Biopharmaceuticals antibody-based

At least 1000 potential biopharmaceuticals are currently being evaluated in clinical trials, although the majority of these are in early stage trials. Vaccines and monoclonal antibody-based products represent the two biggest product categories. Regulatory factors (e.g. hormones and... 

Following recent advances in antibody engineering, it is now possible to s)mthesize humanized antibodies [35]. Because of clinical applicability, antibody-based medicines are one of the biopharmaceutical categories that have attracted close attention in recent years [36]. IgG has been most frequently used for the prevention and treatment of various diseases. The CH2 region of IgG has A-linked carbohydrates (usually complex type double stranded chains) in diverse manners (O Scheme 14). It has recently been revealed that differences in the carbohydrate structure affect the effecter activity of antibodies such as antibody-dependent cellular cytotoxicity (ADCC) and their half-life in blood, inviting close attention from the viewpoint of improving the responses to antibody-based medicines [37,38,39]. 

Some of the now commercially available antibody-based products have blockbuster potential, and the overall development of the sector is very strong. MAbs represent the fastest growing segment within biopharmaceuticals, and are outperform-... 

The initial promise of antibody-based biopharmaceuticals has taken a long time to... 

After the approval of the first product, recombinant insulin, in 1982, progress in the development of new recombinant protein pharmaceuticals was slow ([10], Fig. 17.1). The number of biotechnology-derived drugs and vaccines approved by the US Food and Dmg Administration (FDA) has increased significantly only since 1995. More recently, sales of biologies have skyrocketed, e.g. from 900 million in 1999 to an estimated 3.5 billion in 2001 for monoclonal antibodies [11]. The annual global market for biopharmaceuticals is estimated to have increased from 12 billion US to 30 billion US in 2003 [12]. 500 candidate biopharmaceuticals are undergoing clinical evaluation and over one hundred protein-based therapeutics are in the... 

In addition to recombinant biopharmaceuticals, animal cell culture is used to produce various other biologically based pharmaceuticals. Chief amongst these are a variety of vaccines and hy-bridoma cell-produced monoclonal antibodies (Chapter 13). Earlier interferon preparations were also produced in culture by a particular lymphoblastoid cell line (the Namalwa cell line), which was found to synthesize high levels of several IFN-a s naturally (Chapter 8). 

To date, most approved protein-based drugs are for therapeutic or replacement therapies. They are recombinant versions of natural proteins such as insulin and erythropoietin. Their characteristics and functions are relatively well defined and known. The next phase of biopharmaceuticals, such as antibodies and vaccines, is more complex and requires more tests and characterizations. Controls for the reliability, contamination, and fidelity of expression systems will be high on the agenda in the coming decade. 

In the last two decades, CE has advanced significantly as a technique for biomolecular characterization. It has not only passed the transition from a laboratory curiosity to a mature instrument-based method for micro-scale separation, but has also emerged as an indispensable tool in the biotech and pharmaceutical industries (Chapter 14). CE has become a method of choice in R D for molecular characterization, and in QC for release of therapeutic biomolecules. In the biopharmaceutical industry, more and more CE methods have been validated to meet ICH requirements. To demonstrate the influence of CE in RScD for method development and in manufacturing for the release of therapeutic proteins and antibodies, examples from the pharmaceutical industry are provided in Chapter 14. 

The protein microarray represents an emerging technology. While we have described its potential utility, several key problems remain to be overcome before this tool is fully adopted by the research and biopharmaceutical commxmities. The most likely first embodiment will be an antibody "protein-detecting" microarray. This is understandable based upon the availability and suitability of antibody libraries originally developed for ELISA. We have discussed many demonstrahons of antibody arrays in this chapter but commercial introductions (Pierce, Beckman Coulter) have been limited. 

The considerable list in Table 6.3 illustrates some of the companies that are currently preparing plant-based biopharmaceutical technologies for commercialization. Steps have been taken toward the development and subsequent commercialization of one of these products, currently in Phase 2 clinical trials and known as CaroRx (licensed to Planet Biotechnology Inc., Hayward, CA) a monoclonal antibody designed for treatment of tooth decay by S. mutans is described in the following text. 

In 1996, about 10 years after the introduction of the first recombinant DNA product for human use, the FDA modified and streamlined the approval process for biotechnology products considered to be well characterized. These modifications, in essence, established the direction of how biologic macromolecules are researched and developed today in biotechnology-based and traditional pharmaceutical companies [2]. Well-characterized biotechnology products include (1) synthetic peptides consisting of fewer than 20 amino acids, (2) monoclonal antibodies and derivatives, and (3) recombinant DNA-derived products. Anticipating future developments, the FDA is also prepared to consider DNA plasmid products as well-characterized when the first medicinal in this class is submitted for approval. CBER now approves well-characterized biopharmaceuticals under the BLA process [3]. 

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