CTP-Modified Cytokine Polypeptides for Extended Serum Half-Life
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Solution Overview
Problem
Polypeptides, such as cytokines, have short circulatory half-lives due to susceptibility to denaturation and enzymatic degradation, leading to frequent dosing and discomfort, and pose challenges in maintaining therapeutic levels and avoiding immune responses.
Innovation Solution
Attaching chorionic gonadotropin carboxy-terminal peptides (CTPs) to cytokines, either singly to the amino terminus or in tandem to the carboxy terminus, to enhance stability, prolong half-life, and reduce dosing frequency.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If polypeptides are administered frequently to maintain therapeutic levels, then therapeutic efficacy is maintained, but patient comfort deteriorates due to frequent injections
Solution Approach 1:
The patent changes the molecular weight parameter of the polypeptide by attaching CTP peptides to the cytokine, transforming it from a low molecular weight polypeptide to a higher molecular weight conjugate. This parameter change enables the polypeptide to escape renal filtration and achieve prolonged serum half-life, allowing less frequent dosing while maintaining therapeutic efficacy
Solution Approach 2:
The patent creates a composite polypeptide structure by combining the cytokine with chorionic gonadotropin carboxy-terminal peptides (CTPs). This composite structure integrates the therapeutic function of the cytokine with the pharmacokinetic benefits of the CTP moiety, achieving both therapeutic efficacy and prolonged circulation half-life
2Reliability
If polypeptides are administered by infusion to maintain therapeutic levels, then therapeutic efficacy is maintained, but patient comfort deteriorates due to frequent injections
Solution Approach 1:
The patent changes the molecular weight parameter of the polypeptide by attaching CTP peptides to the cytokine, transforming it from a low molecular weight polypeptide to a higher molecular weight conjugate. This parameter change enables the polypeptide to escape renal filtration and achieve prolonged serum half-life, allowing less frequent dosing while maintaining therapeutic efficacy
3Ease of operation
If low molecular weight polypeptide drugs are used, then ease of administration is improved, but serum half-life deteriorates due to renal filtration
Solution Approach 1:
The patent changes the molecular weight parameter of the polypeptide by attaching CTP peptides to the cytokine, transforming it from a low molecular weight polypeptide to a higher molecular weight conjugate. This parameter change enables the polypeptide to escape renal filtration and achieve prolonged serum half-life
Solution Approach 2:
The patent creates a composite polypeptide structure by combining the cytokine with chorionic gonadotropin carboxy-terminal peptides (CTPs). This composite structure integrates the therapeutic function of the cytokine with the pharmacokinetic benefits of the CTP moiety, achieving both ease of administration and prolonged circulation half-life
Data Source
AI summary
A polypeptide and polynucleotides encoding same comprising one carboxy-terminal peptide (CTP) of chorionic gonadotrophin attached to an amino terminus of a cytokine and two carboxy-terminal peptides (CTP) of chorionic gonadotrophin attached to a carboxy terminus of a cytokine are disclosed. Pharmaceutical compositions comprising the polypeptide and polynucleotides of the invention and methods of using same are also disclosed.