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WO2018195165A8 - Methods for the treatment of subjects having a hepatitis b virus (hbv) infection - Google Patents

Methods for the treatment of subjects having a hepatitis b virus (hbv) infection Download PDF

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Publication number
WO2018195165A8
WO2018195165A8 PCT/US2018/028116 US2018028116W WO2018195165A8 WO 2018195165 A8 WO2018195165 A8 WO 2018195165A8 US 2018028116 W US2018028116 W US 2018028116W WO 2018195165 A8 WO2018195165 A8 WO 2018195165A8
Authority
WO
WIPO (PCT)
Prior art keywords
hbv
polypeptide
infection
hbcag
hbsag
Prior art date
Application number
PCT/US2018/028116
Other languages
French (fr)
Other versions
WO2018195165A1 (en
Inventor
Laura Sepp-Lorenzino
Ulrike Protzer
Thomas MICHLER
Original Assignee
Alnylam Pharmaceuticals, Inc.
Technische Universität München
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 EP18722367.2A priority Critical patent/EP3612219A1/en
Priority to IL269927A priority patent/IL269927B2/en
Priority to CN202410340606.3A priority patent/CN118384268A/en
Priority to KR1020197033885A priority patent/KR102720270B1/en
Priority to CA3059446A priority patent/CA3059446A1/en
Priority to MYPI2019006106A priority patent/MY205546A/en
Priority to JP2019556314A priority patent/JP7688480B2/en
Priority to AU2018254437A priority patent/AU2018254437B2/en
Priority to SG11201909572Q priority patent/SG11201909572QA/en
Application filed by Alnylam Pharmaceuticals, Inc., Technische Universität München filed Critical Alnylam Pharmaceuticals, Inc.
Priority to EA201992473A priority patent/EA201992473A1/en
Priority to BR112019021852-1A priority patent/BR112019021852A2/en
Priority to US16/606,069 priority patent/US11324820B2/en
Priority to CN201880035565.XA priority patent/CN110913898B/en
Publication of WO2018195165A1 publication Critical patent/WO2018195165A1/en
Publication of WO2018195165A8 publication Critical patent/WO2018195165A8/en
Priority to PH12019550220A priority patent/PH12019550220A1/en
Priority to JP2023088820A priority patent/JP2023123449A/en

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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
    • A61K39/29—Hepatitis virus
    • A61K39/292—Serum hepatitis virus, hepatitis B virus, e.g. Australia antigen
    • 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
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7088—Compounds having three or more nucleosides or nucleotides
    • A61K31/713—Double-stranded nucleic acids or oligonucleotides
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
    • A61K47/54—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic compound
    • A61K47/549—Sugars, nucleosides, nucleotides or nucleic acids
    • 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
    • A61P31/20—Antivirals for DNA viruses
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    • 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
    • C12N15/113—Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing
    • C12N15/1131—Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing against viruses
    • C—CHEMISTRY; METALLURGY
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    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K2039/51—Medicinal preparations containing antigens or antibodies comprising whole cells, viruses or DNA/RNA
    • A61K2039/525—Virus
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    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K2039/54—Medicinal preparations containing antigens or antibodies characterised by the route of administration
    • 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
    • A61K2039/545—Medicinal preparations containing antigens or antibodies characterised by the dose, timing or administration schedule
    • 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
    • A61K2039/55555—Liposomes; Vesicles, e.g. nanoparticles; Spheres, e.g. nanospheres; Polymers
    • 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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    • C12N2310/00—Structure or type of the nucleic acid
    • C12N2310/10—Type of nucleic acid
    • C12N2310/14—Type of nucleic acid interfering nucleic acids [NA]
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    • C12N2310/00—Structure or type of the nucleic acid
    • C12N2310/30—Chemical structure
    • C12N2310/31—Chemical structure of the backbone
    • C12N2310/315—Phosphorothioates
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    • C12N2310/00—Structure or type of the nucleic acid
    • C12N2310/30—Chemical structure
    • C12N2310/35—Nature of the modification
    • C12N2310/351—Conjugate
    • C12N2310/3515—Lipophilic moiety, e.g. cholesterol
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
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    • C12N2310/00—Structure or type of the nucleic acid
    • C12N2310/30—Chemical structure
    • C12N2310/35—Nature of the modification
    • C12N2310/352—Nature of the modification linked to the nucleic acid via a carbon atom
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    • C12N2310/30—Chemical structure
    • C12N2310/35—Nature of the modification
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    • C12N2730/00—Reverse transcribing DNA viruses
    • C12N2730/00011—Details
    • C12N2730/10011—Hepadnaviridae
    • C12N2730/10111—Orthohepadnavirus, e.g. hepatitis B virus
    • C12N2730/10134—Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
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  • Engineering & Computer Science (AREA)
  • Virology (AREA)
  • General Health & Medical Sciences (AREA)
  • Genetics & Genomics (AREA)
  • Molecular Biology (AREA)
  • Public Health (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pharmacology & Pharmacy (AREA)
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  • Biomedical Technology (AREA)
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  • Wood Science & Technology (AREA)
  • General Engineering & Computer Science (AREA)
  • Microbiology (AREA)
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  • Chemical Kinetics & Catalysis (AREA)
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  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Oncology (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Micro-Organisms Or Cultivation Processes Thereof (AREA)
  • Medicines Containing Material From Animals Or Micro-Organisms (AREA)

Abstract

The present invention provides methods for the treatment of a subject having a Hepatitis B virus (HBV) infection, e.g., a chronic HBV infection, using a combination of an RNAi agent that targets HBV and an HBV vaccine. It is disclosed a RNAi agent and an HBV vaccine for use in treatment of HBV infection, comprising sequentially administering to the subject having an HBV infection: a) an RNAi agent that inhibits expression of at least three HBV transcripts, wherein the RNAi agent forms a double stranded region; b) a protein-based vaccine comprising a first HBV core antigen (HBcAg) polypeptide, and a first HBV surface antigen (HBsAg) polypeptide; and c) a nucleic acid-based vaccine comprising an expression vector construct encoding a second HBcAg polypeptide, and/or a second HBsAg polypeptide, wherein the second HBcAg polypeptide, and/or the second HBsAg polypeptide, shares at least one epitope with at least one of the first HBcAg polypeptide, and/or the first HBsAg polypeptide.
PCT/US2018/028116 2017-04-18 2018-04-18 Methods for the treatment of subjects having a hepatitis b virus (hbv) infection WO2018195165A1 (en)

Priority Applications (15)

Application Number Priority Date Filing Date Title
SG11201909572Q SG11201909572QA (en) 2017-04-18 2018-04-18 Methods for the treatment of subjects having a hepatitis b virus (hbv) infection
CN202410340606.3A CN118384268A (en) 2017-04-18 2018-04-18 Treatment of subjects with hepatitis B virus (HBV) infection
KR1020197033885A KR102720270B1 (en) 2017-04-18 2018-04-18 Methods for treating subjects infected with hepatitis B virus (HBV)
CA3059446A CA3059446A1 (en) 2017-04-18 2018-04-18 Methods for the treatment of subjects having a hepatitis b virus (hbv) infection
MYPI2019006106A MY205546A (en) 2017-04-18 2018-04-18 Methods for the treatment of subjects having a hepatitis b virus (hbv) infection
JP2019556314A JP7688480B2 (en) 2017-04-18 2018-04-18 Methods of Treating a Subject Having Hepatitis B Virus (HBV) Infection
AU2018254437A AU2018254437B2 (en) 2017-04-18 2018-04-18 Methods for the treatment of subjects having a hepatitis B virus (HBV) infection
EP18722367.2A EP3612219A1 (en) 2017-04-18 2018-04-18 Methods for the treatment of subjects having a hepatitis b virus (hbv) infection
EA201992473A EA201992473A1 (en) 2018-04-11 2018-04-18 METHODS FOR TREATING SUBJECTS INFECTED WITH HEPATITIS B VIRUS (HBV)
IL269927A IL269927B2 (en) 2017-04-18 2018-04-18 Methods for the treatment of subjects having a hepatitis b virus (hbv) infection
BR112019021852-1A BR112019021852A2 (en) 2017-04-18 2018-04-18 RNAI AGENT AND A VACCINE AGAINST HBV, USE OR METHOD AND KIT FOR TREATMENT
US16/606,069 US11324820B2 (en) 2017-04-18 2018-04-18 Methods for the treatment of subjects having a hepatitis b virus (HBV) infection
CN201880035565.XA CN110913898B (en) 2017-04-18 2018-04-18 Treatment of subjects with hepatitis B virus (HBV) infection
PH12019550220A PH12019550220A1 (en) 2017-04-18 2019-10-17 Methods for the treatment of subjects having a hepatitis b virus (hbv) infection
JP2023088820A JP2023123449A (en) 2017-04-18 2023-05-30 Methods for treating subjects having hepatitis b virus (hbv) infection

Applications Claiming Priority (8)

Application Number Priority Date Filing Date Title
US201762486618P 2017-04-18 2017-04-18
US62/486,618 2017-04-18
US201762553358P 2017-09-01 2017-09-01
US62/553,358 2017-09-01
US201862646978P 2018-03-23 2018-03-23
US62/646,978 2018-03-23
US201862655862P 2018-04-11 2018-04-11
US62/655,862 2018-04-11

Publications (2)

Publication Number Publication Date
WO2018195165A1 WO2018195165A1 (en) 2018-10-25
WO2018195165A8 true WO2018195165A8 (en) 2018-11-22

Family

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Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US2018/028116 WO2018195165A1 (en) 2017-04-18 2018-04-18 Methods for the treatment of subjects having a hepatitis b virus (hbv) infection

Country Status (13)

Country Link
EP (1) EP3612219A1 (en)
KR (1) KR102720270B1 (en)
CN (2) CN110913898B (en)
AU (1) AU2018254437B2 (en)
BR (1) BR112019021852A2 (en)
CA (1) CA3059446A1 (en)
IL (1) IL269927B2 (en)
MA (1) MA50278A (en)
MY (1) MY205546A (en)
PH (1) PH12019550220A1 (en)
SG (1) SG11201909572QA (en)
TW (1) TWI801377B (en)
WO (1) WO2018195165A1 (en)

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