DK2655623T3 - Ikke-kodende immunmodulatorisk DNA-konstrukt - Google Patents
Ikke-kodende immunmodulatorisk DNA-konstrukt Download PDFInfo
- Publication number
- DK2655623T3 DK2655623T3 DK11805869.2T DK11805869T DK2655623T3 DK 2655623 T3 DK2655623 T3 DK 2655623T3 DK 11805869 T DK11805869 T DK 11805869T DK 2655623 T3 DK2655623 T3 DK 2655623T3
- Authority
- DK
- Denmark
- Prior art keywords
- dna
- nucleotides
- conformation
- construct
- motif
- Prior art date
Links
- 230000002519 immonomodulatory effect Effects 0.000 title description 8
- 125000003729 nucleotide group Chemical group 0.000 claims description 175
- 239000002773 nucleotide Substances 0.000 claims description 174
- 108020004414 DNA Proteins 0.000 claims description 147
- 206010028980 Neoplasm Diseases 0.000 claims description 18
- 102000053602 DNA Human genes 0.000 claims description 17
- 108090000623 proteins and genes Proteins 0.000 claims description 15
- 238000011282 treatment Methods 0.000 claims description 15
- 108091028043 Nucleic acid sequence Proteins 0.000 claims description 14
- 201000011510 cancer Diseases 0.000 claims description 10
- 229960005486 vaccine Drugs 0.000 claims description 10
- 102000004169 proteins and genes Human genes 0.000 claims description 8
- 239000008194 pharmaceutical composition Substances 0.000 claims description 7
- 208000023275 Autoimmune disease Diseases 0.000 claims description 6
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 6
- OIRDTQYFTABQOQ-KQYNXXCUSA-N adenosine Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O OIRDTQYFTABQOQ-KQYNXXCUSA-N 0.000 claims description 6
- 102000004196 processed proteins & peptides Human genes 0.000 claims description 6
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 6
- 239000007790 solid phase Substances 0.000 claims description 6
- YKBGVTZYEHREMT-KVQBGUIXSA-N 2'-deoxyguanosine Chemical compound C1=NC=2C(=O)NC(N)=NC=2N1[C@H]1C[C@H](O)[C@@H](CO)O1 YKBGVTZYEHREMT-KVQBGUIXSA-N 0.000 claims description 5
- 239000002671 adjuvant Substances 0.000 claims description 5
- 150000001875 compounds Chemical group 0.000 claims description 5
- 229920000642 polymer Polymers 0.000 claims description 5
- BWGNESOTFCXPMA-UHFFFAOYSA-N Dihydrogen disulfide Chemical compound SS BWGNESOTFCXPMA-UHFFFAOYSA-N 0.000 claims description 3
- DHKHKXVYLBGOIT-UHFFFAOYSA-N acetaldehyde Diethyl Acetal Natural products CCOC(C)OCC DHKHKXVYLBGOIT-UHFFFAOYSA-N 0.000 claims description 3
- 150000004705 aldimines Chemical class 0.000 claims description 3
- 150000001408 amides Chemical class 0.000 claims description 3
- 150000001412 amines Chemical class 0.000 claims description 3
- 150000001720 carbohydrates Chemical class 0.000 claims description 3
- 235000014633 carbohydrates Nutrition 0.000 claims description 3
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 3
- 150000002148 esters Chemical class 0.000 claims description 3
- 125000000524 functional group Chemical group 0.000 claims description 3
- 150000002632 lipids Chemical class 0.000 claims description 3
- 239000002923 metal particle Substances 0.000 claims description 3
- 239000000693 micelle Substances 0.000 claims description 3
- 150000003573 thiols Chemical class 0.000 claims description 3
- CKTSBUTUHBMZGZ-ULQXZJNLSA-N 4-amino-1-[(2r,4s,5r)-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-5-tritiopyrimidin-2-one Chemical compound O=C1N=C(N)C([3H])=CN1[C@@H]1O[C@H](CO)[C@@H](O)C1 CKTSBUTUHBMZGZ-ULQXZJNLSA-N 0.000 claims description 2
- 239000002082 metal nanoparticle Substances 0.000 claims description 2
- 108091092724 Noncoding DNA Proteins 0.000 claims 1
- 125000002777 acetyl group Chemical class [H]C([H])([H])C(*)=O 0.000 claims 1
- 239000002246 antineoplastic agent Substances 0.000 claims 1
- 229940127089 cytotoxic agent Drugs 0.000 claims 1
- 125000002485 formyl group Chemical class [H]C(*)=O 0.000 claims 1
- 229940046166 oligodeoxynucleotide Drugs 0.000 description 52
- 210000004027 cell Anatomy 0.000 description 40
- 230000000694 effects Effects 0.000 description 29
- 230000028327 secretion Effects 0.000 description 28
- 230000000638 stimulation Effects 0.000 description 28
- 102000004890 Interleukin-8 Human genes 0.000 description 25
- 108090001007 Interleukin-8 Proteins 0.000 description 25
- 230000004936 stimulating effect Effects 0.000 description 23
- 102000006992 Interferon-alpha Human genes 0.000 description 18
- 108010047761 Interferon-alpha Proteins 0.000 description 18
- OHDXDNUPVVYWOV-UHFFFAOYSA-N n-methyl-1-(2-naphthalen-1-ylsulfanylphenyl)methanamine Chemical compound CNCC1=CC=CC=C1SC1=CC=CC2=CC=CC=C12 OHDXDNUPVVYWOV-UHFFFAOYSA-N 0.000 description 17
- PYMYPHUHKUWMLA-UHFFFAOYSA-N arabinose Natural products OCC(O)C(O)C(O)C=O PYMYPHUHKUWMLA-UHFFFAOYSA-N 0.000 description 15
- 210000000987 immune system Anatomy 0.000 description 15
- 210000003819 peripheral blood mononuclear cell Anatomy 0.000 description 15
- HMFHBZSHGGEWLO-UHFFFAOYSA-N alpha-D-Furanose-Ribose Natural products OCC1OC(O)C(O)C1O HMFHBZSHGGEWLO-UHFFFAOYSA-N 0.000 description 14
- 230000004913 activation Effects 0.000 description 13
- 238000001415 gene therapy Methods 0.000 description 13
- 230000028993 immune response Effects 0.000 description 13
- PYMYPHUHKUWMLA-MROZADKFSA-N aldehydo-L-ribose Chemical compound OC[C@H](O)[C@H](O)[C@H](O)C=O PYMYPHUHKUWMLA-MROZADKFSA-N 0.000 description 12
- 210000004544 dc2 Anatomy 0.000 description 12
- 230000003308 immunostimulating effect Effects 0.000 description 12
- 108091034117 Oligonucleotide Proteins 0.000 description 11
- 102000008235 Toll-Like Receptor 9 Human genes 0.000 description 11
- 108010060818 Toll-Like Receptor 9 Proteins 0.000 description 11
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 11
- 102000039446 nucleic acids Human genes 0.000 description 11
- 108020004707 nucleic acids Proteins 0.000 description 11
- 150000007523 nucleic acids Chemical class 0.000 description 11
- 210000005134 plasmacytoid dendritic cell Anatomy 0.000 description 11
- 201000010099 disease Diseases 0.000 description 10
- 230000004048 modification Effects 0.000 description 10
- 238000012986 modification Methods 0.000 description 10
- 102100021943 C-C motif chemokine 2 Human genes 0.000 description 8
- 101710155857 C-C motif chemokine 2 Proteins 0.000 description 8
- 102000004127 Cytokines Human genes 0.000 description 8
- 108090000695 Cytokines Proteins 0.000 description 8
- 238000013459 approach Methods 0.000 description 8
- 230000015556 catabolic process Effects 0.000 description 8
- 238000006731 degradation reaction Methods 0.000 description 8
- 230000006698 induction Effects 0.000 description 7
- 238000000034 method Methods 0.000 description 7
- 210000001744 T-lymphocyte Anatomy 0.000 description 6
- 239000000427 antigen Substances 0.000 description 6
- 102000036639 antigens Human genes 0.000 description 6
- 108091007433 antigens Proteins 0.000 description 6
- 210000003719 b-lymphocyte Anatomy 0.000 description 6
- 230000008901 benefit Effects 0.000 description 6
- 238000002474 experimental method Methods 0.000 description 6
- 239000003550 marker Substances 0.000 description 6
- OGIAAULPRXAQEV-UHFFFAOYSA-N odn 2216 Chemical compound O=C1NC(=O)C(C)=CN1C1OC(COP(O)(=O)OC2C(OC(C2)N2C3=NC=NC(N)=C3N=C2)COP(O)(=O)OC2C(OC(C2)N2C3=C(C(NC(N)=N3)=O)N=C2)COP(O)(=O)OC2C(OC(C2)N2C(N=C(N)C=C2)=O)COP(O)(=O)OC2C(OC(C2)N2C3=NC=NC(N)=C3N=C2)COP(O)(=O)OC2C(OC(C2)N2C3=C(C(NC(N)=N3)=O)N=C2)COP(O)(=O)OC2C(OC(C2)N2C3=C(C(NC(N)=N3)=O)N=C2)COP(O)(=O)OC2C(OC(C2)N2C3=C(C(NC(N)=N3)=O)N=C2)COP(O)(=O)OC2C(OC(C2)N2C3=C(C(NC(N)=N3)=O)N=C2)COP(O)(=O)OC2C(OC(C2)N2C3=C(C(NC(N)=N3)=O)N=C2)COP(O)(O)=O)C(OP(O)(=O)OCC2C(CC(O2)N2C(N=C(N)C=C2)=O)OP(O)(=O)OCC2C(CC(O2)N2C3=C(C(NC(N)=N3)=O)N=C2)OP(O)(=O)OCC2C(CC(O2)N2C(NC(=O)C(C)=C2)=O)OP(O)(=O)OCC2C(CC(O2)N2C(N=C(N)C=C2)=O)OP(O)(=O)OCC2C(CC(O2)N2C3=C(C(NC(N)=N3)=O)N=C2)OP(O)(=O)OCC2C(CC(O2)N2C3=C(C(NC(N)=N3)=O)N=C2)OP(O)(=O)OCC2C(CC(O2)N2C3=C(C(NC(N)=N3)=O)N=C2)OP(O)(=O)OCC2C(CC(O2)N2C3=C(C(NC(N)=N3)=O)N=C2)OP(O)(=O)OCC2C(CC(O2)N2C3=C(C(NC(N)=N3)=O)N=C2)OP(O)(=O)OCC2C(CC(O2)N2C3=C(C(NC(N)=N3)=O)N=C2)O)C1 OGIAAULPRXAQEV-UHFFFAOYSA-N 0.000 description 6
- 238000002255 vaccination Methods 0.000 description 6
- 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 Polymers 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 5
- 208000006673 asthma Diseases 0.000 description 5
- 230000009286 beneficial effect Effects 0.000 description 5
- 210000002540 macrophage Anatomy 0.000 description 5
- 230000001225 therapeutic effect Effects 0.000 description 5
- RYYWUUFWQRZTIU-UHFFFAOYSA-K thiophosphate Chemical group [O-]P([O-])([O-])=S RYYWUUFWQRZTIU-UHFFFAOYSA-K 0.000 description 5
- 229940044655 toll-like receptor 9 agonist Drugs 0.000 description 5
- 102000006354 HLA-DR Antigens Human genes 0.000 description 4
- 108010058597 HLA-DR Antigens Proteins 0.000 description 4
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 4
- IQFYYKKMVGJFEH-XLPZGREQSA-N Thymidine Chemical group O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](CO)[C@@H](O)C1 IQFYYKKMVGJFEH-XLPZGREQSA-N 0.000 description 4
- 102000002689 Toll-like receptor Human genes 0.000 description 4
- 108020000411 Toll-like receptor Proteins 0.000 description 4
- 108060008682 Tumor Necrosis Factor Proteins 0.000 description 4
- 230000027455 binding Effects 0.000 description 4
- 210000003958 hematopoietic stem cell Anatomy 0.000 description 4
- 238000001727 in vivo Methods 0.000 description 4
- 208000015181 infectious disease Diseases 0.000 description 4
- 238000004519 manufacturing process Methods 0.000 description 4
- 239000000463 material Substances 0.000 description 4
- 230000001404 mediated effect Effects 0.000 description 4
- 239000002777 nucleoside Substances 0.000 description 4
- 230000003389 potentiating effect Effects 0.000 description 4
- 230000004044 response Effects 0.000 description 4
- 238000002560 therapeutic procedure Methods 0.000 description 4
- 210000001519 tissue Anatomy 0.000 description 4
- 210000004881 tumor cell Anatomy 0.000 description 4
- 241000894006 Bacteria Species 0.000 description 3
- 108700012434 CCL3 Proteins 0.000 description 3
- 102000000013 Chemokine CCL3 Human genes 0.000 description 3
- 208000035473 Communicable disease Diseases 0.000 description 3
- 206010020751 Hypersensitivity Diseases 0.000 description 3
- 206010062016 Immunosuppression Diseases 0.000 description 3
- 108020004682 Single-Stranded DNA Proteins 0.000 description 3
- 241000700605 Viruses Species 0.000 description 3
- 230000003213 activating effect Effects 0.000 description 3
- 208000026935 allergic disease Diseases 0.000 description 3
- 230000007815 allergy Effects 0.000 description 3
- 230000000259 anti-tumor effect Effects 0.000 description 3
- 210000004443 dendritic cell Anatomy 0.000 description 3
- 229910003460 diamond Inorganic materials 0.000 description 3
- 239000010432 diamond Substances 0.000 description 3
- 239000003814 drug Substances 0.000 description 3
- 210000004602 germ cell Anatomy 0.000 description 3
- 239000011521 glass Substances 0.000 description 3
- 230000008105 immune reaction Effects 0.000 description 3
- 230000001506 immunosuppresive effect Effects 0.000 description 3
- 238000011534 incubation Methods 0.000 description 3
- 230000037431 insertion Effects 0.000 description 3
- 238000003780 insertion Methods 0.000 description 3
- 244000052769 pathogen Species 0.000 description 3
- 125000005642 phosphothioate group Chemical group 0.000 description 3
- 229920001184 polypeptide Polymers 0.000 description 3
- -1 polypropylene Polymers 0.000 description 3
- UCSJYZPVAKXKNQ-HZYVHMACSA-N streptomycin Chemical compound CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](NC(N)=N)[C@H](O)[C@@H](NC(N)=N)[C@H](O)[C@H]1O UCSJYZPVAKXKNQ-HZYVHMACSA-N 0.000 description 3
- MZOFCQQQCNRIBI-VMXHOPILSA-N (3s)-4-[[(2s)-1-[[(2s)-1-[[(1s)-1-carboxy-2-hydroxyethyl]amino]-4-methyl-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-3-[[2-[[(2s)-2,6-diaminohexanoyl]amino]acetyl]amino]-4-oxobutanoic acid Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CC(O)=O)NC(=O)CNC(=O)[C@@H](N)CCCCN MZOFCQQQCNRIBI-VMXHOPILSA-N 0.000 description 2
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 2
- 101150013553 CD40 gene Proteins 0.000 description 2
- 201000009030 Carcinoma Diseases 0.000 description 2
- 102000001326 Chemokine CCL4 Human genes 0.000 description 2
- 108010055165 Chemokine CCL4 Proteins 0.000 description 2
- 206010009944 Colon cancer Diseases 0.000 description 2
- 208000011231 Crohn disease Diseases 0.000 description 2
- 108010041986 DNA Vaccines Proteins 0.000 description 2
- 238000011238 DNA vaccination Methods 0.000 description 2
- 229940021995 DNA vaccine Drugs 0.000 description 2
- 102000016911 Deoxyribonucleases Human genes 0.000 description 2
- 108010053770 Deoxyribonucleases Proteins 0.000 description 2
- 102100025137 Early activation antigen CD69 Human genes 0.000 description 2
- 102000004190 Enzymes Human genes 0.000 description 2
- 108090000790 Enzymes Proteins 0.000 description 2
- ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 2
- NYHBQMYGNKIUIF-UUOKFMHZSA-N Guanosine Chemical compound C1=NC=2C(=O)NC(N)=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O NYHBQMYGNKIUIF-UUOKFMHZSA-N 0.000 description 2
- 208000030836 Hashimoto thyroiditis Diseases 0.000 description 2
- 101000934374 Homo sapiens Early activation antigen CD69 Proteins 0.000 description 2
- 208000026350 Inborn Genetic disease Diseases 0.000 description 2
- 102100037850 Interferon gamma Human genes 0.000 description 2
- 108010074328 Interferon-gamma Proteins 0.000 description 2
- 102000014150 Interferons Human genes 0.000 description 2
- 108010050904 Interferons Proteins 0.000 description 2
- 102000004889 Interleukin-6 Human genes 0.000 description 2
- 108090001005 Interleukin-6 Proteins 0.000 description 2
- 102000015696 Interleukins Human genes 0.000 description 2
- 108010063738 Interleukins Proteins 0.000 description 2
- 125000003376 L-ribosyl group Chemical group C1([C@@H](O)[C@@H](O)[C@@H](O1)CO)* 0.000 description 2
- 102000009571 Macrophage Inflammatory Proteins Human genes 0.000 description 2
- 108010009474 Macrophage Inflammatory Proteins Proteins 0.000 description 2
- 102000014962 Monocyte Chemoattractant Proteins Human genes 0.000 description 2
- 108010064136 Monocyte Chemoattractant Proteins Proteins 0.000 description 2
- 229930182555 Penicillin Natural products 0.000 description 2
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 2
- 239000012980 RPMI-1640 medium Substances 0.000 description 2
- PPBRXRYQALVLMV-UHFFFAOYSA-N Styrene Chemical compound C=CC1=CC=CC=C1 PPBRXRYQALVLMV-UHFFFAOYSA-N 0.000 description 2
- RYYWUUFWQRZTIU-UHFFFAOYSA-N Thiophosphoric acid Chemical class OP(O)(S)=O RYYWUUFWQRZTIU-UHFFFAOYSA-N 0.000 description 2
- 102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 description 2
- 102100040245 Tumor necrosis factor receptor superfamily member 5 Human genes 0.000 description 2
- 208000036142 Viral infection Diseases 0.000 description 2
- 150000001241 acetals Chemical class 0.000 description 2
- 125000003172 aldehyde group Chemical group 0.000 description 2
- PYMYPHUHKUWMLA-LMVFSUKVSA-N aldehydo-D-ribose Chemical compound OC[C@@H](O)[C@@H](O)[C@@H](O)C=O PYMYPHUHKUWMLA-LMVFSUKVSA-N 0.000 description 2
- 201000009961 allergic asthma Diseases 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- 238000007385 chemical modification Methods 0.000 description 2
- 238000002512 chemotherapy Methods 0.000 description 2
- 210000001151 cytotoxic T lymphocyte Anatomy 0.000 description 2
- 230000001419 dependent effect Effects 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 239000012636 effector Substances 0.000 description 2
- 230000007515 enzymatic degradation Effects 0.000 description 2
- 239000012894 fetal calf serum Substances 0.000 description 2
- 238000000684 flow cytometry Methods 0.000 description 2
- 238000001943 fluorescence-activated cell sorting Methods 0.000 description 2
- 239000012634 fragment Substances 0.000 description 2
- 238000012239 gene modification Methods 0.000 description 2
- 230000005017 genetic modification Effects 0.000 description 2
- 235000013617 genetically modified food Nutrition 0.000 description 2
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 2
- 230000036039 immunity Effects 0.000 description 2
- 230000002458 infectious effect Effects 0.000 description 2
- 230000003993 interaction Effects 0.000 description 2
- 229940079322 interferon Drugs 0.000 description 2
- 230000007246 mechanism Effects 0.000 description 2
- 239000002609 medium Substances 0.000 description 2
- 210000001616 monocyte Anatomy 0.000 description 2
- 239000002105 nanoparticle Substances 0.000 description 2
- 210000000822 natural killer cell Anatomy 0.000 description 2
- 238000011275 oncology therapy Methods 0.000 description 2
- 229940049954 penicillin Drugs 0.000 description 2
- 239000004033 plastic Substances 0.000 description 2
- 229920003023 plastic Polymers 0.000 description 2
- 230000002265 prevention Effects 0.000 description 2
- 230000000069 prophylactic effect Effects 0.000 description 2
- 238000001959 radiotherapy Methods 0.000 description 2
- 206010039073 rheumatoid arthritis Diseases 0.000 description 2
- 239000000377 silicon dioxide Substances 0.000 description 2
- 230000000392 somatic effect Effects 0.000 description 2
- 238000010186 staining Methods 0.000 description 2
- 238000012546 transfer Methods 0.000 description 2
- 102000003390 tumor necrosis factor Human genes 0.000 description 2
- 239000013598 vector Substances 0.000 description 2
- 230000009385 viral infection Effects 0.000 description 2
- UHDGCWIWMRVCDJ-UHFFFAOYSA-N 1-beta-D-Xylofuranosyl-NH-Cytosine Natural products O=C1N=C(N)C=CN1C1C(O)C(O)C(CO)O1 UHDGCWIWMRVCDJ-UHFFFAOYSA-N 0.000 description 1
- 208000026872 Addison Disease Diseases 0.000 description 1
- 102000004550 Angiostatic Proteins Human genes 0.000 description 1
- 108010017551 Angiostatic Proteins Proteins 0.000 description 1
- 102100024222 B-lymphocyte antigen CD19 Human genes 0.000 description 1
- 208000023328 Basedow disease Diseases 0.000 description 1
- DWRXFEITVBNRMK-UHFFFAOYSA-N Beta-D-1-Arabinofuranosylthymine Natural products O=C1NC(=O)C(C)=CN1C1C(O)C(O)C(CO)O1 DWRXFEITVBNRMK-UHFFFAOYSA-N 0.000 description 1
- 239000002126 C01EB10 - Adenosine Substances 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- 206010057248 Cell death Diseases 0.000 description 1
- 102000019034 Chemokines Human genes 0.000 description 1
- 108010012236 Chemokines Proteins 0.000 description 1
- 208000015943 Coeliac disease Diseases 0.000 description 1
- MIKUYHXYGGJMLM-GIMIYPNGSA-N Crotonoside Natural products C1=NC2=C(N)NC(=O)N=C2N1[C@H]1O[C@@H](CO)[C@H](O)[C@@H]1O MIKUYHXYGGJMLM-GIMIYPNGSA-N 0.000 description 1
- UHDGCWIWMRVCDJ-PSQAKQOGSA-N Cytidine Natural products O=C1N=C(N)C=CN1[C@@H]1[C@@H](O)[C@@H](O)[C@H](CO)O1 UHDGCWIWMRVCDJ-PSQAKQOGSA-N 0.000 description 1
- NYHBQMYGNKIUIF-UHFFFAOYSA-N D-guanosine Natural products C1=2NC(N)=NC(=O)C=2N=CN1C1OC(CO)C(O)C1O NYHBQMYGNKIUIF-UHFFFAOYSA-N 0.000 description 1
- 230000004568 DNA-binding Effects 0.000 description 1
- 208000002699 Digestive System Neoplasms Diseases 0.000 description 1
- 238000002965 ELISA Methods 0.000 description 1
- 241000701867 Enterobacteria phage T7 Species 0.000 description 1
- 241000206602 Eukaryota Species 0.000 description 1
- 108060002716 Exonuclease Proteins 0.000 description 1
- 229920001917 Ficoll Polymers 0.000 description 1
- 241000233866 Fungi Species 0.000 description 1
- 208000009329 Graft vs Host Disease Diseases 0.000 description 1
- 208000015023 Graves' disease Diseases 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 101000980825 Homo sapiens B-lymphocyte antigen CD19 Proteins 0.000 description 1
- 101000851054 Homo sapiens Elastin Proteins 0.000 description 1
- 101000914484 Homo sapiens T-lymphocyte activation antigen CD80 Proteins 0.000 description 1
- 108010002386 Interleukin-3 Proteins 0.000 description 1
- 150000001100 L-ribose derivatives Chemical class 0.000 description 1
- 206010058467 Lung neoplasm malignant Diseases 0.000 description 1
- 206010025323 Lymphomas Diseases 0.000 description 1
- 208000024556 Mendelian disease Diseases 0.000 description 1
- 206010027457 Metastases to liver Diseases 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 241001529936 Murinae Species 0.000 description 1
- 206010029113 Neovascularisation Diseases 0.000 description 1
- 239000000020 Nitrocellulose Substances 0.000 description 1
- 208000031662 Noncommunicable disease Diseases 0.000 description 1
- 239000004677 Nylon Substances 0.000 description 1
- 206010033128 Ovarian cancer Diseases 0.000 description 1
- 206010061535 Ovarian neoplasm Diseases 0.000 description 1
- 108091081548 Palindromic sequence Proteins 0.000 description 1
- 108091005804 Peptidases Proteins 0.000 description 1
- 239000004698 Polyethylene Substances 0.000 description 1
- 239000004743 Polypropylene Substances 0.000 description 1
- 239000004793 Polystyrene Substances 0.000 description 1
- 206010060862 Prostate cancer Diseases 0.000 description 1
- 208000000236 Prostatic Neoplasms Diseases 0.000 description 1
- 239000004365 Protease Substances 0.000 description 1
- 108091027981 Response element Proteins 0.000 description 1
- 102100037486 Reverse transcriptase/ribonuclease H Human genes 0.000 description 1
- 208000000453 Skin Neoplasms Diseases 0.000 description 1
- 102100027222 T-lymphocyte activation antigen CD80 Human genes 0.000 description 1
- 210000000447 Th1 cell Anatomy 0.000 description 1
- 108091023040 Transcription factor Proteins 0.000 description 1
- 102000040945 Transcription factor Human genes 0.000 description 1
- 208000027418 Wounds and injury Diseases 0.000 description 1
- 229920006397 acrylic thermoplastic Polymers 0.000 description 1
- 230000004721 adaptive immunity Effects 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 229960005305 adenosine Drugs 0.000 description 1
- 239000011543 agarose gel Substances 0.000 description 1
- 238000000246 agarose gel electrophoresis Methods 0.000 description 1
- 230000004075 alteration Effects 0.000 description 1
- 230000033115 angiogenesis Effects 0.000 description 1
- 239000003587 angiostatic protein Substances 0.000 description 1
- 210000004102 animal cell Anatomy 0.000 description 1
- 239000005557 antagonist Substances 0.000 description 1
- 230000000840 anti-viral effect Effects 0.000 description 1
- 210000000628 antibody-producing cell Anatomy 0.000 description 1
- 230000030741 antigen processing and presentation Effects 0.000 description 1
- 210000000612 antigen-presenting cell Anatomy 0.000 description 1
- 230000000890 antigenic effect Effects 0.000 description 1
- 230000002238 attenuated effect Effects 0.000 description 1
- 230000001580 bacterial effect Effects 0.000 description 1
- 210000003651 basophil Anatomy 0.000 description 1
- 239000011324 bead Substances 0.000 description 1
- SRBFZHDQGSBBOR-UHFFFAOYSA-N beta-D-Pyranose-Lyxose Natural products OC1COC(O)C(O)C1O SRBFZHDQGSBBOR-UHFFFAOYSA-N 0.000 description 1
- IQFYYKKMVGJFEH-UHFFFAOYSA-N beta-L-thymidine Natural products O=C1NC(=O)C(C)=CN1C1OC(CO)C(O)C1 IQFYYKKMVGJFEH-UHFFFAOYSA-N 0.000 description 1
- 230000003115 biocidal effect Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 210000001185 bone marrow Anatomy 0.000 description 1
- 201000008275 breast carcinoma Diseases 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 230000011712 cell development Effects 0.000 description 1
- 230000004663 cell proliferation Effects 0.000 description 1
- 208000019065 cervical carcinoma Diseases 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 230000003399 chemotactic effect Effects 0.000 description 1
- 230000000973 chemotherapeutic effect Effects 0.000 description 1
- 208000025302 chronic primary adrenal insufficiency Diseases 0.000 description 1
- 208000029742 colonic neoplasm Diseases 0.000 description 1
- 230000000295 complement effect Effects 0.000 description 1
- 238000010276 construction Methods 0.000 description 1
- 229940028617 conventional vaccine Drugs 0.000 description 1
- 229920001577 copolymer Polymers 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
- 238000000315 cryotherapy Methods 0.000 description 1
- UHDGCWIWMRVCDJ-ZAKLUEHWSA-N cytidine Chemical compound O=C1N=C(N)C=CN1[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O1 UHDGCWIWMRVCDJ-ZAKLUEHWSA-N 0.000 description 1
- 230000016396 cytokine production Effects 0.000 description 1
- 230000009089 cytolysis Effects 0.000 description 1
- 239000000824 cytostatic agent Substances 0.000 description 1
- 230000001085 cytostatic effect Effects 0.000 description 1
- 231100000135 cytotoxicity Toxicity 0.000 description 1
- 230000003013 cytotoxicity Effects 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 230000029087 digestion Effects 0.000 description 1
- 235000013601 eggs Nutrition 0.000 description 1
- 230000006862 enzymatic digestion Effects 0.000 description 1
- 210000003527 eukaryotic cell Anatomy 0.000 description 1
- 208000021045 exocrine pancreatic carcinoma Diseases 0.000 description 1
- 102000013165 exonuclease Human genes 0.000 description 1
- 238000010230 functional analysis Methods 0.000 description 1
- 206010017758 gastric cancer Diseases 0.000 description 1
- 208000010749 gastric carcinoma Diseases 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 208000016361 genetic disease Diseases 0.000 description 1
- 230000002068 genetic effect Effects 0.000 description 1
- 150000004676 glycans Chemical class 0.000 description 1
- 208000024908 graft versus host disease Diseases 0.000 description 1
- 229940029575 guanosine Drugs 0.000 description 1
- 210000002443 helper t lymphocyte Anatomy 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 102000054289 human ELN Human genes 0.000 description 1
- 210000005260 human cell Anatomy 0.000 description 1
- 230000001900 immune effect Effects 0.000 description 1
- 238000002649 immunization Methods 0.000 description 1
- 230000003136 immunomodifying effect Effects 0.000 description 1
- 229960001438 immunostimulant agent Drugs 0.000 description 1
- 239000003022 immunostimulating agent Substances 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 230000008595 infiltration Effects 0.000 description 1
- 238000001764 infiltration Methods 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 238000013383 initial experiment Methods 0.000 description 1
- 208000014674 injury Diseases 0.000 description 1
- 210000005007 innate immune system Anatomy 0.000 description 1
- 210000003292 kidney cell Anatomy 0.000 description 1
- 231100001231 less toxic Toxicity 0.000 description 1
- 208000032839 leukemia Diseases 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 201000005202 lung cancer Diseases 0.000 description 1
- 208000020816 lung neoplasm Diseases 0.000 description 1
- 206010025135 lupus erythematosus Diseases 0.000 description 1
- 230000036210 malignancy Effects 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- 230000035800 maturation Effects 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 201000001441 melanoma Diseases 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 150000002739 metals Chemical class 0.000 description 1
- 239000011325 microbead Substances 0.000 description 1
- 230000005012 migration Effects 0.000 description 1
- 238000013508 migration Methods 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 201000006417 multiple sclerosis Diseases 0.000 description 1
- 230000035772 mutation Effects 0.000 description 1
- 206010028417 myasthenia gravis Diseases 0.000 description 1
- 210000000581 natural killer T-cell Anatomy 0.000 description 1
- 210000000440 neutrophil Anatomy 0.000 description 1
- 230000003448 neutrophilic effect Effects 0.000 description 1
- 229920001220 nitrocellulos Polymers 0.000 description 1
- 238000010899 nucleation Methods 0.000 description 1
- 229940127073 nucleoside analogue Drugs 0.000 description 1
- 229920001778 nylon Polymers 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 208000008443 pancreatic carcinoma Diseases 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 210000005259 peripheral blood Anatomy 0.000 description 1
- 239000011886 peripheral blood Substances 0.000 description 1
- 150000008300 phosphoramidites Chemical class 0.000 description 1
- 230000001766 physiological effect Effects 0.000 description 1
- 239000013612 plasmid Substances 0.000 description 1
- 229920003229 poly(methyl methacrylate) Polymers 0.000 description 1
- 229920001748 polybutylene Polymers 0.000 description 1
- 229920000573 polyethylene Polymers 0.000 description 1
- 229920001155 polypropylene Polymers 0.000 description 1
- 229920001282 polysaccharide Polymers 0.000 description 1
- 239000005017 polysaccharide Substances 0.000 description 1
- 229920002223 polystyrene Polymers 0.000 description 1
- 229920002635 polyurethane Polymers 0.000 description 1
- 239000004814 polyurethane Substances 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 230000000770 proinflammatory effect Effects 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 244000000040 protozoan parasite Species 0.000 description 1
- 239000013014 purified material Substances 0.000 description 1
- 102000005962 receptors Human genes 0.000 description 1
- 108020003175 receptors Proteins 0.000 description 1
- 230000007115 recruitment Effects 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 210000003289 regulatory T cell Anatomy 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 229920005989 resin Polymers 0.000 description 1
- 239000011347 resin Substances 0.000 description 1
- 230000000717 retained effect Effects 0.000 description 1
- 238000004904 shortening Methods 0.000 description 1
- 229910052710 silicon Inorganic materials 0.000 description 1
- 239000010703 silicon Substances 0.000 description 1
- 201000002314 small intestine cancer Diseases 0.000 description 1
- 210000001082 somatic cell Anatomy 0.000 description 1
- 238000001179 sorption measurement Methods 0.000 description 1
- 230000006641 stabilisation Effects 0.000 description 1
- 230000003019 stabilising effect Effects 0.000 description 1
- 238000011105 stabilization Methods 0.000 description 1
- 230000000087 stabilizing effect Effects 0.000 description 1
- 201000000498 stomach carcinoma Diseases 0.000 description 1
- 229960005322 streptomycin Drugs 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- ISXSCDLOGDJUNJ-UHFFFAOYSA-N tert-butyl prop-2-enoate Chemical compound CC(C)(C)OC(=O)C=C ISXSCDLOGDJUNJ-UHFFFAOYSA-N 0.000 description 1
- 229940104230 thymidine Drugs 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 238000013518 transcription Methods 0.000 description 1
- 230000035897 transcription Effects 0.000 description 1
- 238000001890 transfection Methods 0.000 description 1
- 230000001052 transient effect Effects 0.000 description 1
- 230000004614 tumor growth Effects 0.000 description 1
- 230000003827 upregulation Effects 0.000 description 1
- 244000052613 viral pathogen Species 0.000 description 1
- 239000013603 viral vector Substances 0.000 description 1
Classifications
-
- 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
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7088—Compounds having three or more nucleosides or nucleotides
- A61K31/711—Natural deoxyribonucleic acids, i.e. containing only 2'-deoxyriboses attached to adenine, guanine, cytosine or thymine 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
-
- 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
- A61K39/0005—Vertebrate antigens
- A61K39/0008—Antigens related to auto-immune diseases; Preparations to induce self-tolerance
-
- 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
- A61K39/0005—Vertebrate antigens
- A61K39/0011—Cancer antigens
-
- 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
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- 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
-
- 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
- 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
-
- 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
- C12N2310/30—Chemical structure
- C12N2310/31—Chemical structure of the backbone
- C12N2310/315—Phosphorothioates
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Immunology (AREA)
- Genetics & Genomics (AREA)
- Epidemiology (AREA)
- Microbiology (AREA)
- Biomedical Technology (AREA)
- Organic Chemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Molecular Biology (AREA)
- Mycology (AREA)
- Wood Science & Technology (AREA)
- Zoology (AREA)
- Biotechnology (AREA)
- General Engineering & Computer Science (AREA)
- Biochemistry (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Plant Pathology (AREA)
- Biophysics (AREA)
- Physics & Mathematics (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Oncology (AREA)
- Transplantation (AREA)
- Rheumatology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Claims (13)
1. Ikke-kodende DNA-konstrukt omfattende mindst ét sekvensmotiv N1N2CGN3N4, hvor N1N2 og N3N4 er en hvilken som helst kombination af A, C, T og G, og C er deoxy-cytidin, G er deoxyguanosin, A er deoxyadenosin, og T erdeoxythymidin, og hvor mindst ét nukleotid af de terminale fem nukleotider, som befinder sig ved 5'- og/eller 3'-enden af en DNA-enkeltstreng, er i L-konformation.
2. Konstrukt ifølge krav 1, hvor N1N2 er et element, som er valgt fra gruppen omfattende GT, GG, GA, AT eller AA, N3N4 er et element, som er valgt fra gruppen omfattende CT eller TT.
3. Konstrukt ifølge et hvilket som helst af kravene 1 eller 2, hvor DNA-konstruktet omfatter mindst én ende med et enkeltstrenget loop.
4. Konstrukt ifølge et hvilket som helst af kravene 1 til 3, hvor sekvensmotivet N1N2CGN3N4 befinder sig inden for en enkeltstrenget og/eller dobbeltstrenget region af DNA-sekvensen.
5. Konstrukt ifølge et hvilket som helst af kravene 1 til 4, som omfatter inter- og/eller intramolekylære basepar og mindst én uparret, enkeltstrenget region.
6. Konstrukt ifølge 5, hvor mindst to konstrukter ligerer med hinanden.
7. Konstrukt ifølge et hvilket som helst af kravene 1 til 6, hvor mindst ét nukleotid i L-eller D-konformation er modificeret med en funktionel gruppe, som er valgt fra gruppen omfattende carboxyl, amin, amid, aldimin, ketal, acetal, ester, ether, disulfid, thiol og aldehyd.
8. Konstrukt ifølge krav 7, hvor det modificerede nukleotid er bundet til en forbindelse, som er valgt fra gruppen omfattende peptider, proteiner, kulhydrater, antistoffer, lipider, miceller, vesikler, syntetiske molekyler, polymerer, mikroprojektiler, metalpartikler, na-nopartikler eller en fast fase.
9. Farmaceutisk præparat, som omfatter et DNA-konstrukt ifølge et hvilket som helst af kravene 1 til 8.
10. Farmaceutisk præparat ifølge krav 11, som desuden omfatter et kemoterapeutisk middel.
11. Vaccine, som omfatter et DNA-konstrukt ifølge et hvilket som helst af kravene 1 til 8.
12. Vaccine ifølge krav 11, hvor DNA-konstruktet er en adjuvans.
13. DNA-konstrukt ifølge et hvilket som helst af kravene 1 til 8, farmaceutisk præparat ifølge krav 9 eller 10 eller vaccine ifølge krav 11 eller 12 til anvendelse til behandling af cancer eller autoimmune sygdomme.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GBGB1021867.5A GB201021867D0 (en) | 2010-12-23 | 2010-12-23 | Non-coding immunomodulatory DNA construct |
| PCT/EP2011/074033 WO2012085291A1 (en) | 2010-12-23 | 2011-12-23 | Non-coding immunomodulatory dna construct |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| DK2655623T3 true DK2655623T3 (da) | 2017-04-03 |
Family
ID=43598913
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DK11805869.2T DK2655623T3 (da) | 2010-12-23 | 2011-12-23 | Ikke-kodende immunmodulatorisk DNA-konstrukt |
Country Status (18)
| Country | Link |
|---|---|
| US (2) | US20140010830A1 (da) |
| EP (1) | EP2655623B2 (da) |
| JP (1) | JP6027542B2 (da) |
| KR (2) | KR101862271B1 (da) |
| CN (3) | CN107299101A (da) |
| AU (1) | AU2011347095B2 (da) |
| BR (1) | BR112013015816B1 (da) |
| CA (1) | CA2822377C (da) |
| DK (1) | DK2655623T3 (da) |
| ES (1) | ES2618783T5 (da) |
| GB (1) | GB201021867D0 (da) |
| IL (1) | IL227105A (da) |
| MX (1) | MX343918B (da) |
| PL (1) | PL2655623T3 (da) |
| RU (1) | RU2583291C2 (da) |
| SG (1) | SG191328A1 (da) |
| WO (1) | WO2012085291A1 (da) |
| ZA (1) | ZA201304999B (da) |
Families Citing this family (18)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB201021867D0 (en) | 2010-12-23 | 2011-02-02 | Mologen Ag | Non-coding immunomodulatory DNA construct |
| AR095882A1 (es) | 2013-04-22 | 2015-11-18 | Hoffmann La Roche | Terapia de combinación de anticuerpos contra csf-1r humano con un agonista de tlr9 |
| GB2514591A (en) * | 2013-05-30 | 2014-12-03 | Mologen Ag | Predictive biomarker for cancer therapy |
| AR097584A1 (es) | 2013-09-12 | 2016-03-23 | Hoffmann La Roche | Terapia de combinación de anticuerpos contra el csf-1r humano y anticuerpos contra el pd-l1 humano |
| EP3508198A1 (en) | 2014-06-04 | 2019-07-10 | Exicure, Inc. | Multivalent delivery of immune modulators by liposomal spherical nucleic acids for prophylactic or therapeutic applications |
| CA2968531A1 (en) | 2014-11-21 | 2016-05-26 | Northwestern University | The sequence-specific cellular uptake of spherical nucleic acid nanoparticle conjugates |
| US10347146B2 (en) * | 2014-12-23 | 2019-07-09 | International Business Machines Corporation | Managing answer feasibility |
| LU92821B1 (en) * | 2015-09-09 | 2017-03-20 | Mologen Ag | Combination comprising immunostimulatory oligonucleotides |
| GB2542425A (en) | 2015-09-21 | 2017-03-22 | Mologen Ag | Means for the treatment of HIV |
| WO2018036852A1 (en) | 2016-08-25 | 2018-03-01 | F. Hoffmann-La Roche Ag | Intermittent dosing of an anti-csf-1r antibody in combination with macrophage activating agent |
| EP3558360A1 (en) | 2016-12-22 | 2019-10-30 | F. Hoffmann-La Roche AG | Treatment of tumors with an anti-csf-1r antibody in combination with an anti-pd-l1 antibody after failure of anti-pd-l1/pd1 treatment |
| CA3058966A1 (en) | 2017-04-14 | 2018-10-18 | Tollnine, Inc. | Immunomodulating polynucleotides, antibody conjugates thereof, and methods of their use |
| EP3392345A1 (en) | 2017-04-22 | 2018-10-24 | Mologen AG | Biomarker for small cell lung cancer therapy |
| US11433131B2 (en) | 2017-05-11 | 2022-09-06 | Northwestern University | Adoptive cell therapy using spherical nucleic acids (SNAs) |
| US20210155933A1 (en) | 2017-08-31 | 2021-05-27 | Gilead Sciences, Inc. | Tlr-9 agonists for modulation of tumor microenvironment |
| US11806364B2 (en) | 2017-09-28 | 2023-11-07 | Industry-Academic Cooperation Foundation, Yonsei University | Method for producing myeloid-derived suppressor cells, myeloid-derived suppressor cells produced thereby, and methods thereof |
| US10685050B2 (en) * | 2018-04-23 | 2020-06-16 | Adobe Inc. | Generating a topic-based summary of textual content |
| KR20200138597A (ko) | 2019-06-01 | 2020-12-10 | 서미주 | 클렌징 마스크팩 |
Family Cites Families (27)
| 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 |
| PT1027359E (pt) * | 1996-10-16 | 2003-09-30 | Ribapharm Inc | L-nucleosideos monociclicos analogos e suas utilizacoes |
| US6251666B1 (en) | 1997-03-31 | 2001-06-26 | Ribozyme Pharmaceuticals, Inc. | Nucleic acid catalysts comprising L-nucleotide analogs |
| DE19935756A1 (de) * | 1999-07-27 | 2001-02-08 | Mologen Forschungs Entwicklung | Kovalent geschlossenes Nukleinsäuremolekül zur Immunstimulation |
| AU1656601A (en) * | 1999-11-12 | 2001-06-12 | Isis Pharmaceuticals, Inc. | Gapped oligomers having site specific chiral phosphorothioate internucleoside linkages |
| KR100865706B1 (ko) | 2000-09-26 | 2008-10-28 | 이데라 파마슈티칼즈, 인코포레이티드 | 화학적인 위치 변화에 의해 면역자극 올리고누클레오티드유사체의 면역자극 활성을 조절하는 방법 |
| JP2005504020A (ja) * | 2001-07-03 | 2005-02-10 | アイシス・ファーマシューティカルス・インコーポレーテッド | ヌクレアーゼ耐性キメラオリゴヌクレオチド |
| US7276489B2 (en) * | 2002-10-24 | 2007-10-02 | Idera Pharmaceuticals, Inc. | Modulation of immunostimulatory properties of oligonucleotide-based compounds by optimal presentation of 5′ ends |
| WO2003035836A2 (en) | 2001-10-24 | 2003-05-01 | Hybridon Inc. | Modulation of immunostimulatory properties of oligonucleotide-based compounds by optimal presentation of 5' ends |
| DE10211558A1 (de) * | 2002-03-15 | 2003-10-09 | Noxxon Pharma Ag | Neue Formen RNAi |
| US8158768B2 (en) * | 2002-12-23 | 2012-04-17 | Dynavax Technologies Corporation | Immunostimulatory sequence oligonucleotides and methods of using the same |
| US7517520B2 (en) * | 2003-03-26 | 2009-04-14 | Cytos Biotechnology Ag | Packaging of immunostimulatory oligonucleotides into virus-like particles: method of preparation and use |
| KR101107818B1 (ko) | 2003-10-30 | 2012-01-31 | 콜레이 파마시티컬 그룹, 인코포레이티드 | 향상된 면역자극 효능을 가진 ｃ-부류 올리고뉴클레오티드유사체 |
| MXPA06008855A (es) | 2004-02-03 | 2007-04-17 | Univ California | Metodos para tratar sindrome de intestino irritable. |
| JP3976742B2 (ja) * | 2004-02-27 | 2007-09-19 | 江守商事株式会社 | インターフェロンアルファを誘導する免疫刺激オリゴヌクレオチド |
| BRPI0512110A (pt) | 2004-06-15 | 2007-10-23 | Idera Pharmaceutical Inc | multìmeros de oligonucleotìdeos imunoestimulatórios |
| US7879992B2 (en) | 2005-01-31 | 2011-02-01 | Isis Pharmaceuticals, Inc. | Modification of MyD88 splicing using modified oligonucleotides |
| EP1937812A2 (en) | 2005-10-12 | 2008-07-02 | Cancer Research Technology Limited | Methods and compositions for treating immune disorders |
| CN101287742B (zh) | 2005-10-12 | 2016-01-06 | 艾德拉药物股份有限公司 | 基于变异应答调制Toll样受体的免疫调节寡核苷酸(IRO)化合物 |
| WO2007147007A2 (en) * | 2006-06-13 | 2007-12-21 | Bayhill Therapeutics, Inc. | Methods and immune modulatory nucleic acid compositions for preventing and treating disease |
| US20080260820A1 (en) * | 2007-04-19 | 2008-10-23 | Gilles Borrelly | Oral dosage formulations of protease-resistant polypeptides |
| AU2008262478B9 (en) * | 2007-05-29 | 2014-06-19 | Aldevron, L.L.C. | Vectors and methods for genetic immunization |
| WO2009035554A2 (en) * | 2007-09-07 | 2009-03-19 | University Of Florida Research Foundation, Inc. | Superior structure stability and selectivity of hairpin nucleic acid probes with an l-dna stem |
| CN101820908A (zh) * | 2007-10-09 | 2010-09-01 | 科利制药公司 | 包含改性糖部分的免疫刺激寡核苷酸类似物 |
| WO2010039137A1 (en) * | 2008-10-02 | 2010-04-08 | Idera Pharmaceuticals, Inc. | Immune regulatory oligonucleotide (iro) compounds to modulate toll-like receptor based immune response |
| EP2246433A1 (de) * | 2009-04-30 | 2010-11-03 | Mologen AG | Concatemere zur Immunmodulation |
| GB201021867D0 (en) | 2010-12-23 | 2011-02-02 | Mologen Ag | Non-coding immunomodulatory DNA construct |
-
2010
- 2010-12-23 GB GBGB1021867.5A patent/GB201021867D0/en not_active Ceased
-
2011
- 2011-12-23 PL PL11805869T patent/PL2655623T3/pl unknown
- 2011-12-23 CN CN201710516200.6A patent/CN107299101A/zh active Pending
- 2011-12-23 CA CA2822377A patent/CA2822377C/en active Active
- 2011-12-23 KR KR1020137019446A patent/KR101862271B1/ko active IP Right Grant
- 2011-12-23 CN CN2011800677990A patent/CN103370417A/zh active Pending
- 2011-12-23 ES ES11805869T patent/ES2618783T5/es active Active
- 2011-12-23 JP JP2013545438A patent/JP6027542B2/ja active Active
- 2011-12-23 DK DK11805869.2T patent/DK2655623T3/da active
- 2011-12-23 SG SG2013048673A patent/SG191328A1/en unknown
- 2011-12-23 BR BR112013015816-6A patent/BR112013015816B1/pt not_active IP Right Cessation
- 2011-12-23 EP EP11805869.2A patent/EP2655623B2/en active Active
- 2011-12-23 RU RU2013132151/10A patent/RU2583291C2/ru active
- 2011-12-23 US US13/996,791 patent/US20140010830A1/en not_active Abandoned
- 2011-12-23 KR KR1020167025908A patent/KR102022031B1/ko active IP Right Grant
- 2011-12-23 CN CN201710517071.2A patent/CN107384930B/zh active Active
- 2011-12-23 MX MX2013007286A patent/MX343918B/es active IP Right Grant
- 2011-12-23 WO PCT/EP2011/074033 patent/WO2012085291A1/en active Application Filing
- 2011-12-23 AU AU2011347095A patent/AU2011347095B2/en active Active
-
2013
- 2013-06-20 IL IL227105A patent/IL227105A/en active IP Right Grant
- 2013-07-04 ZA ZA2013/04999A patent/ZA201304999B/en unknown
-
2020
- 2020-09-11 US US17/018,088 patent/US20210340543A1/en active Pending
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| DK2655623T3 (da) | Ikke-kodende immunmodulatorisk DNA-konstrukt | |
| JP4874801B2 (ja) | 安定化免疫調節オリゴヌクレオチド | |
| DK2999787T3 (da) | Kovalent lukket, ikke-kodende immunmodulerende dna-konstrukt | |
| JP2007500018A6 (ja) | 安定化免疫調節オリゴヌクレオチド | |
| KR20140009258A (ko) | 톨-유사 수용체 기반 면역 반응을 조절하기 위한 면역 조절 올리고뉴클레오타이드(ｉｒｏ) 화합물 | |
| KR101898177B1 (ko) | 톨－유사 수용체 기반 면역 반응을 조절하기 위한 면역 조절 올리고누클레오티드 （ｉｒｏ） 화합물 | |
| Mohri et al. | Increased immunostimulatory activity of polypod-like structured DNA by ligation of the terminal loop structures |