Antibody Screening for Pathological Protein Neoepitopes
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Solution Overview
Problem
Current monoclonal antibodies, including humanized ones, often cause side effects due to cross-reactivity with physiological proteins, leading to autoimmune responses, and are not specific enough for pathological variants of endogenous proteins, posing risks in treating diseases like Alzheimer's and Parkinson's.
Innovation Solution
Development of methods to identify and produce antibodies that specifically target pathologically altered proteins by isolating binding molecules from clinically stable individuals, which recognize neoepitopes formed due to pathological changes, avoiding cross-reactivity with normal physiological proteins.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If monoclonal antibodies are used to target disease-associated proteins, then therapeutic efficacy is improved, but cross-reactivity with physiological proteins causes autoimmune responses and side effects
Solution Approach 1:
The patent applies local quality by directing antibodies to bind specifically to pathological variants of proteins (such as misfolded or aggregated forms) rather than the entire protein structure. This localized binding to disease-specific conformations allows therapeutic action on pathological forms while leaving physiological forms unaffected, thereby maintaining efficacy while reducing autoimmune responses
Solution Approach 2:
The invention inverts the traditional approach by not trying to prevent cross-reactivity through generic humanization, but rather by selecting antibodies that naturally bind to pathological variants. This inversion transforms the problem from preventing unwanted binding to actively selecting for desired specificity through screening methods that identify antibodies binding to disease-associated protein forms
2Manufacturing precision
If antibodies are designed to recognize pathological variants of endogenous proteins, then specificity is improved, but difficulty in identifying such specific binding molecules increases
Solution Approach 1:
The patent applies preliminary action by pre-screening antibody candidates using disease-specific assays that test binding to pathological protein variants before full therapeutic development. This preliminary identification and validation of specificity reduces the risk of cross-reactivity early in the development process and streamlines subsequent manufacturing and clinical trials
Solution Approach 2:
The invention uses disease-specific assay systems and screening methods as intermediaries to identify antibodies with the desired specificity. These intermediary tools facilitate the detection and measurement of binding characteristics, making the identification process more systematic and less difficult
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 approach allows for the creation of antibodies that effectively target disease-associated proteins without interfering with normal protein function, reducing the risk of autoimmune responses and improving therapeutic specificity and safety.
Implementation Method 1
identifying and isolating a binding molecule which binds to said specimen but not to corresponding cells or tissues without such pathological characteristics
Data Source
AI summary
Provided are novel specific binding molecules, particularly human antibodies as well as fragments, derivatives and variants thereof that recognize neoepitopes of disease-associated proteins which derive from native endogenous proteins but are prevalent in the body of a patient in a variant form and/or out of their normal physiological context. In addition, pharmaceutical compositions comprising such binding molecules, antibodies and mimics thereof and methods of screening for novel binding molecules, which may or may not be antibodies as well as targets in the treatment of neurological disorders such as Alzheimer's disease are described.