Modular IL-13 and TSLP ISVD Polypeptides for Stable Dual Targeting
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Solution Overview
Problem
Current treatments for type 2 inflammatory diseases such as asthma and atopic dermatitis are inadequate, and dual targeting of TSLP and IL-13 with a single agent is needed to enhance efficacy, while existing bispecific antibody formats face challenges like high viscosity, stability issues, and production complexities.
Innovation Solution
Development of a polypeptide comprising immunoglobulin single variable domains (ISVDs) that specifically bind to both IL-13 and TSLP, optionally linked via peptidic linkers, with additional moieties for increased half-life and stability, produced in microbial hosts.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If dual targeting of TSLP and IL-13 with a single agent is implemented, then therapeutic efficacy is improved, but production complexity and stability issues worsen
Solution Approach 1:
The patent segments the dual-targeting function into separate single-variable domains (SVDs), where each SVD independently targets one antigen (TSLP or IL-13). These segmented domains are then assembled into a single polypeptide molecule, resolving the production complexity by using modular, independently producible units that can be recombined.
Solution Approach 2:
The patent creates a universal polypeptide platform that can target multiple antigens (TSLP and IL-13) through a standardized architecture of SVDs connected by linkers. This multi-functional design allows a single agent to address multiple disease pathways, improving therapeutic efficacy while maintaining production efficiency through standardized assembly protocols.
2Adaptability or versatility
If bispecific antibody formats are used, then dual targeting capability is improved, but viscosity and stability issues worsen
Solution Approach 1:
The patent extracts only the essential antigen-binding function into minimized single-variable domains (SVDs), removing the complex constant regions and Fc portions of traditional antibodies that contribute to viscosity and stability problems. These extracted SVDs retain dual-targeting capability while presenting a simplified, more stable molecular architecture.
Solution Approach 2:
The patent changes the molecular parameters by using small variable domains (approximately 15 kDa each) instead of full-sized antibody fragments, and by optimizing linker length and composition. These parameter changes reduce molecular weight and complexity, improving stability and reducing viscosity while maintaining dual-targeting functionality.
3Adaptability or versatility
If multiple separate biologicals are co-administered, then dual targeting is achieved, but treatment convenience worsens
Solution Approach 1:
The patent merges two separate therapeutic agents (anti-TSLP and anti-IL-13) into a single dual-specific polypeptide molecule. This consolidation allows patients to receive dual targeting therapy through a single injection, dramatically improving treatment convenience while eliminating the need for coordinated administration of multiple biologicals.
4Ease of manufacture
If conventional antibody formats are used, then production is established, but half-life and stability in subjects worsen
Solution Approach 1:
The patent creates composite polypeptide structures by combining SVDs with half-life extension moieties such as albumin-binding domains or Fc portions. This composite architecture integrates the proven manufacturability of conventional antibody formats with enhanced pharmacokinetic properties, achieving both ease of production and extended half-life in subjects.
Data Source
AI summary
The present technology aims at providing a novel type of drug for treating a subject suffering from an inflammatory disease. Specifically, the present technology provides polypeptides comprising at least four immunoglobulin single variable domains (ISVDs), characterized in that at least two ISVDs bind to IL-13 and at least two ISVDs binds to TSLP. The present technology also provides nucleic acids, vectors and compositions.