Licensing model: the starting point for the pharmaceutical industry to connect with the world

China's pharmaceutical industry is on the way to connect with the world The traditional generic pharmaceutical model in China has been challenged There are fewer and fewer varieties of drugs that can be imitated In addition, the lack of real significance in the development of innovative drugs in the history of our country has resulted in the limited experience and ability in the development of innovative drugs in the current national pharmaceutical industry In the face of this situation, it is a very effective way to "lay eggs on the back of chickens", which is the licensing mode to be discussed in this paper 1 Licensing mode is one of the main modes for the development of international pharmaceutical industry Licensing mode is a mode of technology transfer, which means that the owner of technology or intellectual property authorizes the other party to use the technology, and the user of technology pays for the former, but the owner of intellectual property does not change In short, license is a kind of authorization given by the Licensor to the licensee to use the licensed substance In the pharmaceutical industry, the licensed substances can be patents or other rights, such as the right to sell Non patented substances can also be licensed, but most of the licensed substances are patents Licensing mode is one of the main development modes of the international pharmaceutical industry, especially in recent years, the international licensing market competition is very fierce, and the number and price of licensing transactions are greatly increased In 2003, for most foreign pharmaceutical companies, licensed products represented an important but moderate proportion of the product line A few companies, such as Johnson & Johnson, have broken through this proportion, and the proportion of licensed products is higher than that of self-developed products, while other companies, such as MSD, Sanofi Aventis and Bayer, still focus on self-development However, by 2006, great changes had taken place More than 50% of the new drugs on the market of most international pharmaceutical companies came from the compounds of licensed products Nowadays, licensed products have become the key products of a company's product line Therefore, the evaluation of a company's stock value cannot be separated from the evaluation of the company's licensed products Recently, many companies, such as GlaxoSmithKline, even claimed to double the number of licensed products as a strategic component of their extended development 2 The licensing model allows the company to quickly enter into new fields The licensing model can provide unique strategic initiative The licensing model enables pharmaceutical companies to quickly capture new and changing technologies and enter new and promising fields at double speed In order to concentrate advantageous resources in one area, pharmaceutical companies can license products in areas they don't want to do to another company, so that better companies can continue to develop products As a result, the licensing model allows pharmaceutical companies to respond quickly to changing external environments 3 The rapid development of patent licensing mode in the pharmaceutical industry of Asian countries is rapidly becoming the development strategy of Asian pharmaceutical enterprises Among them, Japan is the best Asian country in this field, with the earliest and most complete patent licensing mechanism in Asia Of the rest of Asia, South Korea has the best license out For example, lglifesciences licensed lb-80380 (a small molecule compound for the treatment of hepatitis B virus infection) to Anadys company in the United States The former still retains the market development rights of the drug in South Korea, China, India and Southeast Asia, while the latter has the market development rights in North America, Europe, Japan and the rest of the world India has the world's leading generic pharmaceutical industry, but its patent licensing model has only been developed in recent years due to the introduction of truly meaningful patent laws and regulations to protect chemicals in 2005 The main reason is the rapid development of foreign licensing For example, Dr Reddy, s licensing ballaglitazone To Novo Nordisk in Denmark is the first time a new drug from an Indian laboratory has been licensed to a pharmaceutical giant 4 the licensing model is a good way for China 's pharmaceutical industry to overcome the current difficulties China formulated the first patent law in 1985 Since then, China' s pharmaceutical industry has embarked on the road of integrating with the world In particular, with the revision of the patent law in 1993, China's pharmaceutical industry has been under the management of patent laws and regulations with the same standards as those in Europe and the United States At the same time, the model of generic drugs in China's pharmaceutical industry has been challenged unprecedentedly, which is manifested in the following aspects: first, there are fewer and fewer generic drugs that can be imitated and profitable, which leads to a serious surplus of production capacity in China's pharmaceutical industry, with about 50% of the production capacity vacant, and the competition for generic drugs is becoming more and more fierce, so we have to keep reducing prices Second, global integration, foreign-funded enterprises have settled and rooted in China, and the development of existing products and new products in China's pharmaceutical market are under pressure of global competition Third, due to China's neglect of research and development of patented innovative drugs in the past, there is a serious lack of platform and talents for new drug discovery, which is the key to research and development of patented drugs The research and development of modern new drugs usually go through several stages, including the identification and confirmation of targets, the screening of lead compounds, the research and creation (optimization) of candidate compounds, preclinical research and clinical trials The pre clinical research stage is called "new drug discovery" before and "new drug development" after The stage of new drug discovery is the stage of innovation with the most gold content and the stage of key compound patent production In the history of China, there is a lack of innovative drug development In the past, most of the so-called new drug research and development belong to the category of "new drug development" There is no compound patent, which is essentially imitation On the big side, if China's pharmaceutical industry wants to survive and develop, if it wants to develop "blockbuster" drugs based on patents, if it wants to rank among the world's top pharmaceutical companies, it needs to make new drug discovery; on the small side, if it wants to survive in China's pharmaceutical industry and reduce the risk of being eliminated, it needs to make patent drugs However, due to the long-term neglect of research and development of patented innovative drugs in the past, it will take quite a long time for Chinese pharmaceutical enterprises to develop their own patented drugs and new drugs with high technical barriers Obviously, in order to overcome the current difficulties, it should be a very effective way, and the licensing mode is such an effective way, especially those non patent drugs that may become the patent drugs or high-tech barriers of blockbuster drugs 5 Licensing model is a long-term and effective model Licensing model can not only solve the current difficulties of China's pharmaceutical industry, but also should be a long-term strategic model According to the characteristics of various large pharmaceutical enterprises in the world, they can be classified into four categories: large multinational pharmaceutical companies; large regional pharmaceutical companies; large multinational generic pharmaceutical companies; large regional generic pharmaceutical companies Comparing the characteristics of all kinds of pharmaceutical companies, we can see that, first of all, multinational large pharmaceutical companies are mainly selling patent drugs and fully using the mode of patent licensing to develop new drugs; second, multinational large generic pharmaceutical companies, whose sales volume (in the range of 1 billion to 10 billion US dollars) is far lower than that of multinational large pharmaceutical companies (in the range of 10 billion to 45 billion US dollars), and China's generic pharmaceutical companies take the place of them Table of the regional large generic pharmaceutical companies, its sales volume is only 1 billion US dollars Therefore, if Chinese pharmaceutical companies want to be bigger and stronger and become world-class pharmaceutical companies, they should develop patent drugs, and patent licensing mode is a long-term and effective mode To sum up, we can see that licensing mode is the development mode of modern pharmaceutical industry, and its position is becoming more and more important This mode is not the "patent" of the pharmaceutical industry in Europe and America, and it can also be applied to other countries including China In addition to the licensing model, the international drug innovation can be summarized into six major models: 1 Creating novel molecular structure type: research and development of breakthrough new drugs Under the guidance of certain medical theories and scientific ideas, through repeated new drug design, synthesis and pharmacological or biological screening, new structured drugs are created, which is the main research direction of many famous pharmaceutical enterprises in the world In order to reduce the risk and improve the success rate, the research and development of breakthrough new drugs can start from natural product research, biotechnology drug development, computer-aided design of new drugs, combinatorial chemistry and the application of high-throughput screening technology 2 To create "me too" new drug - imitative new drug research and development me too is to modify and transform the chemical structure on the basis of other people's patented drugs, and to develop its own patented drugs This method has the advantages of less investment, short cycle, high success rate and good market prospect 3 Pharmaceutics research of existing drugs - research and development of new products pharmaceutical dosage form is a shortcut to create new drugs Due to the increasing difficulties in the research and development of new drugs and the low success rate, the pharmaceutical industry at home and abroad pays more and more attention to the research of new dosage forms, focusing on the dynamic process of absorption, distribution, metabolism and elimination of preparations in vivo, as well as bioavailability, so that the dosage forms tend to micro, directional, quantitative, timing or constant speed release, to achieve the optimization of drug effects and the precision of drug delivery scheme At present, the pharmaceutical formulations have been developed from traditional ones (tablets, injections, etc.) to sustained-release, controlled-release and transdermal preparations 4 Further research of known drugs: research and development of new extensible drugs, biotransformation and metabolites A new generation of lead compounds can be found by studying the biotransformation and metabolites of drugs Research and development of chiral drugs The research of chiral drugs has become one of the new directions of new drug research in the world The development of chiral technology has made great progress The chiral pharmaceutical industry is developing rapidly The world market of single enantiomer drugs is growing by more than 20% every year 5 In recent years, with the development of new biochemical drugs and the continuous development of molecular biology and biotechnology, the micro existing substances such as transfer factor, thymosin, insulin and other active substances are continuously separated and purified At present, not only the structure and function of many biochemical substances have been described, but also they have been used as the host of Escherichia coli, yeast or animal cells to produce these substances on a large scale, which provides a basis for the development of biochemical drugs 6 The application of high and new technology to the innovation of traditional production process and the transformation of microbial fermentation is an important means for the pharmaceutical industry to produce microbial drugs For example, the use of enzyme conversion, especially the application of fixed bioreactor to improve the pharmaceutical process, has achieved remarkable results in the fields of organic acids, amino acids, nucleotides and so on Research on Biotechnology of Chinese herbal medicine Using plant culture technology to culture meristem in vitro, establish asexual propagation system and induce differentiation into plants, this method is the most effective way to preserve, breed and purify some rare and endangered Chinese herbal medicines At present, scientists in China have been exploring the genetic engineering of Astragalus Polysaccharides and artemisinin Adopt new technology and new process to transform traditional process For example, the compound Danshen dropping pill was modified from the traditional compound danshen tablet, mainly changing the fat soluble extract of Danshen in the original formula into the soluble component (mainly Danshensu), changing the triphenyl crude drug powder into the total saponin extract of notoginseng, reducing the amount of borneol and preparing the dropping pill.