Activated-Ester Antibody Reagent for Long-Term Storage

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Solution Overview

Problem

Existing antibody modification reagents used in CCAP methods are chemically unstable and cannot withstand long-term storage, leading to concerns about the stability and longevity of antibody medicaments like ADCs.

Innovation Solution

A chemically stable compound and its salt are developed, which can be used to produce a modified antibody by reacting with IgG via an IgG-binding peptide, ensuring the peptide does not remain in the final product, thereby improving storage stability and enabling site-specific modification.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Manufacturing precision

If NHS group is used in antibody modification reagent, then site-specific modification capability is achieved, but chemical stability and storage longevity deteriorate due to hydrolysis

Engineering Contradiction:

Improvesite-specific modification capabilityVSAvoidchemical stability

Core Design Contradiction:

Manufacturing precisionVSStability of the object's composition

Solution Approach 1:

The patent changes the chemical parameter of the reactive group from NHS ester to activated ester with enhanced stability. The activated ester maintains the ability to react with amino groups while resisting hydrolysis, thus preserving site-specific modification capability while improving chemical stability for long-term storage.

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The patent replaces the unstable NHS group with a more stable activated ester group that does not require immediate use. This allows the modification reagent to be stored for extended periods without degradation, eliminating the need for fresh preparation and enabling industrial application.

Inventive Principle:

Principle #27Cheap short-living objects (Disposable)

2Manufacturing precision

If IgG-BP remains in modified antibody, then site-specific binding is achieved, but antigenicity concerns arise for medicament application

Engineering Contradiction:

Improvesite-specific bindingVSAvoidantigenicity

Core Design Contradiction:

Manufacturing precisionVSObject-generated harmful factors

Solution Approach 1:

The patent extracts or removes the IgG-binding peptide from the final modified antibody product. The reagent design allows the IgG-BP to facilitate the modification process but then be eliminated, leaving only the desired modification without the peptide that could cause antigenicity issues.

Inventive Principle:

Principle #2Taking out (Extraction)

Solution Approach 2:

The IgG-binding peptide serves as a temporary intermediary during the modification process, enabling site-specific binding to the Fc region. After the modification is complete, the peptide is removed as it was only needed as a mediator during the process and not in the final product.

Inventive Principle:

Principle #24Intermediary (Mediator)

3Ease of manufacture

If conventional CCAP method is used, then antibody modification is achieved, but long-term storage stability deteriorates due to NHS group hydrolysis

Engineering Contradiction:

Improveantibody modification capabilityVSAvoidstorage stability

Core Design Contradiction:

Ease of manufactureVSDuration of action of stationary object

Solution Approach 1:

The patent changes the chemical stability parameter of the modification reagent by replacing NHS ester with a more stable activated ester. This allows the reagent to maintain its modification capability while being stable enough for long-term storage under various conditions, enabling industrial manufacturing and storage.

Inventive Principle:

Principle #35Parameter changes

4Power

If NHS group is used for IgG-BP modification, then reaction activity is maintained, but hydrolysis resistance and storage longevity worsen

Engineering Contradiction:

Improvereaction activityVSAvoidhydrolysis resistance

Core Design Contradiction:

PowerVSReliability

Solution Approach 1:

The patent optimizes the chemical structure by using an activated ester with enhanced hydrolysis resistance while maintaining adequate reaction activity. The activated ester group provides sufficient reactivity toward amino groups while being resistant to spontaneous hydrolysis, enabling both effective modification and stable storage.

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 compound and its salt provide a chemically stable antibody modification reagent that can be stored for a long period, facilitating the production of a novel modified antibody with improved stability and reduced antigenicity concerns.

Implementation Method 1

R2 or R3 has an IgG-binding peptide that specifically binds to an Fc region of an IgG

Methodology Applied

Scientific EffectSpecific binding:

Implementation Method 2

In the reaction between the antibody modification reagent and the antibody, the IgG-BP binds to a specific region of the Fc domain via NHS group

Methodology Applied

Scientific EffectChemical reaction: Chemical Bonding

Data Source

PatentUS20250304617A1Compound, salt of compound, antibody modification reagent, method for producing modified antibody, and modified antibody

Publication Date: 2025.10.02 PEPTIDE INSTITUTE INC

AI summary

A compound represented by Formula I described below or a salt of the compound:wherein R1 is a substituent and R1—H has a pKa of 4 to 14, R2 or R3 has an IgG-binding peptide that specifically binds to an Fc region of an IgG, and R4 is H or a substituted or unsubstituted alkyl group having 1 to 8 carbon atoms.