JP5808536B2 - 抗rsvgタンパク質抗体 - Google Patents

抗rsvgタンパク質抗体 Download PDF

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JP5808536B2
JP5808536B2 JP2010531283A JP2010531283A JP5808536B2 JP 5808536 B2 JP5808536 B2 JP 5808536B2 JP 2010531283 A JP2010531283 A JP 2010531283A JP 2010531283 A JP2010531283 A JP 2010531283A JP 5808536 B2 JP5808536 B2 JP 5808536B2
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seq
positions
rsv
region
antibody
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JP2011500091A (ja
JP2011500091A5 (enExample
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カウバー、ローレンス、エム.
コラリーニ、エレン、ジェイ.
キート、ブルース
フォード、オリット
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トレリス バイオサイエンス、インク.
トレリス バイオサイエンス、インク.
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    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K16/00Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies
    • C07K16/08Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from viruses
    • C07K16/10RNA viruses
    • C07K16/11Paramyxoviridae (F); Pneumoviridae (F), e.g. respiratory syncytial virus [RSV]
    • 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
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00Drugs for disorders of the respiratory system
    • 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
    • A61P31/12Antivirals
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12Antivirals
    • A61P31/14Antivirals for RNA viruses
    • 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
    • C07K2317/20Immunoglobulins 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
    • C07K2317/34Identification 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
    • C07K2317/54F(ab')2
    • 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
    • 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
    • C12N2740/00Reverse transcribing RNA viruses
    • C12N2740/00011Details
    • C12N2740/10011Retroviridae
    • C12N2740/11011Alpharetrovirus, e.g. avian leucosis virus

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Virology (AREA)
  • Medicinal Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Animal Behavior & Ethology (AREA)
  • Molecular Biology (AREA)
  • Immunology (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Genetics & Genomics (AREA)
  • Biophysics (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Biochemistry (AREA)
  • Oncology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Communicable Diseases (AREA)
  • Pulmonology (AREA)
  • Pain & Pain Management (AREA)
  • Rheumatology (AREA)
  • Microbiology (AREA)
  • Mycology (AREA)
  • Epidemiology (AREA)
  • Peptides Or Proteins (AREA)
  • Preparation Of Compounds By Using Micro-Organisms (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
  • Micro-Organisms Or Cultivation Processes Thereof (AREA)
  • Breeding Of Plants And Reproduction By Means Of Culturing (AREA)
JP2010531283A 2007-10-25 2008-10-24 抗rsvgタンパク質抗体 Active JP5808536B2 (ja)

Applications Claiming Priority (5)

Application Number Priority Date Filing Date Title
US46907P 2007-10-25 2007-10-25
US61/000,469 2007-10-25
US8940108P 2008-08-15 2008-08-15
US61/089,401 2008-08-15
PCT/US2008/081175 WO2009055711A2 (en) 2007-10-25 2008-10-24 Anti-rsv g protein antibodies

Related Child Applications (1)

Application Number Title Priority Date Filing Date
JP2015006644A Division JP2015078231A (ja) 2007-10-25 2015-01-16 抗rsvgタンパク質抗体

Publications (3)

Publication Number Publication Date
JP2011500091A JP2011500091A (ja) 2011-01-06
JP2011500091A5 JP2011500091A5 (enExample) 2011-10-27
JP5808536B2 true JP5808536B2 (ja) 2015-11-10

Family

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Family Applications (2)

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JP2010531283A Active JP5808536B2 (ja) 2007-10-25 2008-10-24 抗rsvgタンパク質抗体
JP2015006644A Withdrawn JP2015078231A (ja) 2007-10-25 2015-01-16 抗rsvgタンパク質抗体

Family Applications After (1)

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JP2015006644A Withdrawn JP2015078231A (ja) 2007-10-25 2015-01-16 抗rsvgタンパク質抗体

Country Status (14)

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US (3) US7736648B2 (enExample)
EP (1) EP2214711B1 (enExample)
JP (2) JP5808536B2 (enExample)
KR (1) KR101671452B1 (enExample)
CN (1) CN101808663B (enExample)
AU (1) AU2008316703B2 (enExample)
BR (1) BRPI0819210A2 (enExample)
CA (1) CA2703667C (enExample)
IL (1) IL205257A (enExample)
MX (1) MX2010004482A (enExample)
NZ (1) NZ585589A (enExample)
RU (1) RU2526517C2 (enExample)
WO (1) WO2009055711A2 (enExample)
ZA (1) ZA201003131B (enExample)

Families Citing this family (30)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2004047800A2 (en) * 2002-11-26 2004-06-10 Gilead Sciences, Inc. Method of drug loading in liposomes by gradient
KR101671452B1 (ko) * 2007-10-25 2016-11-17 트렐리스 바이오싸이언스 인코포레이티드 항rsv g 단백질 항체
EP2780366A2 (en) 2011-11-17 2014-09-24 AIMM Therapeutics B.V. Rsv g protein specific antibodies
US10131709B2 (en) 2011-12-28 2018-11-20 Immunoqure Ag Nucleic acid molecules encoding monoclonal antibodies specific for IL-22
EP2797952B1 (en) * 2011-12-28 2019-02-27 ImmunoQure AG Method of providing monoclonal auto-antibodies with desired specificity
US9546219B2 (en) 2012-02-08 2017-01-17 North Carolina State University Treatment of allergic diseases with recombinant antibodies
TWI659968B (zh) 2013-03-14 2019-05-21 再生元醫藥公司 針對呼吸道融合病毒f蛋白質的人類抗體及其使用方法
CN111303278B (zh) * 2013-04-15 2022-09-06 扬森疫苗与预防公司 结合到rsv g蛋白的人类抗体
CA2908878C (en) * 2013-04-15 2021-06-29 Crucell Holland B.V. Human antibodies binding to rsv g protein
AU2014255865B2 (en) * 2013-04-15 2019-07-18 Janssen Vaccines & Prevention B.V. Human antibodies binding to RSV G proteins
DK3105250T3 (da) * 2014-02-10 2020-09-28 Igm Biosciences Inc Multispecifikke iga-bindingsmolekyler
CN103911389A (zh) * 2014-04-09 2014-07-09 南昌大学 一种检测人呼吸道合胞病毒抗体的g和f蛋白的制备方法
CN113968912B (zh) 2014-12-05 2025-05-16 纪念斯隆-凯特琳癌症中心 靶向g-蛋白偶联受体的嵌合抗原受体及其用途
KR102602417B1 (ko) 2014-12-05 2023-11-16 메모리얼 슬로안 케터링 캔서 센터 G-단백질 커플화 수용체를 표적화하는 항체 및 이의 사용 방법
CN106496324B (zh) 2015-11-30 2020-01-14 天津昊免生物技术有限公司 一种抗呼吸道合胞病毒的全人源抗体
CN109232737A (zh) * 2016-03-01 2019-01-18 苏州博泰神州生物技术有限公司 一种针对rsv粘附g蛋白表面抗原的全人源单克隆抗体
EP3538558A4 (en) 2016-11-09 2020-07-15 North Carolina State University TREATMENT OF ALLERGIC DISEASES USING CHIMERIC PROTEIN
BR112019015479A2 (pt) 2017-01-27 2020-03-31 Ngm Biopharmaceuticals, Inc. Anticorpo e seu uso, célula, composição, molécula polinucleotídica, vetor, método para inibir a sinalização de gcgr, método para reduzir ou baixar os níveis de glicose, método para aumentar o nível de peptídeo c, método para aumentar o nível de insulina, método para tratar diabetes, método para tratar hiperglicemia, método para tratar uma doença, método para melhorar a função das células
US11773143B2 (en) * 2017-10-13 2023-10-03 Trellis Bioscience, Llc Conformational epitopes in respiratory syncytial virus G protein central conserved region
US12060437B2 (en) 2018-03-23 2024-08-13 North Carolina State University Methods and compositions for antibody to high affinity receptor for IgE
US10961315B2 (en) 2018-07-27 2021-03-30 Ngm Biopharmaceuticals, Inc. Method of treating type I diabetes by administering a combination of a glucagon receptor antagonist and an anti-CD3 antibody
EP3833677A4 (en) * 2018-08-08 2022-04-27 Trellis Bioscience, Inc. IMPROVED RSV PASSIVE AND ACTIVE VACCINES
AU2020227545B2 (en) 2019-02-28 2023-10-19 Km Biologics Co., Ltd. RSV F/G chimeric vaccine
WO2021046413A1 (en) 2019-09-06 2021-03-11 Silgan White Cap LLC Tethered, hinged closure
EP4031171A1 (en) * 2019-09-20 2022-07-27 Universiteit Antwerpen A novel human respiratory syncytial virus strain and its use
CN115335399A (zh) 2019-12-06 2022-11-11 朱诺治疗学股份有限公司 针对gprc5d靶结合结构域的抗独特型抗体以及相关组合物和方法
EP4429966A4 (en) 2021-11-08 2026-01-14 Silgan White Cap LLC PROJECTION ON THE NECK OF A CONTAINER
CN119907693A (zh) * 2022-08-02 2025-04-29 诺纳生物(苏州)有限公司 Msln抗体药物偶联物
WO2025106427A1 (en) * 2023-11-14 2025-05-22 The United States Of America, As Represented By The Secretary, Department Of Health And Human Services Neutralizing and protective monoclonal antibodies against respiratory syncytial virus (rsv)
WO2025194126A1 (en) * 2024-03-15 2025-09-18 The United States Of America, As Represented By The Secretary, Department Of Health And Human Services Respiratory syncytial virus (rsv) g and f antibodies with high rsv-neutralizing potency

Family Cites Families (14)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
ATE196737T1 (de) * 1993-05-25 2000-10-15 American Cyanamid Co Adjuvantien für impfstoffe gegen das respiratorische synzitialvirus
US6020182A (en) * 1996-07-12 2000-02-01 Connaught Laboratories Limited Subunit respiratory syncytial virus vaccine preparation
FR2766192B1 (fr) * 1997-07-17 2001-07-13 Pf Medicament Epitopes du vrs et anticorps les comportant, utiles dans le diagnostic et la therapie
US6642062B2 (en) 1998-09-03 2003-11-04 Trellis Bioinformatics, Inc. Multihued labels
US7083950B2 (en) 1998-09-25 2006-08-01 Regeneron Pharmaceuticals, Inc. High affinity fusion proteins and therapeutic and diagnostic methods for use
EP1638603A1 (en) 1999-01-22 2006-03-29 The Government of the United States represented by the Secretary of the Department of Health and Human Services Methods for the prevention and treatment of diseases caused by an inflammatory response mediated by endogenous substance p by using anti-substance p antibodies
ES2316487T5 (es) 2000-10-18 2019-05-13 The Government Of The Us Secretary Department Of Health And Human Services Composiciones y métodos para modular la inmunidad e infección de RSV
US7413868B2 (en) 2003-11-05 2008-08-19 Trellis Bioscience, Inc. Use of particulate labels in bioanalyte detection methods
JP4736037B2 (ja) * 2005-10-26 2011-07-27 株式会社イーベック ヒトgm−csfに結合するヒトのモノクローナル抗体並びにその抗原結合部分
CN1986569A (zh) * 2005-12-23 2007-06-27 首都儿科研究所 人源抗呼吸道合胞病毒中和性基因工程Fab抗体
WO2007094423A1 (ja) * 2006-02-15 2007-08-23 Evec Incorporated ヒトサイトメガロウイルスに結合するヒトのモノクローナル抗体並びにその抗原結合部分
MX2008011280A (es) * 2006-03-06 2008-09-12 Symphogen As Anticuerpor policlonal recombinante para el tratamiento de infecciones por el virus sincitial respiratorio.
WO2008008858A2 (en) 2006-07-12 2008-01-17 Trellis Bioscience, Inc. Cellspot™ applications
KR101671452B1 (ko) * 2007-10-25 2016-11-17 트렐리스 바이오싸이언스 인코포레이티드 항rsv g 단백질 항체

Also Published As

Publication number Publication date
EP2214711A4 (en) 2011-12-21
CN101808663A (zh) 2010-08-18
US7736648B2 (en) 2010-06-15
JP2015078231A (ja) 2015-04-23
NZ585589A (en) 2012-07-27
US9321830B2 (en) 2016-04-26
US20100285022A1 (en) 2010-11-11
US8273354B2 (en) 2012-09-25
IL205257A (en) 2014-12-31
CA2703667C (en) 2015-12-29
CA2703667A1 (en) 2009-04-30
AU2008316703A2 (en) 2010-07-22
MX2010004482A (es) 2010-07-06
WO2009055711A2 (en) 2009-04-30
WO2009055711A3 (en) 2009-09-24
BRPI0819210A2 (pt) 2015-06-23
IL205257A0 (en) 2010-12-30
AU2008316703A1 (en) 2009-04-30
KR20100091195A (ko) 2010-08-18
RU2010120879A (ru) 2011-11-27
EP2214711B1 (en) 2018-08-15
JP2011500091A (ja) 2011-01-06
CN101808663B (zh) 2015-09-30
RU2526517C2 (ru) 2014-08-20
US20090130120A1 (en) 2009-05-21
ZA201003131B (en) 2011-03-30
EP2214711A2 (en) 2010-08-11
KR101671452B1 (ko) 2016-11-17
US20130034564A1 (en) 2013-02-07
AU2008316703B2 (en) 2012-09-27

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