bullous pemphigoid, interstitial cystitis, nasal polyps, and idiopathic angioedema. Roles in non-allergic diseases Several groups have reported clinical trial results that omalizumab may be effective in patients with non-allergic asthma. This seems to be contrary to the general understanding of the pharmacological mechanisms of the anti-IgE therapy discussed above. Furthermore, among the diseases in which omalizumab has been studied for efficacy and safety, some are not allergic diseases, because hypersensitivity reactions toward external antigens is not involved. For example, a portion of the cases of chronic idiopathic urticaria and all cases of bullous pemphigoid are clearly autoimmune diseases. For the remaining cases of chronic idiopathic urticaria and those of the different subtypes of physical urticaria, the internal abnormalities leading to the disease manifestation have not been identified. Notwithstanding these developments, it is apparent that many of those diseases involve inflammatory reactions in the skin and the activation of mast cells. An increasing series of papers have shown that IgE potentiates the activities of mast cells, while omalizumab can function as a mast cell-stabilizing agent, rendering these inflammatory cells less active. Chemistry and formulations Omalizumab is a glycosylated IgG1 monoclonal antibody produced by cells of an adapted Chinese hamster ovary (CHO) cell line. The antibody molecules are secreted by the host cells in a cell culture process employing large-scale bioreactors. At the end of culturing, the IgG contained in the medium is purified by an affinity-column using Protein A as the adsorbent, followed by chromatography steps, and finally concentrated by UF/DF (paired ultra filtration/depth filtration). Omalizumab is manufactured at the Novartis' Huningue manufacturing site (France) through a partnership agreement with Genentech. Omalizumab was for several years provided only in a dry powder formulation, which requires the reconstitution with a prepacked solvent with the help of a shaker at the treating clinician's office before injection. A prefilled syringe liquid formulation has become available in many countries. History The product concept of anti-IgE antibodies against autologous IgE epitopes was discovered by perinatal monoclonal IgE immunization in rodents prior to the emergence of endogenous self IgE by Swey-Shen Chen at the Scripps Research Institute (TSRI) and in Case Western Reserve University (CWRU), and later confirmed by Dr. Alfred Nisonoff at Brandeis University using monoclonal IgE in incomplete Freund's adjuvant in perinates. Immunized or vaccinated rodents will develop low or undetectable levels of circulating IgE in a long-term IgE tolerance. Consequently, the passive monoclonal antibodies