PL3882275T3 - Przeciwciało dwufunkcyjne anty-pd-1 i anty-vegfa, kompozycja farmaceutyczna i zastosowanie tych przeciwciał - Google Patents

Przeciwciało dwufunkcyjne anty-pd-1 i anty-vegfa, kompozycja farmaceutyczna i zastosowanie tych przeciwciał

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Publication number
PL3882275T3
PL3882275T3 PL19853809.2T PL19853809T PL3882275T3 PL 3882275 T3 PL3882275 T3 PL 3882275T3 PL 19853809 T PL19853809 T PL 19853809T PL 3882275 T3 PL3882275 T3 PL 3882275T3
Authority
PL
Poland
Prior art keywords
antibodies
pharmaceutical composition
bifunctional
vegfa antibody
vegfa
Prior art date
Application number
PL19853809.2T
Other languages
English (en)
Inventor
Baiyong Li
Yu Xia
Zhongmin Maxwell WANG
Peng Zhang
Original Assignee
Akeso Biopharma, Inc.
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
Family has litigation
First worldwide family litigation filed litigation Critical https://patents.darts-ip.com/?family=64758699&utm_source=google_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=PL3882275(T3) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.
Application filed by Akeso Biopharma, Inc. filed Critical Akeso Biopharma, Inc.
Publication of PL3882275T3 publication Critical patent/PL3882275T3/pl

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    • 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
    • A61K47/6835Medicinal 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 the modifying agent being an antibody or an immunoglobulin bearing at least one antigen-binding site
    • A61K47/6849Medicinal 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 the modifying agent being an antibody or an immunoglobulin bearing at least one antigen-binding site the antibody targeting a receptor, a cell surface antigen or a cell surface determinant
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00Antineoplastic agents
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00Antineoplastic agents
    • A61P35/02Antineoplastic agents specific for leukemia
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K16/00Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies
    • C07K16/18Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/22Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against growth factors ; against growth regulators
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K16/00Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies
    • C07K16/18Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/28Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
    • C07K16/2803Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the immunoglobulin superfamily
    • C07K16/2818Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the immunoglobulin superfamily against CD28 or CD152
    • 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
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/53Immunoassay; Biospecific binding assay; Materials therefor
    • G01N33/531Production of immunochemical test materials
    • G01N33/532Production of labelled immunochemicals
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/68Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/68Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids
    • G01N33/6854Immunoglobulins
    • G01N33/6857Antibody fragments
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/68Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids
    • G01N33/6872Intracellular protein regulatory factors and their receptors, e.g. including ion channels
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/74Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving hormones or other non-cytokine intercellular protein regulatory factors such as growth factors, including receptors to hormones and growth factors
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00Medicinal preparations containing antigens or antibodies
    • A61K2039/505Medicinal preparations containing antigens or antibodies comprising antibodies
    • 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
    • C07K2317/30Immunoglobulins specific features characterized by aspects of specificity or valency
    • C07K2317/31Immunoglobulins specific features characterized by aspects of specificity or valency multispecific
    • 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
    • C07K2317/565Complementarity determining region [CDR]
    • 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
    • C07K2317/60Immunoglobulins specific features characterized by non-natural combinations of immunoglobulin fragments
    • C07K2317/64Immunoglobulins specific features characterized by non-natural combinations of immunoglobulin fragments comprising a combination of variable region and constant region components
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K2317/00Immunoglobulins specific features
    • C07K2317/70Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K2317/00Immunoglobulins specific features
    • C07K2317/70Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
    • C07K2317/73Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K2317/00Immunoglobulins specific features
    • C07K2317/70Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
    • C07K2317/76Antagonist effect on antigen, e.g. neutralization or inhibition of binding
    • 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
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2333/00Assays involving biological materials from specific organisms or of a specific nature
    • G01N2333/435Assays involving biological materials from specific organisms or of a specific nature from animals; from humans
    • G01N2333/475Assays involving growth factors
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2333/00Assays involving biological materials from specific organisms or of a specific nature
    • G01N2333/435Assays involving biological materials from specific organisms or of a specific nature from animals; from humans
    • G01N2333/705Assays involving receptors, cell surface antigens or cell surface determinants
    • G01N2333/70503Immunoglobulin superfamily, e.g. VCAMs, PECAM, LFA-3
    • G01N2333/70521CD28, CD152
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2333/00Assays involving biological materials from specific organisms or of a specific nature
    • G01N2333/435Assays involving biological materials from specific organisms or of a specific nature from animals; from humans
    • G01N2333/705Assays involving receptors, cell surface antigens or cell surface determinants
    • G01N2333/70596Molecules with a "CD"-designation not provided for elsewhere in G01N2333/705

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  • Engineering & Computer Science (AREA)
  • Biochemistry (AREA)
  • Biomedical Technology (AREA)
  • Hematology (AREA)
  • Genetics & Genomics (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Urology & Nephrology (AREA)
  • Biophysics (AREA)
  • Cell Biology (AREA)
  • Animal Behavior & Ethology (AREA)
  • Veterinary Medicine (AREA)
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  • Pharmacology & Pharmacy (AREA)
  • Biotechnology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Microbiology (AREA)
  • Physics & Mathematics (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • General Physics & Mathematics (AREA)
  • Pathology (AREA)
  • Analytical Chemistry (AREA)
  • Food Science & Technology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Oncology (AREA)
  • Zoology (AREA)
  • General Engineering & Computer Science (AREA)
  • Wood Science & Technology (AREA)
  • Epidemiology (AREA)
  • Plant Pathology (AREA)
  • Endocrinology (AREA)
  • Peptides Or Proteins (AREA)
PL19853809.2T 2018-08-30 2019-08-30 Przeciwciało dwufunkcyjne anty-pd-1 i anty-vegfa, kompozycja farmaceutyczna i zastosowanie tych przeciwciał PL3882275T3 (pl)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
CN201811002548.4A CN109053895B (zh) 2018-08-30 2018-08-30 抗pd-1-抗vegfa的双功能抗体、其药物组合物及其用途
PCT/CN2019/103618 WO2020043184A1 (zh) 2018-08-30 2019-08-30 抗pd-1-抗vegfa的双功能抗体、其药物组合物及其用途

Publications (1)

Publication Number Publication Date
PL3882275T3 true PL3882275T3 (pl) 2025-02-10

Family

ID=64758699

Family Applications (1)

Application Number Title Priority Date Filing Date
PL19853809.2T PL3882275T3 (pl) 2018-08-30 2019-08-30 Przeciwciało dwufunkcyjne anty-pd-1 i anty-vegfa, kompozycja farmaceutyczna i zastosowanie tych przeciwciał

Country Status (25)

Country Link
US (3) US20210340239A1 (pl)
EP (2) EP4461746A3 (pl)
JP (3) JP7374995B2 (pl)
KR (1) KR102924276B1 (pl)
CN (1) CN109053895B (pl)
AU (2) AU2019332708B2 (pl)
BR (1) BR112021003559A2 (pl)
CA (1) CA3110749A1 (pl)
DK (1) DK3882275T5 (pl)
EA (1) EA202190535A1 (pl)
ES (1) ES2989584T3 (pl)
FI (1) FI3882275T3 (pl)
HR (1) HRP20241417T1 (pl)
HU (1) HUE068809T2 (pl)
IL (1) IL281116A (pl)
LT (1) LT3882275T (pl)
MX (1) MX2021002312A (pl)
PH (1) PH12021550407A1 (pl)
PL (1) PL3882275T3 (pl)
PT (1) PT3882275T (pl)
RS (1) RS66073B1 (pl)
SG (1) SG11202101985TA (pl)
SI (1) SI3882275T1 (pl)
WO (1) WO2020043184A1 (pl)
ZA (1) ZA202101894B (pl)

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CN109053895B (zh) 2018-08-30 2020-06-09 中山康方生物医药有限公司 抗pd-1-抗vegfa的双功能抗体、其药物组合物及其用途
CN111423512B (zh) * 2019-01-10 2024-01-05 北京比洋生物技术有限公司 阻断血管内皮细胞生长且活化t细胞的多靶向融合蛋白和包含其的药物组合物
CN109942712B (zh) * 2019-04-01 2022-12-20 华博生物医药技术(上海)有限公司 抗pd-l1/vegf双功能抗体及其用途
EP4008351A4 (en) * 2019-08-02 2023-08-09 CTTQ-Akeso (ShangHai) Biomed. Tech. Co., Ltd. Anti-pd-1 antibody and medical use thereof
CN112480253B (zh) 2019-09-12 2022-09-20 普米斯生物技术(珠海)有限公司 一种抗pd-l1纳米抗体及其衍生物和用途
US11912784B2 (en) 2019-10-10 2024-02-27 Kodiak Sciences Inc. Methods of treating an eye disorder
GB201914747D0 (en) * 2019-10-11 2019-11-27 Ultrahuman Eight Ltd PD1 and vegfr2 dual-binding agents
KR20220104033A (ko) * 2019-11-25 2022-07-25 아케소 바이오파마, 인크. 항-pd-1-항-vegfa 이중특이항체, 약학 조성물 및 이의 용도
JP7692422B2 (ja) * 2020-01-21 2025-06-13 ウーシー・バイオロジクス・(シャンハイ)・カンパニー・リミテッド 二重特異性抗pd-l1/vegf抗体及びその使用
PH12022552785A1 (en) * 2020-04-22 2024-03-25 Akeso Biopharma Inc Anti-cd73-anti-pd-1 bispecific antibody and use thereof
AU2021263650A1 (en) * 2020-04-29 2023-01-19 Chia Tai Tianqing Pharmaceutical Group Co., Ltd. Bifunctional protein against PD-1 and TGF-beta
CN114057883B (zh) * 2020-07-31 2024-04-16 江苏恒瑞医药股份有限公司 双特异性抗原结合分子及其医药用途
CN114106190B (zh) * 2020-08-31 2025-04-08 普米斯生物技术(珠海)有限公司 一种抗vegf/pd-l1双特异性抗体及其用途
WO2022068894A1 (zh) * 2020-09-30 2022-04-07 上海齐鲁制药研究中心有限公司 同时靶向pd-l1和vegf的双功能分子及其医药用途
CN114316025B (zh) * 2020-12-25 2025-01-03 百奥赛图(北京)医药科技股份有限公司 Vegfr2基因人源化的非人动物及其构建方法和应用
WO2022188832A1 (zh) * 2021-03-12 2022-09-15 中山康方生物医药有限公司 含有抗pd-1-抗vegfa双特异性抗体的药物组合及其用途
KR20230162942A (ko) * 2021-03-31 2023-11-29 우시 바이올로직스 아일랜드 리미티드 이중특이성 항 pd-l1/vegf 항체 및 이의 용도
CN115197325A (zh) * 2021-04-14 2022-10-18 康方药业有限公司 抗体在抗肿瘤治疗中的用途
AU2022258273A1 (en) * 2021-04-14 2023-09-14 Akeso Biopharma, Inc Anti-cd47 monoclonal antibody and use thereof
CN116143935A (zh) * 2021-11-22 2023-05-23 杭州翰思生物医药有限公司 重组抗体及其应用
CN114181310B (zh) * 2022-02-14 2022-07-05 中山康方生物医药有限公司 抗tigit抗体、其药物组合物及用途
US20260035463A1 (en) * 2022-07-20 2026-02-05 Minghui Pharmaceutical (Hangzhou) Limited Multispecific antibody and use thereof
WO2024032662A1 (zh) * 2022-08-09 2024-02-15 上海济煜医药科技有限公司 一种靶向pd-1和vegf的抗体及其应用
CN117679505A (zh) * 2022-09-09 2024-03-12 中山康方生物医药有限公司 药物组合及用途
EP4582447A4 (en) * 2022-09-14 2026-01-21 Quaerite Biopharm Res Beijing Co Ltd ANTI-VEGFA ANTIBODY OR ANTIGEN BINDING FRAGMENT OF THESE AND ITS USE
CN116003619B (zh) * 2022-12-12 2023-08-04 三门峡市眼科医院 人源化抗Ang-2和VEGF双功能抗体及其医药用途
KR20250167678A (ko) * 2022-12-30 2025-12-01 레메젠 (상하이) 씨오., 엘티디. 이중특이적 항체 및 이의 응용
CN119039450A (zh) * 2023-05-22 2024-11-29 上海君实生物医药科技股份有限公司 抗pd-1-抗vegf的双特异性抗体、其药物组合物及其用途
CN121620530A (zh) * 2023-06-29 2026-03-06 英创安博生物技术有限公司 HER2-CD3ε 双特异性抗体
WO2025056056A1 (zh) * 2023-09-14 2025-03-20 中山康方生物医药有限公司 药物组合及用途
CN120361206A (zh) * 2024-01-25 2025-07-25 中山康方生物医药有限公司 抗pd-1-抗vegfa的双特异性抗体的医药用途
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