BR112015001390A2 - vacina de proteína de fusão multimérica e imunoterápicos - Google Patents
vacina de proteína de fusão multimérica e imunoterápicosInfo
- Publication number
- BR112015001390A2 BR112015001390A2 BR112015001390A BR112015001390A BR112015001390A2 BR 112015001390 A2 BR112015001390 A2 BR 112015001390A2 BR 112015001390 A BR112015001390 A BR 112015001390A BR 112015001390 A BR112015001390 A BR 112015001390A BR 112015001390 A2 BR112015001390 A2 BR 112015001390A2
- Authority
- BR
- Brazil
- Prior art keywords
- fusion protein
- proteins
- protein
- vaccine
- fusion
- Prior art date
Links
- 102000037865 fusion proteins Human genes 0.000 title abstract 8
- 108020001507 fusion proteins Proteins 0.000 title abstract 8
- 230000001024 immunotherapeutic effect Effects 0.000 title abstract 2
- 229940023143 protein vaccine Drugs 0.000 title abstract 2
- 239000000427 antigen Substances 0.000 abstract 4
- 102000036639 antigens Human genes 0.000 abstract 4
- 108091007433 antigens Proteins 0.000 abstract 4
- 102000004169 proteins and genes Human genes 0.000 abstract 4
- 108090000623 proteins and genes Proteins 0.000 abstract 4
- 102000039446 nucleic acids Human genes 0.000 abstract 2
- 108020004707 nucleic acids Proteins 0.000 abstract 2
- 150000007523 nucleic acids Chemical class 0.000 abstract 2
- 229960005486 vaccine Drugs 0.000 abstract 2
- 239000002671 adjuvant Substances 0.000 abstract 1
- 230000028993 immune response Effects 0.000 abstract 1
- 230000005847 immunogenicity Effects 0.000 abstract 1
- 230000001939 inductive effect Effects 0.000 abstract 1
- 230000007246 mechanism Effects 0.000 abstract 1
- 238000000034 method Methods 0.000 abstract 1
- 238000006384 oligomerization reaction Methods 0.000 abstract 1
Classifications
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- 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
- A61K39/245—Herpetoviridae, e.g. herpes simplex virus
-
- 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
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/12—Viral antigens
- A61K39/21—Retroviridae, e.g. equine infectious anemia virus
-
- 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
- A61P31/04—Antibacterial agents
-
- 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
-
- 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
- A61P31/14—Antivirals for RNA viruses
- A61P31/18—Antivirals for RNA viruses for HIV
-
- 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
- A61P31/22—Antivirals for DNA viruses for herpes viruses
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P33/00—Antiparasitic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/04—Immunostimulants
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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
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- 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
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- 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
- A61K2039/555—Medicinal preparations containing antigens or antibodies characterised by a specific combination antigen/adjuvant
- A61K2039/55505—Inorganic adjuvants
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- 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
- A61K2039/555—Medicinal preparations containing antigens or antibodies characterised by a specific combination antigen/adjuvant
- A61K2039/55511—Organic adjuvants
- A61K2039/55561—CpG containing adjuvants; Oligonucleotide containing adjuvants
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- 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
- A61K2039/57—Medicinal preparations containing antigens or antibodies characterised by the type of response, e.g. Th1, Th2
-
- 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
- A61K2039/70—Multivalent vaccine
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
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- 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
- C12N2710/16011—Herpesviridae
- C12N2710/16211—Lymphocryptovirus, e.g. human herpesvirus 4, Epstein-Barr Virus
- C12N2710/16234—Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein
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- 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
- C12N2740/00—Reverse transcribing RNA viruses
- C12N2740/00011—Details
- C12N2740/10011—Retroviridae
- C12N2740/15011—Lentivirus, not HIV, e.g. FIV, SIV
- C12N2740/15022—New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes
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- 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
- C12N2740/00—Reverse transcribing RNA viruses
- C12N2740/00011—Details
- C12N2740/10011—Retroviridae
- C12N2740/15011—Lentivirus, not HIV, e.g. FIV, SIV
- C12N2740/15034—Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein
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- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Virology (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Organic Chemistry (AREA)
- Immunology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Epidemiology (AREA)
- Mycology (AREA)
- Microbiology (AREA)
- Communicable Diseases (AREA)
- Molecular Biology (AREA)
- Oncology (AREA)
- Biochemistry (AREA)
- Genetics & Genomics (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Biophysics (AREA)
- Gastroenterology & Hepatology (AREA)
- Hematology (AREA)
- Tropical Medicine & Parasitology (AREA)
- Engineering & Computer Science (AREA)
- Biotechnology (AREA)
- AIDS & HIV (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Peptides Or Proteins (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
Abstract
resumo patente de invenção: "vacina de proteína de fusão multimérica e imunoterápicos". a presente invenção proporciona proteínas de fusão que incorporam mecanismos únicos para multimerizar antígenos para melhorar a sua imunogenicidade. as proteínas de fusão compreendem pelo menos dois antígenos, ou outras proteínas relacionadas a vacinas, separadas por uma sequência de ligante e um domínio de oligomerização. quando expressa, a proteína de fusão forma um complexo proteico multimérico. esta abordagem pode ser utilizada para multimerizar um único antígeno/proteína ou para criar multímeros compreendendo dois ou mais diferentes antígenos/proteínas. também proporcionados são ácidos nucleicos que codificam as proteínas de fusão, ainda um outro aspecto refere-se a métodos para induzir ou suprimir uma resposta imune em um indivíduo por administração ao indivíduo de uma composição de vacina compreendendo uma proteína de fusão ou de ácido nucleico que codifica a proteína de fusão, opcionalmente sem a utilização de um adjuvante.
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US201261675948P | 2012-07-26 | 2012-07-26 | |
US61/675,948 | 2012-07-26 | ||
PCT/US2013/052270 WO2014018858A2 (en) | 2012-07-26 | 2013-07-26 | Multimeric fusion protein vaccine and immunotherapeutic |
Publications (2)
Publication Number | Publication Date |
---|---|
BR112015001390A2 true BR112015001390A2 (pt) | 2017-09-26 |
BR112015001390B1 BR112015001390B1 (pt) | 2024-04-30 |
Family
ID=49997985
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
BR112015001390-2A BR112015001390B1 (pt) | 2012-07-26 | 2013-07-26 | Proteína de fusão, ácido nucleico isolado e uso de uma composição de vacina |
Country Status (7)
Country | Link |
---|---|
US (2) | US9962436B2 (pt) |
EP (1) | EP2877205A4 (pt) |
JP (2) | JP6373836B2 (pt) |
AU (2) | AU2013295647B2 (pt) |
BR (1) | BR112015001390B1 (pt) |
CA (1) | CA2878427A1 (pt) |
WO (1) | WO2014018858A2 (pt) |
Families Citing this family (23)
Publication number | Priority date | Publication date | Assignee | Title |
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US20220332772A1 (en) * | 2010-11-15 | 2022-10-20 | The Board Of Trustees Of The University Of Illinois | Vaccine and methods for detecting and preventing filariasis |
US10016494B2 (en) | 2014-02-07 | 2018-07-10 | Valorisation-Hsj, Limited Partnership | Antigenic epitopes from EBV gp350/220 and uses thereof |
US10314906B2 (en) | 2015-03-18 | 2019-06-11 | University Of Massachusetts | Virus-like particle compositions and vaccines against Epstein-Barr virus infection and disease |
WO2017011380A1 (en) * | 2015-07-14 | 2017-01-19 | The Board Of Trustees Of The University Of Illinois | Vaccine and methods for detecting and preventing filariasis |
WO2017172853A1 (en) * | 2016-03-30 | 2017-10-05 | Ab Biosciences, Inc. | Recombinant intravenous immunoglobulin (rivig) compositions and methods for their production and use |
WO2018074558A1 (ja) * | 2016-10-23 | 2018-04-26 | デンカ株式会社 | 複合ポリペプチド単量体、細胞浸透機能を有する当該複合ポリペプチドの単量体の会合体、及び、当該会合体を有効成分とする皮下、皮内、経皮又は筋肉内投与用ノロウイルスコンポーネントワクチン |
WO2018115305A1 (en) * | 2016-12-22 | 2018-06-28 | Leibniz-Institut für Pflanzengenetik Und Kulturpflanzenforschung (IPK) | Oligomeric vaccines from plants by s-tag-s-protein fusions |
WO2018140733A1 (en) * | 2017-01-27 | 2018-08-02 | The Henry M. Jackson Foundation For The Advancement Of Military Medicine, Inc. | Vaccine compositions of herpesvirus envelope protein combinations to induce immune response |
US11793873B2 (en) | 2017-05-10 | 2023-10-24 | University Of Massachusetts | Bivalent dengue/hepatitis B vaccines |
GB2568550B (en) * | 2017-11-21 | 2021-06-30 | Univ Cape Town | Method of synthesising 6-deoxy-6-amino-ß-d-glucopyranoside-containing polymers |
EP3730620A4 (en) * | 2017-12-21 | 2022-01-05 | Green Biomed, Inc. | CROSS-IMMUNIZATION ANTIGENIC VACCINE AND PROCESS FOR PREPARATION |
KR20210018205A (ko) | 2018-04-03 | 2021-02-17 | 사노피 | 항원성 OspA 폴리펩타이드 |
JP2021519596A (ja) | 2018-04-03 | 2021-08-12 | サノフイSanofi | フェリチンタンパク質 |
JP2021519598A (ja) * | 2018-04-03 | 2021-08-12 | サノフイSanofi | 抗原性エプスタインバーウイルスポリペプチド |
WO2019213550A1 (en) * | 2018-05-03 | 2019-11-07 | Duke University | Vaccine compositions and methods for enhanced antigen-specific vaccination |
CN111658770A (zh) * | 2019-03-05 | 2020-09-15 | 周文云 | P14.7蛋白质及其作为疫苗佐剂的用途 |
WO2021002855A1 (en) * | 2019-07-02 | 2021-01-07 | Virago Vax Inc. | Mammary tumor virus vaccine |
AU2021287508B2 (en) * | 2020-06-09 | 2023-11-09 | Km Biologics Co., Ltd. | Fusion protein of pentamer and gB of cytomegalovirus, and vaccine containing said fusion protein |
CN111662390A (zh) * | 2020-06-17 | 2020-09-15 | 天康生物(上海)有限公司 | 禽流感HA-Fd融合蛋白及其制备方法和疫苗 |
JPWO2022085648A1 (pt) * | 2020-10-19 | 2022-04-28 | ||
WO2022238381A2 (en) * | 2021-05-10 | 2022-11-17 | Nykode Therapeutics ASA | Immunotherapy constructs for treatment of disease |
CA3212784A1 (en) * | 2021-05-10 | 2022-11-17 | Agnete Brunsvik Fredriksen | Tolerance-inducing constructs and compositions and their use for the treatment of immune disorders |
WO2023240225A1 (en) * | 2022-06-09 | 2023-12-14 | The University Of North Carolina At Chapel Hill | Constitutively active polymeric sting mimics for antitumor immunity |
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US4737462A (en) | 1982-10-19 | 1988-04-12 | Cetus Corporation | Structural genes, plasmids and transformed cells for producing cysteine depleted muteins of interferon-β |
US4518584A (en) | 1983-04-15 | 1985-05-21 | Cetus Corporation | Human recombinant interleukin-2 muteins |
US4751180A (en) | 1985-03-28 | 1988-06-14 | Chiron Corporation | Expression using fused genes providing for protein product |
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CA2146559A1 (en) | 1992-10-23 | 1994-05-11 | Melanie K. Spriggs | Methods of preparing soluble, oligomeric proteins |
GB9615726D0 (en) * | 1996-07-26 | 1996-09-04 | Medical Res Council | Anti-viral agent 11 |
KR20010022452A (ko) | 1997-07-31 | 2001-03-15 | 추후제출 | 플라비바이러스 감염에 대한 재조합 다이머형 엔벨롭 백신 |
JP5138844B2 (ja) * | 1998-06-12 | 2013-02-06 | ザ・ヘンリー・エム・ジャクソン・ファンデイション・フォー・ジ・アドヴァンスメント・オヴ・ミリタリー・メディシン、インコーポレイテッド | 抗原およびEBVGp350/220の受容体の同時刺激によるB細胞活性化および免疫グロブリン分泌の増強 |
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GB0605735D0 (en) * | 2006-03-22 | 2006-05-03 | Immunobiology Ltd | Composition and method for mediating an immune response |
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AU2008214344B2 (en) | 2007-02-08 | 2012-06-07 | Merck Sharp & Dohme Corp. | Antibodies specific for Dkk-1 |
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CA2705373A1 (en) * | 2007-11-12 | 2009-08-20 | The Henry M. Jackson Foundation For The Advancement Of Military Medicine , Inc. | Hiv-1 envelope glycoprotein oligomer and methods of use |
DK2257307T3 (en) | 2008-02-20 | 2018-08-20 | Glaxosmithkline Biologicals Sa | BIOCONJUGATES MANUFACTURED FROM RECOMBINANT N-Glycosylated PROTEINS FROM PROCARYOTIC CELLS |
EP2313108A4 (en) | 2008-06-30 | 2013-06-12 | Us Army As Represented By The Secretary Of The Army | ANTIPALUDE VACCINE OF SELF-ASSEMBLED POLYPEPTIDE NANOPARTICLES |
WO2010057501A1 (en) | 2008-11-21 | 2010-05-27 | Københavns Universitet (University Of Copenhagen) | Priming of an immune response |
JP6339366B2 (ja) | 2010-05-06 | 2018-06-06 | グリコヴァキシン アーゲー | 莢膜グラム陽性菌のバイオコンジュゲートワクチン |
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2013
- 2013-07-26 WO PCT/US2013/052270 patent/WO2014018858A2/en active Application Filing
- 2013-07-26 JP JP2015524466A patent/JP6373836B2/ja active Active
- 2013-07-26 BR BR112015001390-2A patent/BR112015001390B1/pt active IP Right Grant
- 2013-07-26 EP EP13823370.5A patent/EP2877205A4/en active Pending
- 2013-07-26 CA CA 2878427 patent/CA2878427A1/en active Pending
- 2013-07-26 US US14/416,780 patent/US9962436B2/en active Active
- 2013-07-26 AU AU2013295647A patent/AU2013295647B2/en active Active
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2018
- 2018-04-19 JP JP2018080293A patent/JP2018138581A/ja active Pending
- 2018-05-04 US US15/971,025 patent/US10821173B2/en active Active
- 2018-05-07 AU AU2018203170A patent/AU2018203170B2/en active Active
Also Published As
Publication number | Publication date |
---|---|
US20180303931A1 (en) | 2018-10-25 |
US9962436B2 (en) | 2018-05-08 |
US10821173B2 (en) | 2020-11-03 |
WO2014018858A3 (en) | 2015-04-16 |
JP6373836B2 (ja) | 2018-08-15 |
WO2014018858A2 (en) | 2014-01-30 |
JP2015530369A (ja) | 2015-10-15 |
AU2013295647A1 (en) | 2015-01-29 |
US20150174237A1 (en) | 2015-06-25 |
JP2018138581A (ja) | 2018-09-06 |
EP2877205A2 (en) | 2015-06-03 |
AU2018203170A1 (en) | 2018-05-24 |
EP2877205A4 (en) | 2016-04-06 |
BR112015001390B1 (pt) | 2024-04-30 |
AU2018203170B2 (en) | 2020-03-26 |
AU2013295647B2 (en) | 2018-02-08 |
CA2878427A1 (en) | 2014-01-30 |
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