Methods and Compositions for the Treatment of Celiac Disease, Non-Celiac Gluten Sensitivity, and Refractory Celiac Disease

Abstract

Methods and pharmaceutical compositions are provided herein for the treatment of inflammatory disorders, in particular celiac disease, refractory celiac disease and non-celiac gluten sensitivity.

1 . A method of treating celiac disease or non-celiac gluten sensitivity in a subject in need thereof, comprising administering a therapeutically effective amount of an anti-IL-15 antibody or antigen-binding fragment thereof to the subject, wherein the therapeutically effective amount comprises 1-20 unit doses each administered at about about 300 mg or about 600 mg of the anti-IL-15 antibody or antigen-binding fragment thereof, wherein the anti-IL-15 antibody or antigen-binding fragment thereof comprises a heavy chain variable region comprising complementarity determining regions (CDRs) set forth in SEQ ID NOs: 5-7, and a light chain variable region comprising CDRs set forth in SEQ ID NOs: 8-10. 
     
     
         2 . (canceled) 
     
     
         3 . (canceled) 
     
     
         4 . The method of  claim 1 , wherein the anti-IL-15 antibody or antigen-binding fragment thereof comprises a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 2, and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 4. 
     
     
         5 . (canceled) 
     
     
         6 . The method of  claim 1 , wherein the therapeutically effective amount comprises 6 unit doses administered at about 2 week intervals. 
     
     
         7 . The method of  claim 1 , wherein the anti-IL-15 antibody or antigen-binding fragment thereof is administered by subcutaneous injection. 
     
     
         8 - 14 . (canceled) 
     
     
         15 . A method of treating refractory celiac disease in a subject in need thereof, comprising administering a therapeutically effective amount of an anti-IL-15 antibody or antigen-binding fragment thereof to the subject, wherein the therapeutically effective amount comprises 1-20 unit doses each administered at about 2 week intervals, each unit dose comprising about 8 mg/kg of the anti-IL-15 antibody or antigen-binding fragment thereof, wherein the anti-IL-15 antibody or antigen-binding fragment thereof comprises a heavy chain variable region comprising complementarity determining regions (CDRs) set forth in SEQ ID NOs: 5-7, and a light chain variable region comprising CDRs set forth in SEQ ID NOs: 8-10. 
     
     
         16 . (canceled) 
     
     
         17 . (canceled) 
     
     
         18 . The method of  claim 15 , wherein the anti-IL-15 antibody or antigen-binding fragment thereof comprises a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 2, and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 4. 
     
     
         19 . (canceled) 
     
     
         20 . The method of  claim 15 , wherein the therapeutically effective amount comprises 6 unit doses administered at 2 week intervals, and an optional additional loading dose at week 1. 
     
     
         21 . The method of  claim 15 , wherein each unit dose is administered by intravenous injection. 
     
     
         22 . The method of  claim 15 , wherein the refractory celiac disease is type II. 
     
     
         23 - 30 . (canceled) 
     
     
         31 . The method of  claim 15 , wherein the anti-IL-15 antibody or antigen-binding fragment thereof is administered by subcutaneous injection. 
     
     
         32 . The method of  claim 1 , wherein the anti-IL-15 antibody or antigen-binding fragment thereof is administered by intravenous injection. 
     
     
         33 . The method of  claim 1 , wherein each unit dose comprises about 300 mg of the anti-IL-15 antibody or antigen-binding fragment thereof. 
     
     
         34 . The method of  claim 1 , wherein each unit dose comprises about 600 mg of the anti-IL-15 antibody or antigen-binding fragment thereof. 
     
     
         35 . The method of  claim 15 , wherein the refractory celiac disease is type I. 
     
     
         36 . The method of  claim 1 , wherein the method treats celiac disease. 
     
     
         37 . The method of  claim 1 , wherein the method treats non-celiac gluten sensitivity.