Anionic
Anionic polyelectrolytes (polyanion polyelectrolytes) include copolymers of acrylic acid, methacrylic acid and methyl methacrylate (US 8362217), polyacrylic acid (PAA), polystyrenesulfonic acid (PSS, poly(4-vinylbenzenesulfonate metal soat)), polymethacrylate (PMA), polyacrylamidomethylpropanesulfonate (PAMPS), carboxymethylcellulose (CMC), maleic anhydride-styrene copolymer (MAS, maleic anhydride-vinylmethyl ether copolymer (MAVE), polyaspartate, polyglutamate, dextrane sulfate, pectin, alginate and glycosaminoglycans such as chondroitin sulfate, heparin/heparan sulfate and hyaluronic acid (Fahrner 2008/0193981).
Precipitation of antibodies using anionic polyelectrolytes
McDonald (Biotechnology and bioengineering, 102(4), 2009) discloses antibody precipitation using polyelectrolytes such as poly-acrylic acid (PAA) and polystyrenesulfonic aicd (PSS). McDonald also evaluted the impact of solution pH, ionic strengh and polyelectrolyte molecular weight on the degree of presicpitation using the polyelectrolytes. At a given pH, increasing solution ionic strenght prevented the ionic interaction between the polyelectrolyte and the antibody, reducing antibody precipitation. With increasing pH, there was an increase in impurity clearance. Increasing polyelectrolyte MW allowed the precipitation to be performed under conditions of higher ionic strenght.
Moya (US 2008/0255027) also teaches a method for purifying a biomolecule such as an antibody by providing the mixture at a set of conditions, adding one or more polymers which can consist of anionic polyelectrolytes and precipitating the polymer and bound biomolecule out of solution by changing the set of conditions in the mixture followed by spearating the precipitated polymer and bound biomolcule from the mixture.
Fahrner (US2008/0193981; see also WO/2008/091740) teaches a method of purifying antibodies by adjusting the acidity or salt concentration of amixture containg the antibody, adding a negatively charged polyelectrolyte such as polyacrylic acid (PAA) and polyvinylsulfonic acid (PVS) and their anions, polyacrylate and polyvinylsulfonate, separting the antibody-polyelectrolyte precipitate from impurities and resuspending the precipitte in an aqueous solution.
Van Alstin (WO2010/082894) discloses a method of isolating a biomolecule such as an antibody by mixing an aqueous sample containing the antibody with a negatively charged polymer in the presence of a salt under conditions such that the polymer selectively complex and flocculate the antibody to form a mixture of precipitate including the antibody. The antibody precipitate is then separated from the aqeuous liquid and resuspended in buffer. Negatively charged, carboxyl group containing polymers. Specific polymers include polycarboxylic acid (PCA), polyacrylic acid or carboxymethyldextran polymers of various molecular weights. Other polymers include CM cellulose or CM starch. In preferred embodiments, the flocculate (precipitate) containing the biomolecule is formed in the presence of the polymer at around neutral pH and relatively high conductivity (e.g., >50mM NaPhosphate).
Precipitation of impurities using anionic polymers
Itol (US 15/748736, published as US 2019/0010188) discloses a method for purifying an antibody which includes preapring a composition which includes the antibody so that the omcomposition includes an anionic polymer at pH lower than the pI of teh antibody and removing an inpurity insolubilized by teh antionic polymer such as by filtration.