Co-precipitation of non-IgG contaminants with positvely chartged polymers parallels the selectivity of AEX. These reagents selectively co-precipitate acidic host cell protins, DNA and varous cell culture additivies. (Pete Gagnon, J. Chromatography A 1221 (2012) 57-70)

Positively charged soluble polymers (polyallylamine, polyarginine) as well as certain divalent cation (ethacridine, metal ions) have been employed to co-precipitate negatively charged contaminants form antibody preparations. (Gagnon, US 14/555060)

Cationic polyelectrolytes (polycation polyelectrolytes): include chitosan, polyvinylpyriddines, primary amine containing polymers, secondary amine containing polymers and tertiary amine containing polymers (Moya, US 8362217), polyarginine (PLA, including poly-L-arginine hydrochloride and poly-L-arginine sulfate, polylysine (e.g., poly-L-lysine hydrochloride, polyomithine, polyvinylguanidine (poly-(vinyguanidine), polymethylacrylamidopropyltrimethylammonium chloride, polyvinylbenzyltrimethylammonium chloride and polyhistidine (Fahrner, 2008/0193981).

Specific Types of Cationic Polyelectrolytes

Chitsan is inexpensive and available in a highly purified form that is low in heavy metals, volatile organics and microbial materials. It is a cationic linear polymer of beta-(1-4) linked D-glucosamine monomers generated by the chemical deacetylation of chitin and has been used fro the removal of nucleic acid and endotoxin and the flocculation of cell debris of yeast and bacteria. (Liu, “Recovery and purification process development for monoclonal antibody production” mAbs,  2:5: 480-499 (2010).

Fahrner (US2008/0193981; see also WO/2008/091740) teaches a method of purifying antibodies by adjusting the acidity or salt concentration of a mixture containing the antibody, adding a positively charged polycation polyelectrolyte such as polyargiine (PLA) to the mixture whereby a precipitate is formed comprising the positively charged polycation polyelectrolyte and impurities, and separating the the precipitate from the mixture comprising the antibody. 

Polyamines: Polyamines are cationic polyelectroytes with multiple repeating amine functional groups. Due to this nature of these amine functional groups, they are protonated under a wide pH range and thus pisitively charged. The polyamines can be used to precipitate negatively charged proteins in solution. Ma (J. Chromatography B, 878 (2010) 798-806) discloses polyamines, which are cationic polyelectrolytes, which can be used to precipitate hamster ovary (CHO) host cell proteins (CHOP). If precipitation is carried out at the appropriate pH, at which the most basic monoclonal antibody of interest has net positive charges, the polyamines selectively precipitate and remove the negatively charged CHOP impurities leaving the monoclonal antibody intact and soluble in HCFF.

Jaber, Moya, etc. (US8,691,918) disclose separating a target molecule by providing a sample containing the target molecule, contacting the sample with a soluble stimulate responisve polymer comprising a cationic polyelectrolyte backbone which can be a polyallylamine (BzMPAA) backbone modified with a hydrophobic groups attached to the backbone to form a complex of the polymer and one or more impurities, adding a stimulus to the sample to precipitate the complex out of solution to thereby separate the target molecule from one or more impurities.

Ethacridine lactate: Lester discloses a method for purifying a desired polypeptide such as an antibody by adding to the broth 6.9-diamino-2-ethoxyacrdine lactate (ethacridine lactate) to precipitate host cell impurities under conditions wherein the majority of polypeptide remains soluble and then separating the desired polypeptide.

PVP and Co-Polymer of PVP (Polyvinyl pyridine-containing polymers):

 Moya (US 8,362,217 and and WO2008/079280A1) (See also Moya, US2008/0255027 and US 13/747495) discloses a Ph dependent polymer such as poly(4-vinylpyridine-co-styrene) which has an affinity for a desired biomolecule such as an antibody in the insoluble state. In a first step, a mixture is harvested from cell broth, then the mixture is conditioned to the correct pH (e.g., below 5) to maintain the polymer in solution, then the mixture conditions are changed to cause the polymer to precipitate out of solution by altering the pH (e.g., 7.0) and the antibody recovered such as by elution. 

Moya (US2013/0123476) also disclosess a method purifying a biomolecule of itnerest from negative charged impurities by adjusting the pH of the mixture, adding a cationic polyelectrolyte selected from PVP and a co-polymer of PVP, creasing the pH of the mixture to precipitate the polymer and form a supernatant wehre the precipitated polymer binds the impurities and recovering the supernatant containing the biomoecule of interest. Examples of copolymers of PVP are poly(2 vinylpyridine)(P2VP) or poly(4 vinylpyridine) (P4VP), polyvinylpyridine-co-styrene (PVP-A), polyvinylpyridine-co-butyl methacrylate (PVP-BMA) as well as other primary, secondary and tertiary amine containing polymers. These polymers are soluble at a pH lower than about 6-7 and are insoluble at a pH greater than about 5-7. When in solution, these polymers will precipitate if the pH is raised above this critical range (pH=5-7). Such a cationic polyelectroyte can be added to a fluid containing the biomolecule either as a solution in a carrier liquid at a pH of about 4.5 or as a solid particulate in which the fluid is either modified to a pH of about 4.5 either before, during or after the introduction of the polymer to it so that the polymer binds all negatively charged impurites such as cells, cell fragmetns, nucleic acids, ciruses, endotoxins, etc. The biomoecule of interest does nto interact with teh polymer given its postive net charge due to its basic pI. The pH is then raised to 5-7 or more if desired and the polymer precipitates out of solution, carrying with it all the impurities as well as any excess polymer. The precipitate can then be easily removed by centrifugation or filtration resulting in a purified biomolecule containing solution.