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Etrolizumab
Etrolizumab (rhuMAb Beta7) is a biopharmaceutical drug candidate being developed for the treatment of ulcerative colitis and Crohn's disease. It is a humanized monoclonal antibody against the β7 subunit of integrins α4β7 and αEβ7. Etrolizumab was developed by GenentechUK Medicines Informationetrolizumab at UKMI Page accessed May 10, 2016 by engineering the FIB504 antibody to include human IgGl-heavy chain and κ-light chain frameworks; it is manufactured in CHO cells. As of 2016, it was in phase III studies for induction and maintenance therapy in people with ulcerative colitis and Crohn's. According to data of one meta-analysis efficacy of Etrolizumab is comparable with conventional therapies such as Infliximab with less adverse events Phase III clinical trials produced mixed results; and, on October 14, 2020, Hoffmann-La Roche, the parent company of Genentech, abandoned further efforts to develop etrolizumab for ulcerative colitis, but continues development for Crohn's ...
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Ulcerative Colitis
Ulcerative colitis (UC) is a long-term condition that results in inflammation and ulcers of the colon and rectum. The primary symptoms of active disease are abdominal pain and diarrhea mixed with blood ( hematochezia). Weight loss, fever, and anemia may also occur. Often, symptoms come on slowly and can range from mild to severe. Symptoms typically occur intermittently with periods of no symptoms between flares. Complications may include abnormal dilation of the colon (megacolon), inflammation of the eye, joints, or liver, and colon cancer. The cause of UC is unknown. Theories involve immune system dysfunction, genetics, changes in the normal gut bacteria, and environmental factors. Rates tend to be higher in the developed world with some proposing this to be the result of less exposure to intestinal infections, or to a Western diet and lifestyle. The removal of the appendix at an early age may be protective. Diagnosis is typically by colonoscopy with tissue biopsies. I ...
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Biopharmaceutical
A biopharmaceutical, also known as a biological medical product, or biologic, is any pharmaceutical drug product manufactured in, extracted from, or semisynthesized from biological sources. Different from totally synthesized pharmaceuticals, they include vaccines, whole blood, blood components, allergenics, somatic cells, gene therapies, tissues, recombinant therapeutic protein, and living medicines used in cell therapy. Biologics can be composed of sugars, proteins, nucleic acids, or complex combinations of these substances, or may be living cells or tissues. They (or their precursors or components) are isolated from living sources—human, animal, plant, fungal, or microbial. They can be used in both human and animal medicine. Terminology surrounding biopharmaceuticals varies between groups and entities, with different terms referring to different subsets of therapeutics within the general biopharmaceutical category. Some regulatory agencies use the terms ''biolog ...
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Crohn's Disease
Crohn's disease is a type of inflammatory bowel disease (IBD) that may affect any segment of the gastrointestinal tract. Symptoms often include abdominal pain, diarrhea (which may be bloody if inflammation is severe), fever, abdominal distension, and weight loss. Complications outside of the gastrointestinal tract may include anemia, skin rashes, arthritis, inflammation of the eye, and fatigue. The skin rashes may be due to infections as well as pyoderma gangrenosum or erythema nodosum. Bowel obstruction may occur as a complication of chronic inflammation, and those with the disease are at greater risk of colon cancer and small bowel cancer. While the precise causes of Crohn's disease (CD) are unknown, it is believed to be caused by a combination of environmental, immune, and bacterial factors in genetically susceptible individuals. It results in a chronic inflammatory disorder, in which the body's immune system defends the gastrointestinal tract, possibly targeting microbial ...
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ITGB7
Integrin beta-7 is an integrin protein that in humans is encoded by the ''ITGB7'' gene. It can pair with ITGA4 (CD49d) to form the heterodimeric integrin receptor αβ, or with ITGAE (CD103) to form αβ. Structure Like all integrin subunits, β is a highly flexible, membrane-bound, extracellular protein that must pair with an α subunit for stability. The molecule's flexibility allows it to dynamically regulate its affinity for ligand through conformational changes. Beginning with the apical end of the protein, farthest from the cell membrane, the β is composed of a head and upper legs, collectively known as the headpiece, lower legs, a transmembrane domain and a cytoplasmic tail. The top of the head is the I-like domain, sometimes called the βI domain, which, in combination with the α subunit, binds ligand. Just below this is the hybrid domain, a portion of which is N-terminal to the I-like domain. Below the hybrid domain is the PSI domain, which completes the headpiece. ...
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Integrin
Integrins are transmembrane receptors that facilitate cell-cell and cell-extracellular matrix (ECM) adhesion. Upon ligand binding, integrins activate signal transduction pathways that mediate cellular signals such as regulation of the cell cycle, organization of the intracellular cytoskeleton, and movement of new receptors to the cell membrane. The presence of integrins allows rapid and flexible responses to events at the cell surface (''e.g''. signal platelets to initiate an interaction with coagulation factors). Several types of integrins exist, and one cell generally has multiple different types on its surface. Integrins are found in all animals while integrin-like receptors are found in plant cells. Integrins work alongside other proteins such as cadherins, the immunoglobulin superfamily cell adhesion molecules, selectins and syndecans, to mediate cell–cell and cell–matrix interaction. Ligands for integrins include fibronectin, vitronectin, collagen and laminin. ...
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Genentech
Genentech, Inc., is an American biotechnology corporation headquartered in South San Francisco, California. It became an independent subsidiary of Roche in 2009. Genentech Research and Early Development operates as an independent center within Roche. Historically, the company is regarded as the world's first biotechnology company. As of July 2021, Genentech employed 13,539 people. History The company was founded in 1976 by venture capitalist Robert A. Swanson and biochemist Herbert Boyer. Boyer is considered to be a pioneer in the field of recombinant DNA technology. In 1973, Boyer and his colleague Stanley Norman Cohen demonstrated that restriction enzymes could be used as "scissors" to cut DNA fragments of interest from one source, to be ligated into a similarly cut plasmid vector. While Cohen returned to the laboratory in academia, Swanson contacted Boyer to found the company. Boyer worked with Arthur Riggs and Keiichi Itakura from the Beckman Research Institute, ...
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Chinese Hamster Ovary Cell
Chinese hamster ovary (CHO) cells are an epithelial cell line derived from the ovary of the Chinese hamster, often used in biological and medical research and commercially in the production of recombinant therapeutic proteins. They have found wide use in studies of genetics, toxicity screening, nutrition and gene expression, particularly to express recombinant proteins. CHO cells are the most commonly used mammalian hosts for industrial production of recombinant protein therapeutics. History Chinese hamsters had been used in research since 1919, where they were used in place of mice for typing pneumococci. They were subsequently found to be excellent vectors for transmission of kala-azar ( visceral leishmaniasis), facilitating ''Leishmania'' research. In 1948, the Chinese hamster was first used in the United States for breeding in research laboratories. In 1957, Theodore T. Puck obtained a female Chinese hamster from Dr. George Yerganian's laboratory at the Boston Cancer Resear ...
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Hoffmann-La Roche
F. Hoffmann-La Roche AG, commonly known as Roche, is a Swiss multinational healthcare company that operates worldwide under two divisions: Pharmaceuticals and Diagnostics. Its holding company, Roche Holding AG, has shares listed on the SIX Swiss Exchange. The company headquarters are located in Basel. Roche is the fifth largest pharmaceutical company in the world by revenue, and the leading provider of cancer treatments globally. The company controls the American biotechnology company Genentech, which is a wholly owned affiliate, and the Japanese biotechnology company Chugai Pharmaceuticals, as well as the United States-based companies Ventana and Foundation Medicine. Roche's revenues during fiscal year 2020 were 58.32 billion Swiss francs. Descendants of the founding Hoffmann and Oeri families own slightly over half of the bearer shares with voting rights (a pool of family shareholders 45%, and Maja Oeri a further 5% apart), with Swiss pharma firm Novartis owning a fu ...
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