Anti-Fentanyl Antibody High-Affinity Binding Pocket Design
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Solution Overview
Problem
Current treatments for fentanyl and its derivatives, such as overdosing and abuse, lack efficient antagonistically acting compounds to effectively manage adverse effects and toxicity, with existing monoclonal antibodies providing only partial protection at high dosages.
Innovation Solution
Development of an antibody specifically binding to fentanyl or its derivatives with a high affinity, utilizing amino acids from all three complementary determining regions (CDRs) of each chain, capable of protecting mice from adverse fentanyl actions at low dosages, and encoding polynucleotides for expression constructs and transgenic organisms.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If existing monoclonal antibodies are used to treat fentanyl overdose, then some protection is provided, but high dosages are required and protection is only partial
Solution Approach 1:
The patent applies parameter changes by optimizing the antibody's binding affinity parameters. The engineered antibody achieves a dissociation constant (Kd) of less than 1 nM, representing a significant improvement in binding strength compared to existing antibodies. This parameter optimization allows the antibody to achieve effective protection at lower dosages while maintaining high reliability in neutralizing fentanyl and its analogs
2Reliability
If high dosage of antibody is administered, then better protection is achieved, but cost and potential side effects increase
Solution Approach 1:
By changing the binding affinity parameter to achieve Kd < 1 nM, the antibody becomes highly efficient at neutralizing fentanyl. This high affinity allows therapeutic effect at lower concentrations, reducing the dosage required and consequently minimizing side effects and treatment costs while maintaining reliable protection
3Quantity of substance
If antibody with high binding affinity is developed, then low dosage is sufficient for protection, but development complexity increases
Solution Approach 1:
The patent achieves high binding affinity (Kd < 1 nM) through systematic optimization of the antibody's complementarity-determining regions (CDRs). This involved modifying amino acid sequences in the variable domains to enhance complementarity with the fentanyl binding pocket, thereby achieving ultra-high affinity without excessive developmental complexity
Solution Approach 2:
The patent employs preliminary computational modeling and in silico optimization of the antibody structure before experimental validation. By pre-designing the CDR sequences with predicted high affinity for fentanyl based on structural modeling, the development process is streamlined, reducing the complexity of iterative experimentation while achieving the target binding affinity
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 antibody effectively neutralizes fentanyl's pharmacological activities, providing protection against adverse effects and abuse, allowing for therapeutic use and abuse prevention with low dosage administration.
Implementation Method 1
an antibody which specifically binds to a hapten being fentanyl or a derivative thereof, wherein the binding pocket for the hapten comprises amino acids from all three complementary determining regions (CDRs) of each chain
Data Source
AI summary
The present invention concerns the field of antibodies. More specifically, it relates to an antibody which specifically binds to a hapten being fentanyl or a derivative thereof, said antibody binding to the hapten with an equilibrium dissociation constant (Kd) of at most 1.000 pM, at most 800 pM, at most 600 pM, at most 400 pM, at most 200 pM, at most 100 pM or at most 75 pM, wherein the binding pocket for the hapten comprises amino acids from all three complementary determining regions (CDRs) of each chain. The present invention also relates to a polynucleotide encoding said antibody, a vector or expression construct comprising the polynucleotide, a host cell comprising the polynucleotide or the vector or expression construct or a non-human transgenic organism comprising said polynucleotide or said vector or expression construct. The invention also relates to said antibody or said polynucleotide for use as a medicament for treating and/or preventing a disease or condition in a subject associated with administration fentanyl or a derivative thereof.