Protein-based therapeutics

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... 

Dudzinski DM (2004), Reflections on historical, scientific, and legal issues relevant to designing approval pathways for generic versions of recombinant protein-based therapeutics and monoclonal antibodies, Flarvard Law School, Thesis. Available at http //leda.law.harvard.edu/leda/data/630/(accessed February 2006). 

As the biotechnology industry comes of age, and protein-based therapeutics become a practical reahty, the importance of protein-stabilizing technologies comes increasingly to the fore. The therapeutic efficacy of many of these biopharmaceuticals is impeded by the hosts natural immune defense system [23]. When a host encounters a foreign protein in its circulation, the hosts immune system initiates an immune response, which results in the production of protein-inactivating antibodies that dear the protein from the circulation. When the immune system develops an abihty to inactivate the protein, the therapy becomes ineffective. Hence, to counteract... 

In some cases, such as the one mentioned, such binders are quite straightforward to select, as the receptor contact surface is large. Indeed, TNF-a is a popular target for antibody and other protein-based therapeutic approaches, developers being encouraged by the success of etanercept (Enbrel, a soluble receptor-Fc fusion pro-... 

Small molecule drugs, defined as drugs with typical molecular weights <500 daltons, have been the main drivers of sales growth for Big Pharma. The projections lean toward a change in this trend by the turn of this decade. The pharmaceutical industry is expected to move rapidly toward biologic products, defined usually, but not exclusively, as protein-based therapeutic agents. Therapeutic... 

Protein-based therapeutics represent a significant portion of the pharmaceutical market, with over 130 proteins currently approved for clinical use by the FDA for a wide variety of indications (1). Many protein therapeutics are manufactured in bacterial or mammalian cells in large bioreactors, which is in contrast to the laboratory synthesis... 

Proteins are inherently nnstable and may produce degraded forms which are harmful when used in treatment of human diseases. On the other hand, protein-based therapeutic preparation are the fastest growing ikw drags nnder development. This calls for use of aggregation suppressing additives which rednce risk of instability. Theory of aggregation prevention and practical applications of preventive measnres are broadly discussed in this review. ... 

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