Receptor specific transepithelial transport of therapeutics

• US 6,485,726 B1
• Filed: 07/24/1998
• Issued: 11/26/2002
• Est. Priority Date: 01/17/1995
• Status: Expired due to Term

• Current Assignee: Brandeis University, Brigham and Women's Hospital Incorporated
• Original Assignee: Brandeis University, Brigham and Women's Hospital Incorporated
• Inventors: Blumberg, Richard S., Simister, Neil E., Lencer, Wayne I.
• Primary Examiner(s): SAUNDERS, DAVID A
• Application Number:
  US09/122,144
• Time in Patent Office: 1,586 Days
• Field of Search: 424/133.1, 424/134.1, 424/185.1, 424/227.1, 424/192.1, 424/193.1, 424/277.1, 424/178.1, 530/387.1, 530/387.3
• US Class Current: 424/178.1
• CPC Class Codes: A61K 2039/505 comprising antibodies
• CPC Class Codes: A61K 2039/541 Mucosal route
• CPC Class Codes: A61K 2039/542 oral/gastrointestinal
• CPC Class Codes: A61K 2039/543 intranasal
• CPC Class Codes: A61K 2039/55516 Proteins; Peptides
• CPC Class Codes: A61K 2039/55544 Bacterial toxins
• CPC Class Codes: A61K 2039/6056 Antibodies
• CPC Class Codes: A61K 38/28 Insulins
• CPC Class Codes: A61K 39/00 Medicinal preparations containing antigens or antibodies materials for immunoassay G01N33/53
• CPC Class Codes: A61K 39/385 Haptens or antigens, bound to carriers
• 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 47/68 the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
• CPC Class Codes: A61K 47/6811 the drug being a protein or peptide, e.g. transferrin or bleomycin
• CPC Class Codes: C07K 2319/30 Non-immunoglobulin-derived peptide or protein having an immunoglobulin constant or Fc region, or a fragment thereof, attached thereto
• CPC Class Codes: Y10S 424/809 involving immunoglobulin or antibody fragment, e.g. fab', fv, fc, heavy chain or light chain
• CPC Class Codes: Y10S 424/81 involving autoimmunity, allergy, immediate hypersensitivity, delayed hypersensitivity, immunosuppression, immunotolerance, or anergy
• CPC Class Codes: Y10S 530/866 involving immunoglobulin or antibody fragment, e.g. fab', fab, fv, fc, heavy chain or light chain
• CPC Class Codes: Y10S 530/868 involving autoimmunity, allergy, immediate hypersensitivity, delayed hypersensitivity, immunosuppression, or immunotolerance

Abstract

The present invention relates in general to methods and products for initiating an immune response against an antigen, and in particular relates to transepithelial delivery of antigens to provoke tolerance and immunity. The present invention further relates to methods and products for the transepithelial delivery of therapeutics. In particular, the invention relates to methods and compositions for the delivery of therapeutics conjugated to a FcRn binding partner to intestinal epithelium, mucosal epithelium and epithelium of the lung. The present invention further relates to the synthesis, preparation and use of the FcRn binding partner conjugates as, or in, pharmaceutical compositions for oral systemic delivery of drugs and vaccines.

Claims

1. A pharmaceutical preparation for activating an immune response comprising

a conjugate of an antigen and a neonatal Fc receptor (“

FcRn”

) binding partner, wherein the antigen is selected from the group consisting of;

an antigen that elicits an immune response to a pathogen, and

an antigen that elicits an immune response to a tumor; and

a pharmaceutically-acceptable carrier, wherein the preparation is formulated as a unit dosage containing the conjugate in an amount effective for activating the immune response of a mammal when administered to an apical surface of an epithelial barrier of the mammal, and wherein the pharmaceutical preparation is an oral formulation, an aerosol formulation or a nasal formulation.

2. The pharmaceutical preparation of claim 1, wherein the FcRn binding partner is non-specific IgG or a FcRn binding fragment of IgG.

3. The pharmaceutical preparation of claim 1, wherein the FcRn binding partner is an Fc fragment of IgG.

4. The pharmaceutical preparation of claim 1, wherein the antigen is covalently coupled to the FcRn binding partner.

5. The pharmaceutical preparation of any one of claims 1, 2, 3 and 4, wherein the unit dosage is an oral formulation.

6. The pharmaceutical preparation of claim 5, wherein the oral formulation is a solid oral formulation, an elixir or a syrup.

7. The pharmaceutical preparation of any one of claims 1, 2, 3 and 4, wherein the unit dosage is an aerosol formulation.

8. The pharmaceutical preparation of claim 7, wherein the aerosol formulation comprises a propellant.

9. The pharmaceutical preparation of any one of claims 1, 2, 3 and 4, wherein the pharmaceutical preparation is a nasal formulation.

10. The pharmaceutical preparation of any one of claims 1, 2, 3 and 4, wherein the formulation is nonaseptic.