Mutation-Specific IgA Antibodies for Targeting KRAS Oncogenes

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Solution Overview

Problem

Current cancer treatments are inefficient in targeting and eliminating cancer cells, despite significant investment and research.

Innovation Solution

Development of dimeric or pentameric antigen binding molecules, such as dimeric IgA, dimeric IgG4, or pentameric IgM, that specifically bind to oncogenes like KRASG12D, AKT1, IDH1, and others, allowing for targeted therapy.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If conventional cancer treatments are used, then broad coverage is achieved, but specificity in targeting cancer cells is poor

Engineering Contradiction:

Improvetargeting precisionVSAvoidtreatment efficiency

Core Design Contradiction:

Measurement precisionVSProductivity

Solution Approach 1:

The patent applies local quality by engineering antibodies with mutation-specific paratopes that recognize only specific oncogenic mutations (e.g., KRAS G12C, G12D, G12V). Each antibody is locally optimized to bind exclusively to its target mutation while ignoring wild-type and other mutant forms, achieving high specificity without requiring broad-spectrum coverage from the same molecule.

Inventive Principle:

Principle #3Local quality

Solution Approach 2:

The patent utilizes parameter changes by modifying the antibody structure to include specific complementarity-determining regions (CDRs) with unique amino acid sequences that confer mutation-specific binding. By changing the molecular parameters of the antibody (particularly the CDR sequences), the patent achieves selective recognition of different oncogenic mutations, transforming a general antibody into a precision-targeting agent.

Inventive Principle:

Principle #35Parameter changes

2Reliability

If dimeric or pentameric antigen binding molecules are used, then binding specificity to mutant oncogenes is improved, but molecular complexity increases

Engineering Contradiction:

Improvebinding specificityVSAvoidmolecular structure complexity

Core Design Contradiction:

ReliabilityVSDevice complexity

Solution Approach 1:

The patent applies merging by combining multiple identical or similar antibody monomers (dimeric or pentameric structures) that each possess the same mutation-specific binding capability. This merging amplifies the binding effect and ensures reliable recognition of the target mutation while maintaining structural symmetry that simplifies production and characterization compared to completely asymmetric multi-specific antibodies.

Inventive Principle:

Principle #5Merging (Combining)

Solution Approach 2:

The patent achieves universality by designing dimeric or pentameric structures where each monomer performs the same function (binding to the specific mutation). This modular approach allows the system to maintain high specificity through repeated identical binding units, reducing the complexity of designing and characterizing multiple different binding sites while achieving enhanced binding reliability.

Inventive Principle:

Principle #6Universality (Multi-functionality)

Data Source

PatentUS20250122308A1Targeting mutant KRAS with a mutation specific iga

Publication Date: 2025.04.17 H LEE MOFFITT CANCER CENTER & RESEARCH INSTITUTE INC

AI summary

Disclosed herein are dimeric or pentameric antigen binding molecules and methods for making said dimeric or pentameric antigen binding molecules, wherein the isotype of the immunoglobulin monomers is IgA, 1gG4, or IgM. Also disclosed herein are methods of using dimeric antigen binding molecules to treat cancer associated with expression of an oncogene, gene overexpression, or a gene fusion.