Grant Application Support

If your research proposal incorporates milligram-to-gram scale purification of recombinant proteins and antibodies or miligram-to-gram scale chiral and other challenging, small molecule separation, SMBC technology can significantly improve your results and productivity.

Semba can assist you with SMBC technology incorporation in your grant application. Please feel free to excerpt and modify the prewritten desciptions on SMBC technology, below. They are divided into two main sections, protein purification, and small molecule/chiral separation.

Additional resources available here include links to SMBC poster presentations, a full list of citations for the technology, and a letter of US manufacturing, which may be helpful in securing American Recovery and Reinvestment Act (ARRA).

The ARRA has provisions for $8 billion in NIH research, primarily though the R01 process. We encourage you to review the application requirements and funding opportunities through ARRA and the NIH. There are an unprecedented number of new funding opportunities currently available. One notable example specific to molecular separation technologies is a recent solicitation from the National Science Foundation.

Please contact us regarding your SMBC - related grant applications and research proposals. Semba can also provide customized support letters. We want to help you succeed in securing funding and in your research objectives.

The text boxes within each section, below, are editable - you can edit the copy live on the page, then simply select and copy the text (control - A then control - C for Windows or command - A then command - C for Mac). The text is now in the clipboard and ready to be pasted directly into your application.

Recombinant Protein and Antibody Purification
Expand this section to review, edit and copy text describing protein purification with the Octave System...

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Recombinant protein purification using affinity media in a traditional single-column (SC) elution chromatography mode is a well established technique. Usually, recombinant proteins are expressed with N- or C-terminal fusion tag such as a hexahistidine peptide and purified by immobilized metal affinity chromatography (IMAC). For many proteins, the level of purity achieved with the SC-IMAC step alone is not sufficient to allow further studies, such as functional characterization, X-ray crystallography, or drug target validation. In these cases additional purification steps are required which result in higher cost, delays and lower yields. Improvements such as increased purity and efficiency at any of these steps, IMAC in particular, would increase the throughput and lower the cost of purification.

Monoclonal antibodies represent one of the fastest growing areas of new drug development within the pharmaceutical industry. Several blockbuster products have been approved over the past several years including Rituxan, Remicade, Avastin, Humira, and Herceptin. In addition, over 300 new drugs are currently in clinical trials. With both large, established biotechnology companies and small start-ups involved in the development of this important class of molecules, monoclonal antibody products will become increasingly prevalent over the next decade. The dramatic rise in cell culture productivity achieved in the last few years has been a mixed blessing for bioprocessors. Although desirable from a cost of goods perspective, protein concentrations in the gram-plus per liter range stress the capabilities of processes designed for much lower titers. Higher protein titers place increasing demands on chromatography and process development scientists, not necessarily for higher capacity resins but for overall improved productivity.

The countercurrent flow, central to Simulated Moving Bed Chromatography (SMBC), enables the highest yields of purified proteins with the smallest investment in chromatography resins and mobile phases, bringing dramatic increases in operational efficiency and productivity. The countercurrent ﬂow of mobile and solid phases allows highly efficient use of chromatography resin and substantially increased resolution of target protein from other proteins with similar, but not identical, chromatographic properties. In single-column systems, separation actually occurs in a small fraction of the column at any one time, with the rest of the column performing no function other than occupying solvent and broadening bands. With SMBC, a series of small columns is used instead of one large column. Typically 50-70% of the solid phase is engaged in the separation zone, while the rest of the column material is being prepared for the next cycle of purification. Moreover, SMBC provides essentially an “infinite” column bed length without the costs associated with obtaining, operating, and maintaining large single columns. The column resin can be anything that is used in conventional chromatography, including ion exchange and affinity resins.

The same benefits SMBC brings to large scale chromatography are realized on a smaller scale with the innovative Semba Octave™ System. The Octave Chromatography System is a fully automated, benchtop deployable, continuous flow chromatography system for research and preparative scale molecular purification of high-value chemical and biological compounds. This versatile bench top multicolumn system is capable of simulated moving bed protocols at fluid pressures up to 300 psi and flow rates up to 10 or 100 ml/min. The system is compatible with many commercially available chromatography columns and process media. The Octave Chromatography System includes Mac Mini computer with pre-loaded SembaPro™ software application and protein purification scripts to program a wide variety of flow configuration with up to 8 columns for optimizing separation performance. With its compact footprint and simple operation, the Semba Octave Chromatography System enables researchers to take advantage of the power of SMBC on the bench top.

Small Molecule and Chiral Separation
Expand this section to review, edit and copy text describing chiral separation with the Octave System...

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Demand for enantiopure compounds continues to rise, primarily for use in pharmaceuticals but also for flavor and aroma chemicals, agricultural chemicals, and specialty materials. Single-enantiomer active pharmaceutical ingredients (APIs) have come to dominate the list of blockbuster drugs. As of 2005, the six of the seven top-selling drug formulations were single-enantiomer products. At present, the FDA imposes stringent rules on chiral purity of the final APIs; this has a big impact on development of new chiral drugs. As enantiomers of a chiral active pharmaceutical ingredient (API) could have dramatically different biological activities, they have to be evaluated early in the pre-clinical, lead optimization stage of drug discovery, and small amounts of each enantiomer (milligrams to grams) have to be obtained. Ideally, the methods used to produce required amounts of a chiral drug in the pre-clinical phase should be transferable to larger scale chiral API production.

Simulated moving bed chromatography (SMBC), a powerful approach to chromatographic fractionation, has been well-established for industrial scale production, including chiral separations. The SMBC process has been successfully utilized in the large-scale production of several pure enantiomer APIs, including one of the top-selling drugs manufactured by Pfizer, Zoloft.

SMBC is ideally suited for chiral API development since the fractionation process was developed for binary mixtures. Significant advantages of SMBC over single column batch chromatography are more efficient use of expensive chiral stationary phases (CSP), continuous sample processing, reduced solvent requirement, and more reliable scalability (Juza et al., 2000). The counter-current flow of mobile and solid phases in SMBC gives increased resolution of enantiomers from the racemix mixture. In single- column systems, separation actually occurs in a small fraction of the column at any one time, with the rest of the column performing no function other than occupying solvent and broadening bands. With SMBC, a series of small columns is used instead of one large column. Typically 50-70% of the solid phase is engaged in the separation zone, while the rest of the column material is being prepared for the next cycle of purification. Moreover, SMBC provides essentially an “infinite” column bed length without the costs associated with obtaining, operating, and maintaining large single columns.

The same benefits SMBC brings to large scale chromatography are realized on a smaller scale with the innovative Semba Octave™ System. The Octave Chromatography System is a fully automated, benchtop deployable, continuous flow chromatography system for research and preparative scale molecular purification of high-value chemical and biological compounds. This versatile bench top multicolumn system is capable of simulated moving bed protocols at fluid pressures up to 300 psi and flow rates up to 10 or 100 ml/min. The system is compatible with many commercially available chromatography columns and process media. The Octave Chromatography System includes Mac Mini computer with pre-loaded SembaPro™ software application and scripts to program a wide variety of flow configuration with up to 8 columns for optimizing separation performance.

With its compact footprint and simple operation, the Semba Octave Chromatography System enables researchers to take advantage of the power of SMBC on the bench top in addition to being the ideal method development tool for potential production scale-up.