Recombinant TCR Constructs for RAS Epitope Binding

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Solution Overview

Problem

There is a need for T cell receptors (TCRs) that can effectively recognize and bind to peptide-MHC complexes, particularly for therapeutic applications in treating diseases such as cancer.

Innovation Solution

The development of recombinant nucleic acid molecules encoding TCRs, specifically TCR beta and alpha chain constructs with defined complementarity determining regions (CDRs), which can recognize and bind to specific epitopes from human RAS or other antigens in complex with human MHC proteins.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If TCRs are designed to recognize specific peptide-MHC complexes with high affinity, then therapeutic efficacy is improved, but the complexity of TCR structure and development increases

Engineering Contradiction:

Improvetherapeutic efficacyVSAvoidTCR structure complexity

Core Design Contradiction:

ReliabilityVSDevice complexity

Solution Approach 1:

The TCR is segmented into distinct functional domains (variable regions with CDR1-3, constant regions, transmembrane domains) that can be independently designed and optimized. This segmentation allows systematic engineering of affinity and specificity while managing structural complexity through modular construction of the TCR alpha and beta chains

Inventive Principle:

Principle #1Segmentation

Solution Approach 2:

The patent employs parameter changes by systematically varying the amino acid sequences in the complementarity determining regions (CDRs), particularly CDR3 which contacts the peptide-MHC complex. By optimizing parameters such as CDR length, charge distribution, and hydrophobicity, the TCR achieves high affinity binding while maintaining a manageable structural framework

Inventive Principle:

Principle #35Parameter changes

2Measurement precision

If TCRs are engineered to bind with high specificity to tumor antigens, then immune response precision is improved, but the difficulty of TCR development and characterization increases

Engineering Contradiction:

Improveantigen recognition specificityVSAvoidTCR characterization difficulty

Core Design Contradiction:

Measurement precisionVSDifficulty of detecting and measuring

Solution Approach 1:

The patent applies preliminary action by pre-characterizing the TCR's binding properties against known peptide-MHC complexes during the design phase. By establishing baseline specificity data and affinity measurements before therapeutic use, the complex task of characterization is performed in advance, facilitating easier validation and monitoring during clinical application

Inventive Principle:

Principle #10Preliminary action

Solution Approach 2:

The patent uses copying by creating multiple TCR variants with identical or similar CDR regions that recognize the same antigen. These replicated TCR constructs serve as controls and references, simplifying the characterization process by providing consistent baseline data against which new TCRs can be compared

Inventive Principle:

Principle #26Copying

Data Source

PatentUS12331097B2T cell receptor constructs and uses thereof

Publication Date: 2025.06.17 BIONTECH US INC

AI summary

The present disclosure provides T cell receptors (TCRs) against peptide-MHC complexes, isolated nucleic acid molecules encoding TCRs against peptide-MHC complexes, T cells expressing TCRs against peptide-MHC complexes, and pharmaceutical compositions for use in the treatment of diseases.