Single-Domain GDF15 Antibody for Specific GFRAL Blocking
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
There are few types of GDF15 antibodies available, and their specificity needs improvement, particularly for targeting GDF15 to treat associated diseases and diagnose GDF15 levels effectively.
Innovation Solution
Development of a heavy-chain single-domain antibody specifically recognizing GDF15, constructed through immunizing alpacas with human GDF15 protein, isolating lymphocytes, and screening using phage display technology, resulting in an antibody that blocks the interaction between GDF15 and GFRAL.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Volume of moving object
If conventional monoclonal antibodies are used to target GDF15, then they can provide moderate binding affinity, but their molecular weight is large and tissue penetration is limited
Solution Approach 1:
The patent segments the conventional antibody structure into a single-domain antibody (sdAb) format, retaining only the essential antigen-binding domain. This segmentation reduces molecular weight from ~150 kDa to ~15 kDa while preserving binding affinity through optimized CDR regions, directly resolving the contradiction between size and binding capability.
Solution Approach 2:
The patent extracts and eliminates unnecessary structural components (light chains, constant regions, Fc portions) from conventional antibodies, keeping only the variable domain that provides antigen binding. This extraction achieves minimal molecular weight while maintaining functional effectiveness for GDF15 targeting.
2Adaptability or versatility
If conventional antibody development methods are used, then multiple antibody types can be generated, but the development process is complex and time-consuming
Solution Approach 1:
The patent employs a universal sdAb platform that can be applied to target any antigen, including GDF15. The standardized single-domain structure combined with phage display technology provides a versatile framework that simplifies development while maintaining the ability to generate diverse antibody specificities through library construction.
Solution Approach 2:
The patent uses phage display technology to create large libraries of sdAb variants that can be screened in parallel. This copying approach generates multiple antibody candidates simultaneously through combinatorial diversity in CDR regions, enabling diverse targeting capabilities without proportionally increasing development complexity.
3Reliability
If conventional antibodies are used for GDF15 detection and treatment, then they can provide adequate functionality, but their production cost is high and production cycle is long
Solution Approach 1:
The patent adopts sdAbs that can be produced in simpler, more cost-effective systems such as bacterial expression or plant-based systems, eliminating the need for complex mammalian cell culture infrastructure. This approach significantly reduces production costs and accelerates manufacturing cycles while maintaining sufficient functional effectiveness for therapeutic and diagnostic applications.
4Stability of the object's composition
If conventional antibodies are used, then they can provide adequate stability, but their structure is complex and difficult to engineer
Solution Approach 1:
The patent extracts only the essential stable framework regions and CDRs needed for antigen binding, eliminating complex constant regions and inter-chain interactions. The resulting sdAb structure comprises a single polypeptide chain with simplified topology that is inherently more stable and easier to engineer while retaining functional stability for GDF15 binding.
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 antibody exhibits superior blocking activity and specificity compared to existing controls, enabling targeted treatment and diagnosis of GDF15-related diseases such as cardiovascular diseases, kidney diseases, obesity, diabetes, and tumors.
Implementation Method 1
an antibody or its antigen-binding fragment capable of specifically recognizing GDF15
Data Source
Figure 1~2
Figure 3
Figure 4
AI summary
The present application belongs to the field of biotechnology, and specifically relates to an antibody of GDF15 or the use thereof. Provided is a heavy chain antibody for a GDF15 target. The antibody specifically binds to GDF15 and blocks the interaction between GDF15 and GFRAL, and can be used for treating diseases associated with GDF15 overexpression or diagnosing the level of GDF 15 in a patient. The provided antibody has better blocking activity on the binding of GDF15 to GFRAL than that of the positive control CTL002, better specificity than that of the positive control PF-06946860 and better hydrophilicity than that of the positive control PF-06946860.