CA2749539C - Compositions and methods comprising interleukin-2 mutants for treating inflammatory and autoimmune diseases - Google Patents
Compositions and methods comprising interleukin-2 mutants for treating inflammatory and autoimmune diseases Download PDFInfo
- Publication number
- CA2749539C CA2749539C CA2749539A CA2749539A CA2749539C CA 2749539 C CA2749539 C CA 2749539C CA 2749539 A CA2749539 A CA 2749539A CA 2749539 A CA2749539 A CA 2749539A CA 2749539 C CA2749539 C CA 2749539C
- Authority
- CA
- Canada
- Prior art keywords
- seq
- use according
- amino acid
- set forth
- variant
- 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
- 108010002350 Interleukin-2 Proteins 0.000 title claims abstract description 158
- 208000027866 inflammatory disease Diseases 0.000 title claims abstract description 18
- 102000000588 Interleukin-2 Human genes 0.000 title claims description 157
- 239000000203 mixture Substances 0.000 title claims description 31
- 208000023275 Autoimmune disease Diseases 0.000 title abstract description 6
- 230000002757 inflammatory effect Effects 0.000 title abstract description 5
- 238000000034 method Methods 0.000 title description 27
- 230000035772 mutation Effects 0.000 claims description 52
- 210000001744 T-lymphocyte Anatomy 0.000 claims description 50
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 40
- 102000004196 processed proteins & peptides Human genes 0.000 claims description 39
- 229920001184 polypeptide Polymers 0.000 claims description 38
- 150000001413 amino acids Chemical class 0.000 claims description 35
- 102100027581 Forkhead box protein P3 Human genes 0.000 claims description 32
- 101000861452 Homo sapiens Forkhead box protein P3 Proteins 0.000 claims description 32
- 108010029477 STAT5 Transcription Factor Proteins 0.000 claims description 26
- 102100024481 Signal transducer and activator of transcription 5A Human genes 0.000 claims description 26
- 230000026731 phosphorylation Effects 0.000 claims description 22
- 238000006366 phosphorylation reaction Methods 0.000 claims description 22
- 230000004083 survival effect Effects 0.000 claims description 18
- 239000003814 drug Substances 0.000 claims description 13
- 210000003289 regulatory T cell Anatomy 0.000 claims description 10
- 108010038453 Interleukin-2 Receptors Proteins 0.000 claims description 8
- 102000010789 Interleukin-2 Receptors Human genes 0.000 claims description 8
- 230000010261 cell growth Effects 0.000 claims description 7
- 102220274636 rs144712084 Human genes 0.000 claims description 7
- 201000000596 systemic lupus erythematosus Diseases 0.000 claims description 7
- 206010039710 Scleroderma Diseases 0.000 claims description 6
- 230000028993 immune response Effects 0.000 claims description 6
- 239000000126 substance Substances 0.000 claims description 6
- 230000001629 suppression Effects 0.000 claims description 6
- 208000022559 Inflammatory bowel disease Diseases 0.000 claims description 5
- 206010047115 Vasculitis Diseases 0.000 claims description 5
- 208000024908 graft versus host disease Diseases 0.000 claims description 5
- 210000000056 organ Anatomy 0.000 claims description 5
- 206010002556 Ankylosing Spondylitis Diseases 0.000 claims description 4
- 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 claims description 4
- 208000015943 Coeliac disease Diseases 0.000 claims description 4
- 206010009900 Colitis ulcerative Diseases 0.000 claims description 4
- 208000011231 Crohn disease Diseases 0.000 claims description 4
- 208000009329 Graft vs Host Disease Diseases 0.000 claims description 4
- 102220494399 Signal transducer and activator of transcription 5A_Y31H_mutation Human genes 0.000 claims description 4
- 208000021386 Sjogren Syndrome Diseases 0.000 claims description 4
- 206010067584 Type 1 diabetes mellitus Diseases 0.000 claims description 4
- 201000006704 Ulcerative Colitis Diseases 0.000 claims description 4
- 206010003246 arthritis Diseases 0.000 claims description 4
- 208000006673 asthma Diseases 0.000 claims description 4
- 238000001727 in vivo Methods 0.000 claims description 4
- 238000004519 manufacturing process Methods 0.000 claims description 4
- 102200053439 rs72466487 Human genes 0.000 claims description 4
- 102220148530 rs886061344 Human genes 0.000 claims description 4
- 210000002966 serum Anatomy 0.000 claims description 4
- 206010052779 Transplant rejections Diseases 0.000 claims description 3
- 102220044643 rs587781450 Human genes 0.000 claims description 3
- 125000003275 alpha amino acid group Chemical group 0.000 claims 24
- 206010020751 Hypersensitivity Diseases 0.000 claims 3
- 208000026935 allergic disease Diseases 0.000 claims 3
- 230000007815 allergy Effects 0.000 claims 3
- 206010012601 diabetes mellitus Diseases 0.000 claims 3
- 238000000338 in vitro Methods 0.000 claims 3
- 201000006417 multiple sclerosis Diseases 0.000 claims 3
- 102220050130 rs187015338 Human genes 0.000 claims 3
- 230000001506 immunosuppresive effect Effects 0.000 abstract description 13
- 210000004027 cell Anatomy 0.000 description 39
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 17
- 108090000623 proteins and genes Proteins 0.000 description 15
- 235000001014 amino acid Nutrition 0.000 description 14
- 230000011664 signaling Effects 0.000 description 14
- 229940024606 amino acid Drugs 0.000 description 13
- 201000010099 disease Diseases 0.000 description 12
- 230000004913 activation Effects 0.000 description 11
- 108091028043 Nucleic acid sequence Proteins 0.000 description 10
- 102100033810 RAC-alpha serine/threonine-protein kinase Human genes 0.000 description 10
- 230000006870 function Effects 0.000 description 10
- 239000013598 vector Substances 0.000 description 10
- 238000011282 treatment Methods 0.000 description 9
- 239000003795 chemical substances by application Substances 0.000 description 8
- 108040006849 interleukin-2 receptor activity proteins Proteins 0.000 description 8
- 102000004169 proteins and genes Human genes 0.000 description 8
- 108010076504 Protein Sorting Signals Proteins 0.000 description 7
- 230000000694 effects Effects 0.000 description 7
- 230000012010 growth Effects 0.000 description 7
- 239000008194 pharmaceutical composition Substances 0.000 description 7
- 235000018102 proteins Nutrition 0.000 description 7
- 206010061218 Inflammation Diseases 0.000 description 6
- 108010065917 TOR Serine-Threonine Kinases Proteins 0.000 description 6
- 102000013530 TOR Serine-Threonine Kinases Human genes 0.000 description 6
- 230000004054 inflammatory process Effects 0.000 description 6
- 230000000366 juvenile effect Effects 0.000 description 6
- 208000011580 syndromic disease Diseases 0.000 description 6
- 238000003786 synthesis reaction Methods 0.000 description 6
- 229940124597 therapeutic agent Drugs 0.000 description 6
- 108020004705 Codon Proteins 0.000 description 5
- 206010059176 Juvenile idiopathic arthritis Diseases 0.000 description 5
- 238000003556 assay Methods 0.000 description 5
- 238000004113 cell culture Methods 0.000 description 5
- 208000035475 disorder Diseases 0.000 description 5
- -1 e.g. Proteins 0.000 description 5
- 230000001965 increasing effect Effects 0.000 description 5
- 230000035755 proliferation Effects 0.000 description 5
- 210000001266 CD8-positive T-lymphocyte Anatomy 0.000 description 4
- 238000002965 ELISA Methods 0.000 description 4
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 4
- 208000003456 Juvenile Arthritis Diseases 0.000 description 4
- 206010028980 Neoplasm Diseases 0.000 description 4
- 108091034117 Oligonucleotide Proteins 0.000 description 4
- 239000002202 Polyethylene glycol Substances 0.000 description 4
- 210000004102 animal cell Anatomy 0.000 description 4
- 201000011510 cancer Diseases 0.000 description 4
- 239000012636 effector Substances 0.000 description 4
- 238000009472 formulation Methods 0.000 description 4
- 210000000822 natural killer cell Anatomy 0.000 description 4
- 230000037361 pathway Effects 0.000 description 4
- 229920001223 polyethylene glycol Polymers 0.000 description 4
- 206010039073 rheumatoid arthritis Diseases 0.000 description 4
- 238000002741 site-directed mutagenesis Methods 0.000 description 4
- 230000000638 stimulation Effects 0.000 description 4
- 231100000419 toxicity Toxicity 0.000 description 4
- 230000001988 toxicity Effects 0.000 description 4
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 3
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 3
- 108020004414 DNA Proteins 0.000 description 3
- 241000196324 Embryophyta Species 0.000 description 3
- 229930195725 Mannitol Natural products 0.000 description 3
- 108010071690 Prealbumin Proteins 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- 201000004681 Psoriasis Diseases 0.000 description 3
- 102000009190 Transthyretin Human genes 0.000 description 3
- JLCPHMBAVCMARE-UHFFFAOYSA-N [3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-hydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methyl [5-(6-aminopurin-9-yl)-2-(hydroxymethyl)oxolan-3-yl] hydrogen phosphate Polymers Cc1cn(C2CC(OP(O)(=O)OCC3OC(CC3OP(O)(=O)OCC3OC(CC3O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c3nc(N)[nH]c4=O)C(COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3CO)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cc(C)c(=O)[nH]c3=O)n3cc(C)c(=O)[nH]c3=O)n3ccc(N)nc3=O)n3cc(C)c(=O)[nH]c3=O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)O2)c(=O)[nH]c1=O JLCPHMBAVCMARE-UHFFFAOYSA-N 0.000 description 3
- 230000004663 cell proliferation Effects 0.000 description 3
- 210000004978 chinese hamster ovary cell Anatomy 0.000 description 3
- 239000003085 diluting agent Substances 0.000 description 3
- 238000000684 flow cytometry Methods 0.000 description 3
- 238000002513 implantation Methods 0.000 description 3
- 201000002215 juvenile rheumatoid arthritis Diseases 0.000 description 3
- 239000000594 mannitol Substances 0.000 description 3
- 235000010355 mannitol Nutrition 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- 230000009467 reduction Effects 0.000 description 3
- 230000007781 signaling event Effects 0.000 description 3
- 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 3
- 239000000600 sorbitol Substances 0.000 description 3
- 230000004936 stimulating effect Effects 0.000 description 3
- 238000006467 substitution reaction Methods 0.000 description 3
- 208000024891 symptom Diseases 0.000 description 3
- 230000001225 therapeutic effect Effects 0.000 description 3
- 210000001519 tissue Anatomy 0.000 description 3
- 230000003827 upregulation Effects 0.000 description 3
- WRMNZCZEMHIOCP-UHFFFAOYSA-N 2-phenylethanol Chemical compound OCCC1=CC=CC=C1 WRMNZCZEMHIOCP-UHFFFAOYSA-N 0.000 description 2
- 206010003253 Arthritis enteropathic Diseases 0.000 description 2
- 206010003267 Arthritis reactive Diseases 0.000 description 2
- 208000036487 Arthropathies Diseases 0.000 description 2
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
- 241000894006 Bacteria Species 0.000 description 2
- 208000035473 Communicable disease Diseases 0.000 description 2
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 2
- 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 2
- 241000233866 Fungi Species 0.000 description 2
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 2
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
- 239000004471 Glycine Substances 0.000 description 2
- 241000238631 Hexapoda Species 0.000 description 2
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 2
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 2
- 208000012659 Joint disease Diseases 0.000 description 2
- 101800001155 Latency-associated peptide Proteins 0.000 description 2
- 102400000401 Latency-associated peptide Human genes 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 description 2
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 2
- 208000034189 Sclerosis Diseases 0.000 description 2
- 241000256251 Spodoptera frugiperda Species 0.000 description 2
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 2
- 229930006000 Sucrose Natural products 0.000 description 2
- 210000000662 T-lymphocyte subset Anatomy 0.000 description 2
- 230000003321 amplification Effects 0.000 description 2
- 230000009286 beneficial effect Effects 0.000 description 2
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 239000000872 buffer Substances 0.000 description 2
- RYYVLZVUVIJVGH-UHFFFAOYSA-N caffeine Chemical compound CN1C(=O)N(C)C(=O)C2=C1N=CN2C RYYVLZVUVIJVGH-UHFFFAOYSA-N 0.000 description 2
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 2
- 208000019069 chronic childhood arthritis Diseases 0.000 description 2
- 238000002648 combination therapy Methods 0.000 description 2
- 201000001981 dermatomyositis Diseases 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 239000003995 emulsifying agent Substances 0.000 description 2
- 206010014910 enthesopathy Diseases 0.000 description 2
- 239000013604 expression vector Substances 0.000 description 2
- 239000008103 glucose Substances 0.000 description 2
- 230000003308 immunostimulating effect Effects 0.000 description 2
- 238000001802 infusion Methods 0.000 description 2
- 239000003112 inhibitor Substances 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 230000003993 interaction Effects 0.000 description 2
- 230000007774 longterm Effects 0.000 description 2
- 125000003588 lysine group Chemical group [H]N([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 description 2
- LXCFILQKKLGQFO-UHFFFAOYSA-N methylparaben Chemical compound COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 description 2
- 230000000869 mutational effect Effects 0.000 description 2
- 238000003199 nucleic acid amplification method Methods 0.000 description 2
- 239000002773 nucleotide Substances 0.000 description 2
- 125000003729 nucleotide group Chemical group 0.000 description 2
- 230000010412 perfusion Effects 0.000 description 2
- 239000000546 pharmaceutical excipient Substances 0.000 description 2
- 229920000136 polysorbate Polymers 0.000 description 2
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 2
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 2
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 2
- 230000003389 potentiating effect Effects 0.000 description 2
- 239000003755 preservative agent Substances 0.000 description 2
- 230000001737 promoting effect Effects 0.000 description 2
- QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical compound CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 description 2
- 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 2
- 208000002574 reactive arthritis Diseases 0.000 description 2
- YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 2
- 229960002930 sirolimus Drugs 0.000 description 2
- GEHJYWRUCIMESM-UHFFFAOYSA-L sodium sulfite Chemical compound [Na+].[Na+].[O-]S([O-])=O GEHJYWRUCIMESM-UHFFFAOYSA-L 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 238000010186 staining Methods 0.000 description 2
- 239000005720 sucrose Substances 0.000 description 2
- 230000002459 sustained effect Effects 0.000 description 2
- 230000009885 systemic effect Effects 0.000 description 2
- JNYAEWCLZODPBN-JGWLITMVSA-N (2r,3r,4s)-2-[(1r)-1,2-dihydroxyethyl]oxolane-3,4-diol Chemical class OC[C@@H](O)[C@H]1OC[C@H](O)[C@H]1O JNYAEWCLZODPBN-JGWLITMVSA-N 0.000 description 1
- IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 description 1
- 102000010400 1-phosphatidylinositol-3-kinase activity proteins Human genes 0.000 description 1
- 208000026872 Addison Disease Diseases 0.000 description 1
- 230000007730 Akt signaling Effects 0.000 description 1
- 239000004475 Arginine Substances 0.000 description 1
- DCXYFEDJOCDNAF-UHFFFAOYSA-N Asparagine Natural products OC(=O)C(N)CC(N)=O DCXYFEDJOCDNAF-UHFFFAOYSA-N 0.000 description 1
- 201000001320 Atherosclerosis Diseases 0.000 description 1
- 206010003827 Autoimmune hepatitis Diseases 0.000 description 1
- 241000193830 Bacillus <bacterium> Species 0.000 description 1
- 208000023328 Basedow disease Diseases 0.000 description 1
- 239000005711 Benzoic acid Substances 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 1
- BTBUEUYNUDRHOZ-UHFFFAOYSA-N Borate Chemical compound [O-]B([O-])[O-] BTBUEUYNUDRHOZ-UHFFFAOYSA-N 0.000 description 1
- GHXZTYHSJHQHIJ-UHFFFAOYSA-N Chlorhexidine Chemical compound C=1C=C(Cl)C=CC=1NC(N)=NC(N)=NCCCCCCN=C(N)N=C(N)NC1=CC=C(Cl)C=C1 GHXZTYHSJHQHIJ-UHFFFAOYSA-N 0.000 description 1
- 241000282552 Chlorocebus aethiops Species 0.000 description 1
- 206010008609 Cholangitis sclerosing Diseases 0.000 description 1
- 241000699802 Cricetulus griseus Species 0.000 description 1
- 229920000858 Cyclodextrin Polymers 0.000 description 1
- WQZGKKKJIJFFOK-QTVWNMPRSA-N D-mannopyranose Chemical compound OC[C@H]1OC(O)[C@@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-QTVWNMPRSA-N 0.000 description 1
- 201000004624 Dermatitis Diseases 0.000 description 1
- 206010012438 Dermatitis atopic Diseases 0.000 description 1
- 239000004375 Dextrin Substances 0.000 description 1
- 229920001353 Dextrin Polymers 0.000 description 1
- 102100024746 Dihydrofolate reductase Human genes 0.000 description 1
- 206010015278 Erythrodermic psoriasis Diseases 0.000 description 1
- 241000588724 Escherichia coli Species 0.000 description 1
- 102000007665 Extracellular Signal-Regulated MAP Kinases Human genes 0.000 description 1
- 239000001116 FEMA 4028 Substances 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 206010072579 Granulomatosis with polyangiitis Diseases 0.000 description 1
- 208000015023 Graves' disease Diseases 0.000 description 1
- 102000015779 HDL Lipoproteins Human genes 0.000 description 1
- 108010010234 HDL Lipoproteins Proteins 0.000 description 1
- 108060003951 Immunoglobulin Proteins 0.000 description 1
- 108090000467 Interferon-beta Proteins 0.000 description 1
- 102220470904 Interferon-induced protein with tetratricopeptide repeats 5_K48E_mutation Human genes 0.000 description 1
- LPHGQDQBBGAPDZ-UHFFFAOYSA-N Isocaffeine Natural products CN1C(=O)N(C)C(=O)C2=C1N(C)C=N2 LPHGQDQBBGAPDZ-UHFFFAOYSA-N 0.000 description 1
- 208000012528 Juvenile dermatomyositis Diseases 0.000 description 1
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 1
- DCXYFEDJOCDNAF-REOHCLBHSA-N L-asparagine Chemical compound OC(=O)[C@@H](N)CC(N)=O DCXYFEDJOCDNAF-REOHCLBHSA-N 0.000 description 1
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 1
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 1
- 102000007330 LDL Lipoproteins Human genes 0.000 description 1
- 108010007622 LDL Lipoproteins Proteins 0.000 description 1
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
- 239000004472 Lysine Substances 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 102000004316 Oxidoreductases Human genes 0.000 description 1
- 108090000854 Oxidoreductases Proteins 0.000 description 1
- 108091007960 PI3Ks Proteins 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 229920001213 Polysorbate 20 Polymers 0.000 description 1
- 241000589516 Pseudomonas Species 0.000 description 1
- 208000020410 Psoriasis-related juvenile idiopathic arthritis Diseases 0.000 description 1
- 201000001263 Psoriatic Arthritis Diseases 0.000 description 1
- 208000036824 Psoriatic arthropathy Diseases 0.000 description 1
- 206010037575 Pustular psoriasis Diseases 0.000 description 1
- 208000012322 Raynaud phenomenon Diseases 0.000 description 1
- 108020004511 Recombinant DNA Proteins 0.000 description 1
- 102000007562 Serum Albumin Human genes 0.000 description 1
- 108010071390 Serum Albumin Proteins 0.000 description 1
- DWAQJAXMDSEUJJ-UHFFFAOYSA-M Sodium bisulfite Chemical compound [Na+].OS([O-])=O DWAQJAXMDSEUJJ-UHFFFAOYSA-M 0.000 description 1
- 241000187747 Streptomyces Species 0.000 description 1
- 102220500923 Telomerase reverse transcriptase_K35D_mutation Human genes 0.000 description 1
- 102220500914 Telomerase reverse transcriptase_K35R_mutation Human genes 0.000 description 1
- 102220572243 Toll-interacting protein_N29S_mutation Human genes 0.000 description 1
- 102100024036 Tyrosine-protein kinase Lck Human genes 0.000 description 1
- 102100038183 Tyrosine-protein kinase SYK Human genes 0.000 description 1
- 238000009825 accumulation Methods 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 125000003295 alanine group Chemical group N[C@@H](C)C(=O)* 0.000 description 1
- 229910001508 alkali metal halide Inorganic materials 0.000 description 1
- 150000008045 alkali metal halides Chemical class 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 230000005809 anti-tumor immunity Effects 0.000 description 1
- 239000004599 antimicrobial Substances 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 235000006708 antioxidants Nutrition 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
- 206010003230 arteritis Diseases 0.000 description 1
- 235000010323 ascorbic acid Nutrition 0.000 description 1
- 239000011668 ascorbic acid Substances 0.000 description 1
- 229960005070 ascorbic acid Drugs 0.000 description 1
- 229960001230 asparagine Drugs 0.000 description 1
- 235000009582 asparagine Nutrition 0.000 description 1
- 201000008937 atopic dermatitis Diseases 0.000 description 1
- 230000001363 autoimmune Effects 0.000 description 1
- 230000005784 autoimmunity Effects 0.000 description 1
- 229960000686 benzalkonium chloride Drugs 0.000 description 1
- 235000010233 benzoic acid Nutrition 0.000 description 1
- 229960004365 benzoic acid Drugs 0.000 description 1
- CADWTSSKOVRVJC-UHFFFAOYSA-N benzyl(dimethyl)azanium;chloride Chemical compound [Cl-].C[NH+](C)CC1=CC=CC=C1 CADWTSSKOVRVJC-UHFFFAOYSA-N 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- WHGYBXFWUBPSRW-FOUAGVGXSA-N beta-cyclodextrin Chemical compound OC[C@H]([C@H]([C@@H]([C@H]1O)O)O[C@H]2O[C@@H]([C@@H](O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O3)[C@H](O)[C@H]2O)CO)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@@H]3O[C@@H]1CO WHGYBXFWUBPSRW-FOUAGVGXSA-N 0.000 description 1
- 235000011175 beta-cyclodextrine Nutrition 0.000 description 1
- 229960004853 betadex Drugs 0.000 description 1
- 230000003115 biocidal effect Effects 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 210000000988 bone and bone Anatomy 0.000 description 1
- 239000004067 bulking agent Substances 0.000 description 1
- 229960001948 caffeine Drugs 0.000 description 1
- VJEONQKOZGKCAK-UHFFFAOYSA-N caffeine Natural products CN1C(=O)N(C)C(=O)C2=C1C=CN2C VJEONQKOZGKCAK-UHFFFAOYSA-N 0.000 description 1
- 150000001720 carbohydrates Chemical class 0.000 description 1
- 235000014633 carbohydrates Nutrition 0.000 description 1
- 210000000845 cartilage Anatomy 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 239000013592 cell lysate Substances 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 230000005754 cellular signaling Effects 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 239000002738 chelating agent Substances 0.000 description 1
- 201000010415 childhood type dermatomyositis Diseases 0.000 description 1
- 229960003260 chlorhexidine Drugs 0.000 description 1
- 229940107161 cholesterol Drugs 0.000 description 1
- 235000012000 cholesterol Nutrition 0.000 description 1
- 208000025302 chronic primary adrenal insufficiency Diseases 0.000 description 1
- 150000001860 citric acid derivatives Chemical class 0.000 description 1
- 238000011260 co-administration Methods 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 238000004040 coloring Methods 0.000 description 1
- 230000000295 complement effect Effects 0.000 description 1
- 239000002299 complementary DNA Substances 0.000 description 1
- 239000008139 complexing agent Substances 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 238000010276 construction Methods 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 238000012217 deletion Methods 0.000 description 1
- 230000037430 deletion Effects 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 235000019425 dextrin Nutrition 0.000 description 1
- 108020001096 dihydrofolate reductase Proteins 0.000 description 1
- 239000000539 dimer Substances 0.000 description 1
- 230000003292 diminished effect Effects 0.000 description 1
- 150000002016 disaccharides Chemical class 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 230000012202 endocytosis Effects 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- BEFDCLMNVWHSGT-UHFFFAOYSA-N ethenylcyclopentane Chemical compound C=CC1CCCC1 BEFDCLMNVWHSGT-UHFFFAOYSA-N 0.000 description 1
- 210000003527 eukaryotic cell Anatomy 0.000 description 1
- 230000001747 exhibiting effect Effects 0.000 description 1
- 230000003176 fibrotic effect Effects 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 239000012634 fragment Substances 0.000 description 1
- 239000012737 fresh medium Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 230000002068 genetic effect Effects 0.000 description 1
- 210000004602 germ cell Anatomy 0.000 description 1
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 1
- 102000005396 glutamine synthetase Human genes 0.000 description 1
- 108020002326 glutamine synthetase Proteins 0.000 description 1
- 235000011187 glycerol Nutrition 0.000 description 1
- 239000001963 growth medium Substances 0.000 description 1
- 206010018797 guttate psoriasis Diseases 0.000 description 1
- 229940093915 gynecological organic acid Drugs 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 230000013632 homeostatic process Effects 0.000 description 1
- 210000005260 human cell Anatomy 0.000 description 1
- 229960002163 hydrogen peroxide Drugs 0.000 description 1
- 229920001477 hydrophilic polymer Polymers 0.000 description 1
- 230000003463 hyperproliferative effect Effects 0.000 description 1
- 210000000987 immune system Anatomy 0.000 description 1
- 230000006058 immune tolerance Effects 0.000 description 1
- 102000018358 immunoglobulin Human genes 0.000 description 1
- 229940072221 immunoglobulins Drugs 0.000 description 1
- 229940125721 immunosuppressive agent Drugs 0.000 description 1
- 239000003018 immunosuppressive agent Substances 0.000 description 1
- 238000009169 immunotherapy Methods 0.000 description 1
- 230000001976 improved effect Effects 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 230000036512 infertility Effects 0.000 description 1
- 238000003780 insertion Methods 0.000 description 1
- 230000037431 insertion Effects 0.000 description 1
- 238000001361 intraarterial administration Methods 0.000 description 1
- 230000004068 intracellular signaling Effects 0.000 description 1
- 238000000185 intracerebroventricular administration Methods 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000007912 intraperitoneal administration Methods 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 201000004990 juvenile ankylosing spondylitis Diseases 0.000 description 1
- 239000000787 lecithin Substances 0.000 description 1
- 235000010445 lecithin Nutrition 0.000 description 1
- 229940067606 lecithin Drugs 0.000 description 1
- 206010025135 lupus erythematosus Diseases 0.000 description 1
- 239000006166 lysate Substances 0.000 description 1
- 239000012139 lysis buffer Substances 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- 210000004962 mammalian cell Anatomy 0.000 description 1
- 238000013507 mapping Methods 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 1
- 239000004292 methyl p-hydroxybenzoate Substances 0.000 description 1
- 229960002216 methylparaben Drugs 0.000 description 1
- 239000000178 monomer Substances 0.000 description 1
- 150000002772 monosaccharides Chemical class 0.000 description 1
- 206010028417 myasthenia gravis Diseases 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 201000008482 osteoarthritis Diseases 0.000 description 1
- 210000001672 ovary Anatomy 0.000 description 1
- 102000002574 p38 Mitogen-Activated Protein Kinases Human genes 0.000 description 1
- FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
- 230000035515 penetration Effects 0.000 description 1
- 210000003819 peripheral blood mononuclear cell Anatomy 0.000 description 1
- 230000002085 persistent effect Effects 0.000 description 1
- 235000021317 phosphate Nutrition 0.000 description 1
- 150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
- 229920001983 poloxamer Polymers 0.000 description 1
- 208000012102 polyarticular juvenile rheumatoid arthritis Diseases 0.000 description 1
- 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 1
- 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 1
- 229950008882 polysorbate Drugs 0.000 description 1
- 229940068977 polysorbate 20 Drugs 0.000 description 1
- 229940068965 polysorbates Drugs 0.000 description 1
- 239000001103 potassium chloride Substances 0.000 description 1
- 235000011164 potassium chloride Nutrition 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 230000002335 preservative effect Effects 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 230000004647 pro-inflammatory pathway Effects 0.000 description 1
- 230000000770 proinflammatory effect Effects 0.000 description 1
- 230000000069 prophylactic effect Effects 0.000 description 1
- 235000010232 propyl p-hydroxybenzoate Nutrition 0.000 description 1
- 239000004405 propyl p-hydroxybenzoate Substances 0.000 description 1
- 229960003415 propylparaben Drugs 0.000 description 1
- 229940099538 rapamune Drugs 0.000 description 1
- 102000005962 receptors Human genes 0.000 description 1
- 108020003175 receptors Proteins 0.000 description 1
- 238000010188 recombinant method Methods 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 230000009711 regulatory function Effects 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 102200006514 rs121913236 Human genes 0.000 description 1
- 102220289727 rs1253463092 Human genes 0.000 description 1
- 102200038856 rs150565592 Human genes 0.000 description 1
- 102200108023 rs199473051 Human genes 0.000 description 1
- 102200100726 rs61752874 Human genes 0.000 description 1
- 229960004889 salicylic acid Drugs 0.000 description 1
- 201000000306 sarcoidosis Diseases 0.000 description 1
- 208000010157 sclerosing cholangitis Diseases 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 238000012163 sequencing technique Methods 0.000 description 1
- 150000003384 small molecules Chemical class 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 235000015424 sodium Nutrition 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M sodium chloride Inorganic materials [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 229940079827 sodium hydrogen sulfite Drugs 0.000 description 1
- 235000010267 sodium hydrogen sulphite Nutrition 0.000 description 1
- 229940001482 sodium sulfite Drugs 0.000 description 1
- 235000010265 sodium sulphite Nutrition 0.000 description 1
- 235000010199 sorbic acid Nutrition 0.000 description 1
- 239000004334 sorbic acid Substances 0.000 description 1
- 229940075582 sorbic acid Drugs 0.000 description 1
- 238000001179 sorption measurement Methods 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 150000005846 sugar alcohols Chemical class 0.000 description 1
- 239000004173 sunset yellow FCF Substances 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 238000013268 sustained release Methods 0.000 description 1
- 239000012730 sustained-release form Substances 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 230000002123 temporal effect Effects 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- RTKIYNMVFMVABJ-UHFFFAOYSA-L thimerosal Chemical compound [Na+].CC[Hg]SC1=CC=CC=C1C([O-])=O RTKIYNMVFMVABJ-UHFFFAOYSA-L 0.000 description 1
- 229940033663 thimerosal Drugs 0.000 description 1
- 206010043778 thyroiditis Diseases 0.000 description 1
- 239000012443 tonicity enhancing agent Substances 0.000 description 1
- 238000013518 transcription Methods 0.000 description 1
- 230000035897 transcription Effects 0.000 description 1
- 230000002103 transcriptional effect Effects 0.000 description 1
- 230000009261 transgenic effect Effects 0.000 description 1
- 102000027257 transmembrane receptors Human genes 0.000 description 1
- 108091008578 transmembrane receptors Proteins 0.000 description 1
- 238000002054 transplantation Methods 0.000 description 1
- ODLHGICHYURWBS-LKONHMLTSA-N trappsol cyclo Chemical compound CC(O)COC[C@H]([C@H]([C@@H]([C@H]1O)O)O[C@H]2O[C@@H]([C@@H](O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O3)[C@H](O)[C@H]2O)COCC(O)C)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@@H]3O[C@@H]1COCC(C)O ODLHGICHYURWBS-LKONHMLTSA-N 0.000 description 1
- 238000011269 treatment regimen Methods 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- GPRLSGONYQIRFK-MNYXATJNSA-N triton Chemical compound [3H+] GPRLSGONYQIRFK-MNYXATJNSA-N 0.000 description 1
- 229960000281 trometamol Drugs 0.000 description 1
- 230000003612 virological effect Effects 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 229920003169 water-soluble polymer Polymers 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
Classifications
-
- 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]
- C07K14/55—IL-2
-
- 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
- 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
- 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
- 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
- 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
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/08—Antiallergic agents
-
- 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
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmacology & Pharmacy (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Chemical & Material Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Engineering & Computer Science (AREA)
- Immunology (AREA)
- Pulmonology (AREA)
- Diabetes (AREA)
- Toxicology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Molecular Biology (AREA)
- Genetics & Genomics (AREA)
- Biophysics (AREA)
- Biochemistry (AREA)
- Gastroenterology & Hepatology (AREA)
- Zoology (AREA)
- Rheumatology (AREA)
- Endocrinology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Emergency Medicine (AREA)
- Pain & Pain Management (AREA)
- Transplantation (AREA)
- Physical Education & Sports Medicine (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Peptides Or Proteins (AREA)
- Medicinal Preparation (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US14611109P | 2009-01-21 | 2009-01-21 | |
| US61/146,111 | 2009-01-21 | ||
| PCT/US2010/021519 WO2010085495A1 (en) | 2009-01-21 | 2010-01-20 | Compositions and methods of treating inflammatory and autoimmune diseases |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CA2749539A1 CA2749539A1 (en) | 2010-07-29 |
| CA2749539C true CA2749539C (en) | 2022-07-19 |
Family
ID=42356180
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2749539A Active CA2749539C (en) | 2009-01-21 | 2010-01-20 | Compositions and methods comprising interleukin-2 mutants for treating inflammatory and autoimmune diseases |
Country Status (8)
| Country | Link |
|---|---|
| US (5) | US20110274650A1 (enExample) |
| EP (1) | EP2382228B1 (enExample) |
| JP (7) | JP5766124B2 (enExample) |
| AU (1) | AU2010206840B2 (enExample) |
| CA (1) | CA2749539C (enExample) |
| ES (1) | ES2825173T3 (enExample) |
| MX (1) | MX2011007647A (enExample) |
| WO (1) | WO2010085495A1 (enExample) |
Families Citing this family (89)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA2749539C (en) | 2009-01-21 | 2022-07-19 | Amgen Inc. | Compositions and methods comprising interleukin-2 mutants for treating inflammatory and autoimmune diseases |
| CU23923B1 (es) * | 2010-11-12 | 2013-07-31 | Ct De Inmunología Molecular | Polipéptidos derivados de la il-2 con actividad agonista |
| CA2860170C (en) | 2010-12-22 | 2022-06-14 | The Board Of Trustees Of The Leland Stanford Junior University | Superagonists and antagonists of interleukin-2 |
| ES2694564T3 (es) | 2011-02-10 | 2018-12-21 | Roche Glycart Ag | Polipéptidos de interleucina-2 mutantes |
| KR102220006B1 (ko) | 2011-03-11 | 2021-02-24 | 아시스땅스 퍼블리끄-오삐또 드 빠리 | 자가면역 - 관련 또는 염증성 장애를 치료하기 위한 저용량 ｉｌ２ 의 용도 |
| US9669071B2 (en) | 2011-03-11 | 2017-06-06 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Method for stimulating T lymphocytes with IL-2 |
| EA201892619A1 (ru) | 2011-04-29 | 2019-04-30 | Роше Гликарт Аг | Иммуноконъюгаты, содержащие мутантные полипептиды интерлейкина-2 |
| US9481866B2 (en) * | 2011-12-16 | 2016-11-01 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Methods of producing T cell populations enriched for stable regulatory T-cells |
| US20140044675A1 (en) | 2012-08-10 | 2014-02-13 | Roche Glycart Ag | Interleukin-2 fusion proteins and uses thereof |
| US9546203B2 (en) * | 2013-03-14 | 2017-01-17 | Amgen Inc. | Aglycosylated Fc-containing polypeptides with cysteine substitutions |
| CA2925421C (en) | 2013-09-24 | 2023-08-29 | Medicenna Therapeutics, Inc. | Interleukin-2 fusion proteins and uses thereof |
| EA201992609A1 (ru) * | 2014-02-06 | 2020-03-04 | Ф.Хоффманн-Ля Рош Аг | Слитые белки, содержащие интерлейкин-2, и их применения |
| WO2015164815A1 (en) * | 2014-04-24 | 2015-10-29 | The Board Of Trustees Of The Leland Stanford Junior University | Superagonists, partial agonists and antagonists of interleukin-2 |
| DK3172227T3 (da) * | 2014-07-21 | 2019-12-02 | Delinia Inc | Molekyler der selektivt aktiverer regulatoriske t-celler til behandlingen af autoimmune sygdomme |
| CN113234138A (zh) * | 2014-08-11 | 2021-08-10 | 德里尼亚公司 | 选择性地活化调节性t细胞用于治疗自身免疫病的修饰的il-2变体 |
| IL304950A (en) | 2015-04-10 | 2023-10-01 | Amgen Inc | Interleukin for the expansion of myotonic control T-2 cells |
| AU2016246152A1 (en) * | 2015-04-10 | 2017-11-02 | Amgen Inc. | Interleukin-2 muteins for the expansion of T-regulatory cells |
| US20170204154A1 (en) | 2016-01-20 | 2017-07-20 | Delinia, Inc. | Molecules that selectively activate regulatory t cells for the treatment of autoimmune diseases |
| CN115073581A (zh) * | 2016-05-04 | 2022-09-20 | 美国安进公司 | 用于扩增t调节性细胞的白细胞介素-2突变蛋白 |
| CA3019005A1 (en) | 2016-05-18 | 2017-11-23 | Cue Biopharma, Inc. | T-cell modulatory multimeric polypeptides and methods of use thereof |
| EA201991142A1 (ru) | 2016-11-08 | 2019-10-31 | Варианты il-2 для лечения аутоиммунных заболеваний | |
| JP7250677B2 (ja) | 2016-12-22 | 2023-04-03 | キュー バイオファーマ， インコーポレイテッド | Ｔ細胞調節多量体ポリペプチド及びその使用方法 |
| US11851471B2 (en) | 2017-01-09 | 2023-12-26 | Cue Biopharma, Inc. | T-cell modulatory multimeric polypeptides and methods of use thereof |
| KR102619015B1 (ko) | 2017-03-15 | 2023-12-28 | 큐 바이오파마, 인크. | 면역 반응을 조절하는 방법 |
| BR112019018915A2 (pt) | 2017-03-15 | 2020-04-14 | Pandion Therapeutics Inc | imunotolerância direcionada |
| CN111010866A (zh) | 2017-05-24 | 2020-04-14 | 潘迪恩治疗公司 | 靶向免疫耐受性 |
| US11542312B2 (en) | 2017-06-19 | 2023-01-03 | Medicenna Therapeutics, Inc. | IL-2 superagonists in combination with anti-PD-1 antibodies |
| CN111051512A (zh) | 2017-07-11 | 2020-04-21 | 辛索克斯公司 | 非天然核苷酸的掺入及其方法 |
| SG11202000939PA (en) | 2017-08-03 | 2020-02-27 | Synthorx Inc | Cytokine conjugates for the treatment of proliferative and infectious diseases |
| CN111278864A (zh) * | 2017-09-07 | 2020-06-12 | 库尔生物制药有限公司 | 抗原呈递多肽及其使用方法 |
| PH12020550661A1 (en) | 2017-11-21 | 2021-04-19 | Univ Leland Stanford Junior | Partial agonists of interleukin-2 |
| US10174092B1 (en) | 2017-12-06 | 2019-01-08 | Pandion Therapeutics, Inc. | IL-2 muteins |
| USRE50550E1 (en) | 2017-12-06 | 2025-08-26 | Pandion Operations, Inc. | IL-2 muteins and uses thereof |
| US10946068B2 (en) | 2017-12-06 | 2021-03-16 | Pandion Operations, Inc. | IL-2 muteins and uses thereof |
| KR102722731B1 (ko) | 2017-12-19 | 2024-10-25 | 젠코어 인코포레이티드 | 조작된 il-2 fc 융합 단백질 |
| CA3086842A1 (en) * | 2017-12-27 | 2019-07-04 | Kyowa Kirin Co., Ltd. | Il-2 variant |
| EP3737689A4 (en) | 2018-01-09 | 2021-12-01 | Cue Biopharma, Inc. | MULTIMER POLYPEPTIDES T-LYMPHOCYTE MODULATORS AND THEIR METHODS OF USE |
| US11534479B2 (en) | 2018-02-16 | 2022-12-27 | Iltoo Pharma | Use of interleukin 2 for treating Sjögren's syndrome |
| CA3115461A1 (en) | 2018-03-09 | 2019-09-12 | AskGene Pharma, Inc. | Novel cytokine prodrugs |
| CN120590539A (zh) | 2018-03-28 | 2025-09-05 | 百时美施贵宝公司 | 白介素-2/白介素-2受体α融合蛋白以及使用方法 |
| WO2020007937A1 (en) | 2018-07-03 | 2020-01-09 | Iltoo Pharma | Use of interleukin-2 for treating systemic sclerosis |
| JP2021530243A (ja) | 2018-07-25 | 2021-11-11 | アスクジーン・ファーマ・インコーポレイテッドAskGene Pharma, Inc. | 新規ｉｌ−２１プロドラッグおよびそれを使用する方法 |
| WO2020035482A1 (en) | 2018-08-13 | 2020-02-20 | Iltoo Pharma | Combination of interleukin-2 with an interleukin 1 inhibitor, conjugates and therapeutic uses thereof |
| AU2019376076B9 (en) | 2018-11-08 | 2025-06-19 | Synthorx, Inc. | Interleukin 10 conjugates and uses thereof |
| TW202034945A (zh) | 2018-12-21 | 2020-10-01 | 大陸商江蘇恆瑞醫藥股份有限公司 | 一種人白細胞介素２變體或其衍生物 |
| AU2020218203A1 (en) | 2019-02-06 | 2021-08-26 | Synthorx, Inc. | IL-2 conjugates and methods of use thereof |
| CN113661175A (zh) | 2019-02-15 | 2021-11-16 | 整体分子公司 | 包含共同轻链的抗体及其用途 |
| CA3129834A1 (en) | 2019-02-15 | 2020-08-20 | Integral Molecular, Inc. | Claudin 6 antibodies and uses thereof |
| CN114126637A (zh) | 2019-03-29 | 2022-03-01 | 居里研究所 | 具有经修饰的生物活性的白介素-2变体 |
| US11739146B2 (en) | 2019-05-20 | 2023-08-29 | Pandion Operations, Inc. | MAdCAM targeted immunotolerance |
| EP3980051A4 (en) * | 2019-06-05 | 2023-09-13 | Asher Biotherapeutics, Inc. | FUSIONS OF MUTANT INTERLEUKIN-2 POLYPEPTIDES WITH ANTIGEN-BINDING MOLECULES TO MODULATE THE FUNCTION OF IMMUNE CELLS |
| WO2020252264A1 (en) | 2019-06-12 | 2020-12-17 | AskGene Pharma, Inc. | Novel il-15 prodrugs and methods of use thereof |
| MX2022001061A (es) | 2019-07-26 | 2022-02-14 | Visterra Inc | Agentes de interleuquina-2 y usos de los mismos. |
| UY38836A (es) | 2019-08-13 | 2021-02-26 | Amgen Inc | Muteínas de interleucina-2 para la expansión de células t reguladoras |
| CA3150978A1 (en) * | 2019-08-15 | 2021-02-18 | Cytimm Therapeutics, Inc. | Modified interleukin 2 (il-2) polypeptides, conjugates and uses thereof |
| WO2021041206A1 (en) | 2019-08-23 | 2021-03-04 | Synthorx, Inc. | Il-15 conjugates and uses thereof |
| TW202124385A (zh) | 2019-09-10 | 2021-07-01 | 美商欣爍克斯公司 | 治療自體免疫疾病之il-2接合物及使用方法 |
| WO2021102063A1 (en) | 2019-11-20 | 2021-05-27 | Anwita Biosciences, Inc. | Cytokine fusion proteins, and their pharmaceutical compositions and therapeutic applications |
| US20230036793A1 (en) | 2019-12-12 | 2023-02-02 | Iltoo Pharma | Interleukin 2 chimeric constructs |
| BR112022011949A2 (pt) | 2019-12-17 | 2022-11-22 | Amgen Inc | Dupla de interleucina-2/agonista do receptor tnf para uso em terapia |
| US20210188934A1 (en) | 2019-12-20 | 2021-06-24 | Regeneron Pharmaceuticals, Inc. | Novel il2 agonists and methods of use thereof |
| AU2021206449A1 (en) | 2020-01-10 | 2022-07-21 | Bright Peak Therapeutics Ag | Modified IL-2 polypeptides and uses thereof |
| JP7303391B2 (ja) | 2020-01-14 | 2023-07-04 | シンセカイン インコーポレイテッド | バイアス型ｉｌ２ムテイン、方法、および組成物 |
| IL294070A (en) * | 2020-01-14 | 2022-08-01 | Synthekine Inc | Il2 muteins |
| US11981715B2 (en) | 2020-02-21 | 2024-05-14 | Pandion Operations, Inc. | Tissue targeted immunotolerance with a CD39 effector |
| EP4139340A1 (en) | 2020-04-22 | 2023-03-01 | Merck Sharp & Dohme LLC | Human interleukin-2 conjugates biased for the interleukin-2 receptor beta gammac dimer and conjugated to a nonpeptidic, water-soluble polymer |
| WO2021222150A2 (en) | 2020-04-28 | 2021-11-04 | Anwita Biosciences, Inc. | Interleukin-2 polypeptides and fusion proteins thereof, and their pharmaceutical compositions and therapeutic applications |
| CA3169949A1 (en) | 2020-05-12 | 2021-11-18 | Cue Biopharma, Inc. | Multimeric t-cell modulatory polypeptides and methods of use thereof |
| JP2023527919A (ja) | 2020-06-03 | 2023-06-30 | アセンディス ファーマ オンコロジー ディヴィジョン エー／エス | Ｉｌ－２配列及びその使用 |
| JP2023533567A (ja) * | 2020-07-14 | 2023-08-03 | ファイザー・インク | 組み換えワクシニアウイルス |
| TW202219060A (zh) * | 2020-08-28 | 2022-05-16 | 丹麥商阿森迪斯腫瘤製藥有限公司 | 醣基化il-2蛋白及其用途 |
| JP2023541366A (ja) | 2020-09-09 | 2023-10-02 | キュー バイオファーマ， インコーポレイテッド | １型真性糖尿病（ｔ１ｄ）を治療するためのｍｈｃクラスｉｉ ｔ細胞調節多量体ポリペプチド及びその使用方法 |
| IL302276A (en) | 2020-10-23 | 2023-06-01 | Asher Biotherapeutics Inc | Fusions with cd8 antigen binding molecules for modulating immune cell function |
| EP4236962A1 (en) | 2020-10-29 | 2023-09-06 | Bristol-Myers Squibb Company | Fusion proteins for the treatment of disease |
| CN112279906B (zh) * | 2020-10-30 | 2022-09-20 | 浙江新码生物医药有限公司 | 人白细胞介素2-聚乙二醇偶联物及其制备方法与应用 |
| JP2023549191A (ja) | 2020-11-13 | 2023-11-22 | 江蘇恒瑞医薬股▲ふん▼有限公司 | ヒトインターロイキン２の変異体又はその誘導体を含む医薬組成物及びその用途 |
| AU2021391924A1 (en) * | 2020-12-04 | 2023-06-22 | The General Hospital Corporation | Methods of using interleukin-2 agents |
| CN113321722A (zh) * | 2021-04-13 | 2021-08-31 | 苏州复融生物技术有限公司 | 白介素2突变体及其应用 |
| KR20240034221A (ko) | 2021-07-09 | 2024-03-13 | 브라이트 피크 테라퓨틱스 아게 | 염증성 질환 및 자가면역 질환의 치료를 위한 변형된 il-2 폴리펩티드 |
| KR20240040134A (ko) | 2021-07-09 | 2024-03-27 | 브라이트 피크 테라퓨틱스 아게 | 항체 접합체 및 이의 제조 |
| JP7618848B2 (ja) | 2021-07-30 | 2025-01-21 | ドラコターピン バイオメディスン エルエルシー | ヒトインターロイキン－２変異体およびその使用 |
| JP2024533848A (ja) | 2021-10-06 | 2024-09-12 | イルトゥー・ファルマ | 炎症組織へのターゲティング特異性を備えるインターロイキン２キメラコンストラクト |
| WO2023133595A2 (en) | 2022-01-10 | 2023-07-13 | Sana Biotechnology, Inc. | Methods of ex vivo dosing and administration of lipid particles or viral vectors and related systems and uses |
| US20250222027A1 (en) | 2022-04-01 | 2025-07-10 | Sana Biotechnology, Inc. | Cytokine receptor agonist and viral vector combination therapies |
| WO2024056154A1 (en) | 2022-09-12 | 2024-03-21 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Interleukin-2 for use in treating autism spectrum disorder |
| EP4626933A1 (en) | 2022-11-30 | 2025-10-08 | Integral Molecular, Inc. | Antibodies directed to claudin 6, including bispecific formats thereof |
| TW202444749A (zh) | 2023-01-09 | 2024-11-16 | 美商奧迪希治療公司 | 抗tnfr2抗原結合蛋白及其用途 |
| WO2025217240A1 (en) | 2024-04-10 | 2025-10-16 | Odyssey Therapeutics, Inc. | Anti-tnfr2 antigen-binding proteins and uses thereof |
| WO2025221954A1 (en) | 2024-04-17 | 2025-10-23 | Visterra, Inc. | Use of il-2 variant for treating kidney transplant rejection |
Family Cites Families (37)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4470461A (en) | 1982-09-30 | 1984-09-11 | Phillips Petroleum Company | Organic nitro compounds as cosurfactants in enhanced oil recovery processes |
| US4588585A (en) | 1982-10-19 | 1986-05-13 | Cetus Corporation | Human recombinant cysteine depleted interferon-β muteins |
| US4518584A (en) | 1983-04-15 | 1985-05-21 | Cetus Corporation | Human recombinant interleukin-2 muteins |
| GB8601597D0 (en) | 1986-01-23 | 1986-02-26 | Wilson R H | Nucleotide sequences |
| EP0262802A3 (en) | 1986-09-01 | 1990-01-31 | Takeda Chemical Industries, Ltd. | Medicament for the treatment or improvement of rheumatoid arthritis or systemic lupus erythematosus |
| GB8809129D0 (en) | 1988-04-18 | 1988-05-18 | Celltech Ltd | Recombinant dna methods vectors and host cells |
| US5466447A (en) | 1988-06-29 | 1995-11-14 | Amgen Inc. | Method for treating psoriasis |
| WO1990000565A1 (en) | 1988-07-05 | 1990-01-25 | Amgen Inc. | Interleukin ii analogs |
| CA2062582C (en) | 1991-03-27 | 1996-03-26 | Tse-Wen Chang | Methods and substances for recruiting therapeutic agents to solid tissues |
| US5229109A (en) | 1992-04-14 | 1993-07-20 | Board Of Regents, The University Of Texas System | Low toxicity interleukin-2 analogues for use in immunotherapy |
| DZ2788A1 (fr) | 1998-05-15 | 2003-12-01 | Bayer Ag | Agonistes et antagonistes selectifs à IL-2. |
| US6955807B1 (en) | 1998-05-15 | 2005-10-18 | Bayer Pharmaceuticals Corporation | IL-2 selective agonists and antagonists |
| US6737056B1 (en) | 1999-01-15 | 2004-05-18 | Genentech, Inc. | Polypeptide variants with altered effector function |
| US6348192B1 (en) | 1999-05-11 | 2002-02-19 | Bayer Corporation | Interleukin-2 mutein expressed from mammalian cells |
| AU4314801A (en) | 2000-02-11 | 2001-08-20 | Lexigen Pharm Corp | Enhancing the circulating half-life of antibody-based fusion proteins |
| WO2003015697A2 (en) | 2001-08-13 | 2003-02-27 | University Of Southern California | Interleukin-2 mutants with reduced toxicity |
| DK1454138T3 (da) | 2001-12-04 | 2012-02-13 | Merck Patent Gmbh | Immunocytokiner med moduleret selektivitet |
| US20030191056A1 (en) | 2002-04-04 | 2003-10-09 | Kenneth Walker | Use of transthyretin peptide/protein fusions to increase the serum half-life of pharmacologically active peptides/proteins |
| AR043504A1 (es) * | 2003-03-17 | 2005-08-03 | Novartis Ag | Composiciones farmaceuticas que comprenden rapamicina para el tratamiento de enfermedades inflamatorias |
| US7569215B2 (en) * | 2003-07-18 | 2009-08-04 | Massachusetts Institute Of Technology | Mutant interleukin-2 (IL-2) polypeptides |
| KR20070003934A (ko) | 2004-03-05 | 2007-01-05 | 노바티스 백신즈 앤드 다이아그노스틱스 인코포레이티드 | 치료제의 환자 내약성을 예측하기 위한 시험관 내 테스트시스템 |
| AU2006232374B2 (en) * | 2005-04-01 | 2011-08-25 | University Of Southern California | Preventing rejection of transplanted tissue using regulatory T cells |
| EP1987065A4 (en) | 2006-02-16 | 2010-01-20 | Nascent Biolog Inc | METHOD FOR IMPROVING THE IMMUNE FUNCTION AND METHOD FOR PREVENTING OR TREATING DISEASES IN MAMMALS |
| LT2676967T (lt) | 2006-02-28 | 2019-09-10 | Biogen Ma Inc. | Uždegiminių ir autoimuninių ligų gydymo būdai su natalizumabu |
| WO2008004373A1 (en) | 2006-07-06 | 2008-01-10 | Mitsubishi Electric Corporation | Navigation device |
| JP2009542592A (ja) | 2006-07-06 | 2009-12-03 | メルク パテント ゲゼルシャフト ミット ベシュレンクテル ハフツング | Ｉｌ−２媒介性免疫応答の有効性を高める組成物および方法 |
| WO2008112325A2 (en) | 2007-03-15 | 2008-09-18 | Biogen Idec Ma Inc. | Treatment of autoimmune disorders |
| GB0623539D0 (en) | 2006-11-24 | 2007-01-03 | Avidex Ltd | Polypeptides |
| RU2009135824A (ru) | 2007-02-27 | 2011-04-10 | Дженентек, Инк. (Us) | Антитела-антагонисты против ох40 и их применение в лечении воспалительных и аутоиммунных заболеваний |
| WO2009061853A2 (en) | 2007-11-05 | 2009-05-14 | Massachusetts Institute Of Technology | Mutant interleukin-2 (il-2) polypeptides |
| ES2563027T3 (es) | 2008-01-07 | 2016-03-10 | Amgen Inc. | Método para fabricación de moléculas heterodímeras Fc de anticuerpos utilizando efectos de conducción electrostática |
| DE102008023820A1 (de) | 2008-05-08 | 2009-11-12 | Aicuris Gmbh & Co. Kg | Mittel zur Behandlung und/oder Prophylaxe einer Autoimmunerkrankung und zur Bildung von Regulatorischen T-Zellen |
| WO2010017220A1 (en) | 2008-08-04 | 2010-02-11 | The Trustees Of The University Of Pennsylvania | Methods for expanding regulatory t-cells |
| US20110200534A1 (en) | 2008-08-21 | 2011-08-18 | Industry-Academic Cooperation Foundation, Yonsei U | T1-T2 Dual Modal MRI Contrast Agents |
| CA2749539C (en) * | 2009-01-21 | 2022-07-19 | Amgen Inc. | Compositions and methods comprising interleukin-2 mutants for treating inflammatory and autoimmune diseases |
| KR102220006B1 (ko) | 2011-03-11 | 2021-02-24 | 아시스땅스 퍼블리끄-오삐또 드 빠리 | 자가면역 - 관련 또는 염증성 장애를 치료하기 위한 저용량 ｉｌ２ 의 용도 |
| JP5972915B2 (ja) | 2011-03-16 | 2016-08-17 | アムジエン・インコーポレーテツド | Ｆｃ変異体 |
-
2010
- 2010-01-20 CA CA2749539A patent/CA2749539C/en active Active
- 2010-01-20 EP EP10733814.7A patent/EP2382228B1/en active Active
- 2010-01-20 JP JP2011548074A patent/JP5766124B2/ja active Active
- 2010-01-20 US US13/145,537 patent/US20110274650A1/en not_active Abandoned
- 2010-01-20 AU AU2010206840A patent/AU2010206840B2/en active Active
- 2010-01-20 ES ES10733814T patent/ES2825173T3/es active Active
- 2010-01-20 WO PCT/US2010/021519 patent/WO2010085495A1/en not_active Ceased
- 2010-01-20 MX MX2011007647A patent/MX2011007647A/es active IP Right Grant
-
2012
- 2012-11-08 US US13/672,417 patent/US9732134B2/en active Active
-
2014
- 2014-04-15 JP JP2014083388A patent/JP2014133756A/ja not_active Withdrawn
-
2016
- 2016-05-06 JP JP2016092985A patent/JP2016138140A/ja not_active Withdrawn
-
2017
- 2017-07-13 US US15/649,520 patent/US11560415B2/en active Active
-
2018
- 2018-02-26 JP JP2018031926A patent/JP2018087244A/ja not_active Withdrawn
-
2019
- 2019-10-18 JP JP2019191112A patent/JP2020023550A/ja not_active Withdrawn
-
2021
- 2021-09-03 JP JP2021143804A patent/JP2021185191A/ja not_active Withdrawn
-
2022
- 2022-12-20 US US18/068,970 patent/US12297248B2/en active Active
-
2024
- 2024-05-27 JP JP2024085664A patent/JP2024105721A/ja active Pending
-
2025
- 2025-01-17 US US19/028,861 patent/US20250270271A1/en active Pending
Also Published As
| Publication number | Publication date |
|---|---|
| JP2018087244A (ja) | 2018-06-07 |
| EP2382228B1 (en) | 2020-08-26 |
| US20250270271A1 (en) | 2025-08-28 |
| US20130195795A1 (en) | 2013-08-01 |
| US9732134B2 (en) | 2017-08-15 |
| US20170313753A1 (en) | 2017-11-02 |
| WO2010085495A1 (en) | 2010-07-29 |
| JP2024105721A (ja) | 2024-08-06 |
| JP5766124B2 (ja) | 2015-08-19 |
| AU2010206840B2 (en) | 2015-02-05 |
| CA2749539A1 (en) | 2010-07-29 |
| US20110274650A1 (en) | 2011-11-10 |
| US12297248B2 (en) | 2025-05-13 |
| MX2011007647A (es) | 2011-09-01 |
| ES2825173T3 (es) | 2021-05-14 |
| JP2012515778A (ja) | 2012-07-12 |
| US11560415B2 (en) | 2023-01-24 |
| JP2014133756A (ja) | 2014-07-24 |
| EP2382228A4 (en) | 2013-01-09 |
| JP2021185191A (ja) | 2021-12-09 |
| AU2010206840A1 (en) | 2011-07-21 |
| JP2016138140A (ja) | 2016-08-04 |
| EP2382228A1 (en) | 2011-11-02 |
| US20230139534A1 (en) | 2023-05-04 |
| JP2020023550A (ja) | 2020-02-13 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US12297248B2 (en) | Methods of treating graft versus host disease using IL-2 muteins | |
| JP7272663B2 (ja) | インターロイキン－２／インターロイキン－２受容体アルファ融合タンパク質および使用方法 | |
| KR100607609B1 (ko) | Ｉｌ-2 선택성 작용제 및 길항제 | |
| JP4502580B2 (ja) | 敗血症の治療または予防のためのｉｌ−１８阻害剤の使用 | |
| US6955807B1 (en) | IL-2 selective agonists and antagonists | |
| KR20220008323A (ko) | 면역 세포를 증식하는 il-2 돌연변이 단백질 | |
| TW202143996A (zh) | 使用可溶性ｃｄ２４治療病毒性肺炎之方法 | |
| JP2006513990A5 (enExample) | ||
| AU2002309887B2 (en) | Use of IL-18 inhibitors for the treatment or prevention of sepsis | |
| AU2002309887A1 (en) | Use of IL-18 inhibitors for the treatment or prevention of sepsis | |
| HK1066723B (en) | Use of il-18 inhibitors for the treatment or prevention of sepsis |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request |
Effective date: 20150106 |
|
| EEER | Examination request |
Effective date: 20150106 |