in the treatment of neurodegenerative diseases, such as Alzheimer's disease.

&bgr;-secretase enzyme compositions and methods

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Guriqbal Basi