Amyloid-Beta Binding Proteins Targeting Soluble Globulomers
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Solution Overview
Problem
Current therapies targeting amyloid-beta (Aβ) peptides for Alzheimer's disease often result in severe side effects, such as microhemorrhages, and there is a need for biologics that can effectively bind to soluble Aβ globulomers to prevent or slow disease progression without adverse effects.
Innovation Solution
Development of a novel family of Aβ binding proteins, including murine monoclonal antibodies, chimeric antibodies, and humanized antibodies, specifically designed to bind to soluble Aβ globulomers like Aβ(20-42), which are capable of inhibiting the activity of targeted Aβ forms associated with Alzheimer's disease.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If polyclonal and monoclonal antibodies are used to target Aβ peptides, then therapeutic effect is achieved, but severe side effects such as microhemorrhages occur
Solution Approach 1:
The patent applies local quality by directing antibodies to specifically target soluble Aβ globulomers rather than all Aβ forms. The antibodies are designed with specific binding characteristics that recognize and bind to the globulomer conformation, allowing selective neutralization of harmful soluble oligomers while leaving insoluble deposits and other Aβ forms unaffected, thereby avoiding the microhemorrhage side effects associated with broad-spectrum anti-Aβ therapies
2Reliability
If antibodies target monomeric Aβ(1-42), then some therapeutic effect is produced, but serious side effects occur in animals and humans
Solution Approach 1:
The patent applies parameter changes by shifting the target from monomeric Aβ(1-42) to soluble Aβ globulomers, which represent a different conformational state and aggregation level. This parameter change in target selection allows the antibodies to neutralize the most pathogenic soluble forms without triggering the severe inflammatory and hemorrhagic responses associated with targeting monomers, thus improving the therapeutic safety profile
3Reliability
If passive immunization is administered to very old APP23 mice, then therapeutically relevant effects are observed, but increase in microhemorrhages occurs
Solution Approach 1:
The patent applies the intermediary principle by using soluble Aβ globulomers as a mediator to bridge the therapeutic action and safety requirements. The antibodies bind specifically to these globulomers, which act as intermediaries that can be neutralized without triggering the harmful cascade leading to microhemorrhages. This intermediary target allows therapeutic intervention while avoiding the direct harmful interactions that occur with broader anti-Aβ approaches
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
These binding proteins effectively target Aβ globulomers, reducing their activity and potentially slowing disease progression while minimizing harmful side effects, offering a diagnostic and therapeutic tool for Alzheimer's disease.
Implementation Method 1
These binding proteins effectively target Aβ globulomers, reducing their activity
Data Source
AI summary
The present invention relates to amyloid-beta (Aβ) binding proteins. Antibodies of the invention have high affinity to Λβ(20-42) globulomer or any Λβ form that comprises the globulomer epitope. Method of making and method of using the antibodies of the invention are also provided.