Antibody Stabilization with Dipeptides in Intestinal Fluid
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Solution Overview
Problem
Current biopharmaceuticals, such as antibodies, face significant stability challenges in the intestinal fluid of the ileum and colon, leading to ineffective oral or rectal administration and necessitating inconvenient intravenous or subcutaneous delivery.
Innovation Solution
A pharmaceutical composition comprising an antibody or antigen binding fragment, combined with carnosine and/or diglycine, and optionally aprotinin as an enzyme inhibitor, which stabilizes the antibody in intestinal fluid, enabling effective delivery to the ileum and/or colon via oral or rectal administration.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of operation
If oral or rectal administration is used for antibody delivery, then patient convenience is improved, but antibody stability in intestinal fluid deteriorates
Solution Approach 1:
The patent introduces dipeptides (carnosine and/or diglycine) as intermediary substances that mediate between the antibody and the harsh intestinal environment. These dipeptides act as stabilizing agents that protect the antibody from degradation by proteolytic enzymes in intestinal fluid, thereby enabling oral or rectal administration while maintaining antibody stability
Solution Approach 2:
The patent changes the chemical environment parameters by adding dipeptides that alter the proteolytic activity in intestinal fluid. The dipeptides modify the biochemical parameters of the intestinal environment to create conditions favorable for antibody stability, allowing the antibody to survive passage through the gastrointestinal tract
2Stability of the object's composition
If intravenous or subcutaneous delivery is used for antibody delivery, then antibody stability is improved, but patient convenience and compliance deteriorate
Solution Approach 1:
The dipeptides serve as protective intermediaries that enable the antibody to withstand the intestinal environment, thereby allowing convenient oral or rectal administration routes to replace inconvenient parenteral routes while maintaining therapeutic efficacy
3Reliability
If high systemic doses of mAbs are administered, then therapeutic effect is improved, but systemic adverse effects and anti-drug antibody formation increase
Solution Approach 1:
The patent enables localized delivery of antibodies to the gastrointestinal tract through oral or rectal administration with dipeptide stabilization. This allows the antibody to act locally at the site of need (intestinal mucosa) rather than requiring high systemic doses, thereby reducing systemic exposure and associated adverse effects while maintaining therapeutic efficacy at the target site
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
The composition significantly reduces antibody degradation in intestinal fluids, allowing for sustained therapeutic effects and improved patient convenience by facilitating oral or rectal administration.
Implementation Method 1
The use of camostat mesylate for stabilization of the therapeutic proteins against degradation in the intestinal environment is disclosed in WO 2014/030052
Data Source
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AI summary
This invention relates pharmaceutical compositions comprising a protein as the active ingredient together with one or more dipeptides as stabilising agents, and optionally an enzyme inhibitor. The compositions are particularly useful for administration to the intestinal tract.