循環遊離 DNA / RNA：專利情況分析 (2021)
Circulating DNA/RNA Patent Landscape Analysis 2021
在當今的臨床實踐中，最受期待的技術之一是液體活檢，更具體地說是分析循環遊離 DNA，這是一種比固體活檢更安全的替代方法。它是實現個性化醫療的有用且必不可少的要素。它也是一種通過血液、尿液、唾液、腦脊液、胸腔積液等體液中的標誌物（突變等）來診斷和預測疾病的微創方法。循環遊離 DNA/RNA 分析的使用不僅限於腫瘤，該領域的研究和需求尤其增長。它還可以應用於產前診斷、心血管/神經系統疾病或移植。尤其是在腫瘤領域，自這三種產品獲得 FDA 批准以來，過去五年取得了重大進展。與此同時，觀察循環核酸的臨床研究數量持續增長，反映了對該主題的興趣和企業的經濟利益日益增長。
從知識產權 (IP) 的角度來看，循環 DNA/RNA 對大型公司和初創公司都很感興趣，瞭解各種公司的 IP 位置和戰略很重要。事實上，最近提交了大量程序和異議，顯示了知識產權在該領域的戰略作用。這些知識有助於我們發現業務風險和機遇，預測新技術，並製定戰略決策以加強我們在市場中的地位。
本報告分析了循環遊離 DNA/RNA 相關專利的發展趨勢，並提供了當前主要技術的概覽、未來有潛力的技術列表、相關專利在全球的應用、認證和利用狀況。我們將提供為您提供有關各種訴訟動向、主要公司的知識產權 (IP) 組合以及主要專利簡介（總共 2440 多個案例）的信息。
In clinical practice today, one of the most eagerly awaited technologies is the liquid biopsy, and, more specifically, the analysis of circulating DNA, which is a safer alternative to solid biopsy. It is a useful and essential element for achieving personalized medicine. It is also a minimally invasive approach for diagnosing or prognosing a disease through markers (e.g. mutations) in body fluids such as blood, urine, saliva, cerebrospinal fluid or pleural fluid. Circulating DNA/RNA analysis is not restricted to oncology, though the research and needs in this area are immense and eagerly awaited. This technology is also applicable to prenatal diagnostics, cardiovascular and nervous system diseases or transplantation. In addition, the development of technologies to intercept and analyze these circulating nucleic acids steeply increased in the last 10 years, as did the number of companies supplying them (e.g. Grail, Guardant Health, Roche, Illumina). In the cancer area, great progress has been made in the last 5 years, since 3 medical devices have arrived on the market and have been FDA approved: the cobas® EGFR Mutation Test and FoundationOne® Liquid CDx by Roche; and the Guardant360® CDx by Guardant Health. The FDA has also granted three Breakthrough Device Designations for a Natera test. At the same time, the number of clinical studies observing circulating nucleic acids continues to increase, reflecting the growing interest in this topic as well as the economic stakes for companies. Despite this, multiple issues are delaying the widespread incorporation of ctDNA into routine patient care. Future focus should be on establishing optimal techniques for sample collection, cfDNA isolation and analysis. In addition, further studies are required to better understand the biological characteristics of cfDNA.
In terms of intellectual property (IP), circulating DNA/RNA is of interest to big companies and start-ups alike, and it is crucial to understand the IP position and strategy of these different players. Indeed, significant numbers of litigations and oppositions have been filed recently, showing the strategic role of IP in this area. Such knowledge can help detect business risks and opportunities, anticipate emerging technologies, and enable strategic decisions to strengthen one's market position.
The analysis of the time evolution of patent publications shows that Circulating DNA/RNA started to be investigated in the late 1980s with a first patent published in 1987 by a French Academic player, Inserm. Until 2009, there was a latent period, although highly specialized companies in the field started to emerge, such as CLS Therapeutics, Sequenom (acquired by Integrated Genetics) and OncoMEDx. Some academics also started to take an interest in this field of research, such as American universities (Pennsylvania and John Hopkins) and Chinese universities. Since 2010, an acceleration in patenting activity has been observed, with the arrival of big newcomers such as Roche, Natera, Illumina and BGI.
Circulating DNA/RNA has been investigated and the selected patent families labeled according to applications or technologies to which they relate. This IP landscape features the following 2 types of segmentation:
There is a significant number of EP oppositions (>30) and US litigations for patent infringement (>20), which reflects the strategic issues of circulating DNA/RNA for companies. Most of the proceedings are recent, filed in the past 3 years, and are still pending.
Among the players owning patent families related to circulating DNA/RNA, over 100 newcomers were identified. These companies are either established companies or start-up firms developing their first methods and/or products in the cell-free DNA/RNA field. These technologies are mainly related to cancer or prenatal diagnostics. Numerous IP newcomers are based in the US and in Asia while some are based in Europe. It is possible that one of these innovative companies could become one of the next healthcare unicorns that the big corporations will be tempted to acquire.
This IP study includes a selection and description of key patents. The key patent analysis includes the legal status of the family for each of the main territories, the number of received citations, the review of the main claim(s), the description of interesting features about the innovation disclosures and relevant figures illustrating how the innovation works. The description also contains information about litigation over the patent family in the USA.
Moreover, the report also includes an Excel database with the >2,240 patents analyzed in this study. This useful patent database allows for multi-criteria searches and includes patent publication numbers, hyperlinks to the original documents, priority dates, titles, abstracts, patent assignees, each patent's current legal status and segmentation.