IL4R/IL13R Heterodimeric Proteins for Companion Animal Cytokine Binding
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Solution Overview
Problem
Companion animals such as cats, dogs, and horses suffer from allergic diseases like atopic dermatitis and asthma, and there is a need for methods and compounds that can specifically bind to IL4 and/or IL13 to treat these conditions and reduce IL4/IL13 signaling activity.
Innovation Solution
Development of heterodimeric proteins comprising IL13R and IL4R extracellular domains fused with Fc polypeptides derived from companion animals, which bind to IL4 and/or IL13 with high affinity, thereby reducing IL13 and/or IL4 signaling.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If heterodimeric proteins with Fc polypeptides are developed to bind IL4 and IL13, then binding affinity and therapeutic efficacy are improved, but protein structure complexity and manufacturing difficulty increase
Solution Approach 1:
The patent combines IL4R ECD and IL13R ECD into a single heterodimeric protein structure, where the two receptor extracellular domains are fused together and linked to Fc polypeptides. This merging approach enables simultaneous binding to both IL4 and IL13 cytokines, achieving high binding affinity and broad therapeutic efficacy against multiple allergic conditions while maintaining a unified protein architecture that can be manufactured as a single molecular entity.
Solution Approach 2:
The invention creates a composite protein structure by fusing extracellular domains of different receptors (IL4R ECD and IL13R ECD) with Fc polypeptides from companion animals. This composite design integrates multiple functional elements into one molecule: the receptor domains provide cytokine-specific binding, while the Fc portion contributes to stability, half-life extension, and potential Fc-receptor interactions. The composite structure achieves high affinity binding without requiring separate administration of multiple proteins.
2Adaptability or versatility
If species-specific IL4R and IL13R ECDs are used to bind companion animal IL4 and IL13, then binding specificity is improved, but cross-reactivity and manufacturing complexity increase
Solution Approach 1:
The patent applies local quality by using species-specific extracellular domains (from canine, feline, or equine sources) only at the cytokine-binding interface, while the Fc polypeptide portion can be from any suitable species. This localized application of species specificity ensures high binding affinity and specificity for companion animal IL4 and IL13 at the critical interaction site, while the Fc region provides universal structural support and stability that can be manufactured using well-established mammalian cell expression systems.
Solution Approach 2:
The Fc polypeptide acts as an intermediary that connects the species-specific receptor domains to universal structural and functional elements. The Fc portion mediates the connection between the IL4R/IL13R ECDs and the production system, enabling the species-specific binding domains to be expressed and folded correctly while providing a standardized platform for manufacturing, purification, and quality control across different batch productions.
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
The heterodimeric proteins effectively bind to IL4 and IL13 with low dissociation constants, reducing IL13 and/or IL4 signaling in companion animals, providing therapeutic benefits for conditions like atopic dermatitis and asthma.
Implementation Method 1
Extracellular domains of IL4Ra or IL13Ra1 may bind to IL4 and/or IL13 and reduce the free concentrations of the cytokines, thus diminishing the clinical signs and symptoms associated with dermatitis, asthma and other disorders
Data Source
AI summary
Provided are various embodiments relating to IL13R/IL4R heterodimeric proteins derived from companion animal species and that bind to IL13 and/or IL4. Such heterodimeric proteins can be used in methods to treat IL13 and/or IL4-induced conditions in companion animals, such as canines, felines, and equines.