Method of producing FR901228

Drug – bio-affecting and body treating compositions – Preparations characterized by special physical form

Reexamination Certificate

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C530S317000, C514S009100

Reexamination Certificate

active

07611724

ABSTRACT:
Depsipeptides and congeners thereof are disclosed having structure (I), wherein m, n, p, q, X, R1, R2 and R3 are as defined herein. These compounds, including FR901228, have activity as, for example, immunosuppressants, as well as for the prevention or treatment of patients suffering or at risk of suffering from inflammatory, autoimmune or immune system-related diseases including graft-versus-host disease and enhancement of graft/tissue survival following transplant. Also provided are methods for inhibiting lymphocyte activation, proliferation, and/or suppression of IL-2 secretion. Also provided are crystalline forms of FR901228, e.g., type A and type B crystalline forms of FR901228.

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Hirotsugu Ueda et al, “FR901228, A Novel Antitumor Bicyclic Depsipeptide Produced byChromobacterium violaceumNo. 968”, I. “Taxonomy, Fermentation, Isolation, Physico-Chemical and Biological Properties, and Antitumor Activity”, The Journal of Anitibiotics (1994), vol. 47, No. 3, pp. 301-310.
Nobuharu Shigematsu et al, “FR901228, A Novel Antitumor Bicyclic Depsipeptide Produced byChromobacterium violaceumNo. 968”, II. “Structure Determination”, The Journal of Antibiotics (1994). vol. 47, No. 3, pp. 311-314.
Khan W. Li et al, “Total Synthesis of the Antitumor Depsipeptide FR-901,228”, J. Am. Chem. Soc., 1996, 118, pp. 7237-7238.
Material Safety Data Sheet: (E-(1S, 4S, 10S, 21R)-7-[(Z)-ethylidene]4,21-diisopropy1-2-oxa-12,13-dithia-5,8,20,23-tetraaza-3,6,9,19-pentaoxobibyclo[8,7,6]-tricos-16-ene (1993).

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