Immunex Corporation

Vertex Pharmaceuticals, Inc.

Sanofi

Wyeth

Sterling Winthrop Inc.

Max-planck-institute for Biochemistry

Roy A Black

Douglas Pat Cerretti

Carl J March

Charles Rauch

Paul R Sleath

Shirley R Kronheim

Jeffrey N Fitzner

Jeremy Ian Levin

James Ming Chen

William C Fanslow, Iii

Raymond J Paxton

Wolfram Bode

Klaus Maskos

Carlos Fernandez-Catalan

Kurt M Poindexter

A metalloprotease that converts TNF-&#x3b1; from the 26 kD cell form to the 17 kD form has been isolated and purified and the cDNA sequence known. In particular, the protease has a molecular weight of approximately 80 kD. The isolated and purified protease is useful for designing an inhibitor thereof, and may find use as a therapeutic agent. Assays for detecting the protease-inhibiting activity of a molecule are also an aspect of the invention.

Antibodies that bind TNF-&#x3b1; converting enzyme

The present invention provides methods and compositions for inhibiting the biological activity of integrins, for inhibiting endothelial cell migration. and for inhibiting angiogenesis. In particular, the invention provides compositions comprising ADAM disintegrin domains and methods for using said compositions. In preferred embodiments the methods and compositions of the invention are used to inhibit angiogenesis and to treat diseases or conditions mediated by angiogenesis.

Use of integrin antagonists to inhibit angiogenesis

There is disclosed an isolated polypeptide and derivatives thereof having protease biological activity for human precursor IL-1&#x3b2; and for a substrate comprising:R&#x2014;Asp&#x2014;R&#x2014;Rwherein Rand Rare independently any D or L isomer amino acid, Ris Ala or Gly, and wherein the specific protease cleavage site is between Asp and R. Inhibitor compounds, compositions and methods for inhibiting Interleukin 1&#x3b2; protease activity are also disclosed. The inhibitor compounds comprise an amino acid sequence of from 1 to about 5 amino acids having an N-terminal blocking group and a C-terminal Asp residue connected to an electronegative leaving group, wherein the amino acid sequence corresponds to the sequence Ala-Tyr-Val-His-Asp.

Interleukin 1&#x3b2; protease and interleukin 1&#x3b2; protease inhibitors

A tumor necrosis factor-&#x3b1; converting enzyme (TACE) is produced, purified, and crystallized. The three-dimensional coordinates of the crystal are obtained by X-ray diffraction. The coordinates can be recorded on a computer readable medium, or are part of a video memory, where they can be used as part of a system for studying for studying TACE. The coordinates are also used in designing, screening, and developing compounds that associate with TACE.

Crystalline TNF-&#x3b1;-converting enzyme and uses thereof

A metalloprotease that converts TNF-&agr; from the 26 kD cell form to the 17 kD form has been isolated and purified and the cDNA sequence known. In particular, the protease has a molecular weight of approximately 80 kD. The isolated and purified protease is useful for designing an inhibitor thereof, and may find use as a therapeutic agent. Assays for detecting the protease-inhibiting activity of a molecule are also an aspect of the invention.

TNF-&agr; converting enzyme

TNF-a converting enzyme

There is disclosed an isolated polypeptide and derivatives thereof having protease biological activity for human precursor IL-1.beta. and for a substrate comprising:

Interleukin 1.beta. protease and interleukin 1.beta. protease inhibitors

A metalloprotease that converts TNF-.alpha. from the 26 kD cell form to the 17 kD form has been isolated and purified and the cDNA sequence known. In particular, the protease has a molecular weight of approximately 80 kD. The isolated and purified protease is useful for designing an inhibitor thereof, and may find use as a therapeutic agent. Assays for detecting the protease-inhibiting activity of a molecule are also an aspect of the invention.

TNF-.alpha. converting enzyme

Compounds and methods are disclosed that are useful in inhibiting the TNF-.alpha. converting enzyme (TACE) responsible for cleavage of TNF-.alpha. precursor to provide biologically active TNF-.alpha.. The compounds employed in the invention are peptidyl derivatives having active groups capable of inhibiting TACE such as, hydroxamates, thiols, phosphoryls and carboxyls.

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Seattle, WA, United States of America

Roy A Black