CN110520445A - 抗pd-l1/抗pd-1天然抗体结构样异源二聚体形式双特异抗体及其制备 - Google Patents

抗pd-l1/抗pd-1天然抗体结构样异源二聚体形式双特异抗体及其制备 Download PDF

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CN110520445A
CN110520445A CN201880021099.XA CN201880021099A CN110520445A CN 110520445 A CN110520445 A CN 110520445A CN 201880021099 A CN201880021099 A CN 201880021099A CN 110520445 A CN110520445 A CN 110520445A
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chain
cells
substitution
bispecific antibody
antigen
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CN110520445B (zh
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刘家望
宋楠萌
杨亚平
金孟燮
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Beijing Hanmi Pharmaceutical Co Ltd
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Abstract

本发明涉及抗PD‑L1/抗PD‑1天然抗体结构样异源二聚体形式双特异抗体及其制备。具体而言，本发明提供了一种具有天然IgG特点、并且没有重轻链错配的高度稳定的异源二聚体形式的抗PD‑L1/抗PD‑1双特异抗体及其制备方法。该双特异抗体能同时结合两种靶分子并且在治疗复杂疾病方面会更有效。

Description

PCT国内申请，说明书已公开。

Claims (28)

  1. PCT国内申请，权利要求书已公开。
CN201880021099.XA 2017-04-01 2018-03-28 抗pd-l1/抗pd-1天然抗体结构样异源二聚体形式双特异抗体及其制备 Active CN110520445B (zh)

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CN201710214705 2017-04-01
CN2017102147057 2017-04-01
PCT/CN2018/080858 WO2018177324A1 (zh) 2017-04-01 2018-03-28 抗pd‐l1/抗pd‐1天然抗体结构样异源二聚体形式双特异抗体及其制备

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US (1) US11591409B2 (zh)
EP (1) EP3608341A4 (zh)
JP (1) JP2020512836A (zh)
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CN (1) CN110520445B (zh)
AU (1) AU2018243104A1 (zh)
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CA (1) CA3058009A1 (zh)
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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2021227782A1 (zh) * 2020-05-15 2021-11-18 三生国健药业（上海）股份有限公司 一种抗pd-1和pd-l1的四价双特异性抗体

Families Citing this family (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
MX2019003563A (es) * 2016-09-29 2019-08-12 Beijing Hanmi Pharmaceutical Co Ltd Construcciones de inmunoglobulina heterodimericas y metodos de preparacion de las mismas.
TN2019000161A1 (en) 2016-11-18 2020-10-05 Beijing Hanmi Pharmaceutical Co Ltd Anti-pd-1/anti-her2 natural antibody structure-like bispecific antibody of heterodimeric form and preparation thereof
WO2019153200A1 (zh) 2018-02-08 2019-08-15 北京韩美药品有限公司 抗pd-1/抗her2天然抗体结构样异源二聚体形式双特异抗体及其制备
US20220010006A1 (en) * 2018-11-05 2022-01-13 Beijing Hanmi Pharmaceutical Co., Ltd. Anti-tnfalpha/anti il - 17a natural antibody structure-like heterodimer form of bispecific antibody and preparation method therefor
AU2019379576A1 (en) 2018-11-13 2021-06-03 Compass Therapeutics Llc Multispecific binding constructs against checkpoint molecules and uses thereof
US20230331871A1 (en) * 2020-03-27 2023-10-19 Ddbio.Co, Ltd., (Shang Hai) Method for displaying bispecific antibody on surface of mammalian cell and vector
JP2023116826A (ja) * 2020-05-20 2023-08-23 中外製薬株式会社 抗原結合分子
CA3191387A1 (en) 2020-09-30 2022-04-07 Nobell Foods, Inc. Recombinant milk proteins and food compositions comprising the same
US10894812B1 (en) 2020-09-30 2021-01-19 Alpine Roads, Inc. Recombinant milk proteins
US10947552B1 (en) 2020-09-30 2021-03-16 Alpine Roads, Inc. Recombinant fusion proteins for producing milk proteins in plants

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN104080811A (zh) * 2011-11-04 2014-10-01 酵活有限公司 在Fc结构域中具有突变的稳定异源二聚的抗体设计
CN104114579A (zh) * 2011-10-27 2014-10-22 根马布股份公司 异二聚体蛋白的生成

Family Cites Families (13)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5731168A (en) 1995-03-01 1998-03-24 Genentech, Inc. Method for making heteromultimeric polypeptides
US20060074225A1 (en) * 2004-09-14 2006-04-06 Xencor, Inc. Monomeric immunoglobulin Fc domains
SI2235064T1 (sl) 2008-01-07 2016-04-29 Amgen Inc. Metoda za izdelavo heterodimernih molekul - protitelesa fc z uporabo elektrostatičnih usmerjevalnih učinkov
CN103429620B (zh) 2010-11-05 2018-03-06 酵活有限公司 在Fc结构域中具有突变的稳定异源二聚的抗体设计
LT2699264T (lt) * 2011-04-20 2018-07-10 Medimmune, Llc Antikūnai ir kitos molekulės, kurios jungiasi prie b7-h1 ir pd-1
ES2743399T3 (es) 2012-04-20 2020-02-19 Merus Nv Métodos y medios para la producción de moléculas heterodiméricas similares a Ig
TWI641382B (zh) * 2013-01-31 2018-11-21 韓美藥品股份有限公司 於包含因子ｖｉｉ之組成物中使病毒失活之方法
TWI681969B (zh) 2014-01-23 2020-01-11 美商再生元醫藥公司 針對ｐｄ-１的人類抗體
JOP20200094A1 (ar) * 2014-01-24 2017-06-16 Dana Farber Cancer Inst Inc جزيئات جسم مضاد لـ pd-1 واستخداماتها
CN114409783A (zh) 2015-06-24 2022-04-29 Jcr制药股份有限公司 通过血脑屏障的抗人转铁蛋白受体抗体
WO2016207312A1 (en) * 2015-06-24 2016-12-29 F. Hoffmann-La Roche Ag Antibodies against human csf-1r for use in inducing lymphocytosis in lymphomas or leukemias
MX2019003563A (es) * 2016-09-29 2019-08-12 Beijing Hanmi Pharmaceutical Co Ltd Construcciones de inmunoglobulina heterodimericas y metodos de preparacion de las mismas.
AR112603A1 (es) 2017-07-10 2019-11-20 Lilly Co Eli Anticuerpos biespecíficos inhibidores de punto de control

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN104114579A (zh) * 2011-10-27 2014-10-22 根马布股份公司 异二聚体蛋白的生成
CN104080811A (zh) * 2011-11-04 2014-10-01 酵活有限公司 在Fc结构域中具有突变的稳定异源二聚的抗体设计

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
景楚瑜等: "抗PD-1/PD-L1治疗在肿瘤治疗中的研究进展", 《复旦学报（医学版）》 *

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2021227782A1 (zh) * 2020-05-15 2021-11-18 三生国健药业（上海）股份有限公司 一种抗pd-1和pd-l1的四价双特异性抗体
CN113993903A (zh) * 2020-05-15 2022-01-28 三生国健药业（上海）股份有限公司 一种抗pd-1和pd-l1的四价双特异性抗体

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JP2020512836A (ja) 2020-04-30
WO2018177324A1 (zh) 2018-10-04
AU2018243104A1 (en) 2019-10-17
KR20190139909A (ko) 2019-12-18
MX2019011748A (es) 2020-01-23
CN110520445B (zh) 2023-03-14
EP3608341A1 (en) 2020-02-12
ZA201906457B (en) 2020-08-26
EA201992311A1 (ru) 2020-05-15
BR112019020448A2 (pt) 2020-06-09
CA3058009A1 (en) 2018-10-04
KR102629905B1 (ko) 2024-01-30
SG10201913676QA (en) 2020-03-30
US11591409B2 (en) 2023-02-28
US20200299412A1 (en) 2020-09-24
SG11201909156RA (en) 2019-10-30
EP3608341A4 (en) 2021-01-06

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