TW202310841A - 用於治療多發性硬化症之ｌｏｕ０６４ - Google Patents
用於治療多發性硬化症之ｌｏｕ０６４ Download PDFInfo
- Publication number
- TW202310841A TW202310841A TW111133216A TW111133216A TW202310841A TW 202310841 A TW202310841 A TW 202310841A TW 111133216 A TW111133216 A TW 111133216A TW 111133216 A TW111133216 A TW 111133216A TW 202310841 A TW202310841 A TW 202310841A
- Authority
- TW
- Taiwan
- Prior art keywords
- lou064
- treatment
- administered
- multiple sclerosis
- btk
- Prior art date
Links
- 201000006417 multiple sclerosis Diseases 0.000 title claims abstract description 133
- CUABMPOJOBCXJI-UHFFFAOYSA-N remibrutinib Chemical compound CN(CCOc1c(N)ncnc1-c1cc(F)cc(NC(=O)c2ccc(cc2F)C2CC2)c1C)C(=O)C=C CUABMPOJOBCXJI-UHFFFAOYSA-N 0.000 claims abstract description 751
- 238000011282 treatment Methods 0.000 claims abstract description 167
- 150000003839 salts Chemical class 0.000 claims abstract description 11
- 210000003719 b-lymphocyte Anatomy 0.000 claims description 78
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 63
- UTNUDOFZCWSZMS-YFHOEESVSA-N teriflunomide Chemical compound C\C(O)=C(/C#N)C(=O)NC1=CC=C(C(F)(F)F)C=C1 UTNUDOFZCWSZMS-YFHOEESVSA-N 0.000 claims description 60
- 229960000331 teriflunomide Drugs 0.000 claims description 60
- 201000010099 disease Diseases 0.000 claims description 57
- 238000011979 disease modifying therapy Methods 0.000 claims description 48
- 230000003902 lesion Effects 0.000 claims description 45
- 102000014150 Interferons Human genes 0.000 claims description 42
- 108010050904 Interferons Proteins 0.000 claims description 42
- 229940079322 interferon Drugs 0.000 claims description 41
- 238000002560 therapeutic procedure Methods 0.000 claims description 36
- 208000007118 chronic progressive multiple sclerosis Diseases 0.000 claims description 32
- LDCRTTXIJACKKU-ONEGZZNKSA-N dimethyl fumarate Chemical compound COC(=O)\C=C\C(=O)OC LDCRTTXIJACKKU-ONEGZZNKSA-N 0.000 claims description 31
- 229960004419 dimethyl fumarate Drugs 0.000 claims description 31
- 239000003814 drug Substances 0.000 claims description 30
- 210000001744 T-lymphocyte Anatomy 0.000 claims description 28
- 201000008628 secondary progressive multiple sclerosis Diseases 0.000 claims description 27
- 238000000034 method Methods 0.000 claims description 25
- 229940079593 drug Drugs 0.000 claims description 24
- 230000002829 reductive effect Effects 0.000 claims description 21
- 108010072051 Glatiramer Acetate Proteins 0.000 claims description 19
- 208000007400 Relapsing-Remitting Multiple Sclerosis Diseases 0.000 claims description 19
- FHEAIOHRHQGZPC-KIWGSFCNSA-N acetic acid;(2s)-2-amino-3-(4-hydroxyphenyl)propanoic acid;(2s)-2-aminopentanedioic acid;(2s)-2-aminopropanoic acid;(2s)-2,6-diaminohexanoic acid Chemical compound CC(O)=O.C[C@H](N)C(O)=O.NCCCC[C@H](N)C(O)=O.OC(=O)[C@@H](N)CCC(O)=O.OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 FHEAIOHRHQGZPC-KIWGSFCNSA-N 0.000 claims description 19
- 229960003776 glatiramer acetate Drugs 0.000 claims description 19
- 208000015181 infectious disease Diseases 0.000 claims description 19
- 239000002245 particle Substances 0.000 claims description 18
- 206010071068 Clinically isolated syndrome Diseases 0.000 claims description 15
- 239000011230 binding agent Substances 0.000 claims description 13
- 239000003112 inhibitor Substances 0.000 claims description 13
- 239000004094 surface-active agent Substances 0.000 claims description 11
- 208000025721 COVID-19 Diseases 0.000 claims description 10
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 claims description 10
- 235000019333 sodium laurylsulphate Nutrition 0.000 claims description 10
- 102100036475 Alanine aminotransferase 1 Human genes 0.000 claims description 9
- 108010082126 Alanine transaminase Proteins 0.000 claims description 9
- 102100022005 B-lymphocyte antigen CD20 Human genes 0.000 claims description 8
- 101000897405 Homo sapiens B-lymphocyte antigen CD20 Proteins 0.000 claims description 8
- 229960000556 fingolimod Drugs 0.000 claims description 8
- KKGQTZUTZRNORY-UHFFFAOYSA-N fingolimod Chemical compound CCCCCCCCC1=CC=C(CCC(N)(CO)CO)C=C1 KKGQTZUTZRNORY-UHFFFAOYSA-N 0.000 claims description 8
- 102000003996 Interferon-beta Human genes 0.000 claims description 6
- 108090000467 Interferon-beta Proteins 0.000 claims description 6
- 102000004328 Cytochrome P-450 CYP3A Human genes 0.000 claims description 5
- 108010081668 Cytochrome P-450 CYP3A Proteins 0.000 claims description 5
- 238000001514 detection method Methods 0.000 claims description 5
- 238000004519 manufacturing process Methods 0.000 claims description 5
- 239000002105 nanoparticle Substances 0.000 claims description 5
- 239000004349 Polyvinylpyrrolidone-vinyl acetate copolymer Substances 0.000 claims description 4
- 230000001684 chronic effect Effects 0.000 claims description 4
- 239000000411 inducer Substances 0.000 claims description 4
- KKZJGLLVHKMTCM-UHFFFAOYSA-N mitoxantrone Chemical compound O=C1C2=C(O)C=CC(O)=C2C(=O)C2=C1C(NCCNCCO)=CC=C2NCCNCCO KKZJGLLVHKMTCM-UHFFFAOYSA-N 0.000 claims description 4
- 229960001156 mitoxantrone Drugs 0.000 claims description 4
- 229940127234 oral contraceptive Drugs 0.000 claims description 4
- 239000003539 oral contraceptive agent Substances 0.000 claims description 4
- 235000019448 polyvinylpyrrolidone-vinyl acetate copolymer Nutrition 0.000 claims description 4
- 238000009097 single-agent therapy Methods 0.000 claims description 4
- UAXOELSVPTZZQG-UHFFFAOYSA-N trimethyl acrylic acid Chemical compound CC(C)=C(C)C(O)=O UAXOELSVPTZZQG-UHFFFAOYSA-N 0.000 claims description 4
- 108010003415 Aspartate Aminotransferases Proteins 0.000 claims description 3
- 102000004625 Aspartate Aminotransferases Human genes 0.000 claims description 3
- 239000004367 Lipase Substances 0.000 claims description 3
- 102000004882 Lipase Human genes 0.000 claims description 3
- 108090001060 Lipase Proteins 0.000 claims description 3
- LPAUOXUZGSBGDU-STDDISTJSA-N chembl1096146 Chemical compound O=C1N(C=2C(=CC=CC=2)C)C(=N/CCC)/S\C1=C/C1=CC=C(OC[C@H](O)CO)C(Cl)=C1 LPAUOXUZGSBGDU-STDDISTJSA-N 0.000 claims description 3
- 239000003795 chemical substances by application Substances 0.000 claims description 3
- 235000019421 lipase Nutrition 0.000 claims description 3
- 229950009275 ponesimod Drugs 0.000 claims description 3
- -1 sinimod Chemical compound 0.000 claims description 3
- 238000002512 chemotherapy Methods 0.000 claims description 2
- 229940031462 non-live vaccine Drugs 0.000 claims description 2
- 239000008203 oral pharmaceutical composition Substances 0.000 claims 7
- 206010053395 Progressive multiple sclerosis Diseases 0.000 claims 1
- 229940047124 interferons Drugs 0.000 claims 1
- 108010029445 Agammaglobulinaemia Tyrosine Kinase Proteins 0.000 description 130
- 102000001714 Agammaglobulinaemia Tyrosine Kinase Human genes 0.000 description 130
- 210000004556 brain Anatomy 0.000 description 48
- 230000002354 daily effect Effects 0.000 description 48
- 210000004027 cell Anatomy 0.000 description 40
- 230000000694 effects Effects 0.000 description 39
- 239000012071 phase Substances 0.000 description 36
- 229940124291 BTK inhibitor Drugs 0.000 description 34
- 238000012360 testing method Methods 0.000 description 33
- 238000002595 magnetic resonance imaging Methods 0.000 description 30
- 230000009467 reduction Effects 0.000 description 30
- 241000699670 Mus sp. Species 0.000 description 29
- 208000024891 symptom Diseases 0.000 description 28
- 210000004369 blood Anatomy 0.000 description 27
- 239000008280 blood Substances 0.000 description 27
- 150000001875 compounds Chemical class 0.000 description 27
- 210000000952 spleen Anatomy 0.000 description 26
- 102000002233 Myelin-Oligodendrocyte Glycoprotein Human genes 0.000 description 25
- 108010000123 Myelin-Oligodendrocyte Glycoprotein Proteins 0.000 description 25
- 230000002411 adverse Effects 0.000 description 25
- 230000004044 response Effects 0.000 description 25
- 238000004458 analytical method Methods 0.000 description 24
- 239000000902 placebo Substances 0.000 description 21
- 229940068196 placebo Drugs 0.000 description 21
- 208000002193 Pain Diseases 0.000 description 20
- 230000008859 change Effects 0.000 description 20
- 238000002255 vaccination Methods 0.000 description 20
- 101001115699 Homo sapiens Myelin-oligodendrocyte glycoprotein Proteins 0.000 description 19
- 206010072757 chronic spontaneous urticaria Diseases 0.000 description 19
- 208000024376 chronic urticaria Diseases 0.000 description 19
- 102000047972 human MOG Human genes 0.000 description 19
- 210000001519 tissue Anatomy 0.000 description 19
- 230000006872 improvement Effects 0.000 description 18
- 210000001165 lymph node Anatomy 0.000 description 18
- 210000002966 serum Anatomy 0.000 description 18
- 229960005486 vaccine Drugs 0.000 description 17
- 102100023057 Neurofilament light polypeptide Human genes 0.000 description 16
- 210000003169 central nervous system Anatomy 0.000 description 16
- 229940027941 immunoglobulin g Drugs 0.000 description 16
- 230000005764 inhibitory process Effects 0.000 description 16
- 241001465754 Metazoa Species 0.000 description 14
- 241000700159 Rattus Species 0.000 description 14
- 101100077710 Rattus norvegicus Mog gene Proteins 0.000 description 14
- 230000006870 function Effects 0.000 description 14
- 239000008194 pharmaceutical composition Substances 0.000 description 13
- 206010061218 Inflammation Diseases 0.000 description 12
- 230000009266 disease activity Effects 0.000 description 12
- 230000004054 inflammatory process Effects 0.000 description 12
- 239000002775 capsule Substances 0.000 description 11
- 230000036541 health Effects 0.000 description 11
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 10
- 230000000069 prophylactic effect Effects 0.000 description 10
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 10
- 230000001419 dependent effect Effects 0.000 description 9
- 230000001976 improved effect Effects 0.000 description 9
- 230000002427 irreversible effect Effects 0.000 description 9
- 230000001717 pathogenic effect Effects 0.000 description 9
- 210000000278 spinal cord Anatomy 0.000 description 9
- 206010006895 Cachexia Diseases 0.000 description 8
- 206010019233 Headaches Diseases 0.000 description 8
- 101000979333 Homo sapiens Neurofilament light polypeptide Proteins 0.000 description 8
- 208000021386 Sjogren Syndrome Diseases 0.000 description 8
- 230000005713 exacerbation Effects 0.000 description 8
- 231100000869 headache Toxicity 0.000 description 8
- 230000007774 longterm Effects 0.000 description 8
- 108010090677 neurofilament protein L Proteins 0.000 description 8
- 230000003389 potentiating effect Effects 0.000 description 8
- 206010063401 primary progressive multiple sclerosis Diseases 0.000 description 8
- 108090000623 proteins and genes Proteins 0.000 description 8
- 238000011160 research Methods 0.000 description 8
- 108091008875 B cell receptors Proteins 0.000 description 7
- 229930105110 Cyclosporin A Natural products 0.000 description 7
- PMATZTZNYRCHOR-CGLBZJNRSA-N Cyclosporin A Chemical compound CC[C@@H]1NC(=O)[C@H]([C@H](O)[C@H](C)C\C=C\C)N(C)C(=O)[C@H](C(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)N(C)C(=O)CN(C)C1=O PMATZTZNYRCHOR-CGLBZJNRSA-N 0.000 description 7
- 108010036949 Cyclosporine Proteins 0.000 description 7
- NCDNCNXCDXHOMX-UHFFFAOYSA-N Ritonavir Natural products C=1C=CC=CC=1CC(NC(=O)OCC=1SC=NC=1)C(O)CC(CC=1C=CC=CC=1)NC(=O)C(C(C)C)NC(=O)N(C)CC1=CSC(C(C)C)=N1 NCDNCNXCDXHOMX-UHFFFAOYSA-N 0.000 description 7
- 230000005875 antibody response Effects 0.000 description 7
- 230000037396 body weight Effects 0.000 description 7
- 230000007423 decrease Effects 0.000 description 7
- 206010016256 fatigue Diseases 0.000 description 7
- 238000001727 in vivo Methods 0.000 description 7
- 206010022000 influenza Diseases 0.000 description 7
- 230000002452 interceptive effect Effects 0.000 description 7
- 210000000274 microglia Anatomy 0.000 description 7
- 239000000203 mixture Substances 0.000 description 7
- 210000000056 organ Anatomy 0.000 description 7
- 230000000750 progressive effect Effects 0.000 description 7
- 230000035755 proliferation Effects 0.000 description 7
- 229960000311 ritonavir Drugs 0.000 description 7
- NCDNCNXCDXHOMX-XGKFQTDJSA-N ritonavir Chemical compound N([C@@H](C(C)C)C(=O)N[C@H](C[C@H](O)[C@H](CC=1C=CC=CC=1)NC(=O)OCC=1SC=NC=1)CC=1C=CC=CC=1)C(=O)N(C)CC1=CSC(C(C)C)=N1 NCDNCNXCDXHOMX-XGKFQTDJSA-N 0.000 description 7
- KOEUOFPEZFUWRF-LJQANCHMSA-N 4-amino-3-(4-phenoxyphenyl)-1-[(3R)-1-prop-2-enoylpiperidin-3-yl]imidazo[4,5-c]pyridin-2-one Chemical compound C(C=C)(=O)N1C[C@@H](CCC1)N1C(N(C=2C(=NC=CC=21)N)C1=CC=C(C=C1)OC1=CC=CC=C1)=O KOEUOFPEZFUWRF-LJQANCHMSA-N 0.000 description 6
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
- 206010061818 Disease progression Diseases 0.000 description 6
- 108060003951 Immunoglobulin Proteins 0.000 description 6
- VREFGVBLTWBCJP-UHFFFAOYSA-N alprazolam Chemical compound C12=CC(Cl)=CC=C2N2C(C)=NN=C2CN=C1C1=CC=CC=C1 VREFGVBLTWBCJP-UHFFFAOYSA-N 0.000 description 6
- 238000000540 analysis of variance Methods 0.000 description 6
- 239000000427 antigen Substances 0.000 description 6
- 102000036639 antigens Human genes 0.000 description 6
- 108091007433 antigens Proteins 0.000 description 6
- 210000001175 cerebrospinal fluid Anatomy 0.000 description 6
- 230000003247 decreasing effect Effects 0.000 description 6
- 230000005750 disease progression Effects 0.000 description 6
- 208000035475 disorder Diseases 0.000 description 6
- 230000003203 everyday effect Effects 0.000 description 6
- 102000018358 immunoglobulin Human genes 0.000 description 6
- 230000001965 increasing effect Effects 0.000 description 6
- 230000000977 initiatory effect Effects 0.000 description 6
- 230000002045 lasting effect Effects 0.000 description 6
- 230000001404 mediated effect Effects 0.000 description 6
- 230000035699 permeability Effects 0.000 description 6
- 238000012216 screening Methods 0.000 description 6
- 230000001225 therapeutic effect Effects 0.000 description 6
- 229940073613 tolebrutinib Drugs 0.000 description 6
- 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 5
- 241000282412 Homo Species 0.000 description 5
- 239000002177 L01XE27 - Ibrutinib Substances 0.000 description 5
- 241000699666 Mus <mouse, genus> Species 0.000 description 5
- 230000030741 antigen processing and presentation Effects 0.000 description 5
- 239000011248 coating agent Substances 0.000 description 5
- 238000000576 coating method Methods 0.000 description 5
- 230000019771 cognition Effects 0.000 description 5
- 230000006378 damage Effects 0.000 description 5
- 235000019253 formic acid Nutrition 0.000 description 5
- 229960001507 ibrutinib Drugs 0.000 description 5
- XYFPWWZEPKGCCK-GOSISDBHSA-N ibrutinib Chemical compound C1=2C(N)=NC=NC=2N([C@H]2CN(CCC2)C(=O)C=C)N=C1C(C=C1)=CC=C1OC1=CC=CC=C1 XYFPWWZEPKGCCK-GOSISDBHSA-N 0.000 description 5
- 238000011068 loading method Methods 0.000 description 5
- 238000012423 maintenance Methods 0.000 description 5
- 238000005259 measurement Methods 0.000 description 5
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 5
- 230000037452 priming Effects 0.000 description 5
- 238000012545 processing Methods 0.000 description 5
- 229940124740 quadrivalent influenza vaccine Drugs 0.000 description 5
- 230000002459 sustained effect Effects 0.000 description 5
- 238000011269 treatment regimen Methods 0.000 description 5
- 230000009184 walking Effects 0.000 description 5
- 208000032116 Autoimmune Experimental Encephalomyelitis Diseases 0.000 description 4
- 208000009011 Cytochrome P-450 CYP3A Inhibitors Diseases 0.000 description 4
- 102000004190 Enzymes Human genes 0.000 description 4
- 108090000790 Enzymes Proteins 0.000 description 4
- 208000011688 Generalised anxiety disease Diseases 0.000 description 4
- 206010062016 Immunosuppression Diseases 0.000 description 4
- 102000006386 Myelin Proteins Human genes 0.000 description 4
- 108010083674 Myelin Proteins Proteins 0.000 description 4
- 206010060860 Neurological symptom Diseases 0.000 description 4
- 206010033799 Paralysis Diseases 0.000 description 4
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 4
- 239000000853 adhesive Substances 0.000 description 4
- 230000001070 adhesive effect Effects 0.000 description 4
- 230000002776 aggregation Effects 0.000 description 4
- 238000004220 aggregation Methods 0.000 description 4
- 229960000548 alemtuzumab Drugs 0.000 description 4
- 238000003556 assay Methods 0.000 description 4
- 239000000090 biomarker Substances 0.000 description 4
- 229920001531 copovidone Polymers 0.000 description 4
- 210000000877 corpus callosum Anatomy 0.000 description 4
- 230000003111 delayed effect Effects 0.000 description 4
- 238000002296 dynamic light scattering Methods 0.000 description 4
- 238000011156 evaluation Methods 0.000 description 4
- 208000012997 experimental autoimmune encephalomyelitis Diseases 0.000 description 4
- 230000004438 eyesight Effects 0.000 description 4
- 230000002349 favourable effect Effects 0.000 description 4
- 239000007888 film coating Substances 0.000 description 4
- 238000009501 film coating Methods 0.000 description 4
- 208000029364 generalized anxiety disease Diseases 0.000 description 4
- 238000002649 immunization Methods 0.000 description 4
- 230000003053 immunization Effects 0.000 description 4
- 230000001506 immunosuppresive effect Effects 0.000 description 4
- 230000002757 inflammatory effect Effects 0.000 description 4
- 230000002401 inhibitory effect Effects 0.000 description 4
- 150000002500 ions Chemical class 0.000 description 4
- 238000011866 long-term treatment Methods 0.000 description 4
- 210000002540 macrophage Anatomy 0.000 description 4
- 230000036651 mood Effects 0.000 description 4
- 201000009240 nasopharyngitis Diseases 0.000 description 4
- 229960005027 natalizumab Drugs 0.000 description 4
- 230000003959 neuroinflammation Effects 0.000 description 4
- 230000007971 neurological deficit Effects 0.000 description 4
- 230000000926 neurological effect Effects 0.000 description 4
- 230000007658 neurological function Effects 0.000 description 4
- 238000012316 non-parametric ANOVA Methods 0.000 description 4
- 230000000144 pharmacologic effect Effects 0.000 description 4
- 238000012552 review Methods 0.000 description 4
- 229960004641 rituximab Drugs 0.000 description 4
- 238000012174 single-cell RNA sequencing Methods 0.000 description 4
- 208000017520 skin disease Diseases 0.000 description 4
- 210000004988 splenocyte Anatomy 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- 230000008685 targeting Effects 0.000 description 4
- 210000001364 upper extremity Anatomy 0.000 description 4
- RNOAOAWBMHREKO-QFIPXVFZSA-N (7S)-2-(4-phenoxyphenyl)-7-(1-prop-2-enoylpiperidin-4-yl)-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrimidine-3-carboxamide Chemical compound C(C=C)(=O)N1CCC(CC1)[C@@H]1CCNC=2N1N=C(C=2C(=O)N)C1=CC=C(C=C1)OC1=CC=CC=C1 RNOAOAWBMHREKO-QFIPXVFZSA-N 0.000 description 3
- 206010002869 Anxiety symptoms Diseases 0.000 description 3
- 229940125814 BTK kinase inhibitor Drugs 0.000 description 3
- 208000031648 Body Weight Changes Diseases 0.000 description 3
- 201000010717 Bruton-type agammaglobulinemia Diseases 0.000 description 3
- 206010010904 Convulsion Diseases 0.000 description 3
- 102000004127 Cytokines Human genes 0.000 description 3
- 108090000695 Cytokines Proteins 0.000 description 3
- 208000016192 Demyelinating disease Diseases 0.000 description 3
- 229910052688 Gadolinium Inorganic materials 0.000 description 3
- 208000032843 Hemorrhage Diseases 0.000 description 3
- 206010020751 Hypersensitivity Diseases 0.000 description 3
- 206010051792 Infusion related reaction Diseases 0.000 description 3
- 208000001344 Macular Edema Diseases 0.000 description 3
- 206010025415 Macular oedema Diseases 0.000 description 3
- 208000025205 Mantle-Cell Lymphoma Diseases 0.000 description 3
- 208000010428 Muscle Weakness Diseases 0.000 description 3
- 206010028372 Muscular weakness Diseases 0.000 description 3
- 206010028980 Neoplasm Diseases 0.000 description 3
- 208000012902 Nervous system disease Diseases 0.000 description 3
- 208000036110 Neuroinflammatory disease Diseases 0.000 description 3
- 108091000080 Phosphotransferase Proteins 0.000 description 3
- 239000002202 Polyethylene glycol Substances 0.000 description 3
- 241000288906 Primates Species 0.000 description 3
- 208000035415 Reinfection Diseases 0.000 description 3
- 208000019498 Skin and subcutaneous tissue disease Diseases 0.000 description 3
- GWEVSGVZZGPLCZ-UHFFFAOYSA-N Titan oxide Chemical compound O=[Ti]=O GWEVSGVZZGPLCZ-UHFFFAOYSA-N 0.000 description 3
- 208000016349 X-linked agammaglobulinemia Diseases 0.000 description 3
- 238000009825 accumulation Methods 0.000 description 3
- 210000000612 antigen-presenting cell Anatomy 0.000 description 3
- 230000008901 benefit Effects 0.000 description 3
- 230000033228 biological regulation Effects 0.000 description 3
- 230000008499 blood brain barrier function Effects 0.000 description 3
- 210000001218 blood-brain barrier Anatomy 0.000 description 3
- 230000004579 body weight change Effects 0.000 description 3
- 230000003915 cell function Effects 0.000 description 3
- 230000011748 cell maturation Effects 0.000 description 3
- 230000002596 correlated effect Effects 0.000 description 3
- 230000009089 cytolysis Effects 0.000 description 3
- 230000034994 death Effects 0.000 description 3
- 231100000517 death Toxicity 0.000 description 3
- 230000003210 demyelinating effect Effects 0.000 description 3
- 210000004443 dendritic cell Anatomy 0.000 description 3
- 230000000779 depleting effect Effects 0.000 description 3
- 238000013461 design Methods 0.000 description 3
- 230000006866 deterioration Effects 0.000 description 3
- 238000011161 development Methods 0.000 description 3
- 230000018109 developmental process Effects 0.000 description 3
- 230000035487 diastolic blood pressure Effects 0.000 description 3
- 208000002173 dizziness Diseases 0.000 description 3
- 231100000673 dose–response relationship Toxicity 0.000 description 3
- 238000001647 drug administration Methods 0.000 description 3
- 239000007941 film coated tablet Substances 0.000 description 3
- UIWYJDYFSGRHKR-UHFFFAOYSA-N gadolinium atom Chemical compound [Gd] UIWYJDYFSGRHKR-UHFFFAOYSA-N 0.000 description 3
- 239000000185 hemagglutinin Substances 0.000 description 3
- 238000004128 high performance liquid chromatography Methods 0.000 description 3
- 210000002865 immune cell Anatomy 0.000 description 3
- 230000028993 immune response Effects 0.000 description 3
- 229940072221 immunoglobulins Drugs 0.000 description 3
- 210000004698 lymphocyte Anatomy 0.000 description 3
- 201000010230 macular retinal edema Diseases 0.000 description 3
- 230000035800 maturation Effects 0.000 description 3
- 230000007246 mechanism Effects 0.000 description 3
- 210000005012 myelin Anatomy 0.000 description 3
- 210000000066 myeloid cell Anatomy 0.000 description 3
- 210000002569 neuron Anatomy 0.000 description 3
- 239000002547 new drug Substances 0.000 description 3
- 229950005751 ocrelizumab Drugs 0.000 description 3
- 229960002450 ofatumumab Drugs 0.000 description 3
- 230000002093 peripheral effect Effects 0.000 description 3
- 102000020233 phosphotransferase Human genes 0.000 description 3
- 229920001223 polyethylene glycol Polymers 0.000 description 3
- 210000001948 pro-b lymphocyte Anatomy 0.000 description 3
- 230000002035 prolonged effect Effects 0.000 description 3
- 239000008213 purified water Substances 0.000 description 3
- 238000003908 quality control method Methods 0.000 description 3
- 238000011084 recovery Methods 0.000 description 3
- 206010039073 rheumatoid arthritis Diseases 0.000 description 3
- 230000011664 signaling Effects 0.000 description 3
- 238000004088 simulation Methods 0.000 description 3
- 201000000596 systemic lupus erythematosus Diseases 0.000 description 3
- 230000035488 systolic blood pressure Effects 0.000 description 3
- 208000016261 weight loss Diseases 0.000 description 3
- 230000004580 weight loss Effects 0.000 description 3
- VJPPLCNBDLZIFG-ZDUSSCGKSA-N 4-[(3S)-3-(but-2-ynoylamino)piperidin-1-yl]-5-fluoro-2,3-dimethyl-1H-indole-7-carboxamide Chemical compound C(C#CC)(=O)N[C@@H]1CN(CCC1)C1=C2C(=C(NC2=C(C=C1F)C(=O)N)C)C VJPPLCNBDLZIFG-ZDUSSCGKSA-N 0.000 description 2
- 102100033350 ATP-dependent translocase ABCB1 Human genes 0.000 description 2
- 208000030767 Autoimmune encephalitis Diseases 0.000 description 2
- 102100024222 B-lymphocyte antigen CD19 Human genes 0.000 description 2
- 238000011740 C57BL/6 mouse Methods 0.000 description 2
- 241000282465 Canis Species 0.000 description 2
- PTHCMJGKKRQCBF-UHFFFAOYSA-N Cellulose, microcrystalline Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC)C(CO)O1 PTHCMJGKKRQCBF-UHFFFAOYSA-N 0.000 description 2
- PTOAARAWEBMLNO-KVQBGUIXSA-N Cladribine Chemical compound C1=NC=2C(N)=NC(Cl)=NC=2N1[C@H]1C[C@H](O)[C@@H](CO)O1 PTOAARAWEBMLNO-KVQBGUIXSA-N 0.000 description 2
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 2
- 206010012735 Diarrhoea Diseases 0.000 description 2
- 108010087819 Fc receptors Proteins 0.000 description 2
- 102000009109 Fc receptors Human genes 0.000 description 2
- 208000018522 Gastrointestinal disease Diseases 0.000 description 2
- WZUVPPKBWHMQCE-UHFFFAOYSA-N Haematoxylin Chemical compound C12=CC(O)=C(O)C=C2CC2(O)C1C1=CC=C(O)C(O)=C1OC2 WZUVPPKBWHMQCE-UHFFFAOYSA-N 0.000 description 2
- 208000007514 Herpes zoster Diseases 0.000 description 2
- 101000980825 Homo sapiens B-lymphocyte antigen CD19 Proteins 0.000 description 2
- 101000914514 Homo sapiens T-cell-specific surface glycoprotein CD28 Proteins 0.000 description 2
- 102000015696 Interleukins Human genes 0.000 description 2
- 108010063738 Interleukins Proteins 0.000 description 2
- UQSXHKLRYXJYBZ-UHFFFAOYSA-N Iron oxide Chemical compound [Fe]=O UQSXHKLRYXJYBZ-UHFFFAOYSA-N 0.000 description 2
- 208000008771 Lymphadenopathy Diseases 0.000 description 2
- 229930195725 Mannitol Natural products 0.000 description 2
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 2
- 101100400865 Mus musculus Abcb1b gene Proteins 0.000 description 2
- 206010028813 Nausea Diseases 0.000 description 2
- 206010067482 No adverse event Diseases 0.000 description 2
- 206010057249 Phagocytosis Diseases 0.000 description 2
- 208000013544 Platelet disease Diseases 0.000 description 2
- 102000004022 Protein-Tyrosine Kinases Human genes 0.000 description 2
- 108090000412 Protein-Tyrosine Kinases Proteins 0.000 description 2
- 206010037660 Pyrexia Diseases 0.000 description 2
- 241000283984 Rodentia Species 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 206010065604 Suicidal behaviour Diseases 0.000 description 2
- 206010042458 Suicidal ideation Diseases 0.000 description 2
- 102100027213 T-cell-specific surface glycoprotein CD28 Human genes 0.000 description 2
- 108010009978 Tec protein-tyrosine kinase Proteins 0.000 description 2
- 210000000068 Th17 cell Anatomy 0.000 description 2
- IQFYYKKMVGJFEH-XLPZGREQSA-N Thymidine Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](CO)[C@@H](O)C1 IQFYYKKMVGJFEH-XLPZGREQSA-N 0.000 description 2
- 102000002689 Toll-like receptor Human genes 0.000 description 2
- 108020000411 Toll-like receptor Proteins 0.000 description 2
- 208000018452 Torsade de pointes Diseases 0.000 description 2
- 208000002363 Torsades de Pointes Diseases 0.000 description 2
- 108090000340 Transaminases Proteins 0.000 description 2
- 230000002159 abnormal effect Effects 0.000 description 2
- 230000005856 abnormality Effects 0.000 description 2
- 238000010521 absorption reaction Methods 0.000 description 2
- 239000008186 active pharmaceutical agent Substances 0.000 description 2
- 230000001154 acute effect Effects 0.000 description 2
- 210000005006 adaptive immune system Anatomy 0.000 description 2
- 238000010171 animal model Methods 0.000 description 2
- 230000010056 antibody-dependent cellular cytotoxicity Effects 0.000 description 2
- 238000013459 approach Methods 0.000 description 2
- 229940031567 attenuated vaccine Drugs 0.000 description 2
- 230000003376 axonal effect Effects 0.000 description 2
- 230000000740 bleeding effect Effects 0.000 description 2
- 210000001185 bone marrow Anatomy 0.000 description 2
- 210000000133 brain stem Anatomy 0.000 description 2
- 229940010845 branebrutinib Drugs 0.000 description 2
- 230000011128 cardiac conduction Effects 0.000 description 2
- 230000011712 cell development Effects 0.000 description 2
- 210000001638 cerebellum Anatomy 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 229960002436 cladribine Drugs 0.000 description 2
- 239000002872 contrast media Substances 0.000 description 2
- 230000000875 corresponding effect Effects 0.000 description 2
- 229940125808 covalent inhibitor Drugs 0.000 description 2
- DDRJAANPRJIHGJ-UHFFFAOYSA-N creatinine Chemical compound CN1CC(=O)NC1=N DDRJAANPRJIHGJ-UHFFFAOYSA-N 0.000 description 2
- 230000001186 cumulative effect Effects 0.000 description 2
- 229960002806 daclizumab Drugs 0.000 description 2
- 230000006735 deficit Effects 0.000 description 2
- 238000003745 diagnosis Methods 0.000 description 2
- 208000010643 digestive system disease Diseases 0.000 description 2
- 239000002270 dispersing agent Substances 0.000 description 2
- 238000009826 distribution Methods 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 230000002708 enhancing effect Effects 0.000 description 2
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 2
- 230000003325 follicular Effects 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 239000007789 gas Substances 0.000 description 2
- 208000018685 gastrointestinal system disease Diseases 0.000 description 2
- 239000007903 gelatin capsule Substances 0.000 description 2
- 230000003862 health status Effects 0.000 description 2
- 230000002440 hepatic effect Effects 0.000 description 2
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 2
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 2
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 2
- 238000011532 immunohistochemical staining Methods 0.000 description 2
- 238000000338 in vitro Methods 0.000 description 2
- 238000010348 incorporation Methods 0.000 description 2
- 229960001936 indinavir Drugs 0.000 description 2
- CBVCZFGXHXORBI-PXQQMZJSSA-N indinavir Chemical compound C([C@H](N(CC1)C[C@@H](O)C[C@@H](CC=2C=CC=CC=2)C(=O)N[C@H]2C3=CC=CC=C3C[C@H]2O)C(=O)NC(C)(C)C)N1CC1=CC=CN=C1 CBVCZFGXHXORBI-PXQQMZJSSA-N 0.000 description 2
- 230000006698 induction Effects 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 229960001388 interferon-beta Drugs 0.000 description 2
- 238000001294 liquid chromatography-tandem mass spectrometry Methods 0.000 description 2
- 210000004185 liver Anatomy 0.000 description 2
- 239000000314 lubricant Substances 0.000 description 2
- 210000004072 lung Anatomy 0.000 description 2
- 208000018555 lymphatic system disease Diseases 0.000 description 2
- 210000003563 lymphoid tissue Anatomy 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 230000036210 malignancy Effects 0.000 description 2
- 239000000594 mannitol Substances 0.000 description 2
- 235000010355 mannitol Nutrition 0.000 description 2
- 229940016286 microcrystalline cellulose Drugs 0.000 description 2
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 2
- 239000008108 microcrystalline cellulose Substances 0.000 description 2
- 238000012544 monitoring process Methods 0.000 description 2
- 230000008693 nausea Effects 0.000 description 2
- 210000005036 nerve Anatomy 0.000 description 2
- 230000002314 neuroinflammatory effect Effects 0.000 description 2
- 230000003961 neuronal insult Effects 0.000 description 2
- 210000000440 neutrophil Anatomy 0.000 description 2
- 102000039446 nucleic acids Human genes 0.000 description 2
- 108020004707 nucleic acids Proteins 0.000 description 2
- 150000007523 nucleic acids Chemical class 0.000 description 2
- 230000036961 partial effect Effects 0.000 description 2
- 230000008782 phagocytosis Effects 0.000 description 2
- 230000003285 pharmacodynamic effect Effects 0.000 description 2
- 210000004180 plasmocyte Anatomy 0.000 description 2
- 229940049548 pneumovax Drugs 0.000 description 2
- 239000013641 positive control Substances 0.000 description 2
- 230000002516 postimmunization Effects 0.000 description 2
- 239000002243 precursor Substances 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 230000009696 proliferative response Effects 0.000 description 2
- 230000001737 promoting effect Effects 0.000 description 2
- 238000012113 quantitative test Methods 0.000 description 2
- 239000003642 reactive oxygen metabolite Substances 0.000 description 2
- 206010038351 renal abscess Diseases 0.000 description 2
- 230000001850 reproductive effect Effects 0.000 description 2
- 230000000717 retained effect Effects 0.000 description 2
- 230000002441 reversible effect Effects 0.000 description 2
- 230000033764 rhythmic process Effects 0.000 description 2
- 239000000523 sample Substances 0.000 description 2
- 229960001852 saquinavir Drugs 0.000 description 2
- QWAXKHKRTORLEM-UGJKXSETSA-N saquinavir Chemical compound C([C@@H]([C@H](O)CN1C[C@H]2CCCC[C@H]2C[C@H]1C(=O)NC(C)(C)C)NC(=O)[C@H](CC(N)=O)NC(=O)C=1N=C2C=CC=CC2=CC=1)C1=CC=CC=C1 QWAXKHKRTORLEM-UGJKXSETSA-N 0.000 description 2
- 230000001932 seasonal effect Effects 0.000 description 2
- 230000028327 secretion Effects 0.000 description 2
- 230000009919 sequestration Effects 0.000 description 2
- 230000019491 signal transduction Effects 0.000 description 2
- 235000017557 sodium bicarbonate Nutrition 0.000 description 2
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 241000894007 species Species 0.000 description 2
- 208000010110 spontaneous platelet aggregation Diseases 0.000 description 2
- 230000006641 stabilisation Effects 0.000 description 2
- 238000011105 stabilization Methods 0.000 description 2
- 230000000638 stimulation Effects 0.000 description 2
- 239000000375 suspending agent Substances 0.000 description 2
- 208000011580 syndromic disease Diseases 0.000 description 2
- 230000009885 systemic effect Effects 0.000 description 2
- 238000004885 tandem mass spectrometry Methods 0.000 description 2
- 239000004408 titanium dioxide Substances 0.000 description 2
- 230000007306 turnover Effects 0.000 description 2
- 238000005303 weighing Methods 0.000 description 2
- 235000019786 weight gain Nutrition 0.000 description 2
- 229950007153 zanubrutinib Drugs 0.000 description 2
- WWYNJERNGUHSAO-XUDSTZEESA-N (+)-Norgestrel Chemical compound O=C1CC[C@@H]2[C@H]3CC[C@](CC)([C@](CC4)(O)C#C)[C@@H]4[C@@H]3CCC2=C1 WWYNJERNGUHSAO-XUDSTZEESA-N 0.000 description 1
- XMAYWYJOQHXEEK-OZXSUGGESA-N (2R,4S)-ketoconazole Chemical compound C1CN(C(=O)C)CCN1C(C=C1)=CC=C1OC[C@@H]1O[C@@](CN2C=NC=C2)(C=2C(=CC(Cl)=CC=2)Cl)OC1 XMAYWYJOQHXEEK-OZXSUGGESA-N 0.000 description 1
- UFPFGVNKHCLJJO-SSKFGXFMSA-N (2s)-n-[(1s)-1-cyclohexyl-2-[(2s)-2-[4-(4-fluorobenzoyl)-1,3-thiazol-2-yl]pyrrolidin-1-yl]-2-oxoethyl]-2-(methylamino)propanamide Chemical compound C1([C@H](NC(=O)[C@H](C)NC)C(=O)N2[C@@H](CCC2)C=2SC=C(N=2)C(=O)C=2C=CC(F)=CC=2)CCCCC1 UFPFGVNKHCLJJO-SSKFGXFMSA-N 0.000 description 1
- JGTNAGYHADQMCM-UHFFFAOYSA-M 1,1,2,2,3,3,4,4,4-nonafluorobutane-1-sulfonate Chemical compound [O-]S(=O)(=O)C(F)(F)C(F)(F)C(F)(F)C(F)(F)F JGTNAGYHADQMCM-UHFFFAOYSA-M 0.000 description 1
- JSAQBOQCZJHWMA-XMMPIXPASA-N 1-tert-butyl-N-[(5R)-8-[2-[(1-methylpyrazol-4-yl)amino]pyrimidin-4-yl]-2-(oxetan-3-yl)-1,3,4,5-tetrahydro-2-benzazepin-5-yl]triazole-4-carboxamide Chemical compound C(C)(C)(C)N1N=NC(=C1)C(=O)N[C@H]1C2=C(CN(CC1)C1COC1)C=C(C=C2)C1=NC(=NC=C1)NC=1C=NN(C=1)C JSAQBOQCZJHWMA-XMMPIXPASA-N 0.000 description 1
- BFPYWIDHMRZLRN-UHFFFAOYSA-N 17alpha-ethynyl estradiol Natural products OC1=CC=C2C3CCC(C)(C(CC4)(O)C#C)C4C3CCC2=C1 BFPYWIDHMRZLRN-UHFFFAOYSA-N 0.000 description 1
- VHVPQPYKVGDNFY-DFMJLFEVSA-N 2-[(2r)-butan-2-yl]-4-[4-[4-[4-[[(2r,4s)-2-(2,4-dichlorophenyl)-2-(1,2,4-triazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy]phenyl]piperazin-1-yl]phenyl]-1,2,4-triazol-3-one Chemical compound O=C1N([C@H](C)CC)N=CN1C1=CC=C(N2CCN(CC2)C=2C=CC(OC[C@@H]3O[C@](CN4N=CN=C4)(OC3)C=3C(=CC(Cl)=CC=3)Cl)=CC=2)C=C1 VHVPQPYKVGDNFY-DFMJLFEVSA-N 0.000 description 1
- JWEQLWMZHJSMEC-AFJTUFCWSA-N 4-[8-amino-3-[(2S)-1-but-2-ynoylpyrrolidin-2-yl]imidazo[1,5-a]pyrazin-1-yl]-N-pyridin-2-ylbenzamide (Z)-but-2-enedioic acid Chemical compound OC(=O)\C=C/C(O)=O.CC#CC(=O)N1CCC[C@H]1c1nc(-c2ccc(cc2)C(=O)Nc2ccccn2)c2c(N)nccn12 JWEQLWMZHJSMEC-AFJTUFCWSA-N 0.000 description 1
- SEJLPXCPMNSRAM-GOSISDBHSA-N 6-amino-9-[(3r)-1-but-2-ynoylpyrrolidin-3-yl]-7-(4-phenoxyphenyl)purin-8-one Chemical compound C1N(C(=O)C#CC)CC[C@H]1N1C(=O)N(C=2C=CC(OC=3C=CC=CC=3)=CC=2)C2=C(N)N=CN=C21 SEJLPXCPMNSRAM-GOSISDBHSA-N 0.000 description 1
- 206010003011 Appendicitis Diseases 0.000 description 1
- 206010003591 Ataxia Diseases 0.000 description 1
- 208000023275 Autoimmune disease Diseases 0.000 description 1
- 208000010839 B-cell chronic lymphocytic leukemia Diseases 0.000 description 1
- 229940123121 B-cell inhibitor Drugs 0.000 description 1
- 229940125889 BIIB091 Drugs 0.000 description 1
- 206010004146 Basal cell carcinoma Diseases 0.000 description 1
- 201000004569 Blindness Diseases 0.000 description 1
- 208000037403 Blood and lymphatic system disease Diseases 0.000 description 1
- 102100025222 CD63 antigen Human genes 0.000 description 1
- QAGYKUNXZHXKMR-UHFFFAOYSA-N CPD000469186 Natural products CC1=C(O)C=CC=C1C(=O)NC(C(O)CN1C(CC2CCCCC2C1)C(=O)NC(C)(C)C)CSC1=CC=CC=C1 QAGYKUNXZHXKMR-UHFFFAOYSA-N 0.000 description 1
- 101100348341 Caenorhabditis elegans gas-1 gene Proteins 0.000 description 1
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 1
- 208000024172 Cardiovascular disease Diseases 0.000 description 1
- 206010057248 Cell death Diseases 0.000 description 1
- 206010051290 Central nervous system lesion Diseases 0.000 description 1
- 206010061809 Cervix carcinoma stage 0 Diseases 0.000 description 1
- 206010008479 Chest Pain Diseases 0.000 description 1
- VYZAMTAEIAYCRO-UHFFFAOYSA-N Chromium Chemical compound [Cr] VYZAMTAEIAYCRO-UHFFFAOYSA-N 0.000 description 1
- 208000017667 Chronic Disease Diseases 0.000 description 1
- 208000035473 Communicable disease Diseases 0.000 description 1
- 229920002785 Croscarmellose sodium Polymers 0.000 description 1
- 208000000130 Cytochrome P-450 CYP3A Inducers Diseases 0.000 description 1
- 206010012305 Demyelination Diseases 0.000 description 1
- 208000020401 Depressive disease Diseases 0.000 description 1
- 206010013887 Dysarthria Diseases 0.000 description 1
- 208000017701 Endocrine disease Diseases 0.000 description 1
- BFPYWIDHMRZLRN-SLHNCBLASA-N Ethinyl estradiol Chemical compound OC1=CC=C2[C@H]3CC[C@](C)([C@](CC4)(O)C#C)[C@@H]4[C@@H]3CCC2=C1 BFPYWIDHMRZLRN-SLHNCBLASA-N 0.000 description 1
- KRHYYFGTRYWZRS-UHFFFAOYSA-M Fluoride anion Chemical compound [F-] KRHYYFGTRYWZRS-UHFFFAOYSA-M 0.000 description 1
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 1
- 208000005577 Gastroenteritis Diseases 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 206010019280 Heart failures Diseases 0.000 description 1
- 208000010670 Hemic and Lymphatic disease Diseases 0.000 description 1
- 101000934368 Homo sapiens CD63 antigen Proteins 0.000 description 1
- 101000897042 Homo sapiens Nucleotide pyrophosphatase Proteins 0.000 description 1
- 239000004354 Hydroxyethyl cellulose Substances 0.000 description 1
- 229920000663 Hydroxyethyl cellulose Polymers 0.000 description 1
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 description 1
- 206010020772 Hypertension Diseases 0.000 description 1
- 208000019025 Hypokalemia Diseases 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 108010008212 Integrin alpha4beta1 Proteins 0.000 description 1
- 108010002586 Interleukin-7 Proteins 0.000 description 1
- OFFWOVJBSQMVPI-RMLGOCCBSA-N Kaletra Chemical compound N1([C@@H](C(C)C)C(=O)N[C@H](C[C@H](O)[C@H](CC=2C=CC=CC=2)NC(=O)COC=2C(=CC=CC=2C)C)CC=2C=CC=CC=2)CCCNC1=O.N([C@@H](C(C)C)C(=O)N[C@H](C[C@H](O)[C@H](CC=1C=CC=CC=1)NC(=O)OCC=1SC=NC=1)CC=1C=CC=CC=1)C(=O)N(C)CC1=CSC(C(C)C)=N1 OFFWOVJBSQMVPI-RMLGOCCBSA-N 0.000 description 1
- 208000034800 Leukoencephalopathies Diseases 0.000 description 1
- 208000019693 Lung disease Diseases 0.000 description 1
- 206010025327 Lymphopenia Diseases 0.000 description 1
- 102000043131 MHC class II family Human genes 0.000 description 1
- 108091054438 MHC class II family Proteins 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 238000000585 Mann–Whitney U test Methods 0.000 description 1
- 108010047230 Member 1 Subfamily B ATP Binding Cassette Transporter Proteins 0.000 description 1
- 206010027476 Metastases Diseases 0.000 description 1
- 208000016285 Movement disease Diseases 0.000 description 1
- 101100447658 Mus musculus Gas1 gene Proteins 0.000 description 1
- 101100447665 Mus musculus Gas2 gene Proteins 0.000 description 1
- 101100341868 Mus musculus Kcp gene Proteins 0.000 description 1
- 208000029027 Musculoskeletal and connective tissue disease Diseases 0.000 description 1
- UNHZLHSLZZWMNP-LLVKDONJSA-N NC(=O)c1ccc([C@@H]2CCCN(C2)C(=O)C=C)c2cc[nH]c12 Chemical compound NC(=O)c1ccc([C@@H]2CCCN(C2)C(=O)C=C)c2cc[nH]c12 UNHZLHSLZZWMNP-LLVKDONJSA-N 0.000 description 1
- 208000025966 Neurological disease Diseases 0.000 description 1
- 102100021969 Nucleotide pyrophosphatase Human genes 0.000 description 1
- 208000001388 Opportunistic Infections Diseases 0.000 description 1
- 208000025157 Oral disease Diseases 0.000 description 1
- 206010033661 Pancytopenia Diseases 0.000 description 1
- 208000007542 Paresis Diseases 0.000 description 1
- 206010073391 Platelet dysfunction Diseases 0.000 description 1
- 206010059440 Platelet toxicity Diseases 0.000 description 1
- 239000004372 Polyvinyl alcohol Substances 0.000 description 1
- 102000007056 Recombinant Fusion Proteins Human genes 0.000 description 1
- 108010008281 Recombinant Fusion Proteins Proteins 0.000 description 1
- 206010040030 Sensory loss Diseases 0.000 description 1
- 229920001800 Shellac Polymers 0.000 description 1
- 244000258044 Solanum gilo Species 0.000 description 1
- 208000030962 Subcutaneous tissue disease Diseases 0.000 description 1
- 108091008874 T cell receptors Proteins 0.000 description 1
- 230000005867 T cell response Effects 0.000 description 1
- 102000016266 T-Cell Antigen Receptors Human genes 0.000 description 1
- 210000000447 Th1 cell Anatomy 0.000 description 1
- SUJUHGSWHZTSEU-UHFFFAOYSA-N Tipranavir Natural products C1C(O)=C(C(CC)C=2C=C(NS(=O)(=O)C=3N=CC(=CC=3)C(F)(F)F)C=CC=2)C(=O)OC1(CCC)CCC1=CC=CC=C1 SUJUHGSWHZTSEU-UHFFFAOYSA-N 0.000 description 1
- 102000003929 Transaminases Human genes 0.000 description 1
- 206010066901 Treatment failure Diseases 0.000 description 1
- 206010044565 Tremor Diseases 0.000 description 1
- 208000024780 Urticaria Diseases 0.000 description 1
- 241000271897 Viperidae Species 0.000 description 1
- 206010047555 Visual field defect Diseases 0.000 description 1
- 208000033559 Waldenström macroglobulinemia Diseases 0.000 description 1
- 208000027418 Wounds and injury Diseases 0.000 description 1
- 101100341869 Xenopus laevis kcp gene Proteins 0.000 description 1
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 230000009798 acute exacerbation Effects 0.000 description 1
- 230000003044 adaptive effect Effects 0.000 description 1
- 230000033289 adaptive immune response Effects 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 125000000539 amino acid group Chemical group 0.000 description 1
- BTBJBAZGXNKLQC-UHFFFAOYSA-N ammonium lauryl sulfate Chemical compound [NH4+].CCCCCCCCCCCCOS([O-])(=O)=O BTBJBAZGXNKLQC-UHFFFAOYSA-N 0.000 description 1
- 229940063953 ammonium lauryl sulfate Drugs 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 229940125715 antihistaminic agent Drugs 0.000 description 1
- 239000000739 antihistaminic agent Substances 0.000 description 1
- 201000007201 aphasia Diseases 0.000 description 1
- 230000006793 arrhythmia Effects 0.000 description 1
- 206010003119 arrhythmia Diseases 0.000 description 1
- 210000001130 astrocyte Anatomy 0.000 description 1
- 210000000649 b-lymphocyte subset Anatomy 0.000 description 1
- 210000003651 basophil Anatomy 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000008275 binding mechanism Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 238000004820 blood count Methods 0.000 description 1
- 229960000517 boceprevir Drugs 0.000 description 1
- LHHCSNFAOIFYRV-DOVBMPENSA-N boceprevir Chemical compound O=C([C@@H]1[C@@H]2[C@@H](C2(C)C)CN1C(=O)[C@@H](NC(=O)NC(C)(C)C)C(C)(C)C)NC(C(=O)C(N)=O)CC1CCC1 LHHCSNFAOIFYRV-DOVBMPENSA-N 0.000 description 1
- 210000002798 bone marrow cell Anatomy 0.000 description 1
- 230000003925 brain function Effects 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 239000001768 carboxy methyl cellulose Substances 0.000 description 1
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 1
- 229920003064 carboxyethyl cellulose Polymers 0.000 description 1
- 229920003090 carboxymethyl hydroxyethyl cellulose Polymers 0.000 description 1
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 1
- 230000001364 causal effect Effects 0.000 description 1
- 238000000423 cell based assay Methods 0.000 description 1
- 239000013553 cell monolayer Substances 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 235000010980 cellulose Nutrition 0.000 description 1
- 210000004720 cerebrum Anatomy 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 229910052804 chromium Inorganic materials 0.000 description 1
- 239000011651 chromium Substances 0.000 description 1
- 208000017760 chronic graft versus host disease Diseases 0.000 description 1
- 229960001265 ciclosporin Drugs 0.000 description 1
- 229960002626 clarithromycin Drugs 0.000 description 1
- AGOYDEPGAOXOCK-KCBOHYOISA-N clarithromycin Chemical compound O([C@@H]1[C@@H](C)C(=O)O[C@@H]([C@@]([C@H](O)[C@@H](C)C(=O)[C@H](C)C[C@](C)([C@H](O[C@H]2[C@@H]([C@H](C[C@@H](C)O2)N(C)C)O)[C@H]1C)OC)(C)O)CC)[C@H]1C[C@@](C)(OC)[C@@H](O)[C@H](C)O1 AGOYDEPGAOXOCK-KCBOHYOISA-N 0.000 description 1
- 238000003759 clinical diagnosis Methods 0.000 description 1
- 229960002402 cobicistat Drugs 0.000 description 1
- ZCIGNRJZKPOIKD-CQXVEOKZSA-N cobicistat Chemical compound S1C(C(C)C)=NC(CN(C)C(=O)N[C@@H](CCN2CCOCC2)C(=O)N[C@H](CC[C@H](CC=2C=CC=CC=2)NC(=O)OCC=2SC=NC=2)CC=2C=CC=CC=2)=C1 ZCIGNRJZKPOIKD-CQXVEOKZSA-N 0.000 description 1
- 230000001149 cognitive effect Effects 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 238000004891 communication Methods 0.000 description 1
- 230000009850 completed effect Effects 0.000 description 1
- 239000002131 composite material Substances 0.000 description 1
- 230000001010 compromised effect Effects 0.000 description 1
- 229960000562 conivaptan Drugs 0.000 description 1
- JGBBVDFNZSRLIF-UHFFFAOYSA-N conivaptan Chemical compound C12=CC=CC=C2C=2[N]C(C)=NC=2CCN1C(=O)C(C=C1)=CC=C1NC(=O)C1=CC=CC=C1C1=CC=CC=C1 JGBBVDFNZSRLIF-UHFFFAOYSA-N 0.000 description 1
- 238000011109 contamination Methods 0.000 description 1
- 230000001276 controlling effect Effects 0.000 description 1
- 229920001577 copolymer Polymers 0.000 description 1
- 238000012937 correction Methods 0.000 description 1
- 229940109239 creatinine Drugs 0.000 description 1
- 229960001681 croscarmellose sodium Drugs 0.000 description 1
- 235000010947 crosslinked sodium carboxy methyl cellulose Nutrition 0.000 description 1
- 238000009109 curative therapy Methods 0.000 description 1
- 208000024389 cytopenia Diseases 0.000 description 1
- 210000004292 cytoskeleton Anatomy 0.000 description 1
- 230000001086 cytosolic effect Effects 0.000 description 1
- 229950002891 danoprevir Drugs 0.000 description 1
- ZVTDLPBHTSMEJZ-UPZRXNBOSA-N danoprevir Chemical compound O=C([C@@]12C[C@H]1\C=C/CCCCC[C@H](C(N1C[C@@H](C[C@H]1C(=O)N2)OC(=O)N1CC2=C(F)C=CC=C2C1)=O)NC(=O)OC(C)(C)C)NS(=O)(=O)C1CC1 ZVTDLPBHTSMEJZ-UPZRXNBOSA-N 0.000 description 1
- 229960005107 darunavir Drugs 0.000 description 1
- CJBJHOAVZSMMDJ-HEXNFIEUSA-N darunavir Chemical compound C([C@@H]([C@H](O)CN(CC(C)C)S(=O)(=O)C=1C=CC(N)=CC=1)NC(=O)O[C@@H]1[C@@H]2CCO[C@@H]2OC1)C1=CC=CC=C1 CJBJHOAVZSMMDJ-HEXNFIEUSA-N 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 235000005911 diet Nutrition 0.000 description 1
- 230000037213 diet Effects 0.000 description 1
- 208000016097 disease of metabolism Diseases 0.000 description 1
- 230000009433 disease-worsening effect Effects 0.000 description 1
- SMVRDGHCVNAOIN-UHFFFAOYSA-L disodium;1-dodecoxydodecane;sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O.CCCCCCCCCCCCOCCCCCCCCCCCC SMVRDGHCVNAOIN-UHFFFAOYSA-L 0.000 description 1
- 230000003828 downregulation Effects 0.000 description 1
- 229940000406 drug candidate Drugs 0.000 description 1
- 229940126534 drug product Drugs 0.000 description 1
- 230000004821 effect on bone Effects 0.000 description 1
- 230000002526 effect on cardiovascular system Effects 0.000 description 1
- 238000010828 elution Methods 0.000 description 1
- 230000002124 endocrine Effects 0.000 description 1
- 208000030172 endocrine system disease Diseases 0.000 description 1
- 210000002889 endothelial cell Anatomy 0.000 description 1
- 238000010201 enrichment analysis Methods 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 239000002532 enzyme inhibitor Substances 0.000 description 1
- 206010015037 epilepsy Diseases 0.000 description 1
- 238000011067 equilibration Methods 0.000 description 1
- 229960002568 ethinylestradiol Drugs 0.000 description 1
- MVPICKVDHDWCJQ-UHFFFAOYSA-N ethyl 3-pyrrolidin-1-ylpropanoate Chemical compound CCOC(=O)CCN1CCCC1 MVPICKVDHDWCJQ-UHFFFAOYSA-N 0.000 description 1
- QUIWHXQETADMGN-UHFFFAOYSA-N evobrutinib Chemical compound C=1C=C(OC=2C=CC=CC=2)C=CC=1C=1C(N)=NC=NC=1NCC1CCN(C(=O)C=C)CC1 QUIWHXQETADMGN-UHFFFAOYSA-N 0.000 description 1
- 229950003411 evobrutinib Drugs 0.000 description 1
- 230000007717 exclusion Effects 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 210000003414 extremity Anatomy 0.000 description 1
- 210000002950 fibroblast Anatomy 0.000 description 1
- 238000011049 filling Methods 0.000 description 1
- 235000013373 food additive Nutrition 0.000 description 1
- 239000002778 food additive Substances 0.000 description 1
- 229940050411 fumarate Drugs 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 238000010199 gene set enrichment analysis Methods 0.000 description 1
- 230000004547 gene signature Effects 0.000 description 1
- 230000002068 genetic effect Effects 0.000 description 1
- 230000007614 genetic variation Effects 0.000 description 1
- 229940012229 genone Drugs 0.000 description 1
- 230000036449 good health Effects 0.000 description 1
- 235000015201 grapefruit juice Nutrition 0.000 description 1
- 208000014951 hematologic disease Diseases 0.000 description 1
- 230000002489 hematologic effect Effects 0.000 description 1
- 210000000777 hematopoietic system Anatomy 0.000 description 1
- 208000018706 hematopoietic system disease Diseases 0.000 description 1
- 206010073071 hepatocellular carcinoma Diseases 0.000 description 1
- 231100000844 hepatocellular carcinoma Toxicity 0.000 description 1
- 238000010562 histological examination Methods 0.000 description 1
- 230000003284 homeostatic effect Effects 0.000 description 1
- 235000019447 hydroxyethyl cellulose Nutrition 0.000 description 1
- 239000001863 hydroxypropyl cellulose Substances 0.000 description 1
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 1
- UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 description 1
- 229960003943 hypromellose Drugs 0.000 description 1
- 230000008102 immune modulation Effects 0.000 description 1
- 210000000987 immune system Anatomy 0.000 description 1
- 230000036039 immunity Effects 0.000 description 1
- 239000002955 immunomodulating agent Substances 0.000 description 1
- 229940121354 immunomodulator Drugs 0.000 description 1
- 238000002650 immunosuppressive therapy Methods 0.000 description 1
- 230000001771 impaired effect Effects 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 230000008595 infiltration Effects 0.000 description 1
- 238000001764 infiltration Methods 0.000 description 1
- 208000014674 injury Diseases 0.000 description 1
- 210000005007 innate immune system Anatomy 0.000 description 1
- 229940047122 interleukins Drugs 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- LIKBJVNGSGBSGK-UHFFFAOYSA-N iron(3+);oxygen(2-) Chemical compound [O-2].[O-2].[O-2].[Fe+3].[Fe+3] LIKBJVNGSGBSGK-UHFFFAOYSA-N 0.000 description 1
- YOBAEOGBNPPUQV-UHFFFAOYSA-N iron;trihydrate Chemical compound O.O.O.[Fe].[Fe] YOBAEOGBNPPUQV-UHFFFAOYSA-N 0.000 description 1
- 229960004130 itraconazole Drugs 0.000 description 1
- 229960004125 ketoconazole Drugs 0.000 description 1
- 235000020887 ketogenic diet Nutrition 0.000 description 1
- 208000017169 kidney disease Diseases 0.000 description 1
- 238000009533 lab test Methods 0.000 description 1
- 230000006651 lactation Effects 0.000 description 1
- 210000000265 leukocyte Anatomy 0.000 description 1
- 229960004400 levonorgestrel Drugs 0.000 description 1
- 238000012417 linear regression Methods 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 208000019423 liver disease Diseases 0.000 description 1
- 230000003908 liver function Effects 0.000 description 1
- 229940113983 lopinavir / ritonavir Drugs 0.000 description 1
- 208000018883 loss of balance Diseases 0.000 description 1
- 210000005210 lymphoid organ Anatomy 0.000 description 1
- 231100001023 lymphopenia Toxicity 0.000 description 1
- 201000000564 macroglobulinemia Diseases 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 238000013507 mapping Methods 0.000 description 1
- 201000007924 marginal zone B-cell lymphoma Diseases 0.000 description 1
- 208000021937 marginal zone lymphoma Diseases 0.000 description 1
- 239000003550 marker Substances 0.000 description 1
- 230000010534 mechanism of action Effects 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 230000006996 mental state Effects 0.000 description 1
- 208000030159 metabolic disease Diseases 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- 230000009401 metastasis Effects 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- 150000004702 methyl esters Chemical class 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- 235000010981 methylcellulose Nutrition 0.000 description 1
- 238000010232 migration assay Methods 0.000 description 1
- 230000002438 mitochondrial effect Effects 0.000 description 1
- 210000001616 monocyte Anatomy 0.000 description 1
- 230000004660 morphological change Effects 0.000 description 1
- 238000010172 mouse model Methods 0.000 description 1
- 208000030194 mouth disease Diseases 0.000 description 1
- 210000000822 natural killer cell Anatomy 0.000 description 1
- 229960001800 nefazodone Drugs 0.000 description 1
- VRBKIVRKKCLPHA-UHFFFAOYSA-N nefazodone Chemical compound O=C1N(CCOC=2C=CC=CC=2)C(CC)=NN1CCCN(CC1)CCN1C1=CC=CC(Cl)=C1 VRBKIVRKKCLPHA-UHFFFAOYSA-N 0.000 description 1
- 229960000884 nelfinavir Drugs 0.000 description 1
- QAGYKUNXZHXKMR-HKWSIXNMSA-N nelfinavir Chemical compound CC1=C(O)C=CC=C1C(=O)N[C@H]([C@H](O)CN1[C@@H](C[C@@H]2CCCC[C@@H]2C1)C(=O)NC(C)(C)C)CSC1=CC=CC=C1 QAGYKUNXZHXKMR-HKWSIXNMSA-N 0.000 description 1
- 230000001537 neural effect Effects 0.000 description 1
- 210000000461 neuroepithelial cell Anatomy 0.000 description 1
- 230000009251 neurologic dysfunction Effects 0.000 description 1
- 208000015015 neurological dysfunction Diseases 0.000 description 1
- 230000007171 neuropathology Effects 0.000 description 1
- 238000002414 normal-phase solid-phase extraction Methods 0.000 description 1
- 238000010606 normalization Methods 0.000 description 1
- 231100000862 numbness Toxicity 0.000 description 1
- 206010029864 nystagmus Diseases 0.000 description 1
- 229960003347 obinutuzumab Drugs 0.000 description 1
- 230000009437 off-target effect Effects 0.000 description 1
- 210000004248 oligodendroglia Anatomy 0.000 description 1
- 210000001328 optic nerve Anatomy 0.000 description 1
- 229940126701 oral medication Drugs 0.000 description 1
- 210000004789 organ system Anatomy 0.000 description 1
- 208000025661 ovarian cyst Diseases 0.000 description 1
- 229940124583 pain medication Drugs 0.000 description 1
- 208000021090 palsy Diseases 0.000 description 1
- 230000003950 pathogenic mechanism Effects 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 230000007170 pathology Effects 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 230000008447 perception Effects 0.000 description 1
- 210000005259 peripheral blood Anatomy 0.000 description 1
- 239000011886 peripheral blood Substances 0.000 description 1
- 230000002085 persistent effect Effects 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 210000003720 plasmablast Anatomy 0.000 description 1
- 231100000201 platelet toxicity Toxicity 0.000 description 1
- 229940033515 pneumovax 23 Drugs 0.000 description 1
- 229950008882 polysorbate Drugs 0.000 description 1
- 229920000136 polysorbate Polymers 0.000 description 1
- 229920002451 polyvinyl alcohol Polymers 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 238000011176 pooling Methods 0.000 description 1
- 229960001589 posaconazole Drugs 0.000 description 1
- RAGOYPUPXAKGKH-XAKZXMRKSA-N posaconazole Chemical compound O=C1N([C@H]([C@H](C)O)CC)N=CN1C1=CC=C(N2CCN(CC2)C=2C=CC(OC[C@H]3C[C@@](CN4N=CN=C4)(OC3)C=3C(=CC(F)=CC=3)F)=CC=2)C=C1 RAGOYPUPXAKGKH-XAKZXMRKSA-N 0.000 description 1
- 208000024896 potassium deficiency disease Diseases 0.000 description 1
- ONQDVAFWWYYXHM-UHFFFAOYSA-M potassium lauryl sulfate Chemical compound [K+].CCCCCCCCCCCCOS([O-])(=O)=O ONQDVAFWWYYXHM-UHFFFAOYSA-M 0.000 description 1
- 229940116985 potassium lauryl sulfate Drugs 0.000 description 1
- 230000035935 pregnancy Effects 0.000 description 1
- 238000009101 premedication Methods 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 238000000513 principal component analysis Methods 0.000 description 1
- 238000011321 prophylaxis Methods 0.000 description 1
- DNIAPMSPPWPWGF-UHFFFAOYSA-N propylene glycol Substances CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 1
- 238000001243 protein synthesis Methods 0.000 description 1
- 208000020016 psychiatric disease Diseases 0.000 description 1
- 230000002685 pulmonary effect Effects 0.000 description 1
- 238000000718 qrs complex Methods 0.000 description 1
- 230000007420 reactivation Effects 0.000 description 1
- 230000007115 recruitment Effects 0.000 description 1
- 230000000306 recurrent effect Effects 0.000 description 1
- 210000003289 regulatory T cell Anatomy 0.000 description 1
- 210000002707 regulatory b cell Anatomy 0.000 description 1
- 230000002336 repolarization Effects 0.000 description 1
- 230000004202 respiratory function Effects 0.000 description 1
- 230000000284 resting effect Effects 0.000 description 1
- 238000011519 second-line treatment Methods 0.000 description 1
- 230000003248 secreting effect Effects 0.000 description 1
- 230000035807 sensation Effects 0.000 description 1
- 238000012163 sequencing technique Methods 0.000 description 1
- 239000004208 shellac Substances 0.000 description 1
- 229940113147 shellac Drugs 0.000 description 1
- ZLGIYFNHBLSMPS-ATJNOEHPSA-N shellac Chemical compound OCCCCCC(O)C(O)CCCCCCCC(O)=O.C1C23[C@H](C(O)=O)CCC2[C@](C)(CO)[C@@H]1C(C(O)=O)=C[C@@H]3O ZLGIYFNHBLSMPS-ATJNOEHPSA-N 0.000 description 1
- 235000013874 shellac Nutrition 0.000 description 1
- 235000015170 shellfish Nutrition 0.000 description 1
- 238000010181 skin prick test Methods 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 229940045902 sodium stearyl fumarate Drugs 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- GOLXNESZZPUPJE-UHFFFAOYSA-N spiromesifen Chemical compound CC1=CC(C)=CC(C)=C1C(C(O1)=O)=C(OC(=O)CC(C)(C)C)C11CCCC1 GOLXNESZZPUPJE-UHFFFAOYSA-N 0.000 description 1
- 230000002269 spontaneous effect Effects 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 238000010186 staining Methods 0.000 description 1
- 210000002536 stromal cell Anatomy 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 230000008093 supporting effect Effects 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 230000009747 swallowing Effects 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- LJVAJPDWBABPEJ-PNUFFHFMSA-N telithromycin Chemical compound O([C@@H]1[C@@H](C)C(=O)[C@@H](C)C(=O)O[C@@H]([C@]2(OC(=O)N(CCCCN3C=C(N=C3)C=3C=NC=CC=3)[C@@H]2[C@@H](C)C(=O)[C@H](C)C[C@@]1(C)OC)C)CC)[C@@H]1O[C@H](C)C[C@H](N(C)C)[C@H]1O LJVAJPDWBABPEJ-PNUFFHFMSA-N 0.000 description 1
- 229960003250 telithromycin Drugs 0.000 description 1
- 229940057406 teriflunomide 14 mg Drugs 0.000 description 1
- 229940031351 tetravalent vaccine Drugs 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 238000011285 therapeutic regimen Methods 0.000 description 1
- 210000001541 thymus gland Anatomy 0.000 description 1
- 229960000838 tipranavir Drugs 0.000 description 1
- SUJUHGSWHZTSEU-FYBSXPHGSA-N tipranavir Chemical compound C([C@@]1(CCC)OC(=O)C([C@H](CC)C=2C=C(NS(=O)(=O)C=3N=CC(=CC=3)C(F)(F)F)C=CC=2)=C(O)C1)CC1=CC=CC=C1 SUJUHGSWHZTSEU-FYBSXPHGSA-N 0.000 description 1
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
- 102000014898 transaminase activity proteins Human genes 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 230000001052 transient effect Effects 0.000 description 1
- 230000014616 translation Effects 0.000 description 1
- 230000032258 transport Effects 0.000 description 1
- 229960005041 troleandomycin Drugs 0.000 description 1
- LQCLVBQBTUVCEQ-QTFUVMRISA-N troleandomycin Chemical compound O1[C@@H](C)[C@H](OC(C)=O)[C@@H](OC)C[C@@H]1O[C@@H]1[C@@H](C)C(=O)O[C@H](C)[C@H](C)[C@H](OC(C)=O)[C@@H](C)C(=O)[C@@]2(OC2)C[C@H](C)[C@H](O[C@H]2[C@@H]([C@H](C[C@@H](C)O2)N(C)C)OC(C)=O)[C@H]1C LQCLVBQBTUVCEQ-QTFUVMRISA-N 0.000 description 1
- 238000011870 unpaired t-test Methods 0.000 description 1
- 238000002562 urinalysis Methods 0.000 description 1
- 210000003462 vein Anatomy 0.000 description 1
- 229920002554 vinyl polymer Polymers 0.000 description 1
- 230000004382 visual function Effects 0.000 description 1
- 229960004740 voriconazole Drugs 0.000 description 1
- BCEHBSKCWLPMDN-MGPLVRAMSA-N voriconazole Chemical compound C1([C@H](C)[C@](O)(CN2N=CN=C2)C=2C(=CC(F)=CC=2)F)=NC=NC=C1F BCEHBSKCWLPMDN-MGPLVRAMSA-N 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 238000010947 wet-dispersion method Methods 0.000 description 1
- 210000004885 white matter Anatomy 0.000 description 1
Images
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
-
- 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
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2013—Organic compounds, e.g. phospholipids, fats
-
- 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
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2013—Organic compounds, e.g. phospholipids, fats
- A61K9/2018—Sugars, or sugar alcohols, e.g. lactose, mannitol; Derivatives thereof, e.g. polysorbates
-
- 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
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2022—Organic macromolecular compounds
- A61K9/2027—Organic macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
-
- 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
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2022—Organic macromolecular compounds
- A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
- A61K9/2054—Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
-
- 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
- A61K9/20—Pills, tablets, discs, rods
- A61K9/28—Dragees; Coated pills or tablets, e.g. with film or compression coating
- A61K9/2806—Coating materials
- A61K9/282—Organic compounds, e.g. fats
- A61K9/2826—Sugars or sugar alcohols, e.g. sucrose; Derivatives thereof
-
- 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
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/4841—Filling excipients; Inactive ingredients
- A61K9/4858—Organic compounds
-
- 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
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/4841—Filling excipients; Inactive ingredients
- A61K9/4866—Organic macromolecular compounds
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P21/00—Drugs for disorders of the muscular or neuromuscular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2300/00—Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
-
- 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
- A61K9/20—Pills, tablets, discs, rods
- A61K9/28—Dragees; Coated pills or tablets, e.g. with film or compression coating
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Chemical & Material Sciences (AREA)
- Epidemiology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Neurology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Neurosurgery (AREA)
- Biomedical Technology (AREA)
- Biophysics (AREA)
- Molecular Biology (AREA)
- Psychiatry (AREA)
- Hospice & Palliative Care (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Physical Education & Sports Medicine (AREA)
- Immunology (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Peptides Or Proteins (AREA)
- Medicinal Preparation (AREA)
Applications Claiming Priority (10)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US202163240444P | 2021-09-03 | 2021-09-03 | |
| US63/240,444 | 2021-09-03 | ||
| US202163282363P | 2021-11-23 | 2021-11-23 | |
| US63/282,363 | 2021-11-23 | ||
| US202263304106P | 2022-01-28 | 2022-01-28 | |
| US63/304,106 | 2022-01-28 | ||
| US202263353866P | 2022-06-21 | 2022-06-21 | |
| US63/353,866 | 2022-06-21 | ||
| US202263369008P | 2022-07-21 | 2022-07-21 | |
| US63/369,008 | 2022-07-21 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| TW202310841A true TW202310841A (zh) | 2023-03-16 |
Family
ID=83438454
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| TW111133216A TW202310841A (zh) | 2021-09-03 | 2022-09-01 | 用於治療多發性硬化症之ｌｏｕ０６４ |
Country Status (10)
| Country | Link |
|---|---|
| US (1) | US20240350489A1 (https=) |
| EP (1) | EP4395779A1 (https=) |
| JP (2) | JP7564347B2 (https=) |
| KR (1) | KR20240055038A (https=) |
| AU (1) | AU2022337087A1 (https=) |
| CA (1) | CA3229887A1 (https=) |
| IL (1) | IL310975A (https=) |
| MX (1) | MX2024002581A (https=) |
| TW (1) | TW202310841A (https=) |
| WO (1) | WO2023031840A1 (https=) |
Families Citing this family (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU2021398051A1 (en) | 2020-12-10 | 2023-07-27 | Principia Biopharma Inc. | Crystal form of tolebrutinib, preparation method therefor and use thereof |
| US20260027100A1 (en) * | 2022-05-13 | 2026-01-29 | Principia Biopharma Inc. | Therapeutic tyrosine kinase inhibitors for myelin oligodendrocyte glycoprotein antibody disease (mogad) |
| CA3260242A1 (en) * | 2022-06-24 | 2023-12-28 | Merck Patent Gmbh | TREATMENT REGIMEN FOR AUTOIMMUNE AND INFLAMMATORY DISEASES |
| US20250243170A1 (en) * | 2024-01-26 | 2025-07-31 | Novartis Ag | Remibrutinib drug substance and drug product substantially free of nitrosamine impurity |
Family Cites Families (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20130197080A1 (en) * | 2010-08-02 | 2013-08-01 | Sanofi | Use of teriflunomide for treating multiple sclerosis |
| US9512084B2 (en) | 2013-11-29 | 2016-12-06 | Novartis Ag | Amino pyrimidine derivatives |
| EP3738084A4 (en) * | 2018-01-08 | 2021-11-17 | G1 Therapeutics, Inc. | SUPERIOR G1T38 DOSING SCHEMES |
| CN117285467A (zh) * | 2018-07-31 | 2023-12-26 | 罗索肿瘤学公司 | 喷雾干燥的分散体和制剂 |
| RS67141B1 (sr) | 2019-05-23 | 2025-09-30 | Novartis Ag | Inhibitor brutonove tirozin kinaze za upotrebu u lečenju hronične spontane urtikarije |
| CN113840821A (zh) | 2019-05-23 | 2021-12-24 | 诺华股份有限公司 | Btk抑制剂的晶型 |
| BR112021023110A2 (pt) | 2019-05-23 | 2022-04-12 | Novartis Ag | Métodos de tratamento de síndrome de sjögren com o uso de um inibidor de tirosina quinase de bruton |
| WO2022081512A1 (en) * | 2020-10-12 | 2022-04-21 | Synubi Pharmaceuticals Llc | Compositions and methods of treatment of neuroinflammatory diseases with bruton's tyrosine kinase inhibitors |
| MX2023008671A (es) * | 2021-01-26 | 2023-09-25 | Novartis Ag | Composicion farmaceutica. |
| BR112023017648A2 (pt) * | 2021-03-03 | 2023-11-14 | Janssen Pharmaceutica Nv | Terapia de combinação com o uso de um inibidor de malt1 e um inibidor de btk |
-
2022
- 2022-09-01 JP JP2023517239A patent/JP7564347B2/ja active Active
- 2022-09-01 US US18/685,551 patent/US20240350489A1/en active Pending
- 2022-09-01 CA CA3229887A patent/CA3229887A1/en active Pending
- 2022-09-01 KR KR1020247010451A patent/KR20240055038A/ko active Pending
- 2022-09-01 AU AU2022337087A patent/AU2022337087A1/en active Pending
- 2022-09-01 TW TW111133216A patent/TW202310841A/zh unknown
- 2022-09-01 WO PCT/IB2022/058205 patent/WO2023031840A1/en not_active Ceased
- 2022-09-01 EP EP22777001.3A patent/EP4395779A1/en active Pending
- 2022-09-01 IL IL310975A patent/IL310975A/en unknown
- 2022-09-01 MX MX2024002581A patent/MX2024002581A/es unknown
-
2024
- 2024-09-26 JP JP2024167085A patent/JP2024178420A/ja active Pending
Also Published As
| Publication number | Publication date |
|---|---|
| JP7564347B2 (ja) | 2024-10-08 |
| US20240350489A1 (en) | 2024-10-24 |
| JP2023542878A (ja) | 2023-10-12 |
| JP2024178420A (ja) | 2024-12-24 |
| EP4395779A1 (en) | 2024-07-10 |
| KR20240055038A (ko) | 2024-04-26 |
| IL310975A (en) | 2024-04-01 |
| CA3229887A1 (en) | 2023-03-09 |
| WO2023031840A1 (en) | 2023-03-09 |
| MX2024002581A (es) | 2024-03-20 |
| AU2022337087A1 (en) | 2024-03-14 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| TW202310841A (zh) | 用於治療多發性硬化症之ｌｏｕ０６４ | |
| JP6887212B2 (ja) | Ｉｌ−３１アンタゴニストを有効成分として含有する、アトピー性皮膚炎の予防用及び／又は治療用医薬組成物 | |
| TW202140002A (zh) | 用於復發型多發性硬化症的治療性酪胺酸激酶抑制劑 | |
| US20240059783A1 (en) | Anti-ox40 antagonistic antibodies and dosage for the treatment of ox40-mediated disorders | |
| D’Amico et al. | Oral drugs in multiple sclerosis therapy: an overview and a critical appraisal | |
| EP3864053B1 (en) | Treatment of rms by switching therapy | |
| JP2024516698A (ja) | Ｉｌｔ７結合タンパク質を使用する、自己免疫疾患の治療方法 | |
| TW202133877A (zh) | 全身性紅斑狼瘡中之ｉ型干擾素抑制 | |
| TW202304513A (zh) | 用於治療亞洲患者之ms之奧法木單抗(ofatumumab) | |
| EP4707302A2 (en) | Ofatumumab for treating ms while maintaining serum igg | |
| US20250032488A1 (en) | Methods of treatment using lou064 | |
| EA051716B1 (ru) | Lou064 для лечения рассеянного склероза | |
| CN118019540A (zh) | 用于治疗多发性硬化的lou064 | |
| JP7784995B2 (ja) | （ｒ）－２－［３－［４－アミノ－３－（２－フルオロ－４－フェノキシ－フェニル）ピラゾロ［３，４－ｄ］ピリミジン－１－イル］ピペリジン－１－カルボニル］－４－メチル－４－［４－（オキセタン－３－イル）ピペラジン－１－イル］ペンタ－２－エンニトリルを投与することによる天疱瘡を処置する方法 | |
| IL315866A (en) | Tyk2 inhibitors and uses thereof | |
| JP2024518410A (ja) | 重症筋無力症を治療するための抗ｃｄ１９抗体の使用 | |
| US12570664B2 (en) | Processes for the preparation of (3S,4R)-3-ethyl-4-(3H-imidazo[1,2-α]pyrrolo[2,3-e]-pyrazin-8-yl)-N-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide and solid state forms thereof | |
| JP2022502441A (ja) | Ｃｃｒ３阻害剤を用いて、加齢性機能障害を治療するための方法および組成物 | |
| US20230338356A1 (en) | Treatment of autoimmune skin disease | |
| TWI922445B (zh) | 藉由投予(R)-2-[3-[4-胺基-3-(2-氟-4-苯氧基-苯基)吡唑并[3,4-d]嘧啶-1-基]哌啶-1-羰基]-4-甲基-4-[4-(氧呾-3-基)哌-1-基]戊-2-烯腈治療天皰瘡之方法 | |
| CN117561076A (zh) | 使用ilt7结合蛋白治疗自体免疫病症的方法 | |
| JP2024518787A (ja) | 全身型重症筋無力症の処置のための補体因子ｄ阻害剤の使用 | |
| CN121335699A (zh) | 使用布雷泊替尼治疗皮肌炎的方法 | |
| HK40051003B (en) | Treatment of rms by switching therapy | |
| HK40051003A (en) | Treatment of rms by switching therapy |