Biogen Idec Ma Inc.

Curis, Inc.

Other

Biogen Idec, Inc.

Amphora Discovery Corporation

Kevin P Williams

Michele Sanicola-Nadel

Susan Gail Schiffer

Paul Rayhorn

R Blake Pepinsky

Ellen A Garber

Frederick Robbins Taylor

Jeffrey A Porter

Dingyi Wen

Darren P Baker

Alphonse Galdes

Russell Colyn Petter

Paul H Weinreb

Bruno Domon

John Kenneth Dickson, Jr

Steven Donald Miklasz

Kathryn Strauch

Carl Nicholas Hodge

Susan Foley

Chenhui Zeng

Heather Adkins

The invention provides Cripto blocking antibodies, or biologically functional fragments thereof, and uses thereof. Antibodies which bind Cripto and modulate Cripto signaling are provided. Antibodies which bind Cripto and block the interaction between Cripto and ALK4 are provided. Antibodies which bind Cripto and modulate tumor growth are also provided. Antibodies which bind Cripto, modulate signaling, and modulate tumor growth are also provided. Antibodies which bind Cripto, block the interaction between Cripto and ALK4 and modulate tumor growth are provided. The invention also provides methods of using these antibodies in therapeutic, diagnostic, and research applications.

Cripto blocking antibodies and uses thereof

Variants of hedgehog protein that contain N-terminal modifications are described that can block hedgehog function; thus allowing these variants to serve as functional antagonists. These peptides have a primary amino acid sequence lacking the ability to elicit a hedgehog-dependent response in C3H 10T1/2 cells but having the ability to bind to the hedgehog receptor, patched-1. Methods for producing such functional antagonists and methods of using the functional antagonists are also described.

Functional antagonists of hedgehog activity

The present invention is based on the discovery that CRIPTO mutants each comprising at least one amino acid substitution from a CRIPTO polypeptide demonstrate tumor blocking activity.

Cripto mutant and uses thereof

The invention provides Cripto-specific antibodies, or biologically functional fragments thereof, and uses thereof. Antibodies which bind Cripto and inhibit Cripto activity are provided. Antibodies which bind Cripto and inhibit the interaction between Cripto and ALK4 and/or between Cripto and Activin B are provided. Antibodies which bind Cripto and inhibit tumor growth are also provided. Antibodies which bind Cripto, inhibit Cripto activity, and inhibit tumor growth are also provided. The invention also provides methods of using these antibodies in therapeutic, diagnostic, and research applications.

Cripto-specific antibodies

Quinoline- and isoquinoline-based compounds exhibiting ATP-utilizing enzyme inhibitory activity, methods of using compounds exhibiting ATP-utilizing enzyme inhibitory activity, and compositions comprising compounds exhibiting ATP-utilizing enzyme inhibitory activity, are disclosed.

Quinoline- and isoquinoline-based compounds exhibiting ATP-utilizing enzyme inhibitory activity, and compositions, and uses thereof

Hydrophobically-modified proteins and methods of making them are described. A hydrophobic moiety is attached to a surface amino acid residue of the protein. The hydrophobic moiety can be a lipid or a peptide. Alternatively, the protein can be derivatized by a wide variety of chemical reactions that append a hydrophobic structure to the protein. The preferred protein is of mammalian origin and is selected from the group consisting of Sonic, Indian, and Desert hedgehog. The hydrophobic moiety is used as a convenient tether to which may be attached a vesicle such as a cell membrane, liposome, or micelle.

Hydrophobically-modified protein compositions and methods

Hydrophobically-modified hedgehog protein compositions and methods

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Chapel Hill, NC, United States of America

Kevin P Williams