mRNA Therapeutics for Targeted Tumor Reduction

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Solution Overview

Problem

Current cancer treatments, such as chemotherapy and radiotherapy, have undesirable side effects and random genomic integration issues, necessitating a more targeted and safer approach for cancer therapy.

Innovation Solution

Development of mRNA therapeutics using modified nucleotides and lipid nanoparticle delivery systems to deliver immune-modulating polypeptides, such as IL-23, IL-36 gamma, and OX40L, to tumors for targeted protein synthesis and immune stimulation, minimizing immune activation and optimizing translation efficiency.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If standard treatments such as chemotherapy and radiotherapy are used, then cancer treatment is achieved, but undesirable side effects and random genomic integration issues occur

Engineering Contradiction:

Improvesafety of cancer treatmentVSAvoidside effects and genomic integration issues

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent uses lipid nanoparticle (LNP) delivery systems as intermediaries to transport mRNA encoding immune modulating polypeptides to tumor cells. This mediator approach enables targeted delivery without random genomic integration, avoiding the harmful effects of traditional chemotherapy and radiotherapy while maintaining treatment efficacy.

Inventive Principle:

Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent replaces the mechanical/direct toxic approach of chemotherapy and radiotherapy with a biological approach using mRNA therapeutics. The modified nucleotides in the mRNA molecules enable targeted protein synthesis within tumor cells, substituting the harmful mechanical destruction methods with a more precise biological mechanism that reduces side effects.

Inventive Principle:

Principle #28Mechanics substitution (Replace mechanical system)

2Productivity

If mRNA encoding immune modulating polypeptides is introduced into cells, then de novo synthesis of functional proteins occurs, but innate immune response activation may occur

Engineering Contradiction:

Improveprotein synthesis efficiencyVSAvoidinnate immune response activation

Core Design Contradiction:

ProductivityVSObject-generated harmful factors

Solution Approach 1:

The patent modifies the chemical parameters of the mRNA molecules by incorporating pseudouridine and other modified nucleotides. These parameter changes in the nucleotide structure reduce the recognition of mRNA by innate immune sensors while maintaining or enhancing translation efficiency, thus resolving the contradiction between protein synthesis productivity and immune activation.

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The patent applies different modifications at different regions of the mRNA molecule. The 5' untranslated region contains specific modifications for optimal translation initiation, the coding region has modifications to maintain protein synthesis efficiency, and the 3' untranslated region contains modifications for stability and reduced immune recognition. This localized quality adjustment resolves the contradiction between productivity and harmful immune responses.

Inventive Principle:

Principle #3Local quality

Data Source

PatentUS11596609B2Combinations of mRNAs encoding immune modulating polypeptides and uses thereof

Publication Date: 2023.03.07 MODERNATX INC

AI summary

The disclosure relates to compositions and methods for the preparation, manufacture and therapeutic use of combinations of immunomodulatory polynucleotides (e.g., mRNAs) encoding an immune response primer polypeptide (e.g., an interleukin 23 (IL-23) polypeptide or an interleukin 36γ (IL-36-gamma) polypeptide), and an immune response co-stimulatory signal polypeptide (e.g., an OX40L polypeptide).