Glucocorticoid receptor agonist and immunoconjugates thereof

Abstract

Provided herein are glucocorticoid receptor agonist immunoconjugates, glucocorticoid receptor agonists, and methods of using the same.

What is claimed is: 
     
         1 . An antibody drug conjugate comprising:
 (a) an anti-TNFα antibody comprising a heavy chain set forth as SEQ ID NO: 3 and a light chain set forth as SEQ ID NO: 4; and   (b) a glucocorticoid receptor agonist comprising a radical represented by the formula:   
       
         
           
           
               
               
           
         
         wherein the antibody is conjugated to the glucocorticoid receptor agonist via a linker represented by the formula: 
       
       
         
           
           
               
               
           
         
       
     
     
         2 . The antibody drug conjugate of  claim 1 , according to the formula: 
       
         
           
           
               
               
           
         
         wherein A is the antibody and n is an integer from 1-10. 
       
     
     
         3 . The antibody drug conjugate of  claim 2 , wherein n is 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10. 
     
     
         4 . The antibody drug conjugate of  claim 2 , wherein n is 4. 
     
     
         5 . The antibody drug conjugate of  claim 2 , wherein n is 2. 
     
     
         6 . A pharmaceutical composition comprising the antibody drug conjugate of  claim 4  and a pharmaceutically acceptable carrier. 
     
     
         7 . A method of treating a condition selected from rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, plaque psoriasis, ulcerative colitis, adult Crohn's disease, pediatric Crohn's disease, uveitis, hidradenitis suppurativa, and juvenile idiopathic arthritis in a subject, comprising administering an effective amount of the antibody drug conjugate of  claim 4  to the subject. 
     
     
         8 . A kit comprising:
 (a) a container comprising the antibody drug conjugate of  claim 4  or the pharmaceutical composition of  claim 6 ; and   (b) a label or package insert on or associated with the one or more containers, wherein the label or package insert indicates that the antibody drug conjugate or pharmaceutical composition is used for treating a condition selected from rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, plaque psoriasis, ulcerative colitis, adult Crohn's disease, pediatric Crohn's disease, uveitis, hidradenitis suppurativa, and juvenile idiopathic arthritis.   
     
     
         9 . A method of delivering a glucocorticoid receptor agonist to a TNFα-expressing cell, comprising the step of contacting the cell with the antibody drug conjugate of  claim 4 . 
     
     
         10 . An antibody drug conjugate according to the formula: 
       
         
           
           
               
               
           
         
         wherein A is adalimumab and n is 4. 
       
     
     
         11 . An antibody drug conjugate according to the formula: 
       
         
           
           
               
               
           
         
         wherein A is adalimumab and n is 2.