USPTO grants Semafore method patent for PI3K inhibitors

Jul 1 2010

Semafore Pharmaceuticals today announced the United States Patent and Trademark Office (PTO) has issued United States Patent Number 7,745,485 entitled "Compositions and methods for identifying agents which modulate PTEN function and PI-3 kinase pathways." This patent covers methods of inhibiting the spread of cancer in patients using phosphoinositide-3-kinase (PI3K) inhibitors alone or in combination with chemotherapeutic agents.

“Compositions and methods for identifying agents which modulate PTEN function and PI-3 kinase pathways.”

SF1126 and the PI3K Pathway

The phosphatidylinositol 3-kinase (PI3K) signaling pathway is vital to several essential biological processes, such as cell growth, survival, motility, and metabolism. PI3K is commonly altered in human cancers, making inhibition of the target attractive for cancer therapy. However, the role of PI3K in a wide range of normal biologic processes raises potential concerns about its inhibition in non-cancerous tissues.

As the only PI3K/mTOR inhibitor prodrug currently in development, Semafore's SF1126 product candidate is designed to overcome these concerns by accumulating preferentially in tumor tissue in an attempt to maximize efficacy and minimize toxicity. SF1126 is a peptidic prodrug that converts to LY294002, one of the most widely studied dual PI3K/mTOR inhibitors that historically suffered from poor solubility. LY294002 is conjugated to an Arg-Gly-Asp (RGD) peptide via a cleavable linker to form SF1126, which has improved properties for clinical use. As a prodrug with improved solubility and site selectivity due to targeting of RGD-recognizing integrin receptors, SF1126 opened up a new avenue for the clinical development of LY294002.

To date, nearly 50 patients with solid tumors or hematological malignancies have been treated with SF1126 in Phase I trials. Administration of SF1126 at doses ranging from 90 to 1,110 mg/m2 has been generally well tolerated with the most common treatment-related adverse events have been nausea, vomiting, diarrhea, fever, and fatigue.