The patented method – dubbed the Crystalomics formulation technology – uses whole antibody crystals to seed crystallization according to Don Paul Kovarcik, who told us the CMO uses an iterative process to identify the optimum conditions to accelerate the process.
“Althea typically screens over a thousand crystallization conditions. Variables include the types and concentrations of salts, precipitants and buffers as well as combinations of pH and temperature.
“The best crystallization conditions use pharmaceutically acceptable ingredients and are selected to give the highest yield of uniform crystals of a narrow size range in a relatively short amount of time, usually less than 24 hours.”
This is much faster than current antibody crystallization process, which can take weeks according to Kovarcik.
Targeted approach
Crystallization is often described as being more of an art than a science because choosing the optimum conditions for a successful reaction conducted using established methods requires a combination of luck and judgement.
Ajinomoto Althea’s method differs according to Kovarcik, who said: “We are taking a more targeted approachby doing a complete characterization of the molecule. The more information we have upfront, the more specific/targeted we can get with our screen.
“There are an infinite number of excipients, additives and combinations thereof, so the ability to narrow down the possibilities greatly improves efficiency. In the end each molecule is different, so there is no formula that will necessarily give good results.”
The method is intended for use in the crystallisation of whole antibodies or fragments at commercial-scaleKovarcik said, adding that: “Althea has successfully crystalized over 100 molecules including antibodies, hormones, enzymes, peptides, and nucleic acids from human, animal and microbial sources.”