Post-fermentation Processing
Table 3. Antibody fragment structures expressed to date using pAVEway
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Avecia also has assembled an antibody fragment toolkit to address the needs of post-fermentation processing. Components of
the toolkit include those described below:
Refolding Screens
Although soluble expression is targeted as the preferred option, the diversity of antibody fragment properties means that
cannot always be achieved and insoluble expression may be the most effective way forward. There is a need, therefore, to have
refolding approaches that can identify high-yielding refolding approaches and are suitable for large-scale applications.
Pegylation
As discussed earlier, the small size of some antibody fragments allows more effective access to disease targets than full-length
antibodies. However, this also means that serum permanence is low (~2 h).22 In some therapeutic applications, this rapid clearance is desirable, while for others a longer in vivo half-life is necessary. Protein conjugation to polyethylene glycol (PEG) is a recognized approach to extend half-life and
has a 20-year history of use in human therapies.23 Cimzia is an example of the application of PEGylation to an antibody fragment for desired pharmokinetics.
Fig 6. Polytherics' novel disulphide bond pegylation chemistry
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The application of novel approaches to PEGylation is beneficial for production. The PEGylation of disulphide bridges developed
by Polytherics (Figure 6) is a technology which is likely to have application in the field of antibody fragments.24,25
Conclusion
Antibody fragments are a rapidly developing therapeutic area underpinned by the success of whole antibodies and scientific
insights, allowing the generation of a diverse range of antibody fragment domain-based therapeutics. Fragment antibody production
is possible with microbial systems such as E. coli and yeasts, translating into lower CoGs and wider application of the benefits of such therapeutic molecules.
J.M.LIDDELL, PhD, is head of process science at Avecia Biologics Ltd, Billingham, UK, +44 (0)1642 364016, john.liddell@avecia.com
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