雙特異性抗體和癌症專利態勢分析

雙特異性抗體是癌症治療的突破性IP。

BsAbs 為新藥的設計和開發提供了令人興奮的機會，並具有持久的治療效果的潛力。

雙特異性抗體 (bsAbs) 在癌症領域的發展呈現快速成長，並取得了顯著的臨床進展。最近的數據顯示，臨床試驗中超過 85% 的 bsAb 用於癌症治療，目前約有 600 種 bsAb 正在臨床試驗中。截至目前，已有 11 種 bsAb 獲得批准用於治療癌症，其中 10 種獲得了美國 FDA 的批准。這種擴展反映了人們對這種創新治療劑日益增長的興趣。雙特異性抗體是指旨在同時結合兩種不同抗原的蛋白質。雙特異性抗體既可以連接兩種類型的細胞（反式結合），也可以結合單一細胞膜上的兩個分子（順式結合）。橋接細胞 BsAbs 佔最大群體，其中 T 細胞重定向最為常見。 T 細胞接合劑可與細胞毒性 T 細胞和腫瘤細胞結合，促進對腫瘤的免疫反應。近年來已有多種 bsAb 獲得批准。 2024年12月，美國FDA加速批准HER2 x HER3 bsAb用於治療全身治療之前或之後攜帶神經調節蛋白1（NRG1）基因融合且病情進展的不可切除或轉移性晚期非小細胞肺癌（NSCLC）成年患者，或全身治療之前或之後攜帶NRG1基因融合且病情進展的不可切除或晚期胰腺腺癌成年患者。然而，課題依然存在，包括生產的複雜性、毒性（細胞激素釋放症候群、免疫效應細胞相關神經毒性症候群、輸液相關反應）以及需要優化分子的穩定性和半衰期。為了克服這些障礙，我們正在探索創新方法，例如先進的抗體工程技術和新分子形式的開發。

從 1986 年到 21 世紀初，專利出版的數量雖然不多，但呈現成長趨勢。自 2010 年以來，該領域發展顯著，到 2023 年將擁有超過 400 個專利家族。 20 世紀 80 年代、90 年代和 21 世紀初，學術研究取得了許多進展，包括開發第一個不對稱格式、首次展示 T 細胞重定向、第一個基於重組片段的格式、第一個通過物種限制性 LC 配對解決輕鏈 (LC) 關聯問題、第一個通過使用互補重鏈 (HC) 和共同 LC 配對解決鏈對稱問題、第一個對稱物理所有這些創新都促進了 bsAbs 的建立。隨後在2009年，bsAb catumaxomab（T淋巴細胞抗原CD3 x上皮細胞黏附分子（EpCAM））獲得歐盟（EU）批准用於治療惡性腹水。五年後，blinatumomab（CD3xB-淋巴細胞抗原-CD19）獲得FDA批准。該藥物於2015年在歐盟獲得批准。

市場區隔分析

主要企業的IP簡介

本報告研究了雙特異性抗體和癌症專利格局，並提供了智慧財產權趨勢，例如已發布專利的時間序列、專利申請國家和專利的法律狀態。

目錄

簡介

摘要整理

專利形勢概要

• 專利發佈時間表
• 專利申請數量最多的公司排名
• 各大公司的現行法律地位
• 專利主體的法律地位
• 繪製目前主要智慧財產權持有者的地圖
• 主要專利持有者的時間序列

新加入企業

• Start-Ups企業
• 老字號企業

聯盟

主要的申請者的IP地位

• 專利申請者的IP龍頭
• 專利申請者的IP領先技術的區域的可能性
• 主要專利
• 專利組合的強度指數

主要的EP專利異議提出申述

專利的市場區隔

• 定義
• 主要的發明專利權者:各技術
• CD3
• 免疫查核點
• 腫瘤抗原

主要企業的IP簡介

概要，主要專利，臨床試驗

• Amgen
• Genentech
• Roche
• GenMab
• Janssen
• Regeneron
• Xencor

調查手法

KnowMade的簡報

諮詢方式

Bispecific Antibodies Mark a Breakthrough in Cancer Therapy Intellectual Property.

Report's Key Features:

• IP trends, including time evolution of published patents, countries of patent filings and patents' legal status
• Ranking of main patent assignees
• Key players' IP position and relative strength of their patent portfolios
• Segmentation: Tumor Antigens (ERBB family, BCMA, BRCA, mesothelin, PSMA, CEA, claudin, EPCAM, mucin, NKG2D, VEGF, CEACAM, MAGE, ROR1, c-Met and nectin), Immune Checkpoints (PD1 / PDL1, CTLA-4, LAG-3, TIM-3, OX40, ICOS, B7-H3, TIGIT and BTLA) and T cells (CD3).
• Analysis of collaborations and EP patent oppositions.
• Excel database containing all patents analyzed in the report, including segmentations + hyperlink to updated online database (legal status, documents etc.)

BsAbs offer exciting opportunities for the design and development of new drugs, and are expected to have lasting therapeutic impact

The development of bispecific antibodies (bsAbs) in oncology is experiencing rapid growth, accompanied by significant clinical advancements. According to recent data, more than 85% of bsAbs in clinical trials are cancer treatments, with approximately 600 bsAbs currently in clinical trials. To date, 11 bsAbs have received regulatory approval for use in cancer, ten of them by the US FDA. This expansion reflects the growing interest in these innovative therapeutic agents. Bispecific antibodies are engineered proteins designed to bind simultaneously to two distinct antigens. They can bridge two cell types (in-trans binding) or engage two molecules on the membrane of one cell (in-cis binding). BsAbs that bridge cells represent the largest group, with T cell redirection as the most common denominator. T-cell engagers bind both cytotoxic T cells and tumor cells, promoting a direct immune response against the tumor. Several bsAbs have recently received regulatory approvals. In December 2024, the U.S. FDA granted accelerated approval of a HER2 x HER3 bsAb for adults with advanced, unresectable, or metastatic non-small cell lung cancer (NSCLC) harboring a neuregulin 1 (NRG1) gene fusion with disease progression on or after prior systemic therapy, or advanced, unresectable, or metastatic pancreatic adenocarcinoma harboring an NRG1 gene fusion with disease progression on or after prior systemic therapy. However, challenges remain, such as the complexity of production, toxicities (cytokine release syndrome, immune effector cell-associated neurotoxicity syndrome, infusion-related reactions), and the need to optimize the stability and half-life of the molecules. Innovative approaches, such as advanced antibody engineering technologies and the development of new molecular formats, are being explored to overcome these obstacles. Understanding the intellectual property position and strategy of these various players is crucial in this evolving context. Detecting business risks and opportunities, anticipating emerging technologies, and enabling strategic decisions to strengthen market position can be achieved through this knowledge.

Between 1986 and the early 2000s, the number of patent publications is low but increasing. From 2010, the field is experiencing a significant acceleration, culminating in 2023 with more than 400 patent families. In the 1980s and 1990s and early 2000s, many advances were made in academic research such as the generation of the 1st asymmetric format, the 1st demonstration of T cell redirection, the 1st recombinant fragment-based formats, the 1st solution to light chain (LC) association issue through species-restricted LC pairing, the 1st solution to chain-association issue through use of complementary heavy chain (HC) (knobs into holes) and common LC, the 1st symmetric format, the discovery that natural human IgG4 is bispecific, the dual variable domain-Ig symmetric format pioneered, etc. All these innovations have contributed to the establishment of bsAbs. Then, in 2009, the bsAb catumaxomab (a T lymphocyte antigen CD3 x epithelial cell adhesion molecule (EpCAM)) received the European Union approval for the treatment of malignant ascites. Five years later, the blinatumomab (CD3xB lymphocyte antigen CD19) was FDA approved. It has been approved in the EU in 2015.

Analysis by segment

Bispecific Ab & Cancer have been investigated and the selected patent families labeled according to technologies to which they relate. This IP landscape features the following 3 types of segmentation: Tumor Antigens (ERBB family, BCMA, BRCA, mesothelin, PSMA, CEA, claudin, EPCAM, mucin, NKG2D, VEGF, CEACAM, MAGE, ROR1, c-Met and nectin), Immune Checkpoints (PD1 / PDL1, CTLA-4, LAG-3, TIM-3, OX40, ICOS, B7-H3, TIGIT and BTLA) and T cells (CD3).

EP oppositions

Currently, there is a significant number of EP oppositions which reflects the strategic issues of bispecific antibody & cancer for companies. For each opposed patent, the application date, assignee, opponent, opposition year, and results are detailed.

Identifying the companies that have recently emerged in the IP landscape

Among the players owning patent families related to Bispecific Ab & cancer, 52 newcomers were identified. These companies are either start-up firms (6) or established companies (46) developing their first technology in the field. Most IP newcomers are based in the U.S. and in Asia. 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.

IP profile of key players

This IP study includes a selection and description of main players. The patent portfolio analysis of main players includes a description of the assignee, patent portfolio description, time evolution of patent publication, main geographical coverage and live patents by technical segment. This IP profile overview is followed by the description of the technological content of their key patents and by a table with its clinical trials.

Moreover, the report includes an Excel spreadsheet with the 2895 patent families 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. The report also includes a Patent Online Database which legal status are updated for each patent document.

Companies mentioned in this report (non-exhaustive list):

ROCHE, AMGEN, JANSSEN, GENMAB, XENCOR, REGENERON PHARMACEUTICALS, GENENTECH - ROCHE, MACROGENICS, DRAGONFLY THERAPEUTICS, SANOFI, CHUGAI PHARMACEUTICAL, MERCK MSD, MERUS, BMS, SAMSUNG, JIANGSU HENGRUI PHARMACEUTICALS, ABBVIE, HEFEI TG IMMUNOPHARMA, MARENGO THERAPEUTICS, etc.

TABLE OF CONTENTS

INTRODUCTION

• BsAb for cancer therapy
• Scope of the report
• Reading guide
• Main patent assignees

EXECUTIVE SUMMARY

PATENT LANDSCAPE OVERVIEW

• Time evolution of patent publications
• 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
• Time evolution of main patent assignees

NEWCOMERS

• Startup companies
• Established companies

COLLABORATIONS

IP POSITION OF MAIN APPLICANTS

• IP leadership of patent applicants
• IP prior art blocking potential of patent applicants
• Key patents
• Strength index of patent portfolios

MAIN EP PATENT OPPOSITIONS

PATENT SEGMENTATION

• Definition
• Main assignees by technology
• CD3
• Immune Checkpoint
• Tumor Antigen

IP PROFILE OF KEY PLAYERS

Overview, key patents & clinical trials of:

• Amgen
• Genentech
• Roche
• GenMab
• Janssen
• Regeneron
• Xencor

METHODOLOGY

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

KNOWMADE PRESENTATION

CONTACT