Recombinant Interferon Mutants Enhancing Anti-Viral Potency

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Solution Overview

Problem

Current human interferon proteins have limitations such as short circulation half-lives, frequent and inconvenient administration, severe side effects, and antibody neutralization, necessitating the development of novel interferon proteins with enhanced potency and reduced side effects for applications like anti-cancer and anti-viral therapies.

Innovation Solution

A recombinant polynucleotide encoding a protein with at least 93% identity to a specific sequence, known as Novaferon, which exhibits enhanced anti-viral and anti-proliferative activities, is developed, offering 12.5-fold greater anti-viral activity and 400-fold greater anti-proliferative inhibition compared to human interferon alpha 2b, and is used in recombinant vectors and host cells for therapeutic purposes.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Duration of action of moving object

If current human interferon proteins are used for therapy, then anti-viral and anti-proliferative effects are achieved, but circulation half-life is short and administration frequency is high

Engineering Contradiction:

Improvecirculation half-lifeVSAvoidadministration frequency

Core Design Contradiction:

Duration of action of moving objectVSEase of operation

Solution Approach 1:

The patent applies parameter changes by modifying the amino acid sequence of interferon proteins through site-directed mutagenesis. Specific residues are altered to enhance serum stability and extend circulation half-life, directly resolving the contradiction between duration of action and administration frequency

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The patent creates composite interferon molecules by combining functional domains from different interferon subtypes (e.g., IFN-α and IFN-ω) to generate chimeric proteins with enhanced pharmacokinetic properties, including extended half-life and improved resistance to neutralizing antibodies

Inventive Principle:

Principle #40Composite materials

2Reliability

If current human interferon proteins are used for therapy, then anti-viral and anti-proliferative effects are achieved, but severe side effects occur

Engineering Contradiction:

Improvetherapeutic efficacyVSAvoidside effects

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent applies local quality by making targeted amino acid substitutions at specific positions in the interferon molecule. These localized changes enhance therapeutic efficacy while reducing immunogenicity and side effects, allowing the protein to maintain function with improved safety profile

Inventive Principle:

Principle #3Local quality

Solution Approach 2:

The patent converts the harmful effect of high immunogenicity into a benefit by designing mutants with reduced antigenicity. The modifications decrease antibody neutralization while preserving or enhancing biological activity, turning the previously harmful immune response into a more favorable therapeutic profile

Inventive Principle:

Principle #22Blessing in disguise (Convert harm into benefit)

3Reliability

If current human interferon proteins are used for therapy, then therapeutic effects are achieved, but antibody neutralization occurs

Engineering Contradiction:

Improvetherapeutic effectVSAvoidantibody neutralization

Core Design Contradiction:

ReliabilityVSObject-generated harmful factors

Solution Approach 1:

The patent changes the amino acid sequence parameters through site-directed mutagenesis to reduce immunogenic epitopes. Specific residues are modified to decrease antibody binding affinity while maintaining receptor interaction, thereby reducing neutralization and extending therapeutic efficacy

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The patent constructs chimeric interferon molecules combining regions from different interferon subtypes to create novel structures that escape pre-existing antibody neutralization while retaining biological activity, effectively converting the limitation into a therapeutic advantage

Inventive Principle:

Principle #40Composite materials

4Reliability

If recombinant polynucleotide encoding Novaferon is developed, then enhanced anti-viral and anti-proliferative activities are achieved, but manufacturing complexity increases

Engineering Contradiction:

ImprovepotencyVSAvoidmanufacturing complexity

Core Design Contradiction:

ReliabilityVSEase of manufacture

Solution Approach 1:

The patent uses site-directed mutagenesis to create specific amino acid substitutions in the interferon coding sequence. This precise parameter change approach enables enhanced potency while maintaining a relatively simple and scalable manufacturing process through standard recombinant DNA technology

Inventive Principle:

Principle #35Parameter changes

Data Source

PatentUS10538565B2Method of treating diseases with recombinant human interferon-like proteins

Publication Date: 2020.01.21 NOVAGEN HLDG CORP

AI summary

This application relates to recombinant human interferon-like proteins. In one embodiment a recombinant protein created by gene shuffling technology is described having enhanced anti-viral and anti-proliferative activities in comparison to naturally occurring human inteferon like alpha 2b (HuIFN-α2b). The invention encompasses a polynucleotide encoding the protein and recombinant vectors and host cells comprising the polynucleotide. Preferably the polynucleotide is selected from the group of polynucleotides each having a sequence at least 93% identical to SEQ ID: No. 1 and the protein is selected from the group of proteins each having an amino acid sequence at least 85% identical to SEQ ID No: 2. The proteins and compositions comprising the proteins can be used for treatment of conditions responsive to interferon, therapy, such as viral diseases and cancer.