Stapled Dual GIP/GLP-1 Peptide Conjugates for Extended Half-Life
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Solution Overview
Problem
Therapeutic agents often have short half-lives, requiring frequent administration and higher dosages, which can lead to reduced compliance, higher costs, and increased side effects.
Innovation Solution
Development of peptide conjugates with a staple attached to specific amino acids, enhancing the half-life of peptides by stabilizing their structure and increasing their circulatory stability.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Duration of action of moving object
If therapeutic agents are administered more frequently with higher dosages to compensate for short half-lives, then the pharmacologic activity is maintained, but patient compliance decreases and side effects increase
Solution Approach 1:
The patent modifies the peptide structure by introducing staples (cyclic constraints) and PEGylating chains to change the physical and chemical parameters of the therapeutic agent. These structural modifications increase the molecular weight and alter the hydrodynamic radius, thereby extending the half-life of the peptide in circulation without requiring more frequent administration
Solution Approach 2:
The patent creates composite structures by combining peptides with synthetic staples and PEGylating chains. This composite approach integrates the biological activity of the peptide with the stability and extended circulation properties of the synthetic components, achieving both maintained efficacy and reduced administration frequency
2Duration of action of moving object
If therapeutic agents are administered more frequently with higher dosages to compensate for short half-lives, then the pharmacologic activity is maintained, but treatment costs increase
Solution Approach 1:
By changing the structural parameters of the peptide through stapling and PEGylation, the patent achieves extended half-life that allows for less frequent administration. This reduces the total quantity of substance required over time, as the drug remains active in the system for longer periods between doses
3Duration of action of moving object
If therapeutic agents are administered more frequently with higher dosages to compensate for short half-lives, then the pharmacologic activity is maintained, but the risk of side effects increases
Solution Approach 1:
The structural modifications through stapling and PEGylation change the pharmacokinetic parameters of the peptide, extending its half-life and reducing the frequency of administration. This reduces the cumulative exposure to side effects while maintaining therapeutic efficacy through sustained drug levels
4Duration of action of moving object
If peptide structure is stabilized by attaching staples to extend half-life, then the duration of action increases, but the molecular complexity increases
Solution Approach 1:
The patent applies systematic parameter changes by introducing standardized staple structures and PEGylating chains with defined architectures. While this increases molecular complexity, the modifications follow predictable patterns that allow for rational design and optimization, balancing the increased complexity against the significant benefit of extended half-life
Data Source
AI summary
Provided herein are peptides and peptide conjugates comprising a dual glucose-dependent insulinotropic polypeptide (GIP) and GLP-1 receptor agonist. The peptides may be used for blood glucose management and treating conditions such as diabetes, obesity, non-alcoholic fatty liver disease (NAFLD), and non-alcoholic steatohepatitis (NASH).