Combination of kinase inhibitors and uses thereof
AssigneeIntellikine LLC
InventorsPingda Ren, Yi Liu, Katayoun Jessen, Xin Guo, Christian Rommel, Troy Edward Wilson
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Abstract
The present invention provides for a method for treating a disease condition associated with PI3-kinase α and/or mTOR in a subject. In another aspect, the invention provides for a method for treating a disease condition associated with PI3-kinase α and/or mTOR in a subject. In yet another aspect, a method of inhibiting phosphorylation of both Akt (S473) and Akt (T308) in a cell is set forth. The present invention also provides a pharmaceutical kit effective for treating a disease condition associated with PI3-kinase α and/or mTOR in a subject.
Claims33
A method for treating a disease condition associated with PI3-kinase α and/or mTOR in a subject, comprising administering to said subject simultaneously or sequentially a combination of (a) a therapeutically effective amount of a PI3-kinase α inhibitor according to a first dosing regimen and (b) a therapeutically effective amount of an mTOR inhibitor according to a second dosing regimen, wherein the PI3-kinase α inhibitor exhibits selective inhibition of PI3-kinase α relative to one or more type I phosphatidylinositol 3-kinases (PI3-kinase) ascertained by an in vitro kinase assay, wherein the one or more type I PI3-kinase is selected from the group consisting of PI3-kinase β, PI3-kinase γ, and PI3-kinase δ, wherein each dosing regimen independently comprising repeating cycles of a treatment period followed by a rest period, wherein at least one dosing regimen has one rest period of more than 0 day, wherein the disease condition associated with PI3-kinase α and/or mTOR is selected from neoplastic condition, autoimmune disease, inflammatory disease, fibrotic disease or kidney disease.
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A method for treating a disease condition associated with PI3-kinase α and/or mTOR in a subject, comprising administering to said subject simultaneously or sequentially a combination of (a) a therapeutically effective amount of a PI3-kinase α inhibitor and (b) a therapeutically effective amount of an mTOR inhibitor, wherein the PI3-kinase α inhibitor exhibits selective inhibition of PI3-kinase α relative to one or more type I phosphatidylinositol 3-kinases (PI3-kinase) ascertained by an in vitro kinase assay, wherein the one or more type I PI3-kinase is selected from the group consisting of PI3-kinase β, PI3-kinase γ, and PI3-kinase δ, wherein the clinical and therapeutic effects of the treatment of the disease condition continue for a durability of effect period of at least as long as the administration period.
A method of treating a disease condition associated with PI3-kinase α and/or mTOR in a subject, comprising administering to the subject simultaneously or sequentially a combination of (a) a therapeutically effective amount of a PI3-kinase α inhibitor and (b) a therapeutically effective amount of an mTOR inhibitor according to an intermittent regimen effective to achieve (a) higher therapeutic efficacy, (b) similar or better tolerability of the PI3-kinase α inhibitor and/or mTOR inhibitor, and (c) similar or smaller area under the curve, as compared to administering an equivalent dose of the PI3-kinase α inhibitor and/or mTOR inhibitor once daily;
- wherein the PI3-kinase α inhibitor exhibits selective inhibition of PI3-kinase α relative to one or more type I phosphatidylinositol 3-kinases (PI3-kinase) ascertained by an in vitro kinase assay, wherein the one or more type I PI3-kinase is selected from the group consisting of PI3-kinase β, PI3-kinase γ, and PI3-kinase δ.
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Dependencies are inferred from the claim text.