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 1-12 week intervals, each unit dose independently comprising about 50-1000 mg, preferably 75-600 mg, more preferably about 75 mg, about 150 mg, about 300 mg or about 450 mg or about 600 mg of the anti-IL-15 antibody or antigen-binding fragment thereof. 
     
     
         2 . The method of  claim 1 , wherein the antibody has a heavy chain variable region comprising one or more complementarity determining regions of SEQ ID NOs:5-7, or a sequence having at least 80% sequence identity thereto. 
     
     
         3 . The method of  claim 1 , wherein the antibody has a light chain variable region comprising one or more complementarity determining regions of SEQ ID NOs:8-10, or a sequence having at least 80% sequence identity thereto. 
     
     
         4 . The method of  claim 1 , wherein the antibody has a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:2, or a sequence having at least 80% sequence identity thereto. 
     
     
         5 . The method of  claim 3 , wherein the antibody has a light chain variable region comprising the amino acid sequence of SEQ ID NO:4, or a sequence having at least 80% sequence identity thereto. 
     
     
         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 each unit dose is administered by subcutaneous injection or intravenous injection. 
     
     
         8 . A pharmaceutical composition for the treatment of celiac disease or non-celiac gluten sensitivity, comprising a therapeutically effective amount of an anti-IL-15 antibody or antigen-binding fragment thereof, wherein the therapeutically effective amount comprises 1-20 unit doses each to be administered at about 1-12 week intervals, each unit dose independently comprising about 50-1000 mg, preferably 75-600 mg, more preferably about 75 mg, about 150 mg, about 300 mg or about 450 mg or about 600 mg of the anti-IL-15 antibody or antigen-binding fragment thereof. 
     
     
         9 . The pharmaceutical composition of  claim 8 , wherein the antibody has a heavy chain variable region comprising one or more complementarity determining regions of SEQ ID NOs:5-7, or a sequence having at least 80% sequence identity thereto. 
     
     
         10 . The pharmaceutical composition of  claim 8 , wherein the antibody has a light chain variable region comprising one or more complementarity determining regions of SEQ ID NOs:8-10, or a sequence having at least 80% sequence identity thereto. 
     
     
         11 . The pharmaceutical composition of  claim 8 , wherein the antibody has a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:2, or a sequence having at least 80% sequence identity thereto. 
     
     
         12 . The pharmaceutical composition of  claim 10 , wherein the antibody has a light chain variable region comprising the amino acid sequence of SEQ ID NO:4, or a sequence having at least 80% sequence identity thereto. 
     
     
         13 . The pharmaceutical composition of  claim 8 , wherein the therapeutically effective amount comprises 6 unit doses to be administered at 2 week intervals. 
     
     
         14 . The pharmaceutical composition of  claim 8 , wherein each unit dose is administered by subcutaneous injection or intravenous injection. 
     
     
         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 1-12 week intervals, each unit dose independently comprising about 1-50 mg/kg, preferably about 4-16 mg/kg, more preferably about 4 mg/kg, about 8 mg/kg, about 12 mg/kg or about 16 mg/kg of the anti-IL-15 antibody or antigen-binding fragment thereof. 
     
     
         16 . The method of  claim 15 , wherein the antibody has a heavy chain variable region comprising one or more complementarity determining regions of SEQ ID NOs:5-7, or a sequence having at least 80% sequence identity thereto. 
     
     
         17 . The method of  claim 15 , wherein the antibody has a light chain variable region comprising one or more complementarity determining regions of SEQ ID NOs:8-10, or a sequence having at least 80% sequence identity thereto. 
     
     
         18 . The method of  claim 15 , wherein the antibody has a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:2, or a sequence having at least 80% sequence identity thereto. 
     
     
         19 . The method of  claim 17 , wherein the antibody has a light chain variable region comprising the amino acid sequence of SEQ ID NO:4, or a sequence having at least 80% sequence identity thereto. 
     
     
         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 subcutaneous injection or intravenous injection. 
     
     
         22 . The method of  claim 15 , wherein the refractory celiac disease is type I or type II. 
     
     
         23 . A pharmaceutical composition for the treatment of refractory celiac disease, comprising a therapeutically effective amount of an anti-IL-15 antibody or antigen-binding fragment thereof, wherein the therapeutically effective amount comprises 1-20 unit doses each administered at about 1-12 week intervals, each unit dose independently comprising about 1-50 mg/kg, preferably about 4-16 mg/kg, more preferably about 4 mg/kg, about 8 mg/kg, about 12 mg/kg or about 16 mg/kg of the anti-IL-15 antibody or antigen-binding fragment thereof. 
     
     
         24 . The pharmaceutical composition of  claim 23 , wherein the antibody has a heavy chain variable region comprising one or more complementarity determining regions of SEQ ID NOs:5-7, or a sequence having at least 80% sequence identity thereto. 
     
     
         25 . The pharmaceutical composition of  claim 23 , wherein the antibody has a light chain variable region comprising one or more complementarity determining regions of SEQ ID NOs:8-10, or a sequence having at least 80% sequence identity thereto. 
     
     
         26 . The pharmaceutical composition of  claim 23 , wherein the antibody has a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:2, or a sequence having at least 80% sequence identity thereto. 
     
     
         27 . The pharmaceutical composition of  claim 25 , wherein the antibody has a light chain variable region comprising the amino acid sequence of SEQ ID NO:4, or a sequence having at least 80% sequence identity thereto. 
     
     
         28 . The pharmaceutical composition of  claim 23 , wherein the therapeutically effective amount comprises 6 unit doses to be administered at 2 week intervals, and an optional additional loading dose to be administered at week 1. 
     
     
         29 . The pharmaceutical composition of  claim 23 , wherein each unit dose is administered by subcutaneous injection or intravenous injection. 
     
     
         30 . The pharmaceutical composition of  claim 23 , wherein the refractory celiac disease is type I or type II.