CA2877397A1 - Antibodies to tau - Google Patents
Antibodies to tau Download PDFInfo
- Publication number
- CA2877397A1 CA2877397A1 CA2877397A CA2877397A CA2877397A1 CA 2877397 A1 CA2877397 A1 CA 2877397A1 CA 2877397 A CA2877397 A CA 2877397A CA 2877397 A CA2877397 A CA 2877397A CA 2877397 A1 CA2877397 A1 CA 2877397A1
- Authority
- CA
- Canada
- Prior art keywords
- tau
- antibody
- seq
- antibodies
- cells
- 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.)
- Abandoned
Links
- 238000000034 method Methods 0.000 claims abstract description 85
- 238000004220 aggregation Methods 0.000 claims description 123
- 230000002776 aggregation Effects 0.000 claims description 119
- 230000000694 effects Effects 0.000 claims description 116
- 210000004556 brain Anatomy 0.000 claims description 97
- 238000010899 nucleation Methods 0.000 claims description 63
- 230000007170 pathology Effects 0.000 claims description 58
- 208000024891 symptom Diseases 0.000 claims description 40
- 238000003556 assay Methods 0.000 claims description 37
- 238000001514 detection method Methods 0.000 claims description 32
- 239000013060 biological fluid Substances 0.000 claims description 29
- 208000024827 Alzheimer disease Diseases 0.000 claims description 27
- 230000001965 increasing effect Effects 0.000 claims description 23
- 238000006467 substitution reaction Methods 0.000 claims description 21
- 230000006399 behavior Effects 0.000 claims description 12
- 230000001413 cellular effect Effects 0.000 claims description 11
- FWMNVWWHGCHHJJ-SKKKGAJSSA-N 4-amino-1-[(2r)-6-amino-2-[[(2r)-2-[[(2r)-2-[[(2r)-2-amino-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]hexanoyl]piperidine-4-carboxylic acid Chemical compound C([C@H](C(=O)N[C@H](CC(C)C)C(=O)N[C@H](CCCCN)C(=O)N1CCC(N)(CC1)C(O)=O)NC(=O)[C@H](N)CC=1C=CC=CC=1)C1=CC=CC=C1 FWMNVWWHGCHHJJ-SKKKGAJSSA-N 0.000 claims description 9
- 238000011161 development Methods 0.000 claims description 9
- 238000003018 immunoassay Methods 0.000 claims description 9
- 108091028043 Nucleic acid sequence Proteins 0.000 claims description 8
- 210000003169 central nervous system Anatomy 0.000 claims description 8
- 230000006870 function Effects 0.000 claims description 8
- 150000007523 nucleic acids Chemical group 0.000 claims description 8
- 230000001771 impaired effect Effects 0.000 claims description 6
- 206010010904 Convulsion Diseases 0.000 claims description 5
- 230000003920 cognitive function Effects 0.000 claims description 5
- 230000010483 emotional dysregulation Effects 0.000 claims description 3
- 210000000653 nervous system Anatomy 0.000 claims description 3
- 108010021625 Immunoglobulin Fragments Proteins 0.000 claims description 2
- 102000008394 Immunoglobulin Fragments Human genes 0.000 claims description 2
- 230000002159 abnormal effect Effects 0.000 claims description 2
- 230000008449 language Effects 0.000 claims description 2
- 125000003275 alpha amino acid group Chemical group 0.000 claims 6
- 230000009885 systemic effect Effects 0.000 claims 1
- 108010026424 tau Proteins Proteins 0.000 description 580
- 102000013498 tau Proteins Human genes 0.000 description 579
- 210000004027 cell Anatomy 0.000 description 324
- 241000699670 Mus sp. Species 0.000 description 132
- 150000001413 amino acids Chemical group 0.000 description 131
- 238000002866 fluorescence resonance energy transfer Methods 0.000 description 95
- 239000002953 phosphate buffered saline Substances 0.000 description 76
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 75
- 238000010186 staining Methods 0.000 description 70
- 101000891579 Homo sapiens Microtubule-associated protein tau Proteins 0.000 description 69
- 238000011282 treatment Methods 0.000 description 67
- 108090000623 proteins and genes Proteins 0.000 description 65
- 102000004169 proteins and genes Human genes 0.000 description 65
- 102000057063 human MAPT Human genes 0.000 description 61
- 241000282414 Homo sapiens Species 0.000 description 58
- 108091005957 yellow fluorescent proteins Proteins 0.000 description 58
- 101100480715 Mus musculus Mapt gene Proteins 0.000 description 54
- 241000699666 Mus <mouse, genus> Species 0.000 description 53
- 239000000523 sample Substances 0.000 description 51
- 238000012360 testing method Methods 0.000 description 48
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 38
- 238000002965 ELISA Methods 0.000 description 35
- 239000006166 lysate Substances 0.000 description 35
- 241000894007 species Species 0.000 description 33
- 238000004458 analytical method Methods 0.000 description 28
- 230000027455 binding Effects 0.000 description 26
- 238000007710 freezing Methods 0.000 description 26
- 230000008014 freezing Effects 0.000 description 26
- 238000003501 co-culture Methods 0.000 description 24
- 230000002829 reductive effect Effects 0.000 description 24
- 230000003834 intracellular effect Effects 0.000 description 22
- 208000034799 Tauopathies Diseases 0.000 description 21
- 230000033001 locomotion Effects 0.000 description 21
- 239000000178 monomer Substances 0.000 description 21
- 238000001262 western blot Methods 0.000 description 21
- 241001465754 Metazoa Species 0.000 description 20
- 238000002474 experimental method Methods 0.000 description 20
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 19
- 108060003951 Immunoglobulin Proteins 0.000 description 19
- 235000019253 formic acid Nutrition 0.000 description 19
- 102000018358 immunoglobulin Human genes 0.000 description 19
- 238000001802 infusion Methods 0.000 description 19
- 238000000185 intracerebroventricular administration Methods 0.000 description 19
- 230000007246 mechanism Effects 0.000 description 19
- 238000012546 transfer Methods 0.000 description 19
- 108010029485 Protein Isoforms Proteins 0.000 description 18
- 102000001708 Protein Isoforms Human genes 0.000 description 18
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 18
- 230000000903 blocking effect Effects 0.000 description 17
- 239000000203 mixture Substances 0.000 description 17
- 229940126619 mouse monoclonal antibody Drugs 0.000 description 17
- 210000002966 serum Anatomy 0.000 description 17
- 206010012289 Dementia Diseases 0.000 description 16
- 230000015572 biosynthetic process Effects 0.000 description 16
- 210000001175 cerebrospinal fluid Anatomy 0.000 description 16
- 201000010099 disease Diseases 0.000 description 16
- 239000012634 fragment Substances 0.000 description 16
- 230000003053 immunization Effects 0.000 description 16
- 238000002198 surface plasmon resonance spectroscopy Methods 0.000 description 16
- 230000003247 decreasing effect Effects 0.000 description 15
- 238000001727 in vivo Methods 0.000 description 15
- 210000003140 lateral ventricle Anatomy 0.000 description 15
- 239000011324 bead Substances 0.000 description 14
- 210000001723 extracellular space Anatomy 0.000 description 14
- 239000007924 injection Substances 0.000 description 14
- 238000002347 injection Methods 0.000 description 14
- 230000003993 interaction Effects 0.000 description 14
- 239000002609 medium Substances 0.000 description 14
- 210000002682 neurofibrillary tangle Anatomy 0.000 description 14
- 210000002381 plasma Anatomy 0.000 description 14
- 210000004727 amygdala Anatomy 0.000 description 13
- 230000014509 gene expression Effects 0.000 description 13
- 239000012528 membrane Substances 0.000 description 13
- 230000001575 pathological effect Effects 0.000 description 13
- 230000001225 therapeutic effect Effects 0.000 description 13
- 238000002649 immunization Methods 0.000 description 12
- 238000003119 immunoblot Methods 0.000 description 12
- 238000000386 microscopy Methods 0.000 description 12
- 230000003204 osmotic effect Effects 0.000 description 12
- 238000011830 transgenic mouse model Methods 0.000 description 12
- 229930040373 Paraformaldehyde Natural products 0.000 description 11
- 238000004630 atomic force microscopy Methods 0.000 description 11
- 239000003636 conditioned culture medium Substances 0.000 description 11
- 230000001143 conditioned effect Effects 0.000 description 11
- 230000007423 decrease Effects 0.000 description 11
- 210000001353 entorhinal cortex Anatomy 0.000 description 11
- 230000006698 induction Effects 0.000 description 11
- 230000007326 intracellular aggregation Effects 0.000 description 11
- 229920002866 paraformaldehyde Polymers 0.000 description 11
- 239000000243 solution Substances 0.000 description 11
- 101710117290 Aldo-keto reductase family 1 member C4 Proteins 0.000 description 10
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 10
- 238000004624 confocal microscopy Methods 0.000 description 10
- 230000000875 corresponding effect Effects 0.000 description 10
- 238000000684 flow cytometry Methods 0.000 description 10
- 210000001320 hippocampus Anatomy 0.000 description 10
- 230000035772 mutation Effects 0.000 description 10
- 108090000765 processed proteins & peptides Proteins 0.000 description 10
- 241000283707 Capra Species 0.000 description 9
- 238000012286 ELISA Assay Methods 0.000 description 9
- 238000009472 formulation Methods 0.000 description 9
- 210000004408 hybridoma Anatomy 0.000 description 9
- 238000001114 immunoprecipitation Methods 0.000 description 9
- ZAINTDRBUHCDPZ-UHFFFAOYSA-M Alexa Fluor 546 Chemical compound [H+].[Na+].CC1CC(C)(C)NC(C(=C2OC3=C(C4=NC(C)(C)CC(C)C4=CC3=3)S([O-])(=O)=O)S([O-])(=O)=O)=C1C=C2C=3C(C(=C(Cl)C=1Cl)C(O)=O)=C(Cl)C=1SCC(=O)NCCCCCC(=O)ON1C(=O)CCC1=O ZAINTDRBUHCDPZ-UHFFFAOYSA-M 0.000 description 8
- 201000011240 Frontotemporal dementia Diseases 0.000 description 8
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 8
- 241000699660 Mus musculus Species 0.000 description 8
- 241000283973 Oryctolagus cuniculus Species 0.000 description 8
- 238000013459 approach Methods 0.000 description 8
- 239000000872 buffer Substances 0.000 description 8
- 230000006735 deficit Effects 0.000 description 8
- 230000018109 developmental process Effects 0.000 description 8
- 238000010790 dilution Methods 0.000 description 8
- 239000012895 dilution Substances 0.000 description 8
- 239000000499 gel Substances 0.000 description 8
- 238000011534 incubation Methods 0.000 description 8
- 239000013642 negative control Substances 0.000 description 8
- 208000015122 neurodegenerative disease Diseases 0.000 description 8
- 239000008188 pellet Substances 0.000 description 8
- 230000008569 process Effects 0.000 description 8
- 230000009467 reduction Effects 0.000 description 8
- 239000003656 tris buffered saline Substances 0.000 description 8
- 101001071233 Homo sapiens PHD finger protein 1 Proteins 0.000 description 7
- 102000029749 Microtubule Human genes 0.000 description 7
- 108091022875 Microtubule Proteins 0.000 description 7
- 241001529936 Murinae Species 0.000 description 7
- 102100036879 PHD finger protein 1 Human genes 0.000 description 7
- 239000007983 Tris buffer Substances 0.000 description 7
- 239000013504 Triton X-100 Substances 0.000 description 7
- 229920004890 Triton X-100 Polymers 0.000 description 7
- 230000003321 amplification Effects 0.000 description 7
- 239000000427 antigen Substances 0.000 description 7
- 108091007433 antigens Proteins 0.000 description 7
- 102000036639 antigens Human genes 0.000 description 7
- 238000010494 dissociation reaction Methods 0.000 description 7
- 230000005593 dissociations Effects 0.000 description 7
- 238000005516 engineering process Methods 0.000 description 7
- 239000012530 fluid Substances 0.000 description 7
- 230000001976 improved effect Effects 0.000 description 7
- 238000005259 measurement Methods 0.000 description 7
- 230000006724 microglial activation Effects 0.000 description 7
- 210000004688 microtubule Anatomy 0.000 description 7
- 230000004770 neurodegeneration Effects 0.000 description 7
- 238000003199 nucleic acid amplification method Methods 0.000 description 7
- 239000000137 peptide hydrolase inhibitor Substances 0.000 description 7
- 238000010814 radioimmunoprecipitation assay Methods 0.000 description 7
- 239000000126 substance Substances 0.000 description 7
- 239000000758 substrate Substances 0.000 description 7
- 239000006228 supernatant Substances 0.000 description 7
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 7
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 6
- 101710154606 Hemagglutinin Proteins 0.000 description 6
- 101000934372 Homo sapiens Macrosialin Proteins 0.000 description 6
- 102100025136 Macrosialin Human genes 0.000 description 6
- 101710093908 Outer capsid protein VP4 Proteins 0.000 description 6
- 101710135467 Outer capsid protein sigma-1 Proteins 0.000 description 6
- 108091000054 Prion Proteins 0.000 description 6
- 101710176177 Protein A56 Proteins 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- 102000004142 Trypsin Human genes 0.000 description 6
- 108090000631 Trypsin Proteins 0.000 description 6
- ZHAFUINZIZIXFC-UHFFFAOYSA-N [9-(dimethylamino)-10-methylbenzo[a]phenoxazin-5-ylidene]azanium;chloride Chemical compound [Cl-].O1C2=CC(=[NH2+])C3=CC=CC=C3C2=NC2=C1C=C(N(C)C)C(C)=C2 ZHAFUINZIZIXFC-UHFFFAOYSA-N 0.000 description 6
- 238000006243 chemical reaction Methods 0.000 description 6
- 150000001875 compounds Chemical class 0.000 description 6
- 230000003750 conditioning effect Effects 0.000 description 6
- 239000003599 detergent Substances 0.000 description 6
- 230000009977 dual effect Effects 0.000 description 6
- 238000003384 imaging method Methods 0.000 description 6
- 230000005764 inhibitory process Effects 0.000 description 6
- 238000011813 knockout mouse model Methods 0.000 description 6
- 210000002569 neuron Anatomy 0.000 description 6
- 230000004845 protein aggregation Effects 0.000 description 6
- 239000012723 sample buffer Substances 0.000 description 6
- 230000003595 spectral effect Effects 0.000 description 6
- 230000008685 targeting Effects 0.000 description 6
- 210000001519 tissue Anatomy 0.000 description 6
- 239000012588 trypsin Substances 0.000 description 6
- 239000003981 vehicle Substances 0.000 description 6
- 238000005406 washing Methods 0.000 description 6
- 229920000936 Agarose Polymers 0.000 description 5
- NQTADLQHYWFPDB-UHFFFAOYSA-N N-Hydroxysuccinimide Chemical compound ON1C(=O)CCC1=O NQTADLQHYWFPDB-UHFFFAOYSA-N 0.000 description 5
- 102000029797 Prion Human genes 0.000 description 5
- 241000700159 Rattus Species 0.000 description 5
- 230000003542 behavioural effect Effects 0.000 description 5
- 210000005056 cell body Anatomy 0.000 description 5
- 230000030833 cell death Effects 0.000 description 5
- 230000008859 change Effects 0.000 description 5
- 239000003795 chemical substances by application Substances 0.000 description 5
- 239000011248 coating agent Substances 0.000 description 5
- 238000000576 coating method Methods 0.000 description 5
- 230000002596 correlated effect Effects 0.000 description 5
- 210000004748 cultured cell Anatomy 0.000 description 5
- 108010082025 cyan fluorescent protein Proteins 0.000 description 5
- 230000004907 flux Effects 0.000 description 5
- 239000000185 hemagglutinin Substances 0.000 description 5
- 230000008506 pathogenesis Effects 0.000 description 5
- 230000002093 peripheral effect Effects 0.000 description 5
- -1 phospho Chemical class 0.000 description 5
- 229920001184 polypeptide Polymers 0.000 description 5
- 230000003389 potentiating effect Effects 0.000 description 5
- XJMOSONTPMZWPB-UHFFFAOYSA-M propidium iodide Chemical compound [I-].[I-].C12=CC(N)=CC=C2C2=CC=C(N)C=C2[N+](CCC[N+](C)(CC)CC)=C1C1=CC=CC=C1 XJMOSONTPMZWPB-UHFFFAOYSA-M 0.000 description 5
- 239000013074 reference sample Substances 0.000 description 5
- 239000004094 surface-active agent Substances 0.000 description 5
- 238000002560 therapeutic procedure Methods 0.000 description 5
- 238000007492 two-way ANOVA Methods 0.000 description 5
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 4
- 108020004414 DNA Proteins 0.000 description 4
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 4
- 239000004471 Glycine Substances 0.000 description 4
- 241000283984 Rodentia Species 0.000 description 4
- 238000000540 analysis of variance Methods 0.000 description 4
- 238000010171 animal model Methods 0.000 description 4
- 238000012512 characterization method Methods 0.000 description 4
- 229940042399 direct acting antivirals protease inhibitors Drugs 0.000 description 4
- 238000010828 elution Methods 0.000 description 4
- 210000001808 exosome Anatomy 0.000 description 4
- 238000000605 extraction Methods 0.000 description 4
- 238000005194 fractionation Methods 0.000 description 4
- 125000000524 functional group Chemical group 0.000 description 4
- 238000003364 immunohistochemistry Methods 0.000 description 4
- 238000000338 in vitro Methods 0.000 description 4
- 230000006742 locomotor activity Effects 0.000 description 4
- 235000013336 milk Nutrition 0.000 description 4
- 239000008267 milk Substances 0.000 description 4
- 210000004080 milk Anatomy 0.000 description 4
- 238000010172 mouse model Methods 0.000 description 4
- 210000004179 neuropil Anatomy 0.000 description 4
- 239000013612 plasmid Substances 0.000 description 4
- 102000004196 processed proteins & peptides Human genes 0.000 description 4
- 230000035945 sensitivity Effects 0.000 description 4
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 4
- UCSJYZPVAKXKNQ-HZYVHMACSA-N streptomycin Chemical compound CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](NC(N)=N)[C@H](O)[C@@H](NC(N)=N)[C@H](O)[C@H]1O UCSJYZPVAKXKNQ-HZYVHMACSA-N 0.000 description 4
- 238000001890 transfection Methods 0.000 description 4
- 238000002255 vaccination Methods 0.000 description 4
- JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 3
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 3
- 208000011990 Corticobasal Degeneration Diseases 0.000 description 3
- 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 3
- 102000004190 Enzymes Human genes 0.000 description 3
- 108090000790 Enzymes Proteins 0.000 description 3
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- HVLSXIKZNLPZJJ-TXZCQADKSA-N HA peptide Chemical compound C([C@@H](C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](C(C)C)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](C)C(O)=O)NC(=O)[C@H]1N(CCC1)C(=O)[C@@H](N)CC=1C=CC(O)=CC=1)C1=CC=C(O)C=C1 HVLSXIKZNLPZJJ-TXZCQADKSA-N 0.000 description 3
- 241000282412 Homo Species 0.000 description 3
- 206010061218 Inflammation Diseases 0.000 description 3
- 101710115937 Microtubule-associated protein tau Proteins 0.000 description 3
- 102100040243 Microtubule-associated protein tau Human genes 0.000 description 3
- 208000018737 Parkinson disease Diseases 0.000 description 3
- 101710171330 Peroxidase 40 Proteins 0.000 description 3
- 229940124158 Protease/peptidase inhibitor Drugs 0.000 description 3
- 108010090804 Streptavidin Proteins 0.000 description 3
- 108010021188 Superoxide Dismutase-1 Proteins 0.000 description 3
- 210000001642 activated microglia Anatomy 0.000 description 3
- 230000004913 activation Effects 0.000 description 3
- 238000000246 agarose gel electrophoresis Methods 0.000 description 3
- 230000006736 behavioral deficit Effects 0.000 description 3
- 238000012742 biochemical analysis Methods 0.000 description 3
- 239000012472 biological sample Substances 0.000 description 3
- OWMVSZAMULFTJU-UHFFFAOYSA-N bis-tris Chemical compound OCCN(CCO)C(CO)(CO)CO OWMVSZAMULFTJU-UHFFFAOYSA-N 0.000 description 3
- 210000004899 c-terminal region Anatomy 0.000 description 3
- 235000011089 carbon dioxide Nutrition 0.000 description 3
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 3
- 238000000423 cell based assay Methods 0.000 description 3
- 238000004113 cell culture Methods 0.000 description 3
- 239000006143 cell culture medium Substances 0.000 description 3
- 230000001684 chronic effect Effects 0.000 description 3
- 230000008045 co-localization Effects 0.000 description 3
- 230000019771 cognition Effects 0.000 description 3
- 238000004163 cytometry Methods 0.000 description 3
- 230000001086 cytosolic effect Effects 0.000 description 3
- 238000013461 design Methods 0.000 description 3
- 238000007865 diluting Methods 0.000 description 3
- HKSZLNNOFSGOKW-UHFFFAOYSA-N ent-staurosporine Natural products C12=C3N4C5=CC=CC=C5C3=C3CNC(=O)C3=C2C2=CC=CC=C2N1C1CC(NC)C(OC)C4(C)O1 HKSZLNNOFSGOKW-UHFFFAOYSA-N 0.000 description 3
- 239000000284 extract Substances 0.000 description 3
- 239000012091 fetal bovine serum Substances 0.000 description 3
- 239000012737 fresh medium Substances 0.000 description 3
- 230000000971 hippocampal effect Effects 0.000 description 3
- 230000001900 immune effect Effects 0.000 description 3
- 238000010166 immunofluorescence Methods 0.000 description 3
- 230000004054 inflammatory process Effects 0.000 description 3
- 230000000977 initiatory effect Effects 0.000 description 3
- 238000001990 intravenous administration Methods 0.000 description 3
- 244000144972 livestock Species 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- 230000001404 mediated effect Effects 0.000 description 3
- 239000002071 nanotube Substances 0.000 description 3
- 238000001543 one-way ANOVA Methods 0.000 description 3
- 230000001737 promoting effect Effects 0.000 description 3
- 230000004044 response Effects 0.000 description 3
- 238000012216 screening Methods 0.000 description 3
- 230000007480 spreading Effects 0.000 description 3
- 238000003892 spreading Methods 0.000 description 3
- 238000010561 standard procedure Methods 0.000 description 3
- 238000007619 statistical method Methods 0.000 description 3
- HKSZLNNOFSGOKW-FYTWVXJKSA-N staurosporine Chemical compound C12=C3N4C5=CC=CC=C5C3=C3CNC(=O)C3=C2C2=CC=CC=C2N1[C@H]1C[C@@H](NC)[C@@H](OC)[C@]4(C)O1 HKSZLNNOFSGOKW-FYTWVXJKSA-N 0.000 description 3
- CGPUWJWCVCFERF-UHFFFAOYSA-N staurosporine Natural products C12=C3N4C5=CC=CC=C5C3=C3CNC(=O)C3=C2C2=CC=CC=C2N1C1CC(NC)C(OC)C4(OC)O1 CGPUWJWCVCFERF-UHFFFAOYSA-N 0.000 description 3
- 238000007920 subcutaneous administration Methods 0.000 description 3
- GPRLSGONYQIRFK-MNYXATJNSA-N triton Chemical compound [3H+] GPRLSGONYQIRFK-MNYXATJNSA-N 0.000 description 3
- 230000005641 tunneling Effects 0.000 description 3
- 230000000007 visual effect Effects 0.000 description 3
- YBJHBAHKTGYVGT-ZKWXMUAHSA-N (+)-Biotin Chemical compound N1C(=O)N[C@@H]2[C@H](CCCCC(=O)O)SC[C@@H]21 YBJHBAHKTGYVGT-ZKWXMUAHSA-N 0.000 description 2
- FWBHETKCLVMNFS-UHFFFAOYSA-N 4',6-Diamino-2-phenylindol Chemical compound C1=CC(C(=N)N)=CC=C1C1=CC2=CC=C(C(N)=N)C=C2N1 FWBHETKCLVMNFS-UHFFFAOYSA-N 0.000 description 2
- VIBDVOOELVZGDU-UHFFFAOYSA-N 4-(1h-indol-2-yl)benzene-1,3-dicarboximidamide Chemical compound NC(=N)C1=CC(C(=N)N)=CC=C1C1=CC2=CC=CC=C2N1 VIBDVOOELVZGDU-UHFFFAOYSA-N 0.000 description 2
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 2
- 238000011740 C57BL/6 mouse Methods 0.000 description 2
- 241001569772 Celithemis elisa Species 0.000 description 2
- 101000746263 Conus leopardus Conotoxin Lp5.1 Proteins 0.000 description 2
- 238000011537 Coomassie blue staining Methods 0.000 description 2
- 206010052804 Drug tolerance Diseases 0.000 description 2
- 102100023431 E3 ubiquitin-protein ligase TRIM21 Human genes 0.000 description 2
- 108700024394 Exon Proteins 0.000 description 2
- 241000282326 Felis catus Species 0.000 description 2
- HTTJABKRGRZYRN-UHFFFAOYSA-N Heparin Chemical compound OC1C(NC(=O)C)C(O)OC(COS(O)(=O)=O)C1OC1C(OS(O)(=O)=O)C(O)C(OC2C(C(OS(O)(=O)=O)C(OC3C(C(O)C(O)C(O3)C(O)=O)OS(O)(=O)=O)C(CO)O2)NS(O)(=O)=O)C(C(O)=O)O1 HTTJABKRGRZYRN-UHFFFAOYSA-N 0.000 description 2
- 101000685877 Homo sapiens E3 ubiquitin-protein ligase TRIM21 Proteins 0.000 description 2
- 102000016252 Huntingtin Human genes 0.000 description 2
- 108050004784 Huntingtin Proteins 0.000 description 2
- 241000713666 Lentivirus Species 0.000 description 2
- 241000124008 Mammalia Species 0.000 description 2
- 239000000020 Nitrocellulose Substances 0.000 description 2
- 239000002033 PVDF binder Substances 0.000 description 2
- 208000007542 Paresis Diseases 0.000 description 2
- 208000037658 Parkinson-dementia complex of Guam Diseases 0.000 description 2
- 208000027089 Parkinsonian disease Diseases 0.000 description 2
- 206010034010 Parkinsonism Diseases 0.000 description 2
- 229930182555 Penicillin Natural products 0.000 description 2
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 2
- 102000003992 Peroxidases Human genes 0.000 description 2
- 229940122907 Phosphatase inhibitor Drugs 0.000 description 2
- 235000009074 Phytolacca americana Nutrition 0.000 description 2
- 240000007643 Phytolacca americana Species 0.000 description 2
- 229920001213 Polysorbate 20 Polymers 0.000 description 2
- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 2
- 102000007056 Recombinant Fusion Proteins Human genes 0.000 description 2
- 108010008281 Recombinant Fusion Proteins Proteins 0.000 description 2
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 2
- 229930006000 Sucrose Natural products 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
- 102100038836 Superoxide dismutase [Cu-Zn] Human genes 0.000 description 2
- 101710120037 Toxin CcdB Proteins 0.000 description 2
- 241000700605 Viruses Species 0.000 description 2
- 238000001261 affinity purification Methods 0.000 description 2
- 102000003802 alpha-Synuclein Human genes 0.000 description 2
- 108090000185 alpha-Synuclein Proteins 0.000 description 2
- 229910052786 argon Inorganic materials 0.000 description 2
- 238000000429 assembly Methods 0.000 description 2
- 230000000712 assembly Effects 0.000 description 2
- 230000035045 associative learning Effects 0.000 description 2
- 239000012298 atmosphere Substances 0.000 description 2
- 230000009286 beneficial effect Effects 0.000 description 2
- 239000012148 binding buffer Substances 0.000 description 2
- 210000004369 blood Anatomy 0.000 description 2
- 239000008280 blood Substances 0.000 description 2
- 210000005013 brain tissue Anatomy 0.000 description 2
- 239000013553 cell monolayer Substances 0.000 description 2
- 230000004700 cellular uptake Effects 0.000 description 2
- 238000005119 centrifugation Methods 0.000 description 2
- 210000000349 chromosome Anatomy 0.000 description 2
- 238000013270 controlled release Methods 0.000 description 2
- 230000001054 cortical effect Effects 0.000 description 2
- 238000012258 culturing Methods 0.000 description 2
- 238000007405 data analysis Methods 0.000 description 2
- 239000007857 degradation product Substances 0.000 description 2
- 208000017004 dementia pugilistica Diseases 0.000 description 2
- 210000001947 dentate gyrus Anatomy 0.000 description 2
- 238000003745 diagnosis Methods 0.000 description 2
- 208000035475 disorder Diseases 0.000 description 2
- 239000006185 dispersion Substances 0.000 description 2
- 231100000673 dose–response relationship Toxicity 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 230000004064 dysfunction Effects 0.000 description 2
- 230000008482 dysregulation Effects 0.000 description 2
- 238000001962 electrophoresis Methods 0.000 description 2
- 239000012149 elution buffer Substances 0.000 description 2
- 210000001163 endosome Anatomy 0.000 description 2
- 230000005284 excitation Effects 0.000 description 2
- 238000013401 experimental design Methods 0.000 description 2
- 239000007850 fluorescent dye Substances 0.000 description 2
- 108020001507 fusion proteins Proteins 0.000 description 2
- 102000037865 fusion proteins Human genes 0.000 description 2
- 238000001502 gel electrophoresis Methods 0.000 description 2
- 210000004602 germ cell Anatomy 0.000 description 2
- 235000011187 glycerol Nutrition 0.000 description 2
- 230000026781 habituation Effects 0.000 description 2
- 230000036541 health Effects 0.000 description 2
- 229960002897 heparin Drugs 0.000 description 2
- 229920000669 heparin Polymers 0.000 description 2
- 239000005556 hormone Substances 0.000 description 2
- 229940088597 hormone Drugs 0.000 description 2
- 210000000987 immune system Anatomy 0.000 description 2
- 229940072221 immunoglobulins Drugs 0.000 description 2
- 239000012133 immunoprecipitate Substances 0.000 description 2
- 238000012744 immunostaining Methods 0.000 description 2
- 230000006872 improvement Effects 0.000 description 2
- 230000001939 inductive effect Effects 0.000 description 2
- 239000002198 insoluble material Substances 0.000 description 2
- 239000000543 intermediate Substances 0.000 description 2
- 230000010039 intracellular degradation Effects 0.000 description 2
- 238000007912 intraperitoneal administration Methods 0.000 description 2
- 238000007914 intraventricular administration Methods 0.000 description 2
- 230000013016 learning Effects 0.000 description 2
- 239000003446 ligand Substances 0.000 description 2
- 239000003550 marker Substances 0.000 description 2
- 230000006996 mental state Effects 0.000 description 2
- 210000000274 microglia Anatomy 0.000 description 2
- 230000002025 microglial effect Effects 0.000 description 2
- 238000001000 micrograph Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 210000004897 n-terminal region Anatomy 0.000 description 2
- 229920001220 nitrocellulos Polymers 0.000 description 2
- 229920002113 octoxynol Polymers 0.000 description 2
- 238000005457 optimization Methods 0.000 description 2
- 230000036961 partial effect Effects 0.000 description 2
- 229940049954 penicillin Drugs 0.000 description 2
- WEXRUCMBJFQVBZ-UHFFFAOYSA-N pentobarbital Chemical compound CCCC(C)C1(CC)C(=O)NC(=O)NC1=O WEXRUCMBJFQVBZ-UHFFFAOYSA-N 0.000 description 2
- 108040007629 peroxidase activity proteins Proteins 0.000 description 2
- 238000002823 phage display Methods 0.000 description 2
- 230000000144 pharmacologic effect Effects 0.000 description 2
- 229920002401 polyacrylamide Polymers 0.000 description 2
- 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 2
- 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 2
- 229920002981 polyvinylidene fluoride Polymers 0.000 description 2
- 239000013641 positive control Substances 0.000 description 2
- 238000010149 post-hoc-test Methods 0.000 description 2
- 230000036515 potency Effects 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 230000002265 prevention Effects 0.000 description 2
- 230000000750 progressive effect Effects 0.000 description 2
- 201000002212 progressive supranuclear palsy Diseases 0.000 description 2
- 238000011002 quantification Methods 0.000 description 2
- 238000004445 quantitative analysis Methods 0.000 description 2
- 238000010791 quenching Methods 0.000 description 2
- 230000000171 quenching effect Effects 0.000 description 2
- 230000009257 reactivity Effects 0.000 description 2
- 102000005962 receptors Human genes 0.000 description 2
- 108020003175 receptors Proteins 0.000 description 2
- 238000003118 sandwich ELISA Methods 0.000 description 2
- 230000036362 sensorimotor function Effects 0.000 description 2
- 230000035939 shock Effects 0.000 description 2
- 239000001632 sodium acetate Substances 0.000 description 2
- 235000017281 sodium acetate Nutrition 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 238000012421 spiking Methods 0.000 description 2
- 230000002269 spontaneous effect Effects 0.000 description 2
- 229960005322 streptomycin Drugs 0.000 description 2
- 239000005720 sucrose Substances 0.000 description 2
- 239000000829 suppository Substances 0.000 description 2
- 238000001356 surgical procedure Methods 0.000 description 2
- 230000036962 time dependent Effects 0.000 description 2
- 238000012549 training Methods 0.000 description 2
- 238000003146 transient transfection Methods 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 description 1
- NFGXHKASABOEEW-UHFFFAOYSA-N 1-methylethyl 11-methoxy-3,7,11-trimethyl-2,4-dodecadienoate Chemical compound COC(C)(C)CCCC(C)CC=CC(C)=CC(=O)OC(C)C NFGXHKASABOEEW-UHFFFAOYSA-N 0.000 description 1
- LDGWQMRUWMSZIU-LQDDAWAPSA-M 2,3-bis[(z)-octadec-9-enoxy]propyl-trimethylazanium;chloride Chemical compound [Cl-].CCCCCCCC\C=C/CCCCCCCCOCC(C[N+](C)(C)C)OCCCCCCCC\C=C/CCCCCCCC LDGWQMRUWMSZIU-LQDDAWAPSA-M 0.000 description 1
- QFVHZQCOUORWEI-UHFFFAOYSA-N 4-[(4-anilino-5-sulfonaphthalen-1-yl)diazenyl]-5-hydroxynaphthalene-2,7-disulfonic acid Chemical compound C=12C(O)=CC(S(O)(=O)=O)=CC2=CC(S(O)(=O)=O)=CC=1N=NC(C1=CC=CC(=C11)S(O)(=O)=O)=CC=C1NC1=CC=CC=C1 QFVHZQCOUORWEI-UHFFFAOYSA-N 0.000 description 1
- FHVDTGUDJYJELY-UHFFFAOYSA-N 6-{[2-carboxy-4,5-dihydroxy-6-(phosphanyloxy)oxan-3-yl]oxy}-4,5-dihydroxy-3-phosphanyloxane-2-carboxylic acid Chemical compound O1C(C(O)=O)C(P)C(O)C(O)C1OC1C(C(O)=O)OC(OP)C(O)C1O FHVDTGUDJYJELY-UHFFFAOYSA-N 0.000 description 1
- 206010054196 Affect lability Diseases 0.000 description 1
- 102000002260 Alkaline Phosphatase Human genes 0.000 description 1
- 108020004774 Alkaline Phosphatase Proteins 0.000 description 1
- 102100034452 Alternative prion protein Human genes 0.000 description 1
- 208000000044 Amnesia Diseases 0.000 description 1
- 206010002091 Anaesthesia Diseases 0.000 description 1
- 102100032187 Androgen receptor Human genes 0.000 description 1
- 235000002198 Annona diversifolia Nutrition 0.000 description 1
- 108010032595 Antibody Binding Sites Proteins 0.000 description 1
- 208000019901 Anxiety disease Diseases 0.000 description 1
- 206010002942 Apathy Diseases 0.000 description 1
- 206010003591 Ataxia Diseases 0.000 description 1
- 241000271566 Aves Species 0.000 description 1
- 108090001008 Avidin Proteins 0.000 description 1
- 206010058504 Ballismus Diseases 0.000 description 1
- 206010069632 Bladder dysfunction Diseases 0.000 description 1
- 238000010152 Bonferroni least significant difference Methods 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- 208000014644 Brain disease Diseases 0.000 description 1
- 238000011746 C57BL/6J (JAX™ mouse strain) Methods 0.000 description 1
- 241000282421 Canidae Species 0.000 description 1
- 241000282465 Canis Species 0.000 description 1
- 241000282472 Canis lupus familiaris Species 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
- 241000700198 Cavia Species 0.000 description 1
- 241000700199 Cavia porcellus Species 0.000 description 1
- 208000004051 Chronic Traumatic Encephalopathy Diseases 0.000 description 1
- 108091026890 Coding region Proteins 0.000 description 1
- 102000008186 Collagen Human genes 0.000 description 1
- 108010035532 Collagen Proteins 0.000 description 1
- 108010047041 Complementarity Determining Regions Proteins 0.000 description 1
- 208000033001 Complex partial seizures Diseases 0.000 description 1
- 102000004127 Cytokines Human genes 0.000 description 1
- 108090000695 Cytokines Proteins 0.000 description 1
- KDXKERNSBIXSRK-RXMQYKEDSA-N D-lysine Chemical compound NCCCC[C@@H](N)C(O)=O KDXKERNSBIXSRK-RXMQYKEDSA-N 0.000 description 1
- 102000053602 DNA Human genes 0.000 description 1
- 206010012335 Dependence Diseases 0.000 description 1
- 229920002307 Dextran Polymers 0.000 description 1
- 206010061818 Disease progression Diseases 0.000 description 1
- 208000012661 Dyskinesia Diseases 0.000 description 1
- 208000032274 Encephalopathy Diseases 0.000 description 1
- 241000283086 Equidae Species 0.000 description 1
- 241000283074 Equus asinus Species 0.000 description 1
- 102000009109 Fc receptors Human genes 0.000 description 1
- 108010087819 Fc receptors Proteins 0.000 description 1
- 241000282324 Felis Species 0.000 description 1
- 102000012673 Follicle Stimulating Hormone Human genes 0.000 description 1
- 108010079345 Follicle Stimulating Hormone Proteins 0.000 description 1
- 208000002339 Frontotemporal Lobar Degeneration Diseases 0.000 description 1
- 208000014540 Functional gastrointestinal disease Diseases 0.000 description 1
- 201000004066 Ganglioglioma Diseases 0.000 description 1
- 239000000579 Gonadotropin-Releasing Hormone Substances 0.000 description 1
- 108010051696 Growth Hormone Proteins 0.000 description 1
- 239000007995 HEPES buffer Substances 0.000 description 1
- 101000690301 Homo sapiens Aldo-keto reductase family 1 member C4 Proteins 0.000 description 1
- 101001116548 Homo sapiens Protein CBFA2T1 Proteins 0.000 description 1
- 101000659324 Homo sapiens Twinfilin-1 Proteins 0.000 description 1
- 101000579613 Homo sapiens U6 snRNA-associated Sm-like protein LSm5 Proteins 0.000 description 1
- 206010062767 Hypophysitis Diseases 0.000 description 1
- 102000009490 IgG Receptors Human genes 0.000 description 1
- 108010073807 IgG Receptors Proteins 0.000 description 1
- 102000009786 Immunoglobulin Constant Regions Human genes 0.000 description 1
- 108010009817 Immunoglobulin Constant Regions Proteins 0.000 description 1
- 108010029660 Intrinsically Disordered Proteins Proteins 0.000 description 1
- 206010022998 Irritability Diseases 0.000 description 1
- PIWKPBJCKXDKJR-UHFFFAOYSA-N Isoflurane Chemical compound FC(F)OC(Cl)C(F)(F)F PIWKPBJCKXDKJR-UHFFFAOYSA-N 0.000 description 1
- ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-N 0.000 description 1
- 241000282838 Lama Species 0.000 description 1
- 239000012097 Lipofectamine 2000 Substances 0.000 description 1
- 108060001084 Luciferase Proteins 0.000 description 1
- 239000005089 Luciferase Substances 0.000 description 1
- 206010026749 Mania Diseases 0.000 description 1
- 102000009664 Microtubule-Associated Proteins Human genes 0.000 description 1
- 108010020004 Microtubule-Associated Proteins Proteins 0.000 description 1
- 206010027925 Monoparesis Diseases 0.000 description 1
- 206010061296 Motor dysfunction Diseases 0.000 description 1
- 229910020700 Na3VO4 Inorganic materials 0.000 description 1
- 208000008457 Neurologic Manifestations Diseases 0.000 description 1
- 241000208125 Nicotiana Species 0.000 description 1
- 235000002637 Nicotiana tabacum Nutrition 0.000 description 1
- 101710163270 Nuclease Proteins 0.000 description 1
- 206010033799 Paralysis Diseases 0.000 description 1
- 241001494479 Pecora Species 0.000 description 1
- 108091005804 Peptidases Proteins 0.000 description 1
- 108010001441 Phosphopeptides Proteins 0.000 description 1
- 102000004160 Phosphoric Monoester Hydrolases Human genes 0.000 description 1
- 108090000608 Phosphoric Monoester Hydrolases Proteins 0.000 description 1
- 208000000609 Pick Disease of the Brain Diseases 0.000 description 1
- 229920005372 Plexiglas® Polymers 0.000 description 1
- 102000003946 Prolactin Human genes 0.000 description 1
- 108010057464 Prolactin Proteins 0.000 description 1
- 239000004365 Protease Substances 0.000 description 1
- 102000004245 Proteasome Endopeptidase Complex Human genes 0.000 description 1
- 108090000708 Proteasome Endopeptidase Complex Proteins 0.000 description 1
- 206010058895 Psychogenic seizure Diseases 0.000 description 1
- 208000028017 Psychotic disease Diseases 0.000 description 1
- 239000012083 RIPA buffer Substances 0.000 description 1
- 241000501085 Rakaia media Species 0.000 description 1
- 108020004511 Recombinant DNA Proteins 0.000 description 1
- 102100037486 Reverse transcriptase/ribonuclease H Human genes 0.000 description 1
- 206010040030 Sensory loss Diseases 0.000 description 1
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 1
- 108010034546 Serratia marcescens nuclease Proteins 0.000 description 1
- 201000001880 Sexual dysfunction Diseases 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 102100038803 Somatotropin Human genes 0.000 description 1
- 101000857870 Squalus acanthias Gonadoliberin Proteins 0.000 description 1
- 208000037065 Subacute sclerosing leukoencephalitis Diseases 0.000 description 1
- 206010042297 Subacute sclerosing panencephalitis Diseases 0.000 description 1
- 241000282887 Suidae Species 0.000 description 1
- 102000008221 Superoxide Dismutase-1 Human genes 0.000 description 1
- 101150057615 Syn gene Proteins 0.000 description 1
- 102000019355 Synuclein Human genes 0.000 description 1
- 108050006783 Synuclein Proteins 0.000 description 1
- 208000032859 Synucleinopathies Diseases 0.000 description 1
- AYFVYJQAPQTCCC-UHFFFAOYSA-N THREONINE Chemical compound CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 description 1
- 102000011923 Thyrotropin Human genes 0.000 description 1
- 108010061174 Thyrotropin Proteins 0.000 description 1
- 206010044565 Tremor Diseases 0.000 description 1
- 208000026911 Tuberous sclerosis complex Diseases 0.000 description 1
- 102100028261 U6 snRNA-associated Sm-like protein LSm5 Human genes 0.000 description 1
- 241000282458 Ursus sp. Species 0.000 description 1
- 241001416177 Vicugna pacos Species 0.000 description 1
- 238000002835 absorbance Methods 0.000 description 1
- 108010050735 acetyl-lysyl-prolyl-seryl-seryl-prolyl-prolyl-glutamyl-glutamic acid amide Proteins 0.000 description 1
- 230000006978 adaptation Effects 0.000 description 1
- 239000000443 aerosol Substances 0.000 description 1
- 239000011543 agarose gel Substances 0.000 description 1
- 230000016571 aggressive behavior Effects 0.000 description 1
- 230000032683 aging Effects 0.000 description 1
- 229940072056 alginate Drugs 0.000 description 1
- 235000010443 alginic acid Nutrition 0.000 description 1
- 229920000615 alginic acid 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
- 230000004075 alteration Effects 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- 230000003941 amyloidogenesis Effects 0.000 description 1
- 208000013968 amyotrophic lateral sclerosis-parkinsonism-dementia complex Diseases 0.000 description 1
- 208000014450 amyotrophic lateral sclerosis-parkinsonism/dementia complex 1 Diseases 0.000 description 1
- 230000037005 anaesthesia Effects 0.000 description 1
- 239000012491 analyte Substances 0.000 description 1
- 108010080146 androgen receptors Proteins 0.000 description 1
- 230000002205 anti-dementic effect Effects 0.000 description 1
- 238000009175 antibody therapy Methods 0.000 description 1
- 238000011230 antibody-based therapy Methods 0.000 description 1
- 210000000628 antibody-producing cell Anatomy 0.000 description 1
- 230000036506 anxiety Effects 0.000 description 1
- 239000012062 aqueous buffer Substances 0.000 description 1
- 238000013528 artificial neural network Methods 0.000 description 1
- 210000003403 autonomic nervous system Anatomy 0.000 description 1
- 230000003376 axonal effect Effects 0.000 description 1
- 238000009227 behaviour therapy Methods 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 239000003124 biologic agent Substances 0.000 description 1
- 229960002685 biotin Drugs 0.000 description 1
- 235000020958 biotin Nutrition 0.000 description 1
- 239000011616 biotin Substances 0.000 description 1
- 230000006287 biotinylation Effects 0.000 description 1
- 238000007413 biotinylation Methods 0.000 description 1
- 230000036772 blood pressure Effects 0.000 description 1
- 239000001045 blue dye Substances 0.000 description 1
- 201000007637 bowel dysfunction Diseases 0.000 description 1
- UDSAIICHUKSCKT-UHFFFAOYSA-N bromophenol blue Chemical compound C1=C(Br)C(O)=C(Br)C=C1C1(C=2C=C(Br)C(O)=C(Br)C=2)C2=CC=CC=C2S(=O)(=O)O1 UDSAIICHUKSCKT-UHFFFAOYSA-N 0.000 description 1
- 239000007853 buffer solution Substances 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 125000002091 cationic group Chemical group 0.000 description 1
- 230000000453 cell autonomous effect Effects 0.000 description 1
- 230000005779 cell damage Effects 0.000 description 1
- 238000010822 cell death assay Methods 0.000 description 1
- 208000037887 cell injury Diseases 0.000 description 1
- 210000000170 cell membrane Anatomy 0.000 description 1
- 230000030570 cellular localization Effects 0.000 description 1
- 239000004568 cement Substances 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- WLNARFZDISHUGS-MIXBDBMTSA-N cholesteryl hemisuccinate Chemical compound C1C=C2C[C@@H](OC(=O)CCC(O)=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 WLNARFZDISHUGS-MIXBDBMTSA-N 0.000 description 1
- 230000004186 co-expression Effects 0.000 description 1
- 238000012761 co-transfection Methods 0.000 description 1
- 230000007278 cognition impairment Effects 0.000 description 1
- 230000003930 cognitive ability Effects 0.000 description 1
- 230000006999 cognitive decline Effects 0.000 description 1
- 208000010877 cognitive disease Diseases 0.000 description 1
- 230000001149 cognitive effect Effects 0.000 description 1
- 229920001436 collagen Polymers 0.000 description 1
- 230000000295 complement effect Effects 0.000 description 1
- 238000012790 confirmation Methods 0.000 description 1
- 238000012937 correction Methods 0.000 description 1
- 210000005257 cortical tissue Anatomy 0.000 description 1
- 239000002577 cryoprotective agent Substances 0.000 description 1
- 230000002354 daily effect Effects 0.000 description 1
- 238000005034 decoration Methods 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 230000003111 delayed effect Effects 0.000 description 1
- 239000003479 dental cement Substances 0.000 description 1
- KXGVEGMKQFWNSR-LLQZFEROSA-N deoxycholic acid Chemical compound C([C@H]1CC2)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(O)=O)C)[C@@]2(C)[C@@H](O)C1 KXGVEGMKQFWNSR-LLQZFEROSA-N 0.000 description 1
- 229960003964 deoxycholic acid Drugs 0.000 description 1
- KXGVEGMKQFWNSR-UHFFFAOYSA-N deoxycholic acid Natural products C1CC2CC(O)CCC2(C)C2C1C1CCC(C(CCC(O)=O)C)C1(C)C(O)C2 KXGVEGMKQFWNSR-UHFFFAOYSA-N 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 230000008021 deposition Effects 0.000 description 1
- 230000029087 digestion Effects 0.000 description 1
- 239000000539 dimer Substances 0.000 description 1
- 230000005750 disease progression Effects 0.000 description 1
- 239000002270 dispersing agent Substances 0.000 description 1
- 238000002224 dissection Methods 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- VHJLVAABSRFDPM-QWWZWVQMSA-N dithiothreitol Chemical compound SC[C@@H](O)[C@H](O)CS VHJLVAABSRFDPM-QWWZWVQMSA-N 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000000975 dye Substances 0.000 description 1
- 239000012636 effector Substances 0.000 description 1
- 239000003623 enhancer Substances 0.000 description 1
- 238000006911 enzymatic reaction Methods 0.000 description 1
- 230000001037 epileptic effect Effects 0.000 description 1
- 230000003203 everyday effect Effects 0.000 description 1
- 230000021824 exploration behavior Effects 0.000 description 1
- 210000003722 extracellular fluid Anatomy 0.000 description 1
- 239000000835 fiber Substances 0.000 description 1
- 108091006047 fluorescent proteins Proteins 0.000 description 1
- 102000034287 fluorescent proteins Human genes 0.000 description 1
- 229940028334 follicle stimulating hormone Drugs 0.000 description 1
- 238000013467 fragmentation Methods 0.000 description 1
- 238000006062 fragmentation reaction Methods 0.000 description 1
- 238000004108 freeze drying Methods 0.000 description 1
- 210000005153 frontal cortex Anatomy 0.000 description 1
- 230000008717 functional decline Effects 0.000 description 1
- 230000004927 fusion Effects 0.000 description 1
- 201000005649 gangliocytoma Diseases 0.000 description 1
- 201000008361 ganglioneuroma Diseases 0.000 description 1
- 230000002068 genetic effect Effects 0.000 description 1
- 238000010353 genetic engineering Methods 0.000 description 1
- 230000013595 glycosylation Effects 0.000 description 1
- 238000006206 glycosylation reaction Methods 0.000 description 1
- XLXSAKCOAKORKW-AQJXLSMYSA-N gonadorelin Chemical compound C([C@@H](C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N1[C@@H](CCC1)C(=O)NCC(N)=O)NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@H]1NC(=O)CC1)C1=CC=C(O)C=C1 XLXSAKCOAKORKW-AQJXLSMYSA-N 0.000 description 1
- 229940035638 gonadotropin-releasing hormone Drugs 0.000 description 1
- 230000036433 growing body Effects 0.000 description 1
- 239000000122 growth hormone Substances 0.000 description 1
- 239000001963 growth medium Substances 0.000 description 1
- 230000001339 gustatory effect Effects 0.000 description 1
- 238000003306 harvesting Methods 0.000 description 1
- 229910001385 heavy metal Inorganic materials 0.000 description 1
- 206010019465 hemiparesis Diseases 0.000 description 1
- 239000012145 high-salt buffer Substances 0.000 description 1
- 210000001879 hippocampal ca1 region Anatomy 0.000 description 1
- 230000003054 hormonal effect Effects 0.000 description 1
- 102000054751 human RUNX1T1 Human genes 0.000 description 1
- 102000050945 human TWF1 Human genes 0.000 description 1
- 210000005260 human cell Anatomy 0.000 description 1
- 208000003906 hydrocephalus Diseases 0.000 description 1
- 210000003016 hypothalamus Anatomy 0.000 description 1
- 230000003100 immobilizing effect Effects 0.000 description 1
- 230000005847 immunogenicity Effects 0.000 description 1
- 238000013388 immunohistochemistry analysis Methods 0.000 description 1
- 238000009169 immunotherapy Methods 0.000 description 1
- 238000002513 implantation Methods 0.000 description 1
- 238000000099 in vitro assay Methods 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 230000002458 infectious effect Effects 0.000 description 1
- 208000030309 inherited neurodegenerative disease Diseases 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 210000005007 innate immune system Anatomy 0.000 description 1
- 230000009878 intermolecular interaction Effects 0.000 description 1
- 230000008316 intracellular mechanism Effects 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 239000007928 intraperitoneal injection Substances 0.000 description 1
- 229960002725 isoflurane Drugs 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 239000002502 liposome Substances 0.000 description 1
- 239000012160 loading buffer Substances 0.000 description 1
- 238000011068 loading method Methods 0.000 description 1
- 230000004807 localization Effects 0.000 description 1
- 231100000863 loss of memory Toxicity 0.000 description 1
- 230000006674 lysosomal degradation Effects 0.000 description 1
- 238000012423 maintenance Methods 0.000 description 1
- 210000004962 mammalian cell Anatomy 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- 230000010534 mechanism of action Effects 0.000 description 1
- 230000003340 mental effect Effects 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- 239000010445 mica Substances 0.000 description 1
- 229910052618 mica group Inorganic materials 0.000 description 1
- 238000001690 micro-dialysis Methods 0.000 description 1
- 230000007388 microgliosis Effects 0.000 description 1
- 230000003278 mimic effect Effects 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- 230000007659 motor function Effects 0.000 description 1
- 230000001537 neural effect Effects 0.000 description 1
- 210000002241 neurite Anatomy 0.000 description 1
- 210000004498 neuroglial cell Anatomy 0.000 description 1
- 230000007971 neurological deficit Effects 0.000 description 1
- 230000006764 neuronal dysfunction Effects 0.000 description 1
- 230000002981 neuropathic effect Effects 0.000 description 1
- 230000007171 neuropathology Effects 0.000 description 1
- 210000002511 neuropil thread Anatomy 0.000 description 1
- 238000006386 neutralization reaction Methods 0.000 description 1
- 230000003472 neutralizing effect Effects 0.000 description 1
- 108020004707 nucleic acids Proteins 0.000 description 1
- 102000039446 nucleic acids Human genes 0.000 description 1
- 230000008520 organization Effects 0.000 description 1
- 125000004043 oxo group Chemical group O=* 0.000 description 1
- 208000021090 palsy Diseases 0.000 description 1
- 208000002593 pantothenate kinase-associated neurodegeneration Diseases 0.000 description 1
- 238000010827 pathological analysis Methods 0.000 description 1
- 229960001412 pentobarbital Drugs 0.000 description 1
- 230000010412 perfusion Effects 0.000 description 1
- 230000008823 permeabilization Effects 0.000 description 1
- 239000008194 pharmaceutical composition Substances 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 239000002831 pharmacologic agent Substances 0.000 description 1
- 239000008363 phosphate buffer Substances 0.000 description 1
- 238000000206 photolithography Methods 0.000 description 1
- 210000003635 pituitary gland Anatomy 0.000 description 1
- 229920002704 polyhistidine Polymers 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 239000004926 polymethyl methacrylate Substances 0.000 description 1
- 229920000136 polysorbate Polymers 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000000328 pro-aggregatory effect Effects 0.000 description 1
- 229940097325 prolactin Drugs 0.000 description 1
- 125000001500 prolyl group Chemical group [H]N1C([H])(C(=O)[*])C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
- 230000000644 propagated effect Effects 0.000 description 1
- 230000001902 propagating effect Effects 0.000 description 1
- 238000012342 propidium iodide staining Methods 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 230000012743 protein tagging Effects 0.000 description 1
- 230000004850 protein–protein interaction Effects 0.000 description 1
- 230000005180 public health Effects 0.000 description 1
- 230000002685 pulmonary effect Effects 0.000 description 1
- 238000003127 radioimmunoassay Methods 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 239000011347 resin Substances 0.000 description 1
- 229920005989 resin Polymers 0.000 description 1
- 230000029058 respiratory gaseous exchange Effects 0.000 description 1
- 230000000717 retained effect Effects 0.000 description 1
- 238000010825 rotarod performance test Methods 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 230000035807 sensation Effects 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 230000009919 sequestration Effects 0.000 description 1
- 231100000872 sexual dysfunction Toxicity 0.000 description 1
- 230000011664 signaling Effects 0.000 description 1
- 208000019116 sleep disease Diseases 0.000 description 1
- 239000002002 slurry Substances 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- JJGWLCLUQNFDIS-GTSONSFRSA-M sodium;1-[6-[5-[(3as,4s,6ar)-2-oxo-1,3,3a,4,6,6a-hexahydrothieno[3,4-d]imidazol-4-yl]pentanoylamino]hexanoyloxy]-2,5-dioxopyrrolidine-3-sulfonate Chemical compound [Na+].O=C1C(S(=O)(=O)[O-])CC(=O)N1OC(=O)CCCCCNC(=O)CCCC[C@H]1[C@H]2NC(=O)N[C@H]2CS1 JJGWLCLUQNFDIS-GTSONSFRSA-M 0.000 description 1
- 239000007790 solid phase Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 229910001220 stainless steel Inorganic materials 0.000 description 1
- 239000010935 stainless steel Substances 0.000 description 1
- 150000003431 steroids Chemical class 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 239000007929 subcutaneous injection Substances 0.000 description 1
- 238000010254 subcutaneous injection Methods 0.000 description 1
- 230000007470 synaptic degeneration Effects 0.000 description 1
- 230000002195 synergetic effect Effects 0.000 description 1
- 238000012385 systemic delivery Methods 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 125000003396 thiol group Chemical group [H]S* 0.000 description 1
- 238000004448 titration Methods 0.000 description 1
- 239000003053 toxin Substances 0.000 description 1
- 231100000765 toxin Toxicity 0.000 description 1
- 238000012034 trail making test Methods 0.000 description 1
- 230000009261 transgenic effect Effects 0.000 description 1
- 238000012301 transgenic model Methods 0.000 description 1
- 238000012384 transportation and delivery Methods 0.000 description 1
- 230000003363 transsynaptic effect Effects 0.000 description 1
- 238000011269 treatment regimen Methods 0.000 description 1
- IHIXIJGXTJIKRB-UHFFFAOYSA-N trisodium vanadate Chemical compound [Na+].[Na+].[Na+].[O-][V]([O-])([O-])=O IHIXIJGXTJIKRB-UHFFFAOYSA-N 0.000 description 1
- 208000009999 tuberous sclerosis Diseases 0.000 description 1
- 210000002700 urine Anatomy 0.000 description 1
- 238000012800 visualization Methods 0.000 description 1
- 230000001755 vocal effect Effects 0.000 description 1
- 239000011534 wash buffer Substances 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/395—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
- A61K39/39533—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals
- A61K39/3955—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals against proteinaceous materials, e.g. enzymes, hormones, lymphokines
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
-
- 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
- A61P25/18—Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- 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
- G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
-
- 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
- G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
- G01N33/566—Immunoassay; Biospecific binding assay; Materials therefor using specific carrier or receptor proteins as ligand binding reagents where possible specific carrier or receptor proteins are classified with their target compounds
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/68—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids
- G01N33/6893—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids related to diseases not provided for elsewhere
- G01N33/6896—Neurological disorders, e.g. Alzheimer's disease
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/505—Medicinal preparations containing antigens or antibodies comprising antibodies
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/30—Immunoglobulins specific features characterized by aspects of specificity or valency
- C07K2317/34—Identification of a linear epitope shorter than 20 amino acid residues or of a conformational epitope defined by amino acid residues
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
- C07K2317/56—Immunoglobulins specific features characterized by immunoglobulin fragments variable (Fv) region, i.e. VH and/or VL
- C07K2317/565—Complementarity determining region [CDR]
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
- C07K2317/76—Antagonist effect on antigen, e.g. neutralization or inhibition of binding
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/90—Immunoglobulins specific features characterized by (pharmaco)kinetic aspects or by stability of the immunoglobulin
- C07K2317/92—Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2800/00—Detection or diagnosis of diseases
- G01N2800/28—Neurological disorders
- G01N2800/2814—Dementia; Cognitive disorders
- G01N2800/2821—Alzheimer
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Medicinal Chemistry (AREA)
- Biomedical Technology (AREA)
- General Health & Medical Sciences (AREA)
- Immunology (AREA)
- Organic Chemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Molecular Biology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Hematology (AREA)
- Urology & Nephrology (AREA)
- Biochemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Microbiology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Food Science & Technology (AREA)
- Analytical Chemistry (AREA)
- Biotechnology (AREA)
- Cell Biology (AREA)
- Pathology (AREA)
- General Physics & Mathematics (AREA)
- Physics & Mathematics (AREA)
- Biophysics (AREA)
- Genetics & Genomics (AREA)
- Psychiatry (AREA)
- Hospice & Palliative Care (AREA)
- Endocrinology (AREA)
- Mycology (AREA)
- Epidemiology (AREA)
- Psychology (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201261667515P | 2012-07-03 | 2012-07-03 | |
| US61/667,515 | 2012-07-03 | ||
| US201261694989P | 2012-08-30 | 2012-08-30 | |
| US61/694,989 | 2012-08-30 | ||
| PCT/US2013/049333 WO2014008404A1 (en) | 2012-07-03 | 2013-07-03 | Antibodies to tau |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2877397A1 true CA2877397A1 (en) | 2014-01-09 |
Family
ID=49882495
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2877397A Abandoned CA2877397A1 (en) | 2012-07-03 | 2013-07-03 | Antibodies to tau |
Country Status (17)
Families Citing this family (51)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR102494798B1 (ko) | 2012-07-03 | 2023-02-06 | 워싱턴 유니버시티 | Tau에 대한 항체 |
| WO2014028777A2 (en) * | 2012-08-16 | 2014-02-20 | Ipierian, Inc. | Methods of treating a tauopathy |
| US8980270B2 (en) | 2013-01-18 | 2015-03-17 | Ipierian, Inc. | Methods of treating a tauopathy |
| AU2014248515B2 (en) | 2013-03-13 | 2019-03-07 | Prothena Biosciences Limited | Tau immunotherapy |
| CN105939722A (zh) | 2014-02-14 | 2016-09-14 | 伊皮埃里安股份有限公司 | Tau肽，抗Tau抗体，及其使用方法 |
| WO2015165961A1 (en) | 2014-04-29 | 2015-11-05 | Affiris Ag | Treatment and prevention of alzheimer's disease (ad) |
| ZA201608812B (en) | 2014-06-26 | 2019-08-28 | Janssen Vaccines & Prevention Bv | Antibodies and antigen-binding fragments that specifically bind to microtubule-associated protein tau |
| JP2017521063A (ja) * | 2014-06-26 | 2017-08-03 | ヤンセン ファッシンズ アンド プリベンション ベーフェーＪａｎｓｓｅｎ Ｖａｃｃｉｎｅｓ ＆ Ｐｒｅｖｅｎｔｉｏｎ Ｂ．Ｖ． | 微小管結合タンパク質タウに特異的に結合する抗体及び抗原結合断片 |
| TWI664190B (zh) * | 2014-06-27 | 2019-07-01 | 美商Ｃ２Ｎ醫療診斷有限責任公司 | 人類化抗－ｔａｕ抗體 |
| BR112017006419A2 (pt) | 2014-09-30 | 2017-12-19 | Univ Washington | medições cinéticas de tau |
| MA41451A (fr) * | 2015-02-04 | 2017-12-12 | Univ Washington | Constructions anti-tau |
| AR103713A1 (es) | 2015-02-26 | 2017-05-31 | Lilly Co Eli | Anticuerpos contra tau y sus usos |
| TWI827405B (zh) | 2015-06-05 | 2023-12-21 | 美商建南德克公司 | 抗-ｔａｕ抗體及使用方法 |
| CA2991451A1 (en) * | 2015-07-06 | 2017-01-12 | Ucb Biopharma Sprl | Tau-binding antibodies |
| CN107849105B (zh) | 2015-07-06 | 2021-09-17 | Ucb生物制药有限责任公司 | Tau结合抗体 |
| JO3711B1 (ar) | 2015-07-13 | 2021-01-31 | H Lundbeck As | أجسام مضادة محددة لبروتين تاو وطرق استعمالها |
| GB201512203D0 (en) | 2015-07-13 | 2015-08-19 | Lundbeck & Co As H | Agents,uses and methods |
| PT3334761T (pt) * | 2015-08-13 | 2023-08-17 | Univ New York | Moléculas baseadas em anticorpo seletivo para o epítopo {p}ser404 da tau e os seus usos no diagnóstico e tratamento de tauopatias |
| CN105158483A (zh) * | 2015-09-16 | 2015-12-16 | 北京九强生物技术股份有限公司 | 一种人肌钙蛋白i的超敏定量测定试剂盒及其检测方法 |
| JP7481726B2 (ja) | 2016-05-02 | 2024-05-13 | プロセナ バイオサイエンシーズ リミテッド | タウ認識抗体 |
| ES2933491T3 (es) | 2016-05-02 | 2023-02-09 | Prothena Biosciences Ltd | Inmunoterapia tau |
| CA3022765A1 (en) | 2016-05-02 | 2017-11-09 | Prothena Biosciences Limited | Antibodies recognizing tau |
| JOP20180117B1 (ar) | 2016-07-12 | 2022-03-14 | H Lundbeck As | أجسام مضادة انتقائية لـ tau فائق المعالجة بفوسفوريلات وطرق لاستخدامها |
| JP6949102B2 (ja) | 2016-08-09 | 2021-10-13 | イーライ リリー アンド カンパニー | 併用療法 |
| BR112018014281A2 (pt) | 2016-11-15 | 2018-12-18 | H Lundbeck As | agentes, usos e métodos para o tratamento da sinucleinopatia |
| CA3045294A1 (en) | 2016-12-07 | 2018-06-14 | Genentech, Inc. | Anti-tau antibodies and methods of use |
| JP7193457B2 (ja) | 2016-12-07 | 2022-12-20 | ジェネンテック， インコーポレイテッド | 抗ｔａｕ抗体及び使用方法 |
| CN106749658B (zh) * | 2016-12-15 | 2019-11-12 | 北京师范大学 | 抑制Tau蛋白聚集的抗体型分子伴侣 |
| WO2018109058A1 (en) | 2016-12-16 | 2018-06-21 | H. Lundbeck A/S | Agents, uses and methods |
| US10364286B2 (en) * | 2016-12-22 | 2019-07-30 | H. Lundbeck A/S | Monoclonal anti-alpha-synuclein antibodies for preventing tau aggregation |
| MA47499A (fr) * | 2017-02-17 | 2019-12-25 | Denali Therapeutics Inc | Anticorps anti-tau et leurs procédés d'utilisation |
| CA3055957A1 (en) * | 2017-03-09 | 2018-09-13 | The Board Of Trustees Of The Leland Stanford Junior University | Treatment of pediatric brain tumors with targeting of cd47 pathway |
| KR20200030029A (ko) | 2017-05-02 | 2020-03-19 | 프로테나 바이오사이언시즈 리미티드 | 타우 인식 항체 |
| JOP20200074A1 (ar) | 2017-10-16 | 2020-04-30 | Eisai R&D Man Co Ltd | أجسام مضادة ضد tau واستخداماتها |
| WO2019180261A1 (en) | 2018-03-23 | 2019-09-26 | AbbVie Deutschland GmbH & Co. KG | Stable aqueous anti-tau antibody formulations |
| US11629175B2 (en) | 2018-04-27 | 2023-04-18 | Ecole Polytechnique Federale De Lausanne (Epfl) | Method for preparing PHFS-like Tau aggregates |
| JP2021530552A (ja) | 2018-07-31 | 2021-11-11 | イーライ リリー アンド カンパニー | 併用療法 |
| CN109613242A (zh) * | 2018-11-01 | 2019-04-12 | 深圳天辰医疗科技有限公司 | 一种肌酸激酶同工酶检测试剂盒及其制备方法 |
| TW202100550A (zh) | 2019-03-03 | 2021-01-01 | 愛爾蘭商普羅帝納生物科學公司 | 識別ｔａｕ之抗體 |
| JP7461368B2 (ja) * | 2019-03-18 | 2024-04-03 | リジェネロン・ファーマシューティカルズ・インコーポレイテッド | タウの播種または凝集の遺伝的修飾因子を同定するためのｃｒｉｓｐｒ／ｃａｓスクリーニングプラットフォーム |
| US11781131B2 (en) | 2019-03-18 | 2023-10-10 | Regeneron Pharmaceuticals, Inc. | CRISPR/Cas dropout screening platform to reveal genetic vulnerabilities associated with tau aggregation |
| CN110055280A (zh) * | 2019-03-19 | 2019-07-26 | 深圳大学 | 一种稳定表达mCherry-tau的细胞系及其构建方法与应用 |
| CA3143811A1 (en) * | 2019-07-15 | 2021-01-21 | Seung-Yong Yoon | Anti-tau antibody and use of same |
| CA3147548A1 (en) * | 2019-08-13 | 2021-02-18 | Randall Bateman | Methods to detect mtbr tau isoforms and use thereof |
| US20240060047A1 (en) | 2019-10-09 | 2024-02-22 | Bluerock Therapeutics Lp | Cells with sustained transgene expression |
| CN115151562A (zh) * | 2019-12-04 | 2022-10-04 | Ac免疫有限公司 | 用于治疗和诊断的新分子 |
| WO2022099314A1 (en) * | 2020-11-09 | 2022-05-12 | Meso Scale Technologies, Llc. | Methods and kits for detecting tau |
| WO2022144406A1 (en) | 2020-12-29 | 2022-07-07 | Neurimmune Ag | Human anti-tau antibodies |
| BR112023019546A2 (pt) | 2021-03-26 | 2023-10-31 | Janssen Biotech Inc | Anticorpos anti-tau e usos dos mesmos |
| KR20230162793A (ko) | 2021-03-26 | 2023-11-28 | 얀센 바이오테크 인코포레이티드 | 쌍 나선형 필라멘트 타우에 대한 인간화 항체 및 이의 용도 |
| WO2024044637A2 (en) * | 2022-08-23 | 2024-02-29 | Washington University | Anti-tau mtbr antibodies and methods to detect cleaved fragments of tau and uses thereof |
Family Cites Families (77)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FI884505A (fi) | 1987-10-02 | 1989-04-03 | Du Pont | Immunoanalys, i vilken anvaends igg-uppsnappande antikroppar och detekteringssystem foer flera monoklonala antikroppar. |
| WO1993003369A1 (en) | 1991-08-01 | 1993-02-18 | Voorheis Paul H | Diagnostic method for alzheimer's disease |
| US5733734A (en) | 1991-08-14 | 1998-03-31 | The Trustees Of The University Of Pennsylvania | Method of screening for Alzheimer's disease or disease associated with the accumulation of paired helical filaments |
| ATE154642T1 (de) | 1991-10-25 | 1997-07-15 | Innogenetics Nv | Monoklonale antikörper gegen das mikrotubulusassoziierte protein tau. |
| DE69233767D1 (de) | 1991-12-06 | 2009-09-17 | Max Planck Gesellschaft | Verwendung von Protein-Kinasen zur Diagnose und Behandlung der Alzheimer-Krankheit |
| US7408027B1 (en) | 1991-12-06 | 2008-08-05 | Max-Planck-Gesellschaft Zur Forderung Der Wissenchaften | Tools for the diagnosis and treatment of Alzheimer's disease |
| JPH06239899A (ja) | 1993-02-12 | 1994-08-30 | Teijin Ltd | ヒトタウ蛋白に対する抗体、並びに該抗体を利用する体液中のヒトタウ蛋白の測定方法 |
| EP0772634B1 (en) | 1994-07-29 | 2003-03-12 | Innogenetics N.V. | Monoclonal antibodies specific for an epitope of a particular subclass or form of phosphorylated tau, hybridomas secreting them, antigen recognition of these antibodies and their applications |
| WO1997034145A1 (fr) | 1996-03-13 | 1997-09-18 | Mitsubishi Chemical Corporation | Anticorps a proteine tau antiphosphorylee et procede de detection de la maladie d'alzheimer l'utilisant |
| AU5508798A (en) | 1996-11-19 | 1998-06-10 | Trustees Of The University Of Pennsylvania, The | Diagnostic and therapeutic reagents for alzheimer's disease |
| US6797478B1 (en) | 1998-03-05 | 2004-09-28 | University Of Cincinnati | Method of detecting axonal damage, from associated disease states using tau monoclonal antibodies |
| RU2238947C2 (ru) * | 1998-07-14 | 2004-10-27 | Янссен Фармацевтика Н.В. | Нейротрофический фактор роста человека (эновин), кодирующая его выделенная молекула нуклеиновой кислоты, вектор (варианты), фармацевтическая композиция (варианты), антитело, способ обнаружения фактора роста, набор, способ идентификации агониста или антагониста (варианты) |
| CA2340433A1 (en) | 1998-09-08 | 2000-03-16 | Innogenetics N.V. | Tau as a marker for early cns damage |
| US6495376B1 (en) * | 1999-02-18 | 2002-12-17 | Beth Israel Deaconess Medical Center | Methods and compositions for regulating protein-protein interactions |
| US6589746B1 (en) | 1999-10-21 | 2003-07-08 | University Of Cincinnati | Method of detecting axonally-derived protein tau in patients with traumatic CNS injury |
| US20020182660A1 (en) | 2000-02-18 | 2002-12-05 | Fong Kei-Lai L. | N- and C-terminus specific immunoassays for full length beta-amyloid peptide-Abeta(1-40), Abeta(1-39), Abeta(1-40), Abeta(1-42) , and Abeta(1-43) |
| AT500379B8 (de) | 2001-02-02 | 2009-08-15 | Axon Neuroscience | Tau-proteine |
| AR035119A1 (es) | 2001-08-16 | 2004-04-14 | Lilly Co Eli | Anticuerpos humanos antagonistas anti-htnfsf13b |
| AU2002362197A1 (en) | 2001-12-28 | 2003-07-24 | Chugai Seiyaku Kabushiki Kaisha | Method of stabilizing protein |
| GB0210121D0 (en) | 2002-05-02 | 2002-06-12 | Celltech R&D Ltd | Biological products |
| HUE057124T2 (hu) | 2002-05-02 | 2022-04-28 | Wyeth Holdings Llc | Calicheamicin származék - hordozó konjugátumok |
| ES2311734T3 (es) | 2002-07-12 | 2009-02-16 | Axon Neuroscience Forschungs- Und Entwicklungs Gmbh | Proteinas tau truncadas. |
| AU2003257850A1 (en) | 2002-08-14 | 2004-03-03 | Mitsubishi Kagaku Iatron, Inc. | ANTIBODY SPECIFIC TO CENTRAL Tau-PROTEIN |
| FI20030652A0 (fi) | 2003-04-30 | 2003-04-30 | Susann Eriksson | Parannettu immunomääritys |
| CN1871259A (zh) | 2003-08-22 | 2006-11-29 | 比奥根艾迪克Ma公司 | 具有改变的效应物功能的经改进的抗体和制备它的方法 |
| WO2005080986A1 (en) | 2004-02-18 | 2005-09-01 | University Of Iowa Research Foundation | Antibodies to phosphorylated tau, methods of making and methods of use |
| JP4772065B2 (ja) | 2005-02-19 | 2011-09-14 | ピープルバイオ アイ エヌ シー | 多量体形成ポリペプチドの単量体型から多量体型を分別検出する方法 |
| EP1940442A4 (en) | 2005-08-04 | 2009-08-19 | Einstein Coll Med | PHOSPHORYLATION OF TAU BY ABL |
| ES2321996B1 (es) | 2006-01-26 | 2010-03-05 | Consejo Superior Investig. Cientificas | Uso de compuestos que se unen al dominio de union a microtubulos de tau en la elaboracion de composiciones farmaceuticas, dichas composiciones farmaceuticas y su aplicacion en el tratamiento de tauopatias. |
| US8012936B2 (en) | 2006-03-29 | 2011-09-06 | New York University | Tau fragments for immunotherapy |
| US20080220449A1 (en) | 2007-02-08 | 2008-09-11 | Oligomerix, Inc. | Biomarkers and assays for Alzheimer's disease |
| NZ588555A (en) | 2008-04-24 | 2012-06-29 | Bristol Myers Squibb Co | Use of epothilone d in treating tau-associated diseases including alzheimer's disease |
| CN101307108B (zh) | 2008-06-25 | 2012-04-04 | 南京川博生物技术有限公司 | 抗磷酸化Tau蛋白抗体及其在AD症异常磷酸化Tau蛋白水平测定上的用途 |
| CA2937492C (en) * | 2008-11-11 | 2019-08-13 | The Board Of Regents Of The University Of Texas System | Inhibition of mammalian target of rapamycin |
| US20110305706A1 (en) | 2009-02-23 | 2011-12-15 | Scott Thomas Brady | Compositions and Methods for Treating a Disease Mediated by Soluble Oligomeric Amyloid Beta |
| US9605054B2 (en) | 2009-02-23 | 2017-03-28 | The Board Of Trustees Of The University Of Illinois | Composition and method for treating a tauopathy |
| UA107571C2 (xx) | 2009-04-03 | 2015-01-26 | Фармацевтична композиція | |
| US8409584B2 (en) | 2009-05-05 | 2013-04-02 | New York University | Immunotherapy targeting of the shared abnormal conformational state of amyloidogenic peptides/proteins |
| EP2440234A4 (en) * | 2009-06-10 | 2013-11-06 | Univ New York | IMMUNOLOGICAL TARGETING OF PATHOLOGICAL TAU PROTEINS |
| EP2459214A1 (en) * | 2009-07-30 | 2012-06-06 | Pfizer Vaccines LLC | Antigenic tau peptides and uses thereof |
| WO2011026031A1 (en) | 2009-08-28 | 2011-03-03 | The Board Of Regents Of The University Of Texas System | Antibodies that bind tau oligomers |
| AU2010291933B2 (en) * | 2009-09-14 | 2016-09-08 | Banyan Biomarkers, Inc. | Micro-RNA, autoantibody and protein markers for diagnosis of neuronal injury |
| WO2011045166A1 (en) | 2009-09-24 | 2011-04-21 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Fkbp52-tau interaction as a novel therapeutical target for treating the neurological disorders involving tau dysfunction |
| WO2011109112A2 (en) | 2010-03-05 | 2011-09-09 | Albert Einstein College Of Medicine Of Yeshiva University | Method of detecting tau protein and tau fragments in serum |
| JP6371526B2 (ja) | 2010-10-07 | 2018-08-08 | エーシー イミューン エス．エー． | タウを認識するリン酸化部位特異的抗体 |
| AU2013205313B2 (en) | 2010-10-07 | 2016-05-19 | Ac Immune S.A. | Phosphospecific antibodies recognising tau |
| NZ609984A (en) * | 2010-10-11 | 2015-05-29 | Biogen Idec Internat Neuroscience Gmbh | Human anti-tau antibodies |
| EP2670434B1 (en) * | 2011-01-31 | 2018-12-26 | Tau Bio-Logic Corp. | Treatment of tauopathies |
| US8697076B2 (en) | 2011-04-27 | 2014-04-15 | Northwestern University | Antibodies selective for pathological tau dimers and prefibrillar pathological tau oligomers and their uses in treatment, diagnosis and monitoring of tauopathies |
| US20120321594A1 (en) | 2011-05-06 | 2012-12-20 | New York University | Methods of controlling axon or dendrite development of neuronal cells |
| WO2012162179A1 (en) | 2011-05-20 | 2012-11-29 | Oligomerix, Inc. | Tau protease compositions and methods of use |
| GB201111361D0 (en) * | 2011-07-04 | 2011-08-17 | Nordic Bioscience As | Biochemical markers for neurodegenerative conditions |
| GB201112056D0 (en) | 2011-07-14 | 2011-08-31 | Univ Leuven Kath | Antibodies |
| US9926353B2 (en) | 2011-07-19 | 2018-03-27 | New York University | Immunotherapeutic modulation of amyloidogenic disease using non-fibrillogenic, non-amyloidogenic polymerized proteins and peptides |
| SG10201912955PA (en) | 2011-09-19 | 2020-02-27 | Axon Neuroscience Se | Protein-based therapy and diagnosis of tau-mediated pathology in alzheimer's disease |
| CA2850686C (en) | 2011-10-07 | 2020-09-08 | Ac Immune S.A. | Phosphospecific antibodies recognising tau |
| WO2013063086A1 (en) | 2011-10-24 | 2013-05-02 | Intellect Neurosciences, Inc. | Compositions and methods for treatment of proteinopathies |
| NZ626269A (en) | 2011-12-20 | 2016-06-24 | Janssen Biotech Inc | Anti-phf-tau antibodies and their uses |
| WO2013151762A1 (en) | 2012-04-05 | 2013-10-10 | Ac Immune S.A. | Humanized tau antibody |
| WO2013177104A2 (en) | 2012-05-21 | 2013-11-28 | Felder Mitchell S | Treatment for tauopathies |
| ES2763361T3 (es) | 2012-05-31 | 2020-05-28 | Univ Osaka City | Agente terapéutico o agente profiláctico para la demencia |
| KR102494798B1 (ko) | 2012-07-03 | 2023-02-06 | 워싱턴 유니버시티 | Tau에 대한 항체 |
| WO2014028777A2 (en) | 2012-08-16 | 2014-02-20 | Ipierian, Inc. | Methods of treating a tauopathy |
| US20140056901A1 (en) | 2012-08-21 | 2014-02-27 | The Institute For Molecular Medicine | Anti-tau antibodies and compositions for and methods of making and using in treatment, diagnosis and monitoring of tauopathies |
| CA2885924C (en) | 2012-08-21 | 2022-12-13 | Institute For Molecular Medicine, Inc. | Compositions and methods related to diseases associated with deposits of amyloid, tau, and alpha-synuclein |
| US9650436B2 (en) | 2012-10-12 | 2017-05-16 | Arizona Board Of Regents On Behalf Of Arizona State University | Antibody based reagents that specifically recognize toxic oligomeric forms of tau |
| US9910048B2 (en) | 2012-12-03 | 2018-03-06 | Washington University | Method for detection of aggregates in biological samples |
| US8921150B2 (en) | 2012-12-06 | 2014-12-30 | Taiwan Semiconductor Manufacturing Co., Ltd. | Process to achieve contact protrusion for single damascene via |
| US9200068B2 (en) | 2012-12-18 | 2015-12-01 | Regents Of The University Of Minnesota | Compositions and methods related to tauopathy |
| WO2014096321A1 (en) | 2012-12-21 | 2014-06-26 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Antibodies specific to tau phosphorylated at serine 422 and uses for the treatment and diagnosis of tauopathies |
| EP3792278A3 (en) | 2012-12-21 | 2021-05-26 | Biogen MA Inc. | Human anti-tau antibodies |
| US8980270B2 (en) | 2013-01-18 | 2015-03-17 | Ipierian, Inc. | Methods of treating a tauopathy |
| AU2014248515B2 (en) | 2013-03-13 | 2019-03-07 | Prothena Biosciences Limited | Tau immunotherapy |
| WO2014159244A2 (en) | 2013-03-14 | 2014-10-02 | Merck Patent Gmbh | O-GlcNAc TAU ANTIBODY AND USE THEREOF |
| JP6568514B2 (ja) | 2013-03-15 | 2019-08-28 | エーシー イミューン エス．エー． | 抗タウ抗体及び使用方法 |
| CA2903091C (en) | 2013-03-15 | 2022-09-06 | Beth Israel Deaconess Medical Center, Inc. | Methods and compositions for the generation and use of conformation-specific antibodies |
| TWI664190B (zh) | 2014-06-27 | 2019-07-01 | 美商Ｃ２Ｎ醫療診斷有限責任公司 | 人類化抗－ｔａｕ抗體 |
-
2013
- 2013-07-03 KR KR1020207033554A patent/KR102494798B1/ko active IP Right Grant
- 2013-07-03 EP EP13813988.6A patent/EP2870176A4/en not_active Withdrawn
- 2013-07-03 RU RU2015103228A patent/RU2668159C2/ru active
- 2013-07-03 RU RU2018132044A patent/RU2018132044A/ru unknown
- 2013-07-03 US US14/412,309 patent/US9834596B2/en active Active
- 2013-07-03 NZ NZ739622A patent/NZ739622A/en not_active IP Right Cessation
- 2013-07-03 CN CN201810507442.3A patent/CN108623682A/zh active Pending
- 2013-07-03 JP JP2015520685A patent/JP6345655B2/ja not_active Expired - Fee Related
- 2013-07-03 BR BR112014033116-2A patent/BR112014033116B1/pt active IP Right Grant
- 2013-07-03 MY MYPI2014704038A patent/MY171473A/en unknown
- 2013-07-03 MX MX2014016024A patent/MX359555B/es active IP Right Grant
- 2013-07-03 EP EP20199802.8A patent/EP3838921A3/en not_active Withdrawn
- 2013-07-03 AU AU2013286680A patent/AU2013286680B2/en active Active
- 2013-07-03 WO PCT/US2013/049333 patent/WO2014008404A1/en active Application Filing
- 2013-07-03 KR KR20157002867A patent/KR20150036346A/ko active IP Right Grant
- 2013-07-03 CA CA2877397A patent/CA2877397A1/en not_active Abandoned
- 2013-07-03 SG SG11201408626YA patent/SG11201408626YA/en unknown
- 2013-07-03 SG SG10201913370PA patent/SG10201913370PA/en unknown
- 2013-07-03 SG SG10201708959WA patent/SG10201708959WA/en unknown
- 2013-07-03 NZ NZ703423A patent/NZ703423A/en not_active IP Right Cessation
- 2013-07-03 CN CN201380045706.3A patent/CN104781278B/zh active Active
- 2013-07-03 IN IN7KON2015 patent/IN2015KN00007A/en unknown
- 2013-07-03 KR KR1020207002242A patent/KR20200013072A/ko not_active Application Discontinuation
-
2014
- 2014-12-19 MX MX2022000026A patent/MX2022000026A/es unknown
- 2014-12-23 IL IL236409A patent/IL236409B/en active IP Right Grant
-
2015
- 2015-10-28 HK HK15110657.6A patent/HK1209768A1/xx unknown
-
2017
- 2017-06-02 US US15/612,695 patent/US20180037641A1/en not_active Abandoned
-
2018
- 2018-05-23 JP JP2018098889A patent/JP2018184398A/ja active Pending
- 2018-09-17 AU AU2018229564A patent/AU2018229564A1/en not_active Abandoned
-
2020
- 2020-04-09 JP JP2020070416A patent/JP2020125310A/ja active Pending
- 2020-08-28 AU AU2020223765A patent/AU2020223765A1/en not_active Abandoned
- 2020-09-29 IL IL277643A patent/IL277643A/en unknown
-
2021
- 2021-12-21 IL IL289241A patent/IL289241A/en unknown
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US9834596B2 (en) | Antibodies to tau | |
| Schofield et al. | Preclinical development of a high affinity α-synuclein antibody, MEDI1341, that can enter the brain, sequester extracellular α-synuclein and attenuate α-synuclein spreading in vivo | |
| JP6878395B2 (ja) | 過リン酸化タウに特異的な抗体およびその使用方法 | |
| CN104080806B (zh) | 识别Tau的磷酸化特异抗体 | |
| TWI516500B (zh) | 抗β類澱粉蛋白單株抗體 | |
| US9090680B2 (en) | Antibodies that specifically bind to abeta oligomers and uses thereof | |
| DK2361638T3 (en) | Beta-1-42-specific monoclonal antibodies with therapeutic properties | |
| EP2074145B1 (en) | Humanized antibody against amyloid beta | |
| RU2607368C2 (ru) | Безопасные и функциональные гуманизированные антитела | |
| WO2015066279A2 (en) | Activatable antibodies that bind epidermal growth factor receptor and methods of use thereof | |
| KR20190028436A (ko) | 과인산화된 타우에 특이적인 항체 및 이의 사용 방법 | |
| HRP20090221A2 (hr) | Humanizirano protutijelo | |
| CN106397588A (zh) | 原细纤维结合抗体及其治疗和诊断帕金森氏症、路易体痴呆和其他α‑共核蛋白病的应用 | |
| BR112020018868A2 (pt) | métodos baseados em anticorpo para detectar e tratar doença de alzheimer | |
| JP7144755B2 (ja) | 薬剤、使用および方法 | |
| US20190315846A1 (en) | Antibodies to Human Alpha-Synuclein | |
| US20230365665A1 (en) | ANTIBODY COMPOSITIONS TARGETING NON-PHOSPHORYLATED a-SYNUCLEIN AGGREGATES | |
| WO2022060236A1 (en) | ANTIBODY COMPOSITIONS TARGETING NON-PHOSPHORYLATED α-SYNUCLEIN AGGREGATES | |
| CA3174805A1 (en) | Novel alpha-synuclein binding antibodies, or antigen binding portions thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request |
Effective date: 20180628 |
|
| EEER | Examination request |
Effective date: 20180628 |
|
| FZDE | Discontinued |
Effective date: 20221021 |