WO2018071849A2 - Engineered meganucleases specific for recognition sequences in the hepatitis b virus genome - Google Patents

Engineered meganucleases specific for recognition sequences in the hepatitis b virus genome Download PDF

Info

Publication number
WO2018071849A2
WO2018071849A2 PCT/US2017/056638 US2017056638W WO2018071849A2 WO 2018071849 A2 WO2018071849 A2 WO 2018071849A2 US 2017056638 W US2017056638 W US 2017056638W WO 2018071849 A2 WO2018071849 A2 WO 2018071849A2
Authority
WO
WIPO (PCT)
Prior art keywords
seq
hbv
meganuclease
engineered meganuclease
engineered
Prior art date
Legal status (The legal status 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 status listed.)
Ceased
Application number
PCT/US2017/056638
Other languages
English (en)
French (fr)
Other versions
WO2018071849A3 (en
Inventor
Derek Jantz
James Jefferson Smith
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Precision Biosciences Inc
Original Assignee
Precision Biosciences Inc
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
Priority to AU2017342536A priority Critical patent/AU2017342536A1/en
Priority to KR1020197013312A priority patent/KR102305215B1/ko
Priority to IL317537A priority patent/IL317537A/en
Priority to EA201990792A priority patent/EA201990792A1/ru
Priority to EP23164434.5A priority patent/EP4234691A3/en
Priority to IL308894A priority patent/IL308894A/en
Priority to CN201780074346.8A priority patent/CN110023495A/zh
Priority to DK17804977.1T priority patent/DK3526323T5/da
Priority to FIEP17804977.1T priority patent/FI3526323T3/fi
Priority to SG11201903042VA priority patent/SG11201903042VA/en
Priority to CN202311305067.1A priority patent/CN117402852A/zh
Priority to PE2019000817A priority patent/PE20191353A1/es
Priority to KR1020237000425A priority patent/KR20230010826A/ko
Priority to US16/342,169 priority patent/US10662416B2/en
Priority to KR1020217029958A priority patent/KR20210118240A/ko
Priority to BR112019007450-3A priority patent/BR112019007450A2/pt
Priority to CR20190181A priority patent/CR20190181A/es
Priority to EP17804977.1A priority patent/EP3526323B1/en
Application filed by Precision Biosciences Inc filed Critical Precision Biosciences Inc
Priority to JP2019520125A priority patent/JP6811857B2/ja
Priority to CA3040143A priority patent/CA3040143A1/en
Priority to KR1020247026203A priority patent/KR20240123417A/ko
Priority to MX2019004349A priority patent/MX2019004349A/es
Priority to IL265921A priority patent/IL265921B2/en
Publication of WO2018071849A2 publication Critical patent/WO2018071849A2/en
Publication of WO2018071849A3 publication Critical patent/WO2018071849A3/en
Priority to PH12019500788A priority patent/PH12019500788A1/en
Priority to CONC2019/0003675A priority patent/CO2019003675A2/es
Anticipated expiration legal-status Critical
Priority to US16/852,296 priority patent/US10851358B2/en
Priority to US17/083,171 priority patent/US11274285B2/en
Priority to US17/665,265 priority patent/US20220243187A1/en
Priority to AU2023263542A priority patent/AU2023263542A1/en
Priority to US18/424,277 priority patent/US20240271111A1/en
Priority to US19/029,948 priority patent/US20250154486A1/en
Ceased legal-status Critical Current

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/43—Enzymes; Proenzymes; Derivatives thereof
    • A61K38/46—Hydrolases (3)
    • A61K38/465—Hydrolases (3) acting on ester bonds (3.1), e.g. lipases, ribonucleases
    • 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
    • C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
    • C12N9/14—Hydrolases (3)
    • C12N9/16—Hydrolases (3) acting on ester bonds (3.1)
    • C12N9/22—Ribonucleases [RNase]; Deoxyribonucleases [DNase]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/43—Enzymes; Proenzymes; Derivatives thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K48/00—Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
    • A61K48/005—Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy characterised by an aspect of the 'active' part of the composition delivered, i.e. the nucleic acid delivered
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
    • A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
    • A61K9/51—Nanocapsules; Nanoparticles
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
    • 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
    • A61P31/20—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
    • C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09—Recombinant DNA-technology
    • C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
    • C12N15/52—Genes encoding for enzymes or proenzymes
    • 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
    • C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09—Recombinant DNA-technology
    • C12N15/63—Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
    • C12N15/79—Vectors or expression systems specially adapted for eukaryotic hosts
    • C12N15/85—Vectors or expression systems specially adapted for eukaryotic hosts for animal cells
    • C12N15/86—Viral vectors
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Y—ENZYMES
    • C12Y301/00—Hydrolases acting on ester bonds (3.1)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • 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
    • C12N2730/00—Reverse transcribing DNA viruses
    • C12N2730/00011—Details
    • C12N2730/10011—Hepadnaviridae
    • C12N2730/10111—Orthohepadnavirus, e.g. hepatitis B virus
    • C12N2730/10122—New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes
    • 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
    • C12N2750/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA ssDNA viruses
    • C12N2750/00011—Details
    • C12N2750/14011—Parvoviridae
    • C12N2750/14111—Dependovirus, e.g. adenoassociated viruses
    • C12N2750/14141—Use of virus, viral particle or viral elements as a vector
    • 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
    • C12N2750/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA ssDNA viruses
    • C12N2750/00011—Details
    • C12N2750/14011—Parvoviridae
    • C12N2750/14111—Dependovirus, e.g. adenoassociated viruses
    • C12N2750/14141—Use of virus, viral particle or viral elements as a vector
    • C12N2750/14143—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
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2800/00—Nucleic acids vectors
    • C12N2800/10—Plasmid DNA
    • C12N2800/106—Plasmid DNA for vertebrates
    • C12N2800/107—Plasmid DNA for vertebrates for mammalian

Definitions

  • the viral DNA is found in the nucleus soon after infection of the cell.
  • the partially double-stranded DNA is rendered fully double-stranded by completion of the (+) sense strand and removal of a protein molecule from the (-) sense strand and a short sequence of RNA from the (+) sense strand.
  • Non-coding bases are removed from the ends of the (-) sense strand and the ends are rejoined.
  • the first subunit can comprise an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, or more, sequence identity to residues 7-153 of SEQ ID NO: 18 or 19 or residues 198-344 of SEQ ID NO: 20 or 21, and the second subunit can comprise an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, or more, sequence identity to residues 198-344 of SEQ ID NO: 18 or 19 or residues 7-153 of SEQ ID NO: 20 or 21.
  • the first subunit can comprise residues 7-153 of SEQ ID NO: 18 or 19 or residues 198-344 of SEQ ID NO: 20 or 21.
  • the second subunit can comprise residues 198-344 of SEQ ID NO: 18 or 19 or residues 7-153 of SEQ ID NO: 20 or 21.
  • the viral vector comprises two or more cassettes, wherein each cassette comprises a promoter and a nucleic acid sequence encoding an engineered meganuclease described herein, and wherein each engineered meganuclease has specificity for a different HBV recognition sequence disclosed herein.
  • the viral vector comprises one cassette comprising a promoter and a polycistronic nucleic acid sequence, wherein the promoter drives expression of the polycistronic nucleic acid sequence to generate a polycistronic mRNA described herein in a target cell.
  • the pharmaceutical composition can comprise two or more engineered meganuclease proteins described herein, wherein the engineered
  • the methods of treatment for HBV infection or HCC comprise administering to the subject any pharmaceutical composition of the invention described herein which comprises, at least, a pharmaceutically acceptable carrier and (a) a nucleic acid encoding an engineered meganuclease described herein, wherein the engineered meganuclease is expressed in a target cell in vivo; or (b) an engineered meganuclease protein described herein.
  • Figure 9 Evaluation of HBV meganucleases for their ability to recognize and cleave recognition sequences within episomal DNA plasmids in an E. coli reporter system.
  • Figure 9A shows plasmid pARCUS and plasmid pHBVa.
  • Figure 9B shows the number of colonies present on each selective plate, providing evidence of the ability of HBV
  • the cells were washed and 24 hours later (day 2 post-infection) were transduced with either a lentivirus encoding RFP, HBV 5-6x.33, HBV l l-12x.26, or a 1 : 1 mixture of the lentiviruses encoding the HBV meganucleases.
  • infected cells were treated with DMSO.
  • Cell supernatants were harvested and medium was replaced on days 4, 8, 11, and 13 post-transduction.
  • HBsAg and HBeAg was measured in the cell supernatants by ELISA. Extracellular DNA in the supernatant was also measured at day 13 post-infection.
  • SEQ ID NO: 25 sets forth the amino acid sequence of the HBV 5-6x.4 meganuclease.
  • SEQ ID NO: 51 sets forth the amino acid sequence of the HBV 5-6x.4 meganuclease HBV5-binding subunit.
  • SEQ ID NO: 85 sets forth the nucleic acid sequence of the recognition sequence present in HBV genotype F that corresponds to the HBV 5-6 recognition sequence in HBV genotype A with a G to C substitution at position -3 of the first half-site.
  • SEQ ID NO: 86 sets forth the nucleic acid sequence of the recognition sequence present in HBV genotype E that corresponds to the HBV 7-8 recognition sequence in HBV genotype A with a C to T substitution at position -1 of the first half-site.
  • DNA-binding affinity or "binding affinity” means the tendency of a meganuclease to non-covalently associate with a reference DNA molecule (e.g., a recognition sequence or an arbitrary sequence). Binding affinity is measured by a dissociation constant, Kd.
  • Kd dissociation constant
  • a nuclease has "altered” binding affinity if the Kd of the nuclease for a reference recognition sequence is increased or decreased by a statistically significant (p ⁇ 0.05) amount relative to a reference nuclease.
  • a variable which is described as having values between 0 and 2 can take the values 0, 1 or 2 if the variable is inherently discrete, and can take the values 0.0, 0.1, 0.01, 0.001, or any other real values ⁇ 0 and ⁇ 2 if the variable is inherently continuous.
  • HBV1 Subunit % and "HBV2 Subunit %" represent the amino acid sequence identity between the HBVl -binding and HBV2-binding subunit regions of each meganuclease and the HBVl -binding and HBV2-binding subunit regions, respectively, of the HBV l-2x.2 meganuclease.
  • HBV7 Subunit % and "HBV8 Subunit %" represent the amino acid sequence identity between the HBV7-binding and HBV8-binding subunit regions of each meganuclease and the HBV7-binding and HBV8-binding subunit regions, respectively, of the HBV 7-8x.2 meganuclease.
  • the recombinant DNA construct can comprise two cassettes, three cassettes, four cassettes, or more.
  • a cassette or combination of cassettes can encode any number or combination of an HBV 1-2 meganuclease, an HBV 5-6 meganuclease, an HBV 7-8 meganuclease, and an HBV 11-12 meganuclease.
  • a single cassette can encode an HBV 1-2 meganuclease, an HBV 5-6 meganuclease, an HBV 7-8 meganuclease, and an HBV 11-12 meganuclease.
  • a cassette or combination of cassettes can encode an HBV 5-6 meganuclease and an HBV 11-12 meganuclease.
  • meganucleases of the invention can be delivered as purified protein or as RNA or DNA encoding the meganuclease.
  • meganuclease proteins, or mRNA, or DNA vectors encoding endonucleases are supplied to target cells (e.g., cells in the liver) via injection directly to the target tissue.
  • endonuclease proteins or DNA/mRNA encoding endonucleases, are coupled covalently or, preferably, non-covalently to a nanoparticle or encapsulated within such a nanoparticle using methods known in the art (Sharma, et al.
  • a retroviral, pseudotype or adenoviral associated vector is constructed which encodes the engineered meganuclease and is administered to the subject.
  • the pharmaceutical composition can comprise one or more mRNAs described herein encapsulated within lipid nanoparticles, which are described elsewhere herein.
  • lipid nanoparticles can comprise two or more mRNAs described herein, each encoding an engineered meganuclease of the invention having specificity for a different HBV recognition sequence described herein.
  • lipid nanoparticles can comprise two, three, or four mRNAs described herein, each encoding an engineered meganuclease of the invention having specificity for a different HBV recognition sequence.
  • lipid nanoparticles can comprise two, three, or four mRNAs described herein, each encoding an engineered meganuclease of the invention having specificity for a different HBV recognition sequence.
  • lipid nanoparticles can comprise two, three, or four mRNAs described herein, each encoding an engineered meganuclease of the invention having specificity for a different HBV recognition sequence.
  • lipid nanoparticles
  • Cationic lipids can include, for example, one or more of the following:
  • palmitoyi-oleoyl-nor-arginine PONA
  • MPDACA GUADACA
  • MC3 heptatriaconta-6,9,28,31-tetraen-19-yl 4-(dimethylamino)butanoate)
  • MC3 LenMC3, CP- LenMC3, y-LenMC3, CP-y-LenMC3, MC3MC, MC2MC, MC3 Ether, MC4 Ether, MC3 Amide, Pan-MC3, Pan-MC4 and Pan MC5, l,2-dilinoleyloxy-N,N-dimethylaminopropane (DLinDMA), l,2-dilinolenyloxy-N,N-dimethylaminopropane (DLenDMA), 2,2-dilinoleyl-4- (2-dimethylaminoethyl)-[l,3]-diox
  • the endonuclease can be placed under the control of a tissue-specific promoter that is not active in the packaging cells.
  • a tissue-specific promoter that is not active in the packaging cells.
  • a muscle-specific promoter can be used.
  • muscle-specific promoters include C5-12 (Liu, et al. (2004) Hum Gene Ther. 15:783-92), the muscle-specific creatine kinase (MCK) promoter (Yuasa, et al. (2002) Gene Ther. 9: 1576-88), or the smooth muscle 22 (SM22) promoter (Haase, et al. (2013) BMC Biotechnol.
  • recombinant AAV particles are produced in a mammalian cell line that expresses a transcription repressor that prevents expression of the endonuclease.
  • Transcription repressors are known in the art and include the Tet-Repressor, the Lac-Repressor, the Cro repressor, and the Lambda-repressor.
  • Many nuclear hormone receptors such as the ecdysone receptor also act as transcription repressors in the absence of their cognate hormone ligand.

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Genetics & Genomics (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Organic Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Molecular Biology (AREA)
  • Medicinal Chemistry (AREA)
  • Wood Science & Technology (AREA)
  • Zoology (AREA)
  • Biotechnology (AREA)
  • Biomedical Technology (AREA)
  • Veterinary Medicine (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • General Engineering & Computer Science (AREA)
  • Virology (AREA)
  • Biochemistry (AREA)
  • Microbiology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Physics & Mathematics (AREA)
  • Epidemiology (AREA)
  • Oncology (AREA)
  • Communicable Diseases (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Biophysics (AREA)
  • Plant Pathology (AREA)
  • Immunology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Nanotechnology (AREA)
  • Optics & Photonics (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Enzymes And Modification Thereof (AREA)
  • Micro-Organisms Or Cultivation Processes Thereof (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
PCT/US2017/056638 2016-10-14 2017-10-13 Engineered meganucleases specific for recognition sequences in the hepatitis b virus genome Ceased WO2018071849A2 (en)

Priority Applications (31)

Application Number Priority Date Filing Date Title
KR1020197013312A KR102305215B1 (ko) 2016-10-14 2017-10-13 B형 간염 바이러스 게놈 내의 인식 서열에 대해 특이적인 조작된 메가뉴클레아제
IL317537A IL317537A (en) 2016-10-14 2017-10-13 Engineered megacannolyases specific for recognition sequences in the hepatitis B virus genome
EA201990792A EA201990792A1 (ru) 2017-06-30 2017-10-13 Сконструированные мегануклеазы, специфичные к последовательностям распознавания в геноме вируса гепатита b
EP23164434.5A EP4234691A3 (en) 2016-10-14 2017-10-13 Engineered meganucleases specific for recognition sequences in the hepatitis b virus genome
IL308894A IL308894A (en) 2016-10-14 2017-10-13 Engineered meganucleases specific for recognition sequences in the hepatitis b virus genome
CN201780074346.8A CN110023495A (zh) 2016-10-14 2017-10-13 对乙肝病毒基因组中的识别序列特异性的工程化大范围核酸酶
DK17804977.1T DK3526323T5 (da) 2016-10-14 2017-10-13 Modificerede meganucleaser der er specifikke for en genkendelsessekvens i hepatitis b virusgenomet
FIEP17804977.1T FI3526323T3 (fi) 2016-10-14 2017-10-13 Hepatiitti B -viruksen genomissa oleville tunnistussekvensseille spesifisiä muokattuja meganukleaaseja
SG11201903042VA SG11201903042VA (en) 2016-10-14 2017-10-13 Engineered meganucleases specific for recognition sequences in the hepatitis b virus genome
CN202311305067.1A CN117402852A (zh) 2016-10-14 2017-10-13 对乙肝病毒基因组中的识别序列特异性的工程化大范围核酸酶
PE2019000817A PE20191353A1 (es) 2016-10-14 2017-10-13 Meganucleasas disenadas especificamente para el reconocimiento de secuencias en el genoma del virus de la hepatitis b
KR1020237000425A KR20230010826A (ko) 2016-10-14 2017-10-13 B형 간염 바이러스 게놈 내의 인식 서열에 대해 특이적인 조작된 메가뉴클레아제
US16/342,169 US10662416B2 (en) 2016-10-14 2017-10-13 Engineered meganucleases specific for recognition sequences in the hepatitis B virus genome
KR1020217029958A KR20210118240A (ko) 2016-10-14 2017-10-13 B형 간염 바이러스 게놈 내의 인식 서열에 대해 특이적인 조작된 메가뉴클레아제
BR112019007450-3A BR112019007450A2 (pt) 2016-10-14 2017-10-13 meganucleases modificadas específicas para sequências de reconhecimento no genoma do vírus da hepatite b
EP17804977.1A EP3526323B1 (en) 2016-10-14 2017-10-13 Engineered meganucleases specific for recognition sequences in the hepatitis b virus genome
CR20190181A CR20190181A (es) 2016-10-14 2017-10-13 Meganucleasas diseñadas específicamente para el reconocimiento de secuencias en el genoma del virus de la hepatitis b.
AU2017342536A AU2017342536A1 (en) 2016-10-14 2017-10-13 Engineered meganucleases specific for recognition sequences in the Hepatitis B virus genome
JP2019520125A JP6811857B2 (ja) 2016-10-14 2017-10-13 Ｂ型肝炎ウイルスゲノムの認識配列に特異的な遺伝子操作メガヌクレアーゼ
CA3040143A CA3040143A1 (en) 2016-10-14 2017-10-13 Engineered meganucleases specific for recognition sequences in the hepatitis b virus genome
KR1020247026203A KR20240123417A (ko) 2016-10-14 2017-10-13 B형 간염 바이러스 게놈 내의 인식 서열에 대해 특이적인 조작된 메가뉴클레아제
MX2019004349A MX2019004349A (es) 2016-10-14 2017-10-13 Meganucleasas manipuladas específicamente para el reconocimiento de secuencias en el genoma del virus de la hepatitis b.
IL265921A IL265921B2 (en) 2016-10-14 2017-10-13 Engineered meganucleases specific for recognition sequences in the hepatitis b virus genome
PH12019500788A PH12019500788A1 (en) 2016-10-14 2019-04-11 Engineered meganucleases specific for recgonition sequences in the hepatitis b virus genome
CONC2019/0003675A CO2019003675A2 (es) 2016-10-14 2019-04-12 Meganucleasas diseñadas especificamente para el reconocimiento de secuencias en el genoma del virus de la hepatitis b.
US16/852,296 US10851358B2 (en) 2016-10-14 2020-04-17 Engineered meganucleases specific for recognition sequences in the hepatitis B virus genome
US17/083,171 US11274285B2 (en) 2016-10-14 2020-10-28 Engineered meganucleases specific for recognition sequences in the Hepatitis B virus genome
US17/665,265 US20220243187A1 (en) 2016-10-14 2022-02-04 Engineered meganucleases specific for recognition sequences in the hepatitis b virus genome
AU2023263542A AU2023263542A1 (en) 2016-10-14 2023-11-10 Engineered meganucleases specific for recognition sequences in the Hepatitis B virus genome
US18/424,277 US20240271111A1 (en) 2016-10-14 2024-01-26 Engineered meganucleases specific for recognition sequences in the hepatitis b virus genome
US19/029,948 US20250154486A1 (en) 2016-10-14 2025-01-17 Engineered meganucleases specific for recognition sequences in the hepatitis b virus genome

Applications Claiming Priority (8)

Application Number Priority Date Filing Date Title
US201662408356P 2016-10-14 2016-10-14
US62/408,356 2016-10-14
US201762452506P 2017-01-31 2017-01-31
US62/452,506 2017-01-31
US201762527159P 2017-06-30 2017-06-30
US201762527196P 2017-06-30 2017-06-30
US62/527,159 2017-06-30
US62/527,196 2017-06-30

Related Child Applications (2)

Application Number Title Priority Date Filing Date
US16/342,169 A-371-Of-International US10662416B2 (en) 2016-10-14 2017-10-13 Engineered meganucleases specific for recognition sequences in the hepatitis B virus genome
US16/852,296 Continuation US10851358B2 (en) 2016-10-14 2020-04-17 Engineered meganucleases specific for recognition sequences in the hepatitis B virus genome

Publications (2)

Publication Number Publication Date
WO2018071849A2 true WO2018071849A2 (en) 2018-04-19
WO2018071849A3 WO2018071849A3 (en) 2018-05-24

Family

ID=60480360

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US2017/056638 Ceased WO2018071849A2 (en) 2016-10-14 2017-10-13 Engineered meganucleases specific for recognition sequences in the hepatitis b virus genome

Country Status (21)

Country Link
US (6) US10662416B2 (OSRAM)
EP (2) EP3526323B1 (OSRAM)
JP (5) JP6811857B2 (OSRAM)
KR (4) KR20240123417A (OSRAM)
CN (2) CN117402852A (OSRAM)
AU (2) AU2017342536A1 (OSRAM)
BR (1) BR112019007450A2 (OSRAM)
CA (1) CA3040143A1 (OSRAM)
CL (1) CL2019000993A1 (OSRAM)
CO (1) CO2019003675A2 (OSRAM)
CR (1) CR20190181A (OSRAM)
DK (1) DK3526323T5 (OSRAM)
DO (1) DOP2019000097A (OSRAM)
FI (1) FI3526323T3 (OSRAM)
IL (3) IL317537A (OSRAM)
MA (1) MA46535A (OSRAM)
MX (2) MX2019004349A (OSRAM)
PE (1) PE20191353A1 (OSRAM)
PH (1) PH12019500788A1 (OSRAM)
SG (2) SG10201914029RA (OSRAM)
WO (1) WO2018071849A2 (OSRAM)

Cited By (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2019200247A1 (en) * 2018-04-12 2019-10-17 Precision Biosciences, Inc. Optimized engineered meganucleases having specificity for a recognition sequence in the hepatitis b virus genome
US10662416B2 (en) 2016-10-14 2020-05-26 Precision Biosciences, Inc. Engineered meganucleases specific for recognition sequences in the hepatitis B virus genome
WO2020227534A1 (en) 2019-05-07 2020-11-12 Precision Biosciences, Inc. Optimization of engineered meganucleases for recognition sequences
WO2021231259A1 (en) 2020-05-11 2021-11-18 Precision Biosciences, Inc. Self-limiting viral vectors encoding nucleases
US12390538B2 (en) 2023-05-15 2025-08-19 Nchroma Bio, Inc. Compositions and methods for epigenetic regulation of HBV gene expression
US12410418B2 (en) 2019-12-06 2025-09-09 Precision Biosciences, Inc. Optimized engineered meganucleases having specificity for a recognition sequence in the Hepatitis B virus genome

Families Citing this family (15)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
HRP20241379T1 (hr) 2019-09-30 2024-12-20 Gilead Sciences, Inc. Cjepiva za hbv i postupci za liječenje hbv
TWI845826B (zh) 2020-03-20 2024-06-21 美商基利科學股份有限公司 4'-c-經取代-2-鹵基-2'-去氧腺苷核苷之前藥及其製造與使用方法
TWI815194B (zh) 2020-10-22 2023-09-11 美商基利科學股份有限公司 介白素2-Fc融合蛋白及使用方法
IL317538A (en) * 2020-11-12 2025-02-01 Prec Biosciences Inc Engineered nucleases with specificity for recognition sequences in the dystrophin gene
TW202348237A (zh) 2021-05-13 2023-12-16 美商基利科學股份有限公司 TLR8調節化合物及抗HBV siRNA療法之組合
WO2024124044A1 (en) 2022-12-07 2024-06-13 The Brigham And Women’S Hospital, Inc. Compositions and methods targeting sat1 for enhancing anti¬ tumor immunity during tumor progression
WO2024192141A1 (en) 2023-03-13 2024-09-19 Dana-Farber Cancer Institute, Inc. Treatment of cancers having a drug-resistant mesenchymal cell state
WO2024226838A2 (en) 2023-04-25 2024-10-31 The Brigham And Women's Hospital, Inc. Treatment of autoimmune diseases having a pathogenic t cell state
WO2025049788A1 (en) 2023-08-29 2025-03-06 The Broad Institute, Inc. Optical genetic screens of intracellular and intercellular transcriptional circuits with perturb-fish
WO2025096916A1 (en) 2023-11-03 2025-05-08 The Broad Institute, Inc. Multi-site editing in living cells
WO2025129158A1 (en) 2023-12-15 2025-06-19 The Broad Institute, Inc. Engineered arc delivery vesicles and uses thereof
WO2025240246A1 (en) 2024-05-13 2025-11-20 Gilead Sciences, Inc. Combination therapies with ribavirin
WO2025240242A1 (en) 2024-05-13 2025-11-20 Gilead Sciences, Inc. Combination therapies with ribavirin
US20250345389A1 (en) 2024-05-13 2025-11-13 Gilead Sciences, Inc. Combination therapies
US20250345390A1 (en) 2024-05-13 2025-11-13 Gilead Sciences, Inc. Combination therapies

Citations (12)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4873192A (en) 1987-02-17 1989-10-10 The United States Of America As Represented By The Department Of Health And Human Services Process for site specific mutagenesis without phenotypic selection
US6015832A (en) 1997-12-31 2000-01-18 The Regents Of The University Of Michigan Methods of inactivating bacteria including bacterial spores
WO2002012514A2 (en) 2000-08-09 2002-02-14 Nsgene A/S Jet, an artificial promoter for gene expression
US20020045667A1 (en) 1999-04-28 2002-04-18 The Regents Of The University Of Michigan Non-toxic antimicrobial compositions and methods of use
US6506803B1 (en) 1999-04-28 2003-01-14 Regents Of The University Of Michigan Methods of preventing and treating microbial infections
US6635676B2 (en) 1999-04-28 2003-10-21 Regents Of The University Of Michigan Non-toxic antimicrobial compositions and methods of use
US20040043041A1 (en) 1999-04-28 2004-03-04 The Regents Of The University Of Michigan Antimicrobial compositions and methods of use
WO2007047859A2 (en) 2005-10-18 2007-04-26 Precision Biosciences Rationally-designed meganucleases with altered sequence specificity and dna-binding affinity
US7404969B2 (en) 2005-02-14 2008-07-29 Sirna Therapeutics, Inc. Lipid nanoparticle based compositions and methods for the delivery of biologically active molecules
WO2009059195A2 (en) 2007-10-31 2009-05-07 Precision Biosciences Rationally-designed single-chain meganucleases with non-palindromic recognition sequences
WO2010136841A2 (en) 2009-05-26 2010-12-02 Cellectis Meganuclease variants cleaving the genome of a non-genomically integrating virus and uses thereof
WO2012167192A2 (en) 2011-06-01 2012-12-06 Precision Biosciences, Inc. Methods and products for producing engineered mammalian cell lines with amplified transgenes

Family Cites Families (260)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CA2124928C (en) 1991-12-23 2003-06-17 Bruce D. Irvine Hbv amplifier probes for use in solution phase sandwich hybridization assays
EP1288296A3 (en) * 1992-05-11 2003-03-12 Ribozyme Pharmaceuticals, Inc. Method and reagent for inhibiting HBV viral replication
CN1204248C (zh) * 2002-02-05 2005-06-01 中国人民解放军第四军医大学 治疗乙肝病毒感染的靶向核糖核酸酶的制备工艺
US7074596B2 (en) 2002-03-25 2006-07-11 Board Of Supervisors Of Louisiana State University And Agricultural And Mechanical College Synthesis and use of anti-reverse mRNA cap analogues
TWI382019B (zh) 2005-08-19 2013-01-11 Array Biopharma Inc 作為類鐸受體（ｔｏｌｌ-ｌｉｋｅ ｒｅｃｅｐｔｏｒ）調節劑之胺基二氮雜呯
TWI404537B (zh) 2005-08-19 2013-08-11 Array Biopharma Inc 作為類鐸受體（ｔｏｌｌ-ｌｉｋｅ ｒｅｃｅｐｔｏｒ）調節劑之８-經取代苯并氮雜呯
ES2937245T3 (es) 2005-08-23 2023-03-27 Univ Pennsylvania ARN que contiene nucleósidos modificados y métodos de uso del mismo
JP4235837B2 (ja) 2006-04-04 2009-03-11 セイコーエプソン株式会社 粒状性の予測、プロファイルの作成および印刷装置
AU2007269557B2 (en) 2006-07-07 2013-11-07 Gilead Sciences, Inc. Modulators of toll-like receptor 7
WO2009001159A1 (en) 2007-06-25 2008-12-31 Cellectis Method for enhancing the cleavage activity of i-crei derived meganucleases
US8748373B2 (en) * 2007-02-21 2014-06-10 Fox Chase Cancer Center Hepatitis B virus compositions and methods of use
EA021463B1 (ru) 2007-06-29 2015-06-30 Джилид Сайэнс, Инк. Пуриновые производные и их применение в качестве модуляторов толл-подобного рецептора 7
CA2709875C (en) 2008-01-02 2019-07-16 Tekmira Pharmaceuticals Corporation Improved compositions and methods for the delivery of nucleic acids
SG10201805844QA (en) 2008-07-08 2018-08-30 Incyte Holdings Corp 1,2,5-oxadiazoles as inhibitors of indoleamine 2,3-dioxygenase
PT2313111E (pt) 2008-08-01 2013-12-05 Ventirx Pharmaceuticals Inc Formulações de agonista de receptor do tipo toll e seus usos
TW201639852A (zh) 2008-12-09 2016-11-16 吉李德科學股份有限公司 用於製備可用作類鐸受體調節劑之化合物的中間體化合物
WO2010136981A2 (en) 2009-05-26 2010-12-02 Cellectis Meganuclease variants cleaving the genome of a pathogenic non-integrating virus and uses thereof
WO2011022509A2 (en) 2009-08-18 2011-02-24 Ventirx Pharmaceuticals, Inc. Substituted benzoazepines as toll-like receptor modulators
PL2467377T3 (pl) 2009-08-18 2017-10-31 Ventirx Pharmaceuticals Inc Podstawione benzoazepiny jako modulatory receptora toll-podobnego
WO2011049825A1 (en) 2009-10-22 2011-04-28 Gilead Sciences, Inc. Derivatives of purine or deazapurine useful for the treatment of (inter alia) viral infections
US9186337B2 (en) 2010-02-24 2015-11-17 Oryzon Genomics S.A. Lysine demethylase inhibitors for diseases and disorders associated with Hepadnaviridae
MY169745A (en) 2010-05-31 2019-05-14 Ono Pharmaceutical Co Purinone derivative
US8907053B2 (en) 2010-06-25 2014-12-09 Aurigene Discovery Technologies Limited Immunosuppression modulating compounds
BR112013007678A2 (pt) 2010-10-01 2017-07-04 Ventirx Pharmaceuticals Inc método para tratamento de doenças alérgicas
MX340290B (es) 2010-10-01 2016-07-04 Ventirx Pharmaceuticals Inc Uso terapéutico de un agonista de receptor tipo toll y terapia de combinación.
AR084217A1 (es) 2010-12-10 2013-05-02 Gilead Sciences Inc Inhibidores macrociclicos de virus flaviviridae
BR112013017947A2 (pt) 2011-01-12 2018-12-18 Array Biopharma Inc benzoazepinas substituídas como moduladores de receptor toll-like
US9718796B2 (en) 2011-01-12 2017-08-01 Ventirx Pharmaceuticals, Inc. Substituted benzoazepines as toll-like receptor modulators
CN103476426B (zh) 2011-02-12 2021-08-10 全球免疫股份有限公司 用于慢性乙型肝炎病毒感染的基于酵母的治疗剂
LT3590928T (lt) 2011-04-08 2021-08-25 Janssen Sciences Ireland Unlimited Company Pirimidino dariniai, skirti virusinės infekcijos gydymui
US8916575B2 (en) 2011-05-18 2014-12-23 Janssen R&D Ireland Quinazoline derivatives for the treatment of viral infections and further diseases
WO2012168944A1 (en) 2011-06-08 2012-12-13 Aurigene Discovery Technologies Limited Therapeutic compounds for immunomodulation
TW202244278A (zh) * 2011-06-30 2022-11-16 美商艾羅海德製藥公司 用於抑制ｂ型肝炎病毒基因表現之組合物及方法
US20140120106A1 (en) * 2011-07-06 2014-05-01 Yale University Stimulation of Arterial Collateral Growth and Lymphogenesis
NZ626750A (en) 2011-11-29 2015-08-28 Ono Pharmaceutical Co Purinone derivative hydrochloride
KR101699822B1 (ko) 2011-12-21 2017-01-25 노비라 테라퓨틱스, 인코포레이티드 B형 간염의 항바이러스성 제제
BR112014019699B1 (pt) 2012-02-08 2021-12-07 Janssen Sciences Ireland Uc Derivados de piperidino-pirimidina, seu uso no tratamento de infecções virais e composição farmacêutica que os compreende
CN104159911A (zh) 2012-03-07 2014-11-19 奥瑞基尼探索技术有限公司 作为免疫调节剂的模拟肽化合物
RU2014143443A (ru) 2012-03-29 2016-05-20 Ориджин Дискавери Текнолоджиз Лимитед Иммуномодулирующие циклические соединения
US20130267517A1 (en) 2012-03-31 2013-10-10 Hoffmann-La Roche Inc. Novel 4-methyl-dihydropyrimidines for the treatment and prophylaxis of hepatitis b virus infection
MX2014011749A (es) 2012-03-31 2015-01-22 Hoffmann La Roche 4-metil-dihidropirimidinas novedosas para el tratamiento y la prolifaxis de la infeccion por el virus de la hepatitis b.
WO2013159109A1 (en) 2012-04-20 2013-10-24 Isis Pharmaceuticals, Inc. Modulation of hepatitis b virus (hbv) expression
KR102702287B1 (ko) 2012-05-15 2024-09-04 브리스톨-마이어스 스큅 컴퍼니 Pd-1/pd-l1 신호전달을 방해하는 것에 의한 암 면역요법
WO2013185103A1 (en) 2012-06-08 2013-12-12 Gilead Sciences, Inc. Macrocyclic inhibitors of flaviviridae viruses
NZ724616A (en) 2012-06-08 2018-06-29 Gilead Sciences Inc Macrocyclic inhibitors of flaviviridae viruses
AR091279A1 (es) 2012-06-08 2015-01-21 Gilead Sciences Inc Inhibidores macrociclicos de virus flaviviridae
BR112015002524B1 (pt) 2012-08-10 2021-11-03 Janssen Sciences Ireland Uc Derivados de alquilpirimidina, composição farmacêutica que os compreende e uso dos mesmos
AR092269A1 (es) 2012-08-28 2015-04-08 Janssen R&D Ireland Sulfamoilarilamidas y su uso como medicamentos para el tratamiento de la hepatitis b
CN104797561B (zh) 2012-08-28 2017-03-01 爱尔兰詹森科学公司 稠合二环的氨磺酰基衍生物及其作为药物用于治疗乙型肝炎的用途
EP2892893B2 (en) 2012-09-10 2019-10-16 F.Hoffmann-La Roche Ag 6-amino acid heteroaryldihydropyrimidines for the treatment and prophylaxis of hepatitis b virus infection
KR102160320B1 (ko) 2012-10-02 2020-09-28 에피테라퓨틱스 에이피에스 히스톤 탈메틸효소의 저해제
SI2906563T1 (en) 2012-10-10 2018-06-29 Janssen Sciences Ireland Uc Derivatives of pyrrolo (3,2-d) pyrimidine for the treatment of viral infections and other diseases
MY171115A (en) 2012-11-16 2019-09-26 Janssen Sciences Ireland Uc Heterocyclic substituted 2-amino-quinazoline derivatives for the treatment of viral infections
ES2834959T3 (es) 2012-12-06 2021-06-21 Celgene Quanticel Res Inc Inhibidores de histona desmetilasa
PT2934145T (pt) 2012-12-19 2018-02-13 Celgene Quanticel Res Inc Inibidores de histona demetilase
PE20151417A1 (es) 2012-12-21 2015-10-10 Quanticel Pharmaceuticals Inc Inhibidores de histona desmetilasa
UA118751C2 (uk) 2013-02-21 2019-03-11 ЯНССЕН САЙЄНСІЗ АЙРЛЕНД ЮСі Похідні 2-амінопіримідину для лікування вірусних інфекцій
SI2961736T1 (en) 2013-02-27 2018-06-29 Gilead Sciences, Inc. Histone demethylase inhibitors
SI2961732T1 (sl) 2013-02-28 2017-07-31 Janssen Sciences Ireland Uc Sulfamoil-arilamidi in njihova uporaba kot zdravila za zdravljenje hepatitisa B
US8993771B2 (en) 2013-03-12 2015-03-31 Novira Therapeutics, Inc. Hepatitis B antiviral agents
EP2968282B1 (en) 2013-03-12 2018-05-09 Celgene Quanticel Research, Inc. Histone dementhylase inhibitors
US10035801B2 (en) 2013-03-13 2018-07-31 Genentech, Inc. Pyrazolo compounds and uses thereof
US9133166B2 (en) 2013-03-14 2015-09-15 Quanticel Pharmaceuticals, Inc. Histone demethylase inhibitors
US9308236B2 (en) 2013-03-15 2016-04-12 Bristol-Myers Squibb Company Macrocyclic inhibitors of the PD-1/PD-L1 and CD80(B7-1)/PD-L1 protein/protein interactions
SI2970211T1 (sl) 2013-03-15 2017-12-29 Quanticel Pharmaceuticals Inc. Inhibitorji histon demetilaze
HUE033542T2 (en) 2013-04-03 2017-12-28 Janssen Sciences Ireland Uc Their use as medicaments for the treatment of N-phenylcarboxamide derivatives and hepatitis B
JP2016518140A (ja) 2013-05-03 2016-06-23 ザ リージェンツ オブ ザ ユニバーシティ オブ カリフォルニア Ｉ型インターフェロンの環状ジヌクレオチド誘導法
US10160743B2 (en) 2013-05-17 2018-12-25 Janssen Sciences Ireland Uc Sulphamoylthiophenamide derivatives and the use thereof as medicaments for the treatment of hepatitis B
JO3603B1 (ar) 2013-05-17 2020-07-05 Janssen Sciences Ireland Uc مشتقات سلفامويل بيرولاميد واستخدامها كادوية لمعالجة التهاب الكبد نوع بي
CN105209470B (zh) 2013-05-17 2018-02-06 豪夫迈·罗氏有限公司 用于治疗和预防乙型肝炎病毒感染的6‑桥连的杂芳基二氢嘧啶
SG10201805033XA (en) 2013-07-25 2018-07-30 Janssen Sciences Ireland Uc Glyoxamide substituted pyrrolamide derivatives and the use thereof as medicaments for the treatment of hepatitis b
ES2836881T3 (es) 2013-07-30 2021-06-28 Janssen Sciences Ireland Unlimited Co Derivados de tieno[3,2-d]pirimidinas para el tratamiento de infecciones virales
JP2016527303A (ja) 2013-08-05 2016-09-08 ケンブリッジ エンタープライズ リミテッド がん免疫療法におけるｃｘｃｒ４シグナル伝達の阻害
WO2015023958A1 (en) 2013-08-15 2015-02-19 The University Of Kansas Toll-like receptor agonists
AU2014315457B2 (en) 2013-09-04 2018-05-10 Bristol-Myers Squibb Company Compounds useful as immunomodulators
JP2016532711A (ja) 2013-09-06 2016-10-20 オーリジーン ディスカバリー テクノロジーズ リミテッドＡｕｒｉｇｅｎｅ Ｄｉｓｃｏｖｅｒｙ Ｔｅｃｈｎｏｌｏｇｉｅｓ Ｌｉｍｉｔｅｄ 免疫調節剤としての１，３，４−オキサジアゾール及び１，３，４−チアジアゾールの誘導体
JP6521977B2 (ja) 2013-09-06 2019-05-29 オーリジーン ディスカバリー テクノロジーズ リミテッドＡｕｒｉｇｅｎｅ Ｄｉｓｃｏｖｅｒｙ Ｔｅｃｈｎｏｌｏｇｉｅｓ Ｌｉｍｉｔｅｄ 免疫調節剤としての１，２，４−オキサジアゾール誘導体
KR20160075506A (ko) 2013-09-06 2016-06-29 오리진 디스커버리 테크놀로지스 리미티드 면역조절제로서 사이클릭 펩티도미메틱 화합물
WO2015036927A1 (en) 2013-09-10 2015-03-19 Aurigene Discovery Technologies Limited Immunomodulating peptidomimetic derivatives
DK3043865T3 (da) 2013-09-11 2021-02-01 Univ Claude Bernard Lyon Fremgangsmåder og farmaceutiske sammensætningr til behandlingen af hepatitis b-virusinfektion
WO2015044900A1 (en) 2013-09-27 2015-04-02 Aurigene Discovery Technologies Limited Therapeutic immunomodulating compounds
WO2015057655A1 (en) 2013-10-14 2015-04-23 Eisai R&D Management Co., Ltd. Selectively substituted quinoline compounds
MD4635C1 (ro) 2013-10-14 2020-01-31 Eisai R&D Management Co., Ltd. Compuşi de chinolină substituiţi selectiv
JP6452119B2 (ja) 2013-10-23 2019-01-16 ヤンセン・サイエンシズ・アイルランド・アンリミテッド・カンパニー カルボキサミド誘導体およびｂ型肝炎の処置のための医薬品としてのその使用
KR20160127714A (ko) 2013-11-14 2016-11-04 노비라 테라퓨틱스, 인코포레이티드 아제판 유도체 및 b형 간염 감염의 치료 방법
KR20160089530A (ko) * 2013-12-12 2016-07-27 더 브로드 인스티튜트, 인코퍼레이티드 Ｈｂｖ 및 바이러스 질병 및 질환을 위한 ｃｒｉｓｐｒ­ｃａｓ 시스템 및 조성물의 전달，용도 및 치료적 적용
WO2015088045A1 (en) 2013-12-13 2015-06-18 Takeda Pharmaceutical Company Limited Pyrrolo[3,2-c]pyridine derivatives as tlr inhibitors
US10654807B2 (en) 2013-12-20 2020-05-19 The University Of Kansas Toll-like receptor 8 agonists
US9181288B2 (en) 2014-01-16 2015-11-10 Novira Therapeutics, Inc. Azepane derivatives and methods of treating hepatitis B infections
US9169212B2 (en) 2014-01-16 2015-10-27 Novira Therapeutics, Inc. Azepane derivatives and methods of treating hepatitis B infections
CA2931329A1 (en) 2014-01-30 2015-08-06 F. Hoffmann-La Roche Ag Novel dihydroquinolizinones for the treatment and prophylaxis of hepatitis b virus infection
JP2017508785A (ja) 2014-02-04 2017-03-30 インサイト・コーポレイションＩｎｃｙｔｅ Ｃｏｒｐｏｒａｔｉｏｎ 癌を治療するためのｐｄ−１アンタゴニストおよびｉｄｏ１阻害剤の組み合わせ
US11078193B2 (en) 2014-02-06 2021-08-03 Janssen Sciences Ireland Uc Sulphamoylpyrrolamide derivatives and the use thereof as medicaments for the treatment of hepatitis B
KR20220127940A (ko) 2014-03-05 2022-09-20 브리스톨-마이어스 스큅 컴퍼니 항-pd-1 항체 및 또 다른 항암제의 조합물을 이용한 신장암의 치료
KR101926243B1 (ko) 2014-03-07 2018-12-06 에프. 호프만-라 로슈 아게 B형 간염 바이러스 감염의 치료 및 예방을 위한 6-융합된 헤테로아릴다이하이드로피리미딘
US9400280B2 (en) 2014-03-27 2016-07-26 Novira Therapeutics, Inc. Piperidine derivatives and methods of treating hepatitis B infections
US9850225B2 (en) 2014-04-14 2017-12-26 Bristol-Myers Squibb Company Compounds useful as immunomodulators
SI3134402T1 (sl) 2014-04-22 2020-08-31 F. Hoffmann-La Roche Ag 4-amino-imidazokinolinske spojine
AU2015253225B2 (en) 2014-05-01 2017-04-06 Novartis Ag Compounds and compositions as Toll-Like Receptor 7 agonists
MX362341B (es) 2014-05-01 2019-01-11 Novartis Ag Compuestos y composiciones como agonistas del receptor tipo toll 7.
CN106459032B (zh) 2014-05-13 2019-04-05 豪夫迈·罗氏有限公司 治疗和预防乙型肝炎病毒感染的新的二氢喹嗪酮类
CN106572993B (zh) 2014-05-23 2019-07-16 卫材R&D管理有限公司 Ep4拮抗剂在制备治疗癌症的药物中的应用
AU2015266770A1 (en) 2014-05-30 2016-12-08 The Board Of Trustees Of The Leland Stanford Junior University Compositions and methods of delivering treatments for latent viral infections
CN106535884A (zh) 2014-06-06 2017-03-22 弗雷克萨斯生物科学公司 免疫调节剂
WO2016012470A1 (en) 2014-07-25 2016-01-28 F. Hoffmann-La Roche Ag New amorphous and crystalline forms of (3s)-4-[[(4r)-4-(2-chloro-4-fluoro-phenyl)-5-methoxycarbonyl-2-thiazol-2-yl-1, 4-dihydropyrimidin-6-yl]methyl]morpholine-3-carboxylic acid
AU2015296214B2 (en) 2014-08-01 2019-11-07 Board Of Regents, The University Of Texas System Methods and therapeutic combinations for treating tumors
JP6506836B2 (ja) 2014-08-14 2019-04-24 エフ．ホフマン−ラ ロシュ アーゲーＦ． Ｈｏｆｆｍａｎｎ−Ｌａ Ｒｏｃｈｅ Ａｋｔｉｅｎｇｅｓｅｌｌｓｃｈａｆｔ Ｂ型肝炎ウイルス感染症の処置および予防のための新規ピリダゾンおよびトリアジノン
SI3190113T1 (sl) 2014-08-15 2021-09-30 Chia Tai Tianqing Pharmaceutical Group Co., Ltd. Pirolopirimidinske spojine, ki se uporabljajo kot agonist TLR7
US20170275287A1 (en) 2014-08-22 2017-09-28 Janus Biotherapeutics, Inc. Novel n2, n4, n7, 6-tetrasubstituted pteridine-2,4,7-triamine and 2, 4, 6, 7-tetrasubstituted pteridine compounds and methods of synthesis and use thereof
MX2017002451A (es) 2014-08-27 2017-05-23 Gilead Sciences Inc Compuestos y metodos para inhibir histona desmetilasas.
US9884866B2 (en) 2014-09-08 2018-02-06 Regents Of The University Of Minnesota Immunomodulators and immunomodulator conjugates
EP3191113B1 (en) 2014-09-11 2019-11-06 Bristol-Myers Squibb Company Macrocyclic inhibitors of the pd-1/pd-l1 and cd80 (b7-1)/pd-l1 protein/protein interactions
US9732119B2 (en) 2014-10-10 2017-08-15 Bristol-Myers Squibb Company Immunomodulators
CN107912040B (zh) 2014-10-10 2021-04-06 基因泰克公司 作为组蛋白脱甲基酶抑制剂的吡咯烷酰胺化合物
EP3204392A1 (en) 2014-10-11 2017-08-16 F. Hoffmann-La Roche AG Compounds for use in the treatment of infectious diseases
US9637485B2 (en) 2014-11-03 2017-05-02 Hoffmann-La Roche Inc. 6,7-dihydrobenzo[a]quinolizin-2-one derivatives for the treatment and prophylaxis of hepatitis B virus infection
BR112017008809A2 (pt) 2014-11-05 2017-12-19 Flexus Biosciences Inc agentes imunorreguladores
UY36390A (es) 2014-11-05 2016-06-01 Flexus Biosciences Inc Compuestos moduladores de la enzima indolamina 2,3-dioxigenasa (ido), sus métodos de síntesis y composiciones farmacéuticas que los contienen
MX2017006302A (es) 2014-11-13 2018-02-16 Glaxosmithkline Biologicals Sa Derivados de adenina que son utiles en el tratamiento de enfermedades alergicas u otras afecciones inflamatorias.
US9856292B2 (en) 2014-11-14 2018-01-02 Bristol-Myers Squibb Company Immunomodulators
SG11201704512PA (en) 2014-12-08 2017-07-28 Hoffmann La Roche 3-substituted 5-amino-6h-thiazolo[4,5-d]pyrimidine-2,7-dione compounds for the treatment and prophylaxis of virus infection
EP3233835B1 (en) 2014-12-18 2019-01-23 F.Hoffmann-La Roche Ag Benzazepine sulfonamide compounds
US9861680B2 (en) 2014-12-18 2018-01-09 Bristol-Myers Squibb Company Immunomodulators
US9944678B2 (en) 2014-12-19 2018-04-17 Bristol-Myers Squibb Company Immunomodulators
US9676793B2 (en) 2014-12-23 2017-06-13 Hoffmann-Laroche Inc. Co-crystals of 5-amino-2-oxothiazolo[4,5-d]pyrimidin-3(2H)-yl-5-hydroxymethyl tetrahydrofuran-3-yl acetate and methods for preparing and using the same
AR103222A1 (es) 2014-12-23 2017-04-26 Hoffmann La Roche Procedimiento para la preparación de análogos de 4-fenil-5-alcoxicarbonil-2-tiazol-2-il-1,4-dihidropirimidina
CN105732635A (zh) 2014-12-29 2016-07-06 南京明德新药研发股份有限公司 一类Toll样受体7激动剂
JP6506845B2 (ja) 2014-12-30 2019-04-24 エフ．ホフマン−ラ ロシュ アーゲーＦ． Ｈｏｆｆｍａｎｎ−Ｌａ Ｒｏｃｈｅ Ａｋｔｉｅｎｇｅｓｅｌｌｓｃｈａｆｔ Ｂ型肝炎ウイルス感染症の治療及び予防のための新規テトラヒドロピリドピリミジン類及びテトラヒドロピリドピリジン類
WO2016109684A2 (en) 2014-12-30 2016-07-07 Novira Therapeutics, Inc. Derivatives and methods of treating hepatitis b infections
JP2018504891A (ja) 2014-12-31 2018-02-22 エフ．ホフマン−ラ ロシュ アーゲーＦ． Ｈｏｆｆｍａｎｎ−Ｌａ Ｒｏｃｈｅ Ａｋｔｉｅｎｇｅｓｅｌｌｓｃｈａｆｔ リアルタイムＰＣＲによる細胞溶解物からのＨＢＶ ｃｃｃＤＮＡ定量化のための新規ハイスループット法
MA41338B1 (fr) 2015-01-16 2019-07-31 Hoffmann La Roche Composés de pyrazine pour le traitement de maladies infectieuses
EP3250685A1 (en) 2015-01-27 2017-12-06 F. Hoffmann-La Roche AG Recombinant hbv cccdna, the method to generate thereof and the use thereof
US20160222060A1 (en) 2015-02-04 2016-08-04 Bristol-Myers Squibb Company Immunomodulators
HK1244281B (zh) 2015-02-11 2020-02-07 F. Hoffmann-La Roche Ag 治疗和预防乙型肝炎病毒感染的2-氧代-6，7-二氢苯并[a]喹嗪-3-甲酸衍生物
EP3722297A1 (en) 2015-03-04 2020-10-14 Gilead Sciences, Inc. Toll-like receptor modulating 4,6-diamino-pyrido[3,2-d]pyrimidine compounds
SI3265458T1 (sl) 2015-03-06 2019-03-29 F. Hoffmann-La Roche Ag Benzazepin dikarboksamidne spojine
BR112017019305A2 (pt) 2015-03-10 2018-05-08 Aurigene Discovery Technologies Limited compostos cíclicos terapêuticos como imunomoduladores
MX2017011611A (es) 2015-03-10 2018-03-23 Aurigene Discovery Tech Ltd Compuestos de tiadiazol y 1,3,4-oxadiazol 3-sustituidos como inmunomoduladores.
SG11201706902SA (en) 2015-03-10 2017-09-28 Aurigene Discovery Tech Ltd 3-substituted-1,2,4-oxadiazole and thiadiazole compounds as immunomodulators
SMT202200163T1 (it) 2015-03-10 2022-05-12 Aurigene Discovery Tech Ltd Composti di 1,2,4-0ssadiazolo e tiadiazolo come immunomodulatori
EA201791629A1 (ru) 2015-03-10 2018-02-28 Ауриджен Дискавери Текнолоджис Лимитед 1,3,4-оксадиазольные и тиадиазольные соединения в качестве иммуномодуляторов
US9809625B2 (en) 2015-03-18 2017-11-07 Bristol-Myers Squibb Company Immunomodulators
US10442788B2 (en) 2015-04-01 2019-10-15 Enanta Pharmaceuticals, Inc. Hepatitis B antiviral agents
US10273228B2 (en) 2015-04-17 2019-04-30 Indiana University Research And Technology Corporation Hepatitis B viral assembly effectors
EP3292120B1 (en) 2015-05-04 2019-06-19 H. Hoffnabb-La Roche Ag Tetrahydropyridopyrimidines and tetrahydropyridopyridines as inhibitors of hbsag (hbv surface antigen) and hbv dna production for the treatment of hepatitis b virus infections
WO2016180743A1 (en) 2015-05-12 2016-11-17 F. Hoffmann-La Roche Ag Novel substituted aminothiazolopyrimidinedione for the treatment and prophylaxis of virus infection
US10196701B2 (en) 2015-06-01 2019-02-05 The Penn State Research Foundation Hepatitis B virus capsid assembly
EP3317289B1 (en) 2015-06-30 2021-10-27 F. Hoffmann-La Roche AG Novel substituted aminothiazolopyrimidinedione for the treatment and prophylaxis of virus infection
GB201511477D0 (en) 2015-06-30 2015-08-12 Redx Pharma Plc Antiviral compounds
US10875876B2 (en) 2015-07-02 2020-12-29 Janssen Sciences Ireland Uc Cyclized sulfamoylarylamide derivatives and the use thereof as medicaments for the treatment of hepatitis B
WO2017007701A1 (en) 2015-07-07 2017-01-12 Merck Sharp & Dohme Corp. Antiviral phosphodiamide compounds
JP6598974B2 (ja) 2015-07-21 2019-10-30 エフ．ホフマン−ラ ロシュ アーゲー Ｂ型肝炎ウイルス感染症の治療および予防のための新規な三環式４−ピリドン−３−カルボン酸誘導体
WO2017016960A1 (en) 2015-07-24 2017-02-02 F. Hoffmann-La Roche Ag Process for the preparation of (6s)-6-alkyl-10-alkoxy-9-(substituted alkoxy)-2-oxo-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid analogues
CN107820496B (zh) 2015-07-27 2020-11-03 豪夫迈·罗氏有限公司 用于治疗和预防乙型肝炎病毒感染的新的四环4-氧代-吡啶-3-甲酸衍生物
CN107835813B (zh) 2015-07-28 2020-04-24 豪夫迈·罗氏有限公司 用于治疗和预防乙型肝炎病毒感染的6,7-二氢吡啶并[2,1-a]酞嗪-2-酮类化合物
EP3328407A1 (en) 2015-07-29 2018-06-06 Novartis AG Combination of pd-1 antagonist with an egfr inhibitor
KR102163611B1 (ko) 2015-08-10 2020-10-08 머크 샤프 앤드 돔 코포레이션 항바이러스 베타-아미노산 에스테르 포스포디아미드 화합물
CA2995365C (en) 2015-08-13 2021-10-12 Merck Sharp & Dohme Corp. Cyclic di-nucleotide compounds as sting agonists
US11130736B2 (en) 2015-08-21 2021-09-28 University Of Kansas Human TLR8-selective agonists
WO2017038909A1 (en) 2015-08-28 2017-03-09 Takeda Pharmaceutical Company Limited Heterocyclic compounds
US10150768B2 (en) 2015-08-31 2018-12-11 3M Innovative Properties Company Guanidine substituted imidazo[4,5-c] ring compounds
TWI786639B (zh) 2015-09-15 2022-12-11 美商艾森伯利生物科學公司 B型肝炎核心蛋白質調節劑
JP6856900B2 (ja) 2015-09-17 2021-04-14 国立大学法人富山大学 トール様受容体７またはトール様受容体９の活性化阻害剤
EP3350168B1 (en) 2015-09-17 2019-12-18 H. Hoffnabb-La Roche Ag Sulfinylphenyl or sulfonimidoylphenyl benzazepines
CN108135891B (zh) 2015-10-05 2021-07-20 富士胶片富山化学株式会社 抗乙型肝炎病毒药
CA3001283C (en) 2015-10-07 2023-10-10 Sumitomo Dainippon Pharma Co., Ltd. Pyrimidine compound
US10745382B2 (en) 2015-10-15 2020-08-18 Bristol-Myers Squibb Company Compounds useful as immunomodulators
WO2017070089A1 (en) 2015-10-19 2017-04-27 Incyte Corporation Heterocyclic compounds as immunomodulators
AU2016343993A1 (en) 2015-10-28 2018-05-10 Aduro Biotech, Inc. Compositions and methods for activating "stimulator of interferon gene"-dependent signalling
CN108472245A (zh) 2015-11-04 2018-08-31 因赛特公司 用于吲哚胺2,3-双加氧酶抑制及其适应症的药物组合物和方法
SG11201803474UA (en) 2015-11-04 2018-05-30 Hookipa Biotech Ag Vaccines against hepatitis b virus
UA121345C2 (uk) 2015-11-05 2020-05-12 Чіа Тай Тяньцин Фармасьютікал Груп Ко., Лтд. 7-(тіазол-5-іл)піролопіримідин як агоніст рецептора tlr7
JP6983776B2 (ja) 2015-11-19 2021-12-17 ブリストル−マイヤーズ スクイブ カンパニーBristol−Myers Squibb Company グルココルチコイド誘発腫瘍壊死因子受容体（ｇｉｔｒ）に対する抗体およびその使用
DK3377488T3 (da) 2015-11-19 2022-10-03 Incyte Corp Heterocykliske forbindelser som immunomodulatorer
CR20180286A (es) 2015-12-03 2018-07-16 Glaxosmithkline Ip Dev Ltd Dinucleotidos de purina cíclicos como moduladores de sting
US10745428B2 (en) 2015-12-10 2020-08-18 Idenix Pharmaceuticals Llc Antiviral phosphodiamide prodrugs of tenofovir
WO2017106740A1 (en) 2015-12-16 2017-06-22 Aduro Biotech, Inc. Methods for identifying inhibitors of "stimulator of interferon gene"-dependent interferon production
SMT202400141T1 (it) 2015-12-17 2024-05-14 Merck Patent Gmbh 8-ciano-5-piperidino-chinoline come antagonisti di tlr7/8 e loro usi per trattamento di disturbi immunitari
MA44075A (fr) 2015-12-17 2021-05-19 Incyte Corp Dérivés de n-phényl-pyridine-2-carboxamide et leur utilisation en tant que modulateurs des interactions protéine/protéine pd-1/pd-l1
MY199705A (en) 2015-12-22 2023-11-20 Incyte Corp Heterocyclic compounds as immunomodulators
WO2017112859A1 (en) * 2015-12-23 2017-06-29 Precision Biosciences, Inc. Engineered meganucleases with recognition sequences found in the human beta-2 microglobulin gene
US20200270265A1 (en) 2016-02-19 2020-08-27 Novartis Ag Tetracyclic pyridone compounds as antivirals
MX390014B (es) 2016-03-18 2025-03-20 Immune Sensor Llc Compuestos de dinucleótidos cíclicos y métodos de uso.
EP3433249B1 (en) 2016-03-21 2022-11-09 Council Of Scientific & Industrial Research Blocking toll-like receptor 9 signaling with small molecule antagonist
US10358463B2 (en) 2016-04-05 2019-07-23 Bristol-Myers Squibb Company Immunomodulators
WO2017184735A1 (en) 2016-04-19 2017-10-26 Ifm Therapeutics, Inc Nlrp3 modulators
AU2017252640A1 (en) 2016-04-19 2018-12-06 Innate Tumor Immunity, Inc. NLRP3 modulators
EP3448393A1 (en) 2016-04-25 2019-03-06 Invivogen Novel complexes of immunostimulatory compounds, and uses thereof
DK3452583T3 (da) * 2016-05-03 2022-01-10 Prec Biosciences Inc Konstruerede nukleaser, der er nyttige til behandling af hæmofili a
HRP20220577T1 (hr) 2016-05-06 2022-06-24 Shanghai De Novo Pharmatech Co., Ltd. Derivat benzazepina, metoda pripreme, farmaceutski sastav i njegova upotreba
TW201808950A (zh) 2016-05-06 2018-03-16 英塞特公司 作為免疫調節劑之雜環化合物
WO2017198744A1 (en) 2016-05-20 2017-11-23 F. Hoffmann-La Roche Ag Novel pyrazine compounds with oxygen, sulfur and nitrogen linker for the treatment of infectious diseases
CN109311854B (zh) 2016-05-23 2021-08-10 豪夫迈·罗氏有限公司 具有仲酰胺官能团的苯并氮杂卓二甲酰胺化合物
WO2017202704A1 (en) 2016-05-23 2017-11-30 F. Hoffmann-La Roche Ag Benzazepine dicarboxamide compounds with tertiary amide function
WO2017202798A1 (en) 2016-05-26 2017-11-30 F. Hoffmann-La Roche Ag Xanthone derivatives for the treatment and prophylaxis of hepatitis b virus disease
US20170342060A1 (en) 2016-05-26 2017-11-30 Incyte Corporation Heterocyclic compounds as immunomodulators
WO2017211791A1 (en) 2016-06-07 2017-12-14 F. Hoffmann-La Roche Ag Combination therapy of an hbsag inhibitor and a tlr7 agonist
EP3468561A4 (en) 2016-06-10 2019-12-04 Enanta Pharmaceuticals, Inc. ANTIVIRAL AGENTS AGAINST HEPATITIS B
EP3468963B1 (en) 2016-06-12 2021-10-27 F. Hoffmann-La Roche AG Dihydropyrimidinyl benzazepine carboxamide compounds
WO2017216686A1 (en) 2016-06-16 2017-12-21 Novartis Ag 8,9-fused 2-oxo-6,7-dihydropyrido-isoquinoline compounds as antivirals
WO2017216685A1 (en) 2016-06-16 2017-12-21 Novartis Ag Pentacyclic pyridone compounds as antivirals
SG11201811414TA (en) 2016-06-20 2019-01-30 Incyte Corp Heterocyclic compounds as immunomodulators
CN108290893B (zh) 2016-06-22 2021-01-05 四川科伦博泰生物医药股份有限公司 二氢蝶啶酮类衍生物、其制备方法及其用途
CN109415367B (zh) 2016-06-29 2021-04-16 豪夫迈·罗氏有限公司 用于治疗和预防乙型肝炎病毒感染的新的二氢吡咯并嘧啶类化合物
WO2018005883A1 (en) 2016-06-29 2018-01-04 Novira Therapeutics, Inc. Diazepinone derivatives and their use in the treatment of hepatitis b infections
CA3029688A1 (en) 2016-06-29 2018-01-04 Novira Therapeutics, Inc. Oxadiazepinone derivatives and their use in the treatment of hepatitis b infections
JP6742452B2 (ja) 2016-06-29 2020-08-19 エフ．ホフマン−ラ ロシュ アーゲーＦ． Ｈｏｆｆｍａｎｎ−Ｌａ Ｒｏｃｈｅ Ａｋｔｉｅｎｇｅｓｅｌｌｓｃｈａｆｔ Ｈｂｖ感染の処置および予防のための新規のテトラヒドロピリドピリミジン
US10071079B2 (en) 2016-06-29 2018-09-11 Bristol-Myers Squibb Company [1,2,4]triazolo[1,5-a]pyridinyl substituted indole compounds
KR102468272B1 (ko) 2016-06-30 2022-11-18 삼성전자주식회사 음향 출력 장치 및 그 제어 방법
CA3027471A1 (en) 2016-07-01 2018-01-04 Janssen Sciences Ireland Unlimited Company Dihydropyranopyrimidines for the treatment of viral infections
EP3507367A4 (en) 2016-07-05 2020-03-25 Aduro BioTech, Inc. CYCLIC DINUCLEOTID COMPOUNDS WITH INCLUDED NUCLEIC ACIDS AND USES THEREOF
AU2017292758A1 (en) 2016-07-08 2019-02-21 Bristol-Myers Squibb Company 1,3-dihydroxy-phenyl derivatives useful as immunomodulators
CN109476668B (zh) 2016-07-14 2022-03-22 豪夫迈·罗氏有限公司 用于治疗感染性疾病的6,7-二氢-4H-吡唑并[1,5-a]吡嗪和6,7-二氢-4H-三唑并[1,5-a]吡嗪化合物
WO2018011100A1 (en) 2016-07-14 2018-01-18 F. Hoffmann-La Roche Ag Novel tetrahydropyrazolopyridine compounds for the treatment of infectious diseases
EP3484885B1 (en) 2016-07-14 2020-03-04 H. Hoffnabb-La Roche Ag Carboxy 6,7-dihydro-4h-pyrazolo[1,5-a]pyrazine compounds for the treatment of infectious diseases
EP3484866B1 (en) 2016-07-14 2022-09-07 Incyte Corporation Heterocyclic compounds as immunomodulators
WO2018011160A1 (en) 2016-07-14 2018-01-18 F. Hoffmann-La Roche Ag 6,7-dihydro-4h-pyrazolo[1,5-a]pyrazine compounds for the treatment of infectious diseases
CN109715624B (zh) 2016-07-29 2022-08-16 广州麓鹏制药有限公司 用于治疗hbv感染的新颖治疗剂
WO2018019297A1 (zh) 2016-07-29 2018-02-01 银杏树药业(苏州)有限公司 异喹啉酮类化合物及其制备抗病毒药物的应用
CA3031675A1 (en) 2016-07-30 2018-02-08 Bristol-Myers Squibb Company Dimethoxyphenyl substituted indole compounds as tlr7, tlr8 or tlr9 inhibitors
EP3493804A1 (en) 2016-08-03 2019-06-12 Arising International, Inc. Symmetric or semi-symmetric compounds useful as immunomodulators
JP7125385B2 (ja) 2016-08-08 2022-08-24 メルク パテント ゲゼルシャフト ミット ベシュレンクテル ハフツング Ｔｌｒ７／８アンタゴニストおよびそれらの使用
EP3503894A1 (en) 2016-08-24 2019-07-03 H. Hoffnabb-La Roche Ag Combination therapy of an hbv capsid assembly inhibitor and a nucleos(t)ide analogue
CN109641920A (zh) 2016-08-26 2019-04-16 3M创新有限公司 由胍基基团取代的稠合[1,2]咪唑并[4,5-c]环化合物
MA46045A (fr) 2016-08-29 2021-04-28 Incyte Corp Composés hétérocycliques utilisés comme immunomodulateurs
US10144706B2 (en) 2016-09-01 2018-12-04 Bristol-Myers Squibb Company Compounds useful as immunomodulators
ES2906581T3 (es) 2016-09-02 2022-04-19 Gilead Sciences Inc Compuestos moduladores de los receptores tipo Toll
US10640499B2 (en) 2016-09-02 2020-05-05 Gilead Sciences, Inc. Toll like receptor modulator compounds
WO2018043747A1 (ja) 2016-09-05 2018-03-08 国立大学法人京都大学 抗ｂ型肝炎ウイルス剤
BE1024865B1 (fr) 2016-09-07 2018-07-31 Glaxosmithkline Biologicals Sa Derives d'imidazoquinoleine
TWI670266B (zh) 2016-09-09 2019-09-01 大陸商浙江海正藥業股份有限公司 二氫嘧啶類化合物及其製備方法和用途
NZ750781A (en) 2016-09-09 2025-06-27 Novartis Ag Compounds and compositions as inhibitors of endosomal toll-like receptors
WO2018049089A1 (en) 2016-09-09 2018-03-15 Bristol-Myers Squibb Company Pyridyl substituted indole compounds
WO2018051255A1 (en) 2016-09-14 2018-03-22 Aurigene Discovery Technologies Limited Cyclic substituted-1,3,4-oxadiazole and thiadiazole compounds as immunomodulators
WO2018051254A1 (en) 2016-09-14 2018-03-22 Aurigene Discovery Technologies Limited Cyclic substituted-1,2,4-oxadiazole compounds as immunomodulators
US10537590B2 (en) 2016-09-30 2020-01-21 Boehringer Ingelheim International Gmbh Cyclic dinucleotide compounds
CR20190168A (es) 2016-10-04 2019-05-17 Merck Sharp & Dohme Compuestos de benzo[b]tiofeno como agonistas de sting
US11001605B2 (en) 2016-10-07 2021-05-11 Biolog Life Science Institute Gmbh & Co. Kg Cyclic dinucleotides containing benzimidazole, method for the production of same, and use of same to activate stimulator of interferon genes (sting)-dependent signaling pathways
BR112019007450A2 (pt) 2016-10-14 2020-07-07 Precision Biosciences, Inc. meganucleases modificadas específicas para sequências de reconhecimento no genoma do vírus da hepatite b
EA201990997A1 (ru) 2016-10-20 2019-08-30 Ориджин Дискавери Текнолоджиз Лимитед Двойные ингибиторы vista и путей pd-1
WO2018080903A1 (en) 2016-10-26 2018-05-03 Merck Sharp & Dohme Corp. Antiviral aryl-amide phosphodiamide compounds
WO2018078149A1 (en) 2016-10-31 2018-05-03 F. Hoffmann-La Roche Ag Novel cyclicsulfonimidoylpurinone compounds and derivatives for the treatment and prophylaxis of virus infection
WO2018085750A2 (en) 2016-11-07 2018-05-11 Bristol-Myers Squibb Company Immunomodulators
EP3538513A1 (en) 2016-11-11 2019-09-18 Dynavax Technologies Corporation Toll-like receptor antagonist compounds and methods of use
CN108069969B (zh) 2016-11-11 2020-09-18 南京海璞医药科技有限公司 含氮杂环化合物、制备方法、中间体、药物组合物和应用
JOP20170188A1 (ar) 2016-11-25 2019-01-30 Janssen Biotech Inc ثنائي النوكليوتيدات الحلقية كمنبهات ستينغ (sting)
ES2886973T3 (es) 2016-11-28 2021-12-21 Jiangsu Hengrui Medicine Co Derivado pirazolo-heteroarilo, método de preparación y uso médico del mismo
JOP20170192A1 (ar) 2016-12-01 2019-01-30 Takeda Pharmaceuticals Co داي نوكليوتيد حلقي
JP2020511420A (ja) 2016-12-20 2020-04-16 メルク・シャープ・アンド・ドーム・コーポレーションＭｅｒｃｋ Ｓｈａｒｐ ＆ Ｄｏｈｍｅ Ｃｏｒｐ． がんの処置のためのｐｄ−１アンタゴニストと環状ジヌクレオチドｓｔｉｎｇアゴニストとの組み合わせ
JP2020503303A (ja) 2016-12-20 2020-01-30 メルク・シャープ・アンド・ドーム・コーポレーションＭｅｒｃｋ Ｓｈａｒｐ ＆ Ｄｏｈｍｅ Ｃｏｒｐ． がんの処置のための環状ジヌクレオチドｓｔｉｎｇアゴニスト
CN110072860B (zh) 2016-12-20 2022-09-02 百时美施贵宝公司 可用作免疫调节剂的化合物
US20180177784A1 (en) 2016-12-22 2018-06-28 Incyte Corporation Heterocyclic compounds as immunomodulators
WO2018119266A1 (en) 2016-12-22 2018-06-28 Incyte Corporation Benzooxazole derivatives as immunomodulators
US20180179202A1 (en) 2016-12-22 2018-06-28 Incyte Corporation Heterocyclic compounds as immunomodulators
WO2018119221A1 (en) 2016-12-22 2018-06-28 Incyte Corporation Pyridine derivatives as immunomodulators
WO2018119236A1 (en) 2016-12-22 2018-06-28 Incyte Corporation Triazolo[1,5-a]pyridine derivatives as immunomodulators
AU2017378893A1 (en) 2016-12-22 2019-05-16 Idenix Pharmaceuticals Llc Antiviral benzyl-amine phosphodiamide compounds
JP6938637B2 (ja) 2016-12-22 2021-09-22 メルク・シャープ・アンド・ドーム・コーポレーションＭｅｒｃｋ Ｓｈａｒｐ ＆ Ｄｏｈｍｅ Ｃｏｒｐ． テノホビルの抗ウイルス性脂肪族エステルプロドラッグ
WO2018199338A1 (ja) * 2017-04-27 2018-11-01 国立大学法人広島大学 Ｂ型肝炎治療用核酸分子
US11142750B2 (en) 2018-04-12 2021-10-12 Precision Biosciences, Inc. Optimized engineered meganucleases having specificity for a recognition sequence in the Hepatitis B virus genome

Patent Citations (16)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4873192A (en) 1987-02-17 1989-10-10 The United States Of America As Represented By The Department Of Health And Human Services Process for site specific mutagenesis without phenotypic selection
US6015832A (en) 1997-12-31 2000-01-18 The Regents Of The University Of Michigan Methods of inactivating bacteria including bacterial spores
US20020045667A1 (en) 1999-04-28 2002-04-18 The Regents Of The University Of Michigan Non-toxic antimicrobial compositions and methods of use
US6506803B1 (en) 1999-04-28 2003-01-14 Regents Of The University Of Michigan Methods of preventing and treating microbial infections
US6559189B2 (en) 1999-04-28 2003-05-06 Regents Of The University Of Michigan Non-toxic antimicrobial compositions and methods of use
US6635676B2 (en) 1999-04-28 2003-10-21 Regents Of The University Of Michigan Non-toxic antimicrobial compositions and methods of use
US20040043041A1 (en) 1999-04-28 2004-03-04 The Regents Of The University Of Michigan Antimicrobial compositions and methods of use
WO2002012514A2 (en) 2000-08-09 2002-02-14 Nsgene A/S Jet, an artificial promoter for gene expression
US7404969B2 (en) 2005-02-14 2008-07-29 Sirna Therapeutics, Inc. Lipid nanoparticle based compositions and methods for the delivery of biologically active molecules
WO2007047859A2 (en) 2005-10-18 2007-04-26 Precision Biosciences Rationally-designed meganucleases with altered sequence specificity and dna-binding affinity
US8021867B2 (en) 2005-10-18 2011-09-20 Duke University Rationally-designed meganucleases with altered sequence specificity and DNA-binding affinity
WO2009059195A2 (en) 2007-10-31 2009-05-07 Precision Biosciences Rationally-designed single-chain meganucleases with non-palindromic recognition sequences
US8445251B2 (en) 2007-10-31 2013-05-21 Precision Biosciences, Inc. Rationally-designed single-chain meganucleases with non-palindromic recognition sequences
US9434931B2 (en) 2007-10-31 2016-09-06 Precision Biosciences, Inc. Rationally-designed single-chain meganucleases with non-palindromic recognition sequences
WO2010136841A2 (en) 2009-05-26 2010-12-02 Cellectis Meganuclease variants cleaving the genome of a non-genomically integrating virus and uses thereof
WO2012167192A2 (en) 2011-06-01 2012-12-06 Precision Biosciences, Inc. Methods and products for producing engineered mammalian cell lines with amplified transgenes

Non-Patent Citations (59)

* Cited by examiner, † Cited by third party
Title
.: "LIPOFECTAMINE transfection reagent", LIFE TECHNOLOGIES CORP.
AIRENNE, KJ ET AL., MOL. THER., vol. 21, no. 4, 2013, pages 739 - 49
ALTSCHUL ET AL., J. MOL. BIOL., vol. 215, 1990, pages 403 - 410
ALTSCHUL ET AL., NUCLEIC ACIDS RES., vol. 25, no. 33, 1997, pages 89 - 3402
ARNOULD ET AL., J. MOL. BIOL., vol. 355, 2006, pages 443 - 58
BENOIST; CHAMBON, NATURE, vol. 290, no. 5804, 1981, pages 304 - 10
CAHILL ET AL., FRONT. BIOSCI., vol. 11, 2006, pages 1958 - 1976
CHAMES ET AL., NUCLEIC ACIDS RES., vol. 33, 2005, pages el78
CHANG BD; RONINSON IB, GENE, vol. 183, 1996, pages 137 - 42
CHEN H. ET AL., BMC BIOTECHNOL, vol. 15, no. 1, 2015, pages 4
CHEN, H, MOL THER NUCLEIC ACIDS., vol. 1, no. 11, 2012, pages e57
CHENG ET AL., J PHARM SCI., vol. 97, no. 1, 2008, pages 123 - 43
CHEVALIER ET AL., NUCLEIC ACIDS RES., vol. 29, no. 18, 2001, pages 3757 - 3774
COTS D; BOSCH A; CHILLON M, CURR. GENE THER., vol. 13, no. 5, 2013, pages 370 - 81
DAYHOFF ET AL.: "Atlas of Protein Sequence and Structure", NATL. BIOMED. RES. FOUND., 1978
DESHAYES ET AL., BIOCHEMISTRY, vol. 43, 2004, pages 7698 - 7706
DESHAYES ET AL., CELL MOL LIFE SCI., vol. 62, 2005, pages 1839 - 49
DINDA ET AL., CURR PHARM BIOTECHNOL., vol. 14, 2013, pages 1264 - 74
DINGERMANN ET AL., MOL CELL BIOL., vol. 12, no. 9, 1992, pages 4038 - 45
GAO, H. ET AL., J. BIOTECHNOL., vol. 131, no. 2, 2007, pages 138 - 43
GISH; STATES, NATURE GENET., vol. 3, 1993, pages 266 - 272
GRIZOT ET AL., NUCLEIC ACIDS RES., vol. 37, 2009, pages 5405 - 19
HAASE ET AL., BMC BIOTECHNOL., vol. 13, 2013, pages 49 - 54
HUDECZ ET AL., MED. RES. REV., vol. 25, 2005, pages 679 - 736
JACOX E ET AL., PLOS ONE, vol. 5, no. 8, 2010, pages e12274
JEARAWIRIYAPAISARN ET AL., MOL THER., vol. 16, 2008, pages 1624 - 9
JIAN ET AL., BIOMATERIALS, vol. 33, no. 30, 2012, pages 7621 - 30
KANG DERWENT ET AL., TRANS AM OPHTHALMOL SOC., vol. 106, 2008, pages 206 - 214
KANG ET AL., CURR PHARM BIOTECHNOL., vol. 15, no. 3, 2014, pages 220 - 30
KRAMER, MG ET AL., MOL. THERAPY, vol. 7, 2003, pages 375 - 85
KUNKEL ET AL., METHODS IN ENZYMOL., vol. 154, 1987, pages 367 - 382
KUNKEL, PROC. NATL. ACAD. SCI. USA, vol. 82, 1985, pages 488 - 492
LENTZ ET AL., NEUROBIOL DIS., vol. 48, 2012, pages 179 - 88
LI ET AL., NUCLEIC ACIDS RES., vol. 37, 2009, pages 1650 - 62
LIU ET AL., HUM GENE THER., vol. 15, 2004, pages 783 - 92
MADDEN ET AL., METH. ENZYMOL., vol. 266, 1996, pages 131 - 141
MARTIN KRG; KLEIN RL; QUIGLEY HA, METHODS, vol. 28, 2002, pages 267 - 75
MASTORAKOS ET AL., NANOSCALE, vol. 7, no. 9, 2015, pages 3845 - 56
MCCALL ET AL., TISSUE BARRIERS., vol. 2, no. 4, 2014, pages e944449
MCCARTY ET AL., GENE THER., vol. 8, 2001, pages 1248 - 54
MISHRA ET AL., J DRUG DELIV., 2011, pages 863734
QIAN ET AL., EXPERT OPIN DRUG METAB TOXICOL, vol. 10, no. 11, 2014, pages 1491 - 508
REMINGTON: "The Science And Practice of Pharmacy, 21st ed.,", 2005
SANDS, METHODS MOL. BIOL., vol. 807, 2011, pages 141 - 157
SELIGMAN ET AL., NUCLEIC ACIDS RES., vol. 30, 2002, pages 3870 - 9
SHARMA ET AL., BIOMED RES INT., 2014
SIMEONI ET AL., NUCLEIC ACIDS RES., vol. 31, 2003, pages 2717 - 2724
SOWA G. ET AL., SPINE, vol. 36, no. 10, 2011, pages E623 - 8
STODDARD, Q. REV. BIOPHYS., vol. 38, 2006, pages 49 - 95
SUSSMAN ET AL., J. MOL. BIOL., vol. 342, 2004, pages 31 - 41
TAMBOLI ET AL., THER DELIV, vol. 2, no. 4, 2011, pages 523 - 536
THOMSEN ET AL., PROC NATL ACAD SCI USA., vol. 81, no. 3, 1984, pages 659 - 63
TONG ET AL., J GENE MED., vol. 9, no. 11, 2007, pages 956 - 66
TONG Y ET AL., J GENE MED, vol. 9, 2007, pages 956 - 66
VANNUCCI ET AL., NEW MICROBIOL., vol. 36, 2013, pages 1 - 22
WALKER AND GAASTRA: "Techniques in Molecular Biology", 1983, MACMILLAN PUBLISHING COMPANY
YUASA ET AL., GENE THER., vol. 9, 2002, pages 1576 - 88
ZHANG ET AL., J. COMPUT. BIOL., vol. 7, no. 1-2, 2000, pages 203 - 14
ZURIS ET AL., NAT BIOTECHNOL., vol. 33, 2015, pages 73 - 80

Cited By (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US10662416B2 (en) 2016-10-14 2020-05-26 Precision Biosciences, Inc. Engineered meganucleases specific for recognition sequences in the hepatitis B virus genome
US11274285B2 (en) 2016-10-14 2022-03-15 Precision Biosciences, Inc. Engineered meganucleases specific for recognition sequences in the Hepatitis B virus genome
WO2019200247A1 (en) * 2018-04-12 2019-10-17 Precision Biosciences, Inc. Optimized engineered meganucleases having specificity for a recognition sequence in the hepatitis b virus genome
US11142750B2 (en) 2018-04-12 2021-10-12 Precision Biosciences, Inc. Optimized engineered meganucleases having specificity for a recognition sequence in the Hepatitis B virus genome
US11788077B2 (en) 2018-04-12 2023-10-17 Precision Biosciences, Inc. Polynucleotides encoding optimized engineered meganucleases having specificity for a recognition sequence in the Hepatitis B virus genome
WO2020227534A1 (en) 2019-05-07 2020-11-12 Precision Biosciences, Inc. Optimization of engineered meganucleases for recognition sequences
US12410418B2 (en) 2019-12-06 2025-09-09 Precision Biosciences, Inc. Optimized engineered meganucleases having specificity for a recognition sequence in the Hepatitis B virus genome
WO2021231259A1 (en) 2020-05-11 2021-11-18 Precision Biosciences, Inc. Self-limiting viral vectors encoding nucleases
US12390538B2 (en) 2023-05-15 2025-08-19 Nchroma Bio, Inc. Compositions and methods for epigenetic regulation of HBV gene expression

Also Published As

Publication number Publication date
MX2024001134A (es) 2024-02-27
EP4234691A2 (en) 2023-08-30
AU2023263542A1 (en) 2023-11-30
US10851358B2 (en) 2020-12-01
US20210180038A1 (en) 2021-06-17
JP6811857B2 (ja) 2021-01-13
SG10201914029RA (en) 2020-03-30
WO2018071849A3 (en) 2018-05-24
KR20190064628A (ko) 2019-06-10
FI3526323T3 (fi) 2023-06-06
CL2019000993A1 (es) 2019-08-30
JP2025138637A (ja) 2025-09-25
KR102305215B1 (ko) 2021-09-28
IL308894A (en) 2024-01-01
US20220243187A1 (en) 2022-08-04
EP3526323B1 (en) 2023-03-29
DK3526323T3 (da) 2023-06-26
DOP2019000097A (es) 2019-07-31
CN117402852A (zh) 2024-01-16
US20200239864A1 (en) 2020-07-30
JP2021061841A (ja) 2021-04-22
SG11201903042VA (en) 2019-05-30
JP2023153824A (ja) 2023-10-18
US20190284543A1 (en) 2019-09-19
IL265921A (en) 2019-06-30
PE20191353A1 (es) 2019-10-01
US10662416B2 (en) 2020-05-26
US20240271111A1 (en) 2024-08-15
MA46535A (fr) 2019-08-21
DK3526323T5 (da) 2024-09-02
AU2017342536A1 (en) 2019-05-02
PH12019500788A1 (en) 2019-11-11
JP2019530462A (ja) 2019-10-24
KR20210118240A (ko) 2021-09-29
MX2019004349A (es) 2019-09-26
IL317537A (en) 2025-02-01
EP3526323A2 (en) 2019-08-21
EP4234691A3 (en) 2023-10-18
CR20190181A (es) 2019-08-21
JP2021180665A (ja) 2021-11-25
KR20230010826A (ko) 2023-01-19
JP6919049B2 (ja) 2021-08-11
BR112019007450A2 (pt) 2020-07-07
CO2019003675A2 (es) 2019-04-30
IL265921B1 (en) 2024-01-01
US11274285B2 (en) 2022-03-15
CA3040143A1 (en) 2018-04-19
KR20240123417A (ko) 2024-08-13
CN110023495A (zh) 2019-07-16
IL265921B2 (en) 2024-05-01
US20250154486A1 (en) 2025-05-15

Similar Documents

Publication Publication Date Title
US20250154486A1 (en) Engineered meganucleases specific for recognition sequences in the hepatitis b virus genome
US11788077B2 (en) Polynucleotides encoding optimized engineered meganucleases having specificity for a recognition sequence in the Hepatitis B virus genome
US20230340434A1 (en) Optimization of engineered meganucleases for recognition sequences
CA3172292A1 (en) Engineered meganucleases having specificity for a recognition sequence in the transthyretin gene
HK40006308B (en) Engineered meganucleases specific for recognition sequences in the hepatitis b virus genome
HK40006308A (en) Engineered meganucleases specific for recognition sequences in the hepatitis b virus genome
US20240408235A1 (en) Gene editing methods for treating alpha-1 antitrypsin (aat) deficiency
EA042452B1 (ru) Сконструированные мегануклеазы, специфичные к последовательностям распознавания в геноме вируса гепатита b
EP4150068A1 (en) Treatment of retinitis pigmentosa using improved engineered meganucleases
HK40012293A (en) Engineered meganucleases specific for recognition sequences in the hepatitis b virus genome

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 17804977

Country of ref document: EP

Kind code of ref document: A2

ENP Entry into the national phase

Ref document number: 3040143

Country of ref document: CA

ENP Entry into the national phase

Ref document number: 2019520125

Country of ref document: JP

Kind code of ref document: A

WWE Wipo information: entry into national phase

Ref document number: NC2019/0003675

Country of ref document: CO

NENP Non-entry into the national phase

Ref country code: DE

REG Reference to national code

Ref country code: BR

Ref legal event code: B01A

Ref document number: 112019007450

Country of ref document: BR

WWP Wipo information: published in national office

Ref document number: NC2019/0003675

Country of ref document: CO

ENP Entry into the national phase

Ref document number: 2017342536

Country of ref document: AU

Date of ref document: 20171013

Kind code of ref document: A

ENP Entry into the national phase

Ref document number: 20197013312

Country of ref document: KR

Kind code of ref document: A

ENP Entry into the national phase

Ref document number: 2017804977

Country of ref document: EP

Effective date: 20190514

ENP Entry into the national phase

Ref document number: 112019007450

Country of ref document: BR

Kind code of ref document: A2

Effective date: 20190412

WWR Wipo information: refused in national office

Ref document number: 1020247026203

Country of ref document: KR

WWW Wipo information: withdrawn in national office

Ref document number: 308894

Country of ref document: IL