IL-10 Conjugates With Extended Half-Life for T Cell Modulation
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Solution Overview
Problem
Existing treatments for modulating T cell populations to treat diseases like cancer are limited in efficacy and stability, particularly in maintaining immune homeostasis and targeting cancerous cells effectively.
Innovation Solution
Development of interleukin 10 (IL-10) conjugates with modified amino acid sequences and conjugating moieties, such as PEG molecules, to enhance plasma half-life and maintain functional activity, allowing for targeted immune modulation.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If existing treatments are used to modulate T cell populations, then immune homeostasis can be maintained to some extent, but the efficacy and stability are limited
Solution Approach 1:
The patent creates composite therapeutic agents by combining IL-10 polypeptides with targeting moieties (such as antibodies or ligands) that specifically bind to cancer-associated antigens. This composite structure enables the IL-10 to simultaneously maintain immune homeostasis through its anti-inflammatory properties while being directed to cancerous cells via the targeting component, thereby resolving the contradiction between reliability of immune modulation and adaptability to target specific cancer cells
Solution Approach 2:
The invention applies local quality by modifying the IL-10 molecule with site-specific conjugation of targeting moieties at defined positions on the IL-10 polypeptide chain. This ensures that the therapeutic effect is localized to cancerous tissues while preserving the systemic immune homeostatic function of IL-10, allowing differential action in different tissue contexts
2Duration of action of stationary object
If IL-10 conjugates with modified amino acid sequences are developed, then plasma half-life is enhanced, but structural complexity increases
Solution Approach 1:
The patent employs parameter changes by systematically modifying specific amino acid residues in the IL-10 polypeptide sequence (such as replacing surface-exposed residues with unnatural amino acids containing bioconjugation handles) to enhance plasma half-life. These controlled parameter modifications allow extension of circulation time while maintaining the overall fold and functional integrity of the IL-10 molecule, balancing durability with manageable structural complexity
Solution Approach 2:
The invention uses intermediary unnatural amino acids (containing azide, alkyne, or other bioorthogonal functional groups) as mediators between the IL-10 core structure and the conjugating moieties. These intermediaries are incorporated at specific positions to enable stable protein conjugation that extends plasma half-life without requiring extensive structural redesign of the IL-10 molecule itself
3Reliability
If conjugating moieties such as PEG molecules are added to IL-10, then functional activity is maintained, but manufacturing complexity increases
Solution Approach 1:
The patent applies preliminary action by pre-installing bioconjugation handles (unnatural amino acids with reactive groups) into the IL-10 polypeptide during recombinant expression in mammalian cell lines. This preliminary incorporation allows subsequent conjugation of PEG or other moieties to proceed under mild conditions with high efficiency, avoiding complex chemical synthesis steps and simplifying the overall manufacturing process while maintaining functional activity
Solution Approach 2:
The invention replaces complex mechanical/chemical conjugation systems with biochemical ligation methods. By using unnatural amino acids with bioorthogonal functional groups (such as azide-alkyne click chemistry handles) incorporated during protein expression, the conjugation process occurs under physiological conditions with high specificity and efficiency, eliminating the need for harsh chemical reagents and complex purification steps associated with traditional PEGylation methods
Data Source
AI summary
Disclosed herein are interleukin 10 conjugates and uses in the treatment of one or more indications. Also described herein are pharmaceutical compositions and kits comprising one or more of the IL-10 conjugates.