Humanized Antibodies Targeting Beta-Amyloid Epitopes

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Solution Overview

Problem

Current methods for diagnosing and treating amyloidosis, particularly Alzheimer's Disease and age-related macular degeneration, are inadequate as they fail to effectively prevent or address the formation and progression of amyloid plaques, leading to significant cognitive and visual impairments with limited treatment options and side effects from existing medications.

Innovation Solution

Development of highly specific and effective humanized antibodies that recognize and bind to distinct binding sites on β-amyloid proteins, capable of preventing the formation and dissolving existing amyloid plaques, thereby reducing amyloid burden in the brain and eyes, specifically designed to target β-amyloid antigens in their monomeric, dimeric, or polymeric forms.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If current diagnostic and treatment methods are used for amyloidosis, then existing medications can be administered, but they fail to effectively prevent or address amyloid plaque formation and progression, leading to significant cognitive and visual impairments

Engineering Contradiction:

Improveeffectiveness of treatmentVSAvoidamyloid plaque formation and progression

Core Design Contradiction:

ReliabilityVSObject-generated harmful factors

Solution Approach 1:

The patent employs anti-amyloid beta antibodies as intermediary molecules that specifically bind to amyloid beta aggregates and plaques. These antibodies act as mediators between the immune system and amyloid deposits, facilitating their clearance while preventing further accumulation. The antibodies serve as a bridge that targets the harmful amyloid structures without directly interfering with normal physiological processes.

Inventive Principle:

Principle #24Intermediary (Mediator)

Solution Approach 2:

The invention converts the harmful amyloid beta aggregates into beneficial targets for therapeutic intervention. By designing antibodies that specifically recognize and bind to amyloid beta structures, the treatment transforms the previously harmful accumulation into a targetable condition that can be actively cleared by the immune system, thereby converting the disease mechanism into a treatable condition.

Inventive Principle:

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

2Adaptability or versatility

If existing medications are administered to treat amyloidosis, then treatment can be provided, but side effects occur and treatment options remain limited

Engineering Contradiction:

Improvetreatment optionsVSAvoidside effects

Core Design Contradiction:

Adaptability or versatilityVSObject-affected harmful factors

Solution Approach 1:

The patent utilizes parameter changes in antibody structure and specificity to achieve selective targeting of amyloid beta. By engineering antibodies with specific binding affinities and epitope specificities, the treatment can distinguish between pathological amyloid aggregates and normal physiological proteins. This parameter optimization allows for effective amyloid clearance while minimizing off-target effects and side effects.

Inventive Principle:

Principle #35Parameter changes

3Reliability

If humanized antibodies are designed to recognize multiple binding sites on beta-amyloid proteins, then effectiveness against various amyloid forms increases, but antibody complexity increases

Engineering Contradiction:

Improveeffectiveness against amyloid formsVSAvoidantibody structure

Core Design Contradiction:

ReliabilityVSDevice complexity

Solution Approach 1:

The patent designs humanized antibodies with multi-functional capabilities to recognize and bind to multiple distinct binding sites on beta-amyloid proteins. This multi-functionality allows a single antibody molecule to target different conformational states and aggregate forms of amyloid beta, including monomers, oligomers, and mature plaques. The antibody structure is engineered to accommodate diverse binding modes while maintaining humanized characteristics for reduced immunogenicity.

Inventive Principle:

Principle #6Universality (Multi-functionality)

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 humanized antibodies effectively inhibit the aggregation of β-amyloid monomers into fibrils, disaggregate preformed fibrils, and reduce the plaque load in the brain and eyes, potentially alleviating symptoms and slowing disease progression with reduced side effects.

Implementation Method 1

highly specific and effective humanized antibodies that recognize and bind to distinct binding sites on β-amyloid proteins

Methodology Applied

Scientific EffectAntibody-antigen binding:

Implementation Method 2

The humanized antibodies effectively inhibit the aggregation of β-amyloid monomers into fibrils

Methodology Applied

Scientific EffectAmyloid aggregation inhibition:

Implementation Method 3

disaggregate preformed fibrils, and reduce the plaque load in the brain and eyes

Methodology Applied

Scientific EffectAmyloid disaggregation:

Data Source

PatentEP2205632B1Use of Anti-amyloid beta antibody in ocular diseases

Publication Date: 2016.11.16 GENENTECH INC

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AI summary

The present invention provides novel methods and compositions comprising highly specific and highly effective antibodies that specifically recognize and bind to specific epitopes from a range of ?-amyloid proteins. The antibodies of the present invention are particularly useful for the treatment of ocular diseases associated with pathological abnormalities/changes in the tissues of the visual system, particularly associated with amyloid-beta-related pathological abnormalities/changes in the tissues of the visual system.