Recombinant IFNa2 Variants for Viral Infection Treatment

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Solution Overview

Problem

Current treatments for viral infections, particularly those caused by HBV and HIV, using interferon alpha 2 (IFNa2) are limited by low efficacy and high side effects, and other interferon alpha subtypes like IFNa14, IFNa5, IFNa6, and IFNa16 have not been clinically tested due to high development costs.

Innovation Solution

Development of recombinant IFNa2 polypeptides with specific amino acid substitutions derived from IFNa5, IFNa6, and IFNa14 sequences, which maintain a high sequence identity with IFNa2 but exhibit enhanced antiviral activity, including variants with specific point mutations at defined positions.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If interferon alpha 2 (IFNa2) is used for treatment of viral infections, then antiviral activity is achieved, but efficacy is low and side effects are high

Engineering Contradiction:
Improveantiviral efficacyVSAvoidside effects
Core Design Contradiction:
ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent applies parameter changes by modifying the amino acid sequence of IFNa2 through specific point mutations at defined positions (e.g., positions 2, 10, 11, 14, 15, 16, 17, 18, 22, 26, 34, 37, 42, 51, 52, 54, 55, 56, 59, 60, 63, 74, 75, 79, 82, 84, 86, 89, 92, 99, 100, 102, 104, 106, 107, 108, 109, 112, 113, 118, 120, 131, 132, 153, 155, 159, 160, 163, and 165). These sequence variations alter the protein's biological properties to enhance antiviral efficacy while reducing side effects, directly addressing the contradiction between reliability and harmful factors.

Inventive Principle:
Principle #35Parameter changes

2Reliability

If other interferon alpha subtypes (IFNa14, IFNa5, IFNa6, IFNa16) are developed for clinical use, then antiviral activity is improved, but development costs are high

Engineering Contradiction:
Improveantiviral activityVSAvoiddevelopment cost
Core Design Contradiction:
ReliabilityVSEase of manufacture

Solution Approach 1:

The patent segments the development approach by focusing on specific defined positions in the IFNa2 sequence rather than developing entirely new interferon subtypes. This segmentation allows targeted mutations at specific locations to achieve improved antiviral activity against HBV, HIV, and other viruses while maintaining the clinical infrastructure for IFNa2 production, thereby reducing development costs.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The patent changes the amino acid sequence parameters of IFNa2 through specific point mutations, creating variants with enhanced antiviral activity. This approach avoids the high development costs associated with creating new interferon subtypes from scratch, as it builds upon the existing IFNa2 clinical infrastructure while improving performance through sequence optimization.

Inventive Principle:
Principle #35Parameter changes

3Reliability

If recombinant IFNa2 polypeptides with amino acid substitutions are created, then antiviral activity is enhanced, but manufacturing complexity increases

Engineering Contradiction:
Improveantiviral activityVSAvoidmanufacturing complexity
Core Design Contradiction:
ReliabilityVSDevice complexity

Solution Approach 1:

The patent modifies the amino acid sequence parameters of IFNa2 through specific point mutations at defined positions. These controlled parameter changes enhance antiviral activity while maintaining a manageable manufacturing complexity, as the modifications are precise and targeted rather than fundamental redesigns of the protein structure.

Inventive Principle:
Principle #35Parameter changes

Data Source

PatentUS20230174606A1Interferon alpha 2 variants and uses thereof
Publication Date: 2023.06.08 UNIV DUISBURG ESSEN
  • US20230174606A1 patent drawing
  • US20230174606A1 patent drawing
  • US20230174606A1 patent drawing

AI summary

The present disclosure relates to recombinant interferon alpha 2 (IFNa2) mutants and variants as well as fragments thereof, nucleic acids encoding them, pharmaceutical compositions containing them, and methods of use thereof.