Domestic imitation research and development of the world's best-selling biological and chemical drugs

The sales volume of Yaowang xiumeile has been increasing year by year, reaching nearly 20 billion US dollars in 2018, accounting for more than half of the total revenue of Aberdeen, becoming the best-selling biological medicine for many years At the beginning of 2019, Bristol Myers Squibb purchased Xinji with us $74 billion, and the sales volume of lenalidomide, the largest target product, increased year by year In 2017, the sales volume was US $8.187 billion, and in 2018, the sales volume reached US $9.685 billion It is predicted that it will reach US $13.4 billion in 2022, making it the fastest selling chemical medicine As the best-selling variety in the world, its generic medicine also has a considerable market space Therefore, when the patent is not expired, some enterprises want to challenge the patent If it does, and when the patent expires, more enterprises are competing to copy Therefore, the domestic R & D companies of adalimumab and lenalidomide were arranged to see the domestic imitation of the best-selling biological and chemical drugs in the world 01 Adalimumab an all human IgG1 monoclonal antibody was developed by abbvie It can prevent TNF - α from activating TNF receptor on the surface of p55 and p75 cells by specifically binding with TNF - α The drug was first approved by the FDA on December 31, 2002, and then successively approved in the European Union and Japan It was first approved for marketing in China on April 16, 2008, under the trade name of Humira ® (sumil ®) By the end of 2018, 14 indications were approved in the United States, the European Union and China, including rheumatoid arthritis (RA), juvenile idiopathic arthritis (JIA), psoriatic arthritis (PSA), ankylosing spondylitis (as), adult Crohn's disease (CD), Crohn's disease in children, ulcerative colitis (UC), plaque psoriasis (PSO), suppurative hidrosis (HS), uveitis (UV), children's plaque psoriasis, children's uveitis, etc., and three of them have been approved in China: rheumatoid arthritis (RA), ankylosing spondylitis (as), moderate and severe plaque psoriasis (PSO, second line, later modified label as first line) At the end of January 2019, the fourth indication application in China was included in the priority review, while in China, two clinical studies on Crohn's disease were completed The patent of adamumumab in the United States has expired in 2016, and that in Europe and other countries is 2018 There are many domestic R & D enterprises of adamumumab, but most of them are in the early stage of research and are used to treat rheumatoid arthritis At present, adamumumab of Zhejiang Haizheng, baiaotai biotechnology and Xinda biology has entered the BLA stage for ankylosing spondylitis, and Fuhong Hanlin has also entered the BLA stage for plaque psoriasis It remains to be seen who can take the lead in Haizheng and baiaotai 02 Lenalidomide Lenalidomide, a thalidomide analogue developed by new group, targeting crbn, COX-2, TNF α, etc., was first approved for marketing in the United States on December 27, 2005, and then successively approved in the European Union and Japan It was first approved in China on January 23, 2013, under the trade name of Revlimid ® (refumex ®), mainly approved for the treatment of multiple myeloma (mm) In addition, it also has the treatment of myelodysplastic syndrome MDS, or extended for lymphoma In February 2017, the new indication of lenalidomide 10mg capsule was approved by FDA for maintenance treatment of patients with multiple myeloma after auto HSCT, becoming the only maintenance drug approved by FDA after auto HSCT The authorization of lenalidomide's compound patent (zl97180299.8) expired in July 2017, but there are three indication patents on the market, among which two are zl97180299.8 and zl03825567.7 for MDS use, zl20061015048.3 for lymphoma use, all of which have been authorized, and the protection period of one indication patent (zl03816899.5) is 2023 Domestic lenalidomide imitation enterprises include Shuanglu pharmaceutical, Qilu pharmaceutical, Zhengda Tianqing, Haosen pharmaceutical, etc., among which Shuanglu pharmaceutical is the top one, applying for new drugs, and obtained the approval number in December 2017, with the trade name of Lisheng At that time, because the original research patent has not yet expired, the domestic imitation and marketing need to circumvent the original research patent Shuanglu pharmaceutical industry successfully circumvented the original research patent limit by inventing a new synthesis route and using three new polycrystalline forms Apart from the domestic patent authorization, lenalidomide of Shuanglu pharmaceutical has also applied for patents in the United States, Europe, South Korea, Japan, Australia, India and other countries Some patents have been granted in the United States, Europe, South Korea, Japan and Australia For the difference between the synthesis route and the original research, see lenalidomide - A comparative analysis of the patent route of Shuanglu pharmaceutical industry and the original research route of Xinji But at the beginning of 2018, Shuanglu pharmaceutical and Cavendish biology, a multi-year partner and the actual developer of lenalidomide, broke out a dispute When lenalidomide went public, they had differences on the right to sell lenalidomide In addition, Zhengda Tianqing 25mg lenalidomide capsule has also obtained the approval number Recently, the company announced that it has obtained the approval document for drug registration, and the trade name is Anxian See the table below for other R & D enterprises of lenalidomide.