IL-21 Variant Nucleic Acids for Extended Half-Life
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Solution Overview
Problem
Current IL-21 variants face limitations in activity, selectivity, stability, and circulation time, necessitating the development of improved variants with enhanced biological properties for therapeutic applications.
Innovation Solution
The development of IL-21 variants involves deleting and/or substituting amino acids in specific regions of the peptide, particularly in the 65-96 and 71-92 regions, to maintain or improve activity while allowing for conservative amino acid substitutions, which are encoded by nucleic acid constructs and expressed in cells for collection and use.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Duration of action of stationary object
If amino acids in region 66-98 are deleted or substituted to improve stability and circulation time, then biological half-life is extended, but activity may be reduced
Solution Approach 1:
The patent applies parameter changes by systematically modifying amino acid sequences in region 66-98 of IL-21, testing various deletion and substitution patterns to identify variants that maintain activity while extending half-life. This involves changing the chemical parameters of the peptide structure to achieve improved pharmacokinetic properties without sacrificing biological function.
Solution Approach 2:
The invention applies local quality by making targeted modifications specifically in region 66-98 of the IL-21 sequence, rather than throughout the entire molecule. This localized approach allows the core active regions to remain intact while modifying specific areas to improve stability and circulation time, thereby maintaining activity while achieving the desired pharmacokinetic improvements.
2Adaptability or versatility
If amino acid substitutions are made to improve selectivity, then target specificity is enhanced, but manufacturing complexity increases
Solution Approach 1:
The patent employs parameter changes by introducing specific amino acid substitutions at defined positions within region 66-98 to enhance selectivity for the IL-21 receptor. These controlled sequence modifications allow for improved target specificity while maintaining a relatively simple manufacturing process, as the changes are limited to specific residues rather than requiring complex multi-step synthesis procedures.
Data Source
AI summary
IL-21 variants nucleic acid sequences are provided that encode a peptide having deletions and zero to ten conservative amino acid substitutions in the region of amino acid residues 65-96 of SEQ ID. NO:2.