The action of Tumor Necrosis Factor alpha (TNF-alpha) has been implicated in such diseases as arthritis, sepsis, ulcerative colitis, multiple sclerosis, Crohn's disease, septic shock, graft rejection, cachexia, insulin resistance, post-ischemic reperfusion injury, tumor metastasis, tissue ulceration, abnormal wound healing, periodontal disease, bone disease, proteinuria, aneurismal aortic disease, degenerative cartilage loss, demyelinating diseases of the nervous system, and HIV infection. TNF-alpha converting enzyme (TACE) or ADAM 17 (A Disintegrin And Metalloprotease) is a member of a family of zinc metalloproteases, and is an important regulator of inflammation, immune regulation, and cellular proliferation as a consequence of its ability to catalyze the activation of TNF-alpha from a membrane bound to a soluble form.

The NIH announces the identification of a protein, corresponding to the amino-terminus of the TACE prodomain, that possesses a TACE inhibitory activity that is independent of a cysteine-switch mechanism. This TACE inhibitory protein could be used as a new therapeutic agent against chronic inflammatory diseases that are mediated by TNF-alpha.

U.S. Provisional Application No. 60/505,394 filed 24 Sep 2003 (HHS Reference No. E-208-2003/0-US-01)

PCT Application No. PCT/US2004/031608 filed 24 Sep 2004, which published as WO 2005/030798 on 07 Apr 2005 (HHS Reference No. E- 208-2003/0-PCT-02)

U.S. Patent Application No. 11/389,675 filed 23 Mar 2006 (HHS Reference No. E-208-2003/0-US-03)

Inventors:
Stewart J. Levine et al. (NHLBI)

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