CTP-Modified Growth Hormone for Reduced Dosing Frequency
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Solution Overview
Problem
Peptide drugs face challenges due to short circulatory half-lives and instability, leading to frequent administration and discomfort, as well as potential immune responses and toxic side effects, limiting their therapeutic effectiveness.
Innovation Solution
Modification of growth hormone with chorionic gonadotropin carboxy-terminal peptides (CTPs) to extend half-life, enhance stability, and reduce dosing frequency, while maintaining biological activity.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If growth hormone is administered frequently to maintain effective plasma concentration, then therapeutic efficacy is maintained, but patient comfort deteriorates and dosing complexity increases
Solution Approach 1:
The patent modifies the growth hormone molecule by attaching carboxy-terminal peptides from chorionic gonadotropin, which changes the pharmacokinetic parameters of the hormone. This structural modification extends the circulatory half-life from several hours to a prolonged duration, allowing less frequent administration while maintaining therapeutic efficacy
Solution Approach 2:
The invention creates a composite peptide structure by combining growth hormone with carboxy-terminal peptides from chorionic gonadotropin. This hybrid molecule integrates the therapeutic function of growth hormone with the extended circulation properties of the chorionic gonadotropin peptide, achieving both efficacy and reduced dosing frequency
2Reliability
If growth hormone is administered frequently to maintain therapeutic levels, then pharmacological efficacy is maintained, but treatment complexity increases
Solution Approach 1:
By modifying the molecular structure of growth hormone with attached peptides, the patent changes the clearance rate and half-life parameters. This allows the drug to maintain therapeutic levels for extended periods, simplifying the dosing regimen from frequent administrations to less frequent injections
3Reliability
If peptide drugs are administered by frequent infusion, then effective plasma concentration is maintained, but patient comfort and compliance deteriorate
Solution Approach 1:
The patent alters the pharmacokinetic parameters of growth hormone by attaching carboxy-terminal peptides, extending the circulatory half-life and enabling sustained effective plasma concentrations with less frequent dosing, thereby improving patient comfort and compliance
4Reliability
If dosing frequency is increased to maintain therapeutic levels, then treatment reliability is improved, but loss of time and treatment burden increase
Solution Approach 1:
The structural modification of growth hormone with carboxy-terminal peptides changes the elimination kinetics, extending the duration of action. This allows treatment reliability to be maintained with reduced dosing frequency, thereby reducing the time burden on patients
Data Source
Figure 1~2
Figure 3
Figure 4A~4B
AI summary
A chorionic gonadotropin carboxy terminal peptide (CTP)-modified polypeptide comprising a growth hormone for use in a method of reducing the dosing frequency of a growth hormone in a human adult subject, wherein the CTP-modified polypeptide comprises one chorionic gonadotropin carboxy terminal peptide (CTP) attached to the amino terminus of the growth hormone, and two chorionic gonadotropin CTPs attached to the carboxy terminus of the growth hormone, and optionally a signal peptide attached to the amino terminus of the amino terminal CTP, wherein the method comprises administering to the subject a therapeutically effective amount of the CTP-modified polypeptide.