Genetic immunization

• US 5,817,637 A
• Filed: 01/13/1997
• Issued: 10/06/1998
• Est. Priority Date: 01/26/1993
• Status: Expired due to Term

• Current Assignee: The Wistar Institute, Trustees Of The University Of Pennsylvania (University of Pennsylvania)
• Original Assignee: The Wistar Institute, Trustees Of The University Of Pennsylvania (University of Pennsylvania)
• Inventors: Wang, Bin, Weiner, David B., Williams, William V.
• Primary Examiner(s): RAILEY, JOHNNY F
• Application Number:
  US08/783,818
• Time in Patent Office: 631 Days
• Field of Search: 514/44, 514/615, 514/818, 424/278.1, 435/975
• US Class Current: 514/44.00R
• CPC Class Codes: A61K 2039/53 DNA (RNA) vaccination
• CPC Class Codes: A61K 39/00 Medicinal preparations containing antigens or antibodies materials for immunoassay G01N33/53
• CPC Class Codes: A61K 39/12 Viral antigens
• CPC Class Codes: A61K 39/21 Retroviridae, e.g. equine infectious anemia virus
• CPC Class Codes: C07K 14/005 from viruses
• CPC Class Codes: C12N 15/87 Introduction of foreign genetic material using processes not otherwise provided for, e.g. co-transformation
• CPC Class Codes: C12N 2740/16034 Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein
• CPC Class Codes: C12N 2740/16122 New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes
• CPC Class Codes: C12N 2740/16134 Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein
• CPC Class Codes: C12N 2740/16222 New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes
• CPC Class Codes: C12N 2740/16234 Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein
• CPC Class Codes: C12N 2740/16322 New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes
• CPC Class Codes: C12N 2740/16334 Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein
• CPC Class Codes: Y02A 50/30 Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
• CPC Class Codes: Y02A 90/10 Information and communication technologies [ICT] supporting adaptation to climate change, e.g. for weather forecasting or climate simulation
• CPC Class Codes: Y10S 435/975 Kit

Abstract

Methods of prophylactic and therapeutic immunization of an individual against pathogen infection, diseases associated with hyperproliferative cells and autoimmune diseases are disclosed. The methods comprise the steps of administering to cells of an individual, a nucleic acid molecule that comprises a nucleotide sequence that encodes a protein which comprises at least one epitope that is identical or substantially similar to an epitope of a pathogen antigen, a hyperproliferative cell associated protein or a protein associated with autoimmune disease respectively. In each case, nucleotide sequence is operably linked to regulatory sequences to enable expression in the cells. The nucleic acid molecule is free of viral particles and capable of being expressed in said cells. The cells may be contacted cells with a cell stimulating agent. Methods of prophylactically and therapeutically immunizing an individual against HIV are disclosed. Pharmaceutical compositions and kits for practicing methods of the present invention are disclosed.

Claims

1. An pharmaceutical immunizing kit comprising:

a) a first inoculant comprising;

i) a pharmaceutically acceptable carrier or diluent; and

,

ii) a first nucleic acid molecule comprising a nucleotide sequence that encodes at least one HIV protein operatively linked to regulatory sequences;

wherein said nucleotide sequence is capable of being expressed in human cells;

b) a second inoculant comprising;

i) a pharmaceutically acceptable carrier or diluent; and

,

ii) a second nucleic acid molecule comprising a nucleotide sequence that encodes at least one HIV protein operatively linked to regulatory sequences;

wherein said nucleotide sequence is capable of being expressed in human cells;

wherein said first nucleic acid molecule is not identical to said second nucleic acid molecule and, taken together, said first nucleic acid molecule and said second nucleic acid molecule encode HIV proteins gag, pol and env; and

c) a third inoculant comprising bupivacaine.

2. A pharmaceutical composition comprising:

a) a compound selected from the group consisting of;

bupivacaine, mepivacaine, lidocaine, procaine, carbocaine and methyl bupivacaine; and

b) a DNA molecule that comprises a DNA sequence that encodes an antigen;

wherein said DNA sequence operatively linked to regulatory sequences which control the expression of said DNA sequence.

3. The pharmaceutical composition of claim 2 wherein said composition comprises bupivacaine.

4. The pharmaceutical composition of claim 2 wherein said DNA molecule is a plasmid.

5. The pharmaceutical composition of claim 2 wherein said DNA sequence encodes a variable region of a T cell receptor.

6. The pharmaceutical composition of claim 2 wherein said DNA sequence encodes a pathogen antigen.

7. The pharmaceutical composition of claim 6 wherein said DNA sequence encodes an antigen from an intracellular pathogen.

8. The pharmaceutical composition of claim 7 wherein said antigen is a viral antigen.

9. The pharmaceutical composition of claim 8 wherein said pathogen is a virus selected from the group consisting of:

human immunodeficiency virus, HIV;

human T cell leukemia virus, HTLV;

influenza virus;

hepatitis A virus;

hepatitis B virus;

hepatitis C virus;

human papilloma virus, HPV;

Herpes simplex 1 virus, HSV1;

Herpes simplex 2 virus, HSV2;

Cytomegalovirus, CMV;

Epstein-Barr virus, EBR;

rhinovirus; and

, coronavirus.

10. The pharmaceutical composition of claim 9 wherein said pathogen is Herpes simplex 2 virus, HSV2.

11. The pharmaceutical composition of claim 9 wherein said pathogen is Hepatitis B virus, HBV.

12. The pharmaceutical composition of claim 9 wherein said pathogen is human T cell leukemia virus, HTLV.

13. The pharmaceutical composition of claim 9 wherein said pathogen is a human immunodeficiency virus.

14. The pharmaceutical composition of claim 2 wherein said DNA sequence encodes a hyperproliferative disease associated protein.

15. The pharmaceutical composition of claim 13 wherein said hyperproliferative disease is cancer.

16. The pharmaceutical composition of claim 14 wherein said hyperproliferative disease is a lymphoma.

17. The pharmaceutical composition of claim 14 wherein said hyperproliferative disease is a melanoma.

18. a method of immunizing an individual against an antigen comprising administering to tissue of said individual'"'"'s body,

a) a compound selected from the group consisting of bupivacaine, mepivacaine, lidocaine, procaine, carbocaine and methyl bupivacaine, and

b) a DNA molecule that comprises a DNA sequence that encodes said antigen, said DNA sequence operatively linked to regulatory sequences which control the expression of said DNA sequence;

wherein said DNA molecule is taken up by cells, said DNA sequence is expressed in said cells and an immune response is generated against said antigen.

19. The method of claim 18 wherein said compound is bupivacaine.

20. The method of claim 18 wherein said DNA molecule is a plasmid.

21. The method of claim 18 wherein said immune response generated against said antigen is an immune response against a pathogen antigen.

22. The method of claim 21 wherein said pathogen is an intracellular pathogen.

23. The method of claim 22 wherein said pathogen is a virus selected from the group consisting of:

human immunodeficiency virus, HIV;

human T cell leukemia virus, HTLV;

influenza virus;

hepatitis a virus;

hepatitis B virus;

hepatitis C virus;

human papilloma virus, HPV;

Herpes simplex 1 virus, HSV1;

Herpes simplex 2 virus, HSV2;

Cytomegalovirus, CMV;

Epstein-Barr virus, EBR;

rhinovirus; and

, coronavirus.

24. The method of claim 23 wherein said pathogen is HIV and said DNA molecule comprises a DNA sequence that encodes an HIV antigen.

25. The method of claim 18 wherein said immune response generated against said antigen is an immune response against a hyperproliferative disease-associated protein.

26. The method of claim 25 wherein said hyperproliferative disease-associated protein is selected from the group consisting of:

protein products of oncogenes myb, myc, fyn, ras, src, neu and trk;

protein products of translocation gene bcr/abl;

P53;

variable regions of antibodies made by B cell lymphomas; and

variable regions of T cell receptors of T cell lymphomas.

27. The method of claim 18 wherein said immune response generated against said antigen is an immune response against an autoimmune disease-associated protein.

28. The method of claim 27 wherein said autoimmune disease-associated protein is selected from the group consisting of:

variable regions of antibodies involved in B cell mediated autoimmune disease; and

variable regions of T cell receptors involved in T cell mediated autoimmune disease.

29. The method of claim 18 wherein said bupivacaine and a DNA molecule are administered subcutaneously.

30. The method of claim 18 wherein said bupivacaine and a DNA molecule are administered intramuscularly, intraperitoneally, intravenously, intraarterially, intraoccularly, orally transdermally and/or by inhalation.

31. The method of claim 18 wherein said bupivacaine and a DNA molecule are administered intradermally.

32. The method of claim 31 wherein said immune response generated against said antigen is an immune response against a pathogen antigen.

33. The method of claim 31 wherein said immune response generated against said antigen is an immune response against a hyperproliferative disease-associated protein.

34. The method of claim 31 wherein said immune response generated against said antigen is an immune response against an autoimmune disease-associated protein.