CA2774460C - Inhibition of endosomal toll-like receptor activation - Google Patents
Inhibition of endosomal toll-like receptor activation Download PDFInfo
- Publication number
- CA2774460C CA2774460C CA2774460A CA2774460A CA2774460C CA 2774460 C CA2774460 C CA 2774460C CA 2774460 A CA2774460 A CA 2774460A CA 2774460 A CA2774460 A CA 2774460A CA 2774460 C CA2774460 C CA 2774460C
- Authority
- CA
- Canada
- Prior art keywords
- nucleic acid
- tlr9
- tlr3
- activation
- agent
- 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.)
- Active
Links
- 230000004913 activation Effects 0.000 title claims abstract description 84
- 230000005764 inhibitory process Effects 0.000 title claims description 18
- 102000002689 Toll-like receptor Human genes 0.000 title abstract description 68
- 108020000411 Toll-like receptor Proteins 0.000 title abstract description 68
- 102000039446 nucleic acids Human genes 0.000 claims abstract description 127
- 108020004707 nucleic acids Proteins 0.000 claims abstract description 127
- 150000007523 nucleic acids Chemical class 0.000 claims abstract description 127
- 239000003795 chemical substances by application Substances 0.000 claims abstract description 64
- 239000011230 binding agent Substances 0.000 claims abstract description 40
- 238000000034 method Methods 0.000 claims abstract description 28
- 230000002401 inhibitory effect Effects 0.000 claims abstract description 19
- 108010060885 Toll-like receptor 3 Proteins 0.000 claims description 88
- 102000008230 Toll-like receptor 3 Human genes 0.000 claims description 88
- 108010060818 Toll-Like Receptor 9 Proteins 0.000 claims description 83
- 229920000962 poly(amidoamine) Polymers 0.000 claims description 57
- 210000004027 cell Anatomy 0.000 claims description 51
- 230000006698 induction Effects 0.000 claims description 46
- 229920000642 polymer Polymers 0.000 claims description 44
- 229920000209 Hexadimethrine bromide Polymers 0.000 claims description 40
- 229920000858 Cyclodextrin Polymers 0.000 claims description 25
- HFHDHCJBZVLPGP-UHFFFAOYSA-N schardinger α-dextrin Chemical compound O1C(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(O)C2O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC2C(O)C(O)C1OC2CO HFHDHCJBZVLPGP-UHFFFAOYSA-N 0.000 claims description 24
- KZKAYEGOIJEWQB-UHFFFAOYSA-N 1,3-dibromopropane;n,n,n',n'-tetramethylhexane-1,6-diamine Chemical compound BrCCCBr.CN(C)CCCCCCN(C)C KZKAYEGOIJEWQB-UHFFFAOYSA-N 0.000 claims description 18
- 229950007870 hexadimethrine bromide Drugs 0.000 claims description 18
- 230000028709 inflammatory response Effects 0.000 claims description 17
- 239000003814 drug Substances 0.000 claims description 16
- 210000002540 macrophage Anatomy 0.000 claims description 15
- 239000002158 endotoxin Substances 0.000 claims description 14
- 229920006008 lipopolysaccharide Polymers 0.000 claims description 14
- 244000052769 pathogen Species 0.000 claims description 12
- 108090001005 Interleukin-6 Proteins 0.000 claims description 11
- 239000000556 agonist Substances 0.000 claims description 10
- 230000006472 autoimmune response Effects 0.000 claims description 10
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 10
- 238000004519 manufacturing process Methods 0.000 claims description 10
- 230000001404 mediated effect Effects 0.000 claims description 10
- 230000001717 pathogenic effect Effects 0.000 claims description 9
- 229940044655 toll-like receptor 9 agonist Drugs 0.000 claims description 9
- 208000007536 Thrombosis Diseases 0.000 claims description 8
- 201000010099 disease Diseases 0.000 claims description 8
- 206010028980 Neoplasm Diseases 0.000 claims description 7
- 230000028993 immune response Effects 0.000 claims description 7
- 230000017306 interleukin-6 production Effects 0.000 claims description 7
- 239000008194 pharmaceutical composition Substances 0.000 claims description 7
- 201000000596 systemic lupus erythematosus Diseases 0.000 claims description 7
- 238000012360 testing method Methods 0.000 claims description 7
- 201000011510 cancer Diseases 0.000 claims description 6
- 239000003937 drug carrier Substances 0.000 claims description 6
- 206010039073 rheumatoid arthritis Diseases 0.000 claims description 6
- 208000035473 Communicable disease Diseases 0.000 claims description 5
- 206010061218 Inflammation Diseases 0.000 claims description 5
- 201000005008 bacterial sepsis Diseases 0.000 claims description 5
- 230000004054 inflammatory process Effects 0.000 claims description 5
- 201000006417 multiple sclerosis Diseases 0.000 claims description 5
- 208000024172 Cardiovascular disease Diseases 0.000 claims description 4
- 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 claims description 4
- 208000008589 Obesity Diseases 0.000 claims description 4
- 201000004681 Psoriasis Diseases 0.000 claims description 4
- 230000010398 acute inflammatory response Effects 0.000 claims description 4
- 235000020824 obesity Nutrition 0.000 claims description 4
- 238000012258 culturing Methods 0.000 claims description 3
- 239000000523 sample Substances 0.000 claims description 3
- 239000013595 supernatant sample Substances 0.000 claims description 3
- 108060008682 Tumor Necrosis Factor Proteins 0.000 claims description 2
- 102100040247 Tumor necrosis factor Human genes 0.000 claims description 2
- 102000008235 Toll-Like Receptor 9 Human genes 0.000 claims 35
- 208000015181 infectious disease Diseases 0.000 claims 3
- 230000001684 chronic effect Effects 0.000 claims 1
- 230000000414 obstructive effect Effects 0.000 claims 1
- 102000007863 pattern recognition receptors Human genes 0.000 abstract description 10
- 108010089193 pattern recognition receptors Proteins 0.000 abstract description 10
- 108090000623 proteins and genes Proteins 0.000 abstract description 9
- 102000004169 proteins and genes Human genes 0.000 abstract description 6
- 239000002773 nucleotide Substances 0.000 abstract description 5
- 125000003729 nucleotide group Chemical group 0.000 abstract description 5
- 230000001939 inductive effect Effects 0.000 abstract description 4
- 238000012986 modification Methods 0.000 abstract description 4
- 230000004048 modification Effects 0.000 abstract description 4
- 102100033117 Toll-like receptor 9 Human genes 0.000 description 48
- 108020004414 DNA Proteins 0.000 description 40
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 25
- 229940115272 polyinosinic:polycytidylic acid Drugs 0.000 description 22
- 108091036414 Polyinosinic:polycytidylic acid Proteins 0.000 description 21
- -1 poly(ethyleneimine) Polymers 0.000 description 18
- 241000699670 Mus sp. Species 0.000 description 16
- 229920006317 cationic polymer Polymers 0.000 description 16
- 102000007327 Protamines Human genes 0.000 description 15
- 108010007568 Protamines Proteins 0.000 description 15
- 108700012920 TNF Proteins 0.000 description 14
- 229920000729 poly(L-lysine) polymer Polymers 0.000 description 14
- 102000040650 (ribonucleotides)n+m Human genes 0.000 description 13
- 229940048914 protamine Drugs 0.000 description 13
- 125000002091 cationic group Chemical group 0.000 description 11
- MSWZFWKMSRAUBD-GASJEMHNSA-N 2-amino-2-deoxy-D-galactopyranose Chemical compound N[C@H]1C(O)O[C@H](CO)[C@H](O)[C@@H]1O MSWZFWKMSRAUBD-GASJEMHNSA-N 0.000 description 10
- MSWZFWKMSRAUBD-UHFFFAOYSA-N beta-D-galactosamine Natural products NC1C(O)OC(CO)C(O)C1O MSWZFWKMSRAUBD-UHFFFAOYSA-N 0.000 description 10
- 229920002873 Polyethylenimine Polymers 0.000 description 9
- 102100039390 Toll-like receptor 7 Human genes 0.000 description 9
- 230000000694 effects Effects 0.000 description 9
- 230000002757 inflammatory effect Effects 0.000 description 9
- 101000669447 Homo sapiens Toll-like receptor 4 Proteins 0.000 description 8
- 102100039360 Toll-like receptor 4 Human genes 0.000 description 8
- 230000016396 cytokine production Effects 0.000 description 8
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 8
- 101000669402 Homo sapiens Toll-like receptor 7 Proteins 0.000 description 7
- 230000003013 cytotoxicity Effects 0.000 description 7
- 231100000135 cytotoxicity Toxicity 0.000 description 7
- 239000000412 dendrimer Substances 0.000 description 7
- 229920000736 dendritic polymer Polymers 0.000 description 7
- 108090000695 Cytokines Proteins 0.000 description 6
- 102000004127 Cytokines Human genes 0.000 description 6
- 241001465754 Metazoa Species 0.000 description 6
- 102100033110 Toll-like receptor 8 Human genes 0.000 description 6
- 239000012228 culture supernatant Substances 0.000 description 6
- 238000002965 ELISA Methods 0.000 description 5
- 208000027866 inflammatory disease Diseases 0.000 description 5
- 239000003446 ligand Substances 0.000 description 5
- 150000004032 porphyrins Chemical class 0.000 description 5
- 235000018102 proteins Nutrition 0.000 description 5
- 101001082073 Homo sapiens Interferon-induced helicase C domain-containing protein 1 Proteins 0.000 description 4
- 101000800483 Homo sapiens Toll-like receptor 8 Proteins 0.000 description 4
- 102100027353 Interferon-induced helicase C domain-containing protein 1 Human genes 0.000 description 4
- 102100034170 Interferon-induced, double-stranded RNA-activated protein kinase Human genes 0.000 description 4
- 101710089751 Interferon-induced, double-stranded RNA-activated protein kinase Proteins 0.000 description 4
- 241000699666 Mus <mouse, genus> Species 0.000 description 4
- 108091005685 RIG-I-like receptors Proteins 0.000 description 4
- 230000001580 bacterial effect Effects 0.000 description 4
- 150000001875 compounds Chemical class 0.000 description 4
- 231100000673 dose–response relationship Toxicity 0.000 description 4
- 238000001727 in vivo Methods 0.000 description 4
- 239000003112 inhibitor Substances 0.000 description 4
- 238000002347 injection Methods 0.000 description 4
- 239000007924 injection Substances 0.000 description 4
- 102000005962 receptors Human genes 0.000 description 4
- 108020003175 receptors Proteins 0.000 description 4
- 230000004044 response Effects 0.000 description 4
- 230000011664 signaling Effects 0.000 description 4
- 230000004936 stimulating effect Effects 0.000 description 4
- 208000023275 Autoimmune disease Diseases 0.000 description 3
- 206010067125 Liver injury Diseases 0.000 description 3
- 241001529936 Murinae Species 0.000 description 3
- 108020004459 Small interfering RNA Proteins 0.000 description 3
- 239000012620 biological material Substances 0.000 description 3
- 229920001577 copolymer Polymers 0.000 description 3
- 230000001086 cytosolic effect Effects 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- 229910052739 hydrogen Inorganic materials 0.000 description 3
- 230000036039 immunity Effects 0.000 description 3
- 238000011534 incubation Methods 0.000 description 3
- 230000003993 interaction Effects 0.000 description 3
- 230000004068 intracellular signaling Effects 0.000 description 3
- 210000004185 liver Anatomy 0.000 description 3
- 210000004962 mammalian cell Anatomy 0.000 description 3
- 239000002609 medium Substances 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- 239000002245 particle Substances 0.000 description 3
- 230000008506 pathogenesis Effects 0.000 description 3
- 229920000768 polyamine Polymers 0.000 description 3
- 102000004196 processed proteins & peptides Human genes 0.000 description 3
- 108090000765 processed proteins & peptides Proteins 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- KIDHWZJUCRJVML-UHFFFAOYSA-N putrescine Chemical compound NCCCCN KIDHWZJUCRJVML-UHFFFAOYSA-N 0.000 description 3
- 150000003839 salts Chemical class 0.000 description 3
- 230000004083 survival effect Effects 0.000 description 3
- 229940124597 therapeutic agent Drugs 0.000 description 3
- 238000012056 up-stream process Methods 0.000 description 3
- 230000035899 viability Effects 0.000 description 3
- 230000003612 virological effect Effects 0.000 description 3
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 2
- 108091023037 Aptamer Proteins 0.000 description 2
- 238000011740 C57BL/6 mouse Methods 0.000 description 2
- 241000282472 Canis lupus familiaris Species 0.000 description 2
- 102000021350 Caspase recruitment domains Human genes 0.000 description 2
- 108091011189 Caspase recruitment domains Proteins 0.000 description 2
- 229920001661 Chitosan Polymers 0.000 description 2
- AOJJSUZBOXZQNB-TZSSRYMLSA-N Doxorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 AOJJSUZBOXZQNB-TZSSRYMLSA-N 0.000 description 2
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
- WZUVPPKBWHMQCE-UHFFFAOYSA-N Haematoxylin Chemical compound C12=CC(O)=C(O)C=C2CC2(O)C1C1=CC=C(O)C(O)=C1OC2 WZUVPPKBWHMQCE-UHFFFAOYSA-N 0.000 description 2
- HTTJABKRGRZYRN-UHFFFAOYSA-N Heparin Chemical compound OC1C(NC(=O)C)C(O)OC(COS(O)(=O)=O)C1OC1C(OS(O)(=O)=O)C(O)C(OC2C(C(OS(O)(=O)=O)C(OC3C(C(O)C(O)C(O3)C(O)=O)OS(O)(=O)=O)C(CO)O2)NS(O)(=O)=O)C(C(O)=O)O1 HTTJABKRGRZYRN-UHFFFAOYSA-N 0.000 description 2
- 102000006479 Heterogeneous-Nuclear Ribonucleoproteins Human genes 0.000 description 2
- 108010019372 Heterogeneous-Nuclear Ribonucleoproteins Proteins 0.000 description 2
- 101000595548 Homo sapiens TIR domain-containing adapter molecule 1 Proteins 0.000 description 2
- 101000763579 Homo sapiens Toll-like receptor 1 Proteins 0.000 description 2
- 101000831567 Homo sapiens Toll-like receptor 2 Proteins 0.000 description 2
- 108010002352 Interleukin-1 Proteins 0.000 description 2
- 102000000589 Interleukin-1 Human genes 0.000 description 2
- 241001082241 Lythrum hyssopifolia Species 0.000 description 2
- 102000043136 MAP kinase family Human genes 0.000 description 2
- 108091054455 MAP kinase family Proteins 0.000 description 2
- 102000010168 Myeloid Differentiation Factor 88 Human genes 0.000 description 2
- 108010077432 Myeloid Differentiation Factor 88 Proteins 0.000 description 2
- 108091034117 Oligonucleotide Proteins 0.000 description 2
- 108010004729 Phycoerythrin Proteins 0.000 description 2
- 206010040047 Sepsis Diseases 0.000 description 2
- 241000282898 Sus scrofa Species 0.000 description 2
- 102100036073 TIR domain-containing adapter molecule 1 Human genes 0.000 description 2
- 208000034841 Thrombotic Microangiopathies Diseases 0.000 description 2
- 108010060825 Toll-Like Receptor 7 Proteins 0.000 description 2
- 108010060752 Toll-Like Receptor 8 Proteins 0.000 description 2
- 102100027010 Toll-like receptor 1 Human genes 0.000 description 2
- 102100024333 Toll-like receptor 2 Human genes 0.000 description 2
- 241000282485 Vulpes vulpes Species 0.000 description 2
- 231100000439 acute liver injury Toxicity 0.000 description 2
- 150000001412 amines Chemical group 0.000 description 2
- 239000005557 antagonist Substances 0.000 description 2
- 238000013459 approach Methods 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 230000023555 blood coagulation Effects 0.000 description 2
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 2
- 230000030833 cell death Effects 0.000 description 2
- 230000004700 cellular uptake Effects 0.000 description 2
- 238000009833 condensation Methods 0.000 description 2
- 230000005494 condensation Effects 0.000 description 2
- 239000010432 diamond Substances 0.000 description 2
- 208000035475 disorder Diseases 0.000 description 2
- LYCAIKOWRPUZTN-UHFFFAOYSA-N ethylene glycol Natural products OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 238000001943 fluorescence-activated cell sorting Methods 0.000 description 2
- 229920000669 heparin Polymers 0.000 description 2
- 229960002897 heparin Drugs 0.000 description 2
- 239000001257 hydrogen Substances 0.000 description 2
- 210000002865 immune cell Anatomy 0.000 description 2
- 230000003834 intracellular effect Effects 0.000 description 2
- WSFSSNUMVMOOMR-NJFSPNSNSA-N methanone Chemical compound O=[14CH2] WSFSSNUMVMOOMR-NJFSPNSNSA-N 0.000 description 2
- 230000000813 microbial effect Effects 0.000 description 2
- DAZSWUUAFHBCGE-KRWDZBQOSA-N n-[(2s)-3-methyl-1-oxo-1-pyrrolidin-1-ylbutan-2-yl]-3-phenylpropanamide Chemical compound N([C@@H](C(C)C)C(=O)N1CCCC1)C(=O)CCC1=CC=CC=C1 DAZSWUUAFHBCGE-KRWDZBQOSA-N 0.000 description 2
- 230000037361 pathway Effects 0.000 description 2
- 229920000333 poly(propyleneimine) Polymers 0.000 description 2
- 229920002851 polycationic polymer Polymers 0.000 description 2
- 229940070353 protamines Drugs 0.000 description 2
- 230000002829 reductive effect Effects 0.000 description 2
- 230000006641 stabilisation Effects 0.000 description 2
- 238000011105 stabilization Methods 0.000 description 2
- 238000010186 staining Methods 0.000 description 2
- 230000000638 stimulation Effects 0.000 description 2
- 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 2
- 230000009897 systematic effect Effects 0.000 description 2
- RYYWUUFWQRZTIU-UHFFFAOYSA-K thiophosphate Chemical compound [O-]P([O-])([O-])=S RYYWUUFWQRZTIU-UHFFFAOYSA-K 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 description 1
- QKPLRMLTKYXDST-NSEZLWDYSA-N (3r,4r,5s,6r)-3-amino-6-(hydroxymethyl)oxane-2,4,5-triol;hydrochloride Chemical compound Cl.N[C@H]1C(O)O[C@H](CO)[C@@H](O)[C@@H]1O QKPLRMLTKYXDST-NSEZLWDYSA-N 0.000 description 1
- LDGWQMRUWMSZIU-LQDDAWAPSA-M 2,3-bis[(z)-octadec-9-enoxy]propyl-trimethylazanium;chloride Chemical compound [Cl-].CCCCCCCC\C=C/CCCCCCCCOCC(C[N+](C)(C)C)OCCCCCCCC\C=C/CCCCCCCC LDGWQMRUWMSZIU-LQDDAWAPSA-M 0.000 description 1
- RSMRWWHFJMENJH-LQDDAWAPSA-M 2,3-bis[[(z)-octadec-9-enoyl]oxy]propyl-trimethylazanium;methyl sulfate Chemical compound COS([O-])(=O)=O.CCCCCCCC\C=C/CCCCCCCC(=O)OCC(C[N+](C)(C)C)OC(=O)CCCCCCC\C=C/CCCCCCCC RSMRWWHFJMENJH-LQDDAWAPSA-M 0.000 description 1
- WALUVDCNGPQPOD-UHFFFAOYSA-M 2,3-di(tetradecoxy)propyl-(2-hydroxyethyl)-dimethylazanium;bromide Chemical compound [Br-].CCCCCCCCCCCCCCOCC(C[N+](C)(C)CCO)OCCCCCCCCCCCCCC WALUVDCNGPQPOD-UHFFFAOYSA-M 0.000 description 1
- UEJJHQNACJXSKW-UHFFFAOYSA-N 2-(2,6-dioxopiperidin-3-yl)-1H-isoindole-1,3(2H)-dione Chemical compound O=C1C2=CC=CC=C2C(=O)N1C1CCC(=O)NC1=O UEJJHQNACJXSKW-UHFFFAOYSA-N 0.000 description 1
- NJNFCDQQEIAOIF-UHFFFAOYSA-N 2-(3,4-dimethoxy-2-methylsulfanylphenyl)ethanamine Chemical compound COC1=CC=C(CCN)C(SC)=C1OC NJNFCDQQEIAOIF-UHFFFAOYSA-N 0.000 description 1
- BSKHPKMHTQYZBB-UHFFFAOYSA-N 2-methylpyridine Chemical compound CC1=CC=CC=N1 BSKHPKMHTQYZBB-UHFFFAOYSA-N 0.000 description 1
- AWGBKZRMLNVLAF-UHFFFAOYSA-N 3,5-dibromo-n,2-dihydroxybenzamide Chemical compound ONC(=O)C1=CC(Br)=CC(Br)=C1O AWGBKZRMLNVLAF-UHFFFAOYSA-N 0.000 description 1
- WHNPOQXWAMXPTA-UHFFFAOYSA-N 3-methylbut-2-enamide Chemical compound CC(C)=CC(N)=O WHNPOQXWAMXPTA-UHFFFAOYSA-N 0.000 description 1
- BZTDTCNHAFUJOG-UHFFFAOYSA-N 6-carboxyfluorescein Chemical compound C12=CC=C(O)C=C2OC2=CC(O)=CC=C2C11OC(=O)C2=CC=C(C(=O)O)C=C21 BZTDTCNHAFUJOG-UHFFFAOYSA-N 0.000 description 1
- STQGQHZAVUOBTE-UHFFFAOYSA-N 7-Cyan-hept-2t-en-4,6-diinsaeure Natural products C1=2C(O)=C3C(=O)C=4C(OC)=CC=CC=4C(=O)C3=C(O)C=2CC(O)(C(C)=O)CC1OC1CC(N)C(O)C(C)O1 STQGQHZAVUOBTE-UHFFFAOYSA-N 0.000 description 1
- 241000251468 Actinopterygii Species 0.000 description 1
- 102100034613 Annexin A2 Human genes 0.000 description 1
- 108090000668 Annexin A2 Proteins 0.000 description 1
- 239000004475 Arginine Substances 0.000 description 1
- 241000972773 Aulopiformes Species 0.000 description 1
- 206010003827 Autoimmune hepatitis Diseases 0.000 description 1
- 108010039209 Blood Coagulation Factors Proteins 0.000 description 1
- 102000015081 Blood Coagulation Factors Human genes 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- 208000003174 Brain Neoplasms Diseases 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
- 241000283707 Capra Species 0.000 description 1
- 108010012236 Chemokines Proteins 0.000 description 1
- 102000019034 Chemokines Human genes 0.000 description 1
- 229920002101 Chitin Polymers 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- 102000053602 DNA Human genes 0.000 description 1
- WEAHRLBPCANXCN-UHFFFAOYSA-N Daunomycin Natural products CCC1(O)CC(OC2CC(N)C(O)C(C)O2)c3cc4C(=O)c5c(OC)cccc5C(=O)c4c(O)c3C1 WEAHRLBPCANXCN-UHFFFAOYSA-N 0.000 description 1
- 206010051055 Deep vein thrombosis Diseases 0.000 description 1
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 241000283073 Equus caballus Species 0.000 description 1
- 101710177291 Gag polyprotein Proteins 0.000 description 1
- 239000004471 Glycine Substances 0.000 description 1
- 229920002683 Glycosaminoglycan Polymers 0.000 description 1
- 208000032843 Hemorrhage Diseases 0.000 description 1
- 101001011382 Homo sapiens Interferon regulatory factor 3 Proteins 0.000 description 1
- 101001011442 Homo sapiens Interferon regulatory factor 5 Proteins 0.000 description 1
- 101001032342 Homo sapiens Interferon regulatory factor 7 Proteins 0.000 description 1
- 101000964436 Homo sapiens Z-DNA-binding protein 1 Proteins 0.000 description 1
- 102100029843 Interferon regulatory factor 3 Human genes 0.000 description 1
- 102100030131 Interferon regulatory factor 5 Human genes 0.000 description 1
- 102100038070 Interferon regulatory factor 7 Human genes 0.000 description 1
- 102100036342 Interleukin-1 receptor-associated kinase 1 Human genes 0.000 description 1
- 101710199015 Interleukin-1 receptor-associated kinase 1 Proteins 0.000 description 1
- ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-N 0.000 description 1
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 1
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 1
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 1
- 229930182816 L-glutamine Natural products 0.000 description 1
- AGPKZVBTJJNPAG-WHFBIAKZSA-N L-isoleucine Chemical compound CC[C@H](C)[C@H](N)C(O)=O AGPKZVBTJJNPAG-WHFBIAKZSA-N 0.000 description 1
- KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 description 1
- 101710125418 Major capsid protein Proteins 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- MSFSPUZXLOGKHJ-UHFFFAOYSA-N Muraminsaeure Natural products OC(=O)C(C)OC1C(N)C(O)OC(CO)C1O MSFSPUZXLOGKHJ-UHFFFAOYSA-N 0.000 description 1
- 206010067482 No adverse event Diseases 0.000 description 1
- 108091028043 Nucleic acid sequence Proteins 0.000 description 1
- 101150072055 PAL1 gene Proteins 0.000 description 1
- 241001494479 Pecora Species 0.000 description 1
- 229930182555 Penicillin Natural products 0.000 description 1
- 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 1
- 108091093037 Peptide nucleic acid Proteins 0.000 description 1
- 108010013639 Peptidoglycan Proteins 0.000 description 1
- 239000004952 Polyamide Substances 0.000 description 1
- WDVSHHCDHLJJJR-UHFFFAOYSA-N Proflavine Chemical compound C1=CC(N)=CC2=NC3=CC(N)=CC=C3C=C21 WDVSHHCDHLJJJR-UHFFFAOYSA-N 0.000 description 1
- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 1
- 108010067787 Proteoglycans Proteins 0.000 description 1
- 102000016611 Proteoglycans Human genes 0.000 description 1
- 239000005700 Putrescine Substances 0.000 description 1
- 102000004409 RNA Helicases Human genes 0.000 description 1
- 101500027983 Rattus norvegicus Octadecaneuropeptide Proteins 0.000 description 1
- 206010039710 Scleroderma Diseases 0.000 description 1
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 1
- 208000021386 Sjogren Syndrome Diseases 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 208000006011 Stroke Diseases 0.000 description 1
- 238000000692 Student's t-test Methods 0.000 description 1
- 108091061763 Triple-stranded DNA Proteins 0.000 description 1
- GLNADSQYFUSGOU-GPTZEZBUSA-J Trypan blue Chemical compound [Na+].[Na+].[Na+].[Na+].C1=C(S([O-])(=O)=O)C=C2C=C(S([O-])(=O)=O)C(/N=N/C3=CC=C(C=C3C)C=3C=C(C(=CC=3)\N=N\C=3C(=CC4=CC(=CC(N)=C4C=3O)S([O-])(=O)=O)S([O-])(=O)=O)C)=C(O)C2=C1N GLNADSQYFUSGOU-GPTZEZBUSA-J 0.000 description 1
- 108091005906 Type I transmembrane proteins Proteins 0.000 description 1
- KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Natural products CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 description 1
- 206010047249 Venous thrombosis Diseases 0.000 description 1
- 108010067390 Viral Proteins Proteins 0.000 description 1
- 241000700605 Viruses Species 0.000 description 1
- 102100040310 Z-DNA-binding protein 1 Human genes 0.000 description 1
- HIHOWBSBBDRPDW-PTHRTHQKSA-N [(3s,8s,9s,10r,13r,14s,17r)-10,13-dimethyl-17-[(2r)-6-methylheptan-2-yl]-2,3,4,7,8,9,11,12,14,15,16,17-dodecahydro-1h-cyclopenta[a]phenanthren-3-yl] n-[2-(dimethylamino)ethyl]carbamate Chemical compound C1C=C2C[C@@H](OC(=O)NCCN(C)C)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 HIHOWBSBBDRPDW-PTHRTHQKSA-N 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 239000012190 activator Substances 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 235000004279 alanine Nutrition 0.000 description 1
- 235000001014 amino acid Nutrition 0.000 description 1
- 229940024606 amino acid Drugs 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- 235000019270 ammonium chloride Nutrition 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 230000003042 antagnostic effect Effects 0.000 description 1
- 230000002429 anti-coagulating effect Effects 0.000 description 1
- 230000003460 anti-nuclear Effects 0.000 description 1
- 239000000729 antidote Substances 0.000 description 1
- 229940075522 antidotes Drugs 0.000 description 1
- 230000006907 apoptotic process Effects 0.000 description 1
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
- 125000000637 arginyl group Chemical group N[C@@H](CCCNC(N)=N)C(=O)* 0.000 description 1
- 239000012298 atmosphere Substances 0.000 description 1
- 239000011324 bead Substances 0.000 description 1
- 229920000249 biocompatible polymer Polymers 0.000 description 1
- 239000004621 biodegradable polymer Substances 0.000 description 1
- 229920002988 biodegradable polymer Polymers 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 239000003114 blood coagulation factor Substances 0.000 description 1
- 210000004899 c-terminal region Anatomy 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 230000030570 cellular localization Effects 0.000 description 1
- 230000007541 cellular toxicity Effects 0.000 description 1
- 150000001793 charged compounds Chemical class 0.000 description 1
- 108091006116 chimeric peptides Proteins 0.000 description 1
- 230000015271 coagulation Effects 0.000 description 1
- 238000005345 coagulation Methods 0.000 description 1
- 239000013256 coordination polymer Substances 0.000 description 1
- 108091008878 cytoplasmic PRRs Proteins 0.000 description 1
- 108091092330 cytoplasmic RNA Proteins 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- STQGQHZAVUOBTE-VGBVRHCVSA-N daunorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(C)=O)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 STQGQHZAVUOBTE-VGBVRHCVSA-N 0.000 description 1
- 230000034994 death Effects 0.000 description 1
- 210000004443 dendritic cell Anatomy 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 201000001981 dermatomyositis Diseases 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 229960004679 doxorubicin Drugs 0.000 description 1
- 210000001163 endosome Anatomy 0.000 description 1
- YQGOJNYOYNNSMM-UHFFFAOYSA-N eosin Chemical compound [Na+].OC(=O)C1=CC=CC=C1C1=C2C=C(Br)C(=O)C(Br)=C2OC2=C(Br)C(O)=C(Br)C=C21 YQGOJNYOYNNSMM-UHFFFAOYSA-N 0.000 description 1
- ZMMJGEGLRURXTF-UHFFFAOYSA-N ethidium bromide Chemical compound [Br-].C12=CC(N)=CC=C2C2=CC=C(N)C=C2[N+](CC)=C1C1=CC=CC=C1 ZMMJGEGLRURXTF-UHFFFAOYSA-N 0.000 description 1
- 229960005542 ethidium bromide Drugs 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 235000019688 fish Nutrition 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 239000012634 fragment Substances 0.000 description 1
- 238000001476 gene delivery Methods 0.000 description 1
- 229960002743 glutamine Drugs 0.000 description 1
- 150000004676 glycans Chemical class 0.000 description 1
- 239000001963 growth medium Substances 0.000 description 1
- 238000007490 hematoxylin and eosin (H&E) staining Methods 0.000 description 1
- 231100000234 hepatic damage Toxicity 0.000 description 1
- 210000005161 hepatic lobe Anatomy 0.000 description 1
- 208000006454 hepatitis Diseases 0.000 description 1
- 238000010562 histological examination Methods 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 230000002519 immonomodulatory effect Effects 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 239000000138 intercalating agent Substances 0.000 description 1
- 230000011488 interferon-alpha production Effects 0.000 description 1
- 230000010189 intracellular transport Effects 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- 229960000310 isoleucine Drugs 0.000 description 1
- AGPKZVBTJJNPAG-UHFFFAOYSA-N isoleucine Natural products CCC(C)C(N)C(O)=O AGPKZVBTJJNPAG-UHFFFAOYSA-N 0.000 description 1
- 230000002147 killing effect Effects 0.000 description 1
- 210000004901 leucine-rich repeat Anatomy 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 230000008818 liver damage Effects 0.000 description 1
- 208000018191 liver inflammation Diseases 0.000 description 1
- 238000001325 log-rank test Methods 0.000 description 1
- 231100000053 low toxicity Toxicity 0.000 description 1
- 206010025135 lupus erythematosus Diseases 0.000 description 1
- 230000035800 maturation Effects 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 108020004999 messenger RNA Proteins 0.000 description 1
- 239000011859 microparticle Substances 0.000 description 1
- 208000010125 myocardial infarction Diseases 0.000 description 1
- 239000002105 nanoparticle Substances 0.000 description 1
- 210000000822 natural killer cell Anatomy 0.000 description 1
- 229920005615 natural polymer Polymers 0.000 description 1
- 239000013642 negative control Substances 0.000 description 1
- 210000000440 neutrophil Anatomy 0.000 description 1
- 229940046166 oligodeoxynucleotide Drugs 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 229940049954 penicillin Drugs 0.000 description 1
- 210000003819 peripheral blood mononuclear cell Anatomy 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 239000008363 phosphate buffer Substances 0.000 description 1
- 125000002467 phosphate group Chemical group [H]OP(=O)(O[H])O[*] 0.000 description 1
- 150000004713 phosphodiesters Chemical group 0.000 description 1
- 229950004354 phosphorylcholine Drugs 0.000 description 1
- PYJNAPOPMIJKJZ-UHFFFAOYSA-N phosphorylcholine chloride Chemical compound [Cl-].C[N+](C)(C)CCOP(O)(O)=O PYJNAPOPMIJKJZ-UHFFFAOYSA-N 0.000 description 1
- 210000005134 plasmacytoid dendritic cell Anatomy 0.000 description 1
- 229920002939 poly(N,N-dimethylacrylamides) Polymers 0.000 description 1
- 229920000083 poly(allylamine) Polymers 0.000 description 1
- 229920002946 poly[2-(methacryloxy)ethyl phosphorylcholine] polymer Polymers 0.000 description 1
- 229920002796 poly[α-(4-aminobutyl)-L-glycolic acid) Polymers 0.000 description 1
- 229920002647 polyamide Polymers 0.000 description 1
- 229920000728 polyester Polymers 0.000 description 1
- 229920000570 polyether Polymers 0.000 description 1
- 208000005987 polymyositis Diseases 0.000 description 1
- 108010055896 polyornithine Proteins 0.000 description 1
- 229920001282 polysaccharide Polymers 0.000 description 1
- 239000005017 polysaccharide Substances 0.000 description 1
- 229920002635 polyurethane Polymers 0.000 description 1
- 239000004814 polyurethane Substances 0.000 description 1
- 231100000683 possible toxicity Toxicity 0.000 description 1
- 238000002203 pretreatment Methods 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 229960000286 proflavine Drugs 0.000 description 1
- 238000000159 protein binding assay Methods 0.000 description 1
- 230000011514 reflex Effects 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 235000019515 salmon Nutrition 0.000 description 1
- 230000002000 scavenging effect Effects 0.000 description 1
- 150000003335 secondary amines Chemical class 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 230000035939 shock Effects 0.000 description 1
- 230000019491 signal transduction Effects 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 230000000087 stabilizing effect Effects 0.000 description 1
- 238000007619 statistical method Methods 0.000 description 1
- 229960005322 streptomycin Drugs 0.000 description 1
- 150000003467 sulfuric acid derivatives Chemical class 0.000 description 1
- 238000002198 surface plasmon resonance spectroscopy Methods 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 229920001059 synthetic polymer Polymers 0.000 description 1
- 230000008718 systemic inflammatory response Effects 0.000 description 1
- 229960003433 thalidomide Drugs 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 229940044616 toll-like receptor 7 agonist Drugs 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 239000003053 toxin Substances 0.000 description 1
- 231100000765 toxin Toxicity 0.000 description 1
- 239000001226 triphosphate Substances 0.000 description 1
- 230000014567 type I interferon production Effects 0.000 description 1
- 230000003827 upregulation Effects 0.000 description 1
- 239000004474 valine Substances 0.000 description 1
- 239000013598 vector Substances 0.000 description 1
- 238000005406 washing Methods 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
- A61K31/74—Synthetic polymeric materials
- A61K31/785—Polymers containing nitrogen
-
- 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
- A61K31/13—Amines
-
- 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
-
- 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
- A61K31/715—Polysaccharides, i.e. having more than five saccharide radicals attached to each other by glycosidic linkages; Derivatives thereof, e.g. ethers, esters
- A61K31/716—Glucans
- A61K31/722—Chitin, chitosan
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/1703—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
- A61K38/1709—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/06—Antipsoriatics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/04—Anorexiants; Antiobesity agents
-
- 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
-
- 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
- A61P31/04—Antibacterial agents
-
- 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
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Chemical & Material Sciences (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Immunology (AREA)
- Gastroenterology & Hepatology (AREA)
- Molecular Biology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Marine Sciences & Fisheries (AREA)
- Zoology (AREA)
- Diabetes (AREA)
- Rheumatology (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- Hematology (AREA)
- Neurosurgery (AREA)
- Obesity (AREA)
- Pain & Pain Management (AREA)
- Cardiology (AREA)
- Neurology (AREA)
- Biomedical Technology (AREA)
- Heart & Thoracic Surgery (AREA)
- Child & Adolescent Psychology (AREA)
- Pulmonology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Physical Education & Sports Medicine (AREA)
- Dermatology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US24309009P | 2009-09-16 | 2009-09-16 | |
| US61/243,090 | 2009-09-16 | ||
| PCT/US2010/002516 WO2011034583A2 (en) | 2009-09-16 | 2010-09-16 | Inhibition of endosomal toll-like receptor activation |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CA2774460A1 CA2774460A1 (en) | 2011-03-24 |
| CA2774460C true CA2774460C (en) | 2016-08-09 |
Family
ID=43759220
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2774460A Active CA2774460C (en) | 2009-09-16 | 2010-09-16 | Inhibition of endosomal toll-like receptor activation |
Country Status (6)
| Country | Link |
|---|---|
| US (3) | US9468650B2 (cg-RX-API-DMAC7.html) |
| EP (1) | EP2477641B1 (cg-RX-API-DMAC7.html) |
| CN (1) | CN102639142A (cg-RX-API-DMAC7.html) |
| CA (1) | CA2774460C (cg-RX-API-DMAC7.html) |
| IN (1) | IN2012DN02345A (cg-RX-API-DMAC7.html) |
| WO (1) | WO2011034583A2 (cg-RX-API-DMAC7.html) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP4249913A1 (en) * | 2022-03-22 | 2023-09-27 | Centre Hospitalier Universitaire de Nîmes | Toll-like-receptor 3 inhibitor for preventing and/or treating disorders in patients with a personal history of venous thromboembolism (vte) |
Families Citing this family (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2008121354A1 (en) | 2007-03-30 | 2008-10-09 | Duke University | A method of modulating the activity of a nucleic acid molecule |
| IN2012DN02345A (cg-RX-API-DMAC7.html) | 2009-09-16 | 2015-08-21 | Univ Duke | |
| WO2012151575A2 (en) | 2011-05-05 | 2012-11-08 | Duke University | A method of controlling coagulation |
| WO2014169043A1 (en) * | 2013-04-09 | 2014-10-16 | Duke University | Anti-inflammatory agents and methods of using the same |
| US10066323B2 (en) | 2014-04-16 | 2018-09-04 | Duke University | Electrospun cationic nanofibers and methods of making and using the same |
| CN109982707A (zh) | 2016-09-16 | 2019-07-05 | 杜克大学 | 血管性血友病因子（vwf）靶向剂及其使用方法 |
| US12447464B2 (en) | 2016-12-22 | 2025-10-21 | Duke University | Polycationic microfibers and methods of using the same |
| EP3601592A4 (en) | 2017-03-23 | 2020-11-25 | Duke University | ANTIDOTE MEDIA INVERSION OF EXTRACELLULAR APTAMER COLOR |
| EP3630194A4 (en) * | 2017-05-30 | 2021-03-17 | The Trustees of Columbia University in the City of New York | CATIONIC NUCLEIC ACID TRAP AND ITS USES |
| EP3678708A4 (en) | 2017-09-08 | 2021-12-08 | Duke University | NUCLEOLINE TARGETING APTAMERS AND THEIR METHODS FOR USE |
| WO2021016924A1 (zh) * | 2019-07-31 | 2021-02-04 | 中山大学 | 可用于治疗银屑病的阳离子聚合物及颗粒 |
Family Cites Families (35)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5919761A (en) | 1992-08-14 | 1999-07-06 | The Board Of Regents Of The University Of Michigan | Peptides for heparin and low molecular weight heparin anticoagulation reversal |
| US6037329A (en) | 1994-03-15 | 2000-03-14 | Selective Genetics, Inc. | Compositions containing nucleic acids and ligands for therapeutic treatment |
| US6624141B1 (en) | 1999-03-17 | 2003-09-23 | The Regents Of The University Of Michigan | Protamine fragment compositions and methods of use |
| JP2004508023A (ja) | 2000-09-08 | 2004-03-18 | インビトロジェン コーポレイション | 核酸合成の感度および特異性を増強するための化合物および方法 |
| USRE43612E1 (en) | 2000-10-10 | 2012-08-28 | Massachusetts Institute Of Technology | Biodegradable poly(β-amino esters) and uses thereof |
| EP1347776A2 (en) | 2001-01-05 | 2003-10-01 | Intercell Biomedizinische Forschungs- und Entwicklungs AG | Anti-inflammatory use of polycationic compounds |
| BR0207905A (pt) | 2001-03-08 | 2004-07-27 | Merck Patent Ges Mit Beschroen | Protamina modificada com imunogenicidade reduzida |
| EP2070939B1 (en) | 2001-05-25 | 2014-04-02 | Duke University | Modulators of pharmacological agents |
| AUPR604101A0 (en) | 2001-06-29 | 2001-07-26 | Unisearch Limited | Aptamers |
| US20050136040A1 (en) * | 2001-10-11 | 2005-06-23 | Imperial College Innovations Limited | Control of gene expression using a complex of an oligonucleotide and a regulatory peptide |
| US20030157030A1 (en) | 2001-11-02 | 2003-08-21 | Insert Therapeutics, Inc. | Methods and compositions for therapeutic use of rna interference |
| US20040063654A1 (en) | 2001-11-02 | 2004-04-01 | Davis Mark E. | Methods and compositions for therapeutic use of RNA interference |
| US20030180250A1 (en) * | 2002-03-22 | 2003-09-25 | Council Of Scientific And Industrial Research | Compositions and complexes containing a macromolecular compound as potential anti-inflammatory agents |
| BR0315198A (pt) | 2002-10-09 | 2005-08-30 | Insert Therapeutics Inc | Materiais e composições à base de ciclodextrina e usos relacionados aos mesmos |
| CN1849396A (zh) | 2003-07-15 | 2006-10-18 | 加州理工学院 | 改进的抑制剂核酸 |
| US20050256071A1 (en) | 2003-07-15 | 2005-11-17 | California Institute Of Technology | Inhibitor nucleic acids |
| AU2005238490B2 (en) | 2004-04-22 | 2010-11-18 | Tobira Therapeutics, Inc. | Improved modulators of coagulation factors |
| WO2007001332A2 (en) * | 2004-08-04 | 2007-01-04 | University Of Massachusetts | Anti-pathogen immunoadhesins |
| GB0422877D0 (en) | 2004-10-14 | 2004-11-17 | Univ Glasgow | Bioactive polymers |
| ATE541928T1 (de) | 2005-03-31 | 2012-02-15 | Calando Pharmaceuticals Inc | Inhibitoren der untereinheit 2 der ribonukleotidreduktase und ihre verwendungen |
| US7611835B2 (en) | 2005-09-30 | 2009-11-03 | Battelle Memorial Institute | Process for preparing multilayer enzyme coating on a fiber |
| US9267937B2 (en) | 2005-12-15 | 2016-02-23 | Massachusetts Institute Of Technology | System for screening particles |
| JP2009538325A (ja) | 2006-05-26 | 2009-11-05 | リガド・バイオサイエンシーズ・インコーポレーテツド | Ｒｅｇ１抗凝固系の投与 |
| EP3669894A3 (en) * | 2006-06-30 | 2020-08-26 | Syntab Therapeutics GmbH | Novel multifunctional compounds for pharmaceutical purposes |
| WO2008066621A2 (en) | 2006-10-19 | 2008-06-05 | Duke University | Reversible platelet inhibition |
| US20100028402A1 (en) | 2006-10-25 | 2010-02-04 | Marina Dobrovolskaia | Nanoparticle-based anticoagulant |
| CA2678353A1 (en) * | 2007-02-15 | 2008-08-21 | Mannkind Corporation | A method for enhancing t cell response |
| WO2008121354A1 (en) | 2007-03-30 | 2008-10-09 | Duke University | A method of modulating the activity of a nucleic acid molecule |
| EP2209552A4 (en) | 2007-09-27 | 2010-12-08 | Sca Hygiene Prod Ab | TONE-NETWORKED POLYMER YELLOW |
| WO2009064767A2 (en) | 2007-11-12 | 2009-05-22 | Massachusetts Institute Of Technology | Bactericidal nanofibers, and methods of use thereof |
| WO2010020008A1 (en) | 2008-08-22 | 2010-02-25 | Polymers Crc Limited | Polymer coatings |
| WO2010132879A2 (en) | 2009-05-15 | 2010-11-18 | The Johns Hopkins University | Multicomponent degradable cationic polymers |
| IN2012DN02345A (cg-RX-API-DMAC7.html) | 2009-09-16 | 2015-08-21 | Univ Duke | |
| WO2012088059A2 (en) | 2010-12-20 | 2012-06-28 | Virginia Commonwealth University | A facile method for crosslinking and incorporating bioactive molecules into electrospun fiber scaffolds |
| US20140234373A1 (en) | 2011-09-16 | 2014-08-21 | Georfia Regents University | Methods of Promoting Immune Tolerance |
-
2010
- 2010-09-16 IN IN2345DEN2012 patent/IN2012DN02345A/en unknown
- 2010-09-16 WO PCT/US2010/002516 patent/WO2011034583A2/en not_active Ceased
- 2010-09-16 CN CN2010800511149A patent/CN102639142A/zh active Pending
- 2010-09-16 EP EP10817556.3A patent/EP2477641B1/en active Active
- 2010-09-16 CA CA2774460A patent/CA2774460C/en active Active
- 2010-09-16 US US13/496,313 patent/US9468650B2/en active Active
-
2016
- 2016-10-12 US US15/291,849 patent/US11617779B2/en active Active
-
2023
- 2023-03-30 US US18/128,957 patent/US20230248805A1/en active Pending
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP4249913A1 (en) * | 2022-03-22 | 2023-09-27 | Centre Hospitalier Universitaire de Nîmes | Toll-like-receptor 3 inhibitor for preventing and/or treating disorders in patients with a personal history of venous thromboembolism (vte) |
Also Published As
| Publication number | Publication date |
|---|---|
| EP2477641B1 (en) | 2024-03-27 |
| WO2011034583A2 (en) | 2011-03-24 |
| CN102639142A (zh) | 2012-08-15 |
| US20230248805A1 (en) | 2023-08-10 |
| WO2011034583A3 (en) | 2011-10-06 |
| US11617779B2 (en) | 2023-04-04 |
| CA2774460A1 (en) | 2011-03-24 |
| EP2477641A4 (en) | 2013-08-07 |
| US9468650B2 (en) | 2016-10-18 |
| IN2012DN02345A (cg-RX-API-DMAC7.html) | 2015-08-21 |
| EP2477641A2 (en) | 2012-07-25 |
| US20170095503A1 (en) | 2017-04-06 |
| US20120183564A1 (en) | 2012-07-19 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CA2774460C (en) | Inhibition of endosomal toll-like receptor activation | |
| US20210393806A1 (en) | Cross-linked polymer modified nanoparticles | |
| US12447464B2 (en) | Polycationic microfibers and methods of using the same | |
| Lee et al. | Nucleic acid-binding polymers as anti-inflammatory agents | |
| Toy et al. | TLR7 and RIG-I dual-adjuvant loaded nanoparticles drive broadened and synergistic responses in dendritic cells in vitro and generate unique cellular immune responses in influenza vaccination | |
| WO2008121354A1 (en) | A method of modulating the activity of a nucleic acid molecule | |
| HRP20160136T1 (hr) | Peptidno posredovana ne-kovalentna isporuka aktivnih sredstava kroz krvno moždanu barijeru | |
| US20100130425A1 (en) | Use of toll-like receptor ligands in treating excitotoxic injury, ischemia and/or hypoxia | |
| WO2014201276A1 (en) | Polycation-functionalized nanoporous silicon carrier for systemic delivery of gene silencing agents | |
| CN107412260A (zh) | cGAS-STING通路激活剂及其用途 | |
| JP2010535479A (ja) | Ｓｄｆ−１結合核酸およびその使用 | |
| CN105377305A (zh) | 靶向脂肪细胞的非病毒基因递送体系 | |
| US10111898B2 (en) | Anti-tumor compositions and methods | |
| KR20110083919A (ko) | 복합 유전자를 표적하는 ｓｉＲＮＡ 다중 접합체 및 이의 제조방법 | |
| US20200171167A1 (en) | Cationic nucleic acid scavenger and uses thereof | |
| Chan et al. | Synthesis and characterization of PEGylated toll like receptor 7 ligands | |
| Ji et al. | Dual Functioned Hexapeptide‐Coated Lipid‐Core Nanomicelles Suppress Toll‐Like Receptor‐Mediated Inflammatory Responses through Endotoxin Scavenging and Endosomal pH Modulation | |
| JP7193083B2 (ja) | エクソソームの遺伝子機能を抑制することができる複合体、がんの増殖及び／又は転移抑制剤 | |
| US11613756B2 (en) | Compositions and methods for differential induction of cell death and interferon expression | |
| RU2681213C2 (ru) | Ингибиторы метастазирования | |
| WO2017159835A1 (ja) | 形質細胞性腫瘍治療剤 | |
| US12427183B2 (en) | Methods of treating cancer, infectious disease, and autoimmune disease using chemokines | |
| Petkova | Gene therapy in combination with an approach targeting the tumour microenvironment in glioblastoma | |
| Oza | Large Peritoneal Macrophage Tropism Towards Acute Injury and Its Potential for the Treatment of Acetaminophen-Induced Liver Toxicity | |
| US20120258117A1 (en) | Methods and compositions for modulation of histone ubiquitination |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request |