JP2011042658A - Il−17産生の阻害 - Google Patents
Il−17産生の阻害 Download PDFInfo
- Publication number
- JP2011042658A JP2011042658A JP2010210980A JP2010210980A JP2011042658A JP 2011042658 A JP2011042658 A JP 2011042658A JP 2010210980 A JP2010210980 A JP 2010210980A JP 2010210980 A JP2010210980 A JP 2010210980A JP 2011042658 A JP2011042658 A JP 2011042658A
- Authority
- JP
- Japan
- Prior art keywords
- antibody
- cells
- cell
- inflammatory
- human
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
- 230000024949 interleukin-17 production Effects 0.000 title claims description 33
- 230000005764 inhibitory process Effects 0.000 title description 2
- 108010065637 Interleukin-23 Proteins 0.000 claims abstract description 153
- 102000013264 Interleukin-23 Human genes 0.000 claims abstract description 152
- 229940124829 interleukin-23 Drugs 0.000 claims abstract description 145
- 102000013691 Interleukin-17 Human genes 0.000 claims abstract description 103
- 108050003558 Interleukin-17 Proteins 0.000 claims abstract description 103
- 210000001744 T-lymphocyte Anatomy 0.000 claims abstract description 60
- 239000005557 antagonist Substances 0.000 claims abstract description 38
- 238000011282 treatment Methods 0.000 claims abstract description 26
- 238000004519 manufacturing process Methods 0.000 claims abstract description 20
- 239000000556 agonist Substances 0.000 claims abstract description 19
- 208000027866 inflammatory disease Diseases 0.000 claims abstract description 16
- 238000000034 method Methods 0.000 claims description 103
- 210000004027 cell Anatomy 0.000 claims description 83
- 238000002965 ELISA Methods 0.000 claims description 26
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 24
- 108010021625 Immunoglobulin Fragments Proteins 0.000 claims description 21
- 102000008394 Immunoglobulin Fragments Human genes 0.000 claims description 21
- 102000004196 processed proteins & peptides Human genes 0.000 claims description 19
- 229920001184 polypeptide Polymers 0.000 claims description 17
- 239000003814 drug Substances 0.000 claims description 16
- 230000014509 gene expression Effects 0.000 claims description 14
- 201000006417 multiple sclerosis Diseases 0.000 claims description 14
- 108020003175 receptors Proteins 0.000 claims description 11
- 102000005962 receptors Human genes 0.000 claims description 10
- 206010039073 rheumatoid arthritis Diseases 0.000 claims description 10
- 238000001727 in vivo Methods 0.000 claims description 9
- 230000001939 inductive effect Effects 0.000 claims description 9
- 208000015181 infectious disease Diseases 0.000 claims description 9
- 208000022559 Inflammatory bowel disease Diseases 0.000 claims description 8
- 201000004681 Psoriasis Diseases 0.000 claims description 8
- 241000187479 Mycobacterium tuberculosis Species 0.000 claims description 6
- 239000002260 anti-inflammatory agent Substances 0.000 claims description 6
- 229940121363 anti-inflammatory agent Drugs 0.000 claims description 6
- 230000001684 chronic effect Effects 0.000 claims description 6
- 208000037976 chronic inflammation Diseases 0.000 claims description 6
- 208000009137 Behcet syndrome Diseases 0.000 claims description 5
- 208000024908 graft versus host disease Diseases 0.000 claims description 5
- 206010009900 Colitis ulcerative Diseases 0.000 claims description 4
- 208000011231 Crohn disease Diseases 0.000 claims description 4
- 201000006704 Ulcerative Colitis Diseases 0.000 claims description 4
- 208000006673 asthma Diseases 0.000 claims description 4
- 230000002401 inhibitory effect Effects 0.000 claims description 4
- 229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 claims description 4
- 201000000596 systemic lupus erythematosus Diseases 0.000 claims description 4
- 208000024827 Alzheimer disease Diseases 0.000 claims description 3
- 206010002556 Ankylosing Spondylitis Diseases 0.000 claims description 3
- 201000005569 Gout Diseases 0.000 claims description 3
- 206010018634 Gouty Arthritis Diseases 0.000 claims description 3
- 206010037660 Pyrexia Diseases 0.000 claims description 3
- 206010067584 Type 1 diabetes mellitus Diseases 0.000 claims description 3
- 230000002917 arthritic effect Effects 0.000 claims description 3
- 230000006020 chronic inflammation Effects 0.000 claims description 3
- 208000037893 chronic inflammatory disorder Diseases 0.000 claims description 3
- 229940124597 therapeutic agent Drugs 0.000 claims description 3
- 208000035143 Bacterial infection Diseases 0.000 claims description 2
- 208000022362 bacterial infectious disease Diseases 0.000 claims description 2
- 239000003246 corticosteroid Substances 0.000 claims description 2
- 229960001334 corticosteroids Drugs 0.000 claims description 2
- 208000011580 syndromic disease Diseases 0.000 claims description 2
- 230000003110 anti-inflammatory effect Effects 0.000 claims 2
- 230000009429 distress Effects 0.000 claims 1
- 210000004072 lung Anatomy 0.000 claims 1
- 238000012544 monitoring process Methods 0.000 claims 1
- 230000029058 respiratory gaseous exchange Effects 0.000 claims 1
- 230000027455 binding Effects 0.000 abstract description 18
- 102000004127 Cytokines Human genes 0.000 abstract description 17
- 108090000695 Cytokines Proteins 0.000 abstract description 17
- 230000000770 proinflammatory effect Effects 0.000 abstract description 4
- 102000004554 Interleukin-17 Receptors Human genes 0.000 abstract 1
- 108010017525 Interleukin-17 Receptors Proteins 0.000 abstract 1
- 241000699670 Mus sp. Species 0.000 description 92
- 108010076561 Interleukin-23 Subunit p19 Proteins 0.000 description 36
- 102100036705 Interleukin-23 subunit alpha Human genes 0.000 description 35
- 108090000623 proteins and genes Proteins 0.000 description 35
- 108060003951 Immunoglobulin Proteins 0.000 description 31
- 102000018358 immunoglobulin Human genes 0.000 description 31
- 102100036672 Interleukin-23 receptor Human genes 0.000 description 23
- 230000000694 effects Effects 0.000 description 23
- 241000699666 Mus <mouse, genus> Species 0.000 description 21
- 108091007433 antigens Proteins 0.000 description 21
- 102000036639 antigens Human genes 0.000 description 21
- 239000012634 fragment Substances 0.000 description 21
- 101710195550 Interleukin-23 receptor Proteins 0.000 description 20
- 108010058846 Ovalbumin Proteins 0.000 description 20
- 239000000427 antigen Substances 0.000 description 20
- 230000002950 deficient Effects 0.000 description 20
- 229940092253 ovalbumin Drugs 0.000 description 20
- 230000004044 response Effects 0.000 description 20
- 102000013462 Interleukin-12 Human genes 0.000 description 19
- 108010065805 Interleukin-12 Proteins 0.000 description 19
- 229940117681 interleukin-12 Drugs 0.000 description 19
- 108020004999 messenger RNA Proteins 0.000 description 19
- 150000001875 compounds Chemical class 0.000 description 18
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 18
- 230000003053 immunization Effects 0.000 description 17
- 210000003719 b-lymphocyte Anatomy 0.000 description 16
- 201000010099 disease Diseases 0.000 description 16
- 239000002158 endotoxin Substances 0.000 description 16
- 238000002649 immunization Methods 0.000 description 16
- 230000001965 increasing effect Effects 0.000 description 16
- 102000014158 Interleukin-12 Subunit p40 Human genes 0.000 description 15
- 108010011429 Interleukin-12 Subunit p40 Proteins 0.000 description 15
- 238000006243 chemical reaction Methods 0.000 description 15
- 210000004443 dendritic cell Anatomy 0.000 description 15
- 102000004169 proteins and genes Human genes 0.000 description 15
- 238000002474 experimental method Methods 0.000 description 14
- 230000028996 humoral immune response Effects 0.000 description 14
- 210000002966 serum Anatomy 0.000 description 14
- 210000004988 splenocyte Anatomy 0.000 description 14
- 238000004458 analytical method Methods 0.000 description 13
- 229940079593 drug Drugs 0.000 description 13
- 210000005087 mononuclear cell Anatomy 0.000 description 13
- 239000006228 supernatant Substances 0.000 description 13
- 108020004414 DNA Proteins 0.000 description 12
- 235000018102 proteins Nutrition 0.000 description 12
- 101001018097 Homo sapiens L-selectin Proteins 0.000 description 11
- 102100033467 L-selectin Human genes 0.000 description 11
- 210000003071 memory t lymphocyte Anatomy 0.000 description 11
- 210000004989 spleen cell Anatomy 0.000 description 11
- 108010047041 Complementarity Determining Regions Proteins 0.000 description 10
- 210000004408 hybridoma Anatomy 0.000 description 10
- 238000000338 in vitro Methods 0.000 description 10
- 238000012360 testing method Methods 0.000 description 10
- 102100032912 CD44 antigen Human genes 0.000 description 9
- 101000868273 Homo sapiens CD44 antigen Proteins 0.000 description 9
- 230000036039 immunity Effects 0.000 description 9
- 230000006698 induction Effects 0.000 description 9
- 230000000692 anti-sense effect Effects 0.000 description 8
- 238000003556 assay Methods 0.000 description 8
- 239000003795 chemical substances by application Substances 0.000 description 8
- 230000001419 dependent effect Effects 0.000 description 8
- 108010048367 enhanced green fluorescent protein Proteins 0.000 description 8
- 230000006870 function Effects 0.000 description 8
- 108010045069 keyhole-limpet hemocyanin Proteins 0.000 description 8
- 239000000203 mixture Substances 0.000 description 8
- 239000000523 sample Substances 0.000 description 8
- 238000007423 screening assay Methods 0.000 description 8
- 210000000952 spleen Anatomy 0.000 description 8
- 108700028369 Alleles Proteins 0.000 description 7
- 108010002350 Interleukin-2 Proteins 0.000 description 7
- 241001465754 Metazoa Species 0.000 description 7
- IQFYYKKMVGJFEH-XLPZGREQSA-N Thymidine Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](CO)[C@@H](O)C1 IQFYYKKMVGJFEH-XLPZGREQSA-N 0.000 description 7
- 230000004071 biological effect Effects 0.000 description 7
- 239000006285 cell suspension Substances 0.000 description 7
- 230000007812 deficiency Effects 0.000 description 7
- 238000001514 detection method Methods 0.000 description 7
- 230000003993 interaction Effects 0.000 description 7
- 230000001404 mediated effect Effects 0.000 description 7
- 102100024458 Cyclin-dependent kinase inhibitor 2A Human genes 0.000 description 6
- 108010028921 Lipopeptides Proteins 0.000 description 6
- 230000008859 change Effects 0.000 description 6
- 238000005516 engineering process Methods 0.000 description 6
- 210000002683 foot Anatomy 0.000 description 6
- 238000009472 formulation Methods 0.000 description 6
- 210000002540 macrophage Anatomy 0.000 description 6
- 238000002823 phage display Methods 0.000 description 6
- 230000035755 proliferation Effects 0.000 description 6
- 230000001737 promoting effect Effects 0.000 description 6
- 230000000638 stimulation Effects 0.000 description 6
- 102100020792 Interleukin-12 receptor subunit beta-2 Human genes 0.000 description 5
- 101710103840 Interleukin-12 receptor subunit beta-2 Proteins 0.000 description 5
- 206010035226 Plasma cell myeloma Diseases 0.000 description 5
- 230000005867 T cell response Effects 0.000 description 5
- 239000000074 antisense oligonucleotide Substances 0.000 description 5
- 238000012230 antisense oligonucleotides Methods 0.000 description 5
- 230000015572 biosynthetic process Effects 0.000 description 5
- 230000036755 cellular response Effects 0.000 description 5
- 238000004132 cross linking Methods 0.000 description 5
- 230000002068 genetic effect Effects 0.000 description 5
- 230000028993 immune response Effects 0.000 description 5
- 230000004968 inflammatory condition Effects 0.000 description 5
- 210000001165 lymph node Anatomy 0.000 description 5
- 239000002609 medium Substances 0.000 description 5
- 201000000050 myeloid neoplasm Diseases 0.000 description 5
- 244000052769 pathogen Species 0.000 description 5
- 239000007787 solid Substances 0.000 description 5
- 230000008961 swelling Effects 0.000 description 5
- 210000001519 tissue Anatomy 0.000 description 5
- 208000035473 Communicable disease Diseases 0.000 description 4
- 229920001917 Ficoll Polymers 0.000 description 4
- 102100039556 Galectin-4 Human genes 0.000 description 4
- 241000282412 Homo Species 0.000 description 4
- 101000608765 Homo sapiens Galectin-4 Proteins 0.000 description 4
- 102000018251 Hypoxanthine Phosphoribosyltransferase Human genes 0.000 description 4
- 108010091358 Hypoxanthine Phosphoribosyltransferase Proteins 0.000 description 4
- 102000009786 Immunoglobulin Constant Regions Human genes 0.000 description 4
- 108010009817 Immunoglobulin Constant Regions Proteins 0.000 description 4
- 206010061218 Inflammation Diseases 0.000 description 4
- 102100022297 Integrin alpha-X Human genes 0.000 description 4
- 102100037850 Interferon gamma Human genes 0.000 description 4
- 108010074328 Interferon-gamma Proteins 0.000 description 4
- 102100020790 Interleukin-12 receptor subunit beta-1 Human genes 0.000 description 4
- 101710103841 Interleukin-12 receptor subunit beta-1 Proteins 0.000 description 4
- 102100030698 Interleukin-12 subunit alpha Human genes 0.000 description 4
- 241000124008 Mammalia Species 0.000 description 4
- PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 4
- 108091034117 Oligonucleotide Proteins 0.000 description 4
- 230000009471 action Effects 0.000 description 4
- 239000002671 adjuvant Substances 0.000 description 4
- 125000000539 amino acid group Chemical group 0.000 description 4
- 150000001413 amino acids Chemical class 0.000 description 4
- 210000000612 antigen-presenting cell Anatomy 0.000 description 4
- 210000004369 blood Anatomy 0.000 description 4
- 239000008280 blood Substances 0.000 description 4
- 239000003153 chemical reaction reagent Substances 0.000 description 4
- 238000011161 development Methods 0.000 description 4
- 230000018109 developmental process Effects 0.000 description 4
- 238000010790 dilution Methods 0.000 description 4
- 239000012895 dilution Substances 0.000 description 4
- 210000004602 germ cell Anatomy 0.000 description 4
- 230000004054 inflammatory process Effects 0.000 description 4
- 108040001844 interleukin-23 receptor activity proteins Proteins 0.000 description 4
- 230000007246 mechanism Effects 0.000 description 4
- 108010077055 methylated bovine serum albumin Proteins 0.000 description 4
- 230000000813 microbial effect Effects 0.000 description 4
- 239000003094 microcapsule Substances 0.000 description 4
- 230000003472 neutralizing effect Effects 0.000 description 4
- 230000008569 process Effects 0.000 description 4
- 230000001681 protective effect Effects 0.000 description 4
- 230000004850 protein–protein interaction Effects 0.000 description 4
- 150000003384 small molecules Chemical class 0.000 description 4
- 239000000243 solution Substances 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- 230000008685 targeting Effects 0.000 description 4
- 229940104230 thymidine Drugs 0.000 description 4
- 238000013519 translation Methods 0.000 description 4
- 201000008827 tuberculosis Diseases 0.000 description 4
- 206010001052 Acute respiratory distress syndrome Diseases 0.000 description 3
- 108020000948 Antisense Oligonucleotides Proteins 0.000 description 3
- DWRXFEITVBNRMK-UHFFFAOYSA-N Beta-D-1-Arabinofuranosylthymine Natural products O=C1NC(=O)C(C)=CN1C1C(O)C(O)C(CO)O1 DWRXFEITVBNRMK-UHFFFAOYSA-N 0.000 description 3
- 108010037462 Cyclooxygenase 2 Proteins 0.000 description 3
- 108010054576 Deoxyribonuclease EcoRI Proteins 0.000 description 3
- 201000004624 Dermatitis Diseases 0.000 description 3
- 238000008157 ELISA kit Methods 0.000 description 3
- 206010020751 Hypersensitivity Diseases 0.000 description 3
- 102000014154 Interleukin-12 Subunit p35 Human genes 0.000 description 3
- 108010011301 Interleukin-12 Subunit p35 Proteins 0.000 description 3
- 206010035664 Pneumonia Diseases 0.000 description 3
- 102100038280 Prostaglandin G/H synthase 2 Human genes 0.000 description 3
- 241000700159 Rattus Species 0.000 description 3
- 108700008625 Reporter Genes Proteins 0.000 description 3
- 208000013616 Respiratory Distress Syndrome Diseases 0.000 description 3
- 241000219061 Rheum Species 0.000 description 3
- 241000283984 Rodentia Species 0.000 description 3
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 3
- 238000002105 Southern blotting Methods 0.000 description 3
- 230000024932 T cell mediated immunity Effects 0.000 description 3
- 102100040247 Tumor necrosis factor Human genes 0.000 description 3
- 230000005856 abnormality Effects 0.000 description 3
- 230000004913 activation Effects 0.000 description 3
- 208000011341 adult acute respiratory distress syndrome Diseases 0.000 description 3
- 201000000028 adult respiratory distress syndrome Diseases 0.000 description 3
- 208000026935 allergic disease Diseases 0.000 description 3
- 238000013459 approach Methods 0.000 description 3
- 206010003246 arthritis Diseases 0.000 description 3
- 230000001580 bacterial effect Effects 0.000 description 3
- 230000009286 beneficial effect Effects 0.000 description 3
- IQFYYKKMVGJFEH-UHFFFAOYSA-N beta-L-thymidine Natural products O=C1NC(=O)C(C)=CN1C1OC(CO)C(O)C1 IQFYYKKMVGJFEH-UHFFFAOYSA-N 0.000 description 3
- 244000309466 calf Species 0.000 description 3
- 238000004113 cell culture Methods 0.000 description 3
- 230000003915 cell function Effects 0.000 description 3
- 229920001577 copolymer Polymers 0.000 description 3
- 239000012228 culture supernatant Substances 0.000 description 3
- 230000003247 decreasing effect Effects 0.000 description 3
- 230000003111 delayed effect Effects 0.000 description 3
- 230000012010 growth Effects 0.000 description 3
- 229940124452 immunizing agent Drugs 0.000 description 3
- 230000003834 intracellular effect Effects 0.000 description 3
- 238000002955 isolation Methods 0.000 description 3
- 210000000265 leukocyte Anatomy 0.000 description 3
- 210000004698 lymphocyte Anatomy 0.000 description 3
- 230000004048 modification Effects 0.000 description 3
- 238000012986 modification Methods 0.000 description 3
- 238000010369 molecular cloning Methods 0.000 description 3
- 108020004707 nucleic acids Proteins 0.000 description 3
- 102000039446 nucleic acids Human genes 0.000 description 3
- 150000007523 nucleic acids Chemical class 0.000 description 3
- 210000000056 organ Anatomy 0.000 description 3
- 210000002997 osteoclast Anatomy 0.000 description 3
- 229920000642 polymer Polymers 0.000 description 3
- 238000000746 purification Methods 0.000 description 3
- 230000028327 secretion Effects 0.000 description 3
- 230000001629 suppression Effects 0.000 description 3
- 230000004083 survival effect Effects 0.000 description 3
- 238000013268 sustained release Methods 0.000 description 3
- 239000012730 sustained-release form Substances 0.000 description 3
- 238000013518 transcription Methods 0.000 description 3
- 230000035897 transcription Effects 0.000 description 3
- 230000005945 translocation Effects 0.000 description 3
- 238000010396 two-hybrid screening Methods 0.000 description 3
- YBJHBAHKTGYVGT-ZKWXMUAHSA-N (+)-Biotin Chemical compound N1C(=O)N[C@@H]2[C@H](CCCCC(=O)O)SC[C@@H]21 YBJHBAHKTGYVGT-ZKWXMUAHSA-N 0.000 description 2
- 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
- 206010003445 Ascites Diseases 0.000 description 2
- 241000283690 Bos taurus Species 0.000 description 2
- 108010012236 Chemokines Proteins 0.000 description 2
- 102000019034 Chemokines Human genes 0.000 description 2
- 108091026890 Coding region Proteins 0.000 description 2
- 230000004568 DNA-binding Effects 0.000 description 2
- 241000588724 Escherichia coli Species 0.000 description 2
- 108700024394 Exon Proteins 0.000 description 2
- AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical compound OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 description 2
- 108010017080 Granulocyte Colony-Stimulating Factor Proteins 0.000 description 2
- 102100039619 Granulocyte colony-stimulating factor Human genes 0.000 description 2
- 108010017213 Granulocyte-Macrophage Colony-Stimulating Factor Proteins 0.000 description 2
- 102100039620 Granulocyte-macrophage colony-stimulating factor Human genes 0.000 description 2
- 239000012981 Hank's balanced salt solution Substances 0.000 description 2
- 201000009794 Idiopathic Pulmonary Fibrosis Diseases 0.000 description 2
- 102000000589 Interleukin-1 Human genes 0.000 description 2
- 108010002352 Interleukin-1 Proteins 0.000 description 2
- 102000004560 Interleukin-12 Receptors Human genes 0.000 description 2
- 108010017515 Interleukin-12 Receptors Proteins 0.000 description 2
- 102000004388 Interleukin-4 Human genes 0.000 description 2
- 108090000978 Interleukin-4 Proteins 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
- 229930193140 Neomycin Natural products 0.000 description 2
- 241000283973 Oryctolagus cuniculus Species 0.000 description 2
- 108020004511 Recombinant DNA Proteins 0.000 description 2
- 206010040047 Sepsis Diseases 0.000 description 2
- 206010042953 Systemic sclerosis Diseases 0.000 description 2
- 230000006044 T cell activation Effects 0.000 description 2
- 102000006601 Thymidine Kinase Human genes 0.000 description 2
- 108020004440 Thymidine kinase Proteins 0.000 description 2
- 108060008682 Tumor Necrosis Factor Proteins 0.000 description 2
- 206010047115 Vasculitis Diseases 0.000 description 2
- 230000002159 abnormal effect Effects 0.000 description 2
- 230000001464 adherent effect Effects 0.000 description 2
- 230000001270 agonistic effect Effects 0.000 description 2
- 230000007815 allergy Effects 0.000 description 2
- -1 aminoprotein Chemical compound 0.000 description 2
- 239000003435 antirheumatic agent Substances 0.000 description 2
- 239000011324 bead Substances 0.000 description 2
- 239000000872 buffer Substances 0.000 description 2
- DQXBYHZEEUGOBF-UHFFFAOYSA-N but-3-enoic acid;ethene Chemical compound C=C.OC(=O)CC=C DQXBYHZEEUGOBF-UHFFFAOYSA-N 0.000 description 2
- 210000004899 c-terminal region Anatomy 0.000 description 2
- 230000024245 cell differentiation Effects 0.000 description 2
- 210000003169 central nervous system Anatomy 0.000 description 2
- 230000000295 complement effect Effects 0.000 description 2
- 239000003636 conditioned culture medium Substances 0.000 description 2
- 238000000432 density-gradient centrifugation Methods 0.000 description 2
- 239000002988 disease modifying antirheumatic drug Substances 0.000 description 2
- 239000012636 effector Substances 0.000 description 2
- 239000000839 emulsion Substances 0.000 description 2
- 239000005038 ethylene vinyl acetate Substances 0.000 description 2
- 238000000684 flow cytometry Methods 0.000 description 2
- 230000002489 hematologic effect Effects 0.000 description 2
- 230000008348 humoral response Effects 0.000 description 2
- 239000000017 hydrogel Substances 0.000 description 2
- FDGQSTZJBFJUBT-UHFFFAOYSA-N hypoxanthine Chemical compound O=C1NC=NC2=C1NC=N2 FDGQSTZJBFJUBT-UHFFFAOYSA-N 0.000 description 2
- 229940072221 immunoglobulins Drugs 0.000 description 2
- 239000000367 immunologic factor Substances 0.000 description 2
- 238000010348 incorporation Methods 0.000 description 2
- CGIGDMFJXJATDK-UHFFFAOYSA-N indomethacin Chemical compound CC1=C(CC(O)=O)C2=CC(OC)=CC=C2N1C(=O)C1=CC=C(Cl)C=C1 CGIGDMFJXJATDK-UHFFFAOYSA-N 0.000 description 2
- 239000000411 inducer Substances 0.000 description 2
- 230000002757 inflammatory effect Effects 0.000 description 2
- 239000003112 inhibitor Substances 0.000 description 2
- 208000014674 injury Diseases 0.000 description 2
- 230000003704 interleukin-23 production Effects 0.000 description 2
- 208000036971 interstitial lung disease 2 Diseases 0.000 description 2
- 210000003292 kidney cell Anatomy 0.000 description 2
- 238000011813 knockout mouse model Methods 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
- RGLRXNKKBLIBQS-XNHQSDQCSA-N leuprolide acetate Chemical compound CC(O)=O.CCNC(=O)[C@@H]1CCCN1C(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](CC(C)C)NC(=O)[C@@H](NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@H]1NC(=O)CC1)CC1=CC=C(O)C=C1 RGLRXNKKBLIBQS-XNHQSDQCSA-N 0.000 description 2
- 206010025135 lupus erythematosus Diseases 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 238000005259 measurement Methods 0.000 description 2
- 230000010534 mechanism of action Effects 0.000 description 2
- 239000004530 micro-emulsion Substances 0.000 description 2
- 230000035772 mutation Effects 0.000 description 2
- 229960004927 neomycin Drugs 0.000 description 2
- 229910052759 nickel Inorganic materials 0.000 description 2
- 201000008482 osteoarthritis Diseases 0.000 description 2
- 239000002245 particle Substances 0.000 description 2
- 230000001717 pathogenic effect Effects 0.000 description 2
- 210000005259 peripheral blood Anatomy 0.000 description 2
- 239000011886 peripheral blood Substances 0.000 description 2
- 239000008194 pharmaceutical composition Substances 0.000 description 2
- 229920001200 poly(ethylene-vinyl acetate) Polymers 0.000 description 2
- 230000003389 potentiating effect Effects 0.000 description 2
- 238000000159 protein binding assay Methods 0.000 description 2
- 230000002685 pulmonary effect Effects 0.000 description 2
- 239000011541 reaction mixture Substances 0.000 description 2
- 230000007420 reactivation Effects 0.000 description 2
- 238000003753 real-time PCR Methods 0.000 description 2
- 230000010410 reperfusion Effects 0.000 description 2
- 229920005989 resin Polymers 0.000 description 2
- 239000011347 resin Substances 0.000 description 2
- 238000003757 reverse transcription PCR Methods 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- 241000894007 species Species 0.000 description 2
- 230000006641 stabilisation Effects 0.000 description 2
- 238000011105 stabilization Methods 0.000 description 2
- 238000010561 standard procedure Methods 0.000 description 2
- 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 2
- 229960005322 streptomycin Drugs 0.000 description 2
- 230000008093 supporting effect Effects 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 210000001258 synovial membrane Anatomy 0.000 description 2
- 230000009885 systemic effect Effects 0.000 description 2
- 230000008733 trauma Effects 0.000 description 2
- 239000013598 vector Substances 0.000 description 2
- WHBMMWSBFZVSSR-GSVOUGTGSA-N (R)-3-hydroxybutyric acid Chemical compound C[C@@H](O)CC(O)=O WHBMMWSBFZVSSR-GSVOUGTGSA-N 0.000 description 1
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 1
- XBBVURRQGJPTHH-UHFFFAOYSA-N 2-hydroxyacetic acid;2-hydroxypropanoic acid Chemical compound OCC(O)=O.CC(O)C(O)=O XBBVURRQGJPTHH-UHFFFAOYSA-N 0.000 description 1
- FWMNVWWHGCHHJJ-SKKKGAJSSA-N 4-amino-1-[(2r)-6-amino-2-[[(2r)-2-[[(2r)-2-[[(2r)-2-amino-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]hexanoyl]piperidine-4-carboxylic acid Chemical compound C([C@H](C(=O)N[C@H](CC(C)C)C(=O)N[C@H](CCCCN)C(=O)N1CCC(N)(CC1)C(O)=O)NC(=O)[C@H](N)CC=1C=CC=CC=1)C1=CC=CC=C1 FWMNVWWHGCHHJJ-SKKKGAJSSA-N 0.000 description 1
- UZOVYGYOLBIAJR-UHFFFAOYSA-N 4-isocyanato-4'-methyldiphenylmethane Chemical compound C1=CC(C)=CC=C1CC1=CC=C(N=C=O)C=C1 UZOVYGYOLBIAJR-UHFFFAOYSA-N 0.000 description 1
- 108010088751 Albumins Proteins 0.000 description 1
- 102000009027 Albumins Human genes 0.000 description 1
- 206010001889 Alveolitis Diseases 0.000 description 1
- 101100107610 Arabidopsis thaliana ABCF4 gene Proteins 0.000 description 1
- 206010003497 Asphyxia Diseases 0.000 description 1
- BSYNRYMUTXBXSQ-UHFFFAOYSA-N Aspirin Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O BSYNRYMUTXBXSQ-UHFFFAOYSA-N 0.000 description 1
- 101710192393 Attachment protein G3P Proteins 0.000 description 1
- 208000023275 Autoimmune disease Diseases 0.000 description 1
- 102000019260 B-Cell Antigen Receptors Human genes 0.000 description 1
- 108010012919 B-Cell Antigen Receptors Proteins 0.000 description 1
- 230000003844 B-cell-activation Effects 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- 201000001178 Bacterial Pneumonia Diseases 0.000 description 1
- 102100026189 Beta-galactosidase Human genes 0.000 description 1
- 208000006386 Bone Resorption Diseases 0.000 description 1
- 206010051728 Bone erosion Diseases 0.000 description 1
- 206010048962 Brain oedema Diseases 0.000 description 1
- 206010006458 Bronchitis chronic Diseases 0.000 description 1
- 102100021943 C-C motif chemokine 2 Human genes 0.000 description 1
- 101710155857 C-C motif chemokine 2 Proteins 0.000 description 1
- 108050006947 CXC Chemokine Proteins 0.000 description 1
- 102000019388 CXC chemokine Human genes 0.000 description 1
- 241000282472 Canis lupus familiaris Species 0.000 description 1
- 101710169873 Capsid protein G8P Proteins 0.000 description 1
- 102000053642 Catalytic RNA Human genes 0.000 description 1
- 108090000994 Catalytic RNA Proteins 0.000 description 1
- 102000000844 Cell Surface Receptors Human genes 0.000 description 1
- 108010001857 Cell Surface Receptors Proteins 0.000 description 1
- 206010053567 Coagulopathies Diseases 0.000 description 1
- 108091035707 Consensus sequence Proteins 0.000 description 1
- 241000699800 Cricetinae Species 0.000 description 1
- 241000699802 Cricetulus griseus Species 0.000 description 1
- PMATZTZNYRCHOR-CGLBZJNRSA-N Cyclosporin A Chemical compound CC[C@@H]1NC(=O)[C@H]([C@H](O)[C@H](C)C\C=C\C)N(C)C(=O)[C@H](C(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)N(C)C(=O)CN(C)C1=O PMATZTZNYRCHOR-CGLBZJNRSA-N 0.000 description 1
- 108010036949 Cyclosporine Proteins 0.000 description 1
- 201000003883 Cystic fibrosis Diseases 0.000 description 1
- VVNCNSJFMMFHPL-VKHMYHEASA-N D-penicillamine Chemical compound CC(C)(S)[C@@H](N)C(O)=O VVNCNSJFMMFHPL-VKHMYHEASA-N 0.000 description 1
- 102000053602 DNA Human genes 0.000 description 1
- 206010061818 Disease progression Diseases 0.000 description 1
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 1
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 1
- 241000283086 Equidae Species 0.000 description 1
- 206010015866 Extravasation Diseases 0.000 description 1
- 102000009109 Fc receptors Human genes 0.000 description 1
- 108010087819 Fc receptors Proteins 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- 241000724791 Filamentous phage Species 0.000 description 1
- 241000192125 Firmicutes Species 0.000 description 1
- 238000012413 Fluorescence activated cell sorting analysis Methods 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 102000006395 Globulins Human genes 0.000 description 1
- 108010044091 Globulins Proteins 0.000 description 1
- 208000009329 Graft vs Host Disease Diseases 0.000 description 1
- 208000031886 HIV Infections Diseases 0.000 description 1
- 208000037357 HIV infectious disease Diseases 0.000 description 1
- 208000010496 Heart Arrest Diseases 0.000 description 1
- 206010019728 Hepatitis alcoholic Diseases 0.000 description 1
- 101000852980 Homo sapiens Interleukin-23 subunit alpha Proteins 0.000 description 1
- 101000946889 Homo sapiens Monocyte differentiation antigen CD14 Proteins 0.000 description 1
- 101000622137 Homo sapiens P-selectin Proteins 0.000 description 1
- 101000800116 Homo sapiens Thy-1 membrane glycoprotein Proteins 0.000 description 1
- 101000669447 Homo sapiens Toll-like receptor 4 Proteins 0.000 description 1
- 206010021137 Hypovolaemia Diseases 0.000 description 1
- UGQMRVRMYYASKQ-UHFFFAOYSA-N Hypoxanthine nucleoside Natural products OC1C(O)C(CO)OC1N1C(NC=NC2=O)=C2N=C1 UGQMRVRMYYASKQ-UHFFFAOYSA-N 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
- 206010061598 Immunodeficiency Diseases 0.000 description 1
- 108700005091 Immunoglobulin Genes Proteins 0.000 description 1
- 102000013463 Immunoglobulin Light Chains Human genes 0.000 description 1
- 108010065825 Immunoglobulin Light Chains Proteins 0.000 description 1
- 102000012745 Immunoglobulin Subunits Human genes 0.000 description 1
- 108010079585 Immunoglobulin Subunits Proteins 0.000 description 1
- 108010067060 Immunoglobulin Variable Region Proteins 0.000 description 1
- 102000017727 Immunoglobulin Variable Region Human genes 0.000 description 1
- 238000012695 Interfacial polymerization Methods 0.000 description 1
- 108010050904 Interferons Proteins 0.000 description 1
- 102000014150 Interferons Human genes 0.000 description 1
- 108090001005 Interleukin-6 Proteins 0.000 description 1
- 102000004889 Interleukin-6 Human genes 0.000 description 1
- 108090001007 Interleukin-8 Proteins 0.000 description 1
- 102000004890 Interleukin-8 Human genes 0.000 description 1
- 102000015696 Interleukins Human genes 0.000 description 1
- 108010063738 Interleukins Proteins 0.000 description 1
- UETNIIAIRMUTSM-UHFFFAOYSA-N Jacareubin Natural products CC1(C)OC2=CC3Oc4c(O)c(O)ccc4C(=O)C3C(=C2C=C1)O UETNIIAIRMUTSM-UHFFFAOYSA-N 0.000 description 1
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 description 1
- FBOZXECLQNJBKD-ZDUSSCGKSA-N L-methotrexate Chemical compound C=1N=C2N=C(N)N=C(N)C2=NC=1CN(C)C1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 FBOZXECLQNJBKD-ZDUSSCGKSA-N 0.000 description 1
- ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 1
- 108010000817 Leuprolide Proteins 0.000 description 1
- 208000005777 Lupus Nephritis Diseases 0.000 description 1
- 208000016604 Lyme disease Diseases 0.000 description 1
- 206010025323 Lymphomas Diseases 0.000 description 1
- 102000043131 MHC class II family Human genes 0.000 description 1
- 108091054438 MHC class II family Proteins 0.000 description 1
- 241000282553 Macaca Species 0.000 description 1
- 101710125418 Major capsid protein Proteins 0.000 description 1
- 101710156564 Major tail protein Gp23 Proteins 0.000 description 1
- 102100035877 Monocyte differentiation antigen CD14 Human genes 0.000 description 1
- 101000852978 Mus musculus Interleukin-23 subunit alpha Proteins 0.000 description 1
- 206010062207 Mycobacterial infection Diseases 0.000 description 1
- 108020005187 Oligonucleotide Probes Proteins 0.000 description 1
- 102100023472 P-selectin Human genes 0.000 description 1
- 208000031481 Pathologic Constriction Diseases 0.000 description 1
- 241001494479 Pecora 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
- 108010004729 Phycoerythrin Proteins 0.000 description 1
- 241000276498 Pollachius virens Species 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 239000012980 RPMI-1640 medium Substances 0.000 description 1
- 206010063837 Reperfusion injury Diseases 0.000 description 1
- 101100068078 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) GCN4 gene Proteins 0.000 description 1
- 229940124639 Selective inhibitor Drugs 0.000 description 1
- 229920002684 Sepharose Polymers 0.000 description 1
- 108020004682 Single-Stranded DNA Proteins 0.000 description 1
- 208000021386 Sjogren Syndrome Diseases 0.000 description 1
- 241000589970 Spirochaetales Species 0.000 description 1
- 241000269319 Squalius cephalus Species 0.000 description 1
- 108010090804 Streptavidin Proteins 0.000 description 1
- 201000009594 Systemic Scleroderma Diseases 0.000 description 1
- 230000037453 T cell priming Effects 0.000 description 1
- 102100034922 T-cell surface glycoprotein CD8 alpha chain Human genes 0.000 description 1
- 102100033523 Thy-1 membrane glycoprotein Human genes 0.000 description 1
- 102100024333 Toll-like receptor 2 Human genes 0.000 description 1
- 108010060888 Toll-like receptor 2 Proteins 0.000 description 1
- 102100039360 Toll-like receptor 4 Human genes 0.000 description 1
- 206010046851 Uveitis Diseases 0.000 description 1
- 101150117115 V gene Proteins 0.000 description 1
- 241000251539 Vertebrata <Metazoa> Species 0.000 description 1
- 238000012452 Xenomouse strains Methods 0.000 description 1
- 210000001015 abdomen Anatomy 0.000 description 1
- 208000002223 abdominal aortic aneurysm Diseases 0.000 description 1
- 229960001138 acetylsalicylic acid Drugs 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 239000003929 acidic solution Substances 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 206010069351 acute lung injury Diseases 0.000 description 1
- 230000008649 adaptation response Effects 0.000 description 1
- 230000033289 adaptive immune response Effects 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 238000001042 affinity chromatography Methods 0.000 description 1
- 230000002776 aggregation Effects 0.000 description 1
- 238000004220 aggregation Methods 0.000 description 1
- 208000002353 alcoholic hepatitis Diseases 0.000 description 1
- 208000030961 allergic reaction Diseases 0.000 description 1
- 230000002187 allostimulatory effect Effects 0.000 description 1
- 229940024606 amino acid Drugs 0.000 description 1
- 235000001014 amino acid Nutrition 0.000 description 1
- 210000000628 antibody-producing cell Anatomy 0.000 description 1
- 208000007474 aortic aneurysm Diseases 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 230000002238 attenuated effect Effects 0.000 description 1
- 229960002170 azathioprine Drugs 0.000 description 1
- LMEKQMALGUDUQG-UHFFFAOYSA-N azathioprine Chemical compound CN1C=NC([N+]([O-])=O)=C1SC1=NC=NC2=C1NC=N2 LMEKQMALGUDUQG-UHFFFAOYSA-N 0.000 description 1
- 108010005774 beta-Galactosidase Proteins 0.000 description 1
- 230000005540 biological transmission Effects 0.000 description 1
- 229960002685 biotin Drugs 0.000 description 1
- 235000020958 biotin Nutrition 0.000 description 1
- 239000011616 biotin Substances 0.000 description 1
- 210000000601 blood cell Anatomy 0.000 description 1
- 210000001124 body fluid Anatomy 0.000 description 1
- 239000010839 body fluid Substances 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 210000000988 bone and bone Anatomy 0.000 description 1
- 210000002798 bone marrow cell Anatomy 0.000 description 1
- 230000024279 bone resorption Effects 0.000 description 1
- 208000006752 brain edema Diseases 0.000 description 1
- 201000009267 bronchiectasis Diseases 0.000 description 1
- 206010006451 bronchitis Diseases 0.000 description 1
- FPEIKXWFKBWWNT-UHFFFAOYSA-N butanoic acid;2-hydroxyacetic acid Chemical compound OCC(O)=O.CCCC(O)=O FPEIKXWFKBWWNT-UHFFFAOYSA-N 0.000 description 1
- 230000000747 cardiac effect Effects 0.000 description 1
- 238000012754 cardiac puncture Methods 0.000 description 1
- 238000007675 cardiac surgery Methods 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 238000000423 cell based assay Methods 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 230000007969 cellular immunity Effects 0.000 description 1
- 230000014564 chemokine production Effects 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 239000003593 chromogenic compound Substances 0.000 description 1
- 210000000349 chromosome Anatomy 0.000 description 1
- 208000007451 chronic bronchitis Diseases 0.000 description 1
- 229960001265 ciclosporin Drugs 0.000 description 1
- 238000003776 cleavage reaction Methods 0.000 description 1
- 238000010367 cloning Methods 0.000 description 1
- 230000035602 clotting Effects 0.000 description 1
- 238000003501 co-culture Methods 0.000 description 1
- 230000004186 co-expression Effects 0.000 description 1
- 238000000975 co-precipitation Methods 0.000 description 1
- 238000005354 coacervation Methods 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 230000001143 conditioned effect Effects 0.000 description 1
- 230000021615 conjugation Effects 0.000 description 1
- 239000000470 constituent Substances 0.000 description 1
- 238000011109 contamination Methods 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 238000007887 coronary angioplasty Methods 0.000 description 1
- 239000003431 cross linking reagent Substances 0.000 description 1
- 229930182912 cyclosporin Natural products 0.000 description 1
- 125000000151 cysteine group Chemical group N[C@@H](CS)C(=O)* 0.000 description 1
- 230000016396 cytokine production Effects 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 230000034994 death Effects 0.000 description 1
- 201000001981 dermatomyositis Diseases 0.000 description 1
- 238000000502 dialysis Methods 0.000 description 1
- 230000004069 differentiation Effects 0.000 description 1
- 206010062952 diffuse panbronchiolitis Diseases 0.000 description 1
- 230000029087 digestion Effects 0.000 description 1
- 238000003113 dilution method Methods 0.000 description 1
- 230000005750 disease progression Effects 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 238000004520 electroporation Methods 0.000 description 1
- 206010014599 encephalitis Diseases 0.000 description 1
- 210000002889 endothelial cell Anatomy 0.000 description 1
- 210000002919 epithelial cell Anatomy 0.000 description 1
- 230000003628 erosive effect Effects 0.000 description 1
- 210000003743 erythrocyte Anatomy 0.000 description 1
- 230000007717 exclusion Effects 0.000 description 1
- 230000001747 exhibiting effect Effects 0.000 description 1
- 239000013604 expression vector Substances 0.000 description 1
- 230000036251 extravasation Effects 0.000 description 1
- 201000001155 extrinsic allergic alveolitis Diseases 0.000 description 1
- 210000002950 fibroblast Anatomy 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 238000004108 freeze drying Methods 0.000 description 1
- 239000012737 fresh medium Substances 0.000 description 1
- 108020001507 fusion proteins Proteins 0.000 description 1
- 102000037865 fusion proteins Human genes 0.000 description 1
- 229960002963 ganciclovir Drugs 0.000 description 1
- IRSCQMHQWWYFCW-UHFFFAOYSA-N ganciclovir Chemical compound O=C1NC(N)=NC2=C1N=CN2COC(CO)CO IRSCQMHQWWYFCW-UHFFFAOYSA-N 0.000 description 1
- 238000001502 gel electrophoresis Methods 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 238000003205 genotyping method Methods 0.000 description 1
- 229960002989 glutamic acid Drugs 0.000 description 1
- 108020004445 glyceraldehyde-3-phosphate dehydrogenase Proteins 0.000 description 1
- 102000006602 glyceraldehyde-3-phosphate dehydrogenase Human genes 0.000 description 1
- 239000001963 growth medium Substances 0.000 description 1
- 210000003958 hematopoietic stem cell Anatomy 0.000 description 1
- 238000013537 high throughput screening Methods 0.000 description 1
- 210000000548 hind-foot Anatomy 0.000 description 1
- 238000002744 homologous recombination Methods 0.000 description 1
- 230000006801 homologous recombination Effects 0.000 description 1
- 208000033519 human immunodeficiency virus infectious disease Diseases 0.000 description 1
- 230000002209 hydrophobic effect Effects 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
- 229960004171 hydroxychloroquine Drugs 0.000 description 1
- 229910052588 hydroxylapatite Inorganic materials 0.000 description 1
- 229940031574 hydroxymethyl cellulose Drugs 0.000 description 1
- 229920003063 hydroxymethyl cellulose Polymers 0.000 description 1
- 208000022098 hypersensitivity pneumonitis Diseases 0.000 description 1
- 229960001680 ibuprofen Drugs 0.000 description 1
- 210000000987 immune system Anatomy 0.000 description 1
- 238000003018 immunoassay Methods 0.000 description 1
- 230000005847 immunogenicity Effects 0.000 description 1
- 230000016784 immunoglobulin production Effects 0.000 description 1
- 238000001114 immunoprecipitation Methods 0.000 description 1
- 239000003547 immunosorbent Substances 0.000 description 1
- 238000012744 immunostaining Methods 0.000 description 1
- 230000001771 impaired effect Effects 0.000 description 1
- 230000001976 improved effect Effects 0.000 description 1
- 229960000905 indomethacin Drugs 0.000 description 1
- 230000028709 inflammatory response Effects 0.000 description 1
- 230000015788 innate immune response Effects 0.000 description 1
- 230000010354 integration Effects 0.000 description 1
- 230000002452 interceptive effect Effects 0.000 description 1
- 230000000302 ischemic effect Effects 0.000 description 1
- 210000001503 joint Anatomy 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- VHOGYURTWQBHIL-UHFFFAOYSA-N leflunomide Chemical compound O1N=CC(C(=O)NC=2C=CC(=CC=2)C(F)(F)F)=C1C VHOGYURTWQBHIL-UHFFFAOYSA-N 0.000 description 1
- 229960000681 leflunomide Drugs 0.000 description 1
- 229960004338 leuprorelin Drugs 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 239000002502 liposome Substances 0.000 description 1
- 239000012139 lysis buffer Substances 0.000 description 1
- 210000004962 mammalian cell Anatomy 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- 210000004379 membrane Anatomy 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 210000001806 memory b lymphocyte Anatomy 0.000 description 1
- 210000002418 meninge Anatomy 0.000 description 1
- 229960000485 methotrexate Drugs 0.000 description 1
- 239000013586 microbial product Substances 0.000 description 1
- 239000004005 microsphere Substances 0.000 description 1
- 210000001616 monocyte Anatomy 0.000 description 1
- 208000037890 multiple organ injury Diseases 0.000 description 1
- 208000027531 mycobacterial infectious disease Diseases 0.000 description 1
- 208000010125 myocardial infarction Diseases 0.000 description 1
- 208000031225 myocardial ischemia Diseases 0.000 description 1
- 239000002088 nanocapsule Substances 0.000 description 1
- 239000002105 nanoparticle Substances 0.000 description 1
- 201000008383 nephritis Diseases 0.000 description 1
- 208000004235 neutropenia Diseases 0.000 description 1
- 210000000440 neutrophil Anatomy 0.000 description 1
- 230000011242 neutrophil chemotaxis Effects 0.000 description 1
- 229940046166 oligodeoxynucleotide Drugs 0.000 description 1
- 239000002751 oligonucleotide probe Substances 0.000 description 1
- 238000002515 oligonucleotide synthesis Methods 0.000 description 1
- 238000011275 oncology therapy Methods 0.000 description 1
- 210000000963 osteoblast Anatomy 0.000 description 1
- 210000001672 ovary Anatomy 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 230000036961 partial effect Effects 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 229960001639 penicillamine Drugs 0.000 description 1
- 229940049954 penicillin Drugs 0.000 description 1
- XYJRXVWERLGGKC-UHFFFAOYSA-D pentacalcium;hydroxide;triphosphate Chemical compound [OH-].[Ca+2].[Ca+2].[Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O XYJRXVWERLGGKC-UHFFFAOYSA-D 0.000 description 1
- 230000000737 periodic effect Effects 0.000 description 1
- 210000005105 peripheral blood lymphocyte Anatomy 0.000 description 1
- 210000001539 phagocyte Anatomy 0.000 description 1
- 230000004962 physiological condition Effects 0.000 description 1
- 208000008423 pleurisy Diseases 0.000 description 1
- 229920000747 poly(lactic acid) Polymers 0.000 description 1
- 229920000728 polyester Polymers 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 229920002338 polyhydroxyethylmethacrylate Polymers 0.000 description 1
- 208000005987 polymyositis Diseases 0.000 description 1
- 229920002451 polyvinyl alcohol Polymers 0.000 description 1
- 239000013641 positive control Substances 0.000 description 1
- 230000029279 positive regulation of transcription, DNA-dependent Effects 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 230000003449 preventive effect Effects 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 230000006916 protein interaction Effects 0.000 description 1
- 230000017854 proteolysis Effects 0.000 description 1
- 238000003127 radioimmunoassay Methods 0.000 description 1
- 238000003259 recombinant expression Methods 0.000 description 1
- 230000007115 recruitment Effects 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 230000002829 reductive effect Effects 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 108091092562 ribozyme Proteins 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
- 239000012898 sample dilution Substances 0.000 description 1
- 201000000306 sarcoidosis Diseases 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 230000035939 shock Effects 0.000 description 1
- 210000003625 skull Anatomy 0.000 description 1
- 239000007790 solid phase Substances 0.000 description 1
- 230000000392 somatic effect Effects 0.000 description 1
- 229940043517 specific immunoglobulins Drugs 0.000 description 1
- 210000000130 stem cell Anatomy 0.000 description 1
- 230000036262 stenosis Effects 0.000 description 1
- 208000037804 stenosis Diseases 0.000 description 1
- 238000011146 sterile filtration Methods 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 210000002536 stromal cell Anatomy 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- NCEXYHBECQHGNR-QZQOTICOSA-N sulfasalazine Chemical compound C1=C(O)C(C(=O)O)=CC(\N=N\C=2C=CC(=CC=2)S(=O)(=O)NC=2N=CC=CC=2)=C1 NCEXYHBECQHGNR-QZQOTICOSA-N 0.000 description 1
- 229960001940 sulfasalazine Drugs 0.000 description 1
- NCEXYHBECQHGNR-UHFFFAOYSA-N sulfasalazine Natural products 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 1
- 208000024891 symptom Diseases 0.000 description 1
- 210000001179 synovial fluid Anatomy 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 210000001541 thymus gland Anatomy 0.000 description 1
- 108091006106 transcriptional activators Proteins 0.000 description 1
- 238000011830 transgenic mouse model Methods 0.000 description 1
- 238000002054 transplantation Methods 0.000 description 1
- 229940087652 vioxx Drugs 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Images
Classifications
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/52—Cytokines; Lymphokines; Interferons
- C07K14/54—Interleukins [IL]
-
- 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
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
-
- 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
-
- 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
- A61K39/3955—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals against proteinaceous materials, e.g. enzymes, hormones, lymphokines
-
- 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
- A61P11/00—Drugs for disorders of the respiratory system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/06—Antiasthmatics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/06—Antipsoriatics
-
- 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
- A61P19/00—Drugs for skeletal disorders
- A61P19/06—Antigout agents, e.g. antihyperuricemic or uricosuric agents
-
- 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
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
- A61P29/02—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID] without antiinflammatory effect
-
- 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
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial 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
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- C07K16/24—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against cytokines, lymphokines or interferons
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- C07K16/24—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against cytokines, lymphokines or interferons
- C07K16/244—Interleukins [IL]
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
- C07K16/2866—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against receptors for cytokines, lymphokines, interferons
-
- 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
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/68—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids
- G01N33/6863—Cytokines, i.e. immune system proteins modifying a biological response such as cell growth proliferation or differentiation, e.g. TNF, CNF, GM-CSF, lymphotoxin, MIF or their receptors
- G01N33/6869—Interleukin
-
- 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
- A61K2039/505—Medicinal preparations containing antigens or antibodies comprising antibodies
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/20—Immunoglobulins specific features characterized by taxonomic origin
- C07K2317/21—Immunoglobulins specific features characterized by taxonomic origin from primates, e.g. man
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/20—Immunoglobulins specific features characterized by taxonomic origin
- C07K2317/24—Immunoglobulins specific features characterized by taxonomic origin containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
- C07K2317/76—Antagonist effect on antigen, e.g. neutralization or inhibition of binding
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
- C07K2319/30—Non-immunoglobulin-derived peptide or protein having an immunoglobulin constant or Fc region, or a fragment thereof, attached thereto
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2500/00—Screening for compounds of potential therapeutic value
- G01N2500/02—Screening involving studying the effect of compounds C on the interaction between interacting molecules A and B (e.g. A = enzyme and B = substrate for A, or A = receptor and B = ligand for the receptor)
Abstract
【解決手段】さらに本発明は、IL−17濃度の上昇がみられることを特徴とする炎症性疾患の治療において、IL−23アンタゴニストを使用することに関係する。IL−23アンタゴニストには、サブユニットあるいはIL−17あるいはIL−17受容体に特異的に結合する抗体が含まれるがこれらに限定されない。さらに本発明はIL−23アゴニストを用いることによるIL−17産生に関係する。
【選択図】なし
Description
(発明の分野)
本発明は、インターロイキン23(IL−23)のアンタゴニストを用いた、炎症誘発性サイトカインであるインターロイキン17(IL−17)のT細胞による産生の抑制に関係する。さらに本発明は、IL−17濃度の上昇がみられることを特徴とする炎症性疾患の治療において、IL−23アンタゴニストを使用することに関係する。
IL−17はT細胞由来の炎症誘発分子であり、上皮細胞及び内皮細胞、線維芽細胞性細胞を刺激して、IL−6、IL−8、G−CSF、MCP−1等他の炎症性サイトカイン及びケモカインを産出させる(S.Aggarwal,A.L.Gurney,J Leukoc Biol 71,1(2002);Z.Yao et al.,Immunity 3,811(1995);J.Kennedy et al.,J Interferon Cytokine Res 16,611(1996);F.Fossiea et al.,J Exp Med 183,2593(1996);A.Linden,H.Hoshino,M.Laan,Eur Respir J 15,973(2000);X.Y.Cai,C.P.Gommoll,Jr.,L.Justice,S.K.Narula,J.S.Fine,Immunol Lett 62,51(1998);D.V.Jovanovic et al.,J Immunol 160,3513(1998);M.Laan et al.,J Immunol 162,2347(1999))。
IL−17並びにIL−23サイトカインの発現と生物学的役割との関連性はこれまでのところ確立されていない。
一側面では、本発明はT細胞によるインターロイキン17(IL−17)産生を抑制する方法に関するものであり、この方法にはインターロイキン23(IL−23)のアンタゴニストでT細胞を処理することが含まれる。
(a)T細胞にIL−23を加え、候補薬の有る無しで培養する;
(b)培養物中のIL−17濃度を追跡測定する;
(c)当該候補薬分子が存在しない場合よりも存在する場合の方がIL−17の濃度が低ければ、候補薬分子が抗炎症剤であると確認される。
(A.定義)
他に定義されていない限り、ここで使用されている科学技術用語は、本発明が属する分野の普通の技術者によって一般に理解されているものと同じ意味を持つ。例えば、Singleton et al.,Dictionary of Microbiology and Molecular Biology 2nd ed.,J.Wiley & Sons(New York,NY 1994);Sambrook et al.,Molecular Cloning,A Laboratory Manual,Cold Springs Harbor Press(Cold Springs Harbor,NY 1989)を参照する。本発明の目的のため以下の用語を下記に定義する。
本発明を実施するには、他に指定のない限り、分子生物学(組換え技術を含む。)、微生物学及び細胞生物学、生化学、免疫学の通常の手法を使用することとなり、これらは当分野の技術の範囲内である。当該手法は、「Molecular Cloning:A Laboratory Manual」,2nd edition(Sambrook et al.,1989);並びに「Oligonucleotide Synthesis」(M.J.Gait,ed.,1984);「Animal Cell Culture」(R.I.Freshney,ed.,1987);「Methods in Enzymology」(Academic Press,Inc.);「Handbook of Experimental Immunology」,4th edition(D.M.Weir & C.C.Blackwell,eds.,Blackwell Science Inc.,1987);「Gene Transfer Vectors for Mammalian Cells」(J.M.Miller & M.P.Calos,eds.,1987);「Current Protocols in Molecular Biology」(F.M.Ausubel et al.,eds.,1987);「PCR:The Polymerase Chain Reaction」,(Mullis et al.,eds.,1994);「Current Protocols in Immunology」(J.E.Coligan et al.,eds.,1991)等の文献において詳細に説明されている。
本発明はIL−23のアンタゴニストを同定するためのスクリーニングアッセイを含み、このアッセイではIL−17濃度の上昇がみられることを特徴とする炎症状態の治療における有効性を確認する。さらに本発明はIL−23アゴニストを同定するためのスクリーニングアッセイを含み、このアッセイではMycobacterium tuberculosis による感染等感染に対する防御免疫反応の促進における有効性を確認する。
特定の実施例において、IL−23アンタゴニストあるいはアゴニストはIL−23(例えばIL−23のサブユニット)に対するモノクローナル抗体であり、これには抗体フラグメントが含まれる。別の特定の実施例では、IL−23アンタゴニスト並びにアゴニストにはIL−23受容体(例えばIL−23受容体のサブユニット)に対するモノクローナル抗体が含まれる。そのサブユニットを含め、IL−23についてはこの明細の前記に記述している。IL−23受容体はIL−12Rβ1及び、最近発見されたIL−23Rと名付けられたサブユニット(Parham et al.,J.Immunol.168:5699−5798(2002))の、2つのサブユニットから構成される。いずれのサブユニットに対する抗体も、本発明の範囲に明確に収まる。アンタゴニストの場合、IL−23Rに特異的に結合する抗体はIL−23が介する生物学的活性を特異的に遮断するため、IL−23Rに特異的に結合する抗体が特に望ましい。
IL−17はリウマチ様関節炎(RA)を含む様々な炎症性疾患に関係している。RAの基本的な特徴の一つは、関節周囲の骨の侵食である。骨吸収では破骨細胞が鍵となる役割を果たしているが、破骨細胞が前駆細胞から形成されるメカニズムは完全には理解されていない。最近Kotake et al.,(J.Clin.Invest.103:1345(1999))は、マウス造血細胞と1次骨芽細胞との共培養物において、インターロイキン17(IL−17)が破骨細胞様の細胞の形成を誘導する可能性がみられたことを報告している。このIL−17に誘導される破骨細胞形成は、シクロオキシゲナーゼ2(COX−2)の選択的阻害剤であるインドメタシンによって抑制されることが示されている。RA患者の滑液には、変形性関節症患者と比較して著しく高濃度のIL−17が含まれることが認められている。さらに免疫染色を用いて、RA患者の滑液膜組織にてIL−1陽性単核細胞が検出されたが、OA患者の組織からは検出されなかった。これらの結果は、RA患者ではIL−17が骨侵食と関節の損傷に寄与している可能性があり、抑制のための標的となり得ることを示唆すると解釈されている。
IL−23あるいはIL−23受容体に特異的に結合する抗体は、この明細の前記で記載されているスクリーニングアッセイによって同定された他のIL−23アンタゴニスト分子あるいはアゴニスト分子も同様に、特に炎症性疾患あるいは細胞性免疫反応の誘導による疾患等様々な疾患の治療のために薬学的組成物の形態で投与することができる。
インターロイキン23(IL−23)は、インターロイキン17(IL−17)の産生を特徴とする、第三のCD4 T細胞活性化状態を促進する。
細胞培養 − 脾臓単個細胞懸濁液はC57/BL−6マウスから調製し、密度勾配遠心によって懸濁脾細胞から単核細胞を単離した。2x106細胞/mlにIL−2を添加し、様々な刺激の有る無しで培養した(図の説明で示している。)。その後に細胞を回収してELISA(R&D Systems,Minneapolis,MN)を用いてIL−17について分析した。マクロファージ(脾細胞懸濁液から接着性集団として得た)をrGM−CSF(2ng/ml)とrIL−4(1000 units/ml)で4日間処理し、洗浄してLPS(0.5μg/ml)で再活性化することによってマクロファージから樹状細胞を得た。マウス脾細胞の単個細胞懸濁液から単離した単核細胞をCyC−CD4 + PE−CD44あるいはCyC−CD4 + PE−CD62Lで染色し、記憶表現型についてはCD44高/CD62L低、未刺激表現型についてはCD44低/CD62L高であるCD4+細胞を選別することによって、記憶T細胞及び未刺激T細胞を分離した。
最初に、様々な微生物産生物のIL−17産生促進作用を調べた。スピロヘータB.Burgdorferiが引き起こすライム病患者由来の微生物性リポペプチドに応答してIL−17が上昇することが、Infante−Duarte et al.,J Immuno 165,6107(2000)によって認められている。LPS(グラム陰性細菌)あるいはLTA(グラム陽性細菌)、LBP(細菌性リポペプチド)を含む様々な微生物性ペプチドを加えた脾細胞培養物で、IL−17が産生された(図1)。精製T細胞単独、あるいは精製マクロファージ自体はIL−17を産生しなかった。プレート結合抗CD3を用いて受容体架橋形成をした精製T細胞、及び活性化マクロファージあるいは活性化樹状細胞の上清で処理した精製T細胞ではIL−17の産生が上昇した。このことは、T細胞に作用してIL−17の産生を促進する未同定の因子を、これらの細胞が放出していることを示唆している。
まとめると、これらのデータはエフェクターサイトカインとしてIL−17を発現する、第三のT細胞活性化状態の促進におけるIL−23の役割を示唆している。Th1及びTh2系は体液性免疫反応に対して細胞性免疫を促進するものとして記載されている。これらの反応によって、それぞれ細胞内外の病原体に対する重要な防御が提供され、これらの反応のうちの一方でも欠損すると特定の病原体に対する感染性が上昇する。対照的にIL−23は、本質的に先天性免疫反応の媒介体として機能すると考えられている細胞に大きく依存することを特徴とする病原体に対する適応免疫反応を促進する。IL−17はこの反応の主要なエフェクターサイトカインとして、ケモカイン産生を誘導して単球及び好中球のより迅速な動員を促進することができる。さらに、IL−23に応答して高濃度のGM−CSFが観察されたことは、骨髄細胞が増産されたことを支持する。これはさらにIL−17刺激間質細胞からG−CSFが産生することによって増強される。しかしながら、IL−17がIL−17によるICAM誘導を促進し、その結果続いて起こるT細胞応答の重要な共同誘導を提供することがわかっていることから、この適応反応の特性は骨髄系反応の食細胞に排他的に依存するものではない。
(インターロイキン23(IL−23)欠損マウス)
インビボでIL−23とIL−17の関係をさらに調べるため、IL−23欠損マウス表現型をIL−17欠損マウスの表現型と比較した。
マウス:全てのマウスは病原体の存在しない状態で特別に飼育した。IL−12p40−/−マウスはJackson laboratory(Bar Harbor,MA)から、C57BL/6マウスはCharles River laboratories(San Diego,CA)から入手した。
IL−23p19遺伝子欠損:IL−23のインビボ非重複的影響を調べるため、IL−23を欠損するがIL−12を産生する成分を残したマウスを作製した。4つのエキソンから構成される、p19の全コーディング領域を、強化GFP(eGFP)レポーター遺伝子とネオマイシン耐性カセットで置換したターゲティングベクターを構築した(図6)。1c5と3h6の二つの正確にターゲットされたES細胞クローンによって生殖細胞系伝播を行い、変異は、1染色体当たり3つのマーカーを用いたスピードコンジェニック法によってC57BL/6バックグラウンドへ戻し交雑した。この分析に基づき、実験のため、129バックグラウンドからの遺伝的混入が5%未満のマウスを選別した。eGFPの発現パターンは内生p19mRNAの発現パターンに相当した(データは示していない。)。
IL−23p19欠損マウスを用いて、IL−23のインビボでの非重複性機能を分析し、IL−23の欠損が、体液性免疫反応やDTH反応等のT細胞依存的免疫反応を減衰することを見出した。
Claims (49)
- T細胞によるインターロイキン−17(IL−17)産生を阻害するための方法であって、該T細胞を、インターロイキン−23(IL−23)のアンタゴニストで処理する工程を包含する、方法。
- 前記T細胞が、活性化T細胞である、請求項1に記載の方法。
- 前記T細胞が、記憶細胞である、請求項1に記載の方法。
- 前記処理が、インビボで実施される、請求項1に記載の方法。
- 前記処理が、哺乳動物被験体中で実施される、請求項1に記載の方法。
- 前記哺乳動物被験体が、ヒトである、請求項5に記載の方法。
- 前記アンタゴニストが、抗IL−23または抗IL−23レセプター抗体である、請求項6に記載の方法。
- 前記抗体が、抗体フラグメントである、請求項7に記載の方法。
- 前記抗体フラグメントが、Fv、Fab、Fab’、およびF(ab’)2からなる群より選択される、請求項8に記載の方法。
- 前記抗体が、全長抗体である、請求項7に記載の方法。
- 前記抗体が、キメラ抗体である、請求項7に記載の方法。
- 前記抗体が、ヒト化抗体である、請求項7に記載の方法。
- 前記抗体が、ヒト抗体である、請求項7に記載の方法。
- 哺乳動物被験体中のインターロイキン17(IL−17)の上昇した発現によって特徴付けられる炎症疾患の処置のための方法であって、有効量のインターロイキン−23(IL−23)のアンタゴニストを該被験体に投与する工程を包含する、方法。
- 前記哺乳動物被験体が、ヒトである、請求項14に記載の方法。
- 前記炎症疾患が、慢性炎症、自己免疫性糖尿病、慢性関節リウマチ(RA)、リウマチ様脊椎炎、痛風性関節炎および他の関節炎状態、多発性硬化症(MS)、喘息、全身性エリテマトーデス、成人呼吸窮迫症候群、ベーチェット病、乾癬、慢性肺炎症疾患、対宿主性移植片反応、クローン病、潰瘍性大腸炎、炎症性腸疾患(IBD)、アルツハイマー病、ならびに発熱から選択される、請求項15に記載の方法。
- 前記炎症疾患が、慢性炎症疾患である、請求項16に記載の方法。
- 前記慢性炎症疾患が、慢性関節リウマチ(RA)、対宿主性移植片反応、多発性硬化症(MS)、および乾癬からなる群より選択される、請求項17に記載の方法。
- 前記アンタゴニストが、抗IL−23または抗IL−23レセプター抗体である、請求項15に記載の方法。
- 前記抗体が、抗体フラグメントである、請求項19に記載の方法。
- 前記抗体フラグメントが、Fv、Fab、Fab’、およびF(ab’)2からなる群より選択される、請求項20に記載の方法。
- 前記抗体が、全長抗体である、請求項19に記載の方法。
- 前記抗体が、キメラ抗体である、請求項19に記載の方法。
- 前記抗体が、ヒト化抗体である、請求項19に記載の方法。
- 前記抗体が、ヒト抗体である、請求項19に記載の方法。
- 前記アンタゴニストが、さらなる治療薬剤と組み合わせて投与される、請求項15に記載の方法。
- 前記さらなる治療薬剤が、抗炎症分子である、請求項26に記載の方法。
- 前記抗炎症分子が、コルチコステロイドおよび非ステロイド性抗炎症薬物(NSAID)からなる群より選択される、請求項27に記載の方法。
- 抗炎症薬剤を同定するための方法であって、以下の工程:
(a)T細胞の培養物を、IL−23とともに、候補分子の存在下および不存在下でインキュベートする工程;
(b)該培養物中でのIL−17のレベルをモニタリングする工程;および
(c)該候補分子の存在下でのIL−17のレベルが、該候補分子の不存在下においてよりも低い場合に、該候補分子を抗炎症薬剤として同定する工程
を包含する、方法。 - 前記候補分子が、非ペプチド性有機低分子である、請求項29に記載の方法。
- 前記候補分子が、ペプチドである、請求項29に記載の方法。
- 前記候補分子が、ポリペプチドである、請求項29に記載の方法。
- 前記候補分子が、抗体である、請求項29に記載の方法。
- 前記T細胞が、活性化T細胞である、請求項29に記載の方法。
- 前記T細胞が、記憶細胞である、請求項29に記載の方法。
- IL−17のレベルが、ELISAによってモニタリングされる、請求項29に記載の方法。
- 請求項29に記載の方法によって同定された、抗炎症薬剤。
- 哺乳動物被験体中でのIL−17産生を誘導するための方法であって、IL−23アゴニストを該被験体に投与する工程を包含する、方法。
- 前記哺乳動物被験体が、ヒトである、請求項38に記載の方法。
- 前記ヒト被験体が、細菌感染に曝露されている、請求項39に記載の方法。
- 前記ヒト被験体が、Mycobacterium tuberculosisによる感染に曝露されている、請求項40に記載の方法。
- 前記IL−23アゴニストが、抗体である、請求項39に記載の方法。
- 前記抗体が、抗IL−23または抗IL−23レセプター抗体である、請求項42に記載の方法。
- 前記抗体が、抗体フラグメントである、請求項43に記載の方法。
- 前記抗体フラグメントが、Fv、Fab、Fab’、およびF(ab’)2からなる群より選択される、請求項44に記載の方法。
- 前記抗体が、全長抗体である、請求項43に記載の方法。
- 前記抗体が、キメラ抗体である、請求項43に記載の方法。
- 前記抗体が、ヒト化抗体である、請求項43に記載の方法。
- 前記抗体が、ヒト抗体である、請求項43に記載の方法。
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US42309002P | 2002-10-30 | 2002-10-30 | |
US60/423,090 | 2002-10-30 |
Related Parent Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2004550229A Division JP5477998B2 (ja) | 2002-10-30 | 2003-10-29 | Il−17産生の阻害 |
Related Child Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2013123690A Division JP5870067B2 (ja) | 2002-10-30 | 2013-06-12 | Il−17産生の阻害 |
Publications (2)
Publication Number | Publication Date |
---|---|
JP2011042658A true JP2011042658A (ja) | 2011-03-03 |
JP5705483B2 JP5705483B2 (ja) | 2015-04-22 |
Family
ID=32312602
Family Applications (3)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2004550229A Expired - Lifetime JP5477998B2 (ja) | 2002-10-30 | 2003-10-29 | Il−17産生の阻害 |
JP2010210980A Expired - Lifetime JP5705483B2 (ja) | 2002-10-30 | 2010-09-21 | Il−17産生の阻害 |
JP2013123690A Expired - Lifetime JP5870067B2 (ja) | 2002-10-30 | 2013-06-12 | Il−17産生の阻害 |
Family Applications Before (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2004550229A Expired - Lifetime JP5477998B2 (ja) | 2002-10-30 | 2003-10-29 | Il−17産生の阻害 |
Family Applications After (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2013123690A Expired - Lifetime JP5870067B2 (ja) | 2002-10-30 | 2013-06-12 | Il−17産生の阻害 |
Country Status (17)
Country | Link |
---|---|
US (6) | US7510709B2 (ja) |
EP (2) | EP2108660A1 (ja) |
JP (3) | JP5477998B2 (ja) |
KR (2) | KR101076931B1 (ja) |
CN (2) | CN1711282B (ja) |
AT (1) | ATE439166T1 (ja) |
AU (1) | AU2003287257C1 (ja) |
CA (1) | CA2501786C (ja) |
DE (1) | DE60328823D1 (ja) |
DK (1) | DK1576011T3 (ja) |
ES (1) | ES2329673T3 (ja) |
IL (1) | IL167845A (ja) |
MX (1) | MXPA05004512A (ja) |
NZ (1) | NZ539271A (ja) |
PT (1) | PT1576011E (ja) |
WO (1) | WO2004042009A2 (ja) |
ZA (1) | ZA200503013B (ja) |
Families Citing this family (59)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6830751B1 (en) * | 1994-03-14 | 2004-12-14 | Genetics Institute, Llc | Use of IL-12 antagonists in the treatment of rheumatoid arthritis |
US20020137890A1 (en) * | 1997-03-31 | 2002-09-26 | Genentech, Inc. | Secreted and transmembrane polypeptides and nucleic acids encoding the same |
CA2328496C (en) | 1998-05-15 | 2016-01-05 | Genentech, Inc. | Il-17 homologous polypeptides and therapeutic uses thereof |
US7771719B1 (en) * | 2000-01-11 | 2010-08-10 | Genentech, Inc. | Pharmaceutical compositions, kits, and therapeutic uses of antagonist antibodies to IL-17E |
US20040043397A1 (en) * | 2000-01-11 | 2004-03-04 | Genentech, Inc. | IL-17 homologous polypeptides and therapeutic uses thereof |
US7718397B2 (en) | 2000-03-21 | 2010-05-18 | Genentech, Inc. | Nucleic acids encoding receptor for IL-17 homologous polypeptides and uses thereof |
US20030203451A1 (en) * | 2000-08-24 | 2003-10-30 | Genentech, Inc. | IL-17 homologous polypeptides and therapeutic uses thereof |
US7422743B2 (en) * | 2000-05-10 | 2008-09-09 | Schering Corporation | Mammalian receptor protein DCRS5;methods of treatment |
US20030096969A1 (en) * | 2000-06-02 | 2003-05-22 | Genentech, Inc. | Secreted and transmembrane polypeptides and nucleic acids encoding the same |
US20070160576A1 (en) | 2001-06-05 | 2007-07-12 | Genentech, Inc. | IL-17A/F heterologous polypeptides and therapeutic uses thereof |
WO2004071517A2 (en) * | 2003-02-06 | 2004-08-26 | Schering Corporation | Uses of il-23 related reagents |
AU2004239288B2 (en) | 2003-05-09 | 2010-01-28 | Centocor, Inc. | IL-23p40 specific immunoglobulin derived proteins, compositions, methods and uses |
EP2277908A3 (en) | 2003-07-08 | 2011-12-14 | Genentech, Inc. | IL-17A/F heterologous polypeptides, antibodies and therapeutic uses thereof |
HUE026260T2 (en) * | 2003-11-21 | 2016-06-28 | Ucb Biopharma Sprl | A method for treating multiple sclerosis by inhibiting IL-17 activity |
US20050226878A1 (en) * | 2003-12-02 | 2005-10-13 | 3M Innovative Properties Company | Therapeutic combinations and methods including IRM compounds |
US8940755B2 (en) * | 2003-12-02 | 2015-01-27 | 3M Innovative Properties Company | Therapeutic combinations and methods including IRM compounds |
EP1901768B1 (en) * | 2004-02-17 | 2011-11-16 | Schering Corporation | Methods of modulating il-23 activity; related reagents |
AU2005241020B2 (en) * | 2004-05-03 | 2008-07-10 | Merck Sharp & Dohme Corp. | Use of IL-17 expression to predict skin inflammation; methods of treatment |
US20050287593A1 (en) | 2004-05-03 | 2005-12-29 | Schering Corporation | Use of cytokine expression to predict skin inflammation; methods of treatment |
AR051444A1 (es) | 2004-09-24 | 2007-01-17 | Centocor Inc | Proteinas derivadas de inmunoglobulina especifica de il-23p40, composiciones, epitopos, metodos y usos |
EP2292758A3 (en) * | 2004-12-20 | 2013-12-25 | Merck Sharp & Dohme Corp. | Uses of mammalian cytokine; related reagents |
WO2006074179A2 (en) * | 2005-01-04 | 2006-07-13 | University Of Rochester | Blockade of elr+cxc chemokines as a treatment for inflammatory and autoimmune disease |
EP1896073B1 (en) | 2005-06-30 | 2013-03-06 | Janssen Biotech, Inc. | Anti-il-23 antibodies, compositions, methods and uses |
EP1907421A4 (en) * | 2005-06-30 | 2012-03-28 | Abbott Lab | IL-12 / P40 BINDING PROTEINS |
SG165322A1 (en) | 2005-08-31 | 2010-10-28 | Schering Corp | Engineered anti-il-23 antibodies |
AU2006284841B2 (en) * | 2005-09-01 | 2012-11-08 | Merck Sharp & Dohme Corp. | Use of IL-23 and IL-17 antagonists to treat autoimmune ocular inflammatory disease |
JP2009518314A (ja) * | 2005-12-02 | 2009-05-07 | ジェネンテック・インコーポレーテッド | Il−22に結合する抗体およびil−22rに結合する抗体を含む、サイトカインシグナリングに関連する疾患および障害の処置のための組成物および方法 |
RS53685B1 (en) | 2005-12-29 | 2015-04-30 | Janssen Biotech Inc. | HUMAN ANTI-IL-23 ANTIBODIES, COMPOSITIONS, METHODS AND APPLICATIONS |
US7910703B2 (en) | 2006-03-10 | 2011-03-22 | Zymogenetics, Inc. | Antagonists to IL-17A, IL-17F, and IL-23P19 and methods of use |
MY188368A (en) | 2006-09-08 | 2021-12-06 | Abbott Lab | Interleukin-13 binding proteins |
US8414897B1 (en) * | 2006-10-02 | 2013-04-09 | The Uab Research Foundation | Pathway for Th-17 cell development and methods utilizing same |
TWI426918B (zh) | 2007-02-12 | 2014-02-21 | Merck Sharp & Dohme | Il-23拮抗劑於治療感染之用途 |
DK2426144T3 (en) | 2007-02-23 | 2019-01-07 | Merck Sharp & Dohme | Manipulated Anti-IL-23P19 Antibodies |
BRPI0807991A2 (pt) * | 2007-02-28 | 2014-06-17 | Schering Corp | Anticorpos anti-il-23r elaborados. |
JPWO2009054454A1 (ja) | 2007-10-24 | 2011-03-03 | 国立大学法人 東京医科歯科大学 | カテプシン阻害剤を有効成分として含有するToll様受容体のシグナル伝達の調整剤 |
CN104338136A (zh) * | 2008-04-29 | 2015-02-11 | 安进研发(慕尼黑)股份有限公司 | 用于治疗的gm-csf和il-17抑制剂 |
CA2721713C (en) | 2008-05-05 | 2019-07-09 | Novimmune Sa | Anti-il-17a/il-17f cross-reactive antibodies and methods of use thereof |
WO2010056816A2 (en) * | 2008-11-12 | 2010-05-20 | Schering Corporation | βGI-IGG INTRON FOR ENHANCED ANTI-IGF1 R EXPRESSION |
US20100233270A1 (en) | 2009-01-08 | 2010-09-16 | Northwestern University | Delivery of Oligonucleotide-Functionalized Nanoparticles |
JP6053517B2 (ja) | 2009-05-05 | 2016-12-27 | ノヴィミュンヌ エスア | 抗il−17f抗体およびそれらの使用法 |
JP2011032170A (ja) * | 2009-07-29 | 2011-02-17 | Morinaga Milk Ind Co Ltd | ヒト細胞il−17産生抑制剤 |
US9301997B2 (en) | 2009-09-21 | 2016-04-05 | Peptinov Sas | Method of vaccination for limiting articular inflammation in rheumatoid arthritis and multiple sclerosis by administering IL-23 peptides |
JO3244B1 (ar) | 2009-10-26 | 2018-03-08 | Amgen Inc | بروتينات ربط مستضادات il – 23 البشرية |
WO2011062628A1 (en) * | 2009-11-20 | 2011-05-26 | New York University | Methods and compositions for modulation of t cells via the kynurenine pathway |
GB201013975D0 (en) | 2010-08-20 | 2010-10-06 | Imp Innovations Ltd | Method of treating desease |
CN102010903A (zh) * | 2010-08-26 | 2011-04-13 | 中国医学科学院肿瘤研究所 | Il-23在肝癌早期病变诊断中的应用 |
HUE030916T2 (en) | 2010-11-04 | 2017-06-28 | Boehringer Ingelheim Int | Anti-IL-23 antibodies |
WO2013116682A1 (en) | 2012-02-02 | 2013-08-08 | Ensemble Therapeutics Corporation | Macrocyclic compounds for modulating il-17 |
PL3326649T3 (pl) | 2012-05-03 | 2022-04-25 | Boehringer Ingelheim International Gmbh | Przeciwciała anty-il-23p19 |
EP2994490A1 (en) | 2013-05-10 | 2016-03-16 | Numab AG | Bispecific constructs and their use in the treatment of various diseases |
EP3039039B1 (en) | 2013-08-30 | 2021-03-10 | Takeda GmbH | Antibodies neutralizing gm-csf for use in the treatment of rheumatoid arthritis or as analgesics |
WO2016014775A1 (en) | 2014-07-24 | 2016-01-28 | Boehringer Ingelheim International Gmbh | Biomarkers useful in the treatment of il-23a related diseases |
AP2017009776A0 (en) | 2014-09-03 | 2017-02-28 | Boehringer Ingelheim Int | Compound targeting il-23a and tnf-alpha and uses thereof |
AR102417A1 (es) | 2014-11-05 | 2017-03-01 | Lilly Co Eli | Anticuerpos biespecíficos anti-tnf- / anti-il-23 |
US11866700B2 (en) | 2016-05-06 | 2024-01-09 | Exicure Operating Company | Liposomal spherical nucleic acid (SNA) constructs presenting antisense oligonucleotides (ASO) for specific knockdown of interleukin 17 receptor mRNA |
US11548941B2 (en) | 2018-11-20 | 2023-01-10 | Janssen Biotech, Inc. | Safe and effective method of treating psoriasis with anti-IL-23 specific antibody |
KR20220012883A (ko) | 2019-05-23 | 2022-02-04 | 얀센 바이오테크 인코포레이티드 | Il-23 및 tnf 알파에 대한 항체의 병용요법으로 염증성 장질환을 치료하는 방법 |
CN112390890B (zh) * | 2020-11-06 | 2022-06-24 | 江苏荃信生物医药股份有限公司 | 一种定量检测血清中抗人白介素17单克隆抗体含量的酶联免疫分析方法 |
CN116183472B (zh) * | 2023-04-25 | 2023-08-18 | 上海益诺思生物技术股份有限公司 | Cba法检测非人类灵长类动物细胞因子的验证方法 |
Family Cites Families (24)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2001018022A1 (en) | 1999-09-03 | 2001-03-15 | Human Genome Sciences, Inc. | 52 human secreted proteins |
PE20000183A1 (es) | 1997-07-25 | 2000-03-11 | Schering Corp | Citoquinas de mamiferos y reactivos relacionados |
US6060284A (en) * | 1997-07-25 | 2000-05-09 | Schering Corporation | DNA encoding interleukin-B30 |
WO1999054357A1 (fr) * | 1998-04-14 | 1999-10-28 | Chugai Research Institute For Molecular Medicine, Inc. | Nouvelle proteine du type cytokine |
US6448081B1 (en) * | 2001-05-07 | 2002-09-10 | Isis Pharmaceuticals, Inc. | Antisense modulation of interleukin 12 p40 subunit expression |
JP2002534122A (ja) * | 1999-01-11 | 2002-10-15 | シェーリング コーポレイション | インターロイキン−17関連哺乳動物サイトカイン、それをコードするポリヌクレオチド、使用 |
US6914128B1 (en) * | 1999-03-25 | 2005-07-05 | Abbott Gmbh & Co. Kg | Human antibodies that bind human IL-12 and methods for producing |
CA2669512A1 (en) | 1999-03-25 | 2000-09-28 | Abbott Gmbh & Co. Kg | Human antibodies that bind human il-12 and methods for producing |
US20030082734A1 (en) * | 1999-06-01 | 2003-05-01 | Dowling Lynette M. | Mammalian receptor proteins; related reagents and methods |
IL148300A0 (en) | 1999-09-09 | 2002-09-12 | Schering Corp | Mammalian cytokines; related reagents and methods |
AU7445900A (en) * | 1999-09-27 | 2001-04-30 | Chugai Seiyaku Kabushiki Kaisha | Novel hemopoietin receptor protein, nr12 |
US7422743B2 (en) * | 2000-05-10 | 2008-09-09 | Schering Corporation | Mammalian receptor protein DCRS5;methods of treatment |
PT1287130E (pt) * | 2000-05-10 | 2008-09-01 | Schering Corp | Proteínas de subunidades de receptores de citocinas de mamífero, métodos e reagentes relacionados |
US6902734B2 (en) | 2000-08-07 | 2005-06-07 | Centocor, Inc. | Anti-IL-12 antibodies and compositions thereof |
JP3899861B2 (ja) * | 2001-07-13 | 2007-03-28 | 株式会社日立製作所 | 光ディスク、情報再生方法及び記録方法 |
PT1601694E (pt) * | 2003-03-10 | 2009-12-03 | Schering Corp | Utilizações de agonistas e antagonistas de il-23; reagentes relacionados |
US7935698B2 (en) | 2003-11-10 | 2011-05-03 | Synta Pharmaceuticals Corporation | Heteroaryl-hydrazone compounds |
CA2545258A1 (en) | 2003-11-10 | 2005-05-26 | Synta Pharmaceuticals, Corp. | Pyridine compounds |
EP1687002A4 (en) * | 2003-11-10 | 2008-07-23 | Synta Pharmaceuticals Corp | CONDENSED HETEROCYCLIC COMPOUNDS |
EP1901768B1 (en) * | 2004-02-17 | 2011-11-16 | Schering Corporation | Methods of modulating il-23 activity; related reagents |
US20050287593A1 (en) * | 2004-05-03 | 2005-12-29 | Schering Corporation | Use of cytokine expression to predict skin inflammation; methods of treatment |
AU2005241020B2 (en) | 2004-05-03 | 2008-07-10 | Merck Sharp & Dohme Corp. | Use of IL-17 expression to predict skin inflammation; methods of treatment |
AR051444A1 (es) * | 2004-09-24 | 2007-01-17 | Centocor Inc | Proteinas derivadas de inmunoglobulina especifica de il-23p40, composiciones, epitopos, metodos y usos |
KR101004362B1 (ko) | 2010-03-19 | 2010-12-28 | 가톨릭대학교 산학협력단 | 자가 면역 질환 예방 및 치료용 TNF-α와 TWEAK 이중 길항제 |
-
2003
- 2003-10-29 EP EP20090007964 patent/EP2108660A1/en not_active Ceased
- 2003-10-29 EP EP03781490A patent/EP1576011B1/en not_active Revoked
- 2003-10-29 DE DE60328823T patent/DE60328823D1/de not_active Expired - Lifetime
- 2003-10-29 US US10/697,599 patent/US7510709B2/en active Active
- 2003-10-29 AU AU2003287257A patent/AU2003287257C1/en not_active Expired
- 2003-10-29 MX MXPA05004512A patent/MXPA05004512A/es active IP Right Grant
- 2003-10-29 ES ES03781490T patent/ES2329673T3/es not_active Expired - Lifetime
- 2003-10-29 NZ NZ539271A patent/NZ539271A/en not_active IP Right Cessation
- 2003-10-29 PT PT03781490T patent/PT1576011E/pt unknown
- 2003-10-29 CN CN2003801027073A patent/CN1711282B/zh not_active Expired - Lifetime
- 2003-10-29 CA CA2501786A patent/CA2501786C/en not_active Expired - Lifetime
- 2003-10-29 DK DK03781490T patent/DK1576011T3/da active
- 2003-10-29 KR KR1020057007502A patent/KR101076931B1/ko active IP Right Grant
- 2003-10-29 KR KR1020117003939A patent/KR101053412B1/ko active IP Right Grant
- 2003-10-29 WO PCT/US2003/034429 patent/WO2004042009A2/en active Application Filing
- 2003-10-29 AT AT03781490T patent/ATE439166T1/de active
- 2003-10-29 CN CN2010101439342A patent/CN101824088B/zh not_active Expired - Lifetime
- 2003-10-29 JP JP2004550229A patent/JP5477998B2/ja not_active Expired - Lifetime
-
2005
- 2005-04-04 IL IL167845A patent/IL167845A/en unknown
- 2005-04-14 ZA ZA200503013A patent/ZA200503013B/en unknown
-
2009
- 2009-01-07 US US12/350,125 patent/US8287869B2/en active Active
- 2009-01-07 US US12/350,089 patent/US20100266582A1/en not_active Abandoned
-
2010
- 2010-09-21 JP JP2010210980A patent/JP5705483B2/ja not_active Expired - Lifetime
-
2012
- 2012-10-11 US US13/649,810 patent/US20130309194A1/en not_active Abandoned
-
2013
- 2013-06-12 JP JP2013123690A patent/JP5870067B2/ja not_active Expired - Lifetime
-
2016
- 2016-03-10 US US15/066,568 patent/US20160326229A1/en not_active Abandoned
-
2018
- 2018-04-19 US US15/957,879 patent/US20190092829A1/en not_active Abandoned
Non-Patent Citations (2)
Title |
---|
JPN5005010567; Benson,J. et al.: 'The role of IL-23 in experimental autoimmune encephalomyelitis' FASEB J. Vol.16,No.5, 20020322, P.A1045 * |
JPN7009005303; Maeyama,T. et al.: 'Attenuation of bleomycin-induced pneumopathy in mice by monoclonal antibody to interleukin-12' Am. J. Physiol. Lung Cell Mol. Physiol. Vol.280,No.6, 200106, P.L1128-L1137 * |
Also Published As
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JP5870067B2 (ja) | Il−17産生の阻害 | |
JP2006514004A5 (ja) | ||
Gaffen et al. | IL-23-IL-17 immune axis: discovery, mechanistic understanding, and clinical testing | |
US20090142806A1 (en) | Interleukin-17f antibodies and other il-17f signaling antagonists and uses therefor | |
US20140105887A1 (en) | Methods for modulating il-33 activity | |
JP2008532493A (ja) | Il−17fとil−17rとの間の相互作用の特性解析 | |
JP2015524793A (ja) | 炎症阻害用の抗cxcl9、抗cxcl10、抗cxcl11、抗cxcl13、抗cxcr3、及び抗cxcr5作用剤 | |
US20160130350A1 (en) | Anti-cxcl9, anti-cxcl10, anti-cxcl11, anti-cxcl13, anti-cxcr3 and anti-cxcr5 agents for inhibition of inflammation | |
US20100256038A1 (en) | Th-17 cells | |
JP2009543579A (ja) | 抗炎症反応のための標的としてのWSX−1/p28 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20120710 |
|
A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20120925 |
|
A602 | Written permission of extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A602 Effective date: 20120928 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20130109 |
|
A02 | Decision of refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A02 Effective date: 20130212 |
|
A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20150225 |
|
R150 | Certificate of patent or registration of utility model |
Ref document number: 5705483 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 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
EXPY | Cancellation because of completion of term |