JP6317739B2 - 短縮されたCD95−Fc変異体 - Google Patents

短縮されたCD95−Fc変異体 Download PDF

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Publication number
JP6317739B2
JP6317739B2 JP2015522106A JP2015522106A JP6317739B2 JP 6317739 B2 JP6317739 B2 JP 6317739B2 JP 2015522106 A JP2015522106 A JP 2015522106A JP 2015522106 A JP2015522106 A JP 2015522106A JP 6317739 B2 JP6317739 B2 JP 6317739B2
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seq
fusion protein
domain
functional fragment
apg101
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Expired - Fee Related
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JP2015524403A5 (enExample
JP2015524403A (ja
Inventor
オリバー ヒル
オリバー ヒル
クリスチャン ギーファーズ
クリスチャン ギーファーズ
マイノルフ ティーマン
マイノルフ ティーマン
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Apogenix AG
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    • 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
    • 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
    • C07K14/70578NGF-receptor/TNF-receptor superfamily, e.g. CD27, CD30, CD40, CD95
    • 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
    • A61K38/177Receptors; Cell surface antigens; Cell surface determinants
    • A61K38/1793Receptors; Cell surface antigens; Cell surface determinants for cytokines; for lymphokines; for interferons
    • 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
    • A61K39/39533Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals
    • A61K39/3955Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals against proteinaceous materials, e.g. enzymes, hormones, lymphokines
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/16Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P13/00Drugs for disorders of the urinary system
    • A61P13/12Drugs for disorders of the urinary system of the kidneys
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00Drugs for disorders of the nervous 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
    • A61P31/04Antibacterial agents
    • 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
    • A61P31/18Antivirals for RNA viruses for HIV
    • 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
    • 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
    • A61P37/06Immunosuppressants, e.g. drugs for graft rejection
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P7/00Drugs for disorders of the blood or the extracellular fluid
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00Drugs for disorders of the cardiovascular system
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00Drugs for disorders of the cardiovascular system
    • A61P9/10Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
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    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
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    • C07KPEPTIDES
    • C07K14/00Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
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    • 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
    • C07K14/52Cytokines; Lymphokines; Interferons
    • C07K14/525Tumour necrosis factor [TNF]
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K16/00Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K7/00Peptides having 5 to 20 amino acids in a fully defined sequence; Derivatives thereof
    • C07K7/04Linear peptides containing only normal peptide links
    • C07K7/08Linear peptides containing only normal peptide links having 12 to 20 amino acids
    • 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
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
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    • 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
    • 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
    • C07K2317/52Constant or Fc region; Isotype
    • C07K2317/524CH2 domain
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K2317/00Immunoglobulins specific features
    • C07K2317/50Immunoglobulins specific features characterized by immunoglobulin fragments
    • C07K2317/52Constant or Fc region; Isotype
    • C07K2317/526CH3 domain
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K2319/00Fusion polypeptide
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K2319/00Fusion polypeptide
    • C07K2319/01Fusion polypeptide containing a localisation/targetting motif
    • C07K2319/02Fusion polypeptide containing a localisation/targetting motif containing a signal sequence
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K2319/00Fusion polypeptide
    • C07K2319/01Fusion polypeptide containing a localisation/targetting motif
    • C07K2319/03Fusion polypeptide containing a localisation/targetting motif containing a transmembrane segment
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K2319/00Fusion polypeptide
    • C07K2319/30Non-immunoglobulin-derived peptide or protein having an immunoglobulin constant or Fc region, or a fragment thereof, attached thereto
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K2319/00Fusion polypeptide
    • C07K2319/70Fusion polypeptide containing domain for protein-protein interaction
    • C07K2319/74Fusion polypeptide containing domain for protein-protein interaction containing a fusion for binding to a cell surface receptor

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Organic Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Engineering & Computer Science (AREA)
  • Genetics & Genomics (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Molecular Biology (AREA)
  • Veterinary Medicine (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Public Health (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Biochemistry (AREA)
  • Biophysics (AREA)
  • Immunology (AREA)
  • Zoology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Biomedical Technology (AREA)
  • Toxicology (AREA)
  • Cell Biology (AREA)
  • General Engineering & Computer Science (AREA)
  • Biotechnology (AREA)
  • Wood Science & Technology (AREA)
  • Epidemiology (AREA)
  • Microbiology (AREA)
  • Plant Pathology (AREA)
  • Physics & Mathematics (AREA)
  • Oncology (AREA)
  • Endocrinology (AREA)
  • Mycology (AREA)
  • Hematology (AREA)
  • Urology & Nephrology (AREA)
  • Communicable Diseases (AREA)
  • Virology (AREA)
JP2015522106A 2012-07-18 2013-07-18 短縮されたCD95−Fc変異体 Expired - Fee Related JP6317739B2 (ja)

Applications Claiming Priority (5)

Application Number Priority Date Filing Date Title
EP12176978.0 2012-07-18
EP12176978 2012-07-18
EP12176980 2012-07-18
EP12176980.6 2012-07-18
PCT/EP2013/065248 WO2014013037A1 (en) 2012-07-18 2013-07-18 Shortened cd95-fc variants

Publications (3)

Publication Number Publication Date
JP2015524403A JP2015524403A (ja) 2015-08-24
JP2015524403A5 JP2015524403A5 (enExample) 2016-08-12
JP6317739B2 true JP6317739B2 (ja) 2018-04-25

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JP2015522106A Expired - Fee Related JP6317739B2 (ja) 2012-07-18 2013-07-18 短縮されたCD95−Fc変異体
JP2015522107A Active JP6231562B2 (ja) 2012-07-18 2013-07-18 CD95−Fcアイソフォームの混合物を含む組成物

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JP2015522107A Active JP6231562B2 (ja) 2012-07-18 2013-07-18 CD95−Fcアイソフォームの混合物を含む組成物

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US (5) US9434783B2 (enExample)
EP (4) EP3409686B1 (enExample)
JP (2) JP6317739B2 (enExample)
KR (1) KR102201694B1 (enExample)
CN (3) CN109897115A (enExample)
AU (2) AU2013291984B2 (enExample)
BR (1) BR112015000732B1 (enExample)
CA (2) CA2877989C (enExample)
DK (2) DK2875045T3 (enExample)
ES (2) ES2924109T3 (enExample)
HK (1) HK1207095A1 (enExample)
IL (1) IL236659A (enExample)
MX (1) MX371430B (enExample)
NZ (1) NZ703546A (enExample)
RU (2) RU2648146C2 (enExample)
SG (1) SG11201500134QA (enExample)
UA (1) UA116889C2 (enExample)
WO (2) WO2014013039A1 (enExample)

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EP3409686B1 (en) * 2012-07-18 2022-04-13 Apogenix AG Composition comprising a mixture of cd95-fc isoforms
CN105393121B (zh) * 2013-04-29 2018-04-24 阿珀吉尼科斯股份公司 诊断癌症的方法
NO2776305T3 (enExample) * 2014-04-23 2018-01-27
EP3137909B1 (en) 2014-04-29 2018-06-06 Apogenix AG Diagnostic anti-cd95l antibody
US9587215B2 (en) 2014-08-07 2017-03-07 General Electric Company Devices, systems and methods for automated transfer of a sample
EP3236772A4 (en) * 2014-12-22 2018-10-17 Alexion Pharmaceuticals, Inc. Methods of purifying recombinant proteins
US20220177841A1 (en) 2019-03-29 2022-06-09 Myst Therapeutics Llc Ex vivo methods for producing a t cell therapeutic and related compositions and methods
US20230032934A1 (en) 2019-11-27 2023-02-02 Myst Therapeutics, Llc Method of producing tumor-reactive t cell composition using modulatory agents
CN114829371A (zh) * 2019-12-12 2022-07-29 Emd密理博公司 使用透析过滤缓冲液强化的病毒过滤
EP4512828A3 (en) 2020-02-27 2025-05-14 Turnstone Biologics Corp. Methods for ex vivo enrichment and expansion of tumor reactive t cells and related compositions thereof
LT3972987T (lt) * 2020-04-10 2023-09-25 Akston Biosciences Corporation Antigenui specifinė imunoterapija, skirta sulietiems covid-19 baltymams ir naudojimo būdai
CN115894706A (zh) * 2021-09-30 2023-04-04 北京康辰药业股份有限公司 靶向PD-L1和FasL的融合蛋白、核苷酸序列及其应用
WO2026044087A1 (en) 2024-08-21 2026-02-26 Shape Therapeutics Inc. Increased cellular stability for aav production
WO2026073032A1 (en) 2024-09-27 2026-04-02 Shape Therapeutics Inc. Constructs for improved aav production

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US6306395B1 (en) 1996-05-02 2001-10-23 Mochida Pharmaceutical Co., Ltd. Fas antigen derivatives
CA2270423C (en) * 1996-10-31 2009-09-15 Mochida Pharmaceutical Co., Ltd. Prophylactic/therapeutic agent
DE69839582D1 (de) * 1997-02-27 2008-07-17 Ono Pharmaceutical Co Neues polypeptid, dafür kodierende dna und deren verwendungen
CA2309598A1 (en) * 1997-11-10 1999-05-20 Mochida Pharmaceutical Co., Ltd. Preventives and remedies for diffuse lung disease
RU2420537C2 (ru) * 2001-01-17 2011-06-10 Трабьон Фармасьютикалз Инк. Слитые белки связывающий домен-иммуноглобулин
EP1273297A1 (en) * 2001-07-06 2003-01-08 Deutsches Krebsforschungszentrum Stiftung des öffentlichen Rechts Vitamin E for the treatment of diseases in which the binding of the transcription factor NF-KB and/or AP-1 to promoter target sites has a beneficial effect (eg AIDS, cardiac infarction)
PT1606318E (pt) * 2003-03-26 2009-11-10 Deutsches Krebsforsch Proteínas de fusão de fc melhoradas
US20100215637A1 (en) * 2006-03-28 2010-08-26 Biopharmica Ltd Agent for the Treatment of Hormone-Dependent Disorders and Uses Thereof
WO2007147600A2 (en) * 2006-06-21 2007-12-27 Apogenix Gmbh Differential il-4 and/or il-10 cytokine expression in human cancer
SI2428252T1 (sl) * 2006-12-28 2015-01-30 Deutsches Krebsforschungszentrum Stiftung Des Oeffentlichen Rechts Nevtralizacija invazije aktivnostnih blokov cd95 v celicah glioblastoma in vivo
WO2008101671A2 (en) * 2007-02-19 2008-08-28 Apogenix Gmbh Il-4 fc fusion proteins
EP2009022A1 (en) * 2007-06-26 2008-12-31 Apogenix GmbH Trimeric death ligands with enhanced activity (tenascin)
WO2010003766A2 (en) 2008-06-17 2010-01-14 Apogenix Gmbh Multimeric tnf receptors
US8664366B2 (en) * 2009-01-09 2014-03-04 Apogenix Gmbh Fusion proteins forming trimers
CN102497886B (zh) * 2009-07-21 2016-01-20 玛丽皇后与斯特菲尔德学院 用于细胞内药物递送的Fas(Apo-1,CD95)靶向平台
JP2013512674A (ja) * 2009-12-02 2013-04-18 アクセルロン ファーマ, インコーポレイテッド Fc融合タンパク質の血清半減期を増加させるための組成物および方法
EP3409686B1 (en) * 2012-07-18 2022-04-13 Apogenix AG Composition comprising a mixture of cd95-fc isoforms
CN105393121B (zh) * 2013-04-29 2018-04-24 阿珀吉尼科斯股份公司 诊断癌症的方法

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Publication number Publication date
JP6231562B2 (ja) 2017-11-15
US9908928B2 (en) 2018-03-06
US20150166633A1 (en) 2015-06-18
US9315570B2 (en) 2016-04-19
RU2648146C2 (ru) 2018-03-22
RU2015105330A (ru) 2016-09-10
SG11201500134QA (en) 2015-03-30
US9434783B2 (en) 2016-09-06
US10370441B2 (en) 2019-08-06
EP2875045A1 (en) 2015-05-27
WO2014013037A1 (en) 2014-01-23
RU2648157C2 (ru) 2018-03-22
NZ703546A (en) 2018-03-23
IL236659A (en) 2017-02-28
MX2015000731A (es) 2015-09-04
HK1207095A1 (en) 2016-01-22
IL236659A0 (en) 2015-02-26
HK1207096A1 (en) 2016-01-22
DK3409686T3 (da) 2022-07-18
CA2877989C (en) 2021-05-25
AU2013291984A1 (en) 2015-02-05
US20150225475A1 (en) 2015-08-13
MX371430B (es) 2020-01-30
CA2878992C (en) 2020-09-22
EP3406630B1 (en) 2020-09-02
ES2674662T3 (es) 2018-07-03
EP2875045B1 (en) 2018-03-28
EP2875044B1 (en) 2018-04-11
DK2875045T3 (en) 2018-07-02
CN109897115A (zh) 2019-06-18
WO2014013039A1 (en) 2014-01-23
CN104662039B (zh) 2019-10-08
EP3406630A1 (en) 2018-11-28
CA2877989A1 (en) 2014-01-23
US20160362471A1 (en) 2016-12-15
US9657083B2 (en) 2017-05-23
RU2015105328A (ru) 2016-09-10
ES2924109T3 (es) 2022-10-04
JP2015524403A (ja) 2015-08-24
KR20150048120A (ko) 2015-05-06
EP3409686B1 (en) 2022-04-13
EP2875044A1 (en) 2015-05-27
UA116889C2 (uk) 2018-05-25
AU2013291982B2 (en) 2017-01-12
JP2015528006A (ja) 2015-09-24
CA2878992A1 (en) 2014-01-23
US20180186856A1 (en) 2018-07-05
CN104662039A (zh) 2015-05-27
AU2013291982A1 (en) 2015-02-05
BR112015000732B1 (pt) 2023-01-10
BR112015000732A2 (enExample) 2017-08-15
KR102201694B1 (ko) 2021-01-12
CN104640876A (zh) 2015-05-20
EP3409686A1 (en) 2018-12-05
AU2013291984B2 (en) 2018-01-18
US20160235815A1 (en) 2016-08-18

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