CA2291483A1 - Immunostimulatory oligonucleotides, compositions thereof and methods of use thereof - Google Patents

Immunostimulatory oligonucleotides, compositions thereof and methods of use thereof Download PDF

Info

Publication number
CA2291483A1
CA2291483A1 CA002291483A CA2291483A CA2291483A1 CA 2291483 A1 CA2291483 A1 CA 2291483A1 CA 002291483 A CA002291483 A CA 002291483A CA 2291483 A CA2291483 A CA 2291483A CA 2291483 A1 CA2291483 A1 CA 2291483A1
Authority
CA
Canada
Prior art keywords
immunomodulatory
immune response
immunomodulatory composition
antigen
iss
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Granted
Application number
CA002291483A
Other languages
French (fr)
Other versions
CA2291483C (en
Inventor
David Schwartz
Mark Roman
Dino Dina
Eyal Raz
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Dynavax Technologies Corp
Original Assignee
Dynavax Technologies Corporation
David Schwartz
Mark Roman
Dino Dina
Eyal Raz
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Family has litigation
First worldwide family litigation filed litigation Critical https://patents.darts-ip.com/?family=21956478&utm_source=google_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=CA2291483(A1) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.
Application filed by Dynavax Technologies Corporation, David Schwartz, Mark Roman, Dino Dina, Eyal Raz filed Critical Dynavax Technologies Corporation
Publication of CA2291483A1 publication Critical patent/CA2291483A1/en
Application granted granted Critical
Publication of CA2291483C publication Critical patent/CA2291483C/en
Anticipated expiration legal-status Critical
Expired - Lifetime legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
    • C07H21/00—Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K39/39—Medicinal preparations containing antigens or antibodies characterised by the immunostimulating additives, e.g. chemical adjuvants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/02—Immunomodulators
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/02—Immunomodulators
    • A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/46—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
    • C07K14/47—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals
    • C07K14/4701—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals not used
    • C07K14/4702—Regulators; Modulating activity
    • C07K14/4703—Inhibitors; Suppressors
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09—Recombinant DNA-technology
    • C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
    • C12N15/117—Nucleic acids having immunomodulatory properties, e.g. containing CpG-motifs
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K2039/555—Medicinal preparations containing antigens or antibodies characterised by a specific combination antigen/adjuvant
    • A61K2039/55511—Organic adjuvants
    • A61K2039/55561—CpG containing adjuvants; Oligonucleotide containing adjuvants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K2039/57—Medicinal preparations containing antigens or antibodies characterised by the type of response, e.g. Th1, Th2
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2310/00—Structure or type of the nucleic acid
    • C12N2310/10—Type of nucleic acid
    • C12N2310/11—Antisense
    • C12N2310/111—Antisense spanning the whole gene, or a large part of it
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2310/00—Structure or type of the nucleic acid
    • C12N2310/10—Type of nucleic acid
    • C12N2310/17—Immunomodulatory nucleic acids
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2310/00—Structure or type of the nucleic acid
    • C12N2310/10—Type of nucleic acid
    • C12N2310/18—Type of nucleic acid acting by a non-sequence specific mechanism
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2310/00—Structure or type of the nucleic acid
    • C12N2310/30—Chemical structure
    • C12N2310/31—Chemical structure of the backbone
    • C12N2310/315—Phosphorothioates
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2310/00—Structure or type of the nucleic acid
    • C12N2310/30—Chemical structure
    • C12N2310/33—Chemical structure of the base
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2310/00—Structure or type of the nucleic acid
    • C12N2310/30—Chemical structure
    • C12N2310/33—Chemical structure of the base
    • C12N2310/334—Modified C
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2310/00—Structure or type of the nucleic acid
    • C12N2310/30—Chemical structure
    • C12N2310/35—Nature of the modification
    • C12N2310/351—Conjugate
    • C12N2310/3513—Protein; Peptide
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
    • C12Q1/68—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
    • C12Q1/6876—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes
    • C12Q1/6883—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
    • Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
    • Y02A50/30—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 immunostimulatory oligonucleotide compositions. These oligonucleotides comprise an immunostimulatory octanucleotide sequence. These oligonucleotides can be administered in conjunction with an immunostimulatory peptide or antigen. Methods for modulating an immune response upon administration of the oligonucleotide are also disclosed. In addition, an in vitro screening method to identify oligonucleotides with immunostimulatory activity is provided.

Claims (80)

We claim:
1. An immunomodulatory oligonucleotide comprising an immunostimulatory sequence (ISS), wherein the ISS comprises an octanucleotide sequence selected from the group consisting of GACGCTCC; GACGTCCC; AGCGTTCC; AGCGCTCC; AGCGTCCC; AGCGCCCC; AACGTCCC;
AACGCCCC; GGCGTTCC; GGCGCTCC; GGCGTCCC; GGCGCCCC; GACGCTCG; GACGTCCG;
GACGCCCG; AGCGTTCG; AGCGTCCG; AGCGCCCG; AACGTCCG; AACGCCCG; GGCGTTCG;
GGCGCTCG: GGCGTCCG: GGCGCCCG.
2. An immunomodulatory oligonucleotide comprising the sequence of SEQ ID NO:2.
3. An immunomodulatory oligonucleotide comprising the sequence of SEQ ID NO:4.
4. An immunomodulatory oligonucleotide comprising the sequence of SEQ ID NO:1,
5. An immunomodulatory oligonucleotide comprising the sequence of SEQ ID NO:6.
6. An immunomodulatory oligonucleotide comprising the sequence of SEQ ID NO:7.
7. An immunomodulatory oligonucieotide comprising the sequence of SEQ ID
NO:12.
8. An immunomodulatory oligonucleotide comprising the sequence of SEQ ID
NO:15.
9. An immunomodulatory oligonucleotide comprising the sequence of SEQ ID
NO:16.
10. The immunomodulatory oligonucleotide of claim 1, wherein at least one cytosine of the octanucleotide sequence is substituted with a modified cytosine.
11. An immunomodulatory oligonucleotide of claim 10, wherein the modified cytosine comprises an addition of an electron-withdrawing group at least to C-5.
12. An immunomodulatory oligonucleotide of claim 10, wherein the modified cytosine comprises an addition of an electron-withdrawing group at least to C-6.
13. An immunomoduiatory oligonucleotide of claim 10, wherein the modified cytosine is a 5'-bromocytidine.
14. An immunomodulatory ollgonuclevtide of claim 10, wherein the C at the third position from the 5' end of the octanucleotide is substituted with a 5'-bromocytidine.
15. An immunomodulatory oligonucleotide of claim 10, wherein the C at the third position from the 5' end of the ISS octanucleotide is substituted with a 5'-bromocytidine and the C at the seventh-position from the 5' end of the ISS octanucleotide is substituted with a 5'-bromocytidine.
16. An immunomodulatory composition comprising an immunomodulatory oligonucleotide according to claim 1;
and further comprising an antigen.
17. An immunomodulatory composition of claim 16, wherein the antigen is selected from the group consisting of peptides, glycoproteins, polysaccharides, and lipids.
18. An immunomodulatory composition of claim 16, wherein the antigen is conjugated to the immunomodulatory oligonucleotide.
19. An immunomodulatory composition comprising an immunomodulatory oligonucleotide according to claim 1;
and further comprising a facilitator selected from the group consisting of co-stimulatory molecules, cytokines, chemokines, targeting protein ligand, a trans-activating factor, a peptide, and a peptide comprising a modified amino acid.
20. An immunomodulatory composition of claim 19, wherein the facilitator is conjugated to the immunomodulatory oligonucleotide.
21. An immunomodulatory composition comprising an immunomodulatory oligonucleotide according to claim 1;
and further comprising an antigen;
and further comprising an adjuvant.
22. An immunomodulatory composition of claim 21, wherein the antigen is selected from the group consisting of peptides, glycoproteins, polysaccharides, and lipids.
23. An immunomodulatory composition of claim 21, wherein the antigen is conjugated to the immunomodulatory oligonucleotide.
24. An immunomodulatory composition comprising a polynucleotide comprising an immunostimulatory sequence (ISS) and an antigen, wherein the ISS comprises 5'-cytosine, guanine-3', and wherein the ISS and the antigen are not conjugated and are proximately associated at a distance effective to enhance an immune response compared to co-administration of the 1SS
and antigen in solution.
25. The immunomodulatory composition of claim 24, wherein the 1SS comprises a palindromic region, and wherein the palindromic region comprises the sequence 5'-cytosine, guanine-3'.
26. The immunomodulatory composition of claim 25, wherein the ISS comprises 5'-purine, purine, cytosine, guanine, pyrimidine, pyrimidine-3'.
27. The immunomodulatory composition of claim 26, wherein the ISS comprises a sequence selected from the group consisting of AACGTT. AGCGTT, GACGTT, GGCGTT, AACGTC, AGCGTC, GACGTC, GGCGTC, AACGCC, AGCGCC, GACGCC, GGCGCC, AACGCT, AGCGCT, GACGCT, and GGCGCT.
26. The immunomodulatory composition of claim 26, wherein the ISS is selected from the group consisting of GACGCTCC; GACGCCC; AGCGTTCC; AGCGCTCC; AGCGTCCC:
AGCGCCCC; AACGTCCC; AACGCCCC; GGCGTTCC; GGCGCTCC; GGCGTCCC; GGCGCCCC;
GACGCTCG; GACGTCCG; GACGCCCG; AGCGTTCG; AGCGTCCG; AGCGCCCG; AACGTCCG;
AACGCCCG; GGCGTTCG; GGCGCTCG; GGCGTCCG; GGCGCCCG.
29. The immunomodulatory composition of claim 24, wherein the ISS and antigen are proximately associated by encapsulation.
30. The immunomodulatory composition of claim 29, wherein the encapsulation is within liposomes.
31. The immunomodulatory composition of claim 24, wherein the ISS and antigen are proximately associated by linkage to a platform molecule.
32. The immunomodulatory composition of claim 24, wherein the ISS and antigen are proximately associated at a distance from about 0.04 µm to about 100 µm.
33. The immunomodulatory composition of claim 32, wherein the distance is from about 0.1 µm to about 20 µm.
34. The immunomodulatory composition of claim 33, wherein the distance is from about 0.15 µm to about 10 µm.
35. The immunomodulatory composition of claim 24, wherein the ISS and antigen are proximately associated such that the ISS and the antigen are co-delivered to an immune target.
36. The immunomodulatory composition of claim 35, wherein the immune target is a lymphatic structure.
37. An immunomodulatory composition of claim 35, wherein the immune target is a antigen presenting cell.
38. An immunomodulatory composition of claim 37, wherein the antigen presenting cell is a dendritic cell.
39. An immunomodulatory composition of claim 37, wherein the antigen presenting cell is a macrophage cell.
40. An immunomodulatory composition of claim 37, wherein the antigen presenting cell is a lymphocyte.
41. The immunomodulatory composition of claim 24, further comprising an adjuvant.
42. The immunomodulatory composition of claim 40, wherein the ISS and antigen are proximately associated by encapsulation.
43. The immunomodulatory composition of claim 40, wherein the ISS and antigen are proximately associated by linkage to a platform molecule.
44. A method of modulating an immune response in an individual comprising administering the immunomodulatory oligonucleotide of claim 1 to the individual in an amount sufficient to modulate the immune response.
45. The method of claim 44, wherein the modulating of an immune response comprises induction of a Th1 response.
46. A method of modulating an immune response in an individual comprising administering to the individual the immunomodulatory oligonucleotide of SEQ ID NO:2 in an amount sufficient to modulate the immune response.
47. The method of claim 46, wherein the modulating of an immune response comprises induction of a Th1 response.
48. A method of modulating an immune response in an individual comprising administering the immunomodulatory composition of claim 16 to the individual in an amount sufficient to modulate the immune response.
49. The method of claim 48, wherein the modulating of an immune response comprises induction of a Th1 response.
50. A method of modulating an immune response in an individual comprising the administration of an immunomodulatory composition according to claim 18 in an amount sufficient to modulate the immune response.
51. The method of claim 50, wherein the modulating of an immune response comprises induction of a Th1 response.
52. A method of modulating an immune response in an individual comprising the administration of an immunomodulatory composition according to claim 21 in an amount sufficient to modulate the immune response.
53. The method of claim 52, wherein the modulating of an immune response comprises induction of a Th1 response.
54. A method of modulating an immune response in an individual comprising the administration of an immunomodulatory composition according to claim 24 in an amount sufficient to modulate the immune response.
55. The method of claim 54, wherein the modulating of an immune response comprises induction of a Th1 response.
56. A method of modulating an immune response in an individual comprising the administration of an immunomodulatory composition according to claim 28 in an amount sufficient to modulate the immune response.
57. The method of claim 56 wherein the modulating of an immune response comprises induction of a Th1 response.
58. A method of modulating an immune response in an individual comprising the administration of an immunomodulatory composition according to claim 41 in an amount sufficient to modulate the immune response.
59. The method of claim 58 wherein the modulating of an immune response comprises induction of a Th1 response.
60. A method according to claim 44, wherein the individual is suffering from a disorder selected from the group consisting of cancer, allergic disease, asthma and an infectious disease.
61. A method according to claim 60, wherein the infectious disease is caused by a virus selected from the group consisting of hepatitis B virus, papillomavirus and human immunodeficiency virus.
62. A method of preventing an infectious disease in an individual comprising administration of an immunomodulatory composition according to claim 16.
63. A method according to claim 62, wherein the infectious disease is due to a viral infection.
64. A method according to claim 63, wherein the virus is selected from the group consisting of hepatitis B virus, influenza virus, herpes virus, human immunodeficiency virus and papillomavirus.
65. A method according to claim 62, wherein the infectious disease is due to a bacterial infection.
66. A method according to claim 65, wherein the bacteria is selected from the group consisting of Hemophilus influenza, Mycobacterium tuberculosis and Bordetella pertussis.
67. A method according to claim 62, wherein the infectious disease is due to a parasitic infection.
68. A method according to claim 67, wherein the parasitic agent is selected from a group consisting of malarial plasmodia, Leishmania species, Trypanosoma species and Schistosoma species.
69. A method of preventing an infectious disease in an individual comprising administration of an immunomodulatory composition according to claim 2.
70. A method of preventing an infectious disease in an individual comprising administration of an immunomodulatory composition according to claim 18.
71. A method of preventing an infectious disease in an individual comprising administration of an immunomodulatory composition according to claim 21.
72. A method of preventing an infectious disease in an individual comprising administration of an immunomodulatory composition according to claim 24.
73. A method of modulating an immune response comprising the administration of an immunomodulatory composition according to claim 28.
74. A method to screen for human immunostimulatory activity of oligonucleotides comprising the steps of:

(a) providing macrophage cells and an aliquot of an oligonucleotide to be tested;
(b) incubating the cells and oligonucleotide of step a) for an appropriate length of time;
(c) determining the relative amount of Th1-biased cytokines in the cell culture supernatant.
75. A method to screen for human immunostimulatory activity of oligonucleotides according to claim 74, wherein the cells are selected from the 90196B cell line and the P388D1 cell line.
76. A method to screen for human immunostimulatory activity of oligonucleotides according to claim 74, wherein at least one of the Th1-biased cytokines determined is interferon-gamma.
77. A method to screen for human immunostimulatory activity of oligonucleotides according to claim 74, wherein at least one of the Th1-biased cytokines determined is interleukin-12.
78. An immunomodulatory composition comprising a polynucleotide comprising (a) an immunostimulatory sequence (ISS); (b) an antigen; and (c) an adjuvant other than alum, wherein the ISS comprises 5'-cytosine, guanine-3', wherein the ISS and antigen are not conjugated, and wherein the adjuvant is in an amount sufficient to enhance an immune response compared to co-administration of the ISS and antigen without adjuvant.
79. The immunomodulatory composition of claim 78, wherein the ISS comprises a palindromic region, and wherein the palindromic region comprises the sequence 5'-cytosine.
guanine-3'.
80. A method of modulating an immune response in an individual, comprising administering the composition of claim 78 in an amount sufficient to modulate the immune response.
CA2291483A 1997-06-06 1998-06-05 Immunostimulatory oligonucleotides, compositions thereof and methods of use thereof Expired - Lifetime CA2291483C (en)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US4879397P 1997-06-06 1997-06-06
US60/048,793 1997-06-06
PCT/US1998/011578 WO1998055495A2 (en) 1997-06-06 1998-06-05 Immunostimulatory oligonucleotides, compositions thereof and methods of use thereof

Publications (2)

Publication Number Publication Date
CA2291483A1 true CA2291483A1 (en) 1998-12-10
CA2291483C CA2291483C (en) 2012-09-18

Family

ID=21956478

Family Applications (2)

Application Number Title Priority Date Filing Date
CA002293489A Expired - Fee Related CA2293489C (en) 1997-06-06 1998-06-05 Inhibitors of dna immunostimulatory sequence activity
CA2291483A Expired - Lifetime CA2291483C (en) 1997-06-06 1998-06-05 Immunostimulatory oligonucleotides, compositions thereof and methods of use thereof

Family Applications Before (1)

Application Number Title Priority Date Filing Date
CA002293489A Expired - Fee Related CA2293489C (en) 1997-06-06 1998-06-05 Inhibitors of dna immunostimulatory sequence activity

Country Status (13)

Country Link
US (4) US6225292B1 (en)
EP (3) EP2085090A3 (en)
JP (2) JP4101888B2 (en)
AT (2) ATE252596T1 (en)
AU (2) AU753172B2 (en)
CA (2) CA2293489C (en)
CY (1) CY1109287T1 (en)
DE (2) DE69819150T3 (en)
DK (1) DK1003850T3 (en)
ES (1) ES2326848T3 (en)
HK (1) HK1024701A1 (en)
PT (1) PT1003850E (en)
WO (2) WO1998055495A2 (en)

Families Citing this family (199)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6727230B1 (en) 1994-03-25 2004-04-27 Coley Pharmaceutical Group, Inc. Immune stimulation by phosphorothioate oligonucleotide analogs
US7935675B1 (en) * 1994-07-15 2011-05-03 University Of Iowa Research Foundation Immunostimulatory nucleic acid molecules
US6429199B1 (en) * 1994-07-15 2002-08-06 University Of Iowa Research Foundation Immunostimulatory nucleic acid molecules for activating dendritic cells
US20030026782A1 (en) 1995-02-07 2003-02-06 Arthur M. Krieg Immunomodulatory oligonucleotides
US6207646B1 (en) 1994-07-15 2001-03-27 University Of Iowa Research Foundation Immunostimulatory nucleic acid molecules
US6239116B1 (en) 1994-07-15 2001-05-29 University Of Iowa Research Foundation Immunostimulatory nucleic acid molecules
EP0909323B1 (en) 1996-01-04 2007-02-28 Novartis Vaccines and Diagnostics, Inc. Helicobacter pylori bacterioferritin
CA2268825C (en) * 1996-10-11 2006-04-18 The Regents Of The University Of California Immunostimulatory polynucleotide/immunomodulatory molecule conjugates
EP0855184A1 (en) 1997-01-23 1998-07-29 Grayson B. Dr. Lipford Pharmaceutical composition comprising a polynucleotide and an antigen especially for vaccination
JP2001513776A (en) 1997-02-28 2001-09-04 ユニバーシティ オブ アイオワ リサーチ ファウンデーション Use of nucleic acids containing unmethylated CpG dinucleotides in the treatment of LPS-related disorders
US6406705B1 (en) 1997-03-10 2002-06-18 University Of Iowa Research Foundation Use of nucleic acids containing unmethylated CpG dinucleotide as an adjuvant
EP1027033B1 (en) 1997-05-14 2009-07-22 The University Of British Columbia High efficiency encapsulation of nucleic acids in lipid vesicles
JP4101888B2 (en) * 1997-06-06 2008-06-18 ダイナバックス テクノロジーズ コーポレイション Immunostimulatory oligonucleotides, compositions thereof and methods of use thereof
US6589940B1 (en) 1997-06-06 2003-07-08 Dynavax Technologies Corporation Immunostimulatory oligonucleotides, compositions thereof and methods of use thereof
US6221882B1 (en) * 1997-07-03 2001-04-24 University Of Iowa Research Foundation Methods for inhibiting immunostimulatory DNA associated responses
JP4663113B2 (en) * 1997-09-05 2011-03-30 ザ リージェンツ オブ ザ ユニバーシティ オブ カリフォルニア Use of immunostimulatory oligonucleotides to prevent or reduce antigen-stimulated granulocyte-mediated inflammation
DK1077722T3 (en) 1998-05-22 2006-11-27 Ottawa Health Research Inst Methods and products for the induction of mucosa immunity
US6562798B1 (en) * 1998-06-05 2003-05-13 Dynavax Technologies Corp. Immunostimulatory oligonucleotides with modified bases and methods of use thereof
JP4620251B2 (en) 1998-08-10 2011-01-26 アンチジェニックス・インコーポレイテッド Composition of CPG and saponin adjuvant and method thereof
CA2344558A1 (en) * 1998-10-09 2000-04-20 Dynavax Technologies Corporation Anti hiv compositions comprising immunostimulatory polynucleotides and hiv antigens
CA2371994C (en) * 1999-02-26 2010-09-28 Guido Grandi Enhancement of bactericidal activity of neisseria antigens with oligonucleotides containing cg motifs
DE60020677T2 (en) 1999-02-26 2006-05-04 Chiron Corp., Emeryville MICROEMULSIONS WITH ADSORBED MACROMOLECULES AND MICROPARTICLES
GB2348132B (en) * 1999-03-02 2004-08-04 Nedaa Abdul-Ghani Nasif Asthma/allergy therapy that targets t-lymphocytes and/or eosinophils
WO2000054803A2 (en) * 1999-03-16 2000-09-21 Panacea Pharmaceuticals, Llc Immunostimulatory nucleic acids and antigens
FR2790955B1 (en) * 1999-03-19 2003-01-17 Assist Publ Hopitaux De Paris USE OF STABILIZED OLIGONUCLEOTIDES AS ANTI-TUMOR ACTIVE INGREDIENT
US6977245B2 (en) 1999-04-12 2005-12-20 The United States Of America As Represented By The Department Of Health And Human Services Oligodeoxynucleotide and its use to induce an immune response
WO2000061151A2 (en) * 1999-04-12 2000-10-19 The Government Of The United States Of America, Represented By The Secretary, Department Of Health And Human Services Oligodeoxynucleotide and its use to induce an immune response
ES2228497T3 (en) 1999-04-19 2005-04-16 Glaxosmithkline Biologicals S.A. ADJUTIVE COMPOSITION INCLUDING SAPONINA AND AN IMMUNO STIMULANT OLIGONUCLEOTIDE.
US6558670B1 (en) 1999-04-19 2003-05-06 Smithkline Beechman Biologicals S.A. Vaccine adjuvants
US6737066B1 (en) 1999-05-06 2004-05-18 The Immune Response Corporation HIV immunogenic compositions and methods
BR0010323A (en) * 1999-05-06 2002-01-08 Immune Response Corp Inc Immunogenic compositions, kit and method of making it for use in the immunization of a mammal
JP2003507341A (en) 1999-08-19 2003-02-25 ダイナバックス テクノロジーズ コーポレイション Immunostimulatory sequences and methods for modulating an immune response with compositions for using the same and compositions for using the same
ATE376838T1 (en) * 1999-08-27 2007-11-15 Inex Pharmaceuticals Corp COMPOSITIONS FOR STIMULATING CYTOKINE SECRETION AND INDUCING AN IMMUNE RESPONSE
US6949520B1 (en) 1999-09-27 2005-09-27 Coley Pharmaceutical Group, Inc. Methods related to immunostimulatory nucleic acid-induced interferon
CN1796404A (en) 1999-10-29 2006-07-05 启龙有限公司 Neisserial antigenic peptides
US7223398B1 (en) 1999-11-15 2007-05-29 Dynavax Technologies Corporation Immunomodulatory compositions containing an immunostimulatory sequence linked to antigen and methods of use thereof
ATE378348T1 (en) * 2000-01-14 2007-11-15 Us Health OLIGODEOXYNUCLEOTIDES AND THEIR USE FOR INDUCING AN IMMUNE RESPONSE
WO2001095935A1 (en) * 2000-01-20 2001-12-20 Ottawa Health Research Institute Immunostimulatory nucleic acids for inducing a th2 immune response
US20040131628A1 (en) * 2000-03-08 2004-07-08 Bratzler Robert L. Nucleic acids for the treatment of disorders associated with microorganisms
US20010046967A1 (en) * 2000-03-10 2001-11-29 Gary Van Nest Methods of preventing and treating respiratory viral infection using immunomodulatory polynucleotide
US20020028784A1 (en) * 2000-03-10 2002-03-07 Nest Gary Van Methods of preventing and treating viral infections using immunomodulatory polynucleotide sequences
US20020107212A1 (en) * 2000-03-10 2002-08-08 Nest Gary Van Methods of reducing papillomavirus infection using immunomodulatory polynucleotide sequences
US7157437B2 (en) * 2000-03-10 2007-01-02 Dynavax Technologies Corporation Methods of ameliorating symptoms of herpes infection using immunomodulatory polynucleotide sequences
US20020098199A1 (en) 2000-03-10 2002-07-25 Gary Van Nest Methods of suppressing hepatitis virus infection using immunomodulatory polynucleotide sequences
US7129222B2 (en) 2000-03-10 2006-10-31 Dynavax Technologies Corporation Immunomodulatory formulations and methods for use thereof
US20030129251A1 (en) * 2000-03-10 2003-07-10 Gary Van Nest Biodegradable immunomodulatory formulations and methods for use thereof
PT1296713E (en) 2000-06-08 2004-02-27 Intercell Biomediz Forschungs IMMUNOSTIMULATING OLIGODESOXINUCLEOTIDES
CA2420499A1 (en) * 2000-08-25 2002-02-28 Yeda Research And Development Co. Ltd. Methods of treatment or prevention of autoimmune diseases with cpg-containing polynucleotide
AU2002214127B2 (en) 2000-10-27 2007-06-07 J. Craig Venter Institute, Inc. Nucleic acids and proteins from streptococcus groups A and B
EP1350262B8 (en) * 2000-12-08 2008-08-13 Coley Pharmaceuticals GmbH Cpg-like nucleic acids and methods of use thereof
ATE471374T1 (en) * 2000-12-27 2010-07-15 Dynavax Tech Corp IMMUNOMODULATORY POLYNUCLEOTIDES AND METHOD FOR USE THEREOF
EP1390494A2 (en) 2001-05-21 2004-02-25 Intercell AG Method for stabilising of nucleic acids
EP1392341B1 (en) 2001-06-05 2005-03-30 Curevac GmbH Pharmaceutical composition containing a stabilised mrna which is optimised for translation in the coding regions thereof
GB0115176D0 (en) 2001-06-20 2001-08-15 Chiron Spa Capular polysaccharide solubilisation and combination vaccines
US20030199466A1 (en) * 2001-06-21 2003-10-23 Fearon Karen L. Chimeric immunomodulatory compounds and methods of using the same - ll
GB0118249D0 (en) 2001-07-26 2001-09-19 Chiron Spa Histidine vaccines
GB0121591D0 (en) 2001-09-06 2001-10-24 Chiron Spa Hybrid and tandem expression of neisserial proteins
US7666674B2 (en) 2001-07-27 2010-02-23 The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services Use of sterically stabilized cationic liposomes to efficiently deliver CPG oligonucleotides in vivo
WO2003012061A2 (en) * 2001-08-01 2003-02-13 Coley Pharmaceutical Gmbh Methods and compositions relating to plasmacytoid dendritic cells
US20030133988A1 (en) 2001-08-07 2003-07-17 Fearon Karen L. Immunomodulatory compositions, formulations, and methods for use thereof
WO2003020884A2 (en) * 2001-08-14 2003-03-13 The Government Of The United States Of America As Represented By The Secretary Of Health And Human Services Method for rapid generation of mature dendritic cells
ES2335979T3 (en) 2001-09-14 2010-04-07 Cytos Biotechnology Ag IMMUNOSTIMULATOR CPG PACKAGING IN VIRUS SIMILAR PARTICLES: PREPARATION METHOD AND ITS USE.
AR045702A1 (en) 2001-10-03 2005-11-09 Chiron Corp COMPOSITIONS OF ASSISTANTS.
US7544669B2 (en) * 2001-11-21 2009-06-09 The Board Of Trustees Of The Leland Stanford Junior University Polynucleotide therapy
DE10162480A1 (en) 2001-12-19 2003-08-07 Ingmar Hoerr The application of mRNA for use as a therapeutic agent against tumor diseases
AU2002366710A1 (en) * 2001-12-20 2003-07-09 The Government Of The United States Of America As Represented By The Secretary Of The Department Of USE OF CpG OLIGODEOXYNUCLEOTIDES TO INDUCE ANGIOGENESIS
US8466116B2 (en) 2001-12-20 2013-06-18 The Unites States Of America As Represented By The Secretary Of The Department Of Health And Human Services Use of CpG oligodeoxynucleotides to induce epithelial cell growth
EP2572707A3 (en) 2002-02-20 2013-11-06 Novartis Vaccines and Diagnostics, Inc. Microparticles with adsorbed polypeptide-containing molecules
CA2388049A1 (en) 2002-05-30 2003-11-30 Immunotech S.A. Immunostimulatory oligonucleotides and uses thereof
US20040009949A1 (en) * 2002-06-05 2004-01-15 Coley Pharmaceutical Group, Inc. Method for treating autoimmune or inflammatory diseases with combinations of inhibitory oligonucleotides and small molecule antagonists of immunostimulatory CpG nucleic acids
US20040053880A1 (en) 2002-07-03 2004-03-18 Coley Pharmaceutical Group, Inc. Nucleic acid compositions for stimulating immune responses
US7807803B2 (en) 2002-07-03 2010-10-05 Coley Pharmaceutical Group, Inc. Nucleic acid compositions for stimulating immune responses
DE10229872A1 (en) 2002-07-03 2004-01-29 Curevac Gmbh Immune stimulation through chemically modified RNA
EP1551221A4 (en) * 2002-07-03 2007-08-01 Coley Pharm Group Inc Nucleic acid compositions for stimulating immune responses
CN100536852C (en) * 2002-07-15 2009-09-09 基利得科学公司 Application of L-FMAU for preparation of medicament for combination therapies of hepatitis b virus infection
SG172476A1 (en) 2002-08-12 2011-07-28 Dynavax Tech Corp Immunomodulatory compositions comprising a cationic condensing agent, an immunostimulatory compound comprising 5'-cg-3', an a non ionic detergent
GB0220194D0 (en) 2002-08-30 2002-10-09 Chiron Spa Improved vesicles
US8263091B2 (en) * 2002-09-18 2012-09-11 The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services Method of treating and preventing infections in immunocompromised subjects with immunostimulatory CpG oligonucleotides
EP2241325B1 (en) 2002-10-29 2012-02-08 Coley Pharmaceutical Group, Inc. Use of CPG oligonucleotides in the treatment of hepatitis C virus infection
EP1572122A4 (en) * 2002-11-01 2008-04-09 Us Gov Health & Human Serv Method of preventing infections from bioterrorism agents with immunostimulatory cpg oligonucleotides
AU2003288660A1 (en) 2002-11-15 2004-06-15 Chiron Srl Unexpected surface proteins in neisseria meningitidis
EP2329827A3 (en) * 2002-11-21 2011-07-13 Bayhill Therapeutics, Inc. Methods and immune modulatory nucleic acid compositions for preventing and treating disease
GB0227346D0 (en) 2002-11-22 2002-12-31 Chiron Spa 741
JP2006512927A (en) 2002-12-11 2006-04-20 コーリー ファーマシューティカル グループ，インコーポレイテッド 5 'CPG nucleic acids and methods of use thereof
DE60329223D1 (en) 2002-12-23 2009-10-22 Dynavax Tech Corp OLIGONUCLEOTIDES WITH AN IMMUNE SYSTEM STIMULATING SEQUENCE AND METHOD FOR THEIR APPLICATION
JP2006516099A (en) 2002-12-23 2006-06-22 ダイナバックス テクノロジーズ コーポレイション Branched immunomodulatory compounds and methods of using the compounds
US8158768B2 (en) 2002-12-23 2012-04-17 Dynavax Technologies Corporation Immunostimulatory sequence oligonucleotides and methods of using the same
US8034378B2 (en) 2002-12-27 2011-10-11 Novartis Vaccines And Diagnostics, Inc Immunogenic compositions containing phospholipid
WO2004064759A2 (en) 2003-01-21 2004-08-05 Chiron Corporation Use of tryptanthrin compounds for immune potentiation
WO2004074454A2 (en) 2003-02-20 2004-09-02 University Of Connecticut Health Center Methods and compositions for the treatment of cancer and infectious disease using alpha (2) macroglobulin-antigenic molecule complexes
US7537767B2 (en) 2003-03-26 2009-05-26 Cytis Biotechnology Ag Melan-A- carrier conjugates
AU2004224762B2 (en) 2003-03-26 2009-12-24 Kuros Us Llc Packaging of immunostimulatory oligonucleotides into virus-like particles: method of preparation and use
ES2423800T3 (en) 2003-03-28 2013-09-24 Novartis Vaccines And Diagnostics, Inc. Use of organic compounds for immunopotentiation
AU2004226605A1 (en) * 2003-04-02 2004-10-14 Coley Pharmaceutical Group, Ltd. Immunostimulatory nucleic acid oil-in-water formulations for topical application
CN1798563A (en) * 2003-05-15 2006-07-05 独立行政法人科学技术振兴机构 Immunostimulant
CN101410130A (en) * 2003-05-15 2009-04-15 利兰·斯坦福青年大学托管委员会 Novel immunomodulating peptide
EP2179729B1 (en) 2003-06-02 2016-07-20 GlaxoSmithKline Biologicals SA Immunogenic compositions based on microparticles comprising adsorbed toxoid and a polysaccharide-containing antigen
US20060035242A1 (en) 2004-08-13 2006-02-16 Michelitsch Melissa D Prion-specific peptide reagents
US20050239733A1 (en) * 2003-10-31 2005-10-27 Coley Pharmaceutical Gmbh Sequence requirements for inhibitory oligonucleotides
JP4817599B2 (en) * 2003-12-25 2011-11-16 独立行政法人科学技術振興機構 Immune activity enhancer and method for enhancing immune activity using the same
JP3976742B2 (en) 2004-02-27 2007-09-19 江守商事株式会社 Immunostimulatory oligonucleotides that induce interferon alpha
TWI235440B (en) * 2004-03-31 2005-07-01 Advanced Semiconductor Eng Method for making leadless semiconductor package
EP1768662A2 (en) 2004-06-24 2007-04-04 Novartis Vaccines and Diagnostics, Inc. Small molecule immunopotentiators and assays for their detection
EP1765313A2 (en) 2004-06-24 2007-03-28 Novartis Vaccines and Diagnostics, Inc. Compounds for immunopotentiation
US8759305B2 (en) 2004-09-01 2014-06-24 Dynavax Technologies Corporation Methods and compositions for inhibition of innate immune responses and autoimmunity
JP2008000001A (en) * 2004-09-30 2008-01-10 Osaka Univ Immune stimulating oligonucleotide and use in pharmaceutical
US20060135906A1 (en) * 2004-11-16 2006-06-22 Akihiko Matsumura Iontophoretic device and method for administering immune response-enhancing agents and compositions
WO2006066003A2 (en) * 2004-12-17 2006-06-22 Dynavax Technologies Corporation Methods and compositions for induction or promotion of immune tolerance
CA2590974C (en) 2005-01-27 2017-10-03 Children's Hospital & Research Center At Oakland Gna1870-based vesicle vaccines for broad spectrum protection against diseases caused by neisseria meningitidis
US20080009455A9 (en) * 2005-02-24 2008-01-10 Coley Pharmaceutical Group, Inc. Immunostimulatory oligonucleotides
CA2600036A1 (en) 2005-03-04 2006-09-14 Dynavax Technologies Corporation Vaccines comprising oligonucleotides having immunostimulatory sequences (iss) wherein the iss are conjugated to antigens and stabilized by buffer conditions and further excipients
WO2006110656A2 (en) * 2005-04-08 2006-10-19 Chimerix, Inc. Compounds, compositions and methods for the treatment of viral infections and other medical disorders
US8642577B2 (en) 2005-04-08 2014-02-04 Chimerix, Inc. Compounds, compositions and methods for the treatment of poxvirus infections
KR20080066712A (en) * 2005-09-30 2008-07-16 티티아이 엘뷰 가부시키가이샤 Functionalized microneedles transdermal drug delivery systems, devices, and methods
JP2009509634A (en) * 2005-09-30 2009-03-12 Ｔｔｉ・エルビュー株式会社 Functionalized microneedle transdermal drug delivery system, apparatus and method
KR20080080087A (en) * 2005-09-30 2008-09-02 티티아이 엘뷰 가부시키가이샤 Transdermal drug delivery systems, devices, and methods employing novel pharmaceutical vehicles
EP1973608A1 (en) 2005-12-14 2008-10-01 Cytos Biotechnology AG Immunostimulatory nucleic acid packaged particles for the treatment of hypersensitivity
JP2009525048A (en) * 2006-02-01 2009-07-09 ザ ジョンズ ホプキンス ユニバーシティー Polypeptide-nucleic acid complex for immunological prophylaxis or immunotherapy against neoplastic disorders or infections
US20080045473A1 (en) * 2006-02-15 2008-02-21 Coley Pharmaceutical Gmbh Compositions and methods for oligonucleotide formulations
CA2638760A1 (en) 2006-03-07 2007-09-13 Vaxinnate Corporation Compositions that include hemagglutinin, methods of making and methods of use thereof
AU2007268534B2 (en) 2006-05-31 2011-07-14 Osaka University Immunostimulatory oligonucleotide and pharmaceutical application thereof
SG172696A1 (en) 2006-06-12 2011-07-28 Cytos Biotechnology Ag Processes for packaging oligonucleotides into virus-like particles of rna bacteriophages
EP2032144A4 (en) * 2006-06-13 2011-05-04 Bayhill Therapeutics Inc Methods and immune modulatory nucleic acid compositions for preventing and treating disease
DE102006035618A1 (en) * 2006-07-31 2008-02-07 Curevac Gmbh New nucleic acid useful as immuno-stimulating adjuvant for manufacture of a composition for treatment of cancer diseases e.g. colon carcinomas and infectious diseases e.g. influenza and malaria
JP2010507361A (en) 2006-07-31 2010-03-11 キュアバック ゲーエムベーハー Specifically, a nucleic acid represented by the general formula (I): GlXmGn or the general formula (II): ClXmCn as an immunostimulant / adjuvant
PL2094849T3 (en) 2006-11-09 2014-06-30 Dynavax Tech Corp Long term disease modification using immunostimulatory oligonucleotides
WO2009018500A1 (en) * 2007-07-31 2009-02-05 The Johns Hopkins University Polypeptide-nucleic acid conjugate for immunoprophylaxis or immunotherapy for neoplastic or infectious disorders
WO2009018431A2 (en) * 2007-08-01 2009-02-05 Idera Pharmaceuticals, Inc. Novel synthetic agonists of tlr9
WO2009030254A1 (en) 2007-09-04 2009-03-12 Curevac Gmbh Complexes of rna and cationic peptides for transfection and for immunostimulation
AU2008317261B2 (en) 2007-10-26 2015-04-09 Dynavax Technologies Corporation Methods and compositions for inhibition of immune responses and autoimmunity
WO2009058564A2 (en) 2007-11-01 2009-05-07 Maxygen, Inc. Immunosuppressive polypeptides and nucleic acids
AU2008335457B2 (en) 2007-12-07 2015-04-16 Glaxosmithkline Biologicals S.A. Compositions for inducing immune responses
WO2009094190A2 (en) * 2008-01-25 2009-07-30 Chimerix, Inc. Methods of treating viral infections
WO2009114485A2 (en) 2008-03-10 2009-09-17 Children's Hospital & Research Center At Oakland Chimeric factor h binding proteins (fhbp) containing a heterologous b domain and methods of use
AU2009236585B2 (en) 2008-04-18 2013-03-07 Vaxinnate Corporation Deletion mutants of flagellin and methods of use
WO2009140626A2 (en) 2008-05-15 2009-11-19 Dynavax Technologies Corporation Long term disease modification using immunostimulatory oligonucleotides
GB0809476D0 (en) * 2008-05-23 2008-07-02 Cambridge Entpr Ltd Treatment of neurodegenerative disorders
CN104001170B (en) 2008-06-27 2016-08-24 硕腾有限责任公司 Novel adjunvant composition
WO2010037408A1 (en) 2008-09-30 2010-04-08 Curevac Gmbh Composition comprising a complexed (m)rna and a naked mrna for providing or enhancing an immunostimulatory response in a mammal and uses thereof
EP2376108B1 (en) 2008-12-09 2017-02-22 Pfizer Vaccines LLC IgE CH3 PEPTIDE VACCINE
BRPI1005670A8 (en) 2009-01-05 2017-12-26 Epitogenesis Inc adjuvant compositions and processes of use.
MX2011010050A (en) 2009-03-25 2011-12-14 Univ Texas Compositions for stimulation of mammalian innate immune resistance to pathogens.
US8614200B2 (en) 2009-07-21 2013-12-24 Chimerix, Inc. Compounds, compositions and methods for treating ocular conditions
NZ618391A (en) 2009-07-30 2015-07-31 Pfizer Vaccines Llc Antigenic tau peptides and uses thereof
US20110053829A1 (en) 2009-09-03 2011-03-03 Curevac Gmbh Disulfide-linked polyethyleneglycol/peptide conjugates for the transfection of nucleic acids
CN102612558B (en) 2009-09-03 2015-02-11 辉瑞疫苗有限责任公司 Pcsk9 vaccine
US20120282276A1 (en) 2009-11-05 2012-11-08 The Regents Of The University Of Michigan Biomarkers predictive of progression of fibrosis
JP6007105B2 (en) 2009-12-22 2016-10-12 セルデックス・セラピューティクス・インコーポレイテッド Vaccine composition
US9006218B2 (en) 2010-02-12 2015-04-14 Chimerix Inc. Nucleoside phosphonate salts
WO2011109833A2 (en) 2010-03-05 2011-09-09 President And Fellows Of Harvard College Induced dendritic cell compositions and uses thereof
CN110845585A (en) 2010-03-30 2020-02-28 奥克兰儿童医院及研究中心 Modified Factor H Binding Proteins (FHBP) and methods of use thereof
US9278135B2 (en) 2010-04-26 2016-03-08 Chimerix Inc. Methods of treating retroviral infections and related dosage regimes
CA2800774A1 (en) 2010-06-07 2011-12-15 Pfizer Vaccines Llc Ige ch3 peptide vaccine
CA2798837A1 (en) 2010-06-07 2011-12-15 Pfizer Inc. Her-2 peptides and vaccines
KR101810593B1 (en) 2010-06-16 2017-12-22 다이나박스 테크놀로지 코퍼레이션 Methods of treatment using tlr7 and/or tlr9 inhibitors
BR112013002298A2 (en) 2010-07-30 2016-05-24 Curevac Gmbh nucleic acid complexation with disulfide crosslinked cationic components for transfection and immune stimulation.
CA2807552A1 (en) 2010-08-06 2012-02-09 Moderna Therapeutics, Inc. Engineered nucleic acids and methods of use thereof
ES2862955T3 (en) 2010-10-01 2021-10-08 Modernatx Inc Manipulated nucleic acids and methods of using them
US20140004142A1 (en) 2011-03-02 2014-01-02 Pfizer Inc. Pcsk9 vaccine
US8710200B2 (en) 2011-03-31 2014-04-29 Moderna Therapeutics, Inc. Engineered nucleic acids encoding a modified erythropoietin and their expression
US9464124B2 (en) 2011-09-12 2016-10-11 Moderna Therapeutics, Inc. Engineered nucleic acids and methods of use thereof
WO2013052523A1 (en) 2011-10-03 2013-04-11 modeRNA Therapeutics Modified nucleosides, nucleotides, and nucleic acids, and uses thereof
CN104114572A (en) 2011-12-16 2014-10-22 现代治疗公司 Modified nucleoside, nucleotide, and nucleic acid compositions
WO2013113326A1 (en) 2012-01-31 2013-08-08 Curevac Gmbh Pharmaceutical composition comprising a polymeric carrier cargo complex and at least one protein or peptide antigen
EP2833920A2 (en) 2012-04-02 2015-02-11 Moderna Therapeutics, Inc. Modified polynucleotides for the production of biologics and proteins associated with human disease
US9572897B2 (en) 2012-04-02 2017-02-21 Modernatx, Inc. Modified polynucleotides for the production of cytoplasmic and cytoskeletal proteins
US9283287B2 (en) 2012-04-02 2016-03-15 Moderna Therapeutics, Inc. Modified polynucleotides for the production of nuclear proteins
US9878056B2 (en) 2012-04-02 2018-01-30 Modernatx, Inc. Modified polynucleotides for the production of cosmetic proteins and peptides
PL2844282T3 (en) 2012-05-04 2019-11-29 Pfizer Prostate-associated antigens and vaccine-based immunotherapy regimens
US9868955B2 (en) 2012-09-29 2018-01-16 Dynavax Technologies Corporation Human toll-like receptor inhibitors and methods of use thereof
US9228184B2 (en) 2012-09-29 2016-01-05 Dynavax Technologies Corporation Human toll-like receptor inhibitors and methods of use thereof
PL2922554T3 (en) 2012-11-26 2022-06-20 Modernatx, Inc. Terminally modified rna
CA2936092A1 (en) 2013-01-23 2014-07-31 The Board Of Trustees Of The Leland Stanford Junior University Stabilized hepatitis b core polypeptide
CN105229150A (en) 2013-03-14 2016-01-06 安第斯生物技术股份有限公司 Be used for the treatment of the antisense oligonucleotide of cancer stem cell
WO2014153206A2 (en) 2013-03-14 2014-09-25 Andes Biotechnologies S.A. Methods for detecting and treating multiple myeloma
CN105188744A (en) 2013-03-14 2015-12-23 哈佛大学的校长及成员们 Nanoparticle-based compositions
WO2014151994A1 (en) 2013-03-15 2014-09-25 Kambiz Shekdar Genome editing using effector oligonucleotides for therapeutic treatment
US8980864B2 (en) 2013-03-15 2015-03-17 Moderna Therapeutics, Inc. Compositions and methods of altering cholesterol levels
CN112999344A (en) 2013-05-15 2021-06-22 阿尔伯达大学董事会 E1E2HCV vaccine and methods of use
KR20160044566A (en) 2013-08-21 2016-04-25 큐어백 아게 Respiratory syncytial virus (RSV) vaccine
NZ757210A (en) 2013-09-19 2022-12-23 Zoetis Services Llc Oil-based adjuvants
WO2015048744A2 (en) 2013-09-30 2015-04-02 Moderna Therapeutics, Inc. Polynucleotides encoding immune modulating polypeptides
EP3052521A1 (en) 2013-10-03 2016-08-10 Moderna Therapeutics, Inc. Polynucleotides encoding low density lipoprotein receptor
WO2015062738A1 (en) 2013-11-01 2015-05-07 Curevac Gmbh Modified rna with decreased immunostimulatory properties
KR102006527B1 (en) 2013-11-01 2019-08-02 화이자 인코포레이티드 Vectors for expression of prostate-associated antigens
US10279019B2 (en) 2014-02-11 2019-05-07 Stc.Unm PCSK9 peptide vaccine conjugated to a Qbeta carrier and methods of using the same
EP3129050A2 (en) 2014-04-01 2017-02-15 CureVac AG Polymeric carrier cargo complex for use as an immunostimulating agent or as an adjuvant
WO2016044839A2 (en) 2014-09-19 2016-03-24 The Board Of Regents Of The University Of Texas System Compositions and methods for treating viral infections through stimulated innate immunity in combination with antiviral compounds
LT3244920T (en) 2015-01-16 2023-08-25 Zoetis Services Llc Foot-and-mouth disease vaccine
AU2016271018A1 (en) 2015-05-29 2017-11-30 Dynavax Technologies Corporation Combination of a PD-1 antagonist and CPG-C type oligonucleotide for treating cancer
HUE051722T2 (en) 2016-01-19 2021-03-29 Pfizer Cancer vaccines
CN109451729B (en) * 2016-06-08 2022-03-22 哈佛学院院长及董事 Engineered viral vectors reduce induction of inflammation and immune responses
US11826422B2 (en) 2016-11-09 2023-11-28 Board Of Regents, The University Of Texas System Methods and compositions for adaptive immune modulation
WO2019094548A1 (en) * 2017-11-08 2019-05-16 President And Fellows Of Harvard College Compositions and methods for inhibiting viral vector-induced inflammatory responses
US11633471B2 (en) 2018-03-06 2023-04-25 Unm Rainforest Innovations Compositions and methods for reducing serum triglycerides
WO2022147373A1 (en) 2020-12-31 2022-07-07 The United States Of America, As Represented By The Secretary, Department Of Health And Human Services Antibody-guided pcsk9-mimicking immunogens lacking 9-residue sequence overlap with human proteins
CN117441103A (en) 2021-03-16 2024-01-23 国立大学法人大阪大学 Novel medical technology using follicular T cells
WO2022196699A1 (en) 2021-03-16 2022-09-22 国立大学法人大阪大学 Follicular helper t (tfh) cells specific to sars-cov-2 virus
WO2023081486A1 (en) 2021-11-08 2023-05-11 Nurix Therapeutics, Inc. Toll-like receptor therapy combinations with cbl-b inhibitor compounds

Family Cites Families (46)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US1234718A (en) 1914-03-21 1917-07-31 Int Harvester Canada Buckle.
US2811896A (en) 1953-10-05 1957-11-05 Welsh Mfg Co Ophthalmic mounting
US3725545A (en) 1971-02-03 1973-04-03 R Maes Enhancement of antibody production by nucleic acid-polycation complexes
US3906092A (en) 1971-11-26 1975-09-16 Merck & Co Inc Stimulation of antibody response
US4458066A (en) 1980-02-29 1984-07-03 University Patents, Inc. Process for preparing polynucleotides
US4425732A (en) 1981-06-17 1984-01-17 Kania Tadeusz E Animal trap
US4650675A (en) 1983-08-18 1987-03-17 The Children's Medical Center Corporation Oligonucleotide conjugates
US5118802A (en) 1983-12-20 1992-06-02 California Institute Of Technology DNA-reporter conjugates linked via the 2' or 5'-primary amino group of the 5'-terminal nucleoside
US5118800A (en) 1983-12-20 1992-06-02 California Institute Of Technology Oligonucleotides possessing a primary amino group in the terminal nucleotide
US4849513A (en) 1983-12-20 1989-07-18 California Institute Of Technology Deoxyribonucleoside phosphoramidites in which an aliphatic amino group is attached to the sugar ring and their use for the preparation of oligonucleotides containing aliphatic amino groups
US5015733A (en) 1983-12-20 1991-05-14 California Institute Of Technology Nucleosides possessing blocked aliphatic amino groups
DE3583564D1 (en) * 1984-08-23 1991-08-29 Hans Joachim Wolf DNA SEQUENCES OF THE EBV GENOME, RECOMBINANT DNA MOLECULES, METHOD FOR THE PRODUCTION OF EBV-RELATED ANTIGENS, DIAGNOSTIC COMPOSITIONS AND PHARMACEUTICAL COMPOSITIONS CONTAINING THE SAME ANTIGENS.
US5110906A (en) * 1986-08-21 1992-05-05 The Trustees Of Columbia University In The City Of New York Derivatives of soluble T-4
US5276019A (en) 1987-03-25 1994-01-04 The United States Of America As Represented By The Department Of Health And Human Services Inhibitors for replication of retroviruses and for the expression of oncogene products
US5268365A (en) 1988-03-11 1993-12-07 Rudolph Frederick B Nucleotides, nucleosides, and nucleobases in immune function restoration enhancement or maintenance
US5218103A (en) 1988-05-26 1993-06-08 University Patents, Inc. Nucleoside thiophosphoramidites
US5278302A (en) 1988-05-26 1994-01-11 University Patents, Inc. Polynucleotide phosphorodithioates
US5703055A (en) 1989-03-21 1997-12-30 Wisconsin Alumni Research Foundation Generation of antibodies through lipid mediated DNA delivery
US5331090A (en) * 1989-09-08 1994-07-19 California Institute Of Biological Research CR2 ligand compositions and methods for modulating immune cell functions
WO1991003251A1 (en) * 1989-09-08 1991-03-21 California Institute Of Biological Research Cr2 ligand compositions and methods for modulating immune cell functions
US5514577A (en) 1990-02-26 1996-05-07 Isis Pharmaceuticals, Inc. Oligonucleotide therapies for modulating the effects of herpes viruses
US5530114A (en) 1990-04-30 1996-06-25 Isis Pharmaceuticals, Inc. Oligonucleotide modulation of arachidonic acid metabolism
EP0468520A3 (en) * 1990-07-27 1992-07-01 Mitsui Toatsu Chemicals, Inc. Immunostimulatory remedies containing palindromic dna sequences
US5286365A (en) 1992-01-15 1994-02-15 Beckman Instruments, Inc. Graphite-based solid state polymeric membrane ion-selective electrodes
EP0903408A3 (en) 1992-08-21 2005-11-02 Biogen, Inc. Tat-derived transport polypeptide
US5523389A (en) * 1992-09-29 1996-06-04 Isis Pharmaceuticals, Inc. Inhibitors of human immunodeficiency virus
US5552390A (en) * 1993-12-09 1996-09-03 The Board Of Regents Of The University Of Nebraska Phosphorothioate inhibitors of metastatic breast cancer
WO1995026204A1 (en) * 1994-03-25 1995-10-05 Isis Pharmaceuticals, Inc. Immune stimulation by phosphorothioate oligonucleotide analogs
PT772619E (en) * 1994-07-15 2006-10-31 Univ Iowa Res Found OLIGONUCLEOTIDOS IMUNOMODULADORES
US6207646B1 (en) * 1994-07-15 2001-03-27 University Of Iowa Research Foundation Immunostimulatory nucleic acid molecules
US5665347A (en) * 1995-02-02 1997-09-09 Genetics Institute IL-12 inhibition of B1 cell activity
US5968909A (en) * 1995-08-04 1999-10-19 Hybridon, Inc. Method of modulating gene expression with reduced immunostimulatory response
US5840839A (en) * 1996-02-09 1998-11-24 The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services Alternative open reading frame DNA of a normal gene and a novel human cancer antigen encoded therein
EP0929668A1 (en) * 1996-09-04 1999-07-21 Onyx Pharmaceuticals, Inc. Modulators of brca1 activity
CA2268825C (en) * 1996-10-11 2006-04-18 The Regents Of The University Of California Immunostimulatory polynucleotide/immunomodulatory molecule conjugates
JP2001513776A (en) 1997-02-28 2001-09-04 ユニバーシティ オブ アイオワ リサーチ ファウンデーション Use of nucleic acids containing unmethylated CpG dinucleotides in the treatment of LPS-related disorders
DK1005368T3 (en) 1997-03-10 2010-01-04 Ottawa Hospital Res Inst Use of nucleic acids containing non-methylated CpG dinucleotide in combination with alum as adjuvants
EP0983289A4 (en) * 1997-05-19 2001-04-25 Merck & Co Inc Oligonucleotide adjuvant
AU7690898A (en) 1997-05-20 1998-12-11 Ottawa Civic Hospital Loeb Research Institute Vectors and methods for immunization or therapeutic protocols
US6613881B1 (en) * 1997-05-20 2003-09-02 Corixa Corporation Compounds for immunotherapy and diagnosis of tuberculosis and methods of their use
JP4101888B2 (en) 1997-06-06 2008-06-18 ダイナバックス テクノロジーズ コーポレイション Immunostimulatory oligonucleotides, compositions thereof and methods of use thereof
KR20030070092A (en) 2001-01-04 2003-08-27 바스큘라 바이오제닉스 리미티드 Methods employing and compositions containing plaque associated molecules for prevention and treatment of atherosclerosis
JP2005501917A (en) 2001-09-07 2005-01-20 ザ トラスティーズ オブ ボストン ユニバーシティ Methods and compositions for treating immune complex related diseases
EP2329827A3 (en) 2002-11-21 2011-07-13 Bayhill Therapeutics, Inc. Methods and immune modulatory nucleic acid compositions for preventing and treating disease
US20050239733A1 (en) 2003-10-31 2005-10-27 Coley Pharmaceutical Gmbh Sequence requirements for inhibitory oligonucleotides
EP2032144A4 (en) 2006-06-13 2011-05-04 Bayhill Therapeutics Inc Methods and immune modulatory nucleic acid compositions for preventing and treating disease

Also Published As

Publication number Publication date
DK1003850T3 (en) 2009-09-07
WO1998055495A3 (en) 1999-05-27
AU753172B2 (en) 2002-10-10
PT1003850E (en) 2009-08-13
EP0986572B2 (en) 2007-06-13
US20110034541A1 (en) 2011-02-10
CA2291483C (en) 2012-09-18
US20110182927A1 (en) 2011-07-28
WO1998055495A2 (en) 1998-12-10
ATE432348T1 (en) 2009-06-15
EP0986572B1 (en) 2003-10-22
JP4101888B2 (en) 2008-06-18
WO1998055609A1 (en) 1998-12-10
DE69819150T2 (en) 2004-07-22
AU7817898A (en) 1998-12-21
US20020086839A1 (en) 2002-07-04
EP1003850A4 (en) 2005-07-06
EP2085090A2 (en) 2009-08-05
WO1998055495B1 (en) 1999-07-22
DE69819150D1 (en) 2003-11-27
DE69840850D1 (en) 2009-07-09
US6225292B1 (en) 2001-05-01
DE69819150T3 (en) 2007-12-20
JP2002505580A (en) 2002-02-19
AU7811398A (en) 1998-12-21
EP1003850A1 (en) 2000-05-31
JP4280309B2 (en) 2009-06-17
US8729039B2 (en) 2014-05-20
EP1003850B1 (en) 2009-05-27
CA2293489C (en) 2009-09-29
CY1109287T1 (en) 2014-07-02
EP0986572A2 (en) 2000-03-22
JP2002517156A (en) 2002-06-11
HK1024701A1 (en) 2000-10-20
ES2326848T3 (en) 2009-10-20
EP2085090A3 (en) 2012-05-02
ATE252596T1 (en) 2003-11-15
CA2293489A1 (en) 1998-12-10
AU755322B2 (en) 2002-12-12

Similar Documents

Publication Publication Date Title
CA2291483A1 (en) Immunostimulatory oligonucleotides, compositions thereof and methods of use thereof
Illum et al. Chitosan as a novel nasal delivery system for vaccines
US7208478B2 (en) Immunostimulatory polynucleotide/immunomodulatory molecule conjugates
Alpar et al. Biodegradable mucoadhesive particulates for nasal and pulmonary antigen and DNA delivery
O'Hagan et al. Recent advances in vaccine adjuvants: the development of MF59 emulsion and polymeric microparticles
JP2002500159A5 (en)
US20030119773A1 (en) Method for enhancing an immune response
CA2295237A1 (en) Antigen delivery system comprising monoglyceride or diglyceride derivatives as adjuvant
JP2004530629A (en) Immunostimulatory RNA / DNA hybrid molecule
IE910268A1 (en) Liposome-containing intranasal vaccine formulation
AU776288B2 (en) Methods and adjuvants for stimulating mucosal immunity
US7767197B2 (en) Delivery vehicle composition and methods for delivering antigens and other drugs
JP6797022B2 (en) Vaccine delivery system using yeast cell wall particles
CA2655138C (en) Compositions comprising chitin microparticles and their medical uses
Loo et al. Recent advances in inhaled nanoformulations of vaccines and therapeutics targeting respiratory viral infections
Carcaboso et al. Enhancing immunogenicity and reducing dose of microparticulated synthetic vaccines: single intradermal administration
WO2000062802A3 (en) Vaccine comprising rsv antigen and cpg oligonucleotide
Saini et al. Polymeric lamellar substrate particles as carrier adjuvant for recombinant hepatitis B surface antigen vaccine
WO2002074922A2 (en) Compositions and methods for modulating an immune response
JP2004519452A5 (en)
AU768178B2 (en) Immunostimulatory polynucleotide/immunomodulatory molecule conjugates
De Haan et al. Liposomes and antiviral mucosal immunity
Baker Jr et al. Enhanced systemic and mucosal immune responses in mice immunized with recombinant Bacillus anthracis protective antigen (rPA) using a novel nanoemulsion adjuvant
Wang et al. Immunogenicity of a Polyinosinic-Polycytidylic Acid (Poly (I: C))-Adjuvanted Microparticle Vaccine for Leishmaniasis

Legal Events

Date Code Title Description
EEER Examination request
MKEX Expiry

Effective date: 20180605