What Are the Different Types of Biotechnology Programs?

The modern biopharmaceutical industry arises from the discovery of DNA double helix structures and breakthroughs in genetic engineering technology. This industry has subverted the research philosophy of the traditional chemical pharmaceutical industry. Move forward in risk.

Medical biology

The modern biopharmaceutical industry arises from the discovery of DNA double helix structures and breakthroughs in genetic engineering technology. This industry has subverted the research philosophy of the traditional chemical pharmaceutical industry. Move forward in risk.

Chinese name

Medical biology

Rise time

Around 1960

Direction of development

Genetically engineered processing technology to produce protein

Raw materials

Based on natural biomaterials

Technology leader

United States

: Double Helix Temptation Maintains Bullish Ratings

From an industrial perspective, the current development of biopharmaceuticals includes two directions:

-Subverting the new industry in the past

More than 50 years ago, Waterson and Crick described the double-helix structure of DNA at the molecular level, a major discovery that kicked off the modern molecular biology revolution. In the 1970s, Stanley Boyer and Herbert Cohen invented the method of genetic recombination, which made it possible to express proteins in vitro.

It is worth pointing out that these two major discoveries both won Nobel Prizes.

Genetic engineering technologies include core biological technologies such as gene recombination, molecular cloning, and expression purification. Simple to understand, these technologies can solve the following problems: If a protein molecule encoded by a certain gene has the functional activity that people need, they can put useful genes that people need into a controlled environment for a large number of amplifications, and then these genes Converted into corresponding high purity active protein.

The application of biotechnology in the pharmaceutical industry has produced a biopharmaceutical industry that is different from the traditional pharmaceutical industry. Biotechnology has two important effects on drug development.

First, one can develop a completely new class of drugs based on genetically engineered proteins.

In the pathophysiology of human diseases, some diseases are caused by the decrease in the expression of proteins with specific functions in the body, and the normal physiological balance is broken. By using genetic engineering technology to prepare a large amount of target protein in a controlled environment and use it in a patient, the physiological environment of the patient can be adjusted quickly and efficiently to achieve the effect of curing the disease. The emergence of new technologies has created a brand new industry. Since the 1980s, hundreds of biotechnology companies have been established and engaged in commercial research and development.

Second, the new technology can be traced back from the molecular mechanism of known diseases, so as to find or design molecular "keys" to unlock the "locks" of diseases. This method is called "inferential drug design method", and it completely changes The traditional method of drug discovery. In the past, the invention of drugs first required random screening of a large number of organic compounds (called libraries). Success or failure was largely determined by luck. The advent of inferential drug design has enabled pharmaceutical companies to more quickly and efficiently discover therapeutic drugs.

In short, the application of these advanced technologies is mainly reflected in two aspects, one is to use genetic engineering processing technology to produce proteins, and the other is to use advanced technologies in the field of genetics and molecular biology as research tools to improve routine Efficiency of "small molecule" drug development.

Biopharmaceutical raw materials are mainly natural biological materials, including microorganisms, humans, animals, plants, and marine life. With the development of biotechnology, purposefully prepared biological raw materials have become the main source of current biological pharmaceutical raw materials. For example, animal materials made by the immunological method, microorganisms or other cell materials made by changing the genetic structure, and the like. Biological drugs are characterized by high pharmacological activity, low toxic and side effects, and high nutritional value. Biological drugs are mainly proteins, nucleic acids, sugars, lipids and so on. The constituent units of these substances are amino acids, nucleotides, monosaccharides, fatty acids, etc., which are not only harmless to the human body but also important nutrients.

The development of the biopharmaceutical industry can be said to be closely related to the technological innovation of biotechnology. From the invention of genetic engineering in 1973 to its inception in 1990

There is no doubt that the United States is the absolute leader in the biopharmaceutical industry. The United States accounts for more than 60% of global biotechnology drug sales annually, and has the world's most successful biopharmaceutical companies and the most advanced technology. The number of biopharmaceutical companies in the United States also ranks first in the world. The large-scale emergence of small wholly-owned biotechnology R & D companies has become an American phenomenon, but this feature is not so obvious in Europe and Japan. Studying the relationship between the external living environment and industrial competitiveness of the US biopharmaceutical industry is obviously helpful to analyze the current situation and development direction of the Chinese biopharmaceutical industry.

I. Technological breakthroughs drive market enthusiasm

Every Wall Street pursuit of biotechnology stocks is related to major breakthroughs in the field of biotechnology.

From the 1950s to the 1970s, major advances in basic molecular biology research were made. The discovery of reverse transcription processes, restriction enzymes, terminal transferases, ligases, etc. made possible genetic recombination, and many difficult-to-obtain proteins were expressed . These proteins, called "magic bullets," are mostly targeted at diseases that are difficult to cure. Interferon, EPO, and insulin are the products of this period. Major technological breakthroughs have made it possible for the industrialization of biotechnology products. Many biotechnology companies have emerged at the historic moment, and have spurred the enthusiasm of the capital market for the first time in the early 1980s and 1990s.

In the mid-1990s, the U.S. stock market as a whole weakened, for the first time

Industry moves forward in hope

With the development of nearly two decades, China's biopharmaceutical industry has grown into a rising star in China's pharmaceutical industry. So far, China has made certain achievements in biopharmaceutical research, and the preliminary pattern of the biopharmaceutical industry has been formed.

I. Innovation Capability Analysis

1. Top 10 in the world for basic R & D strength

Like the United States, the foundation of China's biopharmaceutical industry is laid by the research activities of universities and public research institutions, both of which are completed with government funding. Funding channels include the National Natural Science Foundation of China, the High-Tech Research and Development Program (the 863 Program), and the National Key Laboratory Program. For more than 20 years since its establishment, the National Natural Science Foundation of China has provided about one-third of its total funding for life sciences and biotechnology each year. In the state key laboratory plan, the number of key laboratories in the field of life sciences and biotechnology ranks first among the seven major scientific fields, accounting for 23.5% of the total. In the China High-Tech Research and Development Plan (863 Plan) promoted by the Ministry of Science and Technology, biotechnology accounts for more than a quarter of the total expenditure in the civilian sector.

In recent years, China has made certain achievements in basic R & D in the field of biopharmaceuticals. China ranks in the top ten in terms of the number of published papers and citations. The Chinese Academy of Sciences is also the only research institution outside the United States to be selected for the top ten in terms of number of publications.

2.How to treat the innovation ability of China's biopharmaceutical industry

Although China's biopharmaceutical industry is at the forefront of basic R & D, at the enterprise level, the industry's R & D level gives most investors the impression of "imitation". For this, we believe that:

(1) Technological innovation has a "threshold effect", and currently Chinese biopharmaceutical companies do not have such a scale

According to the viewpoint of innovation economics, technological innovation follows the "threshold theory", that is, the stable output of research and development results can only be achieved when the research and development resources are concentrated to a certain degree. As we all know, new drug research is a high-input, high-risk, long-term process. China's biopharmaceutical companies are generally small in scale and small in sales revenue. Even if the ratio of R & D investment to sales revenue is high, its absolute value is still small, especially in technology. In terms of industrialization of R & D, it has obvious scale effects. It is extremely difficult for a single company to invest heavily in research on innovative drugs, which is one of the reasons why China's biopharmaceutical companies have less original research, more generic products, and repeated production of products.

Looking at the development of the US biopharmaceutical industry, there are a lot of situations in which a large number of small biopharmaceutical companies cannot obtain financial support. From the development history of successful biopharmaceutical companies, the active participation of capital markets, venture capital, and traditional large-scale chemical pharmaceutical companies is an important reason for their development and growth. In these aspects, China is at the stage of development. Like other early-stage industries, industrial investment in the biopharmaceutical industry is often accompanied by pain, twists, loneliness, and patience, but who would deny that this is a promising industry? The same is true of investments in the secondary market of the biopharmaceutical industry.

(2) Introduction, digestion and absorption are insurmountable processes of technological innovation

Developed economies such as the United States and Japan have introduced the process of digestion and absorption in the process of independent innovation. As a rising country, this process cannot be surpassed. Although China's biopharmaceutical industry is one of the industries with higher levels of technological innovation, However, from the perspective of research and development intensity, there is still a big gap with developed countries, so this also determines that the current research and development of the biopharmaceutical industry is still dominated by imitation.

In the field of biotechnology drugs, biosimilars are defined as generic drugs that are no longer protected by intellectual property rights in biotechnology or the biological field. Traditionally, biosimilars can use the existing clinical data of their brand drugs to simplify their declarations in order to shorten the time to market as much as possible, provided that their dosage forms and dosages are the same as those of the brand drugs and their administration methods It must also be consistent.

In fact, the imitation of recombinant drugs is far more complicated than that of small molecule drugs. Unlike small molecule drugs, even if the same gene is expressed in the same cell and uses a similar processing method, it is difficult for recombinant drug generics to guarantee complete compatibility with the original drug. Similarly, the production cost and the complexity of the processing process are the main considerations. Therefore, for some domestic generic drug products, such as recombinant human insulin, large-scale industrialization is the technical barrier of the enterprise.

The puzzle of industrialization

1. Industrial model thinking

The conversion rate of China's biopharmaceutical scientific and technological achievements is only 0.5%. The deep-seated reason is the industrialization model of scientific research achievements. The transformation of general biotechnology scientific and technological achievements has to go through three stages: research and development, pilot test, and mass production. The ratio of capital investment in these three stages internationally is 1: 10: 100, while China is only 1: 0.7: 100. The direction of research investment in the field of life sciences is mainly scientific research institutions, and the problem of irrational investment structure in the transformation of scientific and technological achievements is the main reason restricting the development of China's biopharmaceutical industry.

Like the United States, a large number of biological enterprises in China are founded by universities, public research institutions or their researchers. For example, under the leadership of Academician Hou Yunde, China Centers for Disease Control established and participated in the establishment of 6 biopharmaceutical companies. Because scientific researchers are not good at business management, there are management bottlenecks in the development of enterprises. The original situation in the United States is the same, but venture capital and traditional large pharmaceutical companies have played a very important role in this regard. Large pharmaceutical companies may cooperate with biopharmaceutical companies through mergers and acquisitions, external alliances, or franchises to support them at multiple levels such as funding, management, and marketing. It is an inevitable trend for China's pharmaceutical industry to develop innovative capabilities and competitiveness by establishing large research institutes or cooperating with other biotechnology companies.

2. Financing channels

Since 2002, China's biotechnology industry's ability to attract venture capital has declined sharply. In the past five years, a total of 1080 enterprises in China have attracted US $ 5 billion in venture capital, but the biomedical industry only accounts for 5.2% of the total financing.

The development of China's venture capital faces the influence of environmental, institutional, and legal factors, and a complete system has not yet been formed.

China's capital market structure is also not perfect, but this situation is gradually changing. The new securities law has revised the company's listing requirements to a total of 30 million shares. It has eliminated the three-year profitability requirement and lowered the threshold, which is conducive to high growth. Companies that are not large, but are not large in scale and have poor performance.

Judging from the development history of the US biopharmaceutical industry, the Nasdaq market has contributed. During the two sessions of China this year, the proposal for the launch of the GEM as soon as possible was high. Although the final listing rules have not yet been issued, the launch of the GEM is already underway. To be sure, the listing conditions of the GEM are lower than the main board, which is more flexible and loose This will be a big plus for biopharmaceutical companies that are in the investment stage as a whole.

Discussion on development direction

1.China's development model is more similar to the United States

Comparing the development models of the biopharmaceutical industry in various countries, China is more similar to the United States for several reasons:

(1) From the perspective of R & D and industrialization, China as a whole is in the first stage of the United States, that is, the stage of "genetically engineered processing technology to produce proteins", but China has developed to The third stage is at the forefront of the world. What is worth mentioning here is the therapeutic hepatitis B vaccine. Similar to the United States, there are a large number of small biotechnology companies born in China from scientific research units, and the sponsors and management are mostly from scientific researchers. Judging from the situation in Europe and Japan, Europe is lagging behind the United States in the research and development of basic biotechnology. European biotechnology innovation is mostly carried out by internal R & D teams of large companies. This is quite different from the form of independent small companies in the United States. While Japan is weaker in basic research and development, the main application area of biotechnology is in fermentation.

(2) From the perspective of the national innovation system, the United States has always invested heavily in basic research and development of scientific research institutions, and attaches great importance to this. This is also one of the main reasons why the United States was the first to make a breakthrough. China also attaches great importance to basic scientific research in life sciences, and ranks first in all disciplines in this field.

2. Recombinant protein drugs still occupy the mainstream, and some areas will make breakthroughs

We divide biopharmaceutical companies into two main categories: companies that use genetic engineering processing technology to produce proteins, and companies that use advanced technologies in the fields of genetics and molecular biology as research tools. The former is represented by Amgen, and the latter is typical.

(1) Producing protein using genetic engineering processing technology

In the next 5-10 years, China's biopharmaceutical industry will still focus on recombinant proteins, which is in line with the development trend of the world's biopharmaceutical industry. The research and development directions of these drugs can be divided into three categories: tracking research and development, improved research and development, and original research and development. Follow-up R & D can be a complete imitation or screening of new indications; improved R & D can make existing products safe (with fewer side effects), effective, and long-lasting (through side effects such as recombination, restructuring, and chemical modification) ( The half-life is prolonged, and the dosage and the number of times of use are reduced. The original research and development is based on the new gene and new molecular mechanism. In the selection of R & D varieties, the "heavy bomb" products will still be the main starting point for research, which is not entirely attributed to the domestic biopharmaceutical companies "crashing up". From a global perspective, the existing "heavy blockbusters" The transformation of "bomb" protein drugs is a major development trend. For example, Aranesp, one of Amgen's "Five Golden Flowers", is actually a long-acting species of Epogen.

Another notable aspect is the increase in production capacity. Not only in China, but insufficient production capacity in the biopharmaceutical industry worldwide has become the bottleneck for the development of recombinant drugs. Inadequate production capacity leads to increased production costs, which limits industrialization to a certain extent. To put it another way, the advantage in terms of production capacity is the barrier.

(2) Using advanced technologies in the field of gene and molecular biology as research tools

This category has a wide scope. From the perspective of industrialization and domestic status, it mainly refers to targeted drugs, including the field of therapeutic monoclonal antibodies and therapeutic vaccines. Targeted drug development will be one of the main development directions of future biopharmaceuticals.

Domestic monoclonal antibody drugs have developed rapidly. There are 11 monoclonal antibody drugs on the market, of which 6 are self-developed in China and 5 are in clinical research. The mouse-derived anti-human T-lymphocyte CD3 antigen monoclonal antibody for injection developed by Wuhan Institute of Biological Products is the earliest domestically developed antibody approved for marketing; a new type I cancer treatment drug developed by Beijing Biotec and Cuba, "Recombinant Human Source" "Chemical anti-human epidermal growth factor receptor monoclonal antibody" (brand name: Taixinsheng) is the first humanized monoclonal antibody drug approved in China; Methoxant, jointly developed by the Fourth Military Medical University and Chengdu Huashen Anti-injection solution (brand name: Licatin) is the first medicine in the world to treat primary liver cancer, and it is also the first antibody medicine with independent intellectual property rights in China.

The most anticipated achievement in the field of therapeutic vaccines in China is the therapeutic hepatitis B vaccine. Investors are advised to refer to our report "Unveiling the Veil of Therapeutic Hepatitis B Vaccine". Like the original therapeutic monoclonal antibodies, R & D in this field has been controversial, both at home and abroad. It is undeniable that this type of technology will become one of the development directions of future biotechnology with its excellent treatment principle. There may be twists and turns, and investors will have to bear greater risks. But looking back at the short history of the development of the biopharmaceutical industry, controversy, twists and turns, and risk are always accompanied, but who can stop the industry from moving forward? Only in the course of the industry's advancement in Dalangtaosha, carefully study and share the growth of the industry / company.