HPV 16 E6 E7 Binding TCRs for Cancer Therapy

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Solution Overview

Problem

Current therapeutic agents targeting HPV 16-expressing cells or cancers are inadequate, necessitating the development of improved molecules that can effectively bind to HPV 16 E6 or E7 oncoproteins to inhibit cancer progression.

Innovation Solution

Development of T cell receptors (TCRs) or antigen-binding fragments with specific variable alpha and beta regions, including complementarity determining regions (CDRs), that recognize peptide epitopes of HPV 16 E6 or E7, potentially used in adoptive cell therapy.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If current therapeutic agents are used to target HPV 16-expressing cells, then some therapeutic effect is achieved, but the effectiveness is inadequate and cannot sufficiently inhibit cancer progression

Engineering Contradiction:
Improvetherapeutic effectivenessVSAvoidcancer progression
Core Design Contradiction:
ReliabilityVSObject-generated harmful factors

Solution Approach 1:

The patent develops TCRs with specific variable alpha and beta region sequences that have optimized binding parameters for HPV 16 E6 and E7 epitopes. By changing the molecular parameters of the binding molecules (amino acid sequences, binding affinity, specificity), the therapeutic effectiveness is significantly improved compared to existing agents, enabling sufficient inhibition of cancer progression

Inventive Principle:
Principle #35Parameter changes

2Measurement precision

If TCRs with high specificity for HPV 16 epitopes are developed, then immune recognition is enhanced, but the complexity of molecular design and production increases

Engineering Contradiction:
Improvebinding specificityVSAvoidmolecular structure complexity
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The TCR is divided into distinct functional segments: variable alpha region, variable beta region, and constant regions. Each variable region contains three complementarity determining regions (CDR1, CDR2, CDR3) that can be independently optimized for binding specificity. This segmentation allows systematic development of high-specificity TCRs while managing design complexity through modular approaches

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The patent develops TCRs that can recognize multiple HPV 16 epitopes (E6 and E7 oncoproteins) while maintaining high specificity. The designed TCRs possess universal applicability against HPV 16-expressing cells through different epitope specificities, allowing one platform to address multiple targets without proportionally increasing complexity

Inventive Principle:
Principle #6Universality (Multi-functionality)

Data Source

PatentUS11952408B2HPV-specific binding molecules
Publication Date: 2024.04.09 JUNO THERAPEUTICS INC
  • US11952408B2 patent drawing
  • US11952408B2 patent drawing
  • US11952408B2 patent drawing

AI summary

Provided are binding molecules, such as TCRs or antigen binding fragments thereof and antibodies and antigen-binding fragments thereof, such as those that recognize or bind human papilloma virus (HPV) 16, including HPV 16 E6 and HPV 16 E7. Also provided are engineered cells containing such binding molecules, compositions containing the binding molecules or engineered cells, and methods of treatment, such as administration of the binding molecules, engineered cells, or compositions.