Anti-GDF15 Antibody CDR Engineering to Block GDF15-GFRAL Binding

Resolve Bottlenecks,
Find Innovative SolutionsGenerate Solutions

Solution Overview

Problem

There is a need for therapeutic antibodies that can effectively inhibit or antagonize GDF15 to treat diseases or conditions mediated through GDF15, such as cancer, cancer cachexia, cancer-induced weight loss, and other metabolic disorders, as existing monoclonal antibodies have limitations.

Innovation Solution

Development of isolated anti-GDF15 antibodies with specific heavy and light chain variable domains, comprising particular complementarity determining regions (CDRs) that bind to GDF15, inhibiting its activity and providing therapeutic benefits.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If existing monoclonal antibodies are used to treat GDF15-mediated diseases, then treatment can be provided, but therapeutic effectiveness is limited due to inability to effectively inhibit or antagonize GDF15

Engineering Contradiction:

Improvetherapeutic effectivenessVSAvoidinhibitory capability against GDF15

Core Design Contradiction:

ReliabilityVSAdaptability or versatility

Solution Approach 1:

The patent modifies the antibody structure by optimizing the CDR regions (complementarity determining regions) to change the binding parameters and affinity for GDF15. Specifically, the antibody comprises a heavy chain variable domain with CDR1: QYDWT, CDR2: MISFSGTTDYASWAKG, CDR3: VVYAGWTYPLGI, and a light chain variable domain with CDR1: QASQSISSVLS, CDR2: EASITLQS, CDR3: QANYDVYNYGNP, which are designed to effectively inhibit GDF15 binding to its receptor GFRAL

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The patent creates a humanized antibody version (Hum-R37-2) based on a parent antibody (R37-2) that demonstrated effective GDF15 inhibition. The humanized version copies the critical CDR regions responsible for GDF15 binding while using human framework regions, thereby maintaining therapeutic effectiveness while reducing immunogenicity

Inventive Principle:

Principle #26Copying

2Ease of operation

If GDF15 activity is inhibited to treat cancer cachexia and metabolic diseases, then weight loss can be reduced and glucose tolerance improved, but the complexity of antibody development and manufacturing increases

Engineering Contradiction:

Improvetreatment efficacyVSAvoidantibody structure complexity

Core Design Contradiction:

Ease of operationVSDevice complexity

Solution Approach 1:

The patent extracts and optimizes only the critical CDR regions (complementarity determining regions) that are responsible for GDF15 binding, while using standardized human framework regions. This allows the antibody to maintain high therapeutic effectiveness for treating cancer cachexia and metabolic diseases while simplifying the overall development and manufacturing process by focusing modifications only on the essential binding regions

Inventive Principle:

Principle #2Taking out (Extraction)

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 antibodies effectively inhibit GDF15 activity, offering potential treatments for cancer cachexia and other metabolic diseases by reducing weight loss, improving glucose tolerance, and enhancing insulin sensitivity.

Implementation Method 1

isolated anti-GDF15 antibodies... comprising particular complementarity determining regions (CDRs) that bind to GDF15, inhibiting its activity

Methodology Applied

Scientific EffectAntigen-antibody binding:

Data Source

PatentUS20250326828A1Antibodies Specifically Recognizing Gdf15 and Uses Thereof

Publication Date: 2025.10.23 STAIDSON (BEIJING) BIOPHARMACEUTICALS CO LTD

AI summary

This application pertains to antibodies or antigen binding fragments that specifically recognize Growth differentiation factor-15 (GDF15), and methods of manufacture and uses thereof.