• 文献检索
  • 文档翻译
  • 深度研究
  • 学术资讯
  • Suppr Zotero 插件Zotero 插件
  • 邀请有礼
  • 套餐&价格
  • 历史记录
应用&插件
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
定价
高级版会员购买积分包购买API积分包
服务
文献检索文档翻译深度研究API 文档MCP 服务
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利：CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2026

文献检索

告别复杂PubMed语法，用中文像聊天一样搜索，搜遍4000万医学文献。AI智能推荐，让科研检索更轻松。

立即免费搜索

文件翻译

保留排版，准确专业，支持PDF/Word/PPT等文件格式，支持 12+语言互译。

免费翻译文档

深度研究

AI帮你快速写综述，25分钟生成高质量综述，智能提取关键信息，辅助科研写作。

立即免费体验

深入洞察 IgG 重链工程专利格局，助力 IgG4 抗体研发。

Insights into the IgG heavy chain engineering patent landscape as applied to IgG4 antibody development.

机构信息

EA7501, Team "Fc Receptors, Antibodies and Microenvironnement", Université de Tours , France.

CHRU de Tours , France.

出版信息

MAbs. 2019 Nov-Dec;11(8):1341-1350. doi: 10.1080/19420862.2019.1664365. Epub 2019 Sep 26.

DOI:10.1080/19420862.2019.1664365
PMID:31556789
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6816381/
Abstract

Despite being the least abundant immunoglobulin G in human plasma, IgG4 are used therapeutically when weak effector functions are needed. The increase in engineered IgG4-based antibodies on the market led us to study the patent landscape of IgG4 Fc engineering, ., patents claiming modifications in the heavy chain. Thirty-seven relevant patent families were identified, comprising hundreds of IgG4 Fc variants focusing on removal of residual effector functions (since IgG4s bind to FcγRI and weakly to other FcγRs), half-life enhancement and IgG4 stability. Given the number of expired or soon to expire major patents in those 3 areas, companies developing blocking antibodies now have, or will in the near future, access to free tools to design silenced, half-life extended and stable IgG4 antibodies.

摘要

尽管 IgG4 在人血浆中含量最少，但当需要较弱的效应功能时，它被用作治疗药物。市场上基于工程化 IgG4 的抗体增加，促使我们研究 IgG4 Fc 工程的专利格局。。。。。。专利主张对重链进行修饰。确定了 37 个相关的专利家族，包括数百种 IgG4 Fc 变体，这些变体主要集中在去除残留的效应功能上（因为 IgG4 与 FcγRI 结合，与其他 FcγRs 结合较弱）、半衰期延长和 IgG4 稳定性上。鉴于这 3 个领域中大量已过期或即将过期的主要专利，现在或不久的将来，开发阻断抗体的公司将可以使用免费工具来设计沉默、半衰期延长和稳定的 IgG4 抗体。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/537d/6816381/e755a1abaee0/kmab-11-08-1664365-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/537d/6816381/b0793aa325b6/kmab-11-08-1664365-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/537d/6816381/7ad45b92b7ab/kmab-11-08-1664365-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/537d/6816381/d7833254714d/kmab-11-08-1664365-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/537d/6816381/e755a1abaee0/kmab-11-08-1664365-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/537d/6816381/b0793aa325b6/kmab-11-08-1664365-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/537d/6816381/7ad45b92b7ab/kmab-11-08-1664365-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/537d/6816381/d7833254714d/kmab-11-08-1664365-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/537d/6816381/e755a1abaee0/kmab-11-08-1664365-g004.jpg

相似文献

1
Insights into the IgG heavy chain engineering patent landscape as applied to IgG4 antibody development.深入洞察 IgG 重链工程专利格局，助力 IgG4 抗体研发。
MAbs. 2019 Nov-Dec;11(8):1341-1350. doi: 10.1080/19420862.2019.1664365. Epub 2019 Sep 26.
2
An engineered Fc variant of an IgG eliminates all immune effector functions via structural perturbations.一种 IgG 的工程化 Fc 变体通过结构干扰消除了所有免疫效应功能。
Methods. 2014 Jan 1;65(1):114-26. doi: 10.1016/j.ymeth.2013.06.035. Epub 2013 Jul 17.
3
Fc-Fc interactions of human IgG4 require dissociation of heavy chains and are formed predominantly by the intra-chain hinge isomer.人 IgG4 的 Fc-Fc 相互作用需要重链解离，并且主要由链内铰链异构体形成。
Mol Immunol. 2013 Jan;53(1-2):35-42. doi: 10.1016/j.molimm.2012.06.012. Epub 2012 Jul 10.
4
Modification of the Fc region of a primatized IgG antibody to human CD4 retains its ability to modulate CD4 receptors but does not deplete CD4(+) T cells in chimpanzees.将人源化IgG抗体针对人CD4的Fc区域进行修饰后，其仍保留调节CD4受体的能力，但不会使黑猩猩体内的CD4(+) T细胞耗竭。
Clin Immunol. 2001 Feb;98(2):164-74. doi: 10.1006/clim.2000.4975.
5
Novel human IgG1 and IgG4 Fc-engineered antibodies with completely abolished immune effector functions.具有完全消除的免疫效应功能的新型人IgG1和IgG4 Fc工程抗体。
Protein Eng Des Sel. 2016 Oct;29(10):457-466. doi: 10.1093/protein/gzw040. Epub 2016 Aug 29.
6
Structural consequences of aglycosylated IgG Fc variants evolved for FcγRI binding.为实现与FcγRI结合而进化的无糖基化IgG Fc变体的结构后果。
Mol Immunol. 2015 Oct;67(2 Pt B):350-6. doi: 10.1016/j.molimm.2015.06.020. Epub 2015 Jul 4.
7
Computationally Designed Bispecific Antibodies using Negative State Repertoires.使用负态库进行计算设计的双特异性抗体。
Structure. 2016 Apr 5;24(4):641-651. doi: 10.1016/j.str.2016.02.013. Epub 2016 Mar 17.
8
The inter-heavy chain disulfide bonds of IgG4 are in equilibrium with intra-chain disulfide bonds.IgG4的重链间二硫键与链内二硫键处于平衡状态。
Mol Immunol. 2001 Jan;38(1):1-8. doi: 10.1016/s0161-5890(01)00050-5.
9
Boosting half-life and effector functions of therapeutic antibodies by Fc-engineering: An interaction-function review.通过 Fc 工程提高治疗性抗体的半衰期和效应功能：相互作用功能综述。
Int J Biol Macromol. 2018 Nov;119:306-311. doi: 10.1016/j.ijbiomac.2018.07.141. Epub 2018 Jul 21.
10
Introduction to heavy chain antibodies and derived Nanobodies.重链抗体及衍生纳米抗体简介。
Methods Mol Biol. 2012;911:15-26. doi: 10.1007/978-1-61779-968-6_2.

引用本文的文献

1
Differentiating IL-23 Inhibitors in Crohn's Disease.区分克罗恩病中的白细胞介素-23抑制剂
Drugs. 2025 May 5. doi: 10.1007/s40265-025-02183-z.
2
Guselkumab binding to CD64 IL-23-producing myeloid cells enhances potency for neutralizing IL-23 signaling.古塞库单抗与产生白细胞介素-23的髓样细胞上的CD64结合，增强了中和白细胞介素-23信号传导的效力。
Front Immunol. 2025 Mar 12;16:1532852. doi: 10.3389/fimmu.2025.1532852. eCollection 2025.
3
FcRn-enhancing mutations lead to increased and prolonged levels of the HIV CCR5-blocking monoclonal antibody leronlimab in the fetuses and newborns of pregnant rhesus macaques.

本文引用的文献

1
Extending human IgG half-life using structure-guided design.利用结构导向设计延长人 IgG 的半衰期。
MAbs. 2018 Oct;10(7):1098-1110. doi: 10.1080/19420862.2018.1490119. Epub 2018 Jul 26.
2
Safety and pharmacokinetics of the Fc-modified HIV-1 human monoclonal antibody VRC01LS: A Phase 1 open-label clinical trial in healthy adults.Fc 修饰的 HIV-1 人源单克隆抗体 VRC01LS 的安全性和药代动力学：一项在健康成年人中进行的 1 期开放标签临床试验。
PLoS Med. 2018 Jan 24;15(1):e1002493. doi: 10.1371/journal.pmed.1002493. eCollection 2018 Jan.
3
Novel human IgG1 and IgG4 Fc-engineered antibodies with completely abolished immune effector functions.
FcRn 增强突变导致怀孕恒河猴胎儿和新生儿体内 HIV CCR5 阻断性单克隆抗体 lerolimumab 的水平升高和持续时间延长。
MAbs. 2024 Jan-Dec;16(1):2406788. doi: 10.1080/19420862.2024.2406788. Epub 2024 Sep 26.
4
Living in LALA land? Forty years of attenuating Fc effector functions.生活在幻想世界？四十年的Fc效应功能衰减
Immunol Rev. 2024 Nov;328(1):422-437. doi: 10.1111/imr.13379. Epub 2024 Aug 19.
5
Fc-Fc interactions and immune inhibitory effects of IgG4: implications for anti-PD-1 immunotherapies.Fc-Fc 相互作用和 IgG4 的免疫抑制作用：对抗 PD-1 免疫疗法的影响。
J Immunother Cancer. 2024 Jun 25;12(6):e009034. doi: 10.1136/jitc-2024-009034.
6
Impact of structural modifications of IgG antibodies on effector functions.IgG 抗体结构修饰对效应功能的影响。
Front Immunol. 2024 Jan 8;14:1304365. doi: 10.3389/fimmu.2023.1304365. eCollection 2023.
7
Therapeutic antibodies for the prevention and treatment of cancer.用于癌症预防和治疗的治疗性抗体。
J Biomed Sci. 2024 Jan 12;31(1):6. doi: 10.1186/s12929-024-00996-w.
8
Harnessing Fc/FcRn Affinity Data from Patents with Different Machine Learning Methods.利用专利中的 Fc/FcRn 亲和力数据采用不同的机器学习方法。
Int J Mol Sci. 2023 Mar 16;24(6):5724. doi: 10.3390/ijms24065724.
9
Optimization of cancer immunotherapy on the basis of programmed death ligand-1 distribution and function.基于程序性死亡配体-1 分布和功能的癌症免疫治疗优化。
Br J Pharmacol. 2024 Jan;181(2):257-272. doi: 10.1111/bph.16054. Epub 2023 Mar 1.
10
Insights into ultra-low affinity lipase-antibody noncovalent complex binding mechanisms.深入了解超低亲和力脂肪酶-抗体非共价复合物结合机制。
MAbs. 2022 Jan-Dec;14(1):2135183. doi: 10.1080/19420862.2022.2135183.
具有完全消除的免疫效应功能的新型人IgG1和IgG4 Fc工程抗体。
Protein Eng Des Sel. 2016 Oct;29(10):457-466. doi: 10.1093/protein/gzw040. Epub 2016 Aug 29.
4
Investigating interactions between phospholipase B-Like 2 and antibodies during Protein A chromatography.研究蛋白A层析过程中磷脂酶B样2与抗体之间的相互作用。
J Chromatogr A. 2016 Mar 18;1438:31-8. doi: 10.1016/j.chroma.2016.01.047. Epub 2016 Jan 22.
5
Structure of full-length human anti-PD1 therapeutic IgG4 antibody pembrolizumab.全长人源抗 PD1 治疗性 IgG4 抗体 pembrolizumab 的结构。
Nat Struct Mol Biol. 2015 Dec;22(12):953-8. doi: 10.1038/nsmb.3129. Epub 2015 Nov 23.
6
pH-dependent binding engineering reveals an FcRn affinity threshold that governs IgG recycling.pH 依赖性结合工程揭示了一个控制 IgG 循环的 FcRn 亲和力阈值。
J Biol Chem. 2015 Feb 13;290(7):4282-90. doi: 10.1074/jbc.M114.603712. Epub 2014 Dec 23.
7
Upregulation of FcγRIIb on monocytes is necessary to promote the superagonist activity of TGN1412.上调单核细胞上的 FcγRIIb 对于促进 TGN1412 的超强激动剂活性是必要的。
Blood. 2015 Jan 1;125(1):102-10. doi: 10.1182/blood-2014-08-593061. Epub 2014 Nov 13.
8
Combined glyco- and protein-Fc engineering simultaneously enhance cytotoxicity and half-life of a therapeutic antibody.糖基化和蛋白质-Fc联合工程同时增强治疗性抗体的细胞毒性和半衰期。
MAbs. 2014 Mar-Apr;6(2):422-36. doi: 10.4161/mabs.27854. Epub 2014 Jan 15.
9
Stability of monoclonal antibodies at high-concentration: head-to-head comparison of the IgG1 and IgG4 subclass.高浓度下单克隆抗体的稳定性：IgG1和IgG4亚类的直接比较
J Pharm Sci. 2014 Jan;103(1):115-27. doi: 10.1002/jps.23788. Epub 2013 Nov 26.
10
A novel investigational Fc-modified humanized monoclonal antibody, motavizumab-YTE, has an extended half-life in healthy adults.一种新型的研究性Fc修饰人源化单克隆抗体莫他维izumab-YTE在健康成年人中具有延长的半衰期。
Antimicrob Agents Chemother. 2013 Dec;57(12):6147-53. doi: 10.1128/AAC.01285-13. Epub 2013 Sep 30.