Reduction of lipase activity in product formulations

Abstract

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.

What is claimed: 
     
         1 . A composition comprising a stable recombinant protein and a polysorbate, wherein the recombinant protein is produced by a host cell, wherein at least one copy of an endogenous gene encoding the endogenous lipoprotein lipase is knocked out from the genome of the host cell, wherein the endogenous lipoprotein lipase is present in the composition in an amount less than 10% by weight, and wherein the endogenous lipoprotein lipase is capable of degrading the polysorbate. 
     
     
         2 . The composition  claim 1 , wherein the recombinant protein is a monoclonal antibody. 
     
     
         3 . The composition of  claim 1 , wherein the polysorbate comprises polysorbate 80, polysorbate 20, polysorbate 40, polysorbate 60, polysorbate 65, or a combination thereof.