Orally Administered RPtag Large Protein Stability
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Solution Overview
Problem
Therapeutic proteins and peptides face challenges in oral delivery due to gastrointestinal epithelium barriers, enzymatic degradation, and acidic environments, making it difficult to administer them effectively and affordably for treating various diseases.
Innovation Solution
Development of stable protein compositions, such as RPtag large, which is resistant to denaturation and degradation, and can be conjugated with absorption tags like B12 to facilitate oral bioavailability and systemic delivery, allowing for targeting specific antigens or tissues within the gastrointestinal tract or elsewhere in the body.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If therapeutic antibodies are administered intravenously to maintain structural integrity, then treatment effectiveness is improved, but treatment cost and complexity increase significantly
Solution Approach 1:
The patent changes the molecular parameters of the antibody by creating truncated variants (e.g., removing constant regions, reducing size from full-length IgG to smaller fragments) that maintain binding functionality while improving stability and reducing complexity of administration
Solution Approach 2:
The patent extracts only the essential functional domains of the antibody (variable regions and part of constant regions) to create minimal viable therapeutic proteins that retain target binding capability but eliminate unnecessary complexity and improve oral stability
2Ease of manufacture
If therapeutic antibodies are made compact like monobodies, then ease of production and stability improve, but binding capability and therapeutic effectiveness may be reduced
Solution Approach 1:
The patent designs truncated antibody variants that can perform multiple functions: maintaining high-affinity binding to targets, resisting gastrointestinal degradation, and being absorbed systemically, all within a compact structure that is easier to produce than full-length antibodies
3Ease of operation
If proteins are delivered orally to reduce cost and increase convenience, then ease of administration improves, but structural integrity and bioavailability are compromised by GI tract conditions
Solution Approach 1:
The patent applies preliminary protective measures by designing proteins with enhanced stability features (disulfide bonds, compact folding, resistant sequences) that pre-counteract the denaturing effects of gastric acid and proteases before the protein encounters these harsh conditions in the GI tract
Solution Approach 2:
The patent uses absorption-enhancing compounds or conjugates as intermediaries that facilitate the transport of truncated antibody proteins across the gastrointestinal epithelium into systemic circulation, protecting the protein during transit and enabling oral bioavailability
Data Source
AI summary
Disclosed herein are compositions comprising one or more therapeutic proteins for oral administration. The disclosed proteins, which may be directed to a variety of GI and systemic target antigens, resist denaturation and degradation in the stomach and intestines of a patient. The disclosed proteins may be delivered intact to a target region within the gut, or anywhere in body to target specific molecules, cells, tissues, or organs. In some embodiments, the disclosed proteins may include two or more proteins for targeting two or more target antigens.