High-purity production of multi-subunit proteins such as antibodies in transformed microbes such as pichia pastoris

摘要

Discloses a method of producing full length antibodies, comprising: (a) providing a growth culture comprising Pichia pastoris cells comprising genes that provide for the expression of said full length antibodies and growing said Pichia yeast in said growth culture for about 12-16 hours (“growth phase”); (b) adding ethanol to said culture after said growth phase in a single bolus addition (“bolus”) which bolus results in a concentration of ethanol in said culture of between 0.5% and 1.5% w/v, and (c) culturing said culture to produce said secreted full length antibodies , wherein said culturing comprises adding a feed comprising a fermentable carbon source to said culture.