Applications & Products
Antibody & Antibody Fragments
Antibodies of all types now dominate the stage when it comes to biotech products under development, in clinical trials and in therapeutic use. Both the number of new antibody products and their scale of manufacture have been increasing steadily, which in combination with growing pressure to reduce the cost of antibody therapeutics now places significant demands upon antibody manufacturers. In particular the industry requires improved methods of antibody production to remove current bottle-necks and improve product yields, provide greater clearance of impurities and reduce manufacturing costs.
Traditionally researchers and manufacturers have turned to Protein A, a recombinant protein ligand produced by genetic engineering, as the principal antibody purification technology. However, increasing concerns about the limitations of Protein A, including its high cost, limited stability and re-use (resulting in protein A leaching into the product), and its biological origins, have resulted in a growing interest in suitable alternatives. Furthermore, Protein A is specific to certain types of IgG antibodies and cannot be used to purify the growing number of engineered antibody fragments in development which lack the protein A binding site associated with the IgG Fc region.
In response to this PBL has established a range of highly stable and inexpensive synthetic-ligand affinity products which are used for the purification of a wide variety of different antibody types. Our MAbsorbent® product range currently includes two antibody binding ligands (MAbsorbent® A1P and MAbsorbent® A2P) with a third currently in advanced stages of development. These adsorbents are derived from PBL's Mimetic LigandTM technology and incorporate small, highly stable synthetic ligands (not based on peptides or proteins) which are specific for various regions of the antibody molecule. MAbsorbent® A2P is currently the most widely used of these adsorbents and is increasingly adopted for human polyclonal IgG manufacture since, unlike Protein A, it is stable to high concentrations of NaOH and selective for all human IgG subclasses. The latest version of MAbosrbent® A2P is constructed using Purabead® High-Flow (a highly cross-linked agarose support matrix with a very uniform particle size) and this material is available in high and low ligand densities for different target applications.
MAbsorbent® A2P HF has been adopted for the manufacture of polyclonal antibodies such as IVIG and hyperimmune IgG where its broad selectivity for all IgG subclasses (including IgG3) and resistance to concentrated sodium hydroxide santisation provides significant advantages over Protein A. In the case of monoclonal antibodies, MAbsorbent® A2P HF may be used, though binding can be subject to interference by the cell culture media additive Pluronic® F68, and if this surfactant is included in the cell culture media, an initial conditioning step has to be performed before application to the MAbsorbent® A2P HF column. The latest MAbsorbent product (currently in development) functions in the presence of Pluronic® F68 and in evaluation trials, has performed competitively in comparison to Protein A for direct capture of monoclonal IgG from culture media.
Recently PBL has launched a new product targeted at the purification of antibody fragments. Fabsorbent™ F1P HF is another synthetic ligand affinity adsorbent, but unlike MAbsorbent® A2P, the ligand is specific for antibody light chain. Fabsorbent™ F1P HF binds both kappa and lambda light chain and so may be considered a universal antibody binding ligand. This adsorbent has been used successfully for the purification of a wide variety of antibody fragment types, including Fab', F(ab')2 and Fv fragments. Consequently, Fabsorbent™ F1P HF is very relevant to the needs of recombinant antibody fragment producers since, unlike full-chain monoclonals, there is currently no established affinity purification platform for Fab's.