Antigen Binding Protein CDR Mutations for PNH
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Solution Overview
Problem
Current treatments for Paroxysmal Nocturnal Hemoglobinuria (PNH) are inadequate, with existing therapies like Eculizumab and Ravulizumab showing limited therapeutic effects, necessitating the development of alternative therapeutics to improve patient outcomes.
Innovation Solution
An isolated antigen binding protein is developed, comprising specific CDR sequences from the heavy and light chain variable regions, which includes amino acid mutations to enhance binding affinity and stability, potentially offering improved therapeutic efficacy against C5-related diseases.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If existing therapies like Eculizumab and Ravulizumab are used for PNH treatment, then patients receive complement-mediated protection, but therapeutic effects are limited and mortality rates remain high
Solution Approach 1:
The patent introduces amino acid mutations in the CDR regions of the antibody sequence, specifically modifying residues in HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 to enhance binding affinity to C5. These parameter changes at the molecular level aim to improve therapeutic efficacy while maintaining complement-mediated protection
2Reliability
If amino acid mutations are introduced to enhance binding affinity, then therapeutic efficacy is improved, but protein stability may be affected
Solution Approach 1:
The patent applies local quality changes by introducing specific amino acid mutations only in the CDR regions (HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, LCDR3) while keeping the framework regions intact. This localized modification approach enhances binding affinity to C5 while preserving the overall structural stability of the antibody protein
Solution Approach 2:
The patent systematically modifies amino acid parameters at specific positions in the CDR regions to optimize binding affinity. The mutations are carefully selected to improve C5 interaction while maintaining protein fold stability through controlled parameter changes in the variable regions
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 antigen binding protein demonstrates enhanced binding capacity and hemolysis inhibition, potentially providing better therapeutic outcomes for PNH patients compared to existing treatments.
Implementation Method 1
The antigen binding protein includes at least one CDR of the heavy chain variable region and at least one CDR of the light chain variable region, wherein the heavy chain variable region includes an amino acid sequence as shown in any one of SEQ ID NOs: 44-46 or a variant
Implementation Method 2
The antigen binding protein demonstrates enhanced binding capacity and hemolysis inhibition, potentially providing better therapeutic outcomes for PNH patients compared to existing treatments
Data Source
AI summary
An isolated antigen binding protein, which includes at least one CDR of a heavy chain variable region and at least one CDR of a light chain variable region and a method to encode an isolated nucleic acid molecule. A vector with the nucleic acid molecule. A cell with the nucleic acid molecule. A pharmaceutical composition with the isolated antigen binding protein. A method for preventing, alleviating or treating a CS-related disease or disorder. A method for detecting C5 in a sample.