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US 10,648,983 B2Granted
Methods for treating cancer and the use of biomarkers as a predictor of clinical sensitivity to therapies
AssigneeCelgene Corporation
InventorsEllen Filvaroff, Antonia Lopez-Girona, Gang Lu
Life of this patent
Estimating the term…
Abstract
A method of identifying a subject having cancer who is likely to be responsive to a treatment compound, comprising administering the treatment compound to the subject having the cancer; obtaining a sample from the subject; determining the level of a biomarker in the sample from the subject; and diagnosing the subject as being likely to be responsive to the treatment compound if the level of the biomarker in the sample of the subject changes as compared to a reference level of the biomarker; wherein the treatment compound is a compound of Formula I:
Claims27
A method of identifying a subject having cancer who is likely to be responsive to a treatment compound, comprising:
- (a) administering the treatment compound to the subject;
- (b) obtaining a sample from the subject;
- (c) determining the level of a biomarker in the sample;
- and
- (d) diagnosing the subject as being likely to be responsive to the treatment compound if the level of the biomarker in the sample is different from a reference level of the biomarker;
- wherein the biomarker is GSPT1 or GSPT2;
- wherein the treatment compound is a compound of Formula I:
- or a stereoisomer or a mixture of stereoisomers, tautomer, pharmaceutically acceptable salt, solvate, isotopologue, prodrug, hydrate, co-crystal, clathrate, or a polymorph thereof, wherein:
- R1 is H, optionally substituted cycloalkyl, optionally substituted aryl, optionally substituted heteroaryl, or optionally substituted heterocyclyl;
- R2 and R3 are each halo;
- where the substituents on R1, when present are one to three groups Q, where each Q is independently alkyl, halo, haloalkyl, hydroxyl, alkoxy, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted aryl, —R4OR5, —R4SR5, —R4N(R6)(R7), —R4OR4N(R6)(R7), or —R4OR4C(J)N(R6)(R7);
- each R4 is independently alkylene, alkenylene, or a direct bond;
- each R5 is independently hydrogen, alkyl, haloalkyl, or hydroxyalkyl;
- J is O or S;
- and
- R6 and R7 are each independently hydrogen or alkyl, or R6 and R7 together with the nitrogen atom on which they are substituted form a 5 or 6-membered heterocyclyl or heteroaryl ring, optionally substituted with one or two halo, alkyl, or haloalkyl.
13 more elements
A method of identifying a subject having cancer who is likely to be responsive to a treatment compound, comprising:
- (a) obtaining a sample from the subject;
- (b) administering the treatment compound to the sample;
- (c) determining the level of a biomarker in the sample;
- and
- (d) diagnosing the subject as being likely to be responsive to the treatment compound if the level of the biomarker in the sample is different from a reference level of the biomarker;
- wherein the biomarker is GSPT1 or GSPT2,
- wherein the treatment compound is a compound of Formula I:
- or a stereoisomer or a mixture of stereoisomers, tautomer, pharmaceutically acceptable salt, solvate, isotopologue, prodrug, hydrate, co-crystal, clathrate, or a polymorph thereof, wherein:
- R1 is H, optionally substituted cycloalkyl, optionally substituted aryl, optionally substituted heteroaryl, or optionally substituted heterocyclyl;
- R2 and R3 are each halo;
- where the substituents on R1, when present are one to three groups Q, where each Q is independently alkyl, halo, haloalkyl, hydroxyl, alkoxy, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted aryl, —R4OR5, —R4SR5, —R4N(R6)(R7), —R4OR4N(R6)(R7), or —R4OR4C(J)N(R6)(R7);
- each R4 is independently alkylene, alkenylene, or a direct bond;
- each R5 is independently hydrogen, alkyl, haloalkyl, or hydroxyalkyl;
- J is O or S;
- and
- R6 and R7 are each independently hydrogen or alkyl, or R6 and R7 together with the nitrogen atom on which they are substituted form a 5 or 6-membered heterocyclyl or heteroaryl ring, optionally substituted with one or two halo, alkyl, or haloalkyl.
13 more elements
A method of treating cancer, comprising:
- (a) obtaining a sample from a subject having the cancer;
- (b) determining the level of a biomarker in the sample;
- (c) diagnosing the subject as being likely to be responsive to the treatment compound if the level of the biomarker in the sample is different from a reference level of the biomarker;
- and
- (d) administering a therapeutically effective amount of the treatment compound to the subject;
- wherein the biomarker is GSPT1 or GSPT2;
- wherein the treatment compound is a compound of Formula I:
- or a stereoisomer or a mixture of stereoisomers, tautomer, pharmaceutically acceptable salt, solvate, isotopologue, prodrug, hydrate, co-crystal, clathrate, or a polymorph thereof, wherein:
- R1 is H, optionally substituted cycloalkyl, optionally substituted aryl, optionally substituted heteroaryl, or optionally substituted heterocyclyl;
- R2 and R3 are each halo;
- where the substituents on R1, when present are one to three groups Q, where each Q is independently alkyl, halo, haloalkyl, hydroxyl, alkoxy, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted aryl, —R4OR5, —R4SR5, —R4N(R6)(R7), —R4OR4N(R6)(R7), or —R4OR4C(J)N(R6)(R7);
- each R4 is independently alkylene, alkenylene, or a direct bond;
- each R5 is independently hydrogen, alkyl, haloalkyl, or hydroxyalkyl;
- J is O or S;
- and
- R6 and R7 are each independently hydrogen or alkyl, or R6 and R7 together with the nitrogen atom on which they are substituted form a 5 or 6-membered heterocyclyl or heteroaryl ring, optionally substituted with one or two halo, alkyl, or haloalkyl.
13 more elements
A method of predicting the responsiveness of a subject having or suspected of having cancer to a treatment compound, comprising:
- (a) administering the treatment compound to the subject;
- (b) obtaining a sample from the subject;
- (c) determining the level of a biomarker in the sample;
- (d) diagnosing the subject as being likely to be responsive to a treatment of the cancer with the treatment compound if the level of the biomarker in the sample is different from the level of the biomarker obtained from a reference sample;
- wherein the biomarker is GSPT1 or GSPT2;
- wherein the treatment compound is a compound of Formula I:
- or a stereoisomer or a mixture of stereoisomers, tautomer, pharmaceutically acceptable salt, solvate, isotopologue, prodrug, hydrate, co-crystal, clathrate, or a polymorph thereof, wherein:
- R1 is H, optionally substituted cycloalkyl, optionally substituted aryl, optionally substituted heteroaryl, or optionally substituted heterocyclyl;
- R2 and R3 are each halo;
- where the substituents on R1, when present are one to three groups Q, where each Q is independently alkyl, halo, haloalkyl, hydroxyl, alkoxy, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted aryl, —R4OR5, —R4SR5, —R4N(R6)(R7), —R4OR4N(R6)(R7), or —R4OR4C(J)N(R6)(R7);
- each R4 is independently alkylene, alkenylene, or a direct bond;
- each R5 is independently hydrogen, alkyl, haloalkyl, or hydroxyalkyl;
- J is O or S;
- and
- R6 and R7 are each independently hydrogen or alkyl, or R6 and R7 together with the nitrogen atom on which they are substituted form a 5 or 6-membered heterocyclyl or heteroaryl ring, optionally substituted with one or two halo, alkyl, or haloalkyl.
12 more elements
A method of predicting the responsiveness of a subject having or suspected of having cancer to a treatment compound, comprising:
- (a) obtaining a sample from the subject;
- (b) administering the treatment compound to the sample;
- (c) determining the level of a biomarker in the sample;
- (d) diagnosing the subject as being likely to be responsive to a treatment of the cancer with the treatment compound if the level of the biomarker in the sample is different from the level of the biomarker obtained from a reference sample;
- wherein the biomarker is GSPT1 or GSPT2;
- wherein the treatment compound is a compound of Formula I:
- or a stereoisomer or a mixture of stereoisomers, tautomer, pharmaceutically acceptable salt, solvate, isotopologue, prodrug, hydrate, co-crystal, clathrate, or a polymorph thereof, wherein:
- R1 is H, optionally substituted cycloalkyl, optionally substituted aryl, optionally substituted heteroaryl, or optionally substituted heterocyclyl;
- R2 and R3 are each halo;
- where the substituents on R1, when present are one to three groups Q, where each Q is independently alkyl, halo, haloalkyl, hydroxyl, alkoxy, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted aryl, —R4OR5, —R4SR5, —R4N(R6)(R7), —R4OR4N(R6)(R7), or —R4OR4C(J)N(R6)(R7);
- each R4 is independently alkylene, alkenylene, or a direct bond;
- each R5 is independently hydrogen, alkyl, haloalkyl, or hydroxyalkyl;
- J is O or S;
- and
- R6 and R7 are each independently hydrogen or alkyl, or R6 and R7 together with the nitrogen atom on which they are substituted form a 5 or 6-membered heterocyclyl or heteroaryl ring, optionally substituted with one or two halo, alkyl, or haloalkyl.
12 more elements
A method of monitoring the efficacy of a treatment compound in treating cancer in a subject, comprising:
- (a) administering the treatment compound to the subject;
- (b) obtaining a sample from the subject;
- (c) determining the level of a biomarker in the sample;
- (d) comparing the level of the biomarker in the sample with the level of the biomarker obtained from a reference sample, wherein a change in the level as compared to the reference is indicative of the efficacy of the treatment compound in treating the cancer in the subject;
- wherein the biomarker is GSPT1 or GSPT2;
- wherein the treatment compound is a compound of Formula I:
- or a stereoisomer or a mixture of stereoisomers, tautomer, pharmaceutically acceptable salt, solvate, isotopologue, prodrug, hydrate, co-crystal, clathrate, or a polymorph thereof, wherein:
- R1 is H, optionally substituted cycloalkyl, optionally substituted aryl, optionally substituted heteroaryl, or optionally substituted heterocyclyl;
- R2 and R3 are each halo;
- where the substituents on R1, when present are one to three groups Q, where each Q is independently alkyl, halo, haloalkyl, hydroxyl, alkoxy, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted aryl, —R4OR5, —R4SR5, —R4N(R6)(R7), —R4OR4N(R6)(R7), or —R4OR4C(J)N(R6)(R7);
- each R4 is independently alkylene, alkenylene, or a direct bond;
- each R5 is independently hydrogen, alkyl, haloalkyl, or hydroxyalkyl;
- J is O or S;
- and
- R6 and R7 are each independently hydrogen or alkyl, or R6 and R7 together with the nitrogen atom on which they are substituted form a 5 or 6-membered heterocyclyl or heteroaryl ring, optionally substituted with one or two halo, alkyl, or haloalkyl.
12 more elements
Dependencies are inferred from the claim text.