Plasmid Vectors Encoding p185neu Fragments for DNA Vaccination

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Solution Overview

Problem

Current cancer therapies lack effective methods for targeting and eliminating tumours expressing the p185neu protein, which is overexpressed in various carcinomas, due to its role in cell proliferation and differentiation, and its ability to evade immune recognition.

Innovation Solution

Development of plasmid vectors containing sequences encoding fragments of the p185neu protein, specifically the transmembrane and extracellular domains, to induce a strong humoral and cellular immune response, combined with CpG motifs to enhance immune activation, for use in DNA vaccination against tumours.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If plasmid vectors encoding p185neu fragments are used for DNA vaccination, then immune response against tumours is induced, but the complexity of the vaccination system increases

Engineering Contradiction:
Improveimmune response inductionVSAvoidvaccination system complexity
Core Design Contradiction:
ReliabilityVSDevice complexity

Solution Approach 1:

The patent divides the p185neu protein into specific functional fragments (extracellular domain, transmembrane domain, cytoplasmic domain) and encodes them in separate plasmid vectors. This segmentation allows the immune system to recognize different epitopes and generates a more comprehensive immune response while maintaining manageable vector design and production complexity

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The plasmid vectors are designed to be universally applicable across different tumour types expressing p185neu. The same vector platform can be used for prevention and treatment in various carcinomas (breast, lung, ovarian, colorectal), eliminating the need for tumour-specific vector designs and simplifying clinical application

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

2Reliability

If full-length p185neu protein is expressed, then complete antigen presentation is achieved, but tumour cells can evade immune recognition through protein degradation

Engineering Contradiction:
Improveantigen presentationVSAvoidimmune evasion
Core Design Contradiction:
ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent extracts and encodes specific critical fragments of the p185neu protein (particularly the extracellular and transmembrane domains) that are most immunogenic and essential for immune recognition. By focusing on these key segments rather than the complete protein, the vaccine ensures robust antigen presentation while avoiding the tumour evasion mechanisms that target full-length protein expression

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The plasmid vectors are designed to express p185neu fragments in a controlled manner before tumour cells can degrade or modify the full-length protein. The vaccine proactively presents immunogenic epitopes to the immune system prior to tumour progression, establishing immune memory that prevents tumour initiation and progression

Inventive Principle:
Principle #10Preliminary action

3Reliability

If CpG motifs are added to enhance immune activation, then immune response strength increases, but the plasmid vector complexity increases

Engineering Contradiction:
Improveimmune activationVSAvoidplasmid vector complexity
Core Design Contradiction:
ReliabilityVSDevice complexity

Solution Approach 1:

The patent incorporates CpG motifs (specific sequences with high immunogenicity) into the plasmid vector to enhance immune activation. These sequence modifications provide a straightforward parameter change that boosts immune response without fundamentally altering the vector structure or adding complex regulatory elements, maintaining ease of construction and delivery

Inventive Principle:
Principle #35Parameter changes

Data Source

PatentUS7795016B2P185 Neu-encoding DNA and therapeutical uses thereof
Publication Date: 2010.09.14 INDENA SPA
  • US7795016B2 patent drawing
  • US7795016B2 patent drawing
  • US7795016B2 patent drawing

AI summary

Plasmids containing sequences encoding different fragments of p185neu oncoprotein, able to induce an immune response against tumours expressing oncogenes of the ErbB family, and pharmaceutical compositions thereof.