Recombinant antibody mixtures: production strategies and cost considerations.
ABSTRACT Recombinant monoclonal antibodies have during the last two decades emerged as a very successful class of biological drugs for the treatment of a variety of different diseases used either as biological mono therapy or in combination with small molecule based drugs. Recombinant antibody mixtures offering targeting of more than one antigen is one of the new promising antibody technologies resulting in higher therapeutic effectiveness and/or broader reactivity. Such recombinant antibody mixtures can in principle be manufactured by different approaches but two main strategies is often applied, either individual manufacturing of the constituent antibodies or single batch manufacturing of the recombinant antibody mixture. Symphogen has developed an expression platform, Sympress™, allowing single batch manufacturing of recombinant antibody mixtures, while other companies are currently using a manufacturing strategy based on production of the individual constituent monoclonal antibodies. An overview and comparison of the different approaches with focus on the challenges in terms of cell banking strategy, manufacturing approach, and strategies for release and characterization will be reviewed in the present manuscript. Furthermore, the two manufacturing approaches are compared based on different parameters such as development timelines, preclinical developmental costs, and manufacturing cost of goods sold (COGS). We conclude that the single batch manufacturing approach expressing a mixture of full length IgG provides a robust and reproducible platform that can be used for cost effective manufacturing of recombinant antibody mixtures.
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Article: Protein purification: an overview.[Show abstract] [Hide abstract]
ABSTRACT: Biological macromolecules such as proteins constitute an important class of products in the food, biotechnology, pharmaceutical, and cosmetics industries. The growing need to develop efficient and rapid protein purification methods is driving research and growth in this area. Advances and progress in the methods and techniques of protein purification have been such that one can reasonably expect that any protein of a given order of stability may be purified to currently acceptable standards of homogeneity. However, protein production cost remains extremely high, with downstream processing constituting a substantial proportion of the overall cost. Understanding of the methods and optimization of experimental conditions have become critical to the manufacturing industry in order to minimize production costs while satisfying all regulatory requirements. New purification protocols exploiting specific, effective, and robust methods and materials are expected to guide the future of the protein purification area.Methods in molecular biology (Clifton, N.J.) 01/2014; 1129:3-10. · 1.29 Impact Factor
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ABSTRACT: A body of evidence suggests that a mixture of therapeutic monoclonal antibodies (mAbs) may be better than a single antibody. Several strategies have been developed to achieve multiple targeting, including the administration of two or more mAbs to the patient, bispecific antibodies and antibody mixtures. Recently, new antibody technologies based on a diverse array of antibodies binding to several different epitopes on any given antigen or antigens have been developed. One of the most promising is the Sympress™ manufacturing technology, which allows the production of an antibody mixture in just one bioreactor as a single drug substance. Recombinant antibody mixtures may be applicable to therapy of neoplastic, autoimmune and infectious diseases.Expert opinion on biological therapy 05/2013; · 3.22 Impact Factor
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ABSTRACT: Induction of autoantibodies (autoAbs) targeting disease drivers / mediators is emerging as a potential immunotherapeutic strategy. Auto-immune complex (IC)-retaining follicular dendritic cells (FDCs) critically regulate pathogenic autoAb production in autoreactive germinal centers (GCs); however, their ability to induce potentially therapeutic autoAbs has not been explored. We hypothesized that deliberate display of clinically targeted antigens (Ags) in the form of ICs on FDC membranes induces target-specific autoreactive GCs and autoAbs that may be exploited therapeutically. To test our hypothesis, three therapeutically relevant Ags: TNF-α, HER2/neu and IgE, were investigated. Our results indicated that TNF-α-, HER2/neu- and IgE-specific autoAbs associated with strong GC reactions were induced by TNF-α-, HER2/neu- and IgE-IC retention on FDCs. Moreover, the induced anti-TNF-α autoAbs neutralized mouse and human TNF-α with half maximal Inhibitory Concentration (IC 50) of 7.1 and 1.6 nM respectively. In addition, we demonstrated that FDC-induced Ab production could be non-specifically inhibited by the IgG-specific Endo-S that accessed the light zones of GCs and interfered with FDC-IC retention. In conclusion, the ability of FDCs to productively present autoAgs raises the potential for a novel immunotherapeutic platform targeting mediators of autoimmune disorders, allergic diseases, and Ab responsive cancers.Human vaccines & immunotherapeutics. 07/2013; 9(11).