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    Anti-dengue vaccines and antibodies
    2.
    发明授权
    Anti-dengue vaccines and antibodies 有权

    公开(公告)号：US11198706B2

    公开(公告)日：2021-12-14

    申请号：US15328441

    申请日：2015-07-23

    申请人： IMPERIAL COLLEGE INNOVATIONS LIMITED ,  Institut Pasteur ,  UNIVERSITÉ PARIS-SACLAY

    发明人： Screaton Gavin ,  Juthathip Mongkolsapaya ,  Alexander Rouvinski ,  Pablo Guardado-Calvo ,  Giovanna Barba-Spaeth ,  Stéphane Duquerroy ,  Marie-Christine Vaney ,  Felix Augusto Rey

    IPC分类号： C07K14/005 ,  A61K39/12 ,  C07K16/10 ,  C07K14/18 ,  A61K47/68 ,  A61K39/00

    摘要： A Dengue virus Envelope Dimer Epitope (EDE) wherein the EDE: c) spans the polypeptides of a Dengue virus Envelope polypeptide dimer; and/or d) is presented on a dimer of Envelope proteins; and/or c) is formed from consecutive or non-consecutive residues of the envelope polypeptide dimer, wherein the dimer is a homodimer or heterodimer of native and/or mutant envelope polypeptides, from any one or two of DENV-1, DENV-2, DENV-3 and DENV-4. The EDE may be a stabilized recombinant dengue virus envelope glycoprotein E ectodomain (sE) dimer, wherein the dimer is: covalently stabilized with at least one disulphide inter-chain bond between the two sE monomers, and/or covalently stabilized with at least one sulfhydryl-reactive crosslinker between the two sE monomers, and/or covalently stabilized by linking the two sE monomers through modified sugars; and/or, covalently stabilised by being formed as a single polypeptide chain, optionally with a linker region, optionally a Glycine Serine rich linker region, separating the sE sequences, and/or non-covalently stabilized by substituting at least one amino acid residue in the amino acid sequence of at least one sE monomer with at least one bulky side chain amino acid, at the dimer interface or in domain 1 (D1)/domain 3 (D3) linker of each monomer. A compound, for example an antibody or antibody fragment that can neutralise more than one Dengue virus serotype, for example an antibody that can bind to an EDE of the invention.

    Neutralising antibody against dengue for use in a method of prevention and/or treatment of zika infection
    4.
    发明授权
    Neutralising antibody against dengue for use in a method of prevention and/or treatment of zika infection 有权

    公开(公告)号：US11111274B2

    公开(公告)日：2021-09-07

    申请号：US16308745

    申请日：2017-06-09

    申请人： IMPERIAL INNOVATIONS LTD ,  INSTITUT PASTEUR

    发明人： Félix Rey ,  Giovanna Barba Spaeth ,  Marie-Christine Vaney ,  Alexander Rouvinski ,  Gavin Screaton ,  Juthathip Mongkolsapaya

    IPC分类号： A61K39/00 ,  A61K35/17 ,  A61K38/00 ,  A61K39/12 ,  C07K14/705 ,  C07K14/005 ,  A61P31/14 ,  C07K16/10 ,  G01N33/569 ,  C07K14/18

    摘要： A flavivirus Envelope Dimer Epitope (EDE) for use in vaccinating an individual against one or more flaviviruses wherein the EDE is a stabilized recombinant flavivirus, optionally dengue virus and/or zika envelope glycoprotein E ectodomain (sE) dimer, wherein the dimer is: covalently stabilized with at least one disulphide inter-chain bond between the two sE monomers, and/or non-covalently stabilized by substituting at least one amino acid residue in the amino acid sequence of at least one sE monomer with at least one bulky side chain amino acid, at the dimer interface or in domain 1 (D1)/domain 3 (D3) linker of each monomer, covalently stabilized with at least one sulfhydryl-reactive crosslinker between the two sE monomers, and/or covalently stabilised by being formed as a single polypeptide chain, optionally with a linker region, optionally a Glycine Serine rich linker region, separating the sE sequences, and/or covalently stabilized by linking the two sE monomers through modified sugars; and/or, wherein the dimer is a homodimer or heterodimer of native and/or mutant envelope polypeptides, from any one or two of DENV-1, DENV-2, DENV-3, DENV-4, Zika or other flavivirus; and wherein the one or more flaviviruses is selected from zika virus; zika virus and dengue virus; zika virus and other flaviviruses; flaviviruses other than dengue. The EDE may be a homodimer or heterodimer of native and/or mutant envelope polypeptides, from any one or two of DENV-1, DENV-2, DENV-3, DENV-4 and Zika. An isolated neutralizing antibody or antigen binding fragment thereof directed against the EDE as defined in any one of claims 1 to 29, optionally wherein said antibody or fragment thereof binds the five polypeptide segments of the dengue virus glycoprotein E ectodomain (sE) consisting of the residues 67-74, residues 97-106, residues 307-314, residues 148-159 and residues 243-251, or corresponding residues of the flavivirus or Zika virus glycoprotein E ectodomain, or consisting of Zika PF13 residues 67-77, residues 97-106, residues 313-315, residues 243-253, residue K373 or corresponding residues of the flavivirus glycoprotein E ectodomain, optionally wherein binding is unaffected by presence or absence of dengue N153 (Zika N154) glycan or corresponding residue, for use in a method for prevention and/or treatment of infection by one or more flaviviruses, wherein the one or more flaviviruses is selected from zika virus; zika virus and dengue virus; zika virus and other flaviviruses; flaviviruses other than dengue.

    NEUTRALISING ANTIBODY AGAINST DENGUE FOR USE IN A METHOD OF PREVENTION AND/OR TREATMENT OF ZIKA INFECTION
    6.
    发明申请
    NEUTRALISING ANTIBODY AGAINST DENGUE FOR USE IN A METHOD OF PREVENTION AND/OR TREATMENT OF ZIKA INFECTION 审中-公开

    公开(公告)号：US20190256560A1

    公开(公告)日：2019-08-22

    申请号：US16308745

    申请日：2017-06-09

    申请人： IMPERIAL INNOVATIONS LTD ,  INSTITUT PASTEUR

    发明人： Félix Rey ,  Giovanna Barba Spaeth ,  Marie-Christine Vaney ,  Alexander Rouvinski ,  Gavin Screaton ,  Juthathip Mongkolsapaya

    IPC分类号： C07K14/005 ,  A61K39/12 ,  A61P31/14 ,  C07K16/10 ,  G01N33/569

    摘要： A flavivirus Envelope Dimer Epitope (EDE) for use in vaccinating an individual against one or more flaviviruses wherein the EDE is a stabilized recombinant flavivirus, optionally dengue virus and/or zika envelope glycoprotein E ectodomain (sE) dimer, wherein the dimer is: covalently stabilized with at least one disulphide inter-chain bond between the two sE monomers, and/or non-covalently stabilized by substituting at least one amino acid residue in the amino acid sequence of at least one sE monomer with at least one bulky side chain amino acid, at the dimer interface or in domain 1 (D1)/domain 3 (D3) linker of each monomer, covalently stabilized with at least one sulfhydryl-reactive crosslinker between the two sE monomers, and/or covalently stabilised by being formed as a single polypeptide chain, optionally with a linker region, optionally a Glycine Serine rich linker region, separating the sE sequences, and/or covalently stabilized by linking the two sE monomers through modified sugars; and/or, wherein the dimer is a homodimer or heterodimer of native and/or mutant envelope polypeptides, from any one or two of DENV-1, DENV-2, DENV-3, DENV-4, Zika or other flavivirus; and wherein the one or more flaviviruses is selected from zika virus; zika virus and dengue virus; zika virus and other flaviviruses; flaviviruses other than dengue. The EDE may be a homodimer or heterodimer of native and/or mutant envelope polypeptides, from any one or two of DENV-1, DENV-2, DENV-3, DENV-4 and Zika. An isolated neutralizing antibody or antigen binding fragment thereof directed against the EDE as defined in any one of claims 1 to 29, optionally wherein said antibody or fragment thereof binds the five polypeptide segments of the dengue virus glycoprotein E ectodomain (sE) consisting of the residues 67-74, residues 97-106, residues 307-314, residues 148-159 and residues 243-251, or corresponding residues of the flavivirus or Zika virus glycoprotein E ectodomain, or consisting of Zika PF13 residues 67-77, residues 97-106, residues 313-315, residues 243-253, residue K373 or corresponding residues of the flavivirus glycoprotein E ectodomain, optionally wherein binding is unaffected by presence or absence of dengue N153 (Zika N154) glycan or corresponding residue, for use in a method for prevention and/or treatment of infection by one or more flaviviruses, wherein the one or more flaviviruses is selected from zika virus; zika virus and dengue virus; zika virus and other flaviviruses; flaviviruses other than dengue.