TW202336034A - 靶向介白素-34之化合物及方法 - Google Patents
靶向介白素-34之化合物及方法 Download PDFInfo
- Publication number
- TW202336034A TW202336034A TW111140796A TW111140796A TW202336034A TW 202336034 A TW202336034 A TW 202336034A TW 111140796 A TW111140796 A TW 111140796A TW 111140796 A TW111140796 A TW 111140796A TW 202336034 A TW202336034 A TW 202336034A
- Authority
- TW
- Taiwan
- Prior art keywords
- human subject
- antibody
- tau
- brain
- disease
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims abstract description 238
- 102100033499 Interleukin-34 Human genes 0.000 title claims abstract description 116
- 101710181549 Interleukin-34 Proteins 0.000 title claims abstract description 112
- 150000001875 compounds Chemical class 0.000 title description 6
- 230000008685 targeting Effects 0.000 title description 5
- 208000024827 Alzheimer disease Diseases 0.000 claims abstract description 205
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 123
- 201000010099 disease Diseases 0.000 claims abstract description 112
- 230000001404 mediated effect Effects 0.000 claims abstract description 45
- 208000034799 Tauopathies Diseases 0.000 claims abstract description 11
- 239000000203 mixture Substances 0.000 claims abstract description 10
- 210000004556 brain Anatomy 0.000 claims description 133
- 238000011282 treatment Methods 0.000 claims description 72
- 210000004027 cell Anatomy 0.000 claims description 67
- 101150037123 APOE gene Proteins 0.000 claims description 51
- 102100029470 Apolipoprotein E Human genes 0.000 claims description 51
- 108700028369 Alleles Proteins 0.000 claims description 50
- 238000012879 PET imaging Methods 0.000 claims description 47
- 101000998132 Homo sapiens Interleukin-34 Proteins 0.000 claims description 46
- 102000002580 human interleukin-34 Human genes 0.000 claims description 42
- 208000037259 Amyloid Plaque Diseases 0.000 claims description 39
- 238000012636 positron electron tomography Methods 0.000 claims description 38
- 125000003275 alpha amino acid group Chemical group 0.000 claims description 37
- 230000027455 binding Effects 0.000 claims description 34
- 108010047041 Complementarity Determining Regions Proteins 0.000 claims description 31
- 238000002610 neuroimaging Methods 0.000 claims description 30
- 230000002123 temporal effect Effects 0.000 claims description 30
- 239000000427 antigen Substances 0.000 claims description 26
- 108091007433 antigens Proteins 0.000 claims description 26
- 102000036639 antigens Human genes 0.000 claims description 26
- 210000003478 temporal lobe Anatomy 0.000 claims description 26
- 108010090849 Amyloid beta-Peptides Proteins 0.000 claims description 24
- 102000013455 Amyloid beta-Peptides Human genes 0.000 claims description 24
- 230000002829 reductive effect Effects 0.000 claims description 24
- 208000008338 non-alcoholic fatty liver disease Diseases 0.000 claims description 23
- 206010039073 rheumatoid arthritis Diseases 0.000 claims description 23
- 208000022559 Inflammatory bowel disease Diseases 0.000 claims description 22
- 239000000090 biomarker Substances 0.000 claims description 20
- 230000006999 cognitive decline Effects 0.000 claims description 20
- 239000003814 drug Substances 0.000 claims description 20
- 230000001936 parietal effect Effects 0.000 claims description 20
- 210000000869 occipital lobe Anatomy 0.000 claims description 18
- 230000002265 prevention Effects 0.000 claims description 18
- 238000004519 manufacturing process Methods 0.000 claims description 17
- 230000009467 reduction Effects 0.000 claims description 17
- 239000012634 fragment Substances 0.000 claims description 16
- 210000001652 frontal lobe Anatomy 0.000 claims description 16
- 239000008194 pharmaceutical composition Substances 0.000 claims description 16
- 210000001175 cerebrospinal fluid Anatomy 0.000 claims description 15
- 210000001152 parietal lobe Anatomy 0.000 claims description 15
- 208000021386 Sjogren Syndrome Diseases 0.000 claims description 14
- 210000004369 blood Anatomy 0.000 claims description 14
- 239000008280 blood Substances 0.000 claims description 14
- 230000002490 cerebral effect Effects 0.000 claims description 14
- 206010012289 Dementia Diseases 0.000 claims description 13
- 108091028043 Nucleic acid sequence Proteins 0.000 claims description 13
- 210000002966 serum Anatomy 0.000 claims description 13
- 206010040047 Sepsis Diseases 0.000 claims description 12
- 229920002472 Starch Polymers 0.000 claims description 12
- 208000017169 kidney disease Diseases 0.000 claims description 12
- 235000019698 starch Nutrition 0.000 claims description 12
- 206010012438 Dermatitis atopic Diseases 0.000 claims description 11
- 201000008937 atopic dermatitis Diseases 0.000 claims description 11
- 210000002381 plasma Anatomy 0.000 claims description 11
- 239000008107 starch Substances 0.000 claims description 11
- 239000013598 vector Substances 0.000 claims description 11
- 150000007523 nucleic acids Chemical class 0.000 claims description 10
- 201000010374 Down Syndrome Diseases 0.000 claims description 9
- 208000011580 syndromic disease Diseases 0.000 claims description 9
- FWMNVWWHGCHHJJ-SKKKGAJSSA-N 4-amino-1-[(2r)-6-amino-2-[[(2r)-2-[[(2r)-2-[[(2r)-2-amino-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]hexanoyl]piperidine-4-carboxylic acid Chemical compound C([C@H](C(=O)N[C@H](CC(C)C)C(=O)N[C@H](CCCCN)C(=O)N1CCC(N)(CC1)C(O)=O)NC(=O)[C@H](N)CC=1C=CC=CC=1)C1=CC=CC=C1 FWMNVWWHGCHHJJ-SKKKGAJSSA-N 0.000 claims description 8
- 230000008717 functional decline Effects 0.000 claims description 8
- 238000002560 therapeutic procedure Methods 0.000 claims description 8
- 229940079593 drug Drugs 0.000 claims description 7
- 239000001963 growth medium Substances 0.000 claims description 7
- 210000001124 body fluid Anatomy 0.000 claims description 6
- 239000010839 body fluid Substances 0.000 claims description 6
- 238000009825 accumulation Methods 0.000 claims description 4
- 206010002026 amyotrophic lateral sclerosis Diseases 0.000 claims description 4
- 239000003085 diluting agent Substances 0.000 claims description 4
- 102000039446 nucleic acids Human genes 0.000 claims description 4
- 108020004707 nucleic acids Proteins 0.000 claims description 4
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 4
- 210000004962 mammalian cell Anatomy 0.000 claims description 3
- 230000006806 disease prevention Effects 0.000 claims description 2
- 206010044688 Trisomy 21 Diseases 0.000 claims 1
- 206010003246 arthritis Diseases 0.000 claims 1
- 238000012258 culturing Methods 0.000 claims 1
- 208000015122 neurodegenerative disease Diseases 0.000 abstract description 8
- 230000004770 neurodegeneration Effects 0.000 abstract description 7
- 108010026424 tau Proteins Proteins 0.000 description 179
- 102000013498 tau Proteins Human genes 0.000 description 179
- NFGXHKASABOEEW-UHFFFAOYSA-N 1-methylethyl 11-methoxy-3,7,11-trimethyl-2,4-dodecadienoate Chemical compound COC(C)(C)CCCC(C)CC=CC(C)=CC(=O)OC(C)C NFGXHKASABOEEW-UHFFFAOYSA-N 0.000 description 67
- 206010072599 Amyloid related imaging abnormalities Diseases 0.000 description 41
- 101000916644 Homo sapiens Macrophage colony-stimulating factor 1 receptor Proteins 0.000 description 40
- 102100028198 Macrophage colony-stimulating factor 1 receptor Human genes 0.000 description 29
- 239000013610 patient sample Substances 0.000 description 22
- 102000015696 Interleukins Human genes 0.000 description 21
- 108010063738 Interleukins Proteins 0.000 description 21
- 230000000926 neurological effect Effects 0.000 description 21
- 230000000694 effects Effects 0.000 description 20
- 230000004044 response Effects 0.000 description 19
- 208000010877 cognitive disease Diseases 0.000 description 18
- 239000004575 stone Substances 0.000 description 18
- 241000282553 Macaca Species 0.000 description 17
- 238000004458 analytical method Methods 0.000 description 17
- 238000003556 assay Methods 0.000 description 17
- 208000036110 Neuroinflammatory disease Diseases 0.000 description 15
- 150000001413 amino acids Chemical class 0.000 description 15
- 108090000765 processed proteins & peptides Proteins 0.000 description 15
- GETAAWDSFUCLBS-SJPDSGJFSA-N 7-(6-fluoranylpyridin-3-yl)-5h-pyrido[4,3-b]indole Chemical compound C1=NC([18F])=CC=C1C1=CC=C2C3=CN=CC=C3NC2=C1 GETAAWDSFUCLBS-SJPDSGJFSA-N 0.000 description 14
- 235000001014 amino acid Nutrition 0.000 description 14
- 229950002167 flortaucipir (18f) Drugs 0.000 description 14
- 230000000750 progressive effect Effects 0.000 description 14
- 108090000623 proteins and genes Proteins 0.000 description 14
- 238000012360 testing method Methods 0.000 description 14
- 230000001225 therapeutic effect Effects 0.000 description 14
- 229940024606 amino acid Drugs 0.000 description 13
- 210000003169 central nervous system Anatomy 0.000 description 13
- 238000005516 engineering process Methods 0.000 description 13
- 230000001965 increasing effect Effects 0.000 description 13
- 210000001616 monocyte Anatomy 0.000 description 12
- 102000004196 processed proteins & peptides Human genes 0.000 description 12
- 235000018102 proteins Nutrition 0.000 description 12
- 102000004169 proteins and genes Human genes 0.000 description 12
- 208000024891 symptom Diseases 0.000 description 12
- 238000006471 dimerization reaction Methods 0.000 description 11
- 102000052833 human CSF1R Human genes 0.000 description 11
- 229940027941 immunoglobulin g Drugs 0.000 description 11
- 210000002540 macrophage Anatomy 0.000 description 11
- 230000003959 neuroinflammation Effects 0.000 description 11
- 210000001519 tissue Anatomy 0.000 description 11
- 108020004414 DNA Proteins 0.000 description 10
- 208000035475 disorder Diseases 0.000 description 10
- 238000003384 imaging method Methods 0.000 description 10
- 102100035360 Cerebellar degeneration-related antigen 1 Human genes 0.000 description 9
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 9
- 206010030113 Oedema Diseases 0.000 description 9
- 108010064539 amyloid beta-protein (1-42) Proteins 0.000 description 9
- 230000007423 decrease Effects 0.000 description 9
- 238000001514 detection method Methods 0.000 description 9
- 230000001976 improved effect Effects 0.000 description 9
- 210000000274 microglia Anatomy 0.000 description 9
- 238000006386 neutralization reaction Methods 0.000 description 9
- 230000002411 adverse Effects 0.000 description 8
- 230000008901 benefit Effects 0.000 description 8
- 230000006870 function Effects 0.000 description 8
- 230000013595 glycosylation Effects 0.000 description 8
- 238000006206 glycosylation reaction Methods 0.000 description 8
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 7
- 102000004127 Cytokines Human genes 0.000 description 7
- 108090000695 Cytokines Proteins 0.000 description 7
- 102000004190 Enzymes Human genes 0.000 description 7
- 108090000790 Enzymes Proteins 0.000 description 7
- 101000946889 Homo sapiens Monocyte differentiation antigen CD14 Proteins 0.000 description 7
- 206010061218 Inflammation Diseases 0.000 description 7
- 102100035877 Monocyte differentiation antigen CD14 Human genes 0.000 description 7
- 229950001863 bapineuzumab Drugs 0.000 description 7
- 210000004443 dendritic cell Anatomy 0.000 description 7
- 238000011161 development Methods 0.000 description 7
- 230000018109 developmental process Effects 0.000 description 7
- 239000012091 fetal bovine serum Substances 0.000 description 7
- 238000000684 flow cytometry Methods 0.000 description 7
- 210000004602 germ cell Anatomy 0.000 description 7
- 230000005847 immunogenicity Effects 0.000 description 7
- 208000027866 inflammatory disease Diseases 0.000 description 7
- 230000002757 inflammatory effect Effects 0.000 description 7
- 230000004054 inflammatory process Effects 0.000 description 7
- 230000007388 microgliosis Effects 0.000 description 7
- 230000004048 modification Effects 0.000 description 7
- 238000012986 modification Methods 0.000 description 7
- 210000002682 neurofibrillary tangle Anatomy 0.000 description 7
- 230000007170 pathology Effects 0.000 description 7
- 229920001184 polypeptide Polymers 0.000 description 7
- 238000004445 quantitative analysis Methods 0.000 description 7
- 102000005962 receptors Human genes 0.000 description 7
- 108020003175 receptors Proteins 0.000 description 7
- 102000007665 Extracellular Signal-Regulated MAP Kinases Human genes 0.000 description 6
- 108010007457 Extracellular Signal-Regulated MAP Kinases Proteins 0.000 description 6
- 229950008995 aducanumab Drugs 0.000 description 6
- 230000008021 deposition Effects 0.000 description 6
- 239000012636 effector Substances 0.000 description 6
- 230000036541 health Effects 0.000 description 6
- 239000012216 imaging agent Substances 0.000 description 6
- 230000002401 inhibitory effect Effects 0.000 description 6
- 238000001990 intravenous administration Methods 0.000 description 6
- 230000003472 neutralizing effect Effects 0.000 description 6
- 125000003729 nucleotide group Chemical group 0.000 description 6
- 210000003819 peripheral blood mononuclear cell Anatomy 0.000 description 6
- 108091033319 polynucleotide Proteins 0.000 description 6
- 102000040430 polynucleotide Human genes 0.000 description 6
- 239000002157 polynucleotide Substances 0.000 description 6
- 239000013641 positive control Substances 0.000 description 6
- 238000013102 re-test Methods 0.000 description 6
- 239000000523 sample Substances 0.000 description 6
- 208000005145 Cerebral amyloid angiopathy Diseases 0.000 description 5
- 238000002965 ELISA Methods 0.000 description 5
- 108060001084 Luciferase Proteins 0.000 description 5
- 239000005089 Luciferase Substances 0.000 description 5
- 239000012979 RPMI medium Substances 0.000 description 5
- VREFGVBLTWBCJP-UHFFFAOYSA-N alprazolam Chemical compound C12=CC(Cl)=CC=C2N2C(C)=NN=C2CN=C1C1=CC=CC=C1 VREFGVBLTWBCJP-UHFFFAOYSA-N 0.000 description 5
- 239000000872 buffer Substances 0.000 description 5
- 238000004364 calculation method Methods 0.000 description 5
- 230000001413 cellular effect Effects 0.000 description 5
- 238000011284 combination treatment Methods 0.000 description 5
- 230000004069 differentiation Effects 0.000 description 5
- 238000002474 experimental method Methods 0.000 description 5
- 239000006166 lysate Substances 0.000 description 5
- 230000007246 mechanism Effects 0.000 description 5
- 239000002609 medium Substances 0.000 description 5
- 230000035772 mutation Effects 0.000 description 5
- 239000002773 nucleotide Chemical group 0.000 description 5
- 230000026731 phosphorylation Effects 0.000 description 5
- 238000006366 phosphorylation reaction Methods 0.000 description 5
- 238000002600 positron emission tomography Methods 0.000 description 5
- 230000008569 process Effects 0.000 description 5
- 230000000770 proinflammatory effect Effects 0.000 description 5
- VBUBYMVULIMEHR-UHFFFAOYSA-N propa-1,2-diene;prop-1-yne Chemical compound CC#C.C=C=C VBUBYMVULIMEHR-UHFFFAOYSA-N 0.000 description 5
- 230000002792 vascular Effects 0.000 description 5
- 208000031124 Dementia Alzheimer type Diseases 0.000 description 4
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 4
- 201000011240 Frontotemporal dementia Diseases 0.000 description 4
- 208000032843 Hemorrhage Diseases 0.000 description 4
- 101000891579 Homo sapiens Microtubule-associated protein tau Proteins 0.000 description 4
- 230000004988 N-glycosylation Effects 0.000 description 4
- 108010064397 amyloid beta-protein (1-40) Proteins 0.000 description 4
- 230000000903 blocking effect Effects 0.000 description 4
- 230000015556 catabolic process Effects 0.000 description 4
- 238000005119 centrifugation Methods 0.000 description 4
- 238000012512 characterization method Methods 0.000 description 4
- 230000001149 cognitive effect Effects 0.000 description 4
- 238000003745 diagnosis Methods 0.000 description 4
- 238000003205 genotyping method Methods 0.000 description 4
- 102000057063 human MAPT Human genes 0.000 description 4
- 230000028993 immune response Effects 0.000 description 4
- 238000001727 in vivo Methods 0.000 description 4
- 238000011534 incubation Methods 0.000 description 4
- 230000005764 inhibitory process Effects 0.000 description 4
- 230000003993 interaction Effects 0.000 description 4
- 230000007774 longterm Effects 0.000 description 4
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 4
- 230000001575 pathological effect Effects 0.000 description 4
- 102220329755 rs373637566 Human genes 0.000 description 4
- 235000000346 sugar Nutrition 0.000 description 4
- ABZLKHKQJHEPAX-UHFFFAOYSA-N tetramethylrhodamine Chemical compound C=12C=CC(N(C)C)=CC2=[O+]C2=CC(N(C)C)=CC=C2C=1C1=CC=CC=C1C([O-])=O ABZLKHKQJHEPAX-UHFFFAOYSA-N 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- 208000028185 Angioedema Diseases 0.000 description 3
- 208000028698 Cognitive impairment Diseases 0.000 description 3
- 102000053602 DNA Human genes 0.000 description 3
- 206010061818 Disease progression Diseases 0.000 description 3
- 208000014197 Fetal anticonvulsant syndrome Diseases 0.000 description 3
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Natural products NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 3
- 108060003951 Immunoglobulin Proteins 0.000 description 3
- 102000019149 MAP kinase activity proteins Human genes 0.000 description 3
- 108040008097 MAP kinase activity proteins Proteins 0.000 description 3
- 241001465754 Metazoa Species 0.000 description 3
- 102000003992 Peroxidases Human genes 0.000 description 3
- 108010029485 Protein Isoforms Proteins 0.000 description 3
- 102000001708 Protein Isoforms Human genes 0.000 description 3
- 108010090804 Streptavidin Proteins 0.000 description 3
- 230000024932 T cell mediated immunity Effects 0.000 description 3
- 210000001744 T-lymphocyte Anatomy 0.000 description 3
- AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 description 3
- 239000004473 Threonine Substances 0.000 description 3
- 230000005856 abnormality Effects 0.000 description 3
- 230000003213 activating effect Effects 0.000 description 3
- 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 3
- 230000010056 antibody-dependent cellular cytotoxicity Effects 0.000 description 3
- 238000013459 approach Methods 0.000 description 3
- 239000012472 biological sample Substances 0.000 description 3
- 239000000969 carrier Substances 0.000 description 3
- 210000001638 cerebellum Anatomy 0.000 description 3
- 238000006243 chemical reaction Methods 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
- 230000004540 complement-dependent cytotoxicity Effects 0.000 description 3
- 230000006378 damage Effects 0.000 description 3
- 238000009792 diffusion process Methods 0.000 description 3
- 239000000539 dimer Substances 0.000 description 3
- 230000005750 disease progression Effects 0.000 description 3
- 238000010494 dissociation reaction Methods 0.000 description 3
- 230000005593 dissociations Effects 0.000 description 3
- 239000003937 drug carrier Substances 0.000 description 3
- 238000011156 evaluation Methods 0.000 description 3
- 238000001943 fluorescence-activated cell sorting Methods 0.000 description 3
- 210000002865 immune cell Anatomy 0.000 description 3
- 102000018358 immunoglobulin Human genes 0.000 description 3
- 238000000338 in vitro Methods 0.000 description 3
- 229940047122 interleukins Drugs 0.000 description 3
- 230000003834 intracellular effect Effects 0.000 description 3
- 230000003902 lesion Effects 0.000 description 3
- 239000003446 ligand Substances 0.000 description 3
- 230000000670 limiting effect Effects 0.000 description 3
- 239000013642 negative control Substances 0.000 description 3
- 238000009206 nuclear medicine Methods 0.000 description 3
- 230000008506 pathogenesis Effects 0.000 description 3
- 108040007629 peroxidase activity proteins Proteins 0.000 description 3
- 230000003389 potentiating effect Effects 0.000 description 3
- 238000012545 processing Methods 0.000 description 3
- 238000012552 review Methods 0.000 description 3
- 230000019491 signal transduction Effects 0.000 description 3
- 230000011664 signaling Effects 0.000 description 3
- 241000894007 species Species 0.000 description 3
- 238000010186 staining Methods 0.000 description 3
- 238000006467 substitution reaction Methods 0.000 description 3
- 208000023366 superficial siderosis Diseases 0.000 description 3
- 238000002198 surface plasmon resonance spectroscopy Methods 0.000 description 3
- 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 2
- NCWZOASIUQVOFA-NSCUHMNNSA-N 4-[(e)-2-[4-[2-[2-(2-fluoroethoxy)ethoxy]ethoxy]phenyl]ethenyl]-n-methylaniline Chemical compound C1=CC(NC)=CC=C1\C=C\C1=CC=C(OCCOCCOCCF)C=C1 NCWZOASIUQVOFA-NSCUHMNNSA-N 0.000 description 2
- ODHCTXKNWHHXJC-VKHMYHEASA-N 5-oxo-L-proline Chemical compound OC(=O)[C@@H]1CCC(=O)N1 ODHCTXKNWHHXJC-VKHMYHEASA-N 0.000 description 2
- 102400000574 Amyloid-beta protein 42 Human genes 0.000 description 2
- 125000001433 C-terminal amino-acid group Chemical group 0.000 description 2
- 241000283707 Capra Species 0.000 description 2
- 208000004051 Chronic Traumatic Encephalopathy Diseases 0.000 description 2
- 208000011990 Corticobasal Degeneration Diseases 0.000 description 2
- SRBFZHDQGSBBOR-IOVATXLUSA-N D-xylopyranose Chemical compound O[C@@H]1COC(O)[C@H](O)[C@H]1O SRBFZHDQGSBBOR-IOVATXLUSA-N 0.000 description 2
- 208000006700 German syndrome Diseases 0.000 description 2
- 239000004471 Glycine Substances 0.000 description 2
- 102000004457 Granulocyte-Macrophage Colony-Stimulating Factor Human genes 0.000 description 2
- 108010017213 Granulocyte-Macrophage Colony-Stimulating Factor Proteins 0.000 description 2
- 108010017480 Hemosiderin Proteins 0.000 description 2
- 102000018713 Histocompatibility Antigens Class II Human genes 0.000 description 2
- 108010027412 Histocompatibility Antigens Class II Proteins 0.000 description 2
- 241000282412 Homo Species 0.000 description 2
- 241000521257 Hydrops Species 0.000 description 2
- 206010020880 Hypertrophy Diseases 0.000 description 2
- 108010021625 Immunoglobulin Fragments Proteins 0.000 description 2
- 102000008394 Immunoglobulin Fragments Human genes 0.000 description 2
- 108090000978 Interleukin-4 Proteins 0.000 description 2
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 2
- 101710105045 Lipoprotein E Proteins 0.000 description 2
- 239000004472 Lysine Substances 0.000 description 2
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 2
- 125000001429 N-terminal alpha-amino-acid group Chemical group 0.000 description 2
- 208000018737 Parkinson disease Diseases 0.000 description 2
- 208000000609 Pick Disease of the Brain Diseases 0.000 description 2
- ODHCTXKNWHHXJC-GSVOUGTGSA-N Pyroglutamic acid Natural products OC(=O)[C@H]1CCC(=O)N1 ODHCTXKNWHHXJC-GSVOUGTGSA-N 0.000 description 2
- PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- 230000005867 T cell response Effects 0.000 description 2
- 208000030886 Traumatic Brain injury Diseases 0.000 description 2
- 208000027418 Wounds and injury Diseases 0.000 description 2
- 230000002159 abnormal effect Effects 0.000 description 2
- 238000002835 absorbance Methods 0.000 description 2
- ODHCTXKNWHHXJC-UHFFFAOYSA-N acide pyroglutamique Natural products OC(=O)C1CCC(=O)N1 ODHCTXKNWHHXJC-UHFFFAOYSA-N 0.000 description 2
- 230000009471 action Effects 0.000 description 2
- 230000001154 acute effect Effects 0.000 description 2
- 238000007792 addition Methods 0.000 description 2
- 230000002776 aggregation Effects 0.000 description 2
- 238000004220 aggregation Methods 0.000 description 2
- 150000001412 amines Chemical class 0.000 description 2
- 230000006933 amyloid-beta aggregation Effects 0.000 description 2
- 230000003110 anti-inflammatory effect Effects 0.000 description 2
- 230000035578 autophosphorylation Effects 0.000 description 2
- 230000033228 biological regulation Effects 0.000 description 2
- 230000000740 bleeding effect Effects 0.000 description 2
- 230000008499 blood brain barrier function Effects 0.000 description 2
- 210000004204 blood vessel Anatomy 0.000 description 2
- 210000001218 blood-brain barrier Anatomy 0.000 description 2
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 2
- 210000000349 chromosome Anatomy 0.000 description 2
- 238000003759 clinical diagnosis Methods 0.000 description 2
- 230000019771 cognition Effects 0.000 description 2
- 230000000295 complement effect Effects 0.000 description 2
- 239000002299 complementary DNA Substances 0.000 description 2
- 238000007796 conventional method Methods 0.000 description 2
- 230000003013 cytotoxicity Effects 0.000 description 2
- 231100000135 cytotoxicity Toxicity 0.000 description 2
- 230000006735 deficit Effects 0.000 description 2
- 230000001934 delay Effects 0.000 description 2
- 208000017004 dementia pugilistica Diseases 0.000 description 2
- 230000001419 dependent effect Effects 0.000 description 2
- 238000011033 desalting Methods 0.000 description 2
- 238000010790 dilution Methods 0.000 description 2
- 239000012895 dilution Substances 0.000 description 2
- 229940121551 donanemab Drugs 0.000 description 2
- 230000008482 dysregulation Effects 0.000 description 2
- 230000002255 enzymatic effect Effects 0.000 description 2
- 238000003174 enzyme fragment complementation Methods 0.000 description 2
- 239000013604 expression vector Substances 0.000 description 2
- 210000000416 exudates and transudate Anatomy 0.000 description 2
- 239000012530 fluid Substances 0.000 description 2
- VVECGOCJFKTUAX-HUYCHCPVSA-N flutemetamol ((18)F) Chemical compound C1=C([18F])C(NC)=CC=C1C1=NC2=CC=C(O)C=C2S1 VVECGOCJFKTUAX-HUYCHCPVSA-N 0.000 description 2
- 235000019253 formic acid Nutrition 0.000 description 2
- 229950002508 gantenerumab Drugs 0.000 description 2
- 150000003278 haem Chemical class 0.000 description 2
- 210000001320 hippocampus Anatomy 0.000 description 2
- 230000013632 homeostatic process Effects 0.000 description 2
- 235000003642 hunger Nutrition 0.000 description 2
- 238000004191 hydrophobic interaction chromatography Methods 0.000 description 2
- 230000002163 immunogen Effects 0.000 description 2
- 229940072221 immunoglobulins Drugs 0.000 description 2
- 230000006872 improvement Effects 0.000 description 2
- 230000004968 inflammatory condition Effects 0.000 description 2
- 208000014674 injury Diseases 0.000 description 2
- 230000015788 innate immune response Effects 0.000 description 2
- 230000000968 intestinal effect Effects 0.000 description 2
- 238000004255 ion exchange chromatography Methods 0.000 description 2
- 210000000265 leukocyte Anatomy 0.000 description 2
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 2
- 238000007726 management method Methods 0.000 description 2
- 238000005259 measurement Methods 0.000 description 2
- 238000012544 monitoring process Methods 0.000 description 2
- 210000002569 neuron Anatomy 0.000 description 2
- 230000016273 neuron death Effects 0.000 description 2
- 230000002981 neuropathic effect Effects 0.000 description 2
- 210000004940 nucleus Anatomy 0.000 description 2
- 230000004983 pleiotropic effect Effects 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 201000002212 progressive supranuclear palsy Diseases 0.000 description 2
- 230000002062 proliferating effect Effects 0.000 description 2
- 230000035755 proliferation Effects 0.000 description 2
- 238000011002 quantification Methods 0.000 description 2
- DAEPDZWVDSPTHF-UHFFFAOYSA-M sodium pyruvate Chemical compound [Na+].CC(=O)C([O-])=O DAEPDZWVDSPTHF-UHFFFAOYSA-M 0.000 description 2
- 229950007874 solanezumab Drugs 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 210000000952 spleen Anatomy 0.000 description 2
- 230000006641 stabilisation Effects 0.000 description 2
- 238000011105 stabilization Methods 0.000 description 2
- 230000037351 starvation Effects 0.000 description 2
- 239000011550 stock solution Substances 0.000 description 2
- 238000007920 subcutaneous administration Methods 0.000 description 2
- 239000000758 substrate Substances 0.000 description 2
- 230000009044 synergistic interaction Effects 0.000 description 2
- 230000001988 toxicity Effects 0.000 description 2
- 231100000419 toxicity Toxicity 0.000 description 2
- 230000009529 traumatic brain injury Effects 0.000 description 2
- 238000005303 weighing Methods 0.000 description 2
- 210000004885 white matter Anatomy 0.000 description 2
- DGVVWUTYPXICAM-UHFFFAOYSA-N β‐Mercaptoethanol Chemical compound OCCS DGVVWUTYPXICAM-UHFFFAOYSA-N 0.000 description 2
- JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 1
- FWBHETKCLVMNFS-UHFFFAOYSA-N 4',6-Diamino-2-phenylindol Chemical compound C1=CC(C(=N)N)=CC=C1C1=CC2=CC=C(C(N)=N)C=C2N1 FWBHETKCLVMNFS-UHFFFAOYSA-N 0.000 description 1
- GETAAWDSFUCLBS-UHFFFAOYSA-N 7-(6-fluoropyridin-3-yl)-5h-pyrido[4,3-b]indole Chemical compound C1=NC(F)=CC=C1C1=CC=C2C3=CN=CC=C3NC2=C1 GETAAWDSFUCLBS-UHFFFAOYSA-N 0.000 description 1
- 208000030090 Acute Disease Diseases 0.000 description 1
- 208000000044 Amnesia Diseases 0.000 description 1
- 101710137189 Amyloid-beta A4 protein Proteins 0.000 description 1
- 102100022704 Amyloid-beta precursor protein Human genes 0.000 description 1
- 101710151993 Amyloid-beta precursor protein Proteins 0.000 description 1
- 102400000573 Amyloid-beta protein 40 Human genes 0.000 description 1
- 108010036280 Aquaporin 4 Proteins 0.000 description 1
- 102100037276 Aquaporin-4 Human genes 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
- 241000283690 Bos taurus Species 0.000 description 1
- 210000001266 CD8-positive T-lymphocyte Anatomy 0.000 description 1
- 102100035793 CD83 antigen Human genes 0.000 description 1
- 208000017667 Chronic Disease Diseases 0.000 description 1
- 206010067276 Cytotoxic oedema Diseases 0.000 description 1
- 102000016928 DNA-directed DNA polymerase Human genes 0.000 description 1
- 108010014303 DNA-directed DNA polymerase Proteins 0.000 description 1
- 108090000626 DNA-directed RNA polymerases Proteins 0.000 description 1
- 102000004163 DNA-directed RNA polymerases Human genes 0.000 description 1
- 102000016911 Deoxyribonucleases Human genes 0.000 description 1
- 108010053770 Deoxyribonucleases Proteins 0.000 description 1
- 201000004624 Dermatitis Diseases 0.000 description 1
- BWGNESOTFCXPMA-UHFFFAOYSA-N Dihydrogen disulfide Chemical compound SS BWGNESOTFCXPMA-UHFFFAOYSA-N 0.000 description 1
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 1
- 108010008177 Fd immunoglobulins Proteins 0.000 description 1
- 229920001917 Ficoll Polymers 0.000 description 1
- 239000007995 HEPES buffer Substances 0.000 description 1
- 102000006354 HLA-DR Antigens Human genes 0.000 description 1
- 108010058597 HLA-DR Antigens Proteins 0.000 description 1
- 206010019233 Headaches Diseases 0.000 description 1
- 101000946856 Homo sapiens CD83 antigen Proteins 0.000 description 1
- 101000914484 Homo sapiens T-lymphocyte activation antigen CD80 Proteins 0.000 description 1
- 208000023105 Huntington disease Diseases 0.000 description 1
- 108010067060 Immunoglobulin Variable Region Proteins 0.000 description 1
- 102000017727 Immunoglobulin Variable Region Human genes 0.000 description 1
- 206010062016 Immunosuppression Diseases 0.000 description 1
- 206010061216 Infarction Diseases 0.000 description 1
- 206010054996 Infusion site reaction Diseases 0.000 description 1
- 206010022095 Injection Site reaction Diseases 0.000 description 1
- 102100022297 Integrin alpha-X Human genes 0.000 description 1
- 102100037850 Interferon gamma Human genes 0.000 description 1
- 108010074328 Interferon-gamma Proteins 0.000 description 1
- 102000004889 Interleukin-6 Human genes 0.000 description 1
- 108090001005 Interleukin-6 Proteins 0.000 description 1
- 108090001007 Interleukin-8 Proteins 0.000 description 1
- 102000004890 Interleukin-8 Human genes 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
- DCXYFEDJOCDNAF-REOHCLBHSA-N L-asparagine Chemical compound OC(=O)[C@@H](N)CC(N)=O DCXYFEDJOCDNAF-REOHCLBHSA-N 0.000 description 1
- 108010046938 Macrophage Colony-Stimulating Factor Proteins 0.000 description 1
- 102100028123 Macrophage colony-stimulating factor 1 Human genes 0.000 description 1
- 101710150918 Macrophage colony-stimulating factor 1 receptor Proteins 0.000 description 1
- 208000026139 Memory disease Diseases 0.000 description 1
- 206010068871 Myotonic dystrophy Diseases 0.000 description 1
- 125000003047 N-acetyl group Chemical group 0.000 description 1
- 229930193140 Neomycin Natural products 0.000 description 1
- 206010029240 Neuritis Diseases 0.000 description 1
- 230000004989 O-glycosylation Effects 0.000 description 1
- 101710149632 Pectinesterase A Proteins 0.000 description 1
- 241000233805 Phoenix Species 0.000 description 1
- 102000004160 Phosphoric Monoester Hydrolases Human genes 0.000 description 1
- 108090000608 Phosphoric Monoester Hydrolases Proteins 0.000 description 1
- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 1
- 108010076504 Protein Sorting Signals Proteins 0.000 description 1
- 239000012083 RIPA buffer Substances 0.000 description 1
- 239000006146 Roswell Park Memorial Institute medium Substances 0.000 description 1
- 101000629318 Severe acute respiratory syndrome coronavirus 2 Spike glycoprotein Proteins 0.000 description 1
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 1
- 230000006052 T cell proliferation Effects 0.000 description 1
- 102100027222 T-lymphocyte activation antigen CD80 Human genes 0.000 description 1
- 239000004098 Tetracycline Substances 0.000 description 1
- 108010022394 Threonine synthase Proteins 0.000 description 1
- 208000007930 Type C Niemann-Pick Disease Diseases 0.000 description 1
- 101710159648 Uncharacterized protein Proteins 0.000 description 1
- 206010047571 Visual impairment Diseases 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 230000033289 adaptive immune response Effects 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 230000000996 additive effect Effects 0.000 description 1
- 230000007000 age related cognitive decline Effects 0.000 description 1
- 230000032683 aging Effects 0.000 description 1
- 235000004279 alanine Nutrition 0.000 description 1
- 230000001476 alcoholic effect Effects 0.000 description 1
- WQZGKKKJIJFFOK-PHYPRBDBSA-N alpha-D-galactose Chemical compound OC[C@H]1O[C@H](O)[C@H](O)[C@@H](O)[C@H]1O WQZGKKKJIJFFOK-PHYPRBDBSA-N 0.000 description 1
- 210000001132 alveolar macrophage Anatomy 0.000 description 1
- 125000000539 amino acid group Chemical group 0.000 description 1
- FEWOUVRMGWFWIH-ILZZQXMPSA-N amyloid-beta polypeptide 40 Chemical compound C([C@@H](C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@H](C(=O)NCC(=O)N[C@@H](CO)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCCN)C(=O)NCC(=O)N[C@@H](C)C(=O)N[C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](C(C)C)C(=O)NCC(=O)NCC(=O)N[C@@H](C(C)C)C(=O)N[C@@H](C(C)C)C(O)=O)[C@@H](C)CC)C(C)C)NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@@H](NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)CNC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CC(O)=O)C(C)C)C(C)C)C1=CC=CC=C1 FEWOUVRMGWFWIH-ILZZQXMPSA-N 0.000 description 1
- 230000003941 amyloidogenesis Effects 0.000 description 1
- 206010002022 amyloidosis Diseases 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 230000003215 anti-neuroinflammatory effect Effects 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- 230000005875 antibody response Effects 0.000 description 1
- 238000009175 antibody therapy Methods 0.000 description 1
- 210000000612 antigen-presenting cell Anatomy 0.000 description 1
- PYMYPHUHKUWMLA-UHFFFAOYSA-N arabinose Natural products OCC(O)C(O)C(O)C=O PYMYPHUHKUWMLA-UHFFFAOYSA-N 0.000 description 1
- 230000001174 ascending effect Effects 0.000 description 1
- 229960001230 asparagine Drugs 0.000 description 1
- 235000009582 asparagine Nutrition 0.000 description 1
- 125000000613 asparagine group Chemical group N[C@@H](CC(N)=O)C(=O)* 0.000 description 1
- 230000001363 autoimmune Effects 0.000 description 1
- 230000004888 barrier function Effects 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- SRBFZHDQGSBBOR-UHFFFAOYSA-N beta-D-Pyranose-Lyxose Natural products OC1COC(O)C(O)C1O SRBFZHDQGSBBOR-UHFFFAOYSA-N 0.000 description 1
- 230000003115 biocidal effect Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 230000006287 biotinylation Effects 0.000 description 1
- 238000007413 biotinylation Methods 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 210000004899 c-terminal region Anatomy 0.000 description 1
- 150000001720 carbohydrates Chemical group 0.000 description 1
- 238000000423 cell based assay Methods 0.000 description 1
- 230000022131 cell cycle Effects 0.000 description 1
- 230000032823 cell division Effects 0.000 description 1
- 230000004663 cell proliferation Effects 0.000 description 1
- 238000001516 cell proliferation assay Methods 0.000 description 1
- 210000003710 cerebral cortex Anatomy 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 238000011210 chromatographic step Methods 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 239000013611 chromosomal DNA Substances 0.000 description 1
- 208000037976 chronic inflammation Diseases 0.000 description 1
- 208000037893 chronic inflammatory disorder Diseases 0.000 description 1
- 238000003776 cleavage reaction Methods 0.000 description 1
- 238000002648 combination therapy Methods 0.000 description 1
- 230000009918 complex formation Effects 0.000 description 1
- 238000013170 computed tomography imaging Methods 0.000 description 1
- 230000021615 conjugation Effects 0.000 description 1
- 239000013068 control sample Substances 0.000 description 1
- 229950001954 crenezumab Drugs 0.000 description 1
- 238000002790 cross-validation Methods 0.000 description 1
- 230000000254 damaging effect Effects 0.000 description 1
- 238000012217 deletion Methods 0.000 description 1
- 230000037430 deletion Effects 0.000 description 1
- 238000000432 density-gradient centrifugation Methods 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 230000001687 destabilization Effects 0.000 description 1
- 239000000032 diagnostic agent Substances 0.000 description 1
- 229940039227 diagnostic agent Drugs 0.000 description 1
- 238000003748 differential diagnosis Methods 0.000 description 1
- 102000004419 dihydrofolate reductase Human genes 0.000 description 1
- 229940042399 direct acting antivirals protease inhibitors Drugs 0.000 description 1
- 230000009266 disease activity Effects 0.000 description 1
- 238000011979 disease modifying therapy Methods 0.000 description 1
- 231100000673 dose–response relationship Toxicity 0.000 description 1
- 238000004980 dosimetry Methods 0.000 description 1
- 230000009977 dual effect Effects 0.000 description 1
- 238000013399 early diagnosis Methods 0.000 description 1
- 208000037902 enteropathy Diseases 0.000 description 1
- 238000007824 enzymatic assay Methods 0.000 description 1
- 210000003743 erythrocyte Anatomy 0.000 description 1
- 239000003797 essential amino acid Substances 0.000 description 1
- 235000020776 essential amino acid Nutrition 0.000 description 1
- 230000007717 exclusion Effects 0.000 description 1
- 239000013613 expression plasmid Substances 0.000 description 1
- 208000010706 fatty liver disease Diseases 0.000 description 1
- 239000012467 final product Substances 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
- 229940113298 flutemetamol Drugs 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 238000013467 fragmentation Methods 0.000 description 1
- 238000006062 fragmentation reaction Methods 0.000 description 1
- 239000012737 fresh medium Substances 0.000 description 1
- 229930182830 galactose Natural products 0.000 description 1
- 102000054767 gene variant Human genes 0.000 description 1
- 230000002068 genetic effect Effects 0.000 description 1
- 229960002989 glutamic acid Drugs 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
- 210000004884 grey matter Anatomy 0.000 description 1
- 230000012010 growth Effects 0.000 description 1
- 231100000869 headache Toxicity 0.000 description 1
- 210000002216 heart Anatomy 0.000 description 1
- 210000003677 hemocyte Anatomy 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 210000003701 histiocyte Anatomy 0.000 description 1
- 239000000710 homodimer Substances 0.000 description 1
- 230000002209 hydrophobic effect Effects 0.000 description 1
- 125000002349 hydroxyamino group Chemical group [H]ON([H])[*] 0.000 description 1
- 229910052588 hydroxylapatite Inorganic materials 0.000 description 1
- 230000003100 immobilizing effect Effects 0.000 description 1
- 230000002519 immonomodulatory effect Effects 0.000 description 1
- 230000005934 immune activation Effects 0.000 description 1
- 230000005931 immune cell recruitment Effects 0.000 description 1
- 230000001900 immune effect Effects 0.000 description 1
- 230000006058 immune tolerance Effects 0.000 description 1
- 230000003053 immunization Effects 0.000 description 1
- 238000002649 immunization Methods 0.000 description 1
- 230000002998 immunogenetic effect Effects 0.000 description 1
- 230000001506 immunosuppresive effect Effects 0.000 description 1
- 238000009169 immunotherapy Methods 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 230000007574 infarction Effects 0.000 description 1
- 230000008595 infiltration Effects 0.000 description 1
- 238000001764 infiltration Methods 0.000 description 1
- 230000000977 initiatory effect Effects 0.000 description 1
- 239000013067 intermediate product Substances 0.000 description 1
- 208000028774 intestinal disease Diseases 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000005342 ion exchange Methods 0.000 description 1
- 238000005040 ion trap Methods 0.000 description 1
- 238000006317 isomerization reaction Methods 0.000 description 1
- 108010045069 keyhole-limpet hemocyanin Proteins 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 210000001865 kupffer cell Anatomy 0.000 description 1
- 238000002372 labelling Methods 0.000 description 1
- 210000001821 langerhans cell Anatomy 0.000 description 1
- 210000002429 large intestine Anatomy 0.000 description 1
- 230000002045 lasting effect Effects 0.000 description 1
- 229940055661 lecanemab Drugs 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 238000004020 luminiscence type Methods 0.000 description 1
- 125000003588 lysine group Chemical group [H]N([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 description 1
- 239000012139 lysis buffer Substances 0.000 description 1
- 239000003550 marker Substances 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 230000010534 mechanism of action Effects 0.000 description 1
- 229940126601 medicinal product Drugs 0.000 description 1
- 230000006984 memory degeneration Effects 0.000 description 1
- 230000006386 memory function Effects 0.000 description 1
- 208000023060 memory loss Diseases 0.000 description 1
- 230000006996 mental state Effects 0.000 description 1
- 239000011325 microbead Substances 0.000 description 1
- 230000006724 microglial activation Effects 0.000 description 1
- 238000000386 microscopy Methods 0.000 description 1
- 208000027061 mild cognitive impairment Diseases 0.000 description 1
- 239000003068 molecular probe Substances 0.000 description 1
- 238000002625 monoclonal antibody therapy Methods 0.000 description 1
- 239000000178 monomer Substances 0.000 description 1
- 238000002703 mutagenesis Methods 0.000 description 1
- 231100000350 mutagenesis Toxicity 0.000 description 1
- 238000010844 nanoflow liquid chromatography Methods 0.000 description 1
- 229960004927 neomycin Drugs 0.000 description 1
- 230000001613 neoplastic effect Effects 0.000 description 1
- 230000000626 neurodegenerative effect Effects 0.000 description 1
- 230000007426 neuronal cell dysfunction Effects 0.000 description 1
- 230000006764 neuronal dysfunction Effects 0.000 description 1
- 230000003955 neuronal function Effects 0.000 description 1
- 230000007121 neuropathological change Effects 0.000 description 1
- 108010087904 neutravidin Proteins 0.000 description 1
- 230000009871 nonspecific binding Effects 0.000 description 1
- 238000010899 nucleation Methods 0.000 description 1
- 235000015097 nutrients Nutrition 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 210000001672 ovary Anatomy 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- XYJRXVWERLGGKC-UHFFFAOYSA-D pentacalcium;hydroxide;triphosphate Chemical compound [OH-].[Ca+2].[Ca+2].[Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O XYJRXVWERLGGKC-UHFFFAOYSA-D 0.000 description 1
- 239000000137 peptide hydrolase inhibitor Substances 0.000 description 1
- 238000002823 phage display Methods 0.000 description 1
- 230000010287 polarization Effects 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 229950003486 ponezumab Drugs 0.000 description 1
- 230000004481 post-translational protein modification Effects 0.000 description 1
- 238000011533 pre-incubation Methods 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 239000000092 prognostic biomarker Substances 0.000 description 1
- 230000000069 prophylactic effect Effects 0.000 description 1
- 238000011321 prophylaxis Methods 0.000 description 1
- 210000002307 prostate Anatomy 0.000 description 1
- 238000000159 protein binding assay Methods 0.000 description 1
- 238000002818 protein evolution Methods 0.000 description 1
- 230000004850 protein–protein interaction Effects 0.000 description 1
- 208000020016 psychiatric disease Diseases 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 238000012207 quantitative assay Methods 0.000 description 1
- 239000012217 radiopharmaceutical Substances 0.000 description 1
- 229940121896 radiopharmaceutical Drugs 0.000 description 1
- 230000002799 radiopharmaceutical effect Effects 0.000 description 1
- 238000001525 receptor binding assay Methods 0.000 description 1
- 230000007115 recruitment Effects 0.000 description 1
- 230000008929 regeneration Effects 0.000 description 1
- 238000011069 regeneration method Methods 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 230000008439 repair process Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000004043 responsiveness Effects 0.000 description 1
- 238000012502 risk assessment Methods 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 238000010845 search algorithm Methods 0.000 description 1
- 230000003248 secreting effect Effects 0.000 description 1
- 239000013049 sediment Substances 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 230000001568 sexual effect Effects 0.000 description 1
- 230000036332 sexual response Effects 0.000 description 1
- 238000004904 shortening Methods 0.000 description 1
- 238000009097 single-agent therapy Methods 0.000 description 1
- 210000000813 small intestine Anatomy 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229940054269 sodium pyruvate Drugs 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 230000009870 specific binding Effects 0.000 description 1
- 230000002269 spontaneous effect Effects 0.000 description 1
- 238000012409 standard PCR amplification Methods 0.000 description 1
- 238000007619 statistical method Methods 0.000 description 1
- 210000000130 stem cell Anatomy 0.000 description 1
- 230000004936 stimulating effect Effects 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 229960005322 streptomycin Drugs 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- 230000002459 sustained effect Effects 0.000 description 1
- 230000008961 swelling Effects 0.000 description 1
- 238000002636 symptomatic treatment Methods 0.000 description 1
- 230000002195 synergetic effect Effects 0.000 description 1
- 210000002437 synoviocyte Anatomy 0.000 description 1
- 230000009897 systematic effect Effects 0.000 description 1
- 201000000596 systemic lupus erythematosus Diseases 0.000 description 1
- 238000004885 tandem mass spectrometry Methods 0.000 description 1
- 238000002626 targeted therapy Methods 0.000 description 1
- 150000003512 tertiary amines Chemical class 0.000 description 1
- 210000001550 testis Anatomy 0.000 description 1
- 229960002180 tetracycline Drugs 0.000 description 1
- 229930101283 tetracycline Natural products 0.000 description 1
- 235000019364 tetracycline Nutrition 0.000 description 1
- 150000003522 tetracyclines Chemical class 0.000 description 1
- 210000001541 thymus gland Anatomy 0.000 description 1
- 230000030968 tissue homeostasis Effects 0.000 description 1
- 238000004448 titration Methods 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 238000011269 treatment regimen Methods 0.000 description 1
- 208000033556 type C1 Niemann-Pick disease Diseases 0.000 description 1
- 230000003827 upregulation Effects 0.000 description 1
- 230000035899 viability Effects 0.000 description 1
- 230000003442 weekly effect Effects 0.000 description 1
- 239000012130 whole-cell lysate Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- C07K16/24—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against cytokines, lymphokines or interferons
- C07K16/244—Interleukins [IL]
-
- 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
- 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
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/68—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids
- G01N33/6863—Cytokines, i.e. immune system proteins modifying a biological response such as cell growth proliferation or differentiation, e.g. TNF, CNF, GM-CSF, lymphotoxin, MIF or their receptors
- G01N33/6869—Interleukin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/505—Medicinal preparations containing antigens or antibodies comprising antibodies
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/505—Medicinal preparations containing antigens or antibodies comprising antibodies
- A61K2039/507—Comprising a combination of two or more separate antibodies
-
- 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
- A61K2039/545—Medicinal preparations containing antigens or antibodies characterised by the dose, timing or administration schedule
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/20—Immunoglobulins specific features characterized by taxonomic origin
- C07K2317/21—Immunoglobulins specific features characterized by taxonomic origin from primates, e.g. man
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/30—Immunoglobulins specific features characterized by aspects of specificity or valency
- C07K2317/33—Crossreactivity, e.g. for species or epitope, or lack of said crossreactivity
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
- C07K2317/76—Antagonist effect on antigen, e.g. neutralization or inhibition of binding
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
- C07K2317/77—Internalization into the cell
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/90—Immunoglobulins specific features characterized by (pharmaco)kinetic aspects or by stability of the immunoglobulin
- C07K2317/92—Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/90—Immunoglobulins specific features characterized by (pharmaco)kinetic aspects or by stability of the immunoglobulin
- C07K2317/94—Stability, e.g. half-life, pH, temperature or enzyme-resistance
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2333/00—Assays involving biological materials from specific organisms or of a specific nature
- G01N2333/435—Assays involving biological materials from specific organisms or of a specific nature from animals; from humans
- G01N2333/52—Assays involving cytokines
- G01N2333/54—Interleukins [IL]
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Immunology (AREA)
- Molecular Biology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Biochemistry (AREA)
- Engineering & Computer Science (AREA)
- Biophysics (AREA)
- Genetics & Genomics (AREA)
- Biomedical Technology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Neurosurgery (AREA)
- Neurology (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Hospice & Palliative Care (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Psychiatry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Cell Biology (AREA)
- Urology & Nephrology (AREA)
- Hematology (AREA)
- Microbiology (AREA)
- Physics & Mathematics (AREA)
- Biotechnology (AREA)
- Analytical Chemistry (AREA)
- Pathology (AREA)
- General Physics & Mathematics (AREA)
- Food Science & Technology (AREA)
- Epidemiology (AREA)
- Mycology (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US202163273216P | 2021-10-29 | 2021-10-29 | |
| US63/273,216 | 2021-10-29 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| TW202336034A true TW202336034A (zh) | 2023-09-16 |
Family
ID=84367272
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| TW111140796A TW202336034A (zh) | 2021-10-29 | 2022-10-27 | 靶向介白素-34之化合物及方法 |
Country Status (18)
| Country | Link |
|---|---|
| US (2) | US11976114B2 (enExample) |
| EP (1) | EP4423127A1 (enExample) |
| JP (3) | JP7622019B2 (enExample) |
| KR (1) | KR20240099349A (enExample) |
| CN (1) | CN118475610A (enExample) |
| AR (1) | AR127484A1 (enExample) |
| AU (1) | AU2022376940A1 (enExample) |
| CA (1) | CA3236555A1 (enExample) |
| CL (1) | CL2024001303A1 (enExample) |
| CO (1) | CO2024005417A2 (enExample) |
| CR (1) | CR20240170A (enExample) |
| DO (1) | DOP2024000076A (enExample) |
| EC (1) | ECSP24032906A (enExample) |
| IL (1) | IL312380A (enExample) |
| MX (1) | MX2024005153A (enExample) |
| PE (1) | PE20241471A1 (enExample) |
| TW (1) | TW202336034A (enExample) |
| WO (1) | WO2023076995A1 (enExample) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR20240145486A (ko) * | 2022-02-03 | 2024-10-07 | 일라이 릴리 앤드 캄파니 | 알츠하이머병을 진단 및 치료하기 위한 국소 타우 영상화 |
Family Cites Families (18)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EA028427B1 (ru) | 2008-07-21 | 2017-11-30 | Пробиодруг Аг | АНТИТЕЛО, СВЯЗЫВАЮЩЕЕСЯ С Aβ-ПЕПТИДАМИ ИЛИ ИХ ВАРИАНТАМИ, КОМПОЗИЦИЯ, СОДЕРЖАЩАЯ ЭТО АНТИТЕЛО, И ЕГО ПРИМЕНЕНИЕ |
| US8795664B2 (en) | 2010-06-04 | 2014-08-05 | Georg-August-Universität Göttingen Stiftung Öffentlichen Rechts, Universitätsmedizin | Monoclonal antibodies targeting amyloid beta oligomers |
| WO2012019061A2 (en) * | 2010-08-05 | 2012-02-09 | Stem Centrx, Inc. | Novel effectors and methods of use |
| PT3042917T (pt) | 2010-08-12 | 2018-05-02 | Lilly Co Eli | Anticorpos do péptido beta amilóide anti-n3pglu e seus usos |
| US9499610B2 (en) | 2011-04-08 | 2016-11-22 | H. Lundbeck A/S | Antibodies specific to pyroglutamated Aβ |
| US9161968B2 (en) | 2011-04-08 | 2015-10-20 | The Board Of Trustees Of The Leland Stanford Junior University | Methods of neuroprotection involving macrophage colony stimulating factor receptor agonists |
| CN104093740B (zh) | 2012-02-06 | 2018-01-09 | 弗·哈夫曼-拉罗切有限公司 | 使用csf1r抑制剂的组合物和方法 |
| EP3174895A1 (en) | 2014-07-28 | 2017-06-07 | Nogra Pharma Limited | Methods and compositions for diagnosing and treating inflammatory bowel disorders |
| WO2016097420A1 (en) | 2014-12-19 | 2016-06-23 | Universite De Nantes | Anti il-34 antibodies |
| AU2016248946C1 (en) * | 2015-04-13 | 2024-10-17 | Pfizer Inc. | Therapeutic antibodies and their uses |
| JP2018516933A (ja) * | 2015-06-02 | 2018-06-28 | ジェネンテック， インコーポレイテッド | 抗ｉｌ−３４抗体を使用して神経学的疾患を治療するための組成物及び方法 |
| JOP20170004B1 (ar) | 2016-01-15 | 2022-09-15 | Lilly Co Eli | الأجسام المضادة لببتيد بيتا النشوي مضاد N3pGlu واستخداماته |
| TWI735600B (zh) * | 2016-07-01 | 2021-08-11 | 美商美國禮來大藥廠 | 抗－N3pGlu類澱粉β肽抗體及其用途 |
| CN109562167A (zh) * | 2016-08-09 | 2019-04-02 | 伊莱利利公司 | 联合治疗 |
| JOP20190247A1 (ar) | 2017-04-20 | 2019-10-20 | Lilly Co Eli | أجسام بيتا ببتيد النشوانية المضادة لـ N3pGlu واستخداماتها |
| CA3091810A1 (en) | 2018-03-02 | 2019-09-06 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Use of il-34 to treat retinal inflammation and neurodegeneration |
| BR112021021062A2 (pt) | 2019-05-31 | 2021-12-14 | Lilly Co Eli | Compostos e métodos que alvejam tau humano |
| TWI799840B (zh) * | 2020-04-30 | 2023-04-21 | 美商美國禮來大藥廠 | 靶向介白素-34之化合物及方法 |
-
2022
- 2022-10-27 US US18/050,227 patent/US11976114B2/en active Active
- 2022-10-27 CR CR20240170A patent/CR20240170A/es unknown
- 2022-10-27 CA CA3236555A patent/CA3236555A1/en active Pending
- 2022-10-27 IL IL312380A patent/IL312380A/en unknown
- 2022-10-27 TW TW111140796A patent/TW202336034A/zh unknown
- 2022-10-27 WO PCT/US2022/078776 patent/WO2023076995A1/en not_active Ceased
- 2022-10-27 KR KR1020247017337A patent/KR20240099349A/ko active Pending
- 2022-10-27 CN CN202280086946.7A patent/CN118475610A/zh active Pending
- 2022-10-27 JP JP2022172479A patent/JP7622019B2/ja active Active
- 2022-10-27 EP EP22814582.7A patent/EP4423127A1/en active Pending
- 2022-10-27 PE PE2024000938A patent/PE20241471A1/es unknown
- 2022-10-27 AR ARP220102931A patent/AR127484A1/es unknown
- 2022-10-27 AU AU2022376940A patent/AU2022376940A1/en active Pending
- 2022-10-27 MX MX2024005153A patent/MX2024005153A/es unknown
-
2024
- 2024-04-05 US US18/628,082 patent/US20240309082A1/en active Pending
- 2024-04-17 JP JP2024066552A patent/JP2024091777A/ja active Pending
- 2024-04-26 CL CL2024001303A patent/CL2024001303A1/es unknown
- 2024-04-26 DO DO2024000076A patent/DOP2024000076A/es unknown
- 2024-04-26 CO CONC2024/0005417A patent/CO2024005417A2/es unknown
- 2024-04-29 EC ECSENADI202432906A patent/ECSP24032906A/es unknown
-
2025
- 2025-01-15 JP JP2025005276A patent/JP2025063187A/ja active Pending
Also Published As
| Publication number | Publication date |
|---|---|
| CN118475610A (zh) | 2024-08-09 |
| KR20240099349A (ko) | 2024-06-28 |
| US20240309082A1 (en) | 2024-09-19 |
| JP2023067832A (ja) | 2023-05-16 |
| CL2024001303A1 (es) | 2024-08-30 |
| JP2025063187A (ja) | 2025-04-15 |
| IL312380A (en) | 2024-06-01 |
| WO2023076995A1 (en) | 2023-05-04 |
| US11976114B2 (en) | 2024-05-07 |
| CO2024005417A2 (es) | 2024-05-30 |
| JP2024091777A (ja) | 2024-07-05 |
| PE20241471A1 (es) | 2024-07-17 |
| AR127484A1 (es) | 2024-01-31 |
| US20230279094A1 (en) | 2023-09-07 |
| CA3236555A1 (en) | 2023-05-04 |
| AU2022376940A1 (en) | 2024-05-02 |
| DOP2024000076A (es) | 2024-06-16 |
| EP4423127A1 (en) | 2024-09-04 |
| ECSP24032906A (es) | 2024-05-31 |
| MX2024005153A (es) | 2024-05-13 |
| CR20240170A (es) | 2024-05-24 |
| JP7622019B2 (ja) | 2025-01-27 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US20230279098A1 (en) | Compounds and methods targeting interleukin-34 | |
| JP2025063187A (ja) | インターロイキン－３４を標的とする化合物及び方法 | |
| JP7780010B2 (ja) | インターロイキン－３４を標的とする化合物及び方法 | |
| TW202334211A (zh) | 靶向介白素-34之化合物及方法 | |
| TW202334210A (zh) | 靶向介白素-34之化合物及方法 | |
| BR112024008165B1 (pt) | Anticorpos direcionados à interleucina-34 e composições que os compreendem | |
| BR122025007149A2 (pt) | Anticorpos direcionados à interleucina-34 e composições que os compreendem | |
| BR122024012949A2 (pt) | Anticorpos direcionados à interleucina-34, composições que os compreendem, usos dos mesmos, combinações, ácidos nucleicos, vetores, células, processos para preparar anticorpos, e método para determinação no nível de il-34 humana em um fluido corporal |