JP6219849B2 - 発癌性ウイルスポリペプチド陽性腫瘍治療用ポリヌクレオチド - Google Patents

発癌性ウイルスポリペプチド陽性腫瘍治療用ポリヌクレオチド Download PDF

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JP6219849B2
JP6219849B2 JP2014554791A JP2014554791A JP6219849B2 JP 6219849 B2 JP6219849 B2 JP 6219849B2 JP 2014554791 A JP2014554791 A JP 2014554791A JP 2014554791 A JP2014554791 A JP 2014554791A JP 6219849 B2 JP6219849 B2 JP 6219849B2
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polypeptide
seq
polynucleotide
amino acid
cells
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JP2015506179A (ja
JP2015506179A5 (https=
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リー，ジョン，エイチ．
フェルメール，ダニエル，ダブリュ．
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サンフォード ヘルス
サンフォード ヘルス
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/005—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from viruses
    • 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
    • A61K39/0005—Vertebrate antigens
    • A61K39/0011—Cancer antigens
    • 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
    • A61K39/12—Viral antigens
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
    • A61P31/20—Antivirals for DNA viruses
    • 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
    • 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
    • C12N7/00—Viruses; Bacteriophages; Compositions thereof; Preparation or purification thereof
    • 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
    • A61K2039/51—Medicinal preparations containing antigens or antibodies comprising whole cells, viruses or DNA/RNA
    • A61K2039/525—Virus
    • A61K2039/5256—Virus expressing foreign proteins
    • 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
    • A61K2039/51—Medicinal preparations containing antigens or antibodies comprising whole cells, viruses or DNA/RNA
    • A61K2039/525—Virus
    • A61K2039/5258—Virus-like particles
    • 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
    • A61K2039/51—Medicinal preparations containing antigens or antibodies comprising whole cells, viruses or DNA/RNA
    • A61K2039/53—DNA (RNA) vaccination
    • 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
    • A61K2039/54—Medicinal preparations containing antigens or antibodies characterised by the route of administration
    • A61K2039/541—Mucosal route
    • A61K2039/543—Mucosal route intranasal
    • 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
    • A61K2039/58—Medicinal preparations containing antigens or antibodies raising an immune response against a target which is not the antigen used for immunisation
    • A61K2039/585—Medicinal preparations containing antigens or antibodies raising an immune response against a target which is not the antigen used for immunisation wherein the target is cancer
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    • C12N2710/00011—Details
    • C12N2710/10011—Adenoviridae
    • C12N2710/10041—Use of virus, viral particle or viral elements as a vector
    • C12N2710/10042—Use of virus, viral particle or viral elements as a vector virus or viral particle as vehicle, e.g. encapsulating small organic molecule
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
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    • C12N2710/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA dsDNA viruses
    • C12N2710/00011—Details
    • C12N2710/10011—Adenoviridae
    • C12N2710/10311—Mastadenovirus, e.g. human or simian adenoviruses
    • C12N2710/10341—Use of virus, viral particle or viral elements as a vector
    • C12N2710/10343—Use of virus, viral particle or viral elements as a vector viral genome or elements thereof as genetic vector
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
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    • C12N2710/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA dsDNA viruses
    • C12N2710/00011—Details
    • C12N2710/20011—Papillomaviridae
    • C12N2710/20022—New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes
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    • C12N2710/00011—Details
    • C12N2710/20011—Papillomaviridae
    • C12N2710/20032—Use of virus as therapeutic agent, other than vaccine, e.g. as cytolytic agent
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
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    • C12N2710/00011—Details
    • C12N2710/20011—Papillomaviridae
    • C12N2710/20034—Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein
    • 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
    • C12N2710/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA dsDNA viruses
    • C12N2710/00011—Details
    • C12N2710/20011—Papillomaviridae
    • C12N2710/20071—Demonstrated in vivo effect

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Organic Chemistry (AREA)
  • Virology (AREA)
  • Public Health (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Veterinary Medicine (AREA)
  • Immunology (AREA)
  • Microbiology (AREA)
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  • Epidemiology (AREA)
  • Genetics & Genomics (AREA)
  • Engineering & Computer Science (AREA)
  • Oncology (AREA)
  • Wood Science & Technology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Zoology (AREA)
  • Biochemistry (AREA)
  • Biotechnology (AREA)
  • Molecular Biology (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Biomedical Technology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Biophysics (AREA)
  • Gastroenterology & Hepatology (AREA)
  • General Engineering & Computer Science (AREA)
  • Communicable Diseases (AREA)
  • Micro-Organisms Or Cultivation Processes Thereof (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Medicines Containing Material From Animals Or Micro-Organisms (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicinal Preparation (AREA)
  • Peptides Or Proteins (AREA)
JP2014554791A 2012-01-24 2013-01-23 発癌性ウイルスポリペプチド陽性腫瘍治療用ポリヌクレオチド Active JP6219849B2 (ja)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US201261590089P 2012-01-24 2012-01-24
US61/590,089 2012-01-24
PCT/US2013/022696 WO2013112549A1 (en) 2012-01-24 2013-01-23 Polynucleotides for treating oncogenic viral polypeptide positive tumors

Related Child Applications (1)

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JP2017188121A Division JP6655051B2 (ja) 2012-01-24 2017-09-28 発癌性ウイルスポリペプチド陽性腫瘍治療用ポリヌクレオチド

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JP2015506179A JP2015506179A (ja) 2015-03-02
JP2015506179A5 JP2015506179A5 (https=) 2016-03-10
JP6219849B2 true JP6219849B2 (ja) 2017-10-25

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JP2014554791A Active JP6219849B2 (ja) 2012-01-24 2013-01-23 発癌性ウイルスポリペプチド陽性腫瘍治療用ポリヌクレオチド
JP2017188121A Active JP6655051B2 (ja) 2012-01-24 2017-09-28 発癌性ウイルスポリペプチド陽性腫瘍治療用ポリヌクレオチド

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US (3) US9492526B2 (https=)
EP (2) EP3269387B1 (https=)
JP (2) JP6219849B2 (https=)
KR (1) KR102195196B1 (https=)
CN (2) CN110042110A (https=)
DK (1) DK2806889T3 (https=)
ES (1) ES2646590T3 (https=)
HK (1) HK1203833A1 (https=)
IN (1) IN2014DN06118A (https=)
WO (1) WO2013112549A1 (https=)

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SI3218504T1 (sl) 2014-11-13 2020-11-30 Universite De Geneve Tri-segmentirani arenavirusi kot vakcinski vektorji
AU2016274655B2 (en) 2015-06-10 2021-06-17 NeoTrail Therapeutics, Inc. HPV vaccines
CA3003557A1 (en) 2015-11-04 2017-05-11 Hookipa Biotech Ag Vaccines against hepatitis b virus
DK3373959T3 (da) 2015-11-12 2022-09-19 Hookipa Biotech Gmbh Arenaviruspartikler som cancervacciner
IL260030B2 (en) 2016-01-08 2025-12-01 Nykode Therapeutics ASA Therapeutic anticancer neoepitope vaccine
GB201605210D0 (en) * 2016-03-29 2016-05-11 Oxford Immunotec Ltd Assay
JP2019517522A (ja) * 2016-06-03 2019-06-24 エトゥビクス コーポレーション ヒトパピローマウイルス（ｈｐｖ）関連疾患の処置のための組成物及び方法
CN106655327A (zh) * 2016-10-18 2017-05-10 云南中烟工业有限责任公司 一种压缩式充电装置
EP3539015B1 (en) * 2016-11-11 2021-08-25 Google LLC Methods, systems, and media for modifying the presentation of video content on a user device based on a consumption of the user device
KR20250136930A (ko) * 2018-03-06 2025-09-16 프레시전 인코포레이티드 사람 파필로마바이러스 백신 및 이의 용도
EP4729636A2 (en) * 2020-03-16 2026-04-22 The University of North Carolina at Chapel Hill Compositions and methods for the selective detection of tumor-derived viral dna
KR102712588B1 (ko) * 2020-05-25 2024-10-02 (주)진매트릭스 사람 파필로마바이러스의 구조적으로 변형된 키메라 폴리펩타이드 및 그 폴리펩타이드를 포함하는 재조합 단백질 및 그 단백질의 용도
AU2021281910C1 (en) * 2020-05-25 2024-09-19 Genematrix Inc. Structurally modified chimeric polypeptide of human papillomavirus, recombinant protein comprising same polypeptide, and use of same protein
CN116425839A (zh) * 2023-04-03 2023-07-14 深圳锦时生物科技有限公司 人乳头瘤病毒多肽及其应用

Family Cites Families (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB9717953D0 (en) * 1997-08-22 1997-10-29 Smithkline Beecham Biolog Vaccine
WO1999061608A2 (en) 1998-05-26 1999-12-02 Institute Of Molecular And Cell Biology Polypeptides from creb binding protein and related protein p300 for use in transcriptional regulation
EP1553966B1 (en) 2002-10-03 2012-08-01 Wyeth Holdings Corporation Fusion peptides comprising the human papillomavirus e7 and e6 polypeptides and immunogenic compositions thereof
RU2462513C2 (ru) 2007-05-15 2012-09-27 Трансген С.А. Векторы для множественной генной экспрессии
BRPI1011902A2 (pt) * 2009-04-28 2019-09-24 Univ Johns Hopkins composições e métodos para potencialização de respostas imunes antígeno-específicas
CN102002105B (zh) * 2009-09-03 2013-01-23 中国疾病预防控制中心病毒病预防控制所 Hpv 16型e7e6融合蛋白基因、表达载体、方法、细胞和用途

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Publication number Publication date
EP3269387A1 (en) 2018-01-17
HK1203833A1 (en) 2015-11-06
US9969779B2 (en) 2018-05-15
JP2015506179A (ja) 2015-03-02
US9492526B2 (en) 2016-11-15
IN2014DN06118A (https=) 2015-08-14
JP2018038405A (ja) 2018-03-15
JP6655051B2 (ja) 2020-02-26
CN104159607A (zh) 2014-11-19
ES2646590T3 (es) 2017-12-14
KR20140131929A (ko) 2014-11-14
KR102195196B1 (ko) 2020-12-28
CN110042110A (zh) 2019-07-23
US20150023996A1 (en) 2015-01-22
EP2806889A4 (en) 2016-04-20
US20180237477A1 (en) 2018-08-23
DK2806889T3 (da) 2017-11-20
EP3269387B1 (en) 2019-07-17
EP2806889A1 (en) 2014-12-03
EP2806889B1 (en) 2017-08-16
US20160376324A1 (en) 2016-12-29
WO2013112549A1 (en) 2013-08-01

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