Wyeth

Dana-farber-cancer Institute Inc.

Oscient Pharmaceuticals Corporation

Anthony Anisowicz

Kristina Allen

Zhiqiang Zou

Ruth Sager

Paul John Yaworsky

Wei Liu

Matthew Olson

James R Graham

Veronique Damagnez

Girija Krishnamurthy

Arturo Morales

John Allen Robinson

Bheem M Bhat

Wei Chen

The invention relates to a novel method of inexpensively synthesizing large quantities of an essentially pure, biologically active, glycosylated Dkk protein, including mammalian and human Dkk proteins (e.g., human Dkk1). The invention further relates to the synthetically produced essentially purified, glycosylated and biologically active Dkk protein, and the characteristics of the protein.

Method of synthesizing and purifying Dkk proteins and Dkk proteins obtained thereby

The present invention provides reagents, compounds, compositions, and methods relating to novel interactions of the extracellular domain of LRP5, HBM (a variant of LRP5), and/or LRP6 with Dkk, including Dkk-1. The various nucleic acids, polypeptides, antibodies, assay methods, diagnostic methods, and methods of treatment of the present invention are related to and impact on Dkk, LRP5, LRP6, HBM, and Wnt signaling. Dkk, LRP5, LRP6, HBM, and Wnt are implicated in bone and lipid cellular signaling. Thus, the present invention provides reagents and methods for modulating lipid levels and/or bone mass and is useful in the treatment and diagnosis of abnormal lipid levels and bone mass disorders, such as osteoporosis.

Reagents and method for modulating Dkk-mediated interactions

The present invention relates to methods and materials used to express an HBM-like polypeptide derived from HBM, LRP5 or LRP6 in animal cells and transgenic animals. The present invention also relates to transgenic animals expressing the HBM-like polypeptides. The invention provides nucleic acids, including coding sequences, oligonucleotide primers and probes, proteins, cloning vectors, expression vectors, transformed hosts, methods of developing pharmaceutical compositions, methods of identifying molecules involved in bone development, and methods of diagnosing and treating diseases involved in bone development and lipid modulation. In preferred embodiments, the present invention is directed to methods for treating, diagnosing and preventing osteoporosis.

HBM variants that modulate bone mass and lipid levels

An isolated DNA encoding a polypeptide substantially identical to maspin (SEQ ID NO:1); a substantially purified preparation of maspin; an antibody specific for maspin; and use of such DNAs and antibodies in diagnostic, screening, and therapeutic methods.

Maspin, a serpin with tumor suppressing activity

Method of detecting cancer

Maspin, a serpin with tumor suppresing activity

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West Newton, MA, United States of America

Anthony Anisowicz