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AssigneeOregon Health & Science University
InventorsR. Stephen Lloyd, Irina G. Minko, Amanda K. McCullough
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Disclosed herein is the identification of human DNA polymerase κ (pol κ) as the polymerase that mediates repair of DNA containing interstrand cros slinks (ICLs). The mechanism of action of a number of chemotherapeutic and antimicrobial agents is the induction of ICLs. Thus, provided herein is a method of enhancing the efficacy of a chemotherapeutic or antimicrobial agent in a subject, including selecting a subject in need of treatment with an ICL-inducing agent and administering to the subject an ICL-inducing agent and a therapeutically effective amount of an inhibitor of pol κ. Subjects in need of treatment with an ICL-inducing agent, include, for example, subjects diagnosed with a hyperproliferative disease, an autoimmune disease or an infectious disease. Also provided is a composition for treating a hyperproliferative disease, an autoimmune disease or an infectious disease, comprising an ICL-inducing agent and an amount of an inhibitor of pol κ sufficient to enhance the efficacy of the ICL-inducing agent. Further provided is a method of identifying a DNA polymerase inhibitor.
A method for enhancing the efficacy of an interstrand crosslink (ICL)-inducing agent in a subject, comprising (i) selecting a subject in need of treatment with an ICL-inducing agent and (ii) administering to the subject an ICL-inducing agent and a therapeutically effective amount of an inhibitor of DNA polymerase kappa (pol κ) sufficient to enhance efficacy of the ICL-inducing agent.
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A method of treating a subject diagnosed with a hyperproliferative disease, infectious disease or an autoimmune disease, comprising administering to the subject a therapeutically effective amount of an interstrand crosslink (ICL)-inducing agent and an inhibitor of pol κ.
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A composition for treating a hyperproliferative disease, an autoimmune disease or an infectious disease, comprising an ICL-inducing agent and an amount of an inhibitor of pol κ sufficient to enhance the efficacy of the ICL-inducing agent.
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A method of identifying an agent that enhances the efficacy of an ICL-inducing agent, comprising screening candidate agents to identify an agent that inhibits activity of pol κ, thereby identifying an agent that enhances the efficacy of an ICL-inducing agent.
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A method of identifying an agent that inhibits the activity of a DNA polymerase, comprising:
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Dependencies are inferred from the claim text.