公开(公告)号：US20210355167A1

公开(公告)日：2021-11-18

申请号：US17241884

申请日：2021-04-27

申请人： IMPERIAL INNOVATIONS LTD ,  INSTITUT PASTEUR

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

IPC分类号： C07K14/005 ,  A61P31/14 ,  A61K39/12 ,  C07K16/10 ,  G01N33/569 ,  C07K14/18

摘要： A flavivirus Envelope Dimer Epitope (EDE) and isolated neutralizing antibody or antigen binding fragment thereof directed against the EDE for use in vaccinating an individual against one or more flaviviruses wherein the EDE is a stabilized recombinant flavivirus are provided. The dimer is: covalently stabilized with at least one disulphide inter-chain bond or one sulfhydryl-reactive crosslinker between the two sE monomers, and/or by being formed as a single polypeptide chain, and/or by linking the two sE monomers through modified sugar, 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. The dimer is a homodimer or heterodimer of native and/or mutant envelope polypeptides, from DENV-1, DENV-2, DENV-3, DENV-4, Zika and/or other flavivirus.

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.

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.

公开(公告)号：US11926648B2

公开(公告)日：2024-03-12

申请号：US17241884

申请日：2021-04-27

申请人： IMPERIAL COLLEGE INNOVATIONS LIMITED ,  INSTITUT PASTEUR

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

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

CPC分类号： C07K14/005 ,  A61K39/12 ,  A61P31/14 ,  C07K14/1825 ,  C07K16/1081 ,  G01N33/56983 ,  C07K2317/21 ,  C07K2317/33 ,  C07K2317/34 ,  C07K2317/565 ,  C07K2317/76 ,  C12N2770/24122 ,  C12N2770/24134 ,  C12N2770/24171 ,  Y02A50/30

摘要： A flavivirus Envelope Dimer Epitope (EDE) and isolated neutralizing antibody or antigen binding fragment thereof directed against the EDE for use in vaccinating an individual against one or more flaviviruses wherein the EDE is a stabilized recombinant flavivirus are provided. The dimer is: covalently stabilized with at least one disulphide inter-chain bond or one sulfhydryl-reactive crosslinker between the two sE monomers, and/or by being formed as a single polypeptide chain, and/or by linking the two sE monomers through modified sugar, 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. The dimer is a homodimer or heterodimer of native and/or mutant envelope polypeptides, from DENV-1, DENV-2, DENV-3, DENV-4, Zika and/or other flavivirus.