Monoclonal antibodies recombinant

Herceptin HER2 receptor monoclonal antibody, recombinant... 

CD20 monoclonal antibody, recombinant [SY] MabThera [TR used by Roche outside of US and Japan]... 

While animal studies are used for safety assessment prior to administration to humans, preclinical testing may not always predict human effect. For example, continuous-infusion therapy with 260F9 monoclonal antibody-recombinant ricin A chain resulted in severe neurotoxic effects in humans that were not demonstrated in monkey toxicology studies [21], In such cases where suitable animal models are not available for safety testing it is important to consider the application of an appropriate safety factor to provide a margin of safety for protection of humans receiving the initial clinical dose [11,18]. 

In addition to ATryn , GTC Biopharmaceuticals has several other products under development in collaboration with Cento-cor, Abbott, Elan, Bristol-Myers Squibbs, Alexion, Progenies Pharmaceuticals, Im-munoGen, and Merrimak Pharmaceuticals. These collaborations and internal programs involve the production of several monoclonal antibodies, recombinant human seram albumin, a malaria vaccine, fusion proteins, and a protein for the treatment of autoimmune conditions. Some of the products that are currently undergoing cHnical trials and will be discussed later [361]. 

The main focus on modem biopharmaceuticals should be directed towards novel products which will be either monoclonal antibodies, recombinant proteins, cell and gene therapeutics, or viral products. Apart from product classes, new approaches to manufacture are also advancing, with transgenic animals and plants complementing existing cell culture-based expression (see Part IV, Chapters 5-11). (For a recent review, see Ref [8].)... 

Product formation kinetics in mammalian cells has been studied extensively for hybridomas. Most monoclonal antibodies are produced at an enhanced rate during the Gq phase of the cell cycle (8—10). A model for antibody production based on this cell cycle dependence and traditional Monod kinetics for cell growth has been proposed (11). However, it is not clear if this cell cycle dependence carries over to recombinant CHO cells. In fact it has been reported that dihydrofolate reductase, the gene for which is co-amplified with the gene for the recombinant protein in CHO cells, synthesis is associated with the S phase of the cell cycle (12). Hence it is possible that the product formation kinetics in recombinant CHO cells is different from that of hybridomas. 

Commercial use of cell and tissue culture continues to expand. Improvement of organisms through recombinant nucleic acid techniques has become commonplace. Formerly, a few laboratories were well ahead of most others, but now the methods have been perfected for routine use. Another technique that is widely practiced is culturing of cells that excrete high concentrations of just one antibody protein. The specificity of antibodies and antigens is exploited in medical testing procedures using these pure monoclonal antibodies. 

Recombinant humanized monoclonal antibodies have been used recently to target antigens that are preferentially located on cancer cells. Examples include trastuzumab and rituximab which are used to treat HER2 positive breast cancer and B-cell type lymphomas, respectively. Unwanted side effects include anaphylactic reactions. 

Biotech products based on recombinant DNA, gene expression or hybridoma/monoclonal antibody technologies. 

Rituximab is a recombinant mouse/human chimeric monoclonal antibody whose in vitro activity varies with the number of terminal galactose moieties glycosylated to the peptide backbone at residue asparagine 301 [8]. The ability to monitor the levels of each discrete species present would allow the manufacturing process to... 

It is critical to keep in mind that existing reagents can be used for multiple formats. Eor example, polyclonal antibodies dominate the environmental field because they generally provide greater sensitivity and specificity for small molecules at a much lower cost than do monoclonal or recombinant antibodies. With some biosensors monoclonal or engineered antibodies or recombinant binding proteins may offer advantages. 

In E. Coli bacterial lysates, the proteome (i.e., the full array of proteins produced) was analyzed by isoelectric focusing and mass spectrometry.97 A comparison of capillary electrophoretic separation and slab gel separation of a recombinant monoclonal antibody demonstrated that the precision, robustness, speed, and ease-of-use of CE were superior.98 Seventy-five proteins from the yeast ribosome were analyzed and identified by capillary electrophoresis coupled with MS/MS tandem mass spectrometry.99 Heavy-chain C-terminal variants of the anti-tumor necrosis factor antibody DE7 have been separated on capillary isoelectric focusing.100 Isoforms differing by about 0.1 pi units represented antibodies with 0,1 or 2 C-terminal lysines. 

Hunt G. and Nashabeh W., Capillary electrophoresis sodium dodecyl sulfate nongel sieving analysis of a therapeutic recombinant monoclonal antibody a biotechnology perspective, Anal. Chem. 71, 2390,1999. 

Adalimumab is a recombinant human IgGl monoclonal antibody specific for human TNF.27 Adalimumab binds to soluble and bound TNF-a. Patients may experience symptomatic relief in as early as 1 week. Adalimumab can be administered in combination with methotrexate or other DMARDs.2... 

Kogenate FS Recombinant Solvent detergent, monoclonal antibody Albumin (fermentation only) sucrose... 

The recombinant monoclonal antibody rituximab is an effective treatment option for some patients with non-Hodgkin s lymphoma as a single agent and enhances the efficacy of combination chemotherapy regimens. 

Biotechnology era beginning First recombinant DNA products Human insulin Human growth hormone Interferons, etc. Monoclonal antibodies Nucleotide blockage Growth in use of natural products and neutraceuticals... 

G. Hunt, T. Hotaling, and A. Chen. Validation of a capillary isoelectric focusing method for the recombinant monoclonal antibody C2B8, J. Chromatogr. A, 800, 355 (1998). 

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