Multispecific sIL-6R and CTGF Binding Proteins for Neuroinflammation
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Solution Overview
Problem
Current treatments for neurological diseases such as ALS do not effectively target the neuroinflammatory and fibrotic processes driven by increased expression of IL-6R and CTGF, which contribute to motor neuron dysfunction and glial-neuronal communication changes.
Innovation Solution
Development of multispecific binding proteins, including VHH antibodies, that selectively bind to both soluble IL-6R and CTGF, potentially conjugated with an anti-transferrin receptor antibody, to modulate their signaling and address the underlying neuroinflammatory and fibrotic processes.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If current treatments are used for neurological diseases, then general symptom management is achieved, but neuroinflammatory and fibrotic processes driven by IL-6R and CTGF are not effectively targeted
Solution Approach 1:
The patent combines multiple binding specificities into a single multispecific binding protein that can bind to both IL-6R and CTGF simultaneously. This merging of targeting capabilities allows the treatment to address multiple pathological processes (neuroinflammation and fibrosis) with one therapeutic agent, resolving the contradiction between treatment effectiveness and targeting versatility.
Solution Approach 2:
The multispecific binding protein is designed to perform multiple functions: binding to IL-6R to modulate neuroinflammatory processes and binding to CTGF to address fibrotic processes. This multi-functionality enables a single agent to target diverse pathological mechanisms, improving treatment reliability while maintaining adaptability to different disease aspects.
2Adaptability or versatility
If multisspecific binding proteins are developed to target both IL-6R and CTGF, then targeting capability is enhanced, but device complexity increases
Solution Approach 1:
The multisspecific binding protein is constructed by segmenting the targeting function into distinct binding domains, each responsible for binding to a specific target (IL-6R or CTGF). These segmented binding specificities are then operatively linked within a single protein structure, allowing complex targeting capability to be achieved through modular assembly rather than monolithic design.
Solution Approach 2:
The binding protein employs a composite structure combining different binding specificities (anti-IL-6R and anti-CTGF) within a single molecular framework. This composite approach integrates multiple functional elements into one unified protein, enhancing targeting capability while managing structural complexity through systematic design.
3Reliability
If binding affinity to soluble IL-6R is enhanced, then therapeutic effectiveness against neuroinflammatory processes is improved, but selectivity challenges arise
Solution Approach 1:
The binding protein exhibits different binding characteristics for different targets: it has high affinity for soluble IL-6R to effectively target neuroinflammatory processes, while maintaining appropriate selectivity through specific binding domain design. Each binding domain is optimized for its specific target, allowing high effectiveness without compromising selectivity.
Data Source
AI summary
Provided herein are soluble interleukin-6 receptor (sIL-6R) and CTGF binding proteins, multispecific binding proteins thereof, conjugates thereof, pharmaceutical compositions thereof, and methods of use thereof. The specific binding proteins can be single heavy chain antibodies (VHH), and the multispecific binding protein can include two variable heavy chain (VHH) immunoglobulin domains targeting sIL-6R and CTGF. The conjugates can include a binding protein or multispecific binding protein, conjugated with an anti-transferrin receptor antibody. The pharmaceutical compositions can include one or more binding proteins and/or multispecific binding proteins. The methods of use include the administration of binding proteins and/or multispecific binding protein for the treatment of neurological diseases.