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Publication Number
US-12584113-B2
Publication Date
2026-03-24
Expiration Date
Abstract
A method of cell culture comprising providing cells in a cell culture medium to start a cell culture process, and, maintaining at least one metabolite selected from 3-(4-hydroxyphenyl)lactate, 4-hydroxyphenylpyruvate, phenyllactate, indolelactate, indolecarboxylic acid, homocysteine, 2-hydroxybutyric acid, isovalerate and formate below a concentration C1 in the cell culture medium, wherein C1 is 3 mM and/or (ii) maintaining at least one amino acid selected from phenylalanine, tyrosine, tryptophan, methionine, leucine, serine, threonine and glycine below a concentration C2 in the cell culture medium, wherein C2 is 2 mM.
Core Innovation
A method of cell culture comprises providing Chinese hamster ovary (CHO) cells in a cell culture medium and starting a fed-batch cell culture process with the cells in the cell culture medium. The cell culture medium comprises histidine at a concentration above 2 mM, and serine at a concentration below 1 mM at the start of the culture process. The fed-batch cell culture process comprises adding more serine to the cell culture medium at one or more times after starting the cell culture process.
Maintaining serine below a concentration of 1 mM in the cell culture medium is performed as part of the fed-batch cell culture process. The method includes measuring the concentration of serine in the cell culture medium prior to adding more serine to the cell culture medium. Based on the measured concentration of serine, an amount of serine is added such that after adding the amount of serine, the concentration of serine is below 1 mM in the cell culture medium.
In the described context of mammalian cell culture, accumulation of growth-inhibiting metabolites in high-density fed-batch culture inhibits growth/productivity. Growth-inhibiting metabolites include 3-(4-hydroxyphenyl)lactate, 4-hydroxyphenylpyruvate, phenyllactate, indolelactate, indolecarboxylic acid, homocysteine, 2-hydroxybutyric acid, isovalerate, and formate, which are maintained below C1 (3 mM) and/or amino acids which are maintained below C2 (2 mM).
Claims Coverage
One independent claim is provided: clm-00001. It contains inventive features centered on fed-batch operation of CHO cells with controlled histidine and serine concentrations, and serine-specific measurement-based addition to keep serine below 1 mM after each addition.
Serine start below threshold with histidine above threshold in fed-batch CHO culture
Providing Chinese hamster ovary (CHO) cells in a cell culture medium, starting a fed-batch cell culture process, having histidine above 2 mM, and having serine below 1 mM at the start of the culture process.
Measurement-based serine addition to keep serine below 1 mM
Maintaining serine below 1 mM in the cell culture medium by measuring the concentration of serine prior to adding more serine and adding an amount of serine such that after adding, the concentration of serine remains below 1 mM.
The independent claim focuses on controlling serine at the start of a fed-batch CHO process and using prior measurement to govern one or more post-start additions of serine so that serine remains below 1 mM after each addition, within a medium containing histidine above 2 mM.
Stated Advantages
Not explicitly described in patent.
Documented Applications
Not explicitly described in patent.
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