Immunostimulatory plasmids

Patent metadata

Field	Value
Publication number	US-10851379-B2
Application number	US-201815962414-A
Country	US
Kind code	B2
Filing date	Apr 25, 2018
Priority date	Feb 28, 2014
Publication date	Dec 1, 2020
Grant date	Dec 1, 2020

Abstract

The present invention relates to immunomodulator compositions and methods of use as well as methods of making. The immunomodulator compositions comprise immunostimulatory plasmids, or DNA sequence, capable of eliciting an immune response in a recipient subject. Further, the immunostimulatory plasmids, or DNA sequence, do not contain antibiotic resistance coding sequence to help reduce the potential of horizontal transfer of antibiotic resistance in a population.

First claim

What is claimed is:

1. A method of stimulating an immune response in a subject comprising administering to the subject an immunostimulatory composition comprising:
a. a nucleic acid molecule having at least 84% sequence homology with the sequence of SEQ ID NO: 4 and at least 200 CpG dinucleotides; and
b. a cationic liposome delivery vehicle,
wherein an immune response is stimulated in the subject.

2. The method of claim 1 , wherein the liposome delivery vehicle comprises lipids selected from the group consisting of multilamellar vesicle lipids and extruded lipids.

3. The method of claim 1 , wherein the liposome delivery vehicle comprises pairs of lipids selected from the group consisting of N-[1-(2,3-dioleyloxy)propyl]-N,N,N-trimethylammonium chloride (DOTMA) and cholesterol; N[1-(2,3-dioleoyloxy)propyl]-N,N,N-trimethylammonium chloride (DOTAP) and cholesterol; 1-[2-(oleoyloxy)ethyl]-2-oleyl-3-(2-hydroxyethyl)imidazolinium chloride (DOTIM) and cholesterol; and dimethyldioctadecylammonium bromide (DDAB) and cholesterol.

4. The method of claim 1 , wherein administration is intravenously, intramuscularly, intradermally, intraperitoneally, subcutaneously, by spray, by aerosol, in ovo, orally, intraocularly, intratracheally, or intranasally.

5. The method of claim 1 , wherein the immunostimulatory composition further comprises a biological agent.

6. The method of claim 5 , wherein the biological agent is an immune enhancer protein, immunogen, vaccine, antimicrobial, or any combination thereof.

7. The method of claim 1 , wherein the administration is before exposure to an infectious agent.

8. The method of claim 1 , wherein the administration is after exposure to an infectious agent.

9. The method of claim 8 , wherein the immune response stimulated is selected from the group consisting of a non-antigen specific immune response, an antigen specific immune response, an innate immune response, an adaptive immune response, a humoral immune response, a cell-mediated immune response, or a combination thereof.

10. The method of claim 1 , wherein the subject is a mammalian species, aquaculture species, or avian species.

11. The method of claim 1 , wherein the nucleic acid molecule does not code for an immunogen.

12. The method of claim 11 , wherein the nucleic acid molecule has at least 90% sequence homology with the sequence of SEQ ID NO: 4.

13. The method of claim 11 , wherein the nucleic acid molecule comprises SEQ ID NO: 4.

14. The method of claim 11 , wherein the nucleic molecule has at least 260 CpG dinucleotides.

15. The method of claim 11 , wherein the nucleic acid molecule has at least 280 CpG dinucleotides.

16. The method of claim 11 , wherein the nucleic acid molecule has 283 CpG dinucleotides.

17. The method of claim 11 , wherein the nucleic acid molecule further comprises a selectable marker.

18. The method of claim 17 , wherein the selectable marker is LacZ.

19. The method of claim 1 , wherein the nucleic acid molecule has at least 91% sequence homology with the sequence of SEQ ID NO: 4.

20. The method of claim 11 , wherein the liposome delivery vehicle comprises pairs of lipids selected from the group consisting of N-[1-(2,3-dioleyloxy)propyl]-N,N,N-trimethylammonium chloride (DOTMA) and cholesterol; N-[1-(2,3-dioleoyloxy)propyl]-N,N,N-trimethylammonium chloride (DOTAP) and cholesterol; 1-[2-(oleoyloxy)ethyl]-2-oleyl-3-(2-hydroxyethyl)imidazolinium chloride (DOTIM) and cholesterol; and dimethyldioctadecylammonium bromide (DDAB) and cholesterol.

Assignees

• Bayer Animal Health Gmbh

Inventors

• Munnes Marc
• Weiss Christian
• Feldhues Elisabeth
• Schauer Romina G
• Abraham Albert
• Eicker Andrea
• Wehlmann Hermann

Classifications

• A61K45/06 Primary

  Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca · CPC title

• C12N15/117 Primary

  Nucleic acids having immunomodulatory properties, e.g. containing CpG-motifs · CPC title

• A61K39/245

  Herpetoviridae, e.g. herpes simplex virus · CPC title

• A61K39/0258

  Escherichia · CPC title

• A61K38/00

  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 title