CN114667297A - 一种抗体融合蛋白及其制法和在抗肿瘤中的应用 - Google Patents

一种抗体融合蛋白及其制法和在抗肿瘤中的应用 Download PDF

Info

Publication number
CN114667297A
CN114667297A CN202080058822.9A CN202080058822A CN114667297A CN 114667297 A CN114667297 A CN 114667297A CN 202080058822 A CN202080058822 A CN 202080058822A CN 114667297 A CN114667297 A CN 114667297A
Authority
CN
China
Prior art keywords
fusion protein
antibody fusion
seq
amino acid
acid sequence
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Granted
Application number
CN202080058822.9A
Other languages
English (en)
Other versions
CN114667297B (zh
Inventor
朱祯平
黄浩旻
顾昌玲
祝海霞
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Sunshine Guojian Pharmaceutical Shanghai Co Ltd
Original Assignee
Sunshine Guojian Pharmaceutical Shanghai Co Ltd
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Sunshine Guojian Pharmaceutical Shanghai Co Ltd filed Critical Sunshine Guojian Pharmaceutical Shanghai Co Ltd
Publication of CN114667297A publication Critical patent/CN114667297A/zh
Application granted granted Critical
Publication of CN114667297B publication Critical patent/CN114667297B/zh
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Images

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
    • C07K16/2863—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against receptors for growth factors, growth regulators
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K39/395—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
    • C07K16/30—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants from tumour cells
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/40—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against enzymes
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/46—Hybrid immunoglobulins
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K19/00—Hybrid peptides, i.e. peptides covalently bound to nucleic acids, or non-covalently bound protein-protein complexes
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09—Recombinant DNA-technology
    • C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
    • C12N15/62—DNA sequences coding for fusion proteins
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09—Recombinant DNA-technology
    • C12N15/63—Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09—Recombinant DNA-technology
    • C12N15/63—Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
    • C12N15/79—Vectors or expression systems specially adapted for eukaryotic hosts
    • C12N15/85—Vectors or expression systems specially adapted for eukaryotic hosts for animal cells
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N5/00—Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
    • C12N5/10—Cells modified by introduction of foreign genetic material
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12P—FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE
    • C12P21/00—Preparation of peptides or proteins
    • C12P21/02—Preparation of peptides or proteins having a known sequence of two or more amino acids, e.g. glutathione
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K2039/505—Medicinal preparations containing antigens or antibodies comprising antibodies
    • A61K2039/507—Comprising a combination of two or more separate antibodies
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/30—Immunoglobulins specific features characterized by aspects of specificity or valency
    • C07K2317/31—Immunoglobulins specific features characterized by aspects of specificity or valency multispecific
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
    • C07K2317/73—Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/90—Immunoglobulins specific features characterized by (pharmaco)kinetic aspects or by stability of the immunoglobulin
    • C07K2317/92—Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/90—Immunoglobulins specific features characterized by (pharmaco)kinetic aspects or by stability of the immunoglobulin
    • C07K2317/94—Stability, e.g. half-life, pH, temperature or enzyme-resistance

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Organic Chemistry (AREA)
  • Genetics & Genomics (AREA)
  • Engineering & Computer Science (AREA)
  • General Health & Medical Sciences (AREA)
  • Biochemistry (AREA)
  • Molecular Biology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Zoology (AREA)
  • Wood Science & Technology (AREA)
  • Biotechnology (AREA)
  • Medicinal Chemistry (AREA)
  • Biomedical Technology (AREA)
  • Biophysics (AREA)
  • General Engineering & Computer Science (AREA)
  • Immunology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Microbiology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Physics & Mathematics (AREA)
  • Plant Pathology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Cell Biology (AREA)
  • Mycology (AREA)
  • Epidemiology (AREA)
  • Peptides Or Proteins (AREA)

Abstract

一种抗体融合蛋白及其制法和在抗肿瘤中的应用，其包含抗HER2单克隆抗体IgG和VEGFR1的D2结构域，VEGFR1的D2结构域通过肽接头L连接至IgG重链的C末端。该抗体融合蛋白能同时阻断HER2和VEGFR2信号通路，具有优于单克隆抗体的抑制肿瘤增殖的作用，为抗肿瘤治疗提供了一种治疗效果更佳的候选药物，在肿瘤疾病的治疗上具有广阔的应用前景。

Description

PCT国内申请，说明书已公开。

Claims (16)

  1. PCT国内申请，权利要求书已公开。
CN202080058822.9A 2019-09-26 2020-09-04 一种抗体融合蛋白及其制法和在抗肿瘤中的应用 Active CN114667297B (zh)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
CN201910916586.9A CN112552410A (zh) 2019-09-26 2019-09-26 一种抗体融合蛋白及其制法和在抗肿瘤中的应用
CN2019109165869 2019-09-26
PCT/CN2020/113556 WO2021057451A1 (zh) 2019-09-26 2020-09-04 一种抗体融合蛋白及其制法和在抗肿瘤中的应用

Publications (2)

Publication Number Publication Date
CN114667297A true CN114667297A (zh) 2022-06-24
CN114667297B CN114667297B (zh) 2024-02-06

Family

ID=75029958

Family Applications (2)

Application Number Title Priority Date Filing Date
CN201910916586.9A Pending CN112552410A (zh) 2019-09-26 2019-09-26 一种抗体融合蛋白及其制法和在抗肿瘤中的应用
CN202080058822.9A Active CN114667297B (zh) 2019-09-26 2020-09-04 一种抗体融合蛋白及其制法和在抗肿瘤中的应用

Family Applications Before (1)

Application Number Title Priority Date Filing Date
CN201910916586.9A Pending CN112552410A (zh) 2019-09-26 2019-09-26 一种抗体融合蛋白及其制法和在抗肿瘤中的应用

Country Status (2)

Country Link
CN (2) CN112552410A (zh)
WO (1) WO2021057451A1 (zh)

Families Citing this family (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN115246886A (zh) * 2021-04-27 2022-10-28 丹生医药技术(上海)有限公司 一种抗egfr/vegf双功能融合蛋白及其用途
CN116102659A (zh) * 2021-11-11 2023-05-12 三生国健药业（上海）股份有限公司 一种抗il-17/vegf双功能融合蛋白及其用途
WO2024055995A1 (zh) * 2022-09-14 2024-03-21 寻济生物科技（北京）有限公司 一种抗vegfa融合蛋白及其制备方法和应用

Citations (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2011080401A1 (en) * 2009-12-31 2011-07-07 Licentia Ltd Receptor tyrosine kinase-binding compositions
WO2011123813A2 (en) * 2010-04-02 2011-10-06 Amunix Operating Inc. Binding fusion proteins, binding fusion protein-drug conjugates, xten-drug conjugates and methods of making and using same
CN104193828A (zh) * 2013-09-12 2014-12-10 北京韩美药品有限公司 同时阻断her2和vegfr信号通路的重组融合蛋白
CN107108757A (zh) * 2015-03-11 2017-08-29 新源生物科技股份有限公司 包含vegf及pdgf的配体结合域的融合蛋白
CN107602702A (zh) * 2017-09-22 2018-01-19 生标（上海）医疗器械科技有限公司 一种同时靶向人p185和血管内皮生长因子的抗体及其应用
CN108430489A (zh) * 2015-06-28 2018-08-21 新源生物科技股份有限公司 用于抑制血管新生的融合蛋白
US20180346952A1 (en) * 2010-04-02 2018-12-06 Amunix Operating Inc. Binding fusion proteins, binding fusion protein-drug conjugates, xten-drug conjugates and methods of making and using same
CN111032092A (zh) * 2017-06-30 2020-04-17 韩国科学技术院 Vegf-grab蛋白与药物的缀合物及其用途

Family Cites Families (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20050232931A1 (en) * 2003-06-13 2005-10-20 Oncomax Acquisition Corp. Preparation and application of anti-tumor bifunctional fusion proteins
WO2011075606A2 (en) * 2009-12-18 2011-06-23 Alios Biopharma, Inc. Hyperglycosylated polypeptide variants and methods of use
TWI775096B (zh) * 2012-05-15 2022-08-21 澳大利亞商艾佛蘭屈澳洲私營有限公司 使用腺相關病毒(aav)sflt-1治療老年性黃斑部退化(amd)
ES2718478T3 (es) * 2012-06-08 2019-07-02 Sutro Biopharma Inc Anticuerpos que comprenden restos de aminoácidos no naturales de localización específica, métodos para su preparación y métodos para su uso

Patent Citations (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2011080401A1 (en) * 2009-12-31 2011-07-07 Licentia Ltd Receptor tyrosine kinase-binding compositions
WO2011123813A2 (en) * 2010-04-02 2011-10-06 Amunix Operating Inc. Binding fusion proteins, binding fusion protein-drug conjugates, xten-drug conjugates and methods of making and using same
US20180346952A1 (en) * 2010-04-02 2018-12-06 Amunix Operating Inc. Binding fusion proteins, binding fusion protein-drug conjugates, xten-drug conjugates and methods of making and using same
CN104193828A (zh) * 2013-09-12 2014-12-10 北京韩美药品有限公司 同时阻断her2和vegfr信号通路的重组融合蛋白
CN107108757A (zh) * 2015-03-11 2017-08-29 新源生物科技股份有限公司 包含vegf及pdgf的配体结合域的融合蛋白
CN108430489A (zh) * 2015-06-28 2018-08-21 新源生物科技股份有限公司 用于抑制血管新生的融合蛋白
CN111032092A (zh) * 2017-06-30 2020-04-17 韩国科学技术院 Vegf-grab蛋白与药物的缀合物及其用途
CN107602702A (zh) * 2017-09-22 2018-01-19 生标（上海）医疗器械科技有限公司 一种同时靶向人p185和血管内皮生长因子的抗体及其应用
CN108892727A (zh) * 2017-09-22 2018-11-27 生标（上海）医疗器械科技有限公司 一种同时靶向人p185和血管内皮生长因子的重组抗体及其制备方法和应用

Non-Patent Citations (3)

* Cited by examiner, † Cited by third party
Title
DAVID P.等: "Combined targeting of HER2 and VEGFR2 for effective treatment of HER2-amplified breast cancer brain metastases" *
ROHIT SINGH等: "Combined blockade of HER2 and VEGF exerts greater growth inhibition of HER2-overexpressing gastric cancer xenografts than individual blockade" *
郭艳等: "靶向ＨＥＲ２／ＥＧＦＲ分子双特异性单链抗体的构建及其 体内外抗乳腺癌的研究" *

Also Published As

Publication number Publication date
CN112552410A (zh) 2021-03-26
CN114667297B (zh) 2024-02-06
WO2021057451A1 (zh) 2021-04-01

Similar Documents

Publication Publication Date Title
WO2018036472A1 (zh) 一种抗pd1单克隆抗体、其药物组合物及其用途
WO2020103629A1 (zh) 抗her2/pd1双特异性抗体
CN114667297B (zh) 一种抗体融合蛋白及其制法和在抗肿瘤中的应用
WO2020103630A1 (zh) 抗egfr/pd-1双特异性抗体
EP2921503A1 (en) Humanized anti-human epidemic growth factor receptor antibody and encoding gene and application thereof
CN111615519A (zh) 结合人il-5的单克隆抗体、其制备方法和用途
CN109627340B (zh) Cd3和prlr双特异性抗体及其构建与应用
CN115991784A (zh) 抗cd47-cldn18.2双特异性抗体及其用途
US11912777B2 (en) Antibodies binding TNFR2 and uses thereof
TWI815184B (zh) Tgfbr2-ecd突變體及包含其的融合蛋白與應用
WO2021244553A1 (zh) 一种抗pd-l1和egfr的四价双特异性抗体
US20230257465A1 (en) ANTI-PDL1 x EGFR BISPECIFIC ANTIBODY
CN114316045A (zh) 抗pd-l1抗体及其用途
CN117736330B (zh) 肿瘤坏死因子超家族受体9的特异性抗原结合蛋白及其应用
CN113321730B (zh) Cldn18.2抗体及其应用
WO2023179392A1 (zh) B7h3抗体及包含其的双功能抗体
CN111018988B (zh) 一种抗cd19的抗体、制备方法及其应用
EP4059963A1 (en) Molecule capable of binding to human 4-1bb, and application of molecule
WO2023222027A1 (zh) 一种抗trop-2/cd3双特异性抗体
CN116496403A (zh) 抗pdl1/igf1r双特异性抗体、其制备方法及用途
CN115244079A (zh) 结合人ngf的抗体、其制备方法和用途
CN116606377A (zh) 靶向cd24和cd47的双特异性抗体融合蛋白及其制备方法与应用
CN117964771A (zh) 一种特异性结合mmp7的抗体及其应用
CN114106173A (zh) 抗ox40抗体、其药物组合物及应用
IL305101A (en) ANTI-PD-L1 antibody and its use

Legal Events

Date Code Title Description
PB01 Publication
PB01 Publication
SE01 Entry into force of request for substantive examination
SE01 Entry into force of request for substantive examination
GR01 Patent grant
GR01 Patent grant