US2014050731A1PendingUtilityA1

Vaccine

Assignee: ISIS INNOVATIONPriority: Sep 30, 1999Filed: Aug 13, 2013Published: Feb 20, 2014
Est. expirySep 30, 2019(expired)· nominal 20-yr term from priority
A61K 2039/505C07K 2317/76A61K 2039/53A61K 39/40C07K 14/22A61P 31/04A61K 39/095A61K 39/385C07K 16/1217
67
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Claims

Abstract

The invention relates to a vaccine for the treatment of disease caused by Neisseria , the vaccine including one or more immunogenic components for Neisseria serogroups, as well as antibodies to the immunogenic components and methods of preventing and treating Neisseria infections. The immunogens are based on elements of the inner core lipopolysaccharide.

Claims

exact text as granted — not AI-modified
1 - 11 . (canceled) 
     
     
         12 . A formulation suitable for delivery to a subject, said formulation comprising an immunogenic component conjugated to a carrier, wherein the immunogenic component comprises an epitope of a  Neisseria  lipopolysaccharide (LPS) inner core, said epitope characterised by the presence of a phosphoethanolamine moiety linked to the 3-position of HepII of the inner core, and wherein the immunogenic component is attached to Lipid A, said immunogenic component having the formula: 
       
         
           
           
               
               
           
         
         where R1 is a substituent at the 3-position of HepII and is phosphoethanolamine; R2 is a substituent at the 6-position of HepII, and is hydrogen; R3 is a substituent at the 7-position of HepII, and is hydrogen, and R4 is acetyl or hydrogen at the 3-position, 4-position or 6-position of the GlcNAc residue, or any combination thereof; and where Glc is D-glucopyranose; Kdo is 3-deoxy-D-manno-2-octulosonic acid; Hep is L-glycero-D-manno-heptose, and GlcNAc is 2-acetamido-2-deoxy-D-glucopyranose. 
       
     
     
         13 . The formulation according to  claim 12 , wherein the carrier is a protein. 
     
     
         14 . The formulation according to  claim 13 , wherein the immunogenic component is in the form of a saccharide peptide conjugate. 
     
     
         15 . The formulation according to  claim 14 , wherein the peptide portion of the saccharide peptide conjugate comprises a T cell activating epitope. 
     
     
         16 . The formulation of  claim 12 , wherein the immunogenic component is free from  Neisseria  outer core lipopolysaccharide. 
     
     
         17 . The formulation according to  claim 12 , wherein the immunogenic component is derived from  Neisseria meningitidis  or  Neisseria lactamica.    
     
     
         18 . A formulation suitable for delivery to a subject, said formulation comprising an immunogenic component, wherein the immunogenic component comprises part or all of the inner core of  Neisseria  lipopolysaccharide (LPS), wherein the immunogenic component comprises an epitope characterised by the presence of a phosphoethanolamine moiety linked to the 3-position of HepII of the inner core;
 and wherein said formulation further comprises at least one immunogenic component selected from:   (i) an immunogenic component comprising part or all of the inner core of a  Neisseria  lipopolysaccharide (LPS), wherein the immunogenic component comprises an epitope on the LPS inner core characterised by the presence of a phosphoethanolamine moiety linked to the 6-position of HepII of the inner core;   and   (ii) an immunogenic component comprising part or all of the inner core of a  Neisseria  lipopolysaccharide (LPS), wherein the immunogenic component has no additional phosphoethanolamine addition on the LPS inner core.   
     
     
         19 . The formulation according to  claim 18 , which comprises immunogenic components comprising part or all of the inner core of  Neisseria  lipopolysaccharide glycoforms that are representative of all possible phosphoethanolamine positions on HepII (phosphoethanolamine at 3-position, exocyclic (6-position or 7-position) or absent). 
     
     
         20 . The formulation according to  claim 18 , wherein the immunogenic component characterised by the presence of a phosphoethanolamine moiety linked to the 3-position at HepII of the inner core comprises the inner core attached to Lipid A and has the formula: 
       
         
           
           
               
               
           
         
       
       where R1 is a substituent at the 3-position of HepII and is phosphoethanolamine; R2 is a substituent at the 6-position of HepII, and is hydrogen; R3 is a substituent at the 7-position of HepII, and is hydrogen, and R4 is acetyl or hydrogen at the 3-position, 4-position or 6-position of the GlcNAc residue, or any combination thereof; and where Glc is D-glucopyranose; Kdo is 3-deoxy-D-manno-2-octulosonic acid; Hep is L-glycero-D-manno-heptose, and GlcNAc is 2-acetamido-2-deoxy-D-glucopyranose. 
     
     
         21 . The formulation of  claim 18 , wherein at least one of the immunogenic components comprises an LPS inner core conjugated to a carrier. 
     
     
         22 . The formulation according to  claim 18 , wherein the immunogenic components are derived from  Neisseria meningitidis, Neisseria lactamica , or a combination thereof. 
     
     
         23 . The formulation according to  claim 18 , wherein the immunogenic component characterised by the presence of a phosphoethanolamine moiety linked to the 3-position at HepII of the inner core is reactive with monoclonal antibody B5 produced by the hybridoma deposited with the accession number IDAC 260900-1. 
     
     
         24 . The formulation according to  claim 18 , wherein the immunogenic component characterised by the presence of a phosphoethanolamine moiety linked to the 6-position at HepII of the inner core is reactive with monoclonal antibody A4 produced by the hybridoma deposited with the accession number IDAC 260900-2. 
     
     
         25 . A composition comprising a first monoclonal antibody which recognises the same epitope as monoclonal antibody B5 produced by the hybridoma deposited with the accession number IDAC 260900-1, in combination with a second monoclonal antibody which recognises the same epitope as monoclonal antibody A4 produced by the hybridoma deposited with the accession number IDAC 260900-2. 
     
     
         26 . The composition of  claim 25 , wherein the first monoclonal antibody is monoclonal antibody B5 produced by the hybridoma deposited with the accession number IDAC 260900-1, and the second monoclonal antibody is monoclonal antibody A4 produced by the hybridoma deposited with the accession number IDAC 260900-2. 
     
     
         27 . A method of raising an immune response against  Neisseria  comprising administering the formulation according to  claim 12  to a subject. 
     
     
         28 . A method of raising an immune response against  Neisseria  comprising administering the formulation according to  claim 18  to a subject.

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