Nucleic acid vaccines

• US 9,872,900 B2
• Filed: 04/05/2016
• Issued: 01/23/2018
• Est. Priority Date: 04/23/2014
• Status: Active Grant

• Current Assignee: Moderna TX, Inc. (Moderna, Inc.)
• Original Assignee: Moderna TX, Inc. (Moderna, Inc.)
• Inventors: Ciaramella, Giuseppe, Bouchon, Axel, Huang, Eric Yi-Chun
• Primary Examiner(s): Blumel, Benjamin P
• Application Number:
  US15/091,123
• Publication Number:
  US 20160331828A1
• Time in Patent Office: 658 Days
• Field of Search: None
• CPC Class Codes: A61K 2039/53 DNA (RNA) vaccination
• CPC Class Codes: A61K 2039/545 characterised by the dose, timing or administration schedule
• CPC Class Codes: A61K 2039/55555 Liposomes; Vesicles, e.g. nanoparticles; Spheres, e.g. nanospheres; Polymers
• CPC Class Codes: A61K 31/7105 Natural ribonucleic acids, i.e. containing only riboses attached to adenine, guanine, cytosine or uracil and having 3'-5' phosphodiester links
• CPC Class Codes: A61K 39/12 Viral antigens
• CPC Class Codes: A61K 39/145 Orthomyxoviridae, e.g. influenza virus
• CPC Class Codes: A61K 39/155 Paramyxoviridae, e.g. parainfluenza virus
• CPC Class Codes: A61K 39/39 characterised by the immunostimulating additives, e.g. chemical adjuvants
• CPC Class Codes: A61K 48/00 Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
• CPC Class Codes: A61K 9/0019 Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner non-active ingredients are additionally classified in A61K47/00
• CPC Class Codes: A61K 9/1271 Non-conventional liposomes, e.g. PEGylated liposomes, liposomes coated with polymers liposome as conjugate A61K47/6911
• CPC Class Codes: A61K 9/5123 Organic compounds, e.g. fats, sugars
• CPC Class Codes: A61K 9/5146 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, polyamines, polyanhydrides
• CPC Class Codes: A61P 31/16 for influenza or rhinoviruses
• CPC Class Codes: C12N 2760/16122 New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes
• CPC Class Codes: C12N 2760/16134 Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein
• CPC Class Codes: C12N 2760/16234 Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein
• CPC Class Codes: C12N 7/00 Viruses; Bacteriophages; Compositions thereof; Preparation or purification thereof preparing medicinal viral antigen or antibody compositions, e.g. virus vaccines, A61K39/00
• 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

Abstract

The invention relates to compositions and methods for the preparation, manufacture and therapeutic use ribonucleic acid vaccines (NAVs) comprising polynucleotide molecules encoding one or more antigens.

Claims

1. A nucleic acid vaccine, comprising:

one or more RNA polynucleotides having an open reading frame encoding a hemagglutinin protein selected from H1, H7 and H10 wherein the hemagglutinin protein is derived from a strain of Influenza A virus, wherein the RNA polynucleotide includes a chemical modification and a pharmaceutically acceptable carrier or excipient, formulated within a lipid nanoparticle, wherein the lipid nanoparticle has about 20-60 mol % ionizable cationic lipid;

about 5-25 mol % non-cationic lipid;

about 25-55 mol % sterol; and

about 0.5-15 mol % PEG-modified lipid.

2. The vaccine of claim 1, wherein the RNA polynucleotide does not encode F protein.

3. The vaccine of claim 1, wherein the RNA polynucleotide further encodes an influenza neuraminidase protein.

4. The vaccine of claim 1, wherein the Influenza virus is selected from H1N1, H7N9, and H10N8.

5. The vaccine of claim 1 wherein the chemical modification is selected from the group consisting of pseudouridine, N1-methylpseudouridine, 2-thiouridine, 4′

-thiouridine, 5-methylcytosine, 2-thio-1-methyl-1-deaza-pseudouridine, 2-thio-1-methyl-pseudouridine, 2-thio-5-aza-uridine, 2-thio-dihydropseudouridine, 2-thio-dihydrouridine, 2-thio-pseudouridine, 4-methoxy-2-thio-pseudouridine, 4-methoxy-pseudouridine, 4-thio-1-methyl-pseudouridine, 4-thio-pseudouridine, 5-aza-uridine, dihydropseudouridine, 5-methoxyuridine, and 2′

-O-methyl uridine.

6. The vaccine of claim 1, wherein the ionizable cationic lipid is selected from the group consisting of 2,2-dilinoleyl-4-dimethylaminoethyl-[1,3]-dioxolane (DLin-KC2-DMA), dilinoleyl-methyl-4-dimethylaminobutyrate (DLin-MC3-DMA), and di((Z)-non-2-en-1-yl) 9-((4-(dimethylamino)butanoyl)oxy)heptadecanedioate (L319).

7. The vaccine of claim 1, wherein the RNA polynucleotide comprises at least one of SEQ ID Nos 941-945.

8. The vaccine of claim 1, wherein the RNA polynucleotide comprises a polynucleotide having at least 80% sequence identity to at least one of SEQ ID NOs 941-945.

9. The vaccine of claim 1, wherein the RNA polynucleotide comprises a polynucleotide encoding an amino acid sequence having at least 90% sequence identity to SEQ ID NO 941.

10. The vaccine of claim 1, wherein the RNA polynucleotide comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO 941.

11. The vaccine of claim 1, wherein the RNA polynucleotide comprises a polynucleotide encoding an amino acid sequence having at least 90% sequence identity to SEQ ID NO 946.

12. The vaccine of claim 1, wherein the RNA polynucleotide comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO 946.

13. The vaccine of claim 1, wherein the RNA polynucleotide comprises a polynucleotide encoding an amino acid sequence having at least 90% sequence identity to at least one of SEQ ID NO 946-950.

14. The vaccine of claim 1, wherein the RNA polynucleotide comprises a polynucleotide encoding the amino acid sequence of at least one of SEQ ID NO 946-950.

15. The vaccine of claim 1, wherein the RNA polynucleotide comprises a polynucleotide having 80-98% sequence identity to SEQ ID NO 395.

16. The vaccine of claim 1, wherein the RNA polynucleotide comprises 80-95% sequence identity to SEQ ID NO 394.

17. The vaccine of claim 1, wherein the RNA polynucleotide comprises SEQ ID NO:

395.

18. The vaccine of claim 1, wherein the lipid nanoparticle comprises a molar ratio of about 40-60 mol % ionizable cationic lipid, about 1-2 mol % PEG lipid, about 30-50 mol % cholesterol and about 5-15 mol % non-cationic lipid.

19. The vaccine of claim 1, wherein the open reading frame is codon-optimized.

20. The vaccine of claim 1, wherein the hemagglutinin protein is H1.

21. The vaccine of claim 1, wherein the hemagglutinin protein is H7.

22. The vaccine of claim 1, wherein the hemagglutinin protein is H10.

23. A nucleic acid immunogenic composition, comprising:

one or more RNA polynucleotides having an open reading frame encoding a hemagglutinin protein selected from H1, H7 and H10 wherein the hemagglutinin protein is derived from a strain of Influenza A virus, wherein the RNA polynucleotide includes a chemical modification and a pharmaceutically acceptable carrier or excipient, formulated within a lipid nanoparticle, wherein the lipid nanoparticle has about 20-60 mol % ionizable cationic lipid;

about 5-25 mol % non-cationic lipid;

about 25-55 mol % sterol; and

about 0.5-15 mol % PEG-modified lipid.

24. The nucleic acid immunogenic composition of claim 23, wherein the hemagglutinin protein does not comprise the head domain (HA1).

25. The nucleic acid immunogenic composition of claim 23, wherein the hemagglutinin protein does not comprise the cytoplasmic domain.

26. The nucleic acid immunogenic composition of claim 23, wherein the hemagglutinin protein does not comprise the transmembrane domain.