Treatment of a disease of the gastrointestinal tract with a chemokine/chemokine receptor inhibitor

Abstract

This disclosure features methods and compositions for treating diseases of the gastrointestinal tract with a chemokine/chemokine receptor inhibitor.

1 .- 383 . (canceled) 
     
     
         384 . A method of treating a disease of the gastrointestinal (GI) tract in a subject, the method comprising:
 orally administering to the subject a pharmaceutical composition comprising a therapeutically effective amount of a chemokine/chemokine receptor inhibitor; and   releasing the pharmaceutical composition at a desired location in the GI tract of the subject;   wherein the release of the pharmaceutical composition results in a concentration of the chemokine/chemokine receptor inhibitor in the GI tissue that is higher than the concentration of the chemokine/chemokine receptor inhibitor in the blood, serum, or plasma.   
     
     
         385 . The method of  claim 384 , wherein the concentration of the chemokine/chemokine receptor inhibitor in the GI tissue is about 2 times, about 3 times, about 4 times, about 5 times, about 6 times, about 7 times, about 8 times, about 9 times, or about 10 times higher than the concentration of the chemokine/chemokine receptor inhibitor in the blood, serum, or plasma. 
     
     
         386 . The method of  claim 384 , wherein the concentration of the chemokine/chemokine receptor inhibitor released at the desired location in the GI tract is 10%, 25%, 50%, 75%, 100%, 200%, 300%, 400%, 500%, 1000%, or 2000% greater than the concentration of chemokine/chemokine receptor inhibitor in plasma. 
     
     
         387 . The method of  claim 384 , wherein the concentration C max  of the chemokine/chemokine receptor inhibitor in the plasma of the subject is less than 1 μg/mL, less than 0.3 μg/mL, less than 0.1 μg/mL, or less than 0.01 μg/mL. 
     
     
         388 . The method of  claim 384 , wherein the amount of the chemokine/chemokine receptor inhibitor administered orally is less than an amount that is therapeutically effective when the chemokine/chemokine receptor inhibitor is administered systemically. 
     
     
         389 . The method of  claim 384 , wherein the pharmaceutical composition is released in the distal portion of the ileum, the cecum, or the ascending colon. 
     
     
         390 . The method of  claim 389 , wherein the distal portion of the ileum, the cecum, or the ascending colon has been predetermined to be proximal to one or more disease sites. 
     
     
         391 . The method of  claim 390 , wherein the one or more disease sites is in the colon. 
     
     
         392 . The method of  claim 389 , wherein releasing the pharmaceutical composition in the distal portion of the ileum, the cecum, or the ascending colon distributes the chemokine/chemokine receptor inhibitor in all segments of the colon. 
     
     
         393 . The method of  claim 384 , wherein the disease of the GI tract is an inflammatory bowel disease. 
     
     
         394 . The method of  claim 384 , wherein the chemokine/chemokine receptor inhibitor is selected from the group consisting of a CXCL10 inhibitor, a CXCR3 inhibitor, a CCL11 inhibitor, an ELR chemokine inhibitor, a CCR2 inhibitor, a CCR9 inhibitor, and combinations thereof. 
     
     
         395 . The method of  claim 384 , wherein the chemokine/chemokine receptor inhibitor is an antibody or an antigen-binding fragment thereof. 
     
     
         396 . The method of  claim 395 , wherein the chemokine/chemokine receptor inhibitor is a monoclonal antibody selected from the group consisting of eldelumab, BMS-986184, LY-3041658, NI-0801, GSK3050002, and E-6011. 
     
     
         397 . The method of  claim 384 , wherein the pharmaceutical composition is a solution of the chemokine/chemokine receptor inhibitor in a liquid medium. 
     
     
         398 . The method of  claim 397 , wherein the pharmaceutical composition is a suspension of the chemokine/chemokine receptor inhibitor in a liquid medium. 
     
     
         399 . The method of  claim 384 , wherein, before being released, the pharmaceutical composition is disposed in an ingestible device. 
     
     
         400 . The method of  claim 399 , wherein the ingestible device comprises:
 a storage reservoir configured to store the pharmaceutical composition before the pharmaceutical composition is released; and   a device configured to provide a gas pressure sufficient to release the pharmaceutical composition from of the ingestible device.   
     
     
         401 . The method of  claim 400 , wherein the ingestible device further comprises a safety device configured to relieve a pressure within the ingestible when the pressure exceeds a threshold level. 
     
     
         402 . The reservoir of  claim 400 , wherein the reservoir is configured to attach to the housing of the ingestible device. 
     
     
         403 . The reservoir of  claim 400 , wherein the reservoir is configured to friction fit with the ingestible device.