JP2004504007A5 - - Google Patents
Download PDFInfo
- Publication number
- JP2004504007A5 JP2004504007A5 JP2001548557A JP2001548557A JP2004504007A5 JP 2004504007 A5 JP2004504007 A5 JP 2004504007A5 JP 2001548557 A JP2001548557 A JP 2001548557A JP 2001548557 A JP2001548557 A JP 2001548557A JP 2004504007 A5 JP2004504007 A5 JP 2004504007A5
- Authority
- JP
- Japan
- Prior art keywords
- scfv
- framework
- library
- protein
- antigen
- 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 description 77
- 210000004027 cell Anatomy 0.000 description 69
- 108090000623 proteins and genes Proteins 0.000 description 66
- 239000000427 antigen Substances 0.000 description 60
- 108091007433 antigens Proteins 0.000 description 58
- 102000036639 antigens Human genes 0.000 description 58
- 102000004169 proteins and genes Human genes 0.000 description 56
- 235000018102 proteins Nutrition 0.000 description 55
- 239000012634 fragment Substances 0.000 description 41
- 230000004913 activation Effects 0.000 description 38
- 108010047041 Complementarity Determining Regions Proteins 0.000 description 33
- 102100039556 Galectin-4 Human genes 0.000 description 31
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 31
- 108010001515 Galectin 4 Proteins 0.000 description 30
- 235000014680 Saccharomyces cerevisiae Nutrition 0.000 description 30
- 239000003550 marker Substances 0.000 description 30
- 230000004927 fusion Effects 0.000 description 28
- 108700008625 Reporter Genes Proteins 0.000 description 23
- 230000003993 interaction Effects 0.000 description 23
- 230000000694 effects Effects 0.000 description 21
- 230000014509 gene expression Effects 0.000 description 20
- 101100112922 Candida albicans CDR3 gene Proteins 0.000 description 19
- 238000012216 screening Methods 0.000 description 19
- 230000004568 DNA-binding Effects 0.000 description 18
- 238000001727 in vivo Methods 0.000 description 18
- 150000001413 amino acids Chemical class 0.000 description 17
- 230000027455 binding Effects 0.000 description 17
- 230000035772 mutation Effects 0.000 description 17
- 108020001507 fusion proteins Proteins 0.000 description 16
- 102000037865 fusion proteins Human genes 0.000 description 16
- KLSJWNVTNUYHDU-UHFFFAOYSA-N Amitrole Chemical compound NC1=NC=NN1 KLSJWNVTNUYHDU-UHFFFAOYSA-N 0.000 description 14
- 230000012010 growth Effects 0.000 description 13
- 238000013518 transcription Methods 0.000 description 13
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 description 12
- ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 12
- 235000001014 amino acid Nutrition 0.000 description 12
- 108010005774 beta-Galactosidase Proteins 0.000 description 11
- 230000035897 transcription Effects 0.000 description 11
- 210000005253 yeast cell Anatomy 0.000 description 11
- 230000001419 dependent effect Effects 0.000 description 10
- 230000003834 intracellular effect Effects 0.000 description 10
- 239000000047 product Substances 0.000 description 10
- 101100107610 Arabidopsis thaliana ABCF4 gene Proteins 0.000 description 9
- 102100026189 Beta-galactosidase Human genes 0.000 description 9
- 101150009006 HIS3 gene Proteins 0.000 description 9
- 108091028043 Nucleic acid sequence Proteins 0.000 description 9
- 101100068078 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) GCN4 gene Proteins 0.000 description 9
- 230000004071 biological effect Effects 0.000 description 9
- 238000000338 in vitro Methods 0.000 description 8
- 230000029279 positive regulation of transcription, DNA-dependent Effects 0.000 description 8
- 102000052510 DNA-Binding Proteins Human genes 0.000 description 7
- 101710096438 DNA-binding protein Proteins 0.000 description 7
- 238000012258 culturing Methods 0.000 description 7
- 108091008146 restriction endonucleases Proteins 0.000 description 7
- 101100394989 Rhodopseudomonas palustris (strain ATCC BAA-98 / CGA009) hisI gene Proteins 0.000 description 6
- 210000003527 eukaryotic cell Anatomy 0.000 description 6
- 230000006870 function Effects 0.000 description 6
- 239000013612 plasmid Substances 0.000 description 6
- 238000003908 quality control method Methods 0.000 description 6
- 230000001131 transforming effect Effects 0.000 description 6
- 238000003160 two-hybrid assay Methods 0.000 description 6
- 238000011144 upstream manufacturing Methods 0.000 description 6
- 108020004414 DNA Proteins 0.000 description 5
- 230000003213 activating effect Effects 0.000 description 5
- 108090000765 processed proteins & peptides Proteins 0.000 description 5
- 230000009466 transformation Effects 0.000 description 5
- 239000013598 vector Substances 0.000 description 5
- 238000001262 western blot Methods 0.000 description 5
- 108010077850 Nuclear Localization Signals Proteins 0.000 description 4
- 238000003556 assay Methods 0.000 description 4
- 230000008901 benefit Effects 0.000 description 4
- 210000004899 c-terminal region Anatomy 0.000 description 4
- 238000006243 chemical reaction Methods 0.000 description 4
- 238000010367 cloning Methods 0.000 description 4
- 210000000805 cytoplasm Anatomy 0.000 description 4
- 238000010790 dilution Methods 0.000 description 4
- 239000012895 dilution Substances 0.000 description 4
- 238000006471 dimerization reaction Methods 0.000 description 4
- 238000002474 experimental method Methods 0.000 description 4
- 239000013604 expression vector Substances 0.000 description 4
- 230000002401 inhibitory effect Effects 0.000 description 4
- 239000013642 negative control Substances 0.000 description 4
- 238000002823 phage display Methods 0.000 description 4
- 230000002829 reductive effect Effects 0.000 description 4
- 230000004083 survival effect Effects 0.000 description 4
- 238000010396 two-hybrid screening Methods 0.000 description 4
- 108700028369 Alleles Proteins 0.000 description 3
- 108091026890 Coding region Proteins 0.000 description 3
- 101001011017 Gallus gallus Gallinacin-11 Proteins 0.000 description 3
- 101001011003 Gallus gallus Gallinacin-13 Proteins 0.000 description 3
- AVKUERGKIZMTKX-NJBDSQKTSA-N ampicillin Chemical compound C1([C@@H](N)C(=O)N[C@H]2[C@H]3SC([C@@H](N3C2=O)C(O)=O)(C)C)=CC=CC=C1 AVKUERGKIZMTKX-NJBDSQKTSA-N 0.000 description 3
- 229960000723 ampicillin Drugs 0.000 description 3
- 238000004458 analytical method Methods 0.000 description 3
- 230000000903 blocking effect Effects 0.000 description 3
- 230000001086 cytosolic effect Effects 0.000 description 3
- 230000004807 localization Effects 0.000 description 3
- 238000004519 manufacturing process Methods 0.000 description 3
- 230000000717 retained effect Effects 0.000 description 3
- 230000028327 secretion Effects 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- OPIFSICVWOWJMJ-AEOCFKNESA-N 5-bromo-4-chloro-3-indolyl beta-D-galactoside Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1OC1=CNC2=CC=C(Br)C(Cl)=C12 OPIFSICVWOWJMJ-AEOCFKNESA-N 0.000 description 2
- 108020004705 Codon Proteins 0.000 description 2
- 102000004190 Enzymes Human genes 0.000 description 2
- 108090000790 Enzymes Proteins 0.000 description 2
- 108010058643 Fungal Proteins Proteins 0.000 description 2
- 101150094690 GAL1 gene Proteins 0.000 description 2
- 102100028501 Galanin peptides Human genes 0.000 description 2
- 101100121078 Homo sapiens GAL gene Proteins 0.000 description 2
- 108091007491 NSP3 Papain-like protease domains Proteins 0.000 description 2
- 108091034117 Oligonucleotide Proteins 0.000 description 2
- 108010067902 Peptide Library Proteins 0.000 description 2
- 108700026226 TATA Box Proteins 0.000 description 2
- 108091023040 Transcription factor Proteins 0.000 description 2
- 102000040945 Transcription factor Human genes 0.000 description 2
- HSRXSKHRSXRCFC-WDSKDSINSA-N Val-Ala Chemical compound CC(C)[C@H](N)C(=O)N[C@@H](C)C(O)=O HSRXSKHRSXRCFC-WDSKDSINSA-N 0.000 description 2
- 230000003042 antagnostic effect Effects 0.000 description 2
- WQZGKKKJIJFFOK-FPRJBGLDSA-N beta-D-galactose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@H]1O WQZGKKKJIJFFOK-FPRJBGLDSA-N 0.000 description 2
- 230000008827 biological function Effects 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 230000010261 cell growth Effects 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 235000018417 cysteine Nutrition 0.000 description 2
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 2
- 238000001514 detection method Methods 0.000 description 2
- 230000002255 enzymatic effect Effects 0.000 description 2
- 239000000284 extract Substances 0.000 description 2
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 2
- 230000005764 inhibitory process Effects 0.000 description 2
- 230000010354 integration Effects 0.000 description 2
- 238000002955 isolation Methods 0.000 description 2
- 108020004999 messenger RNA Proteins 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 102000004196 processed proteins & peptides Human genes 0.000 description 2
- 230000010076 replication Effects 0.000 description 2
- 238000002741 site-directed mutagenesis Methods 0.000 description 2
- 238000010561 standard procedure Methods 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- 230000008685 targeting Effects 0.000 description 2
- 108091006106 transcriptional activators Proteins 0.000 description 2
- 238000013519 translation Methods 0.000 description 2
- 102100030310 5,6-dihydroxyindole-2-carboxylic acid oxidase Human genes 0.000 description 1
- 101710163881 5,6-dihydroxyindole-2-carboxylic acid oxidase Proteins 0.000 description 1
- 101710197633 Actin-1 Proteins 0.000 description 1
- 102000007469 Actins Human genes 0.000 description 1
- 108010085238 Actins Proteins 0.000 description 1
- 244000182625 Dictamnus albus Species 0.000 description 1
- 101150098914 GAL11 gene Proteins 0.000 description 1
- 101000608765 Homo sapiens Galectin-4 Proteins 0.000 description 1
- 108010054477 Immunoglobulin Fab Fragments Proteins 0.000 description 1
- 102000001706 Immunoglobulin Fab Fragments Human genes 0.000 description 1
- 241000235058 Komagataella pastoris Species 0.000 description 1
- ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-N 0.000 description 1
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 1
- 101710128836 Large T antigen Proteins 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- KZNQNBZMBZJQJO-UHFFFAOYSA-N N-glycyl-L-proline Natural products NCC(=O)N1CCCC1C(O)=O KZNQNBZMBZJQJO-UHFFFAOYSA-N 0.000 description 1
- 239000002033 PVDF binder Substances 0.000 description 1
- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 1
- 238000012300 Sequence Analysis Methods 0.000 description 1
- 101150006914 TRP1 gene Proteins 0.000 description 1
- QWXOJIDBSHLIFI-UHFFFAOYSA-N [3-(1-chloro-3'-methoxyspiro[adamantane-4,4'-dioxetane]-3'-yl)phenyl] dihydrogen phosphate Chemical compound O1OC2(C3CC4CC2CC(Cl)(C4)C3)C1(OC)C1=CC=CC(OP(O)(O)=O)=C1 QWXOJIDBSHLIFI-UHFFFAOYSA-N 0.000 description 1
- JLCPHMBAVCMARE-UHFFFAOYSA-N [3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-hydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methyl [5-(6-aminopurin-9-yl)-2-(hydroxymethyl)oxolan-3-yl] hydrogen phosphate Polymers Cc1cn(C2CC(OP(O)(=O)OCC3OC(CC3OP(O)(=O)OCC3OC(CC3O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c3nc(N)[nH]c4=O)C(COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3CO)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cc(C)c(=O)[nH]c3=O)n3cc(C)c(=O)[nH]c3=O)n3ccc(N)nc3=O)n3cc(C)c(=O)[nH]c3=O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)O2)c(=O)[nH]c1=O JLCPHMBAVCMARE-UHFFFAOYSA-N 0.000 description 1
- 239000000556 agonist Substances 0.000 description 1
- 235000004279 alanine Nutrition 0.000 description 1
- 230000004075 alteration Effects 0.000 description 1
- 238000000137 annealing Methods 0.000 description 1
- 125000000637 arginyl group Chemical group N[C@@H](CCCNC(N)=N)C(=O)* 0.000 description 1
- 230000001363 autoimmune Effects 0.000 description 1
- 210000003719 b-lymphocyte Anatomy 0.000 description 1
- 230000001580 bacterial effect Effects 0.000 description 1
- 239000011324 bead Substances 0.000 description 1
- 230000002457 bidirectional effect Effects 0.000 description 1
- 210000002421 cell wall Anatomy 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 210000000349 chromosome Anatomy 0.000 description 1
- 230000002860 competitive effect Effects 0.000 description 1
- 230000000295 complement effect Effects 0.000 description 1
- 230000001276 controlling effect Effects 0.000 description 1
- 230000009089 cytolysis Effects 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 239000003398 denaturant Substances 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 230000000368 destabilizing effect Effects 0.000 description 1
- 239000003599 detergent Substances 0.000 description 1
- 238000003745 diagnosis Methods 0.000 description 1
- 230000029087 digestion Effects 0.000 description 1
- 230000006806 disease prevention Effects 0.000 description 1
- KAKKHKRHCKCAGH-UHFFFAOYSA-L disodium;(4-nitrophenyl) phosphate;hexahydrate Chemical compound O.O.O.O.O.O.[Na+].[Na+].[O-][N+](=O)C1=CC=C(OP([O-])([O-])=O)C=C1 KAKKHKRHCKCAGH-UHFFFAOYSA-L 0.000 description 1
- 238000010494 dissociation reaction Methods 0.000 description 1
- 230000005593 dissociations Effects 0.000 description 1
- 150000002019 disulfides Chemical class 0.000 description 1
- 150000004662 dithiols Chemical group 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 238000005194 fractionation Methods 0.000 description 1
- 238000010230 functional analysis Methods 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- KZNQNBZMBZJQJO-YFKPBYRVSA-N glyclproline Chemical compound NCC(=O)N1CCC[C@H]1C(O)=O KZNQNBZMBZJQJO-YFKPBYRVSA-N 0.000 description 1
- 125000003630 glycyl group Chemical group [H]N([H])C([H])([H])C(*)=O 0.000 description 1
- 108010077515 glycylproline Proteins 0.000 description 1
- 229960002520 hepatitis vaccine Drugs 0.000 description 1
- 210000005260 human cell Anatomy 0.000 description 1
- 210000004408 hybridoma Anatomy 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 230000003053 immunization Effects 0.000 description 1
- 238000002649 immunization Methods 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- AIHDCSAXVMAMJH-GFBKWZILSA-N levan Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)OC[C@@H]1[C@@H](O)[C@H](O)[C@](CO)(CO[C@@H]2[C@H]([C@H](O)[C@@](O)(CO)O2)O)O1 AIHDCSAXVMAMJH-GFBKWZILSA-N 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- XIXADJRWDQXREU-UHFFFAOYSA-M lithium acetate Chemical compound [Li+].CC([O-])=O XIXADJRWDQXREU-UHFFFAOYSA-M 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 230000004001 molecular interaction Effects 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- 239000000178 monomer Substances 0.000 description 1
- 238000002703 mutagenesis Methods 0.000 description 1
- 231100000350 mutagenesis Toxicity 0.000 description 1
- 150000007523 nucleic acids Chemical group 0.000 description 1
- 239000002773 nucleotide Substances 0.000 description 1
- 125000003729 nucleotide group Chemical group 0.000 description 1
- 210000004940 nucleus Anatomy 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 230000001590 oxidative effect Effects 0.000 description 1
- 238000003752 polymerase chain reaction Methods 0.000 description 1
- 229920001184 polypeptide Polymers 0.000 description 1
- 229920002981 polyvinylidene fluoride Polymers 0.000 description 1
- 239000013641 positive control Substances 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 125000001500 prolyl group Chemical group [H]N1C([H])(C(=O)[*])C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
- 230000000069 prophylactic effect Effects 0.000 description 1
- 230000004952 protein activity Effects 0.000 description 1
- 230000006916 protein interaction Effects 0.000 description 1
- 230000004850 protein–protein interaction Effects 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 238000002708 random mutagenesis Methods 0.000 description 1
- 230000022532 regulation of transcription, DNA-dependent Effects 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 238000009877 rendering Methods 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 238000002702 ribosome display Methods 0.000 description 1
- 230000005070 ripening Effects 0.000 description 1
- 102220244406 rs761122171 Human genes 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 238000013207 serial dilution Methods 0.000 description 1
- 235000004400 serine Nutrition 0.000 description 1
- 125000003607 serino group Chemical class [H]N([H])[C@]([H])(C(=O)[*])C(O[H])([H])[H] 0.000 description 1
- 239000013605 shuttle vector Substances 0.000 description 1
- 230000019491 signal transduction Effects 0.000 description 1
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 210000000952 spleen Anatomy 0.000 description 1
- 230000000087 stabilizing effect Effects 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 230000005030 transcription termination Effects 0.000 description 1
- 230000002103 transcriptional effect Effects 0.000 description 1
- 238000000844 transformation Methods 0.000 description 1
- 238000002054 transplantation Methods 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| IB9902054 | 1999-12-28 | ||
| IBPCT/IB99/02054 | 1999-12-28 | ||
| IBPCT/IB00/00218 | 2000-03-01 | ||
| IBPCT/IB00/00218 | 2000-03-01 | ||
| PCT/IB2000/001892 WO2001048017A1 (en) | 1999-12-28 | 2000-12-18 | Intrabodies with defined framework that is stable in a reducing environment and applications thereof |
Related Child Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2010240199A Division JP5783703B2 (ja) | 1999-12-28 | 2010-10-26 | 還元環境下において安定な、規定されたフレームワークを有するイントラボディーおよびそれらの用途 |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2004504007A JP2004504007A (ja) | 2004-02-12 |
| JP2004504007A5 true JP2004504007A5 (https=) | 2010-12-24 |
| JP4698109B2 JP4698109B2 (ja) | 2011-06-08 |
Family
ID=26318608
Family Applications (4)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2001548557A Expired - Fee Related JP4698109B2 (ja) | 1999-12-28 | 2000-12-18 | 還元環境下において安定な、規定されたフレームワークを有するイントラボディーおよびそれらの用途 |
| JP2010240199A Expired - Fee Related JP5783703B2 (ja) | 1999-12-28 | 2010-10-26 | 還元環境下において安定な、規定されたフレームワークを有するイントラボディーおよびそれらの用途 |
| JP2013096838A Withdrawn JP2013224294A (ja) | 1999-12-28 | 2013-05-02 | 還元環境下において安定な、規定されたフレームワークを有するイントラボディーおよびそれらの用途 |
| JP2015208555A Pending JP2016020388A (ja) | 1999-12-28 | 2015-10-23 | 還元環境下において安定な、規定されたフレームワークを有するイントラボディーおよびそれらの用途 |
Family Applications After (3)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2010240199A Expired - Fee Related JP5783703B2 (ja) | 1999-12-28 | 2010-10-26 | 還元環境下において安定な、規定されたフレームワークを有するイントラボディーおよびそれらの用途 |
| JP2013096838A Withdrawn JP2013224294A (ja) | 1999-12-28 | 2013-05-02 | 還元環境下において安定な、規定されたフレームワークを有するイントラボディーおよびそれらの用途 |
| JP2015208555A Pending JP2016020388A (ja) | 1999-12-28 | 2015-10-23 | 還元環境下において安定な、規定されたフレームワークを有するイントラボディーおよびそれらの用途 |
Country Status (10)
| Country | Link |
|---|---|
| US (3) | US7258986B2 (https=) |
| EP (3) | EP1242457B1 (https=) |
| JP (4) | JP4698109B2 (https=) |
| AT (1) | ATE273323T1 (https=) |
| AU (1) | AU768827B2 (https=) |
| CA (1) | CA2396534C (https=) |
| DE (1) | DE60012980T2 (https=) |
| DK (1) | DK1242457T3 (https=) |
| ES (1) | ES2225269T3 (https=) |
| WO (1) | WO2001048017A1 (https=) |
Families Citing this family (65)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1999028502A1 (en) * | 1997-11-28 | 1999-06-10 | Invitrogen Corporation | Single chain monoclonal antibody fusion reagents that regulate transcription in vivo |
| IT1317922B1 (it) * | 2000-10-24 | 2003-07-15 | S I S S A Scuola Internaz Supe | Metodo per identificare in vivo epitopi intracellulari. |
| US6610472B1 (en) * | 2000-10-31 | 2003-08-26 | Genetastix Corporation | Assembly and screening of highly complex and fully human antibody repertoire in yeast |
| US20050037420A1 (en) * | 2001-09-14 | 2005-02-17 | Mei-Yun Zhang | Immunoglobulin having particular framework scaffold and methods of making and using |
| WO2003077945A1 (en) * | 2002-03-14 | 2003-09-25 | Medical Research Council | Intracellular antibodies |
| AU2012211497C1 (en) * | 2002-05-22 | 2021-07-29 | Novartis Ag | Immunoglobulin frameworks which demonstrate enhanced stability in the intracellular environment and methods of identifying same |
| AU2013203285B2 (en) * | 2002-05-22 | 2015-04-23 | Novartis Ag | Immunoglobulin frameworks which demonstrate enhanced stability in the intracellular environment and methods of identifying same |
| JP2006508638A (ja) | 2002-05-22 | 2006-03-16 | エスバテック・アーゲー | 細胞内環境において向上した安定性を示す免疫グロブリンフレームワークおよびそれを同定する方法 |
| AU2015202410B2 (en) * | 2002-05-22 | 2017-09-14 | Novartis Ag | Immunoglobulin frameworks which demonstrate enhanced stability in the intracellular environment and methods of identifying same |
| CA2523912A1 (en) * | 2003-04-30 | 2004-11-11 | Japan Science And Technology Agency | Human antihuman interleukin-18 antibody, fragment thereof and method of using the same |
| US20050226863A1 (en) * | 2003-11-20 | 2005-10-13 | Massachusetts Institute Of Technology | Single-domain antibodies and uses thereof |
| EP1761561B1 (en) * | 2004-01-20 | 2015-08-26 | KaloBios Pharmaceuticals, Inc. | Antibody specificity transfer using minimal essential binding determinants |
| KR100635370B1 (ko) | 2005-03-04 | 2006-10-17 | 주식회사 녹십자홀딩스 | ＳｃＦｖ 형태의 항체 라이브러리를 제작하기 위한 항체 ＳｃＦｖ 발현벡터 |
| JP5171611B2 (ja) * | 2005-03-25 | 2013-03-27 | ナショナル リサーチ カウンシル オブ カナダ | 可溶性ポリペプチドの単離方法 |
| FR2883886B1 (fr) * | 2005-04-05 | 2010-12-03 | Biomethodes | Methode d'obtention de variants solubles ou mieux exprimes d'une proteine d'interet |
| KR101457223B1 (ko) | 2005-06-07 | 2014-11-04 | 에스바테크 - 어 노바티스 컴파니 엘엘씨 | ＴＮＦα를 억제하는 안정적이고 가용성인 항체 |
| JP4938263B2 (ja) * | 2005-08-19 | 2012-05-23 | 独立行政法人農業生物資源研究所 | 一本鎖抗体によるサイトゾルタンパク質の機能阻害法およびその利用 |
| EP2360473A1 (en) * | 2005-08-22 | 2011-08-24 | Cornell Research Foundation | Compositions and methods for analyzing protein interactions |
| BRPI0710971A2 (pt) * | 2006-04-28 | 2011-05-31 | Esbatech Ag | anticorpos que se ligam ao domìnio extracelular do receptor tirosina cinase alk,seu uso, vetor de expressão,método para produção de um antcorpo, vacina e epìtodo de alk |
| ES2820837T3 (es) * | 2006-07-10 | 2021-04-22 | Esbatech Alcon Biomed Res Unit | Anticuerpos scFv que pasan las capas epitelial y/o endotelial |
| US8722584B2 (en) * | 2007-01-12 | 2014-05-13 | Cornell University | Genetic selection for protein folding and solubility in the bacterial periplasm |
| RU2009137582A (ru) | 2007-03-12 | 2011-04-20 | Эсбатек Аг (Ch) | Инженерия и оптимизация одноцепочечных антител на основе последовательности |
| EP2134841B9 (en) * | 2007-03-15 | 2014-06-11 | Inserm | Methods for producing active scfv antibodies and libraries therefor |
| DK2164514T3 (en) * | 2007-05-21 | 2017-02-27 | Alderbio Holdings Llc | Antibodies to IL-6 and its use |
| BRPI0813645A2 (pt) | 2007-06-25 | 2014-12-30 | Esbatech Alcon Biomed Res Unit | Métodos para modificar anticorpos, e anticorpos modificados com propriedades funcionais aperfeiçoadas |
| EP2164961B1 (en) * | 2007-06-25 | 2015-01-07 | ESBATech, an Alcon Biomedical Research Unit LLC | Sequence based engineering and optimization of single chain antibodies |
| US8323647B2 (en) | 2007-09-13 | 2012-12-04 | Delenex Therapeutics Ag | Humanized antibodies against the β-amyloid peptide |
| PL2307458T3 (pl) | 2008-06-25 | 2018-08-31 | Esbatech, An Alcon Biomedical Research Unit Llc | Humanizacja przeciwciał króliczych z zastosowaniem uniwersalnego zrębu przeciwciała |
| KR102050040B1 (ko) * | 2008-06-25 | 2019-11-28 | 에스바테크 - 어 노바티스 컴파니 엘엘씨 | ＴＮＦα를 저해하는 안정한 가용성 항체 |
| CA2728829C (en) | 2008-06-25 | 2018-01-02 | Esbatech, An Alcon Biomedical Research Unit Llc | Solubility optimization of immunobinders |
| PL3628686T3 (pl) | 2008-06-25 | 2022-02-28 | Novartis Ag | Humanizowanie przeciwciał króliczych z zastosowaniem uniwersalnego zrębu przeciwciała |
| BRPI0914251B1 (pt) | 2008-06-25 | 2022-07-19 | Novartis Ag | Imunoligante recombinante, seu fragmento de ligação ao antígeno, uso dos mesmos, e composição |
| US8399625B1 (en) | 2009-06-25 | 2013-03-19 | ESBATech, an Alcon Biomedical Research Unit, LLC | Acceptor framework for CDR grafting |
| UY33679A (es) | 2010-10-22 | 2012-03-30 | Esbatech | Anticuerpos estables y solubles |
| EP2855698A4 (en) | 2012-05-24 | 2016-03-30 | Dana Farber Cancer Inst Inc | OBTAINING TO THE GLUTAMINE-TO-PYRUVAT SIGNAL PATH FOR THE TREATMENT OF CANCER ASSOCIATED WITH THE KRAS ONKOGEN |
| WO2014014518A1 (en) | 2012-07-18 | 2014-01-23 | Dana-Farber Cancer Institute, Inc. | Methods for treating, preventing and predicting risk of developing breast cancer |
| JP2016506974A (ja) * | 2013-02-15 | 2016-03-07 | エスバテック − ア ノバルティスカンパニー エルエルシー | Ｃｄｒグラフトのためのアクセプターフレームワーク |
| CA2896174A1 (en) | 2013-02-20 | 2014-08-28 | Esbatech - A Novartis Company Llc | Acceptor framework for cdr grafting |
| CN105829349B (zh) | 2013-10-15 | 2023-02-03 | 斯克利普斯研究所 | 肽嵌合抗原受体t细胞开关和其用途 |
| WO2015149006A2 (en) | 2014-03-27 | 2015-10-01 | Dana-Farber Cancer Institute, Inc. | Compositions and methods for modulating ncoa4-mediated autophagic targeting of ferritin |
| CN113604491A (zh) | 2014-05-02 | 2021-11-05 | 宾夕法尼亚大学董事会 | 嵌合自身抗体受体t细胞的组合物和方法 |
| GB201409558D0 (en) | 2014-05-29 | 2014-07-16 | Ucb Biopharma Sprl | Method |
| US9212225B1 (en) | 2014-07-01 | 2015-12-15 | Amphivena Therapeutics, Inc. | Bispecific CD33 and CD3 binding proteins |
| US20170219596A1 (en) * | 2014-07-14 | 2017-08-03 | The Regents Of The University Of California | A protein tagging system for in vivo single molecule imaging and control of gene transcription |
| GB201412659D0 (en) | 2014-07-16 | 2014-08-27 | Ucb Biopharma Sprl | Molecules |
| GB201412658D0 (en) | 2014-07-16 | 2014-08-27 | Ucb Biopharma Sprl | Molecules |
| EP3191592A1 (en) | 2014-09-11 | 2017-07-19 | Novartis AG | Inhibition of prmt5 to treat mtap-deficiency-related diseases |
| WO2016089883A1 (en) | 2014-12-01 | 2016-06-09 | Novartis Ag | Compositions and methods for diagnosis and treatment of prostate cancer |
| US10800828B2 (en) | 2015-03-26 | 2020-10-13 | The Scripps Research Institute | Switchable non-scFv chimeric receptors, switches, and methods of use thereof to treat cancer |
| US11091546B2 (en) | 2015-04-15 | 2021-08-17 | The Scripps Research Institute | Optimized PNE-based chimeric receptor T cell switches and uses thereof |
| US10738118B2 (en) | 2015-05-29 | 2020-08-11 | Amphivena Therapeutics, Inc. | Methods of using bispecific CD33 and CD3 binding proteins |
| GB201601073D0 (en) | 2016-01-20 | 2016-03-02 | Ucb Biopharma Sprl | Antibodies |
| GB201601075D0 (en) | 2016-01-20 | 2016-03-02 | Ucb Biopharma Sprl | Antibodies molecules |
| GB201601077D0 (en) | 2016-01-20 | 2016-03-02 | Ucb Biopharma Sprl | Antibody molecule |
| GB201521383D0 (en) | 2015-12-03 | 2016-01-20 | Ucb Biopharma Sprl And Ucb Celltech | Method |
| GB201521391D0 (en) | 2015-12-03 | 2016-01-20 | Ucb Biopharma Sprl | Antibodies |
| GB201521389D0 (en) | 2015-12-03 | 2016-01-20 | Ucb Biopharma Sprl | Method |
| GB201521393D0 (en) | 2015-12-03 | 2016-01-20 | Ucb Biopharma Sprl | Antibodies |
| GB201521382D0 (en) | 2015-12-03 | 2016-01-20 | Ucb Biopharma Sprl | Antibodies |
| EP3529268B1 (en) | 2016-10-19 | 2025-02-26 | The Scripps Research Institute | Chimeric antigen receptor effector cell switches with humanized targeting moieties and/or optimized chimeric antigen receptor interacting domains and uses thereof |
| US11530413B2 (en) | 2017-07-21 | 2022-12-20 | Novartis Ag | Compositions and methods to treat cancer |
| JP7429192B2 (ja) | 2018-04-06 | 2024-02-07 | デイナ ファーバー キャンサー インスティチュート，インコーポレイテッド | Ｈｈｌａ２受容体としてのｋｉｒ３ｄｌ３、抗ｈｈｌａ２抗体、およびその使用 |
| WO2019213276A1 (en) | 2018-05-02 | 2019-11-07 | Novartis Ag | Regulators of human pluripotent stem cells and uses thereof |
| WO2020069349A1 (en) * | 2018-09-27 | 2020-04-02 | Colorado State University Research Foundation | Scfv's for live cell imaging and other uses |
| WO2023229535A1 (en) | 2022-05-27 | 2023-11-30 | Engine Biosciences Pte. Ltd. | Bet polypeptide therapeutic agents for generating synthetic lethality in tumors |
Family Cites Families (18)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5618920A (en) | 1985-11-01 | 1997-04-08 | Xoma Corporation | Modular assembly of antibody genes, antibodies prepared thereby and use |
| FR2627508B1 (fr) | 1988-02-22 | 1990-10-05 | Eurolysine | Procede pour l'integration d'un gene choisi sur le chromosome d'une bacterie et bacterie obtenue par ledit procede |
| FR2648713B1 (fr) | 1989-06-26 | 1994-06-10 | Commissariat Energie Atomique | Proteines hybrides entre une enzyme extracytoplasmique et une autre proteine, leur procede de preparation, ainsi que leur application comme agent de diagnostic |
| WO1992022324A1 (en) | 1991-06-14 | 1992-12-23 | Xoma Corporation | Microbially-produced antibody fragments and their conjugates |
| JPH05105700A (ja) | 1991-07-15 | 1993-04-27 | Tosoh Corp | 酵母に対する血清又は抗体、それらの調製方法及びそれらの使用方法 |
| JPH0597704A (ja) | 1991-10-07 | 1993-04-20 | Hisashi Ishihara | 新抗体ワクチン製造技法 |
| JPH0630778A (ja) | 1992-07-17 | 1994-02-08 | Tosoh Corp | ピキア酵母により抗体を製造するためのベクタ−、該ベクタ−で形質転換されたピキア酵母及び形質転換ピキア酵母を培養することを特徴とする抗体の製造方法 |
| ES2162863T3 (es) | 1993-04-29 | 2002-01-16 | Unilever Nv | Produccion de anticuerpos o fragmentos (funcionalizados) de los mismos derivados de inmunoglobulinas de cadena pesada de camelidae. |
| EP0698097B1 (en) | 1993-04-29 | 2001-08-16 | Unilever N.V. | Production of antibodies or (functionalized) fragments thereof derived from heavy chain immunoglobulins of camelidae |
| JPH0920798A (ja) | 1995-07-11 | 1997-01-21 | Asahi Chem Ind Co Ltd | ヒト抗ＨＢｓ抗体 |
| DK0877752T3 (da) * | 1996-01-23 | 2003-09-15 | Univ Leland Stanford Junior | Fremgangsmåder til screening af transdominante effektorpeptider og RNA molekyler |
| WO1997044447A2 (en) * | 1996-05-03 | 1997-11-27 | President And Fellows Of Harvard College | Transcriptional activation system, activators, and uses therefor |
| US6300065B1 (en) | 1996-05-31 | 2001-10-09 | Board Of Trustees Of The University Of Illinois | Yeast cell surface display of proteins and uses thereof |
| US20030017149A1 (en) * | 1996-10-10 | 2003-01-23 | Hoeffler James P. | Single chain monoclonal antibody fusion reagents that regulate transcription in vivo |
| JP4041913B2 (ja) | 1997-02-13 | 2008-02-06 | 独立行政法人農業・食品産業技術総合研究機構 | 抗腫瘍タンパク質およびその遺伝子 |
| JPH11174A (ja) | 1997-06-13 | 1999-01-06 | Asahi Breweries Ltd | 酵母を用いた抗体Ｆａｂ断片の製造法 |
| WO1999028502A1 (en) * | 1997-11-28 | 1999-06-10 | Invitrogen Corporation | Single chain monoclonal antibody fusion reagents that regulate transcription in vivo |
| GB2344886B (en) * | 1999-03-10 | 2000-11-01 | Medical Res Council | Selection of intracellular immunoglobulins |
-
2000
- 2000-12-18 AT AT00979875T patent/ATE273323T1/de active
- 2000-12-18 JP JP2001548557A patent/JP4698109B2/ja not_active Expired - Fee Related
- 2000-12-18 AU AU17252/01A patent/AU768827B2/en not_active Ceased
- 2000-12-18 EP EP00979875A patent/EP1242457B1/en not_active Expired - Lifetime
- 2000-12-18 DK DK00979875T patent/DK1242457T3/da active
- 2000-12-18 EP EP10010030.4A patent/EP2392596A3/en not_active Withdrawn
- 2000-12-18 US US10/169,179 patent/US7258986B2/en not_active Expired - Lifetime
- 2000-12-18 EP EP04017280.1A patent/EP1479694B1/en not_active Expired - Lifetime
- 2000-12-18 CA CA2396534A patent/CA2396534C/en not_active Expired - Fee Related
- 2000-12-18 ES ES00979875T patent/ES2225269T3/es not_active Expired - Lifetime
- 2000-12-18 WO PCT/IB2000/001892 patent/WO2001048017A1/en not_active Ceased
- 2000-12-18 DE DE60012980T patent/DE60012980T2/de not_active Expired - Lifetime
- 2000-12-28 US US09/750,424 patent/US7258985B2/en not_active Expired - Lifetime
-
2007
- 2007-08-20 US US11/894,097 patent/US20080233110A1/en not_active Abandoned
-
2010
- 2010-10-26 JP JP2010240199A patent/JP5783703B2/ja not_active Expired - Fee Related
-
2013
- 2013-05-02 JP JP2013096838A patent/JP2013224294A/ja not_active Withdrawn
-
2015
- 2015-10-23 JP JP2015208555A patent/JP2016020388A/ja active Pending
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP4698109B2 (ja) | 還元環境下において安定な、規定されたフレームワークを有するイントラボディーおよびそれらの用途 | |
| JP2004504007A5 (https=) | ||
| JP3210342B2 (ja) | 全合成親和性試薬 | |
| CA2681170C (en) | Methods for producing active scfv antibodies and libraries therefor | |
| KR20120118045A (ko) | 효모 세포 표면상에 폴리펩티드를 디스플레이하기 위한 방법들 및 조성물들 | |
| JP2026500340A (ja) | 抗ｃｌｌ１単一ドメイン抗体及びその使用 | |
| JP2013510592A (ja) | 改善された細菌膜タンパク質分泌 | |
| CN110003336B (zh) | Pd-1单域抗体、核苷酸序列及试剂盒 | |
| JP2026508333A (ja) | Ｃｌｌ１タンパク質に特異的に結合する単一ドメイン抗体及びその使用 | |
| AU2010322202B2 (en) | Display of disulfide linked dimeric proteins on filamentous phage | |
| WO2018069416A1 (en) | Triple vector for expressing antibody molecules in full therapeutic format | |
| WO2007114139A1 (ja) | 新規繊維状ファージによるファージディスプレイ | |
| KR20180104675A (ko) | 합성 항체 라이브러리의 생성 방법, 상기 라이브러리 및 그 적용(들) | |
| Silva de Almeida et al. | The phage display technique: advantages and recent patents | |
| HK40051447A (en) | Screening and engineering method of super-stable immunoglobulin variable domains and their uses |