CN110124039A - 使用甲氨蝶呤诱导免疫耐受性 - Google Patents
使用甲氨蝶呤诱导免疫耐受性 Download PDFInfo
- Publication number
- CN110124039A CN110124039A CN201910138372.3A CN201910138372A CN110124039A CN 110124039 A CN110124039 A CN 110124039A CN 201910138372 A CN201910138372 A CN 201910138372A CN 110124039 A CN110124039 A CN 110124039A
- Authority
- CN
- China
- Prior art keywords
- mtx
- methotrexate
- cell
- matg
- alemtuzumab
- 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
- 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 title claims abstract description 1028
- 229960000485 methotrexate Drugs 0.000 title claims abstract description 1028
- 230000001900 immune effect Effects 0.000 title claims abstract description 45
- 230000001939 inductive effect Effects 0.000 title claims abstract description 18
- 239000003814 drug Substances 0.000 claims abstract description 113
- 229940079593 drug Drugs 0.000 claims abstract description 18
- 101001018026 Homo sapiens Lysosomal alpha-glucosidase Proteins 0.000 claims description 118
- 102000045921 human GAA Human genes 0.000 claims description 118
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 claims description 42
- 229910021529 ammonia Inorganic materials 0.000 claims description 21
- KDCGOANMDULRCW-UHFFFAOYSA-N 7H-purine Chemical compound N1=CNC2=NC=NC2=C1 KDCGOANMDULRCW-UHFFFAOYSA-N 0.000 claims description 14
- 108010028144 alpha-Glucosidases Proteins 0.000 claims description 7
- 230000005764 inhibitory process Effects 0.000 claims description 7
- 238000002360 preparation method Methods 0.000 claims description 7
- 239000002253 acid Substances 0.000 claims description 6
- 102100033448 Lysosomal alpha-glucosidase Human genes 0.000 claims 2
- 208000032007 Glycogen storage disease due to acid maltase deficiency Diseases 0.000 claims 1
- 206010053185 Glycogen storage disease type II Diseases 0.000 claims 1
- 201000004502 glycogen storage disease II Diseases 0.000 claims 1
- 210000003719 b-lymphocyte Anatomy 0.000 abstract description 148
- 238000000034 method Methods 0.000 abstract description 112
- 238000011282 treatment Methods 0.000 abstract description 79
- 230000004044 response Effects 0.000 abstract description 60
- 210000001744 T-lymphocyte Anatomy 0.000 abstract description 56
- 230000028993 immune response Effects 0.000 abstract description 25
- 210000004027 cell Anatomy 0.000 description 232
- 238000012545 processing Methods 0.000 description 180
- 229960000548 alemtuzumab Drugs 0.000 description 173
- 241000699666 Mus <mouse, genus> Species 0.000 description 147
- 241001465754 Metazoa Species 0.000 description 109
- 229940124597 therapeutic agent Drugs 0.000 description 83
- 230000000694 effects Effects 0.000 description 61
- 102000003814 Interleukin-10 Human genes 0.000 description 60
- 108090000174 Interleukin-10 Proteins 0.000 description 60
- 108090000623 proteins and genes Proteins 0.000 description 58
- 239000003795 chemical substances by application Substances 0.000 description 57
- 238000011160 research Methods 0.000 description 54
- ZRKFYGHZFMAOKI-QMGMOQQFSA-N tgfbeta Chemical compound C([C@H](NC(=O)[C@H](C(C)C)NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CC(C)C)NC(=O)CNC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](N)CCSC)C(C)C)[C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](C)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(O)=O)C1=CC=C(O)C=C1 ZRKFYGHZFMAOKI-QMGMOQQFSA-N 0.000 description 54
- 102000004887 Transforming Growth Factor beta Human genes 0.000 description 53
- 108090001012 Transforming Growth Factor beta Proteins 0.000 description 53
- 102000004169 proteins and genes Human genes 0.000 description 51
- 238000002560 therapeutic procedure Methods 0.000 description 48
- 210000004698 lymphocyte Anatomy 0.000 description 46
- 210000000952 spleen Anatomy 0.000 description 39
- 230000004913 activation Effects 0.000 description 37
- 210000004369 blood Anatomy 0.000 description 35
- 239000008280 blood Substances 0.000 description 35
- 210000002216 heart Anatomy 0.000 description 33
- 101000716102 Homo sapiens T-cell surface glycoprotein CD4 Proteins 0.000 description 30
- 102100036011 T-cell surface glycoprotein CD4 Human genes 0.000 description 30
- 210000001519 tissue Anatomy 0.000 description 29
- 230000006698 induction Effects 0.000 description 28
- HNXQXTQTPAJEJL-UHFFFAOYSA-N 2-aminopteridin-4-ol Chemical compound C1=CN=C2NC(N)=NC(=O)C2=N1 HNXQXTQTPAJEJL-UHFFFAOYSA-N 0.000 description 26
- 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 24
- 239000002953 phosphate buffered saline Substances 0.000 description 24
- 230000005875 antibody response Effects 0.000 description 22
- 210000000649 b-lymphocyte subset Anatomy 0.000 description 22
- 230000002829 reductive effect Effects 0.000 description 22
- 241000283973 Oryctolagus cuniculus Species 0.000 description 21
- 230000005784 autoimmunity Effects 0.000 description 21
- 230000009467 reduction Effects 0.000 description 21
- 238000002054 transplantation Methods 0.000 description 21
- 238000005259 measurement Methods 0.000 description 20
- 210000002966 serum Anatomy 0.000 description 20
- 102100024222 B-lymphocyte antigen CD19 Human genes 0.000 description 19
- 238000002965 ELISA Methods 0.000 description 19
- 101000980825 Homo sapiens B-lymphocyte antigen CD19 Proteins 0.000 description 19
- 230000003325 follicular Effects 0.000 description 19
- 239000007924 injection Substances 0.000 description 19
- 238000002347 injection Methods 0.000 description 19
- 201000006417 multiple sclerosis Diseases 0.000 description 18
- 230000003442 weekly effect Effects 0.000 description 18
- 241000699670 Mus sp. Species 0.000 description 15
- 230000001965 increasing effect Effects 0.000 description 14
- 210000003826 marginal zone b cell Anatomy 0.000 description 14
- 230000007246 mechanism Effects 0.000 description 14
- 239000012071 phase Substances 0.000 description 14
- 230000004083 survival effect Effects 0.000 description 14
- 238000011740 C57BL/6 mouse Methods 0.000 description 13
- 108010044091 Globulins Proteins 0.000 description 13
- 102000006395 Globulins Human genes 0.000 description 13
- 238000006243 chemical reaction Methods 0.000 description 12
- 201000010099 disease Diseases 0.000 description 12
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 12
- 230000003285 pharmacodynamic effect Effects 0.000 description 12
- 229960004641 rituximab Drugs 0.000 description 12
- 208000023275 Autoimmune disease Diseases 0.000 description 11
- 102000004190 Enzymes Human genes 0.000 description 11
- 108090000790 Enzymes Proteins 0.000 description 11
- 230000001494 anti-thymocyte effect Effects 0.000 description 11
- 229940088598 enzyme Drugs 0.000 description 11
- 238000000684 flow cytometry Methods 0.000 description 11
- 230000008595 infiltration Effects 0.000 description 11
- 238000001764 infiltration Methods 0.000 description 11
- 206010039073 rheumatoid arthritis Diseases 0.000 description 11
- 230000001363 autoimmune Effects 0.000 description 10
- 238000002474 experimental method Methods 0.000 description 10
- 210000001165 lymph node Anatomy 0.000 description 10
- 230000001404 mediated effect Effects 0.000 description 10
- 230000001681 protective effect Effects 0.000 description 10
- 230000001225 therapeutic effect Effects 0.000 description 10
- TVZGACDUOSZQKY-LBPRGKRZSA-N 4-aminofolic acid Chemical compound C1=NC2=NC(N)=NC(N)=C2N=C1CNC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 TVZGACDUOSZQKY-LBPRGKRZSA-N 0.000 description 9
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 9
- 102000004127 Cytokines Human genes 0.000 description 9
- 108090000695 Cytokines Proteins 0.000 description 9
- 229960003896 aminopterin Drugs 0.000 description 9
- 239000000427 antigen Substances 0.000 description 9
- 108091007433 antigens Proteins 0.000 description 9
- 102000036639 antigens Human genes 0.000 description 9
- 230000001413 cellular effect Effects 0.000 description 9
- 230000036755 cellular response Effects 0.000 description 9
- 239000012894 fetal calf serum Substances 0.000 description 9
- 230000007170 pathology Effects 0.000 description 9
- 238000012360 testing method Methods 0.000 description 9
- 101001057504 Homo sapiens Interferon-stimulated gene 20 kDa protein Proteins 0.000 description 8
- 101001055144 Homo sapiens Interleukin-2 receptor subunit alpha Proteins 0.000 description 8
- 102100027268 Interferon-stimulated gene 20 kDa protein Human genes 0.000 description 8
- 230000000779 depleting effect Effects 0.000 description 8
- 230000001976 improved effect Effects 0.000 description 8
- 238000001802 infusion Methods 0.000 description 8
- 239000007928 intraperitoneal injection Substances 0.000 description 8
- 238000001990 intravenous administration Methods 0.000 description 8
- 239000000203 mixture Substances 0.000 description 8
- 230000008569 process Effects 0.000 description 8
- 238000012546 transfer Methods 0.000 description 8
- 241000196324 Embryophyta Species 0.000 description 7
- 108090001005 Interleukin-6 Proteins 0.000 description 7
- 102000004889 Interleukin-6 Human genes 0.000 description 7
- 230000008901 benefit Effects 0.000 description 7
- 230000007365 immunoregulation Effects 0.000 description 7
- 239000012528 membrane Substances 0.000 description 7
- 210000003462 vein Anatomy 0.000 description 7
- 102100025877 Complement component C1q receptor Human genes 0.000 description 6
- 241001269238 Data Species 0.000 description 6
- 101000933665 Homo sapiens Complement component C1q receptor Proteins 0.000 description 6
- 230000005867 T cell response Effects 0.000 description 6
- 206010052779 Transplant rejections Diseases 0.000 description 6
- 102000016679 alpha-Glucosidases Human genes 0.000 description 6
- 238000004458 analytical method Methods 0.000 description 6
- 230000000747 cardiac effect Effects 0.000 description 6
- 238000001514 detection method Methods 0.000 description 6
- 230000002708 enhancing effect Effects 0.000 description 6
- 210000003743 erythrocyte Anatomy 0.000 description 6
- 229960000598 infliximab Drugs 0.000 description 6
- 239000000463 material Substances 0.000 description 6
- 210000001685 thyroid gland Anatomy 0.000 description 6
- 102100024217 CAMPATH-1 antigen Human genes 0.000 description 5
- 108010065524 CD52 Antigen Proteins 0.000 description 5
- 241000283707 Capra Species 0.000 description 5
- 102000003992 Peroxidases Human genes 0.000 description 5
- 241000219061 Rheum Species 0.000 description 5
- 210000000662 T-lymphocyte subset Anatomy 0.000 description 5
- 238000010521 absorption reaction Methods 0.000 description 5
- 230000033228 biological regulation Effects 0.000 description 5
- 239000000872 buffer Substances 0.000 description 5
- 230000007541 cellular toxicity Effects 0.000 description 5
- 238000004140 cleaning Methods 0.000 description 5
- 238000002641 enzyme replacement therapy Methods 0.000 description 5
- 230000006870 function Effects 0.000 description 5
- 239000011521 glass Substances 0.000 description 5
- 208000024908 graft versus host disease Diseases 0.000 description 5
- 210000002443 helper t lymphocyte Anatomy 0.000 description 5
- 239000003018 immunosuppressive agent Substances 0.000 description 5
- 230000007774 longterm Effects 0.000 description 5
- 210000004165 myocardium Anatomy 0.000 description 5
- 210000000056 organ Anatomy 0.000 description 5
- 108040007629 peroxidase activity proteins Proteins 0.000 description 5
- 229920000642 polymer Polymers 0.000 description 5
- UAIUNKRWKOVEES-UHFFFAOYSA-N 3,3',5,5'-tetramethylbenzidine Chemical compound CC1=C(N)C(C)=CC(C=2C=C(C)C(N)=C(C)C=2)=C1 UAIUNKRWKOVEES-UHFFFAOYSA-N 0.000 description 4
- 101000878605 Homo sapiens Low affinity immunoglobulin epsilon Fc receptor Proteins 0.000 description 4
- 102100038007 Low affinity immunoglobulin epsilon Fc receptor Human genes 0.000 description 4
- 208000009525 Myocarditis Diseases 0.000 description 4
- 206010028980 Neoplasm Diseases 0.000 description 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
- 229960002964 adalimumab Drugs 0.000 description 4
- 210000000709 aorta Anatomy 0.000 description 4
- 206010003246 arthritis Diseases 0.000 description 4
- 239000003124 biologic agent Substances 0.000 description 4
- 230000015572 biosynthetic process Effects 0.000 description 4
- 238000001815 biotherapy Methods 0.000 description 4
- 201000011510 cancer Diseases 0.000 description 4
- 239000006285 cell suspension Substances 0.000 description 4
- 239000000975 dye Substances 0.000 description 4
- 210000002950 fibroblast Anatomy 0.000 description 4
- 230000003328 fibroblastic effect Effects 0.000 description 4
- 244000144993 groups of animals Species 0.000 description 4
- 238000003306 harvesting Methods 0.000 description 4
- 210000005003 heart tissue Anatomy 0.000 description 4
- 230000036039 immunity Effects 0.000 description 4
- 230000005847 immunogenicity Effects 0.000 description 4
- 230000002401 inhibitory effect Effects 0.000 description 4
- 230000002045 lasting effect Effects 0.000 description 4
- 210000004185 liver Anatomy 0.000 description 4
- 229940103023 myozyme Drugs 0.000 description 4
- 229960005027 natalizumab Drugs 0.000 description 4
- 239000000047 product Substances 0.000 description 4
- 238000000926 separation method Methods 0.000 description 4
- 239000011780 sodium chloride Substances 0.000 description 4
- 210000004988 splenocyte Anatomy 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- 208000009304 Acute Kidney Injury Diseases 0.000 description 3
- 102100021943 C-C motif chemokine 2 Human genes 0.000 description 3
- 101710155857 C-C motif chemokine 2 Proteins 0.000 description 3
- 102000004366 Glucosidases Human genes 0.000 description 3
- 108010056771 Glucosidases Proteins 0.000 description 3
- 208000009329 Graft vs Host Disease Diseases 0.000 description 3
- WZUVPPKBWHMQCE-UHFFFAOYSA-N Haematoxylin Chemical compound C12=CC(O)=C(O)C=C2CC2(O)C1C1=CC=C(O)C(O)=C1OC2 WZUVPPKBWHMQCE-UHFFFAOYSA-N 0.000 description 3
- 206010020751 Hypersensitivity Diseases 0.000 description 3
- 208000028622 Immune thrombocytopenia Diseases 0.000 description 3
- 102000013462 Interleukin-12 Human genes 0.000 description 3
- 108010065805 Interleukin-12 Proteins 0.000 description 3
- 102000003816 Interleukin-13 Human genes 0.000 description 3
- 108090000176 Interleukin-13 Proteins 0.000 description 3
- 201000004681 Psoriasis Diseases 0.000 description 3
- 208000007400 Relapsing-Remitting Multiple Sclerosis Diseases 0.000 description 3
- 208000033626 Renal failure acute Diseases 0.000 description 3
- 206010043561 Thrombocytopenic purpura Diseases 0.000 description 3
- 102100040247 Tumor necrosis factor Human genes 0.000 description 3
- 241000700605 Viruses Species 0.000 description 3
- 201000011040 acute kidney failure Diseases 0.000 description 3
- 208000012998 acute renal failure Diseases 0.000 description 3
- 208000007502 anemia Diseases 0.000 description 3
- 238000010171 animal model Methods 0.000 description 3
- 239000003146 anticoagulant agent Substances 0.000 description 3
- 210000000612 antigen-presenting cell Anatomy 0.000 description 3
- 201000003710 autoimmune thrombocytopenic purpura Diseases 0.000 description 3
- 239000000090 biomarker Substances 0.000 description 3
- 210000001772 blood platelet Anatomy 0.000 description 3
- 230000024245 cell differentiation Effects 0.000 description 3
- 239000003153 chemical reaction reagent Substances 0.000 description 3
- 238000005520 cutting process Methods 0.000 description 3
- 230000034994 death Effects 0.000 description 3
- 230000009977 dual effect Effects 0.000 description 3
- 238000004043 dyeing Methods 0.000 description 3
- 235000013601 eggs Nutrition 0.000 description 3
- 238000005516 engineering process Methods 0.000 description 3
- 239000008187 granular material Substances 0.000 description 3
- 230000036732 histological change Effects 0.000 description 3
- 210000004408 hybridoma Anatomy 0.000 description 3
- 230000006058 immune tolerance Effects 0.000 description 3
- 238000003364 immunohistochemistry Methods 0.000 description 3
- 238000012744 immunostaining Methods 0.000 description 3
- 230000003834 intracellular effect Effects 0.000 description 3
- 210000003071 memory t lymphocyte Anatomy 0.000 description 3
- 238000012544 monitoring process Methods 0.000 description 3
- 230000017074 necrotic cell death Effects 0.000 description 3
- 239000012188 paraffin wax Substances 0.000 description 3
- 230000001575 pathological effect Effects 0.000 description 3
- 210000005259 peripheral blood Anatomy 0.000 description 3
- 239000011886 peripheral blood Substances 0.000 description 3
- -1 phosphatidylinositols lipid Chemical class 0.000 description 3
- 230000002062 proliferating effect Effects 0.000 description 3
- 238000009256 replacement therapy Methods 0.000 description 3
- 150000003839 salts Chemical class 0.000 description 3
- 238000013207 serial dilution Methods 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- 230000003393 splenic effect Effects 0.000 description 3
- 230000009466 transformation Effects 0.000 description 3
- 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 2
- PGZLPGBQBBTYDR-UHFFFAOYSA-N 2-hydrazinyl-1h-pteridin-4-one Chemical class C1=CN=C2C(=O)NC(NN)=NC2=N1 PGZLPGBQBBTYDR-UHFFFAOYSA-N 0.000 description 2
- 102100032912 CD44 antigen Human genes 0.000 description 2
- 241000702421 Dependoparvovirus Species 0.000 description 2
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 2
- 208000035186 Hemolytic Autoimmune Anemia Diseases 0.000 description 2
- 208000031220 Hemophilia Diseases 0.000 description 2
- 208000009292 Hemophilia A Diseases 0.000 description 2
- 101000718525 Homo sapiens Alpha-galactosidase A Proteins 0.000 description 2
- 101000868273 Homo sapiens CD44 antigen Proteins 0.000 description 2
- 108010001336 Horseradish Peroxidase Proteins 0.000 description 2
- 208000024781 Immune Complex disease Diseases 0.000 description 2
- 241000255777 Lepidoptera Species 0.000 description 2
- 102100033342 Lysosomal acid glucosylceramidase Human genes 0.000 description 2
- 241000551546 Minerva Species 0.000 description 2
- 241000699660 Mus musculus Species 0.000 description 2
- 208000031981 Thrombocytopenic Idiopathic Purpura Diseases 0.000 description 2
- 108060008682 Tumor Necrosis Factor Proteins 0.000 description 2
- 210000001015 abdomen Anatomy 0.000 description 2
- 210000000683 abdominal cavity Anatomy 0.000 description 2
- 230000002378 acidificating effect Effects 0.000 description 2
- 208000030961 allergic reaction Diseases 0.000 description 2
- 102000005840 alpha-Galactosidase Human genes 0.000 description 2
- 108010030291 alpha-Galactosidase Proteins 0.000 description 2
- 230000000702 anti-platelet effect Effects 0.000 description 2
- 238000003556 assay Methods 0.000 description 2
- 201000000448 autoimmune hemolytic anemia Diseases 0.000 description 2
- 229960004669 basiliximab Drugs 0.000 description 2
- 230000010261 cell growth Effects 0.000 description 2
- 230000008614 cellular interaction Effects 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- NCEXYHBECQHGNR-UHFFFAOYSA-N chembl421 Chemical compound C1=C(O)C(C(=O)O)=CC(N=NC=2C=CC(=CC=2)S(=O)(=O)NC=2N=CC=CC=2)=C1 NCEXYHBECQHGNR-UHFFFAOYSA-N 0.000 description 2
- 239000005482 chemotactic factor Substances 0.000 description 2
- 239000011248 coating agent Substances 0.000 description 2
- 238000000576 coating method Methods 0.000 description 2
- 230000001186 cumulative effect Effects 0.000 description 2
- 230000002380 cytological effect Effects 0.000 description 2
- 230000006378 damage Effects 0.000 description 2
- 230000003247 decreasing effect Effects 0.000 description 2
- 230000002950 deficient Effects 0.000 description 2
- 230000007850 degeneration Effects 0.000 description 2
- UREBDLICKHMUKA-CXSFZGCWSA-N dexamethasone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@@H](C)[C@@](C(=O)CO)(O)[C@@]1(C)C[C@@H]2O UREBDLICKHMUKA-CXSFZGCWSA-N 0.000 description 2
- 229960003957 dexamethasone Drugs 0.000 description 2
- 238000010790 dilution Methods 0.000 description 2
- 239000012895 dilution Substances 0.000 description 2
- 235000013399 edible fruits Nutrition 0.000 description 2
- 230000002526 effect on cardiovascular system Effects 0.000 description 2
- 238000011156 evaluation Methods 0.000 description 2
- 238000001943 fluorescence-activated cell sorting Methods 0.000 description 2
- 239000012634 fragment Substances 0.000 description 2
- 229960000578 gemtuzumab Drugs 0.000 description 2
- 102000043404 human GLA Human genes 0.000 description 2
- 208000024326 hypersensitivity reaction type III disease Diseases 0.000 description 2
- 229960002127 imiglucerase Drugs 0.000 description 2
- 108010039650 imiglucerase Proteins 0.000 description 2
- 230000003053 immunization Effects 0.000 description 2
- 238000002649 immunization Methods 0.000 description 2
- 238000001727 in vivo Methods 0.000 description 2
- 210000004969 inflammatory cell Anatomy 0.000 description 2
- 230000028709 inflammatory response Effects 0.000 description 2
- 238000010253 intravenous injection Methods 0.000 description 2
- 238000011835 investigation Methods 0.000 description 2
- PGHMRUGBZOYCAA-UHFFFAOYSA-N ionomycin Natural products 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 2
- PGHMRUGBZOYCAA-ADZNBVRBSA-N ionomycin Chemical compound O1[C@H](C[C@H](O)[C@H](C)[C@H](O)[C@H](C)/C=C/C[C@@H](C)C[C@@H](C)C(/O)=C/C(=O)[C@@H](C)C[C@@H](C)C[C@@H](CCC(O)=O)C)CC[C@@]1(C)[C@@H]1O[C@](C)([C@@H](C)O)CC1 PGHMRUGBZOYCAA-ADZNBVRBSA-N 0.000 description 2
- 210000003734 kidney Anatomy 0.000 description 2
- 238000011813 knockout mouse model Methods 0.000 description 2
- 238000002386 leaching Methods 0.000 description 2
- 230000000670 limiting effect Effects 0.000 description 2
- 206010025135 lupus erythematosus Diseases 0.000 description 2
- 206010025482 malaise Diseases 0.000 description 2
- 238000007726 management method Methods 0.000 description 2
- 239000003550 marker Substances 0.000 description 2
- 230000010534 mechanism of action Effects 0.000 description 2
- 238000010172 mouse model Methods 0.000 description 2
- 230000003387 muscular Effects 0.000 description 2
- 108020004707 nucleic acids Proteins 0.000 description 2
- 102000039446 nucleic acids Human genes 0.000 description 2
- 150000007523 nucleic acids Chemical class 0.000 description 2
- 230000036961 partial effect Effects 0.000 description 2
- 108090000765 processed proteins & peptides Proteins 0.000 description 2
- 230000000770 proinflammatory effect Effects 0.000 description 2
- 210000001147 pulmonary artery Anatomy 0.000 description 2
- 229960003876 ranibizumab Drugs 0.000 description 2
- 108020003175 receptors Proteins 0.000 description 2
- 102000005962 receptors Human genes 0.000 description 2
- 230000006798 recombination Effects 0.000 description 2
- 238000005215 recombination Methods 0.000 description 2
- 238000004064 recycling Methods 0.000 description 2
- 230000008929 regeneration Effects 0.000 description 2
- 238000011069 regeneration method Methods 0.000 description 2
- 210000003289 regulatory T cell Anatomy 0.000 description 2
- 239000012898 sample dilution Substances 0.000 description 2
- 230000028327 secretion Effects 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 210000004989 spleen cell Anatomy 0.000 description 2
- 210000000130 stem cell Anatomy 0.000 description 2
- 208000024891 symptom Diseases 0.000 description 2
- 201000003067 thrombocytopenia due to platelet alloimmunization Diseases 0.000 description 2
- 238000011830 transgenic mouse model Methods 0.000 description 2
- 229960000575 trastuzumab Drugs 0.000 description 2
- 208000025883 type III hypersensitivity disease Diseases 0.000 description 2
- 210000004885 white matter Anatomy 0.000 description 2
- WZUVPPKBWHMQCE-XJKSGUPXSA-N (+)-haematoxylin Chemical compound C12=CC(O)=C(O)C=C2C[C@]2(O)[C@H]1C1=CC=C(O)C(O)=C1OC2 WZUVPPKBWHMQCE-XJKSGUPXSA-N 0.000 description 1
- PXFBZOLANLWPMH-UHFFFAOYSA-N 16-Epiaffinine Natural products C1C(C2=CC=CC=C2N2)=C2C(=O)CC2C(=CC)CN(C)C1C2CO PXFBZOLANLWPMH-UHFFFAOYSA-N 0.000 description 1
- NHBKXEKEPDILRR-UHFFFAOYSA-N 2,3-bis(butanoylsulfanyl)propyl butanoate Chemical compound CCCC(=O)OCC(SC(=O)CCC)CSC(=O)CCC NHBKXEKEPDILRR-UHFFFAOYSA-N 0.000 description 1
- LCSKNASZPVZHEG-UHFFFAOYSA-N 3,6-dimethyl-1,4-dioxane-2,5-dione;1,4-dioxane-2,5-dione Chemical group O=C1COC(=O)CO1.CC1OC(=O)C(C)OC1=O LCSKNASZPVZHEG-UHFFFAOYSA-N 0.000 description 1
- 206010002091 Anaesthesia Diseases 0.000 description 1
- 235000011330 Armoracia rusticana Nutrition 0.000 description 1
- 240000003291 Armoracia rusticana Species 0.000 description 1
- 206010055128 Autoimmune neutropenia Diseases 0.000 description 1
- 208000010839 B-cell chronic lymphocytic leukemia Diseases 0.000 description 1
- 238000011725 BALB/c mouse Methods 0.000 description 1
- 102100027990 Beta/gamma crystallin domain-containing protein 2 Human genes 0.000 description 1
- 229940124296 CD52 monoclonal antibody Drugs 0.000 description 1
- 101100369802 Caenorhabditis elegans tim-1 gene Proteins 0.000 description 1
- 108090000565 Capsid Proteins Proteins 0.000 description 1
- 241001133757 Carpentaria Species 0.000 description 1
- 101150043916 Cd52 gene Proteins 0.000 description 1
- 102100034755 Centrosomal protein of 85 kDa Human genes 0.000 description 1
- 102100023321 Ceruloplasmin Human genes 0.000 description 1
- 241000219104 Cucurbitaceae Species 0.000 description 1
- CMSMOCZEIVJLDB-UHFFFAOYSA-N Cyclophosphamide Chemical compound ClCCN(CCCl)P1(=O)NCCCO1 CMSMOCZEIVJLDB-UHFFFAOYSA-N 0.000 description 1
- 101100136092 Drosophila melanogaster peng gene Proteins 0.000 description 1
- 101100379079 Emericella variicolor andA gene Proteins 0.000 description 1
- 108010008165 Etanercept Proteins 0.000 description 1
- 108060002716 Exonuclease Proteins 0.000 description 1
- 102000001690 Factor VIII Human genes 0.000 description 1
- 108010054218 Factor VIII Proteins 0.000 description 1
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 1
- 108010017213 Granulocyte-Macrophage Colony-Stimulating Factor Proteins 0.000 description 1
- 102100039620 Granulocyte-macrophage colony-stimulating factor Human genes 0.000 description 1
- 101000859450 Homo sapiens Beta/gamma crystallin domain-containing protein 2 Proteins 0.000 description 1
- 101000945822 Homo sapiens Centrosomal protein of 85 kDa Proteins 0.000 description 1
- 101001046686 Homo sapiens Integrin alpha-M Proteins 0.000 description 1
- 101001018097 Homo sapiens L-selectin Proteins 0.000 description 1
- 101000608935 Homo sapiens Leukosialin Proteins 0.000 description 1
- 101000946843 Homo sapiens T-cell surface glycoprotein CD8 alpha chain Proteins 0.000 description 1
- 206010021245 Idiopathic thrombocytopenic purpura Diseases 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
- 108010021625 Immunoglobulin Fragments Proteins 0.000 description 1
- 102000008394 Immunoglobulin Fragments Human genes 0.000 description 1
- 208000026350 Inborn Genetic disease Diseases 0.000 description 1
- 206010021703 Indifference Diseases 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- 102100022338 Integrin alpha-M Human genes 0.000 description 1
- 102000005755 Intercellular Signaling Peptides and Proteins Human genes 0.000 description 1
- 108010070716 Intercellular Signaling Peptides and Proteins Proteins 0.000 description 1
- 102000008070 Interferon-gamma Human genes 0.000 description 1
- 108010074328 Interferon-gamma Proteins 0.000 description 1
- 102000003812 Interleukin-15 Human genes 0.000 description 1
- 108090000172 Interleukin-15 Proteins 0.000 description 1
- 108010002350 Interleukin-2 Proteins 0.000 description 1
- 102000000588 Interleukin-2 Human genes 0.000 description 1
- 108010002616 Interleukin-5 Proteins 0.000 description 1
- 102000000743 Interleukin-5 Human genes 0.000 description 1
- 108010002586 Interleukin-7 Proteins 0.000 description 1
- YQEZLKZALYSWHR-UHFFFAOYSA-N Ketamine Chemical compound C=1C=CC=C(Cl)C=1C1(NC)CCCCC1=O YQEZLKZALYSWHR-UHFFFAOYSA-N 0.000 description 1
- 102100033467 L-selectin Human genes 0.000 description 1
- JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 description 1
- 102100039564 Leukosialin Human genes 0.000 description 1
- 206010058467 Lung neoplasm malignant Diseases 0.000 description 1
- 208000031422 Lymphocytic Chronic B-Cell Leukemia Diseases 0.000 description 1
- 206010025327 Lymphopenia Diseases 0.000 description 1
- 229930191564 Monensin Natural products 0.000 description 1
- GAOZTHIDHYLHMS-UHFFFAOYSA-N Monensin A Natural products O1C(CC)(C2C(CC(O2)C2C(CC(C)C(O)(CO)O2)C)C)CCC1C(O1)(C)CCC21CC(O)C(C)C(C(C)C(OC)C(C)C(O)=O)O2 GAOZTHIDHYLHMS-UHFFFAOYSA-N 0.000 description 1
- 206010056886 Mucopolysaccharidosis I Diseases 0.000 description 1
- 241001529936 Murinae Species 0.000 description 1
- 101100407308 Mus musculus Pdcd1lg2 gene Proteins 0.000 description 1
- 238000011794 NU/NU nude mouse Methods 0.000 description 1
- 101710160107 Outer membrane protein A Proteins 0.000 description 1
- 102000004316 Oxidoreductases Human genes 0.000 description 1
- 108090000854 Oxidoreductases Proteins 0.000 description 1
- 208000004550 Postoperative Pain Diseases 0.000 description 1
- 108700030875 Programmed Cell Death 1 Ligand 2 Proteins 0.000 description 1
- 102100024213 Programmed cell death 1 ligand 2 Human genes 0.000 description 1
- 206010037549 Purpura Diseases 0.000 description 1
- 241001672981 Purpura Species 0.000 description 1
- 102000004389 Ribonucleoproteins Human genes 0.000 description 1
- 108010081734 Ribonucleoproteins Proteins 0.000 description 1
- 101150111548 SH3BGRL3 gene Proteins 0.000 description 1
- 108020004459 Small interfering RNA Proteins 0.000 description 1
- 201000001322 T cell deficiency Diseases 0.000 description 1
- 102100034922 T-cell surface glycoprotein CD8 alpha chain Human genes 0.000 description 1
- 108700019146 Transgenes Proteins 0.000 description 1
- 208000002495 Uterine Neoplasms Diseases 0.000 description 1
- 206010047115 Vasculitis Diseases 0.000 description 1
- 206010052428 Wound Diseases 0.000 description 1
- 208000027418 Wounds and injury Diseases 0.000 description 1
- 241000021375 Xenogenes Species 0.000 description 1
- 101710185494 Zinc finger protein Proteins 0.000 description 1
- 102100023597 Zinc finger protein 816 Human genes 0.000 description 1
- 230000003187 abdominal effect Effects 0.000 description 1
- 210000003489 abdominal muscle Anatomy 0.000 description 1
- 238000002835 absorbance Methods 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- VREFGVBLTWBCJP-UHFFFAOYSA-N alprazolam Chemical compound C12=CC(Cl)=CC=C2N2C(C)=NN=C2CN=C1C1=CC=CC=C1 VREFGVBLTWBCJP-UHFFFAOYSA-N 0.000 description 1
- 230000037005 anaesthesia Effects 0.000 description 1
- 230000008485 antagonism Effects 0.000 description 1
- 239000005557 antagonist Substances 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 230000002529 anti-mitochondrial effect Effects 0.000 description 1
- 230000003460 anti-nuclear Effects 0.000 description 1
- 230000000692 anti-sense effect Effects 0.000 description 1
- 230000003208 anti-thyroid effect Effects 0.000 description 1
- 230000002504 anti-thyrotropic effect Effects 0.000 description 1
- 238000009175 antibody therapy Methods 0.000 description 1
- 230000009831 antigen interaction Effects 0.000 description 1
- 230000030741 antigen processing and presentation Effects 0.000 description 1
- 230000000890 antigenic effect Effects 0.000 description 1
- 229940043671 antithyroid preparations Drugs 0.000 description 1
- 210000000702 aorta abdominal Anatomy 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 208000010928 autoimmune thyroid disease Diseases 0.000 description 1
- 229960003270 belimumab Drugs 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- HFACYLZERDEVSX-UHFFFAOYSA-N benzidine Chemical compound C1=CC(N)=CC=C1C1=CC=C(N)C=C1 HFACYLZERDEVSX-UHFFFAOYSA-N 0.000 description 1
- 229960000397 bevacizumab Drugs 0.000 description 1
- 230000027455 binding Effects 0.000 description 1
- 230000008033 biological extinction Effects 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 238000004159 blood analysis Methods 0.000 description 1
- 238000010241 blood sampling Methods 0.000 description 1
- 210000001124 body fluid Anatomy 0.000 description 1
- 239000010839 body fluid Substances 0.000 description 1
- 230000005907 cancer growth Effects 0.000 description 1
- 150000001720 carbohydrates Chemical class 0.000 description 1
- 230000030833 cell death Effects 0.000 description 1
- 230000004663 cell proliferation Effects 0.000 description 1
- 230000003833 cell viability Effects 0.000 description 1
- 210000003169 central nervous system Anatomy 0.000 description 1
- 229960005395 cetuximab Drugs 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 230000001143 conditioned effect Effects 0.000 description 1
- 238000012790 confirmation Methods 0.000 description 1
- 230000001276 controlling effect Effects 0.000 description 1
- 230000002596 correlated effect Effects 0.000 description 1
- 238000005336 cracking Methods 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- 229960004397 cyclophosphamide Drugs 0.000 description 1
- 210000001151 cytotoxic T lymphocyte Anatomy 0.000 description 1
- 230000003013 cytotoxicity Effects 0.000 description 1
- 231100000135 cytotoxicity Toxicity 0.000 description 1
- 229960002806 daclizumab Drugs 0.000 description 1
- 238000013502 data validation Methods 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 230000003111 delayed effect Effects 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- ZZVUWRFHKOJYTH-UHFFFAOYSA-N diphenhydramine Chemical compound C=1C=CC=CC=1C(OCCN(C)C)C1=CC=CC=C1 ZZVUWRFHKOJYTH-UHFFFAOYSA-N 0.000 description 1
- 229960000520 diphenhydramine Drugs 0.000 description 1
- 230000009266 disease activity Effects 0.000 description 1
- 235000015177 dried meat Nutrition 0.000 description 1
- 229940126534 drug product Drugs 0.000 description 1
- 239000012636 effector Substances 0.000 description 1
- 210000001671 embryonic stem cell Anatomy 0.000 description 1
- YQGOJNYOYNNSMM-UHFFFAOYSA-N eosin Chemical compound [Na+].OC(=O)C1=CC=CC=C1C1=C2C=C(Br)C(=O)C(Br)=C2OC2=C(Br)C(O)=C(Br)C=C21 YQGOJNYOYNNSMM-UHFFFAOYSA-N 0.000 description 1
- 229960000403 etanercept Drugs 0.000 description 1
- 102000013165 exonuclease Human genes 0.000 description 1
- 238000010195 expression analysis Methods 0.000 description 1
- 229960000301 factor viii Drugs 0.000 description 1
- 239000000835 fiber Substances 0.000 description 1
- 230000020764 fibrinolysis Effects 0.000 description 1
- 238000005206 flow analysis 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
- 239000007850 fluorescent dye Substances 0.000 description 1
- 229960000304 folic acid Drugs 0.000 description 1
- 239000011724 folic acid Substances 0.000 description 1
- 210000000285 follicular dendritic cell Anatomy 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 108020001507 fusion proteins Proteins 0.000 description 1
- 102000037865 fusion proteins Human genes 0.000 description 1
- 208000016361 genetic disease Diseases 0.000 description 1
- 210000004907 gland Anatomy 0.000 description 1
- 230000013595 glycosylation Effects 0.000 description 1
- 238000006206 glycosylation reaction Methods 0.000 description 1
- 210000004013 groin Anatomy 0.000 description 1
- 239000005337 ground glass Substances 0.000 description 1
- 239000003102 growth factor Substances 0.000 description 1
- 230000003694 hair properties Effects 0.000 description 1
- 208000014829 head and neck neoplasm Diseases 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 230000023597 hemostasis Effects 0.000 description 1
- 229940088597 hormone Drugs 0.000 description 1
- 239000005556 hormone Substances 0.000 description 1
- 210000003917 human chromosome Anatomy 0.000 description 1
- 210000002865 immune cell Anatomy 0.000 description 1
- 210000000987 immune system Anatomy 0.000 description 1
- 230000002055 immunohistochemical effect Effects 0.000 description 1
- 239000002955 immunomodulating agent Substances 0.000 description 1
- 229940121354 immunomodulator Drugs 0.000 description 1
- 230000002584 immunomodulator Effects 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 238000011065 in-situ storage Methods 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 230000002757 inflammatory effect Effects 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 238000011283 initial treatment period Methods 0.000 description 1
- 238000011081 inoculation Methods 0.000 description 1
- 238000007689 inspection Methods 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 230000002452 interceptive effect Effects 0.000 description 1
- 229960003130 interferon gamma Drugs 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 229960003299 ketamine Drugs 0.000 description 1
- 230000002147 killing effect Effects 0.000 description 1
- 229960002486 laronidase Drugs 0.000 description 1
- 208000032839 leukemia Diseases 0.000 description 1
- 230000021633 leukocyte mediated immunity Effects 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 230000004807 localization Effects 0.000 description 1
- 201000005202 lung cancer Diseases 0.000 description 1
- 208000020816 lung neoplasm Diseases 0.000 description 1
- 210000000207 lymphocyte subset Anatomy 0.000 description 1
- 210000003563 lymphoid tissue Anatomy 0.000 description 1
- 231100001023 lymphopenia Toxicity 0.000 description 1
- 239000012139 lysis buffer Substances 0.000 description 1
- 230000002132 lysosomal effect Effects 0.000 description 1
- 238000003754 machining Methods 0.000 description 1
- 208000026037 malignant tumor of neck Diseases 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 238000002558 medical inspection Methods 0.000 description 1
- 201000001441 melanoma Diseases 0.000 description 1
- 108091070501 miRNA Proteins 0.000 description 1
- HPNSFSBZBAHARI-UHFFFAOYSA-N micophenolic acid Natural products OC1=C(CC=C(C)CCC(O)=O)C(OC)=C(C)C2=C1C(=O)OC2 HPNSFSBZBAHARI-UHFFFAOYSA-N 0.000 description 1
- 239000002679 microRNA Substances 0.000 description 1
- 238000007431 microscopic evaluation Methods 0.000 description 1
- 230000000116 mitigating effect Effects 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 229960005358 monensin Drugs 0.000 description 1
- GAOZTHIDHYLHMS-KEOBGNEYSA-N monensin A Chemical compound C([C@@](O1)(C)[C@H]2CC[C@@](O2)(CC)[C@H]2[C@H](C[C@@H](O2)[C@@H]2[C@H](C[C@@H](C)[C@](O)(CO)O2)C)C)C[C@@]21C[C@H](O)[C@@H](C)[C@@H]([C@@H](C)[C@@H](OC)[C@H](C)C(O)=O)O2 GAOZTHIDHYLHMS-KEOBGNEYSA-N 0.000 description 1
- 238000002625 monoclonal antibody therapy Methods 0.000 description 1
- 229940014456 mycophenolate Drugs 0.000 description 1
- RTGDFNSFWBGLEC-SYZQJQIISA-N mycophenolate mofetil Chemical compound COC1=C(C)C=2COC(=O)C=2C(O)=C1C\C=C(/C)CCC(=O)OCCN1CCOCC1 RTGDFNSFWBGLEC-SYZQJQIISA-N 0.000 description 1
- 229960004866 mycophenolate mofetil Drugs 0.000 description 1
- HPNSFSBZBAHARI-RUDMXATFSA-N mycophenolic acid Chemical compound OC1=C(C\C=C(/C)CCC(O)=O)C(OC)=C(C)C2=C1C(=O)OC2 HPNSFSBZBAHARI-RUDMXATFSA-N 0.000 description 1
- 230000002107 myocardial effect Effects 0.000 description 1
- 239000013642 negative control Substances 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 210000000440 neutrophil Anatomy 0.000 description 1
- VYNDHICBIRRPFP-UHFFFAOYSA-N pacific blue Chemical compound FC1=C(O)C(F)=C2OC(=O)C(C(=O)O)=CC2=C1 VYNDHICBIRRPFP-UHFFFAOYSA-N 0.000 description 1
- 238000002559 palpation Methods 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 244000052769 pathogen Species 0.000 description 1
- 230000001717 pathogenic effect Effects 0.000 description 1
- 230000008447 perception Effects 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 229940067626 phosphatidylinositols Drugs 0.000 description 1
- 230000035479 physiological effects, processes and functions Effects 0.000 description 1
- 210000003720 plasmablast Anatomy 0.000 description 1
- 210000004180 plasmocyte Anatomy 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 229940023143 protein vaccine Drugs 0.000 description 1
- 210000003492 pulmonary vein Anatomy 0.000 description 1
- 230000004144 purine metabolism Effects 0.000 description 1
- ZAHRKKWIAAJSAO-UHFFFAOYSA-N rapamycin Natural products COCC(O)C(=C/C(C)C(=O)CC(OC(=O)C1CCCCN1C(=O)C(=O)C2(O)OC(CC(OC)C(=CC=CC=CC(C)CC(C)C(=O)C)C)CCC2C)C(C)CC3CCC(O)C(C3)OC)C ZAHRKKWIAAJSAO-UHFFFAOYSA-N 0.000 description 1
- 230000009257 reactivity Effects 0.000 description 1
- 230000004043 responsiveness Effects 0.000 description 1
- 230000000717 retained effect Effects 0.000 description 1
- 230000000250 revascularization Effects 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 201000003068 rheumatic fever Diseases 0.000 description 1
- 206010048628 rheumatoid vasculitis Diseases 0.000 description 1
- 208000037921 secondary disease Diseases 0.000 description 1
- 230000009291 secondary effect Effects 0.000 description 1
- 230000003248 secreting effect Effects 0.000 description 1
- 206010040400 serum sickness Diseases 0.000 description 1
- 235000015170 shellfish Nutrition 0.000 description 1
- 230000019491 signal transduction Effects 0.000 description 1
- 229960002930 sirolimus Drugs 0.000 description 1
- QFJCIRLUMZQUOT-HPLJOQBZSA-N sirolimus Chemical compound C1C[C@@H](O)[C@H](OC)C[C@@H]1C[C@@H](C)[C@H]1OC(=O)[C@@H]2CCCCN2C(=O)C(=O)[C@](O)(O2)[C@H](C)CC[C@H]2C[C@H](OC)/C(C)=C/C=C/C=C/[C@@H](C)C[C@@H](C)C(=O)[C@H](OC)[C@H](O)/C(C)=C/[C@@H](C)C(=O)C1 QFJCIRLUMZQUOT-HPLJOQBZSA-N 0.000 description 1
- 210000003491 skin Anatomy 0.000 description 1
- 210000004927 skin cell Anatomy 0.000 description 1
- 150000003384 small molecules Chemical class 0.000 description 1
- 210000002460 smooth muscle Anatomy 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- XOIQMTLWECTKJL-HXPDMXKUSA-M sodium;(3r,4s)-4-[(2s,5r,7s,8r,9s)-2-[(2r,5s)-5-ethyl-5-[(2r,3s,5r)-5-[(2s,3s,5r,6r)-6-hydroxy-6-(hydroxymethyl)-3,5-dimethyloxan-2-yl]-3-methyloxolan-2-yl]oxolan-2-yl]-7-hydroxy-2,8-dimethyl-1,10-dioxaspiro[4.5]decan-9-yl]-3-methoxy-2-methylpentanoate Chemical compound [Na+].C([C@@](O1)(C)[C@H]2CC[C@@](O2)(CC)[C@H]2[C@H](C[C@@H](O2)[C@@H]2[C@H](C[C@@H](C)[C@](O)(CO)O2)C)C)C[C@@]21C[C@H](O)[C@@H](C)[C@@H]([C@@H](C)[C@@H](OC)C(C)C([O-])=O)O2 XOIQMTLWECTKJL-HXPDMXKUSA-M 0.000 description 1
- 239000007790 solid phase Substances 0.000 description 1
- 230000009870 specific binding Effects 0.000 description 1
- 238000010186 staining Methods 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 239000013589 supplement Substances 0.000 description 1
- 230000008093 supporting effect Effects 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 238000005211 surface analysis Methods 0.000 description 1
- 230000002123 temporal effect Effects 0.000 description 1
- 229940126622 therapeutic monoclonal antibody Drugs 0.000 description 1
- DPJRMOMPQZCRJU-UHFFFAOYSA-M thiamine hydrochloride Chemical compound Cl.[Cl-].CC1=C(CCO)SC=[N+]1CC1=CN=C(C)N=C1N DPJRMOMPQZCRJU-UHFFFAOYSA-M 0.000 description 1
- 230000003582 thrombocytopenic effect Effects 0.000 description 1
- 230000002537 thrombolytic effect Effects 0.000 description 1
- 210000001541 thymus gland Anatomy 0.000 description 1
- 230000024664 tolerance induction Effects 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 238000012549 training Methods 0.000 description 1
- 230000009261 transgenic effect Effects 0.000 description 1
- 241000701161 unidentified adenovirus Species 0.000 description 1
- 241001430294 unidentified retrovirus Species 0.000 description 1
- 206010046766 uterine cancer Diseases 0.000 description 1
- 230000002792 vascular Effects 0.000 description 1
- 231100000216 vascular lesion Toxicity 0.000 description 1
- 239000013598 vector Substances 0.000 description 1
- 210000002620 vena cava superior Anatomy 0.000 description 1
- 239000013603 viral vector Substances 0.000 description 1
- 230000003612 virological effect Effects 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
- 239000002023 wood Substances 0.000 description 1
- BPICBUSOMSTKRF-UHFFFAOYSA-N xylazine Chemical compound CC1=CC=CC(C)=C1NC1=NCCCS1 BPICBUSOMSTKRF-UHFFFAOYSA-N 0.000 description 1
- 229960001600 xylazine Drugs 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
-
- 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
- A61K39/0005—Vertebrate antigens
- A61K39/0008—Antigens related to auto-immune diseases; Preparations to induce self-tolerance
-
- 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
- A61K39/39533—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals
- A61K39/39558—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals against tumor tissues, cells, antigens
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/06—Antianaemics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2300/00—Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Immunology (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Epidemiology (AREA)
- Mycology (AREA)
- Microbiology (AREA)
- Biomedical Technology (AREA)
- Oncology (AREA)
- Rheumatology (AREA)
- Diabetes (AREA)
- Hematology (AREA)
- Neurosurgery (AREA)
- Neurology (AREA)
- Transplantation (AREA)
- Obesity (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Peptides Or Proteins (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Materials For Medical Uses (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201161486697P | 2011-05-16 | 2011-05-16 | |
| US61/486,697 | 2011-05-16 | ||
| CN201280035299.3A CN103648501A (zh) | 2011-05-16 | 2012-05-03 | 使用甲氨蝶呤诱导免疫耐受性 |
Related Parent Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201280035299.3A Division CN103648501A (zh) | 2011-05-16 | 2012-05-03 | 使用甲氨蝶呤诱导免疫耐受性 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN110124039A true CN110124039A (zh) | 2019-08-16 |
Family
ID=47177257
Family Applications (4)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202011422509.7A Pending CN113209288A (zh) | 2011-05-16 | 2012-05-03 | 使用甲氨蝶呤诱导免疫耐受性 |
| CN201811398468.5A Pending CN109620830A (zh) | 2011-05-16 | 2012-05-03 | 使用甲氨蝶呤诱导免疫耐受性 |
| CN201910138372.3A Pending CN110124039A (zh) | 2011-05-16 | 2012-05-03 | 使用甲氨蝶呤诱导免疫耐受性 |
| CN201280035299.3A Pending CN103648501A (zh) | 2011-05-16 | 2012-05-03 | 使用甲氨蝶呤诱导免疫耐受性 |
Family Applications Before (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202011422509.7A Pending CN113209288A (zh) | 2011-05-16 | 2012-05-03 | 使用甲氨蝶呤诱导免疫耐受性 |
| CN201811398468.5A Pending CN109620830A (zh) | 2011-05-16 | 2012-05-03 | 使用甲氨蝶呤诱导免疫耐受性 |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201280035299.3A Pending CN103648501A (zh) | 2011-05-16 | 2012-05-03 | 使用甲氨蝶呤诱导免疫耐受性 |
Country Status (28)
| Country | Link |
|---|---|
| US (3) | US20140135337A1 (enExample) |
| EP (2) | EP2709627B1 (enExample) |
| JP (3) | JP6174572B2 (enExample) |
| KR (3) | KR20140040744A (enExample) |
| CN (4) | CN113209288A (enExample) |
| AU (1) | AU2012256281B2 (enExample) |
| BR (1) | BR112013029501A2 (enExample) |
| CA (1) | CA2835819A1 (enExample) |
| CL (1) | CL2013003298A1 (enExample) |
| CO (1) | CO6841993A2 (enExample) |
| DO (1) | DOP2013000268A (enExample) |
| EC (1) | ECSP13013081A (enExample) |
| ES (1) | ES2836823T3 (enExample) |
| GT (1) | GT201300278A (enExample) |
| IL (2) | IL229245B (enExample) |
| MA (1) | MA35165B1 (enExample) |
| MX (1) | MX2013013445A (enExample) |
| MY (1) | MY173304A (enExample) |
| NI (1) | NI201300121A (enExample) |
| PE (1) | PE20140469A1 (enExample) |
| PH (1) | PH12013502256A1 (enExample) |
| PT (1) | PT2709627T (enExample) |
| RU (1) | RU2674036C2 (enExample) |
| SG (1) | SG194802A1 (enExample) |
| TN (1) | TN2013000472A1 (enExample) |
| UA (1) | UA117556C2 (enExample) |
| WO (1) | WO2012158362A1 (enExample) |
| ZA (1) | ZA201308315B (enExample) |
Families Citing this family (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2011139379A2 (en) * | 2010-05-06 | 2011-11-10 | Duke University | A method of treating patients undergoing protein replacement therapy, gene replacement therapy, or other therapeutic modalities |
| AU2012249553A1 (en) | 2011-04-29 | 2013-10-24 | Selecta Biociences, Inc. | Tolerogenic synthetic nanocarriers for allergy therapy |
| MX2013013445A (es) | 2011-05-16 | 2014-07-28 | Genzyme Corp | Induccion de tolerancia inmunologica utilizando metotrexato. |
| MX2015015231A (es) | 2013-05-03 | 2016-07-06 | Selecta Biosciences Inc | Métodos y composiciones para mejorar las células t reguladoras de cd4+. |
| KR102631173B1 (ko) * | 2013-06-04 | 2024-01-31 | 셀렉타 바이오사이언시즈, 인크. | 비-면역억제성 항원 특이적 면역요법제의 반복 투여 |
| IL292575A (en) | 2014-09-07 | 2022-06-01 | Selecta Biosciences Inc | Methods and preparations for weakening immune responses by modulating gene expression in an antiviral transfer system |
| IL255010B2 (en) | 2015-04-15 | 2024-01-01 | Regeneron Pharma | Methods of increasing strength and functionality with gdf8 inhibitors |
| JP2016213236A (ja) * | 2015-04-30 | 2016-12-15 | 日東電工株式会社 | 半導体装置用フィルム、及び、半導体装置の製造方法 |
| AU2018236123B2 (en) | 2017-03-11 | 2024-04-18 | Selecta Biosciences, Inc. | Methods and compositions related to combined treatment with anti-inflammatories and synthetic nanocarriers comprising an immunosuppressant |
| WO2018209300A1 (en) * | 2017-05-12 | 2018-11-15 | Duke University | Methods for the use of low-dose immune modulators transiently for treating patients undergoing protein replacement therapy |
| TWI821227B (zh) * | 2017-12-22 | 2023-11-11 | 美商健臻公司 | 胺甲喋呤誘發的免疫耐受性之生物標記 |
| WO2021159092A1 (en) | 2020-02-08 | 2021-08-12 | Genzyme Corporation | Compositions and methods for treating pompe disease |
| TW202342057A (zh) * | 2022-02-07 | 2023-11-01 | 美商健生生物科技公司 | 用於減少用ｅｇｆｒ／ｍｅｔ雙特異性抗體治療之患者的輸注相關反應之方法 |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20040009906A1 (en) * | 2002-05-06 | 2004-01-15 | Kakkis Emil D. | Induction of antigen specific immunologic tolerance |
Family Cites Families (16)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4080325A (en) | 1976-11-17 | 1978-03-21 | The United States Of America As Represented By The Department Of Health, Education And Welfare | Synthesis of methotrexate |
| US4558690A (en) | 1982-01-26 | 1985-12-17 | University Of Scranton | Method of administration of chemotherapy to tumors |
| US5108987A (en) | 1982-02-25 | 1992-04-28 | Faulk Ward P | Conjugates of proteins with anti-tumor agents |
| US5028697A (en) | 1988-08-08 | 1991-07-02 | Eli Lilly And Company | Cytotoxic antibody conjugates of hydrazide derivatized methotrexate analogs via simple organic linkers |
| DE4000154A1 (de) | 1990-01-04 | 1991-07-11 | Symbiotec Gmbh | Chemotherapeutisches mittel, insbesondere zur behandlung von krebserkrankungen |
| US6015557A (en) | 1999-02-24 | 2000-01-18 | Tobinick; Edward L. | Tumor necrosis factor antagonists for the treatment of neurological disorders |
| WO2005085294A1 (ja) | 2004-03-05 | 2005-09-15 | Denki Kagaku Kogyo Kabushiki Kaisha | ヒアルロン酸−メトトレキサート結合体 |
| US7884196B2 (en) | 2004-10-06 | 2011-02-08 | Oliver Lawless | Vaccine composition comprising methylated DNA and immunomodulatory motifs |
| RU2445975C2 (ru) * | 2006-03-02 | 2012-03-27 | Алексион Фармасьютикалз, Инк. | Продление срока выживаемости аллотрансплантата путем ингибирования активности комплемента |
| WO2008094937A2 (en) | 2007-01-29 | 2008-08-07 | Joslin Diabetes Center, Inc. | Methods of modulating angiogenesis |
| US20090155207A1 (en) * | 2007-11-29 | 2009-06-18 | Hariri Robert J | Use of Immunomodulatory Compounds for the Treatment of Transverse Myelitis, Multiple Sclerosis, and Other Disorders |
| EP2077281A1 (en) * | 2008-01-02 | 2009-07-08 | Bergen Teknologioverforing AS | Anti-CD20 antibodies or fragments thereof for the treatment of chronic fatigue syndrome |
| US7914785B2 (en) * | 2008-01-02 | 2011-03-29 | Bergen Teknologieverforing As | B-cell depleting agents, like anti-CD20 antibodies or fragments thereof for the treatment of chronic fatigue syndrome |
| AU2009302117B2 (en) | 2008-10-08 | 2016-07-28 | Cambridge Enterprise Limited | Methods and compositions for diagnosis and treatment of autoimmune disease secondary to multiple sclerosis |
| BRPI0921258A2 (pt) | 2008-11-07 | 2018-10-23 | 4Sc Ag | terapia combinatória compreendendo inibidor de dhodh e metotrexato para o tratamento de doença autoimune |
| MX2013013445A (es) | 2011-05-16 | 2014-07-28 | Genzyme Corp | Induccion de tolerancia inmunologica utilizando metotrexato. |
-
2012
- 2012-05-03 MX MX2013013445A patent/MX2013013445A/es unknown
- 2012-05-03 CN CN202011422509.7A patent/CN113209288A/zh active Pending
- 2012-05-03 PH PH1/2013/502256A patent/PH12013502256A1/en unknown
- 2012-05-03 CN CN201811398468.5A patent/CN109620830A/zh active Pending
- 2012-05-03 UA UAA201314626A patent/UA117556C2/uk unknown
- 2012-05-03 MY MYPI2013003998A patent/MY173304A/en unknown
- 2012-05-03 RU RU2013155618A patent/RU2674036C2/ru active
- 2012-05-03 KR KR1020137032882A patent/KR20140040744A/ko not_active Ceased
- 2012-05-03 CN CN201910138372.3A patent/CN110124039A/zh active Pending
- 2012-05-03 EP EP12785624.3A patent/EP2709627B1/en active Active
- 2012-05-03 KR KR1020207027913A patent/KR102316283B1/ko active Active
- 2012-05-03 ES ES12785624T patent/ES2836823T3/es active Active
- 2012-05-03 JP JP2014511390A patent/JP6174572B2/ja active Active
- 2012-05-03 PE PE2013002499A patent/PE20140469A1/es not_active Application Discontinuation
- 2012-05-03 US US14/116,486 patent/US20140135337A1/en not_active Abandoned
- 2012-05-03 EP EP20197579.4A patent/EP3824890A1/en active Pending
- 2012-05-03 KR KR1020197033979A patent/KR102163285B1/ko active Active
- 2012-05-03 PT PT127856243T patent/PT2709627T/pt unknown
- 2012-05-03 CN CN201280035299.3A patent/CN103648501A/zh active Pending
- 2012-05-03 AU AU2012256281A patent/AU2012256281B2/en active Active
- 2012-05-03 CA CA2835819A patent/CA2835819A1/en not_active Abandoned
- 2012-05-03 BR BR112013029501A patent/BR112013029501A2/pt not_active Application Discontinuation
- 2012-05-03 SG SG2013082003A patent/SG194802A1/en unknown
- 2012-05-03 WO PCT/US2012/036405 patent/WO2012158362A1/en not_active Ceased
-
2013
- 2013-11-04 IL IL229245A patent/IL229245B/en active IP Right Grant
- 2013-11-06 ZA ZA2013/08315A patent/ZA201308315B/en unknown
- 2013-11-13 TN TNP2013000472A patent/TN2013000472A1/fr unknown
- 2013-11-14 GT GT201300278A patent/GT201300278A/es unknown
- 2013-11-14 NI NI201300121A patent/NI201300121A/es unknown
- 2013-11-15 CL CL2013003298A patent/CL2013003298A1/es unknown
- 2013-11-15 DO DO2013000268A patent/DOP2013000268A/es unknown
- 2013-12-04 MA MA36522A patent/MA35165B1/fr unknown
- 2013-12-05 CO CO13286019A patent/CO6841993A2/es not_active Application Discontinuation
- 2013-12-13 EC ECSP13013081 patent/ECSP13013081A/es unknown
-
2017
- 2017-03-03 JP JP2017040046A patent/JP6381707B2/ja active Active
-
2018
- 2018-08-02 JP JP2018145564A patent/JP6694020B2/ja active Active
-
2020
- 2020-03-24 US US16/828,407 patent/US11672802B2/en active Active
- 2020-08-23 IL IL276879A patent/IL276879B/en unknown
-
2023
- 2023-04-28 US US18/141,128 patent/US20230372347A1/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20040009906A1 (en) * | 2002-05-06 | 2004-01-15 | Kakkis Emil D. | Induction of antigen specific immunologic tolerance |
| CN1652814A (zh) * | 2002-05-06 | 2005-08-10 | 比奥马林药物公司 | 抗原特异性免疫耐受的诱导 |
Non-Patent Citations (1)
| Title |
|---|
| A. JOSEPH，等: "Immune tolerance induction to enzyme-replacement therapy by co-adminstration of short-term, low-dose methotrexate in a murine Pompe disease model", 《CLINICAL AND EXPERIMENTAL IMMUNOLOGY》 * |
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN110124039A (zh) | 使用甲氨蝶呤诱导免疫耐受性 | |
| Serreze et al. | Loss of intra-islet CD20 expression may complicate efficacy of B-cell–directed type 1 diabetes therapies | |
| CN106668852A (zh) | 治疗和/或预防ⅰ型糖尿病的疫苗及其应用 | |
| JP7752414B2 (ja) | 異種移植片寛容を誘導し、免疫適格性及び胸腺機能を回復させるためのハイブリッド胸腺、その製造方法及び使用方法 | |
| Chong et al. | Anti-galactose-α (1, 3) galactose antibody production in α1, 3-galactosyltransferase gene knockout mice after xeno and allo transplantation | |
| EP2351832A1 (en) | Composition for inducing th2 cell, therapeutic composition for th2-type disease, and use of same | |
| HK40053628A (en) | Induction of immune tolerance by using methotrexate | |
| HK40012743A (en) | Induction of immune tolerance by using methotrexate | |
| HK40007634A (en) | Induction of immune tolerance by using methotrexate | |
| HK40053503A (en) | Induction of immune tolerance using methotrexate | |
| Elliott | Neutrophils as the key mediators of antibody-mediated arthritis and edema: The central role of Syk | |
| OA16781A (en) | Induction of immune tolerance by using methotrexate. | |
| NZ716716B2 (en) | Induction of immune tolerance by using methotrexate | |
| NZ617575B2 (en) | Induction of immune tolerance by using methotrexate | |
| HK1194668B (en) | Induction of immune tolerance by using methotrexate | |
| NZ742216B2 (en) | Induction of immune tolerance by using methotrexate | |
| Perng | The Influence of Cd4+ T Cell Affinity for Self-Antigen on the Development of Inflammatory Arthritis |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| REG | Reference to a national code |
Ref country code: HK Ref legal event code: DE Ref document number: 40012743 Country of ref document: HK |
|
| WD01 | Invention patent application deemed withdrawn after publication | ||
| WD01 | Invention patent application deemed withdrawn after publication |
Application publication date: 20190816 |