Protein therapeutic

Therapeutics. Therapeutic materials represent a class of polypeptides that are a low volume, high value product. The production system need not be very efficient but the quaHty of the recombinant protein has to be extremely pure (33,34). Thus high cost mammalian production systems can be tolerated. However, some of the therapeutic proteins such as insulin, human growth hormone, interleukins, interferon, and streptokinase are produced microbially. 

Human growth hormone is one of the largest selling therapeutic proteins produced by recombinant DNA technology. Annual worldwide sales increased from 130,000,000 in 1987 to 575,000,000 in 1992 (47). Upon approval of additional indications, the sales of hGH are expected to increase even more. 

Freeze drying, or lyophilization, is normally reserved for temperature-sensitive materials such as vaccines, enzymes, microorganisms, and therapeutic proteins, as it can account for a significant portion of... 

Chenite et al. reported on thermosensitive chitosan gels for encapsulating living cells and therapeutic proteins they are liquid below room temperature but form monolithic gels at body temperature [220-223]. 

Whole cells are grown for a variety of reasons. The cells may perform a desired transformation of the substrate, e.g., wastewater treatment the cells themselves may be the desired produce, e.g., yeast production or the cells may produce a desired product, e.g., penicillin. In the later case, the desired product may be excreted, as for the penicillin example, and recovered in relatively simple fashion. If the desired product is retained within the cell walls, it is necessary to lyse (rupture) the cells and recover the product from a complex mixture of cellular proteins. This approach is often needed for therapeutic proteins that are created by recombinant DNA technology. The resulting separation problem is one of the more challenging aspects of biochemical engineering. However, culture of the cells can be quite difficult experimentally and is even more demanding theoretically. 

Table 24.3 Specification of therapeutic proteins to be administered parenterally... 

Logan, K. A., Lagerlund, I., and Chamow, S. M., A simple, two-component buffer enhances use of chromatofocusing for processing of therapeutic proteins, Biotechnol. Bioeng., 62, 208, 1999. 

Significantly, therefore, recombinant DNA and hy-bridoma techniques are capable of providing molecules of a well-defined chemical composition and producing them in cell culture media that can be carefully controlled. In short, the critical advance these techniques offer is that supply and purity no longer impede the development and clinical usefulness of therapeutic protein molecules. 

The degradation of proteins in the solid state occur to a lesser extent and typically via different mechanisms than those that occur in solution [109,110]. Lyophilization is currently the more common technique in the manufacture of dried therapeutic proteins however, there is increasing interest in the use of spraydrying, owing to the unique physical nature of the spray-dried powder and its potential usefulness in protein drug delivery. 

Table 1 summarizes several of the experimental methods discussed in this chapter. A need exists for new or revised methods for transport experimentation, particularly for therapeutic proteins or peptides in polymeric systems. An important criterion for the new or revised methods includes in situ sampling using micro techniques which simultaneously sample, separate, and analyze the sample. For example, capillary zone electrophoresis provides a micro technique with high separation resolution and the potential to measure the mobilities and diffusion coefficients of the diffusant in the presence of a polymer. Combining the separation and analytical components adds considerable power and versatility to the method. In addition, up-to-date separation instrumentation is computer-driven, so that methods development is optimized, data are acquired according to a predetermined program, and data analysis is facilitated. 

Swartz, J.R. (2001) Advances in Pichia pastoris production of therapeutic proteins. Current Opinion in Biotechnology, 12 (2), 195-201. 

Misawa, S. and Kumagai, I. (1999) Refolding of therapeutic proteins produced in Pichia pastoris as inclusion bodies. Biopolymers, 51 (4), 297-307. 

Boehm, R. (2007) Bioproduction of therapeutic proteins in the 21st century and the role of plants and plant cells as production platforms. Annals of the New York Academy of Sciences, 1102, 121-134. 

The current accessible information from this company do not show any records on BDS activities, the most recent recorded event correspond to 2000 activities. On November 14, 2001, their report announced a restructuring process of the Company s Scientific Advisory Board, replacing members with scientists and physicians with experience in cancer, production of therapeutic proteins, preclinical development and clinical trials. That indication for a new orientation and focus to the health sector did not last enough, and soon after, the company disappeared from the SEC (and any other financial) listing. 

Kormann MS, Hasenpusch G, Aneja MK, Nica G, Flemmer AW, Herber-Jonat S, Huppmann M, Mays LE, Illenyi M, Schams A, Griese M, Bittmann I, Handgretinger R, Haiti D, Rosenecker J, Rudolph C (2011) Expression of therapeutic proteins after delivery of chemically modified mRNA in mice. Nat Biotechnol 29 154-157... 

Yatuv R, Robinson M, Dayan I, Baru M (2010) Enhancement of the efficacy of therapeutic proteins by formulation with PEGylated liposomes a case of FVIII, FVIIa and G-CSF. Expert Opin Drug Deliv 7 187-201... 

Many therapeutic proteins must be delivered by injection as alternative delivery routes (e.g., oral) result in low bioavailability. This can be difficult,... 

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