Streptavidin Mutant and Modified Biotin for Diagnostic Specificity

Solution Overview

Problem

Low-immunogenic streptavidin mutants still exhibit affinity to endogenous biotin, leading to elevated background levels in diagnostic applications and reduced therapeutic efficacy due to early immunogenic responses in humans.

Innovation Solution

A streptavidin mutant with reduced affinity to natural biotin is developed by introducing specific amino acid mutations, combined with a dimeric compound of modified biotin that has high affinity to the mutant, forming a compound suitable for diagnostic and therapeutic applications.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If streptavidin mutant with reduced affinity to natural biotin is used, then background level in diagnostic applications is reduced, but affinity to modified biotin must be maintained for therapeutic efficacy

Engineering Contradiction:

Improvebackground levelVSAvoidaffinity to modified biotin

Core Design Contradiction:

Measurement precisionVSReliability

Solution Approach 1:

The patent introduces specific amino acid mutations at particular positions (Y43A, S45A, or both) in the streptavidin mutant to selectively reduce affinity for natural biotin while preserving or enhancing affinity for modified biotin. This local modification approach allows differential binding properties at specific binding sites.

Inventive Principle:

Principle #3Local quality

Solution Approach 2:

The patent changes the chemical parameters of the biotin molecule by introducing modifications such as deuterium substitution or structural alterations at specific positions. These parameter changes in the biotin molecule enable selective high-affinity binding to the mutant streptavidin while natural biotin binding is reduced.

Inventive Principle:

Principle #35Parameter changes

2Object-affected harmful factors

If low-immunogenic streptavidin is used, then immunogenicity is reduced, but affinity to endogenous biotin remains causing elevated background levels

Engineering Contradiction:

ImproveimmunogenicityVSAvoidbackground level

Core Design Contradiction:

Object-affected harmful factorsVSMeasurement precision

Solution Approach 1:

The patent modifies the biotin molecule by introducing deuterium substitution or structural changes to create a modified biotin that maintains high affinity for the streptavidin mutant while natural biotin affinity is reduced. This parameter change in the biotin structure solves the background level problem.

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The modified biotin acts as an intermediary that bridges the streptavidin mutant and the diagnostic/therapeutic agent. This intermediary enables specific binding to the mutant while avoiding interference from endogenous biotin, thus reducing background levels.

Inventive Principle:

Principle #24Intermediary (Mediator)

3Reliability

If streptavidin mutant with reduced natural biotin affinity is used, then therapeutic efficacy is improved, but high affinity to modified biotin must be maintained

Engineering Contradiction:

Improvetherapeutic efficacyVSAvoidaffinity to modified biotin

Core Design Contradiction:

ReliabilityVSMeasurement precision

Solution Approach 1:

The patent introduces specific amino acid mutations at particular positions (Y43A, S45A, or both) in the streptavidin mutant to selectively reduce affinity for natural biotin while preserving or enhancing affinity for modified biotin. This local modification approach allows differential binding properties at specific binding sites.

Inventive Principle:

Principle #3Local quality

Solution Approach 2:

The patent changes the chemical parameters of the biotin molecule by introducing modifications such as deuterium substitution or structural alterations at specific positions. These parameter changes in the biotin molecule enable selective high-affinity binding to the mutant streptavidin while natural biotin binding is reduced.

Inventive Principle:

Principle #35Parameter changes

Applied Scientific Principles

This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.

Function Achieved in This Case

The combination of the streptavidin mutant and modified biotin reduces immunogenicity and background biotin affinity, enhancing the specificity and effectiveness of diagnostic and therapeutic processes using the pretargeting method.

Implementation Method 1

a streptavidin mutant having a reduced affinity to the naturally-occurring biotin, and a dimeric compound of modified biotin having a high affinity to such streptavidin mutant

Methodology Applied

Scientific EffectAffinity binding: Adsorption

Data Source

PatentUS11286285B2Modified biotin, streptavidin mutant, and usage of them

Publication Date: 2022.03.29 COMPLECURE INC

AI summary

An object of this invention is to provide a streptavidin mutant reduced in affinity to the naturally-occurring biotin, and to provide a modified biotin which shows a high affinity to such streptavidin mutant reduced in affinity to the naturally-occurring biotin. This invention can provide a compound composed of a dimer of modified biotin, a streptavidin mutant, and usage of them.