Central airway administration for systemic delivery of therapeutics

• US 20060140907A1
• Filed: 01/20/2006
• Published: 06/29/2006
• Est. Priority Date: 03/15/2002
• Status: Abandoned Application

• Current Assignee: Brandeis University, Brigham and Women's Hospital Incorporated, Children's Medical Center Corporation, Syntonix Pharmaceuticals, Inc.
• Original Assignee: Brigham and Women's Hospital Incorporated
• Inventors: Bitonti, Alan J., Blumberg, Richard S., Simister, Neil E., Lencer, Wayne I.
• Application Number:
  US11/336,581
• Publication Number:
  US 20060140907A1
• Time in Patent Office: Days
• US Class Current: 424/85.600
• CPC Class Codes: A61K 47/6849 the antibody targeting a receptor, a cell surface antigen or a cell surface determinant
• CPC Class Codes: A61K 9/0073 Sprays or powders for inhalation; Aerolised or nebulised preparations generated by other means than thermal energy; nasal sprays A61K9/0043; inhalation of vapours of volatile or heated drugs, e.g. essential oils or nicotine, A61K9/007; devices A61M
• CPC Class Codes: A61K 9/0078 for inhalation via a nebulizer such as a jet nebulizer, ultrasonic nebulizer, e.g. in the form of aqueous drug solutions or dispersions
• CPC Class Codes: A61P 15/08 for gonadal disorders or for enhancing fertility, e.g. inducers of ovulation or of spermatogenesis
• CPC Class Codes: A61P 31/12 Antivirals
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 5/10 of the posterior pituitary hormones, e.g. oxytocin, ADH
• CPC Class Codes: A61P 5/30 Oestrogens
• CPC Class Codes: A61P 7/06 Antianaemics

Abstract

The present invention relates to methods and products for the transepithelial systemic delivery of therapeutics. In particular, the invention relates to methods and compositions for the systemic delivery of therapeutics by administering an aerosol containing antibodies or conjugates of a therapeutic agent with an FcRn binding partner to epithelium of central airways of the lung. The methods and products are adaptable to a wide range of therapeutic agents, including proteins and polypeptides, nucleic acids, drugs, and others. The methods and products have the advantage of not requiring administration to the deep lung in order to effect systemic delivery.

Claims

1. A method for systemic delivery of a therapeutic agent, comprising:

administering an effective amount of an aerosol of a conjugate of a therapeutic agent and an FcRn binding partner to lung such that a central lung zone/peripheral lung zone deposition ratio (C/P ratio) is at least 0.7.

2. The method of claim 1, wherein the C/P ratio is at least 1.0.

3. The method of claim 1, wherein the C/P ratio is at least 1.5.

4. The method of claim 1, wherein the C/P ratio is at least 2.0.

5. The method of claim 1, wherein the therapeutic agent is a polypeptide.

6. The method of claim 1, wherein the therapeutic agent is an antigen.

7. The method of claim 6, wherein the antigen is a tumor antigen.

8. The method of claim 1, wherein the therapeutic agent is an oligonucleotide.

9. The method of claim 8, wherein the oligonucleotide is an antisense oligonucleotide.

10. The method of claim 1, wherein the therapeutic agent is erythropoietin (EPO), growth hormone, interferon alpha (IFN-α

), interferon beta (IFN-β

), or follicle stimulating hormone (FSH).

11. The method of claim 1, wherein the therapeutic agent is EPO.

12. The method of claim 1, wherein the therapeutic agent is IFN-β

.

13. The method of claim 1, wherein the therapeutic agent is Factor IX.

14. A method for systemic delivery of a therapeutic agent, comprising:

administering an effective amount of an aerosol of a conjugate of a therapeutic agent and an FcRn binding partner to lung, wherein particles in the aerosol have a mass median aerodynamic diameter (MMAD) of at least 3 micrometers (μ

m).

15. The method of claim 14, wherein the MMAD of the particles is between 3 μ

m and about 8 μ

m.

16. The method of claim 14, wherein the MMAD of the particles is greater than 4 μ

m.

17. The method of claim 14, wherein a majority of the particles are non-respirable.

18. The method of claim 14, wherein the therapeutic agent is a polypeptide.

19. The method of claim 14, wherein the therapeutic agent is an antigen.

20. The method of claim 17, wherein the antigen is a tumor antigen.

21. The method of claim 14, wherein the therapeutic agent is an oligonucleotide.

22. The method of claim 19, wherein the oligonucleotide is an antisense oligonucleotide.

23. The method of claim 14, wherein the therapeutic agent is EPO, growth hormone, IFN-α

, IFN-β

, or FSH.

24. The method of claim 14, wherein the therapeutic agent is EPO.

25. The method of claim 14, wherein the therapeutic agent is IFN-β

.

26. The method of claim 14, wherein the therapeutic agent is Factor IX.

27. An aerosol of a conjugate of a therapeutic agent and an FcRn binding partner, wherein particles in the aerosol have a MMAD of at least 3 μ

m.

28. The aerosol of claim 27, wherein the MMAD of the particles is between 3 μ

m and about 8 μ

m.

29. The aerosol of claim 27, wherein the MMAD of the particles is greater than 4 μ

m.

30. The aerosol of claim 27, wherein a majority of the particles are non-respirable.

31. The aerosol of claim 27, wherein the therapeutic agent is a polypeptide.

32. The aerosol of claim 27, wherein the therapeutic agent is an antigen.

33. The aerosol of claim 28, wherein the antigen is a tumor antigen.

34. The aerosol of claim 27, wherein the therapeutic agent is an oligonucleotide.

35. The aerosol of claim 30, wherein the oligonucleotide is an antisense oligonucleotide.

36. The aerosol of claim 27, wherein the therapeutic agent is EPO, growth hormone, IFN-α

, IFN-β

, or FSH.

37. The aerosol of claim 27, wherein the therapeutic agent is EPO.

38. The aerosol of claim 27, wherein the therapeutic agent is IFN-β

.

39. The aerosol of claim 27, wherein the therapeutic agent is Factor IX.

40. An aerosol delivery system, comprising a container, an aerosol generator connected to the container, and a conjugate of a therapeutic agent and an FcRn binding partner disposed within the container, wherein the aerosol generator is constructed and arranged to generate an aerosol of the conjugate having particles with a MMAD of at least 3 μ

m.

41. The aerosol delivery system of claim 40, wherein the MMAD of the particles is greater than 4 μ

m.

42. The aerosol delivery system of claim 40, wherein a majority of the particles are non-respirable.

43. The aerosol delivery system of claim 40, wherein the aerosol generator comprises a vibrational element in fluid connection with a solution containing the conjugate.

44. The aerosol delivery system of claim 40, wherein the aerosol generator is a nebulizer.

45. The aerosol delivery system of claim 40, wherein the aerosol generator is a mechanical pump.

46. The aerosol delivery system of claim 40, wherein the container is a pressurized container.

47. A method of manufacturing the aerosol delivery system of claim 40, comprising:

providing the container;

providing the aerosol generator connected to the container; and

placing an effective amount of the conjugate in the container.

48. The method of claim 47, wherein the the aerosol generator comprises a vibrational element in fluid connection with a solution containing the conjugate.

49. The method of claim 47, wherein the aerosol generator is a nebulizer

50. The method of claim 47, wherein the aerosol generator is a mechanical pump.

51. The method of claim 47, wherein the container is a pressurized container.