JP2012525385A - 神経変性および神経炎症の治療 - Google Patents
神経変性および神経炎症の治療 Download PDFInfo
- Publication number
- JP2012525385A JP2012525385A JP2012508485A JP2012508485A JP2012525385A JP 2012525385 A JP2012525385 A JP 2012525385A JP 2012508485 A JP2012508485 A JP 2012508485A JP 2012508485 A JP2012508485 A JP 2012508485A JP 2012525385 A JP2012525385 A JP 2012525385A
- Authority
- JP
- Japan
- Prior art keywords
- disease
- compound
- subject
- neuroinflammation
- neurodegeneration
- 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.)
- Withdrawn
Links
- 208000036110 Neuroinflammatory disease Diseases 0.000 title claims abstract description 46
- 230000003959 neuroinflammation Effects 0.000 title claims abstract description 46
- 230000004770 neurodegeneration Effects 0.000 title claims abstract description 45
- 238000011282 treatment Methods 0.000 title description 37
- 150000001875 compounds Chemical class 0.000 claims abstract description 96
- 238000000034 method Methods 0.000 claims abstract description 95
- 150000003839 salts Chemical class 0.000 claims abstract description 30
- 206010018341 Gliosis Diseases 0.000 claims abstract description 29
- 208000037875 astrocytosis Diseases 0.000 claims abstract description 26
- 230000007341 astrogliosis Effects 0.000 claims abstract description 26
- 208000024891 symptom Diseases 0.000 claims abstract description 21
- 230000004112 neuroprotection Effects 0.000 claims abstract description 18
- LDCRTTXIJACKKU-ONEGZZNKSA-N dimethyl fumarate Chemical compound COC(=O)\C=C\C(=O)OC LDCRTTXIJACKKU-ONEGZZNKSA-N 0.000 claims description 117
- 229960004419 dimethyl fumarate Drugs 0.000 claims description 87
- 230000014509 gene expression Effects 0.000 claims description 59
- NKHAVTQWNUWKEO-UHFFFAOYSA-N fumaric acid monomethyl ester Natural products COC(=O)C=CC(O)=O NKHAVTQWNUWKEO-UHFFFAOYSA-N 0.000 claims description 57
- NKHAVTQWNUWKEO-NSCUHMNNSA-N monomethyl fumarate Chemical compound COC(=O)\C=C\C(O)=O NKHAVTQWNUWKEO-NSCUHMNNSA-N 0.000 claims description 57
- 229940005650 monomethyl fumarate Drugs 0.000 claims description 56
- 201000006417 multiple sclerosis Diseases 0.000 claims description 50
- 108090000623 proteins and genes Proteins 0.000 claims description 47
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 43
- 210000004027 cell Anatomy 0.000 claims description 38
- 201000010099 disease Diseases 0.000 claims description 37
- 208000031277 Amaurotic familial idiocy Diseases 0.000 claims description 28
- 239000008194 pharmaceutical composition Substances 0.000 claims description 27
- 210000000278 spinal cord Anatomy 0.000 claims description 27
- 101150102665 CCL20 gene Proteins 0.000 claims description 19
- 101150093802 CXCL1 gene Proteins 0.000 claims description 19
- 101150077124 CXCL10 gene Proteins 0.000 claims description 19
- 101150031350 Cxcl2 gene Proteins 0.000 claims description 19
- 101150102927 Cxcl3 gene Proteins 0.000 claims description 19
- 239000013543 active substance Substances 0.000 claims description 19
- 201000011240 Frontotemporal dementia Diseases 0.000 claims description 17
- -1 Srxn1 Proteins 0.000 claims description 17
- 101150091206 Nfkbia gene Proteins 0.000 claims description 16
- 208000011580 syndromic disease Diseases 0.000 claims description 16
- 201000011452 Adrenoleukodystrophy Diseases 0.000 claims description 14
- 206010008025 Cerebellar ataxia Diseases 0.000 claims description 14
- 208000004986 Diffuse Cerebral Sclerosis of Schilder Diseases 0.000 claims description 14
- 102000009030 Member 1 Subfamily D ATP Binding Cassette Transporter Human genes 0.000 claims description 14
- 108010049137 Member 1 Subfamily D ATP Binding Cassette Transporter Proteins 0.000 claims description 14
- 101100369986 Mus musculus Tnfaip2 gene Proteins 0.000 claims description 14
- 208000021642 Muscular disease Diseases 0.000 claims description 14
- 201000009623 Myopathy Diseases 0.000 claims description 14
- 208000021386 Sjogren Syndrome Diseases 0.000 claims description 14
- 208000018756 Variant Creutzfeldt-Jakob disease Diseases 0.000 claims description 14
- 208000005881 bovine spongiform encephalopathy Diseases 0.000 claims description 14
- ZPUCINDJVBIVPJ-LJISPDSOSA-N cocaine Chemical compound O([C@H]1C[C@@H]2CC[C@@H](N2C)[C@H]1C(=O)OC)C(=O)C1=CC=CC=C1 ZPUCINDJVBIVPJ-LJISPDSOSA-N 0.000 claims description 14
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 13
- 206010033799 Paralysis Diseases 0.000 claims description 13
- 101150101311 Sqstm1 gene Proteins 0.000 claims description 13
- 230000007850 degeneration Effects 0.000 claims description 13
- 101150075804 nqo1 gene Proteins 0.000 claims description 13
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 13
- 101150005894 GCLC gene Proteins 0.000 claims description 12
- 101150096192 GGT1 gene Proteins 0.000 claims description 12
- 101150037699 GSTA2 gene Proteins 0.000 claims description 12
- 206010048804 Kearns-Sayre syndrome Diseases 0.000 claims description 12
- 101150074234 TXNRD1 gene Proteins 0.000 claims description 12
- 101150096281 gsta3 gene Proteins 0.000 claims description 12
- 208000002537 Neuronal Ceroid-Lipofuscinoses Diseases 0.000 claims description 11
- 208000017476 juvenile neuronal ceroid lipofuscinosis Diseases 0.000 claims description 11
- 201000007607 neuronal ceroid lipofuscinosis 3 Diseases 0.000 claims description 11
- 208000000609 Pick Disease of the Brain Diseases 0.000 claims description 10
- 239000003550 marker Substances 0.000 claims description 10
- 210000003205 muscle Anatomy 0.000 claims description 10
- 208000021090 palsy Diseases 0.000 claims description 10
- 230000007170 pathology Effects 0.000 claims description 10
- 230000000750 progressive effect Effects 0.000 claims description 10
- 206010002026 amyotrophic lateral sclerosis Diseases 0.000 claims description 9
- 201000010901 lateral sclerosis Diseases 0.000 claims description 9
- 208000005264 motor neuron disease Diseases 0.000 claims description 9
- 239000002671 adjuvant Substances 0.000 claims description 8
- 239000000969 carrier Substances 0.000 claims description 8
- 239000000835 fiber Substances 0.000 claims description 8
- 201000001119 neuropathy Diseases 0.000 claims description 8
- 230000007823 neuropathy Effects 0.000 claims description 8
- 208000033808 peripheral neuropathy Diseases 0.000 claims description 8
- 230000002829 reductive effect Effects 0.000 claims description 8
- 206010065040 AIDS dementia complex Diseases 0.000 claims description 7
- 208000007848 Alcoholism Diseases 0.000 claims description 7
- 208000011403 Alexander disease Diseases 0.000 claims description 7
- 208000023434 Alpers-Huttenlocher syndrome Diseases 0.000 claims description 7
- 208000024827 Alzheimer disease Diseases 0.000 claims description 7
- 206010003591 Ataxia Diseases 0.000 claims description 7
- 102000014461 Ataxins Human genes 0.000 claims description 7
- 108010078286 Ataxins Proteins 0.000 claims description 7
- 208000014644 Brain disease Diseases 0.000 claims description 7
- 206010068597 Bulbospinal muscular atrophy congenital Diseases 0.000 claims description 7
- 208000022526 Canavan disease Diseases 0.000 claims description 7
- 208000020406 Creutzfeldt Jacob disease Diseases 0.000 claims description 7
- 208000003407 Creutzfeldt-Jakob Syndrome Diseases 0.000 claims description 7
- 208000010859 Creutzfeldt-Jakob disease Diseases 0.000 claims description 7
- 206010049020 Encephalitis periaxialis diffusa Diseases 0.000 claims description 7
- 208000032274 Encephalopathy Diseases 0.000 claims description 7
- 208000024412 Friedreich ataxia Diseases 0.000 claims description 7
- 208000002339 Frontotemporal Lobar Degeneration Diseases 0.000 claims description 7
- 208000010055 Globoid Cell Leukodystrophy Diseases 0.000 claims description 7
- 208000023105 Huntington disease Diseases 0.000 claims description 7
- 208000027747 Kennedy disease Diseases 0.000 claims description 7
- 208000028226 Krabbe disease Diseases 0.000 claims description 7
- 208000016604 Lyme disease Diseases 0.000 claims description 7
- 208000002569 Machado-Joseph Disease Diseases 0.000 claims description 7
- 206010058799 Mitochondrial encephalomyopathy Diseases 0.000 claims description 7
- 208000001089 Multiple system atrophy Diseases 0.000 claims description 7
- 208000036572 Myoclonic epilepsy Diseases 0.000 claims description 7
- 206010052057 Neuroborreliosis Diseases 0.000 claims description 7
- 208000007125 Neurotoxicity Syndromes Diseases 0.000 claims description 7
- 208000032319 Primary lateral sclerosis Diseases 0.000 claims description 7
- 208000024777 Prion disease Diseases 0.000 claims description 7
- 208000005587 Refsum Disease Diseases 0.000 claims description 7
- 208000021811 Sandhoff disease Diseases 0.000 claims description 7
- 208000021235 Schilder disease Diseases 0.000 claims description 7
- 208000009415 Spinocerebellar Ataxias Diseases 0.000 claims description 7
- 206010043189 Telangiectasia Diseases 0.000 claims description 7
- 206010044221 Toxic encephalopathy Diseases 0.000 claims description 7
- 231100000076 Toxic encephalopathy Toxicity 0.000 claims description 7
- 206010046298 Upper motor neurone lesion Diseases 0.000 claims description 7
- 208000006269 X-Linked Bulbo-Spinal Atrophy Diseases 0.000 claims description 7
- 208000030597 adult Refsum disease Diseases 0.000 claims description 7
- 201000007930 alcohol dependence Diseases 0.000 claims description 7
- 201000004562 autosomal dominant cerebellar ataxia Diseases 0.000 claims description 7
- 229960003920 cocaine Drugs 0.000 claims description 7
- 201000009028 early myoclonic encephalopathy Diseases 0.000 claims description 7
- 208000008675 hereditary spastic paraplegia Diseases 0.000 claims description 7
- 208000006443 lactic acidosis Diseases 0.000 claims description 7
- 201000011540 mitochondrial DNA depletion syndrome 4a Diseases 0.000 claims description 7
- 201000003631 narcolepsy Diseases 0.000 claims description 7
- 201000002212 progressive supranuclear palsy Diseases 0.000 claims description 7
- 208000002320 spinal muscular atrophy Diseases 0.000 claims description 7
- 208000009056 telangiectasis Diseases 0.000 claims description 7
- 208000001799 Hereditary Optic Atrophies Diseases 0.000 claims description 6
- 241000124008 Mammalia Species 0.000 claims description 6
- 208000018737 Parkinson disease Diseases 0.000 claims description 6
- 208000017493 Pelizaeus-Merzbacher disease Diseases 0.000 claims description 6
- 101100240886 Rattus norvegicus Nptx2 gene Proteins 0.000 claims description 6
- 230000007423 decrease Effects 0.000 claims description 6
- 210000003470 mitochondria Anatomy 0.000 claims description 6
- 210000001519 tissue Anatomy 0.000 claims description 6
- 208000009829 Lewy Body Disease Diseases 0.000 claims description 5
- 201000002832 Lewy body dementia Diseases 0.000 claims description 5
- 102100026784 Myelin proteolipid protein Human genes 0.000 claims description 5
- 208000031845 Pernicious anaemia Diseases 0.000 claims description 5
- 208000036834 Spinocerebellar ataxia type 3 Diseases 0.000 claims description 5
- 206010008129 cerebral palsy Diseases 0.000 claims description 5
- 230000002496 gastric effect Effects 0.000 claims description 5
- 102000007371 Ataxin-3 Human genes 0.000 claims description 4
- 208000014060 Niemann-Pick disease Diseases 0.000 claims description 4
- 241000206607 Porphyra umbilicalis Species 0.000 claims description 4
- 102000029797 Prion Human genes 0.000 claims description 4
- 108091000054 Prion Proteins 0.000 claims description 4
- 210000004227 basal ganglia Anatomy 0.000 claims description 4
- 201000006061 fatal familial insomnia Diseases 0.000 claims description 4
- 206010030875 ophthalmoplegia Diseases 0.000 claims description 4
- 230000008569 process Effects 0.000 claims description 4
- 206010016717 Fistula Diseases 0.000 claims description 3
- 206010028570 Myelopathy Diseases 0.000 claims description 3
- 208000024571 Pick disease Diseases 0.000 claims description 3
- 230000003890 fistula Effects 0.000 claims description 3
- 210000001035 gastrointestinal tract Anatomy 0.000 claims description 3
- 239000004090 neuroprotective agent Substances 0.000 claims description 3
- 230000001054 cortical effect Effects 0.000 claims description 2
- 230000001939 inductive effect Effects 0.000 claims description 2
- 210000003710 cerebral cortex Anatomy 0.000 claims 2
- 101150084750 1 gene Proteins 0.000 claims 1
- 206010003694 Atrophy Diseases 0.000 claims 1
- 230000037444 atrophy Effects 0.000 claims 1
- 210000001328 optic nerve Anatomy 0.000 claims 1
- 210000001130 astrocyte Anatomy 0.000 description 55
- 241000700159 Rattus Species 0.000 description 25
- 208000007400 Relapsing-Remitting Multiple Sclerosis Diseases 0.000 description 16
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 15
- 210000003169 central nervous system Anatomy 0.000 description 15
- 239000002158 endotoxin Substances 0.000 description 14
- 208000033068 episodic angioedema with eosinophilia Diseases 0.000 description 14
- 229920006008 lipopolysaccharide Polymers 0.000 description 14
- 210000000274 microglia Anatomy 0.000 description 13
- 239000000203 mixture Substances 0.000 description 13
- 102100039289 Glial fibrillary acidic protein Human genes 0.000 description 12
- 101710193519 Glial fibrillary acidic protein Proteins 0.000 description 12
- 210000005046 glial fibrillary acidic protein Anatomy 0.000 description 12
- RWSXRVCMGQZWBV-WDSKDSINSA-N glutathione Chemical compound OC(=O)[C@@H](N)CCC(=O)N[C@@H](CS)C(=O)NCC(O)=O RWSXRVCMGQZWBV-WDSKDSINSA-N 0.000 description 12
- 206010061218 Inflammation Diseases 0.000 description 11
- 230000006870 function Effects 0.000 description 11
- 230000004054 inflammatory process Effects 0.000 description 11
- 239000002775 capsule Substances 0.000 description 10
- 230000004913 activation Effects 0.000 description 9
- 230000001419 dependent effect Effects 0.000 description 9
- 238000010186 staining Methods 0.000 description 8
- 230000000638 stimulation Effects 0.000 description 8
- 239000004480 active ingredient Substances 0.000 description 7
- 239000011575 calcium Substances 0.000 description 7
- 230000001413 cellular effect Effects 0.000 description 7
- 210000004884 grey matter Anatomy 0.000 description 7
- 230000001225 therapeutic effect Effects 0.000 description 7
- 210000004885 white matter Anatomy 0.000 description 7
- 108010024636 Glutathione Proteins 0.000 description 6
- 238000004458 analytical method Methods 0.000 description 6
- 231100000673 dose–response relationship Toxicity 0.000 description 6
- 230000000694 effects Effects 0.000 description 6
- 229960003180 glutathione Drugs 0.000 description 6
- 210000000653 nervous system Anatomy 0.000 description 6
- 230000000770 proinflammatory effect Effects 0.000 description 6
- 230000009467 reduction Effects 0.000 description 6
- 102000004127 Cytokines Human genes 0.000 description 5
- 108090000695 Cytokines Proteins 0.000 description 5
- 206010061818 Disease progression Diseases 0.000 description 5
- 239000002202 Polyethylene glycol Substances 0.000 description 5
- 102100040247 Tumor necrosis factor Human genes 0.000 description 5
- 125000003545 alkoxy group Chemical group 0.000 description 5
- 210000004556 brain Anatomy 0.000 description 5
- 230000006378 damage Effects 0.000 description 5
- 238000011161 development Methods 0.000 description 5
- 230000018109 developmental process Effects 0.000 description 5
- 238000002474 experimental method Methods 0.000 description 5
- 238000009472 formulation Methods 0.000 description 5
- 230000000877 morphologic effect Effects 0.000 description 5
- 230000000324 neuroprotective effect Effects 0.000 description 5
- 238000011002 quantification Methods 0.000 description 5
- 238000011084 recovery Methods 0.000 description 5
- 239000000758 substrate Substances 0.000 description 5
- 208000016192 Demyelinating disease Diseases 0.000 description 4
- 206010012305 Demyelination Diseases 0.000 description 4
- 101000588302 Homo sapiens Nuclear factor erythroid 2-related factor 2 Proteins 0.000 description 4
- 102100031701 Nuclear factor erythroid 2-related factor 2 Human genes 0.000 description 4
- 238000009825 accumulation Methods 0.000 description 4
- 230000003833 cell viability Effects 0.000 description 4
- 238000000576 coating method Methods 0.000 description 4
- 230000001934 delay Effects 0.000 description 4
- 230000005750 disease progression Effects 0.000 description 4
- 239000003814 drug Substances 0.000 description 4
- 238000000338 in vitro Methods 0.000 description 4
- 230000007246 mechanism Effects 0.000 description 4
- 239000012528 membrane Substances 0.000 description 4
- 108020004999 messenger RNA Proteins 0.000 description 4
- 230000002503 metabolic effect Effects 0.000 description 4
- 210000004498 neuroglial cell Anatomy 0.000 description 4
- 210000002569 neuron Anatomy 0.000 description 4
- 238000003753 real-time PCR Methods 0.000 description 4
- 230000004044 response Effects 0.000 description 4
- 201000008628 secondary progressive multiple sclerosis Diseases 0.000 description 4
- LHYQAEFVHIZFLR-UHFFFAOYSA-L 4-(4-diazonio-3-methoxyphenyl)-2-methoxybenzenediazonium;dichloride Chemical compound [Cl-].[Cl-].C1=C([N+]#N)C(OC)=CC(C=2C=C(OC)C([N+]#N)=CC=2)=C1 LHYQAEFVHIZFLR-UHFFFAOYSA-L 0.000 description 3
- 101000973778 Homo sapiens NAD(P)H dehydrogenase [quinone] 1 Proteins 0.000 description 3
- 102000006386 Myelin Proteins Human genes 0.000 description 3
- 108010083674 Myelin Proteins Proteins 0.000 description 3
- 102100022365 NAD(P)H dehydrogenase [quinone] 1 Human genes 0.000 description 3
- 208000013738 Sleep Initiation and Maintenance disease Diseases 0.000 description 3
- 208000027418 Wounds and injury Diseases 0.000 description 3
- 210000001056 activated astrocyte Anatomy 0.000 description 3
- 238000003556 assay Methods 0.000 description 3
- 210000003050 axon Anatomy 0.000 description 3
- 230000001684 chronic effect Effects 0.000 description 3
- 239000011248 coating agent Substances 0.000 description 3
- 230000003247 decreasing effect Effects 0.000 description 3
- 239000003085 diluting agent Substances 0.000 description 3
- 208000035475 disorder Diseases 0.000 description 3
- 238000002649 immunization Methods 0.000 description 3
- 230000003053 immunization Effects 0.000 description 3
- 238000001727 in vivo Methods 0.000 description 3
- 238000011534 incubation Methods 0.000 description 3
- 230000002757 inflammatory effect Effects 0.000 description 3
- 208000014674 injury Diseases 0.000 description 3
- 206010022437 insomnia Diseases 0.000 description 3
- 230000003834 intracellular effect Effects 0.000 description 3
- 230000000670 limiting effect Effects 0.000 description 3
- 210000005230 lumbar spinal cord Anatomy 0.000 description 3
- 210000002540 macrophage Anatomy 0.000 description 3
- 239000002609 medium Substances 0.000 description 3
- 210000005012 myelin Anatomy 0.000 description 3
- 210000004248 oligodendroglia Anatomy 0.000 description 3
- 239000000843 powder Substances 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- 208000037821 progressive disease Diseases 0.000 description 3
- 230000008741 proinflammatory signaling process Effects 0.000 description 3
- 230000004224 protection Effects 0.000 description 3
- 230000000306 recurrent effect Effects 0.000 description 3
- 230000001629 suppression Effects 0.000 description 3
- 239000000725 suspension Substances 0.000 description 3
- 238000004448 titration Methods 0.000 description 3
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 2
- 102100040121 Allograft inflammatory factor 1 Human genes 0.000 description 2
- 102000019034 Chemokines Human genes 0.000 description 2
- 108010012236 Chemokines Proteins 0.000 description 2
- 206010010904 Convulsion Diseases 0.000 description 2
- 229910052688 Gadolinium Inorganic materials 0.000 description 2
- 102100031181 Glyceraldehyde-3-phosphate dehydrogenase Human genes 0.000 description 2
- 239000012981 Hank's balanced salt solution Substances 0.000 description 2
- 101000890626 Homo sapiens Allograft inflammatory factor 1 Proteins 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- 206010028289 Muscle atrophy Diseases 0.000 description 2
- 208000012902 Nervous system disease Diseases 0.000 description 2
- 208000025966 Neurological disease Diseases 0.000 description 2
- 206010067063 Progressive relapsing multiple sclerosis Diseases 0.000 description 2
- PLXBWHJQWKZRKG-UHFFFAOYSA-N Resazurin Chemical compound C1=CC(=O)C=C2OC3=CC(O)=CC=C3[N+]([O-])=C21 PLXBWHJQWKZRKG-UHFFFAOYSA-N 0.000 description 2
- 210000001642 activated microglia Anatomy 0.000 description 2
- 238000001467 acupuncture Methods 0.000 description 2
- 230000001154 acute effect Effects 0.000 description 2
- 208000007502 anemia Diseases 0.000 description 2
- 230000003110 anti-inflammatory effect Effects 0.000 description 2
- 230000003376 axonal effect Effects 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 230000033228 biological regulation Effects 0.000 description 2
- 230000008499 blood brain barrier function Effects 0.000 description 2
- 210000001218 blood-brain barrier Anatomy 0.000 description 2
- 208000029028 brain injury Diseases 0.000 description 2
- BQRGNLJZBFXNCZ-UHFFFAOYSA-N calcein am Chemical compound O1C(=O)C2=CC=CC=C2C21C1=CC(CN(CC(=O)OCOC(C)=O)CC(=O)OCOC(C)=O)=C(OC(C)=O)C=C1OC1=C2C=C(CN(CC(=O)OCOC(C)=O)CC(=O)OCOC(=O)C)C(OC(C)=O)=C1 BQRGNLJZBFXNCZ-UHFFFAOYSA-N 0.000 description 2
- 229910052791 calcium Inorganic materials 0.000 description 2
- 230000002490 cerebral effect Effects 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- 238000004587 chromatography analysis Methods 0.000 description 2
- 229920001577 copolymer Polymers 0.000 description 2
- 230000034994 death Effects 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 230000009977 dual effect Effects 0.000 description 2
- 239000002702 enteric coating Substances 0.000 description 2
- 238000009505 enteric coating Methods 0.000 description 2
- UIWYJDYFSGRHKR-UHFFFAOYSA-N gadolinium atom Chemical compound [Gd] UIWYJDYFSGRHKR-UHFFFAOYSA-N 0.000 description 2
- 230000007387 gliosis Effects 0.000 description 2
- 108020004445 glyceraldehyde-3-phosphate dehydrogenase Proteins 0.000 description 2
- 239000001963 growth medium Substances 0.000 description 2
- 208000010726 hind limb paralysis Diseases 0.000 description 2
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 2
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 2
- 238000003364 immunohistochemistry Methods 0.000 description 2
- 230000006698 induction Effects 0.000 description 2
- 230000005764 inhibitory process Effects 0.000 description 2
- 230000000977 initiatory effect Effects 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N isopropyl alcohol Natural products CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- 231100000518 lethal Toxicity 0.000 description 2
- 230000001665 lethal effect Effects 0.000 description 2
- 210000004558 lewy body Anatomy 0.000 description 2
- 238000012423 maintenance Methods 0.000 description 2
- 230000003211 malignant effect Effects 0.000 description 2
- 230000010534 mechanism of action Effects 0.000 description 2
- 230000004060 metabolic process Effects 0.000 description 2
- 238000013425 morphometry Methods 0.000 description 2
- 230000020763 muscle atrophy Effects 0.000 description 2
- 201000000585 muscular atrophy Diseases 0.000 description 2
- 210000003061 neural cell Anatomy 0.000 description 2
- 230000001575 pathological effect Effects 0.000 description 2
- 239000006187 pill Substances 0.000 description 2
- 229920000642 polymer Polymers 0.000 description 2
- 206010063401 primary progressive multiple sclerosis Diseases 0.000 description 2
- 102000004169 proteins and genes Human genes 0.000 description 2
- 210000001938 protoplast Anatomy 0.000 description 2
- 239000000523 sample Substances 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 229940124597 therapeutic agent Drugs 0.000 description 2
- 230000035899 viability Effects 0.000 description 2
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 description 1
- 208000023275 Autoimmune disease Diseases 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 1
- 208000011990 Corticobasal Degeneration Diseases 0.000 description 1
- 229920000858 Cyclodextrin Polymers 0.000 description 1
- 206010061819 Disease recurrence Diseases 0.000 description 1
- 241000588724 Escherichia coli Species 0.000 description 1
- 108090000371 Esterases Proteins 0.000 description 1
- 239000001856 Ethyl cellulose Substances 0.000 description 1
- ZZSNKZQZMQGXPY-UHFFFAOYSA-N Ethyl cellulose Chemical compound CCOCC1OC(OC)C(OCC)C(OCC)C1OC1C(O)C(O)C(OC)C(CO)O1 ZZSNKZQZMQGXPY-UHFFFAOYSA-N 0.000 description 1
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical class OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 1
- 208000018522 Gastrointestinal disease Diseases 0.000 description 1
- 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 1
- 206010060800 Hot flush Diseases 0.000 description 1
- 208000001953 Hypotension Diseases 0.000 description 1
- 238000000134 MTT assay Methods 0.000 description 1
- 231100000002 MTT assay Toxicity 0.000 description 1
- 208000028389 Nerve injury Diseases 0.000 description 1
- 239000004698 Polyethylene Substances 0.000 description 1
- 241000083869 Polyommatus dorylas Species 0.000 description 1
- 241001510071 Pyrrhocoridae Species 0.000 description 1
- 241000283984 Rodentia Species 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 108060008682 Tumor Necrosis Factor Proteins 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 229920013820 alkyl cellulose Polymers 0.000 description 1
- VREFGVBLTWBCJP-UHFFFAOYSA-N alprazolam Chemical compound C12=CC(Cl)=CC=C2N2C(C)=NN=C2CN=C1C1=CC=CC=C1 VREFGVBLTWBCJP-UHFFFAOYSA-N 0.000 description 1
- 229910052782 aluminium Inorganic materials 0.000 description 1
- 239000000427 antigen Substances 0.000 description 1
- 108091007433 antigens Proteins 0.000 description 1
- 102000036639 antigens Human genes 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 230000003078 antioxidant effect Effects 0.000 description 1
- 230000001640 apoptogenic effect Effects 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 239000007900 aqueous suspension Substances 0.000 description 1
- 230000002238 attenuated effect Effects 0.000 description 1
- 230000001363 autoimmune Effects 0.000 description 1
- 230000007844 axonal damage Effects 0.000 description 1
- 239000002585 base Substances 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 210000004204 blood vessel Anatomy 0.000 description 1
- 230000006931 brain damage Effects 0.000 description 1
- 231100000874 brain damage Toxicity 0.000 description 1
- 238000011685 brown norway rat Methods 0.000 description 1
- 230000001201 calcium accumulation Effects 0.000 description 1
- 239000001768 carboxy methyl cellulose Substances 0.000 description 1
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 1
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 1
- 150000001768 cations Chemical class 0.000 description 1
- 230000030833 cell death Effects 0.000 description 1
- 230000003915 cell function Effects 0.000 description 1
- 239000013592 cell lysate Substances 0.000 description 1
- 230000004663 cell proliferation Effects 0.000 description 1
- 230000019522 cellular metabolic process Effects 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 210000001638 cerebellum Anatomy 0.000 description 1
- 210000001175 cerebrospinal fluid Anatomy 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 210000002932 cholinergic neuron Anatomy 0.000 description 1
- 238000013270 controlled release Methods 0.000 description 1
- 238000011461 current therapy Methods 0.000 description 1
- 229940097362 cyclodextrins Drugs 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 230000003210 demyelinating effect Effects 0.000 description 1
- 238000003745 diagnosis Methods 0.000 description 1
- 235000015872 dietary supplement Nutrition 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 238000004043 dyeing Methods 0.000 description 1
- 230000002888 effect on disease Effects 0.000 description 1
- 230000002505 effect on nervous system Effects 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 229920001249 ethyl cellulose Polymers 0.000 description 1
- 235000019325 ethyl cellulose Nutrition 0.000 description 1
- 238000010195 expression analysis Methods 0.000 description 1
- 238000011049 filling Methods 0.000 description 1
- 210000003194 forelimb Anatomy 0.000 description 1
- 238000011223 gene expression profiling Methods 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 230000035876 healing Effects 0.000 description 1
- 244000144980 herd Species 0.000 description 1
- 230000000971 hippocampal effect Effects 0.000 description 1
- 210000001320 hippocampus Anatomy 0.000 description 1
- 230000001744 histochemical effect Effects 0.000 description 1
- 230000036732 histological change Effects 0.000 description 1
- 108091008147 housekeeping proteins Proteins 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 229920013821 hydroxy alkyl cellulose Polymers 0.000 description 1
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 1
- UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 description 1
- 208000021822 hypotensive Diseases 0.000 description 1
- 230000001077 hypotensive effect Effects 0.000 description 1
- 210000002865 immune cell Anatomy 0.000 description 1
- 230000001900 immune effect Effects 0.000 description 1
- 210000000987 immune system Anatomy 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
- 210000004969 inflammatory cell Anatomy 0.000 description 1
- 230000001788 irregular Effects 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 230000003902 lesion Effects 0.000 description 1
- 231100000225 lethality Toxicity 0.000 description 1
- 210000000265 leukocyte Anatomy 0.000 description 1
- 208000027905 limb weakness Diseases 0.000 description 1
- 231100000861 limb weakness Toxicity 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 239000012669 liquid formulation Substances 0.000 description 1
- 238000011068 loading method Methods 0.000 description 1
- 210000003141 lower extremity Anatomy 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 235000012054 meals Nutrition 0.000 description 1
- 210000001259 mesencephalon Anatomy 0.000 description 1
- 239000002207 metabolite Substances 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 238000007491 morphometric analysis Methods 0.000 description 1
- 210000000337 motor cortex Anatomy 0.000 description 1
- 210000003007 myelin sheath Anatomy 0.000 description 1
- 210000001577 neostriatum Anatomy 0.000 description 1
- 210000005036 nerve Anatomy 0.000 description 1
- 230000008764 nerve damage Effects 0.000 description 1
- 210000002241 neurite Anatomy 0.000 description 1
- 208000015122 neurodegenerative disease Diseases 0.000 description 1
- 230000000626 neurodegenerative effect Effects 0.000 description 1
- 230000009251 neurologic dysfunction Effects 0.000 description 1
- 208000015015 neurological dysfunction Diseases 0.000 description 1
- 230000016273 neuron death Effects 0.000 description 1
- 230000001590 oxidative effect Effects 0.000 description 1
- 230000036542 oxidative stress Effects 0.000 description 1
- 238000004806 packaging method and process Methods 0.000 description 1
- 230000036961 partial effect Effects 0.000 description 1
- 230000007310 pathophysiology Effects 0.000 description 1
- 210000001428 peripheral nervous system Anatomy 0.000 description 1
- 229940124531 pharmaceutical excipient Drugs 0.000 description 1
- 238000009522 phase III clinical trial Methods 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 238000004886 process control Methods 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 210000004129 prosencephalon Anatomy 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 230000007420 reactivation Effects 0.000 description 1
- 230000008929 regeneration Effects 0.000 description 1
- 238000011069 regeneration method Methods 0.000 description 1
- 238000000611 regression analysis Methods 0.000 description 1
- 230000008263 repair mechanism Effects 0.000 description 1
- HSSLDCABUXLXKM-UHFFFAOYSA-N resorufin Chemical compound C1=CC(=O)C=C2OC3=CC(O)=CC=C3N=C21 HSSLDCABUXLXKM-UHFFFAOYSA-N 0.000 description 1
- 230000000717 retained effect Effects 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 230000001568 sexual effect Effects 0.000 description 1
- 230000019491 signal transduction Effects 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 210000004092 somatosensory cortex Anatomy 0.000 description 1
- 230000003595 spectral effect Effects 0.000 description 1
- 238000005507 spraying Methods 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 210000003523 substantia nigra Anatomy 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 230000002459 sustained effect Effects 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
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 230000001052 transient effect Effects 0.000 description 1
- YXZRCLVVNRLPTP-UHFFFAOYSA-J turquoise blue Chemical compound [Na+].[Na+].[Na+].[Na+].[Cu+2].NC1=NC(Cl)=NC(NC=2C=C(NS(=O)(=O)C3=CC=4C(=C5NC=4NC=4[N-]C(=C6C=CC(=CC6=4)S([O-])(=O)=O)NC=4NC(=C6C=C(C=CC6=4)S([O-])(=O)=O)NC=4[N-]C(=C6C=CC(=CC6=4)S([O-])(=O)=O)N5)C=C3)C(=CC=2)S([O-])(=O)=O)=N1 YXZRCLVVNRLPTP-UHFFFAOYSA-J 0.000 description 1
- 238000001262 western blot Methods 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
Classifications
-
- 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
- G01N33/5005—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells
- G01N33/5008—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics
- G01N33/502—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics for testing non-proliferative effects
- G01N33/5023—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics for testing non-proliferative effects on expression patterns
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2072—Pills, tablets, discs, rods characterised by shape, structure or size; Tablets with holes, special break lines or identification marks; Partially coated tablets; Disintegrating flat shaped forms
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
- A61K31/215—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
- A61K31/22—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin
- A61K31/225—Polycarboxylic acids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/28—Dragees; Coated pills or tablets, e.g. with film or compression coating
- A61K9/2806—Coating materials
- A61K9/2833—Organic macromolecular compounds
- A61K9/284—Organic macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone
- A61K9/2846—Poly(meth)acrylates
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
- C12Q1/68—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
- C12Q1/6876—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes
-
- 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
- G01N33/5005—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells
- G01N33/5008—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics
- G01N33/5044—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics involving specific cell types
- G01N33/5058—Neurological cells
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q2600/00—Oligonucleotides characterized by their use
- C12Q2600/136—Screening for pharmacological compounds
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q2600/00—Oligonucleotides characterized by their use
- C12Q2600/158—Expression markers
-
- 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
- G01N2500/10—Screening for compounds of potential therapeutic value involving cells
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Biomedical Technology (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Epidemiology (AREA)
- Immunology (AREA)
- Molecular Biology (AREA)
- Organic Chemistry (AREA)
- Neurosurgery (AREA)
- Neurology (AREA)
- Analytical Chemistry (AREA)
- Urology & Nephrology (AREA)
- Hematology (AREA)
- Biochemistry (AREA)
- Physics & Mathematics (AREA)
- Microbiology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Biotechnology (AREA)
- Cell Biology (AREA)
- Tropical Medicine & Parasitology (AREA)
- Zoology (AREA)
- Food Science & Technology (AREA)
- General Physics & Mathematics (AREA)
- Pathology (AREA)
- Toxicology (AREA)
- Wood Science & Technology (AREA)
- Emergency Medicine (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Psychiatry (AREA)
- Hospice & Palliative Care (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US17379709P | 2009-04-29 | 2009-04-29 | |
| US61/173,797 | 2009-04-29 | ||
| US17527009P | 2009-05-04 | 2009-05-04 | |
| US61/175,270 | 2009-05-04 | ||
| PCT/US2010/001282 WO2010126605A1 (en) | 2009-04-29 | 2010-04-29 | Treatment of neurodegeneration and neuroinflammation |
Related Child Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2014239565A Division JP2015044855A (ja) | 2009-04-29 | 2014-11-27 | 神経変性および神経炎症の治療 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2012525385A true JP2012525385A (ja) | 2012-10-22 |
| JP2012525385A5 JP2012525385A5 (enExample) | 2013-10-10 |
Family
ID=43032484
Family Applications (3)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2012508485A Withdrawn JP2012525385A (ja) | 2009-04-29 | 2010-04-29 | 神経変性および神経炎症の治療 |
| JP2014239565A Pending JP2015044855A (ja) | 2009-04-29 | 2014-11-27 | 神経変性および神経炎症の治療 |
| JP2016090250A Pending JP2016175926A (ja) | 2009-04-29 | 2016-04-28 | 神経変性および神経炎症の治療 |
Family Applications After (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2014239565A Pending JP2015044855A (ja) | 2009-04-29 | 2014-11-27 | 神経変性および神経炎症の治療 |
| JP2016090250A Pending JP2016175926A (ja) | 2009-04-29 | 2016-04-28 | 神経変性および神経炎症の治療 |
Country Status (9)
| Country | Link |
|---|---|
| US (3) | US20120165404A1 (enExample) |
| EP (3) | EP3466420A1 (enExample) |
| JP (3) | JP2012525385A (enExample) |
| CN (2) | CN102427727A (enExample) |
| AU (1) | AU2010242064A1 (enExample) |
| CA (1) | CA2760133A1 (enExample) |
| HK (1) | HK1255133A1 (enExample) |
| NZ (2) | NZ595941A (enExample) |
| WO (1) | WO2010126605A1 (enExample) |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2015044855A (ja) * | 2009-04-29 | 2015-03-12 | バイオジェン・アイデック・エムエイ・インコーポレイテッド | 神経変性および神経炎症の治療 |
| JP2016510317A (ja) * | 2012-12-21 | 2016-04-07 | バイオジェン エムエー インコーポレイテッド | 重水素置換されたフマル酸誘導体 |
| JP2017534667A (ja) * | 2014-11-19 | 2017-11-24 | バイオジェン・エムエイ・インコーポレイテッドＢｉｏｇｅｎ ＭＡ Ｉｎｃ． | フマル酸ジメチルを含む医薬マトリクス製剤 |
| JP2018093753A (ja) * | 2016-12-08 | 2018-06-21 | 公益財団法人東京都医学総合研究所 | 脳組織の異常を伴う非ヒト動物の作製方法およびその利用 |
Families Citing this family (48)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE19853487A1 (de) | 1998-11-19 | 2000-05-25 | Fumapharm Ag Muri | Verwendung von Dialkylfumaraten |
| WO2005023241A1 (en) | 2003-09-09 | 2005-03-17 | Fumapharm Ag | The use of fumaric acid derivatives for treating cardiac insufficiency, and asthma |
| SI2801354T1 (sl) * | 2004-10-08 | 2017-07-31 | Forward Pharma A/S | Farmacevtske sestave z nadzorovanim sproščanjem, ki zajemajo ester fumarne kisline |
| DK2653873T3 (da) | 2007-02-08 | 2022-07-25 | Biogen Ma Inc | Sammensætninger og anvendelser til behandling af multipel sklerose |
| PT2139467T (pt) * | 2007-02-08 | 2016-12-16 | Biogen Ma Inc | Neuroproteção em doenças desmielinizantes |
| DK2334378T3 (da) | 2008-08-19 | 2014-07-07 | Xenoport Inc | Prodrugs af methylhydrogenfumarat, farmaceutiske sammensætninger deraf og fremgangsmåder til anvendelse |
| KR101699912B1 (ko) | 2009-01-09 | 2017-01-25 | 포워드 파마 에이/에스 | 1종 이상의 푸마르산 에스테르를 침식 매트릭스에 함유하는 제제 |
| JPWO2010098429A1 (ja) | 2009-02-27 | 2012-09-06 | 国立大学法人大阪大学 | 免疫アジュバント組成物、及びその利用 |
| US20140142095A1 (en) * | 2011-04-28 | 2014-05-22 | Serket Pharma, Llc | Agents useful for treating friedreich's ataxia and other neurodegenerative diseases |
| EP2713724A4 (en) * | 2011-05-26 | 2015-03-11 | Biogen Idec Inc | METHODS OF TREATING MULTIPLE SCLEROSIS AND PRESERVING AND / OR INCREASING MYELINE CONTENT |
| JP6385273B6 (ja) | 2011-06-08 | 2023-12-15 | バイオジェン・エムエイ・インコーポレイテッド | 高純度結晶性ジメチルフマラートの調製方法 |
| HK1202885A1 (en) * | 2011-12-16 | 2015-10-09 | Biogen Ma Inc. | Silicon-containing fumaric acid esters |
| US20130158077A1 (en) | 2011-12-19 | 2013-06-20 | Ares Trading S.A. | Pharmaceutical compositions |
| CN113244185A (zh) * | 2012-02-07 | 2021-08-13 | 比奥根玛公司 | 含有富马酸二甲酯的药物组合物 |
| US20130259856A1 (en) * | 2012-03-27 | 2013-10-03 | Teva Pharmaceutical Industries, Ltd. | Treatment of multiple sclerosis with combination of laquinimod and dimethyl fumarate |
| JP2013220090A (ja) * | 2012-04-19 | 2013-10-28 | Tohoku Univ | 眼疾患治療に使用する薬剤スクリーニング方法 |
| JP2015527372A (ja) * | 2012-08-22 | 2015-09-17 | ゼノポート，インコーポレイティド | 副作用を低減させるモノメチルフマレートおよびそのプロドラッグの投与方法 |
| US20140348915A9 (en) | 2012-08-22 | 2014-11-27 | Xenoport, Inc. | Oral Dosage Forms of Methyl Hydrogen Fumarate and Prodrugs Thereof |
| US20140171504A1 (en) | 2012-12-14 | 2014-06-19 | Georgia Regents Research Institute, Inc. | Methods of Treating Sickle Cell Disease and Related Disorders Using Fumaric Acid Esters |
| CN103173544B (zh) * | 2013-03-05 | 2015-01-28 | 浙江大学 | Leber病之线粒体T3866C检测试剂盒及应用 |
| CN105452213B (zh) | 2013-03-14 | 2017-09-22 | 阿尔克梅斯制药爱尔兰有限公司 | 富马酸酯前体药物及其在治疗多种疾病中的应用 |
| US8669281B1 (en) | 2013-03-14 | 2014-03-11 | Alkermes Pharma Ireland Limited | Prodrugs of fumarates and their use in treating various diseases |
| WO2014160633A1 (en) | 2013-03-24 | 2014-10-02 | Xenoport, Inc. | Pharmaceutical compositions of dimethyl fumarate |
| US9302977B2 (en) | 2013-06-07 | 2016-04-05 | Xenoport, Inc. | Method of making monomethyl fumarate |
| US9421182B2 (en) | 2013-06-21 | 2016-08-23 | Xenoport, Inc. | Cocrystals of dimethyl fumarate |
| TW201516020A (zh) | 2013-09-06 | 2015-05-01 | Xenoport Inc | （ｎ，ｎ－二乙基胺甲醯基）甲基（２ｅ）丁－２－烯－１，４－二酸甲酯之晶形、合成方法及用途 |
| CN103768045B (zh) * | 2013-10-30 | 2015-10-07 | 苏州大学附属第一医院 | 富马酸二甲酯在制备治疗蛛网膜下腔出血后早期脑损伤药物的应用 |
| US20160310457A1 (en) * | 2013-12-12 | 2016-10-27 | Almirall, S.A. | Pharmaceutical compositions comprising dimethyl fumarate |
| CA2940845C (en) | 2014-02-24 | 2019-09-24 | Alkermes Pharma Ireland Limited | Sulfonamide and sulfinamide prodrugs of fumarates and their use in treating various diseases |
| US10098863B2 (en) | 2014-02-28 | 2018-10-16 | Banner Life Sciences Llc | Fumarate esters |
| US9636318B2 (en) | 2015-08-31 | 2017-05-02 | Banner Life Sciences Llc | Fumarate ester dosage forms |
| US9326947B1 (en) | 2014-02-28 | 2016-05-03 | Banner Life Sciences Llc | Controlled release fumarate esters |
| EP3110408B1 (en) | 2014-02-28 | 2019-01-16 | Banner Life Sciences LLC | Controlled release enteric soft capsules of fumarate esters |
| US9999672B2 (en) | 2014-03-24 | 2018-06-19 | Xenoport, Inc. | Pharmaceutical compositions of fumaric acid esters |
| AU2015381240A1 (en) | 2015-02-08 | 2017-07-06 | Alkermes Pharma Ireland Limited | Monomethylfumarate prodrug compositions |
| MA41785A (fr) | 2015-03-20 | 2018-01-23 | Biogen Ma Inc | Procédés et compositions pour l'administration intraveineuse de fumarates pour le traitement de maladies neurologiques |
| WO2017056107A1 (en) * | 2015-09-28 | 2017-04-06 | Natco Pharma Ltd | Pharmaceutical compositions of dimethyl fumarate |
| GR1009149B (el) * | 2016-10-25 | 2017-10-31 | Φαρματεν Αβεε | Φαρμακευτικα σκευασματα που περιλαμβανουν εναν εστερα φουμαρικου οξεως και μεθοδος παραγωγης αυτων |
| MA49448A (fr) | 2017-06-23 | 2020-04-29 | Almirall Sa | Compositions pharmaceutiques contenant du fumarate de diméthyle |
| US11382889B2 (en) * | 2018-04-19 | 2022-07-12 | Institut D'investigació Biomèdica De Bellvitge (Idibell) | NRF2 activators for the prevention and/or treatment of axonal degeneration |
| CN108904779B (zh) * | 2018-09-29 | 2019-12-03 | 南华大学 | 曲普瑞林的新应用 |
| CN109364058A (zh) * | 2018-12-05 | 2019-02-22 | 中南大学湘雅医院 | 富马酸酯及其可药用盐在制备治疗铁死亡相关疾病的药物中的应用 |
| US20220087942A1 (en) | 2019-05-31 | 2022-03-24 | Curacle Co., Ltd. | Enteric tablet containing dimethyl fumarate |
| WO2021092536A1 (en) * | 2019-11-08 | 2021-05-14 | The Children's Hospital Of Philadelphia | Compositions and methods for treating macrophage activation syndrome |
| CN113117081B (zh) * | 2019-12-30 | 2024-12-24 | 上海海洋大学 | ZC3H12b基因或蛋白的用途及一种肝脏疾病动物模型的建立方法 |
| WO2021142062A1 (en) | 2020-01-10 | 2021-07-15 | Banner Life Sciences Llc | Fumarate ester dosage forms with enhanced gastrointestinal tolerability |
| WO2022203432A1 (ko) | 2021-03-25 | 2022-09-29 | 주식회사 큐라클 | 특정 약동학적 매개변수를 나타내는 디메틸푸마레이트를 유효성분으로 함유한 약학적 조성물 |
| CN115487297A (zh) * | 2021-06-17 | 2022-12-20 | 清华大学 | 治疗神经元蜡样质脂褐质沉积症的方法和药物 |
Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2000513023A (ja) * | 1997-05-20 | 2000-10-03 | フーマファーム アーゲー | フマル酸誘導体の使用 |
| WO2002002190A2 (en) * | 2000-07-05 | 2002-01-10 | Johns Hopkins School Of Medicine | Prevention and treatment of neurodegenerative diseases by glutathione and phase ii detoxification enzymes |
| JP2008515822A (ja) * | 2004-10-08 | 2008-05-15 | アディテック・ファルマ・アクチボラゲット | フマル酸エステルを含む制御放出医薬組成物 |
| WO2008097596A2 (en) * | 2007-02-08 | 2008-08-14 | Biogen Idec Ma Inc. | Nrf2 screening assays and related methods and compositions |
| WO2008096271A2 (en) * | 2007-02-08 | 2008-08-14 | Ralf Gold | Neuroprotection in demyelinating diseases |
| JP2009510137A (ja) * | 2005-10-07 | 2009-03-12 | アディテック・ファルマ・アクチボラゲット | フマル酸エステルを含む制御放出医薬組成物 |
Family Cites Families (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE19853487A1 (de) | 1998-11-19 | 2000-05-25 | Fumapharm Ag Muri | Verwendung von Dialkylfumaraten |
| DE10101307A1 (de) * | 2001-01-12 | 2002-08-01 | Fumapharm Ag Muri | Fumarsäurederivate als NF-kappaB-Inhibitor |
| JP2004041208A (ja) * | 2002-07-15 | 2004-02-12 | Sankyo Co Ltd | インスリン抵抗性改善効果の評価方法 |
| WO2006050730A1 (en) | 2004-11-10 | 2006-05-18 | Aditech Pharma Ab | Novel salts of fumaric acid monoalkylesters and their pharmaceutical use |
| WO2007005879A2 (en) * | 2005-07-01 | 2007-01-11 | The Johns Hopkins University | Compositions and methods for the treatment or prevention of disorders relating to oxidative stress |
| US20100144651A1 (en) | 2005-07-07 | 2010-06-10 | Aditech Pharma Ab | Novel glucopyranose esters and glucofuranose esters of alkyl- fumarates and their pharmaceutical use |
| WO2007006307A2 (en) | 2005-07-07 | 2007-01-18 | Aditech Pharma Ab | Novel salts of fumaric acid monoalkylesters and their pharmaceutical use |
| WO2007042035A2 (en) * | 2005-10-07 | 2007-04-19 | Aditech Pharma Ab | Combination therapy with fumaric acid esters for the treatment of autoimmune and/or inflammatory disorders |
| US20070224638A1 (en) * | 2006-03-27 | 2007-09-27 | Institut Pasteur | Secreted proteins as early markers and drug targets for autoimmunity, tumorigenesis and infections |
| US20080089861A1 (en) * | 2006-07-10 | 2008-04-17 | Went Gregory T | Combination therapy for treatment of demyelinating conditions |
| WO2008039876A1 (en) * | 2006-09-26 | 2008-04-03 | Case Western Reserve University | Cytokine signaling |
| KR101699912B1 (ko) * | 2009-01-09 | 2017-01-25 | 포워드 파마 에이/에스 | 1종 이상의 푸마르산 에스테르를 침식 매트릭스에 함유하는 제제 |
| EP3466420A1 (en) * | 2009-04-29 | 2019-04-10 | Biogen MA Inc. | Dimethyl fumarate for the treatment of friedreich ataxia |
-
2010
- 2010-04-29 EP EP18206136.6A patent/EP3466420A1/en not_active Withdrawn
- 2010-04-29 WO PCT/US2010/001282 patent/WO2010126605A1/en not_active Ceased
- 2010-04-29 JP JP2012508485A patent/JP2012525385A/ja not_active Withdrawn
- 2010-04-29 EP EP17202547.0A patent/EP3318249A1/en not_active Withdrawn
- 2010-04-29 AU AU2010242064A patent/AU2010242064A1/en not_active Abandoned
- 2010-04-29 EP EP10770066A patent/EP2424357A4/en not_active Withdrawn
- 2010-04-29 CN CN2010800215056A patent/CN102427727A/zh active Pending
- 2010-04-29 CA CA2760133A patent/CA2760133A1/en not_active Abandoned
- 2010-04-29 NZ NZ595941A patent/NZ595941A/en not_active IP Right Cessation
- 2010-04-29 NZ NZ617130A patent/NZ617130A/en not_active IP Right Cessation
- 2010-04-29 US US13/266,997 patent/US20120165404A1/en not_active Abandoned
- 2010-04-29 CN CN201410648177.2A patent/CN104523673A/zh active Pending
-
2014
- 2014-11-13 US US14/540,136 patent/US20150132747A1/en not_active Abandoned
- 2014-11-27 JP JP2014239565A patent/JP2015044855A/ja active Pending
-
2016
- 2016-04-28 JP JP2016090250A patent/JP2016175926A/ja active Pending
-
2018
- 2018-11-07 HK HK18114182.9A patent/HK1255133A1/en unknown
- 2018-11-29 US US16/204,076 patent/US20190195860A1/en not_active Abandoned
Patent Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2000513023A (ja) * | 1997-05-20 | 2000-10-03 | フーマファーム アーゲー | フマル酸誘導体の使用 |
| WO2002002190A2 (en) * | 2000-07-05 | 2002-01-10 | Johns Hopkins School Of Medicine | Prevention and treatment of neurodegenerative diseases by glutathione and phase ii detoxification enzymes |
| JP2008515822A (ja) * | 2004-10-08 | 2008-05-15 | アディテック・ファルマ・アクチボラゲット | フマル酸エステルを含む制御放出医薬組成物 |
| JP2009510137A (ja) * | 2005-10-07 | 2009-03-12 | アディテック・ファルマ・アクチボラゲット | フマル酸エステルを含む制御放出医薬組成物 |
| WO2008097596A2 (en) * | 2007-02-08 | 2008-08-14 | Biogen Idec Ma Inc. | Nrf2 screening assays and related methods and compositions |
| WO2008096271A2 (en) * | 2007-02-08 | 2008-08-14 | Ralf Gold | Neuroprotection in demyelinating diseases |
Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2015044855A (ja) * | 2009-04-29 | 2015-03-12 | バイオジェン・アイデック・エムエイ・インコーポレイテッド | 神経変性および神経炎症の治療 |
| JP2016510317A (ja) * | 2012-12-21 | 2016-04-07 | バイオジェン エムエー インコーポレイテッド | 重水素置換されたフマル酸誘導体 |
| JP2019077711A (ja) * | 2012-12-21 | 2019-05-23 | バイオジェン エムエー インコーポレイテッド | 重水素置換されたフマル酸誘導体 |
| JP2017534667A (ja) * | 2014-11-19 | 2017-11-24 | バイオジェン・エムエイ・インコーポレイテッドＢｉｏｇｅｎ ＭＡ Ｉｎｃ． | フマル酸ジメチルを含む医薬マトリクス製剤 |
| JP2021152046A (ja) * | 2014-11-19 | 2021-09-30 | バイオジェン・エムエイ・インコーポレイテッドBiogen MA Inc. | フマル酸ジメチルを含む医薬マトリクス製剤 |
| JP2018093753A (ja) * | 2016-12-08 | 2018-06-21 | 公益財団法人東京都医学総合研究所 | 脳組織の異常を伴う非ヒト動物の作製方法およびその利用 |
| JP7084689B2 (ja) | 2016-12-08 | 2022-06-15 | 公益財団法人東京都医学総合研究所 | 脳組織の異常を伴う非ヒト動物の作製方法およびその利用 |
Also Published As
| Publication number | Publication date |
|---|---|
| CN102427727A (zh) | 2012-04-25 |
| JP2015044855A (ja) | 2015-03-12 |
| AU2010242064A1 (en) | 2011-11-17 |
| US20190195860A1 (en) | 2019-06-27 |
| WO2010126605A1 (en) | 2010-11-04 |
| AU2010242064A2 (en) | 2013-10-10 |
| NZ617130A (en) | 2015-06-26 |
| JP2016175926A (ja) | 2016-10-06 |
| NZ595941A (en) | 2014-02-28 |
| CN104523673A (zh) | 2015-04-22 |
| HK1255133A1 (en) | 2019-08-09 |
| EP3466420A1 (en) | 2019-04-10 |
| EP3318249A1 (en) | 2018-05-09 |
| EP2424357A4 (en) | 2012-10-10 |
| EP2424357A1 (en) | 2012-03-07 |
| US20150132747A1 (en) | 2015-05-14 |
| CA2760133A1 (en) | 2010-11-04 |
| US20120165404A1 (en) | 2012-06-28 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP2016175926A (ja) | 神経変性および神経炎症の治療 | |
| KR102188487B1 (ko) | 글리타존 및 nrf2 활성화제를 포함하는 약학 조성물 | |
| HRP20210686T1 (hr) | Pripravci i postupci za liječenje moždanog udara kod subjekta na istodobnoj terapiji statinom | |
| JP2012525385A5 (enExample) | ||
| AU2021269396A1 (en) | Very-long-chain polyunsaturated fatty acids, elovanoid hydroxylated derivatives, and methods of use | |
| US10363235B2 (en) | Compositions comprising 15-HEPE and methods of treating or preventing fibrosis using same | |
| Yang et al. | Tanshinol suppresses inflammatory factors in a rat model of vascular dementia and protects LPS-treated neurons via the MST1-FOXO3 signaling pathway | |
| BG64167B1 (bg) | Използване на заместени аминометил-хромани за профилактика на невронална дегенерация и за стимулиране на невронална регенерация | |
| EP3091972A1 (en) | Method of treating liver disorders | |
| US7557089B2 (en) | Use of derivatives of succinate esters for the treatment of dementia | |
| US20190030005A1 (en) | Therapeutic agent for dyslipidemia | |
| US20050085553A1 (en) | Remedies for mild recognition deflict | |
| CA3104916C (en) | Pharmaceutical composition for preventing diabetes and use thereof | |
| EP4281118A1 (en) | Improved treatment for globoid cell leukodsytrophy or krabbe disease | |
| TWI527828B (zh) | 新穎的三萜化合物及其用途 | |
| KR20200140384A (ko) | 글리타존 및 nrf2 활성화제를 포함하는 약학 조성물 | |
| HK1245101B (en) | Compositions comprising 15-hepe and its use for treating or preventing idiopathic pulomonary fibrosis | |
| KR20170117463A (ko) | 죽종 형성 치료를 위한 시스템 및 방법 | |
| ITRM20110216A1 (it) | Vitamina b1 per uso nel trattamento di malattie infiammatorie - autoimmunitarie. |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20130423 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20130821 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20140527 |
|
| A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20140826 |
|
| A602 | Written permission of extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A602 Effective date: 20140902 |
|
| A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20140924 |
|
| A602 | Written permission of extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A602 Effective date: 20141001 |
|
| A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20141024 |
|
| A602 | Written permission of extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A602 Effective date: 20141031 |
|
| A02 | Decision of refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A02 Effective date: 20150303 |
|
| A761 | Written withdrawal of application |
Free format text: JAPANESE INTERMEDIATE CODE: A761 Effective date: 20150304 |