Method of inducing a CTL response

• US 8,372,393 B2
• Filed: 05/03/2006
• Issued: 02/12/2013
• Est. Priority Date: 07/10/1997
• Status: Expired due to Fees

• Current Assignee: Mankind
• Original Assignee: Mannkind Corporation
• Inventors: Simard, John J. L., Kndig, Thomas M.
• Primary Examiner(s): HUYNH, PHUONG N
• Application Number:
  US11/418,397
• Publication Number:
  US 20120046638A1
• Time in Patent Office: 2,477 Days
• Field of Search: None
• US Class Current: 424/93.7
• CPC Class Codes: A61K 2039/53 DNA (RNA) vaccination
• CPC Class Codes: A61K 2039/54 characterised by the route of administration
• CPC Class Codes: A61K 2039/55522 Cytokines; Lymphokines; Interferons
• CPC Class Codes: A61K 2039/57 characterised by the type of response, e.g. Th1, Th2
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• 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 39/00 Medicinal preparations containing antigens or antibodies materials for immunoassay G01N33/53
• CPC Class Codes: A61K 39/0011 Cancer antigens
• CPC Class Codes: A61K 39/12 Viral antigens
• CPC Class Codes: A61K 9/0004 Osmotic delivery systems; Sustained release driven by osmosis, thermal energy or gas
• CPC Class Codes: A61P 31/00 Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
• CPC Class Codes: A61P 31/12 Antivirals
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: C07K 14/005 from viruses
• CPC Class Codes: C12N 2760/10022 New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes
• CPC Class Codes: C12N 2760/10034 Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein

Abstract

Disclosed herein are methods for inducing an immunological CTL response to an antigen by sustained, regular delivery of the antigen to a mammal so that the antigen reaches the lymphatic system. Antigen is delivered at a level sufficient to induce an immunologic CTL response in a mammal and the level of the antigen in the mammal'"'"'s lymphatic system is maintained over time sufficient to maintain the immunologic CTL response. Also disclosed is an article of manufacture for delivering an antigen that induces a CTL response in an animal.

Claims

1. A method of inducing or sustaining a CTL response in a mammal, wherein the method comprises:

delivering an antigen to the mammal at a level sufficient to induce a CTL response to the antigen in the mammal, wherein the antigen is delivered to the mammal by pumping a physiologically-acceptable acellular composition of the antigen from a device held external to the mammal'"'"'s body positioned to deliver the antigen-containing composition so that the antigen reaches the mammal'"'"'s lymph system; and

maintaining the antigen in the mammal'"'"'s lymphatic system over time sufficient to induce or maintain the CTL response specific to the antigen.

2. The method of claim 1, wherein said pumping a physiologically-acceptable composition of the antigen comprises pumping from a device held external to the mammal'"'"'s body through a transmission line.

3. The method of claim 2, wherein said transmission line comprises a catheter.

4. The method of claim 3, wherein said catheter is at least 20 mm in length.

5. The method of claim 1, wherein the antigen is delivered to an area of high lymphatic drainage in the mammal.

6. The method of claim 1, wherein said maintaining step comprises maintaining the antigen in the mammal'"'"'s lymphatic system sufficient to maintain the CTL response for a period of time that is substantially co-extensive with a desired duration of the CTL response.

7. The method of claim 1, wherein delivery of the antigen is directly to the lymphatic system.

8. The method of claim 7, wherein said delivery of the antigen directly to the lymphatic system comprises delivery to an inguinal or axillary lymph node.

9. The method of claim 1, wherein said delivering comprises delivering the antigen in the form of a vector comprising a nucleic acid encoding the antigen.

10. The method of claim 1, wherein said delivering comprises delivering the antigen in the form of a peptide.

11. The method of claim 1, wherein said antigen is provided as a component of a microorganism or mammalian cell.

12. The method of claim 1, wherein said antigen is a disease-matched antigen.

13. The method of claim 12, wherein said disease is cancer.

14. The method of claim 13, wherein said antigen is a tumor-associated antigen.

15. The method of claim 12, wherein said disease is an infectious disease.

16. The method of claim 15, wherein said antigen is a microbial antigen.

17. The method of claim 1, wherein said antigen is a non-peptide antigen.

18. The method of claim 1, wherein said level is sufficient to induce an increase in a pre-existing response.

19. A method of sustaining a CTL response in a mammal, wherein the method comprises:

delivering an antigen to the mammal at a level sufficient to sustain a CTL response to the antigen in the mammal, wherein the antigen is delivered to the mammal by pumping a physiologically-acceptable acellular composition of the antigen from a device held external to the mammal'"'"'s body positioned to deliver the antigen-containing composition so that the antigen reaches the mammal'"'"'s lymph system; and

maintaining the antigen in the mammal'"'"'s lymphatic system over time sufficient to sustain the CTL response specific to the antigen.