Modified Interferon Beta Polypeptides for Reduced Immunogenicity

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Solution Overview

Problem

Current interferon beta therapeutics face challenges such as immunogenicity, short serum half-life, poor absorption, and side effects like injection site reactions, limiting their efficacy and safety due to neutralizing antibodies and frequent injections.

Innovation Solution

Development of interferon beta polypeptides modified with non-naturally encoded amino acids, specifically at positions 36 and 111, linked to a water-soluble polymer like polyethylene glycol, to enhance stability, solubility, and reduce immunogenicity, while maintaining or improving biological activity.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If natural interferon beta is used as therapeutic agent, then anti-viral and immunomodulatory activity is achieved, but immunogenicity and formation of neutralizing antibodies occur

Engineering Contradiction:

Improvetherapeutic efficacyVSAvoidimmmunogenicity

Core Design Contradiction:

ReliabilityVSObject-generated harmful factors

Solution Approach 1:

The patent modifies the amino acid sequence parameters of interferon beta by incorporating non-naturally encoded amino acids at specific positions (36 and 111) to alter the protein's immunogenicity while preserving its biological activity. This parameter change approach allows the therapeutic to evade neutralizing antibody formation while maintaining efficacy.

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The patent creates a composite structure by combining interferon beta polypeptide with non-naturally encoded amino acids that have specific chemical properties (such as aromatic rings or heteroatoms). This composite modification reduces immunogenicity while maintaining the therapeutic function of the interferon.

Inventive Principle:

Principle #40Composite materials

2Reliability

If interferon beta is administered frequently to maintain therapeutic levels, then adequate coverage is achieved, but injection site reactions and side effects increase

Engineering Contradiction:

Improvetherapeutic coverageVSAvoidside effects

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent modifies the pharmacokinetic parameters of interferon beta by incorporating non-naturally encoded amino acids that alter protein stability, half-life, and absorption characteristics. This enables reduced dosing frequency while maintaining therapeutic coverage, thereby reducing injection site reactions and side effects associated with frequent administration.

Inventive Principle:

Principle #35Parameter changes

3Reliability

If interferon beta is used to treat viral infections, then anti-viral activity is achieved, but short serum half-life limits efficacy

Engineering Contradiction:

Improveanti-viral activityVSAvoidserum half-life

Core Design Contradiction:

ReliabilityVSDuration of action of moving object

Solution Approach 1:

The patent changes the structural parameters of interferon beta by incorporating non-naturally encoded amino acids that enhance protein stability and resist degradation. This extends the serum half-life of the interferon, allowing for prolonged anti-viral activity and reduced dosing frequency while maintaining effective viral clearance.

Inventive Principle:

Principle #35Parameter changes

Data Source

PatentEP2076533B1Modified interferon beta polypeptides and their uses

Publication Date: 2014.10.08 AMBRX INC

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AI summary

Modified interferon beta polypeptides and uses thereof are provided.