JP2019054796A - フラビウイルス中和抗体およびその使用方法 - Google Patents
フラビウイルス中和抗体およびその使用方法 Download PDFInfo
- Publication number
- JP2019054796A JP2019054796A JP2018202677A JP2018202677A JP2019054796A JP 2019054796 A JP2019054796 A JP 2019054796A JP 2018202677 A JP2018202677 A JP 2018202677A JP 2018202677 A JP2018202677 A JP 2018202677A JP 2019054796 A JP2019054796 A JP 2019054796A
- Authority
- JP
- Japan
- Prior art keywords
- antibody
- flavivirus
- antibodies
- region
- virus
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
- 238000000034 method Methods 0.000 title claims abstract description 110
- 241000710831 Flavivirus Species 0.000 title claims abstract description 94
- 230000003472 neutralizing effect Effects 0.000 title description 10
- 102000009490 IgG Receptors Human genes 0.000 claims abstract description 30
- 108010073807 IgG Receptors Proteins 0.000 claims abstract description 28
- 241000710886 West Nile virus Species 0.000 claims abstract description 18
- 241000725619 Dengue virus Species 0.000 claims abstract description 15
- 230000001419 dependent effect Effects 0.000 claims abstract description 15
- 208000024891 symptom Diseases 0.000 claims abstract description 15
- 125000003275 alpha amino acid group Chemical group 0.000 claims description 42
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 37
- 239000013598 vector Substances 0.000 claims description 37
- 239000000203 mixture Substances 0.000 claims description 35
- 206010054261 Flavivirus infection Diseases 0.000 claims description 34
- 230000035772 mutation Effects 0.000 claims description 33
- 150000007523 nucleic acids Chemical group 0.000 claims description 33
- 208000015181 infectious disease Diseases 0.000 claims description 26
- 102000004196 processed proteins & peptides Human genes 0.000 claims description 26
- 229960005486 vaccine Drugs 0.000 claims description 22
- 229920001184 polypeptide Polymers 0.000 claims description 20
- 108091028043 Nucleic acid sequence Proteins 0.000 claims description 17
- 230000001965 increasing effect Effects 0.000 claims description 17
- 239000003814 drug Substances 0.000 claims description 15
- 102100026120 IgG receptor FcRn large subunit p51 Human genes 0.000 claims description 13
- 239000003443 antiviral agent Substances 0.000 claims description 11
- 229940124597 therapeutic agent Drugs 0.000 claims description 11
- 102000039446 nucleic acids Human genes 0.000 claims description 10
- 108020004707 nucleic acids Proteins 0.000 claims description 10
- 150000003384 small molecules Chemical class 0.000 claims description 10
- 230000004580 weight loss Effects 0.000 claims description 10
- FWMNVWWHGCHHJJ-SKKKGAJSSA-N 4-amino-1-[(2r)-6-amino-2-[[(2r)-2-[[(2r)-2-[[(2r)-2-amino-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]hexanoyl]piperidine-4-carboxylic acid Chemical compound C([C@H](C(=O)N[C@H](CC(C)C)C(=O)N[C@H](CCCCN)C(=O)N1CCC(N)(CC1)C(O)=O)NC(=O)[C@H](N)CC=1C=CC=CC=1)C1=CC=CC=C1 FWMNVWWHGCHHJJ-SKKKGAJSSA-N 0.000 claims description 8
- 102000004127 Cytokines Human genes 0.000 claims description 8
- 108090000695 Cytokines Proteins 0.000 claims description 8
- 239000002773 nucleotide Substances 0.000 claims description 8
- 125000003729 nucleotide group Chemical group 0.000 claims description 8
- 241000710842 Japanese encephalitis virus Species 0.000 claims description 7
- 241000710888 St. Louis encephalitis virus Species 0.000 claims description 7
- 241000710772 Yellow fever virus Species 0.000 claims description 7
- 229940051021 yellow-fever virus Drugs 0.000 claims description 7
- 241000710908 Murray Valley encephalitis virus Species 0.000 claims description 6
- 239000003053 toxin Substances 0.000 claims description 6
- 231100000765 toxin Toxicity 0.000 claims description 6
- 206010037660 Pyrexia Diseases 0.000 claims description 5
- 108010068617 neonatal Fc receptor Proteins 0.000 claims description 5
- 206010033799 Paralysis Diseases 0.000 claims description 4
- 229960004854 viral vaccine Drugs 0.000 claims description 4
- 208000010201 Exanthema Diseases 0.000 claims description 3
- 206010019233 Headaches Diseases 0.000 claims description 3
- 206010028813 Nausea Diseases 0.000 claims description 3
- 208000002193 Pain Diseases 0.000 claims description 3
- 108020004459 Small interfering RNA Proteins 0.000 claims description 3
- 102000004887 Transforming Growth Factor beta Human genes 0.000 claims description 3
- 108090001012 Transforming Growth Factor beta Proteins 0.000 claims description 3
- 206010047700 Vomiting Diseases 0.000 claims description 3
- 201000005884 exanthem Diseases 0.000 claims description 3
- 231100000869 headache Toxicity 0.000 claims description 3
- 230000008693 nausea Effects 0.000 claims description 3
- 206010037844 rash Diseases 0.000 claims description 3
- ZRKFYGHZFMAOKI-QMGMOQQFSA-N tgfbeta Chemical group C([C@H](NC(=O)[C@H](C(C)C)NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CC(C)C)NC(=O)CNC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](N)CCSC)C(C)C)[C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](C)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(O)=O)C1=CC=C(O)C=C1 ZRKFYGHZFMAOKI-QMGMOQQFSA-N 0.000 claims description 3
- 230000008673 vomiting Effects 0.000 claims description 3
- 208000016261 weight loss Diseases 0.000 claims description 3
- 230000009385 viral infection Effects 0.000 abstract description 13
- 208000036142 Viral infection Diseases 0.000 abstract description 8
- 241000710781 Flaviviridae Species 0.000 abstract description 7
- 101710204837 Envelope small membrane protein Proteins 0.000 abstract description 4
- 206010057199 Flaviviral infections Diseases 0.000 abstract 1
- 101710145006 Lysis protein Proteins 0.000 abstract 1
- 239000000427 antigen Substances 0.000 description 60
- 210000004027 cell Anatomy 0.000 description 57
- 241000282414 Homo sapiens Species 0.000 description 52
- 150000001875 compounds Chemical class 0.000 description 51
- 108090000623 proteins and genes Proteins 0.000 description 49
- 108091007433 antigens Proteins 0.000 description 47
- 102000036639 antigens Human genes 0.000 description 47
- 241000196324 Embryophyta Species 0.000 description 43
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 35
- 241000699670 Mus sp. Species 0.000 description 32
- 102000004169 proteins and genes Human genes 0.000 description 32
- 235000018102 proteins Nutrition 0.000 description 31
- 238000012360 testing method Methods 0.000 description 27
- 239000003795 chemical substances by application Substances 0.000 description 24
- 235000001014 amino acid Nutrition 0.000 description 23
- 201000010099 disease Diseases 0.000 description 20
- 108060003951 Immunoglobulin Proteins 0.000 description 18
- 241001465754 Metazoa Species 0.000 description 18
- 102000018358 immunoglobulin Human genes 0.000 description 18
- 241000699666 Mus <mouse, genus> Species 0.000 description 17
- 239000000523 sample Substances 0.000 description 17
- 108020004414 DNA Proteins 0.000 description 16
- 229940024606 amino acid Drugs 0.000 description 16
- 208000035475 disorder Diseases 0.000 description 15
- 239000012634 fragment Substances 0.000 description 15
- 210000004408 hybridoma Anatomy 0.000 description 15
- -1 leucine amino acids Chemical group 0.000 description 15
- 239000000126 substance Substances 0.000 description 15
- YBJHBAHKTGYVGT-ZKWXMUAHSA-N (+)-Biotin Chemical compound N1C(=O)N[C@@H]2[C@H](CCCCC(=O)O)SC[C@@H]21 YBJHBAHKTGYVGT-ZKWXMUAHSA-N 0.000 description 14
- 150000001413 amino acids Chemical group 0.000 description 14
- 238000003556 assay Methods 0.000 description 14
- 150000001720 carbohydrates Chemical class 0.000 description 14
- 238000011282 treatment Methods 0.000 description 14
- 206010012310 Dengue fever Diseases 0.000 description 13
- 241000700605 Viruses Species 0.000 description 13
- 239000012472 biological sample Substances 0.000 description 13
- 208000025729 dengue disease Diseases 0.000 description 13
- 238000000338 in vitro Methods 0.000 description 13
- 208000001490 Dengue Diseases 0.000 description 12
- 102100027723 Endogenous retrovirus group K member 6 Rec protein Human genes 0.000 description 12
- 101710091045 Envelope protein Proteins 0.000 description 12
- 101710188315 Protein X Proteins 0.000 description 12
- 108020001507 fusion proteins Proteins 0.000 description 12
- 102000037865 fusion proteins Human genes 0.000 description 12
- 241000124008 Mammalia Species 0.000 description 10
- 230000003053 immunization Effects 0.000 description 10
- 238000002649 immunization Methods 0.000 description 10
- 238000002372 labelling Methods 0.000 description 10
- 239000002502 liposome Substances 0.000 description 10
- 238000002965 ELISA Methods 0.000 description 9
- 235000004279 alanine Nutrition 0.000 description 9
- 238000001727 in vivo Methods 0.000 description 9
- 230000003993 interaction Effects 0.000 description 9
- 238000004519 manufacturing process Methods 0.000 description 9
- 239000000463 material Substances 0.000 description 9
- 230000001225 therapeutic effect Effects 0.000 description 9
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 8
- 210000003719 b-lymphocyte Anatomy 0.000 description 8
- 239000007790 solid phase Substances 0.000 description 8
- 239000000243 solution Substances 0.000 description 8
- 238000006467 substitution reaction Methods 0.000 description 8
- 230000003612 virological effect Effects 0.000 description 8
- ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 7
- 230000008901 benefit Effects 0.000 description 7
- 230000015572 biosynthetic process Effects 0.000 description 7
- 229960002685 biotin Drugs 0.000 description 7
- 235000020958 biotin Nutrition 0.000 description 7
- 239000011616 biotin Substances 0.000 description 7
- 230000000295 complement effect Effects 0.000 description 7
- 239000007822 coupling agent Substances 0.000 description 7
- 238000005859 coupling reaction Methods 0.000 description 7
- 238000003018 immunoassay Methods 0.000 description 7
- 210000004962 mammalian cell Anatomy 0.000 description 7
- 238000002360 preparation method Methods 0.000 description 7
- 238000012216 screening Methods 0.000 description 7
- 238000007423 screening assay Methods 0.000 description 7
- 230000009261 transgenic effect Effects 0.000 description 7
- 102000004190 Enzymes Human genes 0.000 description 6
- 108090000790 Enzymes Proteins 0.000 description 6
- 102000009109 Fc receptors Human genes 0.000 description 6
- 108010087819 Fc receptors Proteins 0.000 description 6
- 241000282412 Homo Species 0.000 description 6
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 6
- 241000700584 Simplexvirus Species 0.000 description 6
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 6
- 239000012491 analyte Substances 0.000 description 6
- 230000008878 coupling Effects 0.000 description 6
- 238000010168 coupling process Methods 0.000 description 6
- 229940088598 enzyme Drugs 0.000 description 6
- 239000013604 expression vector Substances 0.000 description 6
- 230000001900 immune effect Effects 0.000 description 6
- 230000016784 immunoglobulin production Effects 0.000 description 6
- 231100000518 lethal Toxicity 0.000 description 6
- 230000001665 lethal effect Effects 0.000 description 6
- 239000011159 matrix material Substances 0.000 description 6
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 6
- 239000003094 microcapsule Substances 0.000 description 6
- 230000002265 prevention Effects 0.000 description 6
- 230000000069 prophylactic effect Effects 0.000 description 6
- 230000004224 protection Effects 0.000 description 6
- 230000002829 reductive effect Effects 0.000 description 6
- RPENMORRBUTCPR-UHFFFAOYSA-M sodium;1-hydroxy-2,5-dioxopyrrolidine-3-sulfonate Chemical compound [Na+].ON1C(=O)CC(S([O-])(=O)=O)C1=O RPENMORRBUTCPR-UHFFFAOYSA-M 0.000 description 6
- 239000002904 solvent Substances 0.000 description 6
- 230000004083 survival effect Effects 0.000 description 6
- 210000001519 tissue Anatomy 0.000 description 6
- 108010047041 Complementarity Determining Regions Proteins 0.000 description 5
- 108010041986 DNA Vaccines Proteins 0.000 description 5
- 229940021995 DNA vaccine Drugs 0.000 description 5
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 5
- 108010021625 Immunoglobulin Fragments Proteins 0.000 description 5
- 102000008394 Immunoglobulin Fragments Human genes 0.000 description 5
- 235000002637 Nicotiana tabacum Nutrition 0.000 description 5
- 206010035226 Plasma cell myeloma Diseases 0.000 description 5
- 108010090804 Streptavidin Proteins 0.000 description 5
- 210000000612 antigen-presenting cell Anatomy 0.000 description 5
- 238000013459 approach Methods 0.000 description 5
- 239000011324 bead Substances 0.000 description 5
- 238000001514 detection method Methods 0.000 description 5
- 238000005516 engineering process Methods 0.000 description 5
- 238000009472 formulation Methods 0.000 description 5
- 230000004927 fusion Effects 0.000 description 5
- 239000001963 growth medium Substances 0.000 description 5
- 230000028993 immune response Effects 0.000 description 5
- 238000001114 immunoprecipitation Methods 0.000 description 5
- 201000000050 myeloid neoplasm Diseases 0.000 description 5
- 239000008194 pharmaceutical composition Substances 0.000 description 5
- 230000001681 protective effect Effects 0.000 description 5
- 102000005962 receptors Human genes 0.000 description 5
- 108020003175 receptors Proteins 0.000 description 5
- 210000002966 serum Anatomy 0.000 description 5
- 238000010561 standard procedure Methods 0.000 description 5
- 108700012359 toxins Proteins 0.000 description 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 5
- LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide Substances CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 4
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 4
- 241000702421 Dependoparvovirus Species 0.000 description 4
- 102000018251 Hypoxanthine Phosphoribosyltransferase Human genes 0.000 description 4
- 108010091358 Hypoxanthine Phosphoribosyltransferase Proteins 0.000 description 4
- 102000006496 Immunoglobulin Heavy Chains Human genes 0.000 description 4
- 108010019476 Immunoglobulin Heavy Chains Proteins 0.000 description 4
- 206010028980 Neoplasm Diseases 0.000 description 4
- 244000061176 Nicotiana tabacum Species 0.000 description 4
- 238000001042 affinity chromatography Methods 0.000 description 4
- 230000003441 anti-flavivirus Effects 0.000 description 4
- 201000011510 cancer Diseases 0.000 description 4
- 150000001718 carbodiimides Chemical class 0.000 description 4
- 235000014633 carbohydrates Nutrition 0.000 description 4
- 239000000969 carrier Substances 0.000 description 4
- 210000000170 cell membrane Anatomy 0.000 description 4
- 238000006243 chemical reaction Methods 0.000 description 4
- 229940127089 cytotoxic agent Drugs 0.000 description 4
- 210000004443 dendritic cell Anatomy 0.000 description 4
- 239000006185 dispersion Substances 0.000 description 4
- 238000010494 dissociation reaction Methods 0.000 description 4
- 230000005593 dissociations Effects 0.000 description 4
- 239000003937 drug carrier Substances 0.000 description 4
- 206010014599 encephalitis Diseases 0.000 description 4
- 239000012530 fluid Substances 0.000 description 4
- RWSXRVCMGQZWBV-WDSKDSINSA-N glutathione Chemical compound OC(=O)[C@@H](N)CCC(=O)N[C@@H](CS)C(=O)NCC(O)=O RWSXRVCMGQZWBV-WDSKDSINSA-N 0.000 description 4
- 239000004615 ingredient Substances 0.000 description 4
- 239000003112 inhibitor Substances 0.000 description 4
- 239000003550 marker Substances 0.000 description 4
- 239000012528 membrane Substances 0.000 description 4
- 230000004048 modification Effects 0.000 description 4
- 238000012986 modification Methods 0.000 description 4
- 239000002245 particle Substances 0.000 description 4
- 230000001717 pathogenic effect Effects 0.000 description 4
- 229920001223 polyethylene glycol Polymers 0.000 description 4
- 230000009467 reduction Effects 0.000 description 4
- 239000011780 sodium chloride Substances 0.000 description 4
- 230000009466 transformation Effects 0.000 description 4
- 239000013603 viral vector Substances 0.000 description 4
- GKSPIZSKQWTXQG-UHFFFAOYSA-N (2,5-dioxopyrrolidin-1-yl) 4-[1-(pyridin-2-yldisulfanyl)ethyl]benzoate Chemical compound C=1C=C(C(=O)ON2C(CCC2=O)=O)C=CC=1C(C)SSC1=CC=CC=N1 GKSPIZSKQWTXQG-UHFFFAOYSA-N 0.000 description 3
- 241000894006 Bacteria Species 0.000 description 3
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 3
- 241000255925 Diptera Species 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- 108010010803 Gelatin Proteins 0.000 description 3
- 108010001336 Horseradish Peroxidase Proteins 0.000 description 3
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 3
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 description 3
- 201000009906 Meningitis Diseases 0.000 description 3
- 239000002202 Polyethylene glycol Substances 0.000 description 3
- 108020004511 Recombinant DNA Proteins 0.000 description 3
- 101710088839 Replication initiation protein Proteins 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 238000010521 absorption reaction Methods 0.000 description 3
- 239000003242 anti bacterial agent Substances 0.000 description 3
- 230000010056 antibody-dependent cellular cytotoxicity Effects 0.000 description 3
- 230000000890 antigenic effect Effects 0.000 description 3
- 239000002246 antineoplastic agent Substances 0.000 description 3
- 210000004369 blood Anatomy 0.000 description 3
- 239000008280 blood Substances 0.000 description 3
- 230000037396 body weight Effects 0.000 description 3
- DQXBYHZEEUGOBF-UHFFFAOYSA-N but-3-enoic acid;ethene Chemical compound C=C.OC(=O)CC=C DQXBYHZEEUGOBF-UHFFFAOYSA-N 0.000 description 3
- 239000003153 chemical reaction reagent Substances 0.000 description 3
- 230000004540 complement-dependent cytotoxicity Effects 0.000 description 3
- 229920001577 copolymer Polymers 0.000 description 3
- 230000009260 cross reactivity Effects 0.000 description 3
- 239000002254 cytotoxic agent Substances 0.000 description 3
- 231100000599 cytotoxic agent Toxicity 0.000 description 3
- 230000034994 death Effects 0.000 description 3
- 231100000517 death Toxicity 0.000 description 3
- 238000012217 deletion Methods 0.000 description 3
- 230000037430 deletion Effects 0.000 description 3
- 208000037765 diseases and disorders Diseases 0.000 description 3
- 239000002612 dispersion medium Substances 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 239000005038 ethylene vinyl acetate Substances 0.000 description 3
- 239000008273 gelatin Substances 0.000 description 3
- 229920000159 gelatin Polymers 0.000 description 3
- 235000019322 gelatine Nutrition 0.000 description 3
- 235000011852 gelatine desserts Nutrition 0.000 description 3
- 230000036541 health Effects 0.000 description 3
- 210000000987 immune system Anatomy 0.000 description 3
- 230000036039 immunity Effects 0.000 description 3
- 229940124452 immunizing agent Drugs 0.000 description 3
- 238000011534 incubation Methods 0.000 description 3
- 230000001939 inductive effect Effects 0.000 description 3
- 238000001802 infusion Methods 0.000 description 3
- 239000007924 injection Substances 0.000 description 3
- 238000002347 injection Methods 0.000 description 3
- 238000001990 intravenous administration Methods 0.000 description 3
- 231100000636 lethal dose Toxicity 0.000 description 3
- 150000002632 lipids Chemical class 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 210000004698 lymphocyte Anatomy 0.000 description 3
- 230000007246 mechanism Effects 0.000 description 3
- 230000001404 mediated effect Effects 0.000 description 3
- 239000002609 medium Substances 0.000 description 3
- 230000004899 motility Effects 0.000 description 3
- 238000006386 neutralization reaction Methods 0.000 description 3
- 229920001200 poly(ethylene-vinyl acetate) Polymers 0.000 description 3
- 238000000746 purification Methods 0.000 description 3
- 230000004044 response Effects 0.000 description 3
- 229940031626 subunit vaccine Drugs 0.000 description 3
- 239000003826 tablet Substances 0.000 description 3
- 230000008685 targeting Effects 0.000 description 3
- 238000012384 transportation and delivery Methods 0.000 description 3
- 241000701161 unidentified adenovirus Species 0.000 description 3
- VPFUWHKTPYPNGT-UHFFFAOYSA-N 3-(3,4-dihydroxyphenyl)-1-(5-hydroxy-2,2-dimethylchromen-6-yl)propan-1-one Chemical compound OC1=C2C=CC(C)(C)OC2=CC=C1C(=O)CCC1=CC=C(O)C(O)=C1 VPFUWHKTPYPNGT-UHFFFAOYSA-N 0.000 description 2
- 241000589155 Agrobacterium tumefaciens Species 0.000 description 2
- 102000002260 Alkaline Phosphatase Human genes 0.000 description 2
- 108020004774 Alkaline Phosphatase Proteins 0.000 description 2
- 206010003445 Ascites Diseases 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- 108090001008 Avidin Proteins 0.000 description 2
- 241000283690 Bos taurus Species 0.000 description 2
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
- SRBFZHDQGSBBOR-IOVATXLUSA-N D-xylopyranose Chemical compound O[C@@H]1COC(O)[C@H](O)[C@H]1O SRBFZHDQGSBBOR-IOVATXLUSA-N 0.000 description 2
- 108020003215 DNA Probes Proteins 0.000 description 2
- 239000003298 DNA probe Substances 0.000 description 2
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 2
- 241000233866 Fungi Species 0.000 description 2
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Chemical compound OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 2
- 108010024636 Glutathione Proteins 0.000 description 2
- 101710154606 Hemagglutinin Proteins 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- 102000013463 Immunoglobulin Light Chains Human genes 0.000 description 2
- 108010065825 Immunoglobulin Light Chains Proteins 0.000 description 2
- 108010002350 Interleukin-2 Proteins 0.000 description 2
- 108060001084 Luciferase Proteins 0.000 description 2
- 239000005089 Luciferase Substances 0.000 description 2
- 244000302512 Momordica charantia Species 0.000 description 2
- 235000009811 Momordica charantia Nutrition 0.000 description 2
- 108091061960 Naked DNA Proteins 0.000 description 2
- 241000208125 Nicotiana Species 0.000 description 2
- 101710093908 Outer capsid protein VP4 Proteins 0.000 description 2
- 101710135467 Outer capsid protein sigma-1 Proteins 0.000 description 2
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 2
- 101710176177 Protein A56 Proteins 0.000 description 2
- 108010039491 Ricin Proteins 0.000 description 2
- 229920002684 Sepharose Polymers 0.000 description 2
- IQFYYKKMVGJFEH-XLPZGREQSA-N Thymidine Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](CO)[C@@H](O)C1 IQFYYKKMVGJFEH-XLPZGREQSA-N 0.000 description 2
- 101900324692 West Nile virus Envelope protein E Proteins 0.000 description 2
- 208000003152 Yellow Fever Diseases 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 230000009471 action Effects 0.000 description 2
- 239000004480 active ingredient Substances 0.000 description 2
- 238000007792 addition Methods 0.000 description 2
- 239000002671 adjuvant Substances 0.000 description 2
- 125000000539 amino acid group Chemical group 0.000 description 2
- 230000000844 anti-bacterial effect Effects 0.000 description 2
- 229940121375 antifungal agent Drugs 0.000 description 2
- 239000003429 antifungal agent Substances 0.000 description 2
- 230000030741 antigen processing and presentation Effects 0.000 description 2
- 229940041181 antineoplastic drug Drugs 0.000 description 2
- 235000010323 ascorbic acid Nutrition 0.000 description 2
- 229960005070 ascorbic acid Drugs 0.000 description 2
- 239000011668 ascorbic acid Substances 0.000 description 2
- 230000001580 bacterial effect Effects 0.000 description 2
- 230000001588 bifunctional effect Effects 0.000 description 2
- 239000011230 binding agent Substances 0.000 description 2
- 239000013060 biological fluid Substances 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 239000002738 chelating agent Substances 0.000 description 2
- OSASVXMJTNOKOY-UHFFFAOYSA-N chlorobutanol Chemical compound CC(C)(O)C(Cl)(Cl)Cl OSASVXMJTNOKOY-UHFFFAOYSA-N 0.000 description 2
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 2
- 238000004587 chromatography analysis Methods 0.000 description 2
- 230000002759 chromosomal effect Effects 0.000 description 2
- 238000000576 coating method Methods 0.000 description 2
- 230000021615 conjugation Effects 0.000 description 2
- 238000007796 conventional method Methods 0.000 description 2
- 230000003247 decreasing effect Effects 0.000 description 2
- 239000003405 delayed action preparation Substances 0.000 description 2
- 239000003599 detergent Substances 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 238000003745 diagnosis Methods 0.000 description 2
- 125000005442 diisocyanate group Chemical group 0.000 description 2
- 239000003085 diluting agent Substances 0.000 description 2
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 2
- 125000002228 disulfide group Chemical group 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 238000012377 drug delivery Methods 0.000 description 2
- 238000009510 drug design Methods 0.000 description 2
- 210000001671 embryonic stem cell Anatomy 0.000 description 2
- 230000002708 enhancing effect Effects 0.000 description 2
- 150000002148 esters Chemical class 0.000 description 2
- 239000000284 extract Substances 0.000 description 2
- GNBHRKFJIUUOQI-UHFFFAOYSA-N fluorescein Chemical compound O1C(=O)C2=CC=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 GNBHRKFJIUUOQI-UHFFFAOYSA-N 0.000 description 2
- MHMNJMPURVTYEJ-UHFFFAOYSA-N fluorescein-5-isothiocyanate Chemical compound O1C(=O)C2=CC(N=C=S)=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 MHMNJMPURVTYEJ-UHFFFAOYSA-N 0.000 description 2
- 229960003180 glutathione Drugs 0.000 description 2
- 235000011187 glycerol Nutrition 0.000 description 2
- 230000012010 growth Effects 0.000 description 2
- NAQMVNRVTILPCV-UHFFFAOYSA-N hexane-1,6-diamine Chemical compound NCCCCCCN NAQMVNRVTILPCV-UHFFFAOYSA-N 0.000 description 2
- 230000028996 humoral immune response Effects 0.000 description 2
- 210000004754 hybrid cell Anatomy 0.000 description 2
- 239000000017 hydrogel Substances 0.000 description 2
- FDGQSTZJBFJUBT-UHFFFAOYSA-N hypoxanthine Chemical compound O=C1NC=NC2=C1NC=N2 FDGQSTZJBFJUBT-UHFFFAOYSA-N 0.000 description 2
- 238000003384 imaging method Methods 0.000 description 2
- 230000003100 immobilizing effect Effects 0.000 description 2
- 238000010166 immunofluorescence Methods 0.000 description 2
- 230000002163 immunogen Effects 0.000 description 2
- 229940072221 immunoglobulins Drugs 0.000 description 2
- 230000002637 immunotoxin Effects 0.000 description 2
- 239000002596 immunotoxin Substances 0.000 description 2
- 229940051026 immunotoxin Drugs 0.000 description 2
- 231100000608 immunotoxin Toxicity 0.000 description 2
- 230000002401 inhibitory effect Effects 0.000 description 2
- 239000007951 isotonicity adjuster Substances 0.000 description 2
- 238000005304 joining Methods 0.000 description 2
- 125000001909 leucine group Chemical group [H]N(*)C(C(*)=O)C([H])([H])C(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
- RGLRXNKKBLIBQS-XNHQSDQCSA-N leuprolide acetate Chemical compound CC(O)=O.CCNC(=O)[C@@H]1CCCN1C(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](CC(C)C)NC(=O)[C@@H](NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@H]1NC(=O)CC1)CC1=CC=C(O)C=C1 RGLRXNKKBLIBQS-XNHQSDQCSA-N 0.000 description 2
- 230000000670 limiting effect Effects 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 108020004999 messenger RNA Proteins 0.000 description 2
- OSWPMRLSEDHDFF-UHFFFAOYSA-N methyl salicylate Chemical compound COC(=O)C1=CC=CC=C1O OSWPMRLSEDHDFF-UHFFFAOYSA-N 0.000 description 2
- LXCFILQKKLGQFO-UHFFFAOYSA-N methylparaben Chemical compound COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 description 2
- 244000005700 microbiome Species 0.000 description 2
- 239000000346 nonvolatile oil Substances 0.000 description 2
- 239000002674 ointment Substances 0.000 description 2
- 238000011275 oncology therapy Methods 0.000 description 2
- 244000052769 pathogen Species 0.000 description 2
- 230000007918 pathogenicity Effects 0.000 description 2
- 239000000816 peptidomimetic Substances 0.000 description 2
- 238000002823 phage display Methods 0.000 description 2
- 239000000546 pharmaceutical excipient Substances 0.000 description 2
- 239000002953 phosphate buffered saline Substances 0.000 description 2
- 239000013612 plasmid Substances 0.000 description 2
- 229920000747 poly(lactic acid) Polymers 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 230000002285 radioactive effect Effects 0.000 description 2
- 239000012857 radioactive material Substances 0.000 description 2
- 238000003127 radioimmunoassay Methods 0.000 description 2
- 230000009257 reactivity Effects 0.000 description 2
- 230000008707 rearrangement Effects 0.000 description 2
- PYWVYCXTNDRMGF-UHFFFAOYSA-N rhodamine B Chemical compound [Cl-].C=12C=CC(=[N+](CC)CC)C=C2OC2=CC(N(CC)CC)=CC=C2C=1C1=CC=CC=C1C(O)=O PYWVYCXTNDRMGF-UHFFFAOYSA-N 0.000 description 2
- 241000894007 species Species 0.000 description 2
- 238000007920 subcutaneous administration Methods 0.000 description 2
- 235000000346 sugar Nutrition 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 238000002560 therapeutic procedure Methods 0.000 description 2
- 238000002255 vaccination Methods 0.000 description 2
- 238000001262 western blot Methods 0.000 description 2
- LLXVXPPXELIDGQ-UHFFFAOYSA-N (2,5-dioxopyrrolidin-1-yl) 3-(2,5-dioxopyrrol-1-yl)benzoate Chemical compound C=1C=CC(N2C(C=CC2=O)=O)=CC=1C(=O)ON1C(=O)CCC1=O LLXVXPPXELIDGQ-UHFFFAOYSA-N 0.000 description 1
- YMXHPSHLTSZXKH-RVBZMBCESA-N (2,5-dioxopyrrolidin-1-yl) 5-[(3as,4s,6ar)-2-oxo-1,3,3a,4,6,6a-hexahydrothieno[3,4-d]imidazol-4-yl]pentanoate Chemical compound C([C@H]1[C@H]2NC(=O)N[C@H]2CS1)CCCC(=O)ON1C(=O)CCC1=O YMXHPSHLTSZXKH-RVBZMBCESA-N 0.000 description 1
- MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 description 1
- NLEBIOOXCVAHBD-YHBSTRCHSA-N (2r,3r,4s,5s,6r)-2-[(2r,3s,4r,5r,6s)-6-dodecoxy-4,5-dihydroxy-2-(hydroxymethyl)oxan-3-yl]oxy-6-(hydroxymethyl)oxane-3,4,5-triol Chemical compound O[C@@H]1[C@@H](O)[C@@H](OCCCCCCCCCCCC)O[C@H](CO)[C@H]1O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 NLEBIOOXCVAHBD-YHBSTRCHSA-N 0.000 description 1
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 1
- VILFTWLXLYIEMV-UHFFFAOYSA-N 1,5-difluoro-2,4-dinitrobenzene Chemical compound [O-][N+](=O)C1=CC([N+]([O-])=O)=C(F)C=C1F VILFTWLXLYIEMV-UHFFFAOYSA-N 0.000 description 1
- BBCZJRSZHIFFAB-UHFFFAOYSA-N 1-(dimethylamino)-2-hydroxypropane-1-sulfonic acid Chemical compound CC(O)C(N(C)C)S(O)(=O)=O BBCZJRSZHIFFAB-UHFFFAOYSA-N 0.000 description 1
- NOGLQXZIGOQIBD-UHFFFAOYSA-N 1-(dimethylazaniumyl)propane-1-sulfonate Chemical compound CCC(N(C)C)S(O)(=O)=O NOGLQXZIGOQIBD-UHFFFAOYSA-N 0.000 description 1
- 125000004066 1-hydroxyethyl group Chemical group [H]OC([H])([*])C([H])([H])[H] 0.000 description 1
- IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 description 1
- YBBNVCVOACOHIG-UHFFFAOYSA-N 2,2-diamino-1,4-bis(4-azidophenyl)-3-butylbutane-1,4-dione Chemical compound C=1C=C(N=[N+]=[N-])C=CC=1C(=O)C(N)(N)C(CCCC)C(=O)C1=CC=C(N=[N+]=[N-])C=C1 YBBNVCVOACOHIG-UHFFFAOYSA-N 0.000 description 1
- ASNTZYQMIUCEBV-UHFFFAOYSA-N 2,5-dioxo-1-[6-[3-(pyridin-2-yldisulfanyl)propanoylamino]hexanoyloxy]pyrrolidine-3-sulfonic acid Chemical compound O=C1C(S(=O)(=O)O)CC(=O)N1OC(=O)CCCCCNC(=O)CCSSC1=CC=CC=N1 ASNTZYQMIUCEBV-UHFFFAOYSA-N 0.000 description 1
- GVJXGCIPWAVXJP-UHFFFAOYSA-N 2,5-dioxo-1-oxoniopyrrolidine-3-sulfonate Chemical compound ON1C(=O)CC(S(O)(=O)=O)C1=O GVJXGCIPWAVXJP-UHFFFAOYSA-N 0.000 description 1
- FZDFGHZZPBUTGP-UHFFFAOYSA-N 2-[[2-[bis(carboxymethyl)amino]-3-(4-isothiocyanatophenyl)propyl]-[2-[bis(carboxymethyl)amino]propyl]amino]acetic acid Chemical compound OC(=O)CN(CC(O)=O)C(C)CN(CC(O)=O)CC(N(CC(O)=O)CC(O)=O)CC1=CC=C(N=C=S)C=C1 FZDFGHZZPBUTGP-UHFFFAOYSA-N 0.000 description 1
- FBUTXZSKZCQABC-UHFFFAOYSA-N 2-amino-1-methyl-7h-purine-6-thione Chemical compound S=C1N(C)C(N)=NC2=C1NC=N2 FBUTXZSKZCQABC-UHFFFAOYSA-N 0.000 description 1
- 125000000979 2-amino-2-oxoethyl group Chemical group [H]C([*])([H])C(=O)N([H])[H] 0.000 description 1
- BFSVOASYOCHEOV-UHFFFAOYSA-N 2-diethylaminoethanol Chemical compound CCN(CC)CCO BFSVOASYOCHEOV-UHFFFAOYSA-N 0.000 description 1
- XBBVURRQGJPTHH-UHFFFAOYSA-N 2-hydroxyacetic acid;2-hydroxypropanoic acid Chemical compound OCC(O)=O.CC(O)C(O)=O XBBVURRQGJPTHH-UHFFFAOYSA-N 0.000 description 1
- FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 1
- UMCMPZBLKLEWAF-BCTGSCMUSA-N 3-[(3-cholamidopropyl)dimethylammonio]propane-1-sulfonate Chemical compound C([C@H]1C[C@H]2O)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(=O)NCCC[N+](C)(C)CCCS([O-])(=O)=O)C)[C@@]2(C)[C@@H](O)C1 UMCMPZBLKLEWAF-BCTGSCMUSA-N 0.000 description 1
- GUQQBLRVXOUDTN-XOHPMCGNSA-N 3-[dimethyl-[3-[[(4r)-4-[(3r,5s,7r,8r,9s,10s,12s,13r,14s,17r)-3,7,12-trihydroxy-10,13-dimethyl-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1h-cyclopenta[a]phenanthren-17-yl]pentanoyl]amino]propyl]azaniumyl]-2-hydroxypropane-1-sulfonate Chemical compound C([C@H]1C[C@H]2O)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(=O)NCCC[N+](C)(C)CC(O)CS([O-])(=O)=O)C)[C@@]2(C)[C@@H](O)C1 GUQQBLRVXOUDTN-XOHPMCGNSA-N 0.000 description 1
- CNJLMVZFWLNOEP-UHFFFAOYSA-N 4,7,7-trimethylbicyclo[4.1.0]heptan-5-one Chemical compound O=C1C(C)CCC2C(C)(C)C12 CNJLMVZFWLNOEP-UHFFFAOYSA-N 0.000 description 1
- TVZGACDUOSZQKY-LBPRGKRZSA-N 4-aminofolic acid Chemical compound C1=NC2=NC(N)=NC(N)=C2N=C1CNC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 TVZGACDUOSZQKY-LBPRGKRZSA-N 0.000 description 1
- CJIJXIFQYOPWTF-UHFFFAOYSA-N 7-hydroxycoumarin Natural products O1C(=O)C=CC2=CC(O)=CC=C21 CJIJXIFQYOPWTF-UHFFFAOYSA-N 0.000 description 1
- 108010066676 Abrin Proteins 0.000 description 1
- 241000238876 Acari Species 0.000 description 1
- 102000012440 Acetylcholinesterase Human genes 0.000 description 1
- 108010022752 Acetylcholinesterase Proteins 0.000 description 1
- 241000251468 Actinopterygii Species 0.000 description 1
- 108010000239 Aequorin Proteins 0.000 description 1
- 108010088751 Albumins Proteins 0.000 description 1
- 102000009027 Albumins Human genes 0.000 description 1
- 206010003399 Arthropod bite Diseases 0.000 description 1
- 241000238421 Arthropoda Species 0.000 description 1
- 101000669426 Aspergillus restrictus Ribonuclease mitogillin Proteins 0.000 description 1
- 241000416162 Astragalus gummifer Species 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
- 102100026189 Beta-galactosidase Human genes 0.000 description 1
- 101800001415 Bri23 peptide Proteins 0.000 description 1
- NFSMUNQYUHPFAB-UHFFFAOYSA-N C(CCCCC)(=O)O.N1=C(C=CC=C1)SSCCC(=O)N Chemical compound C(CCCCC)(=O)O.N1=C(C=CC=C1)SSCCC(=O)N NFSMUNQYUHPFAB-UHFFFAOYSA-N 0.000 description 1
- 102100025248 C-X-C motif chemokine 10 Human genes 0.000 description 1
- 101710098275 C-X-C motif chemokine 10 Proteins 0.000 description 1
- 101800000655 C-terminal peptide Proteins 0.000 description 1
- 102400000107 C-terminal peptide Human genes 0.000 description 1
- 101710158575 Cap-specific mRNA (nucleoside-2'-O-)-methyltransferase Proteins 0.000 description 1
- 241000283707 Capra Species 0.000 description 1
- 101710132601 Capsid protein Proteins 0.000 description 1
- OKTJSMMVPCPJKN-NJFSPNSNSA-N Carbon-14 Chemical compound [14C] OKTJSMMVPCPJKN-NJFSPNSNSA-N 0.000 description 1
- 102100035882 Catalase Human genes 0.000 description 1
- 108010053835 Catalase Proteins 0.000 description 1
- 102000000844 Cell Surface Receptors Human genes 0.000 description 1
- 108010001857 Cell Surface Receptors Proteins 0.000 description 1
- 241000282693 Cercopithecidae Species 0.000 description 1
- 102000001327 Chemokine CCL5 Human genes 0.000 description 1
- 108010055166 Chemokine CCL5 Proteins 0.000 description 1
- 102000019034 Chemokines Human genes 0.000 description 1
- 108010012236 Chemokines Proteins 0.000 description 1
- 102000008186 Collagen Human genes 0.000 description 1
- 108010035532 Collagen Proteins 0.000 description 1
- 108010060123 Conjugate Vaccines Proteins 0.000 description 1
- 229920002261 Corn starch Polymers 0.000 description 1
- 241000699800 Cricetinae Species 0.000 description 1
- 241000699802 Cricetulus griseus Species 0.000 description 1
- 108700032819 Croton tiglium crotin II Proteins 0.000 description 1
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
- IGXWBGJHJZYPQS-SSDOTTSWSA-N D-Luciferin Chemical compound OC(=O)[C@H]1CSC(C=2SC3=CC=C(O)C=C3N=2)=N1 IGXWBGJHJZYPQS-SSDOTTSWSA-N 0.000 description 1
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
- SHZGCJCMOBCMKK-UHFFFAOYSA-N D-mannomethylose Natural products CC1OC(O)C(O)C(O)C1O SHZGCJCMOBCMKK-UHFFFAOYSA-N 0.000 description 1
- 102000053602 DNA Human genes 0.000 description 1
- 238000011238 DNA vaccination Methods 0.000 description 1
- XPDXVDYUQZHFPV-UHFFFAOYSA-N Dansyl Chloride Chemical compound C1=CC=C2C(N(C)C)=CC=CC2=C1S(Cl)(=O)=O XPDXVDYUQZHFPV-UHFFFAOYSA-N 0.000 description 1
- CYCGRDQQIOGCKX-UHFFFAOYSA-N Dehydro-luciferin Natural products OC(=O)C1=CSC(C=2SC3=CC(O)=CC=C3N=2)=N1 CYCGRDQQIOGCKX-UHFFFAOYSA-N 0.000 description 1
- 101710088194 Dehydrogenase Proteins 0.000 description 1
- 229920002307 Dextran Polymers 0.000 description 1
- 102000016607 Diphtheria Toxin Human genes 0.000 description 1
- 108010053187 Diphtheria Toxin Proteins 0.000 description 1
- 206010061818 Disease progression Diseases 0.000 description 1
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 1
- 241000792859 Enema Species 0.000 description 1
- 101800001632 Envelope protein E Proteins 0.000 description 1
- 241000283073 Equus caballus Species 0.000 description 1
- 206010015548 Euthanasia Diseases 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- BJGNCJDXODQBOB-UHFFFAOYSA-N Fivefly Luciferin Natural products OC(=O)C1CSC(C=2SC3=CC(O)=CC=C3N=2)=N1 BJGNCJDXODQBOB-UHFFFAOYSA-N 0.000 description 1
- PNNNRSAQSRJVSB-SLPGGIOYSA-N Fucose Natural products C[C@H](O)[C@@H](O)[C@H](O)[C@H](O)C=O PNNNRSAQSRJVSB-SLPGGIOYSA-N 0.000 description 1
- 108700004714 Gelonium multiflorum GEL Proteins 0.000 description 1
- 239000004366 Glucose oxidase Substances 0.000 description 1
- 108010015776 Glucose oxidase Proteins 0.000 description 1
- SXRSQZLOMIGNAQ-UHFFFAOYSA-N Glutaraldehyde Chemical compound O=CCCCC=O SXRSQZLOMIGNAQ-UHFFFAOYSA-N 0.000 description 1
- JZNWSCPGTDBMEW-UHFFFAOYSA-N Glycerophosphorylethanolamin Natural products NCCOP(O)(=O)OCC(O)CO JZNWSCPGTDBMEW-UHFFFAOYSA-N 0.000 description 1
- 108010017213 Granulocyte-Macrophage Colony-Stimulating Factor Proteins 0.000 description 1
- 102000004457 Granulocyte-Macrophage Colony-Stimulating Factor Human genes 0.000 description 1
- 208000031886 HIV Infections Diseases 0.000 description 1
- 208000037357 HIV infectious disease Diseases 0.000 description 1
- 241000700721 Hepatitis B virus Species 0.000 description 1
- 101100005713 Homo sapiens CD4 gene Proteins 0.000 description 1
- 101000917839 Homo sapiens Low affinity immunoglobulin gamma Fc region receptor III-B Proteins 0.000 description 1
- 108090000144 Human Proteins Proteins 0.000 description 1
- 102000003839 Human Proteins Human genes 0.000 description 1
- 102000008100 Human Serum Albumin Human genes 0.000 description 1
- 108091006905 Human Serum Albumin Proteins 0.000 description 1
- 241000713772 Human immunodeficiency virus 1 Species 0.000 description 1
- UGQMRVRMYYASKQ-UHFFFAOYSA-N Hypoxanthine nucleoside Natural products OC1C(O)C(CO)OC1N1C(NC=NC2=O)=C2N=C1 UGQMRVRMYYASKQ-UHFFFAOYSA-N 0.000 description 1
- 108010054477 Immunoglobulin Fab Fragments Proteins 0.000 description 1
- 102000001706 Immunoglobulin Fab Fragments Human genes 0.000 description 1
- 102000018071 Immunoglobulin Fc Fragments Human genes 0.000 description 1
- 108010091135 Immunoglobulin Fc Fragments Proteins 0.000 description 1
- 108700005091 Immunoglobulin Genes Proteins 0.000 description 1
- 238000012695 Interfacial polymerization Methods 0.000 description 1
- 102000008070 Interferon-gamma Human genes 0.000 description 1
- 108010074328 Interferon-gamma Proteins 0.000 description 1
- 102000013462 Interleukin-12 Human genes 0.000 description 1
- 108010065805 Interleukin-12 Proteins 0.000 description 1
- SHZGCJCMOBCMKK-DHVFOXMCSA-N L-fucopyranose Chemical compound C[C@@H]1OC(O)[C@@H](O)[C@H](O)[C@@H]1O SHZGCJCMOBCMKK-DHVFOXMCSA-N 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- 108010000817 Leuprolide Proteins 0.000 description 1
- 102100029193 Low affinity immunoglobulin gamma Fc region receptor III-A Human genes 0.000 description 1
- 101710099301 Low affinity immunoglobulin gamma Fc region receptor III-A Proteins 0.000 description 1
- 102100029185 Low affinity immunoglobulin gamma Fc region receptor III-B Human genes 0.000 description 1
- DDWFXDSYGUXRAY-UHFFFAOYSA-N Luciferin Natural products CCc1c(C)c(CC2NC(=O)C(=C2C=C)C)[nH]c1Cc3[nH]c4C(=C5/NC(CC(=O)O)C(C)C5CC(=O)O)CC(=O)c4c3C DDWFXDSYGUXRAY-UHFFFAOYSA-N 0.000 description 1
- 108010074338 Lymphokines Proteins 0.000 description 1
- 102000008072 Lymphokines Human genes 0.000 description 1
- 102000043131 MHC class II family Human genes 0.000 description 1
- 108091054438 MHC class II family Proteins 0.000 description 1
- 239000004907 Macro-emulsion Substances 0.000 description 1
- 102000018897 Membrane Fusion Proteins Human genes 0.000 description 1
- 108010027796 Membrane Fusion Proteins Proteins 0.000 description 1
- 244000246386 Mentha pulegium Species 0.000 description 1
- 235000016257 Mentha pulegium Nutrition 0.000 description 1
- 235000004357 Mentha x piperita Nutrition 0.000 description 1
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 1
- 241000713869 Moloney murine leukemia virus Species 0.000 description 1
- 241000699660 Mus musculus Species 0.000 description 1
- NQTADLQHYWFPDB-UHFFFAOYSA-N N-Hydroxysuccinimide Chemical compound ON1C(=O)CCC1=O NQTADLQHYWFPDB-UHFFFAOYSA-N 0.000 description 1
- 230000004988 N-glycosylation Effects 0.000 description 1
- 241000207746 Nicotiana benthamiana Species 0.000 description 1
- 230000004989 O-glycosylation Effects 0.000 description 1
- 108020005187 Oligonucleotide Probes Proteins 0.000 description 1
- 108010038807 Oligopeptides Proteins 0.000 description 1
- 102000015636 Oligopeptides Human genes 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 241001494479 Pecora Species 0.000 description 1
- 108010067902 Peptide Library Proteins 0.000 description 1
- 241000009328 Perro Species 0.000 description 1
- 206010057249 Phagocytosis Diseases 0.000 description 1
- 108010053210 Phycocyanin Proteins 0.000 description 1
- 108010004729 Phycoerythrin Proteins 0.000 description 1
- 101100413173 Phytolacca americana PAP2 gene Proteins 0.000 description 1
- 241000276498 Pollachius virens Species 0.000 description 1
- 229920002732 Polyanhydride Polymers 0.000 description 1
- 229920000954 Polyglycolide Polymers 0.000 description 1
- 108010039918 Polylysine Proteins 0.000 description 1
- 229920001710 Polyorthoester Polymers 0.000 description 1
- 229920002685 Polyoxyl 35CastorOil Polymers 0.000 description 1
- 241000288906 Primates Species 0.000 description 1
- 102000007327 Protamines Human genes 0.000 description 1
- 108010007568 Protamines Proteins 0.000 description 1
- 241000589517 Pseudomonas aeruginosa Species 0.000 description 1
- 108091030071 RNAI Proteins 0.000 description 1
- 239000012980 RPMI-1640 medium Substances 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- 241000283984 Rodentia Species 0.000 description 1
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- DWAQJAXMDSEUJJ-UHFFFAOYSA-M Sodium bisulfite Chemical compound [Na+].OS([O-])=O DWAQJAXMDSEUJJ-UHFFFAOYSA-M 0.000 description 1
- 238000002105 Southern blotting Methods 0.000 description 1
- 241000269319 Squalius cephalus Species 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- 241000282898 Sus scrofa Species 0.000 description 1
- 230000024932 T cell mediated immunity Effects 0.000 description 1
- 108091008874 T cell receptors Proteins 0.000 description 1
- 102000016266 T-Cell Antigen Receptors Human genes 0.000 description 1
- 102100036011 T-cell surface glycoprotein CD4 Human genes 0.000 description 1
- 210000001744 T-lymphocyte Anatomy 0.000 description 1
- 101710120037 Toxin CcdB Proteins 0.000 description 1
- 229920001615 Tragacanth Polymers 0.000 description 1
- 235000008322 Trichosanthes cucumerina Nutrition 0.000 description 1
- 229920004929 Triton X-114 Polymers 0.000 description 1
- 240000001866 Vernicia fordii Species 0.000 description 1
- 206010058874 Viraemia Diseases 0.000 description 1
- 108010067390 Viral Proteins Proteins 0.000 description 1
- 201000006449 West Nile encephalitis Diseases 0.000 description 1
- 206010057293 West Nile viral infection Diseases 0.000 description 1
- 238000012452 Xenomouse strains Methods 0.000 description 1
- 239000003070 absorption delaying agent Substances 0.000 description 1
- 150000001242 acetic acid derivatives Chemical class 0.000 description 1
- OFLXLNCGODUUOT-UHFFFAOYSA-N acetohydrazide Chemical class C\C(O)=N\N OFLXLNCGODUUOT-UHFFFAOYSA-N 0.000 description 1
- 229940022698 acetylcholinesterase Drugs 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 239000000443 aerosol Substances 0.000 description 1
- 125000003295 alanine group Chemical group N[C@@H](C)C(=O)* 0.000 description 1
- 150000001299 aldehydes Chemical class 0.000 description 1
- 239000000783 alginic acid Substances 0.000 description 1
- 235000010443 alginic acid Nutrition 0.000 description 1
- 229920000615 alginic acid Polymers 0.000 description 1
- 229960001126 alginic acid Drugs 0.000 description 1
- 150000004781 alginic acids Chemical class 0.000 description 1
- 125000005599 alkyl carboxylate group Chemical group 0.000 description 1
- 108010001818 alpha-sarcin Proteins 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 229960003896 aminopterin Drugs 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 230000000840 anti-viral effect Effects 0.000 description 1
- 238000009175 antibody therapy Methods 0.000 description 1
- 238000011230 antibody-based therapy Methods 0.000 description 1
- 210000000628 antibody-producing cell Anatomy 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 235000006708 antioxidants Nutrition 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- PYMYPHUHKUWMLA-UHFFFAOYSA-N arabinose Natural products OCC(O)C(O)C(O)C=O PYMYPHUHKUWMLA-UHFFFAOYSA-N 0.000 description 1
- 210000001106 artificial yeast chromosome Anatomy 0.000 description 1
- 230000002238 attenuated effect Effects 0.000 description 1
- DMLAVOWQYNRWNQ-UHFFFAOYSA-N azobenzene Chemical compound C1=CC=CC=C1N=NC1=CC=CC=C1 DMLAVOWQYNRWNQ-UHFFFAOYSA-N 0.000 description 1
- 230000003385 bacteriostatic effect Effects 0.000 description 1
- 230000004888 barrier function Effects 0.000 description 1
- 235000019445 benzyl alcohol Nutrition 0.000 description 1
- 102000012740 beta Adrenergic Receptors Human genes 0.000 description 1
- 108010079452 beta Adrenergic Receptors Proteins 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
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- 108010005774 beta-Galactosidase Proteins 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
- 239000003833 bile salt Substances 0.000 description 1
- 229940093761 bile salts Drugs 0.000 description 1
- 229920000249 biocompatible polymer Polymers 0.000 description 1
- 238000001574 biopsy Methods 0.000 description 1
- 238000007413 biotinylation Methods 0.000 description 1
- 230000006287 biotinylation Effects 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 238000009534 blood test Methods 0.000 description 1
- 238000006664 bond formation reaction Methods 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 239000001569 carbon dioxide Substances 0.000 description 1
- 229910002092 carbon dioxide Inorganic materials 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 238000000423 cell based assay Methods 0.000 description 1
- 230000022534 cell killing Effects 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 230000036755 cellular response Effects 0.000 description 1
- 210000003169 central nervous system Anatomy 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 229960004926 chlorobutanol Drugs 0.000 description 1
- 235000012000 cholesterol Nutrition 0.000 description 1
- 150000001860 citric acid derivatives Chemical class 0.000 description 1
- 238000010367 cloning Methods 0.000 description 1
- 238000005354 coacervation Methods 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 229940110456 cocoa butter Drugs 0.000 description 1
- 235000019868 cocoa butter Nutrition 0.000 description 1
- 229920001436 collagen Polymers 0.000 description 1
- 229940075614 colloidal silicon dioxide Drugs 0.000 description 1
- 239000000084 colloidal system Substances 0.000 description 1
- 238000010668 complexation reaction Methods 0.000 description 1
- 238000009833 condensation Methods 0.000 description 1
- 230000005494 condensation Effects 0.000 description 1
- 229940031670 conjugate vaccine Drugs 0.000 description 1
- 230000001268 conjugating effect Effects 0.000 description 1
- 239000000356 contaminant Substances 0.000 description 1
- 238000013270 controlled release Methods 0.000 description 1
- 239000008120 corn starch Substances 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- 239000003431 cross linking reagent Substances 0.000 description 1
- 125000000151 cysteine group Chemical group N[C@@H](CS)C(=O)* 0.000 description 1
- 210000000805 cytoplasm Anatomy 0.000 description 1
- 230000002950 deficient Effects 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 230000001934 delay Effects 0.000 description 1
- 230000003111 delayed effect Effects 0.000 description 1
- 239000008121 dextrose Substances 0.000 description 1
- 238000002405 diagnostic procedure Methods 0.000 description 1
- 238000000502 dialysis Methods 0.000 description 1
- 229930191339 dianthin Natural products 0.000 description 1
- UGMCXQCYOVCMTB-UHFFFAOYSA-K dihydroxy(stearato)aluminium Chemical compound CCCCCCCCCCCCCCCCCC(=O)O[Al](O)O UGMCXQCYOVCMTB-UHFFFAOYSA-K 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 206010013023 diphtheria Diseases 0.000 description 1
- 150000002016 disaccharides Chemical class 0.000 description 1
- 230000005750 disease progression Effects 0.000 description 1
- 239000007884 disintegrant Substances 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- ZWIBGKZDAWNIFC-UHFFFAOYSA-N disuccinimidyl suberate Chemical compound O=C1CCC(=O)N1OC(=O)CCCCCCC(=O)ON1C(=O)CCC1=O ZWIBGKZDAWNIFC-UHFFFAOYSA-N 0.000 description 1
- 230000009977 dual effect Effects 0.000 description 1
- 239000012636 effector Substances 0.000 description 1
- 230000005670 electromagnetic radiation Effects 0.000 description 1
- 238000004520 electroporation Methods 0.000 description 1
- 230000008030 elimination Effects 0.000 description 1
- 238000003379 elimination reaction Methods 0.000 description 1
- 210000002889 endothelial cell Anatomy 0.000 description 1
- 239000002158 endotoxin Substances 0.000 description 1
- 239000007920 enema Substances 0.000 description 1
- 229940079360 enema for constipation Drugs 0.000 description 1
- 108010028531 enomycin Proteins 0.000 description 1
- 230000002255 enzymatic effect Effects 0.000 description 1
- RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 150000002222 fluorine compounds Chemical class 0.000 description 1
- 235000013355 food flavoring agent Nutrition 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- 238000004108 freeze drying Methods 0.000 description 1
- 230000002538 fungal effect Effects 0.000 description 1
- IECPWNUMDGFDKC-MZJAQBGESA-M fusidate Chemical class O[C@@H]([C@@H]12)C[C@H]3\C(=C(/CCC=C(C)C)C([O-])=O)[C@@H](OC(C)=O)C[C@]3(C)[C@@]2(C)CC[C@@H]2[C@]1(C)CC[C@@H](O)[C@H]2C IECPWNUMDGFDKC-MZJAQBGESA-M 0.000 description 1
- 229940044627 gamma-interferon Drugs 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 238000001502 gel electrophoresis Methods 0.000 description 1
- 239000007903 gelatin capsule Substances 0.000 description 1
- 230000009368 gene silencing by RNA Effects 0.000 description 1
- 210000004602 germ cell Anatomy 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 230000005182 global health Effects 0.000 description 1
- 229940116332 glucose oxidase Drugs 0.000 description 1
- 235000019420 glucose oxidase Nutrition 0.000 description 1
- 229930182478 glucoside Natural products 0.000 description 1
- 229930195712 glutamate Natural products 0.000 description 1
- 229940049906 glutamate Drugs 0.000 description 1
- 229960002989 glutamic acid Drugs 0.000 description 1
- 125000005456 glyceride group Chemical group 0.000 description 1
- 150000002337 glycosamines Chemical group 0.000 description 1
- 238000000227 grinding Methods 0.000 description 1
- 239000003966 growth inhibitor Substances 0.000 description 1
- 230000003862 health status Effects 0.000 description 1
- 230000013632 homeostatic process Effects 0.000 description 1
- 235000001050 hortel pimenta Nutrition 0.000 description 1
- 208000033519 human immunodeficiency virus infectious disease Diseases 0.000 description 1
- 230000008348 humoral response Effects 0.000 description 1
- 238000009396 hybridization Methods 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- OUUQCZGPVNCOIJ-UHFFFAOYSA-N hydroperoxyl Chemical compound O[O] OUUQCZGPVNCOIJ-UHFFFAOYSA-N 0.000 description 1
- 229920001600 hydrophobic polymer Polymers 0.000 description 1
- 238000012872 hydroxylapatite chromatography Methods 0.000 description 1
- 229920003063 hydroxymethyl cellulose Polymers 0.000 description 1
- 229940031574 hydroxymethyl cellulose Drugs 0.000 description 1
- 150000002463 imidates Chemical class 0.000 description 1
- 230000002519 immonomodulatory effect Effects 0.000 description 1
- 229940127121 immunoconjugate Drugs 0.000 description 1
- 230000005847 immunogenicity Effects 0.000 description 1
- 230000002480 immunoprotective effect Effects 0.000 description 1
- 230000001024 immunotherapeutic effect Effects 0.000 description 1
- 239000007943 implant Substances 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 238000007901 in situ hybridization Methods 0.000 description 1
- 238000010348 incorporation Methods 0.000 description 1
- 239000003701 inert diluent Substances 0.000 description 1
- 230000002458 infectious effect Effects 0.000 description 1
- 230000008595 infiltration Effects 0.000 description 1
- 238000001764 infiltration Methods 0.000 description 1
- 239000007972 injectable composition Substances 0.000 description 1
- 230000002687 intercalation Effects 0.000 description 1
- 238000009830 intercalation Methods 0.000 description 1
- 230000002452 interceptive effect Effects 0.000 description 1
- 238000000185 intracerebroventricular administration Methods 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000007912 intraperitoneal administration Methods 0.000 description 1
- 239000007928 intraperitoneal injection Substances 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 150000002605 large molecules Chemical class 0.000 description 1
- 230000002045 lasting effect Effects 0.000 description 1
- IZWSFJTYBVKZNK-UHFFFAOYSA-N lauryl sulfobetaine Chemical compound CCCCCCCCCCCC[N+](C)(C)CCCS([O-])(=O)=O IZWSFJTYBVKZNK-UHFFFAOYSA-N 0.000 description 1
- 235000010445 lecithin Nutrition 0.000 description 1
- 239000000787 lecithin Substances 0.000 description 1
- 229940067606 lecithin Drugs 0.000 description 1
- 210000000265 leukocyte Anatomy 0.000 description 1
- 229960004338 leuprorelin Drugs 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- XMGQYMWWDOXHJM-UHFFFAOYSA-N limonene Chemical compound CC(=C)C1CCC(C)=CC1 XMGQYMWWDOXHJM-UHFFFAOYSA-N 0.000 description 1
- 238000001638 lipofection Methods 0.000 description 1
- 239000007791 liquid phase Substances 0.000 description 1
- 238000011068 loading method Methods 0.000 description 1
- 230000004807 localization Effects 0.000 description 1
- 239000007937 lozenge Substances 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- HWYHZTIRURJOHG-UHFFFAOYSA-N luminol Chemical compound O=C1NNC(=O)C2=C1C(N)=CC=C2 HWYHZTIRURJOHG-UHFFFAOYSA-N 0.000 description 1
- 210000002751 lymph Anatomy 0.000 description 1
- 210000001165 lymph node Anatomy 0.000 description 1
- 235000018977 lysine Nutrition 0.000 description 1
- 125000003588 lysine group Chemical group [H]N([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 description 1
- 229920002521 macromolecule Polymers 0.000 description 1
- 210000002540 macrophage Anatomy 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 238000012423 maintenance Methods 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- DFTAZNAEBRBBKP-UHFFFAOYSA-N methyl 4-sulfanylbutanimidate Chemical compound COC(=N)CCCS DFTAZNAEBRBBKP-UHFFFAOYSA-N 0.000 description 1
- 239000004292 methyl p-hydroxybenzoate Substances 0.000 description 1
- 235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 1
- 229960001047 methyl salicylate Drugs 0.000 description 1
- 229960002216 methylparaben Drugs 0.000 description 1
- 239000004530 micro-emulsion Substances 0.000 description 1
- 229940016286 microcrystalline cellulose Drugs 0.000 description 1
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 1
- 239000008108 microcrystalline cellulose Substances 0.000 description 1
- 238000000520 microinjection Methods 0.000 description 1
- 239000004005 microsphere Substances 0.000 description 1
- 150000002772 monosaccharides Chemical class 0.000 description 1
- 239000004570 mortar (masonry) Substances 0.000 description 1
- 239000002324 mouth wash Substances 0.000 description 1
- 229940051866 mouthwash Drugs 0.000 description 1
- ZTLGJPIZUOVDMT-UHFFFAOYSA-N n,n-dichlorotriazin-4-amine Chemical compound ClN(Cl)C1=CC=NN=N1 ZTLGJPIZUOVDMT-UHFFFAOYSA-N 0.000 description 1
- UMWKZHPREXJQGR-XOSAIJSUSA-N n-methyl-n-[(2s,3r,4r,5r)-2,3,4,5,6-pentahydroxyhexyl]decanamide Chemical compound CCCCCCCCCC(=O)N(C)C[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO UMWKZHPREXJQGR-XOSAIJSUSA-N 0.000 description 1
- SBWGZAXBCCNRTM-CTHBEMJXSA-N n-methyl-n-[(2s,3r,4r,5r)-2,3,4,5,6-pentahydroxyhexyl]octanamide Chemical compound CCCCCCCC(=O)N(C)C[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO SBWGZAXBCCNRTM-CTHBEMJXSA-N 0.000 description 1
- 239000002088 nanocapsule Substances 0.000 description 1
- 239000002105 nanoparticle Substances 0.000 description 1
- 239000007922 nasal spray Substances 0.000 description 1
- 239000006218 nasal suppository Substances 0.000 description 1
- 239000006199 nebulizer Substances 0.000 description 1
- 210000002569 neuron Anatomy 0.000 description 1
- 239000002547 new drug Substances 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 239000012457 nonaqueous media Substances 0.000 description 1
- HEGSGKPQLMEBJL-RKQHYHRCSA-N octyl beta-D-glucopyranoside Chemical compound CCCCCCCCO[C@@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O HEGSGKPQLMEBJL-RKQHYHRCSA-N 0.000 description 1
- 239000002751 oligonucleotide probe Substances 0.000 description 1
- 229920001542 oligosaccharide Chemical class 0.000 description 1
- 150000002482 oligosaccharides Chemical class 0.000 description 1
- 239000007968 orange flavor Substances 0.000 description 1
- 150000002894 organic compounds Chemical class 0.000 description 1
- 210000001672 ovary Anatomy 0.000 description 1
- QUANRIQJNFHVEU-UHFFFAOYSA-N oxirane;propane-1,2,3-triol Chemical compound C1CO1.OCC(O)CO QUANRIQJNFHVEU-UHFFFAOYSA-N 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
- 210000005105 peripheral blood lymphocyte Anatomy 0.000 description 1
- 230000002688 persistence Effects 0.000 description 1
- 230000008782 phagocytosis Effects 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- 229960003742 phenol Drugs 0.000 description 1
- 108010076042 phenomycin Proteins 0.000 description 1
- 235000021317 phosphate Nutrition 0.000 description 1
- WTJKGGKOPKCXLL-RRHRGVEJSA-N phosphatidylcholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCCC=CCCCCCCCC WTJKGGKOPKCXLL-RRHRGVEJSA-N 0.000 description 1
- 150000008104 phosphatidylethanolamines Chemical class 0.000 description 1
- 150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
- 230000004962 physiological condition Effects 0.000 description 1
- 239000002504 physiological saline solution Substances 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 210000002381 plasma Anatomy 0.000 description 1
- 229920003023 plastic Polymers 0.000 description 1
- 239000004033 plastic Substances 0.000 description 1
- 229920003229 poly(methyl methacrylate) Polymers 0.000 description 1
- 229920000728 polyester Polymers 0.000 description 1
- 239000008389 polyethoxylated castor oil Substances 0.000 description 1
- 239000004633 polyglycolic acid Substances 0.000 description 1
- 229920002338 polyhydroxyethylmethacrylate Polymers 0.000 description 1
- 239000004626 polylactic acid Substances 0.000 description 1
- 229920000656 polylysine Polymers 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 239000004926 polymethyl methacrylate Substances 0.000 description 1
- 229920005862 polyol Polymers 0.000 description 1
- 150000003077 polyols Chemical class 0.000 description 1
- 229920001282 polysaccharide Chemical class 0.000 description 1
- 239000005017 polysaccharide Chemical class 0.000 description 1
- 150000004804 polysaccharides Chemical class 0.000 description 1
- 229920002451 polyvinyl alcohol Polymers 0.000 description 1
- 239000011148 porous material Substances 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 238000011533 pre-incubation Methods 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 230000003449 preventive effect Effects 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 230000000644 propagated effect Effects 0.000 description 1
- 239000003380 propellant Substances 0.000 description 1
- 229940021993 prophylactic vaccine Drugs 0.000 description 1
- 229940048914 protamine Drugs 0.000 description 1
- 238000000159 protein binding assay Methods 0.000 description 1
- 235000004252 protein component Nutrition 0.000 description 1
- 238000010377 protein imaging Methods 0.000 description 1
- 210000001938 protoplast Anatomy 0.000 description 1
- 238000011002 quantification Methods 0.000 description 1
- 238000003653 radioligand binding assay Methods 0.000 description 1
- 239000000376 reactant Substances 0.000 description 1
- 230000010076 replication Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000001177 retroviral effect Effects 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 description 1
- 229940081974 saccharin Drugs 0.000 description 1
- 235000019204 saccharin Nutrition 0.000 description 1
- 239000000901 saccharin and its Na,K and Ca salt Substances 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 238000013391 scatchard analysis Methods 0.000 description 1
- 238000003345 scintillation counting Methods 0.000 description 1
- 208000037921 secondary disease Diseases 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 230000019491 signal transduction Effects 0.000 description 1
- 235000010267 sodium hydrogen sulphite Nutrition 0.000 description 1
- ZAPNXDUFCQIHFS-UHFFFAOYSA-M sodium;2,5-dioxo-1-[6-[3-(pyridin-2-yldisulfanyl)propanoylamino]hexanoyloxy]pyrrolidine-3-sulfonate Chemical compound [Na+].O=C1C(S(=O)(=O)[O-])CC(=O)N1OC(=O)CCCCCNC(=O)CCSSC1=CC=CC=N1 ZAPNXDUFCQIHFS-UHFFFAOYSA-M 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 210000001082 somatic cell Anatomy 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 210000004989 spleen cell Anatomy 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 238000011146 sterile filtration Methods 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 239000007929 subcutaneous injection Substances 0.000 description 1
- 238000010254 subcutaneous injection Methods 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- KZNICNPSHKQLFF-UHFFFAOYSA-N succinimide Chemical class O=C1CCC(=O)N1 KZNICNPSHKQLFF-UHFFFAOYSA-N 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 150000005846 sugar alcohols Polymers 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- 125000000020 sulfo group Chemical group O=S(=O)([*])O[H] 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000002511 suppository base Substances 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 238000013268 sustained release Methods 0.000 description 1
- 239000012730 sustained-release form Substances 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 230000017960 syncytium formation Effects 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 238000007910 systemic administration Methods 0.000 description 1
- 229940021747 therapeutic vaccine Drugs 0.000 description 1
- RTKIYNMVFMVABJ-UHFFFAOYSA-L thimerosal Chemical compound [Na+].CC[Hg]SC1=CC=CC=C1C([O-])=O RTKIYNMVFMVABJ-UHFFFAOYSA-L 0.000 description 1
- 229940033663 thimerosal Drugs 0.000 description 1
- 150000007970 thio esters Chemical class 0.000 description 1
- CNHYKKNIIGEXAY-UHFFFAOYSA-N thiolan-2-imine Chemical compound N=C1CCCS1 CNHYKKNIIGEXAY-UHFFFAOYSA-N 0.000 description 1
- 229940104230 thymidine Drugs 0.000 description 1
- RUELTTOHQODFPA-UHFFFAOYSA-N toluene 2,6-diisocyanate Chemical compound CC1=C(N=C=O)C=CC=C1N=C=O RUELTTOHQODFPA-UHFFFAOYSA-N 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
- 238000010361 transduction Methods 0.000 description 1
- 230000026683 transduction Effects 0.000 description 1
- 238000001890 transfection Methods 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 238000011830 transgenic mouse model Methods 0.000 description 1
- 238000011269 treatment regimen Methods 0.000 description 1
- 229930013292 trichothecene Natural products 0.000 description 1
- 150000003327 trichothecene derivatives Chemical class 0.000 description 1
- GPRLSGONYQIRFK-MNYXATJNSA-N triton Chemical compound [3H+] GPRLSGONYQIRFK-MNYXATJNSA-N 0.000 description 1
- ORHBXUUXSCNDEV-UHFFFAOYSA-N umbelliferone Chemical compound C1=CC(=O)OC2=CC(O)=CC=C21 ORHBXUUXSCNDEV-UHFFFAOYSA-N 0.000 description 1
- HFTAFOQKODTIJY-UHFFFAOYSA-N umbelliferone Natural products Cc1cc2C=CC(=O)Oc2cc1OCC=CC(C)(C)O HFTAFOQKODTIJY-UHFFFAOYSA-N 0.000 description 1
- 241001529453 unidentified herpesvirus Species 0.000 description 1
- 238000001291 vacuum drying Methods 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
- 230000029812 viral genome replication Effects 0.000 description 1
- 239000008215 water for injection Substances 0.000 description 1
Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/08—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from viruses
- C07K16/10—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from viruses from RNA viruses
- C07K16/1081—Togaviridae, e.g. flavivirus, rubella virus, hog cholera virus
-
- 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
- A61K39/12—Viral antigens
-
- 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]
- A61P29/02—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID] without antiinflammatory effect
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/14—Antivirals for RNA viruses
-
- 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
- A61P37/04—Immunostimulants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- 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
- A61K2039/505—Medicinal preparations containing antigens or antibodies comprising 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
- A61K2039/545—Medicinal preparations containing antigens or antibodies characterised by the dose, timing or administration schedule
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/20—Immunoglobulins specific features characterized by taxonomic origin
- C07K2317/24—Immunoglobulins specific features characterized by taxonomic origin containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
- C07K2317/52—Constant or Fc region; Isotype
- C07K2317/524—CH2 domain
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
- C07K2317/56—Immunoglobulins specific features characterized by immunoglobulin fragments variable (Fv) region, i.e. VH and/or VL
- C07K2317/565—Complementarity determining region [CDR]
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
- C07K2317/71—Decreased effector function due to an Fc-modification
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
- C07K2317/76—Antagonist effect on antigen, e.g. neutralization or inhibition of binding
-
- 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
- C12N2770/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA ssRNA viruses positive-sense
- C12N2770/00011—Details
- C12N2770/24011—Flaviviridae
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Virology (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Immunology (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Molecular Biology (AREA)
- Biophysics (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Genetics & Genomics (AREA)
- Biochemistry (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Oncology (AREA)
- Communicable Diseases (AREA)
- Microbiology (AREA)
- Mycology (AREA)
- Epidemiology (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Peptides Or Proteins (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
Description
本願は2013年3月15日に出願された米国特許出願第61/792,336号の恩典および同出願への優先権を主張し、同出願の内容は参照により本明細書にその全文が組み入れられる。
本発明は、概して、フラビウイルス中和抗体ならびにその使用方法に関する。
本発明は、米国国立衛生研究所によって交付されたAI0703431の下、政府の支援を受けてなされた。米国政府は本発明に一定の権利を有する。
ウエストナイルウイルスやデングウイルスなどのフラビウイルスは地球規模の健康に著しい脅威を与える。ウエストナイルウイルスは複数の種に致命的な髄膜炎または脳炎をもたらしうる熱病の原因になる。鳥と蚊はどちらもウエストナイルウイルスを運ぶことができ、そのことが世界的に驚くべきペースでのこのウイルスの伝播を可能にしてきた。同様に、デングウイルスの4つの血清型も蚊咬傷を介した伝染が可能であり、毎年、500,000例の入院と20,000例の死亡とを含む何千万例というデング熱のヒト症例の原因になり、マラリアに匹敵する経済的負担を伴う。
を、CDR2がアミノ酸配列
を、かつCDR3がアミノ酸配列
をそれぞれ含む、3つのCDRを持つ重鎖と、CDR1がアミノ酸配列
を、CDR2がアミノ酸配列
を、かつCDR3がアミノ酸配列
をそれぞれ含む、3つのCDRを持つ軽鎖とを有する、単離されたヒト化モノクローナル抗体を提供する。本抗体は、Fcγ受容体に結合しないように改変されたFc領域を有し、フラビウイルスに結合する。例示的なFc領域を本明細書において開示する。
a.アミノ酸配列
をそれぞれ含む3つのCDRを持つ、重鎖と、
b.アミノ酸配列
をそれぞれ含む3つのCDRを持つ、軽鎖と、
c. Fcγ受容体に結合しないように改変されたFc領域と
を含み、かつフラビウイルスに結合する、単離されたヒト化モノクローナル抗体。
[本発明1002]
SEQ ID NO: 1を有するVHアミノ酸配列と、SEQ ID NO: 3を有するVLアミノ酸配列と、Fcγ受容体に結合しないように改変されたFc領域とを含み、かつフラビウイルスに結合する、単離されたヒト化モノクローナル抗体。
[本発明1003]
SEQ ID NO: 2を有するVHヌクレオチド配列と、SEQ ID NO: 4を有するVLヌクレオチド配列と、Fcγ受容体に結合しないように改変されたFc領域とを含み、かつフラビウイルスに結合する、単離されたヒト化モノクローナル抗体。
[本発明1004]
フラビウイルス感染の抗体依存性増強に寄与しない、前記本発明のいずれかの抗体。
[本発明1005]
フラビウイルスを中和する、前記本発明のいずれかの抗体。
[本発明1006]
Fc領域がアミノ酸位置234および235に変異を含有する、前記本発明のいずれかの抗体。
[本発明1007]
変異がL234AおよびL235Aである、本発明1006の抗体。
[本発明1008]
Fc領域がSEQ ID NO: 7またはSEQ ID NO: 13のアミノ酸配列を含む、本発明1006の抗体。
[本発明1009]
改変されたFc領域が新生児型Fc受容体に結合する、前記本発明のいずれかの抗体。
[本発明1010]
フラビウイルスが、ウエストナイルウイルス、デングウイルス(血清型1〜4)、セントルイス脳炎ウイルス、黄熱ウイルス、日本脳炎ウイルス、およびマレー渓谷脳炎ウイルスである、前記本発明のいずれかの抗体。
[本発明1011]
植物において産生される、前記本発明のいずれかの抗体。
[本発明1012]
治療用作用物質に連結されている、前記本発明のいずれかの抗体。
[本発明1013]
前記治療用作用物質が、毒素、放射性標識、siRNA、小分子、またはサイトカインである、本発明1012の抗体。
[本発明1014]
前記サイトカインがTGF-βである、本発明1013の抗体。
[本発明1015]
前記本発明のいずれかの抗体を産生する、細胞。
[本発明1016]
対象に本発明1001〜1014のいずれかの抗体を投与する工程を含む、フラビウイルス感染の抗体依存性増強を防止する方法。
[本発明1017]
前記抗体がフラビウイルスによる初回感染後に投与される、本発明1016の方法。
[本発明1018]
本発明1001〜1013のいずれかの抗体とワクチンとを対象に投与する工程を含む、ワクチン効率を増加させる方法。
[本発明1019]
前記抗体と前記ワクチンが逐次的にまたは同時に投与される、本発明1018の方法。
[本発明1020]
前記ワクチンがウイルスワクチンである、本発明1018の方法。
[本発明1021]
フラビウイルス感染の症状を処置または軽減する方法であって、その必要がある対象に本発明1001〜1014のいずれかの抗体を含む組成物を投与する工程を含む、方法。
[本発明1022]
フラビウイルス感染の1つまたは複数の症状の発症を遅延させる方法であって、その必要がある対象に本発明1001〜1014のいずれかの抗体を含む組成物を投与する工程を含む、方法。
[本発明1023]
抗ウイルス剤を投与する工程をさらに含む、本発明1021または1022の方法。
[本発明1024]
抗ウイルス剤が、抗体、治療用作用物質に連結された抗体、または小分子である、本発明1023の方法。
[本発明1025]
前記抗体と抗ウイルス剤が逐次的にまたは同時に投与される、本発明1023の方法。
[本発明1026]
前記1つまたは複数の症状が、体重減少、麻痺、発熱、頭痛、悪心、嘔吐、発疹、および身体痛を含む、本発明1021〜1025のいずれかの方法。
[本発明1027]
前記フラビウイルスが、ウエストナイルウイルス、デングウイルス(血清型1〜4)、セントルイス脳炎ウイルス、黄熱ウイルス、日本脳炎ウイルス、またはマレー渓谷脳炎ウイルスである、本発明1001〜1026のいずれかの方法。
[本発明1028]
SEQ ID NO: 2、4および8の核酸配列を含む、核酸配列。
[本発明1029]
SEQ ID NO: 1、3および7または13を含むポリペプチドをコードする、核酸配列。
[本発明1030]
SEQ ID NO: 1、3および7または13を含むアミノ酸配列を含む、ポリペプチド。
[本発明1031]
本発明1028および1029の核酸を含む、ベクター。
[本発明1032]
本発明1031のベクターを含む、細胞。
[本発明1033]
植物細胞である、本発明1015または1032の細胞。
本発明の他の特徴および利点は、以下の詳細な説明および添付の特許請求の範囲から明らかになり、以下の詳細な説明および添付の特許請求の範囲に包含される。
本発明は、ウイルス感染の抗体依存性増強に寄与することなく、フラビウイルス科のメンバーによる感染を中和する抗体を提供する。ウエストナイルウイルスに結合してウエストナイルウイルスを中和する抗体は国際公開WO2005/123774に記載されており、その内容は参照により本明細書にその全文が組み入れられる。本発明の抗体は、抗体のFc領域がFc-ガンマ受容体に結合しないように、ウエストナイルウイルスに対する抗体mAb11を改変することによって作製された。したがって本改変抗体は、感染の抗体依存性増強に寄与しない。本明細書において開示する抗体および方法は、この抗体と、フラビウイルスによる感染ならびに関連する疾患および障害を処置または防止するための方法とに関係する。本発明の抗体mAB11-LALAは、本明細書において説明し、実施例において実証するとおり、フラビウイルス感染を防止し処置する能力が、野生型mAb11と比較して増加していた。
本明細書において使用する用語「抗体」は、免疫グロブリン分子および免疫グロブリン(Ig)分子の免疫学的に活性な部分、すなわち、抗原に特異的に結合する(抗原と免疫反応する)抗原結合部位を含有する分子を指す。「に特異的に結合する」または「と免疫反応する」とは、抗体が、所望の抗原の1つまたは複数の抗原決定基と反応し、他のポリペプチドとは反応しないことを意味する。抗体には、ポリクローナル抗体、モノクローナル抗体、およびキメラ抗体が含まれるが、それらに限定されるわけではない。
所望の特異性を有する抗体をスクリーニングするための方法として、例えば限定するわけではないが、酵素結合免疫吸着アッセイ(ELISA)および当技術分野内で公知の他の免疫学的に媒介される技法が挙げられる。
本発明の抗体または作用物質(本明細書では「活性化合物」ともいう)ならびにその誘導体、フラグメント、アナログおよびホモログは、投与に適した薬学的組成物に組み入れることができる。そのような組成物は、典型的には、抗体または作用物質と、薬学的に許容される担体とを含む。本明細書において使用する用語「薬学的に許容される担体」は、薬学的投与と適合するありとあらゆる溶媒、分散媒、コーティング、抗細菌剤および抗真菌剤、等張化剤および吸収遅延剤などを包含するものとする。適切な担体は、この分野における標準的参考書であるRemington's Pharmaceutical Sciencesの最新版に記載されており、この文献は参照により本明細書に組み入れられる。そのような担体または希釈剤の好ましい例として、水、食塩水、リンゲル液、デキストロース溶液、および5%ヒト血清アルブミンが挙げられるが、それらに限定されるわけではない。リポソームおよび固定油などの非水性媒体も使用することができる。薬学的に活性な物質のためのそのような媒質および作用物質の使用は、当技術分野において周知である。従来の媒質または作用物質は、それらが活性化合物と不適合でない限り、本組成物における使用が考えられる。補助活性化合物も組成物に組み入れることができる。
本発明は、調整因子、すなわちフラビウイルスと細胞膜との融合を調整するかまたは他の形で妨害する候補化合物もしくは試験化合物または候補作用物質もしくは試験作用物質(例えばペプチド、ペプチドミメティック、小分子または他の薬物)を同定するための方法(本明細書では「スクリーニングアッセイ」ともいう)を提供する。フラビウイルス感染を処置するのに有用な化合物を同定する方法も提供する。本発明は、本明細書に記載するスクリーニングアッセイを使って同定された化合物も包含する。
本発明の抗体は、例えば従来型のイムノアッセイなど、適当なアッセイによって検出することができる。例えば、フラビウイルスエンベロープタンパク質(例えばウエストナイルウイルスタンパク質E)またはそのフラグメントを固相に固定するアッセイを行うことができる。試料中の抗体が固相上の固定化されたポリペプチドに結合することを可能にするのに十分な時間にわたって、インキュベーションを維持する。この第1インキュベーションの後、固相を試料から分離する。未結合の材料と妨害物質、例えば試料中に同様に存在しうる非特異的タンパク質とを除去するために、固相を洗浄する。次に、固定化ポリペプチドに結合した関心対象の抗体を含有する固相を、第2の標識抗体またはビオチンもしくはアビジンなどのカップリング剤に結合した抗体と共にインキュベートする。この第2抗体は、もう一つの抗フラビウイルス抗体またはもう一つの抗体であることができる。抗体用の標識は当技術分野において周知であり、放射性核種、酵素(例えばマレイン酸デヒドロゲナーゼ、セイヨウワサビペルオキシダーゼ、グルコースオキシダーゼ、カタラーゼ)、蛍光物質(フルオレセインイソチオシアネート、ローダミン、フィコシアニン、フルオレスカミン(fluorescarmine))、ビオチンなどが挙げられる。標識抗体を固相と共にインキュベートし、固相に結合した標識を測定する。これらのイムノアッセイおよび他のイムノアッセイは、当業者であれば容易に行うことができる。
受動免疫化は、ウイルス疾患の予防および処置にとって有効で安全な戦略であることが判明している(Keller et al., Clin. Microbiol. Rev. 13:602-14(2000);Casadevall, Nat. Biotechnol. 20:114(2002);Shibata et al, Nat. Med. 5:204-10(1999);およびIgarashi et al., Nat. Med. 5:211-16(1999)参照;これらはそれぞれ参照により本明細書に組み入れられる)。中和ヒトモノクローナル抗体を使った受動免疫化は、フラビウイルス感染ならびに関連疾患および関連障害の緊急予防および緊急処置のための応急処置戦略になりうる。また同時に、これに代わる、もっと時間の掛かるワクチンおよび新薬の開発も進行中である。
免疫系に抗原決定基を効率よく提示するための足場として初めて抗体が使用されてから10年以上が経つ(Zanetti, Nature 355:476-77(1992);Zaghouani et al, Proc. Natl. Acad. Sci. USA 92:631-35(1995))。ペプチドは、IgG分子の不可分の一部として含まれ(例えば本明細書に記載の11Aまたは256IgG1モノクローナル抗体)、ペプチドエピトープの抗原性および免疫原性は遊離のペプチドと比較して著しく強化される。そのような強化は、おそらく、抗原-IgGキメラの長い半減期、より良い提示、およびそれぞれの自然の構造を模倣する束縛されたコンフォメーションによるのであろう。
DNAワクチンは安定であり、抗原に天然のプロセシングを受ける機会を与え、より長時間持続する応答を誘導することができる。DNAワクチンは、非常に魅力的な免疫化戦略であるものの、免疫応答を誘導するその潜在能力は著しく制限されることが多い。注入されたDNAが樹状細胞(DC)などのプロフェッショナルAPCによってあまり取り込まれないことが、そのような制限の主な原因であるだろう。抗原-Igキメラワクチンと組み合わせることで、APC抗原提示の強化に基づく前途有望な新しいDNAワクチン戦略が報告されており(Casares, et al, Viral Immunol. 10:129-36(1997);Gerloni et al, Nat. Biotech. 15:876-81(1997);Gerloni et al, DNA Cell Biol. 16:611-25(1997);You et al, Cancer Res. 61:3704-11(2001)参照)、これは、DCの表面にFc受容体(FcγR)が存在することを利用している。
一般に1種または複数種のモノクローナル抗体またはscFvの混合物およびそれらの組み合わせを含む治療用または予防用組成物が、ここに提供される。予防用ワクチンはフラビウイルス感染を防止するために使用することができ、治療用ワクチンはフラビウイルス感染後に個体を処置するために使用することができる。予防的使用には、ワクチン接種対象におけるフラビウイルスに対する抗体価を増加させることが含まれる。このようにして、フラビウイルスと接触するリスクが高い対象(すなわちウイルスを保因している蚊が生育している亜熱帯地域にいる対象)に、フラビウイルスに対する受動免疫を提供することができる。
本発明のワクチンは、他の抗ウイルスワクチンより優れた免疫防御特性および免疫治療特性を有する。
本発明は、フラビウイルス関連疾患またはフラビウイルス関連障害のリスクがある(または前記疾患もしくは障害にかかりやすい)対象を処置する予防的方法および治療的方法をどちらも提供する。そのような疾患または障害として、例えば発熱、髄膜炎、脳炎、黄熱、デング熱が挙げられるが、それらに限定されるわけではない。
一局面において、本発明は、本発明のモノクローナル抗体または本発明の方法に従って同定された作用物質を対象に投与することによって対象におけるフラビウイルス関連疾患またはフラビウイルス関連障害を防止するための方法を提供する。例えばモノクローナル抗体mAb-11、mAb11-LALA、およびその任意の変種であって、Fc領域が改変されることにより、Fc-ガンマ受容体への結合が低減または抑止されているものを、治療有効量で投与することができる。任意で、2種または3種以上の抗フラビウイルス抗体が同時投与される。
本発明のもう一つの局面は、患者におけるフラビウイルス関連疾患またはフラビウイルス関連障害を処置する方法に関する。一態様において、本方法は、フラビウイルスを中和する作用物質(例えば本明細書に記載するスクリーニングアッセイによって同定される作用物質および/または本発明の方法に従って同定されるモノクローナル抗体)または前記作用物質の組み合わせを、疾患または障害を患っている患者に投与する工程を伴う。
本発明は、2つまたは3つ以上の抗体、例えばmAb11-LALAまたはmAb11の変種であって、変種のFc領域がFcガンマ受容体に結合しないかFcガンマ受容体への結合が低減しているものを、当技術分野において公知の他のフラビウイルス中和抗体、例えばmAb11と共に投与することによる、患者におけるウエストナイル熱、髄膜炎、デング熱、黄熱または脳炎などのフラビウイルス関連疾患またはフラビウイルス関連障害の処置を提供する。もう一つの態様では、本発明は、本発明の抗体、例えば本明細書に記載するmAb11-LALAまたはmAb11変種を、当技術分野において公知の任意の抗ウイルス剤と共に投与することによって、患者におけるフラビウイルス関連疾患またはフラビウイルス関連障害を処置するための方法を提供する。抗ウイルス剤は、ペプチド、核酸、小分子、阻害剤、またはRNAiであることができる。
ここでは、マウスにおけるmAb11抗体(野生型と改変Fc領域を持つ変異型との両方)の投与の予防効果を調べる研究を説明する。この研究では40匹のマウスを評価し、その40匹を各8匹の5群に分割した。第1群では、マウスにアイソタイプ対照IgG対照抗体を投与した。第2群には250μg/マウス(約12.5mg/kg)の野生型mAb11を投与した。第3群には50μg/マウス(約2.5mg/kg)の野生型mAb11(wt mAb)を投与した。第4群には250μg/マウス(約12.5mg/kg)の、Fc領域にLALA変異を持つmAb11(mut mAb)を投与した。第5群には50μg/マウス(約2.5mg/kg)の、Fc領域にLALA変異を持つmAb11(mut mAb)を投与した。
本明細書において説明するように、本発明の抗体は、トランスジェニック植物において産生することができる。他の研究により、ヒトにおける処置のための投与に適したヒト化抗体が、植物中でうまく産生されることが示されている。さらにまた、植物における治療用抗体産生は哺乳動物細胞における抗体産生に代わる安価で効率のよい手段であり、そのうえ、動物病原性夾雑物も含まない。本発明のmAb11抗体(Fc領域にLALA変異を含有するもの;mutAb)の効力を調べるために、哺乳動物発現系から産生された抗体と植物(タバコ植物)から産生された抗体とをインビボで比較した。
本発明をその詳細な説明と共に記載したが、上記の説明は、本発明を例示しようとするものであって、添付の特許請求の範囲によって画定される本発明の範囲を限定する意図はない。他の局面、利点、および変更態様も、添付の特許請求の範囲の範囲内にある。
Claims (33)
- SEQ ID NO: 1を有するVHアミノ酸配列と、SEQ ID NO: 3を有するVLアミノ酸配列と、Fcγ受容体に結合しないように改変されたFc領域とを含み、かつフラビウイルスに結合する、単離されたヒト化モノクローナル抗体。
- SEQ ID NO: 2を有するVHヌクレオチド配列と、SEQ ID NO: 4を有するVLヌクレオチド配列と、Fcγ受容体に結合しないように改変されたFc領域とを含み、かつフラビウイルスに結合する、単離されたヒト化モノクローナル抗体。
- フラビウイルス感染の抗体依存性増強に寄与しない、前記請求項のいずれか一項記載の抗体。
- フラビウイルスを中和する、前記請求項のいずれか一項記載の抗体。
- Fc領域がアミノ酸位置234および235に変異を含有する、前記請求項のいずれか一項記載の抗体。
- 変異がL234AおよびL235Aである、請求項6記載の抗体。
- Fc領域がSEQ ID NO: 7またはSEQ ID NO: 13のアミノ酸配列を含む、請求項6記載の抗体。
- 改変されたFc領域が新生児型Fc受容体に結合する、前記請求項のいずれか一項記載の抗体。
- フラビウイルスが、ウエストナイルウイルス、デングウイルス(血清型1〜4)、セントルイス脳炎ウイルス、黄熱ウイルス、日本脳炎ウイルス、およびマレー渓谷脳炎ウイルスである、前記請求項のいずれか一項記載の抗体。
- 植物において産生される、前記請求項のいずれか一項記載の抗体。
- 治療用作用物質に連結されている、前記請求項のいずれか一項記載の抗体。
- 前記治療用作用物質が、毒素、放射性標識、siRNA、小分子、またはサイトカインである、請求項12記載の抗体。
- 前記サイトカインがTGF-βである、請求項13記載の抗体。
- 前記請求項のいずれか一項記載の抗体を産生する、細胞。
- 対象に請求項1〜14のいずれか一項記載の抗体を投与する工程を含む、フラビウイルス感染の抗体依存性増強を防止する方法。
- 前記抗体がフラビウイルスによる初回感染後に投与される、請求項16記載の方法。
- 請求項1〜13のいずれか一項記載の抗体とワクチンとを対象に投与する工程を含む、ワクチン効率を増加させる方法。
- 前記抗体と前記ワクチンが逐次的にまたは同時に投与される、請求項18記載の方法。
- 前記ワクチンがウイルスワクチンである、請求項18記載の方法。
- フラビウイルス感染の症状を処置または軽減する方法であって、その必要がある対象に請求項1〜14のいずれか一項記載の抗体を含む組成物を投与する工程を含む、方法。
- フラビウイルス感染の1つまたは複数の症状の発症を遅延させる方法であって、その必要がある対象に請求項1〜14のいずれか一項記載の抗体を含む組成物を投与する工程を含む、方法。
- 抗ウイルス剤を投与する工程をさらに含む、請求項21または22記載の方法。
- 抗ウイルス剤が、抗体、治療用作用物質に連結された抗体、または小分子である、請求項23記載の方法。
- 前記抗体と抗ウイルス剤が逐次的にまたは同時に投与される、請求項23記載の方法。
- 前記1つまたは複数の症状が、体重減少、麻痺、発熱、頭痛、悪心、嘔吐、発疹、および身体痛を含む、請求項21〜25のいずれか一項記載の方法。
- 前記フラビウイルスが、ウエストナイルウイルス、デングウイルス(血清型1〜4)、セントルイス脳炎ウイルス、黄熱ウイルス、日本脳炎ウイルス、またはマレー渓谷脳炎ウイルスである、請求項1〜26のいずれか一項記載の方法。
- SEQ ID NO: 2、4および8の核酸配列を含む、核酸配列。
- SEQ ID NO: 1、3および7または13を含むポリペプチドをコードする、核酸配列。
- SEQ ID NO: 1、3および7または13を含むアミノ酸配列を含む、ポリペプチド。
- 請求項28および29記載の核酸を含む、ベクター。
- 請求項31記載のベクターを含む、細胞。
- 植物細胞である、請求項15または32記載の細胞。
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US201361792336P | 2013-03-15 | 2013-03-15 | |
US61/792,336 | 2013-03-15 |
Related Parent Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2016502756A Division JP6427552B2 (ja) | 2013-03-15 | 2014-03-14 | フラビウイルス中和抗体およびその使用方法 |
Publications (2)
Publication Number | Publication Date |
---|---|
JP2019054796A true JP2019054796A (ja) | 2019-04-11 |
JP6734902B2 JP6734902B2 (ja) | 2020-08-05 |
Family
ID=51538297
Family Applications (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2016502756A Active JP6427552B2 (ja) | 2013-03-15 | 2014-03-14 | フラビウイルス中和抗体およびその使用方法 |
JP2018202677A Active JP6734902B2 (ja) | 2013-03-15 | 2018-10-29 | フラビウイルス中和抗体およびその使用方法 |
Family Applications Before (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2016502756A Active JP6427552B2 (ja) | 2013-03-15 | 2014-03-14 | フラビウイルス中和抗体およびその使用方法 |
Country Status (10)
Country | Link |
---|---|
US (3) | US9822166B2 (ja) |
EP (3) | EP4292657A3 (ja) |
JP (2) | JP6427552B2 (ja) |
AU (2) | AU2014227909C1 (ja) |
BR (1) | BR112015021341B1 (ja) |
CA (1) | CA2901358C (ja) |
MX (2) | MX367668B (ja) |
PH (1) | PH12015502164B1 (ja) |
SG (1) | SG11201507359SA (ja) |
WO (1) | WO2014144061A2 (ja) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2021166654A1 (ja) | 2020-02-20 | 2021-08-26 | 国立感染症研究所長が代表する日本国 | フラビウイルス交差中和抗体及び医薬組成物 |
Families Citing this family (8)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US9822166B2 (en) * | 2013-03-15 | 2017-11-21 | Dana-Farber Cancer Institute, Inc. | Flavivirus neutralizing antibodies and methods of use thereof |
WO2018010789A1 (en) * | 2016-07-13 | 2018-01-18 | Humabs Biomed Sa | Novel antibodies specifically binding to zika virus epitopes and uses thereof |
WO2018071913A2 (en) | 2016-10-14 | 2018-04-19 | Dana-Farber Cancer Institute, Inc. | Modular tetrameric bispecific antibody platform |
GB201704126D0 (en) * | 2017-03-15 | 2017-04-26 | Blom Nihlén Kim Andrea | Vaccine |
CA3091144A1 (en) * | 2018-03-01 | 2019-09-06 | Igm Biosciences, Inc. | Igm fc and j-chain mutations that affect igm serum half-life |
EP3773707A1 (en) * | 2018-04-11 | 2021-02-17 | Tychan Pte. Ltd. | Methods and compositions for treating yellow fever |
RU2757488C1 (ru) * | 2020-11-10 | 2021-10-18 | Федеральное бюджетное учреждение науки "Государственный научный центр вирусологии и биотехнологии "Вектор" Федеральной службы по надзору в сфере защиты прав потребителей и благополучия человека (ФБУН ГНЦ ВБ "Вектор" Роспотребнадзора) | Универсальный рекомбинантный вектор pBuc и плазмидная генетическая конструкция pBuc-7B4, обеспечивающая синтез и секрецию антитела 7В4 против вируса Западного Нила в клетках животных и полученная с использованием указанного вектора pBuc |
CN116514963B (zh) * | 2023-04-21 | 2023-09-26 | 中国人民解放军军事科学院军事医学研究院 | 广谱识别黄病毒属病毒e蛋白的抗体fy2及其应用 |
Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2005123774A2 (en) * | 2004-06-15 | 2005-12-29 | Erol Fikrig | Antibodies to west nile virus polypeptides |
JP2012504955A (ja) * | 2008-10-13 | 2012-03-01 | インスティテュート・フォー・リサーチ・イン・バイオメディシン | デングウイルス中和抗体およびその使用 |
Family Cites Families (33)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3773919A (en) | 1969-10-23 | 1973-11-20 | Du Pont | Polylactide-drug mixtures |
FR2413974A1 (fr) | 1978-01-06 | 1979-08-03 | David Bernard | Sechoir pour feuilles imprimees par serigraphie |
US4485045A (en) | 1981-07-06 | 1984-11-27 | Research Corporation | Synthetic phosphatidyl cholines useful in forming liposomes |
US4522811A (en) | 1982-07-08 | 1985-06-11 | Syntex (U.S.A.) Inc. | Serial injection of muramyldipeptides and liposomes enhances the anti-infective activity of muramyldipeptides |
US4816567A (en) | 1983-04-08 | 1989-03-28 | Genentech, Inc. | Recombinant immunoglobin preparations |
US4544545A (en) | 1983-06-20 | 1985-10-01 | Trustees University Of Massachusetts | Liposomes containing modified cholesterol for organ targeting |
US4676980A (en) | 1985-09-23 | 1987-06-30 | The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services | Target specific cross-linked heteroantibodies |
US5030719A (en) | 1986-08-28 | 1991-07-09 | Teijin Limited | Cytotoxic antibody conjugates and a process for preparation thereof |
US5223409A (en) | 1988-09-02 | 1993-06-29 | Protein Engineering Corp. | Directed evolution of novel binding proteins |
GB8823869D0 (en) | 1988-10-12 | 1988-11-16 | Medical Res Council | Production of antibodies |
CA2062795A1 (en) | 1989-06-29 | 1990-12-30 | Michael W. Fanger | Bispecific reagents for aids therapy |
US5013556A (en) | 1989-10-20 | 1991-05-07 | Liposome Technology, Inc. | Liposomes with enhanced circulation time |
DK0710719T3 (da) | 1990-01-12 | 2007-07-09 | Amgen Fremont Inc | Frembringelse af xenogene antistoffer |
US5625126A (en) | 1990-08-29 | 1997-04-29 | Genpharm International, Inc. | Transgenic non-human animals for producing heterologous antibodies |
US5661016A (en) | 1990-08-29 | 1997-08-26 | Genpharm International Inc. | Transgenic non-human animals capable of producing heterologous antibodies of various isotypes |
US5633425A (en) | 1990-08-29 | 1997-05-27 | Genpharm International, Inc. | Transgenic non-human animals capable of producing heterologous antibodies |
US5545806A (en) | 1990-08-29 | 1996-08-13 | Genpharm International, Inc. | Ransgenic non-human animals for producing heterologous antibodies |
EP0814159B1 (en) | 1990-08-29 | 2005-07-27 | GenPharm International, Inc. | Transgenic mice capable of producing heterologous antibodies |
JPH06507398A (ja) | 1991-05-14 | 1994-08-25 | リプリジェン コーポレーション | Hiv感染治療のための異種複合抗体 |
CA2118921A1 (en) | 1991-09-17 | 1993-04-01 | Jose Goulon | Electron detector device for spectroscopic analyses of surfaces under x-ray excitation |
US5233409A (en) | 1992-02-25 | 1993-08-03 | Schwab Karl W | Color analysis of organic constituents in sedimentary rocks for thermal maturity |
JPH07509137A (ja) | 1992-07-24 | 1995-10-12 | セル ジェネシス,インク. | 異種抗体の生産 |
PL174721B1 (pl) | 1992-11-13 | 1998-09-30 | Idec Pharma Corp | Przeciwciało monoklonalne anty-CD20 |
CA2183667A1 (en) | 1994-02-22 | 1995-08-24 | Wayne A. Marasco | Nucleic acid delivery system, method of synthesis and uses thereof |
ATE390933T1 (de) | 1995-04-27 | 2008-04-15 | Amgen Fremont Inc | Aus immunisierten xenomäusen stammende menschliche antikörper gegen il-8 |
EP0823941A4 (en) | 1995-04-28 | 2001-09-19 | Abgenix Inc | HUMAN ANTIBODIES DERIVED FROM IMMUNIZED XENO MOUSES |
US5916771A (en) | 1996-10-11 | 1999-06-29 | Abgenix, Inc. | Production of a multimeric protein by cell fusion method |
US20020029391A1 (en) | 1998-04-15 | 2002-03-07 | Claude Geoffrey Davis | Epitope-driven human antibody production and gene expression profiling |
UA89481C2 (uk) * | 2003-09-30 | 2010-02-10 | Центокор, Инк. | Еритропоетинові міметичні шарнірно-серцевинні міметитіла людини, композиції, способи та застосування |
US20110165122A1 (en) * | 2009-11-10 | 2011-07-07 | The Regents Of The University Of California | Method for targeted and sustained antiviral therapy |
SG193554A1 (en) | 2011-03-29 | 2013-11-29 | Roche Glycart Ag | Antibody fc variants |
US9822166B2 (en) * | 2013-03-15 | 2017-11-21 | Dana-Farber Cancer Institute, Inc. | Flavivirus neutralizing antibodies and methods of use thereof |
US9111624B2 (en) | 2013-03-22 | 2015-08-18 | Katsuyuki Fujita | Semiconductor memory device |
-
2014
- 2014-03-14 US US14/777,324 patent/US9822166B2/en active Active
- 2014-03-14 AU AU2014227909A patent/AU2014227909C1/en active Active
- 2014-03-14 MX MX2015013232A patent/MX367668B/es active IP Right Grant
- 2014-03-14 CA CA2901358A patent/CA2901358C/en active Active
- 2014-03-14 EP EP23181586.1A patent/EP4292657A3/en active Pending
- 2014-03-14 EP EP19213985.5A patent/EP3689902B1/en active Active
- 2014-03-14 BR BR112015021341-3A patent/BR112015021341B1/pt active IP Right Grant
- 2014-03-14 SG SG11201507359SA patent/SG11201507359SA/en unknown
- 2014-03-14 JP JP2016502756A patent/JP6427552B2/ja active Active
- 2014-03-14 WO PCT/US2014/028310 patent/WO2014144061A2/en active Application Filing
- 2014-03-14 EP EP14764455.3A patent/EP2971042B1/en active Active
-
2015
- 2015-09-15 PH PH12015502164A patent/PH12015502164B1/en unknown
- 2015-09-15 MX MX2019010339A patent/MX2019010339A/es unknown
-
2017
- 2017-11-20 US US15/818,491 patent/US10400032B2/en active Active
-
2018
- 2018-06-06 AU AU2018204011A patent/AU2018204011C1/en active Active
- 2018-10-29 JP JP2018202677A patent/JP6734902B2/ja active Active
-
2019
- 2019-07-17 US US16/514,439 patent/US10899825B2/en active Active
Patent Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2005123774A2 (en) * | 2004-06-15 | 2005-12-29 | Erol Fikrig | Antibodies to west nile virus polypeptides |
JP2012504955A (ja) * | 2008-10-13 | 2012-03-01 | インスティテュート・フォー・リサーチ・イン・バイオメディシン | デングウイルス中和抗体およびその使用 |
Non-Patent Citations (3)
Title |
---|
CELLULAR IMMUNOLOGY, vol. 200, JPN6017042178, 2000, pages 16 - 26, ISSN: 0004114209 * |
JORNAL OF VIROLOGY, vol. 79, no. 23, JPN6017042177, 2005, pages 14606 - 14613, ISSN: 0004114208 * |
JOURNAL OF VIROLOGY, vol. 75, no. 24, JPN6017042179, December 2001 (2001-12-01), pages 12161 - 12168, ISSN: 0004114210 * |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2021166654A1 (ja) | 2020-02-20 | 2021-08-26 | 国立感染症研究所長が代表する日本国 | フラビウイルス交差中和抗体及び医薬組成物 |
Also Published As
Similar Documents
Publication | Publication Date | Title |
---|---|---|
US11505597B2 (en) | Middle east respiratory syndrome coronavirus neutralizing antibodies and methods of use thereof | |
JP6734902B2 (ja) | フラビウイルス中和抗体およびその使用方法 | |
US7750123B2 (en) | Antibodies against SARS-CoV and methods of use thereof | |
US20110159001A1 (en) | CROSS-NEUTRALIZING HUMAN MONOCLONAL ANTIBODIES TO SARS-CoV AND METHODS OF USE THEREOF | |
WO2007044695A2 (en) | ANTIBODIES AGAINST SARS-CoV AND METHODS OF USE THEREOF | |
US20230374114A1 (en) | Coronavirus antibodies and methods of use thereof | |
AU2015231164B2 (en) | Immunogenetic restriction on elicitation of antibodies | |
US20190233505A1 (en) | Methods of treating or preventing zika virus infection |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20181126 |
|
A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20181126 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20181207 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20190912 |
|
A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20191210 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20200312 |
|
TRDD | Decision of grant or rejection written | ||
A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 20200624 |
|
A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20200710 |
|
R150 | Certificate of patent or registration of utility model |
Ref document number: 6734902 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
R157 | Certificate of patent or utility model (correction) |
Free format text: JAPANESE INTERMEDIATE CODE: R157 |
|
R157 | Certificate of patent or utility model (correction) |
Free format text: JAPANESE INTERMEDIATE CODE: R157 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |