Topical treatment of inflammatory bowel disease using antibodies and fragments thereof

Abstract

The present invention relates to the therapeutic uses of compositions containing antibody molecules and functional fragments thereof, e.g antibody molecules and functional fragments capable of binding to tumor necrosis factor alpha (TNFα), in the topical treatment of inflammatory bowel diseases, including Crohn's disease and ulcerative colitis.

What is claimed: 
     
         1 . A composition comprising an active agent selected from the group consisting of antibodies specific to tumor necrosis factor alpha (TNFα) and functional fragments thereof, formulated for oral administration for use in the treatment of an inflammatory bowel disease in a human patient, wherein said treatment results in a decrease of a pH in the large intestinal lumen of said patient. 
     
     
         2 . The composition according to  claim 1 , wherein said composition reduces the pH of a local microenvironment of the antibody or functional fragment thereof in the large intestinal lumen. 
     
     
         3 . The composition according to  claim 1 , wherein the decrease of pH in the large intestinal lumen facilitates the uptake and/or penetration of the active agent into the gastrointestinal wall. 
     
     
         4 . The composition according to  claim 1 , wherein said treatment results in a pH in the large intestinal lumen reading that is 6.5. 
     
     
         5 . The composition according to  claim 1 , wherein said treatment results in a pH in the large intestinal lumen that ranges from 5.5 to 6.5. 
     
     
         6 . The composition according to  claim 1 , said composition further comprising at least one additive selected from the group consisting of: buffer agents, acidifiers and combinations thereof. 
     
     
         7 . The composition according to  claim 6 , wherein the at least one additive is an acidifier selected from the group consisting of: acetic acid, adipic acid, ascorbic acid, citric acid, fumaric acid, itaconic acid, lactic acid, maleic acid, malic acid, phosphoric acid, propionic acid, succinic acid, sorbic acid and tartaric acid. 
     
     
         8 . The composition according to  claim 1 , wherein said human patient afflicted with inflammatory bowel disease is in remission or, alternatively, suffers from a mild or moderate form of the inflammatory bowel disease. 
     
     
         9 . The composition according to  claim 1 , wherein said treatment results in a concentration of the anti-TNFα antibody or functional fragment thereof in the large intestinal lumen of said human patient being treated in the range of 0.02 to 1 mg/ml. 
     
     
         10 . The composition according to  claim 1 , wherein the functional antibody fragment specific to TNFα is selected from the group consisting of: a Fab fragment, a F(ab′) 2  fragment, a Fab′ fragment, an scFv, a dsFv, a VHH, a diabody, a triabody, a tetrabody, an Fc fusion protein and a minibody. 
     
     
         11 . The composition according to  claim 1 , wherein the composition is a solid dosage form in the form of a pellet, granule, micro particle, nano particle, mini tablet, capsule or tablet coated with a coating material that prevents release of the active agent before entering the ileocolonic region of the intestine. 
     
     
         12 . The composition according to  claim 11 , wherein the coating material is selected from the group consisting of materials that disintegrate pH-dependently, materials that disintegrate time-dependently, materials that disintegrate due to enzymatic triggers in the large intestinal environment, and combinations thereof. 
     
     
         13 . The composition according to  claim 1 , wherein the pH in the large intestinal lumen of the human patient before the treatment is higher than 6.5. 
     
     
         14 . The composition according to  claim 1 , wherein said treatment results in a pH in the large intestinal lumen that ranges from 5.7 to 6.3. 
     
     
         15 . The composition according to  claim 1 , wherein said treatment results in a pH in the large intestinal lumen that ranges from 5.9 to 6.1. 
     
     
         16 . The composition according to  claim 1 , wherein said treatment results in a concentration of the anti-TNFα antibody or functional fragment thereof in the large intestinal lumen of said human patient being treated in the range of 0.2 to 0.8 mg/ml.