JPWO2020132456A5 - - Google Patents
Download PDFInfo
- Publication number
- JPWO2020132456A5 JPWO2020132456A5 JP2021536271A JP2021536271A JPWO2020132456A5 JP WO2020132456 A5 JPWO2020132456 A5 JP WO2020132456A5 JP 2021536271 A JP2021536271 A JP 2021536271A JP 2021536271 A JP2021536271 A JP 2021536271A JP WO2020132456 A5 JPWO2020132456 A5 JP WO2020132456A5
- Authority
- JP
- Japan
- Prior art keywords
- antibody
- cells
- seq
- antigen
- binding fragment
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- 102000004965 antibodies Human genes 0.000 claims description 465
- 108090001123 antibodies Proteins 0.000 claims description 465
- 210000004027 cells Anatomy 0.000 claims description 436
- 230000027455 binding Effects 0.000 claims description 259
- 239000000427 antigen Substances 0.000 claims description 209
- 108091007172 antigens Proteins 0.000 claims description 191
- 102000038129 antigens Human genes 0.000 claims description 191
- 206010067584 Type 1 diabetes mellitus Diseases 0.000 claims description 169
- 125000003275 alpha amino acid group Chemical group 0.000 claims description 140
- 101700027814 CDR3 Proteins 0.000 claims description 91
- 108091008154 B cell receptors Proteins 0.000 claims description 77
- 230000014509 gene expression Effects 0.000 claims description 77
- 239000000203 mixture Substances 0.000 claims description 61
- 238000006467 substitution reaction Methods 0.000 claims description 54
- 210000004698 Lymphocytes Anatomy 0.000 claims description 49
- 108060001277 CDR2 Proteins 0.000 claims description 48
- 238000003752 polymerase chain reaction Methods 0.000 claims description 38
- 150000001413 amino acids Chemical class 0.000 claims description 35
- 108010047041 Complementarity Determining Regions Proteins 0.000 claims description 32
- 239000000725 suspension Substances 0.000 claims description 31
- 150000007523 nucleic acids Chemical class 0.000 claims description 25
- 238000004519 manufacturing process Methods 0.000 claims description 24
- 206010003816 Autoimmune disease Diseases 0.000 claims description 22
- 108020004707 nucleic acids Proteins 0.000 claims description 21
- 230000035693 Fab Effects 0.000 claims description 20
- 229920001850 Nucleic acid sequence Polymers 0.000 claims description 17
- 239000011886 peripheral blood Substances 0.000 claims description 16
- 108010062347 HLA-DQ Antigens Proteins 0.000 claims description 14
- 241000124008 Mammalia Species 0.000 claims description 14
- 238000001514 detection method Methods 0.000 claims description 14
- 108010047762 HLA-DQ8 antigen Proteins 0.000 claims description 13
- 206010012601 Diabetes mellitus Diseases 0.000 claims description 11
- 239000003937 drug carrier Substances 0.000 claims description 10
- 210000003527 eukaryotic cell Anatomy 0.000 claims description 10
- 230000003321 amplification Effects 0.000 claims description 9
- 239000012472 biological sample Substances 0.000 claims description 9
- 238000007918 intramuscular administration Methods 0.000 claims description 9
- 238000001990 intravenous administration Methods 0.000 claims description 9
- 238000003199 nucleic acid amplification method Methods 0.000 claims description 9
- 201000009596 autoimmune hypersensitivity disease Diseases 0.000 claims description 8
- 238000007912 intraperitoneal administration Methods 0.000 claims description 7
- 108010045618 HLA-DQ7 antigen Proteins 0.000 claims description 6
- 201000006417 multiple sclerosis Diseases 0.000 claims description 6
- 230000003405 preventing Effects 0.000 claims description 6
- 210000001236 prokaryotic cell Anatomy 0.000 claims description 6
- 238000007920 subcutaneous administration Methods 0.000 claims description 6
- 206010039073 Rheumatoid arthritis Diseases 0.000 claims description 5
- 238000007913 intrathecal administration Methods 0.000 claims description 5
- 206010021425 Immune system disease Diseases 0.000 claims 1
- 201000000596 systemic lupus erythematosus Diseases 0.000 claims 1
- 210000001744 T-Lymphocytes Anatomy 0.000 description 92
- 108091008153 T cell receptors Proteins 0.000 description 78
- 102000016266 T-Cell Antigen Receptors Human genes 0.000 description 78
- 108010043156 Immunoglobulin D Proteins 0.000 description 74
- 102100013077 CD4 Human genes 0.000 description 68
- 101700022938 CD4 Proteins 0.000 description 68
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 66
- 238000004458 analytical method Methods 0.000 description 54
- 235000001014 amino acid Nutrition 0.000 description 53
- 201000010099 disease Diseases 0.000 description 41
- 229920001184 polypeptide Polymers 0.000 description 41
- 210000003819 Peripheral blood mononuclear cell Anatomy 0.000 description 40
- 101700073818 CDR1 Proteins 0.000 description 39
- 102100002977 CDR1 Human genes 0.000 description 39
- 108090001061 Insulin Proteins 0.000 description 37
- 102000004877 Insulin Human genes 0.000 description 37
- 235000018102 proteins Nutrition 0.000 description 28
- 102000004169 proteins and genes Human genes 0.000 description 28
- 108090000623 proteins and genes Proteins 0.000 description 28
- 230000000638 stimulation Effects 0.000 description 28
- 102100005826 CD19 Human genes 0.000 description 27
- 101700087100 CD19 Proteins 0.000 description 27
- 239000000523 sample Substances 0.000 description 26
- 230000003993 interaction Effects 0.000 description 24
- 210000003719 B-Lymphocytes Anatomy 0.000 description 23
- 239000003795 chemical substances by application Substances 0.000 description 23
- 230000002483 superagonistic Effects 0.000 description 23
- 210000004602 germ cell Anatomy 0.000 description 21
- 102000018358 Immunoglobulins Human genes 0.000 description 20
- 108060003951 Immunoglobulins Proteins 0.000 description 20
- 239000000463 material Substances 0.000 description 19
- 108090001095 Immunoglobulin G Proteins 0.000 description 18
- 229940021015 I.V. solution additive Amino Acids Drugs 0.000 description 17
- 102000004854 Immunoglobulin M Human genes 0.000 description 17
- 108090001096 Immunoglobulin M Proteins 0.000 description 17
- UIIMBOGNXHQVGW-UHFFFAOYSA-M buffer Substances [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 17
- 238000000329 molecular dynamics simulation Methods 0.000 description 17
- 102000004196 processed proteins & peptides Human genes 0.000 description 17
- 108090000765 processed proteins & peptides Proteins 0.000 description 17
- 230000000694 effects Effects 0.000 description 16
- 101700033362 CD28 Proteins 0.000 description 15
- 102100019461 CD28 Human genes 0.000 description 15
- 108091006028 chimera Proteins 0.000 description 15
- 238000002703 mutagenesis Methods 0.000 description 15
- 231100000350 mutagenesis Toxicity 0.000 description 15
- 230000035755 proliferation Effects 0.000 description 15
- 230000004044 response Effects 0.000 description 15
- 229920000160 (ribonucleotides)n+m Polymers 0.000 description 14
- 101710038213 AKR1C4 Proteins 0.000 description 14
- 101710034060 RUNX1T1 Proteins 0.000 description 14
- 238000006243 chemical reaction Methods 0.000 description 14
- 239000003814 drug Substances 0.000 description 14
- 230000003389 potentiating Effects 0.000 description 14
- 238000004166 bioassay Methods 0.000 description 13
- 229920003013 deoxyribonucleic acid Polymers 0.000 description 13
- 238000010186 staining Methods 0.000 description 13
- 102000004190 Enzymes Human genes 0.000 description 12
- 108090000790 Enzymes Proteins 0.000 description 12
- -1 but not limited to Substances 0.000 description 12
- 238000010367 cloning Methods 0.000 description 12
- 238000002474 experimental method Methods 0.000 description 12
- 239000002773 nucleotide Substances 0.000 description 12
- 125000003729 nucleotide group Chemical group 0.000 description 12
- 239000008194 pharmaceutical composition Substances 0.000 description 12
- 238000010839 reverse transcription Methods 0.000 description 12
- PGHMRUGBZOYCAA-UHFFFAOYSA-N 11,19,21-trihydroxy-22-[5-[5-(1-hydroxyethyl)-5-methyloxolan-2-yl]-5-methyloxolan-2-yl]-4,6,8,12,14,18,20-heptamethyl-9-oxodocosa-10,16-dienoic acid Chemical compound O1C(CC(O)C(C)C(O)C(C)C=CCC(C)CC(C)C(O)=CC(=O)C(C)CC(C)CC(CCC(O)=O)C)CCC1(C)C1OC(C)(C(C)O)CC1 PGHMRUGBZOYCAA-UHFFFAOYSA-N 0.000 description 11
- 101700080416 CD69 Proteins 0.000 description 11
- 102100005832 CD69 Human genes 0.000 description 11
- 125000000539 amino acid group Chemical group 0.000 description 11
- 230000004186 co-expression Effects 0.000 description 11
- 230000035772 mutation Effects 0.000 description 11
- 239000000047 product Substances 0.000 description 11
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 11
- 239000002904 solvent Substances 0.000 description 11
- 238000002198 surface plasmon resonance spectroscopy Methods 0.000 description 11
- 230000003827 upregulation Effects 0.000 description 11
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 10
- 210000002966 Serum Anatomy 0.000 description 10
- 235000004279 alanine Nutrition 0.000 description 10
- 230000001186 cumulative Effects 0.000 description 10
- 238000010586 diagram Methods 0.000 description 10
- 238000010790 dilution Methods 0.000 description 10
- 230000003834 intracellular Effects 0.000 description 10
- 239000002609 media Substances 0.000 description 10
- 238000000034 method Methods 0.000 description 10
- 108020003175 receptors Proteins 0.000 description 10
- 102000005962 receptors Human genes 0.000 description 10
- 239000000243 solution Substances 0.000 description 10
- 201000010874 syndrome Diseases 0.000 description 10
- 230000001225 therapeutic Effects 0.000 description 10
- 229920002676 Complementary DNA Polymers 0.000 description 9
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 9
- 230000003044 adaptive Effects 0.000 description 9
- 230000001363 autoimmune Effects 0.000 description 9
- 230000000295 complement Effects 0.000 description 9
- 239000002299 complementary DNA Substances 0.000 description 9
- 150000001875 compounds Chemical class 0.000 description 9
- 230000029087 digestion Effects 0.000 description 9
- 230000002209 hydrophobic Effects 0.000 description 9
- 230000004048 modification Effects 0.000 description 9
- 238000006011 modification reaction Methods 0.000 description 9
- 108010045030 monoclonal antibodies Proteins 0.000 description 9
- 102000005614 monoclonal antibodies Human genes 0.000 description 9
- 229920000642 polymer Polymers 0.000 description 9
- 238000004088 simulation Methods 0.000 description 9
- 239000011780 sodium chloride Substances 0.000 description 9
- 235000002639 sodium chloride Nutrition 0.000 description 9
- 108010071919 Bispecific Antibodies Proteins 0.000 description 8
- 229940088598 Enzyme Drugs 0.000 description 8
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 8
- 238000007792 addition Methods 0.000 description 8
- 239000006185 dispersion Substances 0.000 description 8
- 239000002552 dosage form Substances 0.000 description 8
- 229940079593 drugs Drugs 0.000 description 8
- 238000000684 flow cytometry Methods 0.000 description 8
- 239000007924 injection Substances 0.000 description 8
- 238000002360 preparation method Methods 0.000 description 8
- 238000000746 purification Methods 0.000 description 8
- 238000007492 two-way ANOVA Methods 0.000 description 8
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 8
- 229960005261 Aspartic Acid Drugs 0.000 description 7
- 210000004369 Blood Anatomy 0.000 description 7
- 241000588724 Escherichia coli Species 0.000 description 7
- 241000701044 Human gammaherpesvirus 4 Species 0.000 description 7
- 101700086956 IFNG Proteins 0.000 description 7
- 102100016020 IFNG Human genes 0.000 description 7
- 108091007229 NSP3 Papain-like protease domain Proteins 0.000 description 7
- 230000002378 acidificating Effects 0.000 description 7
- 125000003118 aryl group Chemical group 0.000 description 7
- 235000003704 aspartic acid Nutrition 0.000 description 7
- 239000008280 blood Substances 0.000 description 7
- 238000004132 cross linking Methods 0.000 description 7
- 238000011161 development Methods 0.000 description 7
- 230000018109 developmental process Effects 0.000 description 7
- 238000000338 in vitro Methods 0.000 description 7
- 229920001223 polyethylene glycol Polymers 0.000 description 7
- BQCADISMDOOEFD-UHFFFAOYSA-N silver Chemical compound [Ag] BQCADISMDOOEFD-UHFFFAOYSA-N 0.000 description 7
- 229910052709 silver Inorganic materials 0.000 description 7
- 239000004332 silver Substances 0.000 description 7
- 239000000126 substance Substances 0.000 description 7
- 108090001122 Immunoglobulin A Proteins 0.000 description 6
- 210000004153 Islets of Langerhans Anatomy 0.000 description 6
- AGPKZVBTJJNPAG-WHFBIAKZSA-N L-isoleucine Chemical compound CC[C@H](C)[C@H](N)C(O)=O AGPKZVBTJJNPAG-WHFBIAKZSA-N 0.000 description 6
- AYFVYJQAPQTCCC-GBXIJSLDSA-N L-threonine Chemical compound C[C@@H](O)[C@H](N)C(O)=O AYFVYJQAPQTCCC-GBXIJSLDSA-N 0.000 description 6
- 239000002202 Polyethylene glycol Substances 0.000 description 6
- 239000011543 agarose gel Substances 0.000 description 6
- 108010092132 anti-IgM Proteins 0.000 description 6
- 230000000903 blocking Effects 0.000 description 6
- 230000012010 growth Effects 0.000 description 6
- 230000001965 increased Effects 0.000 description 6
- 230000001264 neutralization Effects 0.000 description 6
- 229920000023 polynucleotide Polymers 0.000 description 6
- 239000002157 polynucleotide Substances 0.000 description 6
- 239000000843 powder Substances 0.000 description 6
- 238000003757 reverse transcription PCR Methods 0.000 description 6
- FAPWRFPIFSIZLT-UHFFFAOYSA-M sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 6
- 206010004161 Basedow's disease Diseases 0.000 description 5
- 102000004127 Cytokines Human genes 0.000 description 5
- 108090000695 Cytokines Proteins 0.000 description 5
- 208000003807 Graves Disease Diseases 0.000 description 5
- 201000004779 Graves' disease Diseases 0.000 description 5
- 230000036499 Half live Effects 0.000 description 5
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 5
- 108090000526 Papain Proteins 0.000 description 5
- 108090000284 Pepsin A Proteins 0.000 description 5
- 238000010162 Tukey test Methods 0.000 description 5
- 238000010521 absorption reaction Methods 0.000 description 5
- 230000004913 activation Effects 0.000 description 5
- 230000001580 bacterial Effects 0.000 description 5
- 230000015572 biosynthetic process Effects 0.000 description 5
- 238000004364 calculation method Methods 0.000 description 5
- 150000001720 carbohydrates Chemical class 0.000 description 5
- 238000004587 chromatography analysis Methods 0.000 description 5
- 230000000875 corresponding Effects 0.000 description 5
- 230000001809 detectable Effects 0.000 description 5
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 5
- 230000003899 glycosylation Effects 0.000 description 5
- 238000006206 glycosylation reaction Methods 0.000 description 5
- 238000002347 injection Methods 0.000 description 5
- 239000007788 liquid Substances 0.000 description 5
- 239000003550 marker Substances 0.000 description 5
- 239000002245 particle Substances 0.000 description 5
- 238000006366 phosphorylation reaction Methods 0.000 description 5
- 230000000865 phosphorylative Effects 0.000 description 5
- 108010094020 polyglycine Proteins 0.000 description 5
- 229920000232 polyglycine polymer Polymers 0.000 description 5
- 239000003981 vehicle Substances 0.000 description 5
- 239000004475 Arginine Substances 0.000 description 4
- 101700066525 CD5 Proteins 0.000 description 4
- 241000283707 Capra Species 0.000 description 4
- 238000002965 ELISA Methods 0.000 description 4
- 229960002989 Glutamic Acid Drugs 0.000 description 4
- 229960000310 ISOLEUCINE Drugs 0.000 description 4
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 4
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 4
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 4
- KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 description 4
- 229940055729 Papain Drugs 0.000 description 4
- 229940012957 Plasmin Drugs 0.000 description 4
- 239000004365 Protease Substances 0.000 description 4
- 239000004473 Threonine Substances 0.000 description 4
- 230000000890 antigenic Effects 0.000 description 4
- 239000007864 aqueous solution Substances 0.000 description 4
- 229960003121 arginine Drugs 0.000 description 4
- 239000011324 bead Substances 0.000 description 4
- 235000014633 carbohydrates Nutrition 0.000 description 4
- 238000001516 cell proliferation assay Methods 0.000 description 4
- 239000006285 cell suspension Substances 0.000 description 4
- 230000001413 cellular Effects 0.000 description 4
- 230000001684 chronic Effects 0.000 description 4
- 238000007405 data analysis Methods 0.000 description 4
- 239000002612 dispersion media Substances 0.000 description 4
- 239000007850 fluorescent dye Substances 0.000 description 4
- 238000005755 formation reaction Methods 0.000 description 4
- 230000005714 functional activity Effects 0.000 description 4
- 239000000499 gel Substances 0.000 description 4
- 235000013922 glutamic acid Nutrition 0.000 description 4
- 239000004220 glutamic acid Substances 0.000 description 4
- DHMQDGOQFOQNFH-UHFFFAOYSA-N glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 4
- 230000002401 inhibitory effect Effects 0.000 description 4
- 238000002955 isolation Methods 0.000 description 4
- 230000000670 limiting Effects 0.000 description 4
- 239000006193 liquid solution Substances 0.000 description 4
- 230000001404 mediated Effects 0.000 description 4
- 230000000051 modifying Effects 0.000 description 4
- 235000019834 papain Nutrition 0.000 description 4
- 230000001717 pathogenic Effects 0.000 description 4
- 239000008188 pellet Substances 0.000 description 4
- 229940111202 pepsin Drugs 0.000 description 4
- 230000000896 plasminic Effects 0.000 description 4
- DNIAPMSPPWPWGF-UHFFFAOYSA-N propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 4
- 239000011541 reaction mixture Substances 0.000 description 4
- 239000006228 supernatant Substances 0.000 description 4
- 239000004094 surface-active agent Substances 0.000 description 4
- 230000002459 sustained Effects 0.000 description 4
- 210000001519 tissues Anatomy 0.000 description 4
- 125000001493 tyrosinyl group Chemical group [H]OC1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 description 4
- 102000006306 Antigen Receptors Human genes 0.000 description 3
- 108010083359 Antigen Receptors Proteins 0.000 description 3
- 208000005783 Autoimmune Thyroiditis Diseases 0.000 description 3
- 101700072047 BCR Proteins 0.000 description 3
- 102100019443 CD79A Human genes 0.000 description 3
- 101700037975 CD79A Proteins 0.000 description 3
- 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 3
- FBPFZTCFMRRESA-KAZBKCHUSA-N D-Mannitol Natural products OC[C@@H](O)[C@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KAZBKCHUSA-N 0.000 description 3
- 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 3
- CZMRCDWAGMRECN-UGDNZRGBSA-N D-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 3
- QIVBCDIJIAJPQS-SECBINFHSA-N D-tryptophane Chemical compound C1=CC=C2C(C[C@@H](N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-SECBINFHSA-N 0.000 description 3
- 108010058597 HLA-DR Antigens Proteins 0.000 description 3
- 102000006354 HLA-DR Antigens Human genes 0.000 description 3
- 208000001204 Hashimoto Disease Diseases 0.000 description 3
- 102000015434 Humanized Monoclonal Antibodies Human genes 0.000 description 3
- 108010064750 Humanized Monoclonal Antibodies Proteins 0.000 description 3
- 101700008328 IGL1 Proteins 0.000 description 3
- 102100016016 IGLL1 Human genes 0.000 description 3
- 101700077624 IGLL1 Proteins 0.000 description 3
- 201000006889 IgG4-related disease Diseases 0.000 description 3
- 208000004187 Immunoglobulin G4-Related Disease Diseases 0.000 description 3
- 206010061218 Inflammation Diseases 0.000 description 3
- 206010021972 Inflammatory bowel disease Diseases 0.000 description 3
- XUJNEKJLAYXESH-REOHCLBHSA-N L-cysteine Chemical compound SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-N 0.000 description 3
- COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 description 3
- MTCFGRXMJLQNBG-REOHCLBHSA-N L-serine Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 description 3
- FBPFZTCFMRRESA-KVTDHHQDSA-N Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 3
- 241000209094 Oryza Species 0.000 description 3
- 235000007164 Oryza sativa Nutrition 0.000 description 3
- 229920003171 Poly (ethylene oxide) Polymers 0.000 description 3
- 239000004698 Polyethylene (PE) Substances 0.000 description 3
- 229920001451 Polypropylene glycol Polymers 0.000 description 3
- 229920001186 RNA-Seq Polymers 0.000 description 3
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 3
- 241000703392 Tribec virus Species 0.000 description 3
- 206010068760 Ulcers Diseases 0.000 description 3
- 239000003242 anti bacterial agent Substances 0.000 description 3
- 230000003302 anti-idiotype Effects 0.000 description 3
- 125000004429 atoms Chemical group 0.000 description 3
- 229920001400 block copolymer Polymers 0.000 description 3
- 239000003431 cross linking reagent Substances 0.000 description 3
- 235000018417 cysteine Nutrition 0.000 description 3
- 125000000151 cysteine group Chemical group N[C@@H](CS)C(=O)* 0.000 description 3
- 230000003013 cytotoxicity Effects 0.000 description 3
- 231100000135 cytotoxicity Toxicity 0.000 description 3
- 230000002354 daily Effects 0.000 description 3
- 230000001419 dependent Effects 0.000 description 3
- 230000005611 electricity Effects 0.000 description 3
- 230000002708 enhancing Effects 0.000 description 3
- 238000009472 formulation Methods 0.000 description 3
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 3
- 230000004927 fusion Effects 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- 239000000833 heterodimer Substances 0.000 description 3
- 239000000710 homodimer Substances 0.000 description 3
- 238000003384 imaging method Methods 0.000 description 3
- 238000003018 immunoassay Methods 0.000 description 3
- 230000004054 inflammatory process Effects 0.000 description 3
- 238000001802 infusion Methods 0.000 description 3
- 238000001361 intraarterial administration Methods 0.000 description 3
- 238000011068 load Methods 0.000 description 3
- 239000000594 mannitol Substances 0.000 description 3
- 235000010355 mannitol Nutrition 0.000 description 3
- 239000011159 matrix material Substances 0.000 description 3
- 239000000178 monomer Substances 0.000 description 3
- 238000001543 one-way ANOVA Methods 0.000 description 3
- 238000007911 parenteral administration Methods 0.000 description 3
- 230000036961 partial Effects 0.000 description 3
- 239000000825 pharmaceutical preparation Substances 0.000 description 3
- 239000008363 phosphate buffer Substances 0.000 description 3
- 230000002265 prevention Effects 0.000 description 3
- 238000003127 radioimmunoassay Methods 0.000 description 3
- 230000002829 reduced Effects 0.000 description 3
- 235000009566 rice Nutrition 0.000 description 3
- 150000003839 salts Chemical class 0.000 description 3
- 239000011734 sodium Substances 0.000 description 3
- 239000000600 sorbitol Substances 0.000 description 3
- 235000010356 sorbitol Nutrition 0.000 description 3
- 239000003381 stabilizer Substances 0.000 description 3
- 230000003068 static Effects 0.000 description 3
- 235000000346 sugar Nutrition 0.000 description 3
- 231100000397 ulcer Toxicity 0.000 description 3
- 239000004474 valine Substances 0.000 description 3
- FXYPGCIGRDZWNR-UHFFFAOYSA-N (2,5-dioxopyrrolidin-1-yl) 3-[[3-(2,5-dioxopyrrolidin-1-yl)oxy-3-oxopropyl]disulfanyl]propanoate Chemical compound O=C1CCC(=O)N1OC(=O)CCSSCCC(=O)ON1C(=O)CCC1=O FXYPGCIGRDZWNR-UHFFFAOYSA-N 0.000 description 2
- NKCXQMYPWXSLIZ-PSRDDEIFSA-N (2S)-2-[[(2S)-1-[(2S)-5-amino-2-[[2-[[(2S)-6-amino-2-[[2-[[(2S)-2-[[(2S)-4-amino-2-[[(2S)-2-[[(2S,3R)-2-[[(2S)-2-[[(2S,3R)-2-amino-3-hydroxybutanoyl]amino]-3-(1H-indol-3-yl)propanoyl]amino]-3-hydroxybutanoyl]amino]propanoyl]amino]-4-oxobutanoyl]amino]-3-m Chemical compound O=C([C@H](CCC(N)=O)NC(=O)CNC(=O)[C@H](CCCCN)NC(=O)CNC(=O)[C@@H](NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@@H](N)[C@@H](C)O)[C@@H](C)O)C(C)C)N1CCC[C@H]1C(=O)N[C@@H](CO)C(O)=O NKCXQMYPWXSLIZ-PSRDDEIFSA-N 0.000 description 2
- JLPULHDHAOZNQI-ZTIMHPMXSA-N 1-hexadecanoyl-2-(9Z,12Z-octadecadienoyl)-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCC\C=C/C\C=C/CCCCC JLPULHDHAOZNQI-ZTIMHPMXSA-N 0.000 description 2
- QFVHZQCOUORWEI-UHFFFAOYSA-N 4-[(4-anilino-5-sulfonaphthalen-1-yl)diazenyl]-5-hydroxynaphthalene-2,7-disulfonic acid Chemical compound C=12C(O)=CC(S(O)(=O)=O)=CC2=CC(S(O)(=O)=O)=CC=1N=NC(C1=CC=CC(=C11)S(O)(=O)=O)=CC=C1NC1=CC=CC=C1 QFVHZQCOUORWEI-UHFFFAOYSA-N 0.000 description 2
- 208000008190 Agammaglobulinemia Diseases 0.000 description 2
- RCHHVVGSTHAVPF-ZPHPLDECSA-N Apidra Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@H]1CSSC[C@H]2C(=O)N[C@H](C(=O)N[C@@H](CO)C(=O)N[C@H](C(=O)N[C@H](C(N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC=3C=CC(O)=CC=3)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=3C=CC(O)=CC=3)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=3C=CC(O)=CC=3)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=3N=CNC=3)NC(=O)[C@H](CO)NC(=O)CNC1=O)C(=O)NCC(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)NCC(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H]([C@@H](C)O)C(O)=O)C(=O)N[C@@H](CC(N)=O)C(O)=O)=O)CSSC[C@@H](C(N2)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@@H](NC(=O)CN)[C@@H](C)CC)[C@@H](C)CC)[C@@H](C)O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@@H](NC(=O)[C@@H](N)CC=1C=CC=CC=1)C(C)C)C1=CNC=N1 RCHHVVGSTHAVPF-ZPHPLDECSA-N 0.000 description 2
- 206010004661 Biliary cirrhosis primary Diseases 0.000 description 2
- 102100013137 CD40 Human genes 0.000 description 2
- 101710040446 CD40 Proteins 0.000 description 2
- 102100008744 CDR2 Human genes 0.000 description 2
- 229920001405 Coding region Polymers 0.000 description 2
- 229920000453 Consensus sequence Polymers 0.000 description 2
- WQZGKKKJIJFFOK-GASJEMHNSA-N D-Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 2
- 230000036947 Dissociation constant Effects 0.000 description 2
- 108010088842 Fibrinolysin Proteins 0.000 description 2
- 229920001917 Ficoll Polymers 0.000 description 2
- 101710037135 GAPC2 Proteins 0.000 description 2
- 101710037116 GAPC3 Proteins 0.000 description 2
- 101710025049 GAPDG Proteins 0.000 description 2
- 101710008404 GAPDH Proteins 0.000 description 2
- 102100006425 GAPDH Human genes 0.000 description 2
- 101710010461 Gapdh1 Proteins 0.000 description 2
- 108010010803 Gelatin Proteins 0.000 description 2
- 229960002449 Glycine Drugs 0.000 description 2
- 239000004471 Glycine Substances 0.000 description 2
- 229960002885 Histidine Drugs 0.000 description 2
- 108010027412 Histocompatibility Antigens Class II Proteins 0.000 description 2
- 102000018713 Histocompatibility Antigens Class II Human genes 0.000 description 2
- WNRQPCUGRUFHED-DETKDSODSA-N Humalog Chemical compound C([C@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CO)NC(=O)[C@H](CS)NC(=O)[C@H]([C@@H](C)CC)NC(=O)[C@H](CO)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CS)NC(=O)[C@H](CS)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@@H](NC(=O)CN)[C@@H](C)CC)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CS)C(=O)N[C@@H](CC(N)=O)C(O)=O)C1=CC=C(O)C=C1.C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CS)C(=O)NCC(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)NCC(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCCN)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H]([C@@H](C)O)C(O)=O)C(C)C)NC(=O)[C@H](CO)NC(=O)CNC(=O)[C@H](CS)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@@H](NC(=O)[C@@H](N)CC=1C=CC=CC=1)C(C)C)C1=CN=CN1 WNRQPCUGRUFHED-DETKDSODSA-N 0.000 description 2
- 102000008100 Human Serum Albumin Human genes 0.000 description 2
- 108091006822 Human Serum Albumin Proteins 0.000 description 2
- 206010020983 Hypogammaglobulinaemia Diseases 0.000 description 2
- 235000003332 Ilex aquifolium Nutrition 0.000 description 2
- 241000209027 Ilex aquifolium Species 0.000 description 2
- 108090001124 Immunoglobulin E Proteins 0.000 description 2
- 108010054477 Immunoglobulin Fab Fragments Proteins 0.000 description 2
- 102000001706 Immunoglobulin Fab Fragments Human genes 0.000 description 2
- 229940102223 Injectable Solution Drugs 0.000 description 2
- 206010059176 Juvenile idiopathic arthritis Diseases 0.000 description 2
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 2
- HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 0.000 description 2
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 description 2
- ONIBWKKTOPOVIA-BYPYZUCNSA-N L-proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-N 0.000 description 2
- 229940067606 Lecithin Drugs 0.000 description 2
- 206010025135 Lupus erythematosus Diseases 0.000 description 2
- 239000004472 Lysine Substances 0.000 description 2
- 101710025050 MK0970 Proteins 0.000 description 2
- 229960004452 Methionine Drugs 0.000 description 2
- 210000003205 Muscles Anatomy 0.000 description 2
- 206010028372 Muscular weakness Diseases 0.000 description 2
- NQTADLQHYWFPDB-UHFFFAOYSA-N N-hydroxy-Succinimide Chemical compound ON1C(=O)CCC1=O NQTADLQHYWFPDB-UHFFFAOYSA-N 0.000 description 2
- 102100012530 PPIA Human genes 0.000 description 2
- 101700015846 PPIA Proteins 0.000 description 2
- 229960005190 Phenylalanine Drugs 0.000 description 2
- 229920002873 Polyethylenimine Polymers 0.000 description 2
- 108010020346 Polyglutamic Acid Proteins 0.000 description 2
- XJMOSONTPMZWPB-UHFFFAOYSA-M Propidium iodide Chemical compound [I-].[I-].C12=CC(N)=CC=C2C2=CC=C(N)C=C2[N+](CCC[N+](C)(CC)CC)=C1C1=CC=CC=C1 XJMOSONTPMZWPB-UHFFFAOYSA-M 0.000 description 2
- 206010037162 Psoriatic arthropathy Diseases 0.000 description 2
- 208000002098 Purpura, Thrombocytopenic, Idiopathic Diseases 0.000 description 2
- 206010072736 Rheumatic disease Diseases 0.000 description 2
- 206010039710 Scleroderma Diseases 0.000 description 2
- 108010070144 Single-Chain Antibodies Proteins 0.000 description 2
- 102000005632 Single-Chain Antibodies Human genes 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 108060008443 TPPP Proteins 0.000 description 2
- 101710003153 TRB Proteins 0.000 description 2
- 102000033158 TRB Human genes 0.000 description 2
- 206010043207 Temporal arteritis Diseases 0.000 description 2
- 108090000190 Thrombin Proteins 0.000 description 2
- 231100000765 Toxin Toxicity 0.000 description 2
- 206010047115 Vasculitis Diseases 0.000 description 2
- 206010052769 Vertigos Diseases 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 239000000654 additive Substances 0.000 description 2
- 238000001042 affinity chromatography Methods 0.000 description 2
- 238000004220 aggregation Methods 0.000 description 2
- 230000002776 aggregation Effects 0.000 description 2
- 230000004075 alteration Effects 0.000 description 2
- 210000004102 animal cell Anatomy 0.000 description 2
- 230000000692 anti-sense Effects 0.000 description 2
- 239000003429 antifungal agent Substances 0.000 description 2
- 229960000070 antineoplastic Monoclonal antibodies Drugs 0.000 description 2
- 201000003710 autoimmune thrombocytopenic purpura Diseases 0.000 description 2
- 239000007640 basal medium Substances 0.000 description 2
- 238000010804 cDNA synthesis Methods 0.000 description 2
- 238000010805 cDNA synthesis kit Methods 0.000 description 2
- 201000011510 cancer Diseases 0.000 description 2
- 239000000969 carrier Substances 0.000 description 2
- 230000015556 catabolic process Effects 0.000 description 2
- 101710025091 cbbGC Proteins 0.000 description 2
- 238000004113 cell culture Methods 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 239000011248 coating agent Substances 0.000 description 2
- 238000000576 coating method Methods 0.000 description 2
- 230000000052 comparative effect Effects 0.000 description 2
- 230000002860 competitive Effects 0.000 description 2
- 229920001577 copolymer Polymers 0.000 description 2
- 230000001808 coupling Effects 0.000 description 2
- 238000010168 coupling process Methods 0.000 description 2
- 238000005859 coupling reaction Methods 0.000 description 2
- 238000010192 crystallographic characterization Methods 0.000 description 2
- 201000003146 cystitis Diseases 0.000 description 2
- 230000016396 cytokine production Effects 0.000 description 2
- 230000004059 degradation Effects 0.000 description 2
- 238000006731 degradation reaction Methods 0.000 description 2
- 238000004925 denaturation Methods 0.000 description 2
- 230000036425 denaturation Effects 0.000 description 2
- 201000004624 dermatitis Diseases 0.000 description 2
- 231100000406 dermatitis Toxicity 0.000 description 2
- 230000001627 detrimental Effects 0.000 description 2
- 238000003745 diagnosis Methods 0.000 description 2
- 238000004520 electroporation Methods 0.000 description 2
- 239000000839 emulsion Substances 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- 238000002866 fluorescence resonance energy transfer Methods 0.000 description 2
- 238000006062 fragmentation reaction Methods 0.000 description 2
- 101710025070 gapdh-2 Proteins 0.000 description 2
- 229920000159 gelatin Polymers 0.000 description 2
- 239000008273 gelatin Substances 0.000 description 2
- 235000019322 gelatine Nutrition 0.000 description 2
- 235000011852 gelatine desserts Nutrition 0.000 description 2
- 239000008103 glucose Substances 0.000 description 2
- 230000036541 health Effects 0.000 description 2
- 210000002865 immune cell Anatomy 0.000 description 2
- 239000012274 immune-checkpoint protein inhibitor Substances 0.000 description 2
- 229940121650 immune-checkpoint protein inhibitors Drugs 0.000 description 2
- 230000002998 immunogenetic Effects 0.000 description 2
- 238000001114 immunoprecipitation Methods 0.000 description 2
- 238000010348 incorporation Methods 0.000 description 2
- 230000002757 inflammatory Effects 0.000 description 2
- 239000004615 ingredient Substances 0.000 description 2
- 239000007972 injectable composition Substances 0.000 description 2
- 238000003780 insertion Methods 0.000 description 2
- 239000004026 insulin derivative Substances 0.000 description 2
- 230000002601 intratumoral Effects 0.000 description 2
- 239000007951 isotonicity adjuster Substances 0.000 description 2
- 238000002372 labelling Methods 0.000 description 2
- 239000000787 lecithin Substances 0.000 description 2
- 235000010445 lecithin Nutrition 0.000 description 2
- 239000002502 liposome Substances 0.000 description 2
- 229960003646 lysine Drugs 0.000 description 2
- 230000002934 lysing Effects 0.000 description 2
- 238000007403 mPCR Methods 0.000 description 2
- 210000004962 mammalian cells Anatomy 0.000 description 2
- 230000035800 maturation Effects 0.000 description 2
- 238000005259 measurement Methods 0.000 description 2
- OKKJLVBELUTLKV-UHFFFAOYSA-N methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 2
- 244000005700 microbiome Species 0.000 description 2
- 229960000060 monoclonal antibodies Drugs 0.000 description 2
- 238000010172 mouse model Methods 0.000 description 2
- 239000003471 mutagenic agent Substances 0.000 description 2
- 230000036473 myasthenia Effects 0.000 description 2
- 201000002481 myositis Diseases 0.000 description 2
- 201000008383 nephritis Diseases 0.000 description 2
- 238000007857 nested PCR Methods 0.000 description 2
- 244000052769 pathogens Species 0.000 description 2
- 239000002831 pharmacologic agent Substances 0.000 description 2
- 239000002953 phosphate buffered saline Substances 0.000 description 2
- 229920000233 poly(alkylene oxides) Polymers 0.000 description 2
- 201000006292 polyarteritis nodosa Diseases 0.000 description 2
- 229920002643 polyglutamic acid Polymers 0.000 description 2
- 229920005862 polyol Polymers 0.000 description 2
- 150000003077 polyols Chemical class 0.000 description 2
- 229920000136 polysorbate Polymers 0.000 description 2
- 238000001556 precipitation Methods 0.000 description 2
- 230000002335 preservative Effects 0.000 description 2
- 239000003755 preservative agent Substances 0.000 description 2
- 201000002728 primary biliary cirrhosis Diseases 0.000 description 2
- 230000002062 proliferating Effects 0.000 description 2
- 230000002633 protecting Effects 0.000 description 2
- 238000000159 protein binding assay Methods 0.000 description 2
- 230000002797 proteolythic Effects 0.000 description 2
- 201000001263 psoriatic arthritis Diseases 0.000 description 2
- 238000011002 quantification Methods 0.000 description 2
- 238000002708 random mutagenesis Methods 0.000 description 2
- 238000003259 recombinant expression Methods 0.000 description 2
- 238000005215 recombination Methods 0.000 description 2
- 230000000306 recurrent Effects 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 230000028327 secretion Effects 0.000 description 2
- 238000002864 sequence alignment Methods 0.000 description 2
- 230000011664 signaling Effects 0.000 description 2
- KEAYESYHFKHZAL-UHFFFAOYSA-N sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 2
- 229910052708 sodium Inorganic materials 0.000 description 2
- 238000009987 spinning Methods 0.000 description 2
- 230000001954 sterilising Effects 0.000 description 2
- 230000004936 stimulating Effects 0.000 description 2
- 238000003860 storage Methods 0.000 description 2
- 238000010254 subcutaneous injection Methods 0.000 description 2
- 239000007929 subcutaneous injection Substances 0.000 description 2
- 150000008163 sugars Chemical class 0.000 description 2
- 238000002560 therapeutic procedure Methods 0.000 description 2
- 229960004072 thrombin Drugs 0.000 description 2
- 230000001256 tonic Effects 0.000 description 2
- 239000003053 toxin Substances 0.000 description 2
- 108020003112 toxins Proteins 0.000 description 2
- 238000001890 transfection Methods 0.000 description 2
- 229960005486 vaccines Drugs 0.000 description 2
- 238000001291 vacuum drying Methods 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- 230000003442 weekly Effects 0.000 description 2
- WQZGKKKJIJFFOK-VFUOTHLCSA-N β-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
- XUDGDVPXDYGCTG-UHFFFAOYSA-N (2,5-dioxopyrrolidin-1-yl) 2-[2-(2,5-dioxopyrrolidin-1-yl)oxycarbonyloxyethylsulfonyl]ethyl carbonate Chemical compound O=C1CCC(=O)N1OC(=O)OCCS(=O)(=O)CCOC(=O)ON1C(=O)CCC1=O XUDGDVPXDYGCTG-UHFFFAOYSA-N 0.000 description 1
- GZTBUOYDBNSQIK-UHFFFAOYSA-N 1-[3-[(4-acetyl-1,1-dimethylpiperazin-1-ium-2-yl)disulfanyl]-4,4-dimethylpiperazin-4-ium-1-yl]ethanone Chemical compound C1N(C(=O)C)CC[N+](C)(C)C1SSC1[N+](C)(C)CCN(C(C)=O)C1 GZTBUOYDBNSQIK-UHFFFAOYSA-N 0.000 description 1
- HVLGNZWAUGQTTF-UHFFFAOYSA-N 2-(2,5-dioxopyrrolidin-1-yl)butanedioic acid;ethane-1,2-diol Chemical compound OCCO.OC(=O)CC(C(O)=O)N1C(=O)CCC1=O.OC(=O)CC(C(O)=O)N1C(=O)CCC1=O HVLGNZWAUGQTTF-UHFFFAOYSA-N 0.000 description 1
- PITMOJXAHYPVLG-UHFFFAOYSA-N 2-acetyloxybenzoic acid;N-(4-ethoxyphenyl)acetamide;1,3,7-trimethylpurine-2,6-dione Chemical compound CCOC1=CC=C(NC(C)=O)C=C1.CC(=O)OC1=CC=CC=C1C(O)=O.CN1C(=O)N(C)C(=O)C2=C1N=CN2C PITMOJXAHYPVLG-UHFFFAOYSA-N 0.000 description 1
- GHCZTIFQWKKGSB-UHFFFAOYSA-N 2-hydroxypropane-1,2,3-tricarboxylic acid;phosphoric acid Chemical compound OP(O)(O)=O.OC(=O)CC(O)(C(O)=O)CC(O)=O GHCZTIFQWKKGSB-UHFFFAOYSA-N 0.000 description 1
- XZKIHKMTEMTJQX-UHFFFAOYSA-N 4-Nitrophenyl dihydrogen phosphate Chemical compound OP(O)(=O)OC1=CC=C([N+]([O-])=O)C=C1 XZKIHKMTEMTJQX-UHFFFAOYSA-N 0.000 description 1
- MGSKVZWGBWPBTF-UHFFFAOYSA-N AEBSF Chemical compound NCCC1=CC=C(S(F)(=O)=O)C=C1 MGSKVZWGBWPBTF-UHFFFAOYSA-N 0.000 description 1
- 206010069754 Acquired gene mutation Diseases 0.000 description 1
- 208000002552 Acute Disseminated Encephalomyelitis Diseases 0.000 description 1
- 201000004304 Addison's disease Diseases 0.000 description 1
- 102000002260 Alkaline Phosphatase Human genes 0.000 description 1
- 108020004774 Alkaline Phosphatase Proteins 0.000 description 1
- 206010048594 Allergic granulomatous angiitis Diseases 0.000 description 1
- 229920002287 Amplicon Polymers 0.000 description 1
- 206010002022 Amyloidosis Diseases 0.000 description 1
- 206010002023 Amyloidosis Diseases 0.000 description 1
- 208000007502 Anemia Diseases 0.000 description 1
- 235000002198 Annona diversifolia Nutrition 0.000 description 1
- 208000008637 Anti-Glomerular Basement Membrane Disease Diseases 0.000 description 1
- 108010055216 Anti-Idiotypic Antibodies Proteins 0.000 description 1
- 210000000628 Antibody-Producing Cells Anatomy 0.000 description 1
- 208000003343 Antiphospholipid Syndrome Diseases 0.000 description 1
- 229940112930 Apidra Drugs 0.000 description 1
- 206010003230 Arteritis Diseases 0.000 description 1
- 206010003267 Arthritis reactive Diseases 0.000 description 1
- 108090000206 Autoantibodies Proteins 0.000 description 1
- 102000003852 Autoantibodies Human genes 0.000 description 1
- 206010003827 Autoimmune hepatitis Diseases 0.000 description 1
- 206010064539 Autoimmune myocarditis Diseases 0.000 description 1
- 206010069002 Autoimmune pancreatitis Diseases 0.000 description 1
- 206010071578 Autoimmune retinopathy Diseases 0.000 description 1
- 108090001008 Avidin Proteins 0.000 description 1
- 206010060976 Bacillus infection Diseases 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- 229940105426 Basaglar Drugs 0.000 description 1
- 230000035639 Blood Levels Effects 0.000 description 1
- 210000001185 Bone Marrow Anatomy 0.000 description 1
- 208000000594 Bullous Pemphigoid Diseases 0.000 description 1
- JAADVCUGXLIGFU-UHFFFAOYSA-M C(=O)(ON1C(C(C(C1=O)S(=O)(=O)O)S(=O)(=O)O)=O)C(O)C(O)C(=O)[O-] Chemical compound C(=O)(ON1C(C(C(C1=O)S(=O)(=O)O)S(=O)(=O)O)=O)C(O)C(O)C(=O)[O-] JAADVCUGXLIGFU-UHFFFAOYSA-M 0.000 description 1
- CTRCIXFYYQOUNI-UHFFFAOYSA-N C(CCC(=O)O)(=O)O.N1C=NCC1 Chemical compound C(CCC(=O)O)(=O)O.N1C=NCC1 CTRCIXFYYQOUNI-UHFFFAOYSA-N 0.000 description 1
- BRJHNRIXCCGTKK-UHFFFAOYSA-N C1(CCC(OC(=O)OCCS(=O)(=O)O1)=N)=N Chemical compound C1(CCC(OC(=O)OCCS(=O)(=O)O1)=N)=N BRJHNRIXCCGTKK-UHFFFAOYSA-N 0.000 description 1
- 108010029697 CD40 Ligand Proteins 0.000 description 1
- 102100003729 CD40LG Human genes 0.000 description 1
- 102100005828 CD5 Human genes 0.000 description 1
- 102100019451 CD80 Human genes 0.000 description 1
- 101700080477 CD80 Proteins 0.000 description 1
- TZIRZGBAFTZREM-MKAGXXMWSA-N CHEMBL2103758 Chemical compound C([C@@H](C(=O)NCC(=O)N1CCC[C@H]1C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC(C)C)C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](C(C)C)C(=O)NCC(=O)N[C@@H](CO)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H]1NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](C)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@@H](NC(=O)[C@@H](N)CCCCN)CSSC1)[C@@H](C)O)C(C)C)C1=CC=CC=C1 TZIRZGBAFTZREM-MKAGXXMWSA-N 0.000 description 1
- 201000002829 CREST syndrome Diseases 0.000 description 1
- 241000282832 Camelidae Species 0.000 description 1
- LEMUFSYUPGXXCM-JNEQYSBXSA-N Caninsulin Chemical compound [Zn].C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@H]1CSSC[C@H]2C(=O)N[C@H](C(=O)N[C@@H](CO)C(=O)N[C@H](C(=O)N[C@H](C(N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC=3C=CC(O)=CC=3)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=3C=CC(O)=CC=3)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=3C=CC(O)=CC=3)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC3N=CN=C3)NC(=O)[C@H](CO)NC(=O)CNC1=O)C(=O)NCC(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)NCC(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C(C)O)C(O)=O)C(=O)N[C@@H](CC(N)=O)C(O)=O)=O)CSSC[C@@H](C(N2)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@@H](NC(=O)CN)[C@@H](C)CC)[C@@H](C)CC)[C@@H](C)O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@@H](NC(=O)[C@@H](N)CC=1C=CC=CC=1)C(C)C)C1C=NC=N1 LEMUFSYUPGXXCM-JNEQYSBXSA-N 0.000 description 1
- 208000005024 Castleman Disease Diseases 0.000 description 1
- 210000000170 Cell Membrane Anatomy 0.000 description 1
- 210000001175 Cerebrospinal Fluid Anatomy 0.000 description 1
- OSASVXMJTNOKOY-UHFFFAOYSA-N Chlorobutanol Chemical compound CC(C)(O)C(Cl)(Cl)Cl OSASVXMJTNOKOY-UHFFFAOYSA-N 0.000 description 1
- 229960004926 Chlorobutanol Drugs 0.000 description 1
- 206010008609 Cholangitis sclerosing Diseases 0.000 description 1
- 241000251730 Chondrichthyes Species 0.000 description 1
- 206010057645 Chronic inflammatory demyelinating polyradiculoneuropathy Diseases 0.000 description 1
- 208000006344 Churg-Strauss Syndrome Diseases 0.000 description 1
- 235000008733 Citrus aurantifolia Nutrition 0.000 description 1
- 206010053567 Coagulopathy Diseases 0.000 description 1
- 206010009802 Coagulopathy Diseases 0.000 description 1
- 108020004705 Codon Proteins 0.000 description 1
- 206010009839 Coeliac disease Diseases 0.000 description 1
- 208000010007 Cogan Syndrome Diseases 0.000 description 1
- 206010009900 Colitis ulcerative Diseases 0.000 description 1
- 102000008186 Collagen Human genes 0.000 description 1
- 108010035532 Collagen Proteins 0.000 description 1
- 206010010741 Conjunctivitis Diseases 0.000 description 1
- 206010011258 Coxsackie myocarditis Diseases 0.000 description 1
- 241000699802 Cricetulus griseus Species 0.000 description 1
- 206010011401 Crohn's disease Diseases 0.000 description 1
- 206010011732 Cyst Diseases 0.000 description 1
- 101710007887 DHFR Proteins 0.000 description 1
- 102100005838 DHFR Human genes 0.000 description 1
- 206010011968 Decreased immune responsiveness Diseases 0.000 description 1
- 206010061811 Demyelinating polyneuropathy Diseases 0.000 description 1
- 206010013637 Dressler's syndrome Diseases 0.000 description 1
- 206010014004 Ear disease Diseases 0.000 description 1
- 210000003027 Ear, Inner Anatomy 0.000 description 1
- 206010014950 Eosinophilia Diseases 0.000 description 1
- 210000003979 Eosinophils Anatomy 0.000 description 1
- 206010015150 Erythema Diseases 0.000 description 1
- 206010049466 Erythroblastosis Diseases 0.000 description 1
- 208000006881 Esophagitis Diseases 0.000 description 1
- LVGKNOAMLMIIKO-QXMHVHEDSA-N Ethyl oleate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OCC LVGKNOAMLMIIKO-QXMHVHEDSA-N 0.000 description 1
- 208000004332 Evans Syndrome Diseases 0.000 description 1
- 229950010333 Exalamide Drugs 0.000 description 1
- 208000002980 Facial Hemiatrophy Diseases 0.000 description 1
- 108010087819 Fc receptors Proteins 0.000 description 1
- 102000009109 Fc receptors Human genes 0.000 description 1
- 210000003608 Feces Anatomy 0.000 description 1
- 208000001640 Fibromyalgia Diseases 0.000 description 1
- 241000724791 Filamentous phage Species 0.000 description 1
- 241000233866 Fungi Species 0.000 description 1
- 101700014779 GLB1 Proteins 0.000 description 1
- 108060004408 GLRA1 Proteins 0.000 description 1
- 102100003780 GLRA1 Human genes 0.000 description 1
- 208000007465 Giant Cell Arteritis Diseases 0.000 description 1
- COCFEDIXXNGUNL-RFKWWTKHSA-N Glargine Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@H]1CSSC[C@H]2C(=O)N[C@H](C(=O)N[C@@H](CO)C(=O)N[C@H](C(=O)N[C@H](C(N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC=3C=CC(O)=CC=3)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=3C=CC(O)=CC=3)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=3C=CC(O)=CC=3)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=3NC=NC=3)NC(=O)[C@H](CO)NC(=O)CNC1=O)C(=O)NCC(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)NCC(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O)C(=O)NCC(O)=O)=O)CSSC[C@@H](C(N2)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@@H](NC(=O)CN)[C@@H](C)CC)[C@@H](C)CC)[C@@H](C)O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@@H](NC(=O)[C@@H](N)CC=1C=CC=CC=1)C(C)C)C1=CN=CN1 COCFEDIXXNGUNL-RFKWWTKHSA-N 0.000 description 1
- BCCRXDTUTZHDEU-VKHMYHEASA-N Gly-Ser Chemical compound NCC(=O)N[C@@H](CO)C(O)=O BCCRXDTUTZHDEU-VKHMYHEASA-N 0.000 description 1
- 206010018620 Goodpasture's syndrome Diseases 0.000 description 1
- 206010072579 Granulomatosis with polyangiitis Diseases 0.000 description 1
- 206010019263 Heart block congenital Diseases 0.000 description 1
- 208000007475 Hemolytic Anemia Diseases 0.000 description 1
- 201000004331 Henoch-Schoenlein purpura Diseases 0.000 description 1
- 206010019617 Henoch-Schonlein purpura Diseases 0.000 description 1
- 206010062639 Herpes dermatitis Diseases 0.000 description 1
- 229940088597 Hormone Drugs 0.000 description 1
- 229940038661 Humalog Drugs 0.000 description 1
- 206010048643 Hypereosinophilic syndrome Diseases 0.000 description 1
- 208000010159 IGA Glomerulonephritis Diseases 0.000 description 1
- 101710033129 IGHV4-38-2 Proteins 0.000 description 1
- 102100017857 IGHV4-38-2 Human genes 0.000 description 1
- 229940072221 IMMUNOGLOBULINS Drugs 0.000 description 1
- 101710006572 ITGAM Proteins 0.000 description 1
- 102100019441 ITGAM Human genes 0.000 description 1
- 206010021245 Idiopathic thrombocytopenic purpura Diseases 0.000 description 1
- 206010021263 IgA nephropathy Diseases 0.000 description 1
- 108010058683 Immobilized Proteins Proteins 0.000 description 1
- 210000000987 Immune System Anatomy 0.000 description 1
- 108010021625 Immunoglobulin Fragments Proteins 0.000 description 1
- 102000008394 Immunoglobulin Fragments Human genes 0.000 description 1
- 102000006496 Immunoglobulin Heavy Chains Human genes 0.000 description 1
- 108010019476 Immunoglobulin Heavy Chains Proteins 0.000 description 1
- 102000004090 Immunoglobulin Isotypes Human genes 0.000 description 1
- 108090000539 Immunoglobulin Isotypes Proteins 0.000 description 1
- 102000013463 Immunoglobulin Light Chains Human genes 0.000 description 1
- 108010065825 Immunoglobulin Light Chains Proteins 0.000 description 1
- 108010073961 Insulin Aspart Proteins 0.000 description 1
- 101800000896 Insulin B chain Proteins 0.000 description 1
- 102400000454 Insulin B chain Human genes 0.000 description 1
- 108010089308 Insulin Detemir Proteins 0.000 description 1
- 108010057186 Insulin Glargine Proteins 0.000 description 1
- 229960002869 Insulin Glargine Drugs 0.000 description 1
- 108010065920 Insulin Lispro Proteins 0.000 description 1
- 229960002068 Insulin Lispro Drugs 0.000 description 1
- 208000005615 Interstitial Cystitis Diseases 0.000 description 1
- 208000003456 Juvenile Arthritis Diseases 0.000 description 1
- 201000007313 Kawasaki disease Diseases 0.000 description 1
- 210000003734 Kidney Anatomy 0.000 description 1
- LRQKBLKVPFOOQJ-YFKPBYRVSA-N L-2-aminohexanoic acid zwitterion Chemical compound CCCC[C@H]([NH3+])C([O-])=O LRQKBLKVPFOOQJ-YFKPBYRVSA-N 0.000 description 1
- 125000000393 L-methionino group Chemical group [H]OC(=O)[C@@]([H])(N([H])[*])C([H])([H])C(SC([H])([H])[H])([H])[H] 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
- 125000000510 L-tryptophano group Chemical group [H]C1=C([H])C([H])=C2N([H])C([H])=C(C([H])([H])[C@@]([H])(C(O[H])=O)N([H])[*])C2=C1[H] 0.000 description 1
- 241000282838 Lama Species 0.000 description 1
- 210000000265 Leukocytes Anatomy 0.000 description 1
- UGOZVNFCFYTPAZ-IOXYNQHNSA-N Levemir Chemical compound CCCCCCCCCCCCCC(=O)NCCCC[C@@H](C(O)=O)NC(=O)[C@@H]1CCCN1C(=O)[C@H]([C@@H](C)O)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)CNC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCC(O)=O)NC(=O)CNC(=O)[C@H]1NC(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=2C=CC(O)=CC=2)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=2N=CNC=2)NC(=O)[C@H](CO)NC(=O)CNC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=2N=CNC=2)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@@H](NC(=O)[C@@H](N)CC=2C=CC=CC=2)C(C)C)CSSC[C@@H]2NC(=O)[C@@H](NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)CN)[C@@H](C)CC)C(C)C)CSSC[C@H](NC(=O)[C@H]([C@@H](C)CC)NC(=O)[C@H](CO)NC(=O)[C@H]([C@@H](C)O)NC2=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC=2C=CC(O)=CC=2)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=2C=CC(O)=CC=2)C(=O)N[C@@H](CSSC1)C(=O)N[C@@H](CC(N)=O)C(O)=O)CC1=CC=C(O)C=C1 UGOZVNFCFYTPAZ-IOXYNQHNSA-N 0.000 description 1
- 206010024515 Linear IgA disease Diseases 0.000 description 1
- 108010092217 Long-Acting Insulin Proteins 0.000 description 1
- 102000016261 Long-Acting Insulin Human genes 0.000 description 1
- 102000012750 Membrane Glycoproteins Human genes 0.000 description 1
- 108010090054 Membrane Glycoproteins Proteins 0.000 description 1
- 102000018697 Membrane Proteins Human genes 0.000 description 1
- 108010052285 Membrane Proteins Proteins 0.000 description 1
- 206010027183 Meniere's disease Diseases 0.000 description 1
- FEWJPZIEWOKRBE-XIXRPRMCSA-N Mesotartaric acid Chemical compound OC(=O)[C@@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-XIXRPRMCSA-N 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- FQPSGWSUVKBHSU-UHFFFAOYSA-N Methacrylamide Chemical compound CC(=C)C(N)=O FQPSGWSUVKBHSU-UHFFFAOYSA-N 0.000 description 1
- 206010063344 Microscopic polyangiitis Diseases 0.000 description 1
- 101710017500 MitHPPK/DHPS Proteins 0.000 description 1
- 208000003250 Mixed Connective Tissue Disease Diseases 0.000 description 1
- 210000001616 Monocytes Anatomy 0.000 description 1
- 208000001725 Mucocutaneous Lymph Node Syndrome Diseases 0.000 description 1
- 206010065579 Multifocal motor neuropathy Diseases 0.000 description 1
- 108010021466 Mutant Proteins Proteins 0.000 description 1
- 102000008300 Mutant Proteins Human genes 0.000 description 1
- 208000009525 Myocarditis Diseases 0.000 description 1
- 208000008795 Neuromyelitis Optica Diseases 0.000 description 1
- 206010029379 Neutrophilia Diseases 0.000 description 1
- VOMXSOIBEJBQNF-UTTRGDHVSA-N NovoRapid Chemical compound C([C@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CO)NC(=O)[C@H](CS)NC(=O)[C@H]([C@@H](C)CC)NC(=O)[C@H](CO)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CS)NC(=O)[C@H](CS)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@@H](NC(=O)CN)[C@@H](C)CC)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CS)C(=O)N[C@@H](CC(N)=O)C(O)=O)C1=CC=C(O)C=C1.C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CS)C(=O)NCC(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)NCC(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H]([C@@H](C)O)C(O)=O)C(C)C)NC(=O)[C@H](CO)NC(=O)CNC(=O)[C@H](CS)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@@H](NC(=O)[C@@H](N)CC=1C=CC=CC=1)C(C)C)C1=CN=CN1 VOMXSOIBEJBQNF-UTTRGDHVSA-N 0.000 description 1
- 229940098893 Novolin R Drugs 0.000 description 1
- DLMKHTCMVSCZCR-UHFFFAOYSA-N OS(=O)(=O)C1CC(=N)OC(=O)OCCS(=O)(=O)OC1=N Chemical compound OS(=O)(=O)C1CC(=N)OC(=O)OCCS(=O)(=O)OC1=N DLMKHTCMVSCZCR-UHFFFAOYSA-N 0.000 description 1
- HEGSGKPQLMEBJL-RKQHYHRCSA-N Octyl glucoside Chemical compound CCCCCCCCO[C@@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O HEGSGKPQLMEBJL-RKQHYHRCSA-N 0.000 description 1
- 206010030113 Oedema Diseases 0.000 description 1
- 206010030216 Oesophagitis Diseases 0.000 description 1
- 208000003435 Optic Neuritis Diseases 0.000 description 1
- 210000001672 Ovary Anatomy 0.000 description 1
- 101700037337 PIGA Proteins 0.000 description 1
- 102100012341 PIGA Human genes 0.000 description 1
- 101700007624 PLB Proteins 0.000 description 1
- YBYRMVIVWMBXKQ-UHFFFAOYSA-N PMSF Chemical compound FS(=O)(=O)CC1=CC=CC=C1 YBYRMVIVWMBXKQ-UHFFFAOYSA-N 0.000 description 1
- 206010053869 POEMS syndrome Diseases 0.000 description 1
- 208000003473 Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal infection Diseases 0.000 description 1
- 206010034277 Pemphigoid Diseases 0.000 description 1
- 208000008223 Pemphigoid Gestationis Diseases 0.000 description 1
- 208000001293 Peripheral Nervous System Disease Diseases 0.000 description 1
- 206010034606 Peripheral neuropathy Diseases 0.000 description 1
- 210000001322 Periplasm Anatomy 0.000 description 1
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Natural products OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 1
- XLCISDOVNFLSGO-VONOSFMSSA-N Phorbol-12-myristate Chemical compound C([C@]1(O)C(=O)C(C)=C[C@H]1[C@@]1(O)[C@H](C)[C@H]2OC(=O)CCCCCCCCCCCCC)C(CO)=C[C@H]1[C@H]1[C@]2(O)C1(C)C XLCISDOVNFLSGO-VONOSFMSSA-N 0.000 description 1
- 210000002381 Plasma Anatomy 0.000 description 1
- 206010035226 Plasma cell myeloma Diseases 0.000 description 1
- 229920002732 Polyanhydride Polymers 0.000 description 1
- 206010065159 Polychondritis Diseases 0.000 description 1
- 229920000954 Polyglycolide Polymers 0.000 description 1
- 208000005987 Polymyositis Diseases 0.000 description 1
- 229920001710 Polyorthoester Polymers 0.000 description 1
- 229950008882 Polysorbate Drugs 0.000 description 1
- 229920001213 Polysorbate 20 Polymers 0.000 description 1
- 229940068977 Polysorbate 20 Drugs 0.000 description 1
- 229940068968 Polysorbate 80 Drugs 0.000 description 1
- 239000004372 Polyvinyl alcohol Substances 0.000 description 1
- RJKFOVLPORLFTN-STHVQZNPSA-N Progesterone Natural products O=C(C)[C@@H]1[C@@]2(C)[C@H]([C@H]3[C@@H]([C@]4(C)C(=CC(=O)CC4)CC3)CC2)CC1 RJKFOVLPORLFTN-STHVQZNPSA-N 0.000 description 1
- 208000003251 Pruritus Diseases 0.000 description 1
- 208000006311 Pyoderma Diseases 0.000 description 1
- 238000010802 RNA extraction kit Methods 0.000 description 1
- 239000007759 RPMI Media 1640 Substances 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- 208000002574 Reactive Arthritis Diseases 0.000 description 1
- 206010038979 Retroperitoneal fibrosis Diseases 0.000 description 1
- RWYXUDUITJGZJQ-UHFFFAOYSA-M S(=O)(=O)(O)C(C(=O)[O-])(C)N1C(CCC1=O)=O Chemical compound S(=O)(=O)(O)C(C(=O)[O-])(C)N1C(CCC1=O)=O RWYXUDUITJGZJQ-UHFFFAOYSA-M 0.000 description 1
- 210000003296 Saliva Anatomy 0.000 description 1
- 206010039509 Scab Diseases 0.000 description 1
- 208000005511 Schoenlein-Henoch Purpura Diseases 0.000 description 1
- 229920002684 Sepharose Polymers 0.000 description 1
- 206010040767 Sjogren's syndrome Diseases 0.000 description 1
- 241000519995 Stachys sylvatica Species 0.000 description 1
- 206010072148 Stiff person syndrome Diseases 0.000 description 1
- 108010090804 Streptavidin Proteins 0.000 description 1
- 238000000692 Student's t-test Methods 0.000 description 1
- 208000008467 Subacute Bacterial Endocarditis Diseases 0.000 description 1
- 206010042276 Subacute endocarditis Diseases 0.000 description 1
- CZMRCDWAGMRECN-GDQSFJPYSA-N Sucrose Natural products O([C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@H](CO)O1)[C@@]1(CO)[C@H](O)[C@@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-GDQSFJPYSA-N 0.000 description 1
- 210000004243 Sweat Anatomy 0.000 description 1
- 206010042742 Sympathetic ophthalmia Diseases 0.000 description 1
- RJKFOVLPORLFTN-LEKSSAKUSA-N Syngestrets Chemical compound C1CC2=CC(=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H](C(=O)C)[C@@]1(C)CC2 RJKFOVLPORLFTN-LEKSSAKUSA-N 0.000 description 1
- 210000001179 Synovial Fluid Anatomy 0.000 description 1
- 101710042744 TRBV6-5 Proteins 0.000 description 1
- 102100008948 TRBV6-5 Human genes 0.000 description 1
- 206010071574 Testicular autoimmunity Diseases 0.000 description 1
- 229940033663 Thimerosal Drugs 0.000 description 1
- RTKIYNMVFMVABJ-UHFFFAOYSA-L Thiomersal Chemical compound [Na+].CC[Hg]SC1=CC=CC=C1C([O-])=O RTKIYNMVFMVABJ-UHFFFAOYSA-L 0.000 description 1
- 235000015450 Tilia cordata Nutrition 0.000 description 1
- 235000011941 Tilia x europaea Nutrition 0.000 description 1
- 229940110253 Toujeo Drugs 0.000 description 1
- 208000009174 Transverse Myelitis Diseases 0.000 description 1
- HDTRYLNUVZCQOY-LIZSDCNHSA-N 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 1
- 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 1
- QORWJWZARLRLPR-UHFFFAOYSA-H Tricalcium 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 1
- HRXKRNGNAMMEHJ-UHFFFAOYSA-K Trisodium citrate Chemical compound [Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O HRXKRNGNAMMEHJ-UHFFFAOYSA-K 0.000 description 1
- GLNADSQYFUSGOU-GPTZEZBUSA-J Trypan blue Chemical compound [Na+].[Na+].[Na+].[Na+].C1=C(S([O-])(=O)=O)C=C2C=C(S([O-])(=O)=O)C(/N=N/C3=CC=C(C=C3C)C=3C=C(C(=CC=3)\N=N\C=3C(=CC4=CC(=CC(N)=C4C=3O)S([O-])(=O)=O)S([O-])(=O)=O)C)=C(O)C2=C1N GLNADSQYFUSGOU-GPTZEZBUSA-J 0.000 description 1
- 241000223105 Trypanosoma brucei Species 0.000 description 1
- 206010045181 Turner's syndrome Diseases 0.000 description 1
- 210000002700 Urine Anatomy 0.000 description 1
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Vitamin C Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 1
- 201000003087 Vogt-Koyanagi-Harada disease Diseases 0.000 description 1
- 206010047680 Vogt-Koyanagi-Harada syndrome Diseases 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
- 229960002675 Xylitol Drugs 0.000 description 1
- HUCJFAOMUPXHDK-UHFFFAOYSA-N Xylometazoline Chemical compound CC1=CC(C(C)(C)C)=CC(C)=C1CC1=NCCN1 HUCJFAOMUPXHDK-UHFFFAOYSA-N 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K [O-]P([O-])([O-])=O Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 238000002835 absorbance Methods 0.000 description 1
- 239000008351 acetate buffer Substances 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 230000000996 additive Effects 0.000 description 1
- 238000005377 adsorption chromatography Methods 0.000 description 1
- 230000001058 adult Effects 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 230000032683 aging Effects 0.000 description 1
- 239000000556 agonist Substances 0.000 description 1
- 125000003295 alanine group Chemical group N[C@@H](C)C(=O)* 0.000 description 1
- 231100000360 alopecia Toxicity 0.000 description 1
- 201000004384 alopecia Diseases 0.000 description 1
- 239000003708 ampul Substances 0.000 description 1
- 230000000202 analgesic Effects 0.000 description 1
- 239000012491 analyte Substances 0.000 description 1
- 230000003042 antagnostic Effects 0.000 description 1
- 239000005557 antagonist Substances 0.000 description 1
- 108010092993 anti-IgD Proteins 0.000 description 1
- 230000001093 anti-cancer Effects 0.000 description 1
- 230000000111 anti-oxidant Effects 0.000 description 1
- 230000000259 anti-tumor Effects 0.000 description 1
- 230000010056 antibody-dependent cellular cytotoxicity Effects 0.000 description 1
- 108010042982 antiglomerular basement membrane antibody Proteins 0.000 description 1
- 239000002246 antineoplastic agent Substances 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 235000006708 antioxidants Nutrition 0.000 description 1
- 239000008365 aqueous carrier Substances 0.000 description 1
- 239000003125 aqueous solvent Substances 0.000 description 1
- 229960005070 ascorbic acid Drugs 0.000 description 1
- 235000010323 ascorbic acid Nutrition 0.000 description 1
- 239000011668 ascorbic acid Substances 0.000 description 1
- 101700013715 asp-6 Proteins 0.000 description 1
- 238000003149 assay kit Methods 0.000 description 1
- 201000009780 autoimmune polyendocrine syndrome type 2 Diseases 0.000 description 1
- 235000020127 ayran Nutrition 0.000 description 1
- 108010003152 bacteriophage T7 RNA polymerase Proteins 0.000 description 1
- 102000024070 binding proteins Human genes 0.000 description 1
- 108091007650 binding proteins Proteins 0.000 description 1
- 229920000249 biocompatible polymer Polymers 0.000 description 1
- 238000006065 biodegradation reaction Methods 0.000 description 1
- 238000003766 bioinformatics method Methods 0.000 description 1
- 230000005540 biological transmission Effects 0.000 description 1
- 239000000090 biomarker Substances 0.000 description 1
- YBJHBAHKTGYVGT-ZKWXMUAHSA-N biotin Chemical compound N1C(=O)N[C@@H]2[C@H](CCCCC(=O)O)SC[C@@H]21 YBJHBAHKTGYVGT-ZKWXMUAHSA-N 0.000 description 1
- 229960002685 biotin Drugs 0.000 description 1
- 235000020958 biotin Nutrition 0.000 description 1
- 239000011616 biotin Substances 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 239000007853 buffer solution Substances 0.000 description 1
- 230000000981 bystander Effects 0.000 description 1
- UXVMQQNJUSDDNG-UHFFFAOYSA-L cacl2 Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 1
- 239000001110 calcium chloride Substances 0.000 description 1
- 229910001628 calcium chloride Inorganic materials 0.000 description 1
- 239000001506 calcium phosphate Substances 0.000 description 1
- 229910000389 calcium phosphate Inorganic materials 0.000 description 1
- 235000011010 calcium phosphates Nutrition 0.000 description 1
- BPKIGYQJPYCAOW-FFJTTWKXSA-I calcium;potassium;disodium;(2S)-2-hydroxypropanoate;dichloride;dihydroxide;hydrate Chemical compound O.[OH-].[OH-].[Na+].[Na+].[Cl-].[Cl-].[K+].[Ca+2].C[C@H](O)C([O-])=O BPKIGYQJPYCAOW-FFJTTWKXSA-I 0.000 description 1
- 238000004422 calculation algorithm Methods 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 101700018328 ccdB Proteins 0.000 description 1
- 230000020411 cell activation Effects 0.000 description 1
- 230000004663 cell proliferation Effects 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 239000002738 chelating agent Substances 0.000 description 1
- 238000010382 chemical cross-linking Methods 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 238000004140 cleaning Methods 0.000 description 1
- 229920001436 collagen Polymers 0.000 description 1
- 229960005188 collagen Drugs 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 230000001447 compensatory Effects 0.000 description 1
- 201000009541 complex regional pain syndrome Diseases 0.000 description 1
- 201000004395 congenital heart block Diseases 0.000 description 1
- 239000000470 constituent Substances 0.000 description 1
- 239000000356 contaminant Substances 0.000 description 1
- 238000011109 contamination Methods 0.000 description 1
- 201000003278 cryoglobulinemia Diseases 0.000 description 1
- 239000012228 culture supernatant Substances 0.000 description 1
- VOLSCWDWGMWXGO-UHFFFAOYSA-N cyclobuten-1-yl acetate Chemical compound CC(=O)OC1=CCC1 VOLSCWDWGMWXGO-UHFFFAOYSA-N 0.000 description 1
- 230000009089 cytolysis Effects 0.000 description 1
- 230000003247 decreasing Effects 0.000 description 1
- 238000002405 diagnostic procedure Methods 0.000 description 1
- 238000000502 dialysis Methods 0.000 description 1
- 235000015872 dietary supplement Nutrition 0.000 description 1
- UGMCXQCYOVCMTB-UHFFFAOYSA-K dihydroxy(stearato)aluminium Chemical compound CCCCCCCCCCCCCCCCCC(=O)O[Al](O)O UGMCXQCYOVCMTB-UHFFFAOYSA-K 0.000 description 1
- 239000012470 diluted sample Substances 0.000 description 1
- 239000000539 dimer Substances 0.000 description 1
- BFMYDTVEBKDAKJ-UHFFFAOYSA-L disodium;(2',7'-dibromo-3',6'-dioxido-3-oxospiro[2-benzofuran-1,9'-xanthene]-4'-yl)mercury;hydrate Chemical compound O.[Na+].[Na+].O1C(=O)C2=CC=CC=C2C21C1=CC(Br)=C([O-])C([Hg])=C1OC1=C2C=C(Br)C([O-])=C1 BFMYDTVEBKDAKJ-UHFFFAOYSA-L 0.000 description 1
- IYBKWXQWKPSYDT-UHFFFAOYSA-L disodium;1-[4-[2-[4-(2,5-dioxo-3-sulfonatopyrrolidin-1-yl)oxy-4-oxobutanoyl]oxyethoxy]-4-oxobutanoyl]oxy-2,5-dioxopyrrolidine-3-sulfonate Chemical compound [Na+].[Na+].O=C1C(S(=O)(=O)[O-])CC(=O)N1OC(=O)CCC(=O)OCCOC(=O)CCC(=O)ON1C(=O)C(S([O-])(=O)=O)CC1=O IYBKWXQWKPSYDT-UHFFFAOYSA-L 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- 230000004064 dysfunction Effects 0.000 description 1
- 239000003792 electrolyte Substances 0.000 description 1
- 239000008393 encapsulating agent Substances 0.000 description 1
- 201000002491 encephalomyelitis Diseases 0.000 description 1
- 230000002357 endometrial Effects 0.000 description 1
- 201000009273 endometriosis Diseases 0.000 description 1
- 230000002255 enzymatic Effects 0.000 description 1
- 210000002919 epithelial cells Anatomy 0.000 description 1
- 231100000321 erythema Toxicity 0.000 description 1
- 229940093471 ethyl oleate Drugs 0.000 description 1
- 239000005038 ethylene vinyl acetate Substances 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- CKSJXOVLXUMMFF-UHFFFAOYSA-N exalamide Chemical compound CCCCCCOC1=CC=CC=C1C(N)=O CKSJXOVLXUMMFF-UHFFFAOYSA-N 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 230000032686 female pregnancy Effects 0.000 description 1
- 230000001605 fetal Effects 0.000 description 1
- 210000002950 fibroblast Anatomy 0.000 description 1
- 238000007667 floating Methods 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- MHMNJMPURVTYEJ-UHFFFAOYSA-N fluorescein-5-isothiocyanate Chemical compound O1C(=O)C2=CC(N=C=S)=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 MHMNJMPURVTYEJ-UHFFFAOYSA-N 0.000 description 1
- 238000000799 fluorescence microscopy Methods 0.000 description 1
- 239000011888 foil Substances 0.000 description 1
- 230000003325 follicular Effects 0.000 description 1
- WSFSSNUMVMOOMR-UHFFFAOYSA-N formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 1
- 238000004108 freeze drying Methods 0.000 description 1
- 239000012520 frozen sample Substances 0.000 description 1
- 108020001507 fusion proteins Proteins 0.000 description 1
- 102000037240 fusion proteins Human genes 0.000 description 1
- 238000002523 gelfiltration Methods 0.000 description 1
- 230000002068 genetic Effects 0.000 description 1
- 230000001434 glomerular Effects 0.000 description 1
- 125000000267 glycino group Chemical group [H]N([*])C([H])([H])C(=O)O[H] 0.000 description 1
- 150000002338 glycosides Chemical class 0.000 description 1
- 239000003102 growth factor Substances 0.000 description 1
- 239000001963 growth media Substances 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 101710007276 his-24 Proteins 0.000 description 1
- 229920001519 homopolymer Polymers 0.000 description 1
- 239000005556 hormone Substances 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 238000010191 image analysis Methods 0.000 description 1
- 230000003100 immobilizing Effects 0.000 description 1
- 230000002163 immunogen Effects 0.000 description 1
- 108010075597 immunoglobulin M receptor Proteins 0.000 description 1
- 230000016784 immunoglobulin production Effects 0.000 description 1
- 230000001506 immunosuppresive Effects 0.000 description 1
- 238000009169 immunotherapy Methods 0.000 description 1
- 239000007943 implant Substances 0.000 description 1
- 238000011065 in-situ storage Methods 0.000 description 1
- 230000002779 inactivation Effects 0.000 description 1
- 238000010832 independent-sample T-test Methods 0.000 description 1
- 239000011261 inert gas Substances 0.000 description 1
- 238000001764 infiltration Methods 0.000 description 1
- 230000000977 initiatory Effects 0.000 description 1
- 229960004717 insulin aspart Drugs 0.000 description 1
- 108010050259 insulin degludec Proteins 0.000 description 1
- 229960004225 insulin degludec Drugs 0.000 description 1
- 229960003948 insulin detemir Drugs 0.000 description 1
- 229960000696 insulin glulisine Drugs 0.000 description 1
- 238000010255 intramuscular injection Methods 0.000 description 1
- 239000007927 intramuscular injection Substances 0.000 description 1
- 238000009114 investigational therapy Methods 0.000 description 1
- 238000004255 ion exchange chromatography Methods 0.000 description 1
- 230000001788 irregular Effects 0.000 description 1
- 238000001155 isoelectric focusing Methods 0.000 description 1
- 238000005304 joining Methods 0.000 description 1
- 230000000366 juvenile Effects 0.000 description 1
- 230000003902 lesions Effects 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 239000004571 lime Substances 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 239000007791 liquid phase Substances 0.000 description 1
- 201000003265 lymphadenitis Diseases 0.000 description 1
- 239000008176 lyophilized powder Substances 0.000 description 1
- 230000002101 lytic Effects 0.000 description 1
- 230000003211 malignant Effects 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 210000001806 memory B lymphocyte Anatomy 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 229960000485 methotrexate Drugs 0.000 description 1
- 239000004530 micro-emulsion Substances 0.000 description 1
- 238000001823 molecular biology technique Methods 0.000 description 1
- 230000004001 molecular interaction Effects 0.000 description 1
- 238000002887 multiple sequence alignment Methods 0.000 description 1
- 201000000050 myeloid neoplasm Diseases 0.000 description 1
- 230000002956 necrotizing Effects 0.000 description 1
- 230000003472 neutralizing Effects 0.000 description 1
- 239000012457 nonaqueous media Substances 0.000 description 1
- 239000000346 nonvolatile oil Substances 0.000 description 1
- 238000010606 normalization Methods 0.000 description 1
- 239000004006 olive oil Substances 0.000 description 1
- 235000008390 olive oil Nutrition 0.000 description 1
- 230000003287 optical Effects 0.000 description 1
- 238000005457 optimization Methods 0.000 description 1
- 150000002895 organic esters Chemical class 0.000 description 1
- 210000000056 organs Anatomy 0.000 description 1
- 230000001590 oxidative Effects 0.000 description 1
- 229920002866 paraformaldehyde Polymers 0.000 description 1
- 201000003045 paroxysmal nocturnal hemoglobinuria Diseases 0.000 description 1
- 231100000255 pathogenic effect Toxicity 0.000 description 1
- 230000001991 pathophysiological Effects 0.000 description 1
- 201000011152 pemphigus Diseases 0.000 description 1
- 201000001976 pemphigus vulgaris Diseases 0.000 description 1
- 201000001245 periodontitis Diseases 0.000 description 1
- 238000002823 phage display Methods 0.000 description 1
- 239000000546 pharmaceutic aid Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 150000002989 phenols Chemical class 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 239000007981 phosphate-citrate buffer Substances 0.000 description 1
- XVNVFKZODWAQKN-UHFFFAOYSA-N phosphoric acid;heptahydrate Chemical compound O.O.O.O.O.O.O.OP(O)(O)=O XVNVFKZODWAQKN-UHFFFAOYSA-N 0.000 description 1
- 230000004962 physiological condition Effects 0.000 description 1
- 230000001766 physiological effect Effects 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 229920003023 plastic Polymers 0.000 description 1
- 239000004033 plastic Substances 0.000 description 1
- 229920001200 poly(ethylene-vinyl acetate) Polymers 0.000 description 1
- 229920000747 poly(lactic acid) polymer Polymers 0.000 description 1
- 108010054442 polyalanine Proteins 0.000 description 1
- 108091008117 polyclonal antibodies Proteins 0.000 description 1
- 239000004633 polyglycolic acid Substances 0.000 description 1
- 239000004626 polylactic acid Substances 0.000 description 1
- 229920000193 polymethacrylate Polymers 0.000 description 1
- 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 1
- 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 1
- 239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 description 1
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 1
- 229920000053 polysorbate 80 Polymers 0.000 description 1
- 229920002451 polyvinyl alcohol Polymers 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 235000020004 porter Nutrition 0.000 description 1
- 230000004481 post-translational protein modification Effects 0.000 description 1
- 229960003611 pramlintide Drugs 0.000 description 1
- 108010029667 pramlintide Proteins 0.000 description 1
- OZAIFHULBGXAKX-UHFFFAOYSA-N precursor Substances N#CC(C)(C)N=NC(C)(C)C#N OZAIFHULBGXAKX-UHFFFAOYSA-N 0.000 description 1
- 230000035935 pregnancy Effects 0.000 description 1
- 230000003449 preventive Effects 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 201000000742 primary sclerosing cholangitis Diseases 0.000 description 1
- 239000000186 progesterone Substances 0.000 description 1
- 229960003387 progesterone Drugs 0.000 description 1
- 230000004850 protein–protein interaction Effects 0.000 description 1
- 201000004681 psoriasis Diseases 0.000 description 1
- 238000003908 quality control method Methods 0.000 description 1
- 239000000941 radioactive substance Substances 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 239000003638 reducing agent Substances 0.000 description 1
- 201000001947 reflex sympathetic dystrophy Diseases 0.000 description 1
- 230000001172 regenerating Effects 0.000 description 1
- 230000001105 regulatory Effects 0.000 description 1
- 238000004366 reverse phase liquid chromatography Methods 0.000 description 1
- 230000000552 rheumatic Effects 0.000 description 1
- 201000003068 rheumatic fever Diseases 0.000 description 1
- 239000003161 ribonuclease inhibitor Substances 0.000 description 1
- 238000003559 rna-seq method Methods 0.000 description 1
- 238000005185 salting out Methods 0.000 description 1
- 238000005070 sampling Methods 0.000 description 1
- 238000007480 sanger sequencing Methods 0.000 description 1
- 201000000306 sarcoidosis Diseases 0.000 description 1
- 230000037390 scarring Effects 0.000 description 1
- 230000003248 secreting Effects 0.000 description 1
- 239000008299 semisolid dosage form Substances 0.000 description 1
- 125000003607 serino group Chemical group [H]OC(=O)C([H])(N([H])*)C([H])([H])O[H] 0.000 description 1
- 201000007196 sexual disease Diseases 0.000 description 1
- 238000007493 shaping process Methods 0.000 description 1
- 231100000486 side effect Toxicity 0.000 description 1
- 231100000185 significant adverse effect Toxicity 0.000 description 1
- 150000003384 small molecules Chemical class 0.000 description 1
- 239000001509 sodium citrate Substances 0.000 description 1
- 239000001488 sodium phosphate Substances 0.000 description 1
- 229910000162 sodium phosphate Inorganic materials 0.000 description 1
- PHPHRWZFQRLJIA-UZUGEDCSSA-M sodium;(2S,3R,4S,5S,6R)-6-(hydroxymethyl)oxane-2,3,4,5-tetrol;chloride Chemical compound [Na+].[Cl-].OC[C@H]1O[C@H](O)[C@H](O)[C@@H](O)[C@@H]1O PHPHRWZFQRLJIA-UZUGEDCSSA-M 0.000 description 1
- 239000007909 solid dosage form Substances 0.000 description 1
- 239000007790 solid phase Substances 0.000 description 1
- 238000000638 solvent extraction Methods 0.000 description 1
- 239000011877 solvent mixture Substances 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 230000003595 spectral Effects 0.000 description 1
- 201000002661 spondylitis Diseases 0.000 description 1
- 230000002269 spontaneous Effects 0.000 description 1
- 238000011105 stabilization Methods 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 238000007619 statistical method Methods 0.000 description 1
- 210000000130 stem cell Anatomy 0.000 description 1
- 239000008223 sterile water Substances 0.000 description 1
- 238000004659 sterilization and disinfection Methods 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- LSNNMFCWUKXFEE-UHFFFAOYSA-N sulfonic acid Chemical compound OS(O)=O LSNNMFCWUKXFEE-UHFFFAOYSA-N 0.000 description 1
- 230000000576 supplementary Effects 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 230000020382 suppression by virus of host antigen processing and presentation of peptide antigen via MHC class I Effects 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 230000002194 synthesizing Effects 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- 230000004797 therapeutic response Effects 0.000 description 1
- 230000002992 thymic Effects 0.000 description 1
- 239000003104 tissue culture media Substances 0.000 description 1
- 230000002588 toxic Effects 0.000 description 1
- 230000035897 transcription Effects 0.000 description 1
- 239000011778 trisodium citrate 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
- 125000000430 tryptophan group Chemical group [H]N([H])C(C(=O)O*)C([H])([H])C1=C([H])N([H])C2=C([H])C([H])=C([H])C([H])=C12 0.000 description 1
- 201000006704 ulcerative colitis Diseases 0.000 description 1
- 238000000108 ultra-filtration Methods 0.000 description 1
- 238000009777 vacuum freeze-drying Methods 0.000 description 1
- 230000002792 vascular Effects 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 230000035899 viability Effects 0.000 description 1
- 229920002554 vinyl polymer Polymers 0.000 description 1
- 230000003612 virological Effects 0.000 description 1
- 238000011179 visual inspection Methods 0.000 description 1
- 229920003169 water-soluble polymer Polymers 0.000 description 1
- 238000001262 western blot Methods 0.000 description 1
- 239000000811 xylitol Substances 0.000 description 1
- 235000010447 xylitol Nutrition 0.000 description 1
Images
Applications Claiming Priority (9)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US201862782646P | 2018-12-20 | 2018-12-20 | |
US201862782624P | 2018-12-20 | 2018-12-20 | |
US62/782,624 | 2018-12-20 | ||
US62/782,646 | 2018-12-20 | ||
US201962854289P | 2019-05-29 | 2019-05-29 | |
US201962854286P | 2019-05-29 | 2019-05-29 | |
US62/854,289 | 2019-05-29 | ||
US62/854,286 | 2019-05-29 | ||
PCT/US2019/067874 WO2020132456A1 (en) | 2018-12-20 | 2019-12-20 | Treating type 1 diabetes, other autoimmune diseases |
Publications (2)
Publication Number | Publication Date |
---|---|
JP2022515226A JP2022515226A (ja) | 2022-02-17 |
JPWO2020132456A5 true JPWO2020132456A5 (de) | 2023-01-11 |
Family
ID=71101601
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2021536271A Pending JP2022515226A (ja) | 2018-12-20 | 2019-12-20 | 検出・処理の構成と方法 |
Country Status (4)
Country | Link |
---|---|
US (1) | US20220073963A1 (de) |
EP (1) | EP3899039A4 (de) |
JP (1) | JP2022515226A (de) |
WO (1) | WO2020132456A1 (de) |
Family Cites Families (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CA2654502C (en) * | 2006-06-06 | 2015-07-14 | Crucell Holland B.V. | Human binding molecules having killing activity against enterococci and uses thereof |
CN103642902B (zh) * | 2006-11-30 | 2016-01-20 | 纳维哲尼克斯公司 | 遗传分析系统和方法 |
WO2016100615A2 (en) * | 2014-12-18 | 2016-06-23 | The University Of Chicago | Methods and composition for neutralization of influenza |
-
2019
- 2019-12-20 WO PCT/US2019/067874 patent/WO2020132456A1/en unknown
- 2019-12-20 JP JP2021536271A patent/JP2022515226A/ja active Pending
- 2019-12-20 US US17/416,778 patent/US20220073963A1/en active Pending
- 2019-12-20 EP EP19900788.1A patent/EP3899039A4/de active Pending
Similar Documents
Publication | Publication Date | Title |
---|---|---|
ES2848052T3 (es) | Anticuerpos de unión dual anti-PD-L1 y PD-L2 de agente individual y métodos de uso | |
ES2765874T3 (es) | Anticuerpos anti-KIR para el tratamiento de trastornos inflamatorios | |
TW202043280A (zh) | 對受體酪胺酸激酶樣孤兒受體1(ror1)具專一性之抗體及嵌合抗原受體 | |
TW201938203A (zh) | 靶向共有抗原之抗原結合蛋白 | |
SA518390904B1 (ar) | مستقبلات مولد مضاد خيمرية تقوم على أجسام مضادة أحادية الحقل وطرق لاستخدامها | |
KR20190141211A (ko) | Cd19에 대한 인간화 항원-결합 도메인 및 사용 방법 | |
JP2020504171A (ja) | 抗PD−1抗体との組み合わせのための抗Tim−3抗体 | |
US20220396627A1 (en) | Anti-siglec-9 compositions and methods for modulating myeloid cell inflammatory phenotypes and uses thereof | |
JP2021520208A (ja) | Hhla2受容体としてのkir3dl3、抗hhla2抗体、およびその使用 | |
US20230348603A1 (en) | Anti-vsig4 compositions and methods for modulating myeloid cell inflammatory phenotypes and uses thereof | |
JP2021533785A (ja) | 共有抗原を標的指向する抗原結合タンパク質 | |
US20220396632A1 (en) | Anti-psgl-1 compositions and methods for modulating myeloid cell infalmmatory phenotypes and uses thereof | |
US20220363752A1 (en) | Anti-lrrc25 compositions and methods for modulating myeloid cell inflammatory phenotypes and uses thereof | |
KR20220115572A (ko) | 항-b7-h3 단클론성 항체 및 이의 사용 방법 | |
KR20220042128A (ko) | 골수성 세포 염증성 표현형을 조절하기 위한 항-cd53 조성물 및 방법, 그리고 이의 용도 | |
US20220073963A1 (en) | Compositions and methods for detecting and treating type 1 diabetes and other autoimmune diseases | |
JPWO2020132456A5 (de) | ||
US20230128075A1 (en) | Monoclonal antibodies targeting hsp70 and therapeutic uses thereof |