CN112703206A - 靶向肿瘤的重组双功能融合蛋白及其应用 - Google Patents

靶向肿瘤的重组双功能融合蛋白及其应用 Download PDF

Info

Publication number
CN112703206A
CN112703206A CN202080002411.8A CN202080002411A CN112703206A CN 112703206 A CN112703206 A CN 112703206A CN 202080002411 A CN202080002411 A CN 202080002411A CN 112703206 A CN112703206 A CN 112703206A
Authority
CN
China
Prior art keywords
tumor
antibody
tgf
fusion protein
recombinant
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
CN202080002411.8A
Other languages
English (en)
Other versions
CN112703206B (zh
Inventor
余科
任志强
刘亮
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.)
Bailisikang Biomedical Hangzhou Co ltd
Fudan University
Original Assignee
Fudan University
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 Fudan University filed Critical Fudan University
Publication of CN112703206A publication Critical patent/CN112703206A/zh
Application granted granted Critical
Publication of CN112703206B publication Critical patent/CN112703206B/zh
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Images

Classifications

    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K16/00Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/18Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/28Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
    • C07K16/2896Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against molecules with a "CD"-designation, not provided for elsewhere
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00Medicinal preparations containing peptides
    • A61K38/16Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/17Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00Medicinal preparations containing peptides
    • A61K38/16Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/17Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • A61K38/18Growth factors; Growth regulators
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00Medicinal preparations containing antigens or antibodies
    • A61K39/395Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/51Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
    • A61K47/68Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00Antineoplastic agents
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K14/00Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/705Receptors; Cell surface antigens; Cell surface determinants
    • C07K14/71Receptors; Cell surface antigens; Cell surface determinants for growth factors; for growth regulators
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K16/00Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/18Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/28Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K16/00Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/18Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/36Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against blood coagulation factors
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K16/00Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/40Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against enzymes
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K19/00Hybrid peptides, i.e. peptides covalently bound to nucleic acids, or non-covalently bound protein-protein complexes
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N15/00Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09Recombinant DNA-technology
    • C12N15/11DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
    • C12N15/62DNA sequences coding for fusion proteins
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00Medicinal preparations containing peptides
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K2317/00Immunoglobulins specific features
    • C07K2317/20Immunoglobulins specific features characterized by taxonomic origin
    • C07K2317/24Immunoglobulins specific features characterized by taxonomic origin containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K2317/00Immunoglobulins specific features
    • C07K2317/50Immunoglobulins specific features characterized by immunoglobulin fragments
    • C07K2317/51Complete heavy chain or Fd fragment, i.e. VH + CH1
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K2317/00Immunoglobulins specific features
    • C07K2317/50Immunoglobulins specific features characterized by immunoglobulin fragments
    • C07K2317/56Immunoglobulins specific features characterized by immunoglobulin fragments variable (Fv) region, i.e. VH and/or VL
    • C07K2317/567Framework region [FR]
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K2317/00Immunoglobulins specific features
    • C07K2317/60Immunoglobulins specific features characterized by non-natural combinations of immunoglobulin fragments
    • C07K2317/62Immunoglobulins specific features characterized by non-natural combinations of immunoglobulin fragments comprising only variable region components
    • C07K2317/622Single chain antibody (scFv)
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K2317/00Immunoglobulins specific features
    • C07K2317/90Immunoglobulins specific features characterized by (pharmaco)kinetic aspects or by stability of the immunoglobulin
    • C07K2317/92Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K2319/00Fusion polypeptide

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Organic Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Genetics & Genomics (AREA)
  • Immunology (AREA)
  • Engineering & Computer Science (AREA)
  • Biochemistry (AREA)
  • Molecular Biology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Biophysics (AREA)
  • Animal Behavior & Ethology (AREA)
  • Veterinary Medicine (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Public Health (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Zoology (AREA)
  • Epidemiology (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Biomedical Technology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Biotechnology (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Wood Science & Technology (AREA)
  • Microbiology (AREA)
  • General Engineering & Computer Science (AREA)
  • Toxicology (AREA)
  • Physics & Mathematics (AREA)
  • Cell Biology (AREA)
  • Mycology (AREA)
  • Plant Pathology (AREA)
  • Hematology (AREA)
  • Peptides Or Proteins (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)

Abstract

一种靶向肿瘤的重组双功能融合蛋白及其应用,具体提供了一种重组双功能融合蛋白,其包含特异性结合靶分子CD73或TF蛋白的第一结合结构域和特异性结合靶分子TGFβ蛋白的第二结合结构域;以及所述抗体融合蛋白的制备方法及其应用。CD73/TF‑TGFβR融合蛋白通过高特异性地阻抑肿瘤微环境中的CD73‑TGFβ或TF‑TGFβ表达水平,改善肿瘤免疫细胞环境,增强肿瘤治疗的效果。该融合蛋白具有很高的靶向亲和力及显著的抗肿瘤活性。

Description

PCT国内申请,说明书已公开。

Claims (24)

  1. PCT国内申请,权利要求书已公开。
CN202080002411.8A 2019-09-05 2020-09-04 靶向肿瘤的重组双功能融合蛋白及其应用 Active CN112703206B (zh)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
CN2019108386510 2019-09-05
CN201910838651.0A CN112442132A (zh) 2019-09-05 2019-09-05 靶向肿瘤的重组双功能融合蛋白及其应用
PCT/CN2020/113357 WO2021043229A1 (zh) 2019-09-05 2020-09-04 靶向肿瘤的重组双功能融合蛋白及其应用

Publications (2)

Publication Number Publication Date
CN112703206A true CN112703206A (zh) 2021-04-23
CN112703206B CN112703206B (zh) 2023-12-05

Family

ID=74733242

Family Applications (2)

Application Number Title Priority Date Filing Date
CN201910838651.0A Pending CN112442132A (zh) 2019-09-05 2019-09-05 靶向肿瘤的重组双功能融合蛋白及其应用
CN202080002411.8A Active CN112703206B (zh) 2019-09-05 2020-09-04 靶向肿瘤的重组双功能融合蛋白及其应用

Family Applications Before (1)

Application Number Title Priority Date Filing Date
CN201910838651.0A Pending CN112442132A (zh) 2019-09-05 2019-09-05 靶向肿瘤的重组双功能融合蛋白及其应用

Country Status (2)

Country Link
CN (2) CN112442132A (zh)
WO (1) WO2021043229A1 (zh)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN113450877A (zh) * 2021-06-28 2021-09-28 深圳裕泰抗原科技有限公司 一种基于多重免疫组化技术的生物标志物分析方法及其应用

Families Citing this family (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN113773401B (zh) * 2021-09-15 2023-06-20 宜明昂科生物医药技术(上海)股份有限公司 靶向cd47和pd-l1的重组融合蛋白及其制备和用途
WO2023201267A1 (en) 2022-04-13 2023-10-19 Gilead Sciences, Inc. Combination therapy for treating trop-2 expressing cancers
WO2023249425A1 (ko) * 2022-06-22 2023-12-28 ㈜지아이이노베이션 항-cd73 항체 및 il-2를 포함하는 융합단백질 및 이의 용도
CN117482227A (zh) * 2023-11-29 2024-02-02 南京鼓楼医院 Il-33蛋白和csf1r抗体联用及在制备治疗胃癌腹腔转移药物中的应用

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN104788567A (zh) * 2015-01-21 2015-07-22 武汉友芝友生物制药有限公司 一种靶向鼠T淋巴细胞CD3和人肿瘤抗原EpCAM的双特异性抗体制备方法及应用
CN106103488A (zh) * 2014-02-10 2016-11-09 默克专利有限公司 靶向TGFβ抑制
CN106467574A (zh) * 2015-08-20 2017-03-01 复旦大学 靶向于组织因子的抗体、其制备方法和用途
CN107001474A (zh) * 2014-11-21 2017-08-01 百时美施贵宝公司 抗cd73抗体及其用途
CN110869393A (zh) * 2018-03-07 2020-03-06 复旦大学 靶向cd73的抗体及抗体-药物偶联物、其制备方法和用途

Family Cites Families (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2019527706A (ja) * 2016-08-12 2019-10-03 メルク パテント ゲーエムベーハー 癌の併用療法
CN106938051B (zh) * 2016-08-22 2019-10-11 复旦大学 靶向于组织因子的抗体-药物偶联物
SG11201912473PA (en) * 2017-06-22 2020-01-30 Novartis Ag Antibody molecules to cd73 and uses thereof

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN106103488A (zh) * 2014-02-10 2016-11-09 默克专利有限公司 靶向TGFβ抑制
CN107001474A (zh) * 2014-11-21 2017-08-01 百时美施贵宝公司 抗cd73抗体及其用途
CN104788567A (zh) * 2015-01-21 2015-07-22 武汉友芝友生物制药有限公司 一种靶向鼠T淋巴细胞CD3和人肿瘤抗原EpCAM的双特异性抗体制备方法及应用
CN106467574A (zh) * 2015-08-20 2017-03-01 复旦大学 靶向于组织因子的抗体、其制备方法和用途
CN110869393A (zh) * 2018-03-07 2020-03-06 复旦大学 靶向cd73的抗体及抗体-药物偶联物、其制备方法和用途

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
BRINKMANN,U.等: "The making of bispecific antibodies", 《MABS》 *

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN113450877A (zh) * 2021-06-28 2021-09-28 深圳裕泰抗原科技有限公司 一种基于多重免疫组化技术的生物标志物分析方法及其应用
CN113450877B (zh) * 2021-06-28 2022-04-08 深圳裕泰抗原科技有限公司 一种基于多重免疫组化技术的生物标志物分析方法及其应用

Also Published As

Publication number Publication date
CN112442132A (zh) 2021-03-05
CN112703206B (zh) 2023-12-05
WO2021043229A1 (zh) 2021-03-11

Similar Documents

Publication Publication Date Title
US20230025572A1 (en) High avidity antigen recognizing constructs
CN109096396B (zh) 一种抗pd-l1人源化纳米抗体及其应用
EP3369745B1 (en) Anti-pd-l1 nanobody and use thereof
CN112703206B (zh) 靶向肿瘤的重组双功能融合蛋白及其应用
UA125717C2 (uk) Конструкція антитіла до flt3 і cd3
KR20120051603A (ko) 항카드헤린 항체
US11351251B2 (en) Anti-PD-L1-anti-TIM-3 bispecific antibodies
CN110835374A (zh) 抗ccr8×ctla-4双特异性抗体及其应用
EP4209503A1 (en) Il-2 mutant and application thereof
CN113906052A (zh) 一种抗ceacam5的单克隆抗体及其制备方法和用途
CN110885376A (zh) 抗cd47/cd20双特异性抗体及其用途
TW202039578A (zh) Cd3結合分子
EP4269442A1 (en) Mesothelin binding molecule and application thereof
TW202309083A (zh) 抗cldn4-抗cd137雙特異性抗體
US20230365686A1 (en) Humanized antibody specific for cd22 and chimeric antigen receptor using the same
CN115768797A (zh) 抗b7-h3抗体及其制备和应用
CN115109154A (zh) 一种靶向cldn18.2的抗体或其抗原结合片段及其应用
CN110291107B (zh) 靶向cd43的独特唾液酸糖基化的癌症相关表位的单克隆抗体
US20220267436A1 (en) Anti-cd47/anti-lag-3 bispecific antibody, preparation method therefor and use thereof
CN115304680A (zh) 基于Pep42构建的双特异性细胞接合器分子的制备及其应用
US20220332848A1 (en) Anti-cd47/anti-ctla-4 bispecific antibody and preparation method therefor and application thereof
JP2022513321A (ja) 固形腫瘍を治療するための遺伝子操作しているγδ-T細胞及び遺伝子操作していないγδ-T細胞に関する組成物及び方法
CN114773485B (zh) 抗人PD-L1抗体和TGFβRII的双功能融合蛋白分子
US20240182577A1 (en) Anti-pd-1 signal peptide antibody and use thereof
US20240209051A1 (en) Il-2 Mutant And Application Thereof

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
TA01 Transfer of patent application right

Effective date of registration: 20210831

Address after: 200433 No. 220, Handan Road, Shanghai, Yangpu District

Applicant after: FUDAN University

Applicant after: Bailisikang biomedical (Hangzhou) Co.,Ltd.

Address before: 200433 No. 220, Handan Road, Shanghai, Yangpu District

Applicant before: FUDAN University

TA01 Transfer of patent application right
GR01 Patent grant
GR01 Patent grant