Title:
LONG-ACTING CYTOKINE DERIVATIVES AND PHARMACEUTICAL COMPOSITIONS COMPRISING THEM
Document Type and Number:
WIPO Patent Application WO2002036067
Kind Code:
A3
Abstract:
Cytokine derivatives are provided bearing functional groups sensitive to mild basic conditions such as fluorenylmethoxycarbonyl (Fmoc) and 2-sulfo-9-fluorenylmethoxycarbonyl (FMS) and pharmaceutical compositions comprising them. Preferred derivates are those in which amino groups of the cytokine are substituted with FMS, for example FMS7-IFN- alpha 2 and FMS3-IL-2. These cytokine derivatives can be administered as inactive or slightly active prodrugs and are capable of undergoing spontaneous regeneration into the parent bioactive drugs under in vivo physiological conditions and in a hom egenous fashion. The cytokine prodrugs present higher metabolic stability and augmented bioavailability.
Inventors:
SHECHTER YORAM (IL)
FRIDKIN MATITYAHU (IL)
GOLDWASER ITZHAK (IL)
FRIDKIN MATITYAHU (IL)
GOLDWASER ITZHAK (IL)
Application Number:
PCT/IL2001/001005
Publication Date:
January 09, 2003
Filing Date:
October 30, 2001
Export Citation:
Assignee:
YEDA RES & DEV (IL)
SHECHTER YORAM (IL)
FRIDKIN MATITYAHU (IL)
GOLDWASER ITZHAK (IL)
SHECHTER YORAM (IL)
FRIDKIN MATITYAHU (IL)
GOLDWASER ITZHAK (IL)
International Classes:
A61K47/48; (IPC1-7): A61K45/00; A61K38/21; A61K31/785
Other References:
SHECHTER Y. ET AL.: "Prolonging the half-life of human interferon-alpha2 in circulation: Design, preparation and analysis of (2-sulfo-9-fluorenylmethoxycarbonyl)7-interferon-alpha2", PROC. NATL. ACAD. SCI. USA, vol. 98, no. 3, 30 January 2000 (2000-01-30), pages 1212 - 1217, XP002955162
GERSHONOV ET AL.: "A novel approach for a water-soluble long-acting insulin prodrug: Design, preparaton and analysis of ((2-sulfo)-9-fluorenylmethoxycarbonyl)3-insulin", J. MED. CHEM., vol. 43, 2000, pages 2530 - 2537, XP002955163
GERSHONOV ET AL.: "New concept for long-acting insulin, spontaneous conversion of an inactive modified insulin to the active hormone in circulation: 9-fluorenylmethoxycarbonyl derivative of insulin", DIABETES, vol. 48, July 1999 (1999-07-01), pages 1437 - 1442, XP002955164
GERSHONOV ET AL.: "A novel approach for a water-soluble long-acting insulin prodrug: Design, preparaton and analysis of ((2-sulfo)-9-fluorenylmethoxycarbonyl)3-insulin", J. MED. CHEM., vol. 43, 2000, pages 2530 - 2537, XP002955163
GERSHONOV ET AL.: "New concept for long-acting insulin, spontaneous conversion of an inactive modified insulin to the active hormone in circulation: 9-fluorenylmethoxycarbonyl derivative of insulin", DIABETES, vol. 48, July 1999 (1999-07-01), pages 1437 - 1442, XP002955164
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