Treatment of immune-related and inflammatory diseases

Abstract

Provided herein are methods of using compounds and compositions for modulating leukocytic activity, including activity of B cells and/or T cells monocytes, macrophages, and other lymphoid or myeloid-derived cell types, in immune-related diseases or inflammatory diseases. Pharmaceutical compositions and dosing regimens for use in the methods are also provided herein.

1 - 20 . (canceled) 
     
     
         21 . A method of identifying a subject who is likely to be responsive to a treatment of a disease, disorder, or condition with a treatment compound, comprising:
 a) determining the level of a biomarker in a biological sample from the subject, wherein the biomarker is CD44, CD83 or combination thereof, and   b) comparing the level of the biomarker in the biological sample from the subject to a reference level of the biomarker;   wherein the subject is likely to be responsive to the treatment if the level of the biomarker in the biological sample from the subject is altered as compared to the reference level of the biomarker; and   wherein the treatment compound is (S)-3-(4-((4-(morpholinomethyl)benzyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, or a pharmaceutically acceptable salt, solid form, solvate, hydrate, stereoisomer, tautomer or racemic mixture thereof.   
     
     
         22 . A method of identifying a subject who is likely to be responsive to a treatment of a disease, disorder, or condition with a treatment compound, comprising:
 a) determining the level of a biomarker in a biological sample from the subject, wherein the biomarker is CD44, CD83 or combination thereof,   b) determining the level of the biomarker in a control sample; and   c) comparing the level of the biomarker in the biological sample from the subject to the level of the biomarker in the control sample;   wherein the subject is likely to be responsive to the treatment if the level of the biomarker in the biological sample from the subject is altered as compared to the level of the biomarker in the control sample; and   wherein the treatment compound is (S)-3-(4-((4-(morpholinomethyl)benzyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, or a pharmaceutically acceptable salt, solid form, solvate, hydrate, stereoisomer, tautomer or racemic mixture thereof.   
     
     
         23 . A method of predicting the responsiveness of a subject to a treatment of a disease, disorder, or condition with a treatment compound, comprising:
 a) determining the level of a biomarker in a biological sample from the subject, wherein the biomarker is CD44, CD83 or combination thereof, and   b) comparing the level of the biomarker in the biological sample to a reference level of the biomarker;   wherein the difference between the level of the biomarker in the biological sample from the subject and the reference level of the biomarker correlates with the responsiveness of the subject to the treatment; and   wherein the treatment compound is (S)-3-(4-((4-(morpholinomethyl)benzyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, or a pharmaceutically acceptable salt, solid form, solvate, hydrate, stereoisomer, tautomer or racemic mixture thereof.   
     
     
         24 . A method of predicting the responsiveness of a subject to a treatment of a disease, disorder, or condition with a treatment compound, comprising:
 a) determining the level of a biomarker in a biological sample from the subject, wherein the biomarker is CD44, CD83 or combination thereof,   b) determining the level of the biomarker in a control sample; and   c) comparing the level of the biomarker in the biological sample from the subject to the level of the biomarker in the control sample;   wherein the difference between the level of the biomarker in the biological sample from the subject and the level of the biomarker in the control sample correlates with the responsiveness of the subject to the treatment; and   wherein the treatment compound is (S)-3-(4-((4-(morpholinomethyl)benzyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, or a pharmaceutically acceptable salt, solid form, solvate, hydrate, stereoisomer, tautomer or racemic mixture thereof.   
     
     
         25 . A method of monitoring the efficacy of a treatment of a disease, disorder, or condition in a subject treated with a treatment compound, comprising:
 a) obtaining a first biological sample from the subject;   b) determining the level of a biomarker in the first biological sample, wherein the biomarker is the CD44, CD83 or combination thereof;   c) administering the treatment compound to the subject;   d) thereafter obtaining a second biological sample from the subject;   e) determining the level of the biomarker in the second biological sample, and   f) comparing the levels of the biomarker in the first and second biological samples;   wherein the subject is responsive to the treatment if the level of the biomarker in the second biological sample of the subject is altered as compared to the level of the biomarker in the first biological sample of the subject; and   wherein the treatment compound is (S)-3-(4-((4-(morpholinomethyl)benzyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, or a pharmaceutically acceptable salt, solid form, solvate, hydrate, stereoisomer, tautomer or racemic mixture thereof.   
     
     
         26 . A method of monitoring the compliance of a subject with a treatment of a disease, disorder, or condition with a treatment compound, comprising:
 a) obtaining a biological sample from the subject;   b) determining the level of a biomarker in the biological sample, wherein the biomarker is CD44, CD83 or combination thereof; and   c) comparing the level of the biomarker with the level of the biomarker in a control untreated sample from the subject;   wherein the change in the level of the biomarker in the biological sample in comparison with the level of the biomarker in the control sample indicates the compliance of the subject with the treatment; and   wherein the treatment compound is (S)-3-(4-((4-(morpholinomethyl)benzyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, or a pharmaceutically acceptable salt, solid form, solvate, hydrate, stereoisomer, tautomer or racemic mixture thereof.   
     
     
         27 . (canceled) 
     
     
         28 . The method of  claim 21 , wherein the treatment compound is (S)-3-(4-((4-(morpholinomethyl)benzyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione. 
     
     
         29 . The method of  claim 21 , wherein the treatment compound is (S)-3-(4-((4-(morpholinomethyl)benzyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione hydrochloride. 
     
     
         30 . The method of  claim 21 , wherein the biomarker is CD83, and wherein the subject is likely to be responsive to the treatment if the level of the biomarker in the biological sample from the subject is higher than the reference level of the biomarker. 
     
     
         31 . The method of  claim 21 , wherein the biomarker is CD44, and wherein the subject is likely to be responsive to the treatment if the level of the biomarker in the biological sample from the subject is lower than the reference level of the biomarker. 
     
     
         32 . The method of  claim 22 , wherein the biomarker is CD83, and wherein the subject is likely to be responsive to the treatment if the level of the biomarker in the biological sample from the subject is higher than the level of the biomarker in the control sample. 
     
     
         33 . The method of  claim 22 , wherein the biomarker is CD44, and wherein the subject is likely to be responsive to the treatment if the level of the biomarker in the biological sample from the subject is lower than the level of the biomarker in the control sample. 
     
     
         34 . The method of  claim 23 , wherein the biomarker is CD83, and wherein an increased level of the biomarker in the biological sample from the subject in comparison with the reference level of the biomarker correlates with an increased responsiveness of the subject to the treatment. 
     
     
         35 . The method of  claim 23 , wherein the biomarker is CD44, and wherein a decreased level of the biomarker in the biological sample from the subject in comparison with the reference level of the biomarker correlates with an increased responsiveness of the subject to the treatment. 
     
     
         36 . The method of  claim 24 , wherein the biomarker is CD83, and wherein an increased level of the biomarker in the biological sample from the subject in comparison with the level of the biomarker in the control sample correlates with an increased responsiveness of the subject to the treatment. 
     
     
         37 . The method of  claim 24 , wherein the biomarker is CD44, and wherein a decreased level of the biomarker in the biological sample from the subject in comparison with the level of the biomarker in the control sample correlates with an increased responsiveness of the subject to the treatment. 
     
     
         38 . The method of  claim 25 , wherein the biomarker is CD83, and wherein the subject is responsive to the treatment if the level of the biomarker in the second biological sample of the subject is higher than the level of the biomarker in the first biological sample of the subject. 
     
     
         39 . The method of  claim 25 , wherein the biomarker is CD44, and wherein the subject is responsive to the treatment if the level of the biomarker in the second biological sample of the subject is lower than the level of the biomarker in the first biological sample of the subject. 
     
     
         40 . The method of  claim 26 , wherein the biomarker is CD83, and wherein an increased level of the biomarker in the biological sample in comparison with the level of the biomarker in the control sample indicates the compliance of the subject with the treatment. 
     
     
         41 . The method of  claim 26 , wherein the biomarker is CD44, and wherein a decreased level of the biomarker in the biological sample in comparison with the level of the biomarker in the control sample indicates the compliance of the subject with the treatment.