While approval of new therapeutic antibodies has not progressed as rapidly as was forecast 10 years ago, new products are moving through the pipeline. As always, bioprocessing, critical to antibody manufacture, is a key factor in the cost and efficiency of production.
Interviews with company officials and researchers engaged in bioprocessing showed how novel approaches to these challenges are moving the industry forward. All of the experts GEN spoke to will discuss new scientific developments and recent technological advances at BIT’s “International Congress of Antibodies” meeting in Beijing later this month.
“We have more than 60 programs in progress with our partners; the majority of these programs are building on IgG-type antibodies,” states Bodo Brocks, Ph.D., director and group leader of analytics and head of quality control at MorphoSys. “This is our preferred direction and our customers’ favored format. Moreover, our high-throughput systems are designed to move in this direction, producing large quantities of antibody.”
HuCAL, Morphosys’ antibody-development platform, HuCAL, is a phage display technology consisting of a library of 40 billion possible human antibody sequences. Unlike earlier antibody-development platforms, it does not rely on immunization of mice or other animals.
In a typical run, a panel of a few thousand possible candidates can be selected and further analyzed. “We examine biological potency, specificity, and affinity of the antibody, while on the other side we look at the physical chemical properties like thermal stability or aggregation to make the antibodies fit for our pipeline,” explains Dr. Brocks.
The antibodies from the library can be reconfigured, removing and replacing pieces so as to change their binding affinity or biological function without changing their overall human structure. “The strength of our technology is that we can do affinity maturation, bringing antibodies from nanomolar to picomolar affinity. By grafting alternative complementarity determining regions into promising candidates, we can develop highly potent antibodies.”
Alternative scaffolds, based on protein families such as the ankyrins, have been the subject of considerable attention in recent years but have not yet resulted in FDA-approved products. “These are interesting from the standpoint of ease of production in bacterial systems,” Dr. Brocks adds, “but in recent years mammalian upstream systems have improved significantly for antibody production, so that’s not an area that we are pursuing at this time.”