RU2696202C1 - Гуманизация антител кролика с использованием универсального каркаса антитела - Google Patents

Гуманизация антител кролика с использованием универсального каркаса антитела Download PDF

Info

Publication number: RU2696202C1
Authority: RU; Russia
Prior art keywords: framework; molecule; antibody; immunobinding; rabbit
Prior art date: 2008-06-25

Application number

RU2018109506A

Other languages

English (en)

Russian (ru)

Inventor

Леонардо БОРРАС

Дэвид УРЕХ

Original Assignee

ИЭсБиЭйТЕК, ЭН АЛЬКОН БАЙОМЕДИКАЛ РИСЕРЧ ЮНИТ ЭлЭлСи

Priority date (The priority date 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 date listed.)

2008-06-25

Filing date

2018-03-19

Publication date

2019-07-31

2018-03-19 Application filed by ИЭсБиЭйТЕК, ЭН АЛЬКОН БАЙОМЕДИКАЛ РИСЕРЧ ЮНИТ ЭлЭлСи filed Critical ИЭсБиЭйТЕК, ЭН АЛЬКОН БАЙОМЕДИКАЛ РИСЕРЧ ЮНИТ ЭлЭлСи

2019-07-31 Application granted granted Critical

2019-07-31 Publication of RU2696202C1 publication Critical patent/RU2696202C1/ru

Links

241000283973 Oryctolagus cuniculus Species 0.000 title claims description 133
230000027455 binding Effects 0.000 claims abstract description 106
238000000034 method Methods 0.000 claims abstract description 99
AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 claims abstract description 31
239000004473 Threonine Substances 0.000 claims abstract description 31
235000001014 amino acid Nutrition 0.000 claims description 96
150000001413 amino acids Chemical group 0.000 claims description 33
DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 claims description 27
KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 claims description 21
KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Natural products CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 claims description 21
239000004474 valine Substances 0.000 claims description 21
MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 claims description 19
239000004475 Arginine Substances 0.000 claims description 13
239000004471 Glycine Substances 0.000 claims description 13
ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 claims description 13
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 11
KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 claims description 9
239000004472 Lysine Substances 0.000 claims description 9
QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 claims description 6
235000004279 alanine Nutrition 0.000 claims description 6
COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 claims description 5
COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 claims description 5
WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 claims description 4
ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 claims description 4
ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 claims description 4
235000013922 glutamic acid Nutrition 0.000 claims description 4
239000004220 glutamic acid Substances 0.000 claims description 4
239000000126 substance Substances 0.000 abstract description 14
230000001225 therapeutic effect Effects 0.000 abstract description 11
230000000694 effects Effects 0.000 abstract description 7
108010047041 Complementarity Determining Regions Proteins 0.000 description 138
210000004027 cell Anatomy 0.000 description 103
125000003275 alpha amino acid group Chemical group 0.000 description 88
239000000427 antigen Substances 0.000 description 77
108091007433 antigens Proteins 0.000 description 77
102000036639 antigens Human genes 0.000 description 77
239000000203 mixture Substances 0.000 description 63
239000000370 acceptor Substances 0.000 description 53
108090000765 processed proteins & peptides Proteins 0.000 description 49
108090000623 proteins and genes Proteins 0.000 description 46
102000004196 processed proteins & peptides Human genes 0.000 description 44
229920001184 polypeptide Polymers 0.000 description 42
102000004169 proteins and genes Human genes 0.000 description 40
239000012634 fragment Substances 0.000 description 36
235000018102 proteins Nutrition 0.000 description 36
210000003719 b-lymphocyte Anatomy 0.000 description 34
229940024606 amino acid Drugs 0.000 description 28
239000008187 granular material Substances 0.000 description 26
239000013598 vector Substances 0.000 description 24
108020004414 DNA Proteins 0.000 description 23
125000005647 linker group Chemical group 0.000 description 23
102000005789 Vascular Endothelial Growth Factors Human genes 0.000 description 22
108010019530 Vascular Endothelial Growth Factors Proteins 0.000 description 22
229910052717 sulfur Inorganic materials 0.000 description 22
238000004458 analytical method Methods 0.000 description 21
238000002054 transplantation Methods 0.000 description 20
229910052720 vanadium Inorganic materials 0.000 description 19
238000009472 formulation Methods 0.000 description 18
150000007523 nucleic acids Chemical class 0.000 description 18
239000008194 pharmaceutical composition Substances 0.000 description 18
NFGXHKASABOEEW-UHFFFAOYSA-N 1-methylethyl 11-methoxy-3,7,11-trimethyl-2,4-dodecadienoate Chemical compound COC(C)(C)CCCC(C)CC=CC(C)=CC(=O)OC(C)C NFGXHKASABOEEW-UHFFFAOYSA-N 0.000 description 17
125000000539 amino acid group Chemical group 0.000 description 17
239000000872 buffer Substances 0.000 description 17
229910052739 hydrogen Inorganic materials 0.000 description 17
108060008682 Tumor Necrosis Factor Proteins 0.000 description 16
102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 description 16
239000003814 drug Substances 0.000 description 16
MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 description 15
101100112922 Candida albicans CDR3 gene Proteins 0.000 description 15
108091028043 Nucleic acid sequence Proteins 0.000 description 15
210000004978 chinese hamster ovary cell Anatomy 0.000 description 15
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 15
102000039446 nucleic acids Human genes 0.000 description 15
108020004707 nucleic acids Proteins 0.000 description 15
239000013604 expression vector Substances 0.000 description 14
102100035360 Cerebellar degeneration-related antigen 1 Human genes 0.000 description 13
101000737793 Homo sapiens Cerebellar degeneration-related antigen 1 Proteins 0.000 description 13
108060003951 Immunoglobulin Proteins 0.000 description 13
229910052731 fluorine Inorganic materials 0.000 description 13
102000018358 immunoglobulin Human genes 0.000 description 13
239000003755 preservative agent Substances 0.000 description 13
235000000346 sugar Nutrition 0.000 description 13
-1 cytochalazine B Chemical compound 0.000 description 12
230000035772 mutation Effects 0.000 description 12
229920005862 polyol Polymers 0.000 description 12
150000003077 polyols Chemical class 0.000 description 12
238000006467 substitution reaction Methods 0.000 description 12
101000737796 Homo sapiens Cerebellar degeneration-related protein 2 Proteins 0.000 description 11
206010028980 Neoplasm Diseases 0.000 description 11
108091034117 Oligonucleotide Proteins 0.000 description 11
239000004698 Polyethylene Substances 0.000 description 11
210000004602 germ cell Anatomy 0.000 description 11
229910052757 nitrogen Inorganic materials 0.000 description 11
239000000546 pharmaceutical excipient Substances 0.000 description 11
238000002965 ELISA Methods 0.000 description 10
108010067060 Immunoglobulin Variable Region Proteins 0.000 description 10
102000017727 Immunoglobulin Variable Region Human genes 0.000 description 10
231100000599 cytotoxic agent Toxicity 0.000 description 10
MZOFCQQQCNRIBI-VMXHOPILSA-N (3s)-4-[[(2s)-1-[[(2s)-1-[[(1s)-1-carboxy-2-hydroxyethyl]amino]-4-methyl-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-3-[[2-[[(2s)-2,6-diaminohexanoyl]amino]acetyl]amino]-4-oxobutanoic acid Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CC(O)=O)NC(=O)CNC(=O)[C@@H](N)CCCCN MZOFCQQQCNRIBI-VMXHOPILSA-N 0.000 description 9
241000699666 Mus <mouse, genus> Species 0.000 description 9
238000013459 approach Methods 0.000 description 9
230000001580 bacterial effect Effects 0.000 description 9
230000004071 biological effect Effects 0.000 description 9
239000003795 chemical substances by application Substances 0.000 description 9
229940079593 drug Drugs 0.000 description 9
238000005516 engineering process Methods 0.000 description 9
229910052740 iodine Inorganic materials 0.000 description 9
229910052698 phosphorus Inorganic materials 0.000 description 9
230000009870 specific binding Effects 0.000 description 9
239000000725 suspension Substances 0.000 description 9
101000611183 Homo sapiens Tumor necrosis factor Proteins 0.000 description 8
102000001706 Immunoglobulin Fab Fragments Human genes 0.000 description 8
108010054477 Immunoglobulin Fab Fragments Proteins 0.000 description 8
239000004480 active ingredient Substances 0.000 description 8
230000015572 biosynthetic process Effects 0.000 description 8
201000011510 cancer Diseases 0.000 description 8
239000000969 carrier Substances 0.000 description 8
201000010099 disease Diseases 0.000 description 8
230000001404 mediated effect Effects 0.000 description 8
239000000523 sample Substances 0.000 description 8
102000008394 Immunoglobulin Fragments Human genes 0.000 description 7
108010021625 Immunoglobulin Fragments Proteins 0.000 description 7
241000124008 Mammalia Species 0.000 description 7
241001465754 Metazoa Species 0.000 description 7
241000283984 Rodentia Species 0.000 description 7
240000004808 Saccharomyces cerevisiae Species 0.000 description 7
235000014680 Saccharomyces cerevisiae Nutrition 0.000 description 7
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 7
229930006000 Sucrose Natural products 0.000 description 7
102100040247 Tumor necrosis factor Human genes 0.000 description 7
230000008859 change Effects 0.000 description 7
239000002619 cytotoxin Substances 0.000 description 7
208000035475 disorder Diseases 0.000 description 7
238000010494 dissociation reaction Methods 0.000 description 7
230000005593 dissociations Effects 0.000 description 7
238000000684 flow cytometry Methods 0.000 description 7
210000004698 lymphocyte Anatomy 0.000 description 7
238000004519 manufacturing process Methods 0.000 description 7
239000000463 material Substances 0.000 description 7
239000013612 plasmid Substances 0.000 description 7
238000002360 preparation method Methods 0.000 description 7
238000000746 purification Methods 0.000 description 7
239000005720 sucrose Substances 0.000 description 7
238000002198 surface plasmon resonance spectroscopy Methods 0.000 description 7
239000003765 sweetening agent Substances 0.000 description 7
229910052727 yttrium Inorganic materials 0.000 description 7
HDTRYLNUVZCQOY-UHFFFAOYSA-N α-D-glucopyranosyl-α-D-glucopyranoside Natural products OC1C(O)C(O)C(CO)OC1OC1C(O)C(O)C(O)C(CO)O1 HDTRYLNUVZCQOY-UHFFFAOYSA-N 0.000 description 6
238000012300 Sequence Analysis Methods 0.000 description 6
HDTRYLNUVZCQOY-WSWWMNSNSA-N Trehalose Natural products O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@H](O)[C@@H](O)[C@@H](O)[C@@H](CO)O1 HDTRYLNUVZCQOY-WSWWMNSNSA-N 0.000 description 6
HDTRYLNUVZCQOY-LIZSDCNHSA-N alpha,alpha-trehalose Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 HDTRYLNUVZCQOY-LIZSDCNHSA-N 0.000 description 6
238000003556 assay Methods 0.000 description 6
150000001875 compounds Chemical class 0.000 description 6
150000002148 esters Chemical class 0.000 description 6
239000000796 flavoring agent Substances 0.000 description 6
235000003599 food sweetener Nutrition 0.000 description 6
HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 6
229940072221 immunoglobulins Drugs 0.000 description 6
239000011159 matrix material Substances 0.000 description 6
239000002609 medium Substances 0.000 description 6
238000003908 quality control method Methods 0.000 description 6
239000004094 surface-active agent Substances 0.000 description 6
210000001519 tissue Anatomy 0.000 description 6
238000011282 treatment Methods 0.000 description 6
108010075254 C-Peptide Proteins 0.000 description 5
241000588724 Escherichia coli Species 0.000 description 5
102000003688 G-Protein-Coupled Receptors Human genes 0.000 description 5
108090000045 G-Protein-Coupled Receptors Proteins 0.000 description 5
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 5
239000002253 acid Substances 0.000 description 5
238000003776 cleavage reaction Methods 0.000 description 5
230000000295 complement effect Effects 0.000 description 5
235000014113 dietary fatty acids Nutrition 0.000 description 5
238000002474 experimental method Methods 0.000 description 5
239000000194 fatty acid Substances 0.000 description 5
229930195729 fatty acid Natural products 0.000 description 5
150000004665 fatty acids Chemical class 0.000 description 5
230000004927 fusion Effects 0.000 description 5
230000003993 interaction Effects 0.000 description 5
FZWBNHMXJMCXLU-BLAUPYHCSA-N isomaltotriose Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1OC[C@@H]1[C@@H](O)[C@H](O)[C@@H](O)[C@@H](OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C=O)O1 FZWBNHMXJMCXLU-BLAUPYHCSA-N 0.000 description 5
210000004962 mammalian cell Anatomy 0.000 description 5
239000012528 membrane Substances 0.000 description 5
230000004048 modification Effects 0.000 description 5
238000012986 modification Methods 0.000 description 5
238000002703 mutagenesis Methods 0.000 description 5
231100000350 mutagenesis Toxicity 0.000 description 5
PXHVJJICTQNCMI-UHFFFAOYSA-N nickel Substances [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 5
238000005457 optimization Methods 0.000 description 5
229920000642 polymer Polymers 0.000 description 5
108091033319 polynucleotide Proteins 0.000 description 5
102000040430 polynucleotide Human genes 0.000 description 5
239000002157 polynucleotide Substances 0.000 description 5
230000002335 preservative effect Effects 0.000 description 5
230000007017 scission Effects 0.000 description 5
238000012216 screening Methods 0.000 description 5
150000008163 sugars Chemical class 0.000 description 5
239000003826 tablet Substances 0.000 description 5
238000012360 testing method Methods 0.000 description 5
229940124597 therapeutic agent Drugs 0.000 description 5
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
108091008875 B cell receptors Proteins 0.000 description 4
VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 4
108091035707 Consensus sequence Proteins 0.000 description 4
AOJJSUZBOXZQNB-TZSSRYMLSA-N Doxorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 AOJJSUZBOXZQNB-TZSSRYMLSA-N 0.000 description 4
IAYPIBMASNFSPL-UHFFFAOYSA-N Ethylene oxide Chemical compound C1CO1 IAYPIBMASNFSPL-UHFFFAOYSA-N 0.000 description 4
PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 4
101000808011 Homo sapiens Vascular endothelial growth factor A Proteins 0.000 description 4
ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 4
HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 0.000 description 4
ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Natural products OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 4
206010035226 Plasma cell myeloma Diseases 0.000 description 4
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 4
150000007513 acids Chemical class 0.000 description 4
239000007900 aqueous suspension Substances 0.000 description 4
239000011575 calcium Substances 0.000 description 4
238000010367 cloning Methods 0.000 description 4
239000003086 colorant Substances 0.000 description 4
239000007859 condensation product Substances 0.000 description 4
230000001268 conjugating effect Effects 0.000 description 4
125000000151 cysteine group Chemical class N[C@@H](CS)C(=O)* 0.000 description 4
238000001514 detection method Methods 0.000 description 4
239000002270 dispersing agent Substances 0.000 description 4
238000012377 drug delivery Methods 0.000 description 4
239000012636 effector Substances 0.000 description 4
230000002708 enhancing effect Effects 0.000 description 4
230000006870 function Effects 0.000 description 4
102000058223 human VEGFA Human genes 0.000 description 4
239000003906 humectant Substances 0.000 description 4
230000028993 immune response Effects 0.000 description 4
229940127121 immunoconjugate Drugs 0.000 description 4
230000006872 improvement Effects 0.000 description 4
238000001727 in vivo Methods 0.000 description 4
238000001990 intravenous administration Methods 0.000 description 4
239000003446 ligand Substances 0.000 description 4
RLSSMJSEOOYNOY-UHFFFAOYSA-N m-cresol Chemical compound CC1=CC=CC(O)=C1 RLSSMJSEOOYNOY-UHFFFAOYSA-N 0.000 description 4
238000005259 measurement Methods 0.000 description 4
210000001806 memory b lymphocyte Anatomy 0.000 description 4
201000000050 myeloid neoplasm Diseases 0.000 description 4
238000011275 oncology therapy Methods 0.000 description 4
230000036961 partial effect Effects 0.000 description 4
229920001223 polyethylene glycol Polymers 0.000 description 4
QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical compound CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 description 4
238000000159 protein binding assay Methods 0.000 description 4
238000003127 radioimmunoassay Methods 0.000 description 4
229940051022 radioimmunoconjugate Drugs 0.000 description 4
230000004044 response Effects 0.000 description 4
239000000243 solution Substances 0.000 description 4
239000002904 solvent Substances 0.000 description 4
230000000392 somatic effect Effects 0.000 description 4
238000010561 standard procedure Methods 0.000 description 4
UCSJYZPVAKXKNQ-HZYVHMACSA-N streptomycin Chemical compound CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](NC(N)=N)[C@H](O)[C@@H](NC(N)=N)[C@H](O)[C@H]1O UCSJYZPVAKXKNQ-HZYVHMACSA-N 0.000 description 4
239000000375 suspending agent Substances 0.000 description 4
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
FPKVOQKZMBDBKP-UHFFFAOYSA-N 1-[4-[(2,5-dioxopyrrol-1-yl)methyl]cyclohexanecarbonyl]oxy-2,5-dioxopyrrolidine-3-sulfonic acid Chemical compound O=C1C(S(=O)(=O)O)CC(=O)N1OC(=O)C1CCC(CN2C(C=CC2=O)=O)CC1 FPKVOQKZMBDBKP-UHFFFAOYSA-N 0.000 description 3
STQGQHZAVUOBTE-UHFFFAOYSA-N 7-Cyan-hept-2t-en-4,6-diinsaeure Natural products C1=2C(O)=C3C(=O)C=4C(OC)=CC=CC=4C(=O)C3=C(O)C=2CC(O)(C(C)=O)CC1OC1CC(N)C(O)C(C)O1 STQGQHZAVUOBTE-UHFFFAOYSA-N 0.000 description 3
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 3
WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 3
108091003079 Bovine Serum Albumin Proteins 0.000 description 3
101710112752 Cytotoxin Proteins 0.000 description 3
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 3
102000053602 DNA Human genes 0.000 description 3
229920002307 Dextran Polymers 0.000 description 3
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 3
102000004190 Enzymes Human genes 0.000 description 3
108090000790 Enzymes Proteins 0.000 description 3
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
229920000084 Gum arabic Polymers 0.000 description 3
101000690301 Homo sapiens Aldo-keto reductase family 1 member C4 Proteins 0.000 description 3
101001116548 Homo sapiens Protein CBFA2T1 Proteins 0.000 description 3
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 3
229930195725 Mannitol Natural products 0.000 description 3
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
101000808007 Mus musculus Vascular endothelial growth factor A Proteins 0.000 description 3
NWIBSHFKIJFRCO-WUDYKRTCSA-N Mytomycin Chemical compound C1N2C(C(C(C)=C(N)C3=O)=O)=C3[C@@H](COC(N)=O)[C@@]2(OC)[C@@H]2[C@H]1N2 NWIBSHFKIJFRCO-WUDYKRTCSA-N 0.000 description 3
239000005662 Paraffin oil Substances 0.000 description 3
108091005804 Peptidases Proteins 0.000 description 3
102000035195 Peptidases Human genes 0.000 description 3
DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
239000004365 Protease Substances 0.000 description 3
108020004511 Recombinant DNA Proteins 0.000 description 3
102000007056 Recombinant Fusion Proteins Human genes 0.000 description 3
108010008281 Recombinant Fusion Proteins Proteins 0.000 description 3
VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 3
108700019146 Transgenes Proteins 0.000 description 3
235000010489 acacia gum Nutrition 0.000 description 3
239000000205 acacia gum Substances 0.000 description 3
230000009471 action Effects 0.000 description 3
230000002776 aggregation Effects 0.000 description 3
238000004220 aggregation Methods 0.000 description 3
239000003963 antioxidant agent Substances 0.000 description 3
235000006708 antioxidants Nutrition 0.000 description 3
239000001506 calcium phosphate Substances 0.000 description 3
229910000389 calcium phosphate Inorganic materials 0.000 description 3
235000011010 calcium phosphates Nutrition 0.000 description 3
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 3
238000004113 cell culture Methods 0.000 description 3
238000012512 characterization method Methods 0.000 description 3
DQLATGHUWYMOKM-UHFFFAOYSA-L cisplatin Chemical compound N[Pt](N)(Cl)Cl DQLATGHUWYMOKM-UHFFFAOYSA-L 0.000 description 3
230000002860 competitive effect Effects 0.000 description 3
238000007796 conventional method Methods 0.000 description 3
235000018417 cysteine Nutrition 0.000 description 3
229940127089 cytotoxic agent Drugs 0.000 description 3
239000002254 cytotoxic agent Substances 0.000 description 3
231100000135 cytotoxicity Toxicity 0.000 description 3
230000003013 cytotoxicity Effects 0.000 description 3
STQGQHZAVUOBTE-VGBVRHCVSA-N daunorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(C)=O)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 STQGQHZAVUOBTE-VGBVRHCVSA-N 0.000 description 3
238000013461 design Methods 0.000 description 3
239000000539 dimer Substances 0.000 description 3
238000004520 electroporation Methods 0.000 description 3
239000000839 emulsion Substances 0.000 description 3
239000003623 enhancer Substances 0.000 description 3
229940088598 enzyme Drugs 0.000 description 3
235000019441 ethanol Nutrition 0.000 description 3
239000012894 fetal calf serum Substances 0.000 description 3
235000019634 flavors Nutrition 0.000 description 3
239000011521 glass Substances 0.000 description 3
ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 3
CBCIHIVRDWLAME-UHFFFAOYSA-N hexanitrodiphenylamine Chemical compound [O-][N+](=O)C1=CC([N+](=O)[O-])=CC([N+]([O-])=O)=C1NC1=C([N+]([O-])=O)C=C([N+]([O-])=O)C=C1[N+]([O-])=O CBCIHIVRDWLAME-UHFFFAOYSA-N 0.000 description 3
102000054751 human RUNX1T1 Human genes 0.000 description 3
210000004408 hybridoma Anatomy 0.000 description 3
230000001900 immune effect Effects 0.000 description 3
230000005764 inhibitory process Effects 0.000 description 3
239000008101 lactose Substances 0.000 description 3
239000000594 mannitol Substances 0.000 description 3
235000010355 mannitol Nutrition 0.000 description 3
239000002480 mineral oil Substances 0.000 description 3
235000010446 mineral oil Nutrition 0.000 description 3
239000004006 olive oil Substances 0.000 description 3
235000008390 olive oil Nutrition 0.000 description 3
239000008188 pellet Substances 0.000 description 3
238000002823 phage display Methods 0.000 description 3
239000000047 product Substances 0.000 description 3
230000035755 proliferation Effects 0.000 description 3
230000002285 radioactive effect Effects 0.000 description 3
102000005962 receptors Human genes 0.000 description 3
108020003175 receptors Proteins 0.000 description 3
238000010188 recombinant method Methods 0.000 description 3
230000010076 replication Effects 0.000 description 3
150000003839 salts Chemical class 0.000 description 3
239000001632 sodium acetate Substances 0.000 description 3
235000017281 sodium acetate Nutrition 0.000 description 3
210000000952 spleen Anatomy 0.000 description 3
238000007920 subcutaneous administration Methods 0.000 description 3
238000013268 sustained release Methods 0.000 description 3
239000012730 sustained-release form Substances 0.000 description 3
230000000699 topical effect Effects 0.000 description 3
230000001131 transforming effect Effects 0.000 description 3
230000009261 transgenic effect Effects 0.000 description 3
QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 3
235000015112 vegetable and seed oil Nutrition 0.000 description 3
239000008158 vegetable oil Substances 0.000 description 3
PUPZLCDOIYMWBV-UHFFFAOYSA-N (+/-)-1,3-Butanediol Chemical compound CC(O)CCO PUPZLCDOIYMWBV-UHFFFAOYSA-N 0.000 description 2
IAKHMKGGTNLKSZ-INIZCTEOSA-N (S)-colchicine Chemical compound C1([C@@H](NC(C)=O)CC2)=CC(=O)C(OC)=CC=C1C1=C2C=C(OC)C(OC)=C1OC IAKHMKGGTNLKSZ-INIZCTEOSA-N 0.000 description 2
108091032973 (ribonucleotides)n+m Proteins 0.000 description 2
ZORQXIQZAOLNGE-UHFFFAOYSA-N 1,1-difluorocyclohexane Chemical compound FC1(F)CCCCC1 ZORQXIQZAOLNGE-UHFFFAOYSA-N 0.000 description 2
VBICKXHEKHSIBG-UHFFFAOYSA-N 1-monostearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)CO VBICKXHEKHSIBG-UHFFFAOYSA-N 0.000 description 2
OWEGMIWEEQEYGQ-UHFFFAOYSA-N 100676-05-9 Natural products OC1C(O)C(O)C(CO)OC1OCC1C(O)C(O)C(O)C(OC2C(OC(O)C(O)C2O)CO)O1 OWEGMIWEEQEYGQ-UHFFFAOYSA-N 0.000 description 2
IZHVBANLECCAGF-UHFFFAOYSA-N 2-hydroxy-3-(octadecanoyloxy)propyl octadecanoate Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)COC(=O)CCCCCCCCCCCCCCCCC IZHVBANLECCAGF-UHFFFAOYSA-N 0.000 description 2
KIUMMUBSPKGMOY-UHFFFAOYSA-N 3,3'-Dithiobis(6-nitrobenzoic acid) Chemical compound C1=C([N+]([O-])=O)C(C(=O)O)=CC(SSC=2C=C(C(=CC=2)[N+]([O-])=O)C(O)=O)=C1 KIUMMUBSPKGMOY-UHFFFAOYSA-N 0.000 description 2
VXPSQDAMFATNNG-UHFFFAOYSA-N 3-[2-(2,5-dioxopyrrol-3-yl)phenyl]pyrrole-2,5-dione Chemical compound O=C1NC(=O)C(C=2C(=CC=CC=2)C=2C(NC(=O)C=2)=O)=C1 VXPSQDAMFATNNG-UHFFFAOYSA-N 0.000 description 2
244000215068 Acacia senegal Species 0.000 description 2
QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 2
DCXYFEDJOCDNAF-UHFFFAOYSA-N Asparagine Natural products OC(=O)C(N)CC(N)=O DCXYFEDJOCDNAF-UHFFFAOYSA-N 0.000 description 2
244000063299 Bacillus subtilis Species 0.000 description 2
241000894006 Bacteria Species 0.000 description 2
241000283690 Bos taurus Species 0.000 description 2
102000005600 Cathepsins Human genes 0.000 description 2
108010084457 Cathepsins Proteins 0.000 description 2
241000251730 Chondrichthyes Species 0.000 description 2
KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 2
241000699802 Cricetulus griseus Species 0.000 description 2
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 2
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 2
RGHNJXZEOKUKBD-SQOUGZDYSA-M D-gluconate Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O RGHNJXZEOKUKBD-SQOUGZDYSA-M 0.000 description 2
WQZGKKKJIJFFOK-QTVWNMPRSA-N D-mannopyranose Chemical compound OC[C@H]1OC(O)[C@@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-QTVWNMPRSA-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
238000011238 DNA vaccination Methods 0.000 description 2
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 2
UNXHWFMMPAWVPI-UHFFFAOYSA-N Erythritol Natural products OCC(O)C(O)CO UNXHWFMMPAWVPI-UHFFFAOYSA-N 0.000 description 2
WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 2
102000004269 Granulocyte Colony-Stimulating Factor Human genes 0.000 description 2
108010017080 Granulocyte Colony-Stimulating Factor Proteins 0.000 description 2
108010017213 Granulocyte-Macrophage Colony-Stimulating Factor Proteins 0.000 description 2
102100039620 Granulocyte-macrophage colony-stimulating factor Human genes 0.000 description 2
102100026120 IgG receptor FcRn large subunit p51 Human genes 0.000 description 2
101710177940 IgG receptor FcRn large subunit p51 Proteins 0.000 description 2
102000000589 Interleukin-1 Human genes 0.000 description 2
108010002352 Interleukin-1 Proteins 0.000 description 2
102000000588 Interleukin-2 Human genes 0.000 description 2
108010002350 Interleukin-2 Proteins 0.000 description 2
102000004889 Interleukin-6 Human genes 0.000 description 2
108090001005 Interleukin-6 Proteins 0.000 description 2
DCXYFEDJOCDNAF-REOHCLBHSA-N L-asparagine Chemical compound OC(=O)[C@@H](N)CC(N)=O DCXYFEDJOCDNAF-REOHCLBHSA-N 0.000 description 2
CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 2
AGPKZVBTJJNPAG-WHFBIAKZSA-N L-isoleucine Chemical compound CC[C@H](C)[C@H](N)C(O)=O AGPKZVBTJJNPAG-WHFBIAKZSA-N 0.000 description 2
FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 2
AYFVYJQAPQTCCC-GBXIJSLDSA-N L-threonine Chemical compound C[C@@H](O)[C@H](N)C(O)=O AYFVYJQAPQTCCC-GBXIJSLDSA-N 0.000 description 2
QIVBCDIJIAJPQS-VIFPVBQESA-N L-tryptophane Chemical compound C1=CC=C2C(C[C@H](N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-VIFPVBQESA-N 0.000 description 2
OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 2
241000283960 Leporidae Species 0.000 description 2
GUBGYTABKSRVRQ-PICCSMPSSA-N Maltose Natural products O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@@H](CO)OC(O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-PICCSMPSSA-N 0.000 description 2
102000018697 Membrane Proteins Human genes 0.000 description 2
108010052285 Membrane Proteins Proteins 0.000 description 2
241000699670 Mus sp. Species 0.000 description 2
241000283955 Ochotonidae Species 0.000 description 2
235000019483 Peanut oil Nutrition 0.000 description 2
229930182555 Penicillin Natural products 0.000 description 2
JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 2
BELBBZDIHDAJOR-UHFFFAOYSA-N Phenolsulfonephthalein Chemical compound C1=CC(O)=CC=C1C1(C=2C=CC(O)=CC=2)C2=CC=CC=C2S(=O)(=O)O1 BELBBZDIHDAJOR-UHFFFAOYSA-N 0.000 description 2
108010076504 Protein Sorting Signals Proteins 0.000 description 2
239000012980 RPMI-1640 medium Substances 0.000 description 2
101000808006 Rattus norvegicus Vascular endothelial growth factor A Proteins 0.000 description 2
108010003723 Single-Domain Antibodies Proteins 0.000 description 2
CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
229920002472 Starch Polymers 0.000 description 2
229920001615 Tragacanth Polymers 0.000 description 2
QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 description 2
JXLYSJRDGCGARV-WWYNWVTFSA-N Vinblastine Natural products O=C(O[C@H]1[C@](O)(C(=O)OC)[C@@H]2N(C)c3c(cc(c(OC)c3)[C@]3(C(=O)OC)c4[nH]c5c(c4CCN4C[C@](O)(CC)C[C@H](C3)C4)cccc5)[C@@]32[C@H]2[C@@]1(CC)C=CCN2CC3)C JXLYSJRDGCGARV-WWYNWVTFSA-N 0.000 description 2
241000700605 Viruses Species 0.000 description 2
239000000654 additive Substances 0.000 description 2
230000002411 adverse Effects 0.000 description 2
239000000556 agonist Substances 0.000 description 2
WQZGKKKJIJFFOK-PHYPRBDBSA-N alpha-D-galactose Chemical compound OC[C@H]1O[C@H](O)[C@H](O)[C@@H](O)[C@H]1O WQZGKKKJIJFFOK-PHYPRBDBSA-N 0.000 description 2
239000003708 ampul Substances 0.000 description 2
239000012491 analyte Substances 0.000 description 2
PYMYPHUHKUWMLA-UHFFFAOYSA-N arabinose Natural products OCC(O)C(O)C(O)C=O PYMYPHUHKUWMLA-UHFFFAOYSA-N 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
235000009582 asparagine Nutrition 0.000 description 2
229960001230 asparagine Drugs 0.000 description 2
235000003704 aspartic acid Nutrition 0.000 description 2
230000008901 benefit Effects 0.000 description 2
UREZNYTWGJKWBI-UHFFFAOYSA-M benzethonium chloride Chemical compound [Cl-].C1=CC(C(C)(C)CC(C)(C)C)=CC=C1OCCOCC[N+](C)(C)CC1=CC=CC=C1 UREZNYTWGJKWBI-UHFFFAOYSA-M 0.000 description 2
229960001950 benzethonium chloride Drugs 0.000 description 2
SRBFZHDQGSBBOR-UHFFFAOYSA-N beta-D-Pyranose-Lyxose Natural products OC1COC(O)C(O)C1O SRBFZHDQGSBBOR-UHFFFAOYSA-N 0.000 description 2
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 2
OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 description 2
GUBGYTABKSRVRQ-QUYVBRFLSA-N beta-maltose Chemical compound OC[C@H]1O[C@H](O[C@H]2[C@H](O)[C@@H](O)[C@H](O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@@H]1O GUBGYTABKSRVRQ-QUYVBRFLSA-N 0.000 description 2
239000011230 binding agent Substances 0.000 description 2
230000000903 blocking effect Effects 0.000 description 2
210000004369 blood Anatomy 0.000 description 2
239000008280 blood Substances 0.000 description 2
230000037396 body weight Effects 0.000 description 2
229910000019 calcium carbonate Inorganic materials 0.000 description 2
229930195731 calicheamicin Natural products 0.000 description 2
229910052799 carbon Inorganic materials 0.000 description 2
238000012219 cassette mutagenesis Methods 0.000 description 2
YCIMNLLNPGFGHC-UHFFFAOYSA-N catechol Chemical compound OC1=CC=CC=C1O YCIMNLLNPGFGHC-UHFFFAOYSA-N 0.000 description 2
239000002738 chelating agent Substances 0.000 description 2
238000006243 chemical reaction Methods 0.000 description 2
239000003153 chemical reaction reagent 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
238000012790 confirmation Methods 0.000 description 2
230000021615 conjugation Effects 0.000 description 2
238000010276 construction Methods 0.000 description 2
238000012937 correction Methods 0.000 description 2
238000010168 coupling process Methods 0.000 description 2
239000003431 cross linking reagent Substances 0.000 description 2
230000001472 cytotoxic effect Effects 0.000 description 2
229960000975 daunorubicin Drugs 0.000 description 2
230000007423 decrease Effects 0.000 description 2
229910052805 deuterium Inorganic materials 0.000 description 2
238000010790 dilution Methods 0.000 description 2
239000012895 dilution Substances 0.000 description 2
239000002552 dosage form Substances 0.000 description 2
229960004679 doxorubicin Drugs 0.000 description 2
210000002889 endothelial cell Anatomy 0.000 description 2
210000002950 fibroblast Anatomy 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
239000007850 fluorescent dye Substances 0.000 description 2
238000007710 freezing Methods 0.000 description 2
230000008014 freezing Effects 0.000 description 2
229930182830 galactose Natural products 0.000 description 2
238000005227 gel permeation chromatography Methods 0.000 description 2
239000007903 gelatin capsule Substances 0.000 description 2
238000001415 gene therapy Methods 0.000 description 2
230000002068 genetic effect Effects 0.000 description 2
229940050410 gluconate Drugs 0.000 description 2
239000008103 glucose Substances 0.000 description 2
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 2
235000011187 glycerol Nutrition 0.000 description 2
239000003102 growth factor Substances 0.000 description 2
230000036541 health Effects 0.000 description 2
BXWNKGSJHAJOGX-UHFFFAOYSA-N hexadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCO BXWNKGSJHAJOGX-UHFFFAOYSA-N 0.000 description 2
JYGXADMDTFJGBT-VWUMJDOOSA-N hydrocortisone Chemical compound O=C1CC[C@]2(C)[C@H]3[C@@H](O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 JYGXADMDTFJGBT-VWUMJDOOSA-N 0.000 description 2
230000005847 immunogenicity Effects 0.000 description 2
239000002596 immunotoxin Substances 0.000 description 2
239000003701 inert diluent Substances 0.000 description 2
238000001802 infusion Methods 0.000 description 2
238000002347 injection Methods 0.000 description 2
239000007924 injection Substances 0.000 description 2
238000003780 insertion Methods 0.000 description 2
230000037431 insertion Effects 0.000 description 2
230000008611 intercellular interaction Effects 0.000 description 2
230000003834 intracellular effect Effects 0.000 description 2
238000007918 intramuscular administration Methods 0.000 description 2
238000007913 intrathecal administration Methods 0.000 description 2
AGPKZVBTJJNPAG-UHFFFAOYSA-N isoleucine Natural products CCC(C)C(N)C(O)=O AGPKZVBTJJNPAG-UHFFFAOYSA-N 0.000 description 2
229960000310 isoleucine Drugs 0.000 description 2
239000007937 lozenge Substances 0.000 description 2
210000002751 lymph Anatomy 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
GLVAUDGFNGKCSF-UHFFFAOYSA-N mercaptopurine Chemical compound S=C1NC=NC2=C1NC=N2 GLVAUDGFNGKCSF-UHFFFAOYSA-N 0.000 description 2
229910052751 metal Chemical class 0.000 description 2
239000002184 metal Chemical class 0.000 description 2
229930182817 methionine Natural products 0.000 description 2
230000000813 microbial effect Effects 0.000 description 2
238000000520 microinjection Methods 0.000 description 2
229960004857 mitomycin Drugs 0.000 description 2
238000010369 molecular cloning Methods 0.000 description 2
239000001788 mono and diglycerides of fatty acids Substances 0.000 description 2
229940042880 natural phospholipid Drugs 0.000 description 2
230000003472 neutralizing effect Effects 0.000 description 2
229910052759 nickel Inorganic materials 0.000 description 2
210000000056 organ Anatomy 0.000 description 2
150000007524 organic acids Chemical class 0.000 description 2
230000003204 osmotic effect Effects 0.000 description 2
244000052769 pathogen Species 0.000 description 2
230000001717 pathogenic effect Effects 0.000 description 2
239000000312 peanut oil Substances 0.000 description 2
229940049954 penicillin Drugs 0.000 description 2
AQIXEPGDORPWBJ-UHFFFAOYSA-N pentan-3-ol Chemical compound CCC(O)CC AQIXEPGDORPWBJ-UHFFFAOYSA-N 0.000 description 2
229960003531 phenolsulfonphthalein Drugs 0.000 description 2
235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 2
239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 description 2
229920001282 polysaccharide Polymers 0.000 description 2
239000005017 polysaccharide Substances 0.000 description 2
150000004804 polysaccharides Chemical class 0.000 description 2
229920000136 polysorbate Polymers 0.000 description 2
229920000053 polysorbate 80 Polymers 0.000 description 2
229940068965 polysorbates Drugs 0.000 description 2
239000000843 powder Substances 0.000 description 2
238000001556 precipitation Methods 0.000 description 2
239000002243 precursor Substances 0.000 description 2
210000001236 prokaryotic cell Anatomy 0.000 description 2
AQHHHDLHHXJYJD-UHFFFAOYSA-N propranolol Chemical compound C1=CC=C2C(OCC(O)CNC(C)C)=CC=CC2=C1 AQHHHDLHHXJYJD-UHFFFAOYSA-N 0.000 description 2
RXWNCPJZOCPEPQ-NVWDDTSBSA-N puromycin Chemical compound C1=CC(OC)=CC=C1C[C@H](N)C(=O)N[C@H]1[C@@H](O)[C@H](N2C3=NC=NC(=C3N=C2)N(C)C)O[C@@H]1CO RXWNCPJZOCPEPQ-NVWDDTSBSA-N 0.000 description 2
238000003259 recombinant expression Methods 0.000 description 2
230000008929 regeneration Effects 0.000 description 2
238000011069 regeneration method Methods 0.000 description 2
238000011160 research Methods 0.000 description 2
GHMLBKRAJCXXBS-UHFFFAOYSA-N resorcinol Chemical compound OC1=CC=CC(O)=C1 GHMLBKRAJCXXBS-UHFFFAOYSA-N 0.000 description 2
238000003757 reverse transcription PCR Methods 0.000 description 2
238000002864 sequence alignment Methods 0.000 description 2
238000013207 serial dilution Methods 0.000 description 2
230000011664 signaling Effects 0.000 description 2
239000011780 sodium chloride Substances 0.000 description 2
229940074404 sodium succinate Drugs 0.000 description 2
ZDQYSKICYIVCPN-UHFFFAOYSA-L sodium succinate (anhydrous) Chemical compound [Na+].[Na+].[O-]C(=O)CCC([O-])=O ZDQYSKICYIVCPN-UHFFFAOYSA-L 0.000 description 2
239000007787 solid Substances 0.000 description 2
235000011069 sorbitan monooleate Nutrition 0.000 description 2
239000001593 sorbitan monooleate Substances 0.000 description 2
229940035049 sorbitan monooleate Drugs 0.000 description 2
239000000600 sorbitol Substances 0.000 description 2
239000003381 stabilizer Substances 0.000 description 2
238000010186 staining Methods 0.000 description 2
239000008107 starch Substances 0.000 description 2
235000019698 starch Nutrition 0.000 description 2
239000007858 starting material Substances 0.000 description 2
229960005322 streptomycin Drugs 0.000 description 2
KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 2
150000005846 sugar alcohols Chemical class 0.000 description 2
239000006228 supernatant Substances 0.000 description 2
239000006188 syrup Substances 0.000 description 2
235000020357 syrup Nutrition 0.000 description 2
238000002560 therapeutic procedure Methods 0.000 description 2
208000008732 thymoma Diseases 0.000 description 2
WYWHKKSPHMUBEB-UHFFFAOYSA-N tioguanine Chemical compound N1C(N)=NC(=S)C2=C1N=CN2 WYWHKKSPHMUBEB-UHFFFAOYSA-N 0.000 description 2
238000013518 transcription Methods 0.000 description 2
230000035897 transcription Effects 0.000 description 2
238000001890 transfection Methods 0.000 description 2
238000012546 transfer Methods 0.000 description 2
108091005703 transmembrane proteins Proteins 0.000 description 2
102000035160 transmembrane proteins Human genes 0.000 description 2
OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 2
239000002525 vasculotropin inhibitor Substances 0.000 description 2
229960003048 vinblastine Drugs 0.000 description 2
JXLYSJRDGCGARV-XQKSVPLYSA-N vincaleukoblastine Chemical compound C([C@@H](C[C@]1(C(=O)OC)C=2C(=CC3=C([C@]45[C@H]([C@@]([C@H](OC(C)=O)[C@]6(CC)C=CCN([C@H]56)CC4)(O)C(=O)OC)N3C)C=2)OC)C[C@@](C2)(O)CC)N2CCC2=C1NC1=CC=CC=C21 JXLYSJRDGCGARV-XQKSVPLYSA-N 0.000 description 2
OGWKCGZFUXNPDA-UHFFFAOYSA-N vincristine Natural products C1C(CC)(O)CC(CC2(C(=O)OC)C=3C(=CC4=C(C56C(C(C(OC(C)=O)C7(CC)C=CCN(C67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)CN1CCC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-UHFFFAOYSA-N 0.000 description 2
OGWKCGZFUXNPDA-XQKSVPLYSA-N vincristine Chemical compound C([N@]1C[C@@H](C[C@]2(C(=O)OC)C=3C(=CC4=C([C@]56[C@H]([C@@]([C@H](OC(C)=O)[C@]7(CC)C=CCN([C@H]67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)C[C@@](C1)(O)CC)CC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-XQKSVPLYSA-N 0.000 description 2
229960004528 vincristine Drugs 0.000 description 2
230000003612 virological effect Effects 0.000 description 2
238000001262 western blot Methods 0.000 description 2
FLCQLSRLQIPNLM-UHFFFAOYSA-N (2,5-dioxopyrrolidin-1-yl) 2-acetylsulfanylacetate Chemical compound CC(=O)SCC(=O)ON1C(=O)CCC1=O FLCQLSRLQIPNLM-UHFFFAOYSA-N 0.000 description 1
LNAZSHAWQACDHT-XIYTZBAFSA-N (2r,3r,4s,5r,6s)-4,5-dimethoxy-2-(methoxymethyl)-3-[(2s,3r,4s,5r,6r)-3,4,5-trimethoxy-6-(methoxymethyl)oxan-2-yl]oxy-6-[(2r,3r,4s,5r,6r)-4,5,6-trimethoxy-2-(methoxymethyl)oxan-3-yl]oxyoxane Chemical compound CO[C@@H]1[C@@H](OC)[C@H](OC)[C@@H](COC)O[C@H]1O[C@H]1[C@H](OC)[C@@H](OC)[C@H](O[C@H]2[C@@H]([C@@H](OC)[C@H](OC)O[C@@H]2COC)OC)O[C@@H]1COC LNAZSHAWQACDHT-XIYTZBAFSA-N 0.000 description 1
WRIDQFICGBMAFQ-UHFFFAOYSA-N (E)-8-Octadecenoic acid Natural products CCCCCCCCCC=CCCCCCCC(O)=O WRIDQFICGBMAFQ-UHFFFAOYSA-N 0.000 description 1
FDKXTQMXEQVLRF-ZHACJKMWSA-N (E)-dacarbazine Chemical compound CN(C)\N=N\c1[nH]cnc1C(N)=O FDKXTQMXEQVLRF-ZHACJKMWSA-N 0.000 description 1
LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide Chemical compound CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 1
GOODXEAJZGMZKG-UHFFFAOYSA-N 1-hydroxypyrrolidine-2,5-dione;hydrochloride Chemical compound Cl.ON1C(=O)CCC1=O GOODXEAJZGMZKG-UHFFFAOYSA-N 0.000 description 1
IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 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
PNDPGZBMCMUPRI-HVTJNCQCSA-N 10043-66-0 Chemical compound [131I][131I] PNDPGZBMCMUPRI-HVTJNCQCSA-N 0.000 description 1
JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 1
RTQWWZBSTRGEAV-PKHIMPSTSA-N 2-[[(2s)-2-[bis(carboxymethyl)amino]-3-[4-(methylcarbamoylamino)phenyl]propyl]-[2-[bis(carboxymethyl)amino]propyl]amino]acetic acid Chemical compound CNC(=O)NC1=CC=C(C[C@@H](CN(CC(C)N(CC(O)=O)CC(O)=O)CC(O)=O)N(CC(O)=O)CC(O)=O)C=C1 RTQWWZBSTRGEAV-PKHIMPSTSA-N 0.000 description 1
LQJBNNIYVWPHFW-UHFFFAOYSA-N 20:1omega9c fatty acid Natural products CCCCCCCCCCC=CCCCCCCCC(O)=O LQJBNNIYVWPHFW-UHFFFAOYSA-N 0.000 description 1
OSJPPGNTCRNQQC-UWTATZPHSA-N 3-phospho-D-glyceric acid Chemical compound OC(=O)[C@H](O)COP(O)(O)=O OSJPPGNTCRNQQC-UWTATZPHSA-N 0.000 description 1
QSBYPNXLFMSGKH-UHFFFAOYSA-N 9-Heptadecensaeure Natural products CCCCCCCC=CCCCCCCCC(O)=O QSBYPNXLFMSGKH-UHFFFAOYSA-N 0.000 description 1
108010066676 Abrin Proteins 0.000 description 1
102000007698 Alcohol dehydrogenase Human genes 0.000 description 1
108010021809 Alcohol dehydrogenase Proteins 0.000 description 1
239000005995 Aluminium silicate Substances 0.000 description 1
240000002470 Amphicarpaea bracteata Species 0.000 description 1
229920000856 Amylose Polymers 0.000 description 1
241000416162 Astragalus gummifer Species 0.000 description 1
235000014469 Bacillus subtilis Nutrition 0.000 description 1
108010006654 Bleomycin Proteins 0.000 description 1
COVZYZSDYWQREU-UHFFFAOYSA-N Busulfan Chemical compound CS(=O)(=O)OCCCCOS(C)(=O)=O COVZYZSDYWQREU-UHFFFAOYSA-N 0.000 description 1
FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Chemical class CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 1
102000000905 Cadherin Human genes 0.000 description 1
108050007957 Cadherin Proteins 0.000 description 1
UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 1
241000283707 Capra Species 0.000 description 1
DLGOEMSEDOSKAD-UHFFFAOYSA-N Carmustine Chemical compound ClCCNC(=O)N(N=O)CCCl DLGOEMSEDOSKAD-UHFFFAOYSA-N 0.000 description 1
108010012236 Chemokines Proteins 0.000 description 1
102000019034 Chemokines Human genes 0.000 description 1
108091026890 Coding region Proteins 0.000 description 1
108020004705 Codon Proteins 0.000 description 1
241000759568 Corixa Species 0.000 description 1
229920002261 Corn starch Polymers 0.000 description 1
102100021906 Cyclin-O Human genes 0.000 description 1
CMSMOCZEIVJLDB-UHFFFAOYSA-N Cyclophosphamide Chemical compound ClCCN(CCCl)P1(=O)NCCCO1 CMSMOCZEIVJLDB-UHFFFAOYSA-N 0.000 description 1
UHDGCWIWMRVCDJ-CCXZUQQUSA-N Cytarabine Chemical compound O=C1N=C(N)C=CN1[C@H]1[C@@H](O)[C@H](O)[C@@H](CO)O1 UHDGCWIWMRVCDJ-CCXZUQQUSA-N 0.000 description 1
102000004127 Cytokines Human genes 0.000 description 1
108090000695 Cytokines Proteins 0.000 description 1
241000701022 Cytomegalovirus Species 0.000 description 1
MTCFGRXMJLQNBG-UWTATZPHSA-N D-Serine Chemical compound OC[C@@H](N)C(O)=O MTCFGRXMJLQNBG-UWTATZPHSA-N 0.000 description 1
229930195711 D-Serine Natural products 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
HMFHBZSHGGEWLO-SOOFDHNKSA-N D-ribofuranose Chemical compound OC[C@H]1OC(O)[C@H](O)[C@@H]1O HMFHBZSHGGEWLO-SOOFDHNKSA-N 0.000 description 1
UNXHWFMMPAWVPI-QWWZWVQMSA-N D-threitol Chemical compound OC[C@@H](O)[C@H](O)CO UNXHWFMMPAWVPI-QWWZWVQMSA-N 0.000 description 1
230000004568 DNA-binding Effects 0.000 description 1
102000016928 DNA-directed DNA polymerase Human genes 0.000 description 1
108010014303 DNA-directed DNA polymerase Proteins 0.000 description 1
108010092160 Dactinomycin Proteins 0.000 description 1
WEAHRLBPCANXCN-UHFFFAOYSA-N Daunomycin Natural products CCC1(O)CC(OC2CC(N)C(O)C(C)O2)c3cc4C(=O)c5c(OC)cccc5C(=O)c4c(O)c3C1 WEAHRLBPCANXCN-UHFFFAOYSA-N 0.000 description 1
229920001353 Dextrin Polymers 0.000 description 1
239000004375 Dextrin Substances 0.000 description 1
102000016607 Diphtheria Toxin Human genes 0.000 description 1
108010053187 Diphtheria Toxin Proteins 0.000 description 1
238000012286 ELISA Assay Methods 0.000 description 1
241000196324 Embryophyta Species 0.000 description 1
241000588921 Enterobacteriaceae Species 0.000 description 1
102400001368 Epidermal growth factor Human genes 0.000 description 1
101800003838 Epidermal growth factor Proteins 0.000 description 1
YQYJSBFKSSDGFO-UHFFFAOYSA-N Epihygromycin Natural products OC1C(O)C(C(=O)C)OC1OC(C(=C1)O)=CC=C1C=C(C)C(=O)NC1C(O)C(O)C2OCOC2C1O YQYJSBFKSSDGFO-UHFFFAOYSA-N 0.000 description 1
239000004386 Erythritol Substances 0.000 description 1
CTKXFMQHOOWWEB-UHFFFAOYSA-N Ethylene oxide/propylene oxide copolymer Chemical compound CCCOC(C)COCCO CTKXFMQHOOWWEB-UHFFFAOYSA-N 0.000 description 1
244000165918 Eucalyptus papuana Species 0.000 description 1
239000004230 Fast Yellow AB Substances 0.000 description 1
108010087819 Fc receptors Proteins 0.000 description 1
102000009109 Fc receptors Human genes 0.000 description 1
238000012413 Fluorescence activated cell sorting analysis Methods 0.000 description 1
GHASVSINZRGABV-UHFFFAOYSA-N Fluorouracil Chemical compound FC1=CNC(=O)NC1=O GHASVSINZRGABV-UHFFFAOYSA-N 0.000 description 1
229930091371 Fructose Natural products 0.000 description 1
239000005715 Fructose Substances 0.000 description 1
RFSUNEUAIZKAJO-ARQDHWQXSA-N Fructose Chemical compound OC[C@H]1O[C@](O)(CO)[C@@H](O)[C@@H]1O RFSUNEUAIZKAJO-ARQDHWQXSA-N 0.000 description 1
108091006027 G proteins Proteins 0.000 description 1
102000030782 GTP binding Human genes 0.000 description 1
108091000058 GTP-Binding Proteins 0.000 description 1
108010010803 Gelatin Proteins 0.000 description 1
108700028146 Genetic Enhancer Elements Proteins 0.000 description 1
108010024636 Glutathione Proteins 0.000 description 1
229920002527 Glycogen Polymers 0.000 description 1
108010026389 Gramicidin Proteins 0.000 description 1
239000007995 HEPES buffer Substances 0.000 description 1
229920000209 Hexadimethrine bromide Polymers 0.000 description 1
241000282412 Homo Species 0.000 description 1
101000897441 Homo sapiens Cyclin-O Proteins 0.000 description 1
101000595923 Homo sapiens Placenta growth factor Proteins 0.000 description 1
241000701044 Human gammaherpesvirus 4 Species 0.000 description 1
DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
102000012745 Immunoglobulin Subunits Human genes 0.000 description 1
108010079585 Immunoglobulin Subunits Proteins 0.000 description 1
108010074328 Interferon-gamma Proteins 0.000 description 1
102000008070 Interferon-gamma Human genes 0.000 description 1
102000004310 Ion Channels Human genes 0.000 description 1
241000235058 Komagataella pastoris Species 0.000 description 1
LKDRXBCSQODPBY-AMVSKUEXSA-N L-(-)-Sorbose Chemical compound OCC1(O)OC[C@H](O)[C@@H](O)[C@@H]1O LKDRXBCSQODPBY-AMVSKUEXSA-N 0.000 description 1
XUJNEKJLAYXESH-REOHCLBHSA-N L-Cysteine Chemical compound SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-N 0.000 description 1
ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-N 0.000 description 1
ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 1
RGHNJXZEOKUKBD-KLVWXMOXSA-N L-gluconic acid Chemical class OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)C(O)=O RGHNJXZEOKUKBD-KLVWXMOXSA-N 0.000 description 1
WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 1
229930182816 L-glutamine Natural products 0.000 description 1
KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 1
FBOZXECLQNJBKD-ZDUSSCGKSA-N L-methotrexate Chemical compound C=1N=C2N=C(N)N=C(N)C2=NC=1CN(C)C1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 FBOZXECLQNJBKD-ZDUSSCGKSA-N 0.000 description 1
SHZGCJCMOBCMKK-JFNONXLTSA-N L-rhamnopyranose Chemical compound C[C@@H]1OC(O)[C@H](O)[C@H](O)[C@H]1O SHZGCJCMOBCMKK-JFNONXLTSA-N 0.000 description 1
PNNNRSAQSRJVSB-UHFFFAOYSA-N L-rhamnose Natural products CC(O)C(O)C(O)C(O)C=O PNNNRSAQSRJVSB-UHFFFAOYSA-N 0.000 description 1
102000008192 Lactoglobulins Human genes 0.000 description 1
108010060630 Lactoglobulins Proteins 0.000 description 1
241000283953 Lagomorpha Species 0.000 description 1
241000283986 Lepus Species 0.000 description 1
NNJVILVZKWQKPM-UHFFFAOYSA-N Lidocaine Chemical compound CCN(CC)CC(=O)NC1=C(C)C=CC=C1C NNJVILVZKWQKPM-UHFFFAOYSA-N 0.000 description 1
GQYIWUVLTXOXAJ-UHFFFAOYSA-N Lomustine Chemical compound ClCCN(N=O)C(=O)NC1CCCCC1 GQYIWUVLTXOXAJ-UHFFFAOYSA-N 0.000 description 1
102000008072 Lymphokines Human genes 0.000 description 1
108010074338 Lymphokines Proteins 0.000 description 1
241000829100 Macaca mulatta polyomavirus 1 Species 0.000 description 1
VFKZTMPDYBFSTM-KVTDHHQDSA-N Mitobronitol Chemical compound BrC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CBr VFKZTMPDYBFSTM-KVTDHHQDSA-N 0.000 description 1
229930192392 Mitomycin Natural products 0.000 description 1
241000699660 Mus musculus Species 0.000 description 1
229930193140 Neomycin Natural products 0.000 description 1
239000005642 Oleic acid Substances 0.000 description 1
ZQPPMHVWECSIRJ-UHFFFAOYSA-N Oleic acid Natural products CCCCCCCCC=CCCCCCCCC(O)=O ZQPPMHVWECSIRJ-UHFFFAOYSA-N 0.000 description 1
108010058846 Ovalbumin Proteins 0.000 description 1
101150062285 PGF gene Proteins 0.000 description 1
229910019142 PO4 Inorganic materials 0.000 description 1
229930012538 Paclitaxel Natural products 0.000 description 1
101001109571 Pan troglodytes NPC intracellular cholesterol transporter 2 Proteins 0.000 description 1
108090000526 Papain Proteins 0.000 description 1
241001631646 Papillomaviridae Species 0.000 description 1
102000057297 Pepsin A Human genes 0.000 description 1
108090000284 Pepsin A Proteins 0.000 description 1
108091000080 Phosphotransferase Proteins 0.000 description 1
241000235648 Pichia Species 0.000 description 1
102100035194 Placenta growth factor Human genes 0.000 description 1
108010039918 Polylysine Proteins 0.000 description 1
ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 1
241000589516 Pseudomonas Species 0.000 description 1
101000762949 Pseudomonas aeruginosa (strain ATCC 15692 / DSM 22644 / CIP 104116 / JCM 14847 / LMG 12228 / 1C / PRS 101 / PAO1) Exotoxin A Proteins 0.000 description 1
MUPFEKGTMRGPLJ-RMMQSMQOSA-N Raffinose Natural products O(C[C@H]1[C@@H](O)[C@H](O)[C@@H](O)[C@@H](O[C@@]2(CO)[C@H](O)[C@@H](O)[C@@H](CO)O2)O1)[C@@H]1[C@H](O)[C@@H](O)[C@@H](O)[C@@H](CO)O1 MUPFEKGTMRGPLJ-RMMQSMQOSA-N 0.000 description 1
108020005091 Replication Origin Proteins 0.000 description 1
PYMYPHUHKUWMLA-LMVFSUKVSA-N Ribose Natural products OC[C@@H](O)[C@@H](O)[C@@H](O)C=O PYMYPHUHKUWMLA-LMVFSUKVSA-N 0.000 description 1
108010039491 Ricin Proteins 0.000 description 1
AUVVAXYIELKVAI-UHFFFAOYSA-N SJ000285215 Natural products N1CCC2=CC(OC)=C(OC)C=C2C1CC1CC2C3=CC(OC)=C(OC)C=C3CCN2CC1CC AUVVAXYIELKVAI-UHFFFAOYSA-N 0.000 description 1
241000235070 Saccharomyces Species 0.000 description 1
241000607142 Salmonella Species 0.000 description 1
229920002684 Sepharose Polymers 0.000 description 1
241000607720 Serratia Species 0.000 description 1
108010071390 Serum Albumin Proteins 0.000 description 1
102000007562 Serum Albumin Human genes 0.000 description 1
240000006394 Sorghum bicolor Species 0.000 description 1
235000021355 Stearic acid Nutrition 0.000 description 1
ZSJLQEPLLKMAKR-UHFFFAOYSA-N Streptozotocin Natural products O=NN(C)C(=O)NC1C(O)OC(CO)C(O)C1O ZSJLQEPLLKMAKR-UHFFFAOYSA-N 0.000 description 1
210000001744 T-lymphocyte Anatomy 0.000 description 1
239000004098 Tetracycline Substances 0.000 description 1
FOCVUCIESVLUNU-UHFFFAOYSA-N Thiotepa Chemical compound C1CN1P(N1CC1)(=S)N1CC1 FOCVUCIESVLUNU-UHFFFAOYSA-N 0.000 description 1
101710120037 Toxin CcdB Proteins 0.000 description 1
MUPFEKGTMRGPLJ-UHFFFAOYSA-N UNPD196149 Natural products OC1C(O)C(CO)OC1(CO)OC1C(O)C(O)C(O)C(COC2C(C(O)C(O)C(CO)O2)O)O1 MUPFEKGTMRGPLJ-UHFFFAOYSA-N 0.000 description 1
VGQOVCHZGQWAOI-UHFFFAOYSA-N UNPD55612 Natural products N1C(O)C2CC(C=CC(N)=O)=CN2C(=O)C2=CC=C(C)C(O)=C12 VGQOVCHZGQWAOI-UHFFFAOYSA-N 0.000 description 1
108091008605 VEGF receptors Proteins 0.000 description 1
102100033177 Vascular endothelial growth factor receptor 2 Human genes 0.000 description 1
TVXBFESIOXBWNM-UHFFFAOYSA-N Xylitol Natural products OCCC(O)C(O)C(O)CCO TVXBFESIOXBWNM-UHFFFAOYSA-N 0.000 description 1
VWQVUPCCIRVNHF-OUBTZVSYSA-N Yttrium-90 Chemical compound [90Y] VWQVUPCCIRVNHF-OUBTZVSYSA-N 0.000 description 1
238000010521 absorption reaction Methods 0.000 description 1
DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 1
230000002378 acidificating effect Effects 0.000 description 1
229930183665 actinomycin Natural products 0.000 description 1
239000012190 activator Substances 0.000 description 1
230000001154 acute effect Effects 0.000 description 1
239000002671 adjuvant Substances 0.000 description 1
230000009824 affinity maturation Effects 0.000 description 1
235000010443 alginic acid Nutrition 0.000 description 1
239000000783 alginic acid Substances 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
125000000217 alkyl group Chemical group 0.000 description 1
229940100198 alkylating agent Drugs 0.000 description 1
239000002168 alkylating agent Substances 0.000 description 1
239000013566 allergen Substances 0.000 description 1
HMFHBZSHGGEWLO-UHFFFAOYSA-N alpha-D-Furanose-Ribose Natural products OCC1OC(O)C(O)C1O HMFHBZSHGGEWLO-UHFFFAOYSA-N 0.000 description 1
235000012211 aluminium silicate Nutrition 0.000 description 1
150000001412 amines Chemical class 0.000 description 1
125000003277 amino group Chemical group 0.000 description 1
238000012870 ammonium sulfate precipitation Methods 0.000 description 1
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 1
229960000723 ampicillin Drugs 0.000 description 1
150000008064 anhydrides Chemical class 0.000 description 1
210000004102 animal cell Anatomy 0.000 description 1
230000003042 antagnostic effect Effects 0.000 description 1
229940045799 anthracyclines and related substance Drugs 0.000 description 1
VGQOVCHZGQWAOI-HYUHUPJXSA-N anthramycin Chemical compound N1[C@@H](O)[C@@H]2CC(\C=C\C(N)=O)=CN2C(=O)C2=CC=C(C)C(O)=C12 VGQOVCHZGQWAOI-HYUHUPJXSA-N 0.000 description 1
230000000340 anti-metabolite Effects 0.000 description 1
230000009830 antibody antigen interaction Effects 0.000 description 1
230000005875 antibody response Effects 0.000 description 1
230000000890 antigenic effect Effects 0.000 description 1
229940100197 antimetabolite Drugs 0.000 description 1
239000002256 antimetabolite Substances 0.000 description 1
239000003080 antimitotic agent Substances 0.000 description 1
230000003078 antioxidant effect Effects 0.000 description 1
PYMYPHUHKUWMLA-WDCZJNDASA-N arabinose Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)C=O PYMYPHUHKUWMLA-WDCZJNDASA-N 0.000 description 1
235000019568 aromas Nutrition 0.000 description 1
239000000305 astragalus gummifer gum Substances 0.000 description 1
238000000376 autoradiography Methods 0.000 description 1
244000052616 bacterial pathogen Species 0.000 description 1
239000011324 bead Substances 0.000 description 1
235000013871 bee wax Nutrition 0.000 description 1
239000012166 beeswax Substances 0.000 description 1
229960000686 benzalkonium chloride Drugs 0.000 description 1
235000019445 benzyl alcohol Nutrition 0.000 description 1
CADWTSSKOVRVJC-UHFFFAOYSA-N benzyl(dimethyl)azanium;chloride Chemical compound [Cl-].C[NH+](C)CC1=CC=CC=C1 CADWTSSKOVRVJC-UHFFFAOYSA-N 0.000 description 1
238000004166 bioassay Methods 0.000 description 1
229920002988 biodegradable polymer Polymers 0.000 description 1
239000004621 biodegradable polymer Substances 0.000 description 1
230000008512 biological response Effects 0.000 description 1
HUTDDBSSHVOYJR-UHFFFAOYSA-H bis[(2-oxo-1,3,2$l^{5},4$l^{2}-dioxaphosphaplumbetan-2-yl)oxy]lead Chemical compound [Pb+2].[Pb+2].[Pb+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O HUTDDBSSHVOYJR-UHFFFAOYSA-H 0.000 description 1
229960001561 bleomycin Drugs 0.000 description 1
OYVAGSVQBOHSSS-UAPAGMARSA-O bleomycin A2 Chemical compound N([C@H](C(=O)N[C@H](C)[C@@H](O)[C@H](C)C(=O)N[C@@H]([C@H](O)C)C(=O)NCCC=1SC=C(N=1)C=1SC=C(N=1)C(=O)NCCC[S+](C)C)[C@@H](O[C@H]1[C@H]([C@@H](O)[C@H](O)[C@H](CO)O1)O[C@@H]1[C@H]([C@@H](OC(N)=O)[C@H](O)[C@@H](CO)O1)O)C=1N=CNC=1)C(=O)C1=NC([C@H](CC(N)=O)NC[C@H](N)C(N)=O)=NC(N)=C1C OYVAGSVQBOHSSS-UAPAGMARSA-O 0.000 description 1
210000001124 body fluid Anatomy 0.000 description 1
239000010839 body fluid Substances 0.000 description 1
210000000481 breast Anatomy 0.000 description 1
239000007853 buffer solution Substances 0.000 description 1
239000008366 buffered solution Substances 0.000 description 1
239000006172 buffering agent Substances 0.000 description 1
229960002092 busulfan Drugs 0.000 description 1
LRHPLDYGYMQRHN-UHFFFAOYSA-N butyl alcohol Substances CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 1
125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
210000004899 c-terminal region Anatomy 0.000 description 1
DEGAKNSWVGKMLS-UHFFFAOYSA-N calcein Chemical compound O1C(=O)C2=CC=CC=C2C21C1=CC(CN(CC(O)=O)CC(O)=O)=C(O)C=C1OC1=C2C=C(CN(CC(O)=O)CC(=O)O)C(O)=C1 DEGAKNSWVGKMLS-UHFFFAOYSA-N 0.000 description 1
235000010216 calcium carbonate Nutrition 0.000 description 1
239000001110 calcium chloride Substances 0.000 description 1
229910001628 calcium chloride Inorganic materials 0.000 description 1
HXCHCVDVKSCDHU-LULTVBGHSA-N calicheamicin Chemical compound C1[C@H](OC)[C@@H](NCC)CO[C@H]1O[C@H]1[C@H](O[C@@H]2C\3=C(NC(=O)OC)C(=O)C[C@](C/3=C/CSSSC)(O)C#C\C=C/C#C2)O[C@H](C)[C@@H](NO[C@@H]2O[C@H](C)[C@@H](SC(=O)C=3C(=C(OC)C(O[C@H]4[C@@H]([C@H](OC)[C@@H](O)[C@H](C)O4)O)=C(I)C=3C)OC)[C@@H](O)C2)[C@@H]1O HXCHCVDVKSCDHU-LULTVBGHSA-N 0.000 description 1
239000002775 capsule Substances 0.000 description 1
150000001718 carbodiimides Chemical class 0.000 description 1
150000001720 carbohydrates Chemical class 0.000 description 1
235000014633 carbohydrates Nutrition 0.000 description 1
229910002091 carbon monoxide Inorganic materials 0.000 description 1
239000001768 carboxy methyl cellulose Substances 0.000 description 1
229960005243 carmustine Drugs 0.000 description 1
239000012876 carrier material Substances 0.000 description 1
239000005018 casein Substances 0.000 description 1
BECPQYXYKAMYBN-UHFFFAOYSA-N casein, tech. Chemical compound NCCCCC(C(O)=O)N=C(O)C(CC(O)=O)N=C(O)C(CCC(O)=N)N=C(O)C(CC(C)C)N=C(O)C(CCC(O)=O)N=C(O)C(CC(O)=O)N=C(O)C(CCC(O)=O)N=C(O)C(C(C)O)N=C(O)C(CCC(O)=N)N=C(O)C(CCC(O)=N)N=C(O)C(CCC(O)=N)N=C(O)C(CCC(O)=O)N=C(O)C(CCC(O)=O)N=C(O)C(COP(O)(O)=O)N=C(O)C(CCC(O)=N)N=C(O)C(N)CC1=CC=CC=C1 BECPQYXYKAMYBN-UHFFFAOYSA-N 0.000 description 1
235000021240 caseins Nutrition 0.000 description 1
210000000170 cell membrane Anatomy 0.000 description 1
230000004663 cell proliferation Effects 0.000 description 1
239000001913 cellulose Substances 0.000 description 1
229920002678 cellulose Polymers 0.000 description 1
210000001175 cerebrospinal fluid Anatomy 0.000 description 1
229960000541 cetyl alcohol Drugs 0.000 description 1
NDAYQJDHGXTBJL-MWWSRJDJSA-N chembl557217 Chemical compound C1=CC=C2C(C[C@H](NC(=O)[C@@H](CC(C)C)NC(=O)[C@H](CC=3C4=CC=CC=C4NC=3)NC(=O)[C@@H](CC(C)C)NC(=O)[C@H](CC=3C4=CC=CC=C4NC=3)NC(=O)[C@@H](CC(C)C)NC(=O)[C@H](CC=3C4=CC=CC=C4NC=3)NC(=O)[C@@H](C(C)C)NC(=O)[C@H](C(C)C)NC(=O)[C@@H](C(C)C)NC(=O)[C@H](C)NC(=O)[C@H](NC(=O)CNC(=O)[C@@H](NC=O)C(C)C)CC(C)C)C(=O)NCCO)=CNC2=C1 NDAYQJDHGXTBJL-MWWSRJDJSA-N 0.000 description 1
239000003638 chemical reducing agent Substances 0.000 description 1
229960004630 chlorambucil Drugs 0.000 description 1
JCKYGMPEJWAADB-UHFFFAOYSA-N chlorambucil Chemical compound OC(=O)CCCC1=CC=C(N(CCCl)CCCl)C=C1 JCKYGMPEJWAADB-UHFFFAOYSA-N 0.000 description 1
150000001805 chlorine compounds Chemical class 0.000 description 1
229960004926 chlorobutanol Drugs 0.000 description 1
239000003593 chromogenic compound Substances 0.000 description 1
239000013611 chromosomal DNA Substances 0.000 description 1
230000001684 chronic effect Effects 0.000 description 1
229960004316 cisplatin Drugs 0.000 description 1
239000011248 coating agent Substances 0.000 description 1
238000000576 coating method Methods 0.000 description 1
239000003240 coconut oil Substances 0.000 description 1
235000019864 coconut oil Nutrition 0.000 description 1
229960001338 colchicine Drugs 0.000 description 1
238000004440 column chromatography Methods 0.000 description 1
238000004891 communication Methods 0.000 description 1
230000006854 communication Effects 0.000 description 1
230000004154 complement system Effects 0.000 description 1
238000007906 compression Methods 0.000 description 1
230000006835 compression Effects 0.000 description 1
239000000470 constituent Substances 0.000 description 1
239000000599 controlled substance Substances 0.000 description 1
230000001276 controlling effect Effects 0.000 description 1
229920001577 copolymer Polymers 0.000 description 1
239000008120 corn starch Substances 0.000 description 1
230000008878 coupling Effects 0.000 description 1
238000005859 coupling reaction Methods 0.000 description 1
238000012258 culturing Methods 0.000 description 1
HPXRVTGHNJAIIH-UHFFFAOYSA-N cyclohexanol Chemical compound OC1CCCCC1 HPXRVTGHNJAIIH-UHFFFAOYSA-N 0.000 description 1
229960004397 cyclophosphamide Drugs 0.000 description 1
XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 1
229960000684 cytarabine Drugs 0.000 description 1
231100000433 cytotoxic Toxicity 0.000 description 1
238000002784 cytotoxicity assay Methods 0.000 description 1
231100000263 cytotoxicity test Toxicity 0.000 description 1
230000006240 deamidation Effects 0.000 description 1
230000009615 deamination Effects 0.000 description 1
238000006481 deamination reaction Methods 0.000 description 1
230000003247 decreasing effect Effects 0.000 description 1
238000012217 deletion Methods 0.000 description 1
230000037430 deletion Effects 0.000 description 1
238000004925 denaturation Methods 0.000 description 1
230000036425 denaturation Effects 0.000 description 1
238000003795 desorption Methods 0.000 description 1
230000006866 deterioration Effects 0.000 description 1
238000011161 development Methods 0.000 description 1
230000018109 developmental process Effects 0.000 description 1
235000019425 dextrin Nutrition 0.000 description 1
238000003745 diagnosis Methods 0.000 description 1
239000000032 diagnostic agent Substances 0.000 description 1
229940039227 diagnostic agent Drugs 0.000 description 1
230000029087 digestion Effects 0.000 description 1
239000003085 diluting agent Substances 0.000 description 1
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 1
150000002016 disaccharides Chemical class 0.000 description 1
238000004090 dissolution Methods 0.000 description 1
238000009826 distribution Methods 0.000 description 1
150000002019 disulfides Chemical class 0.000 description 1
231100000673 dose–response relationship Toxicity 0.000 description 1
239000003937 drug carrier Substances 0.000 description 1
229930184221 duocarmycin Natural products 0.000 description 1
229960005501 duocarmycin Drugs 0.000 description 1
239000000975 dye Substances 0.000 description 1
235000013601 eggs Nutrition 0.000 description 1
210000001671 embryonic stem cell Anatomy 0.000 description 1
AUVVAXYIELKVAI-CKBKHPSWSA-N emetine Chemical compound N1CCC2=CC(OC)=C(OC)C=C2[C@H]1C[C@H]1C[C@H]2C3=CC(OC)=C(OC)C=C3CCN2C[C@@H]1CC AUVVAXYIELKVAI-CKBKHPSWSA-N 0.000 description 1
229960002694 emetine Drugs 0.000 description 1
239000003995 emulsifying agent Substances 0.000 description 1
230000002124 endocrine Effects 0.000 description 1
210000002472 endoplasmic reticulum Anatomy 0.000 description 1
230000002255 enzymatic effect Effects 0.000 description 1
229940116977 epidermal growth factor Drugs 0.000 description 1
UNXHWFMMPAWVPI-ZXZARUISSA-N erythritol Chemical compound OC[C@H](O)[C@H](O)CO UNXHWFMMPAWVPI-ZXZARUISSA-N 0.000 description 1
235000019414 erythritol Nutrition 0.000 description 1
229940009714 erythritol Drugs 0.000 description 1
239000003797 essential amino acid Substances 0.000 description 1
235000020776 essential amino acid Nutrition 0.000 description 1
ZMMJGEGLRURXTF-UHFFFAOYSA-N ethidium bromide Chemical compound [Br-].C12=CC(N)=CC=C2C2=CC=C(N)C=C2[N+](CC)=C1C1=CC=CC=C1 ZMMJGEGLRURXTF-UHFFFAOYSA-N 0.000 description 1
229960005542 ethidium bromide Drugs 0.000 description 1
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
VJJPUSNTGOMMGY-MRVIYFEKSA-N etoposide Chemical compound COC1=C(O)C(OC)=CC([C@@H]2C3=CC=4OCOC=4C=C3[C@@H](O[C@H]3[C@@H]([C@@H](O)[C@@H]4O[C@H](C)OC[C@H]4O3)O)[C@@H]3[C@@H]2C(OC3)=O)=C1 VJJPUSNTGOMMGY-MRVIYFEKSA-N 0.000 description 1
229960005420 etoposide Drugs 0.000 description 1
210000003527 eukaryotic cell Anatomy 0.000 description 1
238000013401 experimental design Methods 0.000 description 1
210000003722 extracellular fluid Anatomy 0.000 description 1
239000010685 fatty oil Substances 0.000 description 1
238000001914 filtration Methods 0.000 description 1
229960002949 fluorouracil Drugs 0.000 description 1
235000013355 food flavoring agent Nutrition 0.000 description 1
238000004108 freeze drying Methods 0.000 description 1
108020001507 fusion proteins Proteins 0.000 description 1
102000037865 fusion proteins Human genes 0.000 description 1
210000001035 gastrointestinal tract Anatomy 0.000 description 1
238000001502 gel electrophoresis Methods 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
238000007429 general method Methods 0.000 description 1
229960003180 glutathione Drugs 0.000 description 1
229940074045 glyceryl distearate Drugs 0.000 description 1
229940075507 glyceryl monostearate Drugs 0.000 description 1
229940096919 glycogen Drugs 0.000 description 1
230000034659 glycolysis Effects 0.000 description 1
210000004565 granule cell Anatomy 0.000 description 1
230000009036 growth inhibition Effects 0.000 description 1
239000001963 growth medium Substances 0.000 description 1
239000007902 hard capsule Substances 0.000 description 1
208000006454 hepatitis Diseases 0.000 description 1
231100000283 hepatitis Toxicity 0.000 description 1
238000004128 high performance liquid chromatography Methods 0.000 description 1
238000012165 high-throughput sequencing Methods 0.000 description 1
102000049113 human PGF Human genes 0.000 description 1
102000057041 human TNF Human genes 0.000 description 1
238000009396 hybridization Methods 0.000 description 1
150000007857 hydrazones Chemical class 0.000 description 1
229960000890 hydrocortisone Drugs 0.000 description 1
230000002209 hydrophobic effect Effects 0.000 description 1
125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 1
239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 1
229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 1
UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 description 1
229960001001 ibritumomab tiuxetan Drugs 0.000 description 1
239000012216 imaging agent Substances 0.000 description 1
210000000987 immune system Anatomy 0.000 description 1
230000003053 immunization Effects 0.000 description 1
238000002649 immunization Methods 0.000 description 1
230000002163 immunogen Effects 0.000 description 1
239000000367 immunologic factor Substances 0.000 description 1
238000010324 immunological assay Methods 0.000 description 1
239000003018 immunosuppressive agent Substances 0.000 description 1
229940051026 immunotoxin Drugs 0.000 description 1
230000002637 immunotoxin Effects 0.000 description 1
231100000608 immunotoxin Toxicity 0.000 description 1
210000003000 inclusion body Anatomy 0.000 description 1
238000010348 incorporation Methods 0.000 description 1
238000011534 incubation Methods 0.000 description 1
APFVFJFRJDLVQX-AHCXROLUSA-N indium-111 Chemical compound [111In] APFVFJFRJDLVQX-AHCXROLUSA-N 0.000 description 1
230000001939 inductive effect Effects 0.000 description 1
206010022000 influenza Diseases 0.000 description 1
239000007972 injectable composition Substances 0.000 description 1
102000006495 integrins Human genes 0.000 description 1
108010044426 integrins Proteins 0.000 description 1
229960003130 interferon gamma Drugs 0.000 description 1
229940100601 interleukin-6 Drugs 0.000 description 1
238000007917 intracranial administration Methods 0.000 description 1
238000007912 intraperitoneal administration Methods 0.000 description 1
239000007928 intraperitoneal injection Substances 0.000 description 1
238000004255 ion exchange chromatography Methods 0.000 description 1
239000002085 irritant Substances 0.000 description 1
231100000021 irritant Toxicity 0.000 description 1
238000002955 isolation Methods 0.000 description 1
QXJSBBXBKPUZAA-UHFFFAOYSA-N isooleic acid Natural products CCCCCCCC=CCCCCCCCCC(O)=O QXJSBBXBKPUZAA-UHFFFAOYSA-N 0.000 description 1
NLYAJNPCOHFWQQ-UHFFFAOYSA-N kaolin Chemical compound O.O.O=[Al]O[Si](=O)O[Si](=O)O[Al]=O NLYAJNPCOHFWQQ-UHFFFAOYSA-N 0.000 description 1
238000012004 kinetic exclusion assay Methods 0.000 description 1
238000002372 labelling Methods 0.000 description 1
239000004816 latex Substances 0.000 description 1
229920000126 latex Polymers 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
229960004194 lidocaine Drugs 0.000 description 1
230000000670 limiting effect Effects 0.000 description 1
238000001638 lipofection Methods 0.000 description 1
239000002502 liposome Substances 0.000 description 1
239000003589 local anesthetic agent Substances 0.000 description 1
229960005015 local anesthetics Drugs 0.000 description 1
239000000314 lubricant Substances 0.000 description 1
210000004072 lung Anatomy 0.000 description 1
OHSVLFRHMCKCQY-NJFSPNSNSA-N lutetium-177 Chemical compound [177Lu] OHSVLFRHMCKCQY-NJFSPNSNSA-N 0.000 description 1
210000001165 lymph node Anatomy 0.000 description 1
230000002132 lysosomal effect Effects 0.000 description 1
235000019359 magnesium stearate Nutrition 0.000 description 1
229960001855 mannitol Drugs 0.000 description 1
238000013507 mapping Methods 0.000 description 1
238000000816 matrix-assisted laser desorption--ionisation Methods 0.000 description 1
229960004961 mechlorethamine Drugs 0.000 description 1
HAWPXGHAZFHHAD-UHFFFAOYSA-N mechlorethamine Chemical compound ClCCN(C)CCCl HAWPXGHAZFHHAD-UHFFFAOYSA-N 0.000 description 1
229960001924 melphalan Drugs 0.000 description 1
SGDBTWWWUNNDEQ-LBPRGKRZSA-N melphalan Chemical compound OC(=O)[C@@H](N)CC1=CC=C(N(CCCl)CCCl)C=C1 SGDBTWWWUNNDEQ-LBPRGKRZSA-N 0.000 description 1
229960001428 mercaptopurine Drugs 0.000 description 1
HEBKCHPVOIAQTA-UHFFFAOYSA-N meso ribitol Natural products OCC(O)C(O)C(O)CO HEBKCHPVOIAQTA-UHFFFAOYSA-N 0.000 description 1
108020004999 messenger RNA Proteins 0.000 description 1
229910021645 metal ion Inorganic materials 0.000 description 1
150000002739 metals Chemical class 0.000 description 1
229960000485 methotrexate Drugs 0.000 description 1
229920000609 methyl cellulose Polymers 0.000 description 1
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
239000004292 methyl p-hydroxybenzoate Substances 0.000 description 1
235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 1
235000010981 methylcellulose Nutrition 0.000 description 1
239000001923 methylcellulose Substances 0.000 description 1
229960002216 methylparaben Drugs 0.000 description 1
244000005700 microbiome Species 0.000 description 1
239000011859 microparticle Substances 0.000 description 1
235000013336 milk Nutrition 0.000 description 1
239000008267 milk Substances 0.000 description 1
210000004080 milk Anatomy 0.000 description 1
CFCUWKMKBJTWLW-BKHRDMLASA-N mithramycin Chemical compound O([C@@H]1C[C@@H](O[C@H](C)[C@H]1O)OC=1C=C2C=C3C[C@H]([C@@H](C(=O)C3=C(O)C2=C(O)C=1C)O[C@@H]1O[C@H](C)[C@@H](O)[C@H](O[C@@H]2O[C@H](C)[C@H](O)[C@H](O[C@@H]3O[C@H](C)[C@@H](O)[C@@](C)(O)C3)C2)C1)[C@H](OC)C(=O)[C@@H](O)[C@@H](C)O)[C@H]1C[C@@H](O)[C@H](O)[C@@H](C)O1 CFCUWKMKBJTWLW-BKHRDMLASA-N 0.000 description 1
229960005485 mitobronitol Drugs 0.000 description 1
238000002156 mixing Methods 0.000 description 1
150000002772 monosaccharides Chemical class 0.000 description 1
229940126619 mouse monoclonal antibody Drugs 0.000 description 1
229920001206 natural gum Polymers 0.000 description 1
229920005615 natural polymer Polymers 0.000 description 1
239000013642 negative control Substances 0.000 description 1
229960004927 neomycin Drugs 0.000 description 1
230000007935 neutral effect Effects 0.000 description 1
150000002825 nitriles Chemical class 0.000 description 1
239000002736 nonionic surfactant Substances 0.000 description 1
231100000252 nontoxic Toxicity 0.000 description 1
230000003000 nontoxic effect Effects 0.000 description 1
239000000346 nonvolatile oil Substances 0.000 description 1
239000002773 nucleotide Substances 0.000 description 1
125000003729 nucleotide group Chemical group 0.000 description 1
GYCKQBWUSACYIF-UHFFFAOYSA-N o-hydroxybenzoic acid ethyl ester Natural products CCOC(=O)C1=CC=CC=C1O GYCKQBWUSACYIF-UHFFFAOYSA-N 0.000 description 1
QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
229960002378 oftasceine Drugs 0.000 description 1
239000003921 oil Substances 0.000 description 1
235000019198 oils Nutrition 0.000 description 1
ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 1
230000003287 optical effect Effects 0.000 description 1
230000003647 oxidation Effects 0.000 description 1
238000007254 oxidation reaction Methods 0.000 description 1
LXCFILQKKLGQFO-UHFFFAOYSA-N p-hydroxybenzoic acid methyl ester Natural products COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 description 1
229960001592 paclitaxel Drugs 0.000 description 1
235000019629 palatability Nutrition 0.000 description 1
229940055729 papain Drugs 0.000 description 1
235000019834 papain Nutrition 0.000 description 1
239000012188 paraffin wax Substances 0.000 description 1
238000007911 parenteral administration Methods 0.000 description 1
239000002245 particle Substances 0.000 description 1
230000001575 pathological effect Effects 0.000 description 1
235000021400 peanut butter Nutrition 0.000 description 1
229940111202 pepsin Drugs 0.000 description 1
239000000816 peptidomimetic Substances 0.000 description 1
230000000144 pharmacologic effect Effects 0.000 description 1
WVDDGKGOMKODPV-ZQBYOMGUSA-N phenyl(114C)methanol Chemical compound O[14CH2]C1=CC=CC=C1 WVDDGKGOMKODPV-ZQBYOMGUSA-N 0.000 description 1
NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
239000010452 phosphate Substances 0.000 description 1
239000002953 phosphate buffered saline Substances 0.000 description 1
102000020233 phosphotransferase Human genes 0.000 description 1
238000013081 phylogenetic analysis Methods 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
210000004180 plasmocyte Anatomy 0.000 description 1
239000004033 plastic Substances 0.000 description 1
229920003023 plastic Polymers 0.000 description 1
229960003171 plicamycin Drugs 0.000 description 1
229920001983 poloxamer Polymers 0.000 description 1
229920001993 poloxamer 188 Polymers 0.000 description 1
229940044519 poloxamer 188 Drugs 0.000 description 1
229920000962 poly(amidoamine) Polymers 0.000 description 1
229920000058 polyacrylate Polymers 0.000 description 1
230000008488 polyadenylation Effects 0.000 description 1
229920002859 polyalkenylene Polymers 0.000 description 1
229920000728 polyester Polymers 0.000 description 1
229920000573 polyethylene Polymers 0.000 description 1
229920000656 polylysine Polymers 0.000 description 1
229920001451 polypropylene glycol Polymers 0.000 description 1
229920002451 polyvinyl alcohol Polymers 0.000 description 1
239000001267 polyvinylpyrrolidone Substances 0.000 description 1
229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
238000012545 processing Methods 0.000 description 1
230000002035 prolonged effect Effects 0.000 description 1
230000000069 prophylactic effect Effects 0.000 description 1
229960003712 propranolol Drugs 0.000 description 1
239000004405 propyl p-hydroxybenzoate Substances 0.000 description 1
235000010232 propyl p-hydroxybenzoate Nutrition 0.000 description 1
229960003415 propylparaben Drugs 0.000 description 1
238000001742 protein purification Methods 0.000 description 1
210000001938 protoplast Anatomy 0.000 description 1
229950010131 puromycin Drugs 0.000 description 1
239000002287 radioligand Substances 0.000 description 1
239000012217 radiopharmaceutical Substances 0.000 description 1
229940121896 radiopharmaceutical Drugs 0.000 description 1
230000002799 radiopharmaceutical effect Effects 0.000 description 1
231100001258 radiotoxin Toxicity 0.000 description 1
MUPFEKGTMRGPLJ-ZQSKZDJDSA-N raffinose 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[C@@H]2[C@@H]([C@@H](O)[C@@H](O)[C@@H](CO)O2)O)O1 MUPFEKGTMRGPLJ-ZQSKZDJDSA-N 0.000 description 1
230000001105 regulatory effect Effects 0.000 description 1
238000012827 research and development Methods 0.000 description 1
108091008146 restriction endonucleases Proteins 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
239000012723 sample buffer Substances 0.000 description 1
230000003248 secreting effect Effects 0.000 description 1
210000002966 serum Anatomy 0.000 description 1
239000008159 sesame oil Substances 0.000 description 1
235000011803 sesame oil Nutrition 0.000 description 1
230000008054 signal transmission Effects 0.000 description 1
238000002741 site-directed mutagenesis Methods 0.000 description 1
239000011734 sodium Substances 0.000 description 1
229910052708 sodium Inorganic materials 0.000 description 1
235000010413 sodium alginate Nutrition 0.000 description 1
239000000661 sodium alginate Substances 0.000 description 1
229940005550 sodium alginate Drugs 0.000 description 1
229910001467 sodium calcium phosphate Inorganic materials 0.000 description 1
229910000029 sodium carbonate Inorganic materials 0.000 description 1
235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 1
239000001488 sodium phosphate Substances 0.000 description 1
239000007901 soft capsule Substances 0.000 description 1
238000001179 sorption measurement Methods 0.000 description 1
SFVFIFLLYFPGHH-UHFFFAOYSA-M stearalkonium chloride Chemical compound [Cl-].CCCCCCCCCCCCCCCCCC[N+](C)(C)CC1=CC=CC=C1 SFVFIFLLYFPGHH-UHFFFAOYSA-M 0.000 description 1
239000008117 stearic acid Substances 0.000 description 1
238000003756 stirring Methods 0.000 description 1
238000003860 storage Methods 0.000 description 1
ZSJLQEPLLKMAKR-GKHCUFPYSA-N streptozocin Chemical compound O=NN(C)C(=O)N[C@H]1[C@@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O ZSJLQEPLLKMAKR-GKHCUFPYSA-N 0.000 description 1
229960001052 streptozocin Drugs 0.000 description 1
210000001179 synovial fluid Anatomy 0.000 description 1
238000003786 synthesis reaction Methods 0.000 description 1
229920001059 synthetic polymer Polymers 0.000 description 1
230000009885 systemic effect Effects 0.000 description 1
239000000454 talc Substances 0.000 description 1
235000012222 talc Nutrition 0.000 description 1
229910052623 talc Inorganic materials 0.000 description 1
238000002626 targeted therapy Methods 0.000 description 1
RCINICONZNJXQF-MZXODVADSA-N taxol Chemical compound O([C@@H]1[C@@]2(C[C@@H](C(C)=C(C2(C)C)[C@H](C([C@]2(C)[C@@H](O)C[C@H]3OC[C@]3([C@H]21)OC(C)=O)=O)OC(=O)C)OC(=O)[C@H](O)[C@@H](NC(=O)C=1C=CC=CC=1)C=1C=CC=CC=1)O)C(=O)C1=CC=CC=C1 RCINICONZNJXQF-MZXODVADSA-N 0.000 description 1
210000001138 tear Anatomy 0.000 description 1
NRUKOCRGYNPUPR-QBPJDGROSA-N teniposide Chemical compound COC1=C(O)C(OC)=CC([C@@H]2C3=CC=4OCOC=4C=C3[C@@H](O[C@H]3[C@@H]([C@@H](O)[C@@H]4O[C@@H](OC[C@H]4O3)C=3SC=CC=3)O)[C@@H]3[C@@H]2C(OC3)=O)=C1 NRUKOCRGYNPUPR-QBPJDGROSA-N 0.000 description 1
229960001278 teniposide Drugs 0.000 description 1
229930101283 tetracycline Natural products 0.000 description 1
229960002180 tetracycline Drugs 0.000 description 1
235000019364 tetracycline Nutrition 0.000 description 1
150000003522 tetracyclines Chemical class 0.000 description 1
238000010257 thawing Methods 0.000 description 1
239000002562 thickening agent Substances 0.000 description 1
150000003568 thioethers Chemical class 0.000 description 1
125000003396 thiol group Chemical group [H]S* 0.000 description 1
229960001196 thiotepa Drugs 0.000 description 1
238000001269 time-of-flight mass spectrometry Methods 0.000 description 1
229960003087 tioguanine Drugs 0.000 description 1
230000001256 tonic effect Effects 0.000 description 1
239000012929 tonicity agent Substances 0.000 description 1
231100000331 toxic Toxicity 0.000 description 1
230000002588 toxic effect Effects 0.000 description 1
230000001988 toxicity Effects 0.000 description 1
231100000419 toxicity Toxicity 0.000 description 1
239000003053 toxin Substances 0.000 description 1
231100000765 toxin Toxicity 0.000 description 1
238000012549 training Methods 0.000 description 1
230000005030 transcription termination Effects 0.000 description 1
230000002103 transcriptional effect Effects 0.000 description 1
230000009466 transformation Effects 0.000 description 1
238000011830 transgenic mouse model Methods 0.000 description 1
ILJSQTXMGCGYMG-UHFFFAOYSA-N triacetic acid Chemical compound CC(=O)CC(=O)CC(O)=O ILJSQTXMGCGYMG-UHFFFAOYSA-N 0.000 description 1
239000013638 trimer Substances 0.000 description 1
RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 1
210000003606 umbilical vein Anatomy 0.000 description 1
241000701161 unidentified adenovirus Species 0.000 description 1
210000002700 urine Anatomy 0.000 description 1
VBEQCZHXXJYVRD-GACYYNSASA-N uroanthelone Chemical compound C([C@@H](C(=O)N[C@H](C(=O)N[C@@H](CS)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CS)C(=O)N[C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)NCC(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CS)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O)C(C)C)[C@@H](C)O)NC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H](CCSC)NC(=O)[C@H](CS)NC(=O)[C@@H](NC(=O)CNC(=O)CNC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CS)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)CNC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CS)NC(=O)CNC(=O)[C@H]1N(CCC1)C(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC(N)=O)C(C)C)[C@@H](C)CC)C1=CC=C(O)C=C1 VBEQCZHXXJYVRD-GACYYNSASA-N 0.000 description 1
239000013603 viral vector Substances 0.000 description 1
230000000007 visual effect Effects 0.000 description 1
239000000811 xylitol Substances 0.000 description 1
HEBKCHPVOIAQTA-SCDXWVJYSA-N xylitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)CO HEBKCHPVOIAQTA-SCDXWVJYSA-N 0.000 description 1
235000010447 xylitol Nutrition 0.000 description 1
229960002675 xylitol Drugs 0.000 description 1
210000005253 yeast cell Anatomy 0.000 description 1

Images

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- C07K16/24—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against cytokines, lymphokines or interferons
- 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
- A61K39/395—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- C07K16/22—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against growth factors ; against growth regulators

Landscapes

Health & Medical Sciences (AREA)
Chemical & Material Sciences (AREA)
Life Sciences & Earth Sciences (AREA)
Medicinal Chemistry (AREA)
Organic Chemistry (AREA)
Immunology (AREA)
General Health & Medical Sciences (AREA)
Biochemistry (AREA)
Biophysics (AREA)
Genetics & Genomics (AREA)
Molecular Biology (AREA)
Proteomics, Peptides & Aminoacids (AREA)
Engineering & Computer Science (AREA)
Bioinformatics & Cheminformatics (AREA)
Microbiology (AREA)
Mycology (AREA)
Pharmacology & Pharmacy (AREA)
Epidemiology (AREA)
Animal Behavior & Ethology (AREA)
Public Health (AREA)
Veterinary Medicine (AREA)
Peptides Or Proteins (AREA)
Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
Micro-Organisms Or Cultivation Processes Thereof (AREA)
Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)

RU2018109506A 2008-06-25 2018-03-19 Гуманизация антител кролика с использованием универсального каркаса антитела RU2696202C1 (ru)

Applications Claiming Priority (10)

Application Number	Priority Date	Filing Date
US7569208P	2008-06-25	2008-06-25
US7569708P	2008-06-25	2008-06-25
US61/075,692		2008-06-25
US61/075,697		2008-06-25
US15504109P	2009-02-24	2009-02-24
US15510509P	2009-02-24	2009-02-24
US61/155,105		2009-02-24
US61/155,041		2009-02-24
CH8322009		2009-06-02
CH832/09		2009-06-02

Related Parent Applications (1)

Application Number	Title	Priority Date	Filing Date
RU2014111173A Division RU2652907C2 (ru)	2008-06-25	2014-03-24	Гуманизация антител кролика с использованием универсального каркаса антитела

Related Child Applications (1)

Application Number	Title	Priority Date	Filing Date
RU2019119412A Division RU2019119412A (ru)	2008-06-25	2019-06-21	Гуманизация антител кролика с использованием универсального каркаса антитела

Publications (1)

Publication Number	Publication Date
RU2696202C1 true RU2696202C1 (ru)	2019-07-31

Family

ID=53532693

Family Applications (2)

Application Number	Title	Priority Date	Filing Date
RU2018109506A RU2696202C1 (ru)	2008-06-25	2018-03-19	Гуманизация антител кролика с использованием универсального каркаса антитела
RU2019119412A RU2019119412A (ru)	2008-06-25	2019-06-21	Гуманизация антител кролика с использованием универсального каркаса антитела

Family Applications After (1)

Application Number	Title	Priority Date	Filing Date
RU2019119412A RU2019119412A (ru)	2008-06-25	2019-06-21	Гуманизация антител кролика с использованием универсального каркаса антитела

Country Status (9)

Country	Link
JP (5)	JP2015120746A (ja)
KR (2)	KR102284435B1 (ja)
CL (1)	CL2010001539A1 (ja)
ES (1)	ES2771150T3 (ja)
HU (1)	HUE047678T2 (ja)
PH (2)	PH12013502219A1 (ja)
PT (2)	PT2752428T (ja)
RU (2)	RU2696202C1 (ja)
ZA (3)	ZA201008592B (ja)

Citations (2)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
WO2002086093A2 (en) *	2001-04-25	2002-10-31	Weigel Paul H	Methods of using a hyaluronan receptor
EA007958B1 (ru) *	2000-08-03	2007-02-27	Терапеутик Хьюман Поликлоналз Инк.	ТРАНСГЕННЫЙ ВЕКТОР, СОДЕРЖАЩИЙ ГУМАНИЗИРОВАННЫЙ ЛОКУС Ig, И ЕГО ПРИМЕНЕНИЕ ДЛЯ ПОЛУЧЕНИЯ ТРАНСГЕННЫХ ЖИВОТНЫХ

Family Cites Families (12)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
JP2000516452A (ja) *	1996-07-16	2000-12-12	プリュックテュン，アンドレアス	可溶性が増大した免疫グロブリンスーパーファミリードメインおよびフラグメント
WO2003074679A2 (en) *	2002-03-01	2003-09-12	Xencor	Antibody optimization
PT2332989E (pt) *	2002-05-22	2015-08-05	Esbatech Alcon Biomed Res Unit	Estruturas de imunoglobulina que demonstram estabilidade aumentada no ambiente intracelular e métodos de identificação das mesmas
US20040086979A1 (en)	2002-08-15	2004-05-06	Dongxiao Zhang	Humanized rabbit antibodies
US20050033031A1 (en)	2003-08-07	2005-02-10	Couto Fernando Jose Rebelo Do	Methods for humanizing rabbit monoclonal antibodies
AU2004280333A1 (en) *	2003-08-22	2005-04-21	Medimmune, Llc	Humanization of antibodies
US7431927B2 (en) *	2005-03-24	2008-10-07	Epitomics, Inc.	TNFα-neutralizing antibodies
WO2006131013A2 (en) *	2005-06-07	2006-12-14	Esbatech Ag	STABLE AND SOLUBLE ANTIBODIES INHIBITING TNFα
ES2373080T3 (es) *	2005-06-20	2012-01-31	Genentech, Inc.	Anticuerpos que se unen al antígeno tat10772 asociado a tumores para el diagnóstico y tratamiento de un tumor.
GB0520436D0 (en) *	2005-10-07	2005-11-16	Photobiotics Ltd	Biological materials and uses thereof
WO2008004834A1 (en) *	2006-07-06	2008-01-10	Isu Abxis Co., Ltd	Humanized monoclonal antibody highly binding to epidermal growth factor receptor, egf receptor
BRPI0809042B1 (pt) *	2007-03-22	2021-08-31	Biogen Ma Inc.	Proteína de ligação a cd154 isolada, seu uso, e composição

2009
- 2009-06-25 PT PT141626648T patent/PT2752428T/pt unknown
- 2009-06-25 PT PT97686950T patent/PT2307458T/pt unknown
- 2009-06-25 ES ES14162664T patent/ES2771150T3/es active Active
- 2009-06-25 HU HUE14162664A patent/HUE047678T2/hu unknown
- 2009-06-25 KR KR1020197022505A patent/KR102284435B1/ko active Active
- 2009-06-25 KR KR1020217023841A patent/KR20210097819A/ko not_active Withdrawn
2010
- 2010-11-30 ZA ZA2010/08592A patent/ZA201008592B/en unknown
- 2010-12-23 CL CL2010001539A patent/CL2010001539A1/es unknown
2013
- 2013-10-25 PH PH12013502219A patent/PH12013502219A1/en unknown
- 2013-11-21 ZA ZA2013/08755A patent/ZA201308755B/en unknown
2015
- 2015-03-18 JP JP2015054497A patent/JP2015120746A/ja not_active Withdrawn
- 2015-05-11 ZA ZA2015/03267A patent/ZA201503267B/en unknown
2016
- 2016-04-27 JP JP2016088845A patent/JP2016135815A/ja active Pending
2017
- 2017-07-31 JP JP2017148091A patent/JP6568557B2/ja active Active
2018
- 2018-03-19 RU RU2018109506A patent/RU2696202C1/ru active
- 2018-08-13 PH PH12018501715A patent/PH12018501715A1/en unknown
2019
- 2019-02-01 JP JP2019016882A patent/JP6903083B2/ja active Active
- 2019-06-21 RU RU2019119412A patent/RU2019119412A/ru unknown
2020
- 2020-04-30 JP JP2020080224A patent/JP2020114260A/ja not_active Withdrawn

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
EA007958B1 (ru) *	2000-08-03	2007-02-27	Терапеутик Хьюман Поликлоналз Инк.	ТРАНСГЕННЫЙ ВЕКТОР, СОДЕРЖАЩИЙ ГУМАНИЗИРОВАННЫЙ ЛОКУС Ig, И ЕГО ПРИМЕНЕНИЕ ДЛЯ ПОЛУЧЕНИЯ ТРАНСГЕННЫХ ЖИВОТНЫХ
WO2002086093A2 (en) *	2001-04-25	2002-10-31	Weigel Paul H	Methods of using a hyaluronan receptor

Also Published As

Publication number	Publication date
JP6903083B2 (ja)	2021-07-14
JP2015120746A (ja)	2015-07-02
ES2771150T3 (es)	2020-07-06
ZA201308755B (en)	2015-08-26
JP6568557B2 (ja)	2019-08-28
PT2752428T (pt)	2020-02-14
HUE047678T2 (hu)	2020-05-28
RU2019119412A (ru)	2020-12-21
PH12013502219A1 (en)	2016-01-25
JP2016135815A (ja)	2016-07-28
CL2010001539A1 (es)	2012-02-03
KR102284435B1 (ko)	2021-08-02
KR20210097819A (ko)	2021-08-09
KR20190091578A (ko)	2019-08-06
JP2017190352A (ja)	2017-10-19
ZA201503267B (en)	2016-07-27
PH12018501715A1 (en)	2019-08-19
ZA201008592B (en)	2014-02-26
JP2020114260A (ja)	2020-07-30
JP2019065050A (ja)	2019-04-25
PT2307458T (pt)	2018-07-18

Publication	Publication Date	Title
US11858981B2 (en)	2024-01-02	Humanization of rabbit antibodies using a universal antibody framework
JP2022121522A (ja)	2022-08-19	汎用性抗体フレームワークを用いたイエウサギ抗体のヒト化
RU2696202C1 (ru)	2019-07-31	Гуманизация антител кролика с использованием универсального каркаса антитела
RU2652907C2 (ru)	2018-05-03	Гуманизация антител кролика с использованием универсального каркаса антитела
RU2567006C2 (ru)	2015-10-27	Гуманизация антител кролика с использованием универсального каркаса антитела
HK40067518A (en)	2022-09-09	Humanization of rabbit antibodies using a universal antibody framework
AU2013203004B2 (en)	2016-09-08	Humanization of rabbit antibodies using a universal antibody framework
AU2020201002A1 (en)	2020-02-27	Humanization of rabbit antibodies using a universal antibody framework
HK1150842A (en)	2012-01-13	Humanization of rabbit antibodies using a universal antibody framework
HK1150842B (en)	2018-12-28	Humanization of rabbit antibodies using a universal antibody framework
HK1194089A (en)	2014-10-10	Humanization of rabbit antibodies using a universal antibody framework
HK1194089B (en)	2020-12-11	Humanization of rabbit antibodies using a universal antibody framework
HK40023290A (en)	2020-11-27	Humanization of rabbit antibodies using a universal antibody framework
HK40023290B (en)	2022-03-25	Humanization of rabbit antibodies using a universal antibody framework

Legal Events

Date	Code	Title	Description
2020-01-13	PD4A	Correction of name of patent owner
2020-03-10	PC41	Official registration of the transfer of exclusive right	Effective date: 20200310