Engineered HPV Binding Molecules Targeting E6 and E7 Oncoproteins

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Solution Overview

Problem

Current therapies lack targeted approaches to inhibit HPV oncoproteins E6 and E7, which are key drivers of HPV-related malignancies, and there is a need for tools to dissect the host-viral protein molecular interface.

Innovation Solution

Development of novel HPV binding molecules, such as chimeric antigen receptors, immunotoxins, and nanobodies specific to E6 and E7 proteins, which interact with these oncoproteins to inhibit their activity and induce apoptosis in HPV-positive tumor cells.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Loss of information

If gene silencing techniques are used to study HPV oncoprotein interactions, then molecular interface dissection is enabled, but there are no targeted therapies available

Engineering Contradiction:
Improvemolecular interface informationVSAvoidtherapeutic application
Core Design Contradiction:
Loss of informationVSAdaptability or versatility

Solution Approach 1:

The patent uses binding molecules (antibodies, nanobodies, CARs) as intermediary agents that specifically interact with HPV oncoproteins E6 and E7. These intermediaries enable both the dissection of molecular interfaces through controlled binding studies and the development of targeted therapies by blocking oncoprotein-function interactions, thus resolving the contradiction between research tools and therapeutic applications

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The binding molecules disclosed serve multiple functions: they act as research tools for dissecting host-viral protein interfaces, as therapeutic agents for inhibiting oncoprotein activity, and as diagnostic reagents. This multi-functionality allows the same molecular tools to address both the information loss in research and the lack of therapeutic options

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

2Adaptability or versatility

If non-specific therapies are used, then broad coverage is achieved, but targeted inhibition of HPV oncoproteins is not possible

Engineering Contradiction:
Improvetherapeutic coverageVSAvoidtarget specificity
Core Design Contradiction:
Adaptability or versatilityVSManufacturing precision

Solution Approach 1:

The patent applies local quality by designing binding molecules with specific affinity and selectivity for HPV oncoproteins E6 and E7. Each binding molecule is engineered to recognize specific epitopes on the oncoproteins, providing targeted inhibition at the molecular level while maintaining therapeutic efficacy. This localized specificity contrasts with non-specific therapies that lack such precision

Inventive Principle:
Principle #3Local quality

Solution Approach 2:

The patent utilizes parameter changes by modifying the binding characteristics of therapeutic molecules through engineering approaches. By adjusting affinity, specificity, and pharmacokinetic parameters of the binding molecules (such as half-life, tissue distribution), the therapy achieves both targeted inhibition of HPV oncoproteins and effective therapeutic coverage

Inventive Principle:
Principle #35Parameter changes

3Manufacturing precision

If targeted binding molecules are developed, then therapeutic specificity is improved, but device and molecular complexity increases

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

Solution Approach 1:

The patent applies segmentation by dividing the therapeutic approach into distinct binding molecules, each targeting specific oncoproteins (E6 or E7). The binding molecules themselves are segmented into functional regions (variable regions for specificity, constant regions for stability). This segmentation enables high binding specificity while managing complexity through modular design

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The patent uses copying by employing binding molecules that replicate or mimic natural immune responses. The molecules are designed to copy the binding and neutralizing functions of natural antibodies, utilizing well-understood immunological mechanisms to achieve targeted inhibition without the complexity of entirely synthetic approaches

Inventive Principle:
Principle #26Copying

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

These molecules effectively suppress tumor growth and induce apoptosis in HPV-positive cells without off-target effects, providing a targeted therapeutic approach for HPV-related cancers.

Implementation Method 1

comprising a variable domain, wherein the variable domain comprises 3 complementarity determining regions (CDRs), CDR1, CDR2, and CDR3

Methodology Applied
Scientific EffectAntibody-antigen binding:

Data Source

PatentUS20240218053A1Engineering biologics to HPV oncoproteins
Publication Date: 2024.07.04 H LEE MOFFITT CANCER CENTER & RESEARCH INSTITUTE INC
  • US20240218053A1 patent drawing
  • US20240218053A1 patent drawing
  • US20240218053A1 patent drawing

AI summary

Disclosed are novel HPV E6 and HPV E7 binding molecules and methods of their use in the treatment of HPV and cancers resulting from an HPV infection.