BoNT/B Peptide Segmentation for Immunoresistance Management
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Solution Overview
Problem
Clostridial toxin therapies, such as those using Botulinum neurotoxins (BoNTs) and Tetanus neurotoxin (TeNT), face challenges due to the reversible nature of their neuromuscular paralysis effects, requiring periodic treatments and often leading to immune responses that reduce their effectiveness over time.
Innovation Solution
Development of BoNT/B peptides that elicit antibody responses, mapping antigenic regions within the HN and HC domains of BoNT/B, and using these peptides to create compositions that can determine immunoresistance, prevent it, or treat it by inducing a tolerogenic response.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Duration of action of stationary object
If Clostridial toxin therapies are administered periodically to maintain therapeutic effects, then the duration of action is extended, but immune responses develop that reduce effectiveness over time
Solution Approach 1:
The patent segments the full-length BoNT/B toxin into smaller peptide fragments (e.g., HN domain peptides residues 610-871, HC domain peptides residues 872-1291). These segmented peptides retain antigenic properties for immune modulation while having reduced toxicity compared to the complete toxin, allowing repeated administrations without developing full immunoresistance
Solution Approach 2:
The patent extracts specific antigenic regions (HN and HC domains) from the complete BoNT/B toxin molecule. By taking out only the essential antigenic portions that elicit protective antibody responses while excluding the most toxic regions, the therapy can be administered repeatedly to maintain effectiveness without triggering strong neutralizing immune responses
2Reliability
If full-length BoNT/B toxin is used for therapy, then therapeutic effectiveness is high, but immune responses are strongly elicited that reduce responsiveness over time
Solution Approach 1:
The patent divides the full-length BoNT/B toxin into smaller peptide fragments from the HN and HC domains. These segments provide sufficient antigenic stimulation to elicit protective immune responses while being too small to trigger strong neutralizing antibody formation, thus maintaining therapeutic effectiveness across multiple treatments
Solution Approach 2:
The patent applies local quality by using different peptide segments from specific regions of the BoNT/B toxin (HN domain residues 610-871, HC domain residues 872-1291) that have different properties. These local regions provide the necessary antigenic properties for immune modulation while having reduced immunogenicity compared to the complete toxin
Data Source
AI summary
The present invention provides BoNT/B peptides, BoNT/B peptide compositions, tolerogizing compositions, immune response inducing compositions, as well as methods of determining immunoresistance to botulinum toxin therapy in an individual, methods of treating immunoresistance to botulinum toxin therapy in an individual, methods of reducing anti-botulinum toxin antibodies in an individual and methods of inducing a BoNT/B immune response an individual.