How can local generic companies break through the unique patent of hepatitis C in China?

We must be familiar with sofibuvir, the "God drug of hepatitis C", which has just submitted its application for listing in China Such a hot drug, of course, can not avoid a battle around patent attack and defense In the past 25 years, thanks to the development and promotion of new drugs, the cure rate of hepatitis C (SVR originally meant virus response rate) has risen from the single digit at the beginning to 30% after interferon combined with ribavirin By the end of 2014, with the new drug DAA for liver diseases, the cure rate of hepatitis C has exceeded 90% Among all the DAA drugs, the most popular drug for patients and doctors is the Gilead hepatitis C drug "sofibvir", which will be put on the market in China, with a cure rate of nearly 100% On March 15, Gilead announced that sofosbuvir, its "magic drug" for the treatment of hepatitis C, has been accepted for listing in China, which means that sofosbuvir is expected to be listed in China at the beginning of 18 years Why is the approval of sofibwe so much concerned? The soon to be launched sofibvir has greatly reduced the threshold of hepatitis C treatment, with a cure rate of more than 90% and a sharp increase in the number of prescriptions, which is regarded as a great progress in human medicine But at the same time, its high drug price has also been criticized The 12 week no discount price for a course of treatment is $84000, up to $1000 / day Harvoni, which went on the market later, costs as much as $94600 for a 12 week course China is a big country of liver disease, a large number of patients suffer from hepatitis C disease, they urgently need high-efficiency and affordable DAA drugs, which makes the potential market of domestic DAA drugs huge, a battle around the relevant patents of sofibupro After 2011, due to the slowdown of the anti AIDS drug market, Gilead, like other large pharmaceutical companies, tried to find a new breakthrough in the field of antiviral drugs Their goal is to target hepatitis C There are more than 3 million hepatitis C patients in the United States, and 150 million people in the world suffer from the disease For a long time, these patients can only control hepatitis C virus by injecting interferon with obvious side effects They are eager for new drugs However, unlike the traditional R & D method, Gilead's management did not simply increase the R & D investment, but required researchers to search and test each competitive compound under research, in order to find the best prototype of hepatitis C drug as soon as possible At last, the experimental drug psi-7977 developed by pharmaset company fell into the eyes of Gilead management In November 2011, Geely won the psi-7977 for a whopping $11 billion You should know that pharmaset, a start-up company at that time, had no products put into the market In the previous fiscal year, it lost $91 million However, the purchase price of Gilead company was 94% higher than that of pharmaset in the same period But in the end, the acquisition, which was not optimistic at that time, brought more than 11 billion US dollars of revenue to Geely in 2014, which is still a classic case of pharmaceutical enterprises' m & A today 2 Not satisfied with the current situation, the second R & D of Gilead and the global distribution of direct antiviral drugs (DAAS) acquired by Gilead through pharmaset compared with the traditional drug delivery scheme, the curative effect is significantly improved and the adverse reactions are reduced, achieving a breakthrough in the field of hepatitis C treatment However, Gilead is not satisfied with the current situation In the follow-up research and development, DAAS can be divided into NS3 / 4A protease inhibitor, NS5B polymerase inhibitor and NS5A inhibitor according to their different targets According to the clinical data, up to eight compounds have been tested or approved for marketing in the United States and PCT applications have been made for them In addition, Gilead has also carried out clinical research on the response rate of different genotypes of HCV, and developed harvoni (ji-2 generation) and epclusa (Ji-3 generation), the first new combination for the treatment of all six genotypes of hepatitis C, on the basis of suofibuvir, through the combination of compound therapy with other drugs 3 The unique patent strategy to enter the Chinese market: sofibuproir was approved by the European Drug Administration (EMA) human pharmaceutical products Committee (CHMP) in November 2013; approved by the US FDA in December 2013 (as the first drug approved for the full oral treatment of hepatitis C); approved by the European Union in January 2014 (can be used for the antiviral treatment of hepatitis C) The core patents listed in the FDA orange peel book include compound patents us7964580b2, us8334270b2, us8580765b2, us8618076b2, us8633309b2 and composition patents us8889159b2 The same family in China are core substance patents cn101918425a, cn102459299a and composition patents cn104039319a, respectively In addition to the core patents listed in the orange peel book, Gilead company has carried out a systematic patent layout for sofibvir in China, involving the preparation method, crystal form, composition, combined medication, etc For example, cn102858790a requires the protection of sofibvir crystal and its preparation method; cn104144682a requires the protection of a combination preparation containing an effective amount of antiviral compound, ledipasvir, and an effective amount of sofibvir; cn104487442a requires the protection of a pharmaceutical composition containing sofibvir and a general antiviral structural compound; Cn103328480a requests to protect the pharmaceutical composition containing sofibvir and imidazolium, an antiviral compound; cn104244947a requests to protect the pharmaceutical composition containing an effective amount of sofibvir and ribavirin and its therapeutic use in the treatment of HCV infection; Cn104244945a requires the protection of the composition containing sofibvir and the method for reducing the viral load in the human body suffering from HCV, etc How can domestic generic companies break through? There are already enterprises in China that have arranged for the treatment of hepatitis C DAA CFDA has recorded only three domestic enterprises that independently develop hepatitis C DAA: Dong Yangguang, ginkgo tree and Geli NS3 / 4A protease inhibitors include sirarevir from Ginkgo biloba in Suzhou, danoprevir (asc08) from Roche in Geli, Hangzhou, and bl-8030 from bilinerx in Zhengda Tianqing As the original research company's patent related to sofibove has not expired yet, how should domestic enterprises deal with it? 1 Looking for the failure point in Gillette's application At present, Gilead's patent application for sofibove in China is under review The licensing trend, protection scope and stability of rights of these patent applications will ultimately determine whether domestic generic pharmaceutical enterprises can follow up the imitation As Gilead's patent application for sofibwe was rejected in India, it is questionable whether Gilead's patent application in China can be passed At the same time, even if the patent is successfully authorized, whether the scope of patent protection is sufficient and whether the drugs before and after are protected will have an impact In addition, the compound patents of tegobuvir, vedroprevir and ledipasvir have been authorized in China Although the above drugs have not been put on the market alone at present, they will still form effective protection for the implementation of the follow-up drug combination composition, and it is necessary to study them 2 Based on the existing patents, it is not very broad to seek to break through the protection scope of drug patents Therefore, the domestic generic pharmaceutical enterprises should focus on the direction of joint drug use, crystal form, preparation method improvement and structural modification
With reference to Viagra's similar drugs, generic pharmaceutical enterprises have successfully developed and listed vardenafil (Bayer company, Germany), mironafil, and udinafi, which have the same mechanism of action as Viagra, by means of pharmaceutical chemistry They are superior to Viagra in pharmacology, toxicology, clinical effect, etc., and have successfully broken through the original patent The scope of protection realizes the re innovation of patented technology It will take much less time and investment to develop a new drug in order to obtain similar or better therapeutic effect If we can successfully break through the protection scope of suofibuvir patent, we can let the "new drugs" of generic drugs enter the market before the expiration of suofibuvir patent, use the advantage of low R & D cost to compete, and lead other generic companies to occupy the market 4 postscript: the contradiction between the original research drug and the generic drug is always there, and the victory and defeat often lie in the patent layout and processing Gilead's patent operation layout is bold and skillful, so as to obtain the patent pool of heavy weight compounds, derivatives and methods for anti hepatitis C drugs, and it has successfully obtained rich returns Its strategy of M & A, patent application and operation is worthy of attention and reference Domestic enterprises should pay attention to the change of Geely's patent application, increase R & D investment to break the scope of Geely's patent protection, and develop and launch DAA drugs as soon as possible to seize the market in the face of China's huge demand for anti HCV market and the fact that Geely's patent involving sofibove is still early to expire.