US 12,474,342 B2
Methods for treating cancer and the use of biomarkers as a predictor of clinical sensitivity to therapies
Ellen Filvaroff, San Francisco, CA (US); Antonia Lopez-Girona, San Diego, CA (US); and Gang Lu, San Diego, CA (US)
Assigned to Celgene Corporation, Summit, NJ (US)
Filed by CELGENE CORPORATION, Summit, NJ (US)
Filed on Aug. 5, 2022, as Appl. No. 17/882,278.
Application 17/882,278 is a division of application No. 16/840,299, filed on Apr. 3, 2020, granted, now 11,460,471.
Application 16/840,299 is a division of application No. 15/400,766, filed on Jan. 6, 2017, granted, now 10,648,983, issued on May 12, 2020.
Claims priority of provisional application 62/404,638, filed on Oct. 5, 2016.
Claims priority of provisional application 62/276,700, filed on Jan. 8, 2016.
Prior Publication US 2023/0064156 A1, Mar. 2, 2023
Int. Cl. G01N 33/574 (2006.01); A61K 31/454 (2006.01); A61K 45/06 (2006.01); A61P 35/02 (2006.01); C12Q 1/6886 (2018.01)
CPC G01N 33/574 (2013.01) [A61K 31/454 (2013.01); A61K 45/06 (2013.01); C12Q 1/6886 (2013.01); G01N 33/57426 (2013.01); A61P 35/02 (2018.01); C12Q 2600/106 (2013.01); C12Q 2600/136 (2013.01); C12Q 2600/158 (2013.01); G01N 2800/52 (2013.01)] 25 Claims
 
1. 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 selected from the group consisting of IKZF1, eRF1, BIP, GCN2, eIF2α, PPP1R15A, TNFRSF10B, GADD45A, FAS, IRE1, XBP1, SEC24D, DNAJB9, EDEM1, ATF6, Caspase 3, Caspase 7, Caspase 8, Caspase 9, BID, and Mcl-1;
wherein the treatment compound is a compound of Formula I:

OG Complex Work Unit Chemistry
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.