Phosphoramidate alkylator prodrugs for the treatment of cancer
Inventors
Ammons, Steve • Duan, Jian-Xin • Jung, Donald • Matteucci, Mark
Assignees
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Publication Number
US-8552048-B2
Publication Date
2013-10-08
Expiration Date
Abstract
Compositions containing, and, methods administering, TH302, are useful in treatment of cancer and other hyper-proliferative diseases.
Core Innovation
The invention relates to TH302 as a hypoxia activated phosphoramidate alkylator prodrug, and to pharmaceutically acceptable compositions and formulations containing TH302 and pharmaceutically acceptable salts. The document describes suitability of the formulation for intravenous administration comprising TH302 and ethanol.
The document addresses the need for compositions that enable dosing and administration of TH302 for cancer treatment. It further describes formulation characteristics including a sucrose-containing lyophilized unit dose and stable ethanol solutions, with constraints on non-ethanol solvent content, together with disclosed dosing and treatment duration ranges.
The document supports use of TH302 in treating cancers in hypoxia, including preclinical efficacy under oxygen and hypoxia conditions, and combinations with radiation therapy. The document also describes additional therapeutic regimens combining TH302 with anti-cancer agents.
A Phase I clinical trial framework is described, including dose escalation levels and patient eligibility considerations, supported by pharmacokinetic and biodistribution information. The disclosure includes pharmacokinetic metrics and biodistribution assessment to support administration of TH302 in humans.
Claims Coverage
The provided material indicates one independent claim in the formulation family and dependent claim coverage for cancer treatment methods, dosing and schedule constraints, formulation solvent constraints, and combination regimens. The inventive features focus on an intravenous TH302 formulation with ethanol and its use in cancer treatment in specified human dosing contexts and combinations.
Intravenous TH302 formulation comprising ethanol
A pharmaceutically acceptable formulation suitable for intravenous administration comprising TH302 or a pharmaceutically acceptable salt thereof, and ethanol.
Within the provided material, the independent claim is limited to a pharmaceutically acceptable intravenous formulation comprising TH302 or a pharmaceutically acceptable salt and ethanol, while the dependent coverage relates to cancer treatment in humans, specified dosing and scheduling ranges, solvent and non-ethanol content constraints, and combination with selected anti-cancer agents and radiation therapy.
Stated Advantages
Not explicitly described in patent.
Documented Applications
Intravenous administration of TH302 and pharmaceutically acceptable salts as a cancer treatment formulation.
Treatment of cancer in a human patient by intravenously administering the TH302 formulation within specified dose ranges.
Combination regimens administering TH302 together with selected anti-cancer agents and/or radiation therapy.
Preclinical efficacy evaluation under oxygen and hypoxia conditions and combination with radiation therapy.
Phase I clinical trial use with dose escalation levels and patient eligibility framework.
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