Stapled Peptide Lipid Conjugates for Stable Serum Drug Levels
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Solution Overview
Problem
Biological drugs often have short half-lives, requiring frequent administration and leading to reduced compliance, higher costs, and increased risks of side effects due to higher dosages and frequent administration, which current strategies for extending half-lives are not efficient.
Innovation Solution
The development of therapeutic agents comprising a therapeutic agent, a first staple, and a first half-life extending molecule, wherein the therapeutic agent is covalently attached to the first staple via two amino acid residues, with the half-life of the modified therapeutic agent being extended by incorporating a first staple and a first half-life extending molecule, such as a lipid or polyglycol region, to enhance biological, chemical, physiologic, pharmacologic, and/or pharmacokinetic properties.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Duration of action of moving object
If current strategies (PEGylation or albumin fusions) are used to extend half-life, then the biological half-life is prolonged, but the device complexity and manufacturing complexity increase
Solution Approach 1:
The patent changes the chemical parameters of the therapeutic peptide by incorporating non-natural amino acids with specific properties (hydrophobicity, steric bulk) to extend half-life. This modifies the molecular characteristics of the drug itself rather than adding complex external structures like PEG chains or albumin fusion proteins.
Solution Approach 2:
The patent creates composite structures by incorporating non-natural amino acids into the peptide sequence, forming a hybrid molecule that combines natural peptide functionality with synthetic amino acid properties for extended circulation half-life without requiring additional macromolecular conjugates.
2Reliability
If higher dosages are administered more frequently to compensate for short half-life, then the pharmacologic activity is maintained, but the object-generated harmful factors increase due to side effects and reduced compliance
Solution Approach 1:
The patent creates a dynamic balance in drug release by engineering peptides with extended half-lives that maintain stable serum concentrations over time. This allows for less frequent dosing while maintaining therapeutic levels, reducing the peaks and troughs associated with frequent high-dose administration.
3Stability of the object's composition
If frequent administration is required to maintain therapeutic levels, then the pharmacokinetic stability is improved, but the loss of time and reduced compliance increase
Solution Approach 1:
The patent achieves continuous therapeutic action by engineering peptides with extended half-lives that maintain stable serum concentrations over extended periods. This eliminates the need for frequent dosing interruptions while maintaining continuous pharmacologic effect, improving patient compliance and reducing time loss.
Data Source
AI summary
Methods and compositions are provided for extending the half-life of a therapeutic agent A modified therapeutic agent (mTA) comprises a therapeutic agent, a staple, and a half-life extending molecule. The mTAs disclosed herein may be used to treat a disease or a condition in a subject in need thereof.