JP5892931B2 - 細胞治療において使用するための方法および組成物 - Google Patents
細胞治療において使用するための方法および組成物 Download PDFInfo
- Publication number
- JP5892931B2 JP5892931B2 JP2012519080A JP2012519080A JP5892931B2 JP 5892931 B2 JP5892931 B2 JP 5892931B2 JP 2012519080 A JP2012519080 A JP 2012519080A JP 2012519080 A JP2012519080 A JP 2012519080A JP 5892931 B2 JP5892931 B2 JP 5892931B2
- Authority
- JP
- Japan
- Prior art keywords
- cells
- pharmaceutical composition
- cell
- composition according
- administered
- 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.)
- Active
Links
- 239000000203 mixture Substances 0.000 title claims description 32
- 238000000034 method Methods 0.000 title description 76
- 238000002659 cell therapy Methods 0.000 title description 17
- 210000004027 cell Anatomy 0.000 claims description 188
- 239000000427 antigen Substances 0.000 claims description 58
- 108091007433 antigens Proteins 0.000 claims description 58
- 102000036639 antigens Human genes 0.000 claims description 58
- 210000001519 tissue Anatomy 0.000 claims description 43
- 239000008194 pharmaceutical composition Substances 0.000 claims description 38
- 239000003814 drug Substances 0.000 claims description 31
- 239000007924 injection Substances 0.000 claims description 29
- 238000002347 injection Methods 0.000 claims description 29
- 208000027866 inflammatory disease Diseases 0.000 claims description 26
- 208000024891 symptom Diseases 0.000 claims description 23
- 210000004324 lymphatic system Anatomy 0.000 claims description 22
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 21
- 208000026278 immune system disease Diseases 0.000 claims description 20
- 208000015943 Coeliac disease Diseases 0.000 claims description 17
- 108010068370 Glutens Proteins 0.000 claims description 16
- 210000001165 lymph node Anatomy 0.000 claims description 16
- 206010039073 rheumatoid arthritis Diseases 0.000 claims description 14
- 235000021312 gluten Nutrition 0.000 claims description 12
- 208000022559 Inflammatory bowel disease Diseases 0.000 claims description 10
- 210000002901 mesenchymal stem cell Anatomy 0.000 claims description 10
- 201000006417 multiple sclerosis Diseases 0.000 claims description 10
- 102000008186 Collagen Human genes 0.000 claims description 9
- 108010035532 Collagen Proteins 0.000 claims description 9
- 102000006386 Myelin Proteins Human genes 0.000 claims description 9
- 108010083674 Myelin Proteins Proteins 0.000 claims description 9
- 229920001436 collagen Polymers 0.000 claims description 9
- 210000005012 myelin Anatomy 0.000 claims description 9
- 208000035475 disorder Diseases 0.000 claims description 8
- 210000002751 lymph Anatomy 0.000 claims description 6
- 210000001185 bone marrow Anatomy 0.000 claims description 5
- 210000005210 lymphoid organ Anatomy 0.000 claims description 5
- 210000001099 axilla Anatomy 0.000 claims description 4
- 230000005855 radiation Effects 0.000 claims description 4
- 238000003384 imaging method Methods 0.000 claims description 2
- 238000012544 monitoring process Methods 0.000 claims description 2
- 230000002093 peripheral effect Effects 0.000 claims description 2
- 210000004271 bone marrow stromal cell Anatomy 0.000 description 57
- 238000011282 treatment Methods 0.000 description 53
- 210000003289 regulatory T cell Anatomy 0.000 description 44
- 210000002950 fibroblast Anatomy 0.000 description 40
- 102100029647 Apoptosis-associated speck-like protein containing a CARD Human genes 0.000 description 28
- 108010087999 Steryl-Sulfatase Proteins 0.000 description 27
- 210000000130 stem cell Anatomy 0.000 description 27
- 206010003246 arthritis Diseases 0.000 description 22
- 210000000577 adipose tissue Anatomy 0.000 description 20
- 210000002966 serum Anatomy 0.000 description 18
- 208000023275 Autoimmune disease Diseases 0.000 description 17
- 206010061218 Inflammation Diseases 0.000 description 17
- 241001465754 Metazoa Species 0.000 description 17
- 230000004054 inflammatory process Effects 0.000 description 17
- 210000000056 organ Anatomy 0.000 description 14
- 241000699670 Mus sp. Species 0.000 description 13
- 201000010099 disease Diseases 0.000 description 13
- 108020004201 indoleamine 2,3-dioxygenase Proteins 0.000 description 13
- 102000006639 indoleamine 2,3-dioxygenase Human genes 0.000 description 13
- 230000002757 inflammatory effect Effects 0.000 description 13
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 12
- 230000006378 damage Effects 0.000 description 11
- 239000007787 solid Substances 0.000 description 11
- 208000011231 Crohn disease Diseases 0.000 description 10
- 108010074328 Interferon-gamma Proteins 0.000 description 10
- 210000001744 T-lymphocyte Anatomy 0.000 description 10
- 238000007796 conventional method Methods 0.000 description 10
- 230000000694 effects Effects 0.000 description 10
- 230000014509 gene expression Effects 0.000 description 10
- 230000002519 immonomodulatory effect Effects 0.000 description 10
- 230000001225 therapeutic effect Effects 0.000 description 10
- 239000003981 vehicle Substances 0.000 description 10
- 102100037850 Interferon gamma Human genes 0.000 description 9
- NWIBSHFKIJFRCO-WUDYKRTCSA-N Mytomycin Chemical compound C1N2C(C(C(C)=C(N)C3=O)=O)=C3[C@@H](COC(N)=O)[C@@]2(OC)[C@@H]2[C@H]1N2 NWIBSHFKIJFRCO-WUDYKRTCSA-N 0.000 description 9
- 210000000987 immune system Anatomy 0.000 description 9
- 230000004957 immunoregulator effect Effects 0.000 description 9
- 210000003563 lymphoid tissue Anatomy 0.000 description 9
- 239000002609 medium Substances 0.000 description 9
- 239000003795 chemical substances by application Substances 0.000 description 8
- 210000003743 erythrocyte Anatomy 0.000 description 8
- 239000012091 fetal bovine serum Substances 0.000 description 8
- 230000008439 repair process Effects 0.000 description 8
- 208000009386 Experimental Arthritis Diseases 0.000 description 7
- 239000006143 cell culture medium Substances 0.000 description 7
- 210000002808 connective tissue Anatomy 0.000 description 7
- 229940079593 drug Drugs 0.000 description 7
- 108090000623 proteins and genes Proteins 0.000 description 7
- 230000000638 stimulation Effects 0.000 description 7
- 108700018351 Major Histocompatibility Complex Proteins 0.000 description 6
- 102100040247 Tumor necrosis factor Human genes 0.000 description 6
- 238000004113 cell culture Methods 0.000 description 6
- 208000037976 chronic inflammation Diseases 0.000 description 6
- 230000004069 differentiation Effects 0.000 description 6
- 238000001990 intravenous administration Methods 0.000 description 6
- 238000002955 isolation Methods 0.000 description 6
- YGPSJZOEDVAXAB-UHFFFAOYSA-N kynurenine Chemical compound OC(=O)C(N)CC(=O)C1=CC=CC=C1N YGPSJZOEDVAXAB-UHFFFAOYSA-N 0.000 description 6
- 239000003550 marker Substances 0.000 description 6
- 239000000463 material Substances 0.000 description 6
- 230000001404 mediated effect Effects 0.000 description 6
- 230000008569 process Effects 0.000 description 6
- UCSJYZPVAKXKNQ-HZYVHMACSA-N streptomycin Chemical compound CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](NC(N)=N)[C@H](O)[C@@H](NC(N)=N)[C@H](O)[C@H]1O UCSJYZPVAKXKNQ-HZYVHMACSA-N 0.000 description 6
- 229940124597 therapeutic agent Drugs 0.000 description 6
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 5
- 102000004190 Enzymes Human genes 0.000 description 5
- 108090000790 Enzymes Proteins 0.000 description 5
- 230000008901 benefit Effects 0.000 description 5
- 210000004369 blood Anatomy 0.000 description 5
- 239000008280 blood Substances 0.000 description 5
- 230000006020 chronic inflammation Effects 0.000 description 5
- 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 5
- 229940088598 enzyme Drugs 0.000 description 5
- 210000002683 foot Anatomy 0.000 description 5
- 210000004013 groin Anatomy 0.000 description 5
- 230000009931 harmful effect Effects 0.000 description 5
- 230000028993 immune response Effects 0.000 description 5
- 230000006872 improvement Effects 0.000 description 5
- 238000000338 in vitro Methods 0.000 description 5
- 229960004857 mitomycin Drugs 0.000 description 5
- 239000002953 phosphate buffered saline Substances 0.000 description 5
- 230000002265 prevention Effects 0.000 description 5
- 230000020382 suppression by virus of host antigen processing and presentation of peptide antigen via MHC class I Effects 0.000 description 5
- 206010009900 Colitis ulcerative Diseases 0.000 description 4
- 108010061711 Gliadin Proteins 0.000 description 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
- 201000006704 Ulcerative Colitis Diseases 0.000 description 4
- 239000002671 adjuvant Substances 0.000 description 4
- 230000000735 allogeneic effect Effects 0.000 description 4
- 239000003242 anti bacterial agent Substances 0.000 description 4
- 230000001363 autoimmune Effects 0.000 description 4
- 230000005784 autoimmunity Effects 0.000 description 4
- 230000001413 cellular effect Effects 0.000 description 4
- 238000002591 computed tomography Methods 0.000 description 4
- 239000012894 fetal calf serum Substances 0.000 description 4
- 238000001943 fluorescence-activated cell sorting Methods 0.000 description 4
- 239000012634 fragment Substances 0.000 description 4
- 229960000598 infliximab Drugs 0.000 description 4
- 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 4
- 230000000670 limiting effect Effects 0.000 description 4
- 238000007443 liposuction Methods 0.000 description 4
- 230000007246 mechanism Effects 0.000 description 4
- 108020004707 nucleic acids Proteins 0.000 description 4
- 102000039446 nucleic acids Human genes 0.000 description 4
- 150000007523 nucleic acids Chemical class 0.000 description 4
- 230000001575 pathological effect Effects 0.000 description 4
- 241000894007 species Species 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- 230000009885 systemic effect Effects 0.000 description 4
- 238000012360 testing method Methods 0.000 description 4
- 241000894006 Bacteria Species 0.000 description 3
- -1 CD11c Proteins 0.000 description 3
- 102100032912 CD44 antigen Human genes 0.000 description 3
- 102100037904 CD9 antigen Human genes 0.000 description 3
- 102000029816 Collagenase Human genes 0.000 description 3
- 108060005980 Collagenase Proteins 0.000 description 3
- 108090000695 Cytokines Proteins 0.000 description 3
- 102000004127 Cytokines Human genes 0.000 description 3
- 102100025012 Dipeptidyl peptidase 4 Human genes 0.000 description 3
- 102100037241 Endoglin Human genes 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- 102000010834 Extracellular Matrix Proteins Human genes 0.000 description 3
- 108010037362 Extracellular Matrix Proteins Proteins 0.000 description 3
- 208000007465 Giant cell arteritis Diseases 0.000 description 3
- 208000024869 Goodpasture syndrome Diseases 0.000 description 3
- 241000282412 Homo Species 0.000 description 3
- 101000868273 Homo sapiens CD44 antigen Proteins 0.000 description 3
- 101000738354 Homo sapiens CD9 antigen Proteins 0.000 description 3
- 101000908391 Homo sapiens Dipeptidyl peptidase 4 Proteins 0.000 description 3
- 101000881679 Homo sapiens Endoglin Proteins 0.000 description 3
- 101000599852 Homo sapiens Intercellular adhesion molecule 1 Proteins 0.000 description 3
- 101000800116 Homo sapiens Thy-1 membrane glycoprotein Proteins 0.000 description 3
- 102100037877 Intercellular adhesion molecule 1 Human genes 0.000 description 3
- 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 3
- 241000288906 Primates Species 0.000 description 3
- 201000004681 Psoriasis Diseases 0.000 description 3
- 102000007056 Recombinant Fusion Proteins Human genes 0.000 description 3
- 108010008281 Recombinant Fusion Proteins Proteins 0.000 description 3
- 206010039710 Scleroderma Diseases 0.000 description 3
- 208000021386 Sjogren Syndrome Diseases 0.000 description 3
- 108091008874 T cell receptors Proteins 0.000 description 3
- 102000016266 T-Cell Antigen Receptors Human genes 0.000 description 3
- 208000031981 Thrombocytopenic Idiopathic Purpura Diseases 0.000 description 3
- 102100033523 Thy-1 membrane glycoprotein Human genes 0.000 description 3
- 206010067584 Type 1 diabetes mellitus Diseases 0.000 description 3
- 206010047115 Vasculitis Diseases 0.000 description 3
- 241000700605 Viruses Species 0.000 description 3
- 230000001464 adherent effect Effects 0.000 description 3
- 210000001789 adipocyte Anatomy 0.000 description 3
- 239000005557 antagonist Substances 0.000 description 3
- 230000003110 anti-inflammatory effect Effects 0.000 description 3
- 229940088710 antibiotic agent Drugs 0.000 description 3
- 210000000612 antigen-presenting cell Anatomy 0.000 description 3
- 239000002458 cell surface marker Substances 0.000 description 3
- 210000001612 chondrocyte Anatomy 0.000 description 3
- 230000001684 chronic effect Effects 0.000 description 3
- 229960002424 collagenase Drugs 0.000 description 3
- 150000001875 compounds Chemical class 0.000 description 3
- 239000003246 corticosteroid Substances 0.000 description 3
- 229960001334 corticosteroids Drugs 0.000 description 3
- 238000011461 current therapy Methods 0.000 description 3
- 239000003937 drug carrier Substances 0.000 description 3
- 210000002744 extracellular matrix Anatomy 0.000 description 3
- 238000000684 flow cytometry Methods 0.000 description 3
- 210000000548 hind-foot Anatomy 0.000 description 3
- 239000003018 immunosuppressive agent Substances 0.000 description 3
- 238000011534 incubation Methods 0.000 description 3
- 208000036971 interstitial lung disease 2 Diseases 0.000 description 3
- 210000001503 joint Anatomy 0.000 description 3
- 238000004519 manufacturing process Methods 0.000 description 3
- 229960000485 methotrexate Drugs 0.000 description 3
- 235000018102 proteins Nutrition 0.000 description 3
- 102000004169 proteins and genes Human genes 0.000 description 3
- 230000009467 reduction Effects 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- 229960005322 streptomycin Drugs 0.000 description 3
- 238000007920 subcutaneous administration Methods 0.000 description 3
- 239000006228 supernatant Substances 0.000 description 3
- 230000008961 swelling Effects 0.000 description 3
- 208000011580 syndromic disease Diseases 0.000 description 3
- 210000002437 synoviocyte Anatomy 0.000 description 3
- 201000000596 systemic lupus erythematosus Diseases 0.000 description 3
- 206010043207 temporal arteritis Diseases 0.000 description 3
- 238000002560 therapeutic procedure Methods 0.000 description 3
- 238000002604 ultrasonography Methods 0.000 description 3
- 230000035899 viability Effects 0.000 description 3
- 208000026872 Addison Disease Diseases 0.000 description 2
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 2
- 206010002556 Ankylosing Spondylitis Diseases 0.000 description 2
- 208000003343 Antiphospholipid Syndrome Diseases 0.000 description 2
- BSYNRYMUTXBXSQ-UHFFFAOYSA-N Aspirin Chemical class CC(=O)OC1=CC=CC=C1C(O)=O BSYNRYMUTXBXSQ-UHFFFAOYSA-N 0.000 description 2
- 208000023328 Basedow disease Diseases 0.000 description 2
- 208000031229 Cardiomyopathies Diseases 0.000 description 2
- 208000001640 Fibromyalgia Diseases 0.000 description 2
- 241000287828 Gallus gallus Species 0.000 description 2
- 206010018364 Glomerulonephritis Diseases 0.000 description 2
- 208000015023 Graves' disease Diseases 0.000 description 2
- 208000030836 Hashimoto thyroiditis Diseases 0.000 description 2
- 102100031573 Hematopoietic progenitor cell antigen CD34 Human genes 0.000 description 2
- 208000035186 Hemolytic Autoimmune Anemia Diseases 0.000 description 2
- 101000728679 Homo sapiens Apoptosis-associated speck-like protein containing a CARD Proteins 0.000 description 2
- 101000777663 Homo sapiens Hematopoietic progenitor cell antigen CD34 Proteins 0.000 description 2
- 101001046686 Homo sapiens Integrin alpha-M Proteins 0.000 description 2
- 101000946889 Homo sapiens Monocyte differentiation antigen CD14 Proteins 0.000 description 2
- 101000738771 Homo sapiens Receptor-type tyrosine-protein phosphatase C Proteins 0.000 description 2
- 201000009794 Idiopathic Pulmonary Fibrosis Diseases 0.000 description 2
- 206010021245 Idiopathic thrombocytopenic purpura Diseases 0.000 description 2
- 102000004877 Insulin Human genes 0.000 description 2
- 108090001061 Insulin Proteins 0.000 description 2
- 102100022338 Integrin alpha-M Human genes 0.000 description 2
- 102100022297 Integrin alpha-X Human genes 0.000 description 2
- DCXYFEDJOCDNAF-REOHCLBHSA-N L-asparagine Chemical compound OC(=O)[C@@H](N)CC(N)=O DCXYFEDJOCDNAF-REOHCLBHSA-N 0.000 description 2
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 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
- 102100035877 Monocyte differentiation antigen CD14 Human genes 0.000 description 2
- 102000002233 Myelin-Oligodendrocyte Glycoprotein Human genes 0.000 description 2
- 108010000123 Myelin-Oligodendrocyte Glycoprotein Proteins 0.000 description 2
- 208000003076 Osteolysis Diseases 0.000 description 2
- 208000031845 Pernicious anaemia Diseases 0.000 description 2
- 102100024616 Platelet endothelial cell adhesion molecule Human genes 0.000 description 2
- 108010038512 Platelet-Derived Growth Factor Proteins 0.000 description 2
- 102000010780 Platelet-Derived Growth Factor Human genes 0.000 description 2
- RJKFOVLPORLFTN-LEKSSAKUSA-N Progesterone 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 2
- 102100040120 Prominin-1 Human genes 0.000 description 2
- 201000001263 Psoriatic Arthritis Diseases 0.000 description 2
- 208000036824 Psoriatic arthropathy Diseases 0.000 description 2
- 241000700159 Rattus Species 0.000 description 2
- 102100037422 Receptor-type tyrosine-protein phosphatase C Human genes 0.000 description 2
- 239000012891 Ringer solution Substances 0.000 description 2
- 208000018359 Systemic autoimmune disease Diseases 0.000 description 2
- 208000001106 Takayasu Arteritis Diseases 0.000 description 2
- 102000004142 Trypsin Human genes 0.000 description 2
- 108090000631 Trypsin Proteins 0.000 description 2
- 102100023543 Vascular cell adhesion protein 1 Human genes 0.000 description 2
- 241000251539 Vertebrata <Metazoa> Species 0.000 description 2
- 208000027418 Wounds and injury Diseases 0.000 description 2
- 229940024606 amino acid Drugs 0.000 description 2
- 235000001014 amino acid Nutrition 0.000 description 2
- 150000001413 amino acids Chemical class 0.000 description 2
- APKFDSVGJQXUKY-INPOYWNPSA-N amphotericin B Chemical compound O[C@H]1[C@@H](N)[C@H](O)[C@@H](C)O[C@H]1O[C@H]1/C=C/C=C/C=C/C=C/C=C/C=C/C=C/[C@H](C)[C@@H](O)[C@@H](C)[C@H](C)OC(=O)C[C@H](O)C[C@H](O)CC[C@@H](O)[C@H](O)C[C@H](O)C[C@](O)(C[C@H](O)[C@H]2C(O)=O)O[C@H]2C1 APKFDSVGJQXUKY-INPOYWNPSA-N 0.000 description 2
- 229960000723 ampicillin Drugs 0.000 description 2
- AVKUERGKIZMTKX-NJBDSQKTSA-N ampicillin Chemical compound C1([C@@H](N)C(=O)N[C@H]2[C@H]3SC([C@@H](N3C2=O)C(O)=O)(C)C)=CC=CC=C1 AVKUERGKIZMTKX-NJBDSQKTSA-N 0.000 description 2
- 229940124599 anti-inflammatory drug Drugs 0.000 description 2
- 230000030741 antigen processing and presentation Effects 0.000 description 2
- 208000006673 asthma Diseases 0.000 description 2
- 201000003710 autoimmune thrombocytopenic purpura Diseases 0.000 description 2
- LMEKQMALGUDUQG-UHFFFAOYSA-N azathioprine Chemical compound CN1C=NC([N+]([O-])=O)=C1SC1=NC=NC2=C1NC=N2 LMEKQMALGUDUQG-UHFFFAOYSA-N 0.000 description 2
- 229960002170 azathioprine Drugs 0.000 description 2
- 230000009286 beneficial effect Effects 0.000 description 2
- 230000004071 biological effect Effects 0.000 description 2
- 239000012888 bovine serum Substances 0.000 description 2
- 244000309466 calf Species 0.000 description 2
- 210000000845 cartilage Anatomy 0.000 description 2
- 230000005779 cell damage Effects 0.000 description 2
- 208000037887 cell injury Diseases 0.000 description 2
- 239000006285 cell suspension Substances 0.000 description 2
- 238000005119 centrifugation Methods 0.000 description 2
- 208000025302 chronic primary adrenal insufficiency Diseases 0.000 description 2
- 238000010367 cloning Methods 0.000 description 2
- 230000009089 cytolysis Effects 0.000 description 2
- 230000007547 defect Effects 0.000 description 2
- 238000006731 degradation reaction Methods 0.000 description 2
- 201000001981 dermatomyositis Diseases 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 230000018109 developmental process Effects 0.000 description 2
- 206010012601 diabetes mellitus Diseases 0.000 description 2
- 210000002889 endothelial cell Anatomy 0.000 description 2
- 239000012530 fluid Substances 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 238000004128 high performance liquid chromatography Methods 0.000 description 2
- 229940088597 hormone Drugs 0.000 description 2
- 239000005556 hormone Substances 0.000 description 2
- 210000003035 hyaline cartilage Anatomy 0.000 description 2
- JYGXADMDTFJGBT-VWUMJDOOSA-N hydrocortisone Chemical compound O=C1CC[C@]2(C)[C@H]3[C@@H](O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 JYGXADMDTFJGBT-VWUMJDOOSA-N 0.000 description 2
- 210000002865 immune cell Anatomy 0.000 description 2
- 230000001939 inductive effect Effects 0.000 description 2
- 208000015181 infectious disease Diseases 0.000 description 2
- 239000003112 inhibitor Substances 0.000 description 2
- 230000005764 inhibitory process Effects 0.000 description 2
- 208000014674 injury Diseases 0.000 description 2
- 229940125396 insulin Drugs 0.000 description 2
- 238000010253 intravenous injection Methods 0.000 description 2
- 210000000265 leukocyte Anatomy 0.000 description 2
- 239000003446 ligand Substances 0.000 description 2
- 230000007774 longterm Effects 0.000 description 2
- 206010025135 lupus erythematosus Diseases 0.000 description 2
- 210000001365 lymphatic vessel Anatomy 0.000 description 2
- 208000029791 lytic metastatic bone lesion Diseases 0.000 description 2
- 238000012423 maintenance Methods 0.000 description 2
- GLVAUDGFNGKCSF-UHFFFAOYSA-N mercaptopurine Chemical compound S=C1NC=NC2=C1NC=N2 GLVAUDGFNGKCSF-UHFFFAOYSA-N 0.000 description 2
- 108091005601 modified peptides Proteins 0.000 description 2
- 238000010172 mouse model Methods 0.000 description 2
- 210000000663 muscle cell Anatomy 0.000 description 2
- 206010028417 myasthenia gravis Diseases 0.000 description 2
- 239000008188 pellet Substances 0.000 description 2
- 239000004033 plastic Substances 0.000 description 2
- 208000005987 polymyositis Diseases 0.000 description 2
- 108090000765 processed proteins & peptides Proteins 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 108060006613 prolamin Proteins 0.000 description 2
- 230000002062 proliferating effect Effects 0.000 description 2
- 230000004044 response Effects 0.000 description 2
- 238000004062 sedimentation Methods 0.000 description 2
- 230000003637 steroidlike Effects 0.000 description 2
- 210000002536 stromal cell Anatomy 0.000 description 2
- 230000004083 survival effect Effects 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 208000037816 tissue injury Diseases 0.000 description 2
- 238000011269 treatment regimen Methods 0.000 description 2
- 239000012588 trypsin Substances 0.000 description 2
- 210000003462 vein Anatomy 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- JNTMAZFVYNDPLB-PEDHHIEDSA-N (2S,3S)-2-[[[(2S)-1-[(2S,3S)-2-amino-3-methyl-1-oxopentyl]-2-pyrrolidinyl]-oxomethyl]amino]-3-methylpentanoic acid Chemical compound CC[C@H](C)[C@H](N)C(=O)N1CCC[C@H]1C(=O)N[C@@H]([C@@H](C)CC)C(O)=O JNTMAZFVYNDPLB-PEDHHIEDSA-N 0.000 description 1
- ZSOPWZQRZHWYFY-NUXPJIRBSA-N (2s,3s)-2-amino-3-methyl-1-(1,3-thiazolidin-3-yl)pentan-1-one;(e)-but-2-enedioic acid Chemical compound OC(=O)\C=C\C(O)=O.CC[C@H](C)[C@H](N)C(=O)N1CCSC1 ZSOPWZQRZHWYFY-NUXPJIRBSA-N 0.000 description 1
- UCTWMZQNUQWSLP-VIFPVBQESA-N (R)-adrenaline Chemical compound CNC[C@H](O)C1=CC=C(O)C(O)=C1 UCTWMZQNUQWSLP-VIFPVBQESA-N 0.000 description 1
- 229930182837 (R)-adrenaline Natural products 0.000 description 1
- FUFLCEKSBBHCMO-UHFFFAOYSA-N 11-dehydrocorticosterone Natural products O=C1CCC2(C)C3C(=O)CC(C)(C(CC4)C(=O)CO)C4C3CCC2=C1 FUFLCEKSBBHCMO-UHFFFAOYSA-N 0.000 description 1
- KZDCMKVLEYCGQX-UDPGNSCCSA-N 2-(diethylamino)ethyl 4-aminobenzoate;(2s,5r,6r)-3,3-dimethyl-7-oxo-6-[(2-phenylacetyl)amino]-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid;hydrate Chemical group O.CCN(CC)CCOC(=O)C1=CC=C(N)C=C1.N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 KZDCMKVLEYCGQX-UDPGNSCCSA-N 0.000 description 1
- WOXFMYVTSLAQMO-UHFFFAOYSA-N 2-Pyridinemethanamine Chemical compound NCC1=CC=CC=N1 WOXFMYVTSLAQMO-UHFFFAOYSA-N 0.000 description 1
- KISWVXRQTGLFGD-UHFFFAOYSA-N 2-[[2-[[6-amino-2-[[2-[[2-[[5-amino-2-[[2-[[1-[2-[[6-amino-2-[(2,5-diamino-5-oxopentanoyl)amino]hexanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]pyrrolidine-2-carbonyl]amino]-3-hydroxypropanoyl]amino]-5-oxopentanoyl]amino]-5-(diaminomethylideneamino)p Chemical compound C1CCN(C(=O)C(CCCN=C(N)N)NC(=O)C(CCCCN)NC(=O)C(N)CCC(N)=O)C1C(=O)NC(CO)C(=O)NC(CCC(N)=O)C(=O)NC(CCCN=C(N)N)C(=O)NC(CO)C(=O)NC(CCCCN)C(=O)NC(C(=O)NC(CC(C)C)C(O)=O)CC1=CC=C(O)C=C1 KISWVXRQTGLFGD-UHFFFAOYSA-N 0.000 description 1
- HVCOBJNICQPDBP-UHFFFAOYSA-N 3-[3-[3,5-dihydroxy-6-methyl-4-(3,4,5-trihydroxy-6-methyloxan-2-yl)oxyoxan-2-yl]oxydecanoyloxy]decanoic acid;hydrate Chemical compound O.OC1C(OC(CC(=O)OC(CCCCCCC)CC(O)=O)CCCCCCC)OC(C)C(O)C1OC1C(O)C(O)C(O)C(C)O1 HVCOBJNICQPDBP-UHFFFAOYSA-N 0.000 description 1
- WUBBRNOQWQTFEX-UHFFFAOYSA-N 4-aminosalicylic acid Chemical compound NC1=CC=C(C(O)=O)C(O)=C1 WUBBRNOQWQTFEX-UHFFFAOYSA-N 0.000 description 1
- VNACOBVZDCLAEV-GXKRWWSZSA-N 6-[2-[[2-[(2s)-2-cyanopyrrolidin-1-yl]-2-oxoethyl]amino]ethylamino]pyridine-3-carbonitrile;dihydrochloride Chemical compound Cl.Cl.N1([C@@H](CCC1)C#N)C(=O)CNCCNC1=CC=C(C#N)C=N1 VNACOBVZDCLAEV-GXKRWWSZSA-N 0.000 description 1
- 208000004998 Abdominal Pain Diseases 0.000 description 1
- 206010001367 Adrenal insufficiency Diseases 0.000 description 1
- 208000008190 Agammaglobulinemia Diseases 0.000 description 1
- 108010088751 Albumins Proteins 0.000 description 1
- 102000009027 Albumins Human genes 0.000 description 1
- PQSUYGKTWSAVDQ-ZVIOFETBSA-N Aldosterone Chemical compound C([C@@]1([C@@H](C(=O)CO)CC[C@H]1[C@@H]1CC2)C=O)[C@H](O)[C@@H]1[C@]1(C)C2=CC(=O)CC1 PQSUYGKTWSAVDQ-ZVIOFETBSA-N 0.000 description 1
- 208000032671 Allergic granulomatous angiitis Diseases 0.000 description 1
- 229930183010 Amphotericin Natural products 0.000 description 1
- QGGFZZLFKABGNL-UHFFFAOYSA-N Amphotericin A Natural products OC1C(N)C(O)C(C)OC1OC1C=CC=CC=CC=CCCC=CC=CC(C)C(O)C(C)C(C)OC(=O)CC(O)CC(O)CCC(O)C(O)CC(O)CC(O)(CC(O)C2C(O)=O)OC2C1 QGGFZZLFKABGNL-UHFFFAOYSA-N 0.000 description 1
- 206010002091 Anaesthesia Diseases 0.000 description 1
- 208000032467 Aplastic anaemia Diseases 0.000 description 1
- 206010003210 Arteriosclerosis Diseases 0.000 description 1
- 208000036487 Arthropathies Diseases 0.000 description 1
- 201000001320 Atherosclerosis Diseases 0.000 description 1
- 208000012657 Atopic disease Diseases 0.000 description 1
- 206010003827 Autoimmune hepatitis Diseases 0.000 description 1
- 206010050245 Autoimmune thrombocytopenia Diseases 0.000 description 1
- 230000003844 B-cell-activation Effects 0.000 description 1
- 208000035143 Bacterial infection Diseases 0.000 description 1
- 208000009137 Behcet syndrome Diseases 0.000 description 1
- 208000008439 Biliary Liver Cirrhosis Diseases 0.000 description 1
- 208000033222 Biliary cirrhosis primary Diseases 0.000 description 1
- 108010006654 Bleomycin Proteins 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- 201000002829 CREST Syndrome Diseases 0.000 description 1
- 241000282472 Canis lupus familiaris Species 0.000 description 1
- 241000283707 Capra Species 0.000 description 1
- 241000282693 Cercopithecidae Species 0.000 description 1
- 206010008685 Chondritis Diseases 0.000 description 1
- 206010008909 Chronic Hepatitis Diseases 0.000 description 1
- 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 description 1
- 208000030939 Chronic inflammatory demyelinating polyneuropathy Diseases 0.000 description 1
- 208000006344 Churg-Strauss Syndrome Diseases 0.000 description 1
- 208000011038 Cold agglutinin disease Diseases 0.000 description 1
- 206010009868 Cold type haemolytic anaemia Diseases 0.000 description 1
- 102000000503 Collagen Type II Human genes 0.000 description 1
- 108010041390 Collagen Type II Proteins 0.000 description 1
- MFYSYFVPBJMHGN-ZPOLXVRWSA-N Cortisone Chemical compound O=C1CC[C@]2(C)[C@H]3C(=O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 MFYSYFVPBJMHGN-ZPOLXVRWSA-N 0.000 description 1
- MFYSYFVPBJMHGN-UHFFFAOYSA-N Cortisone Natural products O=C1CCC2(C)C3C(=O)CC(C)(C(CC4)(O)C(=O)CO)C4C3CCC2=C1 MFYSYFVPBJMHGN-UHFFFAOYSA-N 0.000 description 1
- 208000019707 Cryoglobulinemic vasculitis Diseases 0.000 description 1
- CMSMOCZEIVJLDB-UHFFFAOYSA-N Cyclophosphamide Chemical compound ClCCN(CCCl)P1(=O)NCCCO1 CMSMOCZEIVJLDB-UHFFFAOYSA-N 0.000 description 1
- CKLJMWTZIZZHCS-UHFFFAOYSA-N D-OH-Asp Natural products OC(=O)C(N)CC(O)=O CKLJMWTZIZZHCS-UHFFFAOYSA-N 0.000 description 1
- QNAYBMKLOCPYGJ-UHFFFAOYSA-N D-alpha-Ala Natural products CC([NH3+])C([O-])=O QNAYBMKLOCPYGJ-UHFFFAOYSA-N 0.000 description 1
- KDXKERNSBIXSRK-RXMQYKEDSA-N D-lysine Chemical compound NCCCC[C@@H](N)C(O)=O KDXKERNSBIXSRK-RXMQYKEDSA-N 0.000 description 1
- URRAHSMDPCMOTH-LNLFQRSKSA-N Denagliptin Chemical compound C=1C=C(F)C=CC=1C([C@H](N)C(=O)N1[C@@H](C[C@H](F)C1)C#N)C1=CC=C(F)C=C1 URRAHSMDPCMOTH-LNLFQRSKSA-N 0.000 description 1
- 201000004624 Dermatitis Diseases 0.000 description 1
- 206010012735 Diarrhoea Diseases 0.000 description 1
- 201000003066 Diffuse Scleroderma Diseases 0.000 description 1
- 206010061818 Disease progression Diseases 0.000 description 1
- 208000004232 Enteritis Diseases 0.000 description 1
- 208000018428 Eosinophilic granulomatosis with polyangiitis Diseases 0.000 description 1
- 241000283086 Equidae Species 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- 102100024785 Fibroblast growth factor 2 Human genes 0.000 description 1
- 108090000379 Fibroblast growth factor 2 Proteins 0.000 description 1
- 238000012413 Fluorescence activated cell sorting analysis Methods 0.000 description 1
- 241000233866 Fungi Species 0.000 description 1
- 101000766307 Gallus gallus Ovotransferrin Proteins 0.000 description 1
- CEAZRRDELHUEMR-URQXQFDESA-N Gentamicin Chemical compound O1[C@H](C(C)NC)CC[C@@H](N)[C@H]1O[C@H]1[C@H](O)[C@@H](O[C@@H]2[C@@H]([C@@H](NC)[C@@](C)(O)CO2)O)[C@H](N)C[C@@H]1N CEAZRRDELHUEMR-URQXQFDESA-N 0.000 description 1
- 229930182566 Gentamicin Natural products 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Chemical compound OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 1
- 229930186217 Glycolipid Natural products 0.000 description 1
- 208000009329 Graft vs Host Disease Diseases 0.000 description 1
- 206010018691 Granuloma Diseases 0.000 description 1
- 208000035895 Guillain-Barré syndrome Diseases 0.000 description 1
- 208000001204 Hashimoto Disease Diseases 0.000 description 1
- 206010062639 Herpes dermatitis Diseases 0.000 description 1
- 101000661600 Homo sapiens Steryl-sulfatase Proteins 0.000 description 1
- 206010020751 Hypersensitivity Diseases 0.000 description 1
- 206010020850 Hyperthyroidism Diseases 0.000 description 1
- 206010020983 Hypogammaglobulinaemia Diseases 0.000 description 1
- 206010021074 Hypoplastic anaemia Diseases 0.000 description 1
- HEFNNWSXXWATRW-UHFFFAOYSA-N Ibuprofen Chemical compound CC(C)CC1=CC=C(C(C)C(O)=O)C=C1 HEFNNWSXXWATRW-UHFFFAOYSA-N 0.000 description 1
- 206010021460 Immunodeficiency syndromes Diseases 0.000 description 1
- 102000008070 Interferon-gamma Human genes 0.000 description 1
- 206010023203 Joint destruction Diseases 0.000 description 1
- 208000012659 Joint disease Diseases 0.000 description 1
- 206010023230 Joint stiffness Diseases 0.000 description 1
- 208000003456 Juvenile Arthritis Diseases 0.000 description 1
- 206010059176 Juvenile idiopathic arthritis Diseases 0.000 description 1
- 238000012313 Kruskal-Wallis test Methods 0.000 description 1
- QNAYBMKLOCPYGJ-UWTATZPHSA-N L-Alanine Natural products C[C@@H](N)C(O)=O QNAYBMKLOCPYGJ-UWTATZPHSA-N 0.000 description 1
- CKLJMWTZIZZHCS-UWTATZPHSA-N L-Aspartic acid Natural products OC(=O)[C@H](N)CC(O)=O CKLJMWTZIZZHCS-UWTATZPHSA-N 0.000 description 1
- XUJNEKJLAYXESH-REOHCLBHSA-N L-Cysteine Chemical compound SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-N 0.000 description 1
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 1
- ODKSFYDXXFIFQN-BYPYZUCNSA-N L-arginine Chemical compound OC(=O)[C@@H](N)CCCN=C(N)N ODKSFYDXXFIFQN-BYPYZUCNSA-N 0.000 description 1
- 229930064664 L-arginine Natural products 0.000 description 1
- 235000014852 L-arginine Nutrition 0.000 description 1
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 1
- LEVWYRKDKASIDU-IMJSIDKUSA-N L-cystine Chemical compound [O-]C(=O)[C@@H]([NH3+])CSSC[C@H]([NH3+])C([O-])=O LEVWYRKDKASIDU-IMJSIDKUSA-N 0.000 description 1
- 235000019393 L-cystine Nutrition 0.000 description 1
- 239000004158 L-cystine Substances 0.000 description 1
- 229930182816 L-glutamine Natural products 0.000 description 1
- QIVBCDIJIAJPQS-VIFPVBQESA-N L-tryptophane Chemical compound C1=CC=C2C(C[C@H](N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-VIFPVBQESA-N 0.000 description 1
- 201000010743 Lambert-Eaton myasthenic syndrome Diseases 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 208000027530 Meniere disease Diseases 0.000 description 1
- 101150076359 Mhc gene Proteins 0.000 description 1
- 206010049567 Miller Fisher syndrome Diseases 0.000 description 1
- 229930192392 Mitomycin Natural products 0.000 description 1
- 208000003250 Mixed connective tissue disease Diseases 0.000 description 1
- 241000699666 Mus <mouse, genus> Species 0.000 description 1
- 206010052904 Musculoskeletal stiffness Diseases 0.000 description 1
- 206010028424 Myasthenic syndrome Diseases 0.000 description 1
- 241000204031 Mycoplasma Species 0.000 description 1
- 208000009525 Myocarditis Diseases 0.000 description 1
- 206010028851 Necrosis Diseases 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 206010030113 Oedema Diseases 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 241001494479 Pecora Species 0.000 description 1
- 206010034277 Pemphigoid Diseases 0.000 description 1
- 201000011152 Pemphigus Diseases 0.000 description 1
- 241000721454 Pemphigus Species 0.000 description 1
- 229930182555 Penicillin Natural products 0.000 description 1
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 1
- 208000007048 Polymyalgia Rheumatica Diseases 0.000 description 1
- 239000004793 Polystyrene Substances 0.000 description 1
- 208000012654 Primary biliary cholangitis Diseases 0.000 description 1
- 102000003946 Prolactin Human genes 0.000 description 1
- 108010057464 Prolactin Proteins 0.000 description 1
- 108010010974 Proteolipids Proteins 0.000 description 1
- 102000016202 Proteolipids Human genes 0.000 description 1
- 206010037660 Pyrexia Diseases 0.000 description 1
- 206010038063 Rectal haemorrhage Diseases 0.000 description 1
- 241000283984 Rodentia Species 0.000 description 1
- 206010039897 Sedation Diseases 0.000 description 1
- BUGBHKTXTAQXES-UHFFFAOYSA-N Selenium Chemical compound [Se] BUGBHKTXTAQXES-UHFFFAOYSA-N 0.000 description 1
- 206010040070 Septic Shock Diseases 0.000 description 1
- 108010071390 Serum Albumin Proteins 0.000 description 1
- 102000007562 Serum Albumin Human genes 0.000 description 1
- 102000005157 Somatostatin Human genes 0.000 description 1
- 108010056088 Somatostatin Proteins 0.000 description 1
- 208000006045 Spondylarthropathies Diseases 0.000 description 1
- 241000282887 Suidae Species 0.000 description 1
- 206010042618 Surgical procedure repeated Diseases 0.000 description 1
- 206010042742 Sympathetic ophthalmia Diseases 0.000 description 1
- 201000009594 Systemic Scleroderma Diseases 0.000 description 1
- 206010042953 Systemic sclerosis Diseases 0.000 description 1
- 206010043561 Thrombocytopenic purpura Diseases 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
- QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 description 1
- 206010054094 Tumour necrosis Diseases 0.000 description 1
- 206010046851 Uveitis Diseases 0.000 description 1
- 108010000134 Vascular Cell Adhesion Molecule-1 Proteins 0.000 description 1
- 208000036142 Viral infection Diseases 0.000 description 1
- 206010047642 Vitiligo Diseases 0.000 description 1
- LEBBDRXHHNYZIA-LDUWYPJVSA-N [(2s,3r,4s,5r,6r)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl] n-[(z)-1,3-dihydroxyoctadec-4-en-2-yl]carbamate Chemical compound CCCCCCCCCCCCC\C=C/C(O)C(CO)NC(=O)O[C@@H]1O[C@H](CO)[C@H](O)[C@H](O)[C@H]1O LEBBDRXHHNYZIA-LDUWYPJVSA-N 0.000 description 1
- 210000003815 abdominal wall Anatomy 0.000 description 1
- 230000001594 aberrant effect Effects 0.000 description 1
- 230000005856 abnormality Effects 0.000 description 1
- 229960001138 acetylsalicylic acid Drugs 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 208000038016 acute inflammation Diseases 0.000 description 1
- 230000006022 acute inflammation Effects 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 230000000996 additive effect Effects 0.000 description 1
- 230000001919 adrenal effect Effects 0.000 description 1
- 208000017515 adrenocortical insufficiency Diseases 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 238000013019 agitation Methods 0.000 description 1
- 229960003767 alanine Drugs 0.000 description 1
- 208000026935 allergic disease Diseases 0.000 description 1
- 230000000172 allergic effect Effects 0.000 description 1
- 230000007815 allergy Effects 0.000 description 1
- 230000000961 alloantigen Effects 0.000 description 1
- 229960001667 alogliptin Drugs 0.000 description 1
- ZSBOMTDTBDDKMP-OAHLLOKOSA-N alogliptin Chemical compound C=1C=CC=C(C#N)C=1CN1C(=O)N(C)C(=O)C=C1N1CCC[C@@H](N)C1 ZSBOMTDTBDDKMP-OAHLLOKOSA-N 0.000 description 1
- 208000004631 alopecia areata Diseases 0.000 description 1
- 230000004075 alteration Effects 0.000 description 1
- 229960004909 aminosalicylic acid Drugs 0.000 description 1
- 235000019270 ammonium chloride Nutrition 0.000 description 1
- 229940009444 amphotericin Drugs 0.000 description 1
- 230000037005 anaesthesia Effects 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 208000007502 anemia Diseases 0.000 description 1
- 230000033115 angiogenesis Effects 0.000 description 1
- 238000002399 angioplasty Methods 0.000 description 1
- 230000000843 anti-fungal effect Effects 0.000 description 1
- 230000000259 anti-tumor effect Effects 0.000 description 1
- 229940121375 antifungal agent Drugs 0.000 description 1
- 208000011775 arteriosclerosis disease Diseases 0.000 description 1
- 230000002917 arthritic effect Effects 0.000 description 1
- 229960001230 asparagine Drugs 0.000 description 1
- 229960005261 aspartic acid Drugs 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 210000001130 astrocyte Anatomy 0.000 description 1
- 239000012298 atmosphere Substances 0.000 description 1
- 208000010668 atopic eczema Diseases 0.000 description 1
- 208000035362 autoimmune disorder of the nervous system Diseases 0.000 description 1
- 201000000448 autoimmune hemolytic anemia Diseases 0.000 description 1
- 208000037979 autoimmune inflammatory disease Diseases 0.000 description 1
- 208000036923 autoimmune primary adrenal insufficiency Diseases 0.000 description 1
- 230000001580 bacterial effect Effects 0.000 description 1
- 208000022362 bacterial infectious disease Diseases 0.000 description 1
- 239000003855 balanced salt solution Substances 0.000 description 1
- 230000003115 biocidal effect Effects 0.000 description 1
- 229940088623 biologically active substance Drugs 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 229960001561 bleomycin Drugs 0.000 description 1
- OYVAGSVQBOHSSS-UAPAGMARSA-O bleomycin A2 Chemical compound N([C@H](C(=O)N[C@H](C)[C@@H](O)[C@H](C)C(=O)N[C@@H]([C@H](O)C)C(=O)NCCC=1SC=C(N=1)C=1SC=C(N=1)C(=O)NCCC[S+](C)C)[C@@H](O[C@H]1[C@H]([C@@H](O)[C@H](O)[C@H](CO)O1)O[C@@H]1[C@H]([C@@H](OC(N)=O)[C@H](O)[C@@H](CO)O1)O)C=1N=CNC=1)C(=O)C1=NC([C@H](CC(N)=O)NC[C@H](N)C(N)=O)=NC(N)=C1C OYVAGSVQBOHSSS-UAPAGMARSA-O 0.000 description 1
- 210000000601 blood cell Anatomy 0.000 description 1
- 230000017531 blood circulation Effects 0.000 description 1
- 210000000988 bone and bone Anatomy 0.000 description 1
- 210000002449 bone cell Anatomy 0.000 description 1
- 208000000594 bullous pemphigoid Diseases 0.000 description 1
- 210000004413 cardiac myocyte Anatomy 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 229960000590 celecoxib Drugs 0.000 description 1
- RZEKVGVHFLEQIL-UHFFFAOYSA-N celecoxib Chemical compound C1=CC(C)=CC=C1C1=CC(C(F)(F)F)=NN1C1=CC=C(S(N)(=O)=O)C=C1 RZEKVGVHFLEQIL-UHFFFAOYSA-N 0.000 description 1
- 230000020411 cell activation Effects 0.000 description 1
- 230000024245 cell differentiation Effects 0.000 description 1
- 230000004663 cell proliferation Effects 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 208000019069 chronic childhood arthritis Diseases 0.000 description 1
- 201000005795 chronic inflammatory demyelinating polyneuritis Diseases 0.000 description 1
- 208000037893 chronic inflammatory disorder Diseases 0.000 description 1
- 230000000112 colonic effect Effects 0.000 description 1
- 238000002648 combination therapy Methods 0.000 description 1
- 230000024203 complement activation Effects 0.000 description 1
- 238000012790 confirmation Methods 0.000 description 1
- 238000011109 contamination Methods 0.000 description 1
- 229960004544 cortisone Drugs 0.000 description 1
- 229940111134 coxibs Drugs 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- 201000003278 cryoglobulinemia Diseases 0.000 description 1
- 239000003255 cyclooxygenase 2 inhibitor Substances 0.000 description 1
- 229960004397 cyclophosphamide Drugs 0.000 description 1
- 229960003067 cystine Drugs 0.000 description 1
- 230000016396 cytokine production Effects 0.000 description 1
- 230000001472 cytotoxic effect Effects 0.000 description 1
- 230000007123 defense Effects 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 230000003111 delayed effect Effects 0.000 description 1
- 229950010300 denagliptin Drugs 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 230000001066 destructive effect Effects 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 229960003957 dexamethasone Drugs 0.000 description 1
- 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 1
- RGLYKWWBQGJZGM-ISLYRVAYSA-N diethylstilbestrol Chemical compound C=1C=C(O)C=CC=1C(/CC)=C(\CC)C1=CC=C(O)C=C1 RGLYKWWBQGJZGM-ISLYRVAYSA-N 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 108010054812 diprotin A Proteins 0.000 description 1
- 231100000676 disease causative agent Toxicity 0.000 description 1
- 230000005750 disease progression Effects 0.000 description 1
- 108010007093 dispase Proteins 0.000 description 1
- 230000004064 dysfunction Effects 0.000 description 1
- 230000008482 dysregulation Effects 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 206010014599 encephalitis Diseases 0.000 description 1
- 230000002124 endocrine Effects 0.000 description 1
- 239000012645 endogenous antigen Substances 0.000 description 1
- 208000010227 enterocolitis Diseases 0.000 description 1
- 230000002255 enzymatic effect Effects 0.000 description 1
- 238000006911 enzymatic reaction Methods 0.000 description 1
- 206010015037 epilepsy Diseases 0.000 description 1
- 229960005139 epinephrine Drugs 0.000 description 1
- 229960005309 estradiol Drugs 0.000 description 1
- 230000007717 exclusion Effects 0.000 description 1
- 238000013401 experimental design Methods 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 208000030533 eye disease Diseases 0.000 description 1
- 210000004700 fetal blood Anatomy 0.000 description 1
- 239000000835 fiber Substances 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 210000004744 fore-foot Anatomy 0.000 description 1
- 238000005194 fractionation Methods 0.000 description 1
- 230000002538 fungal effect Effects 0.000 description 1
- ZZUFCTLCJUWOSV-UHFFFAOYSA-N furosemide Chemical compound C1=C(Cl)C(S(=O)(=O)N)=CC(C(O)=O)=C1NCC1=CC=CO1 ZZUFCTLCJUWOSV-UHFFFAOYSA-N 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- 238000010353 genetic engineering Methods 0.000 description 1
- 229960002518 gentamicin Drugs 0.000 description 1
- 229960002989 glutamic acid Drugs 0.000 description 1
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 1
- 229960002743 glutamine Drugs 0.000 description 1
- PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 description 1
- 239000010931 gold Substances 0.000 description 1
- 229910052737 gold Inorganic materials 0.000 description 1
- 208000024908 graft versus host disease Diseases 0.000 description 1
- 239000003102 growth factor Substances 0.000 description 1
- 230000003394 haemopoietic effect Effects 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 208000007475 hemolytic anemia Diseases 0.000 description 1
- 208000006454 hepatitis Diseases 0.000 description 1
- 210000003494 hepatocyte Anatomy 0.000 description 1
- 102000050702 human PYCARD Human genes 0.000 description 1
- 229960000890 hydrocortisone Drugs 0.000 description 1
- 229960004171 hydroxychloroquine Drugs 0.000 description 1
- XXSMGPRMXLTPCZ-UHFFFAOYSA-N hydroxychloroquine Chemical compound ClC1=CC=C2C(NC(C)CCCN(CCO)CC)=CC=NC2=C1 XXSMGPRMXLTPCZ-UHFFFAOYSA-N 0.000 description 1
- 229960001680 ibuprofen Drugs 0.000 description 1
- 230000005934 immune activation Effects 0.000 description 1
- 230000008102 immune modulation Effects 0.000 description 1
- 230000003053 immunization Effects 0.000 description 1
- 238000002649 immunization Methods 0.000 description 1
- 230000016784 immunoglobulin production Effects 0.000 description 1
- 230000002134 immunopathologic effect Effects 0.000 description 1
- 229960003444 immunosuppressant agent Drugs 0.000 description 1
- 229940125721 immunosuppressive agent Drugs 0.000 description 1
- 229940124589 immunosuppressive drug Drugs 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 208000000509 infertility Diseases 0.000 description 1
- 230000036512 infertility Effects 0.000 description 1
- 231100000535 infertility Toxicity 0.000 description 1
- 230000004968 inflammatory condition Effects 0.000 description 1
- 230000028709 inflammatory response Effects 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 239000003978 infusion fluid Substances 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 229960003130 interferon gamma Drugs 0.000 description 1
- 210000000936 intestine Anatomy 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000007912 intraperitoneal administration Methods 0.000 description 1
- 238000007913 intrathecal administration Methods 0.000 description 1
- 238000007914 intraventricular administration Methods 0.000 description 1
- 230000005865 ionizing radiation Effects 0.000 description 1
- 208000018937 joint inflammation Diseases 0.000 description 1
- 230000000366 juvenile effect Effects 0.000 description 1
- 201000002215 juvenile rheumatoid arthritis Diseases 0.000 description 1
- 229960000318 kanamycin Drugs 0.000 description 1
- 229930027917 kanamycin Natural products 0.000 description 1
- SBUJHOSQTJFQJX-NOAMYHISSA-N kanamycin Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CN)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O[C@@H]2[C@@H]([C@@H](N)[C@H](O)[C@@H](CO)O2)O)[C@H](N)C[C@@H]1N SBUJHOSQTJFQJX-NOAMYHISSA-N 0.000 description 1
- 229930182823 kanamycin A Natural products 0.000 description 1
- 201000011486 lichen planus Diseases 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 239000008297 liquid dosage form Substances 0.000 description 1
- 239000012669 liquid formulation Substances 0.000 description 1
- 239000006193 liquid solution Substances 0.000 description 1
- 239000006194 liquid suspension Substances 0.000 description 1
- 238000002690 local anesthesia Methods 0.000 description 1
- 239000003589 local anesthetic agent Substances 0.000 description 1
- 229960005015 local anesthetics Drugs 0.000 description 1
- 210000003141 lower extremity Anatomy 0.000 description 1
- 230000001050 lubricating effect Effects 0.000 description 1
- 230000001926 lymphatic effect Effects 0.000 description 1
- 210000004698 lymphocyte Anatomy 0.000 description 1
- 239000006166 lysate Substances 0.000 description 1
- 230000002934 lysing effect Effects 0.000 description 1
- 210000002540 macrophage Anatomy 0.000 description 1
- 210000004962 mammalian cell Anatomy 0.000 description 1
- 239000012577 media supplement Substances 0.000 description 1
- 229960001428 mercaptopurine Drugs 0.000 description 1
- 244000005700 microbiome Species 0.000 description 1
- 210000004877 mucosa Anatomy 0.000 description 1
- 210000002894 multi-fate stem cell Anatomy 0.000 description 1
- 208000029766 myalgic encephalomeyelitis/chronic fatigue syndrome Diseases 0.000 description 1
- 230000017074 necrotic cell death Effects 0.000 description 1
- 230000012177 negative regulation of immune response Effects 0.000 description 1
- 230000001613 neoplastic effect Effects 0.000 description 1
- 210000002569 neuron Anatomy 0.000 description 1
- 201000001119 neuropathy Diseases 0.000 description 1
- 230000007823 neuropathy Effects 0.000 description 1
- 238000010899 nucleation Methods 0.000 description 1
- 210000000963 osteoblast Anatomy 0.000 description 1
- 229940094443 oxytocics prostaglandins Drugs 0.000 description 1
- 239000006179 pH buffering agent Substances 0.000 description 1
- 230000003950 pathogenic mechanism Effects 0.000 description 1
- 201000001976 pemphigus vulgaris Diseases 0.000 description 1
- 229940049954 penicillin Drugs 0.000 description 1
- 210000005259 peripheral blood Anatomy 0.000 description 1
- 239000011886 peripheral blood Substances 0.000 description 1
- 210000003819 peripheral blood mononuclear cell Anatomy 0.000 description 1
- 208000033808 peripheral neuropathy Diseases 0.000 description 1
- 230000002085 persistent effect Effects 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 238000007747 plating Methods 0.000 description 1
- 210000001778 pluripotent stem cell Anatomy 0.000 description 1
- 201000006292 polyarteritis nodosa Diseases 0.000 description 1
- 229920002223 polystyrene Polymers 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 229960003387 progesterone Drugs 0.000 description 1
- 239000000186 progesterone Substances 0.000 description 1
- 229940097325 prolactin Drugs 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- 230000000644 propagated effect Effects 0.000 description 1
- 230000000069 prophylactic effect Effects 0.000 description 1
- 150000003180 prostaglandins Chemical class 0.000 description 1
- 208000005069 pulmonary fibrosis Diseases 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
- 108020003175 receptors Proteins 0.000 description 1
- 102000005962 receptors Human genes 0.000 description 1
- 230000000306 recurrent effect Effects 0.000 description 1
- 230000002829 reductive effect Effects 0.000 description 1
- 230000008929 regeneration Effects 0.000 description 1
- 238000011069 regeneration method Methods 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 238000002271 resection Methods 0.000 description 1
- 208000037803 restenosis Diseases 0.000 description 1
- 208000004124 rheumatic heart disease Diseases 0.000 description 1
- 229960000371 rofecoxib Drugs 0.000 description 1
- RZJQGNCSTQAWON-UHFFFAOYSA-N rofecoxib Chemical compound C1=CC(S(=O)(=O)C)=CC=C1C1=C(C=2C=CC=CC=2)C(=O)OC1 RZJQGNCSTQAWON-UHFFFAOYSA-N 0.000 description 1
- 201000000306 sarcoidosis Diseases 0.000 description 1
- 231100000241 scar Toxicity 0.000 description 1
- 230000037390 scarring Effects 0.000 description 1
- 230000009291 secondary effect Effects 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 230000036280 sedation Effects 0.000 description 1
- 229910052711 selenium Inorganic materials 0.000 description 1
- 239000011669 selenium Substances 0.000 description 1
- 239000008299 semisolid dosage form Substances 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 230000036303 septic shock Effects 0.000 description 1
- 230000035938 sexual maturation Effects 0.000 description 1
- 230000011664 signaling 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
- 229960004034 sitagliptin Drugs 0.000 description 1
- MFFMDFFZMYYVKS-SECBINFHSA-N sitagliptin Chemical compound C([C@H](CC(=O)N1CC=2N(C(=NN=2)C(F)(F)F)CC1)N)C1=CC(F)=C(F)C=C1F MFFMDFFZMYYVKS-SECBINFHSA-N 0.000 description 1
- 210000003491 skin Anatomy 0.000 description 1
- 208000017520 skin disease Diseases 0.000 description 1
- 239000002002 slurry Substances 0.000 description 1
- 210000000813 small intestine Anatomy 0.000 description 1
- 210000000329 smooth muscle myocyte Anatomy 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 229960000553 somatostatin Drugs 0.000 description 1
- NHXLMOGPVYXJNR-ATOGVRKGSA-N somatostatin Chemical compound C([C@H]1C(=O)N[C@H](C(N[C@@H](CO)C(=O)N[C@@H](CSSC[C@@H](C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@@H](CC=2C3=CC=CC=C3NC=2)C(=O)N[C@@H](CCCCN)C(=O)N[C@H](C(=O)N1)[C@@H](C)O)NC(=O)CNC(=O)[C@H](C)N)C(O)=O)=O)[C@H](O)C)C1=CC=CC=C1 NHXLMOGPVYXJNR-ATOGVRKGSA-N 0.000 description 1
- 210000000952 spleen Anatomy 0.000 description 1
- 201000005671 spondyloarthropathy Diseases 0.000 description 1
- 238000007619 statistical method Methods 0.000 description 1
- 238000004659 sterilization and disinfection Methods 0.000 description 1
- 150000003431 steroids Chemical class 0.000 description 1
- 238000010254 subcutaneous injection Methods 0.000 description 1
- 239000007929 subcutaneous injection Substances 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 239000013589 supplement Substances 0.000 description 1
- 230000009469 supplementation Effects 0.000 description 1
- 210000001258 synovial membrane Anatomy 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 210000002435 tendon Anatomy 0.000 description 1
- 230000036962 time dependent Effects 0.000 description 1
- 230000000451 tissue damage Effects 0.000 description 1
- 231100000827 tissue damage Toxicity 0.000 description 1
- 230000009772 tissue formation Effects 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 238000001890 transfection Methods 0.000 description 1
- 108091005703 transmembrane proteins Proteins 0.000 description 1
- 102000035160 transmembrane proteins Human genes 0.000 description 1
- 238000002054 transplantation Methods 0.000 description 1
- 230000001960 triggered effect Effects 0.000 description 1
- 201000008827 tuberculosis Diseases 0.000 description 1
- 210000001364 upper extremity Anatomy 0.000 description 1
- 238000002255 vaccination Methods 0.000 description 1
- 210000001215 vagina Anatomy 0.000 description 1
- 230000002792 vascular Effects 0.000 description 1
- 239000005526 vasoconstrictor agent Substances 0.000 description 1
- 229960001254 vildagliptin Drugs 0.000 description 1
- SYOKIDBDQMKNDQ-XWTIBIIYSA-N vildagliptin Chemical compound C1C(O)(C2)CC(C3)CC1CC32NCC(=O)N1CCC[C@H]1C#N SYOKIDBDQMKNDQ-XWTIBIIYSA-N 0.000 description 1
- 230000003612 virological effect Effects 0.000 description 1
- 238000012800 visualization Methods 0.000 description 1
- 238000010792 warming Methods 0.000 description 1
- 230000004580 weight loss Effects 0.000 description 1
- 208000016261 weight loss Diseases 0.000 description 1
- 238000001262 western blot Methods 0.000 description 1
- 239000002676 xenobiotic agent Substances 0.000 description 1
Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N5/00—Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
- C12N5/06—Animal cells or tissues; Human cells or tissues
- C12N5/0602—Vertebrate cells
- C12N5/0652—Cells of skeletal and connective tissues; Mesenchyme
- C12N5/0662—Stem cells
- C12N5/0667—Adipose-derived stem cells [ADSC]; Adipose stromal stem cells
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
- A61K35/12—Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
- A61K35/12—Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells
- A61K35/28—Bone marrow; Haematopoietic stem cells; Mesenchymal stem cells of any origin, e.g. adipose-derived stem cells
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/12—Antidiarrhoeals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/14—Prodigestives, e.g. acids, enzymes, appetite stimulants, antidyspeptics, tonics, antiflatulents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
-
- 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
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N5/00—Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
- C12N5/06—Animal cells or tissues; Human cells or tissues
- C12N5/0602—Vertebrate cells
- C12N5/0652—Cells of skeletal and connective tissues; Mesenchyme
- C12N5/0662—Stem cells
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
- A61K35/12—Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells
- A61K2035/122—Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells for inducing tolerance or supression of immune responses
-
- 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
- A61K2039/545—Medicinal preparations containing antigens or antibodies characterised by the dose, timing or administration schedule
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Chemical & Material Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Organic Chemistry (AREA)
- Biomedical Technology (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Developmental Biology & Embryology (AREA)
- Immunology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Biotechnology (AREA)
- Zoology (AREA)
- General Chemical & Material Sciences (AREA)
- Cell Biology (AREA)
- Wood Science & Technology (AREA)
- Genetics & Genomics (AREA)
- Epidemiology (AREA)
- Rheumatology (AREA)
- Microbiology (AREA)
- General Engineering & Computer Science (AREA)
- Virology (AREA)
- Biochemistry (AREA)
- Neurosurgery (AREA)
- Hematology (AREA)
- Neurology (AREA)
- Dermatology (AREA)
- Pain & Pain Management (AREA)
- Nutrition Science (AREA)
- Psychiatry (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Hospice & Palliative Care (AREA)
- Physical Education & Sports Medicine (AREA)
- Transplantation (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US22427509P | 2009-07-09 | 2009-07-09 | |
| US61/224,275 | 2009-07-09 | ||
| PCT/IB2010/001968 WO2011004264A1 (en) | 2009-07-09 | 2010-07-09 | Methods and compositions for use in cellular therapies |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2012532859A JP2012532859A (ja) | 2012-12-20 |
| JP2012532859A5 JP2012532859A5 (enExample) | 2013-08-15 |
| JP5892931B2 true JP5892931B2 (ja) | 2016-03-23 |
Family
ID=42782196
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2012519080A Active JP5892931B2 (ja) | 2009-07-09 | 2010-07-09 | 細胞治療において使用するための方法および組成物 |
Country Status (19)
| Country | Link |
|---|---|
| US (1) | US8679834B2 (enExample) |
| EP (2) | EP3150703A1 (enExample) |
| JP (1) | JP5892931B2 (enExample) |
| KR (1) | KR101788885B1 (enExample) |
| CN (2) | CN107007626A (enExample) |
| AU (1) | AU2010269962B2 (enExample) |
| BR (1) | BR112012000534A2 (enExample) |
| CA (1) | CA2767300C (enExample) |
| DK (1) | DK2451943T3 (enExample) |
| ES (1) | ES2479542T3 (enExample) |
| HU (1) | HUE031921T2 (enExample) |
| IL (1) | IL217377A (enExample) |
| MX (1) | MX359639B (enExample) |
| NZ (1) | NZ597975A (enExample) |
| PL (1) | PL2451943T3 (enExample) |
| PT (1) | PT2451943T (enExample) |
| RU (1) | RU2610427C2 (enExample) |
| SG (2) | SG10201403758SA (enExample) |
| WO (1) | WO2011004264A1 (enExample) |
Families Citing this family (23)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20060045872A1 (en) | 2004-08-25 | 2006-03-02 | Universidad Autonoma De Madrid Ciudad Universitaria de Cantoblanco | Use of adipose tissue-derived stromal stem cells in treating fistula |
| SG10202001007TA (en) | 2005-09-23 | 2020-03-30 | Tigenix Sau | Cell populations having immunoregulatory activity, method for isolation and uses |
| WO2011006029A1 (en) | 2009-07-10 | 2011-01-13 | University Of Pittsburgh - Of The Commonwealth System Of Higher Education | Artificial cell constructs for inducing immunological tolerance |
| US11090363B2 (en) | 2009-07-10 | 2021-08-17 | University of Pittsburgh—of the Commonwealth System of Higher Education | Vasoactive intestinal peptide release from microparticles |
| JP6018081B2 (ja) * | 2011-01-12 | 2016-11-02 | ティジェニクス エス．エー．ユー． | 自己免疫および炎症性疾患におけるリンパ系内投与用の脂肪由来間葉系幹細胞 |
| US8961956B2 (en) | 2011-11-30 | 2015-02-24 | Ocata Therapeutics, Inc. | Mesenchymal stromal cells and uses related thereto |
| PL2785359T3 (pl) | 2011-11-30 | 2018-12-31 | Astellas Institute For Regenerative Medicine | Mezenchymalne komórki zrębowe i związane z nimi zastosowania |
| EP2833896A2 (en) * | 2012-03-30 | 2015-02-11 | University Of Southern California | Compositions and treatment methods for mesenchymal stem cell-induced immunoregulation |
| CN104471059B (zh) | 2012-07-12 | 2018-04-17 | 珠海横琴爱姆斯坦生物科技有限公司 | 人胚胎干细胞衍生的间充质样干细胞、方法及其应用 |
| WO2016098061A1 (en) | 2014-12-18 | 2016-06-23 | Pluristem Ltd. | Methods and compositions for treating and preventing muscle wasting disorders |
| WO2016107563A1 (zh) * | 2014-12-29 | 2016-07-07 | 西比曼生物科技（上海）有限公司 | 一种用于治疗上呼吸道疾病的脂肪间充质祖细胞复合物 |
| CN107864627A (zh) | 2015-03-23 | 2018-03-30 | 普拉里斯坦有限公司 | 包含粘附基质细胞的方法和组合物 |
| CA3012741A1 (en) | 2016-02-18 | 2017-08-24 | Pluristem Ltd. | Methods and compositions for treating cancer and neoplasms |
| GB201604304D0 (en) | 2016-03-14 | 2016-04-27 | Tigenix S A U | Adipose tissue-derived stromal stem cells for use in treating refractory complex perianal fistulas in crohn's disease |
| EP3478300B1 (en) | 2016-06-30 | 2022-08-24 | Stem Cell Medicine Ltd. | Treatment of inflammatory bowel disease with long acting glatiramer and adipose-derived stem cells |
| EP3624815A4 (en) | 2017-05-15 | 2021-01-20 | Stem Cell Medicine Ltd. | TREATMENT OF MULTIPLE SCLEROSIS WITH LONG-ACTING GLATIRAMER AND ADAPTIVE STEM CELLS |
| IL269893B2 (en) | 2017-05-15 | 2023-10-01 | Stem Cell Medicine Ltd | Treatment of multiple sclerosis with adipose-derived stem cells |
| CN107281469A (zh) * | 2017-07-17 | 2017-10-24 | 广东颜值科技有限公司 | 一种细胞组合物及其制备方法和应用 |
| CN107349419A (zh) * | 2017-07-17 | 2017-11-17 | 广东颜值科技有限公司 | 一种细胞组合物及其制备方法和应用 |
| CN112912087A (zh) * | 2018-09-14 | 2021-06-04 | 卢卡科学株式会社 | 线粒体向淋巴器官中的移植以及用于该移植的组合物 |
| WO2020191036A1 (en) * | 2019-03-19 | 2020-09-24 | Fibrogenesis | Treatment of chronic obstructive pulmonary disease and lung degeneration using activated fibroblasts and exosome derivatives thereof |
| WO2020243504A1 (en) * | 2019-05-31 | 2020-12-03 | Figene, Llc | Concurrent activation of regenerative and tolerogenic processes by fibroblast-based compositions for the treatment of multiple sclerosis |
| WO2021207192A1 (en) * | 2020-04-08 | 2021-10-14 | Figene, Llc | Methods and compositions for allergy and asthma treatment using fibroblasts |
Family Cites Families (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20040115216A1 (en) * | 2002-07-12 | 2004-06-17 | The Johns Hopkins University | Reagents and methods for engaging unique clonotypic lymphocyte receptors |
| CN102600461B (zh) * | 2002-12-06 | 2017-07-14 | 西北生物治疗药物公司 | 给予体外部分成熟的树突细胞治疗肿瘤 |
| SG10202001007TA (en) | 2005-09-23 | 2020-03-30 | Tigenix Sau | Cell populations having immunoregulatory activity, method for isolation and uses |
| US8241621B2 (en) * | 2006-12-18 | 2012-08-14 | Medistem Laboratories | Stem cell mediated treg activation/expansion for therapeutic immune modulation |
| EP2578677A1 (en) * | 2007-08-09 | 2013-04-10 | Genzyme Corporation | Method of treating autoimmune disease with mesenchymal stem cells |
| EP2191835A4 (en) * | 2007-09-07 | 2011-12-14 | Japan Chem Res | THERAPEUTIC AND PROPHYLACTIC AGENTS FOR ARTHRITIS |
| WO2009134429A2 (en) * | 2008-05-02 | 2009-11-05 | Massachusetts Institute Of Technology | Methods and compositions for modulating immunological tolerance |
| GB0814249D0 (en) * | 2008-08-04 | 2008-09-10 | Cellerix Sa | Uses of mesenchymal stem cells |
-
2010
- 2010-07-09 HU HUE10752171A patent/HUE031921T2/en unknown
- 2010-07-09 US US13/382,426 patent/US8679834B2/en active Active
- 2010-07-09 PT PT107521718T patent/PT2451943T/pt unknown
- 2010-07-09 ES ES10752171.8T patent/ES2479542T3/es active Active
- 2010-07-09 BR BR112012000534A patent/BR112012000534A2/pt not_active Application Discontinuation
- 2010-07-09 WO PCT/IB2010/001968 patent/WO2011004264A1/en not_active Ceased
- 2010-07-09 SG SG10201403758SA patent/SG10201403758SA/en unknown
- 2010-07-09 KR KR1020127003364A patent/KR101788885B1/ko active Active
- 2010-07-09 EP EP16199980.0A patent/EP3150703A1/en not_active Withdrawn
- 2010-07-09 EP EP10752171.8A patent/EP2451943B1/en active Active
- 2010-07-09 AU AU2010269962A patent/AU2010269962B2/en active Active
- 2010-07-09 CN CN201710067652.0A patent/CN107007626A/zh active Pending
- 2010-07-09 CA CA2767300A patent/CA2767300C/en active Active
- 2010-07-09 DK DK10752171.8T patent/DK2451943T3/en active
- 2010-07-09 SG SG2012001574A patent/SG177582A1/en unknown
- 2010-07-09 PL PL10752171T patent/PL2451943T3/pl unknown
- 2010-07-09 MX MX2012000396A patent/MX359639B/es active IP Right Grant
- 2010-07-09 JP JP2012519080A patent/JP5892931B2/ja active Active
- 2010-07-09 CN CN2010800308900A patent/CN102549147A/zh active Pending
- 2010-07-09 NZ NZ597975A patent/NZ597975A/en unknown
- 2010-07-09 RU RU2012104529A patent/RU2610427C2/ru active
-
2012
- 2012-01-05 IL IL217377A patent/IL217377A/en active IP Right Grant
Also Published As
| Publication number | Publication date |
|---|---|
| CA2767300A1 (en) | 2011-01-13 |
| JP2012532859A (ja) | 2012-12-20 |
| ES2479542T1 (es) | 2014-08-20 |
| EP3150703A1 (en) | 2017-04-05 |
| KR20120051006A (ko) | 2012-05-21 |
| MX2012000396A (es) | 2012-07-17 |
| SG10201403758SA (en) | 2014-10-30 |
| CN102549147A (zh) | 2012-07-04 |
| EP2451943B1 (en) | 2016-11-23 |
| US8679834B2 (en) | 2014-03-25 |
| RU2610427C2 (ru) | 2017-02-10 |
| RU2012104529A (ru) | 2013-08-20 |
| EP2451943A1 (en) | 2012-05-16 |
| AU2010269962B2 (en) | 2016-04-14 |
| NZ597975A (en) | 2014-06-27 |
| PL2451943T3 (pl) | 2017-04-28 |
| PT2451943T (pt) | 2017-01-20 |
| HUE031921T2 (en) | 2017-08-28 |
| US20120308585A1 (en) | 2012-12-06 |
| KR101788885B1 (ko) | 2017-10-20 |
| MX359639B (es) | 2018-10-04 |
| WO2011004264A1 (en) | 2011-01-13 |
| SG177582A1 (en) | 2012-03-29 |
| DK2451943T3 (en) | 2017-02-06 |
| ES2479542T3 (es) | 2017-05-26 |
| CN107007626A (zh) | 2017-08-04 |
| IL217377A0 (en) | 2012-02-29 |
| CA2767300C (en) | 2020-01-07 |
| BR112012000534A2 (pt) | 2017-06-13 |
| AU2010269962A1 (en) | 2012-03-01 |
| IL217377A (en) | 2017-10-31 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US12186344B2 (en) | Cell populations having immunoregulatory activity, method for isolation and uses | |
| AU2010269962B2 (en) | Methods and compositions for use in cellular therapies | |
| JP6018081B2 (ja) | 自己免疫および炎症性疾患におけるリンパ系内投与用の脂肪由来間葉系幹細胞 | |
| AU2018253517B2 (en) | Cell populations having immunoregulatory activity, method for isolation and uses | |
| HK1173177A (en) | Methods and compositions for use in cellular therapies | |
| HK1173177B (en) | Methods and compositions for use in cellular therapies | |
| AU2012268272A1 (en) | Cell populations having immunoregulatory activity, method for isolation and uses |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20130701 |
|
| A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20130701 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20140725 |
|
| A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20141017 |
|
| A602 | Written permission of extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A602 Effective date: 20141024 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20150126 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20150618 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20150918 |
|
| TRDD | Decision of grant or rejection written | ||
| A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 20160125 |
|
| A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20160223 |
|
| R150 | Certificate of patent or registration of utility model |
Ref document number: 5892931 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| S111 | Request for change of ownership or part of ownership |
Free format text: JAPANESE INTERMEDIATE CODE: R313113 |
|
| S533 | Written request for registration of change of name |
Free format text: JAPANESE INTERMEDIATE CODE: R313533 |
|
| R350 | Written notification of registration of transfer |
Free format text: JAPANESE INTERMEDIATE CODE: R350 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |