Chromatography is a dominant purification technique in the purification of biological materials, e.g., monoclonal antibodies.
Commonly used chromatography methods include one or more of affinity chromatography media, ion exchange chromatography media, hydrophobic interaction, hydrophilic interaction, size exclusion and mixed mode (i.e., combination of various chromatography interactions) chromatography. For example, for the purification of monoclonal antibodies, a typical purification process includes an initial Protein A affinity capture step followed by one or more ion exchange polishing steps, the purpose of which is to reduce the level of one or more impurities such as, e.g., host cell protein (HCP). Further, other chromatography techniques, such as: bind and elute hydrophobic interaction chromatography (HIC); flow-through hydrophobic interaction chromatography (FTHIC); flow-through anion-exchange chromatography (AEX); weak partitioning chromatography with cation-exchange, anion-exchange, or hydrophobic interaction reins; mixed mode chromatography techniques, e.g., bind and elute weak cation and anion exchange, bind and elute hydrophobic and ion exchange interaction and flow-through hydrophobic and ion exchange mixed mode interaction (FTMM), both of which can utilize resins such as Capto™ Adhere, Capto™ MMC, HEA Hypercel™, PPA Hypercel™, may be used. Additionally, hydrophobic charge induction (HCl) chromatography along with others and combinations of various techniques can be used for polishing.
Although, chromatography offers many advantages for protein purification on a smaller scale, on a large scale, packing of chromatography columns is not only labor and time intensive but also expensive. Further, fouling of chromatography columns is a common problem, resulting in a user having to dispose off columns, which is undesirable, especially due to the high cost of chromatography resins.
Recently, there has been a noticeable trend in the industry to try and reduce the number of steps in protein purification processes. Also, use of techniques for obtaining a higher expression titer using bioreactors is a rising trend in the industry. The combination of these two trends has resulted in more product being loaded onto a column, thereby resulting in increased burden of fairly expensive chromatography media as well as lower product purity, both of which are undesirable.
USPTO Backgrounds
USPTO Backgrounds