Polyether Ionophore Modulation of Recombinant Protein Mannosylation
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Solution Overview
Problem
Current methods for controlling the glycosylation profile of recombinant proteins, particularly mannosylation, during cell culture processes often impact cell performance and protein yield, necessitating the development of methods that can modulate glycosylation without compromising production conditions or yields.
Innovation Solution
Incorporating polyether ionophores such as maduramycin, narasin, or salinomycin into the cell culture medium or feed medium to modulate the mannosylation profile of recombinant proteins, specifically increasing the levels of high-mannose species while maintaining viable cell density and protein titre.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Manufacturing precision
If polyether ionophores are added to cell culture medium to modulate mannosylation profile, then mannosylation level of recombinant protein is improved, but cell performance and protein yield may be compromised
Solution Approach 1:
The patent applies parameter changes by carefully controlling the concentration of polyether ionophores (maduramycin, narasin, or salinomycin) in the cell culture medium. By optimizing the dosage parameter, the invention achieves modulation of the mannosylation profile (increasing high-mannose species) while maintaining acceptable protein yield and cell performance, thus resolving the contradiction between glycosylation control and production efficiency
2Manufacturing precision
If polyether ionophores are added to cell culture medium to modulate mannosylation profile, then mannosylation level of recombinant protein is improved, but cell growth may be impacted
Solution Approach 1:
The invention uses parameter changes by optimizing the concentration range of polyether ionophores in the cell culture medium. This allows achieving the desired mannosylation modulation (increased high-mannose species) while keeping cell growth within acceptable parameters, thus resolving the contradiction between glycosylation control and cell proliferation
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
This approach effectively increases the mannosylation level of recombinant proteins, particularly high-mannose species, without significantly impacting cell growth or protein yield, allowing for improved therapeutic efficacy and consistency in recombinant protein production.
Implementation Method 1
The glycosylation profile of a protein, such as a therapeutic protein or an antibody, is an important characteristic that influences biological activity of the protein through changes in half-life and affinity due to effects for instance on folding, stability and antibody-dependent cellular cytotoxicity (ADCC)
Implementation Method 2
Modulation of protein glycosylation, such as mannosylation, is of particular relevance for marketed therapeutic proteins or antibodies as glycosylation (such as mannosylation) can impact therapeutic utility and safety
Data Source
AI summary
The present invention relates to methods and compositions for modulating mannosylation profile of recombinant proteins expressed by mammalian host cells during the cell culture process, using a polyether ionophore.