US20210403879A1 - Method for inactivating zika virus and related methods - Google Patents

Method for inactivating zika virus and related methods Download PDF

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Publication number
US20210403879A1
US20210403879A1 US16/768,550 US201816768550A US2021403879A1 US 20210403879 A1 US20210403879 A1 US 20210403879A1 US 201816768550 A US201816768550 A US 201816768550A US 2021403879 A1 US2021403879 A1 US 2021403879A1
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cells
zika virus
virus
preparation
formaldehyde
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US16/768,550
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Jill A Livengood
Holli GIEBLER
Hansi Dean
Tatsuki Satou
Raman Rao
Jackie Marks
Mark Lyons
Asae Shintani
James Gifford
Nao OGASAWARA
Masafumi Misaki
Satoshi Adachi
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Takeda Vaccines Private Ltd
Takeda Vaccines Inc
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Takeda Vaccines Private Ltd
Takeda Vaccines Inc
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Priority claimed from PCT/US2018/059227 external-priority patent/WO2019090233A2/en
Priority to US16/768,550 priority Critical patent/US20210403879A1/en
Application filed by Takeda Vaccines Private Ltd, Takeda Vaccines Inc filed Critical Takeda Vaccines Private Ltd
Assigned to TAKEDA VACCINES, INC. reassignment TAKEDA VACCINES, INC. ASSIGNMENT OF ASSIGNORS INTEREST (SEE DOCUMENT FOR DETAILS). Assignors: TAKEDA VACCINES PRIVATE LIMITED
Assigned to TAKEDA VACCINES, INC. reassignment TAKEDA VACCINES, INC. ASSIGNMENT OF ASSIGNORS INTEREST (SEE DOCUMENT FOR DETAILS). Assignors: MARKS, Jackie, LIVENGOOD, Jill, LYONS, MARK, Dean, Hansi, GIEBLER, Holli
Assigned to TAKEDA VACCINES PRIVATE LIMITED reassignment TAKEDA VACCINES PRIVATE LIMITED ASSIGNMENT OF ASSIGNORS INTEREST (SEE DOCUMENT FOR DETAILS). Assignors: RAO, RAMAN
Assigned to TAKEDA VACCINES, INC. reassignment TAKEDA VACCINES, INC. ASSIGNMENT OF ASSIGNORS INTEREST (SEE DOCUMENT FOR DETAILS). Assignors: TAKEDA PHARMACEUTICAL COMPANY LIMITED
Assigned to TAKEDA PHARMACEUTICAL COMPANY LIMITED reassignment TAKEDA PHARMACEUTICAL COMPANY LIMITED ASSIGNMENT OF ASSIGNORS INTEREST (SEE DOCUMENT FOR DETAILS). Assignors: ADACHI, SATOSHI, OGASAWARA, NAO, MISAKI, MASAFUMI, SATOU, Tatsuki, SHINTANI, ASAE
Assigned to TAKEDA VACCINES, INC. reassignment TAKEDA VACCINES, INC. ASSIGNMENT OF ASSIGNORS INTEREST (SEE DOCUMENT FOR DETAILS). Assignors: RANDSTAD
Assigned to RANDSTAD reassignment RANDSTAD ASSIGNMENT OF ASSIGNORS INTEREST (SEE DOCUMENT FOR DETAILS). Assignors: GIFFORD, JAMES
Publication of US20210403879A1 publication Critical patent/US20210403879A1/en
Assigned to TAKEDA VACCINES, INC. reassignment TAKEDA VACCINES, INC. ASSIGNMENT OF ASSIGNORS INTEREST (SEE DOCUMENT FOR DETAILS). Assignors: KOMMAREDDY, SUSHMA
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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00Medicinal preparations containing antigens or antibodies
    • A61K39/12Viral antigens
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12Antivirals
    • A61P31/14Antivirals for RNA viruses
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K16/00Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies
    • C07K16/08Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from viruses
    • C07K16/10RNA viruses
    • C07K16/116Togaviridae (F); Matonaviridae (F); Flaviviridae (F)
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    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
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    • C12N7/00Viruses; Bacteriophages; Compositions thereof; Preparation or purification thereof
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    • C12Q1/00Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
    • C12Q1/02Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving viable microorganisms
    • C12Q1/22Testing for sterility conditions
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00Medicinal preparations containing antigens or antibodies
    • A61K2039/51Medicinal preparations containing antigens or antibodies comprising whole cells, viruses or DNA/RNA
    • A61K2039/525Virus
    • A61K2039/5252Virus inactivated (killed)
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00Medicinal preparations containing antigens or antibodies
    • A61K2039/545Medicinal preparations containing antigens or antibodies characterised by the dose, timing or administration schedule
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K2317/00Immunoglobulins specific features
    • C07K2317/70Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
    • C07K2317/76Antagonist effect on antigen, e.g. neutralization or inhibition of binding
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
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    • C12N2770/00MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA ssRNA viruses positive-sense
    • C12N2770/00011Details
    • C12N2770/24011Flaviviridae
    • C12N2770/24111Flavivirus, e.g. yellow fever virus, dengue, JEV
    • C12N2770/24121Viruses as such, e.g. new isolates, mutants or their genomic sequences
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    • C12N2770/00MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA ssRNA viruses positive-sense
    • C12N2770/00011Details
    • C12N2770/24011Flaviviridae
    • C12N2770/24111Flavivirus, e.g. yellow fever virus, dengue, JEV
    • C12N2770/24134Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
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    • C12N2770/00MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA ssRNA viruses positive-sense
    • C12N2770/00011Details
    • C12N2770/24011Flaviviridae
    • C12N2770/24111Flavivirus, e.g. yellow fever virus, dengue, JEV
    • C12N2770/24151Methods of production or purification of viral material
    • CCHEMISTRY; METALLURGY
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    • C12N2770/00MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA ssRNA viruses positive-sense
    • C12N2770/00011Details
    • C12N2770/24011Flaviviridae
    • C12N2770/24111Flavivirus, e.g. yellow fever virus, dengue, JEV
    • C12N2770/24161Methods of inactivation or attenuation
    • C12N2770/24163Methods of inactivation or attenuation by chemical treatment
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N30/00Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
    • G01N30/02Column chromatography
    • G01N30/62Detectors specially adapted therefor
    • G01N30/74Optical detectors
    • YGENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02ATECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
    • Y02A50/00TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
    • Y02A50/30Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Definitions

  • FIG. 19 shows the serum viremia of individual AG129 mice three days post-challenge, reported as PFU/mL.
  • FIG. 25 shows compiled kinetics of inactivation data. Data compares infectious potency (TCID50) to RNA copy, and completeness of inactivation (COI) for samples from the four toxicology lots. These data indicate that the sensitivity of the COI assay is greater than TCID50.
  • WO 97/37000 and WO 97/37001 describe the production of animal cells and cell lines that are capable of growth in suspension and in serum free media and are useful in the production and replication of viruses.
  • the cells used for growing the at least one virus are Vero cells.
  • the viral inoculum and the viral culture are preferably free from (i.e. will have been tested for and given a negative result for contamination by) herpes simplex virus, respiratory syncytial virus, parainfluenza virus 3, SARS coronavirus, adenovirus, rhinovirus, reoviruses, polyomaviruses, birnaviruses, circoviruses, and/or parvoviruses (WO 2006/027698).
  • the numerical result of the multiplication of the formaldehyde concentration as measured in % (w/v) with the period of incubation with formaldehyde as measured in days is 0.025 to 0.5 and the formaldehyde concentration is 0.01% (w/v).
  • the Zika virus preparation is treated with 0.008 to 0.015% (w/v) formalin for nine to eleven days at a temperature of 22° C. In some embodiments, the Zika virus preparation is treated with 0.008 to 0.015% (w/v) formalin for ten days at a temperature of 22° C. In some embodiments, the Zika virus preparation is treated with 0.01% (w/v) formalin for eight to twelve days at a temperature of 22° C. In some embodiments, the Zika virus preparation is treated with 0.01% (w/v) formalin for nine to eleven days at a temperature of 22° C. In some embodiments, the Zika virus preparation is treated with 0.01% (w/v) formalin for ten days at a temperature of 22° C.
  • the vaccines and/or immunogenic compositions of the present disclosure containing one or more antigens from at least one inactivated Zika virus may be useful for treating or preventing Zika virus infection in a subject in need thereof and/or inducing an immune response, such as a protective immune response, against Zika virus in a subject in need thereof.
  • the mixture of 50 parts of the composition comprising a virus which has been treated with formaldehyde with 1 part of 20% phosphoric acid and 2.5 parts of 1.0 mg/ml DNPH is incubated at a temperature of 18° C. to 30° C. for 10 to 30 minutes. In some embodiments the mixture of 50 parts of the composition comprising a virus which has been treated with formaldehyde with 1 part of 20% phosphoric acid and 2.5 parts of 1.0 mg/ml DNPH is incubated at a temperature of 18° C. to 30° C. for 15 to 25 minutes.
  • the step of buffer exchange and/or dilution of the sample comprising the Zika virus preparation involves cross-flow filtration.
  • cross-flow filtration which is also called tangential flow filtration the feed flow travels tangentially across the surface of the filter and not into the filter.
  • the potency was determined by two different methods, TCID50 and plaque titration.
  • the TCID50 was calculated by visual inspection of CPE (microscope) and by measuring the difference in absorbance (A 560 -A 420 ) of the wells displaying CPE (yellow in color) compared with red (no CPE). The plates were read on a plate reader, and applied to the same calculator as the microscopically read-plates (absorbance). The values in TCID50 between the two scoring techniques are quite similar, while the values obtained by plaque titration are lower.
  • COI assay control The titer and back titration controls for this assay were performed using Vero indicator cells and scored in a TCID 50 96-well format with wells scored positive based on the media color change from pink to yellow, as a surrogate for cell death, or the presence of CPE.
  • Virus titer control test Two independent replicates of the control virus (PRVABC59) of known titer were subjected to a 10-fold dilution series in media containing 2% FBS, and 100 ⁇ L of each dilution was added to four wells of a 96-well plate containing Vero cells.
  • the method was validated in terms of specificity, linearity, accuracy, repeatability, intermediate precision, robustness, and stability of the sample.
  • accuracy study the Zika vaccine drug product and aluminum hydroxide gel solution were spiked with a specific amount of formaldehyde, and the sample was mixed well by vortex before following the procedure described in Section 2.3.

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US16/768,550 2017-11-30 2018-11-30 Method for inactivating zika virus and related methods Abandoned US20210403879A1 (en)

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US201762592995P 2017-11-30 2017-11-30
PCT/US2018/059227 WO2019090233A2 (en) 2017-11-03 2018-11-05 Method for inactivating zika virus and for determining the completeness of inactivation
US16/768,550 US20210403879A1 (en) 2017-11-30 2018-11-30 Method for inactivating zika virus and related methods
PCT/US2018/063381 WO2019108976A1 (en) 2017-11-30 2018-11-30 Method for inactivating zika virus and related methods

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PCT/US2018/059227 Continuation WO2019090233A2 (en) 2017-11-03 2018-11-05 Method for inactivating zika virus and for determining the completeness of inactivation
PCT/US2018/063381 A-371-Of-International WO2019108976A1 (en) 2017-11-30 2018-11-30 Method for inactivating zika virus and related methods

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US18/339,553 Abandoned US20240024454A1 (en) 2017-11-30 2023-06-22 Method for inactivating zika virus and related methods
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US18/242,025 Abandoned US20240285747A1 (en) 2017-11-30 2023-09-05 Zika vaccines and immunogenic compositions, and methods of using the same

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US (4) US20210403879A1 (https=)
EP (2) EP3717511A4 (https=)
JP (4) JP2021505549A (https=)
KR (2) KR20200094191A (https=)
CN (4) CN111527104A (https=)
AU (5) AU2018375789B2 (https=)
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Cited By (3)

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US11478541B2 (en) 2017-11-03 2022-10-25 Takeda Vaccines, Inc. Method for inactivating Zika virus and for determining the completeness of inactivation
US11975062B2 (en) 2017-11-30 2024-05-07 Takeda Vaccines, Inc. Zika vaccines and immunogenic compositions, and methods of using the same
WO2024167866A3 (en) * 2023-02-06 2025-01-09 Cyanvac Llc Modified piv5 vaccine vectors: methods of making and uses

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WO2020017765A1 (ko) * 2018-07-18 2020-01-23 (주)진매트릭스 지카 바이러스 변이주와 이를 포함한 지카 백신 조성물
BR112021019845A2 (pt) * 2019-05-08 2022-02-15 Takeda Vaccines Inc Composições de vírus inativado e formulações de vacina contra zika
RU2717993C1 (ru) * 2019-10-22 2020-03-27 Федеральное бюджетное учреждение науки "Государственный научный центр вирусологии и биотехнологии "Вектор" Федеральной службы по надзору в сфере защиты прав потребителей и благополучия человека (ФБУН ГНЦ ВБ "Вектор" Роспотребнадзора) Способ получения антигена вируса Зика, обладающего иммуногенными и антигенными свойствами
EP4476329A1 (en) 2022-02-09 2024-12-18 Takeda Vaccines, Inc. Zika vaccines and immunogenic compositions, and methods of using the same
CN121221758B (zh) * 2025-12-02 2026-03-03 华诺泰生物医药科技(成都)有限公司 一种即用型稳定3d-mla佐剂溶液的制备方法

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