Humanized Agonist Anti-TrkC Antibody for Sensory Neuropathy
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Solution Overview
Problem
Current neurotrophin therapies for neurodegenerative and neurological diseases lack specificity, as they often cross-react with multiple receptors and can cause hyperalgesia, and rodent antibodies elicit a human anti-murine antibody response when used in humans, leading to inefficiencies and safety concerns.
Innovation Solution
Development of a humanized and affinity-matured agonist antibody, A5, specifically binding to the trkC receptor with high affinity, which is designed to target human and rodent trkC receptors, reducing cross-reactivity and improving bioavailability and pharmacokinetic properties.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If rodent antibodies are used to treat human diseases, then therapeutic activity is achieved, but human anti-murine antibody response develops leading to reduced reliability
Solution Approach 1:
The patent creates humanized antibodies that copy the binding specificity of rodent antibodies against trkC receptors while using human immunoglobulin sequences. This allows the antibodies to maintain therapeutic activity against human trkC receptors without eliciting human anti-murine antibody responses, directly resolving the reliability issue.
Solution Approach 2:
The patent modifies the antibody sequences by changing species-specific parameters (from rodent to human immunoglobulin sequences) while preserving the critical binding epitope recognition. This parameter change eliminates the harmful human anti-murine response while maintaining therapeutic effectiveness.
2Reliability
If neurotrophins are used to treat neurodegenerative diseases, then therapeutic effect is achieved, but lack of specificity causes cross-reactivity with multiple receptors and hyperalgesia
Solution Approach 1:
The patent extracts and isolates the specific binding activity against trkC receptors from the broader neurotrophin family. By using monoclonal antibodies specifically targeted at trkC, the therapy eliminates cross-reactivity with other receptors (trkA, trkB) while maintaining specific therapeutic effect, thus removing the harmful cross-reactivity and hyperalgesia effects.
Solution Approach 2:
The patent applies local quality by creating antibodies with highly specific binding characteristics tailored to trkC receptors. The antibodies are designed to recognize specific epitopes on trkC with high affinity, providing localized and specific therapeutic action rather than broad non-specific neurotrophin activity.
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 A5 antibody effectively activates trkC receptors with high affinity and slow dissociation kinetics, providing a specific and efficient therapeutic option for neurodegenerative disorders like sensory neuropathy while minimizing adverse reactions.
Implementation Method 1
The A5 antibody effectively activates trkC receptors with high affinity and slow dissociation kinetics
Data Source
AI summary
The invention concerns agonist anti-trkC antibodies, polypeptides, and polynucleotides encoding the same. The invention further concerns use of such antibodies, polypeptides and/or polynucleotides in the treatment and/or prevention of neuropathies, such as sensory neuropathies, including taxol-induced sensory neuropathy, cisplatin-induced sensory neuropathy, and pyridoxine-induced sensory neuropathy.