Peptoid Affinity Ligands for Antibody Purification
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Solution Overview
Problem
The high cost and instability of Protein A/G-based chromatographic media used in the purification of monoclonal antibodies and Fc-fusion proteins lead to expensive therapies due to high purification costs and potential contamination from chemical and enzymatic degradation.
Innovation Solution
Development of peptoid ligands that specifically bind to antibodies and Fc-fusion proteins, offering higher affinity and resistance to proteolysis, which can be coupled to a solid support for efficient purification.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If Protein A or Protein G affinity chromatography is used for antibody purification, then high selectivity and affinity for IgG is achieved, but the cost of purification becomes very high
Solution Approach 1:
The patent creates simplified copy versions of Protein A/G ligands using peptide sequences that replicate the essential binding functionality. These peptide ligands are cheaper to produce while maintaining the key selectivity advantage, directly addressing the cost issue without sacrificing IgG binding capability
Solution Approach 2:
The invention employs peptide-based ligands that are significantly cheaper to manufacture than protein-based ligands. Although peptides may have shorter operational lifetimes, their low cost allows for economical purification processes, making antibody production more affordable
2Reliability
If Protein A or Protein G ligands are used in chromatography, then high affinity binding to antibodies is achieved, but chemical and biochemical stability becomes poor
Solution Approach 1:
The patent employs peptide ligands that are inherently more chemically and enzymatically stable than protein ligands. The simplified peptide structure resists degradation from alkaline cleaning solutions and proteolytic enzymes, ensuring longer column lifetime and maintaining binding affinity throughout the column's operational life
Solution Approach 2:
The invention changes the chemical parameters of the ligand from complex protein structures to simplified peptide sequences. This parameter change enhances resistance to chemical degradation (alkaline stability) and biochemical degradation (proteolysis) while preserving the essential antibody binding capability
3Productivity
If Protein A or Protein G-based chromatographic media are used, then effective antibody purification is achieved, but column lifetime becomes short due to ligand degradation
Solution Approach 1:
The patent uses peptide ligands with enhanced durability that resist degradation from alkaline cleaning-in-place and sanitisation-in-place procedures. This increased stability directly extends column lifetime, allowing the chromatography media to maintain effective antibody purification capability over longer periods and more regeneration cycles
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
Peptoid ligands provide an economical and stable alternative for antibody purification, reducing costs and minimizing contamination, while maintaining high target specificity and affinity, thus improving the efficiency of the purification process.
Implementation Method 1
a peptoid ligand that specifically binds to an antibody such as IgG, and/or an antibody Fc fragment, and/or an Fc-fusion protein
Implementation Method 2
contacting said composition to said solid support so that antibody or Fc fragments bind to said compound
Data Source
AI summary
Compounds of Formulas I:and shorter variants thereof are described, along with solid supports having such compounds coupled thereto, and the use thereof as affinity ligands for antibodies.