SG11202011201QA - Fully human antibodies against ox40, method for preparing same, and use thereof - Google Patents

Fully human antibodies against ox40, method for preparing same, and use thereof

Info

Publication number
SG11202011201QA
SG11202011201QA SG11202011201QA SG11202011201QA SG11202011201QA SG 11202011201Q A SG11202011201Q A SG 11202011201QA SG 11202011201Q A SG11202011201Q A SG 11202011201QA SG 11202011201Q A SG11202011201Q A SG 11202011201QA SG 11202011201Q A SG11202011201Q A SG 11202011201QA
Authority
SG
Singapore
Prior art keywords
human antibodies
antibodies against
fully human
preparing same
preparing
Prior art date
Application number
SG11202011201QA
Other languages
English (en)
Inventor
Yong Zheng
Baotian Yang
Jing Li
Original Assignee
Wuxi Biologics Shanghai Co Ltd
Wuxi Biologics Ireland 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 Wuxi Biologics Shanghai Co Ltd, Wuxi Biologics Ireland Ltd filed Critical Wuxi Biologics Shanghai Co Ltd
Publication of SG11202011201QA publication Critical patent/SG11202011201QA/en

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    • 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
    • C07K16/2878Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the NGF-receptor/TNF-receptor superfamily, e.g. CD27, CD30, CD40, CD95
    • 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
    • C07K16/2875Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the NGF/TNF superfamily, e.g. CD70, CD95L, CD153, CD154
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • 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
    • A61P35/04Antineoplastic agents specific for metastasis
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00Drugs for immunological or allergic disorders
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00Drugs for immunological or allergic disorders
    • A61P37/02Immunomodulators
    • 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
    • C12N5/00Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
    • C12N5/10Cells modified by introduction of foreign genetic material
    • C12N5/12Fused cells, e.g. hybridomas
    • C12N5/16Animal cells
    • C12N5/163Animal cells one of the fusion partners being a B or a T lymphocyte
    • AHUMAN NECESSITIES
    • A01AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01KANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
    • A01K2227/00Animals characterised by species
    • A01K2227/10Mammal
    • A01K2227/105Murine
    • AHUMAN NECESSITIES
    • A01AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01KANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
    • A01K2267/00Animals characterised by purpose
    • A01K2267/03Animal model, e.g. for test or diseases
    • A01K2267/0331Animal model for proliferative diseases
    • 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
    • C07K2317/21Immunoglobulins specific features characterized by taxonomic origin from primates, e.g. man
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K2317/00Immunoglobulins specific features
    • C07K2317/30Immunoglobulins specific features characterized by aspects of specificity or valency
    • C07K2317/33Crossreactivity, e.g. for species or epitope, or lack of said crossreactivity
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K2317/00Immunoglobulins specific features
    • C07K2317/30Immunoglobulins specific features characterized by aspects of specificity or valency
    • C07K2317/34Identification of a linear epitope shorter than 20 amino acid residues or of a conformational epitope defined by amino acid residues
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K2317/00Immunoglobulins specific features
    • C07K2317/50Immunoglobulins specific features characterized by immunoglobulin fragments
    • C07K2317/52Constant or Fc region; Isotype
    • 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
    • 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
    • C07K2317/70Immunoglobulins 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
    • C07K2317/732Antibody-dependent cellular cytotoxicity [ADCC]
    • 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
    • C07K2317/734Complement-dependent cytotoxicity [CDC]
    • 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
    • C07K2317/75Agonist effect on 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
    • C07K2317/76Antagonist 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

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Immunology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • Genetics & Genomics (AREA)
  • Biochemistry (AREA)
  • Engineering & Computer Science (AREA)
  • Molecular Biology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Biophysics (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Pain & Pain Management (AREA)
  • Rheumatology (AREA)
  • Oncology (AREA)
  • Zoology (AREA)
  • Biomedical Technology (AREA)
  • Biotechnology (AREA)
  • Wood Science & Technology (AREA)
  • Cell Biology (AREA)
  • Microbiology (AREA)
  • Communicable Diseases (AREA)
  • General Engineering & Computer Science (AREA)
  • Peptides Or Proteins (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
  • Preparation Of Compounds By Using Micro-Organisms (AREA)
  • Micro-Organisms Or Cultivation Processes Thereof (AREA)
SG11202011201QA 2018-05-11 2019-05-07 Fully human antibodies against ox40, method for preparing same, and use thereof SG11202011201QA (en)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
CN2018086574 2018-05-11
CN201810529840 2018-05-29
PCT/CN2019/085886 WO2019214624A1 (en) 2018-05-11 2019-05-07 Fully human antibodies against ox40, method for preparing same, and use thereof

Publications (1)

Publication Number Publication Date
SG11202011201QA true SG11202011201QA (en) 2020-12-30

Family

ID=68466901

Family Applications (1)

Application Number Title Priority Date Filing Date
SG11202011201QA SG11202011201QA (en) 2018-05-11 2019-05-07 Fully human antibodies against ox40, method for preparing same, and use thereof

Country Status (12)

Country Link
US (1) US20210171647A1 (es)
EP (2) EP3790903A4 (es)
JP (1) JP7411575B2 (es)
KR (1) KR20210039986A (es)
CN (2) CN114685665A (es)
AU (1) AU2019264712A1 (es)
BR (1) BR112020023026A2 (es)
CA (1) CA3103040A1 (es)
MX (1) MX2020012081A (es)
SG (1) SG11202011201QA (es)
TW (1) TWI831778B (es)
WO (1) WO2019214624A1 (es)

Families Citing this family (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20230022859A1 (en) * 2019-11-21 2023-01-26 Beigene, Ltd. Treatment of cancer with anti-ox40 antibodies and multi-kinase inhibitors
CN113045655A (zh) * 2019-12-27 2021-06-29 高诚生物医药(香港)有限公司 抗ox40抗体及其用途
CN113045654A (zh) * 2019-12-27 2021-06-29 南开大学 抗ox40抗体及其用途
CN111153994B (zh) * 2019-12-31 2021-10-15 武汉班科生物技术股份有限公司 人肿瘤坏死因子的人源单克隆抗体
CN113429483A (zh) * 2020-03-23 2021-09-24 百奥泰生物制药股份有限公司 一种免疫细胞激活剂的开发及应用
CN113527482B (zh) * 2020-04-17 2023-07-21 珠海泰诺麦博制药股份有限公司 抗人神经生长因子的抗体
CN111518209B (zh) * 2020-05-09 2023-07-25 郑州航空港百桥生物科技有限公司 特异性结合人ox40的单克隆抗体及其应用
CN116490209A (zh) * 2020-11-12 2023-07-25 同润生物医药(上海)有限公司 联合疗法及其使用方法

Family Cites Families (36)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4399216A (en) 1980-02-25 1983-08-16 The Trustees Of Columbia University Processes for inserting DNA into eucaryotic cells and for producing proteinaceous materials
US5179017A (en) 1980-02-25 1993-01-12 The Trustees Of Columbia University In The City Of New York Processes for inserting DNA into eucaryotic cells and for producing proteinaceous materials
US4634665A (en) 1980-02-25 1987-01-06 The Trustees Of Columbia University In The City Of New York Processes for inserting DNA into eucaryotic cells and for producing proteinaceous materials
GB8601597D0 (en) 1986-01-23 1986-02-26 Wilson R H Nucleotide sequences
IL85035A0 (en) 1987-01-08 1988-06-30 Int Genetic Eng Polynucleotide molecule,a chimeric antibody with specificity for human b cell surface antigen,a process for the preparation and methods utilizing the same
GB8717430D0 (en) 1987-07-23 1987-08-26 Celltech Ltd Recombinant dna product
GB8809129D0 (en) 1988-04-18 1988-05-18 Celltech Ltd Recombinant dna methods vectors and host cells
GB8823869D0 (en) 1988-10-12 1988-11-16 Medical Res Council Production of antibodies
US5750373A (en) 1990-12-03 1998-05-12 Genentech, Inc. Enrichment method for variant proteins having altered binding properties, M13 phagemids, and growth hormone variants
US6075181A (en) 1990-01-12 2000-06-13 Abgenix, Inc. Human antibodies derived from immunized xenomice
US6150584A (en) 1990-01-12 2000-11-21 Abgenix, Inc. Human antibodies derived from immunized xenomice
US5661016A (en) 1990-08-29 1997-08-26 Genpharm International Inc. Transgenic non-human animals capable of producing heterologous antibodies of various isotypes
US5545806A (en) 1990-08-29 1996-08-13 Genpharm International, Inc. Ransgenic non-human animals for producing heterologous antibodies
US5625126A (en) 1990-08-29 1997-04-29 Genpharm International, Inc. Transgenic non-human animals for producing heterologous antibodies
DE69133476T2 (de) 1990-08-29 2006-01-05 GenPharm International, Inc., Palo Alto Transgene Mäuse fähig zur Produktion heterologer Antikörper
US5633425A (en) 1990-08-29 1997-05-27 Genpharm International, Inc. Transgenic non-human animals capable of producing heterologous antibodies
DK0590058T3 (da) 1991-06-14 2004-03-29 Genentech Inc Humaniseret heregulin-antistof
WO2003048731A2 (en) 2001-12-03 2003-06-12 Abgenix, Inc. Antibody categorization based on binding characteristics
DE60317677T2 (de) 2002-06-13 2008-10-30 Crucell Holland B.V. Ox40 (=cd134) rezeptor agonisten und therapeutische verwendung
TWI461436B (zh) * 2005-11-25 2014-11-21 Kyowa Hakko Kirin Co Ltd 人類cd134(ox40)之人類單株抗體及其製造及使用方法
CN101918447B (zh) 2007-12-14 2014-06-11 布里斯托尔-米尔斯·斯奎布公司 人ox40受体的结合分子
SG187945A1 (en) * 2010-08-23 2013-03-28 Univ Texas Anti-ox40 antibodies and methods of using the same
WO2013008171A1 (en) * 2011-07-11 2013-01-17 Glenmark Pharmaceuticals S.A. Antibodies that bind to ox40 and their uses
GB201116092D0 (en) * 2011-09-16 2011-11-02 Bioceros B V Antibodies and uses thereof
AU2013358958B2 (en) 2012-12-14 2018-09-20 Open Monoclonal Technology, Inc. Polynucleotides encoding rodent antibodies with human idiotypes and animals comprising same
PE20160690A1 (es) 2013-03-18 2016-08-14 Biocerox Prod Bv Anticuerpos anti-cd134 (ox40) humanizados y usos de los mismos
WO2015015401A2 (en) * 2013-08-02 2015-02-05 Pfizer Inc. Anti-cxcr4 antibodies and antibody-drug conjugates
PE20161571A1 (es) * 2014-03-31 2017-02-07 Genentech Inc Anticuerpos anti-ox40 y metodos de uso
TW201619200A (zh) * 2014-10-10 2016-06-01 麥迪紐有限責任公司 人類化抗-ox40抗體及其用途
WO2016179517A1 (en) 2015-05-07 2016-11-10 Agenus Inc. Anti-ox40 antibodies and methods of use thereof
WO2016185016A1 (en) * 2015-05-21 2016-11-24 Alligator Bioscience Ab Novel polypeptides
BR112017025191A2 (pt) * 2015-05-29 2018-07-31 Bristol-Myers Squibb Company anticorpos contra ox40 e uso dos mesmos
CN108137684B (zh) 2015-10-15 2022-03-08 苏州丁孚靶点生物技术有限公司 抗ox40抗体及其应用
EP3383914A4 (en) * 2015-12-02 2019-10-30 Agenus Inc. ANTI-OX40 ANTIBODIES AND METHODS OF USE
US10669344B2 (en) * 2016-08-12 2020-06-02 Janssen Biotech, Inc. Engineered antibodies and other Fc-domain containing molecules with enhanced agonism and effector functions
CN107815465B (zh) * 2016-08-31 2021-03-16 百奥赛图(北京)医药科技股份有限公司 人源化基因改造动物模型的制备方法及应用

Also Published As

Publication number Publication date
AU2019264712A1 (en) 2021-01-07
JP2021522847A (ja) 2021-09-02
TW202003575A (zh) 2020-01-16
KR20210039986A (ko) 2021-04-12
CN110467674B (zh) 2022-05-31
TWI831778B (zh) 2024-02-11
WO2019214624A1 (en) 2019-11-14
CN114685665A (zh) 2022-07-01
CA3103040A1 (en) 2019-11-14
EP4074732A1 (en) 2022-10-19
BR112020023026A2 (pt) 2021-02-09
EP3790903A4 (en) 2022-06-08
MX2020012081A (es) 2021-04-28
JP7411575B2 (ja) 2024-01-11
US20210171647A1 (en) 2021-06-10
EP3790903A1 (en) 2021-03-17
CN110467674A (zh) 2019-11-19

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