Title:
CO-ADMINISTRATION OF AN AGENT LINKED TO AN INTERNALIZATION PEPTIDE WITH AN ANTI-INFLAMMATORY
Document Type and Number:
WIPO Patent Application WO/2010/144742
Kind Code:
A3
Abstract:
The invention provides methods of delivering pharmacologic agents linked to an internalization peptide, in which an inflammatory response inducible by the internalization peptide is inhibited by co-administration of an anti-inflammatory or by linking the internalization peptide to biotin or similar molecule. Such methods are premised in part on the results described in the examples whereby administration of a pharmacological agent linked to tat at high dosages is closely followed by an inflammatory response, which includes mast cell degranulation, histamine release and the typical sequelae of histamine release, such as redness, heat, swelling, and hypotension.
Inventors:
TYMIANKSI MICHAEL (CA)
GARMAN JONATHAN DAVID (CA)
CUI HONG (CA)
GARMAN JONATHAN DAVID (CA)
CUI HONG (CA)
Application Number:
PCT/US2010/038226
Publication Date:
April 21, 2011
Filing Date:
June 10, 2010
Export Citation:
Assignee:
NONO INC (CA)
ARBOR VITA CORP (US)
TYMIANKSI MICHAEL (CA)
GARMAN JONATHAN DAVID (CA)
CUI HONG (CA)
ARBOR VITA CORP (US)
TYMIANKSI MICHAEL (CA)
GARMAN JONATHAN DAVID (CA)
CUI HONG (CA)
International Classes:
A61K38/16; A61K31/275; A61K38/08; A61K38/10; A61P9/00; A61P29/00
Other References:
SUN, H. S. ET AL.: "Effectiveness of PSD95 inhibitors in permanent and transient focal ischemia in the rat.", STROKE., vol. 39, no. 9, 10 July 2008 (2008-07-10), pages 2544 - 2553, XP008148452
BARR, M. L. ET AL.: "Addition of a mast cell stabilizing compound to organ preservation solutions decreases lung reperfusion injury.", J. THORAC. CARDIOVASC. SURG., vol. 115, no. 3, March 1998 (1998-03-01), pages 631 - 636, XP005694196
HERCE, H. D. ET AL.: "Molecular dynamics simulations suggest a mechanism for translocation of the HIV-1 TAT peptide across lipid membranes.", PROC. NATL. ACAD. SCI. U. S. A., vol. 104, no. 52, 18 December 2007 (2007-12-18), pages 20805 - 20810, XP002489697
MACKINS, C. J. ET AL.: "Cardiac mast cell-derived renin promotes local angiotensin formation, norepinephrine release, and arrhythmias in ischemia/ reperfusion.", J. CLIN. INVEST., vol. 116, no. 4, April 2006 (2006-04-01), pages 1063 - 1070, XP008148492
KUROSE, I. ET AL.: "Ischemia/reperfusion-induced microvascular dysfunction: role of oxidants and lipid mediators.", AM. J. PHYSIOL., vol. 272, June 1997 (1997-06-01), pages H2976 - H2982, XP008148454
AARTS, M. ET AL.: "Treatment of ischemic brain damage by perturbing NMDA receptor- PSD-95 protein interactions.", SCIENCE., vol. 298, no. 5594, 25 October 2002 (2002-10-25), pages 846 - 850, XP002456870
BARR, M. L. ET AL.: "Addition of a mast cell stabilizing compound to organ preservation solutions decreases lung reperfusion injury.", J. THORAC. CARDIOVASC. SURG., vol. 115, no. 3, March 1998 (1998-03-01), pages 631 - 636, XP005694196
HERCE, H. D. ET AL.: "Molecular dynamics simulations suggest a mechanism for translocation of the HIV-1 TAT peptide across lipid membranes.", PROC. NATL. ACAD. SCI. U. S. A., vol. 104, no. 52, 18 December 2007 (2007-12-18), pages 20805 - 20810, XP002489697
MACKINS, C. J. ET AL.: "Cardiac mast cell-derived renin promotes local angiotensin formation, norepinephrine release, and arrhythmias in ischemia/ reperfusion.", J. CLIN. INVEST., vol. 116, no. 4, April 2006 (2006-04-01), pages 1063 - 1070, XP008148492
KUROSE, I. ET AL.: "Ischemia/reperfusion-induced microvascular dysfunction: role of oxidants and lipid mediators.", AM. J. PHYSIOL., vol. 272, June 1997 (1997-06-01), pages H2976 - H2982, XP008148454
AARTS, M. ET AL.: "Treatment of ischemic brain damage by perturbing NMDA receptor- PSD-95 protein interactions.", SCIENCE., vol. 298, no. 5594, 25 October 2002 (2002-10-25), pages 846 - 850, XP002456870
Attorney, Agent or Firm:
LIEBESCHUETZ, Joe et al. (Two Embarcadero Center8th Floo, San Francisco California, US)
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