Title:
VASCULAR ENDOTHELIAL GROWTH FACTOR FUSION CONSTRUCTS AND USES THEREOF
Document Type and Number:
WIPO Patent Application WO2004108074
Kind Code:
A3
Abstract:
The 121-amino acid isoform of vascular endothelial growth factor (VEGF121) is linked by a flexible G4S tether to a cytotoxic molecule such as toxin gelonin or granzyme B and expressed as a soluble fusion protein. The VEGF121 fusion protein exhibits significant anti-tumor vascular-ablative effects that inhibit the growth of primary tumors and inhibit metastatic spread and vascularization of metastases. The VEGF121 fusion protein may also target osteoclast precursor cells in vivo and inhibits osteoclastogenesis.
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Inventors:
ROSENBLUM MICHAEL (US)
Application Number:
PCT/US2004/015244
Publication Date:
September 14, 2006
Filing Date:
May 14, 2004
Export Citation:
Assignee:
RES DEV FOUNDATION (US)
ROSENBLUM MICHAEL (US)
ROSENBLUM MICHAEL (US)
International Classes:
C07K14/52; A61K38/00; (IPC1-7): A61K39/395; A61K39/00; C07K14/475
Other References:
VEENENDAAL L.M. ET AL: "In vitro and in vivo studies of a VEGF121/rGelonin chimeric fusion toxin targeting the neovasculature of solid tumors", PNAS, no. 12, June 2002 (2002-06-01), pages 7866 - 7871, XP008070890
GERBER H.-P. ET AL: "Angiogenesis and Bone Growth", TCM, vol. 10, no. 5, 2000, pages 223 - 228, XP008070893
SMYTH M.J. ET AL: "Granzymes: exogenous proteinases that induce target cell apoptosis", TODAY, vol. 16, no. 4, 1995, pages 202 - 206, XP008070889
LIU Y. ET AL: "Mechanistic studies of a novel human fusion toxin composed of vascular endothelial growth factor (VEGF)121 and the serine protease granzyme B: Directed apoptotic events in vascular endothelial cells", MOLECULAR CANCER THERAPEUTICS, vol. 2, 2003, pages 949 - 959, XP002333236
GERBER H.-P. ET AL: "Angiogenesis and Bone Growth", TCM, vol. 10, no. 5, 2000, pages 223 - 228, XP008070893
SMYTH M.J. ET AL: "Granzymes: exogenous proteinases that induce target cell apoptosis", TODAY, vol. 16, no. 4, 1995, pages 202 - 206, XP008070889
LIU Y. ET AL: "Mechanistic studies of a novel human fusion toxin composed of vascular endothelial growth factor (VEGF)121 and the serine protease granzyme B: Directed apoptotic events in vascular endothelial cells", MOLECULAR CANCER THERAPEUTICS, vol. 2, 2003, pages 949 - 959, XP002333236
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