Oligosaccharide Solubility Tags for Antibody-Drug Conjugates
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Antibody-drug conjugates (ADCs) face solubility issues due to hydrophobic payloads, leading to aggregation, reduced efficacy, and increased toxicity, limiting their therapeutic potential and requiring lower drug-to-antibody ratios, which compromises their clinical effectiveness and safety.
Innovation Solution
The covalent attachment of an oligosaccharide-based solubility tag to ADCs increases their solubility, reduces aggregation, and allows for higher drug-to-antibody ratios, enabling the use of hydrophobic payloads that were previously unsuitable, and providing improved clinical characteristics through a modular approach adaptable to various ADCs.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If hydrophobic payloads are used in ADCs, then therapeutic potency is improved, but solubility deteriorates leading to aggregation and reduced stability
Solution Approach 1:
The patent segments the ADC molecule by attaching oligosaccharide solubility tags to the antibody component. These tags are discrete functional units that specifically address solubility without interfering with the therapeutic payload's function. The oligosaccharide tags can be attached at multiple locations on the antibody, creating modular solubility enhancement that works independently of the hydrophobic payload.
Solution Approach 2:
The patent creates a composite ADC structure combining three distinct components: the antibody (targeting component), the hydrophobic payload (therapeutic component), and the oligosaccharide solubility tag (solubility-enhancing component). This composite approach allows each component to fulfill its specific function while the oligosaccharide tags collectively overcome the solubility limitations imposed by the hydrophobic payloads.
2Stability of the object's composition
If drug-to-antibody ratio is reduced to improve solubility, then stability is improved, but therapeutic efficacy deteriorates
Solution Approach 1:
The oligosaccharide solubility tags act as intermediaries between the hydrophobic payload and the aqueous physiological environment. These tags mediate solubility enhancement without requiring reduction of the drug-to-antibody ratio, thereby preserving therapeutic efficacy while improving solubility and stability.
3Reliability
If hydrophobic payloads are used, then therapeutic potency is improved, but aggregation increases leading to reduced manufacturability
Solution Approach 1:
The patent segments the ADC structure by adding oligosaccharide solubility tags that prevent aggregation of the hydrophobic payloads. This segmentation approach allows high drug-to-antibody ratios with potent hydrophobic payloads while maintaining manufacturability through improved solubility and reduced aggregation.
4Stability of the object's composition
If solubility is improved by using hydrophilic linkers or payloads, then solubility is improved, but therapeutic options are limited
Solution Approach 1:
The oligosaccharide solubility tags provide a universal solution that works with diverse hydrophobic payloads and antibody types. Rather than requiring payload or linker modification, the tags can be attached to various ADC configurations, making the solubility enhancement approach broadly applicable across different therapeutic candidates while preserving full payload diversity.
Data Source
AI summary
The present disclosure relates to molecules with a solubility tag, wherein the solubility tag comprises a chito-oligosaccharide, and to methods for increasing the solubility of a molecule. Moreover, the present disclosure relates to antibody-drug conjugates with solubility tag, methods and compounds for preparing such antibody-drug conjugates, methods for increasing the solubility of antibody-drug conjugates, antibody-drug conjugates prepared by such methods, as well as the use of such antibody-drug conjugates in medical treatment.