Title:
INHIBITION OF VEGF-A SECRETION, ANGIOGENESIS AND/OR NEOANGIOGENESIS BY SINA MEDIATED KNOCKDOWN OF VEGF-C AND RHOA
Document Type and Number:
WIPO Patent Application WO/2010/058426
Kind Code:
A3
Abstract:
The invention relates to the use of short interfering nucleic acid molecules (siNAs, such as siRNAs) that modulate the expression of VEGF-C and/or RhoA involved in neovascular angiogenesis. In the present invention, inhibition of VEGF-C and/or RhoA gene expression lead to decreased expression of VEGF-A, which is required for initiation and the sustaining of angiogenesis. Further, the invention also relates to the inhibition of RhoA expression levels along with VEGF-C, so as to derive the benefits of down- regulating two different targets required for angiogenesis. The present invention describes compounds, compositions and methods useful for inhibition of neoangiogenesis. In certain embodiments, the invention relates to methods for inhibiting neovascularization, as well as compounds, such as VEGF-C and RhoA siRNAs, useful in the treatment of ocular disorders such as age related maculardegeneration (AMD), diabetic retinopathy, glaucoma and other neovascular disorders.
Inventors:
MURALI KRISHNA ADDEPALLI (IN)
BHARAT KUMAR (IN)
SHAILAJA CHILE (IN)
BHARAT KUMAR (IN)
SHAILAJA CHILE (IN)
Application Number:
PCT/IN2009/000671
Publication Date:
October 28, 2010
Filing Date:
November 20, 2009
Export Citation:
Assignee:
RELIANCE LIFE SCIENCES PVT LTD (IN)
MURALI KRISHNA ADDEPALLI (IN)
BHARAT KUMAR (IN)
SHAILAJA CHILE (IN)
MURALI KRISHNA ADDEPALLI (IN)
BHARAT KUMAR (IN)
SHAILAJA CHILE (IN)
International Classes:
C12N15/113; A61K31/713; A61P9/00
Other References:
SHIBATA M-A ET AL: "Combination therapy with short interfering RNA vectors against VEGF-C and VEGF-A suppresses lymph node and lung metastasis in a mouse immunocompetent mammary cancer model.", CANCER GENE THERAPY DEC 2008 LNKD- PUBMED:18654613, vol. 15, no. 12, 25 July 2008 (2008-07-25), pages 776 - 786, XP002583086, ISSN: 1476-5500
MARTÍN MARÍA JOSÉ ET AL: "The Galpha12/13 family of heterotrimeric G proteins and the small GTPase RhoA link the Kaposi sarcoma-associated herpes virus G protein-coupled receptor to heme oxygenase-1 expression and tumorigenesis.", THE JOURNAL OF BIOLOGICAL CHEMISTRY 23 NOV 2007 LNKD- PUBMED:17881360, vol. 282, no. 47, 23 November 2007 (2007-11-23), pages 34510 - 34524, XP002583087, ISSN: 0021-9258
SINGLETON P A ET AL: "Methylnaltrexone inhibits opiate and VEGF-induced angiogenesis: Role of receptor transactivation", MICROVASCULAR RESEARCH, ACADEMIC PRESS, US LNKD- DOI:10.1016/J.MVR.2006.04.004, vol. 72, no. 1-2, 1 July 2006 (2006-07-01), pages 3 - 11, XP024919590, ISSN: 0026-2862, [retrieved on 20060701]
MARTÍN MARÍA JOSÉ ET AL: "The Galpha12/13 family of heterotrimeric G proteins and the small GTPase RhoA link the Kaposi sarcoma-associated herpes virus G protein-coupled receptor to heme oxygenase-1 expression and tumorigenesis.", THE JOURNAL OF BIOLOGICAL CHEMISTRY 23 NOV 2007 LNKD- PUBMED:17881360, vol. 282, no. 47, 23 November 2007 (2007-11-23), pages 34510 - 34524, XP002583087, ISSN: 0021-9258
SINGLETON P A ET AL: "Methylnaltrexone inhibits opiate and VEGF-induced angiogenesis: Role of receptor transactivation", MICROVASCULAR RESEARCH, ACADEMIC PRESS, US LNKD- DOI:10.1016/J.MVR.2006.04.004, vol. 72, no. 1-2, 1 July 2006 (2006-07-01), pages 3 - 11, XP024919590, ISSN: 0026-2862, [retrieved on 20060701]
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