Modified NGF Antibody CDR Sequences for Binding Affinity
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Solution Overview
Problem
Current NGF antibodies have sub-optimum pharmacokinetics, stability, and efficacy in vivo, limiting their therapeutic utility for neutralizing NGF activity in pain-related disorders.
Innovation Solution
Development of immunoglobulin heavy and light chain polypeptides with specific amino acid sequence modifications, such as replacements and insertions in complementarity determining regions (CDRs), to enhance binding affinity and stability, thereby effectively neutralizing NGF activity.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If current NGF antibodies are used, then NGF binding capability is achieved, but pharmacokinetics, stability, and efficacy in vivo are sub-optimum
Solution Approach 1:
The patent applies parameter changes by modifying specific amino acid residues in the complementarity determining regions (CDRs) of the antibody sequence. Specific residues were mutated to alter binding affinity and pharmacokinetic properties, transforming the antibody from sub-optimum performance to improved efficacy and stability in vivo
Solution Approach 2:
The invention applies local quality by making targeted modifications only in specific regions (CDRs) of the antibody molecule while maintaining the overall structure. This localized approach allows optimization of binding characteristics without compromising the stability of the entire antibody protein
2Reliability
If current NGF antibodies are used, then NGF binding capability is achieved, but pharmacokinetics are sub-optimum
Solution Approach 1:
The patent modifies amino acid parameters in the CDR regions to optimize pharmacokinetic properties, including half-life and clearance rates. These sequence changes enable the antibody to achieve improved pharmacokinetics and extended duration of action in vivo
3Strength
If current NGF antibodies are used, then NGF binding capability is achieved, but binding affinity is insufficient
Solution Approach 1:
The invention changes amino acid parameters in the complementarity determining regions to enhance binding affinity for NGF. These modifications create stronger interactions between the antibody and its target, improving neutralization efficacy
Solution Approach 2:
The patent utilizes known antibody frameworks and CDR sequences as templates, creating modified versions with improved binding properties. The invention copies successful binding motifs and optimizes them through targeted mutations to achieve superior 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 modified NGF-binding agents demonstrate improved binding affinity and stability, leading to effective neutralization of NGF activity and potential therapeutic benefits in treating NGF-mediated disorders, including pain-related conditions.
Implementation Method 1
The invention provides an isolated immunoglobulin heavy chain polypeptide comprising one or both of the following: (a) a complementarity determining region-1 (CDR1) comprising SEQ ID NO: 1... and (b) a complementarity determining region-2 (CDR2) comprising SEQ ID NO: 2... The modified NGF-binding agents demonstrate improved binding affinity and stability, leading to effective neutralization of NGF activity
Data Source
AI summary
The invention relates to an isolated immunoglobulin heavy chain polypeptide and an isolated immunoglobulin light chain polypeptide that binds to Nerve Growth Factor (NGF). The invention provides an NGF-binding agent that comprises the aforementioned immunoglobulin heavy chain polypeptide and immunoglobulin light chain polypeptide. The invention also provides vectors, compositions, and methods of using the NGF-binding agent to treat an NGF-mediated disease.