Production Strategies for Antibody Fragment Therapeutics - Microbial systems such as E. Coli and yeasts are the most effective production systems for the production of antibody fragments. - BioPharm

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Production Strategies for Antibody Fragment Therapeutics
Microbial systems such as E. Coli and yeasts are the most effective production systems for the production of antibody fragments.


BioPharm International Supplements


Post-fermentation Processing


Table 3. Antibody fragment structures expressed to date using pAVEway
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
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,


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