Topical treatment of inflammatory bowel disease using antibodies and fragments thereof
Inventors
YADAV, Vipul • Basit, Abdul Waseh • OLIVEIRA VARUM, Felipe José • BRAVO GONZALÉZ, Roberto Carlos • FURRER, Esther Maria
Assignees
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Publication Number
US-11717484-B2
Publication Date
2023-08-08
Expiration Date
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.
Core Innovation
The invention relates to topical rectal administration treatment of inflammatory bowel disease in a human patient using a composition containing an active agent selected from antibodies specific to tumor necrosis factor alpha (TNFα) and functional fragments thereof. The composition further includes one or more suitable buffer agents and/or acidifiers effective to reduce the luminal pH in the large intestine, and administration results in local accumulation of the active agent in the gastrointestinal wall.
The invention addresses decreasing the pH in the large intestinal lumen to between 5.5 and 6.5, including narrower ranges such as 5.7 to 6.3. The pH reduction supports delivery into the large intestinal wall and facilitates uptake and/or penetration of the active agent into the gastrointestinal wall, with local microenvironment pH controlled to promote retention and deeper penetration in the mucosal layer and submucosal layer.
The disclosed composition is formulated for rectal administration, including enema, gel, foam, and suppository. The active agent scope includes TNFα-specific antibodies and functional fragments such as Fab, F(ab′)2, Fab′, scFv, dsFv, VHH, diabody, triabody, tetrabody, and Fc fusion protein formats.
Claims Coverage
The document includes one independent claim and defines a rectally administered anti-TNFα antibody composition with pH-reduction constraints in the large intestinal lumen. The independent claim includes two main inventive features, together with post-administration conditions for local accumulation and luminal pH between 5.5 and 6.5.
Rectal anti-TNFα composition with luminal pH reduction
A composition comprising antibodies specific to tumor necrosis factor alpha (TNFα) and functional fragments thereof, and an amount of one or more suitable buffer agents and/or acidifiers effective to reduce the luminal pH in the large intestine, formulated for rectal administration for use in the treatment of inflammatory bowel disease in a human patient.
Local accumulation with large intestinal lumen pH of 5.5 to 6.5
Administration of said composition results in the local accumulation of the active agent in the gastrointestinal wall and a decrease of a pH in the large intestinal lumen of said patient to between 5.5 and 6.5.
Across the claim set, the main inventive focus is on using rectal delivery of TNFα-specific antibodies or functional fragments in combination with buffer agents and/or acidifiers to reduce large intestinal luminal pH to a defined weakly acidic range, while enabling local accumulation in the gastrointestinal wall.
Stated Advantages
Not explicitly described in patent.
Documented Applications
Not explicitly described in patent.
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