Compositions and methods of sphingosine kinase inhibitors in...

Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Carbohydrate doai

Reexamination Certificate

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C536S024500, C600S001000, C378S065000

Reexamination Certificate

active

08084438

ABSTRACT:
The present invention relates to Sphingosine kinase inhibitors that are useful for treating various cancers. The invention further relates to compositions and methods of SPK inhibitors, including siRNAs, which specifically block gene expression of SPK and potentiates the effect of radiation in the treatment of various cancers.

REFERENCES:
patent: 2004/0171037 (2004-09-01), Li et al.
GenBank Accession BC011432 (Nov. 19, 2003).
Samsel et al (The Prostate 58: 382-393, 2004).
Validation of an anti-sphingosine-1 phosphate antibody as a potential therapeutic in reducing growth, invasion, and angiogenesis in multiple tumor lineages (Cancer Cell 2006;9:225-38) by Barbara Visentin, et al.
Sphingosine Kinase Mediates Vascular Endothelial Growth Factor-Induced Activation of Ras and Mitogen-Activated Protein Kinases (Mole) (Cell. Bio 2002;22:77587768) by Xiaodong Shu, et al.
Sphingosine Kinase-1 as a Chemotherapy Sensor in Prostate Adenocarcinoma Cell and Mouse Models (Cancer Res. 2005;65:11667-75) by Dimitri Pchejetski, et al.
Sphingosine kinase 1 is up-regulated in colon carcinogenesis. (FASEB J. 2006; 20:386-8) by Toshihiko Kawamori, et al.
Discovery and Evaluation of Inhibitors of Human Sphingosine Kinase. (Cancer Res. 2003;63;5962-9) by Kevin J. French,et al.
N,N-Dimethylsphingosine Is a Potent Competitive Inhibitor of Sphingosine Kinase but Not of Protein Kinase C: Modulation of Cellular Levels of Sphingosine 1-Phosphate and Ceramide (Biochemistry. 1998;37:12892-8) by Lisa C. Edsall, et al.
Sphingosine Enhances Apoptosis of Radiation-resistant Prostate Cancer Cells (Cancer Res. 2000 Aug. 15;60 (16):4468-74) by Victor E. Nava, et al.
PCT International Search Report mailed Sep. 10, 2008 based on PCT/US2007/086057.

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