The new sharpin in the field of "elite" drugs in immunoglobulins - monoantigen

Single-resistant refers to the immune system of the body under the stimulation of antigens, by B lymphocytes differentiated into the plasma cells produced by the corresponding antigen can be specifically combined with the corresponding antigen of the immune globulinIn 1964, the World Health Organization held a special meeting to call the antibody activity and antibody-related globulin collectively known as immunoglobulin (Ig), such as myeloma protein, hypercyloprotein, cold globulinemia and other patients in the serum of abnormal immunoglobulin and normal human natural presence of immunoglobulin subunitsThus immunoglobulin is the concept of structural chemistry, while antibody is the concept of biological functionIn other words, as long as it is antibodies, it must be immunoglobulins, but not all immunoglobulins are antibodiesGenerally speaking, an antigen has more than one deciding cluster, the larger the molecular weight of the antigen, the more the number of determining clustersAn antigen determines that a cluster produces an antibodyThere are about 100 million different B lymphocytes in the body, each independent B lymphocyte can only receive stimulation of one antigen to form the ability to secrete an antibody, so the self-produced serum antibodies, in fact, are a mixture of many antibodiesIt is called a polyclonal antibodyThis multi-clone antibody has a difference in specificity, low efficacy, limited number of individual differences between animals, difficult to repeat the preparation and other inherent defects, the use of the unsatisfactory1975, British scientists Kay milstein and George Koehler combined antibody-producing B lymphocytes with multiple myeloma cells to form hybrid tumor cellsThis cell has two progenitor cells, both the ability of myeloma cells to grow indefinitely, and the function of B lymphocytes to produce antibodiesAs a result, this hybrid tumor cell can produce a large number of single types of high-purity antibodies in cell cultureThis antibody is called a monoclonal antibodySingle resistance is significantly better than multi-resistance in specificity, efficiency, preparation and so onThe two scientists were also awarded the 1984 Nobel Prize in Medicine and Physiology for their outstanding contribution to hybrid tumor technologythe development of monoclonal antibodies
from monoantigen to date 44 years, monoclonal antibodies have generally experienced the rat-source monoclonal antibodies, human-rat chimeric antibodies, humanized antibodies, whole human-source antibodies Rat-derived monoclonal antibodies due to side effects, metabolic fast shortcomings, has now basically exited the market Instead, human-derived and human-derived monoclonal antibodies, because of their small side reaction, long stay in the body, conducive to the advantages of treatment, in recent years has been developed monoclonal antibodies are basically whole-human single resistance the advantages of mono-resistance compared to chemical drugs
1 Single-resisting targeting, chemical drugs to find a needle in a haystack
the world's largest pharmaceutical giant Pfizer Global CEO Ma Jinlong on the chemical drug research and development experience, he believes: new chemical drug research and development is the world's most risky investment, its risk is even higher than the space exploration On average, only 1 in 10,000 compounds can be used to develop drugs, while only 30 per cent of each drug recovers costs A new drug will take about eight years and more than $1 billion to go from development to market Single-resistance research and development is to determine what specific antigen determination clusters are in the diseased cells of a disease compared to normal cells, and then to develop a monoantigen binding with specific antigen-determined clusters, the goal is very clear 2 The patent protection of monoantigen is weak, the patent protection of chemical drugs is strong
as long as the same antigen decision cluster, single resistance will have similar efficacy But for the same antigen decision cluster, the monoantigen structure can have hundreds or thousands of choices Therefore, therapeutic antibodies are difficult to protect with patents If one or two amino acids can produce mutations, resulting in antibody affinity higher than the original antibody, can be considered a completely innovative product For example, the Same anti-CD20 chimeric antibody, the U.S Patent Office approved two patents - XOMA's Patent (U.S Patent 5500362) and IDEC's Patent (U.S Patent 6399061B1) The two patented light chains are identical to CDR1 and CDR2, with the skeleton region almost identical, except for one or two amino acids in the CDR3 region However, the two patents are not infringing As a result, intellectual property issues pose little barrier to therapeutic antibodies It is possible to develop different monoclonal antibodies without infringing on other people's structural patents And the active ingredient of the chemical drug is a single, molecular structure fixed, so an active ingredient corresponds to a substance, of course, corresponding to a patent 3 Monoantigen research and development has a sustainable chemical stoic often changes different groups in a chemically structured basis after the emergence of an iconic drug, and may have similar drugs But monoantigen development is much easier than chemical lying changes to the group the application of single anti-drug applications
cancer treatment drugs
According to pharmacological data, there are currently 17 monoclonal antibodies listed worldwide for the treatment of tumors, china has 2 Compared with other types of drugs, the efficacy of single anti-target drugs does have clinical advantages: 1, it can be based on the characteristics of genetic mutations, that is, tumor cells and normal cell internal matter molecular structure changes or normal proteins and damaged proteins to distinguish between the two types of cells and proteins, and selectively attack inhibit tumor cell growth, so that the entire tumor treatment process becomemore more efficient and reduce drug toxicity Cytotoxic drugs attack all cells indiscriminately in sharp contrast to monoantigens, and since cytotoxic classes also attack normal cells, the patient's negative impression is given to the larger side effects during treatment 2, single anti-drug can extend the survival time of tumor patients to varying degrees, which is of great significance for tumor treatment Table 1 Global Anti-Tumor Drug (Monoantigen) Market situation
autoimmune diseases China's current research and development of autoimmune diseases for the treatment of rheumatoid arthritis monoantigen, we briefly introduce the drug rheumatoid arthritis Rheumatoid arthritis (RA) is a chronic systemic inflammatory disease with unknown causes, with chronic, symmetrical, polysegene icing arthritis and out-of-the-joint lesions as the main clinical manifestations, which belong to autoimmune inflammatory diseases At present, only Serkujinu single resistance and Adamu mono-resistance listed in China Table 2 Global Autoimmune Disease Drugs (Monoantigen) market global sales
According to New Kangjie data, 2018 full-year sales of the first is undoubtedly the "drug king" Shumeile, in fact, since 2012, Shumeile has been on the list of global drug sales, and still firmly occupy this position In China, the drug is commonly known as Adamu mono-resistant injection, each of which costs more than 7,600 yuan As can be seen from the table, there are five monoclonal antibodies in the top 10 drugs sold globally, and this trend is on the rise, and the market share of monoclonal antibodies will continue to increase in the future Table 3 2018 Global Drug Sales TOP10