Engineered Bispecific Antibodies for Dual TREM1 and IL-17 Targeting
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current therapeutic approaches for treating inflammatory diseases such as rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, psoriasis, ulcerative colitis, Crohn's disease, necrotizing enterocolitis, sepsis, and multiple sclerosis are limited in efficacy and specificity, particularly in targeting TREM1 and interleukin pathways.
Innovation Solution
Development of bispecific antibodies that bind to both TREM1 and interleukin (such as IL-17 family members) to modulate inflammatory responses, utilizing engineered antibody constructs like bispecific IgG, Fab2, bis-scFv, diabody, DVD-Ig, TandAb, tandem scFv-Fc, DART, and DART-Fc molecules with specific binding affinities and domains to enhance therapeutic efficacy.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Adaptability or versatility
If monospecific antibodies are used to target TREM1 or interleukin pathways, then treatment coverage is limited, but therapeutic efficacy is reduced
Solution Approach 1:
The patent combines two monospecific antibody functions into a single bispecific antibody molecule that can simultaneously bind to both TREM1 and interleukin (IL-17A) targets. This merging approach allows the antibody to address multiple inflammatory pathways concurrently, expanding treatment coverage while maintaining therapeutic efficacy through coordinated dual-target inhibition.
Solution Approach 2:
The bispecific antibody is engineered to perform multiple functions: it can bind to TREM1 receptor, bind to IL-17A cytokine, and potentially crosslink both targets simultaneously. This multi-functionality enables a single therapeutic agent to address diverse inflammatory conditions including rheumatoid arthritis, psoriasis, and inflammatory bowel disease with improved efficacy compared to monospecific antibodies.
2Adaptability or versatility
If single-target antibodies are used, then mechanism simplicity is maintained, but pathway coverage is insufficient
Solution Approach 1:
The patent merges the antigen-binding specificities of two separate antibodies into a single bispecific antibody molecule. The molecule contains two distinct variable regions: one specific for TREM1 and another for IL-17A, allowing simultaneous engagement of both targets while maintaining a manageable molecular structure suitable for therapeutic administration.
3Object-affected harmful factors
If broad-spectrum anti-inflammatory agents are used, then inflammation reduction is achieved, but disease specificity is lost
Solution Approach 1:
The bispecific antibody exhibits local quality in its binding specificity by targeting two distinct inflammatory pathways (TREM1 and IL-17A) with equal precision. Each binding site is engineered with high affinity for its specific target, enabling the molecule to reduce inflammation through dual-specific mechanisms while maintaining disease specificity for conditions where both pathways are implicated, such as rheumatoid arthritis and psoriasis.
Data Source
AI summary
Provided herein are bispecific molecules and methods of treating using the bispecific molecules, wherein the bispecific molecules comprise a first domain and a second domain, wherein the first domain binds TREM1 or a functional fragment thereof, and wherein the second domain binds IL-17, IL-17R or a functional fragment thereof.