Methods for determining drug efficacy using cereblon-associated proteins

Abstract

Use of cereblon-associated proteins as biomarkers for clinical sensitivity to cancer, inflammatory diseases, and patient response to drug treatment.

1 .- 21 . (canceled) 
     
     
         22 . A kit of assessing the efficacy of a compound in treating a disease or disorder in a subject comprising an agent for determining the protein level of IKZF1 and/or IKZF3 in a sample obtained from the subject,
 wherein the sample has been treated with the compound;   wherein the disease or disorder is a blood cancer; and   wherein the compound is thalidomide, lenalidomide, pomalidomide, 3-(5-amino-2-methyl-4-oxo-4H-quinazolin-3-yl)-piperidine-2,6-dione or 3-(4-((4-(morpholinomethyl)benzyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, or a pharmaceutically acceptable salt-thereof.   
     
     
         23 . The kit of  claim 22 , wherein the kit further comprises a tool for obtaining the sample from the subject. 
     
     
         24 . The kit of  claim 22 , wherein the tool is suitable for obtaining the sample from a tumor biopsy, node biopsy, or a biopsy from bone marrow, spleen, liver, brain or breast. 
     
     
         25 . The kit of  claim 22 , wherein the kit further comprises an instruction providing a reference protein level of IKZF1 and/or IKZF3. 
     
     
         26 . The kit of  claim 22 , wherein the reference protein level is prepared by using a reference sample obtained from a healthy subject not having the disease or disorder; and wherein the reference sample is from the same source as the first cell sample. 
     
     
         27 . The kit of  claim 22 , wherein the blood cancer is multiple myeloma, chronic lymphocytic leukemia, non-Hodgkin's Lymphoma, or mantle cell lymphoma. 
     
     
         28 . The kit of  claim 27 , wherein the blood cancer is multiple myeloma. 
     
     
         29 . The kit of  claim 27 , wherein the blood cancer is chronic lymphocytic leukemia. 
     
     
         30 . The kit of  claim 27 , wherein the blood cancer is non-Hodgkin's Lymphoma. 
     
     
         31 . The kit of  claim 27 , wherein the blood cancer is mantle cell lymphoma. 
     
     
         32 . A kit of assessing the efficacy of a compound in treating a disease or disorder in a subject comprising an agent for determining the protein level of IKZF1 and/or IKZF3 in a sample obtained from the subject,
 wherein the sample has been treated with the compound;   wherein the disease or disorder is an inflammatory disease selected from the group consisting of: systemic lupus erythematosus, Sjogren syndrome and systemic sclerosis; and   wherein the compound is thalidomide, lenalidomide, pomalidomide, 3-(5-amino-2-methyl-4-oxo-4H-quinazolin-3-yl)-piperidine-2,6-dione or 3-(4-((4-(morpholinomethyl)benzyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, or a pharmaceutically acceptable salt-thereof.   
     
     
         33 . The kit of  claim 32 , wherein the kit further comprises a tool for obtaining the sample from the subject. 
     
     
         34 . The kit of  claim 32 , wherein the kit further comprises an instruction providing a reference protein level of IKZF1 and/or IKZF3. 
     
     
         35 . The kit of  claim 32 , wherein the reference protein level is prepared by using a reference sample obtained from a healthy subject not having the disease or disorder; and wherein the reference sample is from the same source as the first cell sample. 
     
     
         36 . The kit of  claim 32 , wherein the disease or disorder is systemic lupus erythematosus. 
     
     
         37 . The kit of  claim 32 , wherein the disease or disorder is Sjogren syndrome. 
     
     
         38 . The kit of  claim 32 , wherein the disease or disorder is systemic sclerosis.