Oral Polypeptide Constructs for GI Barrier Delivery
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Solution Overview
Problem
Oral administration of therapeutic polypeptides and proteins is challenging due to proteolytic degradation in the gastrointestinal tract and poor absorption, limiting their bioavailability.
Innovation Solution
Development of polypeptide constructs comprising a first polypeptide with a specific amino acid sequence and a heterologous polypeptide linked by an amide bond, which enhances targeted delivery across the gastrointestinal lining.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of operation
If therapeutic polypeptides are administered orally, then convenience and cost-effectiveness are improved, but proteolytic degradation occurs and bioavailability remains poor
Solution Approach 1:
The patent employs a polypeptide carrier (first polypeptide) that acts as an intermediary to deliver the therapeutic polypeptide (second polypeptide) across the gastrointestinal lining. The carrier facilitates transport through the intestinal barrier and into the bloodstream, protecting the therapeutic from degradation while enabling oral administration. This mediator approach resolves the contradiction by maintaining the convenience of oral delivery while achieving reliable bioavailability through the protective carrier function.
2Reliability
If therapeutic polypeptides are administered by injection or infusion, then bioavailability is improved, but convenience and patient burden worsen
Solution Approach 1:
The patent enables the gastrointestinal tract to perform the delivery function that would otherwise require external intervention. The polypeptide construct is designed to be absorbed through the intestinal lining via physiological processes, eliminating the need for injections or infusions. The body's own digestive system serves the dual purpose of delivery and absorption, transforming a passive recipient into an active transport mechanism, thereby improving both bioavailability and ease of administration.
3Reliability
If polypeptide constructs are designed for oral delivery, then bioavailability is improved, but molecular complexity and structural requirements increase
Solution Approach 1:
The patent divides the delivery system into two functional segments: a carrier polypeptide (first polypeptide) responsible for transport and protection, and a therapeutic polypeptide (second polypeptide) providing the desired biological activity. This segmentation allows each component to be optimized independently - the carrier for delivery efficiency and the therapeutic for biological function - while maintaining overall manageable complexity compared to designing a single multifunctional molecule.
Data Source
AI summary
Compositions and methods for the targeted delivery of therapeutic polypeptides and protein-based therapeutics across the gastrointestinal lining are disclosed. In one aspect, provided is a polypeptide construct comprising (a) a first polypeptide comprising an amino acid sequence that is at least 80% identical to an amino acid sequence selected from any one of SEQ ID NO: 1-40; and (b) a second polypeptide, wherein the second polypeptide is heterologous to the first polypeptide. In one aspect, the heterologous polypeptide is a therapeutic polypeptide.