Enlightenment of new changes of orange peel book of American medicine on Chinese patent link

Source: drug magic cube data 2018-01-22 on November 21, 2017, the FDA of the United States added a new publicity content in the orange peel book, that is, the date when the original research drug enterprise applied for patent information to the FDA (hereinafter referred to as the "application date") In this way, FDA further increased the transparency of orange peel book, exposed more information to the sun for the supervision of the public, especially the generic pharmaceutical factory So, why does FDA publish the filing date? What is the significance of the filing date? This should start with the function of the orange book itself and the regulations of the United States on the filing date 1、 Why set up the system of orange book publicity? There are two main lines of the patent link system in the United States One is that generic companies launch a patent challenge to the prior original research drug when they submit a simplified new drug application (anda) The first successful generic company will receive a 180 day market exclusive period reward The other is that the original research company will file an infringement lawsuit to the generic company Regardless of the outcome of the lawsuit, the approval of the generic drug listing will be delayed for 30 months , the original research drug factory can continue to enjoy market monopoly in this period of time known as the "approval waiting period" Both "patent challenge" and "infringement litigation" are based on the patent information disclosed in orange peel book Only by successfully challenging all the patents listed in the orange peel book can generic pharmaceutical companies have the chance to compete for the first generic award Only when the original research pharmaceutical company filed an infringement lawsuit based on the patents listed in the orange peel book, could it put on the shackles of approval waiting period for generic drugs It can be seen that orange book plays the role of "link point" in the whole patent link system, and its importance is self-evident The patent information of orange peel book is usually declared to FDA by the original research drug factory However, the FDA does not take the responsibility of reviewing information, but is entrusted to the generic pharmaceutical factory for supervision The supervision methods include requesting the FDA to correct the wrong information, etc In fact, in order to avoid being hit by mistakes under the patent link system, generic pharmaceutical companies are often motivated to supervise, so as to protect their own rights and interests while maintaining the correctness of information Since we need to be supervised, we need to make it public In particular, all information sufficient to affect the patent link process should be disclosed in the orange book The reason why the FDA added the filing date as a public content is precisely because the filing date can really have such an impact 2、 How does the filing date affect the patent link process? As the Western proverb goes, late justice is unjust When applying for patent information, the original research drug factory should not only ensure that the information is true and accurate and related to the drugs on the market, but also report to the FDA in a timely manner If the time of filing is not specified, the original research drug factory may deliberately delay the filing of patent information, for example, until the eve of submitting the Anda application to the generic drug factory, so as to confuse competitors and disrupt their plans In this way, the patent link system has become the tool of malicious competition of the original research drug factory and lost its original significance Therefore, the U.S has made the following provisions for the filing date: for the patent authorized at the time of filing the new drug application (NDA), patent information shall be submitted together with the NDA application in the form of form 3542a (the patent is the active ingredient, preparation / composition and use method patent, see 21 C.F.R § 314.53 (c) (2) (I)); within 30 days after the approval of NDA or supplementary NDA, patent information can also be declared to FDA in the form of form 3542, and the patent information declared beyond this time limit will not be included in the orange peel book by FDA (see 21 C.F.R § 314.53 (c) (2) (II)) Patents that are not included in orange peel books, of course, cannot be the basis of patent challenges and infringement litigation For patents authorized after NDA approval (hereinafter referred to as "new patents"), the NDA holder must declare patent information to FDA within 30 days after patent authorization (see 21 C.F.R § 314.53 (d) (3)), otherwise, although FDA will still enter the information of new patents into the orange book, applicants of generic anda (and improved new drug NDA) may not submit patent statements for new patents (see 21 C.F.R § 314.94 (a) (12) (VI) and 21 C.F.R § 314.50 (I) (4)) In other words, whether or not the patent linking process is started at this time depends on whether or not the generic pharmaceutical factory that submitted anda first submits the statement in paragraph IV for the new patent If the generic plant does not do so, it will not be able to start the patent link procedure based on the new patent, and the original research and development plant will not be able to file an infringement lawsuit and postpone the listing of generic drugs For ease of understanding, the above provisions are shown as follows through flow chart: To sum up, the NDA applicant or holder in the United States must submit patent information within 30 days of the later of the NDA approval date and patent authorization date, otherwise it will bear adverse consequences to varying degrees 3、 How to deal with the declaration date in the practice of the United States? A typical case is related to focalin XR, a drug for the treatment of ADHD The active ingredient of the drug is dextromethyl hydrochloride The original research factory and NDA applicant are celgene and Novartis, respectively The drug has different dosage specifications, such as 10 mg, 20 mg, 30 mg, 40 mg, etc Let's take a look at the approved listing of generic drugs, as shown in the table below, which lists the first three generic drugs listed for each dose specification From the above table, it can be seen that for 10mg, 20mg and 40mg dose specifications, the approval time of second and third generic drugs is more than 600 days later than that of first generic drugs, indicating that the first generic drugs are likely to win the market exclusive period due to the success of the challenge patent Only with the dosage of 30 mg, the first copy application was approved more than 80 days earlier than the second copy and third copy applications, indicating that mylan, as the first copy applicant, does not seem to enjoy the exclusive market period of 180 days Why is that? One reason may be that Novartis, the NDA applicant, failed to file the patent information on time, which resulted in the failure to start the patent link process NDA of 30 mg dosage specifications was approved on October 23, 2009, which means Novartis must file patent information within 30 days, i.e before November 22, 2009 However, although the author did not find the specific filing date, it is almost certain that Novartis did not file within this period Probably because of this, Novartis couldn't use the patent link to delay the listing of generic drugs, and watched the Anda of the three generic drug companies get approval in just over 80 days At that time, the Orange Book of the United States was not publicly declared, so it would take a lot of work for the imitative pharmaceutical factory to obtain this information Today, the FDA requires that the filing date be made public, which makes it easier for generic pharmaceutical companies to grasp the handle of the filing date 4、 What inspiration does the new changes of American orange book give us? The publicity of the declaration day seems to be a minor issue, but it can reflect some principles of the publication of the orange peel book The principle of "real-time" is embodied in requiring patent information to be filed in time without delay; the principle of "incentive" is embodied in stimulating generic pharmaceutical companies to actively supervise filing date by means of exemption and postponement of listing Therefore, in the process of exploring the establishment of patent link system in China, the author believes that the practice of the United States on the filing date is worth learning On the one hand, China should also specify the time limit for patent information application to prevent malicious delay; on the other hand, the application date can also be publicized in the orange peel book, so as to facilitate the supervision of the imitated pharmaceutical factory, and at the same time, it can also force the original pharmaceutical factory to consciously fulfill the obligation of timely declaration In this way, the credibility of orange book is guaranteed, and it is also conducive to the smooth implementation of the patent link system.