RU2696566C2 - Пептидная вакцина для предупреждения и иммунотерапии деменции альцгеймеровского типа - Google Patents
Пептидная вакцина для предупреждения и иммунотерапии деменции альцгеймеровского типа Download PDFInfo
- Publication number
- RU2696566C2 RU2696566C2 RU2015142996A RU2015142996A RU2696566C2 RU 2696566 C2 RU2696566 C2 RU 2696566C2 RU 2015142996 A RU2015142996 A RU 2015142996A RU 2015142996 A RU2015142996 A RU 2015142996A RU 2696566 C2 RU2696566 C2 RU 2696566C2
- Authority
- RU
- Russia
- Prior art keywords
- peptide
- vaccine
- seq
- alzheimer
- immunogenic
- Prior art date
Links
- 206010012289 Dementia Diseases 0.000 title claims abstract description 40
- 230000002265 prevention Effects 0.000 title claims abstract description 20
- 238000009169 immunotherapy Methods 0.000 title description 10
- 229940023041 peptide vaccine Drugs 0.000 title description 5
- 108090000765 processed proteins & peptides Proteins 0.000 claims abstract description 589
- 208000024827 Alzheimer disease Diseases 0.000 claims abstract description 254
- 230000002163 immunogen Effects 0.000 claims abstract description 207
- 238000000034 method Methods 0.000 claims abstract description 89
- 239000002671 adjuvant Substances 0.000 claims abstract description 72
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 55
- 238000011282 treatment Methods 0.000 claims abstract description 44
- 239000003937 drug carrier Substances 0.000 claims abstract description 8
- 229940046168 CpG oligodeoxynucleotide Drugs 0.000 claims description 65
- 241000282414 Homo sapiens Species 0.000 claims description 56
- 230000003308 immunostimulating effect Effects 0.000 claims description 47
- ILRRQNADMUWWFW-UHFFFAOYSA-K aluminium phosphate Chemical compound O1[Al]2OP1(=O)O2 ILRRQNADMUWWFW-UHFFFAOYSA-K 0.000 claims description 24
- 102000013455 Amyloid beta-Peptides Human genes 0.000 claims description 23
- 108010090849 Amyloid beta-Peptides Proteins 0.000 claims description 23
- 241000282412 Homo Species 0.000 claims description 19
- 238000004519 manufacturing process Methods 0.000 claims description 19
- 229940046166 oligodeoxynucleotide Drugs 0.000 claims description 16
- 239000003981 vehicle Substances 0.000 claims description 14
- 102000004196 processed proteins & peptides Human genes 0.000 abstract description 120
- 230000028993 immune response Effects 0.000 abstract description 46
- 230000000694 effects Effects 0.000 abstract description 22
- 239000003814 drug Substances 0.000 abstract description 16
- 238000010276 construction Methods 0.000 abstract description 13
- 239000000126 substance Substances 0.000 abstract description 6
- 230000001681 protective effect Effects 0.000 abstract description 4
- 230000004936 stimulating effect Effects 0.000 abstract description 3
- 229960005486 vaccine Drugs 0.000 description 340
- 239000000203 mixture Substances 0.000 description 252
- 238000009472 formulation Methods 0.000 description 97
- 230000005847 immunogenicity Effects 0.000 description 97
- 241001465754 Metazoa Species 0.000 description 90
- 230000003053 immunization Effects 0.000 description 89
- 238000002649 immunization Methods 0.000 description 89
- 238000002965 ELISA Methods 0.000 description 65
- 210000002966 serum Anatomy 0.000 description 62
- 241000699670 Mus sp. Species 0.000 description 60
- 210000004556 brain Anatomy 0.000 description 54
- DZHSAHHDTRWUTF-SIQRNXPUSA-N amyloid-beta polypeptide 42 Chemical compound C([C@@H](C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@H](C(=O)NCC(=O)N[C@@H](CO)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCCN)C(=O)NCC(=O)N[C@@H](C)C(=O)N[C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](C(C)C)C(=O)NCC(=O)NCC(=O)N[C@@H](C(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C)C(O)=O)[C@@H](C)CC)C(C)C)NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@@H](NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)CNC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CC(O)=O)C(C)C)C(C)C)C1=CC=CC=C1 DZHSAHHDTRWUTF-SIQRNXPUSA-N 0.000 description 46
- 235000001014 amino acid Nutrition 0.000 description 45
- 230000004044 response Effects 0.000 description 45
- 101710137189 Amyloid-beta A4 protein Proteins 0.000 description 43
- 102100022704 Amyloid-beta precursor protein Human genes 0.000 description 43
- 101710151993 Amyloid-beta precursor protein Proteins 0.000 description 43
- 229940024606 amino acid Drugs 0.000 description 42
- 150000001413 amino acids Chemical class 0.000 description 42
- 235000002639 sodium chloride Nutrition 0.000 description 41
- 241000282520 Papio Species 0.000 description 40
- 238000004458 analytical method Methods 0.000 description 37
- 210000003719 b-lymphocyte Anatomy 0.000 description 37
- 229910052500 inorganic mineral Inorganic materials 0.000 description 37
- 239000011707 mineral Substances 0.000 description 37
- 235000010755 mineral Nutrition 0.000 description 37
- 150000003839 salts Chemical class 0.000 description 36
- 108091007433 antigens Proteins 0.000 description 35
- 102000036639 antigens Human genes 0.000 description 35
- 230000027455 binding Effects 0.000 description 35
- 210000004027 cell Anatomy 0.000 description 35
- 239000000427 antigen Substances 0.000 description 34
- 238000011161 development Methods 0.000 description 34
- 210000003819 peripheral blood mononuclear cell Anatomy 0.000 description 34
- 102000004127 Cytokines Human genes 0.000 description 32
- 108090000695 Cytokines Proteins 0.000 description 32
- 241000700198 Cavia Species 0.000 description 29
- 238000012360 testing method Methods 0.000 description 29
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 26
- 208000037259 Amyloid Plaque Diseases 0.000 description 23
- 210000001744 T-lymphocyte Anatomy 0.000 description 23
- 230000015572 biosynthetic process Effects 0.000 description 23
- 201000010099 disease Diseases 0.000 description 23
- 241000282553 Macaca Species 0.000 description 22
- 230000005875 antibody response Effects 0.000 description 22
- 230000000521 hyperimmunizing effect Effects 0.000 description 22
- 230000001900 immune effect Effects 0.000 description 22
- 230000001965 increasing effect Effects 0.000 description 22
- 230000009257 reactivity Effects 0.000 description 22
- 125000003275 alpha amino acid group Chemical group 0.000 description 21
- 230000008569 process Effects 0.000 description 21
- 229940037003 alum Drugs 0.000 description 20
- 108090000623 proteins and genes Proteins 0.000 description 20
- 108010047620 Phytohemagglutinins Proteins 0.000 description 18
- 230000002708 enhancing effect Effects 0.000 description 18
- 239000000178 monomer Substances 0.000 description 18
- 230000001885 phytohemagglutinin Effects 0.000 description 18
- 239000000902 placebo Substances 0.000 description 18
- 229940068196 placebo Drugs 0.000 description 18
- 210000001519 tissue Anatomy 0.000 description 18
- 102000004169 proteins and genes Human genes 0.000 description 17
- 230000008859 change Effects 0.000 description 16
- 230000002068 genetic effect Effects 0.000 description 16
- 238000013507 mapping Methods 0.000 description 16
- 239000012071 phase Substances 0.000 description 16
- 235000018102 proteins Nutrition 0.000 description 16
- 101000823051 Homo sapiens Amyloid-beta precursor protein Proteins 0.000 description 15
- 125000000539 amino acid group Chemical group 0.000 description 15
- 230000007423 decrease Effects 0.000 description 15
- 239000002552 dosage form Substances 0.000 description 15
- 210000002443 helper t lymphocyte Anatomy 0.000 description 15
- 238000002347 injection Methods 0.000 description 15
- 239000007924 injection Substances 0.000 description 15
- 210000004698 lymphocyte Anatomy 0.000 description 15
- 230000035755 proliferation Effects 0.000 description 15
- 238000011830 transgenic mouse model Methods 0.000 description 15
- 241000699660 Mus musculus Species 0.000 description 14
- 108091034117 Oligonucleotide Proteins 0.000 description 14
- 210000005013 brain tissue Anatomy 0.000 description 14
- 238000000338 in vitro Methods 0.000 description 14
- 210000004898 n-terminal fragment Anatomy 0.000 description 14
- 210000002381 plasma Anatomy 0.000 description 14
- 238000002360 preparation method Methods 0.000 description 14
- 108700018351 Major Histocompatibility Complex Proteins 0.000 description 13
- 210000001175 cerebrospinal fluid Anatomy 0.000 description 13
- 239000000839 emulsion Substances 0.000 description 13
- 239000012634 fragment Substances 0.000 description 13
- 239000000243 solution Substances 0.000 description 13
- 230000020382 suppression by virus of host antigen processing and presentation of peptide antigen via MHC class I Effects 0.000 description 13
- 230000009261 transgenic effect Effects 0.000 description 13
- 241000282567 Macaca fascicularis Species 0.000 description 12
- 229940079593 drug Drugs 0.000 description 12
- 238000011156 evaluation Methods 0.000 description 12
- 239000003226 mitogen Substances 0.000 description 12
- 239000003921 oil Substances 0.000 description 12
- 239000002245 particle Substances 0.000 description 12
- 230000007170 pathology Effects 0.000 description 12
- 238000002255 vaccination Methods 0.000 description 12
- 241001504519 Papio ursinus Species 0.000 description 11
- 210000004369 blood Anatomy 0.000 description 11
- 239000008280 blood Substances 0.000 description 11
- 238000010790 dilution Methods 0.000 description 11
- 239000012895 dilution Substances 0.000 description 11
- 239000000284 extract Substances 0.000 description 11
- 230000002829 reductive effect Effects 0.000 description 11
- 238000003786 synthesis reaction Methods 0.000 description 11
- 102000014914 Carrier Proteins Human genes 0.000 description 10
- 108010078791 Carrier Proteins Proteins 0.000 description 10
- 230000007131 anti Alzheimer effect Effects 0.000 description 10
- 210000000987 immune system Anatomy 0.000 description 10
- 238000003780 insertion Methods 0.000 description 10
- 230000037431 insertion Effects 0.000 description 10
- 230000035772 mutation Effects 0.000 description 10
- 239000000047 product Substances 0.000 description 10
- 238000011160 research Methods 0.000 description 10
- 239000000725 suspension Substances 0.000 description 10
- 208000024891 symptom Diseases 0.000 description 10
- 230000001988 toxicity Effects 0.000 description 10
- 231100000419 toxicity Toxicity 0.000 description 10
- 230000002411 adverse Effects 0.000 description 9
- 125000002091 cationic group Chemical group 0.000 description 9
- 230000009260 cross reactivity Effects 0.000 description 9
- 230000003247 decreasing effect Effects 0.000 description 9
- 238000012217 deletion Methods 0.000 description 9
- 230000037430 deletion Effects 0.000 description 9
- 238000001514 detection method Methods 0.000 description 9
- 238000004128 high performance liquid chromatography Methods 0.000 description 9
- 210000001320 hippocampus Anatomy 0.000 description 9
- 238000010255 intramuscular injection Methods 0.000 description 9
- 239000007927 intramuscular injection Substances 0.000 description 9
- 238000012216 screening Methods 0.000 description 9
- 238000006467 substitution reaction Methods 0.000 description 9
- 108010067409 AN-1792 Proteins 0.000 description 8
- 108090001005 Interleukin-6 Proteins 0.000 description 8
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 8
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 8
- 108060008682 Tumor Necrosis Factor Proteins 0.000 description 8
- 102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 description 8
- 230000004913 activation Effects 0.000 description 8
- 229910052782 aluminium Inorganic materials 0.000 description 8
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 8
- 230000001149 cognitive effect Effects 0.000 description 8
- 238000013461 design Methods 0.000 description 8
- 230000001024 immunotherapeutic effect Effects 0.000 description 8
- 238000001727 in vivo Methods 0.000 description 8
- 230000001939 inductive effect Effects 0.000 description 8
- 230000005764 inhibitory process Effects 0.000 description 8
- 238000007918 intramuscular administration Methods 0.000 description 8
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 8
- 244000052769 pathogen Species 0.000 description 8
- 230000001717 pathogenic effect Effects 0.000 description 8
- 238000003908 quality control method Methods 0.000 description 8
- 230000000405 serological effect Effects 0.000 description 8
- 125000006850 spacer group Chemical group 0.000 description 8
- 241000894007 species Species 0.000 description 8
- 230000000638 stimulation Effects 0.000 description 8
- 102000013498 tau Proteins Human genes 0.000 description 8
- 108010026424 tau Proteins Proteins 0.000 description 8
- 230000002588 toxic effect Effects 0.000 description 8
- MZOFCQQQCNRIBI-VMXHOPILSA-N (3s)-4-[[(2s)-1-[[(2s)-1-[[(1s)-1-carboxy-2-hydroxyethyl]amino]-4-methyl-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-3-[[2-[[(2s)-2,6-diaminohexanoyl]amino]acetyl]amino]-4-oxobutanoic acid Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CC(O)=O)NC(=O)CNC(=O)[C@@H](N)CCCCN MZOFCQQQCNRIBI-VMXHOPILSA-N 0.000 description 7
- 241000700199 Cavia porcellus Species 0.000 description 7
- 108010002350 Interleukin-2 Proteins 0.000 description 7
- 102000000588 Interleukin-2 Human genes 0.000 description 7
- 238000003556 assay Methods 0.000 description 7
- 238000006243 chemical reaction Methods 0.000 description 7
- 150000001875 compounds Chemical class 0.000 description 7
- 239000001963 growth medium Substances 0.000 description 7
- 210000004201 immune sera Anatomy 0.000 description 7
- 229940042743 immune sera Drugs 0.000 description 7
- 239000013642 negative control Substances 0.000 description 7
- 210000002569 neuron Anatomy 0.000 description 7
- 239000013641 positive control Substances 0.000 description 7
- 231100000331 toxic Toxicity 0.000 description 7
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 6
- 102100037850 Interferon gamma Human genes 0.000 description 6
- 108010074328 Interferon-gamma Proteins 0.000 description 6
- 102000003814 Interleukin-10 Human genes 0.000 description 6
- 108090000174 Interleukin-10 Proteins 0.000 description 6
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 6
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 6
- 241000712079 Measles morbillivirus Species 0.000 description 6
- 125000000129 anionic group Chemical group 0.000 description 6
- 230000000890 antigenic effect Effects 0.000 description 6
- 235000003704 aspartic acid Nutrition 0.000 description 6
- 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 6
- 230000037396 body weight Effects 0.000 description 6
- 210000003169 central nervous system Anatomy 0.000 description 6
- 210000003710 cerebral cortex Anatomy 0.000 description 6
- 239000003795 chemical substances by application Substances 0.000 description 6
- 208000010877 cognitive disease Diseases 0.000 description 6
- 238000010828 elution Methods 0.000 description 6
- 230000006870 function Effects 0.000 description 6
- 238000011532 immunohistochemical staining Methods 0.000 description 6
- 230000006872 improvement Effects 0.000 description 6
- 239000007788 liquid Substances 0.000 description 6
- 238000001840 matrix-assisted laser desorption--ionisation time-of-flight mass spectrometry Methods 0.000 description 6
- 210000000274 microglia Anatomy 0.000 description 6
- 238000009520 phase I clinical trial Methods 0.000 description 6
- 229920000136 polysorbate Polymers 0.000 description 6
- 230000000069 prophylactic effect Effects 0.000 description 6
- 239000000758 substrate Substances 0.000 description 6
- 230000008685 targeting Effects 0.000 description 6
- 230000001225 therapeutic effect Effects 0.000 description 6
- 241000283707 Capra Species 0.000 description 5
- 201000010374 Down Syndrome Diseases 0.000 description 5
- 108091054438 MHC class II family Proteins 0.000 description 5
- 239000003153 chemical reaction reagent Substances 0.000 description 5
- 230000016396 cytokine production Effects 0.000 description 5
- 230000008021 deposition Effects 0.000 description 5
- 238000002474 experimental method Methods 0.000 description 5
- 239000000499 gel Substances 0.000 description 5
- 230000008595 infiltration Effects 0.000 description 5
- 238000001764 infiltration Methods 0.000 description 5
- 238000012544 monitoring process Methods 0.000 description 5
- 150000007523 nucleic acids Chemical class 0.000 description 5
- 230000001575 pathological effect Effects 0.000 description 5
- 238000010647 peptide synthesis reaction Methods 0.000 description 5
- 229920000642 polymer Polymers 0.000 description 5
- 239000007790 solid phase Substances 0.000 description 5
- 239000007762 w/o emulsion Substances 0.000 description 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 5
- 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 4
- 229910017119 AlPO Inorganic materials 0.000 description 4
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 4
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 4
- 108010033276 Peptide Fragments Proteins 0.000 description 4
- 102000007079 Peptide Fragments Human genes 0.000 description 4
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 4
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 4
- 239000013504 Triton X-100 Substances 0.000 description 4
- 229920004890 Triton X-100 Polymers 0.000 description 4
- 108010059722 Viral Fusion Proteins Proteins 0.000 description 4
- 230000009471 action Effects 0.000 description 4
- 238000004220 aggregation Methods 0.000 description 4
- AZDRQVAHHNSJOQ-UHFFFAOYSA-N alumane Chemical class [AlH3] AZDRQVAHHNSJOQ-UHFFFAOYSA-N 0.000 description 4
- 210000000612 antigen-presenting cell Anatomy 0.000 description 4
- 238000013459 approach Methods 0.000 description 4
- 238000011888 autopsy Methods 0.000 description 4
- 239000003599 detergent Substances 0.000 description 4
- 206010014599 encephalitis Diseases 0.000 description 4
- 238000005516 engineering process Methods 0.000 description 4
- 235000019253 formic acid Nutrition 0.000 description 4
- 238000003018 immunoassay Methods 0.000 description 4
- 230000001976 improved effect Effects 0.000 description 4
- 239000004615 ingredient Substances 0.000 description 4
- 238000005259 measurement Methods 0.000 description 4
- 230000001404 mediated effect Effects 0.000 description 4
- 208000027061 mild cognitive impairment Diseases 0.000 description 4
- 108020004707 nucleic acids Proteins 0.000 description 4
- 102000039446 nucleic acids Human genes 0.000 description 4
- 230000002093 peripheral effect Effects 0.000 description 4
- 230000036470 plasma concentration Effects 0.000 description 4
- 230000003389 potentiating effect Effects 0.000 description 4
- 238000011533 pre-incubation Methods 0.000 description 4
- 238000012545 processing Methods 0.000 description 4
- 230000001105 regulatory effect Effects 0.000 description 4
- 238000004007 reversed phase HPLC Methods 0.000 description 4
- 230000028327 secretion Effects 0.000 description 4
- 239000011780 sodium chloride Substances 0.000 description 4
- 238000010186 staining Methods 0.000 description 4
- RWQNBRDOKXIBIV-UHFFFAOYSA-N thymine Chemical compound CC1=CNC(=O)NC1=O RWQNBRDOKXIBIV-UHFFFAOYSA-N 0.000 description 4
- 239000003656 tris buffered saline Substances 0.000 description 4
- 238000005406 washing Methods 0.000 description 4
- 102000002659 Amyloid Precursor Protein Secretases Human genes 0.000 description 3
- 108010032595 Antibody Binding Sites Proteins 0.000 description 3
- 241000283690 Bos taurus Species 0.000 description 3
- 102000009016 Cholera Toxin Human genes 0.000 description 3
- 108010049048 Cholera Toxin Proteins 0.000 description 3
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 3
- 108010001336 Horseradish Peroxidase Proteins 0.000 description 3
- 206010061218 Inflammation Diseases 0.000 description 3
- 102000004889 Interleukin-6 Human genes 0.000 description 3
- 102000043131 MHC class II family Human genes 0.000 description 3
- 241000282560 Macaca mulatta Species 0.000 description 3
- 206010029350 Neurotoxicity Diseases 0.000 description 3
- 241000282516 Papio anubis Species 0.000 description 3
- 102000008235 Toll-Like Receptor 9 Human genes 0.000 description 3
- 108010060818 Toll-Like Receptor 9 Proteins 0.000 description 3
- 206010044221 Toxic encephalopathy Diseases 0.000 description 3
- JLCPHMBAVCMARE-UHFFFAOYSA-N [3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-hydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methyl [5-(6-aminopurin-9-yl)-2-(hydroxymethyl)oxolan-3-yl] hydrogen phosphate Polymers Cc1cn(C2CC(OP(O)(=O)OCC3OC(CC3OP(O)(=O)OCC3OC(CC3O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c3nc(N)[nH]c4=O)C(COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3CO)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cc(C)c(=O)[nH]c3=O)n3cc(C)c(=O)[nH]c3=O)n3ccc(N)nc3=O)n3cc(C)c(=O)[nH]c3=O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)O2)c(=O)[nH]c1=O JLCPHMBAVCMARE-UHFFFAOYSA-N 0.000 description 3
- 238000002835 absorbance Methods 0.000 description 3
- 230000007059 acute toxicity Effects 0.000 description 3
- 231100000403 acute toxicity Toxicity 0.000 description 3
- 230000003321 amplification Effects 0.000 description 3
- 230000006933 amyloid-beta aggregation Effects 0.000 description 3
- 230000003941 amyloidogenesis Effects 0.000 description 3
- 150000001450 anions Chemical class 0.000 description 3
- 230000008901 benefit Effects 0.000 description 3
- 210000004204 blood vessel Anatomy 0.000 description 3
- 239000000872 buffer Substances 0.000 description 3
- 210000004899 c-terminal region Anatomy 0.000 description 3
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 3
- 239000000969 carrier Substances 0.000 description 3
- 230000002490 cerebral effect Effects 0.000 description 3
- 230000005591 charge neutralization Effects 0.000 description 3
- 230000007665 chronic toxicity Effects 0.000 description 3
- 231100000160 chronic toxicity Toxicity 0.000 description 3
- 238000003776 cleavage reaction Methods 0.000 description 3
- 230000003920 cognitive function Effects 0.000 description 3
- 230000003013 cytotoxicity Effects 0.000 description 3
- 231100000135 cytotoxicity Toxicity 0.000 description 3
- 230000007812 deficiency Effects 0.000 description 3
- 230000006866 deterioration Effects 0.000 description 3
- 208000035475 disorder Diseases 0.000 description 3
- 235000013922 glutamic acid Nutrition 0.000 description 3
- 239000004220 glutamic acid Substances 0.000 description 3
- 208000002672 hepatitis B Diseases 0.000 description 3
- 230000002209 hydrophobic effect Effects 0.000 description 3
- 238000010348 incorporation Methods 0.000 description 3
- 230000004054 inflammatory process Effects 0.000 description 3
- 230000002401 inhibitory effect Effects 0.000 description 3
- 230000000977 initiatory effect Effects 0.000 description 3
- 239000000543 intermediate Substances 0.000 description 3
- 230000021633 leukocyte mediated immunity Effects 0.000 description 3
- 125000005647 linker group Chemical group 0.000 description 3
- 238000011068 loading method Methods 0.000 description 3
- 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 3
- 230000007246 mechanism Effects 0.000 description 3
- 230000015654 memory Effects 0.000 description 3
- 201000011475 meningoencephalitis Diseases 0.000 description 3
- 230000007135 neurotoxicity Effects 0.000 description 3
- 231100000228 neurotoxicity Toxicity 0.000 description 3
- 238000006386 neutralization reaction Methods 0.000 description 3
- 238000003199 nucleic acid amplification method Methods 0.000 description 3
- 235000019198 oils Nutrition 0.000 description 3
- 230000008506 pathogenesis Effects 0.000 description 3
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 3
- 229920000053 polysorbate 80 Polymers 0.000 description 3
- 230000018491 positive regulation of cytokine secretion Effects 0.000 description 3
- 230000003449 preventive effect Effects 0.000 description 3
- 230000009696 proliferative response Effects 0.000 description 3
- 238000011321 prophylaxis Methods 0.000 description 3
- 208000020016 psychiatric disease Diseases 0.000 description 3
- 238000011002 quantification Methods 0.000 description 3
- 230000009467 reduction Effects 0.000 description 3
- 230000003014 reinforcing effect Effects 0.000 description 3
- 239000011347 resin Substances 0.000 description 3
- 229920005989 resin Polymers 0.000 description 3
- 238000012552 review Methods 0.000 description 3
- 230000007017 scission Effects 0.000 description 3
- 238000010561 standard procedure Methods 0.000 description 3
- 230000002195 synergetic effect Effects 0.000 description 3
- 238000002560 therapeutic procedure Methods 0.000 description 3
- 239000013598 vector Substances 0.000 description 3
- 125000003088 (fluoren-9-ylmethoxy)carbonyl group Chemical group 0.000 description 2
- FWMNVWWHGCHHJJ-SKKKGAJSSA-N 4-amino-1-[(2r)-6-amino-2-[[(2r)-2-[[(2r)-2-[[(2r)-2-amino-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]hexanoyl]piperidine-4-carboxylic acid Chemical compound C([C@H](C(=O)N[C@H](CC(C)C)C(=O)N[C@H](CCCCN)C(=O)N1CCC(N)(CC1)C(O)=O)NC(=O)[C@H](N)CC=1C=CC=CC=1)C1=CC=CC=C1 FWMNVWWHGCHHJJ-SKKKGAJSSA-N 0.000 description 2
- 108010060159 Apolipoprotein E4 Proteins 0.000 description 2
- 239000004475 Arginine Substances 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 2
- 241000282693 Cercopithecidae Species 0.000 description 2
- 241000193449 Clostridium tetani Species 0.000 description 2
- 108020004414 DNA Proteins 0.000 description 2
- 102000053602 DNA Human genes 0.000 description 2
- 238000012286 ELISA Assay Methods 0.000 description 2
- 102000004190 Enzymes Human genes 0.000 description 2
- 108090000790 Enzymes Proteins 0.000 description 2
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 2
- 108091006027 G proteins Proteins 0.000 description 2
- 102000030782 GTP binding Human genes 0.000 description 2
- 108091000058 GTP-Binding Proteins 0.000 description 2
- 108010010803 Gelatin Proteins 0.000 description 2
- 241000700721 Hepatitis B virus Species 0.000 description 2
- 102000018713 Histocompatibility Antigens Class II Human genes 0.000 description 2
- 101001046686 Homo sapiens Integrin alpha-M Proteins 0.000 description 2
- 101000617536 Homo sapiens Presenilin-1 Proteins 0.000 description 2
- 102100022338 Integrin alpha-M Human genes 0.000 description 2
- 108090000176 Interleukin-13 Proteins 0.000 description 2
- 239000004472 Lysine Substances 0.000 description 2
- 101100260568 Mus musculus Thy1 gene Proteins 0.000 description 2
- 125000000729 N-terminal amino-acid group Chemical group 0.000 description 2
- 102000034570 NR1 subfamily Human genes 0.000 description 2
- 108020001305 NR1 subfamily Proteins 0.000 description 2
- 206010067482 No adverse event Diseases 0.000 description 2
- 102000003992 Peroxidases Human genes 0.000 description 2
- 241000223960 Plasmodium falciparum Species 0.000 description 2
- 241000288906 Primates Species 0.000 description 2
- 108010029485 Protein Isoforms Proteins 0.000 description 2
- 102000001708 Protein Isoforms Human genes 0.000 description 2
- 101500027983 Rattus norvegicus Octadecaneuropeptide Proteins 0.000 description 2
- 108020004511 Recombinant DNA Proteins 0.000 description 2
- 102000034527 Retinoid X Receptors Human genes 0.000 description 2
- 108010038912 Retinoid X Receptors Proteins 0.000 description 2
- 108020004682 Single-Stranded DNA Proteins 0.000 description 2
- 108700005078 Synthetic Genes Proteins 0.000 description 2
- 230000024932 T cell mediated immunity Effects 0.000 description 2
- 206010044688 Trisomy 21 Diseases 0.000 description 2
- 238000010521 absorption reaction Methods 0.000 description 2
- 238000009825 accumulation Methods 0.000 description 2
- 239000008186 active pharmaceutical agent Substances 0.000 description 2
- 230000002776 aggregation Effects 0.000 description 2
- 108010064397 amyloid beta-protein (1-40) Proteins 0.000 description 2
- 108010075875 amyloid beta-protein (16-20) Proteins 0.000 description 2
- FEWOUVRMGWFWIH-ILZZQXMPSA-N amyloid-beta polypeptide 40 Chemical compound C([C@@H](C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@H](C(=O)NCC(=O)N[C@@H](CO)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCCN)C(=O)NCC(=O)N[C@@H](C)C(=O)N[C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](C(C)C)C(=O)NCC(=O)NCC(=O)N[C@@H](C(C)C)C(=O)N[C@@H](C(C)C)C(O)=O)[C@@H](C)CC)C(C)C)NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@@H](NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)CNC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CC(O)=O)C(C)C)C(C)C)C1=CC=CC=C1 FEWOUVRMGWFWIH-ILZZQXMPSA-N 0.000 description 2
- 230000030741 antigen processing and presentation Effects 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 2
- 238000003149 assay kit Methods 0.000 description 2
- 230000004888 barrier function Effects 0.000 description 2
- 108091007737 beta-secretases Proteins 0.000 description 2
- 239000000090 biomarker Substances 0.000 description 2
- 239000006227 byproduct Substances 0.000 description 2
- 230000020411 cell activation Effects 0.000 description 2
- 230000001413 cellular effect Effects 0.000 description 2
- 238000005119 centrifugation Methods 0.000 description 2
- 230000003930 cognitive ability Effects 0.000 description 2
- 230000006957 competitive inhibition Effects 0.000 description 2
- 238000012790 confirmation Methods 0.000 description 2
- 230000009089 cytolysis Effects 0.000 description 2
- OPTASPLRGRRNAP-UHFFFAOYSA-N cytosine Chemical compound NC=1C=CNC(=O)N=1 OPTASPLRGRRNAP-UHFFFAOYSA-N 0.000 description 2
- 230000034994 death Effects 0.000 description 2
- 230000006735 deficit Effects 0.000 description 2
- 238000003745 diagnosis Methods 0.000 description 2
- 206010013023 diphtheria Diseases 0.000 description 2
- 238000011979 disease modifying therapy Methods 0.000 description 2
- 238000009826 distribution Methods 0.000 description 2
- 229940088598 enzyme Drugs 0.000 description 2
- 238000012854 evaluation process Methods 0.000 description 2
- 239000013604 expression vector Substances 0.000 description 2
- 238000000605 extraction Methods 0.000 description 2
- 208000015756 familial Alzheimer disease Diseases 0.000 description 2
- 239000012894 fetal calf serum Substances 0.000 description 2
- 230000035557 fibrillogenesis Effects 0.000 description 2
- 230000002600 fibrillogenic effect Effects 0.000 description 2
- 239000012467 final product Substances 0.000 description 2
- 210000005153 frontal cortex Anatomy 0.000 description 2
- 108020001507 fusion proteins Proteins 0.000 description 2
- 102000037865 fusion proteins Human genes 0.000 description 2
- 108091007739 gamma-secretases Proteins 0.000 description 2
- 102000038383 gamma-secretases Human genes 0.000 description 2
- 239000008273 gelatin Substances 0.000 description 2
- 229920000159 gelatin Polymers 0.000 description 2
- 235000019322 gelatine Nutrition 0.000 description 2
- 235000011852 gelatine desserts Nutrition 0.000 description 2
- UYTPUPDQBNUYGX-UHFFFAOYSA-N guanine Chemical compound O=C1NC(N)=NC2=C1N=CN2 UYTPUPDQBNUYGX-UHFFFAOYSA-N 0.000 description 2
- 238000011597 hartley guinea pig Methods 0.000 description 2
- 230000036541 health Effects 0.000 description 2
- 108060003552 hemocyanin Proteins 0.000 description 2
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 2
- 229910052739 hydrogen Inorganic materials 0.000 description 2
- 239000001257 hydrogen Substances 0.000 description 2
- 238000003384 imaging method Methods 0.000 description 2
- 210000002865 immune cell Anatomy 0.000 description 2
- 230000036737 immune function Effects 0.000 description 2
- 238000003364 immunohistochemistry Methods 0.000 description 2
- 239000000568 immunological adjuvant Substances 0.000 description 2
- 239000003547 immunosorbent Substances 0.000 description 2
- 230000003993 interaction Effects 0.000 description 2
- 230000004073 interleukin-2 production Effects 0.000 description 2
- 238000002955 isolation Methods 0.000 description 2
- 238000012417 linear regression Methods 0.000 description 2
- 238000013332 literature search Methods 0.000 description 2
- 230000000527 lymphocytic effect Effects 0.000 description 2
- 238000004949 mass spectrometry Methods 0.000 description 2
- 239000011159 matrix material Substances 0.000 description 2
- 239000011859 microparticle Substances 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- 210000005087 mononuclear cell Anatomy 0.000 description 2
- 229940035032 monophosphoryl lipid a Drugs 0.000 description 2
- 210000004897 n-terminal region Anatomy 0.000 description 2
- 208000015122 neurodegenerative disease Diseases 0.000 description 2
- 210000002682 neurofibrillary tangle Anatomy 0.000 description 2
- 229910052757 nitrogen Inorganic materials 0.000 description 2
- 239000002773 nucleotide Substances 0.000 description 2
- 125000003729 nucleotide group Chemical group 0.000 description 2
- 238000007427 paired t-test Methods 0.000 description 2
- 238000007911 parenteral administration Methods 0.000 description 2
- 210000005259 peripheral blood Anatomy 0.000 description 2
- 239000011886 peripheral blood Substances 0.000 description 2
- 108040007629 peroxidase activity proteins Proteins 0.000 description 2
- 208000028591 pheochromocytoma Diseases 0.000 description 2
- 230000007505 plaque formation Effects 0.000 description 2
- 108091033319 polynucleotide Proteins 0.000 description 2
- 102000040430 polynucleotide Human genes 0.000 description 2
- 239000002157 polynucleotide Substances 0.000 description 2
- 229920001184 polypeptide Polymers 0.000 description 2
- 239000002243 precursor Substances 0.000 description 2
- 230000002028 premature Effects 0.000 description 2
- 238000004321 preservation Methods 0.000 description 2
- 125000006239 protecting group Chemical group 0.000 description 2
- 230000012121 regulation of immune response Effects 0.000 description 2
- 238000003118 sandwich ELISA Methods 0.000 description 2
- 238000001338 self-assembly Methods 0.000 description 2
- 230000001235 sensitizing effect Effects 0.000 description 2
- 238000013207 serial dilution Methods 0.000 description 2
- 238000003860 storage Methods 0.000 description 2
- 239000006228 supernatant Substances 0.000 description 2
- 230000002194 synthesizing effect Effects 0.000 description 2
- 210000001103 thalamus Anatomy 0.000 description 2
- 229940104230 thymidine Drugs 0.000 description 2
- 229940113082 thymine Drugs 0.000 description 2
- 230000002792 vascular Effects 0.000 description 2
- 239000008215 water for injection Substances 0.000 description 2
- MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 description 1
- KYZWKYWGQFCRGN-OASOTCBPSA-N (2s)-2-aminopentanedioic acid;(2r)-2-(methylamino)butanedioic acid Chemical compound CN[C@@H](C(O)=O)CC(O)=O.OC(=O)[C@@H](N)CCC(O)=O KYZWKYWGQFCRGN-OASOTCBPSA-N 0.000 description 1
- YYGNTYWPHWGJRM-UHFFFAOYSA-N (6E,10E,14E,18E)-2,6,10,15,19,23-hexamethyltetracosa-2,6,10,14,18,22-hexaene Chemical compound CC(C)=CCCC(C)=CCCC(C)=CCCC=C(C)CCC=C(C)CCC=C(C)C YYGNTYWPHWGJRM-UHFFFAOYSA-N 0.000 description 1
- SYTBZMRGLBWNTM-SNVBAGLBSA-N (R)-flurbiprofen Chemical compound FC1=CC([C@H](C(O)=O)C)=CC=C1C1=CC=CC=C1 SYTBZMRGLBWNTM-SNVBAGLBSA-N 0.000 description 1
- ZQAQXZBSGZUUNL-BJUDXGSMSA-N 2-[4-(methylamino)phenyl]-1,3-benzothiazol-6-ol Chemical compound C1=CC(N[11CH3])=CC=C1C1=NC2=CC=C(O)C=C2S1 ZQAQXZBSGZUUNL-BJUDXGSMSA-N 0.000 description 1
- ZQAQXZBSGZUUNL-UHFFFAOYSA-N 2-[4-(methylamino)phenyl]-1,3-benzothiazol-6-ol Chemical compound C1=CC(NC)=CC=C1C1=NC2=CC=C(O)C=C2S1 ZQAQXZBSGZUUNL-UHFFFAOYSA-N 0.000 description 1
- ZBQCCTCQUCOXBO-UHFFFAOYSA-N 4-(4-aminophenyl)-2,2,6,6-tetramethylcyclohex-3-en-1-amine Chemical compound CC1(C)C(N)C(C)(C)CC(C=2C=CC(N)=CC=2)=C1 ZBQCCTCQUCOXBO-UHFFFAOYSA-N 0.000 description 1
- WBSCNDJQPKSPII-UHFFFAOYSA-N 6-amino-2-[[6-amino-2-(2,6-diaminohexanoylamino)hexanoyl]amino]hexanoic acid Chemical compound NCCCCC(N)C(=O)NC(CCCCN)C(=O)NC(CCCCN)C(O)=O WBSCNDJQPKSPII-UHFFFAOYSA-N 0.000 description 1
- 229930024421 Adenine Natural products 0.000 description 1
- GFFGJBXGBJISGV-UHFFFAOYSA-N Adenine Chemical compound NC1=NC=NC2=C1N=CN2 GFFGJBXGBJISGV-UHFFFAOYSA-N 0.000 description 1
- 244000291564 Allium cepa Species 0.000 description 1
- 235000002732 Allium cepa var. cepa Nutrition 0.000 description 1
- 108010043324 Amyloid Precursor Protein Secretases Proteins 0.000 description 1
- 101800001718 Amyloid-beta protein Proteins 0.000 description 1
- 102000009091 Amyloidogenic Proteins Human genes 0.000 description 1
- 108010048112 Amyloidogenic Proteins Proteins 0.000 description 1
- 206010059245 Angiopathy Diseases 0.000 description 1
- 206010002556 Ankylosing Spondylitis Diseases 0.000 description 1
- 208000019901 Anxiety disease Diseases 0.000 description 1
- DCXYFEDJOCDNAF-UHFFFAOYSA-N Asparagine Natural products OC(=O)C(N)CC(N)=O DCXYFEDJOCDNAF-UHFFFAOYSA-N 0.000 description 1
- 201000001320 Atherosclerosis Diseases 0.000 description 1
- 206010003694 Atrophy Diseases 0.000 description 1
- 208000023275 Autoimmune disease Diseases 0.000 description 1
- 230000003844 B-cell-activation Effects 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- 241000588832 Bordetella pertussis Species 0.000 description 1
- 241000282472 Canis lupus familiaris Species 0.000 description 1
- 208000024172 Cardiovascular disease Diseases 0.000 description 1
- 208000005145 Cerebral amyloid angiopathy Diseases 0.000 description 1
- 108020004705 Codon Proteins 0.000 description 1
- 208000028698 Cognitive impairment Diseases 0.000 description 1
- 108010062580 Concanavalin A Proteins 0.000 description 1
- 102000016607 Diphtheria Toxin Human genes 0.000 description 1
- 108010053187 Diphtheria Toxin Proteins 0.000 description 1
- 206010061818 Disease progression Diseases 0.000 description 1
- 238000008157 ELISA kit Methods 0.000 description 1
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical class OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 1
- 241000233756 Fabriciana elisa Species 0.000 description 1
- 102100039289 Glial fibrillary acidic protein Human genes 0.000 description 1
- 101710193519 Glial fibrillary acidic protein Proteins 0.000 description 1
- 102000018899 Glutamate Receptors Human genes 0.000 description 1
- 108010027915 Glutamate Receptors Proteins 0.000 description 1
- 239000004471 Glycine Substances 0.000 description 1
- 229930186217 Glycolipid Natural products 0.000 description 1
- 208000032843 Hemorrhage Diseases 0.000 description 1
- 206010019799 Hepatitis viral Diseases 0.000 description 1
- 208000007514 Herpes zoster Diseases 0.000 description 1
- 102000008949 Histocompatibility Antigens Class I Human genes 0.000 description 1
- 108010088652 Histocompatibility Antigens Class I Proteins 0.000 description 1
- 101000617546 Homo sapiens Presenilin-2 Proteins 0.000 description 1
- 208000035150 Hypercholesterolemia Diseases 0.000 description 1
- 108090000978 Interleukin-4 Proteins 0.000 description 1
- 108010002616 Interleukin-5 Proteins 0.000 description 1
- XUJNEKJLAYXESH-REOHCLBHSA-N L-Cysteine Chemical compound SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-N 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
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 1
- DCXYFEDJOCDNAF-REOHCLBHSA-N L-asparagine Chemical compound OC(=O)[C@@H](N)CC(N)=O DCXYFEDJOCDNAF-REOHCLBHSA-N 0.000 description 1
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 1
- HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 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
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 description 1
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 1
- COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 description 1
- AYFVYJQAPQTCCC-GBXIJSLDSA-N L-threonine Chemical compound C[C@@H](O)[C@H](N)C(O)=O AYFVYJQAPQTCCC-GBXIJSLDSA-N 0.000 description 1
- QIVBCDIJIAJPQS-VIFPVBQESA-N L-tryptophane Chemical compound C1=CC=C2C(C[C@H](N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-VIFPVBQESA-N 0.000 description 1
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-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
- WBSCNDJQPKSPII-KKUMJFAQSA-N Lys-Lys-Lys Chemical compound NCCCC[C@H](N)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(O)=O WBSCNDJQPKSPII-KKUMJFAQSA-N 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 201000005505 Measles Diseases 0.000 description 1
- 102000029749 Microtubule Human genes 0.000 description 1
- 108091022875 Microtubule Proteins 0.000 description 1
- 238000012347 Morris Water Maze Methods 0.000 description 1
- 241000699666 Mus <mouse, genus> Species 0.000 description 1
- HOKKHZGPKSLGJE-GSVOUGTGSA-N N-Methyl-D-aspartic acid Chemical compound CN[C@@H](C(O)=O)CC(O)=O HOKKHZGPKSLGJE-GSVOUGTGSA-N 0.000 description 1
- 108091028043 Nucleic acid sequence Proteins 0.000 description 1
- 229930040373 Paraformaldehyde Natural products 0.000 description 1
- 208000018737 Parkinson disease Diseases 0.000 description 1
- 201000005702 Pertussis Diseases 0.000 description 1
- 101000612288 Pinus strobus Putative oxygen-evolving enhancer protein 1 Proteins 0.000 description 1
- 108010050254 Presenilins Proteins 0.000 description 1
- 102000015499 Presenilins Human genes 0.000 description 1
- 238000012356 Product development Methods 0.000 description 1
- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 1
- 239000012980 RPMI-1640 medium Substances 0.000 description 1
- 108010008281 Recombinant Fusion Proteins Proteins 0.000 description 1
- 102000007056 Recombinant Fusion Proteins Human genes 0.000 description 1
- 241000242680 Schistosoma mansoni Species 0.000 description 1
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 1
- 208000006011 Stroke Diseases 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- 241000282887 Suidae Species 0.000 description 1
- 108010008038 Synthetic Vaccines Proteins 0.000 description 1
- 230000006044 T cell activation Effects 0.000 description 1
- 230000005867 T cell response Effects 0.000 description 1
- 208000003217 Tetany Diseases 0.000 description 1
- BHEOSNUKNHRBNM-UHFFFAOYSA-N Tetramethylsqualene Natural products CC(=C)C(C)CCC(=C)C(C)CCC(C)=CCCC=C(C)CCC(C)C(=C)CCC(C)C(C)=C BHEOSNUKNHRBNM-UHFFFAOYSA-N 0.000 description 1
- RYYWUUFWQRZTIU-UHFFFAOYSA-N Thiophosphoric acid Chemical group OP(O)(S)=O RYYWUUFWQRZTIU-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
- 102000002689 Toll-like receptor Human genes 0.000 description 1
- 108020000411 Toll-like receptor Proteins 0.000 description 1
- 108700019146 Transgenes Proteins 0.000 description 1
- 102100023935 Transmembrane glycoprotein NMB Human genes 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
- 238000005411 Van der Waals force Methods 0.000 description 1
- 201000004810 Vascular dementia Diseases 0.000 description 1
- 241000700605 Viruses Species 0.000 description 1
- 238000001793 Wilcoxon signed-rank test Methods 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 210000001642 activated microglia Anatomy 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 210000005006 adaptive immune system Anatomy 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 229960000643 adenine Drugs 0.000 description 1
- 239000000556 agonist Substances 0.000 description 1
- 235000004279 alanine Nutrition 0.000 description 1
- 102000038380 alpha-secretases Human genes 0.000 description 1
- 108091007736 alpha-secretases Proteins 0.000 description 1
- WNROFYMDJYEPJX-UHFFFAOYSA-K aluminium hydroxide Chemical compound [OH-].[OH-].[OH-].[Al+3] WNROFYMDJYEPJX-UHFFFAOYSA-K 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- 230000003942 amyloidogenic effect Effects 0.000 description 1
- 206010002022 amyloidosis Diseases 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 230000001896 anti-amyloidogenic effect Effects 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 230000036506 anxiety Effects 0.000 description 1
- 101150031224 app gene Proteins 0.000 description 1
- 239000007900 aqueous suspension Substances 0.000 description 1
- 235000009582 asparagine Nutrition 0.000 description 1
- 229960001230 asparagine Drugs 0.000 description 1
- 239000012911 assay medium Substances 0.000 description 1
- 238000000429 assembly Methods 0.000 description 1
- 230000000712 assembly Effects 0.000 description 1
- 210000001130 astrocyte Anatomy 0.000 description 1
- 238000004630 atomic force microscopy Methods 0.000 description 1
- 230000037444 atrophy Effects 0.000 description 1
- 230000001363 autoimmune Effects 0.000 description 1
- 230000006472 autoimmune response Effects 0.000 description 1
- 208000013404 behavioral symptom Diseases 0.000 description 1
- 230000003542 behavioural effect Effects 0.000 description 1
- 239000003150 biochemical marker Substances 0.000 description 1
- 239000012620 biological material Substances 0.000 description 1
- 238000001574 biopsy Methods 0.000 description 1
- 229960002685 biotin Drugs 0.000 description 1
- 239000011616 biotin Substances 0.000 description 1
- 208000006752 brain edema Diseases 0.000 description 1
- 238000004364 calculation method Methods 0.000 description 1
- 150000007942 carboxylates Chemical group 0.000 description 1
- 206010061592 cardiac fibrillation Diseases 0.000 description 1
- 238000004113 cell culture Methods 0.000 description 1
- 239000006143 cell culture medium Substances 0.000 description 1
- 230000036755 cellular response Effects 0.000 description 1
- 230000007541 cellular toxicity Effects 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 125000003636 chemical group Chemical group 0.000 description 1
- 238000001311 chemical methods and process Methods 0.000 description 1
- 239000000544 cholinesterase inhibitor Substances 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 239000013599 cloning vector Substances 0.000 description 1
- 238000011260 co-administration Methods 0.000 description 1
- 230000006999 cognitive decline Effects 0.000 description 1
- 230000003931 cognitive performance Effects 0.000 description 1
- 230000002860 competitive effect Effects 0.000 description 1
- 230000000295 complement effect Effects 0.000 description 1
- 230000000536 complexating effect Effects 0.000 description 1
- IQFVPQOLBLOTPF-HKXUKFGYSA-L congo red Chemical compound [Na+].[Na+].C1=CC=CC2=C(N)C(/N=N/C3=CC=C(C=C3)C3=CC=C(C=C3)/N=N/C3=C(C4=CC=CC=C4C(=C3)S([O-])(=O)=O)N)=CC(S([O-])(=O)=O)=C21 IQFVPQOLBLOTPF-HKXUKFGYSA-L 0.000 description 1
- 230000021615 conjugation Effects 0.000 description 1
- 238000013270 controlled release Methods 0.000 description 1
- 230000001054 cortical effect Effects 0.000 description 1
- 230000008878 coupling Effects 0.000 description 1
- 238000010168 coupling process Methods 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- 239000012228 culture supernatant Substances 0.000 description 1
- 238000012258 culturing Methods 0.000 description 1
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 1
- 235000018417 cysteine Nutrition 0.000 description 1
- 125000000151 cysteine group Chemical group N[C@@H](CS)C(=O)* 0.000 description 1
- 229940104302 cytosine Drugs 0.000 description 1
- 210000001151 cytotoxic T lymphocyte Anatomy 0.000 description 1
- 238000002784 cytotoxicity assay Methods 0.000 description 1
- 231100000263 cytotoxicity test Toxicity 0.000 description 1
- 230000003111 delayed effect Effects 0.000 description 1
- 210000004443 dendritic cell Anatomy 0.000 description 1
- 238000000432 density-gradient centrifugation Methods 0.000 description 1
- 238000003795 desorption Methods 0.000 description 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- 238000002405 diagnostic procedure Methods 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- 230000004069 differentiation Effects 0.000 description 1
- 239000012470 diluted sample Substances 0.000 description 1
- 229960003983 diphtheria toxoid Drugs 0.000 description 1
- 230000005750 disease progression Effects 0.000 description 1
- BFMYDTVEBKDAKJ-UHFFFAOYSA-L disodium;(2',7'-dibromo-3',6'-dioxido-3-oxospiro[2-benzofuran-1,9'-xanthene]-4'-yl)mercury;hydrate Chemical compound O.[Na+].[Na+].O1C(=O)C2=CC=CC=C2C21C1=CC(Br)=C([O-])C([Hg])=C1OC1=C2C=C(Br)C([O-])=C1 BFMYDTVEBKDAKJ-UHFFFAOYSA-L 0.000 description 1
- PRAKJMSDJKAYCZ-UHFFFAOYSA-N dodecahydrosqualene Natural products CC(C)CCCC(C)CCCC(C)CCCCC(C)CCCC(C)CCCC(C)C PRAKJMSDJKAYCZ-UHFFFAOYSA-N 0.000 description 1
- 229940000406 drug candidate Drugs 0.000 description 1
- 238000009510 drug design Methods 0.000 description 1
- 208000025688 early-onset autosomal dominant Alzheimer disease Diseases 0.000 description 1
- 230000008030 elimination Effects 0.000 description 1
- 238000003379 elimination reaction Methods 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 210000004696 endometrium Anatomy 0.000 description 1
- 210000002472 endoplasmic reticulum Anatomy 0.000 description 1
- 238000012407 engineering method Methods 0.000 description 1
- 210000003743 erythrocyte Anatomy 0.000 description 1
- YNDIAUKFXKEXSV-CRYLGTRXSA-N florbetapir F-18 Chemical compound C1=CC(NC)=CC=C1\C=C\C1=CC=C(OCCOCCOCC[18F])N=C1 YNDIAUKFXKEXSV-CRYLGTRXSA-N 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 238000005194 fractionation Methods 0.000 description 1
- 238000007710 freezing Methods 0.000 description 1
- 230000008014 freezing Effects 0.000 description 1
- 238000010230 functional analysis Methods 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- 238000011990 functional testing Methods 0.000 description 1
- 238000003205 genotyping method Methods 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 210000005046 glial fibrillary acidic protein Anatomy 0.000 description 1
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 1
- 235000004554 glutamine Nutrition 0.000 description 1
- 201000010235 heart cancer Diseases 0.000 description 1
- 208000019622 heart disease Diseases 0.000 description 1
- 208000024348 heart neoplasm Diseases 0.000 description 1
- 230000000971 hippocampal effect Effects 0.000 description 1
- 238000010562 histological examination Methods 0.000 description 1
- 230000028996 humoral immune response Effects 0.000 description 1
- 239000012729 immediate-release (IR) formulation Substances 0.000 description 1
- 230000008105 immune reaction Effects 0.000 description 1
- 230000036039 immunity Effects 0.000 description 1
- 238000010185 immunofluorescence analysis Methods 0.000 description 1
- 230000016784 immunoglobulin production Effects 0.000 description 1
- 230000002055 immunohistochemical effect Effects 0.000 description 1
- 238000012744 immunostaining Methods 0.000 description 1
- 230000001771 impaired effect Effects 0.000 description 1
- 238000011065 in-situ storage Methods 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 238000009776 industrial production Methods 0.000 description 1
- 239000012678 infectious agent Substances 0.000 description 1
- 210000004969 inflammatory cell Anatomy 0.000 description 1
- 230000002757 inflammatory effect Effects 0.000 description 1
- 230000015788 innate immune response Effects 0.000 description 1
- 238000011081 inoculation Methods 0.000 description 1
- 238000007917 intracranial administration Methods 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
- -1 isooctyl residue Chemical group 0.000 description 1
- 230000002147 killing effect Effects 0.000 description 1
- 238000011005 laboratory method Methods 0.000 description 1
- 150000002605 large molecules Chemical class 0.000 description 1
- 238000011031 large-scale manufacturing process Methods 0.000 description 1
- 210000000265 leukocyte Anatomy 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 239000007791 liquid phase Substances 0.000 description 1
- 239000006193 liquid solution Substances 0.000 description 1
- 239000006194 liquid suspension Substances 0.000 description 1
- 229920002521 macromolecule Polymers 0.000 description 1
- 210000002540 macrophage Anatomy 0.000 description 1
- 239000003550 marker Substances 0.000 description 1
- 230000010534 mechanism of action Effects 0.000 description 1
- 238000002483 medication Methods 0.000 description 1
- 239000002609 medium Substances 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 229930182817 methionine Natural products 0.000 description 1
- 210000004688 microtubule Anatomy 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 229940126619 mouse monoclonal antibody Drugs 0.000 description 1
- 210000003205 muscle Anatomy 0.000 description 1
- 230000001537 neural effect Effects 0.000 description 1
- 238000002610 neuroimaging Methods 0.000 description 1
- 230000000926 neurological effect Effects 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 230000003472 neutralizing effect Effects 0.000 description 1
- 230000009871 nonspecific binding Effects 0.000 description 1
- 239000007764 o/w emulsion Substances 0.000 description 1
- 229940049964 oleate Drugs 0.000 description 1
- ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 1
- 210000002475 olfactory pathway Anatomy 0.000 description 1
- 238000005457 optimization Methods 0.000 description 1
- 238000012261 overproduction Methods 0.000 description 1
- 239000012188 paraffin wax Substances 0.000 description 1
- 229920002866 paraformaldehyde Polymers 0.000 description 1
- 244000045947 parasite Species 0.000 description 1
- 239000013610 patient sample Substances 0.000 description 1
- 230000010412 perfusion Effects 0.000 description 1
- 210000001539 phagocyte Anatomy 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 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
- 150000004713 phosphodiesters Chemical class 0.000 description 1
- 230000004962 physiological condition Effects 0.000 description 1
- 238000006116 polymerization reaction Methods 0.000 description 1
- 239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 description 1
- 229940068968 polysorbate 80 Drugs 0.000 description 1
- 230000027317 positive regulation of immune response Effects 0.000 description 1
- 238000002600 positron emission tomography Methods 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000002335 preservative effect Effects 0.000 description 1
- 230000002062 proliferating effect Effects 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 230000012743 protein tagging Effects 0.000 description 1
- 230000002797 proteolythic effect Effects 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 238000012207 quantitative assay Methods 0.000 description 1
- 239000001397 quillaja saponaria molina bark Substances 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 231100000191 repeated dose toxicity Toxicity 0.000 description 1
- 238000012827 research and development Methods 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 238000012502 risk assessment Methods 0.000 description 1
- 239000000523 sample Substances 0.000 description 1
- 229930182490 saponin Natural products 0.000 description 1
- 150000007949 saponins Chemical class 0.000 description 1
- 238000004062 sedimentation Methods 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 238000012163 sequencing technique Methods 0.000 description 1
- 235000004400 serine Nutrition 0.000 description 1
- 238000012344 serological confirmation Methods 0.000 description 1
- 238000009589 serological test Methods 0.000 description 1
- 230000006403 short-term memory Effects 0.000 description 1
- 230000011664 signaling Effects 0.000 description 1
- 239000001509 sodium citrate Substances 0.000 description 1
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 238000010532 solid phase synthesis reaction Methods 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 210000000278 spinal cord Anatomy 0.000 description 1
- 230000002269 spontaneous effect Effects 0.000 description 1
- 229940031439 squalene Drugs 0.000 description 1
- TUHBEKDERLKLEC-UHFFFAOYSA-N squalene Natural products CC(=CCCC(=CCCC(=CCCC=C(/C)CCC=C(/C)CC=C(C)C)C)C)C TUHBEKDERLKLEC-UHFFFAOYSA-N 0.000 description 1
- 238000013112 stability test Methods 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 230000000087 stabilizing effect Effects 0.000 description 1
- 238000007619 statistical method Methods 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 210000000225 synapse Anatomy 0.000 description 1
- 230000000946 synaptic effect Effects 0.000 description 1
- 230000003977 synaptic function Effects 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 229950005628 tarenflurbil Drugs 0.000 description 1
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 238000010257 thawing Methods 0.000 description 1
- 238000011285 therapeutic regimen Methods 0.000 description 1
- 235000008521 threonine Nutrition 0.000 description 1
- 238000001269 time-of-flight mass spectrometry Methods 0.000 description 1
- 238000004448 titration Methods 0.000 description 1
- 229940044655 toll-like receptor 9 agonist Drugs 0.000 description 1
- 108091007466 transmembrane glycoproteins Proteins 0.000 description 1
- 238000011269 treatment regimen Methods 0.000 description 1
- 230000001960 triggered effect Effects 0.000 description 1
- GPRLSGONYQIRFK-MNYXATJNSA-N triton Chemical compound [3H+] GPRLSGONYQIRFK-MNYXATJNSA-N 0.000 description 1
- 235000002374 tyrosine Nutrition 0.000 description 1
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 1
- 210000004291 uterus Anatomy 0.000 description 1
- 239000012646 vaccine adjuvant Substances 0.000 description 1
- 229940124931 vaccine adjuvant Drugs 0.000 description 1
- 239000004474 valine Substances 0.000 description 1
- 108010084171 vanutide cridificar Proteins 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 239000000277 virosome Substances 0.000 description 1
- 230000031836 visual learning Effects 0.000 description 1
Images
Classifications
-
- 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
-
- 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
- A61K39/0005—Vertebrate antigens
-
- 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
- A61K39/0005—Vertebrate antigens
- A61K39/0007—Nervous system antigens; Prions
-
- 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
- A61K39/39—Medicinal preparations containing antigens or antibodies characterised by the immunostimulating additives, e.g. chemical adjuvants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
-
- 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
- C07K14/195—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from bacteria
- C07K14/34—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from bacteria from Corynebacterium (G)
-
- 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
- C07K14/705—Receptors; Cell surface antigens; Cell surface determinants
-
- 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
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
-
- 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
- C07K7/08—Linear peptides containing only normal peptide links having 12 to 20 amino acids
-
- 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
- C12N7/00—Viruses; Bacteriophages; Compositions thereof; Preparation or purification thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/54—Medicinal preparations containing antigens or antibodies characterised by the route of administration
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/555—Medicinal preparations containing antigens or antibodies characterised by a specific combination antigen/adjuvant
- A61K2039/55505—Inorganic adjuvants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/58—Medicinal preparations containing antigens or antibodies raising an immune response against a target which is not the antigen used for immunisation
-
- 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
- C12N2730/00—Reverse transcribing DNA viruses
- C12N2730/00011—Details
- C12N2730/10011—Hepadnaviridae
- C12N2730/10111—Orthohepadnavirus, e.g. hepatitis B virus
- C12N2730/10134—Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein
-
- 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
- C12N2760/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA ssRNA viruses negative-sense
- C12N2760/00011—Details
- C12N2760/18011—Paramyxoviridae
- C12N2760/18411—Morbillivirus, e.g. Measles virus, canine distemper
- C12N2760/18434—Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Genetics & Genomics (AREA)
- Biochemistry (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Biophysics (AREA)
- Molecular Biology (AREA)
- Immunology (AREA)
- Engineering & Computer Science (AREA)
- Biomedical Technology (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Zoology (AREA)
- Neurology (AREA)
- Microbiology (AREA)
- Epidemiology (AREA)
- Gastroenterology & Hepatology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Mycology (AREA)
- Toxicology (AREA)
- Neurosurgery (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Wood Science & Technology (AREA)
- Virology (AREA)
- Cell Biology (AREA)
- Dermatology (AREA)
- Biotechnology (AREA)
- General Engineering & Computer Science (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Hospice & Palliative Care (AREA)
- Psychiatry (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Peptides Or Proteins (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US13/843,883 US9102752B2 (en) | 2013-03-15 | 2013-03-15 | Peptide vaccine for prevention and immunotherapy of dementia of the Alzheimer's type |
| US13/843,883 | 2013-03-15 | ||
| PCT/US2013/037865 WO2014143087A1 (en) | 2013-03-15 | 2013-04-23 | Peptide vaccine for prevention and immunotherapy of dementia of the alzheimer's type |
Related Child Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| RU2019123453A Division RU2811687C2 (ru) | 2013-03-15 | 2013-04-23 | Пептидная вакцина для предупреждения и иммунотерапии деменции альцгеймеровского типа |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| RU2015142996A RU2015142996A (ru) | 2017-04-24 |
| RU2696566C2 true RU2696566C2 (ru) | 2019-08-05 |
Family
ID=51527985
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| RU2015142996A RU2696566C2 (ru) | 2013-03-15 | 2013-04-23 | Пептидная вакцина для предупреждения и иммунотерапии деменции альцгеймеровского типа |
Country Status (18)
| Country | Link |
|---|---|
| US (4) | US9102752B2 (enExample) |
| EP (1) | EP2968485B1 (enExample) |
| JP (3) | JP6208319B2 (enExample) |
| KR (2) | KR101926030B1 (enExample) |
| CN (2) | CN108794615A (enExample) |
| AU (3) | AU2013381835A1 (enExample) |
| BR (1) | BR112015023105A8 (enExample) |
| CA (1) | CA2906313A1 (enExample) |
| DK (1) | DK2968485T3 (enExample) |
| ES (1) | ES2800028T3 (enExample) |
| IL (2) | IL241597B (enExample) |
| MX (2) | MX364689B (enExample) |
| PT (1) | PT2968485T (enExample) |
| RU (1) | RU2696566C2 (enExample) |
| SG (1) | SG11201507669YA (enExample) |
| TW (1) | TWI561529B (enExample) |
| WO (1) | WO2014143087A1 (enExample) |
| ZA (2) | ZA201507526B (enExample) |
Families Citing this family (29)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US9102752B2 (en) * | 2013-03-15 | 2015-08-11 | United Biomedical, Inc. | Peptide vaccine for prevention and immunotherapy of dementia of the Alzheimer's type |
| WO2015157283A1 (en) * | 2014-04-07 | 2015-10-15 | Merganser Biotech Llc | Hepdicin mimetic peptides and uses thereof |
| EP3409130B1 (en) | 2016-01-27 | 2020-11-25 | Industry-Academic Cooperation Foundation Gyeongsang National University | Composition for preventing, alleviating or treating neurological disorders, containing, as active ingredient, novel peptide activating adiponectin receptors |
| EP3444344A4 (en) * | 2016-04-14 | 2020-02-19 | TAO Health Life Pharma Co., Ltd. | AMYLOSPHEROID TYPE STRUCTURE (ASPD) AND PHARMACEUTICAL COMPOSITION |
| CN106565847B (zh) * | 2016-10-26 | 2020-12-01 | 清华大学 | 化合物、多肽及其用途 |
| BR112019026707A2 (pt) * | 2017-06-16 | 2020-06-30 | United Neuroscience | imunógenos de peptídeo da extremidade c-terminal da proteína alfa-sinucleína e formulações dos mesmos para o tratamento de sinucleinopatias |
| EP3700558A4 (en) * | 2017-10-27 | 2022-03-09 | United Neuroscience | TAU PEPTIDE IMMUNOGENIC CONSTRUCTIONS |
| CA3085318A1 (en) * | 2017-12-11 | 2019-06-20 | Ubi Ip Holdings | Peptide immunogens of il-31 and formulations thereof for the treatment and/or prevention of atopic dermatitis |
| CN111565801B (zh) * | 2017-12-31 | 2023-11-10 | 美国联合生物医学公司 | 用于IgE介导过敏性疾病治疗的靶向膜结合型IgE的肽免疫原及其剂型 |
| WO2019160978A1 (en) * | 2018-02-13 | 2019-08-22 | Cedars-Sinai Medical Center | Methods and systems for identification and treatment of pathological neurodegeneration and age-related cognitive decline |
| US10828351B2 (en) | 2018-04-10 | 2020-11-10 | Ac Immune Sa | Anti-abeta therapeutic vaccines |
| CA3099296A1 (en) * | 2018-05-04 | 2019-11-07 | Ubi Ip Holdings | Artificial promiscuous t helper cell epitopes that facilitate targeted antibody production with limited t cell inflammatory response |
| TWI676635B (zh) * | 2018-06-15 | 2019-11-11 | 英屬開曼群島商聯腦科學公司 | α－突觸核蛋白Ｃ端胜肽免疫原及其用於治療突觸核蛋白疾病的配方 |
| CN113227116A (zh) * | 2018-10-01 | 2021-08-06 | 联脑科学公司 | 针对源自c9orf72二肽重复蛋白的肽免疫原构建体 |
| PE20212156A1 (es) * | 2018-12-19 | 2021-11-09 | United Biomedical Inc | Epitopos artificiales promiscuos de linfocitos t colaboradores como estimuladores inmunes para inmunogenos peptidicos inteticos |
| KR20210110842A (ko) * | 2018-12-28 | 2021-09-09 | 유나이티드 바이오메디칼 인크. | 인터루킨 6(il-6)을 표적화하는 펩타이드 면역원 및 il-6 조절장애에 의해 영향을 받는 질환의 면역요법을 위한 이의 제형 |
| AU2019418627A1 (en) * | 2018-12-31 | 2021-07-29 | United Neuroscience Limited | Peptide immunogens targeting Calcitonin Gene-Related Peptide (CGRP) and formulations thereof for prevention and treatment of migraine |
| CN110759987B (zh) * | 2019-10-29 | 2021-06-08 | 中国人民解放军军事科学院军事医学研究院 | 构象特异性的重组Aβ1-42样寡聚体抗原、其制备方法和应用 |
| WO2021150910A1 (en) * | 2020-01-23 | 2021-07-29 | Ubi Ip Holdings | Peptide immunogens targeting pituitary adenylate cyclase-activating peptide (pacap) and formulations thereof for prevention and treatment of migraine |
| KR20230016164A (ko) | 2020-03-10 | 2023-02-01 | 라이프아크 | 시클릭 펩티드 |
| CN116635517A (zh) | 2020-11-17 | 2023-08-22 | 伊利亚德生物技术有限公司 | 与神经退行性疾病相关的神经病理的治疗和预防 |
| WO2022197651A1 (en) * | 2021-03-16 | 2022-09-22 | Neurovision Imaging, Inc. | Biofluid-based methods for diagnosing alzheimer's disease-associated conditions |
| WO2023034324A2 (en) * | 2021-08-30 | 2023-03-09 | The Brigham And Women’S Hospital, Inc. | Methods and materials to treat neurodegenerative disease |
| US20250057928A1 (en) | 2021-12-08 | 2025-02-20 | Osaka University | Vaccine composition for inducing anti-il-23 antibody |
| EP4486387A1 (en) | 2022-02-28 | 2025-01-08 | Tridem Bioscience GmbH & Co KG | A conjugate consisting of or comprising at least a ss-glucan or a mannan |
| KR102530956B1 (ko) * | 2022-09-08 | 2023-05-11 | 주식회사 알츠코리아 | 아밀로이드 베타 유래 에피토프를 유효성분으로 포함하는 알츠하이머성 치매 백신 조성물 및 이의 용도 |
| CN115417915B (zh) * | 2022-11-03 | 2023-02-24 | 北京引正基因科技有限公司 | 多肽载体及其应用 |
| CN117122612B (zh) * | 2023-07-07 | 2024-08-27 | 河络新图生物科技(上海)有限公司 | 外周血单个核细胞在制备治疗/预防阿尔茨海默病的药物中的用途 |
| WO2025109524A1 (en) | 2023-11-22 | 2025-05-30 | Ac Immune Sa | Assays and methods for assessing vaccine preparations |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20040009897A1 (en) * | 2002-02-14 | 2004-01-15 | Sokoll Kenneth K. | Stabilized synthetic immunogen delivery system |
| US20040247612A1 (en) * | 2001-05-25 | 2004-12-09 | Wang Chang Yi | Immunogenic peptide composition for the prevention and treatment of Alzheimer's Disease |
| WO2008021296A2 (en) * | 2006-08-14 | 2008-02-21 | Thymon, L.L.C. | Compositions and methods for the treatment and prophylaxis of alzheimer's disease |
| US20110171243A1 (en) * | 2008-06-12 | 2011-07-14 | Affiris Ag | Compounds for treating amyloidoses |
Family Cites Families (25)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2980677B2 (ja) | 1990-04-27 | 1999-11-22 | マクマイケル，ジョン | 不正常なアミロイドβタンパク質と関連する中枢神経系疾患状態の治療のための方法および組成物 |
| US5753624A (en) | 1990-04-27 | 1998-05-19 | Milkhaus Laboratory, Inc. | Materials and methods for treatment of plaquing disease |
| WO1994017197A1 (fr) | 1993-01-25 | 1994-08-04 | Takeda Chemical Industries, Ltd. | ANTICORPS DIRIGE CONTRE LE β-AMYLOIDE OU UN DERIVE DE CE DERNIER ET SON UTILISATION |
| US5955317A (en) | 1993-01-25 | 1999-09-21 | Takeda Chemical Industries, Ltd. | Antibodies to β-amyloids or their derivatives and use thereof |
| US5759551A (en) | 1993-04-27 | 1998-06-02 | United Biomedical, Inc. | Immunogenic LHRH peptide constructs and synthetic universal immune stimulators for vaccines |
| WO1994028412A1 (en) | 1993-05-28 | 1994-12-08 | The Miriam Hospital | Composition and method for in vivo imaging of amyloid deposits |
| AU8091694A (en) | 1993-10-26 | 1995-05-22 | United Biomedical Inc. | Structured synthetic antigen libraries as diagnostics, vaccines and therapeutics |
| 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 |
| US7964192B1 (en) | 1997-12-02 | 2011-06-21 | Janssen Alzheimer Immunotherapy | Prevention and treatment of amyloidgenic disease |
| US6750324B1 (en) | 1997-12-02 | 2004-06-15 | Neuralab Limited | Humanized and chimeric N-terminal amyloid beta-antibodies |
| US6787523B1 (en) | 1997-12-02 | 2004-09-07 | Neuralab Limited | Prevention and treatment of amyloidogenic disease |
| US6025468A (en) | 1998-06-20 | 2000-02-15 | United Biomedical, Inc. | Artificial T helper cell epitopes as immune stimulators for synthetic peptide immunogens including immunogenic LHRH peptides |
| TWI229679B (en) | 1998-06-20 | 2005-03-21 | United Biomedical Inc | Artificial T helper cell epitopes as immune stimulators for synthetic peptide immunogens |
| AU784568B2 (en) | 1999-09-03 | 2006-05-04 | Ramot At Tel-Aviv University Ltd | Agents and compositions and methods utilizing same useful in diagnosing and/or treating or preventing plaque forming diseases |
| JP4804690B2 (ja) | 1999-12-08 | 2011-11-02 | インテレクト・ニューロサイエンシズ・インコーポレーテッド | 免疫原としてのキメラペプチド、それに対する抗体、およびキメラペプチドまたは抗体を用いた免疫法 |
| US20030083277A1 (en) * | 2000-02-24 | 2003-05-01 | Hersh Louis B. | Use of insulin degrading enzyme (IDE) for the treatment of alzheimer's disease in patients |
| US20030165481A1 (en) | 2000-02-24 | 2003-09-04 | Hersh Louis B. | Amyloid peptide inactivating enzyme to treat Alzheimer's disease |
| 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 |
| JP2007522119A (ja) * | 2004-01-28 | 2007-08-09 | キュリックス エーピーエス | アミロイド関連疾患用ワクチンとしてのアミロイドタンパク質のコンジュゲート |
| CA2638775A1 (en) * | 2006-02-22 | 2007-08-30 | Kabushiki Kaisha Hayashibara Seibutsu Kagaku Kenkyujo | Peptide vaccine for inducing production of anti-amyloid-.beta.-peptide antibody |
| CN101384279B (zh) * | 2006-02-24 | 2012-02-22 | 奇斯药制品公司 | 抗淀粉样蛋白免疫原性组合物、方法和用途 |
| WO2010035261A2 (en) * | 2008-09-29 | 2010-04-01 | Ben Gurion University Of The Negev Research And Development Authority | Amyloid beta-peptides and methods of use thereof |
| US9067981B1 (en) * | 2008-10-30 | 2015-06-30 | Janssen Sciences Ireland Uc | Hybrid amyloid-beta antibodies |
| WO2012056008A1 (en) * | 2010-10-28 | 2012-05-03 | Jonas Nilsson | Diagnosis and treatment of alzheimer's disease |
| US9102752B2 (en) * | 2013-03-15 | 2015-08-11 | United Biomedical, Inc. | Peptide vaccine for prevention and immunotherapy of dementia of the Alzheimer's type |
-
2013
- 2013-03-15 US US13/843,883 patent/US9102752B2/en active Active
- 2013-04-23 RU RU2015142996A patent/RU2696566C2/ru active IP Right Revival
- 2013-04-23 KR KR1020157029184A patent/KR101926030B1/ko active Active
- 2013-04-23 ES ES13878092T patent/ES2800028T3/es active Active
- 2013-04-23 KR KR1020187034866A patent/KR20180132962A/ko not_active Ceased
- 2013-04-23 DK DK13878092.9T patent/DK2968485T3/da active
- 2013-04-23 CN CN201810667175.6A patent/CN108794615A/zh active Pending
- 2013-04-23 SG SG11201507669YA patent/SG11201507669YA/en unknown
- 2013-04-23 CN CN201380076473.3A patent/CN105228644B/zh active Active
- 2013-04-23 CA CA2906313A patent/CA2906313A1/en not_active Abandoned
- 2013-04-23 JP JP2016500078A patent/JP6208319B2/ja active Active
- 2013-04-23 EP EP13878092.9A patent/EP2968485B1/en active Active
- 2013-04-23 WO PCT/US2013/037865 patent/WO2014143087A1/en not_active Ceased
- 2013-04-23 BR BR112015023105A patent/BR112015023105A8/pt not_active Application Discontinuation
- 2013-04-23 AU AU2013381835A patent/AU2013381835A1/en not_active Abandoned
- 2013-04-23 PT PT138780929T patent/PT2968485T/pt unknown
- 2013-04-23 MX MX2015013235A patent/MX364689B/es active IP Right Grant
-
2014
- 2014-03-14 TW TW103109373A patent/TWI561529B/zh active
-
2015
- 2015-08-11 US US14/824,075 patent/US20160068581A1/en not_active Abandoned
- 2015-09-15 MX MX2019005268A patent/MX2019005268A/es unknown
- 2015-09-16 IL IL241597A patent/IL241597B/en active IP Right Grant
- 2015-10-09 ZA ZA2015/07526A patent/ZA201507526B/en unknown
-
2017
- 2017-05-22 AU AU2017203425A patent/AU2017203425B2/en not_active Ceased
- 2017-06-07 JP JP2017112424A patent/JP6784646B2/ja active Active
-
2018
- 2018-04-19 US US15/957,798 patent/US20180244739A1/en not_active Abandoned
- 2018-12-31 US US16/237,531 patent/US20190194280A1/en not_active Abandoned
-
2019
- 2019-04-08 IL IL265910A patent/IL265910A/en unknown
- 2019-07-26 JP JP2019137534A patent/JP2019196397A/ja active Pending
- 2019-10-10 ZA ZA2019/06683A patent/ZA201906683B/en unknown
- 2019-10-11 AU AU2019246916A patent/AU2019246916A1/en not_active Abandoned
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20040247612A1 (en) * | 2001-05-25 | 2004-12-09 | Wang Chang Yi | Immunogenic peptide composition for the prevention and treatment of Alzheimer's Disease |
| US20040009897A1 (en) * | 2002-02-14 | 2004-01-15 | Sokoll Kenneth K. | Stabilized synthetic immunogen delivery system |
| WO2008021296A2 (en) * | 2006-08-14 | 2008-02-21 | Thymon, L.L.C. | Compositions and methods for the treatment and prophylaxis of alzheimer's disease |
| US20110171243A1 (en) * | 2008-06-12 | 2011-07-14 | Affiris Ag | Compounds for treating amyloidoses |
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| RU2696566C2 (ru) | Пептидная вакцина для предупреждения и иммунотерапии деменции альцгеймеровского типа | |
| KR20240150813A (ko) | 알파-시뉴클린 단백질의 c-말단부로부터의 펩티드 면역원 및 시뉴클레인병증 치료를 위한 그의 제형화 | |
| JP2024178274A (ja) | カルシトニン遺伝子関連ペプチド（ｃｇｒｐ）を標的とするペプチド免疫原ならびに片頭痛の治療及び予防のためのそれらの配合物 | |
| US20240400634A1 (en) | Peptide immunogens targeting islet amyloid polypeptide (iapp) and formulations thereof for prevention and treatment of disorders related to aggregated iapp | |
| TW202438516A (zh) | TAU及β類澱粉肽免疫原組合物及相關方法 | |
| US20220023401A1 (en) | Peptide vaccine for prevention and immunotherapy of dementia of the alzheimer's type | |
| RU2811687C2 (ru) | Пептидная вакцина для предупреждения и иммунотерапии деменции альцгеймеровского типа | |
| TWI609026B (zh) | 抑制與免疫治療阿茲海默型癡呆的胜肽疫苗 | |
| AU2021210391A1 (en) | Peptide immunogens targeting pituitary adenylate cyclase-activating peptide (PACAP) and formulations thereof for prevention and treatment of migraine | |
| HK1212600B (zh) | 預防與免疫治療阿爾茨海默型癡呆的肽疫苗 | |
| KR20240110105A (ko) | Ige 매개 알레르기 질환의 치료를 위한 막 결합 ige를 표적하는 펩티드 면역원 및 이의 제제 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MM4A | The patent is invalid due to non-payment of fees |
Effective date: 20200424 |
|
| NF4A | Reinstatement of patent |
Effective date: 20211122 |