Reduction of lipase activity in product formulations
The invention relates a method for producing a stable recombinant protein, comprising growing a non-naturally occurring host cell in a culture medium to produce a recombinant protein, and making a composition comprising the recombinant protein and a polysorbate. The production of endogenous lipoprotein lipase by the host cell is reduced. The endogenous lipoprotein lipase is present in the composition in a small amount, and is capable of degrading the polysorbate. The invention also relates to the relevant host cells and compositions, and preparation thereof.
1. A non-naturally occurring cultured host cell comprising a nucleic acid sequence encoding a recombinant protein, wherein the host cell expresses the recombinant protein and is a mammalian cell selected from the group consisting of CHO, 3T3, BHK, HeLa, NS0, and HepG2, and wherein at least one copy of an endogenous gene encoding an endogenous lipoprotein lipase is knocked out from the genome of the host cell.
2. The non-naturally occurring cultured host cell of claim 1 , wherein the host cell is CHO.