Liquid high concentration IgG1 antibody formulations by precipitation

Phase Separation of an IgG1 Antibody Solution under a Low Ionic Strength Condition

“…So far, these processes have usually been performed with precipitating agents such as PEG, polyvinylsulfonic acid (PVS), polyacrylic acid (PAA) and polystyrenesulfonic acid (PSS). These macromolecules are required to be subsequently removed (45,46). However, in the case of antibodies having LLPS properties as MAb A does, the purification and concentration steps can be completed without using precipitating agents.…”

Stability of Protein Pharmaceuticals: An Update

“…While our understanding of protein solubility is still imperfect, there have been significant advances in the past 20 years (326,328). Salted-out proteins still retain activity and native-like structure (327,(329)(330)(331), and the precipitation is fully reversible upon dilution.…”

“…One could have a protein that is saltedout, that is, the addition of an excluded solute has caused the chemical potential of the protein to exceed that of the solid phase (326,327). While our understanding of protein solubility is still imperfect, there have been significant advances in the past 20 years (326,328).…”

“…The proteins that are salted out still retain native structure and activity (329,330). Recently, highly concentrated precipitates of native antibodies were prepared by this method (327).…”

Aggregative protein–polyelectrolyte complex for high-concentration formulation of protein drugs

“…If protein precipitates can be fully dissolved by a small amount of a solvent, it is quite easy to obtain a high concentration protein solution. Matheus and co-workers have reported a pioneering example of the concentration of IgG1 by this precipitation-redissolution process using well-used precipitants, such as ammonium sulfate, sodium citrate, and polyethylene glycol [51]. However, the high dose of these precipitants that is required to completely precipitate proteins is unfavorable owing to the concern about several practical limitations, such as cytotoxicity [52].…”