Antibodies Targeting Pathological Beta-Sheet Conformations
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Solution Overview
Problem
Current immunotherapies for amyloid diseases, such as Alzheimer's, face challenges including toxicity, inability to target tau-related pathology, and poor efficacy, with conventional anti-Aβ immunotherapy showing minor cognitive benefits and significant side effects.
Innovation Solution
Development of antibodies and binding fragments that specifically target the β-sheet secondary structure of pathological monomeric or oligomeric non-fibrillar proteins, using a heavy chain variable region with specific CDR sequences and a light chain variable region to inhibit the onset and treatment of amyloidogenic protein-mediated conditions, and diagnose amyloid diseases.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional anti-Aβ immunotherapy is used, then amyloid burden is reduced, but cognitive benefits are minimal and toxicity occurs
Solution Approach 1:
The patent applies local quality by designing antibodies with specific CDR sequences (H-CDR1: SEQ ID NO: 23-26, H-CDR2: SEQ ID NO: 27-30, H-CDR3: SEQ ID NO: 31-34) that confer selective binding affinity for pathological β-sheet conformations. This localized specificity at the molecular binding interface enables the antibody to distinguish between toxic and non-toxic forms, reducing off-target effects and toxicity while maintaining therapeutic efficacy.
Solution Approach 2:
The patent employs parameter changes by modifying the antibody structure through specific CDR sequences and humanization to alter binding characteristics. The heavy chain variable region with defined CDR sequences changes the binding parameters to preferentially recognize pathological conformations, thereby improving therapeutic efficacy while reducing adverse effects associated with conventional therapies.
2Adaptability or versatility
If conventional anti-Aβ immunotherapy is used, then amyloid plaques are cleared, but tau-related pathology is not addressed
Solution Approach 1:
The patent applies universality by creating antibodies that can bind to a broader range of pathological conformations including both Aβ and tau proteins. The heavy chain variable region with specific CDR sequences (particularly H-CDR3: SEQ ID NO: 31-34) is designed to recognize conserved β-sheet structural motifs across different amyloidogenic proteins, enabling a single therapeutic agent to address multiple pathologies simultaneously.
3Measurement precision
If antibodies target Aβ peptides, then amyloid burden reduces, but specificity for pathological conformations is insufficient
Solution Approach 1:
The patent applies local quality by designing antibodies with specific CDR sequences (H-CDR1: SEQ ID NO: 23-26, H-CDR2: SEQ ID NO: 27-30, H-CDR3: SEQ ID NO: 31-34) that confer selective binding affinity for pathological β-sheet conformations. This localized specificity at the molecular binding interface enables the antibody to distinguish between toxic and non-toxic forms, reducing off-target effects and toxicity while maintaining therapeutic efficacy.
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 antibodies effectively recognize and bind to toxic oligomeric forms of amyloidogenic proteins, potentially offering improved therapeutic and diagnostic tools for amyloid diseases by targeting the β-sheet conformation, addressing the limitations of existing immunotherapies.
Implementation Method 1
antibodies and binding fragments thereof that bind β-sheet secondary structures on pathological proteins, such as the β-sheet secondary structures found in toxic oligomeric forms of amyloidogenic proteins
Data Source
AI summary
The present invention relates to antibodies and binding fragments thereof that bind the β-sheet secondary structure of a pathological monomeric or oligomeric non-fibrillar proteins without binding to the non-toxic, non-pathological forms of these proteins or peptides These antibodies and binding fragments thereof are suitable for the diagnosis, prevention, and treatment of protein conformational disorders including all amyloid diseases.