make them more sensitive to chemotherapy used in combination with an anti-CD20 antibody. The combined effect results in the elimination of B cells (including the cancerous ones) from the body, allowing a new population of healthy B cells to develop from lymphoid stem cells. Rituximab binds to amino acids 170–173 and 182–185 on CD20, which are physically close to each other as a result of a disulfide bond between amino acids 167 and 183. History Rituximab was developed by IDEC Pharmaceuticals under the name IDEC-C2B8. The U.S. patent for the drug was issued in 1998 and expired in 2015. Based on its safety and effectiveness in clinical trials, rituximab was approved by the U.S. Food and Drug Administration in 1997 to treat B-cell non-Hodgkin lymphomas resistant to other chemotherapy regimens. Rituximab, in combination with CHOP chemotherapy, is superior to CHOP alone in the treatment of diffuse large B-cell lymphoma and many other B-cell lymphomas. In 2010, it was approved by the European Commission for maintenance treatment after initial treatment of follicular lymphoma. It is on the World Health Organization's List of Essential Medicines. In 2014, Genentech reclassified rituxan as a specialty drug, a class of drugs that are only available through specialty distributors in the US. Because wholesalers discounts and rebates no longer apply, hospitals would pay more. Originally available for intravenous injection (e.g. over 2.5 hrs), in 2016, it gained EU approval in a formulation for subcutaneous injection for B-cell CLL/lymphoma (CLL). Society and culture Economics Patents on the drug expired in Europe in February 2013, and in the US in September 2016. , several biosimilars had been approved in the US, India, the European Union, Switzerland, Japan and Australia. The US FDA approved Truxima (rituximab-abbs) in 2018, Ruxience (rituximab-pvvr) in 2019 and Riabni (rituximab-arrx) in 2020. The latter is about $3600 per 500 mg, wholesale, list. Research Chronic fatigue syndrome Rituximab did not improve symptoms in patients with chronic fatigue syndrome in a trial published in 2019. 22% of participants had serious events. This potential use was investigated after improvements in chronic fatigue syndrome was seen in two cancer patients treated with rituximab. Intrathecal For CNS diseases, rituximab could be administered intrathecally and this possibility is under study. Other anti-CD20 monoclonals The efficacy and success of rituximab has led to some other anti-CD20 monoclonal antibodies being developed: ocrelizumab, humanized (90%-95% human) B cell-depleting agent. ofatumumab (HuMax-CD20) a fully