FI111546B - In vitro -menetelmiä, joilla voidaan monitoroida beta-amyloidiesiasteproteiinin prosessointia solussa, diagnosoida tai monitoroida beta-amyloidiin liittyvää tautia tai tunnistaa beta-amyloidin tuotannon inhibiittoreita, sekä beta-amyloidiesiasteproteiinin liukoinen fragmentti - Google Patents
In vitro -menetelmiä, joilla voidaan monitoroida beta-amyloidiesiasteproteiinin prosessointia solussa, diagnosoida tai monitoroida beta-amyloidiin liittyvää tautia tai tunnistaa beta-amyloidin tuotannon inhibiittoreita, sekä beta-amyloidiesiasteproteiinin liukoinen fragmentti Download PDFInfo
- Publication number
- FI111546B FI111546B FI944847A FI944847A FI111546B FI 111546 B FI111546 B FI 111546B FI 944847 A FI944847 A FI 944847A FI 944847 A FI944847 A FI 944847A FI 111546 B FI111546 B FI 111546B
- Authority
- FI
- Finland
- Prior art keywords
- βαρρ
- fragment
- amyloid
- beta
- residues
- Prior art date
Links
- 239000012634 fragment Substances 0.000 title claims abstract description 52
- 102000013455 Amyloid beta-Peptides Human genes 0.000 title claims abstract description 27
- 108010090849 Amyloid beta-Peptides Proteins 0.000 title claims abstract description 27
- 238000000338 in vitro Methods 0.000 title claims abstract description 20
- 238000012544 monitoring process Methods 0.000 title claims abstract description 18
- 201000010099 disease Diseases 0.000 title claims abstract description 16
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 title claims abstract description 16
- 238000012545 processing Methods 0.000 title claims abstract description 14
- 239000003112 inhibitor Substances 0.000 title claims abstract description 7
- 238000000034 method Methods 0.000 title claims description 51
- 238000003745 diagnosis Methods 0.000 title abstract description 5
- 239000002243 precursor Substances 0.000 title description 5
- 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 claims abstract description 32
- 208000024827 Alzheimer disease Diseases 0.000 claims abstract description 19
- 238000003776 cleavage reaction Methods 0.000 claims abstract description 16
- 230000007017 scission Effects 0.000 claims abstract description 15
- 238000004519 manufacturing process Methods 0.000 claims abstract description 13
- 230000028327 secretion Effects 0.000 claims abstract description 11
- 239000000126 substance Substances 0.000 claims abstract description 6
- 210000004748 cultured cell Anatomy 0.000 claims abstract description 5
- 210000004027 cell Anatomy 0.000 claims description 47
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 35
- 102000001708 Protein Isoforms Human genes 0.000 claims description 27
- 108010029485 Protein Isoforms Proteins 0.000 claims description 27
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 26
- 150000001875 compounds Chemical class 0.000 claims description 21
- 150000001413 amino acids Chemical group 0.000 claims description 17
- 238000012360 testing method Methods 0.000 claims description 16
- 239000000523 sample Substances 0.000 claims description 15
- 210000004899 c-terminal region Anatomy 0.000 claims description 13
- 238000001514 detection method Methods 0.000 claims description 12
- 229930182817 methionine Natural products 0.000 claims description 11
- 125000001433 C-terminal amino-acid group Chemical group 0.000 claims description 10
- 125000001360 methionine group Chemical group N[C@@H](CCSC)C(=O)* 0.000 claims description 9
- 239000012472 biological sample Substances 0.000 claims description 7
- 239000013610 patient sample Substances 0.000 claims description 6
- 230000027455 binding Effects 0.000 claims description 3
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 claims description 2
- 239000004472 Lysine Substances 0.000 claims description 2
- 235000019820 disodium diphosphate Nutrition 0.000 claims 7
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 claims 2
- ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 claims 2
- 206010002022 amyloidosis Diseases 0.000 claims 1
- 238000012258 culturing Methods 0.000 claims 1
- 238000011895 specific detection Methods 0.000 claims 1
- 238000001727 in vivo Methods 0.000 abstract description 5
- 238000004393 prognosis Methods 0.000 abstract description 3
- 230000009870 specific binding Effects 0.000 abstract description 3
- 239000002609 medium Substances 0.000 description 18
- 210000001175 cerebrospinal fluid Anatomy 0.000 description 15
- 239000000463 material Substances 0.000 description 15
- 108090000623 proteins and genes Proteins 0.000 description 15
- 239000011347 resin Substances 0.000 description 15
- 229920005989 resin Polymers 0.000 description 15
- 238000004113 cell culture Methods 0.000 description 14
- 239000000499 gel Substances 0.000 description 14
- 102000004196 processed proteins & peptides Human genes 0.000 description 14
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 13
- 102000004169 proteins and genes Human genes 0.000 description 12
- 101710137189 Amyloid-beta A4 protein Proteins 0.000 description 11
- 102100022704 Amyloid-beta precursor protein Human genes 0.000 description 11
- 101710151993 Amyloid-beta precursor protein Proteins 0.000 description 11
- 229940024606 amino acid Drugs 0.000 description 11
- 229960004452 methionine Drugs 0.000 description 11
- 241000283973 Oryctolagus cuniculus Species 0.000 description 9
- 230000002163 immunogen Effects 0.000 description 9
- 210000004958 brain cell Anatomy 0.000 description 8
- 238000006243 chemical reaction Methods 0.000 description 8
- 230000001605 fetal effect Effects 0.000 description 8
- 238000001114 immunoprecipitation Methods 0.000 description 8
- 230000035772 mutation Effects 0.000 description 8
- 210000004556 brain Anatomy 0.000 description 7
- 210000002966 serum Anatomy 0.000 description 7
- 239000011780 sodium chloride Substances 0.000 description 7
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 6
- 238000002347 injection Methods 0.000 description 6
- 239000007924 injection Substances 0.000 description 6
- 238000012216 screening Methods 0.000 description 6
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 6
- 241000894007 species Species 0.000 description 6
- 210000001519 tissue Anatomy 0.000 description 6
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 5
- GAAKALASJNGQKD-UHFFFAOYSA-N LY-165163 Chemical compound C1=CC(N)=CC=C1CCN1CCN(C=2C=C(C=CC=2)C(F)(F)F)CC1 GAAKALASJNGQKD-UHFFFAOYSA-N 0.000 description 5
- 210000004369 blood Anatomy 0.000 description 5
- 239000008280 blood Substances 0.000 description 5
- 230000001900 immune effect Effects 0.000 description 5
- 210000002569 neuron Anatomy 0.000 description 5
- 210000002381 plasma Anatomy 0.000 description 5
- 208000037259 Amyloid Plaque Diseases 0.000 description 4
- 241001465754 Metazoa Species 0.000 description 4
- 241000699666 Mus <mouse, genus> Species 0.000 description 4
- 108010071390 Serum Albumin Proteins 0.000 description 4
- 102000007562 Serum Albumin Human genes 0.000 description 4
- 239000006180 TBST buffer Substances 0.000 description 4
- 241000251539 Vertebrata <Metazoa> Species 0.000 description 4
- 239000002671 adjuvant Substances 0.000 description 4
- 239000000427 antigen Substances 0.000 description 4
- 102000036639 antigens Human genes 0.000 description 4
- 108091007433 antigens Proteins 0.000 description 4
- 230000002401 inhibitory effect Effects 0.000 description 4
- 239000000203 mixture Substances 0.000 description 4
- 230000037361 pathway Effects 0.000 description 4
- 239000002244 precipitate Substances 0.000 description 4
- 238000011282 treatment Methods 0.000 description 4
- 210000002700 urine Anatomy 0.000 description 4
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 3
- 201000010374 Down Syndrome Diseases 0.000 description 3
- 238000002965 ELISA Methods 0.000 description 3
- 239000004471 Glycine Substances 0.000 description 3
- 239000007983 Tris buffer Substances 0.000 description 3
- 206010044688 Trisomy 21 Diseases 0.000 description 3
- 239000011230 binding agent Substances 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 3
- 230000001413 cellular effect Effects 0.000 description 3
- 230000002452 interceptive effect Effects 0.000 description 3
- 230000001717 pathogenic effect Effects 0.000 description 3
- 229920001184 polypeptide Polymers 0.000 description 3
- 238000002360 preparation method Methods 0.000 description 3
- 230000009257 reactivity Effects 0.000 description 3
- 238000010532 solid phase synthesis reaction Methods 0.000 description 3
- 239000006228 supernatant Substances 0.000 description 3
- YNJBWRMUSHSURL-UHFFFAOYSA-N trichloroacetic acid Chemical compound OC(=O)C(Cl)(Cl)Cl YNJBWRMUSHSURL-UHFFFAOYSA-N 0.000 description 3
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 3
- 229920000936 Agarose Polymers 0.000 description 2
- -1 CSF Substances 0.000 description 2
- 241000283707 Capra Species 0.000 description 2
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 2
- 239000012981 Hank's balanced salt solution Substances 0.000 description 2
- 102000008394 Immunoglobulin Fragments Human genes 0.000 description 2
- 108010021625 Immunoglobulin Fragments Proteins 0.000 description 2
- GDBQQVLCIARPGH-UHFFFAOYSA-N Leupeptin Natural products CC(C)CC(NC(C)=O)C(=O)NC(CC(C)C)C(=O)NC(C=O)CCCN=C(N)N GDBQQVLCIARPGH-UHFFFAOYSA-N 0.000 description 2
- SEQKRHFRPICQDD-UHFFFAOYSA-N N-tris(hydroxymethyl)methylglycine Chemical compound OCC(CO)(CO)[NH2+]CC([O-])=O SEQKRHFRPICQDD-UHFFFAOYSA-N 0.000 description 2
- 108091005804 Peptidases Proteins 0.000 description 2
- RJKFOVLPORLFTN-LEKSSAKUSA-N Progesterone Chemical compound C1CC2=CC(=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H](C(=O)C)[C@@]1(C)CC2 RJKFOVLPORLFTN-LEKSSAKUSA-N 0.000 description 2
- 239000004365 Protease Substances 0.000 description 2
- 102100037486 Reverse transcriptase/ribonuclease H Human genes 0.000 description 2
- 229920002684 Sepharose Polymers 0.000 description 2
- 238000000211 autoradiogram Methods 0.000 description 2
- 238000005119 centrifugation Methods 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- 239000003636 conditioned culture medium Substances 0.000 description 2
- 238000007796 conventional method Methods 0.000 description 2
- 238000005859 coupling reaction Methods 0.000 description 2
- 230000009260 cross reactivity Effects 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 238000011156 evaluation Methods 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 239000012894 fetal calf serum Substances 0.000 description 2
- 239000001963 growth medium Substances 0.000 description 2
- 238000003018 immunoassay Methods 0.000 description 2
- 239000012133 immunoprecipitate Substances 0.000 description 2
- 230000003834 intracellular effect Effects 0.000 description 2
- GDBQQVLCIARPGH-ULQDDVLXSA-N leupeptin Chemical compound CC(C)C[C@H](NC(C)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C=O)CCCN=C(N)N GDBQQVLCIARPGH-ULQDDVLXSA-N 0.000 description 2
- 108010052968 leupeptin Proteins 0.000 description 2
- 238000005259 measurement Methods 0.000 description 2
- 230000037353 metabolic pathway Effects 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
- 238000001556 precipitation Methods 0.000 description 2
- 238000001742 protein purification Methods 0.000 description 2
- 230000002797 proteolythic effect Effects 0.000 description 2
- 230000006337 proteolytic cleavage Effects 0.000 description 2
- KIDHWZJUCRJVML-UHFFFAOYSA-N putrescine Chemical compound NCCCCN KIDHWZJUCRJVML-UHFFFAOYSA-N 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- 210000004989 spleen cell Anatomy 0.000 description 2
- 238000010561 standard procedure Methods 0.000 description 2
- 238000006467 substitution reaction Methods 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- 230000009466 transformation Effects 0.000 description 2
- 238000001262 western blot Methods 0.000 description 2
- WFIYPADYPQQLNN-UHFFFAOYSA-N 2-[2-(4-bromopyrazol-1-yl)ethyl]isoindole-1,3-dione Chemical compound C1=C(Br)C=NN1CCN1C(=O)C2=CC=CC=C2C1=O WFIYPADYPQQLNN-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
- JJMIISFFKMKOIV-UHFFFAOYSA-N 4-benzoyl-4-(2,5-dioxopyrrol-1-yl)-1-hydroxy-2,5-dioxopyrrolidine-3-sulfonic acid Chemical compound O=C1N(O)C(=O)C(S(O)(=O)=O)C1(C(=O)C=1C=CC=CC=1)N1C(=O)C=CC1=O JJMIISFFKMKOIV-UHFFFAOYSA-N 0.000 description 1
- 102000002260 Alkaline Phosphatase Human genes 0.000 description 1
- 108020004774 Alkaline Phosphatase Proteins 0.000 description 1
- 102000002659 Amyloid Precursor Protein Secretases Human genes 0.000 description 1
- 108010043324 Amyloid Precursor Protein Secretases Proteins 0.000 description 1
- 102000009091 Amyloidogenic Proteins Human genes 0.000 description 1
- 108010048112 Amyloidogenic Proteins Proteins 0.000 description 1
- 230000007546 Aβ plaque accumulation Effects 0.000 description 1
- 101001011741 Bos taurus Insulin Proteins 0.000 description 1
- 101100283604 Caenorhabditis elegans pigk-1 gene Proteins 0.000 description 1
- 241000699800 Cricetinae Species 0.000 description 1
- XUIIKFGFIJCVMT-GFCCVEGCSA-N D-thyroxine Chemical compound IC1=CC(C[C@@H](N)C(O)=O)=CC(I)=C1OC1=CC(I)=C(O)C(I)=C1 XUIIKFGFIJCVMT-GFCCVEGCSA-N 0.000 description 1
- 102000016911 Deoxyribonucleases Human genes 0.000 description 1
- 108010053770 Deoxyribonucleases Proteins 0.000 description 1
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 1
- 101000919504 Gallus gallus Beta-crystallin B1 Proteins 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 101000766306 Homo sapiens Serotransferrin Proteins 0.000 description 1
- 108060003951 Immunoglobulin Proteins 0.000 description 1
- AGPKZVBTJJNPAG-WHFBIAKZSA-N L-isoleucine Chemical compound CC[C@H](C)[C@H](N)C(O)=O AGPKZVBTJJNPAG-WHFBIAKZSA-N 0.000 description 1
- COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- 125000000729 N-terminal amino-acid group Chemical group 0.000 description 1
- 239000004677 Nylon Substances 0.000 description 1
- 102000043276 Oncogene Human genes 0.000 description 1
- 108700020796 Oncogene Proteins 0.000 description 1
- 239000002033 PVDF binder Substances 0.000 description 1
- 241000237988 Patellidae Species 0.000 description 1
- 241001494479 Pecora Species 0.000 description 1
- 206010035226 Plasma cell myeloma Diseases 0.000 description 1
- 241000276498 Pollachius virens Species 0.000 description 1
- 229920002873 Polyethylenimine Polymers 0.000 description 1
- 239000005700 Putrescine Substances 0.000 description 1
- LCTONWCANYUPML-UHFFFAOYSA-M Pyruvate Chemical compound CC(=O)C([O-])=O LCTONWCANYUPML-UHFFFAOYSA-M 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- 102000007056 Recombinant Fusion Proteins Human genes 0.000 description 1
- 108010008281 Recombinant Fusion Proteins Proteins 0.000 description 1
- UZMAPBJVXOGOFT-UHFFFAOYSA-N Syringetin Natural products COC1=C(O)C(OC)=CC(C2=C(C(=O)C3=C(O)C=C(O)C=C3O2)O)=C1 UZMAPBJVXOGOFT-UHFFFAOYSA-N 0.000 description 1
- AUYYCJSJGJYCDS-LBPRGKRZSA-N Thyrolar Chemical compound IC1=CC(C[C@H](N)C(O)=O)=CC(I)=C1OC1=CC=C(O)C(I)=C1 AUYYCJSJGJYCDS-LBPRGKRZSA-N 0.000 description 1
- 239000007997 Tricine buffer Substances 0.000 description 1
- XYIPYISRNJUPBA-UHFFFAOYSA-N [3-(3'-methoxyspiro[adamantane-2,4'-dioxetane]-3'-yl)phenyl] dihydrogen phosphate Chemical compound O1OC2(C3CC4CC(C3)CC2C4)C1(OC)C1=CC=CC(OP(O)(O)=O)=C1 XYIPYISRNJUPBA-UHFFFAOYSA-N 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 238000001261 affinity purification Methods 0.000 description 1
- VREFGVBLTWBCJP-UHFFFAOYSA-N alprazolam Chemical compound C12=CC(Cl)=CC=C2N2C(C)=NN=C2CN=C1C1=CC=CC=C1 VREFGVBLTWBCJP-UHFFFAOYSA-N 0.000 description 1
- 230000004075 alteration Effects 0.000 description 1
- 125000000539 amino acid group Chemical group 0.000 description 1
- 230000003942 amyloidogenic effect Effects 0.000 description 1
- 210000004102 animal cell Anatomy 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 210000001130 astrocyte Anatomy 0.000 description 1
- 238000000376 autoradiography Methods 0.000 description 1
- 210000001124 body fluid Anatomy 0.000 description 1
- 239000010839 body fluid Substances 0.000 description 1
- IXIBAKNTJSCKJM-BUBXBXGNSA-N bovine insulin Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@H]1CSSC[C@H]2C(=O)N[C@@H](C)C(=O)N[C@@H](CO)C(=O)N[C@H](C(=O)N[C@H](C(N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC=3C=CC(O)=CC=3)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=3C=CC(O)=CC=3)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=3C=CC(O)=CC=3)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=3NC=NC=3)NC(=O)[C@H](CO)NC(=O)CNC1=O)C(=O)NCC(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)NCC(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(O)=O)C(=O)N[C@@H](CC(N)=O)C(O)=O)=O)CSSC[C@@H](C(N2)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@@H](NC(=O)CN)[C@@H](C)CC)C(C)C)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@@H](NC(=O)[C@@H](N)CC=1C=CC=CC=1)C(C)C)C1=CN=CN1 IXIBAKNTJSCKJM-BUBXBXGNSA-N 0.000 description 1
- 244000309466 calf Species 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 239000006143 cell culture medium Substances 0.000 description 1
- 230000007910 cell fusion Effects 0.000 description 1
- 230000003833 cell viability Effects 0.000 description 1
- 210000003710 cerebral cortex Anatomy 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 238000012761 co-transfection Methods 0.000 description 1
- 230000019771 cognition Effects 0.000 description 1
- 239000002299 complementary DNA Substances 0.000 description 1
- 239000000356 contaminant Substances 0.000 description 1
- 210000005257 cortical tissue Anatomy 0.000 description 1
- 230000008878 coupling Effects 0.000 description 1
- 238000010168 coupling process Methods 0.000 description 1
- 239000012228 culture supernatant Substances 0.000 description 1
- 230000034994 death Effects 0.000 description 1
- 238000012217 deletion Methods 0.000 description 1
- 230000037430 deletion Effects 0.000 description 1
- 238000012631 diagnostic technique Methods 0.000 description 1
- 230000004069 differentiation Effects 0.000 description 1
- KCFYHBSOLOXZIF-UHFFFAOYSA-N dihydrochrysin Natural products COC1=C(O)C(OC)=CC(C2OC3=CC(O)=CC(O)=C3C(=O)C2)=C1 KCFYHBSOLOXZIF-UHFFFAOYSA-N 0.000 description 1
- BVTBRVFYZUCAKH-UHFFFAOYSA-L disodium selenite Chemical compound [Na+].[Na+].[O-][Se]([O-])=O BVTBRVFYZUCAKH-UHFFFAOYSA-L 0.000 description 1
- 238000007877 drug screening Methods 0.000 description 1
- 208000025688 early-onset autosomal dominant Alzheimer disease Diseases 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 239000003480 eluent Substances 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 210000002889 endothelial cell Anatomy 0.000 description 1
- 230000029142 excretion Effects 0.000 description 1
- 238000013401 experimental design Methods 0.000 description 1
- 239000012091 fetal bovine serum Substances 0.000 description 1
- 210000003754 fetus Anatomy 0.000 description 1
- 210000002950 fibroblast Anatomy 0.000 description 1
- 230000008014 freezing Effects 0.000 description 1
- 238000007710 freezing Methods 0.000 description 1
- 230000004927 fusion Effects 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 238000002523 gelfiltration Methods 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 1
- 150000004676 glycans Chemical class 0.000 description 1
- 210000005260 human cell Anatomy 0.000 description 1
- 230000003053 immunization Effects 0.000 description 1
- 238000002649 immunization Methods 0.000 description 1
- 230000005847 immunogenicity Effects 0.000 description 1
- 102000018358 immunoglobulin Human genes 0.000 description 1
- 230000016784 immunoglobulin production Effects 0.000 description 1
- 229940072221 immunoglobulins Drugs 0.000 description 1
- 238000010324 immunological assay Methods 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 238000011081 inoculation Methods 0.000 description 1
- 238000003780 insertion Methods 0.000 description 1
- 230000037431 insertion Effects 0.000 description 1
- 229960000310 isoleucine Drugs 0.000 description 1
- AGPKZVBTJJNPAG-UHFFFAOYSA-N isoleucine Natural products CCC(C)C(N)C(O)=O AGPKZVBTJJNPAG-UHFFFAOYSA-N 0.000 description 1
- YWXYYJSYQOXTPL-SLPGGIOYSA-N isosorbide mononitrate Chemical compound [O-][N+](=O)O[C@@H]1CO[C@@H]2[C@@H](O)CO[C@@H]21 YWXYYJSYQOXTPL-SLPGGIOYSA-N 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 210000003292 kidney cell Anatomy 0.000 description 1
- 238000002372 labelling Methods 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 210000004698 lymphocyte Anatomy 0.000 description 1
- 125000003588 lysine group Chemical group [H]N([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 description 1
- 238000012423 maintenance Methods 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 238000001466 metabolic labeling Methods 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- MYWUZJCMWCOHBA-VIFPVBQESA-N methamphetamine Chemical compound CN[C@@H](C)CC1=CC=CC=C1 MYWUZJCMWCOHBA-VIFPVBQESA-N 0.000 description 1
- 230000003278 mimic effect Effects 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 238000010172 mouse model Methods 0.000 description 1
- 201000000050 myeloid neoplasm Diseases 0.000 description 1
- 230000024717 negative regulation of secretion Effects 0.000 description 1
- 210000000944 nerve tissue Anatomy 0.000 description 1
- 230000001537 neural effect Effects 0.000 description 1
- 210000002682 neurofibrillary tangle Anatomy 0.000 description 1
- 230000016273 neuron death Effects 0.000 description 1
- 229920001778 nylon Polymers 0.000 description 1
- 210000001672 ovary Anatomy 0.000 description 1
- 230000036961 partial effect Effects 0.000 description 1
- 210000004197 pelvis Anatomy 0.000 description 1
- 239000003208 petroleum Substances 0.000 description 1
- COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 description 1
- 239000008363 phosphate buffer Substances 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 102000040430 polynucleotide Human genes 0.000 description 1
- 108091033319 polynucleotide Proteins 0.000 description 1
- 239000002157 polynucleotide Substances 0.000 description 1
- 229920001282 polysaccharide Polymers 0.000 description 1
- 239000005017 polysaccharide Substances 0.000 description 1
- 229920002981 polyvinylidene fluoride Polymers 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 229960003387 progesterone Drugs 0.000 description 1
- 239000000186 progesterone Substances 0.000 description 1
- XNSAINXGIQZQOO-SRVKXCTJSA-N protirelin Chemical compound NC(=O)[C@@H]1CCCN1C(=O)[C@@H](NC(=O)[C@H]1NC(=O)CC1)CC1=CN=CN1 XNSAINXGIQZQOO-SRVKXCTJSA-N 0.000 description 1
- 238000003127 radioimmunoassay Methods 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 239000012723 sample buffer Substances 0.000 description 1
- 230000003248 secreting effect Effects 0.000 description 1
- 150000003384 small molecules Chemical class 0.000 description 1
- 229960001471 sodium selenite Drugs 0.000 description 1
- 235000015921 sodium selenite Nutrition 0.000 description 1
- 239000011781 sodium selenite Substances 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 229940034208 thyroxine Drugs 0.000 description 1
- XUIIKFGFIJCVMT-UHFFFAOYSA-N thyroxine-binding globulin Natural products IC1=CC(CC([NH3+])C([O-])=O)=CC(I)=C1OC1=CC(I)=C(O)C(I)=C1 XUIIKFGFIJCVMT-UHFFFAOYSA-N 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 238000011269 treatment regimen Methods 0.000 description 1
- 238000000539 two dimensional gel electrophoresis Methods 0.000 description 1
- 241001430294 unidentified retrovirus Species 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/5005—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells
- G01N33/5091—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells for testing the pathological state of an organism
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/46—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
- C07K14/47—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals
- C07K14/4701—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals not used
- C07K14/4711—Alzheimer's disease; Amyloid plaque core protein
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/63—Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
- C12N15/79—Vectors or expression systems specially adapted for eukaryotic hosts
- C12N15/85—Vectors or expression systems specially adapted for eukaryotic hosts for animal cells
- C12N15/8509—Vectors or expression systems specially adapted for eukaryotic hosts for animal cells for producing genetically modified animals, e.g. transgenic
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/5005—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells
- G01N33/5008—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/5005—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells
- G01N33/5008—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics
- G01N33/502—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics for testing non-proliferative effects
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/5005—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells
- G01N33/5008—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics
- G01N33/5044—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics involving specific cell types
- G01N33/5058—Neurological cells
-
- 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
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
- A01K2217/00—Genetically modified animals
- A01K2217/05—Animals comprising random inserted nucleic acids (transgenic)
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
- A01K2217/00—Genetically modified animals
- A01K2217/07—Animals genetically altered by homologous recombination
- A01K2217/075—Animals genetically altered by homologous recombination inducing loss of function, i.e. knock out
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
- A01K2267/00—Animals characterised by purpose
- A01K2267/03—Animal model, e.g. for test or diseases
- A01K2267/0306—Animal model for genetic diseases
- A01K2267/0312—Animal model for Alzheimer's disease
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
- A01K2267/00—Animals characterised by purpose
- A01K2267/03—Animal model, e.g. for test or diseases
- A01K2267/0306—Animal model for genetic diseases
- A01K2267/0318—Animal model for neurodegenerative disease, e.g. non- Alzheimer's
-
- 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
- G01N2800/00—Detection or diagnosis of diseases
- G01N2800/28—Neurological disorders
- G01N2800/2814—Dementia; Cognitive disorders
- G01N2800/2821—Alzheimer
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
- Y10S—TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10S436/00—Chemistry: analytical and immunological testing
- Y10S436/811—Test for named disease, body condition or organ function
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Biomedical Technology (AREA)
- Chemical & Material Sciences (AREA)
- Immunology (AREA)
- Molecular Biology (AREA)
- Hematology (AREA)
- Urology & Nephrology (AREA)
- General Health & Medical Sciences (AREA)
- Biochemistry (AREA)
- Medicinal Chemistry (AREA)
- Biotechnology (AREA)
- Organic Chemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Genetics & Genomics (AREA)
- Microbiology (AREA)
- Cell Biology (AREA)
- Physics & Mathematics (AREA)
- Food Science & Technology (AREA)
- Analytical Chemistry (AREA)
- Pathology (AREA)
- General Physics & Mathematics (AREA)
- Tropical Medicine & Parasitology (AREA)
- Toxicology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Zoology (AREA)
- Biophysics (AREA)
- General Engineering & Computer Science (AREA)
- Wood Science & Technology (AREA)
- Veterinary Medicine (AREA)
- Physiology (AREA)
- Plant Pathology (AREA)
- Gastroenterology & Hepatology (AREA)
- Pharmacology & Pharmacy (AREA)
- Psychiatry (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
Applications Claiming Priority (6)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US86894992A | 1992-04-15 | 1992-04-15 | |
US86894992 | 1992-04-15 | ||
US96597192 | 1992-10-26 | ||
US07/965,971 US5441870A (en) | 1992-04-15 | 1992-10-26 | Methods for monitoring cellular processing of β-amyloid precursor protein |
US9301817 | 1993-03-03 | ||
PCT/US1993/001817 WO1993021526A1 (fr) | 1992-04-15 | 1993-03-03 | PROCEDES ET COMPOSITION DE CONTROLE DU TRAITEMENT CELLULAIRE DE LA PROTEINE PRECURSEUR β-AMYLOIDE |
Publications (3)
Publication Number | Publication Date |
---|---|
FI944847A FI944847A (fi) | 1994-10-14 |
FI944847A0 FI944847A0 (fi) | 1994-10-14 |
FI111546B true FI111546B (fi) | 2003-08-15 |
Family
ID=27128086
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
FI944847A FI111546B (fi) | 1992-04-15 | 1994-10-14 | In vitro -menetelmiä, joilla voidaan monitoroida beta-amyloidiesiasteproteiinin prosessointia solussa, diagnosoida tai monitoroida beta-amyloidiin liittyvää tautia tai tunnistaa beta-amyloidin tuotannon inhibiittoreita, sekä beta-amyloidiesiasteproteiinin liukoinen fragmentti |
Country Status (14)
Country | Link |
---|---|
US (3) | US5441870A (fr) |
EP (1) | EP0638172B1 (fr) |
JP (2) | JP3974168B2 (fr) |
AT (1) | ATE251304T1 (fr) |
AU (1) | AU688726B2 (fr) |
CA (1) | CA2118243C (fr) |
DE (1) | DE69333225T2 (fr) |
DK (1) | DK0638172T3 (fr) |
ES (1) | ES2206455T3 (fr) |
FI (1) | FI111546B (fr) |
NO (1) | NO320067B1 (fr) |
NZ (1) | NZ251053A (fr) |
PT (1) | PT638172E (fr) |
WO (1) | WO1993021526A1 (fr) |
Families Citing this family (172)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5525339A (en) * | 1986-08-27 | 1996-06-11 | Dms Pharmaceutical Inc. | Isolated components of dense microspheres derived from mammalian brain tissue and antibodies thereto |
US5441870A (en) * | 1992-04-15 | 1995-08-15 | Athena Neurosciences, Inc. | Methods for monitoring cellular processing of β-amyloid precursor protein |
US5837672A (en) * | 1992-07-10 | 1998-11-17 | Athena Neurosciences, Inc. | Methods and compositions for the detection of soluble β-amyloid peptide |
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 |
US5605811A (en) * | 1992-10-26 | 1997-02-25 | Athena Neurosciences, Inc. | Methods and compositions for monitoring cellular processing of beta-amyloid precursor protein |
DK1298436T3 (da) * | 1992-10-26 | 2010-10-25 | Elan Pharm Inc | Fremgangsmåde til identificering af inhibitorforbindelser for frisætning af beta-amyloidpeptid (BAP) |
DE69426571T2 (de) * | 1993-10-27 | 2001-08-09 | Elan Pharm Inc | TRANSGENE TIERE, DIE APP Allele mit der schwedischen Mutation beherbergen |
US5589154A (en) * | 1994-11-22 | 1996-12-31 | Rutgers, The State University Of New Jersey | Methods for the prevention or treatment of vascular hemorrhaging and Alzheimer's disease |
US5804560A (en) * | 1995-01-06 | 1998-09-08 | Sibia Neurosciences, Inc. | Peptide and peptide analog protease inhibitors |
US6017887A (en) * | 1995-01-06 | 2000-01-25 | Sibia Neurosciences, Inc. | Peptide, peptide analog and amino acid analog protease inhibitors |
CA2221684A1 (fr) * | 1995-06-06 | 1996-12-12 | Athena Neurosciences, Inc. | Nouvelle cathepsine et procedes et compositions d'inhibition de cathepsine |
US5849711A (en) * | 1995-06-06 | 1998-12-15 | Athena Neurosciences, Inc. | Cathepsin and methods and compositions for inhibition thereof |
US5783434A (en) * | 1995-06-06 | 1998-07-21 | Tung; Jay S. | Cathepsin and methods and compositions for inhibition thereof |
US6717031B2 (en) | 1995-06-07 | 2004-04-06 | Kate Dora Games | Method for selecting a transgenic mouse model of alzheimer's disease |
US6136530A (en) * | 1995-11-29 | 2000-10-24 | Texas Tech University Health Sciences Center | Compositions and methods for assessing risk factors in Alzheimer's disease |
WO1997021728A1 (fr) | 1995-12-12 | 1997-06-19 | Karolinska Innovations Ab | PEPTIDE FIXANT LA SEQUENCE KLVFF DE L'AMYLOIDE $g(b) |
JPH09178743A (ja) * | 1995-12-27 | 1997-07-11 | Oriental Yeast Co Ltd | 可溶性appの定量法 |
GB9701684D0 (en) | 1997-01-28 | 1997-03-19 | Smithkline Beecham Plc | Novel compounds |
US8173127B2 (en) * | 1997-04-09 | 2012-05-08 | Intellect Neurosciences, Inc. | Specific antibodies to amyloid beta peptide, pharmaceutical compositions and methods of use thereof |
JP4057781B2 (ja) * | 1997-10-31 | 2008-03-05 | チルドレンズ メディカル センター コーポレーション | 膀胱再構成 |
US6913745B1 (en) | 1997-12-02 | 2005-07-05 | Neuralab Limited | Passive immunization of Alzheimer's disease |
US6923964B1 (en) | 1997-12-02 | 2005-08-02 | Neuralab Limited | Active immunization of AScr for prion disorders |
US7179892B2 (en) * | 2000-12-06 | 2007-02-20 | Neuralab Limited | Humanized antibodies that recognize beta amyloid peptide |
US7790856B2 (en) | 1998-04-07 | 2010-09-07 | Janssen Alzheimer Immunotherapy | Humanized antibodies that recognize beta amyloid peptide |
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 |
US6761888B1 (en) * | 2000-05-26 | 2004-07-13 | Neuralab Limited | Passive immunization treatment of Alzheimer's disease |
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 |
US7588766B1 (en) | 2000-05-26 | 2009-09-15 | Elan Pharma International Limited | Treatment of amyloidogenic disease |
US6750324B1 (en) | 1997-12-02 | 2004-06-15 | Neuralab Limited | Humanized and chimeric N-terminal amyloid beta-antibodies |
US20080050367A1 (en) * | 1998-04-07 | 2008-02-28 | Guriq Basi | Humanized antibodies that recognize beta amyloid peptide |
US7964192B1 (en) | 1997-12-02 | 2011-06-21 | Janssen Alzheimer Immunotherapy | Prevention and treatment of amyloidgenic disease |
US6905686B1 (en) | 1997-12-02 | 2005-06-14 | Neuralab Limited | Active immunization for treatment of alzheimer's disease |
US20050059802A1 (en) * | 1998-04-07 | 2005-03-17 | Neuralab Ltd | Prevention and treatment of amyloidogenic disease |
US20030147882A1 (en) * | 1998-05-21 | 2003-08-07 | Alan Solomon | Methods for amyloid removal using anti-amyloid antibodies |
US7060670B1 (en) * | 1999-05-05 | 2006-06-13 | Neurochem (International) Limited | Stereoselective antifibrillogenic peptides and peptidomimetics thereof |
US20040167634A1 (en) * | 1999-05-26 | 2004-08-26 | Anthony Atala | Prosthetic kidney and its use for treating kidney disease |
US6787637B1 (en) | 1999-05-28 | 2004-09-07 | Neuralab Limited | N-Terminal amyloid-β antibodies |
UA81216C2 (en) * | 1999-06-01 | 2007-12-25 | Prevention and treatment of amyloid disease | |
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 |
US6479064B1 (en) * | 1999-12-29 | 2002-11-12 | Children's Medical Center Corporation | Culturing different cell populations on a decellularized natural biostructure for organ reconstruction |
US6992081B2 (en) | 2000-03-23 | 2006-01-31 | Elan Pharmaceuticals, Inc. | Compounds to treat Alzheimer's disease |
DE60124080T2 (de) * | 2000-03-23 | 2007-03-01 | Elan Pharmaceuticals, Inc., San Francisco | Verbindungen und verfahren zur behandlung der alzheimerschen krankheit |
AU2001257022B2 (en) * | 2000-04-13 | 2005-02-03 | Mayo Foundation For Medical Education And Research | Abeta 42 lowering agents |
PE20020276A1 (es) | 2000-06-30 | 2002-04-06 | Elan Pharm Inc | COMPUESTOS DE AMINA SUSTITUIDA COMO INHIBIDORES DE ß-SECRETASA PARA EL TRATAMIENTO DE ALZHEIMER |
US20030096864A1 (en) * | 2000-06-30 | 2003-05-22 | Fang Lawrence Y. | Compounds to treat alzheimer's disease |
US6846813B2 (en) * | 2000-06-30 | 2005-01-25 | Pharmacia & Upjohn Company | Compounds to treat alzheimer's disease |
EP1666452A2 (fr) | 2000-06-30 | 2006-06-07 | Elan Pharmaceuticals, Inc. | Composés pour le traitement de la maladie d'Alzheimer |
CN1217920C (zh) | 2000-06-30 | 2005-09-07 | 艾兰制药公司 | 治疗早老性痴呆的化合物 |
FR2816411B1 (fr) * | 2000-11-03 | 2003-07-04 | Inst Nat Sante Rech Med | Moyens de detection de la transformation pathologique de la proteine app et leurs applications |
PE20020574A1 (es) | 2000-12-06 | 2002-07-02 | Wyeth Corp | Anticuerpos humanizados que reconocen el peptido amiloideo beta |
US7700751B2 (en) | 2000-12-06 | 2010-04-20 | Janssen Alzheimer Immunotherapy | Humanized antibodies that recognize β-amyloid peptide |
US20030215896A1 (en) * | 2001-04-25 | 2003-11-20 | Yueming Li | Gamma secretase substrates and in vitro assays |
ATE409047T1 (de) * | 2001-04-30 | 2008-10-15 | Lilly Co Eli | Humanisierte antikörper |
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 |
DE60226729D1 (de) * | 2001-06-01 | 2008-07-03 | Elan Pharm Inc | Hydroxyalkylaminderivate als beta-secretase-inhibitoren und deren verwendung zur behandlung der alzheimerschen krankheit oder ähnlicher krankheiten |
JP2004532894A (ja) | 2001-06-13 | 2004-10-28 | イーラン ファーマスーティカルズ、インコーポレイテッド | アルツハイマー病を治療するためのアミンジオール |
BR0210721A (pt) * | 2001-06-27 | 2004-07-20 | Elan Pharm Inc | Composto, sal ou éster farmaceuticamente aceitável, método para fabricar um composto, e, método para tratar um paciente que tem, ou para evitar que o paciente adquira uma doença ou condição |
US20070213407A1 (en) * | 2001-06-29 | 2007-09-13 | Elan Pharmaceuticals And Pharmacia & Upjohn Company Llc | Compounds to treat Alzheimer's disease |
US7067542B2 (en) * | 2001-07-10 | 2006-06-27 | Pharmacia & Upjohn Company | Diaminediols for the treatment of Alzheimer's disease |
CA2453451A1 (fr) * | 2001-07-10 | 2003-01-23 | Elan Pharmaceuticals, Inc. | Aminodiols pour le traitement de la maladie d'alzheimer |
US7297553B2 (en) * | 2002-05-28 | 2007-11-20 | Nanosphere, Inc. | Method for attachment of silylated molecules to glass surfaces |
BR0212078A (pt) * | 2001-08-31 | 2004-09-28 | Neurochem Int Ltd | Método de tratar ou prevenir uma doença relacionada com amilóide em um paciente, composição farmacêutica, composto quìmico, e, uso de um composto |
BR0213139A (pt) * | 2001-10-04 | 2004-08-10 | Elan Pharm Inc | Composto, método de tratamento ou prevenção de doenças e de preparação de um composto, uso de um composto e composição farmacêutica |
EA200400648A1 (ru) | 2001-11-08 | 2005-04-28 | Элан Фармасьютикалз, Инк. | N, n'-замещенные производные 1,3-диамино-2-гидроксипропана |
AU2002340463A1 (en) * | 2001-11-16 | 2003-06-10 | Children's Medical Center Corporation | Augmentation of organ function |
MXPA04004713A (es) * | 2001-11-19 | 2005-08-16 | Pharmacia & Up John Company Ll | Aminoides utiles en el tratamiento de la enfermedad de alzheimer. |
US20050214763A1 (en) * | 2002-02-14 | 2005-09-29 | Rainer Hipfel | Diagnostic and therapeutic use of an activator protein for vesicle secretion for neurodegenerative diseases |
WO2003069347A2 (fr) * | 2002-02-14 | 2003-08-21 | Evotec Neurosciences Gmbh | Utilisation diagnostique et therapeutique d'une proteine activatrice de secretion vesiculaire dans les maladies neurodegeneratives |
EP1578356A4 (fr) * | 2002-02-27 | 2007-08-15 | Merck & Co Inc | Dosages servant a controler la maturation moleculaire d'une proteine precurseur amyloide |
CA2477675C (fr) * | 2002-03-05 | 2013-05-21 | Ramot At Tel-Aviv University Ltd. | Composition immunisante et procede permettant d'induire une reponse immunitaire contre le site de clivage de .beta.-secretase de la proteine du precurseur de l'amyloide |
MY139983A (en) * | 2002-03-12 | 2009-11-30 | Janssen Alzheimer Immunotherap | Humanized antibodies that recognize beta amyloid peptide |
JP2006500006A (ja) * | 2002-04-17 | 2006-01-05 | ファルマシア・アンド・アップジョン・カンパニー・エルエルシー | アルツハイマー病を治療する組成物および方法 |
US7262208B2 (en) * | 2002-04-30 | 2007-08-28 | Elan Pharmaceuticals, Inc. | Hydroxypropyl amides for the treatment of Alzheimer's disease |
WO2004032868A2 (fr) * | 2002-10-09 | 2004-04-22 | Rinat Neuroscience Corp. | Methodes de traitement de la maladie d'alzheimer au moyen d'anticorps diriges contre le peptide $g(b)-amyloide et compositions les comprenant |
KR100520495B1 (ko) * | 2002-10-23 | 2005-10-11 | 한국과학기술연구원 | 베타아밀로이드 특이 단일 클론 항체 및 그의 제조방법 |
DOP2003000765A (es) | 2002-11-27 | 2004-05-31 | Elan Fharmaceuticals Inc | Ureas substituidas y carbamatos utiles para el tratamiento de la enfermedad de alzheimer (substituted ureas and carbamates useful in the treatment of alzheimer`s disease |
DE10303974A1 (de) | 2003-01-31 | 2004-08-05 | Abbott Gmbh & Co. Kg | Amyloid-β(1-42)-Oligomere, Verfahren zu deren Herstellung und deren Verwendung |
EP1594969B1 (fr) * | 2003-02-01 | 2015-05-20 | Janssen Sciences Ireland UC | Immunisation active permettant de produire des anticorps contre a-beta soluble |
WO2004094384A2 (fr) | 2003-04-21 | 2004-11-04 | Elan Pharmaceuticals, Inc. | Benzamide 2-hydroxy-3-diaminoalcanes |
WO2004094413A1 (fr) * | 2003-04-21 | 2004-11-04 | Elan Pharmaceuticals, Inc. | Phenacyl 2-hydroxy-3-diaminoalcanes |
WO2004100998A2 (fr) * | 2003-05-07 | 2004-11-25 | General Electric Company | Compositions et procedes de visualisation non effractive du beta-amyloide soluble |
US20040223912A1 (en) * | 2003-05-07 | 2004-11-11 | Montalto Michael Christopher | Compositions and methods for non-invasive imaging of soluble beta-amyloid |
PE20050627A1 (es) | 2003-05-30 | 2005-08-10 | Wyeth Corp | Anticuerpos humanizados que reconocen el peptido beta amiloideo |
WO2005070407A1 (fr) * | 2004-01-21 | 2005-08-04 | Elan Pharmaceuticals, Inc. | Procedes de traitement d'amyloidose utilisant des inhibiteurs de protease aspartyle |
US7262223B2 (en) * | 2004-01-23 | 2007-08-28 | Neurochem (International) Limited | Amidine derivatives for treating amyloidosis |
CA2556826A1 (fr) * | 2004-03-09 | 2005-09-22 | Elan Pharmaceuticals, Inc. | Procedes de traitement de l'amylose mettant en oeuvre des inhibiteurs de la protease a base d'aspartyle bicyclique |
US20060014737A1 (en) * | 2004-03-09 | 2006-01-19 | Varghese John | Methods of treatment of amyloidosis using bi-aryl aspartyl protease inhibitors |
EP1734942A1 (fr) * | 2004-03-09 | 2006-12-27 | Elan Pharmaceuticals, Inc. | Uree et carbamate substitues, phenacyl-2-hydroxy-3-diaminoalcane, et benzamide-2-hydroxy-3-diaminoalcane inhibiteurs d'aspartyl-protease |
CA2558034A1 (fr) * | 2004-03-09 | 2005-09-22 | Elan Pharmaceuticals, Inc. | Aspartyle a base d'hydroxyethylamine substitue inhibiteurs de la protease |
US20050239790A1 (en) * | 2004-03-09 | 2005-10-27 | Varghese John | Substituted hydroxyethylamine aspartyl protease inhibitors |
CA2573138A1 (fr) * | 2004-07-09 | 2006-01-26 | Elan Pharmaceuticals Inc. | Inhibiteurs d'une aspartyl protease de type hydroxyethylamine substituee par un derive d'oxime |
EP1773758A1 (fr) * | 2004-07-09 | 2007-04-18 | Elan Pharmaceuticals, Inc. | Inhibiteurs d'aspartyl-protease d'hydroxyethylamine derivee des oximes |
WO2006036291A2 (fr) * | 2004-07-30 | 2006-04-06 | Rinat Neuroscience Corp. | Anticorps anti peptide amyloide beta, et leurs procedes d'utilisation |
US20060074098A1 (en) * | 2004-08-27 | 2006-04-06 | Roy Hom | Methods of treatment of amyloidosis using ethanolcyclicamine aspartyl protease inhibitors |
CA2583017A1 (fr) * | 2004-10-13 | 2006-04-20 | Ablynx N.V. | Nanocorps contre la proteine beta-amyloide et polypeptides les renfermant pour le traitement de maladies degeneratives neurales, telles que la maladie d'alzheimer |
EP1838349A1 (fr) * | 2004-12-15 | 2007-10-03 | Neuralab, Ltd. | ANTICORPS AMYLOIDE beta UTILISES AFIN D'AMELIORER LA COGNITION |
WO2006066049A2 (fr) | 2004-12-15 | 2006-06-22 | Neuralab Limited | Anticorps humanises reconnaissant le peptide beta amyloide |
CA2590337C (fr) | 2004-12-15 | 2017-07-11 | Neuralab Limited | Anticorps du peptide beta-amyloide humanises utilises dans l'amelioration de la cognition |
AU2006203819A1 (en) * | 2005-01-07 | 2006-07-13 | Roskamp Research Llc | Compounds for inhibiting beta-amyloid production and methods of identifying the compounds |
PE20061323A1 (es) * | 2005-04-29 | 2007-02-09 | Rinat Neuroscience Corp | Anticuerpos dirigidos contra el peptido amiloide beta y metodos que utilizan los mismos |
JP2009503027A (ja) * | 2005-08-03 | 2009-01-29 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | アルツハイマー病iiの治療のための置換エタン−1,2−ジアミン |
WO2007047305A1 (fr) * | 2005-10-12 | 2007-04-26 | Elan Pharmaceuticals, Inc. | Procedes de traitement de l'amyloïdose en utilisant des derives de cyclopropyle inhibiteurs de l'aspartyle-protease |
WO2007047306A1 (fr) * | 2005-10-12 | 2007-04-26 | Elan Pharmaceuticals, Inc. | Methodes de traitement de l'amylose au moyen de derives aryl-cyclopropyle inhibiteurs d'aspartyl-proteases |
US7838676B2 (en) * | 2005-11-21 | 2010-11-23 | Amgen Inc. | Beta-secretase modulators and methods of use |
US7745484B2 (en) * | 2005-11-21 | 2010-06-29 | Amgen Inc. | Beta-secretase modulators and methods of use |
US7872009B2 (en) * | 2005-11-21 | 2011-01-18 | Amgen Inc. | Beta-Secretase modulators and methods of use |
KR101439828B1 (ko) | 2005-11-30 | 2014-09-17 | 애브비 인코포레이티드 | 아밀로이드 베타 단백질에 대한 모노클로날 항체 및 이의 용도 |
KR20080090408A (ko) | 2005-11-30 | 2008-10-08 | 아보트 러보러터리즈 | 항-Aβ 글로불로머 항체, 이의 항원-결합 잔기, 상응하는하이브리도마, 핵산, 벡터, 숙주 세포, 당해 항체의 제조방법, 당해 항체를 포함하는 조성물, 당해 항체의 용도 및당해 항체의 사용 방법 |
EP2361638B1 (fr) * | 2005-12-12 | 2014-01-15 | AC Immune S.A. | Anticorps monoclonaux spécifiques de A beta 1-42 avec des propriétés thérapeutiques |
US8784810B2 (en) | 2006-04-18 | 2014-07-22 | Janssen Alzheimer Immunotherapy | Treatment of amyloidogenic diseases |
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 |
CA2653628C (fr) * | 2006-06-01 | 2015-07-14 | Elan Pharmaceuticals, Inc. | Fragments neuroactifs de app |
TWI551607B (zh) | 2006-07-14 | 2016-10-01 | Ac免疫公司 | 人類化抗體 |
US8455626B2 (en) | 2006-11-30 | 2013-06-04 | Abbott Laboratories | Aβ conformer selective anti-aβ globulomer monoclonal antibodies |
JP2010514700A (ja) * | 2006-12-22 | 2010-05-06 | ジェネンテック, インコーポレイテッド | Dr6アンタゴニスト及び神経障害の治療におけるその使用法 |
US8895004B2 (en) | 2007-02-27 | 2014-11-25 | AbbVie Deutschland GmbH & Co. KG | Method for the treatment of amyloidoses |
MX2009011127A (es) * | 2007-04-18 | 2010-03-10 | Janssen Alzheimer Immunotherap | Metodo de prevencion y tratamiento de angiopatia amiloide cerebral. |
US8003097B2 (en) | 2007-04-18 | 2011-08-23 | Janssen Alzheimer Immunotherapy | Treatment of cerebral amyloid angiopathy |
WO2008137954A2 (fr) * | 2007-05-07 | 2008-11-13 | Environmental Packaging Technologies Limited | Contenant d'expédition universel |
MX2009012608A (es) * | 2007-05-25 | 2009-12-07 | Amgen Inc | Compuestos de hidroxietil amina substituidos como moduladores de beta-secretasa y metodos de uso. |
WO2008147547A1 (fr) | 2007-05-25 | 2008-12-04 | Amgen Inc. | Composés d'hydroxyéthylamine substitués en tant que modulateurs de la bêta-sécrétase et procédés d'utilisation |
CA2688265C (fr) | 2007-06-08 | 2021-02-16 | Wake Forest University Health Sciences | Therapie cellulaire selective pour le traitement de l'insuffisance renale |
US8613923B2 (en) | 2007-06-12 | 2013-12-24 | Ac Immune S.A. | Monoclonal antibody |
CN104761641A (zh) * | 2007-06-12 | 2015-07-08 | Ac免疫有限公司 | β淀粉样蛋白的人源化抗体 |
US8048420B2 (en) | 2007-06-12 | 2011-11-01 | Ac Immune S.A. | Monoclonal antibody |
US20090023158A1 (en) * | 2007-07-13 | 2009-01-22 | Elan Pharmaceuticals, Inc. | Compositions and Methods for Identifying Substrate Specificity of Inhibitors of Gamma Secretase |
SI2182983T1 (sl) | 2007-07-27 | 2014-09-30 | Janssen Alzheimer Immunotherapy | Zdravljenje amiloidogenih bolezni s humaniziranimi protitelesi proti abeta |
PT2238166E (pt) | 2007-10-05 | 2014-02-11 | Genentech Inc | Utilização do anticorpo anti-amilóide beta em doenças oculares |
AU2008311366B2 (en) * | 2007-10-05 | 2015-03-12 | Ac Immune S.A. | Use of anti-amyloid beta antibody in ocular diseases |
JO3076B1 (ar) | 2007-10-17 | 2017-03-15 | Janssen Alzheimer Immunotherap | نظم العلاج المناعي المعتمد على حالة apoe |
US20090163594A1 (en) * | 2007-10-31 | 2009-06-25 | Elan Pharmaceuticals, Inc. | Triple Assay System for Identifying Substrate Selectivity of Gamma Secretase Inhibitors |
US7803809B2 (en) * | 2008-11-12 | 2010-09-28 | Amgen Inc. | Substituted pyrano [2,3-b] pyridinamine compounds as beta-secretase modulators and methods of use |
WO2009090650A2 (fr) * | 2008-01-16 | 2009-07-23 | Ben-Gurion University Of The Negev Research And Development Authority | Vaccin contre la maladie d'alzheimer |
EP2294413A4 (fr) * | 2008-06-12 | 2012-04-25 | Genentech Inc | Procédé de criblage pour identifier des composés qui inhibent la neurodégénérescence |
BRPI0918449A2 (pt) * | 2008-09-11 | 2019-09-24 | Amgen Inc | compostos de anel espiro-tricíclico como moduladores de beta-secretas e métodos de uso |
EP2342563A1 (fr) * | 2008-10-20 | 2011-07-13 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Procédé de détection de la protéine précurseur amyloïde (app) alpha soluble et/ou de app bêta soluble |
US9067981B1 (en) | 2008-10-30 | 2015-06-30 | Janssen Sciences Ireland Uc | Hybrid amyloid-beta antibodies |
WO2010057013A1 (fr) * | 2008-11-14 | 2010-05-20 | Wake Forest University Health Sciences | Therapie cellulaire selective pour le traitement d'insuffisance renale |
WO2010057015A1 (fr) * | 2008-11-14 | 2010-05-20 | Wake Forest University Health Sciences | Structures de rein et leurs procedes de formation |
WO2010062904A2 (fr) | 2008-11-25 | 2010-06-03 | Biogen Idec Ma Inc. | Utilisation d'antagonistes dr6 et p75 pour favoriser la survie de cellules du systeme nerveux |
KR20120103587A (ko) | 2009-11-12 | 2012-09-19 | 제넨테크, 인크. | 수상돌기 소극 밀도를 증진시키는 방법 |
US9296698B2 (en) | 2009-11-23 | 2016-03-29 | Amgen Inc. | Amino heteroaryl compounds as beta-secretase modulators and methods of use |
EP2504330A1 (fr) | 2009-11-23 | 2012-10-03 | Amgen Inc. | Composés amino hétéroaryliques comme modulateurs de bêta-sécrétase et procédés d'utilisation |
US8735384B2 (en) | 2010-01-19 | 2014-05-27 | Amgen Inc. | Amino heteroaryl compounds as beta-secretase modulators and methods of use |
AU2011227501B9 (en) | 2010-03-15 | 2013-08-22 | Amgen Inc. | Amino -dihydrooxazine and amino - dihydrothiazine spiro compounds as Beta - secretase modulators and their medical use |
AU2011227511B2 (en) | 2010-03-15 | 2014-02-20 | Amgen Inc. | Spiro-tetracyclic ring compounds as Beta - secretase modulators |
WO2011130377A2 (fr) | 2010-04-15 | 2011-10-20 | Abbott Laboratories | Protéines de liaison à la bêta amyloïde |
RU2607368C2 (ru) | 2010-07-30 | 2017-01-10 | Ац Иммуне С.А. | Безопасные и функциональные гуманизированные антитела |
EP2601197B1 (fr) | 2010-08-05 | 2014-06-25 | Amgen Inc. | Composés d'amino-iso-indole, d'amino-aza-iso-indole, d'amino-dihydro-isoquinoléine et d'amino-benzoxazine en tant que modulateurs de la bêta-sécrétase et leurs méthodes d'utilisation |
CN103298833B (zh) | 2010-08-14 | 2015-12-16 | Abbvie公司 | β淀粉样蛋白结合蛋白 |
US8957083B2 (en) | 2010-11-23 | 2015-02-17 | Amgen Inc. | Spiro-amino-imidazolone and spiro-amino-dihydro-pyrimidinone compounds as beta-secretase modulators and methods of use |
WO2012109165A1 (fr) | 2011-02-07 | 2012-08-16 | Amgen Inc. | Composés de 5-amino-oxazépine et 5-amino-thiazépane en tant qu'antagonistes de la bêta-sécrétase et leurs procédés d'utilisation |
EP2675810A1 (fr) | 2011-02-15 | 2013-12-25 | Amgen Inc. | Composés hétérocycliques spiro-amino-imidazo-condensés en tant que modulateurs de la bêta-secrétase et méthodes d'utilisation |
US20140302532A1 (en) | 2011-04-12 | 2014-10-09 | Quanterix Corporation | Methods of determining a treatment protocol for and/or a prognosis of a patient's recovery from a brain injury |
JP2014526560A (ja) | 2011-09-21 | 2014-10-06 | アムジエン・インコーポレーテツド | β‐セクレターゼ調節因子としてのアミノオキサジン化合物およびアミノジヒドロチアジン化合物および使用方法 |
WO2013115348A1 (fr) * | 2012-02-03 | 2013-08-08 | 塩野義製薬株式会社 | ANTI-CORPS ANTI-sAPPβ |
WO2014059185A1 (fr) | 2012-10-12 | 2014-04-17 | Amgen Inc. | Composés amino-dihydrothiazine et amino-dioxydo dihydrothiazine en tant qu'antagonistes de bêta-sécrétase et procédés d'utilisation |
US9725469B2 (en) | 2012-11-15 | 2017-08-08 | Amgen, Inc. | Amino-oxazine and amino-dihydrothiazine compounds as beta-secretase modulators and methods of use |
US9309263B2 (en) | 2013-01-29 | 2016-04-12 | Amgen Inc. | Fused multi-cyclic sulfone compounds as inhibitors of beta-secretase and methods of use thereof |
WO2014134341A1 (fr) | 2013-03-01 | 2014-09-04 | Amgen Inc. | Composés perfluorés 5,6-dihydro-4h-1,3-oxazine-2-amine substitués en tant qu'inhibiteurs de la bêta-sécrétase et procédés d'utilisation correspondants |
AP2015008716A0 (en) | 2013-03-08 | 2015-09-30 | Amgen Inc | Perfluorinated cyclopropyl fused 1,3-oxazin-2-amine compounds as beta-secretase inhibitors and methods of use |
US9096615B2 (en) * | 2013-07-30 | 2015-08-04 | Amgen Inc. | Bridged bicyclic amino thiazine dioxide compounds as inhibitors of beta-secretase and methods of use thereof |
JP6576433B2 (ja) | 2014-08-08 | 2019-09-18 | アムジエン・インコーポレーテツド | β−セクレターゼ阻害剤としてのシクロプロピル縮合チアジン−2−アミン化合物及び使用方法 |
EP3070096A1 (fr) * | 2015-03-19 | 2016-09-21 | Ludwig-Maximilians-Universität München | Peptide ou collection de peptides dérivés de protéine précurseur de l'amyloïde |
US10246429B2 (en) | 2015-08-06 | 2019-04-02 | Amgen Inc. | Vinyl fluoride cyclopropyl fused thiazin-2-amine compounds as beta-secretase inhibitors and methods of use |
CA3047290A1 (fr) | 2016-12-15 | 2018-06-21 | Amgen Inc. | Derives de dioxyde de 1,4-thiazine et de dioxyde de 1,2,4-thiadiazine en tant qu'inhibiteurs de beta-secretase et procedes d'utilisation |
MA52722A (fr) | 2016-12-15 | 2021-04-14 | Amgen Inc | Dérivés d'oxazine en tant qu'inhibiteurs de bêta-sécrétase et procédés d'utilisation |
CA3047288A1 (fr) | 2016-12-15 | 2018-06-21 | Amgen Inc. | Derives de thiazine en tant qu'inhibiteurs de beta-secretase et procedes d'utilisation |
JP7148518B2 (ja) | 2016-12-15 | 2022-10-05 | アムジエン・インコーポレーテツド | β-セクレターゼ阻害剤としての二環式チアジンおよびオキサジン誘導体ならびに使用方法 |
CA3047287A1 (fr) | 2016-12-15 | 2018-06-21 | Amgen Inc. | Derives thiazine fusionnes a un cyclopropyle utilises en tant qu'inhibiteurs de la beta-secretase et procedes d'utilisation |
Family Cites Families (21)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4492760A (en) * | 1983-04-19 | 1985-01-08 | The Wistar Institute Of Anatomy And Biology | HLA D Typing assay |
JPS6147500A (ja) * | 1984-08-15 | 1986-03-07 | Res Dev Corp Of Japan | キメラモノクロ−ナル抗体及びその製造法 |
EP0173494A3 (fr) * | 1984-08-27 | 1987-11-25 | The Board Of Trustees Of The Leland Stanford Junior University | Récepteurs chimériques par liaison et expression de l'ADN |
GB8422238D0 (en) * | 1984-09-03 | 1984-10-10 | Neuberger M S | Chimeric proteins |
JPS61134325A (ja) * | 1984-12-04 | 1986-06-21 | Teijin Ltd | ハイブリツド抗体遺伝子の発現方法 |
US4666829A (en) * | 1985-05-15 | 1987-05-19 | University Of California | Polypeptide marker for Alzheimer's disease and its use for diagnosis |
JPS62100291A (ja) * | 1985-10-28 | 1987-05-09 | Teijin Ltd | 遺伝子断片およびプラスミド |
EP0247091B1 (fr) * | 1985-11-01 | 1993-09-29 | Xoma Corporation | Assemblage modulaire de genes d'anticorps, anticorps ainsi prepares et utilisation |
US5223482A (en) * | 1986-11-17 | 1993-06-29 | Scios Nova Inc. | Recombinant Alzheimer's protease inhibitory amyloid protein and method of use |
EP0331514A3 (fr) * | 1988-03-04 | 1991-07-10 | Ajinomoto Co., Inc. | Essai de la délétion ou du défaut de la protéine de la dystrophie musculaire de Duchenne |
US5134062A (en) * | 1988-03-22 | 1992-07-28 | Cornell Research Foundation, Inc. | Diagnosis of neuronal disorders and screening potential therapeutic agents therefor |
US5262332A (en) * | 1989-04-05 | 1993-11-16 | Brigham And Women's Hospital | Diagnostic method for Alzheimer's disease: examination of non-neural tissue |
US5234814A (en) * | 1989-06-01 | 1993-08-10 | Du Pont Merck Pharmaceutical Company | Diagnostic assay for alzheimer's disease |
CA2079880A1 (fr) * | 1990-04-24 | 1991-10-25 | William E. Van Nostrand | Purification, detection et mode d'utilisation de la protease nexine-2 |
US5213962A (en) * | 1990-04-24 | 1993-05-25 | The Regents Of The University Of California | Purification, detection and methods of use of protease Nexin-2 |
US5385915A (en) * | 1990-05-16 | 1995-01-31 | The Rockefeller University | Treatment of amyloidosis associated with Alzheimer disease using modulators of protein phosphorylation |
AU646877B2 (en) * | 1990-06-15 | 1994-03-10 | Scios Nova Inc. | Transgenic non-human mammal displaying the amyloid-forming pathology of alzheimer's disease |
WO1992000521A1 (fr) * | 1990-06-29 | 1992-01-09 | Case Western Reserve University | Procedes de diagnostic et de pronostic bases sur des derives solubles du precurseur de proteine beta amyloide |
US5200339A (en) * | 1990-08-17 | 1993-04-06 | Abraham Carmela R | Proteases causing abnormal degradation of amyloid β-protein precursor |
BE1003316A5 (fr) * | 1990-11-27 | 1992-02-25 | Will L F & Cie Sa | Anticorps monoclonal utile pour le diagnostic de la maladie d'alzheimer, hybridome secreteur d'un tel anticorps monoclonal et procede pour sa preparation. |
US5441870A (en) * | 1992-04-15 | 1995-08-15 | Athena Neurosciences, Inc. | Methods for monitoring cellular processing of β-amyloid precursor protein |
-
1992
- 1992-10-26 US US07/965,971 patent/US5441870A/en not_active Expired - Lifetime
-
1993
- 1993-03-03 WO PCT/US1993/001817 patent/WO1993021526A1/fr active IP Right Grant
- 1993-03-03 AT AT93907104T patent/ATE251304T1/de active
- 1993-03-03 AU AU37827/93A patent/AU688726B2/en not_active Expired
- 1993-03-03 DE DE69333225T patent/DE69333225T2/de not_active Expired - Lifetime
- 1993-03-03 PT PT93907104T patent/PT638172E/pt unknown
- 1993-03-03 NZ NZ251053A patent/NZ251053A/en not_active IP Right Cessation
- 1993-03-03 JP JP51830393A patent/JP3974168B2/ja not_active Expired - Lifetime
- 1993-03-03 EP EP93907104A patent/EP0638172B1/fr not_active Expired - Lifetime
- 1993-03-03 DK DK93907104T patent/DK0638172T3/da active
- 1993-03-03 ES ES93907104T patent/ES2206455T3/es not_active Expired - Lifetime
- 1993-03-03 CA CA002118243A patent/CA2118243C/fr not_active Expired - Lifetime
-
1994
- 1994-10-14 FI FI944847A patent/FI111546B/fi not_active IP Right Cessation
- 1994-10-14 NO NO19943912A patent/NO320067B1/no not_active IP Right Cessation
-
1995
- 1995-05-12 US US08/440,423 patent/US5721130A/en not_active Expired - Lifetime
-
1997
- 1997-05-01 US US08/846,444 patent/US6018024A/en not_active Expired - Lifetime
-
2005
- 2005-08-08 JP JP2005230075A patent/JP2006051029A/ja active Pending
Also Published As
Publication number | Publication date |
---|---|
EP0638172A4 (fr) | 1997-03-19 |
US5721130A (en) | 1998-02-24 |
NO943912D0 (no) | 1994-10-14 |
AU3782793A (en) | 1993-11-18 |
AU688726B2 (en) | 1998-03-19 |
NO943912L (no) | 1994-11-10 |
ES2206455T3 (es) | 2004-05-16 |
JP2006051029A (ja) | 2006-02-23 |
US6018024A (en) | 2000-01-25 |
CA2118243C (fr) | 2009-11-03 |
NZ251053A (en) | 1996-11-26 |
NO320067B1 (no) | 2005-10-17 |
FI944847A (fi) | 1994-10-14 |
DE69333225D1 (de) | 2003-11-06 |
DE69333225T2 (de) | 2004-05-06 |
FI944847A0 (fi) | 1994-10-14 |
EP0638172B1 (fr) | 2003-10-01 |
CA2118243A1 (fr) | 1993-10-28 |
WO1993021526A1 (fr) | 1993-10-28 |
DK0638172T3 (da) | 2004-02-02 |
EP0638172A1 (fr) | 1995-02-15 |
JP3974168B2 (ja) | 2007-09-12 |
US5441870A (en) | 1995-08-15 |
PT638172E (pt) | 2004-02-27 |
JPH07506967A (ja) | 1995-08-03 |
ATE251304T1 (de) | 2003-10-15 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
FI111546B (fi) | In vitro -menetelmiä, joilla voidaan monitoroida beta-amyloidiesiasteproteiinin prosessointia solussa, diagnosoida tai monitoroida beta-amyloidiin liittyvää tautia tai tunnistaa beta-amyloidin tuotannon inhibiittoreita, sekä beta-amyloidiesiasteproteiinin liukoinen fragmentti | |
US5605811A (en) | Methods and compositions for monitoring cellular processing of beta-amyloid precursor protein | |
EP0667959B1 (fr) | Procédés d'idéntification des inhibiteurs de la production du péptide beta-amyloide | |
EP0736106B1 (fr) | Procede de detection d'inhibiteurs de la production de peptides beta-amyloides | |
US5837672A (en) | Methods and compositions for the detection of soluble β-amyloid peptide | |
US5766846A (en) | Methods of screening for compounds which inhibit soluble β-amyloid peptide production | |
AU2008200489B2 (en) | Methods and compositions for the detection of soluble beta-amyloid peptide | |
AU687747C (en) | Methods and compositions for the detection of soluble beta-amyloid peptide | |
AU722044B2 (en) | Methods and compositions for the detection of soluble beta-amyloid peptide | |
AU2004203875A1 (en) | Methods and compositions for the detection of soluble beta-amyloid peptide |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
PC | Transfer of assignment of patent |
Owner name: ELI LILLY AND COMPANY Free format text: ELI LILLY AND COMPANY Owner name: ELAN PHARMACEUTICALS, INC. Free format text: ELAN PHARMACEUTICALS, INC. |
|
MA | Patent expired |