JP2023506745A - スイッチング結合剤、その製造方法、及びそれを用いた薬学組成物、検査キット及び抗原と抗体との分析方法 - Google Patents
スイッチング結合剤、その製造方法、及びそれを用いた薬学組成物、検査キット及び抗原と抗体との分析方法 Download PDFInfo
- Publication number
- JP2023506745A JP2023506745A JP2022535164A JP2022535164A JP2023506745A JP 2023506745 A JP2023506745 A JP 2023506745A JP 2022535164 A JP2022535164 A JP 2022535164A JP 2022535164 A JP2022535164 A JP 2022535164A JP 2023506745 A JP2023506745 A JP 2023506745A
- Authority
- JP
- Japan
- Prior art keywords
- antibody
- switching
- binding
- binding agent
- amino acid
- 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
- 239000011230 binding agent Substances 0.000 title claims abstract description 495
- 239000000427 antigen Substances 0.000 title claims abstract description 251
- 102000036639 antigens Human genes 0.000 title claims abstract description 250
- 108091007433 antigens Proteins 0.000 title claims abstract description 250
- 238000000034 method Methods 0.000 title claims abstract description 33
- 238000012360 testing method Methods 0.000 title claims abstract description 27
- 239000008194 pharmaceutical composition Substances 0.000 title claims abstract description 12
- 238000004519 manufacturing process Methods 0.000 title claims abstract description 11
- 238000004458 analytical method Methods 0.000 title claims description 118
- 238000009739 binding Methods 0.000 claims abstract description 347
- 230000027455 binding Effects 0.000 claims abstract description 345
- 125000003275 alpha amino acid group Chemical group 0.000 claims abstract description 141
- 108010047041 Complementarity Determining Regions Proteins 0.000 claims description 57
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 51
- 239000000126 substance Substances 0.000 claims description 46
- 102000004169 proteins and genes Human genes 0.000 claims description 44
- 108090000623 proteins and genes Proteins 0.000 claims description 44
- 238000002372 labelling Methods 0.000 claims description 43
- 150000001413 amino acids Chemical class 0.000 claims description 37
- 238000006243 chemical reaction Methods 0.000 claims description 36
- 239000007822 coupling agent Substances 0.000 claims description 36
- 238000003018 immunoassay Methods 0.000 claims description 35
- 239000012491 analyte Substances 0.000 claims description 34
- 125000000539 amino acid group Chemical group 0.000 claims description 31
- 239000000243 solution Substances 0.000 claims description 30
- 241000282414 Homo sapiens Species 0.000 claims description 27
- 238000003556 assay Methods 0.000 claims description 27
- 102000004196 processed proteins & peptides Human genes 0.000 claims description 25
- 108010032595 Antibody Binding Sites Proteins 0.000 claims description 22
- 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 20
- 230000002209 hydrophobic effect Effects 0.000 claims description 20
- 239000011324 bead Substances 0.000 claims description 19
- 230000003993 interaction Effects 0.000 claims description 18
- 108091023037 Aptamer Proteins 0.000 claims description 17
- 239000000758 substrate Substances 0.000 claims description 17
- 229910052739 hydrogen Inorganic materials 0.000 claims description 16
- 239000001257 hydrogen Substances 0.000 claims description 16
- 108010003723 Single-Domain Antibodies Proteins 0.000 claims description 14
- 238000002823 phage display Methods 0.000 claims description 14
- 238000002818 protein evolution Methods 0.000 claims description 12
- 238000003745 diagnosis Methods 0.000 claims description 10
- 201000010099 disease Diseases 0.000 claims description 9
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 9
- 125000000524 functional group Chemical group 0.000 claims description 9
- 230000009881 electrostatic interaction Effects 0.000 claims description 8
- 238000005411 Van der Waals force Methods 0.000 claims description 7
- 238000012216 screening Methods 0.000 claims description 7
- 230000001225 therapeutic effect Effects 0.000 claims description 7
- 238000012286 ELISA Assay Methods 0.000 claims description 6
- 230000010354 integration Effects 0.000 claims description 6
- 238000003127 radioimmunoassay Methods 0.000 claims description 6
- 238000005251 capillar electrophoresis Methods 0.000 claims description 5
- 239000003795 chemical substances by application Substances 0.000 claims description 5
- 239000000835 fiber Substances 0.000 claims description 5
- 239000011259 mixed solution Substances 0.000 claims description 5
- 230000002265 prevention Effects 0.000 claims description 5
- 230000001105 regulatory effect Effects 0.000 claims description 5
- 230000000295 complement effect Effects 0.000 claims description 4
- 238000002493 microarray Methods 0.000 claims description 4
- 238000011510 Elispot assay Methods 0.000 claims description 3
- 238000012413 Fluorescence activated cell sorting analysis Methods 0.000 claims description 3
- 238000002944 PCR assay Methods 0.000 claims description 3
- 238000003114 enzyme-linked immunosorbent spot assay Methods 0.000 claims description 3
- 238000000684 flow cytometry Methods 0.000 claims description 3
- 230000000951 immunodiffusion Effects 0.000 claims description 3
- 238000000760 immunoelectrophoresis Methods 0.000 claims description 3
- 238000003125 immunofluorescent labeling Methods 0.000 claims description 3
- 238000011532 immunohistochemical staining Methods 0.000 claims description 3
- 238000001114 immunoprecipitation Methods 0.000 claims description 3
- 238000012744 immunostaining Methods 0.000 claims description 3
- 230000005764 inhibitory process Effects 0.000 claims description 3
- 238000000746 purification Methods 0.000 claims description 3
- 238000004445 quantitative analysis Methods 0.000 claims description 3
- 238000010814 radioimmunoprecipitation assay Methods 0.000 claims description 3
- 238000004364 calculation method Methods 0.000 claims description 2
- 229910052500 inorganic mineral Inorganic materials 0.000 claims description 2
- 239000011707 mineral Substances 0.000 claims description 2
- 238000011321 prophylaxis Methods 0.000 claims description 2
- 230000008901 benefit Effects 0.000 description 27
- 238000011282 treatment Methods 0.000 description 16
- 230000000670 limiting effect Effects 0.000 description 15
- 238000002198 surface plasmon resonance spectroscopy Methods 0.000 description 15
- 239000007787 solid Substances 0.000 description 14
- 239000012634 fragment Substances 0.000 description 11
- 208000037798 influenza B Diseases 0.000 description 11
- 239000000463 material Substances 0.000 description 9
- 238000005259 measurement Methods 0.000 description 9
- 108060003951 Immunoglobulin Proteins 0.000 description 8
- 238000002866 fluorescence resonance energy transfer Methods 0.000 description 8
- 102000018358 immunoglobulin Human genes 0.000 description 8
- 238000011002 quantification Methods 0.000 description 8
- 241000700605 Viruses Species 0.000 description 7
- 229920001184 polypeptide Polymers 0.000 description 7
- 238000005406 washing Methods 0.000 description 7
- 108010001336 Horseradish Peroxidase Proteins 0.000 description 6
- 241000283973 Oryctolagus cuniculus Species 0.000 description 6
- 108090000526 Papain Proteins 0.000 description 6
- 239000004365 Protease Substances 0.000 description 6
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 6
- 229910052751 metal Inorganic materials 0.000 description 6
- 239000002184 metal Substances 0.000 description 6
- 239000000203 mixture Substances 0.000 description 6
- 229940055729 papain Drugs 0.000 description 6
- 235000019834 papain Nutrition 0.000 description 6
- 229920000642 polymer Polymers 0.000 description 6
- 238000000926 separation method Methods 0.000 description 6
- 241000894007 species Species 0.000 description 6
- 241000283707 Capra Species 0.000 description 5
- 230000000694 effects Effects 0.000 description 5
- XEEYBQQBJWHFJM-UHFFFAOYSA-N iron Substances [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 5
- 230000005291 magnetic effect Effects 0.000 description 5
- 230000009870 specific binding Effects 0.000 description 5
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 4
- 241000699666 Mus <mouse, genus> Species 0.000 description 4
- 210000004899 c-terminal region Anatomy 0.000 description 4
- 210000004027 cell Anatomy 0.000 description 4
- 150000001875 compounds Chemical class 0.000 description 4
- 230000007423 decrease Effects 0.000 description 4
- 238000010586 diagram Methods 0.000 description 4
- 238000002474 experimental method Methods 0.000 description 4
- 238000009472 formulation Methods 0.000 description 4
- -1 i.e. Chemical class 0.000 description 4
- 230000003100 immobilizing effect Effects 0.000 description 4
- 150000002500 ions Chemical class 0.000 description 4
- 230000008569 process Effects 0.000 description 4
- 230000002829 reductive effect Effects 0.000 description 4
- 108010021625 Immunoglobulin Fragments Proteins 0.000 description 3
- 102000008394 Immunoglobulin Fragments Human genes 0.000 description 3
- 108091007491 NSP3 Papain-like protease domains Proteins 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- 230000009471 action Effects 0.000 description 3
- 230000030741 antigen processing and presentation Effects 0.000 description 3
- 230000000903 blocking effect Effects 0.000 description 3
- 238000011033 desalting Methods 0.000 description 3
- 239000011521 glass Substances 0.000 description 3
- PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 description 3
- 239000010931 gold Substances 0.000 description 3
- 229910052737 gold Inorganic materials 0.000 description 3
- 230000003287 optical effect Effects 0.000 description 3
- 230000005298 paramagnetic effect Effects 0.000 description 3
- 238000010647 peptide synthesis reaction Methods 0.000 description 3
- 239000000546 pharmaceutical excipient Substances 0.000 description 3
- 230000009257 reactivity Effects 0.000 description 3
- 239000000377 silicon dioxide Substances 0.000 description 3
- 229910052623 talc Inorganic materials 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 2
- DYAOREPNYXXCOA-UHFFFAOYSA-N 2-sulfanylundecanoic acid Chemical compound CCCCCCCCCC(S)C(O)=O DYAOREPNYXXCOA-UHFFFAOYSA-N 0.000 description 2
- QEYONPKSDTUPAX-UHFFFAOYSA-N 4-bromo-2-chloro-6-fluorophenol Chemical compound OC1=C(F)C=C(Br)C=C1Cl QEYONPKSDTUPAX-UHFFFAOYSA-N 0.000 description 2
- 102000002260 Alkaline Phosphatase Human genes 0.000 description 2
- 108020004774 Alkaline Phosphatase Proteins 0.000 description 2
- 108090000790 Enzymes Proteins 0.000 description 2
- 102000004190 Enzymes Human genes 0.000 description 2
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 2
- 102000006496 Immunoglobulin Heavy Chains Human genes 0.000 description 2
- 108010019476 Immunoglobulin Heavy Chains Proteins 0.000 description 2
- UQSXHKLRYXJYBZ-UHFFFAOYSA-N Iron oxide Chemical compound [Fe]=O UQSXHKLRYXJYBZ-UHFFFAOYSA-N 0.000 description 2
- 229910019142 PO4 Inorganic materials 0.000 description 2
- 102000007056 Recombinant Fusion Proteins Human genes 0.000 description 2
- 108010008281 Recombinant Fusion Proteins Proteins 0.000 description 2
- KJTLSVCANCCWHF-UHFFFAOYSA-N Ruthenium Chemical compound [Ru] KJTLSVCANCCWHF-UHFFFAOYSA-N 0.000 description 2
- 230000010056 antibody-dependent cellular cytotoxicity Effects 0.000 description 2
- 230000000890 antigenic effect Effects 0.000 description 2
- 239000003125 aqueous solvent Substances 0.000 description 2
- 230000004071 biological effect Effects 0.000 description 2
- XJMXIWNOKIEIMX-UHFFFAOYSA-N bromo chloro 1h-indol-2-yl phosphate Chemical group C1=CC=C2NC(OP(=O)(OBr)OCl)=CC2=C1 XJMXIWNOKIEIMX-UHFFFAOYSA-N 0.000 description 2
- 229910000019 calcium carbonate Inorganic materials 0.000 description 2
- 235000010216 calcium carbonate Nutrition 0.000 description 2
- 150000001718 carbodiimides Chemical class 0.000 description 2
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 239000000470 constituent Substances 0.000 description 2
- 239000013078 crystal Substances 0.000 description 2
- 239000012636 effector Substances 0.000 description 2
- 239000000839 emulsion Substances 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 229940088598 enzyme Drugs 0.000 description 2
- 238000000338 in vitro Methods 0.000 description 2
- 229910052742 iron Inorganic materials 0.000 description 2
- 239000003446 ligand Substances 0.000 description 2
- 239000000395 magnesium oxide Substances 0.000 description 2
- CPLXHLVBOLITMK-UHFFFAOYSA-N magnesium oxide Inorganic materials [Mg]=O CPLXHLVBOLITMK-UHFFFAOYSA-N 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
- AXZKOIWUVFPNLO-UHFFFAOYSA-N magnesium;oxygen(2-) Chemical compound [O-2].[Mg+2] AXZKOIWUVFPNLO-UHFFFAOYSA-N 0.000 description 2
- 239000007769 metal material Substances 0.000 description 2
- JPXMTWWFLBLUCD-UHFFFAOYSA-N nitro blue tetrazolium(2+) Chemical compound COC1=CC(C=2C=C(OC)C(=CC=2)[N+]=2N(N=C(N=2)C=2C=CC=CC=2)C=2C=CC(=CC=2)[N+]([O-])=O)=CC=C1[N+]1=NC(C=2C=CC=CC=2)=NN1C1=CC=C([N+]([O-])=O)C=C1 JPXMTWWFLBLUCD-UHFFFAOYSA-N 0.000 description 2
- 150000007523 nucleic acids Chemical group 0.000 description 2
- 239000010452 phosphate Substances 0.000 description 2
- 238000006479 redox reaction Methods 0.000 description 2
- 229910052707 ruthenium Inorganic materials 0.000 description 2
- 238000010187 selection method Methods 0.000 description 2
- 239000010703 silicon Substances 0.000 description 2
- 229910052710 silicon Inorganic materials 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 239000000454 talc Substances 0.000 description 2
- ABZLKHKQJHEPAX-UHFFFAOYSA-N tetramethylrhodamine Chemical compound C=12C=CC(N(C)C)=CC2=[O+]C2=CC(N(C)C)=CC=C2C=1C1=CC=CC=C1C([O-])=O ABZLKHKQJHEPAX-UHFFFAOYSA-N 0.000 description 2
- 239000000080 wetting agent Substances 0.000 description 2
- CHEANNSDVJOIBS-MHZLTWQESA-N (3s)-3-cyclopropyl-3-[3-[[3-(5,5-dimethylcyclopenten-1-yl)-4-(2-fluoro-5-methoxyphenyl)phenyl]methoxy]phenyl]propanoic acid Chemical compound COC1=CC=C(F)C(C=2C(=CC(COC=3C=C(C=CC=3)[C@@H](CC(O)=O)C3CC3)=CC=2)C=2C(CCC=2)(C)C)=C1 CHEANNSDVJOIBS-MHZLTWQESA-N 0.000 description 1
- UAIUNKRWKOVEES-UHFFFAOYSA-N 3,3',5,5'-tetramethylbenzidine Chemical compound CC1=C(N)C(C)=CC(C=2C=C(C)C(N)=C(C)C=2)=C1 UAIUNKRWKOVEES-UHFFFAOYSA-N 0.000 description 1
- UZVMVUUAAXJDIL-UHFFFAOYSA-N 37,38,39,40-tetrazanonacyclo[28.6.1.13,10.112,19.121,28.04,9.013,18.022,27.031,36]tetraconta-1(37),2,4,6,8,10,12(39),13,15,17,19,21,23,25,27,29,31,33,35-nonadecaene zinc Chemical compound [Zn].N1C(C=C2C3=CC=CC=C3C(C=C3C4=CC=CC=C4C(=C4)N3)=N2)=C(C=CC=C2)C2=C1C=C1C2=CC=CC=C2C4=N1 UZVMVUUAAXJDIL-UHFFFAOYSA-N 0.000 description 1
- 229910018072 Al 2 O 3 Inorganic materials 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- 241000271566 Aves Species 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- ODINCKMPIJJUCX-UHFFFAOYSA-N Calcium oxide Chemical compound [Ca]=O ODINCKMPIJJUCX-UHFFFAOYSA-N 0.000 description 1
- 241000282836 Camelus dromedarius Species 0.000 description 1
- 241000282472 Canis lupus familiaris Species 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- 241000251730 Chondrichthyes Species 0.000 description 1
- 229910018871 CoO 2 Inorganic materials 0.000 description 1
- 208000035473 Communicable disease Diseases 0.000 description 1
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 1
- QPLDLSVMHZLSFG-UHFFFAOYSA-N Copper oxide Chemical compound [Cu]=O QPLDLSVMHZLSFG-UHFFFAOYSA-N 0.000 description 1
- 108020004414 DNA Proteins 0.000 description 1
- 238000000018 DNA microarray Methods 0.000 description 1
- BWGNESOTFCXPMA-UHFFFAOYSA-N Dihydrogen disulfide Chemical compound SS BWGNESOTFCXPMA-UHFFFAOYSA-N 0.000 description 1
- 206010013654 Drug abuse Diseases 0.000 description 1
- 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 1
- LVGKNOAMLMIIKO-UHFFFAOYSA-N Elaidinsaeure-aethylester Natural products CCCCCCCCC=CCCCCCCCC(=O)OCC LVGKNOAMLMIIKO-UHFFFAOYSA-N 0.000 description 1
- 229910052691 Erbium Inorganic materials 0.000 description 1
- 229910052693 Europium Inorganic materials 0.000 description 1
- 239000004606 Fillers/Extenders Substances 0.000 description 1
- 229910052688 Gadolinium Inorganic materials 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 102000003886 Glycoproteins Human genes 0.000 description 1
- 108090000288 Glycoproteins Proteins 0.000 description 1
- 201000005569 Gout Diseases 0.000 description 1
- 229910052689 Holmium Inorganic materials 0.000 description 1
- 206010020751 Hypersensitivity Diseases 0.000 description 1
- 108010058683 Immobilized Proteins Proteins 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
- 241000282852 Lama guanicoe Species 0.000 description 1
- 235000019738 Limestone Nutrition 0.000 description 1
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- NQTADLQHYWFPDB-UHFFFAOYSA-N N-Hydroxysuccinimide Chemical compound ON1C(=O)CCC1=O NQTADLQHYWFPDB-UHFFFAOYSA-N 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 239000000020 Nitrocellulose Substances 0.000 description 1
- 206010029719 Nonspecific reaction Diseases 0.000 description 1
- 108091028043 Nucleic acid sequence Proteins 0.000 description 1
- 239000004677 Nylon Substances 0.000 description 1
- 241001494479 Pecora Species 0.000 description 1
- 108091005804 Peptidases Proteins 0.000 description 1
- 102000035195 Peptidases Human genes 0.000 description 1
- 108010033276 Peptide Fragments Proteins 0.000 description 1
- 102000007079 Peptide Fragments Human genes 0.000 description 1
- 108010053210 Phycocyanin Proteins 0.000 description 1
- 108010004729 Phycoerythrin Proteins 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 239000004743 Polypropylene Substances 0.000 description 1
- 229920001213 Polysorbate 20 Polymers 0.000 description 1
- 239000004793 Polystyrene Substances 0.000 description 1
- 241000283984 Rodentia Species 0.000 description 1
- 229910004298 SiO 2 Inorganic materials 0.000 description 1
- BQCADISMDOOEFD-UHFFFAOYSA-N Silver Chemical compound [Ag] BQCADISMDOOEFD-UHFFFAOYSA-N 0.000 description 1
- 229920002472 Starch Polymers 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
- 229930006000 Sucrose Natural products 0.000 description 1
- 241000282887 Suidae Species 0.000 description 1
- GWEVSGVZZGPLCZ-UHFFFAOYSA-N Titan oxide Chemical compound O=[Ti]=O GWEVSGVZZGPLCZ-UHFFFAOYSA-N 0.000 description 1
- 241001416177 Vicugna pacos Species 0.000 description 1
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
- XLOMVQKBTHCTTD-UHFFFAOYSA-N Zinc monoxide Chemical compound [Zn]=O XLOMVQKBTHCTTD-UHFFFAOYSA-N 0.000 description 1
- 230000007815 allergy Effects 0.000 description 1
- 108010004469 allophycocyanin Proteins 0.000 description 1
- 230000004075 alteration Effects 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- 208000007502 anemia Diseases 0.000 description 1
- 230000003302 anti-idiotype Effects 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 239000007900 aqueous suspension Substances 0.000 description 1
- 238000003491 array Methods 0.000 description 1
- 238000003149 assay kit Methods 0.000 description 1
- 210000003719 b-lymphocyte Anatomy 0.000 description 1
- HHSPVTKDOHQBKF-UHFFFAOYSA-J calcium;magnesium;dicarbonate Chemical compound [Mg+2].[Ca+2].[O-]C([O-])=O.[O-]C([O-])=O HHSPVTKDOHQBKF-UHFFFAOYSA-J 0.000 description 1
- VTJUKNSKBAOEHE-UHFFFAOYSA-N calixarene Chemical compound COC(=O)COC1=C(CC=2C(=C(CC=3C(=C(C4)C=C(C=3)C(C)(C)C)OCC(=O)OC)C=C(C=2)C(C)(C)C)OCC(=O)OC)C=C(C(C)(C)C)C=C1CC1=C(OCC(=O)OC)C4=CC(C(C)(C)C)=C1 VTJUKNSKBAOEHE-UHFFFAOYSA-N 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 150000001720 carbohydrates Chemical class 0.000 description 1
- 235000014633 carbohydrates Nutrition 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 239000011203 carbon fibre reinforced carbon Substances 0.000 description 1
- 239000000919 ceramic Substances 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 229910017052 cobalt Inorganic materials 0.000 description 1
- 239000010941 cobalt Substances 0.000 description 1
- GUTLYIVDDKVIGB-UHFFFAOYSA-N cobalt atom Chemical compound [Co] GUTLYIVDDKVIGB-UHFFFAOYSA-N 0.000 description 1
- 229910000428 cobalt oxide Inorganic materials 0.000 description 1
- MPMSMUBQXQALQI-UHFFFAOYSA-N cobalt phthalocyanine Chemical compound [Co+2].C12=CC=CC=C2C(N=C2[N-]C(C3=CC=CC=C32)=N2)=NC1=NC([C]1C=CC=CC1=1)=NC=1N=C1[C]3C=CC=CC3=C2[N-]1 MPMSMUBQXQALQI-UHFFFAOYSA-N 0.000 description 1
- IVMYJDGYRUAWML-UHFFFAOYSA-N cobalt(ii) oxide Chemical compound [Co]=O IVMYJDGYRUAWML-UHFFFAOYSA-N 0.000 description 1
- 238000010835 comparative analysis Methods 0.000 description 1
- 230000004154 complement system Effects 0.000 description 1
- 238000009833 condensation Methods 0.000 description 1
- 230000005494 condensation Effects 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 229910052802 copper Inorganic materials 0.000 description 1
- 239000010949 copper Substances 0.000 description 1
- 150000003983 crown ethers Chemical class 0.000 description 1
- WWXKNUYLTWOLJS-UHFFFAOYSA-N cyclopenta-1,3-diene (4-cyclopenta-2,4-dien-1-ylphenyl)methanol iron(2+) Chemical compound [Fe++].c1cc[cH-]c1.OCc1ccc(cc1)-[c-]1cccc1 WWXKNUYLTWOLJS-UHFFFAOYSA-N 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- QDOXWKRWXJOMAK-UHFFFAOYSA-N dichromium trioxide Chemical compound O=[Cr]O[Cr]=O QDOXWKRWXJOMAK-UHFFFAOYSA-N 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 239000000539 dimer Substances 0.000 description 1
- FZFYOUJTOSBFPQ-UHFFFAOYSA-M dipotassium;hydroxide Chemical compound [OH-].[K+].[K+] FZFYOUJTOSBFPQ-UHFFFAOYSA-M 0.000 description 1
- 239000007884 disintegrant Substances 0.000 description 1
- 238000010494 dissociation reaction Methods 0.000 description 1
- 230000005593 dissociations Effects 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000000975 dye Substances 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- UYAHIZSMUZPPFV-UHFFFAOYSA-N erbium Chemical compound [Er] UYAHIZSMUZPPFV-UHFFFAOYSA-N 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- LVGKNOAMLMIIKO-QXMHVHEDSA-N ethyl oleate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OCC LVGKNOAMLMIIKO-QXMHVHEDSA-N 0.000 description 1
- 229940093471 ethyl oleate Drugs 0.000 description 1
- OGPBJKLSAFTDLK-UHFFFAOYSA-N europium atom Chemical compound [Eu] OGPBJKLSAFTDLK-UHFFFAOYSA-N 0.000 description 1
- 239000013604 expression vector Substances 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- KTWOOEGAPBSYNW-UHFFFAOYSA-N ferrocene Chemical compound [Fe+2].C=1C=C[CH-]C=1.C=1C=C[CH-]C=1 KTWOOEGAPBSYNW-UHFFFAOYSA-N 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 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 1
- 238000012921 fluorescence analysis Methods 0.000 description 1
- 239000007850 fluorescent dye Substances 0.000 description 1
- 238000001215 fluorescent labelling Methods 0.000 description 1
- 238000011010 flushing procedure Methods 0.000 description 1
- 235000013355 food flavoring agent Nutrition 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- UIWYJDYFSGRHKR-UHFFFAOYSA-N gadolinium atom Chemical compound [Gd] UIWYJDYFSGRHKR-UHFFFAOYSA-N 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 150000004676 glycans Chemical class 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- KJZYNXUDTRRSPN-UHFFFAOYSA-N holmium atom Chemical compound [Ho] KJZYNXUDTRRSPN-UHFFFAOYSA-N 0.000 description 1
- 210000004408 hybridoma Anatomy 0.000 description 1
- 230000001900 immune effect Effects 0.000 description 1
- 230000028993 immune response Effects 0.000 description 1
- 210000000987 immune system Anatomy 0.000 description 1
- 229940072221 immunoglobulins Drugs 0.000 description 1
- 239000003547 immunosorbent Substances 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 229910052746 lanthanum Inorganic materials 0.000 description 1
- FZLIPJUXYLNCLC-UHFFFAOYSA-N lanthanum atom Chemical compound [La] FZLIPJUXYLNCLC-UHFFFAOYSA-N 0.000 description 1
- 239000006028 limestone Substances 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 229910052744 lithium Inorganic materials 0.000 description 1
- 230000004807 localization Effects 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 238000004020 luminiscence type Methods 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- WPBNNNQJVZRUHP-UHFFFAOYSA-L manganese(2+);methyl n-[[2-(methoxycarbonylcarbamothioylamino)phenyl]carbamothioyl]carbamate;n-[2-(sulfidocarbothioylamino)ethyl]carbamodithioate Chemical compound [Mn+2].[S-]C(=S)NCCNC([S-])=S.COC(=O)NC(=S)NC1=CC=CC=C1NC(=S)NC(=O)OC WPBNNNQJVZRUHP-UHFFFAOYSA-L 0.000 description 1
- 239000003550 marker Substances 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 150000002739 metals Chemical class 0.000 description 1
- 230000003278 mimic effect Effects 0.000 description 1
- 235000010755 mineral Nutrition 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 239000003607 modifier Substances 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- 230000000877 morphologic effect Effects 0.000 description 1
- 230000035772 mutation Effects 0.000 description 1
- 229920001220 nitrocellulos Polymers 0.000 description 1
- 108020004707 nucleic acids Proteins 0.000 description 1
- 102000039446 nucleic acids Human genes 0.000 description 1
- 239000002773 nucleotide Substances 0.000 description 1
- 125000003729 nucleotide group Chemical group 0.000 description 1
- 229920001778 nylon Polymers 0.000 description 1
- 235000008390 olive oil Nutrition 0.000 description 1
- 239000004006 olive oil Substances 0.000 description 1
- 239000006186 oral dosage form Substances 0.000 description 1
- TWNQGVIAIRXVLR-UHFFFAOYSA-N oxo(oxoalumanyloxy)alumane Chemical compound O=[Al]O[Al]=O TWNQGVIAIRXVLR-UHFFFAOYSA-N 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 239000006201 parenteral dosage form Substances 0.000 description 1
- 150000002978 peroxides Chemical class 0.000 description 1
- 230000000704 physical effect Effects 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 239000004033 plastic Substances 0.000 description 1
- 229920003023 plastic Polymers 0.000 description 1
- 229920000768 polyamine Polymers 0.000 description 1
- 239000004417 polycarbonate Substances 0.000 description 1
- 229920000515 polycarbonate Polymers 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 1
- 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 1
- 229920001155 polypropylene Polymers 0.000 description 1
- 229920001282 polysaccharide Polymers 0.000 description 1
- 239000005017 polysaccharide Substances 0.000 description 1
- 229920002223 polystyrene Polymers 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 230000035935 pregnancy Effects 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 230000004850 protein–protein interaction Effects 0.000 description 1
- 239000004627 regenerated cellulose Substances 0.000 description 1
- 229920005989 resin Polymers 0.000 description 1
- 239000011347 resin Substances 0.000 description 1
- 230000000717 retained effect Effects 0.000 description 1
- 229910052702 rhenium Inorganic materials 0.000 description 1
- WUAPFZMCVAUBPE-UHFFFAOYSA-N rhenium atom Chemical compound [Re] WUAPFZMCVAUBPE-UHFFFAOYSA-N 0.000 description 1
- 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 1
- 150000003839 salts Chemical class 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 235000012239 silicon dioxide Nutrition 0.000 description 1
- 229910052709 silver Inorganic materials 0.000 description 1
- 239000004332 silver Substances 0.000 description 1
- VFWRGKJLLYDFBY-UHFFFAOYSA-N silver;hydrate Chemical compound O.[Ag].[Ag] VFWRGKJLLYDFBY-UHFFFAOYSA-N 0.000 description 1
- 150000003384 small molecules Chemical class 0.000 description 1
- KKCBUQHMOMHUOY-UHFFFAOYSA-N sodium oxide Chemical compound [O-2].[Na+].[Na+] KKCBUQHMOMHUOY-UHFFFAOYSA-N 0.000 description 1
- 239000007790 solid phase Substances 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000004575 stone Substances 0.000 description 1
- 208000011117 substance-related disease Diseases 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 229920002994 synthetic fiber Polymers 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 230000009897 systematic effect Effects 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- BFKJFAAPBSQJPD-UHFFFAOYSA-N tetrafluoroethene Chemical group FC(F)=C(F)F BFKJFAAPBSQJPD-UHFFFAOYSA-N 0.000 description 1
- MPLHNVLQVRSVEE-UHFFFAOYSA-N texas red Chemical compound [O-]S(=O)(=O)C1=CC(S(Cl)(=O)=O)=CC=C1C(C1=CC=2CCCN3CCCC(C=23)=C1O1)=C2C1=C(CCC1)C3=[N+]1CCCC3=C2 MPLHNVLQVRSVEE-UHFFFAOYSA-N 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 210000001685 thyroid gland Anatomy 0.000 description 1
- 230000026683 transduction Effects 0.000 description 1
- 238000010361 transduction Methods 0.000 description 1
- 241001515965 unidentified phage Species 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 210000005253 yeast cell Anatomy 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
Images
Classifications
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
- G01N33/543—Immunoassay; Biospecific binding assay; Materials therefor with an insoluble carrier for immobilising immunochemicals
- G01N33/54366—Apparatus specially adapted for solid-phase testing
- G01N33/54386—Analytical elements
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K7/00—Peptides having 5 to 20 amino acids in a fully defined sequence; Derivatives thereof
- C07K7/04—Linear peptides containing only normal peptide links
- C07K7/08—Linear peptides containing only normal peptide links having 12 to 20 amino acids
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/42—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against immunoglobulins
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
- G01N33/536—Immunoassay; Biospecific binding assay; Materials therefor with immune complex formed in liquid phase
- G01N33/542—Immunoassay; Biospecific binding assay; Materials therefor with immune complex formed in liquid phase with steric inhibition or signal modification, e.g. fluorescent quenching
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
- G01N33/543—Immunoassay; Biospecific binding assay; Materials therefor with an insoluble carrier for immobilising immunochemicals
- G01N33/54306—Solid-phase reaction mechanisms
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
- G01N33/563—Immunoassay; Biospecific binding assay; Materials therefor involving antibody fragments
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/68—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids
- G01N33/6854—Immunoglobulins
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/42—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against immunoglobulins
- C07K16/4208—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against immunoglobulins against an idiotypic determinant on Ig
-
- 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
- C07K2317/567—Framework region [FR]
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2470/00—Immunochemical assays or immunoassays characterised by the reaction format or reaction type
- G01N2470/10—Competitive assay format
- G01N2470/12—Displacement or release-type competition
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Immunology (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Molecular Biology (AREA)
- Biomedical Technology (AREA)
- Hematology (AREA)
- Urology & Nephrology (AREA)
- General Health & Medical Sciences (AREA)
- Biochemistry (AREA)
- Medicinal Chemistry (AREA)
- Cell Biology (AREA)
- General Physics & Mathematics (AREA)
- Microbiology (AREA)
- Physics & Mathematics (AREA)
- Analytical Chemistry (AREA)
- Biotechnology (AREA)
- Pathology (AREA)
- Food Science & Technology (AREA)
- Organic Chemistry (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Biophysics (AREA)
- Genetics & Genomics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Peptides Or Proteins (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Medicinal Preparation (AREA)
Abstract
Description
配列番号2(以下、H2と称する):V-Y-Y-C-A-R-E-P-T-G-T-G-I-Y-F-D-V-W-G-K
配列番号4(以下、L2と称する):V-Y-Y-C-F-Q-G-S-H-V-P-F-T-K
また、定量分析のための測定間の再現性を算出するために、配列番号3の結合剤(L1)を用いて、HBsAg濃度3.4μg/mLで8回繰り返し実験した後、HBsAgの濃度が0であるbaselineでの値でノーマライズした。この際、当該濃度での測定値は、3.1±9.3%(n=8)で算出された。前記結果は、分析物である抗原20HBsAgが含まれた試料をヤギIgG抗体に処理して洗浄なしに一段階でのイムノアッセイによる分析物の測定が高い再現性を示すという点を示す。
Claims (45)
- 抗体のフレームワーク領域(FR)の少なくとも一部に可逆的に結合し、
前記抗体と特異的に反応するターゲット抗原が、前記抗体に結合する場合、前記フレームワーク領域から分離される、スイッチング結合剤。 - 前記スイッチング結合剤は、前記抗体の3次元構造によって、前記フレームワーク領域に結合される、請求項1に記載のスイッチング結合剤。
- 前記スイッチング結合剤は、少なくとも1つ以上の前記フレームワーク領域に結合可能な部分と少なくとも1つ以上の相補性決定領域(CDR)に結合可能な部分とを含む、請求項1に記載のスイッチング結合剤。
- 抗体の抗原結合部位を構成する重鎖のフレームワーク領域から選択されたアミノ酸配列を含み、
前記アミノ酸配列は、前記重鎖と共に前記抗原結合部位を構成する軽鎖のフレームワーク領域に可逆的に結合する第1抗体結合部を含む、スイッチング結合剤。 - 抗体の抗原結合部位を構成する軽鎖のフレームワーク領域から選択されたアミノ酸配列を含み、
前記アミノ酸配列は、前記軽鎖と共に前記抗原結合部位を構成する重鎖のフレームワーク領域に可逆的に結合する第2抗体結合部を含む、スイッチング結合剤。 - 前記アミノ酸配列は、前記重鎖または前記軽鎖のフレームワーク領域に隣接した相補性決定領域にも可逆的に結合する、請求項4または5に記載のスイッチング結合剤。
- 前記スイッチング結合剤は、ペプチド、タンパク質、アプタマー、ナノボディ、ファージディスプレイ、酵母ディスプレイ、及び抗体で構成された群から選択される、請求項4または5に記載のスイッチング結合剤。
- 前記スイッチング結合剤のアミノ酸の一部が、無機物で置換された、請求項4または5に記載のスイッチング結合剤。
- 前記第1抗体結合部は、-Y-、-I-、-W-及び-Q-のうち少なくとも何れか1つ以上のアミノ酸残基を含む、請求項4に記載のスイッチング結合剤。
- 前記第2抗体結合部は、-Y-、-Q-、-P-、-L-及び-F-のうち少なくとも何れか1つ以上のアミノ酸残基を含む、請求項5に記載のスイッチング結合剤。
- 前記スイッチング結合剤は、
配列番号1:S-Y-W-I-H-W-V-K-Q-R-P-G-Q-G-L-E-W-I-G-E
配列番号2:V-Y-Y-C-A-R-E-P-T-G-T-G-I-Y-F-D-V-W-G-K
配列番号3:T-Y-L-E-W-Y-P-Q-K-P-G-Q-S-P-K-L-L-I-Y-K
配列番号4:V-Y-Y-C-F-Q-G-S-H-V-P-F-T-Kのアミノ酸配列のうち何れか1つを含む、請求項4または5に記載のスイッチング結合剤。 - 前記第1抗体結合部は、前記軽鎖のフレームワーク領域と静電相互作用、水素結合、ファンデルワールス力、疎水性相互作用及びこれらの組み合わせのうち少なくとも1つ以上によって結合するアミノ酸残基を含む、請求項4に記載のスイッチング結合剤。
- 前記第2抗体結合部は、前記重鎖のフレームワーク領域と静電相互作用、水素結合、ファンデルワールス力、疎水性相互作用及びこれらの組み合わせのうち少なくとも1つ以上によって結合するアミノ酸残基を含む、請求項5に記載のスイッチング結合剤。
- 前記第1抗体結合部のアミノ酸変調によって抗体結合部位の結合力の調節が可能である、請求項12に記載のスイッチング結合剤。
- 前記第2抗体結合部のアミノ酸変調によって抗体結合部位の結合力の調節が可能である、請求項13に記載のスイッチング結合剤。
- 前記水素結合によって、前記スイッチング結合剤と前記フレームワーク領域との間に側鎖の官能基結合またはペプチド結合の極性部位と結合が行われる、請求項12または13に記載のスイッチング結合剤。
- 前記スイッチング結合剤が、前記抗体の前記抗原結合部位に結合された場合、前記抗体と特異的に反応するターゲット抗原が、前記抗体に結合することにより、前記スイッチング結合剤は、前記抗体から分離される、請求項4または5に記載のスイッチング結合剤。
- 前記スイッチング結合剤の前記抗体結合部は、前記重鎖または前記軽鎖の前記抗原結合部位に4~8Åの範囲内に結合された、請求項4または5に記載のスイッチング結合剤。
- 前記スイッチング結合剤は、自然的または人為的な標識物質で標識された、請求項4または5に記載のスイッチング結合剤。
- 前記スイッチング結合剤は、ヒト抗体、非ヒト抗体、ヒト化された非ヒト抗体またはこれらの組み合わせと結合し、
前記スイッチング結合剤が、前記抗体に結合された状態で前記抗体と前記ターゲット抗原との結合が可能である、請求項4または5に記載のスイッチング結合剤。 - 抗体のフレームワーク領域(FR)のうち少なくとも一部が、前記フレームワーク領域に可逆的に特異的結合する第1抗体結合部または第2抗体結合部と、
前記抗体と特異的に反応するターゲット抗原が、前記抗体に結合する場合、前記抗体結合部を前記フレームワーク領域から分離されるように、前記第1抗体結合部または前記第2抗体結合部の前記フレームワーク領域に対する結合力を調節する結合力調節部と、を含む、スイッチング結合剤。 - 前記結合力調節部は、前記スイッチング結合剤内で前記第1抗体結合部または第2抗体結合部の位置または前記スイッチング結合剤の立体的形状を変調して、前記抗体に対する前記抗体結合部の結合力を調節する、請求項21に記載のスイッチング結合剤。
- 前記結合力調節部は、-S-Y-W-I-H-W-V-K-、-R-P-G-Q-G-L-E-、-I-G-E-、-V-Y-、-C-A-R-E-P-T-G-T-G-、-Y-F-D-V-、-G-K-、-T-Y-L-E-W-Y-、-K-P-G-Q-S-、-K-、L-I-Y-K-、-C-F-Q-G-S-H-V-P-及び-T-K-のアミノ酸配列のうち1つ以上を含む、請求項21に記載のスイッチング結合剤。
- 前記第1抗体結合部または前記第2抗体結合部と前記結合力調節部とを単位構造体として含んで、前記抗体結合部と前記結合力調節部とが交互に連続して結合された、請求項21に記載のスイッチング結合剤。
- 請求項4または5に記載のスイッチング結合剤を含む、疾病スクリーニング、診断、予防または治療統合のための薬学組成物。
- 前記スイッチング結合剤は、ペプチド、タンパク質、アプタマー、ナノボディ、ファージディスプレイ、酵母ディスプレイ、及び抗体で構成された群から選択される、請求項25に記載の疾病スクリーニング、診断、予防または治療統合のための薬学組成物。
- 前記スイッチング結合剤は、
配列番号1:S-Y-W-I-H-W-V-K-Q-R-P-G-Q-G-L-E-W-I-G-E
配列番号2:V-Y-Y-C-A-R-E-P-T-G-T-G-I-Y-F-D-V-W-G-K
配列番号3:T-Y-L-E-W-Y-P-Q-K-P-G-Q-S-P-K-L-L-I-Y-K
配列番号4:V-Y-Y-C-F-Q-G-S-H-V-P-F-T-Kのアミノ酸配列のうち何れか1つを含む、請求項25に記載の疾病スクリーニング、診断、予防または治療統合のための薬学組成物。 - 請求項4または5に記載のスイッチング結合剤を含み、
前記スイッチング結合剤は、自然的または人為的な標識物質で標識され、
前記スイッチング結合剤が、フレームワーク領域に結合及び分離される量を測定して、抗体に対する抗原の結合力を測定する、検査キット。 - 前記スイッチング結合剤は、ペプチド、タンパク質、アプタマー、ナノボディ、ファージディスプレイ、酵母ディスプレイ、及び抗体で構成された群から選択される、請求項28に記載の検査キット。
- 前記結合力は、抗体の抗原結合係数(Kd)の算出を通じて測定される、請求項28に記載の検査キット。
- 前記抗原結合係数(Kd)は、0.7×10-6~3.4×10-6Mの範囲を含む、請求項29に記載の検査キット。
- 前記検査キットは、前記抗体が固定されていない溶液内で前記抗体が抗原と結合する時の抗原結合係数(Kd)を測定する、請求項29に記載の検査キット。
- 請求項4または5に記載のスイッチング結合剤を含み、
前記スイッチング結合剤は、自然的または人為的な標識物質で標識され、
前記スイッチング結合剤が、フレームワーク領域に結合及び分離される量を測定抗体及びターゲット抗原を識別または定量する、検査キット。 - 前記検査キットは、免疫分析用キットであって、
前記免疫分析用キットは、ルミネックス分析、タンパク質マイクロアレイ分析、エライザ分析、免疫-PCR分析、キャプチャー-ELISA分析、ELISPOT分析、放射免疫分析(RIA)、ラテラルフロー免疫分析(LFIA)、フロースルー免疫分析(FTIA)、タンパク質マイクロ流体免疫分析、タンパク質キャピラリー電気泳動分析(CE)、電気化学バイオセンサー、放射性免疫沈降分析、免疫沈降分析、免疫組織化学染色分析、オクタロニー免疫拡散分析、阻害または競合分析、サンドイッチ分析、フローサイトメトリー分析、免疫電気泳動分析、組織免疫染色分析、補体結合分析、FACS分析、タンパク質チップ分析、免疫蛍光染色分析及び免疫親和性精製分析のキットである、請求項33に記載の検査キット。 - 抗体の抗原結合部位を構成するフレームワーク領域からスイッチング結合剤のアミノ酸配列を選択する工程と、
ターゲット抗原と特異的に結合する抗体に前記スイッチング結合剤を提供して、前記抗体のフレームワーク領域(FR)の少なくとも一部に可逆的に結合させる前処理工程と、
前記前処理工程の結果物内に前記ターゲット抗原を含むか否かの判断が必要な被分析物を提供する工程と、
前記フレームワーク領域に結合された残量のスイッチング結合剤または前記フレームワーク領域から分離されたスイッチング結合剤のうち少なくとも何れか1つを定量して、前記被分析物内に前記ターゲット抗原を識別または定量分析する分析工程と、を含む、スイッチング結合剤を利用した分析方法。 - 前記スイッチング結合剤は、ペプチド、タンパク質、アプタマー、ナノボディ、ファージディスプレイ、酵母ディスプレイ、及び抗体で構成された群から選択される、請求項35に記載のスイッチング結合剤を利用した分析方法。
- 前記抗体は、基板、ビーズ、繊維、高分子構造体またはこれらの組み合わせである支持体に固定された、請求項35に記載の分析方法。
- 前記抗体は、固定されず、溶液に溶解された状態である、請求項35に記載の分析方法。
- 前記前処理工程は、
前記抗体に前記スイッチング結合剤を提供して、前記抗体と前記スイッチング結合剤の第1結合体及び前記抗体と結合されていないスイッチング結合剤とを含む混合溶液を得る工程と、
前記混合溶液から前記抗体と前記結合されていないスイッチング結合剤とを除去する工程と、を含む、請求項35に記載のスイッチング結合剤を利用した分析方法。 - 前記スイッチング結合剤は、自然的または人為的な標識物質で標識され、
前記分析工程で、
前記ターゲット抗原の分析は、前記標識反応を測定してなされる、請求項35に記載のスイッチング結合剤を利用した分析方法。 - 前記分析工程は、
前記抗体から分離されたスイッチング結合剤と前記抗体と前記ターゲット抗原の第2結合体とを分離する工程と、
前記分離されたスイッチング結合剤を識別または定量する工程と、をさらに含む、請求項35に記載のスイッチング結合剤を利用した分析方法。 - 抗体のフレームワーク領域(FR)に可逆的に特異的結合し、前記抗体と特異的反応するターゲット抗原が結合される場合、前記フレームワーク領域から分離されるスイッチング結合剤の製造方法であって、
前記抗体の重鎖及び軽鎖の前記フレームワーク領域が互いに自己結合するアミノ酸配列を確認する工程と、
前記アミノ酸配列の疎水性指数を得る工程と、
前記疎水性指数を比較して、前記重鎖及び前記軽鎖の抗原結合部位を構成するフレームワーク領域のアミノ酸配列間の同じ性質を有する部分の前記アミノ酸配列を含むスイッチング結合剤を選択する工程と、を含む、スイッチング結合剤の製造方法。 - 前記アミノ酸配列は、前記フレームワーク領域に隣接した相補性決定領域を含む、請求項35に記載のスイッチング結合剤の製造方法。
- 前記スイッチング結合剤は、ペプチド、アプタマー、タンパク質、ナノボディ、ファージディスプレイ、酵母ディスプレイ、及び抗体で構成された群から選択される、請求項35に記載のスイッチング結合剤の製造方法。
- 前記アミノ酸配列は、静電相互作用、水素結合、ファンデルワールス力、疎水性相互作用及びこれらの組み合わせのうち少なくとも1つ以上によって結合する、請求項35に記載のスイッチング結合剤の製造方法。
Applications Claiming Priority (7)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
KR10-2019-0162707 | 2019-12-09 | ||
KR1020190162707A KR102397684B1 (ko) | 2019-12-09 | 2019-12-09 | 항체의 항원 결합 부위에 결합하는 펩티드 및 이를 이용한 분석 방법 |
KR10-2020-0073508 | 2020-06-17 | ||
KR1020200073508A KR102504175B1 (ko) | 2020-06-17 | 2020-06-17 | 항체의 항원 결합 부위에 결합하는 펩타이드, 이를 이용한 약물 복합체, 바이오센서 및 분석 방법 |
KR1020200138705A KR20220054134A (ko) | 2020-10-23 | 2020-10-23 | 스위칭 결합제, 이의 제조 방법, 및 이를 이용한 약학 조성물, 검사 키트 및 항원과 항체의 분석 방법 |
KR10-2020-0138705 | 2020-10-23 | ||
PCT/KR2020/017497 WO2021118156A2 (ko) | 2019-12-09 | 2020-12-02 | 스위칭 결합제, 이의 제조 방법, 및 이를 이용한 약학 조성물, 검사 키트 및 항원과 항체의 분석 방법 |
Publications (2)
Publication Number | Publication Date |
---|---|
JP2023506745A true JP2023506745A (ja) | 2023-02-20 |
JP7416485B2 JP7416485B2 (ja) | 2024-01-17 |
Family
ID=76330133
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2022535164A Active JP7416485B2 (ja) | 2019-12-09 | 2020-12-02 | スイッチング結合剤、その製造方法、及びそれを用いた薬学組成物、検査キット及び抗原と抗体との分析方法 |
Country Status (5)
Country | Link |
---|---|
US (1) | US20230073007A1 (ja) |
EP (1) | EP4074725A4 (ja) |
JP (1) | JP7416485B2 (ja) |
CN (1) | CN115175919A (ja) |
WO (1) | WO2021118156A2 (ja) |
Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2015501299A (ja) * | 2011-10-10 | 2015-01-15 | シティ・オブ・ホープCity of Hope | メディトープおよびメディトープ結合性抗体ならびにそれらの使用 |
Family Cites Families (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2007090058A2 (en) * | 2006-01-27 | 2007-08-09 | Oxonica, Inc. | Lateral flow immunoassay with encapsulated detection modality |
TW201122101A (en) * | 2009-10-28 | 2011-07-01 | Facet Biotech Corp | Anti-EGFR antibodies and their uses |
WO2012048332A2 (en) * | 2010-10-08 | 2012-04-12 | John Williams | A monoclonal antibody framework binding interface for meditopes, meditope delivery systems and methods for their use |
KR101766271B1 (ko) * | 2015-09-24 | 2017-08-09 | 울산과학기술원 | 면역화학적 분석에서 표적 특이적 신호증폭을 담당하는 범용성 재조합 2차 항체 유사체 |
KR102389214B1 (ko) | 2018-12-14 | 2022-04-21 | 덕산네오룩스 주식회사 | 유기전기 소자용 화합물, 이를 이용한 유기전기소자 및 그 전자 장치 |
KR102338360B1 (ko) | 2019-11-01 | 2021-12-10 | 삼성디스플레이 주식회사 | 유기 발광 표시 장치 |
-
2020
- 2020-12-02 US US17/782,416 patent/US20230073007A1/en active Pending
- 2020-12-02 EP EP20898023.5A patent/EP4074725A4/en active Pending
- 2020-12-02 WO PCT/KR2020/017497 patent/WO2021118156A2/ko unknown
- 2020-12-02 JP JP2022535164A patent/JP7416485B2/ja active Active
- 2020-12-02 CN CN202080096001.4A patent/CN115175919A/zh active Pending
Patent Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2015501299A (ja) * | 2011-10-10 | 2015-01-15 | シティ・オブ・ホープCity of Hope | メディトープおよびメディトープ結合性抗体ならびにそれらの使用 |
Also Published As
Publication number | Publication date |
---|---|
WO2021118156A3 (ko) | 2021-07-29 |
US20230073007A1 (en) | 2023-03-09 |
EP4074725A2 (en) | 2022-10-19 |
CN115175919A (zh) | 2022-10-11 |
EP4074725A4 (en) | 2024-02-28 |
WO2021118156A2 (ko) | 2021-06-17 |
JP7416485B2 (ja) | 2024-01-17 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
US7514226B2 (en) | Antibody pair screening methods | |
JP6602884B2 (ja) | ビタミンdの測定法 | |
RU2636822C2 (ru) | Способ обнаружения мультиспецифического связывающего агента | |
KR20110086182A (ko) | 아밀로이드 β 펩티드에 대한 항체에 대한 항-이디오타입 항체 | |
WO2007003090A1 (fr) | Composition remplaçant un sérum positif utilisée comme témoin dans un agent de diagnostic et application de celle-ci | |
KR20140128314A (ko) | 다중특이적 결합제의 결합 파트너 검출 방법 | |
JP2020170001A (ja) | エフェクター機能抑制型ヒトまたはヒト化薬物抗体に対する抗薬物抗体の決定方法 | |
JP2023099089A (ja) | 干渉抑制薬物動態イムノアッセイ | |
JP7416485B2 (ja) | スイッチング結合剤、その製造方法、及びそれを用いた薬学組成物、検査キット及び抗原と抗体との分析方法 | |
KR20220063139A (ko) | 항체의 항원 결합 부위에 결합하는 펩티드 및 이를 이용한 분석 방법 | |
CN117280214A (zh) | SARS-CoV-2的免疫测定方法及免疫测定试剂盒、以及单克隆抗体或其抗体片段 | |
KR20220054134A (ko) | 스위칭 결합제, 이의 제조 방법, 및 이를 이용한 약학 조성물, 검사 키트 및 항원과 항체의 분석 방법 | |
KR102504175B1 (ko) | 항체의 항원 결합 부위에 결합하는 펩타이드, 이를 이용한 약물 복합체, 바이오센서 및 분석 방법 | |
BR112021005669A2 (pt) | anticorpos contra bcma solúvel | |
WO2022202876A1 (ja) | I型コラーゲンc末端テロペプチドの免疫学的分析方法 | |
WO2017033846A1 (ja) | 免疫試験方法および免疫試験キット | |
WO2023068248A1 (ja) | I型コラーゲン架橋n-テロペプチドの免疫測定方法及び免疫測定キット、並びに抗体又はその抗体断片 | |
JP7105970B1 (ja) | SARS-CoV-2の免疫測定方法及び免疫測定キット | |
JP7366411B2 (ja) | ヒトαディフェンシンHD5を検出する方法及びキット、並びにこれらにおいて用いられる抗体 | |
CN115925924A (zh) | 用于检测tsp-1特异性肽段的抗体及其用途 | |
TW202342979A (zh) | 檢測方法及檢測試劑 | |
JP5585587B2 (ja) | 5.9kDaペプチドの免疫学的測定方法 | |
WO2023203101A1 (en) | Antibody against kynurenine | |
US20210278403A1 (en) | Lateral flow assay for assessing recombinant protein expression or reporter gene expression | |
JPWO2020158857A1 (ja) | 生物学的試料中の遊離aimの免疫学的分析方法及び測定キット |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20220609 |
|
A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20220609 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20230725 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20231024 |
|
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: 20231205 |
|
A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20231222 |
|
R150 | Certificate of patent or registration of utility model |
Ref document number: 7416485 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 |