JP2018119011A - アルツハイマー病治療方法 - Google Patents
アルツハイマー病治療方法 Download PDFInfo
- Publication number
- JP2018119011A JP2018119011A JP2018088643A JP2018088643A JP2018119011A JP 2018119011 A JP2018119011 A JP 2018119011A JP 2018088643 A JP2018088643 A JP 2018088643A JP 2018088643 A JP2018088643 A JP 2018088643A JP 2018119011 A JP2018119011 A JP 2018119011A
- Authority
- JP
- Japan
- Prior art keywords
- peptide
- seq
- peptides
- resulting
- terminal
- 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.)
- Pending
Links
- 238000000034 method Methods 0.000 title claims abstract description 25
- 208000024827 Alzheimer disease Diseases 0.000 title claims abstract description 20
- 238000011282 treatment Methods 0.000 title claims abstract description 11
- 208000037259 Amyloid Plaque Diseases 0.000 claims abstract description 16
- 108010064539 amyloid beta-protein (1-42) Proteins 0.000 claims abstract description 11
- 239000003814 drug Substances 0.000 claims abstract description 9
- 108010064397 amyloid beta-protein (1-40) Proteins 0.000 claims abstract description 7
- 238000002360 preparation method Methods 0.000 claims abstract description 4
- 108010090849 Amyloid beta-Peptides Proteins 0.000 claims abstract description 3
- 102000013455 Amyloid beta-Peptides Human genes 0.000 claims abstract description 3
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 141
- 102000004196 processed proteins & peptides Human genes 0.000 claims description 43
- 108090000623 proteins and genes Proteins 0.000 claims description 34
- 102000004169 proteins and genes Human genes 0.000 claims description 33
- 125000000539 amino acid group Chemical group 0.000 claims description 23
- 230000027455 binding Effects 0.000 claims description 18
- 125000001433 C-terminal amino-acid group Chemical group 0.000 claims description 16
- 239000012634 fragment Substances 0.000 claims description 16
- 230000003053 immunization Effects 0.000 claims description 14
- 238000002649 immunization Methods 0.000 claims description 14
- 201000010099 disease Diseases 0.000 claims description 13
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 13
- 125000001429 N-terminal alpha-amino-acid group Chemical group 0.000 claims description 11
- 241000124008 Mammalia Species 0.000 claims description 10
- 238000009825 accumulation Methods 0.000 claims description 6
- 210000004556 brain Anatomy 0.000 claims description 6
- 230000002265 prevention Effects 0.000 claims description 6
- 125000000729 N-terminal amino-acid group Chemical group 0.000 claims description 5
- 102000054767 gene variant Human genes 0.000 claims description 5
- 230000002163 immunogen Effects 0.000 claims description 5
- 108700003861 Dominant Genes Proteins 0.000 claims description 4
- 241000237988 Patellidae Species 0.000 claims description 2
- 238000004904 shortening Methods 0.000 claims 5
- 102000014914 Carrier Proteins Human genes 0.000 claims 1
- 108091008324 binding proteins Proteins 0.000 claims 1
- 238000004519 manufacturing process Methods 0.000 claims 1
- 230000006806 disease prevention Effects 0.000 abstract description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 22
- 235000018102 proteins Nutrition 0.000 description 21
- 150000001413 amino acids Chemical class 0.000 description 10
- 239000012528 membrane Substances 0.000 description 10
- 235000001014 amino acid Nutrition 0.000 description 9
- 229940024606 amino acid Drugs 0.000 description 9
- 206010002022 amyloidosis Diseases 0.000 description 9
- 239000000872 buffer Substances 0.000 description 7
- 239000000243 solution Substances 0.000 description 7
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 6
- XSLUZOLUJPDNGT-UHFFFAOYSA-N 5-[4-(3,3-dimethylpiperazin-1-yl)phenyl]-2-(5-methyl-1h-indol-4-yl)-1,3-oxazole-4-carboxamide Chemical compound CC1=CC=C2NC=CC2=C1C(O1)=NC(C(N)=O)=C1C(C=C1)=CC=C1N1CCNC(C)(C)C1 XSLUZOLUJPDNGT-UHFFFAOYSA-N 0.000 description 5
- OPWLMVVARKPWEA-UHFFFAOYSA-N 5-[4-(3,3-dimethylpiperazin-1-yl)phenyl]-2-(7-fluoro-5-methyl-1h-indol-4-yl)-1,3-oxazole-4-carboxamide Chemical compound CC1=CC(F)=C2NC=CC2=C1C(O1)=NC(C(N)=O)=C1C(C=C1)=CC=C1N1CCNC(C)(C)C1 OPWLMVVARKPWEA-UHFFFAOYSA-N 0.000 description 5
- 101100148729 Caenorhabditis elegans sar-1 gene Proteins 0.000 description 5
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 5
- 239000007983 Tris buffer Substances 0.000 description 5
- 238000010790 dilution Methods 0.000 description 5
- 239000012895 dilution Substances 0.000 description 5
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 5
- 241000283707 Capra Species 0.000 description 4
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 4
- 238000011161 development Methods 0.000 description 4
- 230000028993 immune response Effects 0.000 description 4
- 210000002966 serum Anatomy 0.000 description 4
- 229960005486 vaccine Drugs 0.000 description 4
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 241000283973 Oryctolagus cuniculus Species 0.000 description 3
- 210000004899 c-terminal region Anatomy 0.000 description 3
- 238000002347 injection Methods 0.000 description 3
- 239000007924 injection Substances 0.000 description 3
- 210000002682 neurofibrillary tangle Anatomy 0.000 description 3
- 239000012188 paraffin wax Substances 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- 210000001519 tissue Anatomy 0.000 description 3
- 238000012546 transfer Methods 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- 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 2
- HRPVXLWXLXDGHG-UHFFFAOYSA-N Acrylamide Chemical compound NC(=O)C=C HRPVXLWXLXDGHG-UHFFFAOYSA-N 0.000 description 2
- 101100298998 Caenorhabditis elegans pbs-3 gene Proteins 0.000 description 2
- 208000020406 Creutzfeldt Jacob disease Diseases 0.000 description 2
- 208000003407 Creutzfeldt-Jakob Syndrome Diseases 0.000 description 2
- 208000010859 Creutzfeldt-Jakob disease Diseases 0.000 description 2
- 239000004593 Epoxy Substances 0.000 description 2
- 206010016207 Familial Mediterranean fever Diseases 0.000 description 2
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 2
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 2
- 239000004471 Glycine Substances 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- DCXYFEDJOCDNAF-REOHCLBHSA-N L-asparagine Chemical compound OC(=O)[C@@H](N)CC(N)=O DCXYFEDJOCDNAF-REOHCLBHSA-N 0.000 description 2
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 2
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 2
- 241001465754 Metazoa Species 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
- 229920001213 Polysorbate 20 Polymers 0.000 description 2
- 239000002671 adjuvant Substances 0.000 description 2
- 239000000427 antigen Substances 0.000 description 2
- 108091007433 antigens Proteins 0.000 description 2
- 102000036639 antigens Human genes 0.000 description 2
- 238000003491 array Methods 0.000 description 2
- HFACYLZERDEVSX-UHFFFAOYSA-N benzidine Chemical compound C1=CC(N)=CC=C1C1=CC=C(N)C=C1 HFACYLZERDEVSX-UHFFFAOYSA-N 0.000 description 2
- 210000004369 blood Anatomy 0.000 description 2
- 239000008280 blood Substances 0.000 description 2
- 230000018044 dehydration Effects 0.000 description 2
- 238000006297 dehydration reaction Methods 0.000 description 2
- 150000004985 diamines Chemical class 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 238000001962 electrophoresis Methods 0.000 description 2
- 206010014599 encephalitis Diseases 0.000 description 2
- 125000000291 glutamic acid group Chemical group N[C@@H](CCC(O)=O)C(=O)* 0.000 description 2
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
- 125000001360 methionine group Chemical group N[C@@H](CCSC)C(=O)* 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 230000001537 neural effect Effects 0.000 description 2
- 230000004770 neurodegeneration Effects 0.000 description 2
- 208000015122 neurodegenerative disease Diseases 0.000 description 2
- 210000000056 organ Anatomy 0.000 description 2
- 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 2
- 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 2
- 229920001184 polypeptide Polymers 0.000 description 2
- 235000008476 powdered milk Nutrition 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- 208000024891 symptom Diseases 0.000 description 2
- 230000009897 systematic effect Effects 0.000 description 2
- 230000007704 transition Effects 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 1
- 239000004475 Arginine Substances 0.000 description 1
- DCXYFEDJOCDNAF-UHFFFAOYSA-N Asparagine Natural products OC(=O)C(N)CC(N)=O DCXYFEDJOCDNAF-UHFFFAOYSA-N 0.000 description 1
- 208000023275 Autoimmune disease Diseases 0.000 description 1
- 101100191768 Caenorhabditis elegans pbs-4 gene Proteins 0.000 description 1
- 101100028791 Caenorhabditis elegans pbs-5 gene Proteins 0.000 description 1
- 229920000298 Cellophane Polymers 0.000 description 1
- 208000005145 Cerebral amyloid angiopathy Diseases 0.000 description 1
- 241000283073 Equus caballus Species 0.000 description 1
- 206010018341 Gliosis Diseases 0.000 description 1
- ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-N 0.000 description 1
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 1
- KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-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
- 239000004472 Lysine Substances 0.000 description 1
- 102000012750 Membrane Glycoproteins Human genes 0.000 description 1
- 108010090054 Membrane Glycoproteins Proteins 0.000 description 1
- 208000034578 Multiple myelomas Diseases 0.000 description 1
- KWYHDKDOAIKMQN-UHFFFAOYSA-N N,N,N',N'-tetramethylethylenediamine Chemical compound CN(C)CCN(C)C KWYHDKDOAIKMQN-UHFFFAOYSA-N 0.000 description 1
- 239000002033 PVDF binder Substances 0.000 description 1
- 102000035195 Peptidases Human genes 0.000 description 1
- 108091005804 Peptidases Proteins 0.000 description 1
- 102000003992 Peroxidases Human genes 0.000 description 1
- 208000037581 Persistent Infection Diseases 0.000 description 1
- 206010035226 Plasma cell myeloma Diseases 0.000 description 1
- 241000288906 Primates Species 0.000 description 1
- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 1
- 239000004365 Protease Substances 0.000 description 1
- 108010078762 Protein Precursors Proteins 0.000 description 1
- 102000014961 Protein Precursors Human genes 0.000 description 1
- 241000282849 Ruminantia Species 0.000 description 1
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 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
- AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 description 1
- 239000004473 Threonine Substances 0.000 description 1
- 239000007997 Tricine buffer Substances 0.000 description 1
- QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 description 1
- KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Natural products CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 230000010398 acute inflammatory response Effects 0.000 description 1
- 235000004279 alanine Nutrition 0.000 description 1
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
- 235000009582 asparagine Nutrition 0.000 description 1
- 229960001230 asparagine Drugs 0.000 description 1
- 235000003704 aspartic acid Nutrition 0.000 description 1
- 208000037875 astrocytosis Diseases 0.000 description 1
- 230000007341 astrogliosis Effects 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 229960002685 biotin Drugs 0.000 description 1
- 239000011616 biotin Substances 0.000 description 1
- 208000005881 bovine spongiform encephalopathy Diseases 0.000 description 1
- 210000005013 brain tissue Anatomy 0.000 description 1
- 210000000170 cell membrane Anatomy 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 208000037976 chronic inflammation Diseases 0.000 description 1
- 230000006020 chronic inflammation Effects 0.000 description 1
- 238000003776 cleavage reaction Methods 0.000 description 1
- 238000012258 culturing Methods 0.000 description 1
- 235000018417 cysteine Nutrition 0.000 description 1
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 1
- 235000013365 dairy product Nutrition 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 230000008021 deposition Effects 0.000 description 1
- 238000011033 desalting Methods 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
- 238000009826 distribution Methods 0.000 description 1
- 238000009509 drug development Methods 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 239000012645 endogenous antigen Substances 0.000 description 1
- 235000019253 formic acid Nutrition 0.000 description 1
- 235000013922 glutamic acid Nutrition 0.000 description 1
- 239000004220 glutamic acid 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
- 125000003630 glycyl group Chemical group [H]N([H])C([H])([H])C(*)=O 0.000 description 1
- 238000001631 haemodialysis Methods 0.000 description 1
- 230000000322 hemodialysis Effects 0.000 description 1
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 1
- 210000000987 immune system Anatomy 0.000 description 1
- 230000036039 immunity Effects 0.000 description 1
- 238000003364 immunohistochemistry Methods 0.000 description 1
- 230000003308 immunostimulating effect Effects 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- AGPKZVBTJJNPAG-UHFFFAOYSA-N isoleucine Natural products CCC(C)C(N)C(O)=O AGPKZVBTJJNPAG-UHFFFAOYSA-N 0.000 description 1
- 229960000310 isoleucine Drugs 0.000 description 1
- 125000000741 isoleucyl group Chemical group [H]N([H])C(C(C([H])([H])[H])C([H])([H])C([H])([H])[H])C(=O)O* 0.000 description 1
- 108010045069 keyhole-limpet hemocyanin Proteins 0.000 description 1
- 125000001909 leucine group Chemical group [H]N(*)C(C(*)=O)C([H])([H])C(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 238000011866 long-term treatment Methods 0.000 description 1
- 239000003550 marker Substances 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- 229930182817 methionine Natural products 0.000 description 1
- 230000005012 migration Effects 0.000 description 1
- 238000013508 migration Methods 0.000 description 1
- 210000005036 nerve Anatomy 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 238000011587 new zealand white rabbit Methods 0.000 description 1
- 230000009871 nonspecific binding Effects 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 108040007629 peroxidase activity proteins Proteins 0.000 description 1
- 238000009522 phase III clinical trial Methods 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
- COLNVLDHVKWLRT-QMMMGPOBSA-N phenylalanine group Chemical group N[C@@H](CC1=CC=CC=C1)C(=O)O COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 description 1
- 230000035790 physiological processes and functions Effects 0.000 description 1
- 229920002981 polyvinylidene fluoride Polymers 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 244000062645 predators Species 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 230000017854 proteolysis Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 208000008864 scrapie Diseases 0.000 description 1
- 125000003607 serino group Chemical group [H]N([H])[C@]([H])(C(=O)[*])C(O[H])([H])[H] 0.000 description 1
- 238000001179 sorption measurement Methods 0.000 description 1
- 239000011550 stock solution Substances 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 125000000341 threoninyl group Chemical group [H]OC([H])(C([H])([H])[H])C([H])(N([H])[H])C(*)=O 0.000 description 1
- 238000011830 transgenic mouse model Methods 0.000 description 1
- GPRLSGONYQIRFK-MNYXATJNSA-N triton Chemical compound [3H+] GPRLSGONYQIRFK-MNYXATJNSA-N 0.000 description 1
- 125000000430 tryptophan group Chemical group [H]N([H])C(C(=O)O*)C([H])([H])C1=C([H])N([H])C2=C([H])C([H])=C([H])C([H])=C12 0.000 description 1
- 201000008827 tuberculosis Diseases 0.000 description 1
- 208000001072 type 2 diabetes mellitus Diseases 0.000 description 1
- 239000004474 valine Substances 0.000 description 1
- 230000002792 vascular Effects 0.000 description 1
- 238000001262 western blot Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K7/00—Peptides having 5 to 20 amino acids in a fully defined sequence; Derivatives thereof
- C07K7/04—Linear peptides containing only normal peptide links
- C07K7/06—Linear peptides containing only normal peptide links having 5 to 11 amino acids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/1703—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
- A61K38/1709—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
- A61K47/62—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being a protein, peptide or polyamino acid
- A61K47/64—Drug-peptide, drug-protein or drug-polyamino acid conjugates, i.e. the modifying agent being a peptide, protein or polyamino acid which is covalently bonded or complexed to a therapeutically active agent
- A61K47/646—Drug-peptide, drug-protein or drug-polyamino acid conjugates, i.e. the modifying agent being a peptide, protein or polyamino acid which is covalently bonded or complexed to a therapeutically active agent the entire peptide or protein drug conjugate elicits an immune response, e.g. conjugate vaccines
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—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
- A61P35/00—Antineoplastic agents
-
- 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
- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Immunology (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Organic Chemistry (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Epidemiology (AREA)
- Molecular Biology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Mycology (AREA)
- Microbiology (AREA)
- Biochemistry (AREA)
- Biophysics (AREA)
- Genetics & Genomics (AREA)
- Biomedical Technology (AREA)
- Neurosurgery (AREA)
- Neurology (AREA)
- Marine Sciences & Fisheries (AREA)
- Zoology (AREA)
- Gastroenterology & Hepatology (AREA)
- Virology (AREA)
- Psychiatry (AREA)
- Hospice & Palliative Care (AREA)
- Peptides Or Proteins (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Medicinal Preparation (AREA)
Abstract
Description
C=Cys=システイン
D=Asp=アスパラギン酸
E=Glu=グルタミン酸
F=Phe=フェニルアラニン
G=Gly=グリシン
H=His=ヒスチジン
I=Ile=イソロイシン
K=Lys=リシン
L=Leu=ロイシン
M=Met=メチオニン
N=Asn=アスパラギン
P=Pro=プロリン
Q=Gln=グルタミン
R=Arg=アルギニン
S=Ser=セリン
T=Thr=スレオニン
V=Val=バリン
W=Trp=トリプトファン
Y=Tyr=トリオシン
SEQ ID NO.1 LVFFAEDV
SEQ ID NO.2 GLMVGGVV
SEQ ID NO.3 GLMVGGVVIA
SEQ ID NO.4 RHDSGYEVHHQK
SEQ ID NO.1 SAR−2
SEQ ID NO.2 SAR−3
SEQ ID NO.3 SAR−4
SEQ ID NO.4 SAR−1
例1 多クーロン抗体の発生
免疫原として使用されたKLHと結合された4つのペプチドに対して4つの多クーロン抗体がニュージーランド産白ウサギにおける免疫処置によって発生された。
1.電気泳動
小さいペプチドの分離を改善することにより変更された1998年、ニューヨーク、ジョン・ウィリー・アンド・サンズ著の、分子バイオロジにける現行のプロトコルに記載されたレムリ方法「The Laemmli method described in Current Protocols in Molecular Biology,John Wiley and Sons,New York,1998,modified by improve the separation of small peptides」が使用された。
貯蔵液 分離ゲル(15%) 堆積ゲル
40%アクリルアミド 3.75ml 500μl
トリス3M,pH=8.45 3.3ml 250μl
グリセロール 1.05ml −
水 1.9ml 4.2μl
SDS20% 50μl 18.6μl
APS10% 50μl 25μl
TEMED 10μl 5μl
24.2gトリスベース(0.2M最終濃度)
H2 Oにより1リットルに希釈
濃縮された塩酸によりpH8.9の調整
1ヶ月まで4℃で貯蔵
12.11gトリスベース(0.1M最終濃度)
12.92gトリシン(0.1M最終濃度)
1gSDS(0.1%最終濃度)
H2 Oにより1リットルに希釈
pH調整しない
1ヶ月まで4℃で貯蔵
ゲル中に分離されたタンパク質は電子吸着(electroblotting)によりPVDF膜に転移された。移転小冊子において、以下が配置された。
グリシン38nM
トリスベース50mM
メタノール40%
抗体及び粉末ミルクがPBS−t(PBS+0.5%トィーン20)内に溶解され、またPBS−Tによる洗浄をも実施している。
最後の洗浄後、その膜はファーマシア(Pharmacia)からのECLキット+Plusを使用して、化学ルミネセンス(chemoluminescence)キットの溶液により培養された。
組織の部分は以下の工程に続いてパラフィン中に固定された。
a)10%での中性ホルマリン内に固定
b)増大するアルコール濃度において連続する工程による脱水
c)キシロール及びパラフィンを通過その工程は60−62℃におけるオーブン中で
d)4ミクロンに切断されかつスライド内に取り付けられるパラフィンブロックの実施
キシロール 100% 10分
キシロール 100% 10分
エタノール 100% 5分
エタノール 100% 5分
エタノール 96% 5分
エタノール 90% 5分
エタノール 70% 5分
PBS 5分×3回
a)換気装置内でかつ攪拌しながら3分間96%蟻酸
b)水での急速洗浄
c)PBS2×5分における洗浄
d)70mlのPBS,30mlkエタノール及び1mlのH2O2 から作られた溶液
中で15分間の内因性ペルオキシダーゼのブロック
e)PBS3×5分における洗浄
f)PBS/T(PBS中0.5%でのトリトン又はトィーン−20)3×5分における洗浄
g)2時間PBS/Tにおける10:100に希釈されたヤギ血清(ノーマルヤギ血清)
による非特定結合のブロック
h)水蒸気室中で4°Cにおいて夜間中最初の抗体の培養
SAR−1・・・PBS中の希釈1:150
SAR−2・・・PBS中の希釈1:1500
SAR−3・・・PBS中の希釈1:1500
SAR−4・・・PBS中の希釈1:2000
i)PBS/T3×5分における洗浄
j)45分の間中のPBS中で1:200に希釈された第2抗体(アンチウサギヤギ)中での培養
k)PBS4×5分における洗浄
l)発育が完了するまでこれらの条件を維持して、暗闇で45分間PBS/T中で1:100の希釈においてベクトル・ラブスのABC(アビディン−ビオチン複合体)の培養
m)PBS3×5分における洗浄
n)ジアミンベンジディン(DAB)中の発育
配列の数:4
配列1についての情報:
配列の特徴:
長さ:8
タイプ:アミノ酸
分子のタイプ:ペプチド
起源:化学合成
配列記載
SEQ ID NO1
LeuValPhePheAlaGluAspVal
1 5
配列2についての情報:
配列の特徴:
長さ:8
タイプ:アミノ酸
分子のタイプ:ペプチド
起源:化学合成
配列記載
SEQ ID NO1
GlyLeuMetValGlyGlyValVal
1 5
配列3についての情報:
配列の特徴:
長さ:10
タイプ:アミノ酸
分子のタイプ:ペプチド
起源:化学合成
配列記載
SEQ ID NO1
GlyLeuMetValGlyGlyValValIleAla
1 5 10
配列4についての情報:
配列の特徴:
長さ:12
タイプ:アミノ酸
分子のタイプ:ペプチド
起源:化学合成
配列記載
SEQ ID NO4
ArgHisAspSerGlyTyrGluValHisHisGlnLys
1 5 10
Claims (15)
- 患者の脳中のアミロイド沈殿物の蓄積によって特徴付けられる疾病を予防及び/又は治療するための薬剤を調製するためにペプチドベータアミロイドAβ40及びAβ42の優性遺伝子変異体をとくに認識することができる抗体を製造するための免疫原として作用するタンパク質に結合されたペプチドを使用するペプチドの使用方法。
- 前記疾病がアルツハイマー病であることを特徴とする請求項1に記載のペプチドの使用方法。
- 前記タンパク質がキーホールリンペットタンパク質(KLH)であることを特徴とする請求項1に記載のペプチドの使用方法。
- 前記ペプチドが、
・SEQ ID No.1のペプチド,SEQ ID No.2のペプチド,SEQ
ID No.3のペプチド,SEQ ID No.4のペプチド;
・SEQ ID No.1,SEQ ID No.2,SEQ ID No.3又はSEQ ID No.4のN末端及び/又はC末端のアミノ酸の残留物の除去によるショートニング(短縮)から生じるペプチド;
・SEQ ID No.1,SEQ ID No.2,SEQ ID No.3又はSEQ ID No.4のいずれかのペプチドにタンパク質を結合するのに適するアミノ酸残留物の添加によるレングスニング(伸張)から生じるペプチド;
からなる群から選択されることを特徴とする請求項1乃至3のいずれか1項に記載のペプチドの使用方法。 - 前記ペプチドが、
・SEQ ID No.1のペプチド;
・SEQ ID No.1のN末端及び/又はC末端のアミノ酸の残留物の除去によるショートニングから生じるペプチド;
・タンパク質結合に必要なアミノ酸残留物の添加によるレングスニングから生じるペプチド;
からなる群から選択されることを特徴とする請求項4に記載のペプチドの使用方法。 - 前記ペプチドが、
・SEQ ID No.2のペプチド;
・SEQ ID No.2のN末端及び/又はC末端のアミノ酸の残留物の除去によるショートニングから生じるペプチド;
・タンパク質結合に必要なアミノ酸残留物の添加によるレングスニングから生じるペプチド;
からなる群から選択されることを特徴とする請求項4に記載のペプチドの使用方法。 - 前記ペプチドが、
・SEQ ID No.3のペプチド;
・SEQ ID No.3のN末端及び/又はC末端のアミノ酸の残留物の除去によるショートニングから生じるペプチド;
・タンパク質結合に必要なアミノ酸残留物の添加によるレングスニングからして生じるペプチド;
からなる群から選択されることを特徴とする請求項4に記載のペプチドの使用方法。 - 前記ペプチドが、
・SEQ ID No.4のペプチド;
・SEQ ID No.4のN末端及び/又はC末端のアミノ酸の残留物の除去によるショートニングから生じるペプチド;
・タンパク質結合に必要なアミノ酸残留物の添加によるレングスニングから生じるペプチド;
からなる群から選択されることを特徴とする請求項4に記載のペプチドの使用方法。 - 患者の脳中のアミロイド沈殿物の蓄積によって特徴付けられる疾病を予防及び/又は治療するための薬剤を調製するためにベータアミロイドペプチドAβ40及びAβ42の優性遺伝子変異体のいずれかをとくに認めることができる抗体又は活性断片又は抗体の誘導体を使用するペプチドの使用方法。
- 前記疾病がアルツハイマー病であることを特徴とする請求項9に記載のペプチドの使用方法。
- ペプチドAβの優性遺伝子変異体のいずれかをとくに認めることができる抗体又は活性断片又は抗体の誘導体がN末端及び/又はC末端のアミノ酸の残留物の除去によって任意にショートニングされかつタンパク質結合に適切なアミノ酸残留物の添加により任意にレングスニングされたSEQ ID No.1,SEQ ID No.2,SEQ ID No.3又はSEQ ID No.4からなる群から選択されたペプチドから得られることを特徴とする請求項9乃至10のいずれか1項に記載のペプチドの使用方法。
- 前記抗体又は活性断片又は抗体の誘導体が、
・SEQ ID No.1のペプチド;
・SEQ ID No.1のN末端及び/又はC末端のアミノ酸の残留物を除去することから生じるペプチド;
・タンパク質結合に必要なアミノ酸残留物を前記配列のいずれかに添加させることから生じるペプチド;
からなる群から選択されるペプチドを有する哺乳動物又は鳥類の免疫処置によって得られることを特徴とする請求項9に記載のペプチドの使用方法。 - 前記抗体又は活性断片又は抗体の誘導体が、
・SEQ ID No.2のペプチド;
・SEQ ID No.2のN末端及び/又はC末端のアミノ酸の残留物を除去することから生じるペプチド;
・タンパク質結合に必要なアミノ酸残留物を前記配列のいずれかに添加させることから生じるペプチド;
からなる群から選択されるペプチドを有する哺乳動物又は鳥類の免疫処置によって得られることを特徴とする請求項9に記載のペプチドの使用方法。 - 前記抗体又は活性断片又は抗体の誘導体が、
・SEQ ID No.3のペプチド;
・SEQ ID No.3のN末端及び/又はC末端のアミノ酸を残留物の除去することから生じるペプチド;
・タンパク質結合に必要なアミノ酸残留物を前記配列のいずれかに添加させることから生じるペプチド;
からなる群から選択されるペプチドを有する哺乳動物又は鳥類の免疫処置によって得られることを特徴とする請求項9に記載のペプチドの使用方法。 - 前記抗体又は活性断片又は抗体の誘導体が、
・SEQ ID No.4のペプチド;
・SEQ ID No.4のN末端及び/又はC末端のアミノ酸の残留物を除去することから生じるペプチド;
・タンパク質結合に必要なアミノ酸残留物を前記配列のいずれかに添加させることから生じるペプチド;
からなる群から選択されるペプチドを有する哺乳動物又は鳥類の免疫処置によって得られることを特徴とする請求項9に記載のペプチドの使用方法。
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
ESP200301054 | 2003-05-08 | ||
ES200301054A ES2246105B1 (es) | 2003-05-08 | 2003-05-08 | Uso de anticuerpos para el tratamiento de enfermedades amiloideas. |
Related Parent Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2016003772A Division JP2016065100A (ja) | 2003-05-08 | 2016-01-12 | アルツハイマー病治療方法 |
Publications (1)
Publication Number | Publication Date |
---|---|
JP2018119011A true JP2018119011A (ja) | 2018-08-02 |
Family
ID=32982086
Family Applications (5)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2006505607A Pending JP2006525288A (ja) | 2003-05-08 | 2004-05-03 | アルツハイマー病治療方法 |
JP2011191515A Pending JP2012006967A (ja) | 2003-05-08 | 2011-09-02 | アルツハイマー病治療方法 |
JP2014038360A Withdrawn JP2014129389A (ja) | 2003-05-08 | 2014-02-28 | アルツハイマー病治療方法 |
JP2016003772A Withdrawn JP2016065100A (ja) | 2003-05-08 | 2016-01-12 | アルツハイマー病治療方法 |
JP2018088643A Pending JP2018119011A (ja) | 2003-05-08 | 2018-05-02 | アルツハイマー病治療方法 |
Family Applications Before (4)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2006505607A Pending JP2006525288A (ja) | 2003-05-08 | 2004-05-03 | アルツハイマー病治療方法 |
JP2011191515A Pending JP2012006967A (ja) | 2003-05-08 | 2011-09-02 | アルツハイマー病治療方法 |
JP2014038360A Withdrawn JP2014129389A (ja) | 2003-05-08 | 2014-02-28 | アルツハイマー病治療方法 |
JP2016003772A Withdrawn JP2016065100A (ja) | 2003-05-08 | 2016-01-12 | アルツハイマー病治療方法 |
Country Status (19)
Country | Link |
---|---|
US (6) | US20090162362A1 (ja) |
EP (5) | EP2082747A3 (ja) |
JP (5) | JP2006525288A (ja) |
CN (2) | CN101264326A (ja) |
AT (1) | ATE435024T1 (ja) |
AU (2) | AU2004237373A1 (ja) |
BR (1) | BRPI0410684A (ja) |
CA (1) | CA2524571C (ja) |
CY (1) | CY1109454T1 (ja) |
DE (1) | DE602004021797D1 (ja) |
DK (3) | DK2075007T3 (ja) |
ES (6) | ES2246177B1 (ja) |
IL (8) | IL171651A (ja) |
MX (1) | MXPA05010914A (ja) |
PL (3) | PL2356996T3 (ja) |
PT (3) | PT2075007E (ja) |
RU (2) | RU2385161C2 (ja) |
SI (1) | SI1623719T1 (ja) |
WO (1) | WO2004098631A1 (ja) |
Families Citing this family (33)
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 |
US7732162B2 (en) | 2003-05-05 | 2010-06-08 | Probiodrug Ag | Inhibitors of glutaminyl cyclase for treating neurodegenerative diseases |
ES2246177B1 (es) * | 2003-05-08 | 2007-03-01 | Universidad De Zaragoza. | Uso de anticuerpos para el tratamiento de enfermedades amiloideas. |
AP2007003890A0 (en) | 2004-07-30 | 2007-02-28 | Rinat Neuroscience Corp | Antibodies directed against amy-loid-beta peptide and methods using same |
PE20061323A1 (es) | 2005-04-29 | 2007-02-09 | Rinat Neuroscience Corp | Anticuerpos dirigidos contra el peptido amiloide beta y metodos que utilizan los mismos |
PL1954718T3 (pl) | 2005-11-30 | 2015-04-30 | Abbvie Inc | Przeciwciała skierowane przeciwko A globulomerowi, ich reszty wiążące antygeny, odpowiednie hybrydomy, kwasy nukleinowe, wektory, komórki gospodarze, sposoby wytwarzania tych przeciwciał, kompozycje zawierające te przeciwciała, zastosowania tych przeciwciał i sposoby stosowania tych przeciwciał |
KR101667623B1 (ko) | 2005-11-30 | 2016-10-19 | 애브비 인코포레이티드 | 아밀로이드 베타 단백질에 대한 모노클로날 항체 및 이의 용도 |
EP2808032B1 (en) * | 2005-12-12 | 2018-08-01 | AC Immune S.A. | A beta 1-42 specific monoclonal antibodies with therapeutic properties |
MX2009000476A (es) * | 2006-07-14 | 2009-01-28 | Ac Immune Sa | Anticuerpo humanizado contra beta amiloide. |
US8455626B2 (en) | 2006-11-30 | 2013-06-04 | Abbott Laboratories | Aβ conformer selective anti-aβ globulomer monoclonal antibodies |
EP2124952A2 (en) | 2007-02-27 | 2009-12-02 | Abbott GmbH & Co. KG | Method for the treatment of amyloidoses |
MX2009009234A (es) | 2007-03-01 | 2009-12-01 | Probiodrug Ag | Uso nuevo de inhibidores de ciclasa de glutaminilo. |
WO2008128985A1 (en) | 2007-04-18 | 2008-10-30 | Probiodrug Ag | Thiourea derivatives as glutaminyl cyclase inhibitors |
US8048420B2 (en) * | 2007-06-12 | 2011-11-01 | Ac Immune S.A. | Monoclonal antibody |
US8613923B2 (en) | 2007-06-12 | 2013-12-24 | Ac Immune S.A. | Monoclonal antibody |
AU2008311367B2 (en) * | 2007-10-05 | 2014-11-13 | Ac Immune S.A. | Use of anti-amyloid beta antibody in ocular diseases |
BRPI0818623A2 (pt) * | 2007-10-05 | 2017-05-23 | Ac Immune Sa | composição farmacêutica, e, métodos para reduzir a carga da placa na camada de célula de gânglio retinal de um animal, para reduzir a quantidade de placas na camada de célula de gânglio retinal de um animal, para diminuir a quantidade total de amilóide-beta solúvel na camada de célula de gânglio retinal de um animal, para prevenir, tratar e/ou aliviar os efeitos de uma doença ocular associada com anormalidades patológicas/mudanças no tecido do sistema visual, para monitorar doença ocular residual mínima associada com anormalidades patológicas/mudanças nos tecidos do sistema visual, para predizer responsividade de um paciente, e para reter ou diminuir a pressão ocular nos olhos de um animal |
EP2149380A1 (en) * | 2008-07-29 | 2010-02-03 | Medivet Pharma, S.L. | Veterinary immunotherapy compositions for the Aged Related Cognitive Dysfunction. |
EP2258398A1 (en) * | 2009-05-26 | 2010-12-08 | Araclón Biotech, S. L. | Albumin-amyloid peptide conjugates and uses thereof |
KR101755737B1 (ko) | 2009-09-11 | 2017-07-07 | 프로비오드룩 아게 | 글루타미닐 사이클라제의 억제제로서 헤테로사이클릭 유도체 |
WO2011070174A1 (en) | 2009-12-11 | 2011-06-16 | Araclon Biotech, S.L. | Methods and reagents for improved detection of amyloid beta peptides |
US9181233B2 (en) | 2010-03-03 | 2015-11-10 | Probiodrug Ag | Inhibitors of glutaminyl cyclase |
CA2789440C (en) | 2010-03-10 | 2020-03-24 | Probiodrug Ag | Heterocyclic inhibitors of glutaminyl cyclase (qc, ec 2.3.2.5) |
MX336196B (es) | 2010-04-15 | 2016-01-11 | Abbvie Inc | Proteinas de union a amiloide beta. |
JP5945532B2 (ja) | 2010-04-21 | 2016-07-05 | プロビオドルグ エージー | グルタミニルシクラーゼの阻害剤としてのベンゾイミダゾール誘導体 |
EP2593475B1 (en) * | 2010-07-14 | 2016-03-02 | Merck Sharp & Dohme Corp. | Anti-addl monoclonal antibody and uses thereof |
CA2806909C (en) * | 2010-07-30 | 2019-12-17 | Ac Immune S.A. | Safe and functional humanized antibodies |
MX358739B (es) | 2010-08-14 | 2018-09-03 | Abbvie Inc Star | Proteinas de union a amiloide beta. |
ES2570167T3 (es) | 2011-03-16 | 2016-05-17 | Probiodrug Ag | Derivados de benzimidazol como inhibidores de glutaminil ciclasa |
WO2015017280A1 (en) | 2013-07-28 | 2015-02-05 | Qantu Therapeutics, Inc. | Vaccine formulations that induce a th2 immune response |
ES2571055B1 (es) * | 2016-02-15 | 2016-12-28 | Araclon Biotech, S.L. | Conjugado amiloide y usos y procedimientos del mismo |
ES2812698T3 (es) | 2017-09-29 | 2021-03-18 | Probiodrug Ag | Inhibidores de glutaminil ciclasa |
PL237739B1 (pl) | 2018-06-06 | 2021-05-17 | Univ Gdanski | Genisteina do zastosowania do leczenia choroby Alzheimera |
Family Cites Families (17)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CA1339014C (en) * | 1987-10-08 | 1997-03-25 | Ronald E. Majocha | Antibodies to a4 amyloid peptide |
AU5525090A (en) * | 1989-04-14 | 1990-11-16 | Research Foundation For Mental Hygiene, Inc. | Monoclonal antibody to amyloid peptide |
EP0526511B1 (en) | 1990-04-27 | 1997-05-28 | MCMICHAEL, John | Method and composition for treatment of central nervous systems disease states associated with abnormal amyloid beta protein |
US7427392B1 (en) * | 1994-11-14 | 2008-09-23 | Elan Pharmaceuticals, Inc. | Methods for aiding in the diagnosis of alzheimer's disease by measuring amyloid-β peptide (x-≧41) and tau |
US8173127B2 (en) * | 1997-04-09 | 2012-05-08 | Intellect Neurosciences, Inc. | Specific antibodies to amyloid beta peptide, pharmaceutical compositions and methods of use thereof |
US7964192B1 (en) * | 1997-12-02 | 2011-06-21 | Janssen Alzheimer Immunotherapy | Prevention and treatment of amyloidgenic 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 |
US6743427B1 (en) * | 1997-12-02 | 2004-06-01 | Neuralab Limited | Prevention and treatment of amyloidogenic disease |
EP1105163A4 (en) * | 1998-08-20 | 2003-05-02 | Univ California | METHOD FOR MARKING AMYLOID PLAQUES AND NEUROFIBRILLIC GIFTS |
UA81216C2 (en) * | 1999-06-01 | 2007-12-25 | Prevention and treatment of amyloid disease | |
CA2500462A1 (en) * | 2001-12-26 | 2004-03-25 | Universidad De Zaragoza | Polyclonal antibodies, preparation method thereof and use of same |
EP1371986A1 (en) * | 2002-06-06 | 2003-12-17 | ABETA GmbH | Diagnosis of Alzheimer's disease based on the hAbeta42:hAbeta40 ratio |
CA2487528A1 (en) * | 2002-07-24 | 2004-02-12 | Innogenetics N.V. | Prevention, treatment and diagnosis of diseases associated with beta-amyloid formation and/or aggregation |
ES2201929B1 (es) * | 2002-09-12 | 2005-05-16 | Araclon Biotech, S.L. | Anticuerpos policlonales, metodo de preparacion y uso de los mismos. |
JP2006519762A (ja) * | 2002-10-09 | 2006-08-31 | ライナット ニューロサイエンス コーポレイション | アミロイドβペプチド及びその組成物に対する抗体を使用して、アルツハイマー病を治療する方法 |
AU2004209981B2 (en) * | 2003-02-01 | 2009-02-26 | Janssen Sciences Ireland Uc | Active immunization to generate antibodies to soluble A-beta |
ES2246177B1 (es) * | 2003-05-08 | 2007-03-01 | Universidad De Zaragoza. | Uso de anticuerpos para el tratamiento de enfermedades amiloideas. |
-
2003
- 2003-05-08 ES ES200403158A patent/ES2246177B1/es not_active Expired - Fee Related
- 2003-05-08 ES ES200301054A patent/ES2246105B1/es not_active Expired - Fee Related
- 2003-05-08 ES ES200403159A patent/ES2246178B1/es not_active Expired - Fee Related
-
2004
- 2004-05-03 ES ES08170222T patent/ES2423281T3/es not_active Expired - Lifetime
- 2004-05-03 DK DK08170222.7T patent/DK2075007T3/da active
- 2004-05-03 SI SI200431235T patent/SI1623719T1/sl unknown
- 2004-05-03 ES ES10012342T patent/ES2423590T3/es not_active Expired - Lifetime
- 2004-05-03 CN CNA2008100898940A patent/CN101264326A/zh active Pending
- 2004-05-03 CN CNA2004800125340A patent/CN1784240A/zh active Pending
- 2004-05-03 AT AT04730882T patent/ATE435024T1/de active
- 2004-05-03 PL PL10012342T patent/PL2356996T3/pl unknown
- 2004-05-03 PL PL04730882T patent/PL1623719T3/pl unknown
- 2004-05-03 DE DE602004021797T patent/DE602004021797D1/de not_active Expired - Lifetime
- 2004-05-03 EP EP08170207A patent/EP2082747A3/en not_active Withdrawn
- 2004-05-03 DK DK10012342.1T patent/DK2356996T5/da active
- 2004-05-03 PT PT81702227T patent/PT2075007E/pt unknown
- 2004-05-03 PL PL08170222T patent/PL2075007T3/pl unknown
- 2004-05-03 WO PCT/ES2004/000194 patent/WO2004098631A1/es active Application Filing
- 2004-05-03 ES ES04730882T patent/ES2329369T3/es not_active Expired - Lifetime
- 2004-05-03 PT PT04730882T patent/PT1623719E/pt unknown
- 2004-05-03 EP EP04730882A patent/EP1623719B1/en not_active Expired - Lifetime
- 2004-05-03 RU RU2005134351/15A patent/RU2385161C2/ru active
- 2004-05-03 EP EP10012342.1A patent/EP2356996B9/en not_active Expired - Lifetime
- 2004-05-03 AU AU2004237373A patent/AU2004237373A1/en not_active Abandoned
- 2004-05-03 MX MXPA05010914A patent/MXPA05010914A/es active IP Right Grant
- 2004-05-03 DK DK04730882T patent/DK1623719T3/da active
- 2004-05-03 JP JP2006505607A patent/JP2006525288A/ja active Pending
- 2004-05-03 CA CA2524571A patent/CA2524571C/en not_active Expired - Fee Related
- 2004-05-03 BR BRPI0410684-9A patent/BRPI0410684A/pt not_active Application Discontinuation
- 2004-05-03 EP EP10012340A patent/EP2305286A3/en not_active Withdrawn
- 2004-05-03 EP EP08170222.7A patent/EP2075007B9/en not_active Expired - Lifetime
- 2004-05-03 PT PT100123421T patent/PT2356996E/pt unknown
- 2004-05-03 US US10/555,865 patent/US20090162362A1/en not_active Abandoned
-
2005
- 2005-10-27 IL IL171651A patent/IL171651A/en active IP Right Grant
-
2009
- 2009-10-02 CY CY20091101026T patent/CY1109454T1/el unknown
- 2009-12-25 RU RU2009148539/15A patent/RU2526155C2/ru active
-
2010
- 2010-08-30 IL IL207878A patent/IL207878A/en active IP Right Grant
- 2010-08-30 IL IL207876A patent/IL207876A/en not_active IP Right Cessation
- 2010-08-30 IL IL207875A patent/IL207875A/en active IP Right Grant
- 2010-08-30 IL IL207877A patent/IL207877A/en not_active IP Right Cessation
- 2010-08-30 IL IL207879A patent/IL207879A/en active IP Right Grant
- 2010-08-30 IL IL207880A patent/IL207880A/en not_active IP Right Cessation
- 2010-08-30 IL IL207881A patent/IL207881A/en not_active IP Right Cessation
-
2011
- 2011-01-17 AU AU2011200170A patent/AU2011200170C1/en not_active Ceased
- 2011-03-17 US US13/050,654 patent/US20110262458A1/en not_active Abandoned
- 2011-09-02 JP JP2011191515A patent/JP2012006967A/ja active Pending
-
2013
- 2013-09-13 US US14/026,374 patent/US20140044725A1/en not_active Abandoned
-
2014
- 2014-02-28 JP JP2014038360A patent/JP2014129389A/ja not_active Withdrawn
-
2016
- 2016-01-12 JP JP2016003772A patent/JP2016065100A/ja not_active Withdrawn
-
2017
- 2017-05-23 US US15/602,779 patent/US20170260234A1/en not_active Abandoned
-
2018
- 2018-05-02 JP JP2018088643A patent/JP2018119011A/ja active Pending
-
2020
- 2020-01-16 US US16/745,067 patent/US20200140488A1/en not_active Abandoned
-
2021
- 2021-03-26 US US17/213,720 patent/US20210214394A1/en active Pending
Also Published As
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JP2018119011A (ja) | アルツハイマー病治療方法 | |
AU2011226926A1 (en) | Alzheimer's disease treatment method |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20180511 |
|
A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20180511 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20190416 |
|
A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20190716 |
|
A02 | Decision of refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A02 Effective date: 20191105 |