Methods of identifying and treating individuals exhibiting mutant kit protein
AssigneesBristol-Myers Squibb Company, Oregon Health & Science University, The United States of America as represented by the Department of Veterans Affairs
InventorsFrancis Y. Lee, Michael C. Heinrich, Christopher L. Corless
Life of this patent
Estimating the term…
Abstract
The invention described herein relates to methods of identifying and treating individuals with protein tyrosine kinase associated disorders that have, or may, become resistant to treatment with a kinase inhibitor such as imatinib due to a gain-of-function mutation in KIT tyrosine kinase.
Claims24
A method for determining the responsiveness of an individual with a protein tyrosine kinase-associated disorder to treatment with ′N-(2-chloro-6-methylphenyl)-2-[[6-[4-(2-hydroxyethyl)-1-piperazinyl]-2-methyl-4-pyrimidinyl]amino]-5-thiazolecarboxamide, or a pharmaceutically acceptable salt or hydrate thereof, wherein said individual has either been previously treated with and developed at least partial resistance to a first kinase inhibitor, or is naïve to treatment with kinase inhibitors, comprising:
- (a) providing a biological sample from said individual;
- (b) screening said biological sample for the presence of at least one mutation in a KIT kinase sequence;
- and (c) assigning the individual to a positive responder group if a mutant KIT kinase is identified.
-11. (canceled)
A method of treating an individual suffering from a protein tyrosine kinase associated disorder comprising the steps of:
- (1) (a) providing a biological sample from said individual;
- (b) assaying said biological sample for the presence of a mutant KIT kinase;
- and if a mutant KIT kinase is identified (c) administering a therapeutically effective amount of ′N-(2-chloro-6-methylphenyl)-2-[[6-[4-(2-hydroxyethyl)-1-piperazinyl]-2-methyl-4-pyrimidinyl]amino]-5-thiazolecarboxamide, or a pharmaceutically acceptable salt or hydrate thereof;
- or
- (2) (a) providing a biological sample from said individual;
- (b) assaying said biological sample for at least partial resistance to a first kinase inhibitor;
- (c) assaying said biological sample for the presence of a mutant KIT kinase;
- and if said biological sample is determined to be at least partially resistant to said first kinase inhibitor and contains a mutant KIT kinase, then (d) administering a therapeutically effective amount of ′N-(2-chloro-6-methylphenyl)-2-[[6-[4-(2-hydroxyethyl)-1-piperazinyl]-2-methyl-4-pyrimidinyl]amino]-5-thiazolecarboxamide, or a pharmaceutically acceptable salt or hydrate thereof.
-19. (canceled)
A method of establishing a treatment regimen for an individual suffering from a protein tyrosine kinase associated disorder comprising the steps of:
- (1) (a) providing a biological sample from said individual;
- (b) screening said biological sample for the presence of at least one mutation in a KIT kinase sequence;
- and, if at least one mutation in a KIT kinase sequence is present in said biological sample, (c) administering to said individual as part of a treatment regimen a pharmaceutical composition comprising ′N-(2-chloro-6-methylphenyl)-2-[[6-[4-(2-hydroxyethyl)-1-piperazinyl]-2-methyl-4-pyrimidinyl]amino]-5-thiazolecarboxamide, or a pharmaceutically acceptable salt or hydrate thereof;
- or
- (2) (a) providing a biological sample from said individual;
- (b) assaying said biological sample for at least partial resistance to a first kinase inhibitor, (c) assaying said biological sample for the presence of at least one mutation in a KIT kinase sequence;
- and, if said biological sample is determined to be at least partially resistant to said first kinase inhibitor and contain a mutant KIT kinase, then (d) administering to said individual as part of a treatment regimen a pharmaceutical composition comprising ′N-(2-chloro-6-methylphenyl)-2-r[6-[4-(2-hydroxyethyl)-1-piperazinyl]-2-methyl-4-pyrimidinyl]amino]-5-thiazolecarboxamide, or a pharmaceutically acceptable salt or hydrate thereof.
(canceled)
-34. (canceled)
A method of treating an individual suffering from a mutant KIT kinase associated disorder comprising administering a therapeutically effective amount of ′N-(2-chloro-6-methylphenyl)-2-[[6-[4-(2-hydroxyethyl)-1-piperazinyl]-2-methyl-4-pyrimidinyl]amino]-5-thiazolecarboxamide, or a pharmaceutically acceptable salt or hydrate thereof.
A kit for use in determining treatment strategy for an individual with a protein tyrosine kinase-associated disorder, comprising:
- (a) a means for detecting a mutant KIT kinase in a biological sample from said patient;
- and optionally (b) instructions for use and interpretation of the kit results.
(canceled)
-45. (canceled)
A method of treating an individual suffering from a mutant KIT kinase associated disorder comprising administering a therapeutically effective amount of ′N-(2-chloro-6-methylphenyl)-2-[[6-[4-(2-hydroxyethyl)-1-piperazinyl]-2-methyl-4-pyrimidinyl]amino]-5-thiazolecarboxamide, or a pharmaceutically acceptable salt or hydrate thereof, in combination with a therapeutically effective amount of mTOR inhibitor.
-49. (canceled)
-53. (canceled)
A method of identifying an individual suffering from a disorder caused by a mutant KIT kinase, comprising the steps of:
- a) obtaining a biological sample from the individual;
- b) providing a first primer that is specific for a nucleic acid encoding the mutant KIT kinase;
- c) providing a second primer that is specific for a nucleic acid encoding wildtype KIT kinase, wherein the second primer is modified so as to prevent amplification of the nucleic acid encoding the wildtype KIT kinase;
- d) selectively amplifying the nucleic acid encoding the mutant KIT kinase from the biological sample using the first and second primers;
- and
- e) detecting the presence of an amplification product, wherein presence of an amplification product indicates that the individual suffers from a disorder caused by a mutant KIT kinase.
-60. (canceled)
Dependencies are inferred from the claim text.