METHODS OF SHIFTING AN ISOELECTRIC PROFILE OF A PROTEIN PRODUCT AND USES THEREOF

摘要

Provided herein are methods shifting the isoelectric profile of a recombinant protein product and the use of such methods in the manufacture of recombinant protein products. Also provided are recombinant protein products produced by such methods.

主权项

1. A method of shifting the isoelectric profile of a recombinant protein product, the method comprising:
(a) culturing mammalian cells comprising a nucleic acid encoding a recombinant protein in a production bioreactor under conditions sufficient to produce the product for a first period of time that consists of a growth phase and/or a stationary phase of the mammalian cells; (b) assaying the product isoelectric profile at the end of the first period of time; and (c) incubating the product under conditions sufficient to shift the isoelectric profile of the product toward a more acidic profile for a second period of time that consists of at least 6 hours of a decline phase of the mammalian cells, or incubating the product under conditions sufficient to shift the isoelectric profile of the product toward a more basic profile for a second period of time of a decline phase of the mammalian cells; and, (d) assaying the product to determine the isoelectric profile and repeating step (c) if the isoelectric profile requires further shifting.