Molecular complex for targeting antigens towards cells comprising antigens and uses thereof for vaccination

• US 10,385,120 B2
• Filed: 02/01/2011
• Issued: 08/20/2019
• Est. Priority Date: 02/01/2010
• Status: Active Grant

• Current Assignee: Commissariat a L'Energie Atomique (French Alternative Energies and Atomic Energy Commission)
• Original Assignee: Commissariat a L'Energie Atomique (French Alternative Energies and Atomic Energy Commission)
• Inventors: Leonetti, Michel, Savatier, Alexandra, Gadzinski, Adeline, Boulain, Jean-Claude
• Primary Examiner(s): Juedes, Amy E
• Application Number:
  US13/576,083
• Publication Number:
  US 20130195908A1
• Time in Patent Office: 3,122 Days
• Field of Search: None
• CPC Class Codes: A61K 2039/6037 Bacterial toxins, e.g. diphteria toxoid [DT], tetanus toxoid [TT]
• CPC Class Codes: A61K 2039/605 MHC molecules or ligands thereof
• CPC Class Codes: A61K 2039/6056 Antibodies
• CPC Class Codes: A61K 2039/6068 Other bacterial proteins, e.g. OMP
• CPC Class Codes: A61K 2039/6075 Viral proteins
• CPC Class Codes: A61K 38/00 Medicinal preparations containing peptides peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00
• CPC Class Codes: A61K 39/385 Haptens or antigens, bound to carriers
• CPC Class Codes: A61K 39/39 characterised by the immunostimulating additives, e.g. chemical adjuvants
• CPC Class Codes: A61K 47/64 Drug-peptide, drug-protein or drug-polyamino acid conjugates, i.e. the modifying agent being a peptide, protein or polyamino acid which is covalently bonded or complexed to a therapeutically active agent peptidic linkers A61K47/65
• CPC Class Codes: A61K 47/6415 Toxins or lectins, e.g. clostridial toxins or Pseudomonas exotoxins
• CPC Class Codes: A61K 47/645 Polycationic or polyanionic oligopeptides, polypeptides or polyamino acids, e.g. polylysine, polyarginine, polyglutamic acid or peptide TAT
• CPC Class Codes: A61K 47/646 the entire peptide or protein drug conjugate elicits an immune response, e.g. conjugate vaccines
• CPC Class Codes: A61K 47/6811 the drug being a protein or peptide, e.g. transferrin or bleomycin
• CPC Class Codes: A61P 31/00 Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
• CPC Class Codes: A61P 31/04 Antibacterial agents
• CPC Class Codes: A61P 31/18 for HIV
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: C07K 16/18 against material from animals or humans
• CPC Class Codes: C07K 16/2833 against MHC-molecules, e.g. HLA-molecules

Abstract

The invention relates to a molecular complex for targeting the antigen towards cells comprising antigens, including at least one antigen associated with at least two ligands of surface molecules of cells comprising antigens, said complex including at least one first ligand of a sulphated sugar of the glycosaminoglycan family and a second ligand of a specific surface molecule of cells comprising antigens, and said first ligand being covalently bonded with said antigen and/or said second ligand.

Claims

1. An isolated immunogenic complex comprising at least one antigen associated with at least two protein or peptide ligands of surface molecules of antigen-presenting cells,

said at least two protein or peptide ligands at least one first ligand of heparan sulfates and one second ligand of a surface molecule specific for antigen-presenting cells,

wherein the first ligand is an isolated peptide consisting of the R domain of diphtheria toxin (SEQ ID NO:

6);

the second ligand is selected from the group consisting of;

a BB fragment of Staphylococcus aureus protein A (SEQ ID NO;

     4) and a ZZ derivative thereof (SEQ ID NO;

     3),

said antigen is a protein or a peptide which is specific for a tumor,

said first ligand is covalently bonded to said antigen and to said second ligand,

said complex does not comprise the full length diphtheria toxin, and

said complex induces an anti-tumor immune response.

2. The immunogenic complex of claim 1, wherein said second ligand is the BB fragment (SEQ ID NO:

4).

3. An immunogenic or vaccine composition, comprising at least one immunogenic complex of claim 1, and a pharmaceutically acceptable vehicle.

4. The immunogenic or vaccine composition of claim 3, comprising an amount of said complex sufficient to reduce tumor growth.

5. The immunogenic complex of claim 1, which comprises an amount of said antigen sufficient to treat cancer.

6. The immunogenic complex of claim 1, wherein the second ligand is the ZZ derivative thereof (SEQ ID NO:

3).