BoNT/A Fermentation Temperature Modulation
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Solution Overview
Problem
Current botulinum toxin pharmaceutical compositions have limitations in terms of potency and stability due to oxidation of methionine residues during the fermentation process of Clostridium botulinum.
Innovation Solution
Modulating the temperature during the fermentation of Clostridium botulinum to reduce the oxidation level of methionine residues in the produced Clostridium botulinum neurotoxin serotype A (BoNT/A), resulting in a composition with enhanced potency.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If standard fermentation temperature is used during Clostridium botulinum fermentation, then fermentation efficiency is maintained, but oxidation level of methionine residues increases leading to reduced potency
Solution Approach 1:
The patent applies parameter changes by modulating the fermentation temperature to lower levels (e.g., 20-30°C instead of standard higher temperatures) during the fermentation process of Clostridium botulinum. This temperature parameter change reduces the oxidation level of methionine residues in the produced BoNT/A neurotoxin, thereby maintaining higher potency and therapeutic efficacy while still achieving effective toxin production
2Reliability
If lower fermentation temperature is used to reduce oxidation, then potency is improved, but fermentation productivity decreases
Solution Approach 1:
The patent implements periodic action by using a two-stage fermentation temperature control strategy: initially maintaining standard fermentation temperature to promote rapid bacterial growth and toxin production, then switching to lower temperature (20-30°C) during later stages to reduce oxidation of methionine residues. This periodic temperature modulation balances productivity in the growth phase with potency preservation in the production phase
Solution Approach 2:
The patent applies dynamics by making the fermentation temperature a dynamic parameter that changes during the fermentation process rather than remaining static. The temperature is adjusted based on the fermentation stage and oxidation level monitoring, allowing the system to optimize both productivity early in the process and potency later in the process through adaptive temperature control
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 results in BoNT/A compositions with reduced oxidation levels, leading to higher potency and improved therapeutic efficacy.
Implementation Method 1
oxidation of methionine residues during the fermentation process of Clostridium botulinum
Implementation Method 2
fermenting Clostridium botulinum bacteria
Data Source
AI summary
The present disclosure relates to Clostridium botulinum neurotoxin serotype A (BoNT/A) compositions with a plurality of 900 kDa Clostridium botulinum neurotoxin serotype A (BoNT/A) complex species. Provided herein are compositions comprising BoNT/A that have a low level of oxidation at specific methionine positions of 150 kDa BoNT/A. Further provided herein are methods of producing a composition comprising BoNT/A using a low temperature during the process of fermenting Clostridium botulinum bacteria