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Monoclonal antibody
TypeWhole antibody
SourceHumanized (from mouse)
TargetIgE Fc region
Clinical data
Trade namesXolair
License data
  • B
Routes of
subcutaneous injection
ATC code
Pharmacokinetic data
Elimination half-life26 days
CAS Number
  • none
Chemical and physical data
Molar mass145058.2 g/mol g·mol−1
 ☒N☑Y (what is this?)  (verify)

Omalizumab, sold under the trade name Xolair, is a medication originally designed to reduce sensitivity to allergens. It has been used to try to control severe allergic asthma, which does not respond to high doses of corticosteroids and less widely for chronic spontaneous urticaria.

Omalizumab is a recombinant DNA-derived humanized IgG1k monoclonal antibody that specifically binds to free human immunoglobulin E (IgE) in the blood and interstitial fluid and to membrane-bound form of IgE (mIgE) on the surface of mIgE-expressing B lymphocytes.[1] Unlike an ordinary anti-IgE antibody, it does not bind to IgE that is already bound by the high affinity IgE receptor (FcεRI) on the surface of mast cells, basophils, and antigen-presenting dendritic cells.[2]

Medical uses[edit]

Allergic asthma[edit]

Omalizumab is used to treat people with severe, persistent allergic asthma, uncontrollable with oral or injectable corticosteroids.[3] Those patients have already failed step I to step IV treatments and are in step V of treatment. Such a treatment scheme is consistent with the widely adopted guidelines for the management and prevention of asthma, issued by Global Initiative of Asthma (GINA), which was a medical guidelines organization launched in 1993 in collaboration with the National Heart, Lung, and Blood Institute, National Institutes of Health, USA, and the World Health Organization.[4]

Chronic spontaneous urticaria[edit]

It is also used to treat people 12 years and above with chronic spontaneous urticaria (also called chronic idiopathic urticaria), which cannot be treated with elevated doses of H1-antihistamines.[medical citation needed]

Adverse effects[edit]

The main adverse effect is anaphylaxis (a life-threatening systemic allergic reaction), with a rate of occurrence of 1 to 2 patients per 1,000.[3][5] Like other protein and antibody drugs, omalizumab also causes anaphylaxis, although at a relatively low frequency among antibody drugs. The allergic reaction is probably not due to the binding characteristics of the antibody drug, but to the protein nature of the antibody[citation needed]. The patients who use omalizumab are generally highly allergic. Thus, even though the drug is administered with the purpose to suppress allergy (including anaphylactic reactions), it does not work immediately after injection.

It also increases the risk of strokes and heart disease by approximately 60%.[6][7]

IgE may play an important role in the immune system's recognition of cancer cells.[8] Therefore, indiscriminate blocking of IgE-receptor interaction with omalizumab may have unforeseen risks. The data pooled in 2003 from the earlier phase I to phase III clinical trials showed a numeric imbalance in malignancies arising in omalizumab recipients (0.5%) compared with control subjects (0.2%).[3] To clarify this imbalance, a more recent study was performed based on pooled analysis using much more comprehensive data from 67 phase I to IV clinical trials. The prespecified primary analysis assessed the incidence of primary malignancy in 32 randomized, double-blind, placebo-controlled (RDBPC) trials. In this analysis, there were 11,459 unique patients in all clinical trials (7,789 received omalizumab). The primary analysis identified malignancies in 25 patients (RDBPC trials): 14 in 4,254 omalizumab-treated patients and 11 in 3,178 placebo-treated patients. Incidence rates per 1,000 patient-years of observation time for omalizumab- and placebo-treated patients were 4.14 (95% CI, 2.26-6.94) and 4.45 (95% CI, 2.22-7.94), respectively; the corresponding rate ratio was 0.93 (95% CI, 0.39-2.27). Primary malignancies were of varying histologic type and occurred in a number of different organ systems; no cluster of histologies was identified. The study thus concluded that in this pooled analysis no association was observed between omalizumab treatment and risk of malignancy in RDBPC trials; the rate ratio was below unity. The data suggest that a causal relationship between omalizumab therapy and malignancy is unlikely.[9]

Concerns were raised earlier about possible induction of eosinophilic granulomatosis with polyangiitis (Churg-Strauss syndrome), a rare form of systemic vasculitis associated with asthma, in patients receiving the drug.[10] A retrospective review, which identified and analyzed cases of Churg-Strauss syndrome using the Novartis Argus global drug safety database for omalizumab in asthma patients, has indicated that Churg-Strauss syndrome may develop in patients who have an underlying eosinophilic disorder that is unmasked by the withdrawal of corticosteroids, which is common among patients receiving this treatment.[11]

Mechanism of action[edit]

People with allergies are sensitized to make immune response to several or many proteins contained in one or more of the hundreds of harmless[clarification needed] environmental substances, which they take in by inhalation (e.g., house dust mites, pollens, molds, pet animal dander, and other airborne allergens) and ingestion (e.g., wheat (gluten), peanuts, nuts, shellfish, and other food allergens), or through the skin (e.g., bee and fire ant stings, latex gloves). In these individuals, the IgE molecules, both allergen-specific and allergen-nonspecific ones, in their bodies bind to the high affinity IgE receptor (FcεRI) on the surface of mast cells and basophils. Under certain conditions, including but not limited to when the allergenic substances are taken in by a sensitized individual at substantial amounts, the allergenic proteins bind to the allergen-specific IgE bound by FcεRI on the surface of mast cells and basophils and trigger the activation of those inflammatory cells, which release a host of pharmacological mediators, such as histamine, leukotrienes, tryptase, inflammatory cytokines, and others, causing various allergic symptoms/diseases.

The rationale for designing the anti-IgE therapeutic antibodies and the pharmacological mechanisms of anti-IgE therapy have been summarized in review articles by the inventor of the anti-IgE therapy, Tse Wen Chang, and his colleagues.[2][12][13] Omalizumab inhibits the binding of IgE to FcεRI on mast cells and basophils by binding to an antigenic epitope on IgE that overlaps with the site to which FcεRI binds. This feature is critical to its pharmacological effects because a typical anti-IgE antibody can cross-link cell surface FcεRI-bound IgE, thereby aggregate FcεRI, and activate mast cells and basophils to discharge the horde of chemical mediators stored in the densely packed sacs inside the cells. However, when IgE is bound to the receptor, the antigenic epitope on IgE to which omalizumab binds is sterically hindered by the receptor and is not accessible to omalizumab binding, thus averting the anaphylactic effects presumably unavoidable with an ordinary anti-IgE antibody . Furthermore, although the peptide elements on IgE involved in binding to low affinity IgE receptor (FcεRII) on many cell types are different from the peptide elements involved in binding to FcεRI, omalizumab, by steric hindrance, also prevents binding of IgE to FcεRII. The reduced binding of IgE to both FcεRI and FcεRII has profound effects on the attenuation of IgE-mediated allergic responses.

Perhaps the most dramatic effect, which was not foreseen at the time when the anti-IgE therapy was designed and which was discovered during the clinical trials, is that as the free IgE in patients is depleted by omalizumab, the FcεRI receptors on basophils, mast cells, and dendritic cells are gradually down-regulated with somewhat different kinetics, rendering those cells much less sensitive to the stimulation by allergens.[14][15][16] Thus, in this regard, therapeutic anti-IgE antibodies represent a new class of potent mast cell stabilizers,[13] providing the fundamental mechanism for omalizumab's effects on various allergic and non-allergic diseases involving mast cell degranulation. Many investigators have identified or elucidated a host of pharmacological effects, which help bring down the inflammatory status in the omalizumab-treated patients.[17][18][19]

IgE in allergic diseases[edit]

Corticosteroids of various chemical structures and formulations, which offer various desired potency and pharmacokinetics and which generally effectively suppress inflammatory processes systemically or locally, have been the mainstay of medicine to treat the severe cases of various allergic diseases. Before the introduction of omalizumab, moderate to severe cases of asthma, regardless of their allergic or non-allergic nature, had been generally treated with corticosteroids and bronchodilators. Clinicians had not had persuasive reasons to dissect the role of IgE, or more precisely, its relative importance among various immune factors and pharmacological mediators, in the pathogenesis of asthma and various other allergic diseases and conditions. The availability of omalizumab as a drug to intervene the IgE pathway has provided many clinical researchers the opportunities to examine the role of IgE in various allergic diseases and, in some cases, diseases that are not obviously considered as allergic diseases.

In conjunction with achieving the practical goal to investigate the applicability of the anti-IgE therapy as a potential treatment for allergic diseases, the many corporate-sponsored clinical trials of TNX-901 and omalizumab on asthma, allergic rhinitis, peanut allergy, chronic idiopathic urticaria, atopic dermatitis, and other allergic diseases, have helped define the role of IgE in the pathogenesis of these prevalent allergic diseases. For example, the clinical trial results of omalizumab on asthma have unambiguously settled the long debate whether IgE plays a central role in the pathogenesis of asthma.[18] The availability of the drug as a treatment option for patients with severe, persistent allergic asthma has gradually persuaded the physicians treating severe asthma patients to determine whether their asthma is allergic or non-allergic in nature.

Numerous investigator-initiated case studies or small-scale pilot studies of omalizumab have been performed on various allergic diseases and several non-allergic diseases, especially inflammatory skin diseases. These diseases include atopic dermatitis, various subtypes of physical urticaria (solar, cold-induced, local heat-induced, or delayed pressure-induced), and a spectrum of relatively less prevalent allergic or non-allergic diseases or conditions, such as allergic bronchopulmonary aspergillosis,[20] cutaneous or systemic mastocytosis, bee venom sensitivity (anaphylaxis),[21] idiopathic anaphylaxis, eosinophil-associated gastrointestinal disorder, bullous pemphigoid,[22] interstitial cystitis,[23] nasal polyps, and idiopathic angiodema,.[24] The generally positive results have suggested that IgE possibly plays a key role, either directly or indirectly, in these diseases and, therefore, intervening the IgE pathway may be an effective therapeutic strategy. The results of some of these case studies and pilot studies have subsequently persuaded the drug companies marketing omalizumab to carry out larger-scale trials on some of the diseases.

Roles in non-allergic diseases[edit]

Several groups have reported clinical trial results that omalizumab may be effective in patients with non-allergic asthma.[25] This seems to be contrary to the general understanding of the pharmacological mechanisms of the anti-IgE therapy discussed above.[26] 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[27][28] and all cases of bullous pemphigoid[22] 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[29] and omalizumab can function as a mast cell-stabilizing agent,[13] rendering these inflammatory cells to be less active.

Chemistry and formulations[edit]

Omalizumab is a glycosylated IgG1 monoclonal antibody produced by cells of an adapted Chinese hamster ovary (CHO) cell line.[2] 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)[30] 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.[31]


Tanox, a biopharmaceutical company based in Houston, Texas, started the anti-IgE program, created antibody drug candidates, and filed its first patent application on the anti-IgE therapeutic approach in 1987.[32] In the next year, the company converted one candidate antibody to a chimeric antibody (which was later named CGP51901 and further developed into a humanized antibody, TNX-901 or talizumab). The anti-IgE therapeutic concept was not well received in the early period of the program. In order to seek funding for the anti-IgE program, the two scientist founders of Tanox, Nancy T. Chang and Tse Wen Chang, visited about 25 pharmaceutical and larger biotech companies in the U.S., Canada, Europe, Japan, and other countries to discuss collaboration throughout 1989. Representatives of Ciba-Geigy (which merged with Sandoz to form Novartis in 1996) thought the anti-IgE program scientifically interesting and executives from Tanox and Ciba-Geigy signed a collaborative agreement in 1990 to develop the anti-IgE program.[32][33]

In 1991, after several rounds of pre-IND ("investigational new drug") meetings with officials/scientists of the FDA, the FDA finally gave a nod for CGP51901 to be tested in human subjects. This approval of IND for an anti-IgE antibody for the first time was regarded a brave demonstration of professionalism for both the FDA officials and the Tanox/Ciba-Geigy team. The scientists participating in the pre-IND discussion comprehended that an ordinary anti-IgE antibody (i.e., one without the set of binding specificity of CGP51901) would invariably activate mast cells and basophils and cause anaphylactic shocks and probably deaths among injected persons. Notwithstanding this concern, they came to the same view that based on the presented scientific data, CGP51901 should have an absolutely required clean distinction from an ordinary anti-IgE antibody in this regard.[34][35] In 1991-1993, researchers from Ciba-Geigy and Tanox and a leading clinical research group (headed by Stephen Holgate) in the asthma/allergy field ran a successful Phase I human clinical trial of CGP51901 in Southampton, England and showed that the tested antibody is safe.[36] In 1994-1995, the Tanox/Ciba-Geigy team conducted a Phase II trial of CGP51901 in patients with severe allergic rhinitis in Texas and showed that CGP51901 is safe and efficacious in relieving allergic symptoms.[37]

While the Tanox/Ciba-Geigy anti-IgE program was gaining momentum, Genentech announced in 1993 that it also had an anti-IgE program for developing antibody therapeutics for asthma and other allergic diseases. Scientists in Genentech had made a mouse anti-IgE monoclonal antibody with the binding specificity similar to that of CGP51901 and subsequently humanized the antibody (the antibody was later named "omalizumab").[38] This caused great concerns in Tanox, because it had disclosed its anti-IgE technology and sent its anti-IgE antibody candidate, which was to become CGP51901 and TNX-901, to Genentech in 1989 for the latter to evaluate for the purpose of considering establishing a corporate partnership.[39] Having failed to receive reconciliation from Genentech, Tanox filed a lawsuit against Genentech for trade secret violation.[39] Coincidentally, Tanox started to receive major patents for its anti-IgE invention from the European Union and from the U.S. in 1995.[40] After a 3-year legal entanglement, Genentech and Tanox settled their lawsuits out-of-court and Tanox, Novartis, and Genentech formed a tripartite partnership to jointly develop the anti-IgE program in 1996.[41] Omalizumab became the drug of choice for further development, because it had a better developed manufacturing process than TNX-901.[41] A large number of corporate-sponsored clinical trials and physician-initiated case series studies on omalizumab have been planned and performed since 1996 and a large number of research reports, especially those of clinical trial results, have been published since around 2000, as described and referenced in other sections of this article. In 2007, Genetech bought Tanox at $20/share for approximately $900 Million.[42][43]

Society and culture[edit]

Due to the requirement for long-term administration and hence the high cost of an omalizumab treatment regimen, and to the concern over long-term safety, treatment is not yet very common, especially in developing countries where medical funds are relatively scarce. Another barrier to wide use is its injectable dosage form, which requires the patient to visit a physician's office or clinic every 2 to 4 weeks during treatment. In August 2010, the National Institute for Clinical Excellence (NICE) in the United Kingdom ruled that omalizumab should not be prescribed on the National Health Service (NHS) to children under 12, causing widespread condemnation from asthma charities.[44] NICE concluded that the high costs of the compound, over £250 per vial, did not represent a sufficiently high increase in quality of life. However, on March 7, 2013, NICE issued “final draft guidance” about the allowance of omalizumab. It recommended the drug as an option for treating severe, persistent allergic asthma in adults, adolescents and children following additional analyses and submission of a patient access scheme (PAS) by Novartis, the manufacturer.[45]

In August 2013, a researcher at Leiden University Medical Center responsible for the TIGER trial was fired for unrelated research fraud. The TIGER trial was halted as a result.[46]


  1. ^ Schulman ES (October 2001). "Development of a monoclonal anti-immunoglobulin E antibody (omalizumab) for the treatment of allergic respiratory disorders". Am J Respir Crit Care Med. 164 (8 Pt 2): S6–11. doi:10.1164/ajrccm.164.supplement_1.2103025. PMID 11704611.
  2. ^ a b c Chang TW, Wu PC, Hsu CL, Hung AF (2007). Anti-IgE antibodies for the treatment of IgE-mediated allergic diseases. Adv. Immunol. Advances in Immunology. 93. pp. 63–119. doi:10.1016/S0065-2776(06)93002-8. ISBN 9780123737076. PMID 17383539.
  3. ^ a b c Davydov L (January 2005). "Omalizumab (Xolair) for treatment of asthma". Am Fam Physician. 71 (2): 341–2. PMID 15686303.
  4. ^ Pocket guide for asthma management and prevention. Global Initiatives for Asthma. 2013. "Archived copy". Archived from the original on 2013-05-21. Retrieved 2013-07-07.CS1 maint: archived copy as title (link)
  5. ^ Fanta CH (March 2009). "Asthma". N. Engl. J. Med. 360 (10): 1002–14. doi:10.1056/NEJMra0804579. PMID 19264689.
  6. ^ "Xolair (omalizumab): Drug Safety Communication - Slightly Elevated Risk of Cardiovascular and Cerebrovascular Serious Adverse Events". 2014-09-26. Archived from the original on 30 September 2014. Retrieved 29 September 2014.
  7. ^ "Allergic Asthma and CIU Treatment - XOLAIR (Omalizumab)". Retrieved 2018-08-14.
  8. ^ Karagiannis SN, Wang Q, East N, Burke F, Riffard S, Bracher MG, Thompson RG, Durham SR, Schwartz LB, Balkwill FR, Gould HJ (April 2003). "Activity of human monocytes in IgE antibody-dependent surveillance and killing of ovarian tumor cells". Eur. J. Immunol. 33 (4): 1030–40. doi:10.1002/eji.200323185. PMID 12672069.
  9. ^ Busse W, Buhl R, Fernandez Vidaurre C, Blogg M, Zhu J, Eisner MD, Canvin J (April 2012). "Omalizumab and the risk of malignancy: results from a pooled analysis". The Journal of Allergy and Clinical Immunology. 129 (4): 983–9.e6. doi:10.1016/j.jaci.2012.01.033. PMID 22365654.
  10. ^ Winchester DE, Jacob A, Murphy T (September 2006). "Omalizumab for asthma". N. Engl. J. Med. 355 (12): 1281–2. doi:10.1056/NEJMc061914. PMID 16990394.
  11. ^ Wechsler ME, Wong DA, Miller MK, Lawrence-Miyasaki L (May 2009). "Churg-strauss syndrome in patients treated with omalizumab". Chest. 136 (2): 507–18. doi:10.1378/chest.08-2990. PMID 19411292.
  12. ^ Chang TW (February 2000). "The pharmacological basis of anti-IgE therapy". Nat. Biotechnol. 18 (2): 157–62. doi:10.1038/72601. PMID 10657120.
  13. ^ a b c Chang TW, Shiung YY (June 2006). "Anti-IgE as a mast cell-stabilizing therapeutic agent". The Journal of Allergy and Clinical Immunology. 117 (6): 1203–12. doi:10.1016/j.jaci.2006.04.005. PMID 16750976.
  14. ^ MacGlashan DW, Bochner BS, Adelman DC, Jardieu PM, Togias A, McKenzie-White J, Sterbinsky SA, Hamilton RG, Lichtenstein LM (February 1997). "Down-regulation of Fc(epsilon)RI expression on human basophils during in vivo treatment of atopic patients with anti-IgE antibody". Journal of Immunology. 158 (3): 1438–45. PMID 9013989.
  15. ^ Prussin C, Griffith DT, Boesel KM, Lin H, Foster B, Casale TB (December 2003). "Omalizumab treatment downregulates dendritic cell FcepsilonRI expression". The Journal of Allergy and Clinical Immunology. 112 (6): 1147–54. doi:10.1016/j.jaci.2003.10.003. PMID 14657874.
  16. ^ Scheinfeld N (2005). "Omalizumab: a recombinant humanized monoclonal IgE-blocking antibody". Dermatol. Online J. 11 (1): 2. PMID 15748543.
  17. ^ Holgate ST, Djukanović R, Casale T, Bousquet J (April 2005). "Anti-immunoglobulin E treatment with omalizumab in allergic diseases: an update on anti-inflammatory activity and clinical efficacy". Clin. Exp. Allergy. 35 (4): 408–16. doi:10.1111/j.1365-2222.2005.02191.x. PMID 15836747.
  18. ^ a b Holgate S, Casale T, Wenzel S, Bousquet J, Deniz Y, Reisner C (March 2005). "The anti-inflammatory effects of omalizumab confirm the central role of IgE in allergic inflammation". The Journal of Allergy and Clinical Immunology. 115 (3): 459–65. doi:10.1016/j.jaci.2004.11.053. PMID 15753888.
  19. ^ Holgate S, Smith N, Massanari M, Jimenez P (December 2009). "Effects of omalizumab on markers of inflammation in patients with allergic asthma". Allergy. 64 (12): 1728–36. doi:10.1111/j.1398-9995.2009.02201.x. PMID 19839977.
  20. ^ van der Ent CK, Hoekstra H, Rijkers GT (March 2007). "Successful treatment of allergic bronchopulmonary aspergillosis with recombinant anti-IgE antibody". Thorax. 62 (3): 276–7. doi:10.1136/thx.2004.035519. PMC 2117163. PMID 17329558.
  21. ^ Kontou-Fili K, Filis CI, Voulgari C, Panayiotidis PG (June 2010). "Omalizumab monotherapy for bee sting and unprovoked "anaphylaxis" in a patient with systemic mastocytosis and undetectable specific IgE". Ann Allergy Asthma Immunol. 104 (6): 537–9. doi:10.1016/j.anai.2010.04.011. PMID 20568389.
  22. ^ a b Fairley JA, Baum CL, Brandt DS, Messingham KA (March 2009). "Pathogenicity of IgE in autoimmunity: successful treatment of bullous pemphigoid with omalizumab". The Journal of Allergy and Clinical Immunology. 123 (3): 704–5. doi:10.1016/j.jaci.2008.11.035. PMC 4784096. PMID 19152970.
  23. ^ Lee J, Doggweiler-Wiygul R, Kim S, Hill BD, Yoo TJ (May 2006). "Is interstitial cystitis an allergic disorder?: A case of interstitial cystitis treated successfully with anti-IgE". Int. J. Urol. 13 (5): 631–4. doi:10.1111/j.1442-2042.2006.01373.x. PMID 16771742.
  24. ^ Sands MF, Blume JW, Schwartz SA (October 2007). "Successful treatment of 3 patients with recurrent idiopathic angioedema with omalizumab". The Journal of Allergy and Clinical Immunology. 120 (4): 979–81. doi:10.1016/j.jaci.2007.07.041. PMID 17931567.
  25. ^ de Llano LP, Vennera Mdel C, Álvarez FJ, Medina JF, Borderías L, Pellicer C, González H, Gullón JA, Martínez-Moragón E, Sabadell C, Zamarro S, Picado C; Spanish Registry (April 2013). "Effects of omalizumab in non-atopic asthma: results from a Spanish multicenter registry". J Asthma. 50 (3): 296–301. doi:10.3109/02770903.2012.757780. PMID 23350994.CS1 maint: multiple names: authors list (link)
  26. ^ Lommatzsch M, Korn S, Buhl R, Virchow JC (May 2013). "Against all odds: anti-IgE for intrinsic asthma?". Thorax. 69 (1): 94–6. doi:10.1136/thoraxjnl-2013-203738. PMC 3888607. PMID 23709757.
  27. ^ Maurer M, Rosén K, Hsieh HJ, Saini S, Grattan C, Gimenéz-Arnau A, Agarwal S, Doyle R, Canvin J, Kaplan A, Casale T (March 2013). "Omalizumab for the treatment of chronic idiopathic or spontaneous urticaria". N Engl J Med. 368 (10): 924–35. doi:10.1056/NEJMoa1215372. PMID 23432142.
  28. ^ Kaplan A, Ledford D, Ashby M, Canvin J, Zazzali JL, Conner E, Veith J, Kamath N, Staubach P, Jakob T, Stirling RG, Kuna P, Berger W, Maurer M, Rosén K (July 2013). "Omalizumab in patients with symptomatic chronic idiopathic/spontaneous urticaria despite standard combination therapy". The Journal of Allergy and Clinical Immunology. 132 (1): 101–9. doi:10.1016/j.jaci.2013.05.013. PMID 23810097.
  29. ^ Kashiwakura J, Otani IM, Kawakami T (2011). Monomeric IgE and mast cell development, survival and function. Adv Exp Med Biol. Advances in Experimental Medicine and Biology. 716. pp. 29–46. doi:10.1007/978-1-4419-9533-9_3. ISBN 978-1-4419-9532-2. PMID 21713650.
  30. ^ "Archived copy". Archived from the original on 2012-01-26. Retrieved 2012-07-23.CS1 maint: archived copy as title (link)
  31. ^ "Community register of medicinal products for human use". Archived from the original on 2014-04-20.
  32. ^ a b Twombly R. Couple Lead Quest for New Allergy Drug. The Scientist January 7, 1991. Archived 2016-08-27 at the Wayback Machine.
  33. ^ Development and Licensing Agreement, between Tanox and Ciba-Geigy 1990. "Development and Licensing Agreement - Tanox Biosystems Inc. And Ciba-Geigy Ltd. - Sample Contracts and Business Forms". Archived from the original on 2013-05-16. Retrieved 2013-07-04.
  34. ^ Chang TW, Davis FM, Sun NC, Sun CR, MacGlashan DW Jr, Hamilton RG (February 1990). "Monoclonal antibodies specific for human IgE-producing B cells: a potential therapeutic for IgE-mediated allergic diseases". Bio/Technology. 8 (2): 122–6. doi:10.1038/nbt0290-122. PMID 1369991.
  35. ^ Davis FM, Gossett LA, Pinkston KL, Liou RS, Sun LK, Kim YW, Chang NT, Chang TW, Wagner K, Bews J, Brinkmann V, Towbin H, Subramanian N, Heusser C (1993). "Can anti-IgE be used to treat allergy?". Springer Semin. Immunopathol. 15 (1): 51–73. doi:10.1007/BF00204626. PMID 8362344.
  36. ^ Corne J, Djukanovic R, Thomas L, Warner J, Botta L, Grandordy B, Gygax D, Heusser C, Patalano F, Richardson W, Kilchherr E, Staehelin T, Davis F, Gordon W, Sun L, Liou R, Wang G, Chang TW, Holgate S (March 1997). "The effect of intravenous administration of a chimeric anti-IgE antibody on serum IgE levels in atopic subjects: efficacy, safety, and pharmacokinetics". J Clin Invest. 99 (5): 879–87. doi:10.1172/JCI119252. PMC 507895. PMID 9062345.
  37. ^ Racine-Poon A, Botta L, Chang TW, Davis FM, Gygax D, Liou RS, Rohane P, Staehelin T, van Steijn AM, Frank W (December 1997). "Efficacy, pharmacodynamics, and pharmacokinetics of CGP 51901, an anti-immunoglobulin E chimeric monoclonal antibody, in patients with seasonal allergic rhinitis". Clin Pharmacol Ther. 62 (6): 675–90. doi:10.1016/S0009-9236(97)90087-4. PMID 9433396.
  38. ^ Presta LG, Lahr SJ, Shields RL, Porter JP, Gorman CM, Fendly BM, Jardieu PM (September 1993). "Humanization of an antibody directed against IgE". Journal of Immunology. 151 (5): 2623–32. PMID 8360482.
  39. ^ a b Thorpe H. Drug war. (small drug firm Tanox takes on Genentech over patent rights) Texas Monthly, April 1, 1995. "About Questia | Questia, Your Online Research Library". Archived from the original on 2013-10-29. Retrieved 2013-07-04.
  40. ^ The family of anti-IgE patents. "Methods for producing high affinity anti-human IgE-monoclonal antibodies which binds to IgE on IgEabearing B cells but not basophils". Archived from the original on 2014-03-19. Retrieved 2012-09-30.; "Chimeric anti-human IgE-monoclonal antibody which binds to secreted IgE and membrane-bound IgE expressed by IgE-expressing B cells but notto IgE bound to FC receptors on basophils". Archived from the original on 2014-03-19. Retrieved 2012-06-23.; "Monoclonal antibodies that bind to soluble IGE but do not bind IGE on IGE expressing B lymphocytes or basophils". Archived from the original on 2014-03-19. Retrieved 2012-09-30.; "Treating hypersensitivities with anti-IGE monoclonal antibodies which bind to IGE-expressing B cells but not basophils". Archived from the original on 2014-03-19. Retrieved 2012-06-23.; "Humanized monoclonal antibodies binding to IgE-bearing B cells but not basophils". Archived from the original on 2014-02-21. Retrieved 2012-06-23..
  41. ^ a b Tripartite Cooperation Agreement, by and between NOVARTIS PHARMA AG, GENENTECH, INC, AND TANOX, INC. "Tripartite Cooperation Agreement". Archived from the original on 2016-08-22. Retrieved 2017-09-07.
  42. ^ "Genentech: Press Releases - Genentech Announces Agreement to Acquire Tanox for $20 Per Share". Archived from the original on 2013-07-06.
  43. ^ "Genentech completes acquisition / $919 million for Tanox is its first purchase ever". 2007-08-03. Archived from the original on 2016-04-14.
  44. ^ "Asthma drug ruling 'nonsensical'". BBC News. August 12, 2010. Archived from the original on August 12, 2010.
  45. ^ NICE says yes to treatment for asthma in final draft guidance. NICE March 7, 2013. "News". Archived from the original on 2013-03-12. Retrieved 2013-07-07.
  46. ^ Sheldon T (23 August 2013). "News: Senior Dutch researcher sacked for manipulating data in rheumatoid arthritis drug trial". BMJ. 347: f5267. doi:10.1136/bmj.f5267. PMID 23974641. Archived from the original on 27 August 2013.

External links[edit]