JP5486808B2 - アミロイドベータタンパク質に対するモノクローナル抗体及びその使用 - Google Patents
アミロイドベータタンパク質に対するモノクローナル抗体及びその使用 Download PDFInfo
- Publication number
- JP5486808B2 JP5486808B2 JP2008543522A JP2008543522A JP5486808B2 JP 5486808 B2 JP5486808 B2 JP 5486808B2 JP 2008543522 A JP2008543522 A JP 2008543522A JP 2008543522 A JP2008543522 A JP 2008543522A JP 5486808 B2 JP5486808 B2 JP 5486808B2
- Authority
- JP
- Japan
- Prior art keywords
- antibody
- antibodies
- sequence
- antigen
- alzheimer
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
- 102000013455 Amyloid beta-Peptides Human genes 0.000 title description 13
- 108010090849 Amyloid beta-Peptides Proteins 0.000 title description 13
- 238000000034 method Methods 0.000 claims description 82
- 208000024827 Alzheimer disease Diseases 0.000 claims description 80
- 108090000623 proteins and genes Proteins 0.000 claims description 72
- 239000000427 antigen Substances 0.000 claims description 71
- 108091007433 antigens Proteins 0.000 claims description 71
- 102000036639 antigens Human genes 0.000 claims description 71
- 102000004169 proteins and genes Human genes 0.000 claims description 46
- 210000004408 hybridoma Anatomy 0.000 claims description 32
- 150000001875 compounds Chemical class 0.000 claims description 31
- 239000000523 sample Substances 0.000 claims description 31
- 239000012472 biological sample Substances 0.000 claims description 12
- 238000003745 diagnosis Methods 0.000 claims description 11
- 230000002265 prevention Effects 0.000 claims description 11
- 239000003814 drug Substances 0.000 claims description 8
- 238000004519 manufacturing process Methods 0.000 claims description 8
- 230000015572 biosynthetic process Effects 0.000 claims description 6
- 239000008194 pharmaceutical composition Substances 0.000 claims description 3
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 90
- 239000000243 solution Substances 0.000 description 90
- 230000027455 binding Effects 0.000 description 70
- 239000000178 monomer Substances 0.000 description 69
- 125000003275 alpha amino acid group Chemical group 0.000 description 64
- 108090000765 processed proteins & peptides Proteins 0.000 description 51
- 239000000872 buffer Substances 0.000 description 48
- 239000011780 sodium chloride Substances 0.000 description 47
- 108010047041 Complementarity Determining Regions Proteins 0.000 description 44
- 238000010186 staining Methods 0.000 description 43
- 235000018102 proteins Nutrition 0.000 description 41
- 235000001014 amino acid Nutrition 0.000 description 40
- UQLDLKMNUJERMK-UHFFFAOYSA-L di(octadecanoyloxy)lead Chemical compound [Pb+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O UQLDLKMNUJERMK-UHFFFAOYSA-L 0.000 description 40
- 241000699666 Mus <mouse, genus> Species 0.000 description 37
- 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 37
- 239000002953 phosphate buffered saline Substances 0.000 description 36
- 210000004027 cell Anatomy 0.000 description 35
- 241000699670 Mus sp. Species 0.000 description 33
- 230000013595 glycosylation Effects 0.000 description 32
- 101710137189 Amyloid-beta A4 protein Proteins 0.000 description 31
- 102100022704 Amyloid-beta precursor protein Human genes 0.000 description 31
- 101710151993 Amyloid-beta precursor protein Proteins 0.000 description 31
- DZHSAHHDTRWUTF-SIQRNXPUSA-N amyloid-beta polypeptide 42 Chemical compound C([C@@H](C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@H](C(=O)NCC(=O)N[C@@H](CO)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCCN)C(=O)NCC(=O)N[C@@H](C)C(=O)N[C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](C(C)C)C(=O)NCC(=O)NCC(=O)N[C@@H](C(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C)C(O)=O)[C@@H](C)CC)C(C)C)NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@@H](NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)CNC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CC(O)=O)C(C)C)C(C)C)C1=CC=CC=C1 DZHSAHHDTRWUTF-SIQRNXPUSA-N 0.000 description 31
- 239000003153 chemical reaction reagent Substances 0.000 description 31
- 239000012634 fragment Substances 0.000 description 31
- 150000007523 nucleic acids Chemical class 0.000 description 31
- 238000006206 glycosylation reaction Methods 0.000 description 27
- 239000002773 nucleotide Substances 0.000 description 27
- 125000003729 nucleotide group Chemical group 0.000 description 27
- 239000000203 mixture Substances 0.000 description 26
- 238000002360 preparation method Methods 0.000 description 26
- 238000011830 transgenic mouse model Methods 0.000 description 25
- 241001465754 Metazoa Species 0.000 description 24
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 24
- 108020004414 DNA Proteins 0.000 description 23
- 241000699660 Mus musculus Species 0.000 description 23
- 230000000903 blocking effect Effects 0.000 description 23
- 239000006228 supernatant Substances 0.000 description 23
- 108091028043 Nucleic acid sequence Proteins 0.000 description 22
- 229940024606 amino acid Drugs 0.000 description 21
- 150000001413 amino acids Chemical class 0.000 description 21
- 230000014509 gene expression Effects 0.000 description 20
- 102000004196 processed proteins & peptides Human genes 0.000 description 20
- 239000004094 surface-active agent Substances 0.000 description 20
- BYEAHWXPCBROCE-UHFFFAOYSA-N 1,1,1,3,3,3-hexafluoropropan-2-ol Chemical compound FC(F)(F)C(O)C(F)(F)F BYEAHWXPCBROCE-UHFFFAOYSA-N 0.000 description 19
- 108091026890 Coding region Proteins 0.000 description 19
- 238000004458 analytical method Methods 0.000 description 19
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 18
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 18
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 17
- 108060003951 Immunoglobulin Proteins 0.000 description 17
- 102000018358 immunoglobulin Human genes 0.000 description 17
- 108020004999 messenger RNA Proteins 0.000 description 17
- 108010064539 amyloid beta-protein (1-42) Proteins 0.000 description 16
- 210000001175 cerebrospinal fluid Anatomy 0.000 description 16
- 230000000295 complement effect Effects 0.000 description 16
- 210000004602 germ cell Anatomy 0.000 description 16
- 239000011550 stock solution Substances 0.000 description 16
- 238000001114 immunoprecipitation Methods 0.000 description 15
- 238000002372 labelling Methods 0.000 description 15
- 229920001213 Polysorbate 20 Polymers 0.000 description 14
- 238000003752 polymerase chain reaction Methods 0.000 description 14
- 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 14
- 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 14
- 241000894007 species Species 0.000 description 14
- 239000000725 suspension Substances 0.000 description 14
- 208000037259 Amyloid Plaque Diseases 0.000 description 13
- 230000000694 effects Effects 0.000 description 13
- 239000000126 substance Substances 0.000 description 13
- 238000012360 testing method Methods 0.000 description 13
- 230000001225 therapeutic effect Effects 0.000 description 13
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 12
- -1 alkali metal cations Chemical class 0.000 description 12
- 108010064397 amyloid beta-protein (1-40) Proteins 0.000 description 12
- 238000009396 hybridization Methods 0.000 description 12
- 230000003053 immunization Effects 0.000 description 12
- 238000001727 in vivo Methods 0.000 description 12
- 108020004707 nucleic acids Proteins 0.000 description 12
- 102000039446 nucleic acids Human genes 0.000 description 12
- 238000002965 ELISA Methods 0.000 description 11
- 102000004190 Enzymes Human genes 0.000 description 11
- 108090000790 Enzymes Proteins 0.000 description 11
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 11
- 229920002684 Sepharose Polymers 0.000 description 11
- 229940088598 enzyme Drugs 0.000 description 11
- 229920001184 polypeptide Polymers 0.000 description 11
- 239000000047 product Substances 0.000 description 11
- 239000012086 standard solution Substances 0.000 description 11
- 239000006180 TBST buffer Substances 0.000 description 10
- 238000010790 dilution Methods 0.000 description 10
- 239000012895 dilution Substances 0.000 description 10
- 238000002649 immunization Methods 0.000 description 10
- 238000001262 western blot Methods 0.000 description 10
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 9
- 239000007983 Tris buffer Substances 0.000 description 9
- 230000009471 action Effects 0.000 description 9
- 208000010877 cognitive disease Diseases 0.000 description 9
- 230000000875 corresponding effect Effects 0.000 description 9
- 238000002474 experimental method Methods 0.000 description 9
- 238000000338 in vitro Methods 0.000 description 9
- 230000008569 process Effects 0.000 description 9
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 9
- 230000009261 transgenic effect Effects 0.000 description 9
- 230000014616 translation Effects 0.000 description 9
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 9
- 102000014914 Carrier Proteins Human genes 0.000 description 8
- 241000196324 Embryophyta Species 0.000 description 8
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 8
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 8
- 108091008324 binding proteins Proteins 0.000 description 8
- 238000005119 centrifugation Methods 0.000 description 8
- IQFVPQOLBLOTPF-HKXUKFGYSA-L congo red Chemical compound [Na+].[Na+].C1=CC=CC2=C(N)C(/N=N/C3=CC=C(C=C3)C3=CC=C(C=C3)/N=N/C3=C(C4=CC=CC=C4C(=C3)S([O-])(=O)=O)N)=CC(S([O-])(=O)=O)=C21 IQFVPQOLBLOTPF-HKXUKFGYSA-L 0.000 description 8
- 230000008021 deposition Effects 0.000 description 8
- 238000002703 mutagenesis Methods 0.000 description 8
- 231100000350 mutagenesis Toxicity 0.000 description 8
- 230000001423 neocortical effect Effects 0.000 description 8
- 238000003860 storage Methods 0.000 description 8
- 238000013519 translation Methods 0.000 description 8
- 238000005406 washing Methods 0.000 description 8
- 241001494479 Pecora Species 0.000 description 7
- 238000006243 chemical reaction Methods 0.000 description 7
- 239000012141 concentrate Substances 0.000 description 7
- 235000008504 concentrate Nutrition 0.000 description 7
- 238000001514 detection method Methods 0.000 description 7
- 238000009472 formulation Methods 0.000 description 7
- 230000003993 interaction Effects 0.000 description 7
- 230000035772 mutation Effects 0.000 description 7
- 239000008188 pellet Substances 0.000 description 7
- 239000000843 powder Substances 0.000 description 7
- 150000003839 salts Chemical class 0.000 description 7
- 239000007787 solid Substances 0.000 description 7
- 208000028698 Cognitive impairment Diseases 0.000 description 6
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 6
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 6
- 239000011324 bead Substances 0.000 description 6
- 238000000576 coating method Methods 0.000 description 6
- 239000003184 complementary RNA Substances 0.000 description 6
- 239000000499 gel Substances 0.000 description 6
- 229910052739 hydrogen Inorganic materials 0.000 description 6
- 238000010191 image analysis Methods 0.000 description 6
- 230000005291 magnetic effect Effects 0.000 description 6
- 239000000463 material Substances 0.000 description 6
- 238000012545 processing Methods 0.000 description 6
- 238000011002 quantification Methods 0.000 description 6
- 238000003118 sandwich ELISA Methods 0.000 description 6
- 239000001632 sodium acetate Substances 0.000 description 6
- 235000017281 sodium acetate Nutrition 0.000 description 6
- 239000007790 solid phase Substances 0.000 description 6
- 238000006467 substitution reaction Methods 0.000 description 6
- 230000009466 transformation Effects 0.000 description 6
- 108020005544 Antisense RNA Proteins 0.000 description 5
- 206010035226 Plasma cell myeloma Diseases 0.000 description 5
- 239000004365 Protease Substances 0.000 description 5
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 5
- 239000002671 adjuvant Substances 0.000 description 5
- 230000003941 amyloidogenesis Effects 0.000 description 5
- 238000000540 analysis of variance Methods 0.000 description 5
- 230000000692 anti-sense effect Effects 0.000 description 5
- 239000007864 aqueous solution Substances 0.000 description 5
- 238000003556 assay Methods 0.000 description 5
- 239000002585 base Substances 0.000 description 5
- 210000004556 brain Anatomy 0.000 description 5
- 150000001720 carbohydrates Chemical group 0.000 description 5
- 239000011248 coating agent Substances 0.000 description 5
- 238000011161 development Methods 0.000 description 5
- 230000018109 developmental process Effects 0.000 description 5
- 238000011156 evaluation Methods 0.000 description 5
- 230000006870 function Effects 0.000 description 5
- 125000003147 glycosyl group Chemical group 0.000 description 5
- 230000001965 increasing effect Effects 0.000 description 5
- 238000011534 incubation Methods 0.000 description 5
- 239000007924 injection Substances 0.000 description 5
- 238000002347 injection Methods 0.000 description 5
- 238000010369 molecular cloning Methods 0.000 description 5
- 230000003287 optical effect Effects 0.000 description 5
- 230000002829 reductive effect Effects 0.000 description 5
- 230000001105 regulatory effect Effects 0.000 description 5
- 239000012089 stop solution Substances 0.000 description 5
- 210000001519 tissue Anatomy 0.000 description 5
- 239000003656 tris buffered saline Substances 0.000 description 5
- 239000003981 vehicle Substances 0.000 description 5
- 239000011534 wash buffer Substances 0.000 description 5
- 102000002260 Alkaline Phosphatase Human genes 0.000 description 4
- 108020004774 Alkaline Phosphatase Proteins 0.000 description 4
- 208000005145 Cerebral amyloid angiopathy Diseases 0.000 description 4
- 102000003886 Glycoproteins Human genes 0.000 description 4
- 108090000288 Glycoproteins Proteins 0.000 description 4
- 208000032843 Hemorrhage Diseases 0.000 description 4
- 101000690301 Homo sapiens Aldo-keto reductase family 1 member C4 Proteins 0.000 description 4
- 101001116548 Homo sapiens Protein CBFA2T1 Proteins 0.000 description 4
- 108010001336 Horseradish Peroxidase Proteins 0.000 description 4
- 108091005804 Peptidases Proteins 0.000 description 4
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 4
- 125000000539 amino acid group Chemical group 0.000 description 4
- 210000004369 blood Anatomy 0.000 description 4
- 239000008280 blood Substances 0.000 description 4
- 210000004204 blood vessel Anatomy 0.000 description 4
- ATDGTVJJHBUTRL-UHFFFAOYSA-N cyanogen bromide Chemical compound BrC#N ATDGTVJJHBUTRL-UHFFFAOYSA-N 0.000 description 4
- 239000006185 dispersion Substances 0.000 description 4
- POULHZVOKOAJMA-UHFFFAOYSA-N dodecanoic acid Chemical compound CCCCCCCCCCCC(O)=O POULHZVOKOAJMA-UHFFFAOYSA-N 0.000 description 4
- 230000008030 elimination Effects 0.000 description 4
- 238000003379 elimination reaction Methods 0.000 description 4
- 102000054751 human RUNX1T1 Human genes 0.000 description 4
- 239000004615 ingredient Substances 0.000 description 4
- 210000004698 lymphocyte Anatomy 0.000 description 4
- 239000003550 marker Substances 0.000 description 4
- 239000011159 matrix material Substances 0.000 description 4
- 201000000050 myeloid neoplasm Diseases 0.000 description 4
- 230000004770 neurodegeneration Effects 0.000 description 4
- 238000006384 oligomerization reaction Methods 0.000 description 4
- 238000002264 polyacrylamide gel electrophoresis Methods 0.000 description 4
- 210000002966 serum Anatomy 0.000 description 4
- 238000003756 stirring Methods 0.000 description 4
- 239000000758 substrate Substances 0.000 description 4
- 235000000346 sugar Nutrition 0.000 description 4
- 238000012353 t test Methods 0.000 description 4
- 229940124597 therapeutic agent Drugs 0.000 description 4
- 238000002560 therapeutic procedure Methods 0.000 description 4
- 239000013598 vector Substances 0.000 description 4
- FWMNVWWHGCHHJJ-SKKKGAJSSA-N 4-amino-1-[(2r)-6-amino-2-[[(2r)-2-[[(2r)-2-[[(2r)-2-amino-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]hexanoyl]piperidine-4-carboxylic acid Chemical compound C([C@H](C(=O)N[C@H](CC(C)C)C(=O)N[C@H](CCCCN)C(=O)N1CCC(N)(CC1)C(O)=O)NC(=O)[C@H](N)CC=1C=CC=CC=1)C1=CC=CC=C1 FWMNVWWHGCHHJJ-SKKKGAJSSA-N 0.000 description 3
- 101800001718 Amyloid-beta protein Proteins 0.000 description 3
- 241000894006 Bacteria Species 0.000 description 3
- LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 description 3
- 108091035707 Consensus sequence Proteins 0.000 description 3
- 241000283074 Equus asinus Species 0.000 description 3
- 239000004471 Glycine Substances 0.000 description 3
- 241000282412 Homo Species 0.000 description 3
- 108700005091 Immunoglobulin Genes Proteins 0.000 description 3
- 102220606690 Neurotrimin_D23N_mutation Human genes 0.000 description 3
- 239000000020 Nitrocellulose Substances 0.000 description 3
- 241000700159 Rattus Species 0.000 description 3
- 108010090804 Streptavidin Proteins 0.000 description 3
- 229930006000 Sucrose Natural products 0.000 description 3
- 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 3
- 102220538768 Superoxide dismutase [Cu-Zn]_E22G_mutation Human genes 0.000 description 3
- 238000013459 approach Methods 0.000 description 3
- 230000008901 benefit Effects 0.000 description 3
- 230000004071 biological effect Effects 0.000 description 3
- 210000005013 brain tissue Anatomy 0.000 description 3
- 230000015556 catabolic process Effects 0.000 description 3
- 230000002490 cerebral effect Effects 0.000 description 3
- 239000002299 complementary DNA Substances 0.000 description 3
- 238000004132 cross linking Methods 0.000 description 3
- 229940127089 cytotoxic agent Drugs 0.000 description 3
- 239000002254 cytotoxic agent Substances 0.000 description 3
- 231100000599 cytotoxic agent Toxicity 0.000 description 3
- 238000006731 degradation reaction Methods 0.000 description 3
- 238000013461 design Methods 0.000 description 3
- 201000010099 disease Diseases 0.000 description 3
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 3
- 238000010494 dissociation reaction Methods 0.000 description 3
- 230000005593 dissociations Effects 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- 239000003937 drug carrier Substances 0.000 description 3
- 239000003623 enhancer Substances 0.000 description 3
- HQPMKSGTIOYHJT-UHFFFAOYSA-N ethane-1,2-diol;propane-1,2-diol Chemical compound OCCO.CC(O)CO HQPMKSGTIOYHJT-UHFFFAOYSA-N 0.000 description 3
- 235000013305 food Nutrition 0.000 description 3
- 230000004927 fusion Effects 0.000 description 3
- 102000035122 glycosylated proteins Human genes 0.000 description 3
- 108091005608 glycosylated proteins Proteins 0.000 description 3
- 210000005260 human cell Anatomy 0.000 description 3
- 238000003018 immunoassay Methods 0.000 description 3
- 230000002163 immunogen Effects 0.000 description 3
- 230000001976 improved effect Effects 0.000 description 3
- 238000001990 intravenous administration Methods 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 229920002521 macromolecule Polymers 0.000 description 3
- 208000027061 mild cognitive impairment Diseases 0.000 description 3
- 230000004048 modification Effects 0.000 description 3
- 238000012986 modification Methods 0.000 description 3
- 229920001220 nitrocellulos Polymers 0.000 description 3
- 239000000041 non-steroidal anti-inflammatory agent Substances 0.000 description 3
- 229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 description 3
- 230000036961 partial effect Effects 0.000 description 3
- 239000002245 particle Substances 0.000 description 3
- 229920001993 poloxamer 188 Polymers 0.000 description 3
- 230000008488 polyadenylation Effects 0.000 description 3
- 229920000642 polymer Polymers 0.000 description 3
- 239000002243 precursor Substances 0.000 description 3
- 230000004044 response Effects 0.000 description 3
- 102200131541 rs121912450 Human genes 0.000 description 3
- 102200158871 rs33955330 Human genes 0.000 description 3
- 102220092852 rs754853086 Human genes 0.000 description 3
- 238000000926 separation method Methods 0.000 description 3
- 238000002741 site-directed mutagenesis Methods 0.000 description 3
- 235000017557 sodium bicarbonate Nutrition 0.000 description 3
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 3
- KSAVQLQVUXSOCR-UHFFFAOYSA-M sodium lauroyl sarcosinate Chemical compound [Na+].CCCCCCCCCCCC(=O)N(C)CC([O-])=O KSAVQLQVUXSOCR-UHFFFAOYSA-M 0.000 description 3
- 239000005720 sucrose Substances 0.000 description 3
- 238000002198 surface plasmon resonance spectroscopy Methods 0.000 description 3
- 239000003826 tablet Substances 0.000 description 3
- 238000013518 transcription Methods 0.000 description 3
- 230000035897 transcription Effects 0.000 description 3
- 238000012546 transfer Methods 0.000 description 3
- GPRLSGONYQIRFK-MNYXATJNSA-N triton Chemical compound [3H+] GPRLSGONYQIRFK-MNYXATJNSA-N 0.000 description 3
- 238000011144 upstream manufacturing Methods 0.000 description 3
- 229960005486 vaccine Drugs 0.000 description 3
- 230000002792 vascular 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
- WRIDQFICGBMAFQ-UHFFFAOYSA-N (E)-8-Octadecenoic acid Natural products CCCCCCCCCC=CCCCCCCC(O)=O WRIDQFICGBMAFQ-UHFFFAOYSA-N 0.000 description 2
- IAKHMKGGTNLKSZ-INIZCTEOSA-N (S)-colchicine Chemical compound C1([C@@H](NC(C)=O)CC2)=CC(=O)C(OC)=CC=C1C1=C2C=C(OC)C(OC)=C1OC IAKHMKGGTNLKSZ-INIZCTEOSA-N 0.000 description 2
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 2
- LQJBNNIYVWPHFW-UHFFFAOYSA-N 20:1omega9c fatty acid Natural products CCCCCCCCCCC=CCCCCCCCC(O)=O LQJBNNIYVWPHFW-UHFFFAOYSA-N 0.000 description 2
- KDCGOANMDULRCW-UHFFFAOYSA-N 7H-purine Chemical compound N1=CNC2=NC=NC2=C1 KDCGOANMDULRCW-UHFFFAOYSA-N 0.000 description 2
- QSBYPNXLFMSGKH-UHFFFAOYSA-N 9-Heptadecensaeure Natural products CCCCCCCC=CCCCCCCCC(O)=O QSBYPNXLFMSGKH-UHFFFAOYSA-N 0.000 description 2
- 206010069754 Acquired gene mutation Diseases 0.000 description 2
- 241000283690 Bos taurus Species 0.000 description 2
- 241000283707 Capra Species 0.000 description 2
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 2
- 102000004594 DNA Polymerase I Human genes 0.000 description 2
- 108010017826 DNA Polymerase I Proteins 0.000 description 2
- AOJJSUZBOXZQNB-TZSSRYMLSA-N Doxorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 AOJJSUZBOXZQNB-TZSSRYMLSA-N 0.000 description 2
- 241000283073 Equus caballus Species 0.000 description 2
- ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 2
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 2
- SXRSQZLOMIGNAQ-UHFFFAOYSA-N Glutaraldehyde Chemical compound O=CCCCC=O SXRSQZLOMIGNAQ-UHFFFAOYSA-N 0.000 description 2
- 101000746373 Homo sapiens Granulocyte-macrophage colony-stimulating factor Proteins 0.000 description 2
- 108010054477 Immunoglobulin Fab Fragments Proteins 0.000 description 2
- 102000001706 Immunoglobulin Fab Fragments Human genes 0.000 description 2
- 108010067060 Immunoglobulin Variable Region Proteins 0.000 description 2
- 102000017727 Immunoglobulin Variable Region Human genes 0.000 description 2
- 108091092195 Intron Proteins 0.000 description 2
- 239000005639 Lauric acid Substances 0.000 description 2
- 108060001084 Luciferase Proteins 0.000 description 2
- 239000005089 Luciferase Substances 0.000 description 2
- 229930195725 Mannitol Natural products 0.000 description 2
- 108091027974 Mature messenger RNA Proteins 0.000 description 2
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 2
- 239000005642 Oleic acid Substances 0.000 description 2
- ZQPPMHVWECSIRJ-UHFFFAOYSA-N Oleic acid Natural products CCCCCCCCC=CCCCCCCCC(O)=O ZQPPMHVWECSIRJ-UHFFFAOYSA-N 0.000 description 2
- 108091034117 Oligonucleotide Proteins 0.000 description 2
- 241000283973 Oryctolagus cuniculus Species 0.000 description 2
- 229930040373 Paraformaldehyde Natural products 0.000 description 2
- 102000035195 Peptidases Human genes 0.000 description 2
- 108010029485 Protein Isoforms Proteins 0.000 description 2
- 102000001708 Protein Isoforms Human genes 0.000 description 2
- 108020004511 Recombinant DNA Proteins 0.000 description 2
- 102100037486 Reverse transcriptase/ribonuclease H Human genes 0.000 description 2
- PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 2
- 241000282898 Sus scrofa Species 0.000 description 2
- 238000002835 absorbance Methods 0.000 description 2
- 230000002378 acidificating effect Effects 0.000 description 2
- RJURFGZVJUQBHK-UHFFFAOYSA-N actinomycin D Natural products CC1OC(=O)C(C(C)C)N(C)C(=O)CN(C)C(=O)C2CCCN2C(=O)C(C(C)C)NC(=O)C1NC(=O)C1=C(N)C(=O)C(C)=C2OC(C(C)=CC=C3C(=O)NC4C(=O)NC(C(N5CCCC5C(=O)N(C)CC(=O)N(C)C(C(C)C)C(=O)OC4C)=O)C(C)C)=C3N=C21 RJURFGZVJUQBHK-UHFFFAOYSA-N 0.000 description 2
- 230000004913 activation Effects 0.000 description 2
- 238000001261 affinity purification Methods 0.000 description 2
- 230000002776 aggregation Effects 0.000 description 2
- 238000004220 aggregation Methods 0.000 description 2
- 125000000217 alkyl group Chemical group 0.000 description 2
- VREFGVBLTWBCJP-UHFFFAOYSA-N alprazolam Chemical compound C12=CC(Cl)=CC=C2N2C(C)=NN=C2CN=C1C1=CC=CC=C1 VREFGVBLTWBCJP-UHFFFAOYSA-N 0.000 description 2
- 230000003321 amplification Effects 0.000 description 2
- 239000003945 anionic surfactant Substances 0.000 description 2
- 238000009175 antibody therapy Methods 0.000 description 2
- 210000003719 b-lymphocyte Anatomy 0.000 description 2
- 238000009227 behaviour therapy Methods 0.000 description 2
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 2
- 230000005540 biological transmission Effects 0.000 description 2
- 125000004057 biotinyl group Chemical group [H]N1C(=O)N([H])[C@]2([H])[C@@]([H])(SC([H])([H])[C@]12[H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C(*)=O 0.000 description 2
- 230000006287 biotinylation Effects 0.000 description 2
- 238000007413 biotinylation Methods 0.000 description 2
- 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 2
- 238000011088 calibration curve Methods 0.000 description 2
- 239000004202 carbamide Substances 0.000 description 2
- 235000014633 carbohydrates Nutrition 0.000 description 2
- 125000004432 carbon atom Chemical group C* 0.000 description 2
- 210000004978 chinese hamster ovary cell Anatomy 0.000 description 2
- 238000013270 controlled release Methods 0.000 description 2
- 210000005257 cortical tissue Anatomy 0.000 description 2
- 239000002577 cryoprotective agent Substances 0.000 description 2
- 239000013078 crystal Substances 0.000 description 2
- OPTASPLRGRRNAP-UHFFFAOYSA-N cytosine Chemical compound NC=1C=CNC(=O)N=1 OPTASPLRGRRNAP-UHFFFAOYSA-N 0.000 description 2
- 238000012217 deletion Methods 0.000 description 2
- 230000037430 deletion Effects 0.000 description 2
- 238000000502 dialysis Methods 0.000 description 2
- 239000003085 diluting agent Substances 0.000 description 2
- 239000002612 dispersion medium Substances 0.000 description 2
- 238000012377 drug delivery Methods 0.000 description 2
- 239000000975 dye Substances 0.000 description 2
- 239000012636 effector Substances 0.000 description 2
- 238000001962 electrophoresis Methods 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- ZMMJGEGLRURXTF-UHFFFAOYSA-N ethidium bromide Chemical compound [Br-].C12=CC(N)=CC=C2C2=CC=C(N)C=C2[N+](CC)=C1C1=CC=CC=C1 ZMMJGEGLRURXTF-UHFFFAOYSA-N 0.000 description 2
- 229960005542 ethidium bromide Drugs 0.000 description 2
- 239000000945 filler Substances 0.000 description 2
- MHMNJMPURVTYEJ-UHFFFAOYSA-N fluorescein-5-isothiocyanate Chemical compound O1C(=O)C2=CC(N=C=S)=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 MHMNJMPURVTYEJ-UHFFFAOYSA-N 0.000 description 2
- 108091006047 fluorescent proteins Proteins 0.000 description 2
- 102000034287 fluorescent proteins Human genes 0.000 description 2
- UYTPUPDQBNUYGX-UHFFFAOYSA-N guanine Chemical compound O=C1NC(N)=NC2=C1N=CN2 UYTPUPDQBNUYGX-UHFFFAOYSA-N 0.000 description 2
- 239000001257 hydrogen Substances 0.000 description 2
- FDGQSTZJBFJUBT-UHFFFAOYSA-N hypoxanthine Chemical compound O=C1NC=NC2=C1NC=N2 FDGQSTZJBFJUBT-UHFFFAOYSA-N 0.000 description 2
- 238000003384 imaging method Methods 0.000 description 2
- 230000002779 inactivation Effects 0.000 description 2
- 238000001802 infusion Methods 0.000 description 2
- 239000003978 infusion fluid Substances 0.000 description 2
- 238000003780 insertion Methods 0.000 description 2
- 230000037431 insertion Effects 0.000 description 2
- 238000007918 intramuscular administration Methods 0.000 description 2
- 239000007928 intraperitoneal injection Substances 0.000 description 2
- 238000002955 isolation Methods 0.000 description 2
- QXJSBBXBKPUZAA-UHFFFAOYSA-N isooleic acid Natural products CCCCCCCC=CCCCCCCCCC(O)=O QXJSBBXBKPUZAA-UHFFFAOYSA-N 0.000 description 2
- 239000007951 isotonicity adjuster Substances 0.000 description 2
- 230000000670 limiting effect Effects 0.000 description 2
- 239000002502 liposome Substances 0.000 description 2
- 239000007791 liquid phase Substances 0.000 description 2
- 239000012931 lyophilized formulation Substances 0.000 description 2
- 239000000594 mannitol Substances 0.000 description 2
- 235000010355 mannitol Nutrition 0.000 description 2
- 230000007246 mechanism Effects 0.000 description 2
- 239000002609 medium Substances 0.000 description 2
- 239000012528 membrane Substances 0.000 description 2
- 210000000478 neocortex Anatomy 0.000 description 2
- 208000015122 neurodegenerative disease Diseases 0.000 description 2
- 231100000189 neurotoxic Toxicity 0.000 description 2
- 230000002887 neurotoxic effect Effects 0.000 description 2
- 230000003472 neutralizing effect Effects 0.000 description 2
- 238000003199 nucleic acid amplification method Methods 0.000 description 2
- 238000007899 nucleic acid hybridization Methods 0.000 description 2
- ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 2
- 229920002866 paraformaldehyde Polymers 0.000 description 2
- 238000007911 parenteral administration Methods 0.000 description 2
- 230000037361 pathway Effects 0.000 description 2
- 239000013610 patient sample Substances 0.000 description 2
- YBYRMVIVWMBXKQ-UHFFFAOYSA-N phenylmethanesulfonyl fluoride Chemical compound FS(=O)(=O)CC1=CC=CC=C1 YBYRMVIVWMBXKQ-UHFFFAOYSA-N 0.000 description 2
- 239000013612 plasmid Substances 0.000 description 2
- 229920001223 polyethylene glycol Polymers 0.000 description 2
- 229920002704 polyhistidine Polymers 0.000 description 2
- 108091033319 polynucleotide Proteins 0.000 description 2
- 102000040430 polynucleotide Human genes 0.000 description 2
- 239000002157 polynucleotide Substances 0.000 description 2
- 230000032361 posttranscriptional gene silencing Effects 0.000 description 2
- 238000001556 precipitation Methods 0.000 description 2
- 230000000069 prophylactic effect Effects 0.000 description 2
- AQHHHDLHHXJYJD-UHFFFAOYSA-N propranolol Chemical compound C1=CC=C2C(OCC(O)CNC(C)C)=CC=CC2=C1 AQHHHDLHHXJYJD-UHFFFAOYSA-N 0.000 description 2
- 235000019419 proteases Nutrition 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- RXWNCPJZOCPEPQ-NVWDDTSBSA-N puromycin Chemical compound C1=CC(OC)=CC=C1C[C@H](N)C(=O)N[C@H]1[C@@H](O)[C@H](N2C3=NC=NC(=C3N=C2)N(C)C)O[C@@H]1CO RXWNCPJZOCPEPQ-NVWDDTSBSA-N 0.000 description 2
- 230000002285 radioactive effect Effects 0.000 description 2
- 238000003127 radioimmunoassay Methods 0.000 description 2
- 238000003259 recombinant expression Methods 0.000 description 2
- 230000009467 reduction Effects 0.000 description 2
- 230000002441 reversible effect Effects 0.000 description 2
- 102220249000 rs200856000 Human genes 0.000 description 2
- 102200151424 rs5198 Human genes 0.000 description 2
- 239000012723 sample buffer Substances 0.000 description 2
- 239000012898 sample dilution Substances 0.000 description 2
- 239000012488 sample solution Substances 0.000 description 2
- 108700004121 sarkosyl Proteins 0.000 description 2
- 238000012216 screening Methods 0.000 description 2
- 230000003248 secreting effect Effects 0.000 description 2
- 235000020183 skimmed milk Nutrition 0.000 description 2
- 239000001509 sodium citrate Substances 0.000 description 2
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 230000037439 somatic mutation Effects 0.000 description 2
- 230000003393 splenic effect Effects 0.000 description 2
- 238000007920 subcutaneous administration Methods 0.000 description 2
- 238000010254 subcutaneous injection Methods 0.000 description 2
- 239000007929 subcutaneous injection Substances 0.000 description 2
- 239000012134 supernatant fraction Substances 0.000 description 2
- 208000024891 symptom Diseases 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 230000008685 targeting Effects 0.000 description 2
- RWQNBRDOKXIBIV-UHFFFAOYSA-N thymine Chemical compound CC1=CNC(=O)NC1=O RWQNBRDOKXIBIV-UHFFFAOYSA-N 0.000 description 2
- 230000001052 transient effect Effects 0.000 description 2
- 230000032258 transport Effects 0.000 description 2
- LWIHDJKSTIGBAC-UHFFFAOYSA-K tripotassium phosphate Chemical compound [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 description 2
- 238000012795 verification Methods 0.000 description 2
- 238000009736 wetting Methods 0.000 description 2
- HDTRYLNUVZCQOY-UHFFFAOYSA-N α-D-glucopyranosyl-α-D-glucopyranoside Natural products OC1C(O)C(O)C(CO)OC1OC1C(O)C(O)C(O)C(CO)O1 HDTRYLNUVZCQOY-UHFFFAOYSA-N 0.000 description 1
- SYTBZMRGLBWNTM-SNVBAGLBSA-N (R)-flurbiprofen Chemical compound FC1=CC([C@H](C(O)=O)C)=CC=C1C1=CC=CC=C1 SYTBZMRGLBWNTM-SNVBAGLBSA-N 0.000 description 1
- AGNGYMCLFWQVGX-AGFFZDDWSA-N (e)-1-[(2s)-2-amino-2-carboxyethoxy]-2-diazonioethenolate Chemical compound OC(=O)[C@@H](N)CO\C([O-])=C\[N+]#N AGNGYMCLFWQVGX-AGFFZDDWSA-N 0.000 description 1
- IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 description 1
- GZCWLCBFPRFLKL-UHFFFAOYSA-N 1-prop-2-ynoxypropan-2-ol Chemical compound CC(O)COCC#C GZCWLCBFPRFLKL-UHFFFAOYSA-N 0.000 description 1
- KHWCHTKSEGGWEX-RRKCRQDMSA-N 2'-deoxyadenosine 5'-monophosphate Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@H]1C[C@H](O)[C@@H](COP(O)(O)=O)O1 KHWCHTKSEGGWEX-RRKCRQDMSA-N 0.000 description 1
- NCMVOABPESMRCP-SHYZEUOFSA-N 2'-deoxycytosine 5'-monophosphate Chemical compound O=C1N=C(N)C=CN1[C@@H]1O[C@H](COP(O)(O)=O)[C@@H](O)C1 NCMVOABPESMRCP-SHYZEUOFSA-N 0.000 description 1
- LTFMZDNNPPEQNG-KVQBGUIXSA-N 2'-deoxyguanosine 5'-monophosphate Chemical compound C1=2NC(N)=NC(=O)C=2N=CN1[C@H]1C[C@H](O)[C@@H](COP(O)(O)=O)O1 LTFMZDNNPPEQNG-KVQBGUIXSA-N 0.000 description 1
- XSXWOBXNYNULJG-UHFFFAOYSA-N 2-(2,4,4-trimethylpentan-2-yl)phenol Chemical class CC(C)(C)CC(C)(C)C1=CC=CC=C1O XSXWOBXNYNULJG-UHFFFAOYSA-N 0.000 description 1
- QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 1
- HMFKFHLTUCJZJO-UHFFFAOYSA-N 2-{2-[3,4-bis(2-hydroxyethoxy)oxolan-2-yl]-2-(2-hydroxyethoxy)ethoxy}ethyl dodecanoate Chemical compound CCCCCCCCCCCC(=O)OCCOCC(OCCO)C1OCC(OCCO)C1OCCO HMFKFHLTUCJZJO-UHFFFAOYSA-N 0.000 description 1
- UMCMPZBLKLEWAF-BCTGSCMUSA-N 3-[(3-cholamidopropyl)dimethylammonio]propane-1-sulfonate Chemical compound C([C@H]1C[C@H]2O)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(=O)NCCC[N+](C)(C)CCCS([O-])(=O)=O)C)[C@@]2(C)[C@@H](O)C1 UMCMPZBLKLEWAF-BCTGSCMUSA-N 0.000 description 1
- QRXMUCSWCMTJGU-UHFFFAOYSA-N 5-bromo-4-chloro-3-indolyl phosphate Chemical compound C1=C(Br)C(Cl)=C2C(OP(O)(=O)O)=CNC2=C1 QRXMUCSWCMTJGU-UHFFFAOYSA-N 0.000 description 1
- STQGQHZAVUOBTE-UHFFFAOYSA-N 7-Cyan-hept-2t-en-4,6-diinsaeure Natural products C1=2C(O)=C3C(=O)C=4C(OC)=CC=CC=4C(=O)C3=C(O)C=2CC(O)(C(C)=O)CC1OC1CC(N)C(O)C(C)O1 STQGQHZAVUOBTE-UHFFFAOYSA-N 0.000 description 1
- 102000013563 Acid Phosphatase Human genes 0.000 description 1
- 108010051457 Acid Phosphatase Proteins 0.000 description 1
- 229930024421 Adenine Natural products 0.000 description 1
- GFFGJBXGBJISGV-UHFFFAOYSA-N Adenine Chemical compound NC1=NC=NC2=C1N=CN2 GFFGJBXGBJISGV-UHFFFAOYSA-N 0.000 description 1
- 241000242764 Aequorea victoria Species 0.000 description 1
- 241000607620 Aliivibrio fischeri Species 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- 108091023037 Aptamer Proteins 0.000 description 1
- 239000004475 Arginine Substances 0.000 description 1
- 108090001008 Avidin Proteins 0.000 description 1
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
- 125000001433 C-terminal amino-acid group Chemical group 0.000 description 1
- 102000008186 Collagen Human genes 0.000 description 1
- 108010035532 Collagen Proteins 0.000 description 1
- 108020004394 Complementary RNA Proteins 0.000 description 1
- 241000195493 Cryptophyta Species 0.000 description 1
- 229930183912 Cytidylic acid Natural products 0.000 description 1
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
- SHZGCJCMOBCMKK-UHFFFAOYSA-N D-mannomethylose Natural products CC1OC(O)C(O)C(O)C1O SHZGCJCMOBCMKK-UHFFFAOYSA-N 0.000 description 1
- WQZGKKKJIJFFOK-QTVWNMPRSA-N D-mannopyranose Chemical compound OC[C@H]1OC(O)[C@@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-QTVWNMPRSA-N 0.000 description 1
- 102000053602 DNA Human genes 0.000 description 1
- 230000006820 DNA synthesis Effects 0.000 description 1
- 108010014303 DNA-directed DNA polymerase Proteins 0.000 description 1
- 102000016928 DNA-directed DNA polymerase Human genes 0.000 description 1
- 102000004163 DNA-directed RNA polymerases Human genes 0.000 description 1
- 108090000626 DNA-directed RNA polymerases Proteins 0.000 description 1
- 108010092160 Dactinomycin Proteins 0.000 description 1
- 206010012289 Dementia Diseases 0.000 description 1
- 229920002307 Dextran Polymers 0.000 description 1
- 206010061818 Disease progression Diseases 0.000 description 1
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 1
- 238000012286 ELISA Assay Methods 0.000 description 1
- 229920005682 EO-PO block copolymer Polymers 0.000 description 1
- MBYXEBXZARTUSS-QLWBXOBMSA-N Emetamine Natural products O(C)c1c(OC)cc2c(c(C[C@@H]3[C@H](CC)CN4[C@H](c5c(cc(OC)c(OC)c5)CC4)C3)ncc2)c1 MBYXEBXZARTUSS-QLWBXOBMSA-N 0.000 description 1
- BDAGIHXWWSANSR-UHFFFAOYSA-N Formic acid Chemical compound OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 1
- PNNNRSAQSRJVSB-SLPGGIOYSA-N Fucose Natural products C[C@H](O)[C@@H](O)[C@H](O)[C@H](O)C=O PNNNRSAQSRJVSB-SLPGGIOYSA-N 0.000 description 1
- 241000233866 Fungi Species 0.000 description 1
- 229910052688 Gadolinium Inorganic materials 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 102000007446 Glucagon-Like Peptide-1 Receptor Human genes 0.000 description 1
- 108010086246 Glucagon-Like Peptide-1 Receptor Proteins 0.000 description 1
- 102000005744 Glycoside Hydrolases Human genes 0.000 description 1
- 108010031186 Glycoside Hydrolases Proteins 0.000 description 1
- 108700023372 Glycosyltransferases Proteins 0.000 description 1
- 108010026389 Gramicidin Proteins 0.000 description 1
- 101000823051 Homo sapiens Amyloid-beta precursor protein Proteins 0.000 description 1
- 108090000144 Human Proteins Proteins 0.000 description 1
- 102000003839 Human Proteins Human genes 0.000 description 1
- UGQMRVRMYYASKQ-UHFFFAOYSA-N Hypoxanthine nucleoside Natural products OC1C(O)C(CO)OC1N1C(NC=NC2=O)=C2N=C1 UGQMRVRMYYASKQ-UHFFFAOYSA-N 0.000 description 1
- 102000009786 Immunoglobulin Constant Regions Human genes 0.000 description 1
- 108010009817 Immunoglobulin Constant Regions Proteins 0.000 description 1
- 229930010555 Inosine Natural products 0.000 description 1
- UGQMRVRMYYASKQ-KQYNXXCUSA-N Inosine Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C2=NC=NC(O)=C2N=C1 UGQMRVRMYYASKQ-KQYNXXCUSA-N 0.000 description 1
- 102100034343 Integrase Human genes 0.000 description 1
- HNDVDQJCIGZPNO-YFKPBYRVSA-N L-Histidine Natural products OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 0.000 description 1
- FFEARJCKVFRZRR-UHFFFAOYSA-N L-Methionine Natural products CSCCC(N)C(O)=O FFEARJCKVFRZRR-UHFFFAOYSA-N 0.000 description 1
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 1
- SHZGCJCMOBCMKK-DHVFOXMCSA-N L-fucopyranose Chemical compound C[C@@H]1OC(O)[C@@H](O)[C@H](O)[C@@H]1O SHZGCJCMOBCMKK-DHVFOXMCSA-N 0.000 description 1
- 125000002066 L-histidyl group Chemical group [H]N1C([H])=NC(C([H])([H])[C@](C(=O)[*])([H])N([H])[H])=C1[H] 0.000 description 1
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 description 1
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 1
- 229930195722 L-methionine Natural products 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 1
- NNJVILVZKWQKPM-UHFFFAOYSA-N Lidocaine Chemical compound CCN(CC)CC(=O)NC1=C(C)C=CC=C1C NNJVILVZKWQKPM-UHFFFAOYSA-N 0.000 description 1
- 241000724182 Macron Species 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 229930192392 Mitomycin Natural products 0.000 description 1
- 241001529936 Murinae Species 0.000 description 1
- 241000238367 Mya arenaria Species 0.000 description 1
- NWIBSHFKIJFRCO-WUDYKRTCSA-N Mytomycin Chemical compound C1N2C(C(C(C)=C(N)C3=O)=O)=C3[C@@H](COC(N)=O)[C@@]2(OC)[C@@H]2[C@H]1N2 NWIBSHFKIJFRCO-WUDYKRTCSA-N 0.000 description 1
- FSVCELGFZIQNCK-UHFFFAOYSA-N N,N-bis(2-hydroxyethyl)glycine Chemical compound OCCN(CCO)CC(O)=O FSVCELGFZIQNCK-UHFFFAOYSA-N 0.000 description 1
- OVRNDRQMDRJTHS-UHFFFAOYSA-N N-acelyl-D-glucosamine Natural products CC(=O)NC1C(O)OC(CO)C(O)C1O OVRNDRQMDRJTHS-UHFFFAOYSA-N 0.000 description 1
- OVRNDRQMDRJTHS-RTRLPJTCSA-N N-acetyl-D-glucosamine Chemical group CC(=O)N[C@H]1C(O)O[C@H](CO)[C@@H](O)[C@@H]1O OVRNDRQMDRJTHS-RTRLPJTCSA-N 0.000 description 1
- OVRNDRQMDRJTHS-FMDGEEDCSA-N N-acetyl-beta-D-glucosamine Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O OVRNDRQMDRJTHS-FMDGEEDCSA-N 0.000 description 1
- MBLBDJOUHNCFQT-LXGUWJNJSA-N N-acetylglucosamine Natural products CC(=O)N[C@@H](C=O)[C@@H](O)[C@H](O)[C@H](O)CO MBLBDJOUHNCFQT-LXGUWJNJSA-N 0.000 description 1
- 230000004988 N-glycosylation Effects 0.000 description 1
- 125000001429 N-terminal alpha-amino-acid group Chemical group 0.000 description 1
- 241000380800 Nordus Species 0.000 description 1
- 108020004711 Nucleic Acid Probes Proteins 0.000 description 1
- 230000004989 O-glycosylation Effects 0.000 description 1
- 229930012538 Paclitaxel Natural products 0.000 description 1
- 108090000526 Papain Proteins 0.000 description 1
- 102000057297 Pepsin A Human genes 0.000 description 1
- 108090000284 Pepsin A Proteins 0.000 description 1
- 108010081690 Pertussis Toxin Proteins 0.000 description 1
- 108010004729 Phycoerythrin Proteins 0.000 description 1
- 229920005372 Plexiglas® Polymers 0.000 description 1
- 241000276498 Pollachius virens Species 0.000 description 1
- 229920002732 Polyanhydride Polymers 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 229920000954 Polyglycolide Polymers 0.000 description 1
- 229920001710 Polyorthoester Polymers 0.000 description 1
- 229940124158 Protease/peptidase inhibitor Drugs 0.000 description 1
- 241000287531 Psittacidae Species 0.000 description 1
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 1
- 108091034057 RNA (poly(A)) Proteins 0.000 description 1
- 108010092799 RNA-directed DNA polymerase Proteins 0.000 description 1
- 238000001069 Raman spectroscopy Methods 0.000 description 1
- 108700005075 Regulator Genes Proteins 0.000 description 1
- 102000006382 Ribonucleases Human genes 0.000 description 1
- 108010083644 Ribonucleases Proteins 0.000 description 1
- 239000012722 SDS sample buffer Substances 0.000 description 1
- AUVVAXYIELKVAI-UHFFFAOYSA-N SJ000285215 Natural products N1CCC2=CC(OC)=C(OC)C=C2C1CC1CC2C3=CC(OC)=C(OC)C=C3CCN2CC1CC AUVVAXYIELKVAI-UHFFFAOYSA-N 0.000 description 1
- 108091081021 Sense strand Proteins 0.000 description 1
- 238000000692 Student's t-test Methods 0.000 description 1
- 108091008874 T cell receptors Proteins 0.000 description 1
- 102000016266 T-Cell Antigen Receptors Human genes 0.000 description 1
- 108090001109 Thermolysin Proteins 0.000 description 1
- 108700019146 Transgenes Proteins 0.000 description 1
- HDTRYLNUVZCQOY-WSWWMNSNSA-N Trehalose Natural products O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@H](O)[C@@H](O)[C@@H](O)[C@@H](CO)O1 HDTRYLNUVZCQOY-WSWWMNSNSA-N 0.000 description 1
- GBOGMAARMMDZGR-UHFFFAOYSA-N UNPD149280 Natural products N1C(=O)C23OC(=O)C=CC(O)CCCC(C)CC=CC3C(O)C(=C)C(C)C2C1CC1=CC=CC=C1 GBOGMAARMMDZGR-UHFFFAOYSA-N 0.000 description 1
- 108090000848 Ubiquitin Proteins 0.000 description 1
- 102000044159 Ubiquitin Human genes 0.000 description 1
- DJJCXFVJDGTHFX-UHFFFAOYSA-N Uridinemonophosphate Natural products OC1C(O)C(COP(O)(O)=O)OC1N1C(=O)NC(=O)C=C1 DJJCXFVJDGTHFX-UHFFFAOYSA-N 0.000 description 1
- FOGRQMPFHUHIGU-UHFFFAOYSA-N Uridylic acid Natural products OC1C(OP(O)(O)=O)C(CO)OC1N1C(=O)NC(=O)C=C1 FOGRQMPFHUHIGU-UHFFFAOYSA-N 0.000 description 1
- JXLYSJRDGCGARV-WWYNWVTFSA-N Vinblastine Natural products O=C(O[C@H]1[C@](O)(C(=O)OC)[C@@H]2N(C)c3c(cc(c(OC)c3)[C@]3(C(=O)OC)c4[nH]c5c(c4CCN4C[C@](O)(CC)C[C@H](C3)C4)cccc5)[C@@]32[C@H]2[C@@]1(CC)C=CCN2CC3)C JXLYSJRDGCGARV-WWYNWVTFSA-N 0.000 description 1
- 238000002441 X-ray diffraction Methods 0.000 description 1
- JLCPHMBAVCMARE-UHFFFAOYSA-N [3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-hydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methyl [5-(6-aminopurin-9-yl)-2-(hydroxymethyl)oxolan-3-yl] hydrogen phosphate Polymers Cc1cn(C2CC(OP(O)(=O)OCC3OC(CC3OP(O)(=O)OCC3OC(CC3O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c3nc(N)[nH]c4=O)C(COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3CO)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cc(C)c(=O)[nH]c3=O)n3cc(C)c(=O)[nH]c3=O)n3ccc(N)nc3=O)n3cc(C)c(=O)[nH]c3=O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)O2)c(=O)[nH]c1=O JLCPHMBAVCMARE-UHFFFAOYSA-N 0.000 description 1
- SXEHKFHPFVVDIR-UHFFFAOYSA-N [4-(4-hydrazinylphenyl)phenyl]hydrazine Chemical compound C1=CC(NN)=CC=C1C1=CC=C(NN)C=C1 SXEHKFHPFVVDIR-UHFFFAOYSA-N 0.000 description 1
- 239000003070 absorption delaying agent Substances 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- DZBUGLKDJFMEHC-UHFFFAOYSA-O acridine;hydron Chemical compound C1=CC=CC2=CC3=CC=CC=C3[NH+]=C21 DZBUGLKDJFMEHC-UHFFFAOYSA-O 0.000 description 1
- RJURFGZVJUQBHK-IIXSONLDSA-N actinomycin D Chemical compound C[C@H]1OC(=O)[C@H](C(C)C)N(C)C(=O)CN(C)C(=O)[C@@H]2CCCN2C(=O)[C@@H](C(C)C)NC(=O)[C@H]1NC(=O)C1=C(N)C(=O)C(C)=C2OC(C(C)=CC=C3C(=O)N[C@@H]4C(=O)N[C@@H](C(N5CCC[C@H]5C(=O)N(C)CC(=O)N(C)[C@@H](C(C)C)C(=O)O[C@@H]4C)=O)C(C)C)=C3N=C21 RJURFGZVJUQBHK-IIXSONLDSA-N 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 230000000996 additive effect Effects 0.000 description 1
- 229960000643 adenine Drugs 0.000 description 1
- UDMBCSSLTHHNCD-KQYNXXCUSA-N adenosine 5'-monophosphate Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](COP(O)(O)=O)[C@@H](O)[C@H]1O UDMBCSSLTHHNCD-KQYNXXCUSA-N 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 230000009824 affinity maturation Effects 0.000 description 1
- 239000011543 agarose gel Substances 0.000 description 1
- 230000032683 aging Effects 0.000 description 1
- 230000001270 agonistic effect Effects 0.000 description 1
- 230000001476 alcoholic effect Effects 0.000 description 1
- 150000001299 aldehydes Chemical class 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 1
- 125000003342 alkenyl group Chemical group 0.000 description 1
- HDTRYLNUVZCQOY-LIZSDCNHSA-N alpha,alpha-trehalose Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 HDTRYLNUVZCQOY-LIZSDCNHSA-N 0.000 description 1
- WQZGKKKJIJFFOK-PHYPRBDBSA-N alpha-D-galactose Chemical compound OC[C@H]1O[C@H](O)[C@H](O)[C@@H](O)[C@H]1O WQZGKKKJIJFFOK-PHYPRBDBSA-N 0.000 description 1
- FEWOUVRMGWFWIH-ILZZQXMPSA-N amyloid-beta polypeptide 40 Chemical compound C([C@@H](C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@H](C(=O)NCC(=O)N[C@@H](CO)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCCN)C(=O)NCC(=O)N[C@@H](C)C(=O)N[C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](C(C)C)C(=O)NCC(=O)NCC(=O)N[C@@H](C(C)C)C(=O)N[C@@H](C(C)C)C(O)=O)[C@@H](C)CC)C(C)C)NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@@H](NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)CNC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CC(O)=O)C(C)C)C(C)C)C1=CC=CC=C1 FEWOUVRMGWFWIH-ILZZQXMPSA-N 0.000 description 1
- 210000004102 animal cell Anatomy 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 230000009830 antibody antigen interaction Effects 0.000 description 1
- 210000000776 antibody secreting cell Anatomy 0.000 description 1
- 230000010056 antibody-dependent cellular cytotoxicity Effects 0.000 description 1
- 210000000628 antibody-producing cell Anatomy 0.000 description 1
- 239000003429 antifungal agent Substances 0.000 description 1
- 229940121375 antifungal agent Drugs 0.000 description 1
- 230000000890 antigenic effect Effects 0.000 description 1
- 239000012062 aqueous buffer Substances 0.000 description 1
- 239000006286 aqueous extract Substances 0.000 description 1
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
- 238000002820 assay format Methods 0.000 description 1
- 238000011888 autopsy Methods 0.000 description 1
- 229950011321 azaserine Drugs 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 102000005936 beta-Galactosidase Human genes 0.000 description 1
- 108010005774 beta-Galactosidase Proteins 0.000 description 1
- SQVRNKJHWKZAKO-UHFFFAOYSA-N beta-N-Acetyl-D-neuraminic acid Natural products CC(=O)NC1C(O)CC(O)(C(O)=O)OC1C(O)C(O)CO SQVRNKJHWKZAKO-UHFFFAOYSA-N 0.000 description 1
- 239000007998 bicine buffer Substances 0.000 description 1
- 230000003115 biocidal effect Effects 0.000 description 1
- 229920000249 biocompatible polymer Polymers 0.000 description 1
- 239000003181 biological factor Substances 0.000 description 1
- 239000012620 biological material Substances 0.000 description 1
- 229960000074 biopharmaceutical Drugs 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
- OWMVSZAMULFTJU-UHFFFAOYSA-N bis-tris Chemical compound OCCN(CCO)C(CO)(CO)CO OWMVSZAMULFTJU-UHFFFAOYSA-N 0.000 description 1
- 230000000740 bleeding effect Effects 0.000 description 1
- 229920001400 block copolymer Polymers 0.000 description 1
- 210000001124 body fluid Anatomy 0.000 description 1
- 239000010839 body fluid Substances 0.000 description 1
- RSIHSRDYCUFFLA-DYKIIFRCSA-N boldenone Chemical compound O=C1C=C[C@]2(C)[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3CCC2=C1 RSIHSRDYCUFFLA-DYKIIFRCSA-N 0.000 description 1
- 239000012267 brine Substances 0.000 description 1
- 239000006189 buccal tablet Substances 0.000 description 1
- 239000006172 buffering agent Substances 0.000 description 1
- DQXBYHZEEUGOBF-UHFFFAOYSA-N but-3-enoic acid;ethene Chemical compound C=C.OC(=O)CC=C DQXBYHZEEUGOBF-UHFFFAOYSA-N 0.000 description 1
- 210000004899 c-terminal region Anatomy 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 150000001767 cationic compounds Chemical class 0.000 description 1
- 238000004113 cell culture Methods 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 230000030570 cellular localization Effects 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- NDAYQJDHGXTBJL-MWWSRJDJSA-N chembl557217 Chemical compound C1=CC=C2C(C[C@H](NC(=O)[C@@H](CC(C)C)NC(=O)[C@H](CC=3C4=CC=CC=C4NC=3)NC(=O)[C@@H](CC(C)C)NC(=O)[C@H](CC=3C4=CC=CC=C4NC=3)NC(=O)[C@@H](CC(C)C)NC(=O)[C@H](CC=3C4=CC=CC=C4NC=3)NC(=O)[C@@H](C(C)C)NC(=O)[C@H](C(C)C)NC(=O)[C@@H](C(C)C)NC(=O)[C@H](C)NC(=O)[C@H](NC(=O)CNC(=O)[C@@H](NC=O)C(C)C)CC(C)C)C(=O)NCCO)=CNC2=C1 NDAYQJDHGXTBJL-MWWSRJDJSA-N 0.000 description 1
- 238000012412 chemical coupling Methods 0.000 description 1
- 238000010382 chemical cross-linking Methods 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 238000010367 cloning Methods 0.000 description 1
- 230000019771 cognition Effects 0.000 description 1
- 230000001149 cognitive effect Effects 0.000 description 1
- 229960001338 colchicine Drugs 0.000 description 1
- 229920001436 collagen Polymers 0.000 description 1
- 238000004737 colorimetric analysis Methods 0.000 description 1
- 239000008139 complexing agent Substances 0.000 description 1
- 239000007891 compressed tablet Substances 0.000 description 1
- 238000004590 computer program Methods 0.000 description 1
- 230000003750 conditioning effect Effects 0.000 description 1
- 238000010276 construction Methods 0.000 description 1
- 230000001276 controlling effect Effects 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- NKLPQNGYXWVELD-UHFFFAOYSA-M coomassie brilliant blue Chemical compound [Na+].C1=CC(OCC)=CC=C1NC1=CC=C(C(=C2C=CC(C=C2)=[N+](CC)CC=2C=C(C=CC=2)S([O-])(=O)=O)C=2C=CC(=CC=2)N(CC)CC=2C=C(C=CC=2)S([O-])(=O)=O)C=C1 NKLPQNGYXWVELD-UHFFFAOYSA-M 0.000 description 1
- 230000002596 correlated effect Effects 0.000 description 1
- 230000008878 coupling Effects 0.000 description 1
- 238000010168 coupling process Methods 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 125000000151 cysteine group Chemical group N[C@@H](CS)C(=O)* 0.000 description 1
- IERHLVCPSMICTF-XVFCMESISA-N cytidine 5'-monophosphate Chemical compound O=C1N=C(N)C=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](COP(O)(O)=O)O1 IERHLVCPSMICTF-XVFCMESISA-N 0.000 description 1
- IERHLVCPSMICTF-UHFFFAOYSA-N cytidine monophosphate Natural products O=C1N=C(N)C=CN1C1C(O)C(O)C(COP(O)(O)=O)O1 IERHLVCPSMICTF-UHFFFAOYSA-N 0.000 description 1
- GBOGMAARMMDZGR-TYHYBEHESA-N cytochalasin B Chemical compound C([C@H]1[C@@H]2[C@@H](C([C@@H](O)[C@@H]3/C=C/C[C@H](C)CCC[C@@H](O)/C=C/C(=O)O[C@@]23C(=O)N1)=C)C)C1=CC=CC=C1 GBOGMAARMMDZGR-TYHYBEHESA-N 0.000 description 1
- GBOGMAARMMDZGR-JREHFAHYSA-N cytochalasin B Natural products C[C@H]1CCC[C@@H](O)C=CC(=O)O[C@@]23[C@H](C=CC1)[C@H](O)C(=C)[C@@H](C)[C@@H]2[C@H](Cc4ccccc4)NC3=O GBOGMAARMMDZGR-JREHFAHYSA-N 0.000 description 1
- 229940104302 cytosine Drugs 0.000 description 1
- GYOZYWVXFNDGLU-XLPZGREQSA-N dTMP Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](COP(O)(O)=O)[C@@H](O)C1 GYOZYWVXFNDGLU-XLPZGREQSA-N 0.000 description 1
- 229960000640 dactinomycin Drugs 0.000 description 1
- 238000007405 data analysis Methods 0.000 description 1
- STQGQHZAVUOBTE-VGBVRHCVSA-N daunorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(C)=O)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 STQGQHZAVUOBTE-VGBVRHCVSA-N 0.000 description 1
- 229960000975 daunorubicin Drugs 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- RSIHSRDYCUFFLA-UHFFFAOYSA-N dehydrotestosterone Natural products O=C1C=CC2(C)C3CCC(C)(C(CC4)O)C4C3CCC2=C1 RSIHSRDYCUFFLA-UHFFFAOYSA-N 0.000 description 1
- 230000002939 deleterious effect Effects 0.000 description 1
- 239000003398 denaturant Substances 0.000 description 1
- LTFMZDNNPPEQNG-UHFFFAOYSA-N deoxyguanylic acid Natural products C1=2NC(N)=NC(=O)C=2N=CN1C1CC(O)C(COP(O)(O)=O)O1 LTFMZDNNPPEQNG-UHFFFAOYSA-N 0.000 description 1
- 239000008121 dextrose Substances 0.000 description 1
- 235000005911 diet Nutrition 0.000 description 1
- 230000037213 diet Effects 0.000 description 1
- 230000029087 digestion Effects 0.000 description 1
- 230000005750 disease progression Effects 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 229960004679 doxorubicin Drugs 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 208000025688 early-onset autosomal dominant Alzheimer disease Diseases 0.000 description 1
- 230000001214 effect on cellular process Effects 0.000 description 1
- 238000001493 electron microscopy Methods 0.000 description 1
- AUVVAXYIELKVAI-CKBKHPSWSA-N emetine Chemical compound N1CCC2=CC(OC)=C(OC)C=C2[C@H]1C[C@H]1C[C@H]2C3=CC(OC)=C(OC)C=C3CCN2C[C@@H]1CC AUVVAXYIELKVAI-CKBKHPSWSA-N 0.000 description 1
- 229960002694 emetine Drugs 0.000 description 1
- AUVVAXYIELKVAI-UWBTVBNJSA-N emetine Natural products N1CCC2=CC(OC)=C(OC)C=C2[C@H]1C[C@H]1C[C@H]2C3=CC(OC)=C(OC)C=C3CCN2C[C@H]1CC AUVVAXYIELKVAI-UWBTVBNJSA-N 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 230000002255 enzymatic effect Effects 0.000 description 1
- 210000003743 erythrocyte Anatomy 0.000 description 1
- 239000005038 ethylene vinyl acetate Substances 0.000 description 1
- VJJPUSNTGOMMGY-MRVIYFEKSA-N etoposide Chemical compound COC1=C(O)C(OC)=CC([C@@H]2C3=CC=4OCOC=4C=C3[C@@H](O[C@H]3[C@@H]([C@@H](O)[C@@H]4O[C@H](C)OC[C@H]4O3)O)[C@@H]3[C@@H]2C(OC3)=O)=C1 VJJPUSNTGOMMGY-MRVIYFEKSA-N 0.000 description 1
- 229960005420 etoposide Drugs 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 239000013604 expression vector Substances 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 208000015756 familial Alzheimer disease Diseases 0.000 description 1
- 230000005294 ferromagnetic effect Effects 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 239000005308 flint glass Substances 0.000 description 1
- 238000007667 floating Methods 0.000 description 1
- 239000007850 fluorescent dye Substances 0.000 description 1
- 238000005187 foaming Methods 0.000 description 1
- 235000019253 formic acid Nutrition 0.000 description 1
- 239000012520 frozen sample Substances 0.000 description 1
- 125000002446 fucosyl group Chemical group C1([C@@H](O)[C@H](O)[C@H](O)[C@@H](O1)C)* 0.000 description 1
- UIWYJDYFSGRHKR-UHFFFAOYSA-N gadolinium atom Chemical compound [Gd] UIWYJDYFSGRHKR-UHFFFAOYSA-N 0.000 description 1
- 229930182830 galactose Natural products 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 239000007903 gelatin capsule Substances 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 230000002068 genetic effect Effects 0.000 description 1
- 238000010353 genetic engineering Methods 0.000 description 1
- 239000003862 glucocorticoid Substances 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 102000045442 glycosyltransferase activity proteins Human genes 0.000 description 1
- 108700014210 glycosyltransferase activity proteins Proteins 0.000 description 1
- PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical group [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 description 1
- 239000010931 gold Substances 0.000 description 1
- 229910052737 gold Inorganic materials 0.000 description 1
- 230000012010 growth Effects 0.000 description 1
- RQFCJASXJCIDSX-UUOKFMHZSA-N guanosine 5'-monophosphate Chemical compound C1=2NC(N)=NC(=O)C=2N=CN1[C@@H]1O[C@H](COP(O)(O)=O)[C@@H](O)[C@H]1O RQFCJASXJCIDSX-UUOKFMHZSA-N 0.000 description 1
- 235000013928 guanylic acid Nutrition 0.000 description 1
- 239000004226 guanylic acid Substances 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 230000002949 hemolytic effect Effects 0.000 description 1
- 229960002885 histidine Drugs 0.000 description 1
- 102000046783 human APP Human genes 0.000 description 1
- GPRLSGONYQIRFK-UHFFFAOYSA-N hydron Chemical compound [H+] GPRLSGONYQIRFK-UHFFFAOYSA-N 0.000 description 1
- 238000007654 immersion Methods 0.000 description 1
- 230000001900 immune effect Effects 0.000 description 1
- 230000028993 immune response Effects 0.000 description 1
- 210000000987 immune system Anatomy 0.000 description 1
- 230000036039 immunity Effects 0.000 description 1
- 229940127121 immunoconjugate Drugs 0.000 description 1
- 230000005847 immunogenicity Effects 0.000 description 1
- 230000016784 immunoglobulin production Effects 0.000 description 1
- 229940072221 immunoglobulins Drugs 0.000 description 1
- 239000007943 implant Substances 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 238000010249 in-situ analysis Methods 0.000 description 1
- 238000010348 incorporation Methods 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 239000003701 inert diluent Substances 0.000 description 1
- 230000002757 inflammatory effect Effects 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 239000007972 injectable composition Substances 0.000 description 1
- 229940102223 injectable solution Drugs 0.000 description 1
- 229960003786 inosine Drugs 0.000 description 1
- 230000010354 integration Effects 0.000 description 1
- 238000010255 intramuscular injection Methods 0.000 description 1
- 239000007927 intramuscular injection Substances 0.000 description 1
- 238000007912 intraperitoneal administration Methods 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- 239000002563 ionic surfactant Substances 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 229910052747 lanthanoid Inorganic materials 0.000 description 1
- 150000002602 lanthanoids Chemical class 0.000 description 1
- 239000004816 latex Substances 0.000 description 1
- 229920000126 latex Polymers 0.000 description 1
- 239000000787 lecithin Substances 0.000 description 1
- 235000010445 lecithin Nutrition 0.000 description 1
- 229940067606 lecithin Drugs 0.000 description 1
- 230000001665 lethal effect Effects 0.000 description 1
- 229960004194 lidocaine Drugs 0.000 description 1
- 239000012669 liquid formulation Substances 0.000 description 1
- 238000011068 loading method Methods 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 239000008176 lyophilized powder Substances 0.000 description 1
- 239000006249 magnetic particle Substances 0.000 description 1
- 238000012423 maintenance Methods 0.000 description 1
- 210000004962 mammalian cell Anatomy 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 229960004452 methionine Drugs 0.000 description 1
- 239000000693 micelle Substances 0.000 description 1
- 239000004530 micro-emulsion Substances 0.000 description 1
- 230000000813 microbial effect Effects 0.000 description 1
- 239000003094 microcapsule Substances 0.000 description 1
- 239000011859 microparticle Substances 0.000 description 1
- CFCUWKMKBJTWLW-BKHRDMLASA-N mithramycin Chemical compound O([C@@H]1C[C@@H](O[C@H](C)[C@H]1O)OC=1C=C2C=C3C[C@H]([C@@H](C(=O)C3=C(O)C2=C(O)C=1C)O[C@@H]1O[C@H](C)[C@@H](O)[C@H](O[C@@H]2O[C@H](C)[C@H](O)[C@H](O[C@@H]3O[C@H](C)[C@@H](O)[C@@](C)(O)C3)C2)C1)[C@H](OC)C(=O)[C@@H](O)[C@@H](C)O)[C@H]1C[C@@H](O)[C@H](O)[C@@H](C)O1 CFCUWKMKBJTWLW-BKHRDMLASA-N 0.000 description 1
- 229960004857 mitomycin Drugs 0.000 description 1
- 229960001156 mitoxantrone Drugs 0.000 description 1
- KKZJGLLVHKMTCM-UHFFFAOYSA-N mitoxantrone Chemical compound O=C1C2=C(O)C=CC(O)=C2C(=O)C2=C1C(NCCNCCO)=CC=C2NCCNCCO KKZJGLLVHKMTCM-UHFFFAOYSA-N 0.000 description 1
- 229940126619 mouse monoclonal antibody Drugs 0.000 description 1
- 229950006780 n-acetylglucosamine Drugs 0.000 description 1
- 230000001537 neural effect Effects 0.000 description 1
- 210000002682 neurofibrillary tangle Anatomy 0.000 description 1
- 230000000926 neurological effect Effects 0.000 description 1
- 230000003227 neuromodulating effect Effects 0.000 description 1
- 230000004007 neuromodulation Effects 0.000 description 1
- 210000002569 neuron Anatomy 0.000 description 1
- 230000006764 neuronal dysfunction Effects 0.000 description 1
- 230000007996 neuronal plasticity Effects 0.000 description 1
- 230000002981 neuropathic effect Effects 0.000 description 1
- 238000006386 neutralization reaction Methods 0.000 description 1
- 238000010899 nucleation Methods 0.000 description 1
- 238000007826 nucleic acid assay Methods 0.000 description 1
- 239000002853 nucleic acid probe Substances 0.000 description 1
- 238000011580 nude mouse model Methods 0.000 description 1
- QYSGYZVSCZSLHT-UHFFFAOYSA-N octafluoropropane Chemical compound FC(F)(F)C(F)(F)C(F)(F)F QYSGYZVSCZSLHT-UHFFFAOYSA-N 0.000 description 1
- 150000002482 oligosaccharides Polymers 0.000 description 1
- 238000005457 optimization Methods 0.000 description 1
- 210000003463 organelle Anatomy 0.000 description 1
- 150000002892 organic cations Chemical class 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 229960001592 paclitaxel Drugs 0.000 description 1
- 229940055729 papain Drugs 0.000 description 1
- 235000019834 papain Nutrition 0.000 description 1
- 230000007170 pathology Effects 0.000 description 1
- 229940111202 pepsin Drugs 0.000 description 1
- 239000000137 peptide hydrolase inhibitor Substances 0.000 description 1
- 230000008447 perception Effects 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- LFGREXWGYUGZLY-UHFFFAOYSA-N phosphoryl Chemical group [P]=O LFGREXWGYUGZLY-UHFFFAOYSA-N 0.000 description 1
- 230000000704 physical effect Effects 0.000 description 1
- 230000035790 physiological processes and functions Effects 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 239000004033 plastic Substances 0.000 description 1
- 229920003023 plastic Polymers 0.000 description 1
- 229960003171 plicamycin Drugs 0.000 description 1
- 229920001983 poloxamer Polymers 0.000 description 1
- 229920001200 poly(ethylene-vinyl acetate) Polymers 0.000 description 1
- 229920000747 poly(lactic acid) Polymers 0.000 description 1
- 239000004633 polyglycolic acid Substances 0.000 description 1
- 239000004626 polylactic acid Substances 0.000 description 1
- 239000004926 polymethyl methacrylate Substances 0.000 description 1
- 239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 description 1
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 1
- 229940068977 polysorbate 20 Drugs 0.000 description 1
- 229920000053 polysorbate 80 Polymers 0.000 description 1
- 229940068968 polysorbate 80 Drugs 0.000 description 1
- 239000011148 porous material Substances 0.000 description 1
- 230000008092 positive effect Effects 0.000 description 1
- 238000010149 post-hoc-test Methods 0.000 description 1
- 230000004481 post-translational protein modification Effects 0.000 description 1
- 230000001124 posttranscriptional effect Effects 0.000 description 1
- 229910000160 potassium phosphate Inorganic materials 0.000 description 1
- 235000011009 potassium phosphates Nutrition 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 239000003761 preservation solution Substances 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 229960004919 procaine Drugs 0.000 description 1
- MFDFERRIHVXMIY-UHFFFAOYSA-N procaine Chemical compound CCN(CC)CCOC(=O)C1=CC=C(N)C=C1 MFDFERRIHVXMIY-UHFFFAOYSA-N 0.000 description 1
- 230000000750 progressive effect Effects 0.000 description 1
- 229960003712 propranolol Drugs 0.000 description 1
- 210000004129 prosencephalon Anatomy 0.000 description 1
- 238000002818 protein evolution Methods 0.000 description 1
- 230000012846 protein folding Effects 0.000 description 1
- 230000004850 protein–protein interaction Effects 0.000 description 1
- 230000002797 proteolythic effect Effects 0.000 description 1
- 229950010131 puromycin Drugs 0.000 description 1
- 238000004445 quantitative analysis Methods 0.000 description 1
- 238000002708 random mutagenesis Methods 0.000 description 1
- 230000009257 reactivity Effects 0.000 description 1
- 238000010223 real-time analysis Methods 0.000 description 1
- 238000011897 real-time detection Methods 0.000 description 1
- 102000005962 receptors Human genes 0.000 description 1
- 108020003175 receptors Proteins 0.000 description 1
- 238000010188 recombinant method Methods 0.000 description 1
- 230000022532 regulation of transcription, DNA-dependent Effects 0.000 description 1
- 230000003252 repetitive effect Effects 0.000 description 1
- 230000010076 replication Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 238000012340 reverse transcriptase PCR Methods 0.000 description 1
- PYWVYCXTNDRMGF-UHFFFAOYSA-N rhodamine B Chemical compound [Cl-].C=12C=CC(=[N+](CC)CC)C=C2OC2=CC(N(CC)CC)=CC=C2C=1C1=CC=CC=C1C(O)=O PYWVYCXTNDRMGF-UHFFFAOYSA-N 0.000 description 1
- 230000033764 rhythmic process Effects 0.000 description 1
- 238000002702 ribosome display Methods 0.000 description 1
- 108091092562 ribozyme Proteins 0.000 description 1
- 239000012146 running buffer Substances 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 230000009919 sequestration Effects 0.000 description 1
- 238000013207 serial dilution Methods 0.000 description 1
- SQVRNKJHWKZAKO-OQPLDHBCSA-N sialic acid Chemical compound CC(=O)N[C@@H]1[C@@H](O)C[C@@](O)(C(O)=O)OC1[C@H](O)[C@H](O)CO SQVRNKJHWKZAKO-OQPLDHBCSA-N 0.000 description 1
- 238000001542 size-exclusion chromatography Methods 0.000 description 1
- 210000003625 skull Anatomy 0.000 description 1
- 238000002791 soaking Methods 0.000 description 1
- 239000001488 sodium phosphate Substances 0.000 description 1
- 229910000162 sodium phosphate Inorganic materials 0.000 description 1
- 229940074404 sodium succinate Drugs 0.000 description 1
- ZDQYSKICYIVCPN-UHFFFAOYSA-L sodium succinate (anhydrous) Chemical compound [Na+].[Na+].[O-]C(=O)CCC([O-])=O ZDQYSKICYIVCPN-UHFFFAOYSA-L 0.000 description 1
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
- 230000000392 somatic effect Effects 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 230000009870 specific binding Effects 0.000 description 1
- 238000005563 spheronization Methods 0.000 description 1
- 210000000952 spleen Anatomy 0.000 description 1
- 210000004989 spleen cell Anatomy 0.000 description 1
- 238000001694 spray drying Methods 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 239000012128 staining reagent Substances 0.000 description 1
- 239000012192 staining solution Substances 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 239000008223 sterile water Substances 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 238000004659 sterilization and disinfection Methods 0.000 description 1
- 150000005846 sugar alcohols Polymers 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 230000002459 sustained effect Effects 0.000 description 1
- 238000013268 sustained release Methods 0.000 description 1
- 230000000946 synaptic effect Effects 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- RCINICONZNJXQF-MZXODVADSA-N taxol Chemical compound O([C@@H]1[C@@]2(C[C@@H](C(C)=C(C2(C)C)[C@H](C([C@]2(C)[C@@H](O)C[C@H]3OC[C@]3([C@H]21)OC(C)=O)=O)OC(=O)C)OC(=O)[C@H](O)[C@@H](NC(=O)C=1C=CC=CC=1)C=1C=CC=CC=1)O)C(=O)C1=CC=CC=C1 RCINICONZNJXQF-MZXODVADSA-N 0.000 description 1
- NRUKOCRGYNPUPR-QBPJDGROSA-N teniposide Chemical compound COC1=C(O)C(OC)=CC([C@@H]2C3=CC=4OCOC=4C=C3[C@@H](O[C@H]3[C@@H]([C@@H](O)[C@@H]4O[C@@H](OC[C@H]4O3)C=3SC=CC=3)O)[C@@H]3[C@@H]2C(OC3)=O)=C1 NRUKOCRGYNPUPR-QBPJDGROSA-N 0.000 description 1
- 229960001278 teniposide Drugs 0.000 description 1
- 229960002372 tetracaine Drugs 0.000 description 1
- GKCBAIGFKIBETG-UHFFFAOYSA-N tetracaine Chemical compound CCCCNC1=CC=C(C(=O)OCCN(C)C)C=C1 GKCBAIGFKIBETG-UHFFFAOYSA-N 0.000 description 1
- 238000010257 thawing Methods 0.000 description 1
- 229940124598 therapeutic candidate Drugs 0.000 description 1
- 229940113082 thymine Drugs 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 230000014621 translational initiation Effects 0.000 description 1
- YNJBWRMUSHSURL-UHFFFAOYSA-N trichloroacetic acid Chemical compound OC(=O)C(Cl)(Cl)Cl YNJBWRMUSHSURL-UHFFFAOYSA-N 0.000 description 1
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 1
- 238000005199 ultracentrifugation Methods 0.000 description 1
- DJJCXFVJDGTHFX-XVFCMESISA-N uridine 5'-monophosphate Chemical compound O[C@@H]1[C@H](O)[C@@H](COP(O)(O)=O)O[C@H]1N1C(=O)NC(=O)C=C1 DJJCXFVJDGTHFX-XVFCMESISA-N 0.000 description 1
- 238000001291 vacuum drying Methods 0.000 description 1
- 229960003048 vinblastine Drugs 0.000 description 1
- JXLYSJRDGCGARV-XQKSVPLYSA-N vincaleukoblastine Chemical compound C([C@@H](C[C@]1(C(=O)OC)C=2C(=CC3=C([C@]45[C@H]([C@@]([C@H](OC(C)=O)[C@]6(CC)C=CCN([C@H]56)CC4)(O)C(=O)OC)N3C)C=2)OC)C[C@@](C2)(O)CC)N2CCC2=C1NC1=CC=CC=C21 JXLYSJRDGCGARV-XQKSVPLYSA-N 0.000 description 1
- 229960004528 vincristine Drugs 0.000 description 1
- OGWKCGZFUXNPDA-XQKSVPLYSA-N vincristine Chemical compound C([N@]1C[C@@H](C[C@]2(C(=O)OC)C=3C(=CC4=C([C@]56[C@H]([C@@]([C@H](OC(C)=O)[C@]7(CC)C=CCN([C@H]67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)C[C@@](C1)(O)CC)CC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-XQKSVPLYSA-N 0.000 description 1
- OGWKCGZFUXNPDA-UHFFFAOYSA-N vincristine Natural products C1C(CC)(O)CC(CC2(C(=O)OC)C=3C(=CC4=C(C56C(C(C(OC(C)=O)C7(CC)C=CCN(C67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)CN1CCC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-UHFFFAOYSA-N 0.000 description 1
- 230000000007 visual effect Effects 0.000 description 1
- 238000012800 visualization Methods 0.000 description 1
- 238000003260 vortexing Methods 0.000 description 1
- 235000012431 wafers Nutrition 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
- DGVVWUTYPXICAM-UHFFFAOYSA-N β‐Mercaptoethanol Chemical compound OCCS DGVVWUTYPXICAM-UHFFFAOYSA-N 0.000 description 1
Images
Classifications
-
- 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
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/395—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
- A61K39/39533—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals
- A61K39/3955—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals against proteinaceous materials, e.g. enzymes, hormones, lymphokines
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- 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
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/04—Immunostimulants
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/46—Hybrid immunoglobulins
-
- 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
- G01N33/577—Immunoassay; Biospecific binding assay; Materials therefor involving monoclonal antibodies binding reaction mechanisms characterised by the use of monoclonal antibodies; monoclonal antibodies per se are classified with their corresponding antigens
-
- 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
-
- 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
- C07K2317/10—Immunoglobulins specific features characterized by their source of isolation or production
- C07K2317/14—Specific host cells or culture conditions, e.g. components, pH or temperature
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/20—Immunoglobulins specific features characterized by taxonomic origin
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/20—Immunoglobulins specific features characterized by taxonomic origin
- C07K2317/21—Immunoglobulins specific features characterized by taxonomic origin from primates, e.g. man
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/20—Immunoglobulins specific features characterized by taxonomic origin
- C07K2317/24—Immunoglobulins specific features characterized by taxonomic origin containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/50—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
-
- 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
- C07K2317/90—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
- G01N2333/00—Assays involving biological materials from specific organisms or of a specific nature
- G01N2333/435—Assays involving biological materials from specific organisms or of a specific nature from animals; from humans
- G01N2333/46—Assays involving biological materials from specific organisms or of a specific nature from animals; from humans from vertebrates
- G01N2333/47—Assays involving proteins of known structure or function as defined in the subgroups
- G01N2333/4701—Details
- G01N2333/4709—Amyloid plaque core protein
-
- 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
- G01N2500/20—Screening for compounds of potential therapeutic value cell-free systems
-
- 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
Description
図1は、Aβ(1−42)単量体、Aβ(1−40)及びsAPPと対比した、球状凝集体への、8F5の選択性を示す。EC50値間の比として、8F5に対する選択性係数を計算することができる(HFIP中でAβ(1−42)単量体に対して:555.8/90.74=6.1;NH4OH中でAβ(1−42)単量体に対して:1007/90.74=11.1;Aβ(1−40)単量体に対して:667.8/90.74=7.4;sAPPに対して:>100)。
本発明は、本明細書中で「8F5」と呼ぶモノクローナル抗体ならびにその他の関連抗体(例えば8C5)に関する。例えば、アルツハイマー病及びその他の神経変性疾患の、診断、予防及び治療において、これらの抗体を使用し得る。
−短縮型Aβ(X−Y)球状凝集体を生じる広域プロテアーゼ(サーモリシン又はエンドプロテイナーゼGluCなど)でのN−末端アミノ酸X−23の切断可能性;
−広域プロテアーゼ及び抗体とのC末端アミノ酸24−Yの非近接性;及び
−これらのAβ(X−Y)球状凝集体の短縮型が、球状凝集体の3次元コア構造(その球状凝集体配座におけるコアエピトープAβ(20−Y)の近接性がより優れている。)を維持する。
R−X
の界面活性剤が使用される(式中、基「R」は、6から20、好ましくは10から14個の炭素原子を有する非分枝もしくは分枝アルキル又は6から20、好ましくは10から14個の炭素原子を有する非分枝もしくは分枝アルケニルであり、基「X」は酸性基又はその塩であり、Xは好ましくは−COC−M+、−SO3 −M+の中から選択され、最も好ましくは−OSO3 −M+であり、M+は、水素陽イオン又は無機もしくは有機陽イオンであり、好ましくは、アルカリ金属陽イオン、アルカリ土類金属陽イオン及びアンモニウム陽イオンから選択される。)。最も有利であるのは、特にRが非分枝アルキルである(そのalk−l−yl基を言及しなければならない。)、式(I)の界面活性剤である。特に好ましいのは、ドデシル硫酸ナトリウム(SDS)である。ラウリン酸及びオレイン酸も有利に使用できる。界面活性剤ラウロイルサルコシンのナトリウム塩(サルコシルNL−30又はGardol(R)としても知られている。)もまた特に有利である。
本発明のモノクローナル抗体(例えば8F5及び8CF)は、多くの興味深い有用性がある。例えば、上述のように、アルツハイマー病の、予防、治療及び診断において、本モノクローナル抗体を使用し得る。さらに、抗−抗体の開発において、本抗体を使用し得る。さらに、個々の抗体を産生するハイブリドーマにより、同一のモノクローナル抗体(即ち試薬)の継続的な源を安定して産生することができ、よって、様々な実験ならびに治療用途における抗体間の同一性が保証される。
モノクローナル抗体8F5及び8C5の産生
CFA(Sigma)中の、Barghornら、2005、J Neurochem、95、834−847に記載のようなA−beta(1−42)球状凝集体50ミリグラムを用いて、Balb/cマウスにsub−qで免疫付与し、1ヵ月間隔で2回免疫促進した。脾臓を回収し、脾臓細胞をマウス骨髄腫SP2/0細胞と5:1の比でPEG法により融合させた。2x105個細胞/mL、ウェルあたり200mLで、アザセリン/ヒポキサンチン選択培地中で96ウェル皿に融合細胞をプレーティングした。目で見えるコロニーが形成されるように細胞を増殖させ、直接ELISAアッセイにより、A−betaオリゴマー反応性について上清をアッセイした。抗体発現が安定になったと思われるまで、限界希釈により、A−betaオリゴマーに対する抗体を分泌するハイブリドーマをサブクローニングした。
Aβ(1−40)及びAβ(1−42)の単量体調製物と比較した、8F5及び8C5の優先的な球状凝集体への結合
8F5の選択性を試験するために、2つの別々に溶解したAβ(1−42)単量体調製物、ならびに単量体に対する代替物として新たに調製したAβ(1−40)を使用した。2種類の実験を行った。第一の実験において、球状凝集体由来であるが配座異性体非特異的MAb 6G1(S.Barghornら、J.Neurochemistry、95:834(2005))を捕捉抗体として用いて、サンドイッチ−ELISAにより、Aβ球状凝集体選択性について8F5を試験した。ビオチン化8F5を第二及び配座異性体選択的抗体として使用した。この実験を下記実施例2.1で述べる。
a)Aβ(1−42)球状凝集体の調製:
9mg Aβ(1−42)Fa.Bachemを1.5mL HFIP(1.1.1.3.3.3ヘキサフルオロ−2−プロパノール)中で溶解し、37℃にて1.5時間インキュベートした。溶液をスピードバック中で蒸発させ、396μL DMSO中で懸濁した(5mM保存溶液)。超音波水浴中で20秒間、試料を超音波破砕し、10分間振盪し、−20℃で一晩保存した。
3mgヒトAβ(1−42)、(Bachem Inc)カタログ番号H−1368を1.7mLエッペンドルフチューブ中の0.5mL HFIP中で溶解し(6mg/mL懸濁液)、透明な溶液が得られるまで37℃にて1.5時間振盪(Eppendorff Thermo mixer、1400rpm)した。スピードバック濃縮器中で試料を乾燥させ(1.5時間)、13.2μL DMSO中で懸濁し、10秒間振盪し、次いで、超音波浴中で破砕処理(20秒)し、10分間振盪した(例えばEppendorff Thermo mixer中で、1400rpm)。
1mg Aβ(1−42)固形粉末(Bachem Inc.カタログ番号H−1368)を0.5mL 0.1%NH4OH水(新たに調製)中で溶解し(2mg/mL)、すぐに30秒間室温で振盪し、透明な溶液を得た。さらなる使用のために−20℃で試料を保存した。
エッペンドルフチューブ中の0.25mL HFIP中で1mg ヒトAβ(1−40)、(Bachem Inc.カタログ番号H−1194)を懸濁した(4mg/mL懸濁液)。37℃にて1.5時間このチューブを振盪し(例えば、Eppendorff Thermo mixer中で、1400rpm)、透明な溶液を得て、その後、スピードバック濃縮器中で乾燥させた(1.5時間)。46μL DMSO中で試料を再溶解し(21.7mg/mL溶液)、10秒間振盪し、次いで超音波浴中で20秒間超音波破砕した。10分間振盪(例えばEppendorff Thermo mixer中、1400rpm)した後、さらなる使用のために−20℃で試料を保存した。
水中で新たに溶解した2μL 20mg/mL スルホ−NHS−ビオチン(Pierce Inc.カタログ番号21420)にPBS中の500μL 抗AβマウスMAb 8F5(0.64mg/mL)を添加し、30分間振盪(例えばEppendorff Thermo mixer中、1400rpm)し、透析チューブ中で6℃で16時間、500mL 20mM Na Pi;140mM NaCl;pH7.4に対して透析した。さらなる使用のために−20℃で透析液を保存した。8C5を適宜にビオチン化した。
1.F96 Cert.Maxisorp NUNC−Immuno Plate カタログ番号:439454
2.結合抗体:抗−AβマウスMAb 6G1、PBS中で溶解;濃度:0.4mg/mL;−20℃で保存。
3.コーティング緩衝液:100mM炭酸水素ナトリウム;pH9.6
4.ELISA用ブロッキング試薬;Roche Diagnostics GmbHカタログ番号:1112589
5.PBST−緩衝液:20mM NaH2PO4;140mM NaCl;0.05%Tween20;pH7.4
6.ウシアルブミン フラクションV、プロテアーゼ不含;Serva カタログ番号:11926.03;4℃で保存。
7.PBST+0.5%BSA−緩衝液:20mM NaH2PO4;140mM NaCl;0.05% Tween20;pH7.4+0.5%BSA
8.Aβ(1−42)−球状凝集体標準保存液:5mM NaH2PO4;35mM NaCl;pH7.4中の溶液;濃度:10.77mg/mL;−20℃で保存。
9.Aβ(1−42)単量体 HFIP処理標準保存液:3mM NaH2PO4;21mM NaCl;0.15%プルロニックF68;pH7.4中の溶液;濃度:0.45mg/mL;−20℃で保存。
10.NH4OH中のAβ(1−42)単量体標準保存液;0.1%NH4OH中の溶液、濃度:2mg/mL;−20℃で保存。
11.Aβ(1−40)単量体HFIP処理標準保存液;DMSO中の溶液;濃度:21.7mg/mL;−20℃で保存。
12.ビオチン化抗−AβマウスMAb クローン8F5;PBS中の溶液;濃度:0.24mg/mL;−80℃で保存。
13.ストレプトアビジン−POD共役物;Fa.Rocheカタログ番号:1089153。
14.染色:TMB;Roche Diagnostics GmbHカタログ番号:92817060;DMSO中42mM;水中3%H2O2;100mM酢酸ナトリウムpH4.9。
15.2Mスルホン酸溶液添加により染色を停止。
1.結合抗体:mMAb 6G1保存溶液を凍結融解し、コーティング緩衝液中で1:400希釈。
2.ブロッキング試薬:ブロッキング試薬を100mLの水中で溶解し、ブロッキング保存溶液を調製し、10mLずつ分注した液を−20℃で保存。ブロッキングするために各プレートに対して、27mL水で3mLブロッキング保存溶液を希釈。
3.Aβ標準溶液:
a)Aβ(1−42)−球状凝集体
−1076μL PBST+0.5%BSAに1μL Aβ(1−42)−球状凝集体標準保存液を添加=10μg/mL
−4950μL PBST+0.5%BSAに50μL 10μg/mL Aβ(1−42)−球状凝集体標準溶液を添加=100ng/mL
b)Aβ(1−42)単量体HFIP−処理
−440μL PBST+0.5%BSAに10μL Aβ(1−42)単量体HFIP−前処理標準保存液を添加=10μg/mL
−4950μL PBST+0.5%BSAに50μL 10μg/mL Aβ(1−42)単量体HFIP−前処理標準溶液を添加=100ng/mL
c)NH4OH中のAβ(1−42)単量体
−995μL PBST+0.5%BSAにNH4OH中の5μL Aβ(1−42)単量体標準保存液を添加=10μg/mL
−4950μL PBST+0.5%BSAにNH4OH中の50μL 10μg/mL Aβ(1−42)単量体標準溶液を添加=100ng/mL
d)Aβ(1−40)単量体HFIP−前処理
−49μL PBST+0.5%BSAに1μL Aβ(1−40)単量体HFIP前処理標準保存液を添加=430μg/mL
−420μL PBST+0.5%BSAに10μL 430μg/mL Aβ(1−40)単量体HFIP前処理標準溶液を添加=10μg/mL
−4950μL PBST+0.5%BSAに50μL 10μg/mL Aβ(1−40)単量体HFIP前処理標準溶液を添加=100ng/mL
1.ウェルあたり100μLの抗−Aβ mMAb 6G1溶液を添加し、4℃で一晩インキュベート。
2.抗体溶液を捨て、250μL PBST−緩衝液でウェルを3回洗浄。
3.ウェルあたり260μLのブロッキング溶液を添加し、室温で2時間インキュベート。
4.ブロッキング溶液を捨て、250μL PBST−緩衝液でウェルを3回洗浄。
5.標準を調製後、ウェルあたり標準100μLをプレートに添加。室温で2時間及び4℃にて一晩インキュベート。
6.標準溶液を捨て、250μL PBST−緩衝液でウェルを3回洗浄。
7.ウェルあたり200μLの一次ビオチン化抗体 8F5溶液を添加し、室温で1.5時間インキュベート。
8.抗体溶液を捨て、250μL PBST−緩衝液でウェルを3回洗浄。
9.ウェルあたり200μLの標識溶液を添加し、室温で1時間インキュベート。
10.標識溶液を捨て、250μL PBST−緩衝液でウェルを3回洗浄。
11.各ウェルにTMB溶液100μLを添加し、室温でインキュベート(5−15分間)。
12.染色を観察し、バックグラウンド染色開始後、停止溶液をウェルあたり50μL添加。
13.450nmでUV読み取り。
14.標準曲線から結果を計算。
15.評価
−ドットブロット法によるAβ球状凝集体に対するAβ単量体の差別化:4G8に対する、8F5及び8C5の比較。
Aβ(1−42)原線維に対する8F5及び8C5の結合
8F5抗体は可溶性球状凝集体に対して生成されたので、8F5は沈着斑又は原線維物質に結合しないはずであるという仮説を立てた。従って、重合化Aβ原線維懸濁液に対する8F5の結合について次の実施例に記載のように試験を行った。
この原線維懸濁液の10μL分注液を次のものとインキュベートした:
a)10μL 20mM Na Pi;140mM NaCl;pH7.4、
b)10μL 0.1μg/μL mMAb 6E10 Signet Inc.カタログ番号9320(20mM c)NaH2PO4;140mM NaCl;pH7.4中)、
d)10μL 0.1μg/μL mMAb 4G8 Signet Inc.カタログ番号9220(20mM Na Pi;140mM NaCl;pH7.4中)、
e)10μL 0.1μg/μL mMAb 8F5(8C5)(20mM Na Pi;140mM NaCl;pH7.4中)。
上清及び再懸濁ペレット試料を98℃にて5分間加熱し、次の条件下で4−20%Tris/グリシンゲルに添加した:
SDS−試料緩衝液:0.3g SDS;0.77g DTT;4mL 1M Tris/HCl pH6.8;8mLグリセロール;1mL 1%ブロモフェノールブルー(エタノール中);50mL 4−20%Tris/グリシンゲル:Invitrogen Inc.、番号EC6025BOXに水を添加。
ランニング緩衝液:7.5g Tris;36gグリシン;2.5g SDS;2.5Lまで水を添加。
20mAでPAGEを行った。クーマシーブルーR250によりゲルを染色した。
原線維結合Ab分画=RD原線維分画x100%/(RD原線維分画+RD上清分画)
Aβ(1−40)と比較した内在性Aβ(1−42)球状凝集体の選択的結合
Aβのオリゴマー概念に基づき、抗−Aβオリゴマー抗体がまたインビボでも、特に軽度認知障害及びAD患者において、Aβ(1−40)よりもAβ(1−42)オリゴマーに対して選択的結合を示し得ることが重要である。Aβ(1−40)よりもAβ(1−42)種を低下させる概念は、NSAIDを介したADの治療に対する治療アプローチにおいて使用されている(Weggenら、Nature 414、212−216(2001))。Aβ(1−40)との関連でAβ(1−42)を低下させるNSAIDは、アルツハイマー病の治療の中で最も高い有効性を示すことが確認されている。Aβ(1−42)/Aβ(1−40)比は、選択的治療ならびに診断目的のために重要である。
CNBr活性化セファロース4Bへの抗−Aβ mMAbの固定化:
a)mMAb 6E10 Signet Inc.、カタログ番号9320
b)mMAb 8F5
0.4g CNBr活性化セファロース4B(Amersham Pharmacia Bio−tech AB、Uppsala、Sweden、Inc.、No.17−0430−01)を10mLの1mM HCl水溶液に添加し、室温で30分間インキュベートした。CNBr活性化セファロース4Bを10mLの1mM HClで3回洗浄し、10mLの100mM NaHCO3;500mM NaCl;pH8.3で2回洗浄した。各固定化抗体に対して、100mM NaHCO3;500mM NaCl;pH8.3中の950μL 0.5mg/mL抗−Aβ mMAb溶液に、100μL CNBr活性化セファロース4Bマトリクスを添加した。室温で2時間振盪後、10000gで5分間、試料を遠心した。次に、500μL 100mMエタノールアミン;100mM NaHCO3;500mM NaCl;pH8.3緩衝液をビーズに添加し、試料を室温で1時間振盪した。抗−Aβ mMAb−セファロース試料を10000gで5分間遠心し、500μLの20mM NaH2PO4;140mM NaCl;pH7.4で5回洗浄した。6℃で保存する前に、0.02%最終濃度までアジ化ナトリウムを添加することにより試料を安定化した。
a)mMAb 6E10−セファロース
b)mMAb 8P5−セファロース
200μL 20mM NaH2PO4NaH2PO4;140mM NaCl;0.05%Tween20;pH7.4でヒト脳脊髄液試料200μLを希釈した。2μL 抗−Aβ mMAb−セファロースマトリクスにこれらの試料を添加し、室温で2時間撹拌した。これらの試料を10000gで5分間遠心した。上清を捨て、50μL PBSで抗−Aβ mMAb−セファロースを2回洗浄し、1分間撹拌し、遠心した(10000gで5分間)。上清を捨て、50μL 2mM NaH2PO4NaH2PO4;14mM NaCl、pH7.4中でセファロースビーズを懸濁し、次いで、室温で1分間撹拌して、10000gで5分間遠心した。次の段階において、抗−Aβ mMAb−セファロースビーズを50μL 50%CH3CN;0.2%TFA(水中)で処理した。室温で10分間振盪した後、試料を10000gで5分間遠心した。上清を回収し、1.5mLエッペンドルフチューブに移した。50μLの水と試料を混合し、スピードバック濃縮器中で蒸発させた。4μL 70%HCOOH中でペレットを再溶解し、室温で10分間振盪し、76μL 1M Tris溶液及び720μL 20mM NaH2PO4NaH2PO4;140mM NaCl;0.05%Tween20;pH7.4で中和した。
a)免疫沈降を行わないCSF試料中のAβ含量:
342μLの20mM NaH2PO4;140mM NaCl;0.05%Tween20;pH7.4で158μLのCSFを希釈した。この1:3.16希釈液をサンドイッチELISAに対して用い、評価中に考慮に入れた。
b)免疫沈降後のCSF試料中のAβ含量:
上述の手順からの試料を分析に用いた。
試薬リスト:
1.F96 Cert.Maxisorp NUNC−Immuno Plateカタログ番号:439454
2.結合抗体抗
抗−Aβ mAbクローン6E10;Signetカタログ番号9320;濃度:0.4mg/mL Bradford(BioRad);−20℃で保存。
3.カップリング緩衝液:100mM炭酸水素ナトリウム;pH9.6
4.ELISA用ブロッキング試薬;Roche Diagnostics GmbHカタログ番号:1112589
5.PBST−緩衝液:20mM NaH2PO4NaH2PO4;140mM NaCl;0.05%Tween20;pH7.4
6.Aβ(1−40)標準物質:Aβ(1−40)固形粉末;Bachemカタログ番号:H−1194;−20℃で保存。
7.一次抗体:抗−Aβ(1−40)ウサギpAb;アフィニティー精製;PBS中の溶液;濃度:0.039mg/mL;Signetカタログ番号9130−005;−20℃で保存。
8.標識試薬:抗−ウサギ−POD共役物;Fa.Jackson ImmunoResearchカタログ番号:111−036−045;
9.染色:TMB;Roche Diagnostics GmbHカタログ番号:92817060;DMSO中42mM;3%H2O2水;100mM酢酸ナトリウムpH4.9
10.停止溶液 2Mスルホン酸
1.結合抗体:抗−Aβ mAb 6E10(Signet Inc、カタログ番号9320)を0.7μg/mLの最終濃度に希釈する。
2.ブロッキング試薬:ブロッキング保存溶液の調製のために、100mL H2O中でブロッキング試薬を溶解させ、10mLずつ分注して−20℃で保存する。1枚のELISAプレートをブロッキングするために、ブロッキング保存溶液3mLを27mL H2Oで希釈する。
3.Aβ(1−40)単量体型標準希釈液:
A)Aβ(1−40)単量体標準保存液:250μL 0.1%NH4OH中で0.5mg Aβ(1−40)を溶解。濃度:2mg/mL;新たに調製;すぐに使用。
B)995μL PBSTに5μL Aβ(1−40)−単量体標準保存液を添加=10μg/mL。
C)4995μL PBSTに5μLの10μg/mL Aβ(1−40)−単量体標準溶液を添加=10ng/mL。
標準曲線
5.二次抗体:凍結乾燥抗−ウサギ−POD共役物を0.5mL H2O中で溶解し、500μLグリセロールと混合する。次に抗体濃縮液を100μLずつ分注して−20℃で保存する。この濃縮液をPBST緩衝液中で1:10,000希釈する。この抗体溶液をすぐに使用する。
6.TMB溶液:100mM酢酸ナトリウム、pH4.9 20mLを200μL TMB溶液及び3%過酸化水素29.5μLと混合する。この溶液をすぐに使用する。
1.ウェルあたり100μLの結合抗体溶液を添加し、4℃で一晩インキュベート。
2.抗体溶液を捨て、250μL PBST−緩衝液でウェルを3回洗浄。
3.ウェルあたり260μLのブロッキング溶液を添加し、室温で2時間インキュベート。
4.ブロッキング溶液を捨て、250μL PBST−緩衝液でウェルを3回洗浄。
5.標準物質及び試料調製後、標準及び試料をウェルあたり100μLプレートに添加し、室温で2時間、及び4℃で一晩インキュベート。
6.標準/試料溶液を捨て、250μL PBST−緩衝液でウェルを3回洗浄。
7.ウェルあたり200μLの一次抗体溶液を添加し、室温で1.5時間インキュベート。
8.抗体溶液を捨て、250μL PBST−緩衝液でウェルを3回洗浄。
9.ウェルあたり200μLの標識溶液を添加し、室温で1時間インキュベート。
10.標識溶液を捨て、250μL PBST−緩衝液でウェルを3回洗浄。
11.各ウェルにTMB溶液100μLを添加し、室温でインキュベート(5−15分間)。
12.発色を観察し、停止溶液をウェルあたり50μL添加。
13.450nmで読み取り。
14.標準曲線から結果を計算。
15.評価。
未知試料からの吸光度が検量線の直線範囲にない場合、適切な試料希釈でELISAを繰り返す。
試薬リスト:
1.F96 Cert.Maxisorp NUNC−Immuno Plateカタログ番号439454
2.結合抗体:抗−Aβ mAbクローン6E10;Signetカタログ番号9320;濃度:0.4mg/mL Bradford(BioRad);−20℃で保存。
3.コーティング緩衝液:100mM 炭酸水素ナトリウム;pH9.6
4.ELISA用ブロッキング試薬;Roche Diagnostics GmbHカタログ番号:1112589
5.PBST−緩衝液:20mM NaH2PO4NaH2PO4;140mM NaCl;0.05%Tween20;pH7.4
6.Aβ(1−42)標準物質:Aβ(1−42)固形粉末;Bachemカタログ番号:H−1368;−20℃で保存。
7.一次抗体:抗−Aβ(1−42)ウサギpAb;アフィニティー精製;ビオチン化;50%グリセロールを含むPBS中の溶液;濃度:0.25mg/mL;Signetカタログ番号9137−005;−20℃で保存。
8.標識試薬:抗−ウサギ−POD共役物;Fa.Jackson ImmunoResearch カタログ番号:111−036−045
9.染色:TMB;Roche Diagnostics GmbHカタログ番号:92817060;DMSO中42mM 3% H2O2(水中)100mM酢酸ナトリウム、pH4.9
停止溶液:2Mスルホン酸
1.結合抗体:抗−Aβ mAbクローン6E10をコーティング緩衝液中で1:400希釈。
2.ブロッキング試薬:100mL水中でブロッキング試薬を溶解し、ブロッキング保存溶液を調製し、10mLずつ分注して−20℃で保存。各プレートをブロッキングするために、3mLブロッキング保存溶液を27mLの水で希釈。
3.Aβ(1−42)単量体型、標準希釈液:
Aβ(1−42)単量体標準保存液:250μL 0.1%NH4OH中で0.5mg Aβ(1−42)を溶解;濃度:2mg/mL;新たに調製;すぐに使用。
995μL PBSTに5μLのAβ(1−42)−単量体標準保存液を添加=10μg/mL。
4995μL PBSTに5μLの10μg/mL Aβ(1−42)−単量体標準溶液を添加=10ng/mL。
1.一次抗体:PBST緩衝液中で抗−Aβ(1−42)pAb濃縮液を希釈。希釈係数は1/1250=0.2μg/mL。すぐに使用。
2.標識試薬:0.5mLの水中で抗−ウサギ−POD共役物の凍結乾燥物を再構成。500μLグリセロールを添加し、さらなる使用のために、−20℃で100μLずつ分注して保存。
PBST−緩衝液中で濃縮標識試薬を希釈。希釈係数は1/5000。すぐに使用。
3.TMB溶液:20mLの100mM酢酸ナトリウム pH4.9をTMB溶液200μL及び29.5μL 3%過酸化水素水と混合。すぐに使用。
1.ウェルあたり100μLの結合抗体溶液を添加し、4℃にて一晩インキュベート。
2.抗体溶液を捨て、250μL PBST−緩衝液でウェルを3回洗浄。
3.ウェルあたり260μLのブロッキング溶液を添加し、室温で2時間インキュベート。
4.ブロッキング溶液を捨て、250μL PBST−緩衝液でウェルを3回洗浄。
5.標準物質及び試料を調製後、標準物質及び試料をウェルあたり100μLプレートに添加。室温で2時間及び4℃で一晩インキュベート。
6.標準/試料溶液を捨て、250μL PBST−緩衝液でウェルを3回洗浄。
7.ウェルあたり200μLの一次抗体溶液を添加し、室温で1.5時間インキュベート。
8.抗体溶液を捨て、250μL PBST−緩衝液でウェルを3回洗浄。
9.ウェルあたり200μLの標識溶液を添加し、室温で1時間インキュベート。
10.標識溶液を捨て、250μL PBST−緩衝液でウェルを3回洗浄。
11.各ウェルにTMB溶液100μLを添加し、室温でインキュベート(5−15分間)。
12.染色を観察し、停止溶液をウェルあたり50μL添加。
13.450nmで読み取り。
14.標準曲線から結果を計算。
15.評価。
未知試料からの吸光度が検量線の直線範囲にない場合、適切な試料希釈でELISAを繰り返す。
a.6E10のような非球状凝集体選択的抗体と比較して、8F5(又は8C5)のような球状凝集体優先的抗体は、病状とは独立に、Aβ40に比してAβ42に選択的に結合する。Aβ40よりもAβ42を優先的に排除することは、AD治療(例えば、R−フルビロフェン、Flurizan(Myriad Inc.により公開された臨床治験でのAD治療において有効性が示されている。)の使用による。)における概念に従うので、この結果は、アルツハイマー病に対する奏功する治療であることを示す。この概念は、S.Weggenら(J Biol Chem.(2003)278(34):31831−7)により発表された。結果を図3で示す。
b1)ダイナビーズM−280 ヒツジ抗−マウスIgGによる免疫沈降(IP)
Aβ−抗体溶液:標準的精製手順に従い、ハイブリドーマから次の純粋な抗体を得た:
−mMAb 6E10;Fa.Signet番号9320;PBS緩衝液中1mg/mL
−mMAb 8F5;PBS緩衝液中1.65mg/mL
−mMAb 8C5;PBS緩衝液中1.44mg/mL
ダイナビーズ M−280ヒツジ抗−マウスIgG:
ヒツジ抗−マウスIgG(Invitrogen Inc.、カタログ番号:112.02)を磁気ビーズ(ダイナビーズ)に共有結合させる。
モノクローナルマウス抗体によるダイナビーズの活性化
−ダイナビーズ(ダイナビーズ M−280 ヒツジ抗−マウスIgG、Invitrogen;製品番号112.02)の保存懸濁液を泡立たないよう慎重に振盪した。
−1mLを無菌的に取り、1.5mL反応バイアルに移した。
−1mL免疫沈降(IP)−洗浄緩衝液(IP−洗浄緩衝液:PBS(20mM NaH2PO4、140mM NaCl、pH7.4)、0.1%(w/v)BSA)でダイナビーズを5分間3回洗浄した。
−洗浄手順中、上清を慎重に除去し、一方、磁気選別機スタンド(MSS)を用いてダイナビーズを反応バイアルの側面に固定化した。
−1mL PBS、0.1%(w/v)BSA中の40μg Aβ−抗体とともに、洗浄したダイナビーズをインキュベートした。
−4℃で振盪しながら、一晩インキュベートすることにより活性化を行った。
−1mL IP−洗浄緩衝液(PBS(20mM NaH2PO4、140mM NaCl、pH7.4)、0.1%(w/v)BSA)で活性化ダイナビーズを30分、4回洗浄した(再びMSSを使用)。
−活性化ダイナビーズを1mL PBS、0.1%(w/v)BSA、0.02(w/v)%Na−アジドで再懸濁し;ボルテックスにかけ、短時間遠心した。
−さらなる使用まで、抗体活性化ダイナビーズを4℃で保存した。
アルツハイマー病患者からの400μL CSFを4μL完全プロテアーゼ阻害剤カクテル(Roche Inc.カタログ番号:1697498、1mLの水中で1錠を溶解)に添加し、0.8μLの500mM PMSFをメタノール中で溶解した。10分後、1.6mLの20mM NaH2PO4、140mM NaCl、0.05%Tween20、pH7.4(PBST)を添加した。
25μLの抗−Aβ−ダイナビーズ懸濁液に調製済みCSF試料の250μL分注液を添加した。
−6℃にて16時間撹拌しながら免疫沈降させた。5分間、3回、1mL PBS/0.1%(w/v)BSAを用いて、最後に1mL 10mM Tris/HCl pH7.5緩衝液を用いて3分間、1回、続くビーズの洗浄を行った。洗浄手順中、上清を慎重に除去し、一方、磁気選別機スタンド(MSS)を用いてダイナビーズを反応バイアルの側面に固定化した。
H.W.Klafkiら、Analytical Biochemistry 237、24−29(1996)により最初に記載された手順及び後にJ.Wiltfangら、J.of Neurochemistry 81、481−496、2002によっても使用された手順に従う、8M尿素ポリアクリルアミドゲル電気泳動系及び続くウエスタンブロット分析により、Aβ1−40及びAβ1−42種の定量を行った。実験手順において2点のみ細かい変更を行った:
1)スタッキングゲル中のSDS濃度を0.1%(w/v)から0.25%(w/v)に調整した。
2)ウエスタンブロットに対して、抗体1E8(Senetek Drug Delivery Technologies Inc.St.Louis、Mo、USA)を抗−ヒトアミロイドβ(N)(82E1)マウスIgG mAb(IBL、カタログ番号:10323)に変更した。
7.5cmx9cmニトロセルロース0.45μm(BioRad Inc.)上でセミドライブロットチャンバー(BioRad Inc.、75mAで45分間)においてウエスタンブロット分析を行った。
ブロッティング緩衝液:6g Tris;28.1gグリシン;500mLメタノール;水で2.5Lに調整。
−露光時間180秒
30秒、60秒、120秒及び180秒後に画像を記録
露光時間が180秒の画像から結果を得た。
8F5は、APPトランスジェニックマウスにおいて新規物体認識を向上させる。
モノクローナル抗体8F5による認識指数の向上:
動物:3ヵ月齢の、FVBxC57B1バックグラウンド(APP/L、ReMYND、Leuven、Belgium)のアルツハイマー病の単一のトランスジェニックマウスモデルの雌マウス及び、FVBxC57B1バックグラウンドの野生型対照として陰性同腹仔を使用した。全マウスの遺伝子型を3週齢でポリメラーゼ連鎖反応(PCR)により調べ、PCRの結果が分かり、試験開始前に2回目のPCRによって二重にチェックした後、固有の識別番号を与えた。全マウスを無作為化し、齢をマッチさせ、即ち、コンピュータによってこれらに無作為の番号を与え、処置に対して無作為に割り振った。動物を新しいケージの状況に慣れさせるために試験開始18日前に処置群により動物をケージに入れた。前もってろ過した滅菌水(UVランプ)及び標準的なマウス餌を自由に摂取できるようにした。通気の良い貯蔵室の乾燥し涼しい状態下で餌を保管した。水及び餌の量を毎日調べ、必要な場合に補給し、1週間に2回新しいものに交換した。標準的な金属性ケージタイプRVS T2(面積540cm2)において逆転昼−夜リズム:(午後7時から開始し、14時間明るくし/10時間暗くする。)でマウスを飼育した。このケージに固体床及び層状の敷料を備え付けた。ケージあたりのマウス数は動物福祉の法律に従い制限した。行動テスト開始の5日前に、マウスをマクロロンタイプ2ケージに移し、行動テストに備え、実験室環境に適応させるために実験室に運んだ。
3種類の別個の実験を行い、これらの実験において、マウス(少なくとも1群あたり9匹)に対して第1、8及び15日に腹腔内注射(240μL/マウスで500μg)を行った。モノクローナル抗体6G1、8P5及びその他の非開示抗体(全てリン酸緩衝食塩水中で溶解)又は320μLリン酸緩衝食塩水でマウスを処置した。
3回目の処置日に新規物体認識テストを行った。使用したプロトコールは、Dewachterら(Journal of Neuroscience、2002、22(9):3445−3453)により記載の方法に従った。垂直壁が黒色で、床が半透明であり、ボックスの下に置かれたランプで薄暗い照明が当てられているプレキシグラスのオープンフィールドボックス(52x52x40cm)に1時間マウスを慣らした。翌日、動物を同じボックスに入れ、10分間の獲得試行を行った。この試行中、2個の同一の物体A(オレンジ色の樽又は緑色の立方体、±4cmの同様のサイズ)があるオープンフィールドにマウスを個別に入れ、持続時間(timeAA)及び物体Aを探る頻度(FreqAA)(動物の鼻が<1cmの距離で物体に向けられ、マウスが物体の方に向いて活発にスニッフィングしている場合)をコンピュータ化システムにより記録した(Ethovision、Noldus information Technology、Wageningen、Netherlands)。2.5時間後に行った10分間の想起試行(2回目の試行)の間、新規物体(物体B、緑色の立方体又はオレンジ色の樽)をオープンフィールドに既に馴染んだ物体(物体A)と一緒に置いた(それぞれ、FreqA及びFreqB及びTimeA及びTimeB)。両方の物体を探った持続時間に対する新規物体を探った持続時間の比[TimeB/(TimeA+TimeB)x100]として定義した認識指数(RI)を使用して、非空間的記憶を測定した。獲得試行中に物体Aを探った持続時間及び頻度(TimeAA及びFreqAA)を使用して、好奇心を測定した。
老齢APPトランスジェニックマウス及びアルツハイマー病患者の髄膜血管におけるアミロイド斑及びアミロイドの形態での、原線維性アミロイドベータペプチドに対する抗体8F5及び8C5の特異的反応のインシトゥ分析
抗体8F5及び8C5の原線維性Aβペプチド沈着に対する染色性が低いことから、これらの治療効果には、Aβペプチドの原線維性沈着型ではなく可溶性球状型への結合が介在することが示唆される。原線維性Aβペプチドへ結合する抗体により、凝集体の分解が速くなり得、可溶性Aβ濃度が続いて上昇し得るので(言い換えると、神経毒性であると考えられ、微小出血を導き得る。)、単量体ではなく可溶性球状凝集体に影響を与える抗体療法が好ましい。
これらの実験に対して、いくつかの脳物質試料を使用した:2名のAD患者(RZ16及びRZ55)からの皮質組織及び19ヵ月齢のTg2576マウス(APPSWE#001349、Taconic、Hudson、NY、USA)又は12ヵ月齢のAPP/Lマウス(ReMYND、Leuven、Belgium)からの皮質組織。
材料:
−アミロイド色素コンゴレッドキット(Sigma−Aldrich;HT−60)、これはアルコール性NaCl溶液、NaOH溶液及びコンゴレッド溶液から成る。
−染色キュベット
−顕微鏡スライド SuperfrostPlus及びカバースリップ
−エタノール、キシロール、包埋剤
試薬:
−NaCl溶液でNaOHを1:100希釈し、アルカリ性食塩水を得る。
−コンゴレッド溶液でアルカリ性食塩水を1:100希釈して、アルカリ性コンゴレッド溶液を得る(調製後15分以内に使用、ろ過)
−切片をスライド上に置き、乾燥させる。
−最初にアルカリ性食塩水中で30−40分間、次いでアルカリ性コンゴレッド溶液中で30−40分間、染色キュベット中でスライドをインキュベート。
材料
−TBS洗浄溶液(Tween20含有Tris緩衝食塩水;10x濃縮液;DakoCytomation S3306、DAKO、Hamburg、Germany)Aqua bidest中で1:10)
−メタノール中0.3%H2O2
−ブロッキング血清として、ロバ血清(Serotec、Dusseldorf、Germany)、TBST中5%
−TBST中で一定濃度に希釈したモノクローナルマウス−抗−球状凝集体抗体
−二次抗体:ビオチン化ロバ−抗−マウス抗体(Jackson Immuno/Dianova、Hamburg、Germany;715−065−150;TBST中で1:500に希釈)
−StreptABComprex(DakoCytomation K0377、DAKO、Hamburg、Germany)
−ペルオキシダーゼ基質キットジアミノベンジジン(=DAB;SK−4100;Vector Laboratories、Burlingame、CA、USA)
−SuperFrost Plus顕微鏡スライド及びカバースリップ
−キシロール不含包埋剤(Medite、Burgdorf、Germany;X−tra Kitt)
手順:
−浮いている切片を氷冷0.3%H2O2に移し、30分間インキュベート
−TBST緩衝液中で5分間洗浄
−ロバ血清/TBSTとともに20分間インキュベート
−一次抗体とともに室温で24時間インキュベート
−TBST緩衝液中で5分間洗浄
−ブロッキング血清とともに20分間インキュベート
−TBST緩衝液中で5分間洗浄
−二次抗体とともに周囲温度で60分間インキュベート
−TBST緩衝液中で5分間洗浄
−StreptABComprexとともに周囲温度で60分間インキュベート
−TBST緩衝液中で5分間洗浄
−DABとともに20分間インキュベート
−切片をスライド上に載せ、スライドを風乾させ、アルコールでスライドを脱水してスライドを包埋
記載の全抗体染色物質がコンゴ染色性のアミロイド沈着であることが分かった(図7(A))。球状凝集体優先的抗体8F5及び8C5は、実質及び髄膜のAβペプチドの好コンゴ性の沈着の染色が抗体6G1及び6E10よりも有意に少なかった(図7(B)−(C)、(H))。実質アミロイド斑染色の定量的分析から、全ての抗体が斑に結合することが明らかになったが(対照を上回る統計的に有意な密度)、抗体8F5及び8C5の結合は、参照抗体6E10(AβのN−末端配列に対して作製)の結合よりも有意に低く、参照抗体4G8(AβのN−末端配列に対して作製)以下であった(図7(D)−図(G))。抗体8F5及び8C5は、Aβ単量体又はAβ配列の一部を認識する抗体よりもアミロイド沈着への結合が少ない。原線維性Aβペプチドに結合する抗体での処置によって、脳組織においてアミロイド斑が急速に分解し、次いで可溶性Aβ濃度が上昇し得(これは、言い換えると、神経毒性であると考えられ、微小出血を引き起こし得る。)及び/又は血管アミロイドが急速に分解し得る(これもまた、微小出血を引き起こし得る。)。従って、単量体でなはく可溶性球状凝集体に影響を与える抗体療法が好ましい。
Claims (9)
- 可変重鎖及び可変軽鎖を含むモノクローナル抗体であって、
a)該可変重鎖は配列番号11によりコードされる可変重鎖であり、並びに、該可変軽鎖は配列番号12によりコードされる可変軽鎖であるか、又は、
b)該可変重鎖は配列番号19を含み、並びに、該可変軽鎖は配列番号20を含むものである、前記モノクローナル抗体。 - 可変重鎖が配列番号19を含み、及び、可変軽鎖が配列番号20を含む、請求項1に記載のモノクローナル抗体。
- American Type Culture Collection指定番号PTA−7407を有するハイブリドーマ。
- 請求項3に記載のハイブリドーマにより産生されるモノクローナル抗体(8C5)。
- アルツハイマー病の治療又は予防において使用するための、請求項1又は4に記載の抗体。
- 請求項1又は4に記載の抗体を含む医薬組成物。
- アルツハイマー病の治療又は予防のための医薬の製造における、請求項1又は4に記載の抗体の使用。
- アルツハイマー病を有する疑いのある患者から単離した生体試料中の抗原/抗体複合体の存在を検出する方法であって、
a)抗原/抗体複合体の形成に十分な時間及び条件下で、請求項1又は4に記載の抗体と該患者由来の生体試料を接触させる段階;及び
b)該試料中の該抗原/抗体複合体の存在(該複合体の存在は、該患者におけるアルツハイマー病の診断を示す)を検出する段階を含む方法。 - アルツハイマー病を有する疑いのある患者から単離した生体試料中の抗原/抗体複合体の存在を検出するためのキットであって、a)請求項1又は4に記載の抗体と、b)検出可能なシグナルを生成することができるシグナル生成化合物に結合された第二Aβタンパク質球状凝集体特異的抗体を含む共役物(該共役物の第二抗体は前記請求項1又は4に記載の抗体とは異なる)とを含むキット。
Applications Claiming Priority (5)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US74086605P | 2005-11-30 | 2005-11-30 | |
US60/740,866 | 2005-11-30 | ||
US77895006P | 2006-03-03 | 2006-03-03 | |
US60/778,950 | 2006-03-03 | ||
PCT/US2006/046148 WO2007064972A2 (en) | 2005-11-30 | 2006-11-30 | Monoclonal antibodies against amyloid beta protein and uses thereof |
Related Child Applications (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2012208727A Division JP2013047228A (ja) | 2005-11-30 | 2012-09-21 | モノクローナル抗体及びその使用 |
JP2013176314A Division JP5816234B2 (ja) | 2005-11-30 | 2013-08-28 | アミロイドベータタンパク質に対するモノクローナル抗体及びその使用 |
Publications (2)
Publication Number | Publication Date |
---|---|
JP2009519012A JP2009519012A (ja) | 2009-05-14 |
JP5486808B2 true JP5486808B2 (ja) | 2014-05-07 |
Family
ID=38069205
Family Applications (8)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2008543522A Active JP5486808B2 (ja) | 2005-11-30 | 2006-11-30 | アミロイドベータタンパク質に対するモノクローナル抗体及びその使用 |
JP2012208727A Pending JP2013047228A (ja) | 2005-11-30 | 2012-09-21 | モノクローナル抗体及びその使用 |
JP2013176314A Active JP5816234B2 (ja) | 2005-11-30 | 2013-08-28 | アミロイドベータタンパク質に対するモノクローナル抗体及びその使用 |
JP2015166837A Pending JP2016053017A (ja) | 2005-11-30 | 2015-08-26 | アミロイドベータタンパク質に対するモノクローナル抗体及びその使用 |
JP2017089395A Pending JP2017178950A (ja) | 2005-11-30 | 2017-04-28 | アミロイドベータタンパク質に対するモノクローナル抗体及びその使用 |
JP2018000073A Active JP7061875B2 (ja) | 2005-11-30 | 2018-01-04 | アミロイドベータタンパク質に対するモノクローナル抗体及びその使用 |
JP2020067220A Withdrawn JP2020143058A (ja) | 2005-11-30 | 2020-04-03 | アミロイドベータタンパク質に対するモノクローナル抗体及びその使用 |
JP2022035500A Withdrawn JP2022091786A (ja) | 2005-11-30 | 2022-03-08 | アミロイドベータタンパク質に対するモノクローナル抗体及びその使用 |
Family Applications After (7)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2012208727A Pending JP2013047228A (ja) | 2005-11-30 | 2012-09-21 | モノクローナル抗体及びその使用 |
JP2013176314A Active JP5816234B2 (ja) | 2005-11-30 | 2013-08-28 | アミロイドベータタンパク質に対するモノクローナル抗体及びその使用 |
JP2015166837A Pending JP2016053017A (ja) | 2005-11-30 | 2015-08-26 | アミロイドベータタンパク質に対するモノクローナル抗体及びその使用 |
JP2017089395A Pending JP2017178950A (ja) | 2005-11-30 | 2017-04-28 | アミロイドベータタンパク質に対するモノクローナル抗体及びその使用 |
JP2018000073A Active JP7061875B2 (ja) | 2005-11-30 | 2018-01-04 | アミロイドベータタンパク質に対するモノクローナル抗体及びその使用 |
JP2020067220A Withdrawn JP2020143058A (ja) | 2005-11-30 | 2020-04-03 | アミロイドベータタンパク質に対するモノクローナル抗体及びその使用 |
JP2022035500A Withdrawn JP2022091786A (ja) | 2005-11-30 | 2022-03-08 | アミロイドベータタンパク質に対するモノクローナル抗体及びその使用 |
Country Status (21)
Country | Link |
---|---|
US (6) | US8497072B2 (ja) |
EP (1) | EP1976877B2 (ja) |
JP (8) | JP5486808B2 (ja) |
KR (6) | KR20180058863A (ja) |
CN (2) | CN102898519B (ja) |
AU (1) | AU2006320392B2 (ja) |
BR (1) | BRPI0619357B8 (ja) |
CA (1) | CA2631195C (ja) |
DK (1) | DK1976877T4 (ja) |
ES (1) | ES2453941T5 (ja) |
HK (1) | HK1119186A1 (ja) |
HR (1) | HRP20140240T4 (ja) |
IL (8) | IL297746A (ja) |
MX (1) | MX2022005782A (ja) |
PL (1) | PL1976877T5 (ja) |
PT (1) | PT1976877E (ja) |
RS (1) | RS53270B2 (ja) |
RU (1) | RU2432362C2 (ja) |
SG (2) | SG10201706600VA (ja) |
WO (1) | WO2007064972A2 (ja) |
ZA (1) | ZA200804686B (ja) |
Families Citing this family (55)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE10303974A1 (de) | 2003-01-31 | 2004-08-05 | Abbott Gmbh & Co. Kg | Amyloid-β(1-42)-Oligomere, Verfahren zu deren Herstellung und deren Verwendung |
DK1954718T3 (en) | 2005-11-30 | 2014-12-15 | Abbvie Inc | Anti-A-globulomer antibodies antigenbindingsgrupper thereof, corresponding hybridomas, nucleic acids, vectors, host cells, methods for producing said antibodies, |
EP1976877B2 (en) | 2005-11-30 | 2016-10-05 | AbbVie Inc. | Monoclonal antibodies against amyloid beta protein and uses thereof |
MX358175B (es) * | 2005-12-12 | 2018-08-08 | Ac Immune Sa | Anticuerpos monoclonales especificos 1-42 beta con propiedades terapeuticas. |
AU2016204956B2 (en) * | 2006-07-14 | 2018-07-26 | Ac Immune S.A. | Humanized antibody against amyloid beta |
AU2013202799C1 (en) * | 2006-07-14 | 2019-01-03 | Ac Immune S.A. | Humanized antibody against amyloid beta |
SI2468770T1 (en) * | 2006-07-14 | 2018-05-31 | Ac Immune S.A. | A humanized antibody against amyloid beta. |
WO2008011348A2 (en) * | 2006-07-14 | 2008-01-24 | Ac Immune S.A. | Humanized antibody against amyloid beta |
SI2074145T1 (sl) * | 2006-10-02 | 2017-12-29 | Ac Immune S.A. | Humanizirano protitelo proti amiloid beta |
US8455626B2 (en) | 2006-11-30 | 2013-06-04 | Abbott Laboratories | Aβ conformer selective anti-aβ globulomer monoclonal antibodies |
IL199534A (en) | 2007-01-05 | 2013-01-31 | Univ Zuerich | An isolated human antibody capable of detecting a neoepitope in a disease-related protein, a polynucleotide encoding an antibody, a vector containing the polynucleotide, a host cell containing the polynucleotide or vector, a preparation containing the antibody and related methods and uses. |
KR101735257B1 (ko) * | 2007-01-05 | 2017-05-12 | 유니버시티 오브 취리히 | 질환 특이적 결합 분자 및 표적을 제공하는 방법 |
DK2104682T3 (en) | 2007-01-11 | 2017-01-16 | Michael Bacher | DIAGNOSIS AND TREATMENT OF ALZHEIMER'S AND OTHER DEMENTIA DISEASES |
EP2486928A1 (en) | 2007-02-27 | 2012-08-15 | Abbott GmbH & Co. KG | Method for the treatment of amyloidoses |
US7931899B2 (en) | 2007-05-14 | 2011-04-26 | Medtronic, Inc | Humanized anti-amyloid beta antibodies |
US8323654B2 (en) | 2007-05-14 | 2012-12-04 | Medtronic, Inc. | Anti-amyloid beta antibodies conjugated to sialic acid-containing molecules |
US20090232801A1 (en) * | 2007-05-30 | 2009-09-17 | Abbot Laboratories | Humanized Antibodies Which Bind To AB (1-42) Globulomer And Uses Thereof |
JP2010528583A (ja) * | 2007-06-11 | 2010-08-26 | エーシー イミューン ソシエテ アノニム | アミロイドβに対するヒト化抗体 |
US8613923B2 (en) | 2007-06-12 | 2013-12-24 | Ac Immune S.A. | Monoclonal antibody |
US8048420B2 (en) | 2007-06-12 | 2011-11-01 | Ac Immune S.A. | Monoclonal antibody |
EP2527366B1 (en) * | 2007-06-12 | 2017-08-16 | AC Immune S.A. | Monoclonal anti beta amyloid antibody |
EP2170389B1 (en) * | 2007-06-12 | 2014-10-29 | AC Immune S.A. | Humanized antibodies to amyloid beta |
CA2701793C (en) | 2007-10-05 | 2017-04-25 | Genentech, Inc. | Use of anti-amyloid beta antibody in ocular diseases |
KR101377535B1 (ko) | 2007-11-16 | 2014-03-27 | 더 락커펠러 유니버시티 | 원섬유 형태의 베타아밀로이드 단백질에 대해 특이적인 항체 |
WO2009070648A2 (en) * | 2007-11-27 | 2009-06-04 | Medtronic, Inc. | Humanized anti-amyloid beta antibodies |
EP2376120A2 (en) | 2008-11-25 | 2011-10-19 | Biogen Idec MA Inc. | Use of dr6 and p75 antagonists to promote survival of cells of the nervous system |
EP2949666B1 (en) | 2008-12-19 | 2018-12-19 | Biogen International Neuroscience GmbH | Human anti-alpha-synuclein antibodies |
US20110110942A1 (en) | 2009-11-12 | 2011-05-12 | Genentech, Inc. | Method of promoting dendritic spine density |
CA2796339C (en) | 2010-04-15 | 2020-03-31 | Abbott Laboratories | Amyloid-beta binding proteins |
WO2011149461A1 (en) * | 2010-05-27 | 2011-12-01 | Medtronic, Inc. | Anti-amyloid beta antibodies conjugated to sialic acid-containing molecules |
CN103179981B (zh) | 2010-07-30 | 2017-02-08 | Ac免疫有限公司 | 安全和功能性的人源化抗β‑淀粉样蛋白抗体 |
US9062101B2 (en) | 2010-08-14 | 2015-06-23 | AbbVie Deutschland GmbH & Co. KG | Amyloid-beta binding proteins |
WO2012082237A1 (en) | 2010-10-26 | 2012-06-21 | Arizona Board Of Regents, A Body Corporate Of The State Of Arizona Acting For And On Behalf Of Arizona State University | Immunization with amyloid-beta oligomers |
WO2012142301A2 (en) | 2011-04-12 | 2012-10-18 | Quanterix Corporation | Methods of determining a treatment protocol for and/or a prognosis of a patients recovery from a brain injury |
PT2723379T (pt) | 2011-06-23 | 2018-11-14 | Univ Of Zuerich | Moléculas de ligação anti-alfa-sinucleína |
KR101190573B1 (ko) | 2011-10-07 | 2012-10-18 | 대한민국 | 혈액 내 아밀로이드-베타 항체에 특이적으로 결합하는 신규 Aβ22(pE)-42 펩티드를 유효성분으로 포함하는 치매 진단용 키트 |
WO2013094614A1 (ja) * | 2011-12-22 | 2013-06-27 | Taoヘルスライフファーマ株式会社 | 合成アミロスフェロイドの製造方法 |
DE102011057021A1 (de) * | 2011-12-23 | 2013-06-27 | Forschungszentrum Jülich GmbH | Verfahren zur selektiven Quantifizierung von A-Beta-Aggregaten |
EP2995679A4 (en) * | 2013-03-11 | 2016-12-14 | Kansai Bunri Sogo Gakuen | PROCESS FOR PREPARING MONOCLONAL IGA ANTIBODIES |
KR102571391B1 (ko) | 2013-09-13 | 2023-08-29 | 제넨테크, 인크. | 정제된 재조합 폴리펩티드를 포함하는 방법 및 조성물 |
PL3044323T3 (pl) | 2013-09-13 | 2022-06-27 | F.Hoffmann-La Roche Ag | Sposoby wykrywania i ilościowego oznaczania białka komórki gospodarza w liniach komórkowych |
WO2015105973A1 (en) | 2014-01-08 | 2015-07-16 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | ANTIBODY TARGETING CELL SURFACE DEPOSITED COMPLEMENT PROTEIN C3d AND USE THEREOF |
EP2899543A1 (en) * | 2014-01-28 | 2015-07-29 | Predemtec GmbH | Biomarker and methods for early diagnosis of Alzheimer's disease |
TR201610497T1 (tr) * | 2014-01-29 | 2017-06-21 | Lg Chemical Ltd | Rekombi̇nant protei̇n galaktosi̇lasyonunu kültür ortaminin opti̇mi̇zasyonu vasitasiyla modüle etme yöntemi̇ |
MY179105A (en) * | 2014-02-08 | 2020-10-28 | Genentech Inc | Methods of treating alzheimer's disease |
WO2015165961A1 (en) | 2014-04-29 | 2015-11-05 | Affiris Ag | Treatment and prevention of alzheimer's disease (ad) |
WO2016014688A2 (en) | 2014-07-22 | 2016-01-28 | Junzhuan Qiu | Anti-pd-1 antibodies |
JP6909153B2 (ja) | 2014-08-05 | 2021-07-28 | アポロミクス インコーポレイテッド | 抗pd−l1抗体 |
MA41115A (fr) | 2014-12-02 | 2017-10-10 | Biogen Int Neuroscience Gmbh | Procédé de traitement de la maladie d'alzheimer |
CA3073066A1 (en) | 2017-08-22 | 2019-02-28 | Biogen Ma Inc. | Pharmaceutical compositions containing anti-beta amyloid antibodies |
US20190185091A1 (en) * | 2017-12-15 | 2019-06-20 | Dejan Mitrovic | Multifunctional motorcycle passenger seat system |
RU2703494C1 (ru) * | 2018-11-12 | 2019-10-18 | Федеральное государственное унитарное предприятие "Государственный научно-исследовательский институт особо чистых биопрепаратов" Федерального медико-биологического агентства | Моноклональное антитело 6g1 к производным морфина |
CN111518205B (zh) * | 2019-02-01 | 2022-03-29 | 长春金赛药业有限责任公司 | 人源化抗Aβ单克隆抗体及其应用 |
JP7373286B2 (ja) * | 2019-02-20 | 2023-11-02 | シスメックス株式会社 | 被検物質の情報の取得方法及び被検物質の捕捉方法 |
WO2022169211A1 (ko) * | 2021-02-03 | 2022-08-11 | 한양대학교 산학협력단 | 베타아밀로이드를 포함하는 만성통증 질환 예방 또는 치료용 조성물 |
Family Cites Families (743)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE2500076C3 (de) | 1975-01-02 | 1982-11-18 | SCHURA Blutderivate GmbH & Co KG, 4150 Krefeld | Verfahren zur Gewinnung von intravenös-verträglichen Gammaglobulinen |
US4634665A (en) * | 1980-02-25 | 1987-01-06 | The Trustees Of Columbia University In The City Of New York | Processes for inserting DNA into eucaryotic cells and for producing proteinaceous materials |
US5179017A (en) * | 1980-02-25 | 1993-01-12 | The Trustees Of Columbia University In The City Of New York | Processes for inserting DNA into eucaryotic cells and for producing proteinaceous materials |
US4399216A (en) | 1980-02-25 | 1983-08-16 | The Trustees Of Columbia University | Processes for inserting DNA into eucaryotic cells and for producing proteinaceous materials |
NO812612L (no) | 1980-08-06 | 1982-02-08 | Ferring Pharma Ltd | Enzym-inhibitorer. |
BR8108820A (pt) | 1980-09-24 | 1982-08-24 | Cetus Corp | Processo e sonda de diagnostico |
US4582788A (en) | 1982-01-22 | 1986-04-15 | Cetus Corporation | HLA typing method and cDNA probes used therein |
EP0084796B1 (en) | 1982-01-22 | 1990-05-02 | Cetus Corporation | Hla typing method and cdna probes used therein |
US4510245A (en) * | 1982-11-18 | 1985-04-09 | Chiron Corporation | Adenovirus promoter system |
GB8308235D0 (en) * | 1983-03-25 | 1983-05-05 | Celltech Ltd | Polypeptides |
US4816567A (en) | 1983-04-08 | 1989-03-28 | Genentech, Inc. | Recombinant immunoglobin preparations |
US4526039A (en) | 1983-06-23 | 1985-07-02 | The United States Of America As Represented By The Secretary Of Transportation | Removable strain gauge fixture and method for measuring accumulated strain in a material |
US4683194A (en) | 1984-05-29 | 1987-07-28 | Cetus Corporation | Method for detection of polymorphic restriction sites and nucleic acid sequences |
US5807715A (en) | 1984-08-27 | 1998-09-15 | The Board Of Trustees Of The Leland Stanford Junior University | Methods and transformed mammalian lymphocyte cells for producing functional antigen-binding protein including chimeric immunoglobulin |
US5128326A (en) | 1984-12-06 | 1992-07-07 | Biomatrix, Inc. | Drug delivery systems based on hyaluronans derivatives thereof and their salts and methods of producing same |
US5168062A (en) | 1985-01-30 | 1992-12-01 | University Of Iowa Research Foundation | Transfer vectors and microorganisms containing human cytomegalovirus immediate-early promoter-regulatory DNA sequence |
US4683202A (en) | 1985-03-28 | 1987-07-28 | Cetus Corporation | Process for amplifying nucleic acid sequences |
DE3590766C2 (ja) | 1985-03-30 | 1991-01-10 | Marc Genf/Geneve Ch Ballivet | |
US4666829A (en) | 1985-05-15 | 1987-05-19 | University Of California | Polypeptide marker for Alzheimer's disease and its use for diagnosis |
US4980286A (en) | 1985-07-05 | 1990-12-25 | Whitehead Institute For Biomedical Research | In vivo introduction and expression of foreign genetic material in epithelial cells |
US5618920A (en) * | 1985-11-01 | 1997-04-08 | Xoma Corporation | Modular assembly of antibody genes, antibodies prepared thereby and use |
US4968615A (en) | 1985-12-18 | 1990-11-06 | Ciba-Geigy Corporation | Deoxyribonucleic acid segment from a virus |
DE3600905A1 (de) | 1986-01-15 | 1987-07-16 | Ant Nachrichtentech | Verfahren zum dekodieren von binaersignalen sowie viterbi-dekoder und anwendungen |
CA1284931C (en) | 1986-03-13 | 1991-06-18 | Henry A. Erlich | Process for detecting specific nucleotide variations and genetic polymorphisms present in nucleic acids |
US5225539A (en) | 1986-03-27 | 1993-07-06 | Medical Research Council | Recombinant altered antibodies and methods of making altered antibodies |
GB8607679D0 (en) | 1986-03-27 | 1986-04-30 | Winter G P | Recombinant dna product |
US5107065A (en) | 1986-03-28 | 1992-04-21 | Calgene, Inc. | Anti-sense regulation of gene expression in plant cells |
CA1338457C (en) | 1986-08-22 | 1996-07-16 | Henry A. Erlich | Purified thermostable enzyme |
US5231170A (en) | 1986-08-27 | 1993-07-27 | Paul Averback | Antibodies to dense microspheres |
US5525339A (en) | 1986-08-27 | 1996-06-11 | Dms Pharmaceutical Inc. | Isolated components of dense microspheres derived from mammalian brain tissue and antibodies thereto |
US4946778A (en) | 1987-09-21 | 1990-08-07 | Genex Corporation | Single polypeptide chain binding molecules |
US5811310A (en) | 1986-09-30 | 1998-09-22 | Albert Einstein College Of Medicine Of Yeshiva Univ. | The Alz-50 monoclonal antibody and diagnostic assay for alzheimer's disease |
JPS63240797A (ja) | 1986-10-14 | 1988-10-06 | Shin Etsu Chem Co Ltd | モノクローナル抗体、その製法およびそれを含有する診断薬 |
AU611122B2 (en) | 1986-11-17 | 1991-06-06 | Scios Nova Inc. | Recombinant alzheimer's amyloid protein |
US5763192A (en) | 1986-11-20 | 1998-06-09 | Ixsys, Incorporated | Process for obtaining DNA, RNA, peptides, polypeptides, or protein, by recombinant DNA technique |
DE3702789A1 (de) | 1987-01-30 | 1988-08-18 | Bayer Ag | Vorlaeuferprotein des apc-polypeptids, dafuer codierende dna und diagnostische verwendung der dna und des proteins |
DE3883899T3 (de) | 1987-03-18 | 1999-04-22 | Sb2 Inc | Geänderte antikörper. |
JPS63245689A (ja) | 1987-03-31 | 1988-10-12 | Suntory Ltd | ヒトアミロイド関連蛋白モノクロ−ナル抗体 |
US5258498A (en) | 1987-05-21 | 1993-11-02 | Creative Biomolecules, Inc. | Polypeptide linkers for production of biosynthetic proteins |
US4880078A (en) | 1987-06-29 | 1989-11-14 | Honda Giken Kogyo Kabushiki Kaisha | Exhaust muffler |
CA1340802C (en) | 1987-08-15 | 1999-10-26 | Yasuyuki Takahashi | Senile amyloid precursor protein and an antibody specific for the same |
US5004697A (en) | 1987-08-17 | 1991-04-02 | Univ. Of Ca | Cationized antibodies for delivery through the blood-brain barrier |
CA1339014C (en) | 1987-10-08 | 1997-03-25 | Ronald E. Majocha | Antibodies to a4 amyloid peptide |
US5231000A (en) | 1987-10-08 | 1993-07-27 | The Mclean Hospital | Antibodies to A4 amyloid peptide |
JP2562623B2 (ja) | 1987-10-28 | 1996-12-11 | 国際電信電話株式会社 | ベースバンド合成法による偏波ダイバーシティ光受信方式 |
WO1989006689A1 (en) | 1988-01-13 | 1989-07-27 | The Mclean Hospital Corporation | Genetic constructs containing the alzheimer brain amyloid gene |
WO1989007657A1 (en) | 1988-02-10 | 1989-08-24 | The Children's Medical Center Corporation | Amyloid protein precursors, genetic probes, antibodies, and methods of use |
US5134062A (en) | 1988-03-22 | 1992-07-28 | Cornell Research Foundation, Inc. | Diagnosis of neuronal disorders and screening potential therapeutic agents therefor |
US5015570A (en) | 1988-05-13 | 1991-05-14 | Molecular Therapeutics, Inc. | Molecular diagnosis of Alzheimer Disease |
US6287793B1 (en) | 1988-08-19 | 2001-09-11 | Elan Pharmaceuticals, Inc. | Diagnostic methods for alzheimer's disease |
US5223409A (en) | 1988-09-02 | 1993-06-29 | Protein Engineering Corp. | Directed evolution of novel binding proteins |
JP3771253B2 (ja) | 1988-09-02 | 2006-04-26 | ダイアックス コープ. | 新規な結合タンパク質の生成と選択 |
AU634186B2 (en) | 1988-11-11 | 1993-02-18 | Medical Research Council | Single domain ligands, receptors comprising said ligands, methods for their production, and use of said ligands and receptors |
US5530101A (en) | 1988-12-28 | 1996-06-25 | Protein Design Labs, Inc. | Humanized immunoglobulins |
US20030229208A1 (en) | 1988-12-28 | 2003-12-11 | Protein Design Labs, Inc. | Humanized immunoglobulins |
IL162181A (en) † | 1988-12-28 | 2006-04-10 | Pdl Biopharma Inc | A method of producing humanized immunoglubulin, and polynucleotides encoding the same |
US5231020A (en) | 1989-03-30 | 1993-07-27 | Dna Plant Technology Corporation | Genetic engineering of novel plant phenotypes |
US5262332A (en) | 1989-04-05 | 1993-11-16 | Brigham And Women's Hospital | Diagnostic method for Alzheimer's disease: examination of non-neural tissue |
AU5525090A (en) | 1989-04-14 | 1990-11-16 | Research Foundation For Mental Hygiene, Inc. | Monoclonal antibody to amyloid peptide |
CA2016842A1 (en) | 1989-05-16 | 1990-11-16 | Richard A. Lerner | Method for tapping the immunological repertoire |
EP0478627A4 (en) | 1989-05-16 | 1992-08-19 | William D. Huse | Co-expression of heteromeric receptors |
CA2016841C (en) | 1989-05-16 | 1999-09-21 | William D. Huse | A method for producing polymers having a preselected activity |
US5234814A (en) | 1989-06-01 | 1993-08-10 | Du Pont Merck Pharmaceutical Company | Diagnostic assay for alzheimer's disease |
EP0411974A1 (en) | 1989-07-05 | 1991-02-06 | N.V. Innogenetics S.A. | Monoclonal antibodies to a neurofibrillary tangle antigen |
EP0415801A1 (en) | 1989-07-05 | 1991-03-06 | N.V. Innogenetics S.A. | Monoclonal antibodies against activated microglial cells |
AU6430190A (en) | 1989-10-10 | 1991-05-16 | Pitman-Moore, Inc. | Sustained release composition for macromolecular proteins |
JP2571874B2 (ja) | 1989-11-06 | 1997-01-16 | アルカーメス コントロールド セラピューティクス,インコーポレイテッド | タンパク質マイクロスフェア組成物 |
GB8928874D0 (en) | 1989-12-21 | 1990-02-28 | Celltech Ltd | Humanised antibodies |
WO1991010737A1 (en) | 1990-01-11 | 1991-07-25 | Molecular Affinities Corporation | Production of antibodies using gene libraries |
US5780225A (en) | 1990-01-12 | 1998-07-14 | Stratagene | Method for generating libaries of antibody genes comprising amplification of diverse antibody DNAs and methods for using these libraries for the production of diverse antigen combining molecules |
CA2050918A1 (en) | 1990-01-12 | 1991-07-13 | Raju Kucherlapati | Generation of xenogeneic antibodies |
US6075181A (en) | 1990-01-12 | 2000-06-13 | Abgenix, Inc. | Human antibodies derived from immunized xenomice |
AU7121191A (en) | 1990-02-26 | 1991-10-10 | Albert Einstein College Of Medicine Of Yeshiva University | Diagnostic assay for alzheimer's disease |
US5753624A (en) | 1990-04-27 | 1998-05-19 | Milkhaus Laboratory, Inc. | Materials and methods for treatment of plaquing disease |
US5427908A (en) | 1990-05-01 | 1995-06-27 | Affymax Technologies N.V. | Recombinant library screening methods |
GB9015198D0 (en) | 1990-07-10 | 1990-08-29 | Brien Caroline J O | Binding substance |
ES2139598T3 (es) | 1990-07-10 | 2000-02-16 | Medical Res Council | Procedimientos para la produccion de miembros de parejas de union especifica. |
DE4022247A1 (de) | 1990-07-12 | 1992-01-16 | Hoechst Ag | Verfahren zur extraktiven abtrennung von 2-alkylthio-5-phenylpyrimidinen aus ihren reaktionsgemischen |
EP0542810A1 (en) | 1990-08-02 | 1993-05-26 | B.R. Centre Limited | Methods for the production of proteins with a desired function |
US6255458B1 (en) | 1990-08-29 | 2001-07-03 | Genpharm International | High affinity human antibodies and human antibodies against digoxin |
US5661016A (en) | 1990-08-29 | 1997-08-26 | Genpharm International Inc. | Transgenic non-human animals capable of producing heterologous antibodies of various isotypes |
US5814318A (en) | 1990-08-29 | 1998-09-29 | Genpharm International Inc. | Transgenic non-human animals for producing heterologous antibodies |
US6300129B1 (en) | 1990-08-29 | 2001-10-09 | Genpharm International | Transgenic non-human animals for producing heterologous antibodies |
US5545806A (en) | 1990-08-29 | 1996-08-13 | Genpharm International, Inc. | Ransgenic non-human animals for producing heterologous antibodies |
US5633425A (en) | 1990-08-29 | 1997-05-27 | Genpharm International, Inc. | Transgenic non-human animals capable of producing heterologous antibodies |
US5625126A (en) * | 1990-08-29 | 1997-04-29 | Genpharm International, Inc. | Transgenic non-human animals for producing heterologous antibodies |
ES2108048T3 (es) | 1990-08-29 | 1997-12-16 | Genpharm Int | Produccion y utilizacion de animales inferiores transgenicos capaces de producir anticuerpos heterologos. |
US5770429A (en) | 1990-08-29 | 1998-06-23 | Genpharm International, Inc. | Transgenic non-human animals capable of producing heterologous antibodies |
US5877397A (en) * | 1990-08-29 | 1999-03-02 | Genpharm International Inc. | Transgenic non-human animals capable of producing heterologous antibodies of various isotypes |
US5698426A (en) | 1990-09-28 | 1997-12-16 | Ixsys, Incorporated | Surface expression libraries of heteromeric receptors |
DE69129154T2 (de) | 1990-12-03 | 1998-08-20 | Genentech Inc | Verfahren zur anreicherung von proteinvarianten mit geänderten bindungseigenschaften |
JPH04252195A (ja) | 1991-01-29 | 1992-09-08 | Asahi Chem Ind Co Ltd | モノクローナル抗体及びハイブリドーマ |
EP1820858B1 (en) | 1991-03-01 | 2009-08-12 | Dyax Corporation | Chimeric protein comprising micro-protein having two or more disulfide bonds and embodiments thereof |
AU662148B2 (en) | 1991-04-10 | 1995-08-24 | Scripps Research Institute, The | Heterodimeric receptor libraries using phagemids |
JPH04320694A (ja) | 1991-04-22 | 1992-11-11 | Ono Pharmaceut Co Ltd | ヒトグリア細胞増殖抑制因子に対するモノクローナル抗体 |
ATE221379T1 (de) | 1991-05-01 | 2002-08-15 | Jackson H M Found Military Med | Verfahren zur behandlung infektiöser respiratorischer erkrankungen |
JPH04342883A (ja) | 1991-05-17 | 1992-11-30 | Sanden Corp | 容量可変型斜板式圧縮機 |
EP0519596B1 (en) | 1991-05-17 | 2005-02-23 | Merck & Co. Inc. | A method for reducing the immunogenicity of antibody variable domains |
WO1994004679A1 (en) | 1991-06-14 | 1994-03-03 | Genentech, Inc. | Method for making humanized antibodies |
WO1992022324A1 (en) | 1991-06-14 | 1992-12-23 | Xoma Corporation | Microbially-produced antibody fragments and their conjugates |
DE4122599C2 (de) | 1991-07-08 | 1993-11-11 | Deutsches Krebsforsch | Phagemid zum Screenen von Antikörpern |
ES2136092T3 (es) | 1991-09-23 | 1999-11-16 | Medical Res Council | Procedimientos para la produccion de anticuerpos humanizados. |
WO1993008302A1 (en) | 1991-10-25 | 1993-04-29 | Itt Automotive Europe Gmbh | Monoclonal antibodies directed against the microtubule-associated protein tau |
JP3277211B2 (ja) | 1991-11-12 | 2002-04-22 | プラナ・バイオテクノロジー・リミテッド | アルツハイマー病の試験方法と治療方法 |
US20020009443A1 (en) | 1991-12-02 | 2002-01-24 | Vanitha Ramakrishman | Inhibitory immunoglobulin polypeptides to human pdgf beta receptor |
WO1993011236A1 (en) | 1991-12-02 | 1993-06-10 | Medical Research Council | Production of anti-self antibodies from antibody segment repertoires and displayed on phage |
WO1993011231A1 (en) | 1991-12-06 | 1993-06-10 | MAX-PLANCK-Gesellschaft zur Förderung der Wissenschaften e.V. | Tools for the diagnosis and treatment of alzheimer's disease |
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 |
CA2103887C (en) | 1991-12-13 | 2005-08-30 | Gary M. Studnicka | Methods and materials for preparation of modified antibody variable domains and therapeutic uses thereof |
US20010029293A1 (en) | 1992-01-27 | 2001-10-11 | Icos Corporation | Icam-related protein |
US5538845A (en) | 1992-02-05 | 1996-07-23 | Athena Neurosciences, Inc. | Beta-amyloid peptide production inhibitors and methods for their identification |
US5714350A (en) | 1992-03-09 | 1998-02-03 | Protein Design Labs, Inc. | Increasing antibody affinity by altering glycosylation in the immunoglobulin variable region |
US5912015A (en) | 1992-03-12 | 1999-06-15 | Alkermes Controlled Therapeutics, Inc. | Modulated release from biocompatible polymers |
US5733743A (en) * | 1992-03-24 | 1998-03-31 | Cambridge Antibody Technology Limited | Methods for producing members of specific binding pairs |
US5912120A (en) | 1992-04-09 | 1999-06-15 | The United States Of America As Represented By The Department Of Health And Human Services, | Cloning, expression and diagnosis of human cytochrome P450 2C19: the principal determinant of s-mephenytoin metabolism |
US5604102A (en) | 1992-04-15 | 1997-02-18 | Athena Neurosciences, Inc. | Methods of screening for β-amyloid peptide production inhibitors |
US5441870A (en) | 1992-04-15 | 1995-08-15 | Athena Neurosciences, Inc. | Methods for monitoring cellular processing of β-amyloid precursor protein |
US5455169A (en) | 1992-06-04 | 1995-10-03 | Alzheimer's Institute Of America, Inc. | Nucleic acids for diagnosing and modeling Alzheimer's disease |
US6610493B1 (en) | 1993-06-17 | 2003-08-26 | Brigham And Women's Hospital | Screening compounds for the ability to alter the production of amyloid-β peptide |
US5766846A (en) | 1992-07-10 | 1998-06-16 | Athena Neurosciences | Methods of screening for compounds which inhibit soluble β-amyloid peptide production |
US5837672A (en) | 1992-07-10 | 1998-11-17 | Athena Neurosciences, Inc. | Methods and compositions for the detection of soluble β-amyloid peptide |
ATE381614T1 (de) | 1992-07-24 | 2008-01-15 | Amgen Fremont Inc | Bildung von xenogenen antikörpern |
US5639641A (en) | 1992-09-09 | 1997-06-17 | Immunogen Inc. | Resurfacing of rodent antibodies |
TW258789B (ja) | 1992-09-28 | 1995-10-01 | Rohm & Haas | |
US5605811A (en) | 1992-10-26 | 1997-02-25 | Athena Neurosciences, Inc. | Methods and compositions for monitoring cellular processing of beta-amyloid precursor protein |
US5891623A (en) | 1992-11-09 | 1999-04-06 | Consorzio Per Le Biotecnologie | Diagnosis and treatment of AIDS onset |
ZA938243B (en) | 1992-11-12 | 1995-05-04 | Hybritech Inc | Altered affinity polypeptides of metal chelate binding antibodies |
US6010913A (en) * | 1992-12-14 | 2000-01-04 | N.V. Innogenetics S.A. | Isolated human tau peptide |
EP0683234B2 (en) | 1993-01-25 | 2007-06-06 | Takeda Chemical Industries, Ltd. | Antibody against beta-amyloid or their derivative and use thereof |
US5955317A (en) | 1993-01-25 | 1999-09-21 | Takeda Chemical Industries, Ltd. | Antibodies to β-amyloids or their derivatives and use thereof |
US5934272A (en) | 1993-01-29 | 1999-08-10 | Aradigm Corporation | Device and method of creating aerosolized mist of respiratory drug |
CA2115900A1 (en) | 1993-02-22 | 1994-08-23 | Gerald W. Becker | Pharmaceutical screens and antibodies |
US5840294A (en) | 1993-03-29 | 1998-11-24 | Queen's University At Kingston | Method for treating amyloidosis |
ES2318848T3 (es) | 1993-09-14 | 2009-05-01 | Pharmexa Inc. | Peptidos que se unen a pan dr para potenciar la respuesta inmunitaria. |
WO1995011311A1 (en) | 1993-10-20 | 1995-04-27 | Duke University | METHOD OF BINDING MATERIAL TO THE β-AMYLOID PEPTIDE |
US5565352A (en) | 1993-11-24 | 1996-10-15 | Arch Development Corporation | Deubiquitinating enzyme: compositions and methods |
JPH09506262A (ja) | 1993-12-08 | 1997-06-24 | ジェンザイム・コーポレイション | 特異的抗体の製造方法 |
AU1397495A (en) | 1993-12-13 | 1995-07-03 | Uab Research Foundation, The | Diagnostic tests and reagents for detecting risk of alzheimer's disease and stroke |
US6432404B1 (en) | 1993-12-23 | 2002-08-13 | Icos Corporation | Methods of inhibiting locomotor damage following spinal cord injury with α D-specific antibodies |
US6251395B1 (en) * | 1993-12-23 | 2001-06-26 | W. Michael Gallatin | Methods of inhibiting inflammation at the site of a central nervous system injury with alphaD-specific antibodies |
US6620915B2 (en) | 1993-12-23 | 2003-09-16 | Icos Corporation | Monoclonal antibodies specific for integrin α-d subunit |
JPH07209295A (ja) | 1994-01-10 | 1995-08-11 | Nikken Chem Co Ltd | 抗体及び酵素標識抗原並びにこれらを用いる酵素免疫測定法及び測定用キット |
JPH07209296A (ja) | 1994-01-10 | 1995-08-11 | Nikken Chem Co Ltd | 抗原及び酵素標識抗体並びにこれらを用いる酵素免疫測定法及び測定用キット |
US5877399A (en) | 1994-01-27 | 1999-03-02 | Johns Hopkins University | Transgenic mice expressing APP-Swedish mutation develop progressive neurologic disease |
DE69531148T2 (de) | 1994-01-31 | 2004-04-29 | Trustees Of Boston University, Boston | Bibliotheken aus polyklonalen antikörpern |
JPH07238096A (ja) | 1994-02-25 | 1995-09-12 | S R L:Kk | 抗ポリユビキチン・モノクローナル抗体およびポリユビキチンの測定方法 |
JPH07245700A (ja) | 1994-03-04 | 1995-09-19 | Minolta Co Ltd | デジタル複写機 |
US7473423B2 (en) | 1994-04-29 | 2009-01-06 | Mayo Foundation For Medical Education And Research | Human IgM antibodies, and diagnostic and therapeutic uses thereof particularly in the central nervous system |
JPH07309900A (ja) | 1994-05-20 | 1995-11-28 | Idemitsu Kosan Co Ltd | 抗ヒトプロカテプシンbモノクローナル抗体、それを産生するハイブリドーマ及びそれを用いたヒトプロカテプシンb又はヒトカテプシンbの測定方法 |
US5516637A (en) | 1994-06-10 | 1996-05-14 | Dade International Inc. | Method involving display of protein binding pairs on the surface of bacterial pili and bacteriophage |
JP3388897B2 (ja) | 1994-08-31 | 2003-03-24 | 三菱重工業株式会社 | 枚葉印刷機の排紙部 |
US6018021A (en) * | 1994-10-19 | 2000-01-25 | The Research Foundation Of State University Of New York | Human transaldolase: an autoantigen with a function in metabolism |
US6114133A (en) | 1994-11-14 | 2000-09-05 | Elan Pharmaceuticals, Inc. | Methods for aiding in the diagnosis of Alzheimer's disease by measuring amyloid-β peptide (x-≧41) |
EP0805678B1 (en) | 1995-01-05 | 2003-10-29 | THE BOARD OF REGENTS acting for and on behalf of THE UNIVERSITY OF MICHIGAN | Surface-modified nanoparticles and method of making and using same |
US5786180A (en) | 1995-02-14 | 1998-07-28 | Bayer Corporation | Monoclonal antibody 369.2B specific for β A4 peptide |
US5505576A (en) | 1995-03-09 | 1996-04-09 | Crane Carrier Company | Side loader for curbside refuse container |
JP3663228B2 (ja) | 1995-03-14 | 2005-06-22 | 株式会社医学生物学研究所 | ニューロプシンに対する抗体 |
WO1996028471A1 (en) | 1995-03-14 | 1996-09-19 | Praecis Pharmaceuticals Incorporated | Modulators of amyloid aggregation |
US6091001A (en) | 1995-03-29 | 2000-07-18 | Abgenix, Inc. | Production of antibodies using Cre-mediated site-specific recombination |
US6130364A (en) | 1995-03-29 | 2000-10-10 | Abgenix, Inc. | Production of antibodies using Cre-mediated site-specific recombination |
US5705330A (en) * | 1995-04-14 | 1998-01-06 | Abbott Laboratories | Chemiluminescent immunoassay for antibody detection |
US6019968A (en) * | 1995-04-14 | 2000-02-01 | Inhale Therapeutic Systems, Inc. | Dispersible antibody compositions and methods for their preparation and use |
KR100479146B1 (ko) | 1995-04-21 | 2005-05-16 | 셀 제네시스, 인코포레이티드 | 큰게놈dna결실유발법 |
KR100654645B1 (ko) | 1995-04-27 | 2007-04-04 | 아브게닉스, 인크. | 면역화된 제노마우스 유래의 인간 항체 |
EP0823941A4 (en) | 1995-04-28 | 2001-09-19 | Abgenix Inc | HUMAN ANTIBODIES DERIVED FROM IMMUNIZED XENO MOUSES |
US5712158A (en) | 1995-06-06 | 1998-01-27 | Warner-Lambert Company | Cell line for the rapid expression of functional calcium channels |
AU6255096A (en) | 1995-06-07 | 1996-12-30 | Mount Sinai School Of Medicine Of The City University Of New York, The | Pegylated modified proteins |
US6717031B2 (en) * | 1995-06-07 | 2004-04-06 | Kate Dora Games | Method for selecting a transgenic mouse model of alzheimer's disease |
JP3767755B2 (ja) | 1995-06-23 | 2006-04-19 | エーザイ株式会社 | 抗jcウイルス抗体 |
US6127977A (en) | 1996-11-08 | 2000-10-03 | Cohen; Nathan | Microstrip patch antenna with fractal structure |
DE69621940T2 (de) | 1995-08-18 | 2003-01-16 | Morphosys Ag | Protein-/(poly)peptidbibliotheken |
US5916597A (en) | 1995-08-31 | 1999-06-29 | Alkermes Controlled Therapeutics, Inc. | Composition and method using solid-phase particles for sustained in vivo release of a biologically active agent |
BR9610580A (pt) | 1995-09-14 | 2000-10-24 | Univ California | Anticorpos especìficos para prpse nativos |
FR2740454B1 (fr) | 1995-10-26 | 1997-11-21 | Rhone Poulenc Rorer Sa | Peptides capables d'inhiber l'endocytose de l'app et sequences nucleotidiques correspondantes |
AUPN649395A0 (en) | 1995-11-10 | 1995-12-07 | Ramsay Health Care Pty Ltd | A method for diagnosing alzheimer's disease |
FR2741881B1 (fr) | 1995-12-01 | 1999-07-30 | Centre Nat Rech Scient | Nouveaux derives de purine possedant notamment des prorietes anti-proliferatives et leurs applications biologiques |
AU1110297A (en) | 1995-12-12 | 1997-07-03 | Kyowa Hakko Kogyo Co. Ltd. | Novel dnas, novel polypeptides and novel antibodies |
JPH09178743A (ja) | 1995-12-27 | 1997-07-11 | Oriental Yeast Co Ltd | 可溶性appの定量法 |
WO1997026537A1 (en) | 1996-01-19 | 1997-07-24 | Research Corporation Technologies, Inc. | Methods for the detection of alzheimer's disease |
JP2978435B2 (ja) | 1996-01-24 | 1999-11-15 | チッソ株式会社 | アクリロキシプロピルシランの製造方法 |
WO1997028188A1 (en) | 1996-01-30 | 1997-08-07 | The Scripps Research Institute | A g protein-coupled receptor with an enlarged extracellular domain |
CZ292465B6 (cs) | 1996-02-09 | 2003-09-17 | Abbott Laboratories (Bermuda) Ltd. | Lidské protilátky k lidskému TNFalfa |
ATE508733T1 (de) | 1996-03-04 | 2011-05-15 | Penn State Res Found | Materialien und verfahren zur steigerung der zellulären internalisierung |
US5714352A (en) * | 1996-03-20 | 1998-02-03 | Xenotech Incorporated | Directed switch-mediated DNA recombination |
US5882644A (en) * | 1996-03-22 | 1999-03-16 | Protein Design Labs, Inc. | Monoclonal antibodies specific for the platelet derived growth factor β receptor and methods of use thereof |
US5855913A (en) * | 1997-01-16 | 1999-01-05 | Massachusetts Instite Of Technology | Particles incorporating surfactants for pulmonary drug delivery |
US5874064A (en) | 1996-05-24 | 1999-02-23 | Massachusetts Institute Of Technology | Aerodynamically light particles for pulmonary drug delivery |
US5985309A (en) | 1996-05-24 | 1999-11-16 | Massachusetts Institute Of Technology | Preparation of particles for inhalation |
US6699658B1 (en) * | 1996-05-31 | 2004-03-02 | Board Of Trustees Of The University Of Illinois | Yeast cell surface display of proteins and uses thereof |
US6300065B1 (en) | 1996-05-31 | 2001-10-09 | Board Of Trustees Of The University Of Illinois | Yeast cell surface display of proteins and uses thereof |
WO1997046678A1 (en) | 1996-06-06 | 1997-12-11 | Bayer Corporation | Nucleic acids and polypeptides related to presenilin |
WO1999009150A1 (en) | 1996-08-15 | 1999-02-25 | Bayer Corporation | Method of introducing modifications into a gene |
CA2183901A1 (en) | 1996-08-22 | 1998-02-23 | Johanna E. Bergmann | Targets for therapy and diagnosis of alzheimer's disease and down syndrome in humans |
US7521531B2 (en) | 1996-08-28 | 2009-04-21 | Immunomedics, Inc. | Methods for the purification of stable radioiodine conjugates |
JPH1075781A (ja) | 1996-08-30 | 1998-03-24 | Sumitomo Electric Ind Ltd | ヒトプロテアソームサブユニットp58蛋白質及びそれに特異的な抗体 |
EP0834561A1 (en) | 1996-09-27 | 1998-04-08 | Rijksuniversiteit te Leiden | A gene related to migraine in man |
US5916771A (en) | 1996-10-11 | 1999-06-29 | Abgenix, Inc. | Production of a multimeric protein by cell fusion method |
WO1998022120A1 (en) | 1996-11-19 | 1998-05-28 | The Wistar Institute Of Anatomy & Biology | Diagnostic and therapeutic reagents for alzheimer's disease |
ATE549918T1 (de) | 1996-12-03 | 2012-04-15 | Amgen Fremont Inc | Menschliche antikörper, die ausdrücklich menschliches tnf alpha binden |
US5919687A (en) | 1996-12-24 | 1999-07-06 | John Hopkins University | Recombinant N-SMases and nucleic acids encoding same |
DE69732306T2 (de) | 1997-01-16 | 2006-01-12 | Massachusetts Institute Of Technology, Cambridge | Zubereitung von partikelhaltigen arzneimitteln zur inhalation |
DE69835143T2 (de) | 1997-01-21 | 2007-06-06 | The General Hospital Corp., Boston | Selektion von proteinen mittels rns-protein fusionen |
JPH10210982A (ja) | 1997-01-31 | 1998-08-11 | Fuji Yakuhin Kogyo Kk | 新規なタンパク質 |
US20030068316A1 (en) | 1997-02-05 | 2003-04-10 | Klein William L. | Anti-ADDL antibodies and uses thereof |
US6218506B1 (en) | 1997-02-05 | 2001-04-17 | Northwestern University | Amyloid β protein (globular assembly and uses thereof) |
US6413940B1 (en) | 1997-02-07 | 2002-07-02 | Nymox Corporation | Pharmaceutically active agents that impede the formation of amyloid by impeding the genesis of DMS |
US7226730B1 (en) | 1997-02-26 | 2007-06-05 | The General Hospital Corporation | Transgenic animals and cell lines for screening drugs effective for the treatment or prevention of Alzheimer's Disease |
US7045531B1 (en) | 1997-03-11 | 2006-05-16 | The General Hospital Corporation | Composition comprising a metal chelator and a method of treating amyloidosis by administering the metal chelator |
RU2224510C2 (ru) | 1997-03-17 | 2004-02-27 | Би Ти Джи Интернэшнл Лимитед | Терапевтические композиции |
EP0985033A4 (en) | 1997-04-04 | 2005-07-13 | Biosite Inc | POLYVALENT AND POLYCLONAL LIBRARIES |
US8173127B2 (en) * | 1997-04-09 | 2012-05-08 | Intellect Neurosciences, Inc. | Specific antibodies to amyloid beta peptide, pharmaceutical compositions and methods of use thereof |
US20020086847A1 (en) | 1997-04-09 | 2002-07-04 | Mindset Biopharmaceuticals (Usa) | Recombinant antibodies specific for beta-amyloid ends, DNA encoding and methods of use thereof |
AU7171098A (en) | 1997-05-01 | 1998-11-24 | Board Of Regents, The University Of Texas System | Directed evolution of enzymes and antibodies |
US6235883B1 (en) | 1997-05-05 | 2001-05-22 | Abgenix, Inc. | Human monoclonal antibodies to epidermal growth factor receptor |
DK0981618T4 (da) | 1997-05-15 | 2011-11-21 | Genentech Inc | Anti-Apo-2-antistof |
BR9810118A (pt) | 1997-07-21 | 2000-08-08 | Arpi Matossian Rogers | Anticorpo monoclonal ou policlonal ou ligando equivalente, uso do mesmo, peptìdeo, oligopeptìdeo, polipeptìdeo ou proteìna, uso dos mesmos, sequência de cdna, rna ou dna genÈmico, clone bacteriofago, plasmìdeo biologicamente funcional ou vetor viral, célula hospedeira, processos para a detecção de um autoanticorpo de ocorrência natural, e, de tratamento |
IT1293511B1 (it) | 1997-07-30 | 1999-03-01 | Gentili Ist Spa | Anticorpi monoclonali catalitici ad attivita' proteasica per la lisi selettiva della componente proteica di placche e aggregati correlati |
US7923216B2 (en) | 1997-08-14 | 2011-04-12 | Institut Pasteur | In vivo modulation of neuronal transport |
ATE352558T1 (de) | 1997-08-14 | 2007-02-15 | Pasteur Institut | Hybdride tetanustoxinproteine die rückwirkend und transsynatisch ins zns migrieren |
NZ503033A (en) | 1997-08-26 | 2003-01-31 | Gliatech Inc | Inhibition of complement activation using anti-properdin agents |
US6666935B1 (en) | 1997-09-09 | 2003-12-23 | The Regents Of The University Of California | Sol-gel manufactured energetic materials |
FR2768346B1 (fr) | 1997-09-15 | 2002-04-19 | Fond Jean Dausset Ceph | Compose assurant l'inhibition de la preseniline 1 pour la preparation d'un medicament et agent de diagnostic |
US20040185039A1 (en) | 2002-08-30 | 2004-09-23 | Heinz Kohler | Therapeutic applications of noncovalent dimerizing antibodies |
US5989463A (en) | 1997-09-24 | 1999-11-23 | Alkermes Controlled Therapeutics, Inc. | Methods for fabricating polymer-based controlled release devices |
SE512663C2 (sv) | 1997-10-23 | 2000-04-17 | Biogram Ab | Inkapslingsförfarande för aktiv substans i en bionedbrytbar polymer |
AU1197599A (en) | 1997-10-24 | 1999-05-17 | Cornel Research Foundation, Inc. | Detection of neurodegenerative diseases |
US6710226B1 (en) * | 1997-12-02 | 2004-03-23 | Neuralab Limited | Transgenic mouse assay to determine the effect of Aβ antibodies and Aβ Fragments on alzheimer's disease characteristics |
US7964192B1 (en) | 1997-12-02 | 2011-06-21 | Janssen Alzheimer Immunotherapy | Prevention and treatment of amyloidgenic disease |
US6761888B1 (en) | 2000-05-26 | 2004-07-13 | Neuralab Limited | Passive immunization treatment of Alzheimer's disease |
US7179892B2 (en) * | 2000-12-06 | 2007-02-20 | Neuralab Limited | Humanized antibodies that recognize beta amyloid peptide |
US6743427B1 (en) | 1997-12-02 | 2004-06-01 | Neuralab Limited | Prevention and treatment of amyloidogenic disease |
US6750324B1 (en) | 1997-12-02 | 2004-06-15 | Neuralab Limited | Humanized and chimeric N-terminal amyloid beta-antibodies |
US6787523B1 (en) * | 1997-12-02 | 2004-09-07 | Neuralab Limited | Prevention and treatment of amyloidogenic disease |
TWI239847B (en) * | 1997-12-02 | 2005-09-21 | Elan Pharm Inc | N-terminal fragment of Abeta peptide and an adjuvant for preventing and treating amyloidogenic disease |
US6913745B1 (en) | 1997-12-02 | 2005-07-05 | Neuralab Limited | Passive immunization of Alzheimer's disease |
JP2002511385A (ja) | 1997-12-03 | 2002-04-16 | ニューララブ リミテッド | アルツハイマー病におけるβ−アミロイド関連変化を抑制する方法 |
WO1999031239A1 (fr) | 1997-12-15 | 1999-06-24 | Kyowa Hakko Kogyo Co., Ltd. | PROTEINE Nap1 HUMAINE |
US6730778B2 (en) | 1997-12-19 | 2004-05-04 | Pharmacia And Upjohn Company | Human sel-10 polypeptides and polynucleotides that encode them |
US6436989B1 (en) | 1997-12-24 | 2002-08-20 | Vertex Pharmaceuticals, Incorporated | Prodrugs of aspartyl protease inhibitors |
US7189703B2 (en) * | 1998-01-09 | 2007-03-13 | Intracell, Llc | Treatment and diagnosis of alzheimer's disease |
MX2008014823A (es) | 1998-02-11 | 2009-03-06 | Neurochem Int Ltd | Metodo para modular la activacion de macrofagos. |
WO1999045031A2 (en) | 1998-03-03 | 1999-09-10 | Abgenix, Inc. | Cd147 binding molecules as therapeutics |
US20050112543A1 (en) | 1998-03-11 | 2005-05-26 | The General Hospital Corporation | Method of screening for drugs useful in treating Alzheimer's disease |
US6323218B1 (en) | 1998-03-11 | 2001-11-27 | The General Hospital Corporation | Agents for use in the treatment of Alzheimer's disease |
US20050059591A1 (en) * | 1998-04-07 | 2005-03-17 | Neuralab Limited | Prevention and treatment of amyloidogenic disease |
US20050059802A1 (en) * | 1998-04-07 | 2005-03-17 | Neuralab Ltd | Prevention and treatment of amyloidogenic disease |
US20020029391A1 (en) | 1998-04-15 | 2002-03-07 | Claude Geoffrey Davis | Epitope-driven human antibody production and gene expression profiling |
DE69942021D1 (de) | 1998-04-20 | 2010-04-01 | Glycart Biotechnology Ag | Glykosylierungs-engineering von antikörpern zur verbesserung der antikörperabhängigen zellvermittelten zytotoxizität |
US6913756B1 (en) | 1998-04-29 | 2005-07-05 | The Uab Research Foundation | Monoclonal antibodies specific for anthrax and peptides derived from the antibodies thereof |
WO1999058157A1 (en) | 1998-05-08 | 1999-11-18 | Cramer Donald V | Method for inhibiting antibody-mediated rejection of xenogeneic tissues |
NO314086B1 (no) | 1998-05-08 | 2003-01-27 | Gemvax As | Peptider og farmasöytiske sammensetninger inneholdende disse, nukleinsyresekvenser som koder for slike peptider, plasmider og virusvektoreromfattende slike DNA-sekvenser samt anvendelse av disse for fremstilling avfarmasöytiske preparater til |
JP2002515429A (ja) | 1998-05-15 | 2002-05-28 | ネウロケム、インク | ニューロン細胞死を調節する方法 |
US20030147882A1 (en) | 1998-05-21 | 2003-08-07 | Alan Solomon | Methods for amyloid removal using anti-amyloid antibodies |
CA2333951C (en) | 1998-06-01 | 2012-02-28 | Ortho-Mcneil Pharmaceutical, Inc. | Method for treating neurodegenerative disorders |
JP2000050885A (ja) | 1998-06-02 | 2000-02-22 | Fuji Chemical Industries Ltd | カテプシンに対する抗体およびそれらの利用 |
DE69907456T2 (de) | 1998-06-24 | 2004-03-25 | Advanced Inhalation Research, Inc., Cambridge | Grosse poröse partikel ausgestossen von einem inhalator |
PT1092767E (pt) | 1998-07-02 | 2007-01-31 | Fuso Pharmaceutical Ind | Anticorpo monoclonal específico de protease de serina e sua utilização |
AU770555B2 (en) | 1998-08-17 | 2004-02-26 | Abgenix, Inc. | Generation of modified molecules with increased serum half-lives |
US7026455B2 (en) | 1998-09-01 | 2006-04-11 | Genentech, Inc. | Anti-pro 1343 antibodies |
BR9913850A (pt) | 1998-09-17 | 2001-10-23 | Otsuka Pharma Co Ltd | Gene ly6h |
US7083950B2 (en) | 1998-09-25 | 2006-08-01 | Regeneron Pharmaceuticals, Inc. | High affinity fusion proteins and therapeutic and diagnostic methods for use |
AU5999199A (en) | 1998-09-29 | 2000-04-17 | Kyowa Hakko Kogyo Co. Ltd. | Novel antibodies, drugs containing these antibodies and methods for screening compounds by using these antibodies |
US6660843B1 (en) | 1998-10-23 | 2003-12-09 | Amgen Inc. | Modified peptides as therapeutic agents |
EP1731913A3 (en) | 1998-12-02 | 2007-01-17 | The Trustees Of The University Of Pennsylvania | Methods and compositions for determining lipid peroxidation levels in oxidant stress syndromes and diseases |
AU769472B2 (en) | 1998-12-02 | 2004-01-29 | Florida Institute Of Technology | Methods and compositions for determining lipid peroxidation levels in oxidant stress syndromes and diseases |
CA2354456A1 (en) | 1998-12-14 | 2000-06-22 | University Of Miami | Connective tissue growth factor fragments and methods and uses thereof |
CN1328571B (zh) | 1998-12-23 | 2016-08-31 | 辉瑞大药厂 | 抗ctla-4的人单克隆抗体 |
DE19902550A1 (de) | 1999-01-22 | 2000-07-27 | Memorec Medical Molecular Rese | Aspartatprotease |
US20030185826A1 (en) | 1999-02-24 | 2003-10-02 | Tobinick Edward L. | Cytokine antagonists for the treatment of localized disorders |
DK2168984T3 (da) | 1999-03-25 | 2012-12-10 | Abbott Gmbh & Co Kg | Humane antistoffer, som binder humant IL-12, og fremgangsmåder til pro-duktion heraf |
FR2791263B1 (fr) | 1999-03-26 | 2001-04-27 | Halina Zofia Malina | Preparations des medicaments bases sur une reponse immunitaire contre l'accumulation de proteines modifiees par l'acide xanthurenique |
DK2270147T4 (da) | 1999-04-09 | 2020-08-31 | Kyowa Kirin Co Ltd | Fremgangsmåde til at kontrollere aktiviteten af immunologisk funktionelt molekyle |
US7527787B2 (en) | 2005-10-19 | 2009-05-05 | Ibc Pharmaceuticals, Inc. | Multivalent immunoglobulin-based bioactive assemblies |
US6787637B1 (en) | 1999-05-28 | 2004-09-07 | Neuralab Limited | N-Terminal amyloid-β antibodies |
PE20010212A1 (es) | 1999-06-01 | 2001-02-22 | Neuralab Ltd | Composiciones del peptido a-beta y procesos para producir las mismas |
UA81216C2 (en) | 1999-06-01 | 2007-12-25 | Prevention and treatment of amyloid disease | |
US20030082554A1 (en) | 1999-06-03 | 2003-05-01 | Curagen Corporation | Novel nucleic acid sequences encoding human cell adhesion molecule protein-like polypeptides |
JP2000354487A (ja) | 1999-06-15 | 2000-12-26 | Takashi Muramatsu | ミッドカイン受容体 |
US6582945B1 (en) | 1999-06-16 | 2003-06-24 | Boston Biomedical Research Institute | Immunological control of β-amyloid levels in vivo |
US20020002270A1 (en) | 1999-06-16 | 2002-01-03 | Raymond P. Zinkowski | Purified antigen for alzheimer's disease, and methods of obtaining and using same |
ATE445639T1 (de) | 1999-08-04 | 2009-10-15 | Univ Southern California | Globularer aufbau vom amyloid-beta- protein und deren verwendungen |
US7605238B2 (en) | 1999-08-24 | 2009-10-20 | Medarex, Inc. | Human CTLA-4 antibodies and their uses |
WO2001014424A2 (en) | 1999-08-24 | 2001-03-01 | Medarex, Inc. | Human ctla-4 antibodies and their uses |
ATE283487T1 (de) | 1999-09-01 | 2004-12-15 | Evotec Neurosciences Gmbh | Verfahren zur diagnose oder prognose von altersbedingter maculadegeneration |
IL142948A0 (en) | 1999-09-03 | 2002-04-21 | Univ Ramot | Agents and compositions and methods utilizing same useful in diagnosing and/or treating or preventing plaque forming diseases |
US20040013647A1 (en) * | 1999-09-03 | 2004-01-22 | Ramot At Tel-Aviv University Ltd. | Methods and compositions for treating a plaque-forming disease |
US6294171B2 (en) | 1999-09-14 | 2001-09-25 | Milkhaus Laboratory, Inc. | Methods for treating disease states comprising administration of low levels of antibodies |
JP2001122900A (ja) | 1999-10-21 | 2001-05-08 | Yasukazu Tanuma | 抗−DNaseγ抗体並びにその製造及び使用 |
EP1230269A2 (en) | 1999-11-03 | 2002-08-14 | Maxygen, Inc. | Antibody diversity generation |
US20070135337A2 (en) * | 1999-11-29 | 2007-06-14 | Neurochem (International) Limited | Vaccine for the Prevention and Treatment of Alzheimer's and Amyloid Related Diseases |
US20020094335A1 (en) | 1999-11-29 | 2002-07-18 | Robert Chalifour | Vaccine for the prevention and treatment of alzheimer's and amyloid related diseases |
AU784312B2 (en) | 1999-11-29 | 2006-03-09 | Bellus Health (International) Limited | Vaccine for the prevention and treatment of alzheimer's and amyloid related diseases |
IL149976A0 (en) | 1999-12-08 | 2002-12-01 | Mindset Biopharmaceuticals Usa | Chimeric peptides as immunogens, antibodies thereto, and methods for immunization using chimeric peptides or antibodies |
EP1752472A3 (en) | 1999-12-08 | 2007-04-25 | Intellect Neurosciences, Inc. | Chimeric amyloid beta peptides |
JP2001231578A (ja) | 1999-12-09 | 2001-08-28 | Kyowa Hakko Kogyo Co Ltd | Il−1ファミリーに属する蛋白質 |
US6670399B2 (en) | 1999-12-23 | 2003-12-30 | Neurochem (International) Limited | Compounds and methods for modulating cerebral amyloid angiopathy |
US20030077757A1 (en) * | 2000-01-11 | 2003-04-24 | Andrews William H. | Method of treating aging-related disorders |
JP2003520987A (ja) | 2000-01-17 | 2003-07-08 | コーニング オー.ティー.アイ.,エスピーエイ | 変調器を有する集積減衰器及びこれを使用するwdmシステムのための伝送モジュール |
US6806254B2 (en) | 2000-02-03 | 2004-10-19 | Nuvelo, Inc. | Methods and materials relating to alpha-2-macroglobulin-like polypeptides and polynucleotides |
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) |
CA2400838C (en) | 2000-02-21 | 2013-04-23 | Pharmexa A/S | Novel method for down-regulation of amyloid |
EP1259251B1 (en) | 2000-02-21 | 2005-10-19 | Pharmexa A/S | Novel method for down-regulation of amyloid |
CZ306683B6 (cs) * | 2000-02-24 | 2017-05-03 | Washington University | Léčivo pro prevenci nebo léčení preklinické nebo klinické Alzheimerovy nemoci |
EP1130032A1 (en) | 2000-02-28 | 2001-09-05 | Gesellschaft für biotechnologische Forschung mbH (GBF) | Single-chain antibodies recognizing the human vascular endothelial growth factor receptor-2 (VEGFR-2/KDR) |
GB0006398D0 (en) | 2000-03-16 | 2000-05-03 | Novartis Ag | Organic compounds |
WO2001071351A1 (en) * | 2000-03-22 | 2001-09-27 | The General Hospital Corporation | Method for treatment of neurodegenerative diseases |
AU2001253020A1 (en) | 2000-03-30 | 2001-10-15 | Elan Pharmaceuticals, Inc. | Screening markers and methods for neurodegenerative disorders |
JP2004505609A (ja) * | 2000-04-03 | 2004-02-26 | オックスフォード グリコサイエンシズ(ユーケー) リミテッド | 核酸分子、ポリペプチド、ならびにアルツハイマー病の診断および処置を含むそれらの使用 |
US7371365B2 (en) | 2000-04-04 | 2008-05-13 | Mayo Foundation For Medical Education And Research | Methods for detecting parenchymal plaques in vivo |
AUPQ712000A0 (en) | 2000-04-27 | 2000-05-18 | Medvet Science Pty. Ltd. | Antigenic peptide fragments of VapA protein, and uses thereof |
US20080009467A1 (en) * | 2000-05-01 | 2008-01-10 | Accera, Inc. | Combinations of medium chain triglycerides and therapeutic agents for the treatment and prevention of alzheimers disease and other diseases resulting from reduced neuronal metabolism |
AU2001259432B2 (en) | 2000-05-03 | 2005-04-21 | Amgen Inc. | Modified peptides, comprising an FC domain, as therapeutic agents |
WO2003105658A2 (en) | 2002-06-14 | 2003-12-24 | Brainsgate Ltd. | Methods and systems for management of alzheimer's disease |
DE60108111T2 (de) * | 2000-05-22 | 2005-12-08 | New York University | Synthetische immunogene jedoch nicht amyloidogene peptide, die homolog zu amyloid beta sind und deren verwendung zur induktion einer immunantwort gegen amyloid beta und amyloidaggregate |
DE60140252D1 (de) * | 2000-06-22 | 2009-12-03 | Genentech Inc | Agonistische monoklonale antikörper gegen trkc |
JP4252195B2 (ja) | 2000-06-27 | 2009-04-08 | 新日本無線株式会社 | 高周波線路の変換器 |
DK1297172T3 (da) | 2000-06-28 | 2006-02-13 | Glycofi Inc | Fremgangsmåder til frembringelse af modificerede glucoproteiner |
US7449308B2 (en) | 2000-06-28 | 2008-11-11 | Glycofi, Inc. | Combinatorial DNA library for producing modified N-glycans in lower eukaryotes |
NZ523428A (en) | 2000-06-28 | 2008-03-28 | Prana Biotechnology Ltd | Neurotoxic oligomers |
US6686449B2 (en) * | 2000-06-30 | 2004-02-03 | Pharmacia & Upjohn Company | Mutant presenilin 1 polypeptides |
WO2002002769A1 (en) | 2000-07-06 | 2002-01-10 | Vlaams Interuniversitair Instituut Voor Biotechnologie Vzw | A novel app mutation associated with an unusual alzheimer's disease pathology |
JP5362164B2 (ja) | 2000-07-07 | 2013-12-11 | バイオアークティック ニューロサイエンス アーベー | アルツハイマー病の予防及び治療 |
AU2007200047B2 (en) | 2000-07-07 | 2009-11-26 | Bioarctic Neuroscience Ab | Prevention and treatment of Alzheimer's disease |
US6524819B1 (en) | 2000-07-11 | 2003-02-25 | Incyte Genomics, Inc. | Down syndrome critical region 1-like proteins |
EP1172378A1 (en) | 2000-07-12 | 2002-01-16 | Richard Dr. Dodel | Human beta-amyloid antibody and use thereof for treatment of alzheimer's disease |
US20020009445A1 (en) | 2000-07-12 | 2002-01-24 | Yansheng Du | Human beta-amyloid antibody and use thereof for treatment of alzheimer's disease |
JP2002040023A (ja) | 2000-07-28 | 2002-02-06 | Mitsubishi Chemicals Corp | アルツハイマー病の検出方法 |
US20070009931A1 (en) * | 2000-08-04 | 2007-01-11 | Kirsch Wolff M | Negative correlation between IRP-2 and Transferrin receptor expression as a diagnostic of Alzheimer's disease |
DK1317479T3 (da) | 2000-09-06 | 2009-11-23 | Aventis Pharma Sa | Fremgangsmåder og sammensætninger for sygdomme, der er associeret med amyloidosis |
GB0024446D0 (en) | 2000-10-05 | 2000-11-22 | Glaxo Group Ltd | Protein |
IT1319277B1 (it) | 2000-10-24 | 2003-09-26 | Chiesi Farma Spa | Proteine di fusione utili per il trattamento di immunizzazione dellamalattia di alzheimer. |
CA2360219A1 (en) | 2000-10-27 | 2002-04-27 | Mount Sinai Hospital | Method for detecting alzheimer's disease |
WO2002036614A2 (en) | 2000-11-01 | 2002-05-10 | Insight Biotechnology Limited | Peptides for use in the treatment of alzheimer's disease |
WO2002094870A2 (en) | 2000-11-02 | 2002-11-28 | Curagen Corporation | Proteins and nucleic acids encoding same |
DE10055703A1 (de) | 2000-11-02 | 2002-05-08 | Peter F Pascoe | Verhinderung der Zellzerstörung und Beseitigung sklrotischer Amyloide verursacht durch organspezifische Antikörperaggregate |
WO2002035987A2 (en) | 2000-11-03 | 2002-05-10 | Massachusetts Institute Of Technology | METHODS FOR IDENTIFYING TREATMENTS FOR NEUROTOXICITY IN ALZHEIMER'S DISEASE CAUSED BY β-AMYLOID PEPTIDES |
US20060062786A1 (en) * | 2000-11-08 | 2006-03-23 | Human Genome Sciences, Inc. | Antibodies that immunospecifically bind to TRAIL receptors |
PT1346041E (pt) | 2000-11-27 | 2007-06-05 | Praecis Pharm Inc | Agentes terapêuticos e métodos para a sua utilização no tratamento de uma doença amiloidogénica. |
PE20020574A1 (es) | 2000-12-06 | 2002-07-02 | Wyeth Corp | Anticuerpos humanizados que reconocen el peptido amiloideo beta |
GB0100110D0 (en) | 2001-01-04 | 2001-02-14 | Univ Leeds | Modulation of calcium channel activity |
DE10101430B4 (de) * | 2001-01-13 | 2008-10-02 | Fraunhofer-Gesellschaft zur Förderung der angewandten Forschung e.V. | Lösliche cyclische Analoga zur Modulation der Amyloidogenese |
US20020132758A1 (en) | 2001-01-18 | 2002-09-19 | Shell John W. | Method for identifying compounds to treat medical pathologies associated with molecular crystallization |
US7264810B2 (en) * | 2001-01-19 | 2007-09-04 | Cytos Biotechnology Ag | Molecular antigen array |
AT500379B8 (de) | 2001-02-02 | 2009-08-15 | Axon Neuroscience | Tau-proteine |
US7175988B2 (en) | 2001-02-09 | 2007-02-13 | Human Genome Sciences, Inc. | Human G-protein Chemokine Receptor (CCR5) HDGNR10 |
US20040191264A1 (en) | 2001-02-19 | 2004-09-30 | Nielsen Klaus Gregorius | Synthetic vaccine agents |
ATE427760T1 (de) | 2001-02-23 | 2009-04-15 | Genentech Inc | Erodierbare polymere zur injektion |
JP4659236B2 (ja) | 2001-03-01 | 2011-03-30 | 大塚製薬株式会社 | 細胞傷害活性の測定法 |
US6815175B2 (en) | 2001-03-16 | 2004-11-09 | Cornell Research Foundation, Inc. | Anti-amyloid peptide antibody based diagnosis and treatment of a neurological disease or disorder |
FR2822238B1 (fr) * | 2001-03-16 | 2003-08-29 | Gemac | Methode et trousse pour le suivi des maladies neurodegeneratives |
DE10117281A1 (de) | 2001-04-06 | 2002-10-24 | Inst Molekulare Biotechnologie | Peptid zur Diagnose und Therapie der Alzheimer-Demenz |
WO2002085922A2 (en) | 2001-04-23 | 2002-10-31 | Curagen Corporation | Proteins and nucleic acids encoding same |
US6451547B1 (en) | 2001-04-25 | 2002-09-17 | Syn X Pharma | Process for differential diagnosis of Alzheimer's dementia and device therefor |
WO2002088307A2 (en) | 2001-04-30 | 2002-11-07 | Eli Lilly And Company | Humanized antibodies |
EP1385545B1 (en) | 2001-04-30 | 2009-01-07 | Eli Lilly And Company | Humanized antibodies recognizing the beta-amyloid peptide |
US7196163B2 (en) * | 2001-05-22 | 2007-03-27 | Merk & Co., Inc. | Assays using amyloid precursor proteins with modified β-secretase cleavage sites to monitor β-secretase activity |
JP4454230B2 (ja) | 2001-05-22 | 2010-04-21 | メルク エンド カムパニー インコーポレーテッド | β−セクレターゼ基質及びその使用 |
US6906169B2 (en) | 2001-05-25 | 2005-06-14 | United Biomedical, Inc. | Immunogenic peptide composition comprising measles virus Fprotein Thelper cell epitope (MUFThl-16) and N-terminus of β-amyloid peptide |
DE50103881D1 (de) | 2001-06-12 | 2004-11-04 | Wiltfang Jens | Monoklonaler Antikörper, mbAb 1E8, welcher für die zwei ersten N-terminalen Aminosäuren von Amyloid-beta-Peptiden spezifisch ist und dessen Verwendung zum Nachweis von Amyloid-beta Peptiden und/oder sAPPa |
JP4298498B2 (ja) | 2001-06-13 | 2009-07-22 | ゲンマブ エー/エス | 上皮成長因子受容体(egfr)に対するヒトモノクローナル抗体 |
US7595378B2 (en) | 2001-06-13 | 2009-09-29 | Genmab A/S | Human monoclonal antibodies to epidermal growth factor receptor (EGFR) |
US7094884B2 (en) | 2001-06-22 | 2006-08-22 | Roche Diagnostics Corporation | Soluble complexes of amylod β peptide and peptidyl prolyl isomerase chaperone and methods of making and using them |
AU2002345843A1 (en) | 2001-06-22 | 2003-01-08 | Panacea Pharmaceuticals, Inc. | Compositions and methods for preventing protein aggregation in neurodegenerative diseases |
CN1396183A (zh) | 2001-07-13 | 2003-02-12 | 张小如 | 降低脑内与老年痴呆有关的淀粉样变纤维的融合人抗体 |
WO2003008626A2 (en) | 2001-07-20 | 2003-01-30 | Oregon Health And Science University | Novel human nucleic acids encoding a pantothenate kinase and methods of use |
DE60226036T9 (de) | 2001-08-03 | 2016-09-29 | Medical & Biological Laboratories Co., Ltd. | ANTIKÖRPER, DER DAS GM1-GANGLIOSID-GEBUNDENE AMYLOID-b-PROTEIN ERKENNT, UND DNA, DIE FÜR DIESEN ANTIKÖRPER CODIERT |
JP4320694B2 (ja) | 2001-08-08 | 2009-08-26 | 株式会社オーク製作所 | 多重露光描画装置および多重露光式描画方法 |
AU2002324787A1 (en) | 2001-08-10 | 2003-02-24 | University Of South Florida | Modulation of angiogenesis by a-beta peptides |
CA2452104A1 (en) | 2001-08-17 | 2003-02-27 | Eli Lilly And Company | Use of antibodies having high affinity for soluble ass to treat conditions and diseases related to ass |
PT1416965E (pt) | 2001-08-17 | 2008-04-01 | Lilly Co Eli | Método de ensaio para a doença de alzheimer |
US20040192898A1 (en) | 2001-08-17 | 2004-09-30 | Jia Audrey Yunhua | Anti-abeta antibodies |
US7771722B2 (en) | 2001-08-17 | 2010-08-10 | Eli Lilly And Company | Assay method for alzheimer's disease |
EP1519740A4 (en) | 2001-08-17 | 2005-11-09 | Lilly Co Eli | FASTER IMPROVEMENT OF COGNITION IN DISEASES ASSOCIATED WITH A-BETA |
MY144532A (en) | 2001-08-20 | 2011-09-30 | Lundbeck & Co As H | Novel method for down-regulation of amyloid |
US20030082191A1 (en) | 2001-08-29 | 2003-05-01 | Poduslo Joseph F. | Treatment for central nervous system disorders |
DE60232672D1 (de) | 2001-10-01 | 2009-07-30 | Dyax Corp | Mehrkettige eukaryontische display-vektoren und deren verwendungen |
JP2003284574A (ja) | 2001-10-03 | 2003-10-07 | Pfizer Prod Inc | 核酸分子、ポリペプチド、ならびにアルツハイマー病の診断および処置を含むそれらの使用 |
EP1463527A4 (en) | 2001-10-04 | 2005-05-11 | Protein Therapeutics Inc | USE OF GAMMAGLOBULIN FOR THE TREATMENT OF IMMUNE-MEDIATED DISEASES |
DE60225821T2 (de) | 2001-10-04 | 2009-04-30 | Immuno-Biological Laboratories Co., Ltd., Takasaki | Reagens zum Nachweis eines Risikofaktors der Alzheimer-Krankheit, Nachweiskit dafür und Verfahren zum Nachweis eines Risikofaktors der Alzheimer-Krankheit unter ihrer Verwendung |
GB0124317D0 (en) * | 2001-10-10 | 2001-11-28 | Celltech R&D Ltd | Biological products |
KR100988949B1 (ko) | 2001-10-25 | 2010-10-20 | 제넨테크, 인크. | 당단백질 조성물 |
CN100488982C (zh) | 2001-11-02 | 2009-05-20 | 迪尔基因国际有限公司 | 与β-淀粉样蛋白结合并引起蛋白质构象转变的单克隆抗体的制备方法 |
CA2466841A1 (en) | 2001-11-21 | 2003-06-05 | New York University | Synthetic immunogenic but non-deposit-forming polypeptides and peptides homologous to amyloid .beta., prion protein, amylin, .alpha.-synuclein, or polyglutamine repeats for induction of an immune response thereto |
US7179606B2 (en) * | 2001-11-23 | 2007-02-20 | Syn X Pharma, Inc. | IG heavy chain, IG kappa, IG lambda biopolymer markers predictive of Alzheimer's disease |
US7026129B2 (en) | 2001-11-23 | 2006-04-11 | Syn X Pharma, Inc. | IG lambda biopolymer markers predictive of Alzheimers disease |
DE10158180A1 (de) * | 2001-11-28 | 2003-09-11 | Biovision Ag | Verfahren zum Nachweis von Morbus Alzheimer und zur Unterscheidung von Morbus Alzheimer gegenüber anderen demenziellen Erkrankungen, zugehörige Peptide und deren Verwendung |
WO2003046012A1 (en) | 2001-11-30 | 2003-06-05 | Crucell Holland B.V. | Antigen presenting cell targeting conjugate, an antigen presenting cell contacted with such conjugate, their use for vaccination or as medicament, and methods for their production or generation |
US7887833B2 (en) | 2001-12-04 | 2011-02-15 | Ben-Gurion University Of The Negev Research And Development Authority | Amphiphilic compounds and vesicles liposomes for organ-specified drug targeting |
WO2003051374A2 (en) | 2001-12-17 | 2003-06-26 | New York State Office Of Mental Health | SEQUESTRATION OF Aβ IN THE PERIPHERY IN THE ABSENCE OF IMMUNOMODULATING AGENT AS A THERAPEUTIC APPROACH FOR THE TREATMENT OR PREVENTION OF BETA-AMYLOID RELATED DISEASES |
EP1975179A1 (en) | 2001-12-26 | 2008-10-01 | Araclon Biotech, S.L. | Polyclonal antibodies, preparation method thereof and use of same |
US7781396B2 (en) | 2002-01-31 | 2010-08-24 | Tel Aviv University Future Technology Development L.P. | Peptides directed for diagnosis and treatment of amyloid-associated disease |
US20050153381A1 (en) | 2002-02-14 | 2005-07-14 | Marusich Michael F. | Immunocapture of mitochondrial protein complexes |
AR038568A1 (es) | 2002-02-20 | 2005-01-19 | Hoffmann La Roche | Anticuerpos anti-a beta y su uso |
DE10208812A1 (de) | 2002-03-01 | 2003-09-11 | Basf Plant Science Gmbh | Verfahren zur Herstellung von ungesättigten Fettsäuren |
AU2003213718A1 (en) | 2002-03-01 | 2003-09-16 | Szu-Yi Chou | Method of producing antigens |
AU2003209446B2 (en) | 2002-03-01 | 2008-09-25 | Immunomedics, Inc. | Bispecific antibody point mutations for enhancing rate of clearance |
EP1480666B1 (en) | 2002-03-05 | 2012-06-13 | Ramot at Tel-Aviv University Ltd. | Immunizing composition and method for inducing an immune response against the beta-secretase cleavage site of amyloid precursor protein |
MY139983A (en) | 2002-03-12 | 2009-11-30 | Janssen Alzheimer Immunotherap | Humanized antibodies that recognize beta amyloid peptide |
CN1305905C (zh) | 2002-03-22 | 2007-03-21 | Aprogen株式会社 | 人源化抗体及其制备方法 |
US20030190689A1 (en) | 2002-04-05 | 2003-10-09 | Cell Signaling Technology,Inc. | Molecular profiling of disease and therapeutic response using phospho-specific antibodies |
US7122374B1 (en) | 2002-04-09 | 2006-10-17 | Takaomi Saido | Amyloid beta-protein 3(pE)-42 antibodies and uses thereof |
WO2003086310A2 (en) | 2002-04-12 | 2003-10-23 | Ramot At Tel Aviv University Ltd. | Prevention of brain inflammation as a result of induced autoimmune response |
MXPA04010255A (es) | 2002-04-19 | 2008-03-04 | Univ Toronto | Metodos inmunologicos y composiciones para el tratamiento de la enfermedad de alzheimier. |
EP1497661B1 (en) | 2002-04-24 | 2009-11-25 | EVOTEC Neurosciences GmbH | Diagnostic use of ensadin-0477 gene and protein for neurodegenerative diseases |
EP1501531B1 (en) | 2002-04-25 | 2009-01-07 | Eli Lilly And Company | Method for treating anxiety in older subjects |
US20060257420A1 (en) | 2002-04-26 | 2006-11-16 | Cel-Sci Corporation | Methods of preparation and composition of peptide constructs useful for treatment of autoimmune and transplant related host versus graft conditions |
DE10221052A1 (de) | 2002-05-10 | 2003-12-04 | Transmit Technologietransfer | Wirkstoffe zu Therapie, Diagnostik und Prophylaxe von Erkrankungen, bei denen abnorme Proteinstrukturen auftreten |
WO2003100419A1 (en) | 2002-05-27 | 2003-12-04 | Bioceros B.V. | Methods for using the cd163 pathway for modulating an immune response |
EP1514118A2 (en) | 2002-06-20 | 2005-03-16 | EVOTEC Neurosciences GmbH | Diagnostic and therapeutic use of ras-gtpase-activating sh3-domain-binding protein 2 (g3bp2) for neurodegenerative diseases |
DE60317671T2 (de) | 2002-06-27 | 2008-10-30 | Evotec Neurosciences Gmbh | Diagnostische und therapeutische verwendung von ensadin-0581 gen und protein für neurodegenerative erkrankungen |
JP2006512895A (ja) | 2002-06-28 | 2006-04-20 | ドマンティス リミテッド | リガンド |
CN100572392C (zh) | 2002-07-12 | 2009-12-23 | 阿克松神经科学研究和发展股份有限公司 | 截短tau蛋白 |
CA2493119A1 (en) | 2002-07-17 | 2004-01-22 | Mindset Biopharmaceuticals Usa Inc. | Peptides and methods of screening immunogenic peptide vaccines against alzheimer's disease |
EP1544210A4 (en) | 2002-07-18 | 2006-01-25 | Masayasu Okochi | NEW NOTCH ORIGIN POLYPEPTIDES AND BIOMARKERS AND REAGENTS FOR WHICH THEY ARE USED |
US20040219142A1 (en) | 2002-07-19 | 2004-11-04 | Abbott Laboratories S.A. | Treatment of skin and nail disorders using TNFalpha inhibitors |
SI1524994T1 (sl) | 2002-07-19 | 2011-08-31 | Cytos Biotechnology Ag | Sestavki cepiv, ki vsebujejo amiloidne beta 1-6 antigenske mreĹľe |
US7250551B2 (en) * | 2002-07-24 | 2007-07-31 | President And Fellows Of Harvard College | Transgenic mice expressing inducible human p25 |
WO2004013172A2 (en) | 2002-07-24 | 2004-02-12 | Innogenetics N.V. | Fragments of beta-amyloid as targets for vaccination against alzheimer disease |
SE0202880D0 (sv) | 2002-07-26 | 2002-09-30 | Wieslab Ab | Complement system deficiency assay |
DE60326153D1 (de) | 2002-07-30 | 2009-03-26 | David Gladstone Inst | Verfahren zur diagnose von morbus alzheimer |
US20040138296A1 (en) | 2002-08-12 | 2004-07-15 | Pharmacia Corporation | Amyloid immunization and Cox-2 inhibitors for the treatment of alzheimer's disease |
AU2003256789A1 (en) | 2002-08-13 | 2004-02-25 | U.S. Department Of Veterans Affairs | Method of detecting and preventing alzheimer's disease, particularly at prodromal and early stages |
EP1535930B1 (en) | 2002-08-14 | 2010-10-06 | Mitsubishi Chemical Medience Corporation | Antibody specific to central nervous system tau protein |
AU2003259965A1 (en) | 2002-08-20 | 2004-03-11 | Neurogenetics, Inc. | Methods and compositions for modulating amyloid beta |
AU2003266302A1 (en) | 2002-08-23 | 2004-03-11 | Proteosys Ag | Method for the diagnosis of alzheimer disease |
JP2006516535A (ja) | 2002-09-12 | 2006-07-06 | ザ、リージェンツ、オブ、ザ、ユニバーシティ、オブ、カリフォルニア | 異なる配列のタンパク質から形成されたアミロイドに共通する高分子量凝集中間体に対して特異的な免疫原および対応する抗体 |
WO2005025516A2 (en) | 2003-09-12 | 2005-03-24 | The Regents Of The University Of California | Monoclonal antibodies specific for conformational epitopes of prefibrillar aggregates |
US7238488B2 (en) * | 2002-09-13 | 2007-07-03 | Grace Maresh | Therapeutic and diagnostic applications of perlecan domain I splice variants |
US20070010657A1 (en) * | 2002-09-13 | 2007-01-11 | Rainer Klocke | Cytoplasmic dynein heavy chain 1 genes, expression products, non-human animal model uses in human neurological diseases |
JP2006502188A (ja) | 2002-09-17 | 2006-01-19 | ニューヨーク ユニバーシティ | 年齢関連記憶欠陥(aami)、中程度認識欠陥(mci)、および痴呆を細胞周期インヒビターで処置する方法 |
JP4242128B2 (ja) | 2002-09-18 | 2009-03-18 | 武田薬品工業株式会社 | 脳アミロイドーシス予防・治療薬のスクリーニング方法 |
WO2004029629A1 (en) | 2002-09-27 | 2004-04-08 | Janssen Pharmaceutica N.V. | N-11 truncated amyloid-beta nomoclonal antibodies, compositions, methods and uses |
US7541440B2 (en) | 2002-09-30 | 2009-06-02 | Immunomedics, Inc. | Chimeric, human and humanized anti-granulocyte antibodies and methods of use |
JP2006508072A (ja) * | 2002-10-01 | 2006-03-09 | ノースウエスタン ユニバーシティ | アミロイドベータ由来拡散性リガンド(ADDLs)、ADDL代替物、ADDL結合性分子、およびそれらの使用 |
US20070213512A1 (en) | 2002-10-01 | 2007-09-13 | Krafft Grant A | Amyloid beta peptide analogs and assemblies thereof |
AU2003272925A1 (en) | 2002-10-04 | 2004-04-23 | Techno Network Shikoku Co., Ltd. | Monoclonal antibody against subtilisin-like proprotein convertase pace4 and utilization thereof |
US20040146512A1 (en) | 2002-10-09 | 2004-07-29 | Arnon Rosenthal | Methods of treating Alzheimer's disease using antibodies directed against amyloid beta peptide and compositions thereof |
US7923433B2 (en) | 2002-10-09 | 2011-04-12 | Activx Biosciences, Inc. | Activity-based probes and methods of their preparation and use |
AU2003279312A1 (en) | 2002-10-24 | 2004-05-13 | Evotec Neurosciences Gmbh | Diagnostic and therapeutic use of ensadin-0289 gene and protein for neurodegenerative diseases |
US20080014194A1 (en) * | 2003-10-31 | 2008-01-17 | Elan Pharmaceuticals, Inc. | Prevention and Treatment of Synucleinopathic and Amyloidogenic Disease |
TW200509968A (en) | 2002-11-01 | 2005-03-16 | Elan Pharm Inc | Prevention and treatment of synucleinopathic disease |
FR2846667B1 (fr) | 2002-11-06 | 2004-12-31 | Pasteur Institut | Fragments variables d'anticorps de camelides a chaine unique diriges contre le peptide beta-amyloide 1-42 et leurs applications pour le diagnostic et le traitement des maladies neuroagregatives |
AU2003295411A1 (en) | 2002-11-07 | 2004-06-03 | Celltech R & D | Human monoclonal antibodies to heparanase |
WO2004045525A2 (en) | 2002-11-15 | 2004-06-03 | Morehouse School Of Medicine | Anti-chemokine and associated receptor antibodies and uses for inhibition of inflammation. |
DE10256900A1 (de) | 2002-11-29 | 2004-06-24 | Nemod Immuntherapie Ag | Tumorspezifische Erkennungsmoleküle |
CN100450551C (zh) | 2002-11-29 | 2009-01-14 | 中国医学科学院基础医学研究所 | 用于治疗和预防阿尔茨海默病的重组腺相关病毒基因疫苗及其用途 |
US20050058649A1 (en) | 2002-12-02 | 2005-03-17 | Landes Gregory M. | Antibodies directed to phospholipase A2 and uses thereof |
US20070010435A1 (en) | 2002-12-19 | 2007-01-11 | New York University | Method for treating amyloid disease |
US20050031651A1 (en) | 2002-12-24 | 2005-02-10 | Francine Gervais | Therapeutic formulations for the treatment of beta-amyloid related diseases |
BR0317747A (pt) | 2002-12-24 | 2005-11-22 | Neurochem Int Ltd | Método de tratamento terapêutico concomitante de um indivìduo, composição farmacêutica, kit, uso de um primeiro agente e um segundo agente, e, métodos de prevenir ou tratar uma doença relacionada com amilóide-b, doença de alzheimer e insuficiência cognitiva suave |
GB0230203D0 (en) | 2002-12-27 | 2003-02-05 | Domantis Ltd | Fc fusion |
AT413945B (de) | 2003-01-14 | 2006-07-15 | Mattner Frank Dr | Impfstoff für die alzheimer-krankheit |
CA2514153A1 (en) | 2003-01-22 | 2004-08-05 | Takeda Pharmaceutical Company Limited | Antibody and use thereof |
JP4532409B2 (ja) | 2003-01-23 | 2010-08-25 | 小野薬品工業株式会社 | ヒトpd−1に対し特異性を有する物質 |
WO2004065569A2 (en) | 2003-01-23 | 2004-08-05 | The Regents Of The University Of California | Multi-functional antibodies |
DE10303974A1 (de) * | 2003-01-31 | 2004-08-05 | Abbott Gmbh & Co. Kg | Amyloid-β(1-42)-Oligomere, Verfahren zu deren Herstellung und deren Verwendung |
CN1745175A (zh) | 2003-02-01 | 2006-03-08 | 神经实验室有限公司 | 自动免疫产生针对可溶性A-β的抗体 |
WO2004068931A2 (en) | 2003-02-07 | 2004-08-19 | Protein Design Labs Inc. | Amphiregulin antibodies and their use to treat cancer and psoriasis |
ES2344645T3 (es) | 2003-02-10 | 2010-09-02 | Applied Molecular Evolution, Inc. | Moleculas de union al abeta. |
US8663650B2 (en) | 2003-02-21 | 2014-03-04 | Ac Immune Sa | Methods and compositions comprising supramolecular constructs |
US20040242845A1 (en) | 2003-02-21 | 2004-12-02 | Nicolau Yves Claude | Methods and compositions comprising supramolecular antigenic constructs and antibodies elicited against them |
DE10307603A1 (de) | 2003-02-22 | 2004-09-02 | Rieter Ingolstadt Spinnereimaschinenbau Ag | Textilmaschine |
KR100595494B1 (ko) | 2003-02-24 | 2006-07-03 | (주) 디지탈바이오텍 | 혈액 내 베타-아밀로이드 항체 농도를 이용한 알츠하이머병 진단키트 |
US20040223970A1 (en) * | 2003-02-28 | 2004-11-11 | Daniel Afar | Antibodies against SLC15A2 and uses thereof |
PT2177620E (pt) | 2003-03-05 | 2015-02-16 | Halozyme Inc | Glicoproteína hialuronidase solúvel (shasegp), processo para preparação da mesma, suas utilizações e composições farmacêuticas que a compreendem |
US20060104968A1 (en) | 2003-03-05 | 2006-05-18 | Halozyme, Inc. | Soluble glycosaminoglycanases and methods of preparing and using soluble glycosaminogly ycanases |
US8545830B2 (en) | 2003-03-24 | 2013-10-01 | University Of Tennessee Research Foundation | Multi-functional polymeric materials and their uses |
WO2004087735A2 (en) | 2003-03-26 | 2004-10-14 | The University Of Texas | Proteolytic and covalent antibodies |
WO2004087733A2 (en) | 2003-03-28 | 2004-10-14 | New York University | Prevention and treatment of alzheimer amyloid deposition |
CN1189210C (zh) | 2003-03-28 | 2005-02-16 | 万选才 | Cb与生物活性多肽的偶联物及其医药用途 |
KR20060054174A (ko) | 2003-03-28 | 2006-05-22 | 센토코 인코포레이티드 | 항-아밀로이드 항체, 조성물, 방법 및 용도 |
DK1625402T3 (en) | 2003-04-09 | 2014-03-10 | Canadian Blood Services | Detection, characterization and treatment of viral infection, and methods therefor |
EP1469312A1 (en) | 2003-04-18 | 2004-10-20 | Friedrich-Alexander-Universität Erlangen-Nürnberg | Diagnosis of Alzheimer's disease |
US20060240485A1 (en) | 2003-04-24 | 2006-10-26 | Universitat Zurich | Method of monitoring immunotherapy |
CA2524737A1 (en) | 2003-05-06 | 2005-02-24 | Human Genome Sciences, Inc. | Antibodies that immunospecifically bind to trail receptors |
US20040223912A1 (en) | 2003-05-07 | 2004-11-11 | Montalto Michael Christopher | Compositions and methods for non-invasive imaging of soluble beta-amyloid |
ES2246178B1 (es) | 2003-05-08 | 2007-03-01 | Universidad De Zaragoza. | Uso de anticuerpos para el tratamiento de enfermedades amiloideas. |
EP1480041A1 (en) | 2003-05-22 | 2004-11-24 | Innogenetics N.V. | Method for the prediction, diagnosis and differential diagnosis of Alzheimer's disease |
WO2005018536A2 (en) | 2003-05-23 | 2005-03-03 | Human Genome Sciences, Inc. | Agonist antibodies that specifically bind the glucagon like peptide-1 receptor |
TWI306458B (en) | 2003-05-30 | 2009-02-21 | Elan Pharma Int Ltd | Humanized antibodies that recognize beta amyloid peptide |
CA2528182A1 (en) | 2003-06-06 | 2005-06-16 | Oncomax Acquisition Corp. | Antibodies specific for cancer associated antigen sm5-1 and uses thereof |
US7892751B2 (en) | 2003-06-09 | 2011-02-22 | Redox-Reactive Reagents Llc | Method of detecting or diagnosing of a neurodegenerative disease or condition |
JP4888876B2 (ja) | 2003-06-13 | 2012-02-29 | 田平 武 | アルツハイマー病の治療のための組換えアデノ随伴ウィルスベクター |
KR20060022289A (ko) | 2003-06-23 | 2006-03-09 | 제네틱스 인스티튜트, 엘엘씨 | 인터류킨-22 에 대한 항체 및 그의 용도 |
CA2530927A1 (en) * | 2003-06-30 | 2005-01-06 | Tel Aviv University Future Technology Development L.P. | Peptides antibodies directed thereagainst and methods using same for diagnosing and treating amyloid-associated diseases |
US20050009110A1 (en) * | 2003-07-08 | 2005-01-13 | Xiao-Jia Chang | Methods of producing antibodies for diagnostics and therapeutics |
WO2005005366A1 (ja) | 2003-07-15 | 2005-01-20 | Ono Pharmaceutical Co., Ltd. | 分枝鎖カルボン酸化合物およびその用途 |
WO2005012330A2 (en) | 2003-07-30 | 2005-02-10 | Brigham And Women's Hospital, Inc. | AMYLOID β-PEPTIDE AND METHODS OF USE |
US20050124016A1 (en) | 2003-08-01 | 2005-06-09 | Enh Research Institute | Antibodies specific for toxic amyloid beta protein oligomers |
US20050079184A1 (en) | 2003-08-08 | 2005-04-14 | Immunomedics, Inc. | Bispecific antibodies for inducing apoptosis of tumor and diseased cells |
JP4239750B2 (ja) * | 2003-08-13 | 2009-03-18 | セイコーエプソン株式会社 | マイクロレンズ及びマイクロレンズの製造方法、光学装置、光伝送装置、レーザプリンタ用ヘッド、並びにレーザプリンタ |
WO2005018424A2 (en) | 2003-08-18 | 2005-03-03 | Research Foundation For Mental Hygiene, Inc. | Antibodies specific for fibrillar amyloid and a procedure to detect fibrillar amyloid deposits |
WO2005035575A2 (en) * | 2003-08-22 | 2005-04-21 | Medimmune, Inc. | Humanization of antibodies |
CA2538220A1 (en) | 2003-09-09 | 2005-03-24 | Takeda Pharmaceutical Company Limited | Use of antibody |
EP1516930A1 (en) | 2003-09-16 | 2005-03-23 | Georg-August Universität Göttingen | Cellular model of tauopathies for lead identification and drug discovery |
EP1666066A4 (en) | 2003-09-19 | 2007-03-28 | Eisai R&D Man Co Ltd | DRUG AGAINST THE DOWN SYNDROME |
EP1670510A1 (en) | 2003-09-24 | 2006-06-21 | Peter Krammer | Antibodies against annexins, use thereof for therapy and diagnosis. use of annexins for therapy and diagnosis. |
IL158287A0 (en) | 2003-10-07 | 2004-05-12 | Yeda Res & Dev | Antibodies to nik, their preparation and use |
WO2005033145A1 (en) | 2003-10-07 | 2005-04-14 | Yeda Research And Development Co. Ltd. | Antibodies to nik, their preparation and use |
CA2542084A1 (en) | 2003-10-14 | 2005-04-28 | University Of South Florida | A method for the separation anti-amyloid beta antibody with amyloid beta peptide |
AU2004282754B9 (en) * | 2003-10-15 | 2009-12-10 | Sekisui Medical Co., Ltd. | Method of selectively assaying adiponectin multimer |
EP1684574A4 (en) | 2003-10-20 | 2008-08-06 | Envivo Pharmaceuticals Inc | TRANSGENIC FLIES EXPRESSING THE MUTANTE ALPHA42 |
EP1680447A2 (en) | 2003-10-24 | 2006-07-19 | Istituto Di Ricerche Di Biologia Molecolare P. Angeletti S.P.A. | Orthogonal gene switches |
SI1682180T1 (sl) | 2003-11-04 | 2010-03-31 | Novartis Vaccines & Diagnostic | Antagonist anti cd monoklonskih antiteles in postopek za njihovo uporabo |
WO2005044847A1 (ja) | 2003-11-05 | 2005-05-19 | Toshiharu Suzuki | アルツハイマー病のマーカーペプチド |
EP1682171A4 (en) | 2003-11-07 | 2008-02-27 | Univ Rochester | COMPOSITIONS AND METHODS OF TREATING NEUROLOGICAL ILLNESSES |
EP2369348A1 (en) | 2003-11-07 | 2011-09-28 | Ciphergen Biosystems, Inc. | Biomarkers for Alzheimer's disease |
US7674599B2 (en) | 2003-11-08 | 2010-03-09 | Elan Pharmaceuticals, Inc. | Methods of using antibodies to detect alpha-synuclein in fluid samples |
KR100556660B1 (ko) * | 2003-11-11 | 2006-03-10 | 국립암센터 | Hgf의 중화가능 에피토프 및 이에 결합하는 중화 항체 |
WO2005052002A2 (en) | 2003-11-20 | 2005-06-09 | Massachusetts Institute Of Technology | Single-domain antibodies and uses thereof |
RU2006122946A (ru) | 2003-11-28 | 2008-01-10 | Астразенека Аб (Se) | Антитела |
JP4870348B2 (ja) | 2003-12-04 | 2012-02-08 | 株式会社ペルセウスプロテオミクス | 細胞表面抗原に対する抗体取得とその抗原同定 |
RU2486199C2 (ru) * | 2003-12-10 | 2013-06-27 | Медарекс, Инк. | Выделенное антитело против ip-10, иммуноконъюгат и биспецифическая молекула на его основе, их композиции, способ лечения (варианты), кодирующая молекула нуклеиновой кислоты, соответствующий экспрессионный вектор, клетка-хозяин и гибридома |
SG182163A1 (en) | 2003-12-17 | 2012-07-30 | Wyeth Corp | Immunogenic peptide carrier conjugates and methods of producing same |
ATE440866T1 (de) * | 2003-12-22 | 2009-09-15 | Glaxo Group Ltd | Nogo-a-neutralisierende immunglobuline zur behandlung neurologischer krankheiten |
PT3718564T (pt) | 2003-12-23 | 2023-11-23 | Genentech Inc | Novos anticorpos anti-il 13 e suas utilizações |
WO2005070965A2 (en) | 2004-01-21 | 2005-08-04 | Five Prime Therapeutics, Inc. | Pharmaceutical compositions containing antagonists to lrp4, lrp8 or megalin for treatment of diseases |
EP1711208A2 (en) | 2004-01-28 | 2006-10-18 | Curix APS | Conjugates of amyloid proteins as vaccines for amyloid-related diseases |
US7238788B2 (en) | 2004-02-18 | 2007-07-03 | University Of Iowa Foundation | Antibodies to phosphorylated tau, methods of making and methods of use |
WO2005080435A1 (ja) * | 2004-02-20 | 2005-09-01 | Immuno-Biological Laboratories Co., Ltd. | モノクローナル抗体およびその利用 |
UA93181C2 (ru) | 2004-02-23 | 2011-01-25 | Эли Лилли Энд Компани | СПОСОБ ПОЛУЧЕНИЯ АНТИТЕЛА K Ab ПЕПТИДУ |
EP1723178A4 (en) | 2004-03-12 | 2007-12-12 | Human Genome Sciences Inc | HUMAN G-PROTEIN CHEMOKIN RECEPTOR (CCR5) HDGNR10 |
US20080057057A1 (en) | 2004-03-18 | 2008-03-06 | Applied Research Systems Ars Holding N.V. | Anti-Lipid Rafts Antibodies |
CN1314805C (zh) | 2004-03-26 | 2007-05-09 | 中国人民解放军军事医学科学院放射与辐射医学研究所 | 一种新型促细胞凋亡素(apo)及其抗体,制备及用途 |
RU2429245C2 (ru) | 2004-03-30 | 2011-09-20 | Глаксо Груп Лимитед | Иммуноглобулины |
US20070202547A1 (en) | 2004-04-02 | 2007-08-30 | Coburn Craig A | Methods For Detecting Substances Which Bind To The Amyloid Precursor Protein Or Beta Amyloid Fragments, And Binding Compounds |
US20060099211A1 (en) | 2004-04-12 | 2006-05-11 | Carmen Monthe | Safer, more potent human immunoglobulin preparations for treating Alzheimer's disease |
JP2007535317A (ja) | 2004-04-15 | 2007-12-06 | グライコフィ, インコーポレイテッド | 下等真核生物におけるガラクトシル化された糖タンパク質の産生 |
CA2564068A1 (en) | 2004-04-15 | 2005-11-17 | Samaritan Pharmaceuticals, Inc. | Use of (4-alkylpiperazinyl) (phenyl) methanones in the treatment of alzheimer's disease |
US7763249B2 (en) | 2004-04-27 | 2010-07-27 | Juridical Foundation The Chemo-Sero-Therapeutic Research Institute | Human anti-amyloid β peptide antibody and fragment of said antibody |
ITRM20040212A1 (it) | 2004-04-30 | 2004-07-30 | Lay Line Genomics Spa | Animale transgenico non umano come modello per malattie neurodegenerative e per la loro diagnosi precoce. |
AU2005244013A1 (en) | 2004-05-14 | 2005-11-24 | Acumen Pharmaceuticals, Inc. | Compositions comprising ADDL receptor syngap |
GR1005016B (el) | 2004-05-14 | 2005-10-11 | BIOMENTIKA@ΛΑΙΦ@ΣΑΙΕΝΣΙΣ@ΑΝΩΝΥΜΗ@ΕΤΑΙΡΕΙΑ@ΦΑΡΜΑΚΕΥΑΤΙΚΩΝ@ΠΡΟΙΟΝΤΩΝ@(συμμετέχει@σε@ποσοστό@50%)@Α | ΑΝΑΠΤΥΞΗ ΑΝΤΙΣΩΜΑΤΩΝ IgG KAI IgY ΕΝΑΝΤΙΟΝ ΕΙΔΙΚΟΥ ΣΥΝΘΕΤΙΚΟΥ ΕΠΙΤΟΠΙΚΟΥ ΠΑΡΑΓΩΓΟΥ ΤΗΣ HUMANIN (24-ΠΕΠΤΙΔΙΟΥ ΣΧΕΤΙΖΟΜΕΝΟΥ ΜΕ ΤΗ ΝΟΣΟ ALZHEIMER) ΙΚΑΝΩΝ ΝΑ ΑΝΙΧΝΕΥΟΥΝ ΤΟ ΒΙΟΔΡΑΣΤΙΚΟ 24-ΠΕΠΤΙΔΙΟ. |
EP1766396B1 (en) | 2004-06-07 | 2010-08-11 | Ramot at Tel-Aviv University Ltd. | Method of passive immunization against disease or disorder characterized by amyloid aggregation with diminished risk of neuroinflammation |
AR049390A1 (es) | 2004-06-09 | 2006-07-26 | Wyeth Corp | Anticuerpos contra la interleuquina-13 humana y usos de los mismos |
US20060018896A1 (en) | 2004-06-10 | 2006-01-26 | University Of Leicester | Methods for treating conditions associated with lectin-dependent complement activation |
US20050276806A1 (en) | 2004-06-15 | 2005-12-15 | Advanced Biotherapy, Inc. | Treatment of autism |
EP1877082A2 (en) | 2004-06-18 | 2008-01-16 | The Government of the United States of America as represented by The Secretary of the Department of Health and Human Services | Anti-lympho- plus anti-monocytes globulin preparation for inhibiting immune responses |
SE0401601D0 (sv) | 2004-06-21 | 2004-06-21 | Bioarctic Neuroscience Ab | Protofibril specific antibodies and uses thereof |
WO2006014478A1 (en) | 2004-07-02 | 2006-02-09 | Northwestern University | MONOLOCAL ANTIBODIES THAT TARGET PATHOLOGICAL ASSEMBLIES OF AMYLOID β (ABETA) |
WO2006005588A1 (en) | 2004-07-12 | 2006-01-19 | Geneprot, Inc. | Polypeptide species useful for the treatment of neurological disorders |
AT500483B1 (de) * | 2004-07-13 | 2006-01-15 | Mattner Frank Dr | Set zur vorbeugung oder behandlung der alzheimer'schen erkrankung |
AT413946B (de) | 2004-07-13 | 2006-07-15 | Mattner Frank Dr | Impfstoff gegen die alzheimer-krankheit |
CN1721437A (zh) | 2004-07-13 | 2006-01-18 | 中南大学 | 一种与Tau蛋白相关的多肽抗原及抗体 |
US20090156471A1 (en) | 2004-07-15 | 2009-06-18 | Ramot At Tel Aviv University Ltd. | Use of anti-amyloid agents for treating and typing pathogen infections |
US7955812B2 (en) | 2004-07-19 | 2011-06-07 | The General Hospital Corporation | Methods of diagnosing alzheimer's disease by detecting antibodies to cross-linked β-amyloid oligomers |
MX2007001102A (es) | 2004-07-28 | 2007-04-13 | Schering Corp | Inhibidores macrociclicos de beta-secretasa. |
US7807165B2 (en) * | 2004-07-30 | 2010-10-05 | Rinat Neuroscience Corp. | Antibodies directed against amyloid-beta peptide and methods using same |
DK1786442T3 (da) | 2004-08-09 | 2008-03-17 | Cellzome Ag | Behandling af neurodegenerative sygdomme under anvendelse af DEGS-inhibitorer |
WO2006015976A1 (en) | 2004-08-11 | 2006-02-16 | Evotec Neurosciences Gmbh | Diagnostic and therapeutic use of a plasma membrane atpase |
CN101080421A (zh) | 2004-08-11 | 2007-11-28 | 三菱化学株式会社 | 抗体以及其利用 |
DE102004039326A1 (de) | 2004-08-12 | 2006-02-16 | Abbott Gmbh & Co. Kg | Neue medizinische Verwendungen und Verfahren |
TWI374935B (en) | 2004-08-27 | 2012-10-21 | Pfizer Ireland Pharmaceuticals | Production of α-abeta |
US20060246075A1 (en) | 2004-09-29 | 2006-11-02 | Marc Mercken | Anti-amyloid antibodies, compositions, methods and uses |
WO2006039327A2 (en) | 2004-10-01 | 2006-04-13 | Merck & Co., Inc. | Methods of treatment or prophylaxis of amyloidogenic diseases of the eye or optic nerve |
DE602005026219D1 (de) | 2004-10-01 | 2011-03-17 | Max Planck Gesellschaft | Gegen das säugetier-eag1-ionenkanalprotein gerichtete antikörper |
ZA200703561B (en) | 2004-10-05 | 2009-09-30 | Wyeth Corp | Methods and compositions for improving recombinant protein production |
KR20070100234A (ko) | 2004-10-06 | 2007-10-10 | 히로시 모리 | 변이형 아밀로이드 단백질 |
KR20070084170A (ko) | 2004-10-13 | 2007-08-24 | 아블린쓰 엔.브이. | 알쯔하이머병 등의 퇴행성 신경 질환의 치료 및 진단을위한 단일 도메인 카멜리드 항-아밀로이드 베타 항체 및이를 포함하는 폴리펩타이드 |
WO2006047254A1 (en) | 2004-10-22 | 2006-05-04 | Regents Of The University Of Minnesota | Assemblies of oligomeric amyloid beta protein and uses thereof |
KR20070094890A (ko) | 2004-10-25 | 2007-09-27 | 머크 앤드 캄파니 인코포레이티드 | 안티 addl 항체 및 그 용도 |
US20060160161A1 (en) | 2004-10-26 | 2006-07-20 | Elan Pharmaceuticals, Inc. | Methods for assessing antibodies to neurodegenerative disease-associated antigens |
WO2006050041A2 (en) | 2004-10-28 | 2006-05-11 | Ramot At Tel Aviv University Ltd. | Methods for reducing or inhibiting brain inflammation or for promoting neurogenesis |
EP1813947A4 (en) | 2004-10-28 | 2008-06-11 | Sanko Junyaku Kk | METHOD FOR THE STUDY OF MORBUS ALZHEIMER AND DIAGNOSTIC REAGENT |
US7709208B2 (en) | 2004-11-08 | 2010-05-04 | New York University | Methods for diagnosis of major depressive disorder |
WO2006052924A2 (en) | 2004-11-08 | 2006-05-18 | Nanobac Life Sciences | Methods and compositions for protein-hydroxy apatite complexes and their application in testing and modulating immunological system including a novel in vitro test for the detection of antibodies against calcium binding protein-hydroxy apatite complexes |
CN1772766A (zh) | 2004-11-12 | 2006-05-17 | 中国科学院上海生命科学研究院 | 抗细胞凋亡相关乙酰胆碱酯酶单克隆抗体及其用途 |
EP1824496A4 (en) | 2004-11-17 | 2008-07-16 | Joanne Mclaurin | COMPOSITIONS OF SCYLLO-INOSITOL DERIVATIVES AND METHOD FOR THE TREATMENT OF PROTEIN AGGREGATION DISORDERS |
AR052051A1 (es) | 2004-12-15 | 2007-02-28 | Neuralab Ltd | Anticuerpos ab humanizados usados en mejorar la cognicion |
US7625560B2 (en) | 2004-12-15 | 2009-12-01 | Janssen Alzheimer Immunotherapy | Humanized antibodies that recognize beta amyloid peptide |
WO2006066233A1 (en) | 2004-12-15 | 2006-06-22 | Neuralab Limited | An immunoprecipitation-based assay for predicting in vivo efficacy of beta-amyloid antibodies |
TW200635608A (en) * | 2004-12-15 | 2006-10-16 | Neuralab Ltd | Aβ antibodies for use in improving cognition |
WO2006066118A2 (en) | 2004-12-15 | 2006-06-22 | Neuralab Limited | Contextual fear test for predicting efficacy of alzheimer immunotherapeutic treatment |
JP2006166879A (ja) | 2004-12-20 | 2006-06-29 | Japan Health Science Foundation | Ab−dip、並びにアルツハイマー病の予防及び治療剤 |
MY146381A (en) | 2004-12-22 | 2012-08-15 | Amgen Inc | Compositions and methods relating relating to anti-igf-1 receptor antibodies |
WO2006067792A2 (en) | 2004-12-22 | 2006-06-29 | Yeda Research And Development Co. Ltd. At The Weizmann Institute Of Science | Aldolase autoantigens useful in diagnosis and treatment of alzheimer's disease |
US20090074775A1 (en) | 2004-12-22 | 2009-03-19 | David Michael Holtzman | Use Of Anti-AB Antibody To Treat Traumatic Brain Injury |
EP1676859A1 (en) | 2004-12-30 | 2006-07-05 | Pevion Biotech Ltd. | Immunogenic compositions of cyclic peptides derived from the beta-amyloid peptide |
CA2593846A1 (en) | 2005-01-14 | 2006-08-10 | The Regents Of The University Of California | Compositions and methods for inhibiting drusen formation and for diagnosing or treating drusen-related disorders |
CA2589860A1 (en) | 2005-01-24 | 2006-08-03 | Amgen Inc. | Humanized anti-amyloid antibody |
GT200600031A (es) | 2005-01-28 | 2006-08-29 | Formulacion anticuerpo anti a beta | |
JP2006213621A (ja) | 2005-02-02 | 2006-08-17 | Japan Health Science Foundation | Adoplinタンパク質、およびその利用 |
US20070082350A1 (en) | 2005-02-09 | 2007-04-12 | Philip Landfield | Assay and method for diagnosing and treating alzheimer's disease |
US7700099B2 (en) | 2005-02-14 | 2010-04-20 | Merck & Co., Inc. | Non-immunostimulatory antibody and compositions containing the same |
US7731962B2 (en) * | 2005-02-14 | 2010-06-08 | Merck & Co., Inc. | Anti-ADDL monoclonal antibody and use thereof |
GB0503434D0 (en) | 2005-02-18 | 2005-03-30 | Senexis Ltd | Amyloid-binding peptides, analogues and uses thereof |
ES2665422T3 (es) | 2005-03-03 | 2018-04-25 | Immunomedics Inc. | Anticuerpos L243 humanizados |
US7678371B2 (en) | 2005-03-04 | 2010-03-16 | Biogen Idec Ma Inc. | Methods of humanizing immunoglobulin variable regions through rational modification of complementarity determining residues |
US20090035295A1 (en) * | 2005-03-05 | 2009-02-05 | Abbott Gmgh & Co. Kg | Screening Method, Process for Purifying of Non-Diffusible A-Beta Oligomers, Selective Antibodies Against Said Non-Diffusible a-Beta Oligomers and a Process for Manufacturing of Said Antibodies |
WO2006096529A2 (en) | 2005-03-07 | 2006-09-14 | Novartis Ag | Genes involved in neurodegenerative conditions |
ES2259270B1 (es) | 2005-03-09 | 2007-11-01 | Consejo Superior De Investigaciones Cientificas | Metodo de diagnostico in vitro de la enfermedad de alzheimer mediante un anticuerpo monoclonal. |
WO2006099543A2 (en) | 2005-03-15 | 2006-09-21 | The Regents Of The University Of California | Methods for assessing antibody-mediated cytotoxicity |
WO2006100679A2 (en) | 2005-03-22 | 2006-09-28 | Quark Pharmaceuticals, Inc. | Recombinant antibodies against human type ii transglutaminase and uses thereof |
JP2006265189A (ja) | 2005-03-24 | 2006-10-05 | Kyoto Univ | βアミロイドペプチド、及びそれを用いたアルツハイマー病治療薬又は予防薬のスクリーニング方法 |
ES2318918B1 (es) | 2005-04-01 | 2010-02-16 | Biotherapix Molecular Medicines, S.L.U. | Anticuerpos humanos con capacidad de union al peptido beta-amiloide y sus aplicaciones. |
WO2006110748A2 (en) | 2005-04-08 | 2006-10-19 | The University Of Maryland, Baltimore | Response gene to complement 32 (rgc-32) in disease |
US20060241038A1 (en) | 2005-04-20 | 2006-10-26 | Eisai Co., Ltd. | Therapeutic agent for Abeta related disorders |
CN101203242A (zh) | 2005-04-22 | 2008-06-18 | 健泰科生物技术公司 | 用cd20抗体治疗痴呆或阿耳茨海默氏病的方法 |
MY148086A (en) | 2005-04-29 | 2013-02-28 | Rinat Neuroscience Corp | Antibodies directed against amyloid-beta peptide and methods using same |
WO2006119449A2 (en) | 2005-05-04 | 2006-11-09 | Vectorlogics, Inc. | Modified adenovirus containing a stabilized antibody |
CA2607868A1 (en) | 2005-05-05 | 2006-11-16 | Merck & Co., Inc. | Peptide conjugate compositions and methods for the prevention and treatment of alzheimer's disease |
US20060272038A1 (en) | 2005-05-27 | 2006-11-30 | Michael De Vivo | Transgenic Alzheimer's mouse model vectors and uses thereof |
EP1888783B1 (en) | 2005-05-27 | 2011-10-26 | EVOTEC Neurosciences GmbH | Kcnn3 as diagnostic and therapeutic target for alzheimer's disease |
KR20080032070A (ko) | 2005-06-06 | 2008-04-14 | 와이어쓰 | 항-TrkB 모노클로날 항체 및 이의 용도 |
ES2402650T3 (es) | 2005-06-17 | 2013-05-07 | Janssen Alzheimer Immunotherapy | Métodos de purificación de anticuerpos anti A beta |
WO2006137354A1 (ja) | 2005-06-21 | 2006-12-28 | Medical & Biological Laboratories Co., Ltd. | アミロイド線維形成に対する阻害活性を有する抗体 |
TW200726482A (en) | 2005-06-30 | 2007-07-16 | Merck & Co Inc | Method for preparing a covalently cross linked oligomer of amyloid beta peptides |
TW200726774A (en) | 2005-06-30 | 2007-07-16 | Merck & Co Inc | Composition and method for producing stable amyloid beta oligomers |
BRPI0613387A2 (pt) | 2005-07-08 | 2011-01-11 | Biogen Idec Inc | anticorpo isolado ou fragmento de ligação de antìgeno deste e o seu uso, polinucleotìdeo isolado, composição, vetor, célula hospedeira, anticorpo anti-sp35 e método para a produção do mesmo, polipeptìdeo isolado, método in vitro para redução da inibição do crescimento axonal e método in vitro para inibição do crescimento do colapso do cone |
WO2007011639A2 (en) | 2005-07-13 | 2007-01-25 | Coimmune Inc. | Catalytic immunoglobulins |
US7666886B2 (en) | 2005-07-15 | 2010-02-23 | The Regents Of The University Of California | Compounds and methods for the diagnosis and treatment of amyloid associated diseases |
US20070092517A1 (en) | 2005-08-10 | 2007-04-26 | Oklahoma Medical Research Foundation | Truncated memapsin 2 compositions and treatments |
EP2578602B1 (en) | 2005-08-11 | 2016-10-19 | Matossian-Rogers Arpi | TCR-V-beta related peptides for treatment and diagnosis of autoimmune disease |
AU2006281980A1 (en) | 2005-08-15 | 2007-02-22 | Cephalon Australia Pty Ltd | Engineered antibodies with new world primate framework regions |
EP1937720B1 (en) | 2005-08-18 | 2014-04-09 | Ramot at Tel-Aviv University Ltd. | Single chain antibodies against beta-amyloid peptide |
US7612181B2 (en) * | 2005-08-19 | 2009-11-03 | Abbott Laboratories | Dual variable domain immunoglobulin and uses thereof |
JP2007077103A (ja) | 2005-09-16 | 2007-03-29 | Yokohama City Univ | アルツハイマー病の予防又は治療剤 |
US20080274096A1 (en) | 2005-10-03 | 2008-11-06 | Astrazeneca Ab | Fusion Proteins Having a Modulated Half-Life in Plasma |
WO2007042261A2 (en) | 2005-10-11 | 2007-04-19 | Micromet Ag | Compositions comprising cross-species-specific antibodies and uses thereof |
WO2007047995A2 (en) | 2005-10-21 | 2007-04-26 | Catalyst Biosciences, Inc. | Modified proteases that inhibit complement activation |
EP1940466B1 (en) | 2005-10-21 | 2012-11-28 | Merck Sharp & Dohme Corp. | Anti-addl monoclonal antibodies and use thereof |
US20070092508A1 (en) | 2005-10-21 | 2007-04-26 | Recombiant Technologies, Llc | Detoxification depot for Alzheimer's disease |
WO2007053661A2 (en) | 2005-11-01 | 2007-05-10 | Novartis Ag | Uses of anti-cd40 antibodies |
US20090181008A1 (en) | 2005-11-10 | 2009-07-16 | Satoris, Inc. | Methods of treating alzheimer's disease |
US8316104B2 (en) | 2005-11-15 | 2012-11-20 | California Institute Of Technology | Method and apparatus for collaborative system |
US20080014596A1 (en) | 2005-11-16 | 2008-01-17 | Jasna Jerecic | ADDL Binding to Hippocampal Neurons |
WO2007062088A1 (en) | 2005-11-22 | 2007-05-31 | The Trustees Of The University Of Pennsylvania | Antibody treatment of alzheimer's and related diseases |
DK1954718T3 (en) | 2005-11-30 | 2014-12-15 | Abbvie Inc | Anti-A-globulomer antibodies antigenbindingsgrupper thereof, corresponding hybridomas, nucleic acids, vectors, host cells, methods for producing said antibodies, |
MX2008006957A (es) | 2005-11-30 | 2008-10-20 | Abbott Lab | Metodos para la preparacion de formas recombinantes de proteina beta-amiloide humana y usos de estas proteinas. |
EP1976877B2 (en) | 2005-11-30 | 2016-10-05 | AbbVie Inc. | Monoclonal antibodies against amyloid beta protein and uses thereof |
WO2007064919A2 (en) | 2005-12-02 | 2007-06-07 | Genentech, Inc. | Binding polypeptides with restricted diversity sequences |
WO2007067512A2 (en) | 2005-12-08 | 2007-06-14 | Merck & Co., Inc. | Method for identifying modulators of adprh useful for treating alzheimer's disease |
NZ568384A (en) | 2005-12-12 | 2011-09-30 | Ac Immune Sa | Therapeutic vaccine comprising Abeta peptide |
MX358175B (es) † | 2005-12-12 | 2018-08-08 | Ac Immune Sa | Anticuerpos monoclonales especificos 1-42 beta con propiedades terapeuticas. |
TWI382990B (zh) | 2005-12-12 | 2013-01-21 | Hoffmann La Roche | 可變區域抗體之糖化 |
EP1973948B1 (en) | 2005-12-15 | 2015-02-11 | Genentech, Inc. | Methods and compositions for targeting polyubiquitin |
US20080058276A1 (en) * | 2006-01-13 | 2008-03-06 | Cornell Research Foundation, Inc. | Alzheimer's disease therapeutics based on pin-1 catalyzed conformational changes in phosphorylated amyloid precursor protein |
EP1811304A1 (en) | 2006-01-18 | 2007-07-25 | Friedrich-Alexander-Universität Erlangen-Nürnberg | Large Aß-peptide binding particles (LAPS) in diagnosis and therapy of Alzheimer's dementia |
CN1329413C (zh) | 2006-01-23 | 2007-08-01 | 南京医科大学 | 一种治疗或预防老年性痴呆的抗体及其表达载体和在制药中的应用 |
JP5697847B2 (ja) | 2006-01-30 | 2015-04-08 | グリフオルス・セラピユーテイクス・インコーポレーテツドGrifols Therapeutics,Inc. | IgMを使用する治療方法および予防方法 |
GB0601976D0 (en) | 2006-02-01 | 2006-03-15 | Merck Sharp & Dohme | Proteins |
US20090304712A1 (en) | 2006-02-02 | 2009-12-10 | National University Corporation Nagoya University | Neuronal Cell Death Inhibitor and Screening Method |
WO2007092861A2 (en) | 2006-02-06 | 2007-08-16 | Elan Pharmaceuticals, Inc. | Inhibitors specific of presenilin-1 and their uses |
CA2637775A1 (en) | 2006-02-09 | 2007-08-16 | Novartis Ag | Antibodies against secreted frizzled related protein-4 (sfrp-4 ) |
AU2007217039A1 (en) | 2006-02-21 | 2007-08-30 | Oklahoma Medical Research Foundation | Treatment of Alzheimer's disease with inhibitors of APoE binding to APoE receptor |
US20070196367A1 (en) | 2006-02-22 | 2007-08-23 | Valentin Dinu | Methods of preventing and treating Alzheimer's disease, age related macular degeneration and other diseases involving extra-cellular debris through the inhibition of the complement system |
CA2638775A1 (en) | 2006-02-22 | 2007-08-30 | Kabushiki Kaisha Hayashibara Seibutsu Kagaku Kenkyujo | Peptide vaccine for inducing production of anti-amyloid-.beta.-peptide antibody |
CA2638841A1 (en) | 2006-02-24 | 2007-08-30 | Chiesi Farmaceutici S.P.A. | Anti-amyloid immunogenic compositions, methods and uses |
US20100196932A1 (en) | 2006-03-02 | 2010-08-05 | The Board Of Trustees Of The University Of Illinois | Yeast Reporter System |
EP2514823B1 (en) | 2006-03-03 | 2018-05-02 | ProMIS Neurosciences Inc. | Methods and compositions to treat and detect misfolded-SOD1 mediated diseases |
WO2007109107A2 (en) | 2006-03-17 | 2007-09-27 | The Trustees Of Columbia University In The City Of New York | Atf4 as a therapeutic target in alzheimers disease and other neurological disorders |
MX2008012023A (es) | 2006-03-21 | 2008-10-01 | Wyeth Corp | Metodos para prevenir y tratar enfermedades amiloidogenicas. |
ATE492561T1 (de) | 2006-03-23 | 2011-01-15 | Bioartic Neuroscience Ab | Verbesserte protofibrilselektive antikörper und deren verwendung |
WO2007112288A2 (en) | 2006-03-23 | 2007-10-04 | Mount Sinai School Of Medicine | Cardiovascular composition and use the same for the treatment of alzheimers disease |
CA2541522A1 (en) | 2006-03-28 | 2007-09-28 | E. Rick Preddie | A double elisa for alzheimer's disease (ad) with applications for therapeutic vaccines to stop the disease |
EA015654B9 (ru) | 2006-03-30 | 2012-01-30 | Глаксо Груп Лимитед | Антитела против бета-амилоидного пептида |
FR2899107B1 (fr) | 2006-03-30 | 2008-06-13 | Neurokin Entpr Unipersonnelle | Utilisation de la (s)-roscovitine pour la fabrication d'un medicament |
KR20090007374A (ko) | 2006-03-31 | 2009-01-16 | 더 리전트 오브 더 유니버시티 오브 캘리포니아 | 신경변성 질환과 알츠하이머병을 치료하고 정상 기억을 향상시키기 위한 방법과 조성물 |
US20090291453A1 (en) | 2006-04-13 | 2009-11-26 | Shigeo Takayama | Method for Testing Alzheimer's Disease by Measuring Degradation Rate of B-Amyloid in Blood and Diagnostic Reagent |
KR101188861B1 (ko) | 2006-04-21 | 2012-10-08 | 주식회사 피플바이오 | 삼차원적 상호작용을 이용하여 멀티머-형성 폴리펩타이드의 모노머로부터 멀티머를 분별 검출하는 방법 |
CN101058608B (zh) | 2006-04-21 | 2011-02-23 | 杜如昱 | 人类抗Aβ1-32淀粉样蛋白抗体、其纯化方法及用途 |
JP5311303B2 (ja) | 2006-04-25 | 2013-10-09 | 国立大学法人 東京大学 | アルツハイマー病および癌の治療薬 |
CA2650376A1 (en) | 2006-04-27 | 2007-11-08 | The Mclean Hospital Corporation | Treatment and screening methods for promoting neurogenesis |
GB0608386D0 (en) | 2006-04-27 | 2006-06-07 | Senexis Ltd | Compounds |
WO2007127448A2 (en) | 2006-04-28 | 2007-11-08 | Northwestern University | Salts of pyridazine compounds |
JP2007300856A (ja) | 2006-05-11 | 2007-11-22 | Hiroshi Mori | アミロイドタンパク質模倣物 |
US20070292895A1 (en) | 2006-05-19 | 2007-12-20 | Xiao-Ping Shi | Assays and methods to detect beta-secretase and its activity in body fluids and tissue extracts |
EP2035448A4 (en) * | 2006-06-01 | 2010-11-03 | Elan Pharm Inc | NEUROACTIVE FRAGMENTS OF APP |
JP4933159B2 (ja) | 2006-06-02 | 2012-05-16 | 国立大学法人金沢大学 | アルツハイマー病の診断方法 |
US7427342B2 (en) | 2006-06-02 | 2008-09-23 | General Electric Company | Method and apparatus for shifting current distribution in electrodeionization systems |
US7479550B2 (en) | 2006-06-02 | 2009-01-20 | The Board Of Regents Of The University Of Texas System | Amyloid β gene vaccines |
EP2032597A2 (en) | 2006-06-16 | 2009-03-11 | UMC Utrecht Holding B.V. | Fplr-1 inhibitors for use in diseases involving amyloid-induced inflammatory events (flipr and flipr-like) and immunecomplex-mediated diseases |
TW200815469A (en) | 2006-06-23 | 2008-04-01 | Astrazeneca Ab | Compounds |
EP2043687A4 (en) | 2006-06-29 | 2010-03-17 | Centocor Ortho Biotech Inc | ANTI-AMYLOID ANTIBODIES, COMPOSITIONS, METHODS AND USES |
WO2008006070A2 (en) * | 2006-07-06 | 2008-01-10 | Roskamp Research Llc | Compounds and combinations thereof for inhibiting beta-amyloid production and methods of use thereof |
US20080012103A1 (en) | 2006-07-13 | 2008-01-17 | Foster Robert H | Emi absorbing gap filling material |
WO2008011348A2 (en) † | 2006-07-14 | 2008-01-24 | Ac Immune S.A. | Humanized antibody against amyloid beta |
WO2008008463A2 (en) | 2006-07-14 | 2008-01-17 | Trustees Of Columbia University In The City Of New York | METHODS AND COMPOSITIONS FOR DETECTING AND QUANTIFYING SAPPβ |
EP1882944B1 (en) | 2006-07-28 | 2009-03-18 | VISTA VENTURES GmbH | Method for the detection of amyloid-beta oligomers in body fluids |
US7705475B2 (en) * | 2006-08-03 | 2010-04-27 | Stats Chippac Ltd. | Integrated circuit package system |
SG173405A1 (en) | 2006-08-04 | 2011-08-29 | Lonza Biologics Plc | Method for predicting protein aggregation and designing aggregation inhibitors |
WO2008021296A2 (en) | 2006-08-14 | 2008-02-21 | Thymon, L.L.C. | Compositions and methods for the treatment and prophylaxis of alzheimer's disease |
WO2008022349A2 (en) | 2006-08-18 | 2008-02-21 | Armagen Technologies, Inc. | Agents for blood-brain barrier delivery |
WO2008051326A2 (en) | 2006-08-21 | 2008-05-02 | President And Fellows Of Harvard College | Identification of contactins and l1- cams as ligands for the amyloid precursor protein |
WO2008070229A2 (en) | 2006-08-28 | 2008-06-12 | Case Western Reserve University | Detection of pathogenic aggregates of protein in a sample by homologous elisa |
JP2010502623A (ja) | 2006-08-31 | 2010-01-28 | 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 | Nogoレセプターポリペプチドの末梢投与に関する方法 |
US8372399B2 (en) * | 2006-08-31 | 2013-02-12 | Cardiac Pacemakers, Inc. | Bispecific antibodies and agents to enhance stem cell homing |
US20080118938A1 (en) | 2006-09-06 | 2008-05-22 | Lisbell Estrada | Methods and Compositions for the Detection of Protein Folding Disorders |
CA2662723A1 (en) | 2006-09-08 | 2008-03-13 | Vib Vzw | Means and methods for the production of amyloid oligomers |
WO2008030251A1 (en) | 2006-09-08 | 2008-03-13 | Georgetown University | Deglycosylated anti-amyloid beta antibodies |
ES2307396B1 (es) | 2006-09-14 | 2009-09-30 | Fundacion Para Investigaciones Neurologicas (Fin) | Sistemas de eliminacion de sustancias neurotoxicas causantes de enfermedades neurodegenerativas mediante su atrapamiento selectivo por inmunoafinidad en el liquido cefalo-raquideo circulante. |
US7375190B2 (en) | 2006-09-19 | 2008-05-20 | National Yang-Ming University | Recombinant protein and method of screening for agents that modulate polypeptide aggregation |
SI2074145T1 (sl) | 2006-10-02 | 2017-12-29 | Ac Immune S.A. | Humanizirano protitelo proti amiloid beta |
WO2008045962A2 (en) | 2006-10-10 | 2008-04-17 | Mayo Foundation For Medical Education And Research | Methods and materials related to anti-a (beta) antibodies |
US9382327B2 (en) | 2006-10-10 | 2016-07-05 | Vaccinex, Inc. | Anti-CD20 antibodies and methods of use |
JP5153114B2 (ja) | 2006-10-12 | 2013-02-27 | 知宏 千葉 | 新規のアルツハイマー病検出方法 |
US20080113444A1 (en) | 2006-10-17 | 2008-05-15 | Pray Todd R | Method for detecting oligermization of soluble amyloid beta oligomers |
GB0620735D0 (en) | 2006-10-18 | 2006-11-29 | Ares Trading Sa | Proteins |
KR100883132B1 (ko) | 2006-10-24 | 2009-02-10 | 재단법인서울대학교산학협력재단 | 아밀로이드 형성 펩타이드 또는 단백질의 가용성 회합체에선택적으로 작용하는 절단제 |
ES2442258T3 (es) | 2006-10-27 | 2014-02-10 | Abbvie Biotechnology Ltd | Anticuerpos cristalinos anti-hTNF alfa |
WO2008064244A2 (en) | 2006-11-20 | 2008-05-29 | The Trustees Of Columbia University In The City Of New York | Phosphoinositide modulation for the treatment of neurodegenerative diseases |
EP2083621A4 (en) | 2006-11-20 | 2010-03-24 | Satori Pharmaceuticals Inc | MODULATORS OF AMYLOID BETA PRODUCTION |
BRPI0719379A2 (pt) | 2006-11-24 | 2014-02-11 | Ac Immune Sa | Composto, composição farmacêutica, uso de composto, mistura, métodos para coletar dados para o diagnóstico de uma doença ou condição associada com amilóide em uma amostra ou um paciente, para determinar a extensão da carga de placa amiloidogênica em um tecido e/ou um fluido corporal, para coletar dados para determinar a predisposição a uma doença ou condição associada com amilóide em um paciente, para coletar dados para monitorar a doença residual mínima em um paciente seguindo o tratamento com um anticorpo ou uma composição de vacina e para coletar dados para predizer a responsividade de um paciente sendo tratado com um anticorpo ou uma composição de vacina, e, kit de teste |
US8455626B2 (en) | 2006-11-30 | 2013-06-04 | Abbott Laboratories | Aβ conformer selective anti-aβ globulomer monoclonal antibodies |
WO2008143708A2 (en) | 2006-12-07 | 2008-11-27 | Mayo Foundation For Medical Education And Research | Methods and materials related to anti-amyloid antibodies |
MX2009006199A (es) | 2006-12-11 | 2009-06-22 | Hoffmann La Roche | Formulacion parenteral de anticuerpos abeta. |
WO2008076262A2 (en) | 2006-12-15 | 2008-06-26 | Merck & Co., Inc. | Receptor for amyloid beta and uses thereof |
DK2104682T3 (en) | 2007-01-11 | 2017-01-16 | Michael Bacher | DIAGNOSIS AND TREATMENT OF ALZHEIMER'S AND OTHER DEMENTIA DISEASES |
WO2008140639A2 (en) | 2007-02-08 | 2008-11-20 | Oligomerix, Inc. | Biomarkers and assays for alzheimer's disease |
KR100806914B1 (ko) | 2007-02-14 | 2008-02-22 | 경북대학교 산학협력단 | 퇴행성 신경질환의 예방 및 치료를 위한 리포칼린 2의 신규한 용도 |
EP2125015A1 (en) | 2007-02-27 | 2009-12-02 | Abbott GmbH & Co. KG | Method for the treatment of amyloidoses |
EP2486928A1 (en) | 2007-02-27 | 2012-08-15 | Abbott GmbH & Co. KG | Method for the treatment of amyloidoses |
GB0704394D0 (en) | 2007-03-07 | 2007-04-11 | Senexis Ltd | Compounds |
US20090022728A1 (en) | 2007-03-09 | 2009-01-22 | Rinat Neuroscience Corporation | Methods of treating ophthalmic diseases |
EP1978035A1 (en) | 2007-04-05 | 2008-10-08 | Hans-Knöll-Institut Leibniz-Institut für Naturstoff-Forschung | Anti-amyloid antibodies and their use in diagnosis and therapy of amyloid diseases |
DK2148667T3 (da) | 2007-04-12 | 2013-08-26 | Waratah Pharmaceuticals Inc | Anvendelse af cyclohexanhexolderivater til behandling af øjensygdomme |
JP2011526240A (ja) | 2007-04-18 | 2011-10-06 | ヤンセン アルツハイマー イミュノセラピー | 脳アミロイド血管症の予防および治療 |
WO2008129023A2 (en) | 2007-04-19 | 2008-10-30 | Vib Vzw | Oligonucleotide compositions for the treatment of alzheimer's disease |
CA2719878C (en) | 2007-04-26 | 2017-08-29 | Yale University | Prion protein as a receptor for amyloid-beta oligomers |
US20100178658A1 (en) | 2007-05-30 | 2010-07-15 | The Regents Of The University Of Michigan | Screening assays for inhibitors of beta amyloid peptide ion channel formation |
US20090232801A1 (en) | 2007-05-30 | 2009-09-17 | Abbot Laboratories | Humanized Antibodies Which Bind To AB (1-42) Globulomer And Uses Thereof |
PE20090329A1 (es) | 2007-05-30 | 2009-03-27 | Abbott Lab | Anticuerpos humanizados contra el globulomero ab(20-42) y sus usos |
EP2527366B1 (en) | 2007-06-12 | 2017-08-16 | AC Immune S.A. | Monoclonal anti beta amyloid antibody |
EP2170389B1 (en) | 2007-06-12 | 2014-10-29 | AC Immune S.A. | Humanized antibodies to amyloid beta |
EP2009445A1 (en) | 2007-06-29 | 2008-12-31 | Institut Pasteur | Use of a camelid single-domain antibody for detecting an oligomeric form of an amyloid beta peptide and its applications |
CN101084909A (zh) | 2007-07-03 | 2007-12-12 | 福建医科大学附属协和医院 | 人参皂苷Rg1的新用途 |
WO2009009768A2 (en) | 2007-07-12 | 2009-01-15 | Acumen Pharmaceuticals, Inc. | METHODS OF INHIBITING THE FORMATION OF AMYLOID-β DIFFUSABLE LIGANDS USING A ACYLHYDRAZIDE COMPOUDS |
US8962677B2 (en) * | 2007-07-12 | 2015-02-24 | Acumen Pharmaceuticals, Inc. | Methods of restoring cognitive ability using non-peptidic compounds |
WO2009008890A1 (en) | 2007-07-12 | 2009-01-15 | Acumen Pharmaceuticals, Inc. | METHODS OF MODIFYING AMYLOID β OLIGOMERS USING NON-PEPTIDIC COMPOUNDS |
WO2009008891A1 (en) | 2007-07-12 | 2009-01-15 | Acumen Pharmaceuticals, Inc. | Methods of enhancing cognitive function using non-peptidic compounds |
SG178809A1 (en) | 2007-10-05 | 2012-03-29 | Genentech Inc | Use of anti-amyloid beta antibody in ocular diseases |
CA2701793C (en) | 2007-10-05 | 2017-04-25 | Genentech, Inc. | Use of anti-amyloid beta antibody in ocular diseases |
GB0719559D0 (en) | 2007-10-05 | 2007-11-14 | Senexis Ltd | Compounds |
EP2205631B1 (en) | 2007-10-05 | 2016-11-23 | Genentech, Inc. | Methods and compositions for diagnosis and treatment of amyloidosis |
CN101152576A (zh) | 2007-10-15 | 2008-04-02 | 王延江 | 防治阿尔茨海默病的药物 |
CR20170001A (es) | 2008-04-28 | 2017-08-10 | Genentech Inc | Anticuerpos anti factor d humanizados |
WO2010010469A2 (en) | 2008-07-25 | 2010-01-28 | Abbott Gmbh & Co. Kg | Abeta (x-38..43) oligomers, and processes, compositions, and uses thereof |
EP2303920A4 (en) | 2008-07-25 | 2011-11-09 | Abbott Lab | SS-AMYLOID PEPTIDE ANALOGUES, OLIGOMERS THEREOF, PREPARATION METHODS AND COMPOSITIONS COMPRISING THE SAME OR OLIGOMERIC ANALOGUES, AND USES THEREOF |
AU2010217100B2 (en) | 2009-02-25 | 2014-03-27 | Academia Sinica | Anti-CepsilonmX antibodies capable of binding to human mIgE on B lymphocytes |
CA2796339C (en) | 2010-04-15 | 2020-03-31 | Abbott Laboratories | Amyloid-beta binding proteins |
JP5740470B2 (ja) | 2010-06-14 | 2015-06-24 | エサブ・アーベー | Mig/mag溶接のための溶接パラメータを自動的に設定する方法およびその方法を実行するための制御装置 |
US9062101B2 (en) | 2010-08-14 | 2015-06-23 | AbbVie Deutschland GmbH & Co. KG | Amyloid-beta binding proteins |
CA2954031A1 (en) | 2014-07-07 | 2016-01-14 | AbbVie Deutschland GmbH & Co. KG | Immunogenic products based on mutein amyloid .beta. (.alpha..beta.) amino acid sequences and uses thereof |
-
2006
- 2006-11-30 EP EP06838873.5A patent/EP1976877B2/en active Active
- 2006-11-30 CA CA2631195A patent/CA2631195C/en active Active
- 2006-11-30 RU RU2008126241/10A patent/RU2432362C2/ru active
- 2006-11-30 KR KR1020187014631A patent/KR20180058863A/ko active Application Filing
- 2006-11-30 RS RS20140180A patent/RS53270B2/sr unknown
- 2006-11-30 PL PL06838873T patent/PL1976877T5/pl unknown
- 2006-11-30 JP JP2008543522A patent/JP5486808B2/ja active Active
- 2006-11-30 DK DK06838873.5T patent/DK1976877T4/en active
- 2006-11-30 US US11/574,847 patent/US8497072B2/en active Active
- 2006-11-30 CN CN201210380708.5A patent/CN102898519B/zh active Active
- 2006-11-30 BR BRPI0619357A patent/BRPI0619357B8/pt active IP Right Grant
- 2006-11-30 KR KR1020137018540A patent/KR101439828B1/ko active IP Right Grant
- 2006-11-30 KR KR1020167028291A patent/KR101906161B1/ko active IP Right Grant
- 2006-11-30 CN CN2006800519854A patent/CN101506236B/zh active Active
- 2006-11-30 ES ES06838873.5T patent/ES2453941T5/es active Active
- 2006-11-30 SG SG10201706600VA patent/SG10201706600VA/en unknown
- 2006-11-30 KR KR1020147017089A patent/KR20140087058A/ko not_active Application Discontinuation
- 2006-11-30 WO PCT/US2006/046148 patent/WO2007064972A2/en active Application Filing
- 2006-11-30 PT PT68388735T patent/PT1976877E/pt unknown
- 2006-11-30 KR KR1020157014072A patent/KR101667623B1/ko active IP Right Grant
- 2006-11-30 IL IL297746A patent/IL297746A/en unknown
- 2006-11-30 SG SG2014013437A patent/SG2014013437A/en unknown
- 2006-11-30 AU AU2006320392A patent/AU2006320392B2/en active Active
- 2006-11-30 KR KR1020087015956A patent/KR101434935B1/ko active IP Right Grant
-
2008
- 2008-05-20 IL IL191587A patent/IL191587A/en active IP Right Grant
- 2008-05-29 ZA ZA200804686A patent/ZA200804686B/xx unknown
- 2008-05-30 MX MX2022005782A patent/MX2022005782A/es unknown
- 2008-11-27 HK HK08112971.0A patent/HK1119186A1/xx unknown
-
2010
- 2010-12-16 IL IL210058A patent/IL210058A/en active IP Right Grant
-
2011
- 2011-07-21 US US13/188,034 patent/US10208109B2/en active Active
-
2012
- 2012-09-21 JP JP2012208727A patent/JP2013047228A/ja active Pending
-
2013
- 2013-08-28 JP JP2013176314A patent/JP5816234B2/ja active Active
- 2013-09-17 IL IL228535A patent/IL228535A/en active IP Right Grant
-
2014
- 2014-03-14 HR HRP20140240TT patent/HRP20140240T4/hr unknown
- 2014-04-01 IL IL231857A patent/IL231857A/en active IP Right Grant
- 2014-06-12 US US14/303,300 patent/US20150071915A1/en not_active Abandoned
-
2015
- 2015-08-26 JP JP2015166837A patent/JP2016053017A/ja active Pending
-
2016
- 2016-01-27 IL IL243807A patent/IL243807B/en active IP Right Grant
- 2016-02-17 US US15/007,726 patent/US20160159891A1/en not_active Abandoned
-
2017
- 2017-04-28 JP JP2017089395A patent/JP2017178950A/ja active Pending
- 2017-07-27 US US15/662,224 patent/US10323084B2/en active Active
-
2018
- 2018-01-04 JP JP2018000073A patent/JP7061875B2/ja active Active
-
2020
- 2020-02-24 IL IL272883A patent/IL272883A/en unknown
- 2020-04-03 JP JP2020067220A patent/JP2020143058A/ja not_active Withdrawn
-
2021
- 2021-02-22 US US17/182,095 patent/US20220017607A1/en active Pending
- 2021-12-24 IL IL289365A patent/IL289365A/en unknown
-
2022
- 2022-03-08 JP JP2022035500A patent/JP2022091786A/ja not_active Withdrawn
Also Published As
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JP5816234B2 (ja) | アミロイドベータタンパク質に対するモノクローナル抗体及びその使用 | |
AU2013200177B2 (en) | Monoclonal antibodies against amyloid beta protein and uses thereof | |
AU2014277712B2 (en) | Monoclonal antibodies against amyloid beta protein and uses thereof | |
MX2008007006A (es) | Anticuerpos monoclonales contra la proteina amiloide beta y usos de los mismos |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20091009 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20120321 |
|
A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20120615 |
|
A602 | Written permission of extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A602 Effective date: 20120622 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20120921 |
|
RD02 | Notification of acceptance of power of attorney |
Free format text: JAPANESE INTERMEDIATE CODE: A7422 Effective date: 20130304 |
|
RD04 | Notification of resignation of power of attorney |
Free format text: JAPANESE INTERMEDIATE CODE: A7424 Effective date: 20130318 |
|
A02 | Decision of refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A02 Effective date: 20130507 |
|
A711 | Notification of change in applicant |
Free format text: JAPANESE INTERMEDIATE CODE: A712 Effective date: 20130701 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20130822 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20130828 |
|
A911 | Transfer to examiner for re-examination before appeal (zenchi) |
Free format text: JAPANESE INTERMEDIATE CODE: A911 Effective date: 20131001 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20131126 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20140114 |
|
TRDD | Decision of grant or rejection written | ||
A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 20140218 |
|
A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20140224 |
|
R150 | Certificate of patent or registration of utility model |
Ref document number: 5486808 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
S111 | Request for change of ownership or part of ownership |
Free format text: JAPANESE INTERMEDIATE CODE: R313115 |
|
R350 | Written notification of registration of transfer |
Free format text: JAPANESE INTERMEDIATE CODE: R350 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
S531 | Written request for registration of change of domicile |
Free format text: JAPANESE INTERMEDIATE CODE: R313531 |
|
R350 | Written notification of registration of transfer |
Free format text: JAPANESE INTERMEDIATE CODE: R350 |
|
RD02 | Notification of acceptance of power of attorney |
Free format text: JAPANESE INTERMEDIATE CODE: R3D02 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |