except for the United States, most countries that have established patent systems implement the first application system. In order to protect the innovation achievements in time, drug development enterprises in various countries usually file patent applications after obtaining the basic pharmacodynamic or pharmacological data of drugs. However, because drugs are related to the national economy and people's livelihood, human health and safety and other major issues, the conditions for market access (production and marketing approval) are very harsh in all countries, and the approval period is very long (usually, the approval period of original drugs is as long as 7-12 years, which requires at least hundreds of millions of investments), which makes it difficult for pharmaceutical companies to recover their high R&D investment by obtaining a relatively long exclusive period of drug market. At present, developed countries such as the United States, Europe and Japan have implemented appropriate extension protection policies for drug patents, but most countries are conservative in extending the protection period of drug patents. Therefore, how pharmaceutical companies use the patent system to reasonably extend the patent protection period and scope of listed drugs in the process of drug research and development, so as to maximize the recovery of R&D investment and maximize profits has become an increasingly concerned and valued issue. In this paper, several commonly used strategies to extend the protection period of patented drugs are briefly analyzed by examples, which can be used as a reference for enterprises to formulate drug patent strategies.

1. Choose an appropriate application opportunity to extend the protection period of patented drugs

Patent application must be in line with the overall patent strategy of the enterprise and serve the industrial manufacturing and sales of the enterprise. When applying for a patent, you should choose an appropriate application opportunity, neither too early nor too late. Early application and disclosure means providing your own technical information to competitors in advance, and wasting the limited patent protection period for no reason; However, if the application is too late, competitors may apply for patents first, which will not only fail to protect the innovation achievements of enterprises, but also be controlled by competitors' patents. Usually, enterprises should consider the following factors when choosing the application opportunity: ① the degree of completion of the invention. Biomedical field usually needs experimental data (effectiveness, safety or stability, etc.) to prove the feasibility of the invention and the effect achieved, so as to meet the minimum requirements for patent application; (2) Pay close attention to the possible progress of competitors, and prevent innovative achievements from being applied for by others first; (3) Market planning: First, give consideration to the progress of patent application and drug registration, and try to synchronize them as much as possible; The second is to take into account the market promotion plan of the company's series of products and the market demand of the products.

when there are many competitors with innovative achievements, or the R&D strength of the enterprise is equal to that of competitors, or the market demand for innovative technologies is strong, or innovative technologies are easy to be imitated, it is suitable to apply first: when the enterprise has completed the R&D of the core technology, the competitors have not yet developed the technology, so the enterprise should pay close attention to the R&D of peripheral technologies, and can apply for patents together after the peripheral technologies are developed; For the technology that the enterprise is leading and not easy to be developed by others, we can also apply for patents when competitors are about to catch up. In addition, according to the needs of the overall patent strategy of the enterprise, we can sometimes apply for patents for peripheral technologies first, and then apply for protection of core technologies at an appropriate time. For example, when planning a patent application involving a listed drug, an enterprise can apply for the compound of the general formula separately from the listed compound at an appropriate time interval, or appropriately delay the time for filing a patent application for the listed compound, so as to relatively extend the patent protection period after the drug is listed.

2. Extending the protection period of patented drugs by choosing inventions

Choosing inventions refers to purposefully selecting narrow or individual inventions with unexpected effects that are not mentioned in the prior art from the wide range disclosed in the prior art.. Although the selected invention usually has a subordinate or dependent relationship with the existing patent, and its implementation is limited by the prior patentee, if the right holder properly applies the selected invention, he can also cross-license the selected invention or negotiate the patent with the prior patentee, so as to effectively reduce the licensing and transfer costs or infringement risks of the enterprise. In addition, if the enterprise owns the core technology of the product itself, and there is no risk that the core technology will be leaked or cracked by others first, it can reserve it when applying for a drug patent for the first time, only disclose the general technical scheme, and keep the preferred scheme or the best scheme, and then apply for an invention patent for the preferred scheme or the best scheme before or after the expiration of the basic patent protection period, so as to reasonably extend the protection period of patented drugs. For example, Lilly Company of the United States applied for an invention patent for benzodiazepine derivatives of general formula in 1975, and in 1995, it selected the preferred compound olanzapine from the range of compounds of general formula and applied for an invention patent, which reasonably extended the protection period of drugs on the market for nearly 2 years. AstraZeneca has filed patent protection for compounds of general formula including omeprazole since 1974, and with the deepening of research, it has successively introduced its preferred compounds (omeprazole), intermediates and their modifications, metabolites, preparations and their compositions, preparation methods and improvement methods, polycrystals (types), second medicinal use, combined use, basic salts, crystals, compositions, Hydrate, S- enantiomer cNexiiJm) and other topics or their improvements, and gradually formed a strict patent protection network for omeprazole, which not only reasonably extended the patent protection period of omeprazole, but also continuously extended the protection scope of omeprazole and expanded its sales market, making it obtain high profits.

3 extending the protection period of patented drugs through peripheral inventions

peripheral patents, that is, developing downstream improved inventions related to and limited by upstream basic inventions. Enterprises can continue to develop their better preparation methods, new uses or other downstream products (such as salts, esters, hydrates, polymorphs or group modifiers) after applying for patents for upstream pharmaceutical products, that is, they can use the subsequent peripheral patents to form an uninterrupted relay for basic patents and apply one after another at a time interval, which can not only protect patented drugs in all directions, but also effectively extend the actual protection period and control period of their market share. Generally, the following aspects can be considered in the development of peripheral patents: ① modifying or improving existing compounds, developing new compounds, intermediates and their modifications, metabolites, new crystal type F), new configurations, salts, esters, hydrates, compositions, different dosage forms or new preparation excipients, etc. (2) Specific selection of existing compounds or compositions: (3) Improvement of existing preparation methods of pharmaceutical compounds or drugs, and development of new preparation methods or preparation methods of intermediates; (4) Improvement of indications or administration routes of existing drugs, and development of new pharmaceutical inventions. If these peripheral technologies or improved technologies have unexpected technical effects, they can apply for patent protection. For example, the inventors of dihydroartemisinin, artemisinin methyl ether, artesunate and other compounds should be able to obtain patents if they submit their applications in time when completing the research: rosiglitazone maleate with better hypoglycemic effect screened by GlaxoSmithKline once monopolized the international market of this kind of hypoglycemic drugs: many companies have benefited handsomely from the research and development of various crystal forms and amorphous patents of adefovir dipivoxil: Takeda, Japan, conducted me―too research on omeprazole, In 1986, lansoprazole with better thermodynamics, oxidation stability, biological activity and low toxicity than Omeprazole was obtained, and a patent application was filed to protect it: after lansoprazole was successfully marketed, the preparation method of optically pure lansoprazole, Its oral preparation and its preparation method, the method of oxidizing thioether group into sulfoxide group, the crystallization method of (r)-or (s)-lansoprazole, the preparation method of magnesium salt of [(substituted pyridyl) methyl] sulfinyl-1h-benzimidazole compound, the composition for inhibiting gastric acid secretion, and the improved preparation method of benzimidazole compound have successively obtained patents in China.

4 using priority to extend the protection period of patented drugs

according to China's patent law, an applicant may file a patent application for the same subject again within 12 months from the date of filing the patent application for the invention or utility model for the first time, and enjoy priority. The legal effect of priority is not only to exclude that the same technology or patent application disclosed between the priority date and the actual application date does not affect the novelty of the invention, but also because the protection period of the patent is counted from the actual application date, claiming priority can extend the protection period of the later application by no more than 12 months, that is, priority can extend the protection period of the drug patent by the time between the application date of the earlier application and the application date of the later application.

5. Extending the protection period of patented drugs by administrative means

Because there are many laws and regulations concerning the protection of intellectual property rights of drugs in China, there are many protective measures such as judicial protection of national laws and administrative protection of departmental regulations, so drug patentees can comprehensively use these laws and regulations to reasonably extend the protection period of patented drugs. For example, the obligee who obtained a foreign drug patent from January 1, 1986 to December 31, 1992 can use the Regulations on the Administrative Protection of Drugs to extend the actual protection period of the patent for the preparation method or use of the drug he applied for later in China; The patentee of Chinese traditional medicine can apply for the protection of Chinese traditional medicine varieties by using the Regulations on the Protection of Chinese Traditional Medicine Varieties before the expiration of the patent protection period, so as to further extend the market monopoly period of its drugs; If it takes a long time for an enterprise to develop a patented drug, and the patent application for the drug is filed earlier, resulting in the expiration of the patent protection period after the drug is listed, the market exclusive period of the drug can be extended with the help of the safety testing period of the new drug not exceeding 5 years and the data exclusive protection period of 6 years.

6 Comprehensive use of technical secrets and patent means to extend the protection period of patented drugs

Based on the limitations of patent protection (such as timeliness, openness and regionality), enterprises need various ways to protect innovation achievements, for example, they can also adopt technical secrets to protect innovation achievements. Technical secrets can be used to protect technologies that have high commercial value but may not meet the patent requirements and cannot be protected by patents. For example, the process, the best conditions, the optimal scheme, the technical links, the process parameters and the process conditions that affect the technical effect, as well as some formulas (the formulas of some medicines and the secret recipes of ethnic medicines) and production processes that are difficult to be cracked by reverse engineering. Moreover, an enterprise does not need to perform any legal procedures to protect the innovation results by using technical secrets. As long as the confidentiality measures are appropriate and it is difficult for competitors to crack the innovation technology, the market monopoly period of the product is not limited by time.

of course, enterprises generally need to comprehensively consider the nature of innovation achievements, relevant market value, the advantages and disadvantages of various systems and other factors when choosing the protection method of innovation achievements. For high technical content. High-tech that is difficult to research and develop, and it is difficult for competitors to complete it in a short period of time or obtain it through reverse engineering can generally be protected by means of technical secrets first. Once competitors are found to have the R&D strength involved in completing related products, they will file a patent application, which not only prolongs the protection period of innovation achievements, but also gives enterprises more time to evaluate the technical and commercial value of inventions and creations for patent decision-making. If the innovative technology has a long life cycle and is just in the embryonic stage, it should be regarded as a technical secret first, and then apply for patent protection after the technology is close to the application stage or after considering the research and development status of competitors. If the innovation not only meets the protection conditions of trade secrets and patents, but also contains many technologies, and the technology has a broad market prospect and a long life cycle, you can apply for patent protection for one or more technologies that are easy to be cracked by reverse engineering, and adopt trade secrets protection for one or more technologies that are not easy to be cracked by reverse engineering. However, when enterprises use technical secrets to protect research and development achievements, they should strengthen the confidentiality management of technical secrets to prevent possible leakage risks.

7 Combining patent and trademark protection to extend the protection period of patented drugs

Based on the timeliness of patent protection and the persistence of trademark protection, pharmaceutical enterprises can use trademark rights to undertake after the drug patent expires, so as to continuously maintain the market advantage of patented drugs. That is to say, pharmaceutical enterprises can use the exclusivity of patent rights to form the monopoly position of products, at the same time, use trademark rights to continue to control the patented drug market before and after the expiration of the patent protection period, and use the brand effect of trademarks to maintain their image as market leaders, so as to effectively maintain their market dominance and maximize the resource efficiency of enterprises.

what kind of strategy should an enterprise choose in actual management? It should also make comprehensive consideration and timely adjustment according to the characteristics of the enterprise, the market situation of drugs, the characteristics of the project and the progress of R&D, and comprehensively apply and cross-apply various strategies to reasonably extend the protection period or market monopoly period of patented drugs, so as to obtain the maximum profit for the enterprise and recover the R&D cost to the maximum extent.