Humanized anti-ACTH antibodies and use thereof
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Solution Overview
Problem
Existing treatments for conditions associated with elevated cortisol and aldosterone levels, such as Cushing's disease and hyperaldosteronism, are inadequate due to the lack of specific and targeted interventions that can modulate ACTH activity without affecting other melanocortin receptor functions.
Innovation Solution
Development of human, humanized, or chimerized anti-ACTH antibodies or antibody fragments that selectively bind to ACTH, avoiding interaction with specific ACTH regions and modulating ACTH-related activities to reduce cortisol and aldosterone levels.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If existing treatments are used to manage elevated cortisol and aldosterone levels, then some therapeutic effect is achieved, but the treatments lack specificity and fail to selectively modulate ACTH activity without affecting other melanocortin receptor functions
Solution Approach 1:
The patent segments the ACTH molecule into distinct functional regions (N-terminal 1-13 residues, C-terminal 18-39 residues, and central 14-22 residues) and designs antibodies with specific binding affinities for different segments. This segmentation allows selective modulation of ACTH activity at specific regions while avoiding interference with other melanocortin substrates that bind to different regions of the melanocortin receptors.
Solution Approach 2:
The patent applies local quality by creating antibodies with differentiated binding characteristics targeting specific local regions of ACTH. The antibodies are designed to bind preferentially to specific epitopes (e.g., N-terminal or C-terminal regions) with distinct affinities, allowing localized therapeutic action on ACTH while preserving activity at other melanocortin receptor binding sites.
2Adaptability or versatility
If broad-spectrum melanocortin receptor antagonists are used, then multiple melanocortin activities are blocked, but ACTH-specific activity cannot be selectively modulated
Solution Approach 1:
The patent segments the melanocortin receptor binding interface into distinct epitope regions on the ACTH molecule. By designing antibodies that target specific segments (N-terminal, C-terminal, or central regions), the invention achieves ACTH-specificity while the Fc region maintains effector functions, effectively separating the specificity function from the effector function.
Solution Approach 2:
The patent uses the Fc region of the antibodies as an intermediary that provides effector functions (such as ADCC, CDC, and complement activation) independent of the binding specificity provided by the Fab region. This intermediary Fc region allows the antibody to selectively bind ACTH while simultaneously providing therapeutic effector mechanisms without directly blocking other melanocortin receptor activities.
3Reliability
If conventional antibody formats are used, then therapeutic coverage is provided, but the complexity of the antibody structure increases manufacturing and clinical development challenges
Solution Approach 1:
The patent segments the antibody into functional modules: the Fab region for specific ACTH binding and the Fc region for effector functions. This modular segmentation allows independent optimization of binding specificity (in Fab) and effector capacity (in Fc), simplifying the overall design and manufacturing process while maintaining comprehensive therapeutic coverage.
Solution Approach 2:
The patent employs a universal Fc region design that can be applied across different antibody formats (IgG1, IgG2, IgG3, IgG4) to provide consistent effector functions. This universal Fc module reduces the complexity of developing multiple antibody formats, as the same Fc region can be used with different Fab specificities or in different isotypes to achieve the same therapeutic effect through different mechanisms.
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 inhibit ACTH activity, providing therapeutic benefits in conditions like Cushing's disease and hyperaldosteronism by reducing steroid hormone levels and addressing associated symptoms.
Implementation Method 1
human, humanized, or chimerized anti-ACTH antibodies or antibody fragments that selectively bind to ACTH
Data Source
AI summary
The present invention is directed to antibodies and fragments thereof having binding specificity for ACTH. Embodiments of this invention relate to the binding fragments of antibodies described herein, comprising the sequences of the VH, VL and/or CDR polypeptides described herein, and the polynucleotides encoding them. The invention also contemplates anti-ACTH antibodies and binding fragments thereof conjugated to one or more functional or detectable moieties. The invention further contemplates methods of making said anti-ACTH antibodies and binding fragments thereof. Embodiments of the invention also pertain to the use of anti-ACTH antibodies and binding fragments thereof for the diagnosis, assessment, prevention and treatment of diseases and disorders associated with ACTH, such as CAH, FGD, Cushing's Disease, Cushing's Syndrome, Parkinson's disease, obesity, diabetes, sleep disorders, depression, anxiety disorders, cancer, muscle atrophy, hypertension, hyperinsulinemia, cognitive dysfunction, Alzheimer's disease, galactorrhea, stress related conditions, cardiac conditions, metabolic syndrome, hyperaldosteronism, Conn's syndrome and familial hyperaldosteronism.