Optimization Of A Two-Step Purification Method For Bispecific Antibodies

Alligator Bioscience AB develops antibody-based pharmaceuticals for cancer treatment, specializing in mono- and bispecific antibodies for tumor-directed immunotherapies. The company is active in the early stages of drug development, from early concepts to clinical phase II studies.

In this article, explore the results from a collaboration with Alligator to develop an efficient downstream purification process for a cancer immunotherapy bispecific antibody (bsAb).

The study's main findings were:

• Exchanging MabSelect SuRe™ to the more recently developed MabSelect PrismA™ resin increased the loading capacity by 53% (using a load of 70% of the Q_b10 for MabSelect PrismA™).
• The stability of the bsAb in respect to pH and salt limited the window of usable conditions for the polishing step, but conditions could be optimized for purification on Capto™ adhere in both bind/elute (B/E) and flow-through (FT) mode.
• The evaluated conditions for elution from Capto™ adhere were considered good conditions for the B/E application in respect to the stability of the bsAb.
• Using the same conditions for the polishing step—but in FT rather than for elution in B/E mode — improved yield significantly (> 90% yield) with acceptable HCP levels and protein A clearance.
• The improved process both increases product yield and process economy.