Research on Drug Patent Link System

【Abstract】 As a special commodity, medicine is closely related to human life and health. Patent protection gives the original drug developer a certain period of market monopoly to compensate for the high cost of developing new drugs, but excessive patent protection may lead to a large number of high-priced drugs, thus affecting the accessibility of drugs to citizens. The drug patent link system is constructed on the basis of taking into account the innovation of medical technology and the protection of citizens' life and health. The author hopes that through the analysis of the Sino-US drug patent link system, the current problems of the system in our country, and put forward corresponding suggestions for its improvement, so as to improve the drug accessibility of our citizens, so that safe, effective and low-cost generic drugs can better benefit our citizens.

【Keywords】 patent linkage; balance of interests; generic drug marketing approval; patent protection

Drug patent linking is usually a system that exists in the process of drug registries refusing to approve generic drugs that are "linked" to existing patents. However, there is no mature definition of this system. Some scholars believe that the patent link system refers to the link between the listing review of generic drugs and the patent status of the original drug, that is to say, the drug registration authority has approved the listing of the first new drug, so as long as it is within the validity period of the patent related to the new drug, the competent authority will no longer approve the listing of other generic drugs. In the author's opinion, drug patent link refers to linking the registration and approval of generic drugs with the existing patent protection under the premise of strengthening the protection of drug patent rights, and through the realization of the function between the drug registration management agency and the patent authorization approval agency Link, form a benign interaction between the two, and finally achieve a balance of interests.

1. the Drug Patent Linkage System in the United States

1. The formation and development of the drug patent linkage system in the United States.

The drug patent link system originated in the United States. As the most powerful original drug research and development country in the world, the United States has established a strong protection system for drug patents. In the 20th century, the global sensation of pregnant women taking thalidomide to give birth to a large number of deformed children was strongly concerned by the U.S. Congress. Subsequently, in 1962, the "Kovor-Harris Amendment" was passed to strictly regulate generic drugs. The bill requires generic drugs to go through a large number of clinical data to prove their safety, effectiveness and quality reliability before they are put on the market, even if the generic drug is completely consistent with the approved safe and effective drug. This provision undoubtedly poses a strong challenge to generic drug companies, to a certain extent, it has caused the stagnation of the development of the generic drug market and affected the life and health rights of citizens.

In view of this, the U.S. Congress passed the Drug Price Competition and Patent Restoration Act (Hatch-Waxman Act, hereinafter referred to as HWA) in 1984, which pioneered the establishment of the drug patent linkage system. Promote drug price competition by changing the FDA's approval requirements for the listing of generic drugs. According to the regulations, generic drug companies only need to prove that their drugs have the same bioequivalence as the original drugs, reducing the time and cost required for generic drugs to go on the market, and taking into account the mutual interests of generic drugs and original drug manufacturers. So far, the United States has formally established the drug patent link system, becoming the first country in the world to establish and provide the most perfect system.

2, the main content of the U.S. drug patent link system.

(1) Functional links between different departments

The functional linkage between the U.S. Federal Food and Drug Administration (hereinafter referred to as FDA) and the U.S. Patent and Trademark Office (hereinafter referred to as USPTO) forms the basis of the U.S. drug patent linkage system. The system stipulates that after a generic drug manufacturer submits an application for listing a generic drug to the FDA, the FDA will submit the relevant information to the USPTO for review when accepting the application, and the USPTO will conduct a substantive review of its relevant patent information status, draw corresponding conclusions, and timely feedback to the FDA.

Through the functional link between the two institutions, the patent infringement phenomenon caused by the confidentiality of information in the process of drug application for listing is effectively avoided.

(2) Orange Book System

HWA stipulates that when a new drug applicant submits a new drug marketing application to the FDA, he or she should also submit relevant patent information. Upon review, the FDA will enter the relevant patent information of the new drugs that meet the conditions and are approved for sale into the "Drugs Subject to Therapeutic Equivalence Evaluation Criteria" (Orange Book). If the applicant is granted a patent after obtaining a marketing license, he shall submit the patent information related to the drug within 30 days and put it on record.

According to the regulations, the content of the orange peel book should be updated on time every month to ensure the timely and authoritative content. The contents of the collection include: the drug approved for marketing and the holder of the approval document; the active ingredient of the drug, the form of administration and its dosage, etc.; the patent number of the patent related to the drug and the expiration date of the patent protection. As the carrier of patent information, orange peel book ensures the openness and transparency of information, provides convenience for applicants to inquire and compare patent information, and promotes the progress of drug marketing approval.

(3) Simplified application system for generic drugs

The system requires the applicant to inquire about the registered patent recorded in the orange peel book before filing an application and submit the following four types of statements: there is no relevant patent; The relevant patent has expired; There is a relevant patent, but it will expire immediately, and the applicant has declared that it will not market its generic drug until then. There are relevant patents, however, the patent is invalid or the production, manufacture, sale or use of the generic drug will not infringe the patent. For the first and second types of statements, FDA can directly grant marketing authorization for generic drugs. For the third type of statement, FDA only needs to approve the ANDA after the expiration of the relevant registered patent. For the fourth type of declaration, generic drug manufacturers can simplify the application system before the expiration of the patent period of the original research drug, and for such cases, HWA and MMA have made detailed provisions.

① Applicant's obligation to inform in a timely manner

The applicant shall inform the patent holder of the original research drug and the holder of the NDA approval document of the relevant information within 20 days after submitting the fourth type of declaration. The content mainly includes the application has been accepted by FDA, the date of declaration, the detailed explanation of the relevant patent invalid or non-infringement of the facts and legal basis, and listed all the valid patents.

The 45-day litigation period

Within 45 days of receipt of the Class IV declaration, the holder of the original drug's patent or NDA approval document may file a lawsuit in the Federal Court requesting the court to determine that the registration number patent recorded on the orange peel is valid and/or the ANDA applicant infringes its patent.

③ Containment period of 30 months

If a holder files a lawsuit within 45 days of receiving a Type IV declaration, the FDA gives them 30 months to resolve the dispute. At the same time, the FDA will automatically delay the approval for 30 months without interrupting the technical review.

④ 180-day market exclusivity period for the first generic drug

HWA has given the first generic drug a 180-day market monopoly period to stimulate the enthusiasm to challenge the original drug patent. During this period, the FDA will not grant marketing authorization for the same generic drug, and the first generic drug can be sold at a lower price to gain market share and profit.

2. the development process of drug patent linkage system in China

Patent linkage system in China refers to the link between drug registration and drug patents. In 1984, my country passed the "Patent Law", which provided for the protection of drug patents for the first time, but only the method of drug production was protected, and whether to protect the chemical structure of drugs was not stipulated. As a result, a large number of generic drug manufacturers use reverse engineering to imitate, which violates the interests of the original drug manufacturers. In 1993, the revised "Patent Law" clearly stipulated that the chemical structure of drugs should also be protected by patent law, which to a certain extent means that a new era of pharmaceutical intellectual property protection is coming.

In 2001, China joined the WTO, which brought about the rapid development of China's pharmaceutical industry. However, based on the current situation of China's pharmaceutical industry, most of the pharmaceutical companies are far from enough innovation ability, are based on imitation, to "imitation" and "development". With the strengthening of drug patent protection, generic drug manufacturers have encountered great challenges. In order to adapt to the international development trend and comply with the relevant provisions of the TIPS agreement, the State Council issued the "Drug Registration Management Measures" in 2002, which established the patent link system for the first time. The Measures were subsequently formally revised twice in 2005 and 2007.

my country's current "Measures for the Administration of Drug Registration" is the 28th version of the Food and Drug Administration Order officially implemented in 2007. The "Measures" stipulate the description, declaration and publicity system of patents and their ownership status. China's drug registration management has formed a normative system consisting of drug-related patent description, declaration, disclosure, dispute resolution and patent drug imitation approval in advance, which provides a basis for the effective maintenance of patent rights and drug registration application approval procedures.

Comparative Analysis of Drug Patent Linkage System between China and the United States in 3.

1. Entity level

(1) The publicity system of patent information.

The United States has established an orange peel system to publicize valid patent information related to NDA applications. The publicity time is after NDA applications are approved and needs to be updated once a month. Article 8 of China's current measures for the Administration of Drug Registration stipulates the information publicity system, and Article 18 stipulates that the explanation or statement submitted by the applicant must be publicized on the website. Although the patent information of related drugs can be found on the website of CFDA in China, compared with the United States, there are no specific regulations on the update time, content and method of information, which leads to the uncertainty and non authority of public information.

(2) Patent declaration system

The U.S. HWA requires generic drug registration applicants to submit instructions related to the status of drug patent information to the FDA, and provides detailed regulations on what they should contain. Compared with the United States, my country's "Measures for the Administration of Drug Registration" requires applicants to submit "statement of ownership status" or "non-infringement statement", which is relatively broad, lacks specific and clear explanations, and is not very operable.

(3) Application for registration of generic drugs

HWA in the United States provides for a simplified application system for generic drugs. For generic drugs to be registered for listing, it is only necessary to prove that they have the same bioequivalence as the original drug that has been approved for listing, which greatly reduces the time and cost of listing generic drugs.

However, before the application for listing of generic drugs in China, a large number of experimental studies are still needed to prove that they are safe, effective and reliable in quality, which undoubtedly increases the difficulty of listing generic drugs and costs a lot of cost. In addition, due to the lack of provisions on the prevention and early warning of generic drug infringement, there are more and more patent disputes after the sale of generic drugs.

2. Procedural level

By analyzing the patent linkage system in the United States, it can be seen that there is a high degree of synergy between drug marketing authorities, courts and patent licensing agencies in the United States. For example, FDA will submit relevant materials to USPTO for filing after accepting the application, and USPTO will feedback the results after examination. If FDA finds any patent dispute during examination and approval, it will leave the patentee 30 months to resolve the dispute without interrupting its technical review.

On the other hand, in China, the synergy between the three is too low, the only functional link is that the CFDA will refer to the results of SIPO and the court before approving the application for drug registration and listing, this lack of mutual cooperation has led to the inevitable increase in the probability of the FDA approving the registration of infringing drugs.

4. the Perfection of Drug Patent Linking System in China

1. Existing problems

(1) The scope of drugs entering the review process is too wide

China's drug patent linkage system requires all drug applications, whether new drugs or generic drugs, to be examined by the patent linkage process.

On the one hand, this provision requires generic drug applications to conduct a thorough search of patent freedom; on the other hand, for new drug applications, not only to accept patent registration, but also to accept the review of patent links is not conducive to its development. Therefore, it is obviously not within the scope of its functions to let the FDA examine and confirm whether the patent is infringing, and to a certain extent, it will restrict the approval of new drugs on the market.

(2) The patent information declaration system is not perfect.

Low credibility of patent search results

In practice, it is very easy for an applicant to submit his own patent information, but there are many obstacles in submitting others' patent information in China. On the one hand, China has not set up a special registered drug patent information retrieval database; on the other hand, the results of patent retrieval are also affected by the search methods, the professional quality of retrieval personnel, the quality of the database and other factors. However, the patent information status of others can only be obtained by searching, and the credibility of the search results is not high, which will lead to the lack of reliability and accuracy of the description of the patent and ownership status of others in China submitted by the applicant, which is not conducive to the smooth progress of the drug registration approval process.

② Formalization of non-infringement claims

If the drug to be applied for registration involves another person's patent in China, the applicant shall submit a non-infringement statement. However, the current "Measures for the Administration of Drug Registration" does not clearly explain the types of non-infringement statements, nor does it stipulate the certification materials that should be provided when submitting non-infringement statements, resulting in non-infringement statements becoming mere formality.

Regarding the notification obligation of the applicant to the patentee, the "Measures" also did not provide for the right holder to obtain relevant information in a timely manner. The lag of this kind of information is not conducive to killing patent infringement in the cradle, and to a certain extent, it will lead to an increase in patent disputes caused by the sale of generic drugs and increase litigation costs.

(3) Patent dispute settlement mechanism is not perfect

The Measures stipulate that the settlement of patent disputes in the drug registration approval process is based on the relevant laws and regulations of patents.

What constitutes a "patent dispute" is not clearly defined. In fact, this kind of dispute mainly includes two kinds: one is that others have obtained patent authorization before the drug registration application, that is, the dispute over infringement of other people's patent right; the other is that after the drug is approved for registration and listing, other people can obtain patent authorization, that is, the dispute over the ownership of patent right. These two patent disputes can not simply apply the same means of relief. In addition, it is resolved in accordance with the corresponding provisions of the relevant patent laws and regulations. This provision is too general. It does not give detailed measures to be taken when patent disputes arise, nor does it stipulate the time limit for resolution, and it does not reflect the functions of the CFDA.

2. Improvement suggestions

(1) Reduce the scope of drugs for patent link examination.

An excessively wide scope of examination is not conducive to the development of the pharmaceutical industry, so for new drug applications, only patent registration is required. Only those generic drug applications that use existing clinical trial data are subject to patent linkage review. This not only realizes the unification of the rights and obligations of generic drug registration applicants, but also enables generic drug registration applications to undertake the cost savings of new drug registration applications.

(2) Establish an authoritative drug patent information retrieval database.

The authoritative drug patent information retrieval database is the technical guarantee for the effective implementation of the patent linkage system. In order to ensure the integrity and accuracy of registered patent information and prevent the occurrence of a large number of unrelated registered patents, improvements can be made from the following aspects: ① only valid patent information directly related to drug registration applications is registered in the database; ② a third party objection mechanism is added to allow third parties to question the validity of registered patents; ③ CFDA actively verifies registered patents that are inconsistent with the patent information recorded by SIPO; ④ Regularly update and improve the contents of the drug patent information retrieval database.

(3) Simplify the application process for the registration of generic drugs.

First, simplify the materials that should be submitted for generic drug registration applications. That is, when filing an application for generic drug registration, the applicant does not need to provide various clinical trial data, but only provides proof data that can prove the same bioequivalence as the original drug. Secondly, reduce the restrictions on the review of generic drug registration applications, cancel the previous "2 years" regulations, and establish a sub-category and more targeted drug data protection system. Finally, the establishment of the "first generic drug" incentive mechanism. Giving the first generic drug a time-limited market exclusivity, allowing it to be sold at a higher price than the subsequent generic drug, thus promoting cheaper and reliable generic drugs to benefit the public more quickly.

(4) Improve the patent dispute settlement mechanism

Remedies for the patentee

The law gives the patentee the right to file a lawsuit within a reasonable period of time prescribed by law after receiving a declaration of non-infringement. After receiving the notice of filing a case from the court, the patentee may apply to the CFDA accordingly to suspend its registration and listing approval process for generic drugs. The CFDA will make a decision to continue or terminate the approval process based on the court's decision.

② Relief for Generic Drug Registration Applicants

For the patentee who fails to respond within a reasonable period of time after receiving the non-infringement statement, the generic drug registration and listing applicant may take the initiative to file a patent non-infringement confirmation lawsuit and request the court to make a judgment to confirm that his behavior is not infringing.

Once the applicant for generic drug registration believes that the original research drug patent is invalid, he can file a request to the Patent Reexamination Board to declare the patent invalid. As everyone knows, in many cases involving drug patent disputes, the focus of litigation requests between the parties is often focused on whether the patent is infringed, and there are very few requests for invalidation. Therefore, based on the consideration of the particularity of drug patent dispute cases, the law can give the court the power to examine the validity of the patent ex officio, so as to obtain an objective, professional, fair and just judgment.

The relevant provisions of the court

Due to the professional and complex characteristics of intellectual property cases, in addition to the power to examine the validity of patents ex officio mentioned above, we can also learn from the relevant provisions of the United States for 30 months. Appropriately extend the time limit for the trial of patent dispute cases by the court. In addition, during the trial of the case, the court has the right to learn about trade secrets that are decisive for the final outcome of the case. For trade secrets that are not the basis for the decision, the court has no right to require the parties to provide them.

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