Receptor specific transepithelial transport of therapeutics

• US 6,030,613 A
• Filed: 07/24/1997
• Issued: 02/29/2000
• 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): TUNG, MARY BETH
• Application Number:
  US08/899,856
• Time in Patent Office: 950 Days
• Field of Search: 424/178.1, 424/179.1, 424/134.1, 530/387.1, 530/388.22
• US Class Current: 424/134.1
• CPC Class Codes: A01K 2217/075 inducing loss of function, i.e. knock out
• CPC Class Codes: A01K 2227/105 Murine
• CPC Class Codes: A01K 2267/03 Animal model, e.g. for test or diseases
• CPC Class Codes: A01K 67/0276 Knock-out vertebrates
• 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 2039/55522 Cytokines; Lymphokines; Interferons
• CPC Class Codes: A61K 2039/6056 Antibodies
• 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: A61P 37/02 Immunomodulators
• CPC Class Codes: A61P 37/04 Immunostimulants
• CPC Class Codes: C07K 14/70539 MHC-molecules, e.g. HLA-molecules
• CPC Class Codes: C07K 16/065 Purification, fragmentation
• 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: C12N 15/8509 : for producing genetically modified animals, e.g. transgenic

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 method of transepithelial delivery of a drug or an antigen to treat therapeutically a mammal comprising:

administering to the luminal side of an epithelial barrier of an epithelial tissue expressing an FcRn receptor an effective amount of a conjugate of an FcRn binding partner and a drug or antigen under conditions suitable for systemic uptake of said conjugate.

2. The method of claim 1, wherein the conjugate is administered orally.

3. The method of claim 1, wherein the conjugate is administered to intestinal epithelial mucosal tissue.

4. The method of claim 1, wherein the conjugate is administered as an aerosol.

5. The method of claim 1, wherein the conjugate is administered to pulmonary epithelial mucosal tissue.

6. The method of claim 1, wherein the conjugate is administered to nasal epithelial mucosal tissue.

7. The method of claim 1, wherein the conjugate is of the drug and the FcRn binding partner.

8. The method of claim 7, wherein the drug is an antineoplastic compound.

9. The method of claim 7, wherein the drug is an immunoactive compound.

10. The method of claim 7, wherein the drug is a cardiovascular drug.

11. The method of claim 7, wherein the drug is a respiratory drug.

12. The method of claim 7, wherein the drug is a neuromuscular blocking drug.

13. The method of claim 7, wherein the drug is an antiparkinson drug.

14. The method of claim 7, wherein the drug is a diuretic drug.

15. The method of claim 7, wherein the drug is an enzyme.

16. The method of claim 7, wherein the drug is an intravenous anesthetic.

17. The method of claim 7, wherein the drug is an antiepileptic.

18. The method of claim 7, wherein the drug is a chemotherapeutic.

19. The method of claim 7, wherein the drug is an antiviral.

20. The method of claim 7, wherein the drug is a hormone.

21. The method of claim 7, wherein the drug is a peptide or a protein.

22. The method of claim 7, wherein the drug is an antihypertensive.

23. The method of claim 7, wherein the drug is insulin.

24. The method of claim 7, wherein the drug is an antimicrobial compound.

25. The method of claim 1, wherein the FcRn binding partner is a Fc fragment of IgG.

26. The method of claim 1, wherein the FcRn binding partner is non-specific IgG or an FcRn binding fragment of non-specific IgG.

27. The method of claim 1, wherein the FcRn binding partner is an Fc fragment of IgG.

28. The method of claim 1, wherein the drug or antigen is covalently bound to the FcRn binding partner.

29. The method of claim 1, wherein the conjugate is of the antigen and the FcRn binding partner.

30. The method of claim 1, wherein the antigen is characteristic of a tumor.

31. The method of claim 1, wherein the mammal is an adult.

32. The method of claim 1, wherein the mammal is a human.

33. The method of claim 32, wherein the human is an adult.

34. The method of claim 32, wherein the human is a child.