China's drug patent link system has a policy basis, the relevant policies to look first.

The drug patent link system refers to the "link" between the approval of generic drugs and the expiration of the patent of innovative drugs. The drug patent link system makes the patent situation of previously listed drugs should be considered before the application for registration of generic drugs, so as to avoid possible patent infringement. The biggest feature of the drug patent linking system is that through the patent linking of drug registration applications, possible infringements can be discovered in time during the drug registration review process, reduce the probability of infringement disputes, and protect the innovation enthusiasm of drug inventors.

The patent linking system originated from the Hatch-Waxman Act of the United States in 1984, which has undergone many amendments and adjustments, and has achieved good results in balancing the interests of the original research and development pharmaceutical companies and generic pharmaceutical companies in the United States.

In recent years, China's pharmaceutical companies have developed significantly, and the demand for drug innovation and drug patent protection in the whole society has become increasingly strong. In 2017-2018, China's central authorities and the State Food and Drug Administration issued a series of documents on the reform of the drug registration and supervision system, aiming to promote the establishment of China's drug patent linkage system.

On May 12, 2017, the State Food and Drug Administration issued the "Relevant Policies on Encouraging Pharmaceutical and Medical Device Innovation and Protecting the Rights and Interests of Innovators (Draft for Comment)". On October 8, 2017, the General Office of the Central Committee of the Communist Party of China and the General Office of the State Council jointly issued the Opinions on Deepening the Reform of the Review and Approval System and Encouraging Innovation in Pharmaceutical and Medical Devices. On October 23, 2017, the State Food and Drug Administration once again solicited opinions from the whole society on the "Administrative Measures for Drug Registration (Revised Draft). On December 28, 2017, the State Food and Drug Administration released the "Catalogue of Chinese Listed Drugs" on the Internet, aiming to establish China's "Orange Book". On April 12, 2018, the executive meeting of the State Council decided to set a data protection period of up to 6 years for innovative chemical drugs. During the protection period, the same variety will not be approved for listing; for innovative drugs that are simultaneously applied for listing in China and overseas, a maximum of 5 years will be given. Compensation for patent protection period. The intensive introduction of this series of policies has released a clear signal that the implementation of China's patent linking system is accelerating.

It is undeniable that the implementation of China's patent linking system will inevitably be affected by the US patent linking system, and on this basis make adjustments to adapt to the Chinese market. The United States patent linkage system includes the following five aspects: drug patent period extension system; market exclusive period provisions; orange book system; ANDA system; patent challenge system. Below, we look at China's relevant policies and regulations from these five aspects.

(I) Drug Patent Extension System

The drug patent period extension system is a system that supplements the patent period lost by drugs and medical devices due to clinical trials and administrative approval. At present, the common phenomenon is that a blockbuster new drug needs to carry out a lot of research work and clinical trials before it is launched. When the drug is launched, the patent validity period of its core patent is already very short, which will seriously weaken the enthusiasm of the original research and development and capital investment of drug companies. In order to strengthen the enthusiasm of the original drug research companies and enable their research and development to achieve generous returns, the Hatch-Waxman Act stipulates that new drug applicants can obtain an extension of the patent period to compensate for the time spent in clinical trials and drug approval, but not more than 5 years, And the sum of the extension period plus the remaining validity period of the patent shall not exceed 14 years.

At the executive meeting of the State Council held on April 12, 2018, Premier Li Keqiang emphasized that the protection of intellectual property rights should be strengthened, and the patent protection period of up to 5 years should be compensated for innovative drugs that apply for listing simultaneously in China and overseas. Premier Li Keqiang's speech at the executive meeting of the State Council can be regarded as that China will also give certain extension protection to drug patents. The specific policies still need to be refined. However, it is foreseeable that China's policy is likely to refer to the U.S. patent period extension. The system will be implemented after relevant adjustments.

(II) Market Exclusivity Provisions

In the United States, in addition to the drug patent period extension system, in order to provide R & D incentives for original drug research companies, the U.S. Food and Drug Administration (FDA) also gives certain market exclusivity periods, including: new chemical entities, which have an exclusivity period of 5 years; Orphan drugs, which have an exclusive period of 7 years; pediatric drugs, which have an exclusive period of 6 months; new dosage forms, new use drugs, its exclusive period is 3 years. During the market exclusivity period, the FDA will not approve the corresponding generic products of the generic drug company, even if the original drug company's patent has expired during that period, it can still monopolize the market.

In China, the relevant policy content also comes from the executive meeting of the State Council held on April 12, 2018. The meeting decided to set a data protection period of up to 6 years for innovative chemical drugs, and the same variety will not be approved for listing during the protection period. At present, the policy has yet to be detailed, for different drugs for different protection period settings.

(III) Orange Book System

The U.S. Orange Book, Drugs with Therapeutic Equivalence Evaluation Criteria, published by the U.S. FDA, provides detailed and complete information on the approved drugs, as well as the patents and exclusivity involved in the drug. According to the regulations, the original research enterprises must provide the corresponding patent information when submitting the application for new drug marketing license to the FDA. When the drug is approved, the corresponding patent will be registered in the orange peel book, providing reference materials for generic drug companies to develop generic drugs, conduct ANDA or patent litigation. The patents included in the orange peel book include patents directed directly to drugs, such as compounds, products, crystal forms, etc., and may also include therapeutic methods. In general, metabolites, intermediates, packaging and manufacturing and process patents are not included.

Corresponding to the American Orange Book is the Catalogue of Listed Drugs in China, which was first released on December 29, 2017. It contains 131 varieties and 203 varieties and specifications, and will include newly approved and listed newly registered classified drugs And drugs that have passed the consistency evaluation of the quality and efficacy of generic drugs are included and updated in real time. The catalogue of Chinese listed drugs published on the official website of the Food and Drug Administration will also be connected to the patent information database, data protection information, market exclusive period database and review and approval/verification/inspection report database. Among the patents that can be listed are: compounds, salts of compounds, compositions, formulations and indications. It is still slightly different from the contents of the orange peel book, and the patents that can be included include "salts of compounds".

(IV) ANDA system

After the passage of the Hatch-Waxman bill, when applying for the listing of generic drugs, the applicant only needs to conduct bioequivalence tests when submitting ANDA, that is, to prove bioequivalence with the reference reagent, without submitting other data; and before the passage of this bill, there is no difference in the approval procedures between generic drugs and original research drugs, and safety and effectiveness tests are required, which makes the production of generic drugs almost unprofitable. The passage of the Hatch-Waxman bill has greatly reduced the cost of generic drugs and accelerated the time to market for generic drugs. Since the implementation of ANDA, generic drug companies in the United States have developed rapidly. From 2011 to 2015 alone, the sales of generic drugs increased by 50%.

At present, China adopts the approval process of "one batch, one report", which is the same as the approval process of FDA in the United States. In the newly disclosed relevant policies, there is no major adjustment to the provisions on examination and approval.

(V) patent challenge system

According to the Hatch-Waxman Act, generic drug companies must submit one of the following four statements when submitting ANDA in accordance with the provisions of the Orange Book. Paragraph I Statement (PI): The drug has no patent; Paragraph II Statement (PII): The drug has a patent, but the patent has expired; Paragraph III Statement (PIII): FDA is not required to approve the generic drug before the relevant patent expires; Paragraph IV Statement (PIV): patents related to the applied generic drug are invalid or the generic drug is not infringing. Among them, the first generic drug applicant to submit ANDA to FDA and contain PⅣ statement will be granted 180 days of market monopoly if the patent challenge is successful. Applicants with PⅣ declaration shall promptly notify the NDA (New Drug Marketing License Application) holder and patentee within 20 working days after their ANDA is accepted, and provide the legal basis for the non-infringement of generic drug products or the invalidity of the patent of the original drug research enterprise. If the NDA holder and/or the patentee file a patent infringement lawsuit within 45 days, the 30-month containment period starts. During this 30-month period, FDA will continue to review the ANDA applicant's materials and grant provisional approval if the materials are qualified, but will not approve its listing. If the lawsuit decides that the patent is invalid or the product is not infringing during the containment period, the provisional approval is converted to a formal approval on the effective date of the judgment, allowing listing and obtaining a 180-day market exclusivity period.

Among a series of policies recently announced by China, the ''Relevant Policies on Encouraging Pharmaceutical and Medical Device Innovation and Protecting the Rights and Interests of Innovators (Draft for Comment) ''stipulates that if a relevant drug patent is challenged, the applicant needs to declare that it does not constitute infringement of the relevant drug patent. Drugs that successfully challenge the patent will be given a data protection period of 1.5 years. During the data protection period, the review agency will no longer approve the listing application of the same variety of other applicants, except for the data obtained by the applicant himself. However, in the "Implementation Measures for Drug Trial Data Protection (Draft for Comment)" issued by the Food and Drug Administration on April 26, 2018, there is no specific data protection period for drugs that have successfully challenged patents. If this 1.5-year data protection period is implemented, it will greatly encourage generic pharmaceutical companies to challenge patents, increase the pressure on the original research pharmaceutical companies, and then force the original research pharmaceutical companies to spend their efforts on patent layout to increase the difficulty of patent challenges.

Regarding the impact of infringement litigation on drug approval, relevant provisions have also been made in the "Relevant Policies on Encouraging Drug and Medical Device Innovation and Protecting the Rights and Interests of Innovators (Draft for Comment)". After the documents, an approval waiting period of no more than 24 months may be set. During this period, the technical review of the accepted drugs will not be stopped.

Of course, these systems are still in the process of soliciting opinions or trial implementation and have not yet been implemented. There is no doubt that for pharmaceutical companies, whether they are original research companies or generic drug companies, the implementation of China's drug patent link system will bring huge market changes. With the improvement of various systems in China, pharmaceutical companies can refer to the US patent link system, make layout and preparation in advance, and occupy a place in the fully competitive market in the future.