循環遊離 DNA / RNA：專利情況分析 (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。

本報告中提到的公司（部分）

• ANNOROAD、AVIIR、BGI、BLUESTAR GENOMICS、CARDIFF ONCOLOGY、CAREDX、CARIS LIFE SCIENCES、CLEVELAND HEARTLAB、EISAI、GRAIL、GUARDANT HEALTH、ILLUMINA、Integrated GENETICS（SEQUENOM）、ROCKED、NATERA、ONRECCOM

目錄

簡介

• 循環遊離 DNA/RNA
• 分析範圍
• 本報告概要
• 分析目的

分析方法

本報告提及的主要專利申請人

執行摘要

專利情況：概述

• 專利公開數量的變化
• 專利出版物數量的變化：按申請國家
• 申請數量最多的專利申請人排名
• 主要公司的當前法律地位
• 專利法律地位
• 當前主要知識產權持有人的映射
• 主要知識產權公司的專利活動
• 主要專利申請人的變化

新進入者

• 初創公司
• 現有公司

商務合作

主要專利申請人的IP位置

• 專利申請人的知識產權領導力
• 專利申請人 IP 封鎖的可能性
• 專利組合強度指數

主要專利

• 專利引用分析
• 主要專利家族

主要程序

• EP專利的主要異議
• 在美國的主要訴訟程序

專利分類

• 定義
• 主要受讓方：按技術
• 按應用：癌症
• 按申請：產前檢測
• 按用途：傳染病
• 按用途：移植
• 按應用：神經系統
• 按應用：心血管系統
• 技術檢測分析
• 技術提取的準備

主要公司的 IP 概況（10 家公司）

結論

關於 KnowMade

Report's Key Features:

• PDF with > 130 slides

• Excel file > 2440 patent families + hyperlink to updated online database (legal status, documents etc.)

• IP trends, including time-evolution of published patents, and countries of patent filings

• Patents' legal status

• Ranking of main patent assignees

• Key players' IP position and relative strength of their patent portfolios

• Summary of the IP related to the applications: infectious diseases, cancer, cardiovascular, nervous system or prenatal.

• Summary of the IP related to the technologies: extraction or detection and isolation.

• Analysis of patent litigations and review of key patents.

Circulating nucleic acids tests, an essential step in prognosis and personalized treatment

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.

Analysis by segment

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:

• Applications: This segmentation includes oncology, prenatal diagnostics, infectious diseases, transplantation, nervous system and cardiovascular system. cfDNA was mainly explored as a diagnostic or prognostic marker and for monitoring treatment efficacy or residual disease.

• Technologies: This segmentation includes Extraction & Preparation of circulating DNA/RNA and the Detection & Analysis of these cfDNA/RNA.

Oppositions and litigations

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.

Identifying the companies that have recently emerged in the IP landscape

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.

Key patent analysis

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.

Useful Excel patent database

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.

Companies mentioned in this report (non-exhaustive list)

ANNOROAD, AVIIR, BGI, BLUESTAR GENOMICS, CARDIFF ONCOLOGY, CAREDX, CARIS LIFE SCIENCES, CLEVELAND HEARTLAB, EISAI, GRAIL, GUARDANT HEALTH, ILLUMINA, INTEGRATED GENETICS (SEQUENOM), NATERA, ONCOMEDX, PERSONAL GENOME DIAGNOSTICS, PREANALYTIX, QIAGEN, RAVGEN, ROCHE, STRECK.

TABLE OF CONTENTS

INTRODUCTION

• Circulating DNA/RNA
• Scope of the report
• Key features of the report
• Objectives of the report

METHODOLOGY

• Patent search, selection and analysis
• Search strategy
• Terminologies for patent analysis
• Strength and blocking potential

MAIN ASSIGNEES MENTIONED

EXECUTIVE SUMMARY

PATENT LANDSCAPE OVERVIEW

• Time evolution of patent publications
• Time evolution by country of filing
• Ranking of most prolific patent applicants
• Current legal status of the main players
• Patent legal status of the corpus
• Mapping of main current IP holders
• Patenting activity of IP leading companies
• Time evolution of main patent assignees

NEWCOMERS

• Start up companies
• Established companies

COLLABORATIONS

IP POSITION OF MAIN APPLICANTS

• IP leadership of patent applicants
• IP blocking potential of patent applicants
• Strength index of patent portfolios

KEY PATENTS

• Patent citation analysis
• Key patent families

MAIN OPPOSITIONS LITIGATIONS

• Main oppositions on EP patents
• Main litigations in the USA

PATENT SEGMENTATION

• Definition
• Main assignees by technology
• Application cancer
• Application prenatal
• Application infectious diseases
• Application transplantation
• Application nervous system
• Application cardiovascular system
• Technology detection analysis
• Technology extraction preparation

IP PROFILE OF KEY PLAYERS 10 companies)

CONCLUSION

KNOWMADE PRESENTATION