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Modern therapeutic antibody drug discovery technologies.

机译：现代治疗性抗体药物发现技术。

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The pharmaceutical field has undergone a series of eras over the last seven decades or so. Prior to the second world war was the era of vitamins. With the development of penicillin during World War II to fight battlefield infections, the natural product antibiotic era began, which lasted until perhaps the 1980s or early 1990s. This was followed by an era in which synthetic small molecule chemicals dominated, with compounds such as atorvastatin (Lipitor?, for cholesterol lowering), sitagliptin (Januvia?, for diabetes), aripiprazole (Abilify?, for depression) and esomeprazole magnesium (Nexium?, for acid reflux disorder) grossing billions of US dollars annually to treat a wide variety of diseases. While still the dominant class of drugs sold today, the growth in sales of synthetic small molecule drugs has leveled off, while most large pharmaceutical companies have begun to devote significant resources towards discovery and development of alternative classes of pharmaceuticals, including vaccines and biologies. The biologies era began in the 1982 with the approval of human insulin (Humulin?) as a replacement therapy in type I diabetes, but did not expand significantly until the beginning of the 21st century. The first monoclonal antibody therapeutic, Orthoclone 0KT3?, was approved for marketing in 1986 for suppression of the immune response to decrease the chance of rejection during kidney transplantation. 0KT3, which was comprised 100% of sequences derived from the mouse, was derived using classical hybridoma-based monoclonal antibody discovery as described by Cesar Milstein and Georges Kohler in then-landmark 1975 paper [1]. Because it was mouse derived and unmodified, however, OKT3 was highly immunogenic, which limited its use throughout the years until it was voluntarily withdrawn from the market by Johnson & Johnson in 2011 [2].
机译：在过去的七十年左右的时间里，制药领域经历了一系列的时代。第二次世界大战之前是维生素时代。随着第二次世界大战期间青霉素的发展，以抗击战场上的感染，天然产物抗生素时代开始了，这种现象一直持续到1980年代或1990年代初。随后的时代是合成的小分子化学物质占主导地位的时代，其化合物包括阿托伐他汀（用于降低胆固醇的Lipitor？），西他列汀（用于糖尿病的Januvia？），阿立哌唑（用于抑郁症的Abilify？）和埃索美拉唑镁（Nexium）。 （用于酸倒流疾病），每年收入数十亿美元，用于治疗各种疾病。尽管仍然是当今销售的主要类别的药物，但合成小分子药物的销售增长已趋于平稳，而大多数大型制药公司已开始投入大量资源用于发现和开发替代类药物，包括疫苗和生物制剂。生物人类学时代始于1982年，当时人类胰岛素（Humulin？）被批准用作I型糖尿病的替代疗法，但直到21世纪初才大为扩展。第一种单克隆抗体治疗药物Orthoclone 0KT3？于1986年获准上市，可抑制免疫反应以减少肾脏移植过程中排斥的机会。 0KT3由100％的小鼠序列组成，是使用经典的基于杂交瘤的单克隆抗体发现的，如Cesar Milstein和Georges Kohler在当时具有里程碑意义的1975年论文中所述[1]。由于它是小鼠衍生且未经修饰的，因此OKT3具有高度免疫原性，多年来一直限制其使用，直到强生公司于2011年自愿将其撤出市场[2]。

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