CA2402312A1 - Treatment of herpes infection using immunomodulatory polynucleotide sequences - Google Patents
Treatment of herpes infection using immunomodulatory polynucleotide sequences Download PDFInfo
- Publication number
- CA2402312A1 CA2402312A1 CA002402312A CA2402312A CA2402312A1 CA 2402312 A1 CA2402312 A1 CA 2402312A1 CA 002402312 A CA002402312 A CA 002402312A CA 2402312 A CA2402312 A CA 2402312A CA 2402312 A1 CA2402312 A1 CA 2402312A1
- Authority
- CA
- Canada
- Prior art keywords
- iss
- infection
- sequence
- individual
- herpes simplex
- 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.)
- Abandoned
Links
- 102000040430 polynucleotide Human genes 0.000 title claims abstract description 122
- 108091033319 polynucleotide Proteins 0.000 title claims abstract description 122
- 239000002157 polynucleotide Substances 0.000 title claims abstract description 122
- 238000011282 treatment Methods 0.000 title description 54
- 230000002519 immonomodulatory effect Effects 0.000 title description 8
- 206010019973 Herpes virus infection Diseases 0.000 title description 2
- 208000024891 symptom Diseases 0.000 claims abstract description 91
- 208000015181 infectious disease Diseases 0.000 claims abstract description 80
- 238000000034 method Methods 0.000 claims abstract description 78
- 108091007433 antigens Proteins 0.000 claims abstract description 37
- 102000036639 antigens Human genes 0.000 claims abstract description 37
- 239000000427 antigen Substances 0.000 claims abstract description 36
- 208000009889 Herpes Simplex Diseases 0.000 claims abstract description 15
- 230000003308 immunostimulating effect Effects 0.000 claims abstract description 15
- 241000701074 Human alphaherpesvirus 2 Species 0.000 claims description 57
- 241000700605 Viruses Species 0.000 claims description 56
- KDCGOANMDULRCW-UHFFFAOYSA-N 7H-purine Chemical compound N1=CNC2=NC=NC2=C1 KDCGOANMDULRCW-UHFFFAOYSA-N 0.000 claims description 52
- 239000000203 mixture Substances 0.000 claims description 42
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 claims description 40
- 241000700584 Simplexvirus Species 0.000 claims description 24
- 230000007485 viral shedding Effects 0.000 claims description 16
- 241000124008 Mammalia Species 0.000 claims description 8
- 241000700587 Alphaherpesvirinae Species 0.000 abstract description 44
- 208000029433 Herpesviridae infectious disease Diseases 0.000 abstract description 19
- 230000002829 reductive effect Effects 0.000 abstract description 11
- 230000003902 lesion Effects 0.000 description 31
- -1 nucleoside phosphoramidite Chemical class 0.000 description 28
- 230000003612 virological effect Effects 0.000 description 27
- 108091034117 Oligonucleotide Proteins 0.000 description 26
- 210000004027 cell Anatomy 0.000 description 24
- 241001465754 Metazoa Species 0.000 description 23
- 235000000346 sugar Nutrition 0.000 description 23
- 241001529453 unidentified herpesvirus Species 0.000 description 22
- 241000701085 Human alphaherpesvirus 3 Species 0.000 description 21
- 241000700588 Human alphaherpesvirus 1 Species 0.000 description 19
- 230000009467 reduction Effects 0.000 description 19
- 208000036142 Viral infection Diseases 0.000 description 18
- 230000009385 viral infection Effects 0.000 description 18
- 230000004048 modification Effects 0.000 description 16
- 238000012986 modification Methods 0.000 description 16
- 102000039446 nucleic acids Human genes 0.000 description 16
- 108020004707 nucleic acids Proteins 0.000 description 16
- 150000007523 nucleic acids Chemical class 0.000 description 16
- 230000000306 recurrent effect Effects 0.000 description 16
- JLCPHMBAVCMARE-UHFFFAOYSA-N [3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-hydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methyl [5-(6-aminopurin-9-yl)-2-(hydroxymethyl)oxolan-3-yl] hydrogen phosphate Chemical class Cc1cn(C2CC(OP(O)(=O)OCC3OC(CC3OP(O)(=O)OCC3OC(CC3O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c3nc(N)[nH]c4=O)C(COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3CO)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cc(C)c(=O)[nH]c3=O)n3cc(C)c(=O)[nH]c3=O)n3ccc(N)nc3=O)n3cc(C)c(=O)[nH]c3=O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)O2)c(=O)[nH]c1=O JLCPHMBAVCMARE-UHFFFAOYSA-N 0.000 description 15
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 15
- 239000002245 particle Substances 0.000 description 15
- 238000012809 post-inoculation Methods 0.000 description 15
- 108020004414 DNA Proteins 0.000 description 14
- 201000010099 disease Diseases 0.000 description 14
- 241000699670 Mus sp. Species 0.000 description 13
- 230000015572 biosynthetic process Effects 0.000 description 12
- 238000011161 development Methods 0.000 description 12
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 12
- 239000002953 phosphate buffered saline Substances 0.000 description 12
- OPTASPLRGRRNAP-UHFFFAOYSA-N cytosine Chemical compound NC=1C=CNC(=O)N=1 OPTASPLRGRRNAP-UHFFFAOYSA-N 0.000 description 11
- 230000000694 effects Effects 0.000 description 11
- 238000009472 formulation Methods 0.000 description 11
- 230000028993 immune response Effects 0.000 description 10
- 238000003786 synthesis reaction Methods 0.000 description 10
- 210000001519 tissue Anatomy 0.000 description 10
- QFVKLKDEXOWFSL-UHFFFAOYSA-N 6-amino-5-bromo-1h-pyrimidin-2-one Chemical group NC=1NC(=O)N=CC=1Br QFVKLKDEXOWFSL-UHFFFAOYSA-N 0.000 description 9
- 229910019142 PO4 Inorganic materials 0.000 description 9
- 210000004392 genitalia Anatomy 0.000 description 9
- 125000003835 nucleoside group Chemical group 0.000 description 9
- 239000010452 phosphate Substances 0.000 description 9
- 239000007787 solid Substances 0.000 description 9
- 229960005486 vaccine Drugs 0.000 description 9
- 238000002347 injection Methods 0.000 description 8
- 239000007924 injection Substances 0.000 description 8
- 238000011081 inoculation Methods 0.000 description 8
- 239000002777 nucleoside Substances 0.000 description 8
- 239000003921 oil Substances 0.000 description 8
- 229920000642 polymer Polymers 0.000 description 8
- 239000000523 sample Substances 0.000 description 8
- 230000004083 survival effect Effects 0.000 description 8
- 108090000695 Cytokines Proteins 0.000 description 7
- 102000004127 Cytokines Human genes 0.000 description 7
- MKUXAQIIEYXACX-UHFFFAOYSA-N aciclovir Chemical compound N1C(N)=NC(=O)C2=C1N(COCCO)C=N2 MKUXAQIIEYXACX-UHFFFAOYSA-N 0.000 description 7
- 239000002671 adjuvant Substances 0.000 description 7
- 230000005540 biological transmission Effects 0.000 description 7
- 210000004369 blood Anatomy 0.000 description 7
- 239000008280 blood Substances 0.000 description 7
- 229940104302 cytosine Drugs 0.000 description 7
- 239000003814 drug Substances 0.000 description 7
- 238000002474 experimental method Methods 0.000 description 7
- 238000004519 manufacturing process Methods 0.000 description 7
- 125000003729 nucleotide group Chemical group 0.000 description 7
- 238000002255 vaccination Methods 0.000 description 7
- 241000700198 Cavia Species 0.000 description 6
- 102000053602 DNA Human genes 0.000 description 6
- 229960004150 aciclovir Drugs 0.000 description 6
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 6
- 230000001186 cumulative effect Effects 0.000 description 6
- 239000000839 emulsion Substances 0.000 description 6
- 125000000623 heterocyclic group Chemical group 0.000 description 6
- 230000002209 hydrophobic effect Effects 0.000 description 6
- 230000003053 immunization Effects 0.000 description 6
- 238000002649 immunization Methods 0.000 description 6
- 239000007788 liquid Substances 0.000 description 6
- 238000005259 measurement Methods 0.000 description 6
- 239000002773 nucleotide Substances 0.000 description 6
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 6
- CXMXRPHRNRROMY-UHFFFAOYSA-N sebacic acid Chemical compound OC(=O)CCCCCCCCC(O)=O CXMXRPHRNRROMY-UHFFFAOYSA-N 0.000 description 6
- 210000002966 serum Anatomy 0.000 description 6
- 239000007790 solid phase Substances 0.000 description 6
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 6
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 5
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 5
- 208000001688 Herpes Genitalis Diseases 0.000 description 5
- 210000001744 T-lymphocyte Anatomy 0.000 description 5
- 230000000692 anti-sense effect Effects 0.000 description 5
- 239000012472 biological sample Substances 0.000 description 5
- 125000002091 cationic group Chemical group 0.000 description 5
- 230000003247 decreasing effect Effects 0.000 description 5
- 201000004946 genital herpes Diseases 0.000 description 5
- 239000007791 liquid phase Substances 0.000 description 5
- 239000004005 microsphere Substances 0.000 description 5
- 238000002360 preparation method Methods 0.000 description 5
- 230000002265 prevention Effects 0.000 description 5
- 230000004044 response Effects 0.000 description 5
- 239000000126 substance Substances 0.000 description 5
- 238000002560 therapeutic procedure Methods 0.000 description 5
- PNWOYKVCNDZOLS-UHFFFAOYSA-N 6-amino-5-chloro-1h-pyrimidin-2-one Chemical compound NC=1NC(=O)N=CC=1Cl PNWOYKVCNDZOLS-UHFFFAOYSA-N 0.000 description 4
- 206010020751 Hypersensitivity Diseases 0.000 description 4
- 206010028980 Neoplasm Diseases 0.000 description 4
- 229920002732 Polyanhydride Polymers 0.000 description 4
- ISAKRJDGNUQOIC-UHFFFAOYSA-N Uracil Chemical compound O=C1C=CNC(=O)N1 ISAKRJDGNUQOIC-UHFFFAOYSA-N 0.000 description 4
- 208000026935 allergic disease Diseases 0.000 description 4
- 230000007815 allergy Effects 0.000 description 4
- 238000004458 analytical method Methods 0.000 description 4
- 230000015556 catabolic process Effects 0.000 description 4
- 239000003795 chemical substances by application Substances 0.000 description 4
- 238000006731 degradation reaction Methods 0.000 description 4
- 238000000338 in vitro Methods 0.000 description 4
- 238000001802 infusion Methods 0.000 description 4
- 238000007918 intramuscular administration Methods 0.000 description 4
- 238000001990 intravenous administration Methods 0.000 description 4
- 239000002502 liposome Substances 0.000 description 4
- 239000012669 liquid formulation Substances 0.000 description 4
- 238000007911 parenteral administration Methods 0.000 description 4
- 239000013612 plasmid Substances 0.000 description 4
- 229920000747 poly(lactic acid) Polymers 0.000 description 4
- 108090000623 proteins and genes Proteins 0.000 description 4
- 230000000717 retained effect Effects 0.000 description 4
- 230000028327 secretion Effects 0.000 description 4
- 238000007920 subcutaneous administration Methods 0.000 description 4
- 239000004094 surface-active agent Substances 0.000 description 4
- RYYWUUFWQRZTIU-UHFFFAOYSA-K thiophosphate Chemical compound [O-]P([O-])([O-])=S RYYWUUFWQRZTIU-UHFFFAOYSA-K 0.000 description 4
- 230000000699 topical effect Effects 0.000 description 4
- 230000014599 transmission of virus Effects 0.000 description 4
- 102000040650 (ribonucleotides)n+m Human genes 0.000 description 3
- ASJSAQIRZKANQN-CRCLSJGQSA-N 2-deoxy-D-ribose Chemical compound OC[C@@H](O)[C@@H](O)CC=O ASJSAQIRZKANQN-CRCLSJGQSA-N 0.000 description 3
- HMFHBZSHGGEWLO-SOOFDHNKSA-N D-ribofuranose Chemical compound OC[C@H]1OC(O)[C@H](O)[C@@H]1O HMFHBZSHGGEWLO-SOOFDHNKSA-N 0.000 description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- 208000007514 Herpes zoster Diseases 0.000 description 3
- 108010052285 Membrane Proteins Proteins 0.000 description 3
- 102000018697 Membrane Proteins Human genes 0.000 description 3
- 239000004793 Polystyrene Substances 0.000 description 3
- PYMYPHUHKUWMLA-LMVFSUKVSA-N Ribose Natural products OC[C@@H](O)[C@@H](O)[C@@H](O)C=O PYMYPHUHKUWMLA-LMVFSUKVSA-N 0.000 description 3
- 108020004682 Single-Stranded DNA Proteins 0.000 description 3
- RYYWUUFWQRZTIU-UHFFFAOYSA-N Thiophosphoric acid Chemical group OP(O)(S)=O RYYWUUFWQRZTIU-UHFFFAOYSA-N 0.000 description 3
- HMFHBZSHGGEWLO-UHFFFAOYSA-N alpha-D-Furanose-Ribose Natural products OCC1OC(O)C(O)C1O HMFHBZSHGGEWLO-UHFFFAOYSA-N 0.000 description 3
- 238000010171 animal model Methods 0.000 description 3
- 230000000840 anti-viral effect Effects 0.000 description 3
- 230000002155 anti-virotic effect Effects 0.000 description 3
- 239000003443 antiviral agent Substances 0.000 description 3
- PYMYPHUHKUWMLA-UHFFFAOYSA-N arabinose Natural products OCC(O)C(O)C(O)C=O PYMYPHUHKUWMLA-UHFFFAOYSA-N 0.000 description 3
- 238000003556 assay Methods 0.000 description 3
- 230000002238 attenuated effect Effects 0.000 description 3
- 239000011324 bead Substances 0.000 description 3
- SRBFZHDQGSBBOR-UHFFFAOYSA-N beta-D-Pyranose-Lyxose Natural products OC1COC(O)C(O)C1O SRBFZHDQGSBBOR-UHFFFAOYSA-N 0.000 description 3
- 201000011510 cancer Diseases 0.000 description 3
- 210000000234 capsid Anatomy 0.000 description 3
- 235000012000 cholesterol Nutrition 0.000 description 3
- 230000001934 delay Effects 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- 238000005516 engineering process Methods 0.000 description 3
- 238000001914 filtration Methods 0.000 description 3
- 239000012530 fluid Substances 0.000 description 3
- 230000002163 immunogen Effects 0.000 description 3
- 230000006872 improvement Effects 0.000 description 3
- 238000010348 incorporation Methods 0.000 description 3
- 238000011534 incubation Methods 0.000 description 3
- 230000002458 infectious effect Effects 0.000 description 3
- 238000007912 intraperitoneal administration Methods 0.000 description 3
- 238000004969 ion scattering spectroscopy Methods 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- 230000001404 mediated effect Effects 0.000 description 3
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
- 244000052769 pathogen Species 0.000 description 3
- 239000012071 phase Substances 0.000 description 3
- 150000003013 phosphoric acid derivatives Chemical class 0.000 description 3
- 239000000843 powder Substances 0.000 description 3
- 235000018102 proteins Nutrition 0.000 description 3
- 102000004169 proteins and genes Human genes 0.000 description 3
- 150000003230 pyrimidines Chemical class 0.000 description 3
- 230000007420 reactivation Effects 0.000 description 3
- 238000010188 recombinant method Methods 0.000 description 3
- 230000001568 sexual effect Effects 0.000 description 3
- 150000008163 sugars Chemical class 0.000 description 3
- 210000001215 vagina Anatomy 0.000 description 3
- 239000003981 vehicle Substances 0.000 description 3
- 230000029812 viral genome replication Effects 0.000 description 3
- YBJHBAHKTGYVGT-ZKWXMUAHSA-N (+)-Biotin Chemical compound N1C(=O)N[C@@H]2[C@H](CCCCC(=O)O)SC[C@@H]21 YBJHBAHKTGYVGT-ZKWXMUAHSA-N 0.000 description 2
- YYGNTYWPHWGJRM-UHFFFAOYSA-N (6E,10E,14E,18E)-2,6,10,15,19,23-hexamethyltetracosa-2,6,10,14,18,22-hexaene Chemical compound CC(C)=CCCC(C)=CCCC(C)=CCCC=C(C)CCC=C(C)CCC=C(C)C YYGNTYWPHWGJRM-UHFFFAOYSA-N 0.000 description 2
- ZNCFMBOWBMPEAC-UHFFFAOYSA-N 3,9-di(ethylidene)-2,4,8,10-tetraoxaspiro[5.5]undecane Chemical compound C1OC(=CC)OCC21COC(=CC)OC2 ZNCFMBOWBMPEAC-UHFFFAOYSA-N 0.000 description 2
- UFVWJVAMULFOMC-UHFFFAOYSA-N 6-amino-5-iodo-1h-pyrimidin-2-one Chemical compound NC=1NC(=O)N=CC=1I UFVWJVAMULFOMC-UHFFFAOYSA-N 0.000 description 2
- 206010067484 Adverse reaction Diseases 0.000 description 2
- 229920000936 Agarose Polymers 0.000 description 2
- 241000271566 Aves Species 0.000 description 2
- LZZYPRNAOMGNLH-UHFFFAOYSA-M Cetrimonium bromide Chemical compound [Br-].CCCCCCCCCCCCCCCC[N+](C)(C)C LZZYPRNAOMGNLH-UHFFFAOYSA-M 0.000 description 2
- 201000006082 Chickenpox Diseases 0.000 description 2
- 102000009016 Cholera Toxin Human genes 0.000 description 2
- 108010049048 Cholera Toxin Proteins 0.000 description 2
- 239000004971 Cross linker Substances 0.000 description 2
- SRBFZHDQGSBBOR-IOVATXLUSA-N D-xylopyranose Chemical compound O[C@@H]1COC(O)[C@H](O)[C@H]1O SRBFZHDQGSBBOR-IOVATXLUSA-N 0.000 description 2
- 208000034423 Delivery Diseases 0.000 description 2
- 238000002965 ELISA Methods 0.000 description 2
- 241000588724 Escherichia coli Species 0.000 description 2
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical class NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
- AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical compound OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 description 2
- 208000037952 HSV-1 infection Diseases 0.000 description 2
- 241000282412 Homo Species 0.000 description 2
- 241000701070 Human herpesvirus 2 strain 186 Species 0.000 description 2
- 108090000978 Interleukin-4 Proteins 0.000 description 2
- 108010002616 Interleukin-5 Proteins 0.000 description 2
- 208000032420 Latent Infection Diseases 0.000 description 2
- 238000010222 PCR analysis Methods 0.000 description 2
- 229920000954 Polyglycolide Polymers 0.000 description 2
- 239000004372 Polyvinyl alcohol Substances 0.000 description 2
- ATUOYWHBWRKTHZ-UHFFFAOYSA-N Propane Chemical compound CCC ATUOYWHBWRKTHZ-UHFFFAOYSA-N 0.000 description 2
- 208000035415 Reinfection Diseases 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- BHEOSNUKNHRBNM-UHFFFAOYSA-N Tetramethylsqualene Natural products CC(=C)C(C)CCC(=C)C(C)CCC(C)=CCCC=C(C)CCC(C)C(=C)CCC(C)C(C)=C BHEOSNUKNHRBNM-UHFFFAOYSA-N 0.000 description 2
- 206010046980 Varicella Diseases 0.000 description 2
- 241000251539 Vertebrata <Metazoa> Species 0.000 description 2
- 230000004913 activation Effects 0.000 description 2
- 230000006838 adverse reaction Effects 0.000 description 2
- 238000000540 analysis of variance Methods 0.000 description 2
- PYMYPHUHKUWMLA-WDCZJNDASA-N arabinose Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)C=O PYMYPHUHKUWMLA-WDCZJNDASA-N 0.000 description 2
- 208000006673 asthma Diseases 0.000 description 2
- 230000007487 asymptomatic viral shedding Effects 0.000 description 2
- 230000009286 beneficial effect Effects 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 229920002988 biodegradable polymer Polymers 0.000 description 2
- 239000004621 biodegradable polymer Substances 0.000 description 2
- 229920001400 block copolymer Polymers 0.000 description 2
- 235000010410 calcium alginate Nutrition 0.000 description 2
- 239000000648 calcium alginate Substances 0.000 description 2
- 229960002681 calcium alginate Drugs 0.000 description 2
- OKHHGHGGPDJQHR-YMOPUZKJSA-L calcium;(2s,3s,4s,5s,6r)-6-[(2r,3s,4r,5s,6r)-2-carboxy-6-[(2r,3s,4r,5s,6r)-2-carboxylato-4,5,6-trihydroxyoxan-3-yl]oxy-4,5-dihydroxyoxan-3-yl]oxy-3,4,5-trihydroxyoxane-2-carboxylate Chemical compound [Ca+2].O[C@@H]1[C@H](O)[C@H](O)O[C@@H](C([O-])=O)[C@H]1O[C@H]1[C@@H](O)[C@@H](O)[C@H](O[C@H]2[C@H]([C@@H](O)[C@H](O)[C@H](O2)C([O-])=O)O)[C@H](C(O)=O)O1 OKHHGHGGPDJQHR-YMOPUZKJSA-L 0.000 description 2
- 238000011260 co-administration Methods 0.000 description 2
- 239000002299 complementary DNA Substances 0.000 description 2
- 230000009918 complex formation Effects 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 230000001276 controlling effect Effects 0.000 description 2
- 229920001577 copolymer Polymers 0.000 description 2
- 230000002596 correlated effect Effects 0.000 description 2
- 230000000875 corresponding effect Effects 0.000 description 2
- 238000004132 cross linking Methods 0.000 description 2
- 230000000120 cytopathologic effect Effects 0.000 description 2
- 210000001151 cytotoxic T lymphocyte Anatomy 0.000 description 2
- 238000001514 detection method Methods 0.000 description 2
- NAGJZTKCGNOGPW-UHFFFAOYSA-K dioxido-sulfanylidene-sulfido-$l^{5}-phosphane Chemical compound [O-]P([O-])([S-])=S NAGJZTKCGNOGPW-UHFFFAOYSA-K 0.000 description 2
- PRAKJMSDJKAYCZ-UHFFFAOYSA-N dodecahydrosqualene Natural products CC(C)CCCC(C)CCCC(C)CCCCC(C)CCCC(C)CCCC(C)C PRAKJMSDJKAYCZ-UHFFFAOYSA-N 0.000 description 2
- 238000002296 dynamic light scattering Methods 0.000 description 2
- 206010014599 encephalitis Diseases 0.000 description 2
- 230000001747 exhibiting effect Effects 0.000 description 2
- 230000001605 fetal effect Effects 0.000 description 2
- XRECTZIEBJDKEO-UHFFFAOYSA-N flucytosine Chemical compound NC1=NC(=O)NC=C1F XRECTZIEBJDKEO-UHFFFAOYSA-N 0.000 description 2
- 229960004413 flucytosine Drugs 0.000 description 2
- 230000006870 function Effects 0.000 description 2
- 125000000524 functional group Chemical group 0.000 description 2
- 230000013595 glycosylation Effects 0.000 description 2
- 238000006206 glycosylation reaction Methods 0.000 description 2
- PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical group [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 description 2
- 239000010931 gold Substances 0.000 description 2
- 229910052737 gold Inorganic materials 0.000 description 2
- 244000144993 groups of animals Species 0.000 description 2
- UYTPUPDQBNUYGX-UHFFFAOYSA-N guanine Chemical compound O=C1NC(N)=NC2=C1N=CN2 UYTPUPDQBNUYGX-UHFFFAOYSA-N 0.000 description 2
- 208000010726 hind limb paralysis Diseases 0.000 description 2
- 210000005260 human cell Anatomy 0.000 description 2
- 238000009396 hybridization Methods 0.000 description 2
- BHEPBYXIRTUNPN-UHFFFAOYSA-N hydridophosphorus(.) (triplet) Chemical class [PH] BHEPBYXIRTUNPN-UHFFFAOYSA-N 0.000 description 2
- 230000001900 immune effect Effects 0.000 description 2
- 230000016784 immunoglobulin production Effects 0.000 description 2
- 230000003993 interaction Effects 0.000 description 2
- 238000002955 isolation Methods 0.000 description 2
- 239000004816 latex Chemical group 0.000 description 2
- 229920000126 latex Chemical group 0.000 description 2
- 231100000518 lethal Toxicity 0.000 description 2
- 230000001665 lethal effect Effects 0.000 description 2
- 150000002632 lipids Chemical class 0.000 description 2
- 239000000693 micelle Substances 0.000 description 2
- 239000011859 microparticle Substances 0.000 description 2
- 238000000386 microscopy Methods 0.000 description 2
- 210000004877 mucosa Anatomy 0.000 description 2
- 230000009854 mucosal lesion Effects 0.000 description 2
- 150000003833 nucleoside derivatives Chemical class 0.000 description 2
- 239000007764 o/w emulsion Substances 0.000 description 2
- 230000003647 oxidation Effects 0.000 description 2
- 238000007254 oxidation reaction Methods 0.000 description 2
- 238000004806 packaging method and process Methods 0.000 description 2
- 125000002467 phosphate group Chemical group [H]OP(=O)(O[H])O[*] 0.000 description 2
- 150000004713 phosphodiesters Chemical class 0.000 description 2
- 150000008298 phosphoramidates Chemical class 0.000 description 2
- 230000004962 physiological condition Effects 0.000 description 2
- 229920002627 poly(phosphazenes) Polymers 0.000 description 2
- 238000003752 polymerase chain reaction Methods 0.000 description 2
- 229920002223 polystyrene Polymers 0.000 description 2
- 229920002451 polyvinyl alcohol Polymers 0.000 description 2
- 235000019422 polyvinyl alcohol Nutrition 0.000 description 2
- 208000037920 primary disease Diseases 0.000 description 2
- 230000000069 prophylactic effect Effects 0.000 description 2
- 238000011321 prophylaxis Methods 0.000 description 2
- 230000002685 pulmonary effect Effects 0.000 description 2
- 210000005000 reproductive tract Anatomy 0.000 description 2
- 238000007423 screening assay Methods 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- 229940031439 squalene Drugs 0.000 description 2
- TUHBEKDERLKLEC-UHFFFAOYSA-N squalene Natural products CC(=CCCC(=CCCC(=CCCC=C(/C)CCC=C(/C)CC=C(C)C)C)C)C TUHBEKDERLKLEC-UHFFFAOYSA-N 0.000 description 2
- 230000004936 stimulating effect Effects 0.000 description 2
- 230000001629 suppression Effects 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- RWQNBRDOKXIBIV-UHFFFAOYSA-N thymine Chemical compound CC1=CNC(=O)NC1=O RWQNBRDOKXIBIV-UHFFFAOYSA-N 0.000 description 2
- 238000011200 topical administration Methods 0.000 description 2
- 229940035893 uracil Drugs 0.000 description 2
- 230000009677 vaginal delivery Effects 0.000 description 2
- 210000003501 vero cell Anatomy 0.000 description 2
- YUKLYKLJUJWGNE-YEUCEMRASA-N (9Z,29Z)-19,20-bis(methylamino)-19-(methylaminomethyl)octatriaconta-9,29-diene-18,21-dione Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)C(NC)C(CNC)(NC)C(=O)CCCCCCC\C=C/CCCCCCCC YUKLYKLJUJWGNE-YEUCEMRASA-N 0.000 description 1
- VUFVGYBIFMCJPB-UHFFFAOYSA-N 1-iodopyrimidine-2,4-dione Chemical compound IN1C=CC(=O)NC1=O VUFVGYBIFMCJPB-UHFFFAOYSA-N 0.000 description 1
- VSNHCAURESNICA-NJFSPNSNSA-N 1-oxidanylurea Chemical compound N[14C](=O)NO VSNHCAURESNICA-NJFSPNSNSA-N 0.000 description 1
- APXRHPDHORGIEB-UHFFFAOYSA-N 1H-pyrazolo[4,3-d]pyrimidine Chemical class N1=CN=C2C=NNC2=C1 APXRHPDHORGIEB-UHFFFAOYSA-N 0.000 description 1
- KSXTUUUQYQYKCR-LQDDAWAPSA-M 2,3-bis[[(z)-octadec-9-enoyl]oxy]propyl-trimethylazanium;chloride Chemical compound [Cl-].CCCCCCCC\C=C/CCCCCCCC(=O)OCC(C[N+](C)(C)C)OC(=O)CCCCCCC\C=C/CCCCCCCC KSXTUUUQYQYKCR-LQDDAWAPSA-M 0.000 description 1
- WAVYAFBQOXCGSZ-UHFFFAOYSA-N 2-fluoropyrimidine Chemical compound FC1=NC=CC=N1 WAVYAFBQOXCGSZ-UHFFFAOYSA-N 0.000 description 1
- FPOVCZDHZSAAIX-UHFFFAOYSA-N 4-amino-5,6-dihydro-1h-pyrimidin-2-one Chemical compound NC1=NC(=O)NCC1 FPOVCZDHZSAAIX-UHFFFAOYSA-N 0.000 description 1
- MFEFTTYGMZOIKO-UHFFFAOYSA-N 5-azacytosine Chemical compound NC1=NC=NC(=O)N1 MFEFTTYGMZOIKO-UHFFFAOYSA-N 0.000 description 1
- LQLQRFGHAALLLE-UHFFFAOYSA-N 5-bromouracil Chemical compound BrC1=CNC(=O)NC1=O LQLQRFGHAALLLE-UHFFFAOYSA-N 0.000 description 1
- SPDBZGFVYQCVIU-UHFFFAOYSA-N 6-amino-5-nitro-1h-pyrimidin-2-one Chemical compound NC=1NC(=O)N=CC=1[N+]([O-])=O SPDBZGFVYQCVIU-UHFFFAOYSA-N 0.000 description 1
- SHZGCJCMOBCMKK-UHFFFAOYSA-N 6-methyloxane-2,3,4,5-tetrol Chemical compound CC1OC(O)C(O)C(O)C1O SHZGCJCMOBCMKK-UHFFFAOYSA-N 0.000 description 1
- GFFGJBXGBJISGV-UHFFFAOYSA-N Adenine Chemical compound NC1=NC=NC2=C1N=CN2 GFFGJBXGBJISGV-UHFFFAOYSA-N 0.000 description 1
- 229930024421 Adenine Natural products 0.000 description 1
- 201000004384 Alopecia Diseases 0.000 description 1
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
- 102100022717 Atypical chemokine receptor 1 Human genes 0.000 description 1
- 108090001008 Avidin Proteins 0.000 description 1
- 230000003844 B-cell-activation Effects 0.000 description 1
- 101100065878 Caenorhabditis elegans sec-10 gene Proteins 0.000 description 1
- 241000700199 Cavia porcellus Species 0.000 description 1
- 241000282552 Chlorocebus aethiops Species 0.000 description 1
- 208000035473 Communicable disease Diseases 0.000 description 1
- 241000938605 Crocodylia Species 0.000 description 1
- 229920001651 Cyanoacrylate Polymers 0.000 description 1
- UHDGCWIWMRVCDJ-CCXZUQQUSA-N Cytarabine Chemical compound O=C1N=C(N)C=CN1[C@H]1[C@@H](O)[C@H](O)[C@@H](CO)O1 UHDGCWIWMRVCDJ-CCXZUQQUSA-N 0.000 description 1
- 241000701022 Cytomegalovirus Species 0.000 description 1
- 108010061982 DNA Ligases Proteins 0.000 description 1
- 206010013710 Drug interaction Diseases 0.000 description 1
- 206010015150 Erythema Diseases 0.000 description 1
- GHASVSINZRGABV-UHFFFAOYSA-N Fluorouracil Chemical compound FC1=CNC(=O)NC1=O GHASVSINZRGABV-UHFFFAOYSA-N 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- 239000004471 Glycine Substances 0.000 description 1
- 108090000288 Glycoproteins Proteins 0.000 description 1
- 102000003886 Glycoproteins Human genes 0.000 description 1
- 241000700586 Herpesviridae Species 0.000 description 1
- 101000678879 Homo sapiens Atypical chemokine receptor 1 Proteins 0.000 description 1
- 241000701024 Human betaherpesvirus 5 Species 0.000 description 1
- 241000701044 Human gammaherpesvirus 4 Species 0.000 description 1
- 101900228213 Human herpesvirus 2 Envelope glycoprotein D Proteins 0.000 description 1
- 206010061598 Immunodeficiency Diseases 0.000 description 1
- 108010050904 Interferons Proteins 0.000 description 1
- 102000014150 Interferons Human genes 0.000 description 1
- 108010002350 Interleukin-2 Proteins 0.000 description 1
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical class C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 1
- 108090000364 Ligases Proteins 0.000 description 1
- 102000003960 Ligases Human genes 0.000 description 1
- 208000008771 Lymphadenopathy Diseases 0.000 description 1
- 239000004472 Lysine Substances 0.000 description 1
- 230000006051 NK cell activation Effects 0.000 description 1
- 108091061960 Naked DNA Proteins 0.000 description 1
- 206010061308 Neonatal infection Diseases 0.000 description 1
- 101710163270 Nuclease Proteins 0.000 description 1
- 108700001237 Nucleic Acid-Based Vaccines Proteins 0.000 description 1
- 108091028043 Nucleic acid sequence Proteins 0.000 description 1
- 108010033276 Peptide Fragments Proteins 0.000 description 1
- 102000007079 Peptide Fragments Human genes 0.000 description 1
- 239000004952 Polyamide Substances 0.000 description 1
- 239000004695 Polyether sulfone Substances 0.000 description 1
- 239000004698 Polyethylene Substances 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 108010039918 Polylysine Proteins 0.000 description 1
- 229920001710 Polyorthoester Polymers 0.000 description 1
- 241000288906 Primates Species 0.000 description 1
- 206010037660 Pyrexia Diseases 0.000 description 1
- 101710086015 RNA ligase Proteins 0.000 description 1
- 108091028664 Ribonucleotide Proteins 0.000 description 1
- 241000283984 Rodentia Species 0.000 description 1
- 229920002684 Sepharose Polymers 0.000 description 1
- 239000004147 Sorbitan trioleate Substances 0.000 description 1
- PRXRUNOAOLTIEF-ADSICKODSA-N Sorbitan trioleate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OC[C@@H](OC(=O)CCCCCCC\C=C/CCCCCCCC)[C@H]1OC[C@H](O)[C@H]1OC(=O)CCCCCCC\C=C/CCCCCCCC PRXRUNOAOLTIEF-ADSICKODSA-N 0.000 description 1
- 229930182558 Sterol Chemical group 0.000 description 1
- 108010090804 Streptavidin Proteins 0.000 description 1
- 230000024932 T cell mediated immunity Effects 0.000 description 1
- 230000006052 T cell proliferation Effects 0.000 description 1
- 108700012920 TNF Proteins 0.000 description 1
- 210000004241 Th2 cell Anatomy 0.000 description 1
- 206010053613 Type IV hypersensitivity reaction Diseases 0.000 description 1
- 208000025865 Ulcer Diseases 0.000 description 1
- 206010046555 Urinary retention Diseases 0.000 description 1
- 108010003533 Viral Envelope Proteins Proteins 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 229960000643 adenine Drugs 0.000 description 1
- 208000013228 adenopathy Diseases 0.000 description 1
- 239000000443 aerosol Substances 0.000 description 1
- 235000004279 alanine Nutrition 0.000 description 1
- 125000005600 alkyl phosphonate group Chemical group 0.000 description 1
- 239000013566 allergen Substances 0.000 description 1
- SRBFZHDQGSBBOR-STGXQOJASA-N alpha-D-lyxopyranose Chemical compound O[C@@H]1CO[C@H](O)[C@@H](O)[C@H]1O SRBFZHDQGSBBOR-STGXQOJASA-N 0.000 description 1
- 229940037003 alum Drugs 0.000 description 1
- 235000001014 amino acid Nutrition 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-N ammonia Natural products N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 1
- 239000003708 ampul Substances 0.000 description 1
- 210000004102 animal cell Anatomy 0.000 description 1
- 230000003602 anti-herpes Effects 0.000 description 1
- 230000000890 antigenic effect Effects 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 239000000074 antisense oligonucleotide Substances 0.000 description 1
- 238000012230 antisense oligonucleotides Methods 0.000 description 1
- 229940121357 antivirals Drugs 0.000 description 1
- 210000003719 b-lymphocyte Anatomy 0.000 description 1
- 230000001580 bacterial effect Effects 0.000 description 1
- 230000004888 barrier function Effects 0.000 description 1
- 230000006399 behavior Effects 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- 229920000229 biodegradable polyester Polymers 0.000 description 1
- 239000004622 biodegradable polyester Substances 0.000 description 1
- 239000013060 biological fluid Substances 0.000 description 1
- 230000008827 biological function Effects 0.000 description 1
- 238000001574 biopsy Methods 0.000 description 1
- 239000011616 biotin Substances 0.000 description 1
- 229960002685 biotin Drugs 0.000 description 1
- 235000020958 biotin Nutrition 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 239000004067 bulking agent Substances 0.000 description 1
- 210000004899 c-terminal region Anatomy 0.000 description 1
- 125000002843 carboxylic acid group Chemical group 0.000 description 1
- 150000001768 cations Chemical class 0.000 description 1
- 238000004113 cell culture Methods 0.000 description 1
- 239000013592 cell lysate Substances 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 230000007969 cellular immunity Effects 0.000 description 1
- 210000003169 central nervous system Anatomy 0.000 description 1
- 208000015114 central nervous system disease Diseases 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 210000003756 cervix mucus Anatomy 0.000 description 1
- 150000001793 charged compounds Chemical class 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 238000002512 chemotherapy Methods 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 230000015271 coagulation Effects 0.000 description 1
- 238000005345 coagulation Methods 0.000 description 1
- 230000000295 complement effect Effects 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 230000008878 coupling Effects 0.000 description 1
- 238000010168 coupling process Methods 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- 239000003431 cross linking reagent Substances 0.000 description 1
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 239000005547 deoxyribonucleotide Substances 0.000 description 1
- 125000002637 deoxyribonucleotide group Chemical group 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 230000001066 destructive effect Effects 0.000 description 1
- 230000010460 detection of virus Effects 0.000 description 1
- 239000003599 detergent Substances 0.000 description 1
- 239000001177 diphosphate Substances 0.000 description 1
- XPPKVPWEQAFLFU-UHFFFAOYSA-J diphosphate(4-) Chemical compound [O-]P([O-])(=O)OP([O-])([O-])=O XPPKVPWEQAFLFU-UHFFFAOYSA-J 0.000 description 1
- 235000011180 diphosphates Nutrition 0.000 description 1
- 208000037771 disease arising from reactivation of latent virus Diseases 0.000 description 1
- 230000006806 disease prevention Effects 0.000 description 1
- 208000035475 disorder Diseases 0.000 description 1
- 238000006073 displacement reaction Methods 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- NAGJZTKCGNOGPW-UHFFFAOYSA-N dithiophosphoric acid Chemical class OP(O)(S)=S NAGJZTKCGNOGPW-UHFFFAOYSA-N 0.000 description 1
- 238000009509 drug development Methods 0.000 description 1
- 230000009881 electrostatic interaction Effects 0.000 description 1
- 230000008030 elimination Effects 0.000 description 1
- 238000003379 elimination reaction Methods 0.000 description 1
- 238000004945 emulsification Methods 0.000 description 1
- 238000006911 enzymatic reaction Methods 0.000 description 1
- 210000000981 epithelium Anatomy 0.000 description 1
- 231100000321 erythema Toxicity 0.000 description 1
- 125000004185 ester group Chemical group 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 210000003527 eukaryotic cell Anatomy 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 230000005713 exacerbation Effects 0.000 description 1
- 230000029142 excretion Effects 0.000 description 1
- 239000013604 expression vector Substances 0.000 description 1
- 230000005294 ferromagnetic effect Effects 0.000 description 1
- 239000003302 ferromagnetic material Substances 0.000 description 1
- 229960002949 fluorouracil Drugs 0.000 description 1
- 238000004108 freeze drying Methods 0.000 description 1
- 125000003843 furanosyl group Chemical group 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 238000011554 guinea pig model Methods 0.000 description 1
- 208000024963 hair loss Diseases 0.000 description 1
- 230000003676 hair loss Effects 0.000 description 1
- 229910052736 halogen Inorganic materials 0.000 description 1
- 150000002367 halogens Chemical class 0.000 description 1
- 238000011597 hartley guinea pig Methods 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 210000002443 helper t lymphocyte Anatomy 0.000 description 1
- 150000002402 hexoses Chemical class 0.000 description 1
- 238000000265 homogenisation Methods 0.000 description 1
- 230000028996 humoral immune response Effects 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 150000003949 imides Chemical class 0.000 description 1
- 230000008102 immune modulation Effects 0.000 description 1
- 230000036039 immunity Effects 0.000 description 1
- 238000003018 immunoassay Methods 0.000 description 1
- 230000009851 immunogenic response Effects 0.000 description 1
- 239000007943 implant Substances 0.000 description 1
- 230000008676 import Effects 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 229940079322 interferon Drugs 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 230000002045 lasting effect Effects 0.000 description 1
- 230000021633 leukocyte mediated immunity Effects 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 210000004698 lymphocyte Anatomy 0.000 description 1
- 210000003563 lymphoid tissue Anatomy 0.000 description 1
- 230000005291 magnetic effect Effects 0.000 description 1
- 239000006249 magnetic particle Chemical group 0.000 description 1
- 210000004962 mammalian cell Anatomy 0.000 description 1
- 210000004779 membrane envelope Anatomy 0.000 description 1
- 229940071648 metered dose inhaler Drugs 0.000 description 1
- YACKEPLHDIMKIO-UHFFFAOYSA-L methylphosphonate(2-) Chemical compound CP([O-])([O-])=O YACKEPLHDIMKIO-UHFFFAOYSA-L 0.000 description 1
- 238000010369 molecular cloning Methods 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- 239000000178 monomer Substances 0.000 description 1
- 150000004712 monophosphates Chemical class 0.000 description 1
- 229940100662 nasal drops Drugs 0.000 description 1
- 210000000822 natural killer cell Anatomy 0.000 description 1
- 239000006199 nebulizer Substances 0.000 description 1
- 210000005036 nerve Anatomy 0.000 description 1
- 230000000926 neurological effect Effects 0.000 description 1
- 230000007823 neuropathy Effects 0.000 description 1
- 201000001119 neuropathy Diseases 0.000 description 1
- 230000003472 neutralizing effect Effects 0.000 description 1
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
- 238000001668 nucleic acid synthesis Methods 0.000 description 1
- 229940023146 nucleic acid vaccine Drugs 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 229940124276 oligodeoxyribonucleotide Drugs 0.000 description 1
- 238000002515 oligonucleotide synthesis Methods 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 230000000065 osmolyte Effects 0.000 description 1
- 230000003204 osmotic effect Effects 0.000 description 1
- 239000006174 pH buffer Substances 0.000 description 1
- 239000002907 paramagnetic material Substances 0.000 description 1
- 230000001717 pathogenic effect Effects 0.000 description 1
- 150000002972 pentoses Chemical class 0.000 description 1
- 230000009984 peri-natal effect Effects 0.000 description 1
- 208000033808 peripheral neuropathy Diseases 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- PTMHPRAIXMAOOB-UHFFFAOYSA-L phosphoramidate Chemical compound NP([O-])([O-])=O PTMHPRAIXMAOOB-UHFFFAOYSA-L 0.000 description 1
- 229920001606 poly(lactic acid-co-glycolic acid) Polymers 0.000 description 1
- 229920002647 polyamide Polymers 0.000 description 1
- 229920001610 polycaprolactone Polymers 0.000 description 1
- 229920000515 polycarbonate Polymers 0.000 description 1
- 239000004417 polycarbonate Substances 0.000 description 1
- 229920006393 polyether sulfone Polymers 0.000 description 1
- 229920000573 polyethylene Polymers 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 229920000656 polylysine Polymers 0.000 description 1
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 1
- 229920000053 polysorbate 80 Polymers 0.000 description 1
- 239000011148 porous material Substances 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 150000003141 primary amines Chemical class 0.000 description 1
- 108090000765 processed proteins & peptides Proteins 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- 239000001294 propane Substances 0.000 description 1
- 229940023143 protein vaccine Drugs 0.000 description 1
- 230000005180 public health Effects 0.000 description 1
- 230000000541 pulsatile effect Effects 0.000 description 1
- 150000003212 purines Chemical class 0.000 description 1
- 125000003132 pyranosyl group Chemical group 0.000 description 1
- 125000004528 pyrimidin-5-yl group Chemical group N1=CN=CC(=C1)* 0.000 description 1
- 150000004944 pyrrolopyrimidines Chemical class 0.000 description 1
- 230000003362 replicative effect Effects 0.000 description 1
- 230000001850 reproductive effect Effects 0.000 description 1
- 238000012827 research and development Methods 0.000 description 1
- 210000001533 respiratory mucosa Anatomy 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 239000002336 ribonucleotide Substances 0.000 description 1
- 125000002652 ribonucleotide group Chemical group 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 238000004626 scanning electron microscopy Methods 0.000 description 1
- 238000007790 scraping Methods 0.000 description 1
- 230000001953 sensory effect Effects 0.000 description 1
- 210000001044 sensory neuron Anatomy 0.000 description 1
- 238000004904 shortening Methods 0.000 description 1
- 230000007928 solubilization Effects 0.000 description 1
- 238000005063 solubilization Methods 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 238000000935 solvent evaporation Methods 0.000 description 1
- 238000000638 solvent extraction Methods 0.000 description 1
- 235000019337 sorbitan trioleate Nutrition 0.000 description 1
- 229960000391 sorbitan trioleate Drugs 0.000 description 1
- 210000003594 spinal ganglia Anatomy 0.000 description 1
- 238000012289 standard assay Methods 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 238000007619 statistical method Methods 0.000 description 1
- 150000003431 steroids Chemical group 0.000 description 1
- 150000003432 sterols Chemical group 0.000 description 1
- 235000003702 sterols Nutrition 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- JJAHTWIKCUJRDK-UHFFFAOYSA-N succinimidyl 4-(N-maleimidomethyl)cyclohexane-1-carboxylate Chemical compound C1CC(CN2C(C=CC2=O)=O)CCC1C(=O)ON1C(=O)CCC1=O JJAHTWIKCUJRDK-UHFFFAOYSA-N 0.000 description 1
- 238000005987 sulfurization reaction Methods 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 150000003505 terpenes Chemical class 0.000 description 1
- 235000007586 terpenes Nutrition 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 229940113082 thymine Drugs 0.000 description 1
- 238000004448 titration Methods 0.000 description 1
- 239000012049 topical pharmaceutical composition Substances 0.000 description 1
- 239000003053 toxin Substances 0.000 description 1
- 231100000765 toxin Toxicity 0.000 description 1
- 108700012359 toxins Proteins 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 238000011269 treatment regimen Methods 0.000 description 1
- 239000001226 triphosphate Substances 0.000 description 1
- 235000011178 triphosphate Nutrition 0.000 description 1
- UNXRWKVEANCORM-UHFFFAOYSA-N triphosphoric acid Chemical compound OP(O)(=O)OP(O)(=O)OP(O)(O)=O UNXRWKVEANCORM-UHFFFAOYSA-N 0.000 description 1
- 230000005951 type IV hypersensitivity Effects 0.000 description 1
- 208000027930 type IV hypersensitivity disease Diseases 0.000 description 1
- 230000002485 urinary effect Effects 0.000 description 1
- 210000001635 urinary tract Anatomy 0.000 description 1
- 210000002700 urine Anatomy 0.000 description 1
- 230000007501 viral attachment Effects 0.000 description 1
- 239000005723 virus inoculator Substances 0.000 description 1
- 239000008215 water for injection Substances 0.000 description 1
- 230000003442 weekly effect Effects 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7088—Compounds having three or more nucleosides or nucleotides
- A61K31/7105—Natural ribonucleic acids, i.e. containing only riboses attached to adenine, guanine, cytosine or uracil and having 3'-5' phosphodiester links
-
- 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
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/20—Antivirals for DNA viruses
- A61P31/22—Antivirals for DNA viruses for herpes viruses
-
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- General Chemical & Material Sciences (AREA)
- Epidemiology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Virology (AREA)
- Molecular Biology (AREA)
- Oncology (AREA)
- Immunology (AREA)
- Communicable Diseases (AREA)
- Mycology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Microbiology (AREA)
- Biochemistry (AREA)
- Engineering & Computer Science (AREA)
- Biotechnology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US18855600P | 2000-03-10 | 2000-03-10 | |
| US60/188,556 | 2000-03-10 | ||
| US09/802,518 | 2001-03-09 | ||
| US09/802,518 US7157437B2 (en) | 2000-03-10 | 2001-03-09 | Methods of ameliorating symptoms of herpes infection using immunomodulatory polynucleotide sequences |
| PCT/US2001/007841 WO2001068103A2 (en) | 2000-03-10 | 2001-03-12 | Treatment of herpes infection using immunomodulatory polynucleotide sequences |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2402312A1 true CA2402312A1 (en) | 2001-09-20 |
Family
ID=26884207
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002402312A Abandoned CA2402312A1 (en) | 2000-03-10 | 2001-03-12 | Treatment of herpes infection using immunomodulatory polynucleotide sequences |
Country Status (8)
| Country | Link |
|---|---|
| US (2) | US7157437B2 (enExample) |
| EP (1) | EP1265622B1 (enExample) |
| JP (1) | JP2003526670A (enExample) |
| AT (1) | ATE476984T1 (enExample) |
| AU (2) | AU8145901A (enExample) |
| CA (1) | CA2402312A1 (enExample) |
| DE (1) | DE60142776D1 (enExample) |
| WO (1) | WO2001068103A2 (enExample) |
Families Citing this family (40)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6207646B1 (en) * | 1994-07-15 | 2001-03-27 | University Of Iowa Research Foundation | Immunostimulatory nucleic acid molecules |
| US20030026782A1 (en) * | 1995-02-07 | 2003-02-06 | Arthur M. Krieg | Immunomodulatory oligonucleotides |
| US6239116B1 (en) | 1994-07-15 | 2001-05-29 | University Of Iowa Research Foundation | Immunostimulatory nucleic acid molecules |
| US6406705B1 (en) | 1997-03-10 | 2002-06-18 | University Of Iowa Research Foundation | Use of nucleic acids containing unmethylated CpG dinucleotide as an adjuvant |
| ES2272069T3 (es) | 1998-05-22 | 2007-04-16 | Ottawa Health Research Institute | Metodos y productos para inducir inmunidad en mucosas. |
| 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 |
| 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 |
| 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 |
| DE60131430T2 (de) | 2000-01-14 | 2008-10-16 | The Government Of The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services | Oligodeoxynukleotide und ihre verwendung zur induktion einer immunreaktion |
| US20020028784A1 (en) * | 2000-03-10 | 2002-03-07 | Nest Gary Van | Methods of preventing and treating viral infections using immunomodulatory polynucleotide sequences |
| US20010046967A1 (en) * | 2000-03-10 | 2001-11-29 | Gary Van Nest | Methods of preventing and treating respiratory viral infection using immunomodulatory polynucleotide |
| 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 |
| US20020107212A1 (en) * | 2000-03-10 | 2002-08-08 | Nest Gary Van | Methods of reducing papillomavirus 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 |
| US20030049266A1 (en) | 2000-12-27 | 2003-03-13 | Fearon Karen L. | Immunomodulatory polynucleotides and methods of using the same |
| DK2423335T3 (da) | 2001-06-21 | 2014-08-18 | Dynavax Tech Corp | Kimæriske immunmodulatoriske forbindelser og fremgangsmåder til anvendelse deraf |
| AU2002326561B2 (en) | 2001-08-07 | 2008-04-03 | Dynavax Technologies Corporation | 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 |
| CA2471968C (en) * | 2001-10-06 | 2013-07-23 | Merial Limited | Immunostimulatory nucleic acids and use thereof |
| 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 |
| EA008777B1 (ru) | 2002-10-29 | 2007-08-31 | Коли Фармасьютикал Груп, Лтд. | Способы и продукты, относящиеся к лечению и предупреждению инфекции вируса гепатита c |
| WO2004098491A2 (en) | 2002-11-01 | 2004-11-18 | The Government Of The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services | METHOD OF PREVENTING INFECTIONS FROM BIOTERRORISM AGENTS WITH IMMUNOSTIMULATORY CpG OLIGONUCLEOTIDES |
| US7956043B2 (en) | 2002-12-11 | 2011-06-07 | Coley Pharmaceutical Group, Inc. | 5′ CpG nucleic acids and methods of use |
| SI1575977T1 (sl) | 2002-12-23 | 2010-01-29 | Dynavax Tech Corp | Imunostimulirni sekvenčni polinukleotidi in postopki za njihovo uporabo |
| US8158768B2 (en) | 2002-12-23 | 2012-04-17 | Dynavax Technologies Corporation | Immunostimulatory sequence oligonucleotides and methods of using the same |
| CA2521050A1 (en) * | 2003-04-02 | 2004-10-14 | Coley Pharmaceutical Group, Ltd. | Immunostimulatory nucleic acid oil-in-water formulations and related methods of use |
| TWI235440B (en) * | 2004-03-31 | 2005-07-01 | Advanced Semiconductor Eng | Method for making leadless semiconductor package |
| CN101171033A (zh) | 2005-03-04 | 2008-04-30 | 戴纳瓦克斯技术公司 | 包含具免疫刺激序列iss之寡核苷酸的疫苗：其中iss与抗原缀合并通过缓冲条件和其他赋形剂稳定 |
| RU2314817C2 (ru) * | 2005-11-22 | 2008-01-20 | Светлана Николаевна Козлова | Способ лечения неврологических повреждений у детей |
| EP2411521B1 (en) | 2009-03-25 | 2015-01-14 | The Board of Regents of The University of Texas System | Compositions for stimulation of mammalian innate immune resistance to pathogens |
| ES2732815T3 (es) | 2009-05-22 | 2019-11-26 | Genocea Biosciences Inc | Vacunas frente al virus del herpes simple de tipo 2: composiciones y métodos para provocar una respuesta inmunitaria |
| NO2575876T3 (enExample) | 2010-05-26 | 2018-05-05 | ||
| EP2640190A4 (en) | 2010-11-05 | 2016-05-11 | Selecta Biosciences Inc | MODIFIED NICOTINIC COMPOUNDS AND ASSOCIATED METHODS |
| EP2643014A4 (en) | 2010-11-24 | 2015-11-11 | Genocea Biosciences Inc | HERPES SIMPLEX TYPE 2 VIRUS VACCINES: COMPOSITIONS AND METHODS FOR STIMULATING AN IMMUNE RESPONSE |
| US20130039954A1 (en) | 2011-07-29 | 2013-02-14 | Selecta Biosciences, Inc. | Control of antibody responses to synthetic nanocarriers |
| JP6199878B2 (ja) | 2011-11-23 | 2017-09-20 | ジェノセア バイオサイエンシーズ， インコーポレイテッド | 単純ヘルペスウイルス２型に対する核酸ワクチン：免疫応答を誘発する組成物及び方法 |
| US10286065B2 (en) | 2014-09-19 | 2019-05-14 | Board Of Regents, The University Of Texas System | Compositions and methods for treating viral infections through stimulated innate immunity in combination with antiviral compounds |
| WO2018064232A1 (en) | 2016-09-28 | 2018-04-05 | Genocea Biosciences, Inc. | Methods and compositions for treating herpes |
Family Cites Families (52)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4458066A (en) * | 1980-02-29 | 1984-07-03 | University Patents, Inc. | Process for preparing polynucleotides |
| US4948882A (en) * | 1983-02-22 | 1990-08-14 | Syngene, Inc. | Single-stranded labelled oligonucleotides, reactive monomers and methods of synthesis |
| US4650675A (en) * | 1983-08-18 | 1987-03-17 | The Children's Medical Center Corporation | Oligonucleotide conjugates |
| US5118800A (en) * | 1983-12-20 | 1992-06-02 | California Institute Of Technology | Oligonucleotides possessing a primary amino group in the terminal nucleotide |
| US5015733A (en) * | 1983-12-20 | 1991-05-14 | California Institute Of Technology | Nucleosides possessing blocked aliphatic amino groups |
| 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 |
| 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 |
| US5093232A (en) * | 1985-12-11 | 1992-03-03 | Chiron Corporation | Nucleic acid probes |
| US4910300A (en) * | 1985-12-11 | 1990-03-20 | Chiron Corporation | Method for making nucleic acid probes |
| US5124246A (en) * | 1987-10-15 | 1992-06-23 | Chiron Corporation | Nucleic acid multimers and amplified nucleic acid hybridization assays using same |
| US5278302A (en) * | 1988-05-26 | 1994-01-11 | University Patents, Inc. | Polynucleotide phosphorodithioates |
| EP0468520A3 (en) | 1990-07-27 | 1992-07-01 | Mitsui Toatsu Chemicals, Inc. | Immunostimulatory remedies containing palindromic dna sequences |
| US5616461A (en) * | 1992-05-14 | 1997-04-01 | Dana-Farber Cancer Institute | Assay for antiviral activity using complex of herpesvirus origin of replication and cellular protein |
| US5849719A (en) * | 1993-08-26 | 1998-12-15 | The Regents Of The University Of California | Method for treating allergic lung disease |
| WO1995026204A1 (en) * | 1994-03-25 | 1995-10-05 | Isis Pharmaceuticals, Inc. | Immune stimulation by phosphorothioate oligonucleotide analogs |
| US6239116B1 (en) * | 1994-07-15 | 2001-05-29 | University Of Iowa Research Foundation | Immunostimulatory nucleic acid molecules |
| US6207646B1 (en) | 1994-07-15 | 2001-03-27 | University Of Iowa Research Foundation | Immunostimulatory nucleic acid molecules |
| JP3468773B2 (ja) | 1994-07-15 | 2003-11-17 | ザ 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 | 免疫調節オリゴヌクレオチド |
| US20030050263A1 (en) * | 1994-07-15 | 2003-03-13 | The University Of Iowa Research Foundation | Methods and products for treating HIV infection |
| US5874089A (en) * | 1995-10-02 | 1999-02-23 | Georgetown University School Of Medicine | Protecting against canine oral papillomavirus (copy) |
| JP4359654B2 (ja) | 1996-01-30 | 2009-11-04 | ザ リージェンツ オブ ザ ユニバーシティー オブ カリフォルニア | 抗原特異的免疫応答を生起させる遺伝子発現ベクターおよびその使用方法 |
| ES2241042T3 (es) | 1996-10-11 | 2005-10-16 | The Regents Of The University Of California | Conjugados de polinucleotido inmunoestimulador/ molecula inmunomoduladora. |
| EP1039935A4 (en) | 1997-02-28 | 2005-04-27 | Univ Iowa Res Found | USE OF NUCLEIC ACIDS CONTAINING UNMETHYLATED CpG DINUCLEOTIDE IN THE TREATMENT OF LPS-ASSOCIATED 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 |
| WO1998040100A1 (en) | 1997-03-10 | 1998-09-17 | Ottawa Civic Loeb Research Institute | USE OF NUCLEIC ACIDS CONTAINING UNMETHYLATED CpG DINUCLEOTIDE AS AN ADJUVANT |
| AU7589398A (en) | 1997-05-19 | 1998-12-11 | Merck & Co., Inc. | Oligonucleotide adjuvant |
| US6339068B1 (en) * | 1997-05-20 | 2002-01-15 | University Of Iowa Research Foundation | Vectors and methods for immunization or therapeutic protocols |
| ATE432348T1 (de) | 1997-06-06 | 2009-06-15 | Univ California | Inhibitoren von immunstimulatorischen dna sequenz aktivität |
| AU757175B2 (en) * | 1997-09-05 | 2003-02-06 | Regents Of The University Of California, The | Use of immunostimulatory oligonucleotides for preventing or reducing antigen-stimulated, granulocyte-mediated inflammation |
| GB9727262D0 (en) | 1997-12-24 | 1998-02-25 | Smithkline Beecham Biolog | Vaccine |
| CA2323929C (en) * | 1998-04-03 | 2004-03-09 | University Of Iowa Research Foundation | Methods and products for stimulating the immune system using immunotherapeutic oligonucleotides and cytokines |
| JP2002513763A (ja) | 1998-05-06 | 2002-05-14 | 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 | Ｃｐｇオリゴヌクレオチドを使用して寄生生物感染および関連する疾患を予防および処置するための方法 |
| NZ508650A (en) * | 1998-05-14 | 2003-05-30 | Coley Pharm Gmbh | Regulating hematopoiesis using unmethylated C and G CpG-oligonucleotides with a phosphorothioate modification |
| US6562798B1 (en) | 1998-06-05 | 2003-05-13 | Dynavax Technologies Corp. | Immunostimulatory oligonucleotides with modified bases and methods of use thereof |
| WO2000006588A1 (en) | 1998-07-27 | 2000-02-10 | University Of Iowa Research Foundation | STEREOISOMERS OF CpG OLIGONUCLEOTIDES AND RELATED METHODS |
| WO2000016804A1 (en) | 1998-09-18 | 2000-03-30 | Dynavax Technologies Corporation | METHODS OF TREATING IgE-ASSOCIATED DISORDERS AND COMPOSITIONS FOR USE THEREIN |
| AU6425999A (en) | 1998-10-09 | 2000-05-01 | Dynavax Technologies Corporation | Anti hiv compositions comprising immunostimulatory polynucleotides and hiv antigens |
| AU762857B2 (en) | 1999-04-20 | 2003-07-10 | Smithkline Beecham Biologicals (Sa) | Vaccine |
| DE60013591T2 (de) | 1999-04-29 | 2005-02-03 | Coley Pharmaceutical Gmbh | Screening nach modulatoren der funktion von immunstimulatorischer dna |
| US6514948B1 (en) | 1999-07-02 | 2003-02-04 | The Regents Of The University Of California | Method for enhancing an immune response |
| US7479285B1 (en) | 1999-08-19 | 2009-01-20 | Dynavax Technologies Corporation | Methods of modulating an immune response using immunostimulatory sequences and compositions for use therein |
| US6552006B2 (en) * | 2000-01-31 | 2003-04-22 | The Regents Of The University Of California | Immunomodulatory polynucleotides in treatment of an infection by an intracellular pathogen |
| AU4175101A (en) * | 2000-02-23 | 2001-09-03 | Univ California | Method for treating inflammatory bowel disease and other forms of gastrointestinal inflammation |
| US20020098199A1 (en) | 2000-03-10 | 2002-07-25 | Gary Van Nest | Methods of suppressing hepatitis virus 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 |
| 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 |
| US20030129251A1 (en) | 2000-03-10 | 2003-07-10 | Gary Van Nest | Biodegradable immunomodulatory formulations and methods for use thereof |
| US7129222B2 (en) | 2000-03-10 | 2006-10-31 | Dynavax Technologies Corporation | Immunomodulatory formulations and methods for use thereof |
| US20010046967A1 (en) | 2000-03-10 | 2001-11-29 | Gary Van Nest | Methods of preventing and treating respiratory viral infection using immunomodulatory polynucleotide |
| CA2404041A1 (en) * | 2000-03-28 | 2001-10-04 | The Regents Of The University Of California | Methods for increasing a cytotoxic t lymphocyte response in vivo |
| EP1278550A4 (en) | 2000-04-07 | 2004-05-12 | Univ California | SYNERGISTIC IMPROVEMENTS OF POLYNUCLEOTIDE VACCINE |
-
2001
- 2001-03-09 US US09/802,518 patent/US7157437B2/en not_active Expired - Fee Related
- 2001-03-12 JP JP2001566667A patent/JP2003526670A/ja active Pending
- 2001-03-12 CA CA002402312A patent/CA2402312A1/en not_active Abandoned
- 2001-03-12 AU AU8145901A patent/AU8145901A/xx active Pending
- 2001-03-12 WO PCT/US2001/007841 patent/WO2001068103A2/en not_active Ceased
- 2001-03-12 EP EP01957594A patent/EP1265622B1/en not_active Expired - Lifetime
- 2001-03-12 DE DE60142776T patent/DE60142776D1/de not_active Expired - Lifetime
- 2001-03-12 AT AT01957594T patent/ATE476984T1/de not_active IP Right Cessation
- 2001-03-12 AU AU2001281459A patent/AU2001281459C1/en not_active Ceased
-
2006
- 2006-11-10 US US11/595,552 patent/US20070060540A1/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| AU2001281459C1 (en) | 2006-08-31 |
| AU8145901A (en) | 2001-09-24 |
| JP2003526670A (ja) | 2003-09-09 |
| WO2001068103A3 (en) | 2002-08-08 |
| WO2001068103A2 (en) | 2001-09-20 |
| US20060264391A1 (en) | 2006-11-23 |
| ATE476984T1 (de) | 2010-08-15 |
| AU2001281459B8 (en) | 2005-09-29 |
| DE60142776D1 (de) | 2010-09-23 |
| WO2001068103A9 (en) | 2003-03-06 |
| EP1265622B1 (en) | 2010-08-11 |
| AU2001281459B2 (en) | 2005-09-15 |
| EP1265622A2 (en) | 2002-12-18 |
| US20070060540A1 (en) | 2007-03-15 |
| US7157437B2 (en) | 2007-01-02 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| EP1265622B1 (en) | Treatment of herpes infection using immunomodulatory polynucleotide sequences | |
| AU2001281459A1 (en) | Treatment of herpes infection using immunomodulatory polynucleotide sequences | |
| CA2402268C (en) | Immunostimulatory polynucleotide sequences for use in preventing and treating respiratory viral infections | |
| AU2001245627B8 (en) | Immunostimulatory polynucleotide sequences for use in preventing and treating viral infections | |
| EP1261353B1 (en) | Immunostimulatory polynucleotide sequences for use in preventing and treating viral infections | |
| AU2001243587A1 (en) | Methods of preventing and treating respiratory viral infection using immunomodulatory polynucleotide sequences. | |
| AU2001242032B2 (en) | Immunostimulatory polynucleotide sequences for use in suppressing hepatitis virus infection | |
| AU2001245627A1 (en) | Immunostimulatory polynucleotide sequences for use in preventing and treating viral infections | |
| AU2001243588A1 (en) | Immunostimulatory polynucleotide sequences for use in preventing and treating viral infections | |
| KR20030064882A (ko) | 면역조절 폴리뉴클레오티드 및 그것의 사용 방법 | |
| AU2001242032A1 (en) | Immunostimulatory polynucleotide sequences for use in suppressing hepatitis virus infection |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request | ||
| FZDE | Discontinued |