TW201825090A - 增強免疫反應之方法 - Google Patents
增強免疫反應之方法 Download PDFInfo
- Publication number
- TW201825090A TW201825090A TW106140519A TW106140519A TW201825090A TW 201825090 A TW201825090 A TW 201825090A TW 106140519 A TW106140519 A TW 106140519A TW 106140519 A TW106140519 A TW 106140519A TW 201825090 A TW201825090 A TW 201825090A
- Authority
- TW
- Taiwan
- Prior art keywords
- acceptable salt
- pharmaceutically acceptable
- bez235
- rad001
- combination
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims abstract description 99
- 230000028993 immune response Effects 0.000 title claims abstract description 59
- 230000002708 enhancing effect Effects 0.000 title abstract description 19
- JOGKUKXHTYWRGZ-UHFFFAOYSA-N dactolisib Chemical compound O=C1N(C)C2=CN=C3C=CC(C=4C=C5C=CC=CC5=NC=4)=CC3=C2N1C1=CC=C(C(C)(C)C#N)C=C1 JOGKUKXHTYWRGZ-UHFFFAOYSA-N 0.000 claims description 233
- 229950006418 dactolisib Drugs 0.000 claims description 227
- 150000003839 salts Chemical class 0.000 claims description 191
- 239000003814 drug Substances 0.000 claims description 87
- 208000015181 infectious disease Diseases 0.000 claims description 73
- 238000011282 treatment Methods 0.000 claims description 65
- 206010057190 Respiratory tract infections Diseases 0.000 claims description 51
- 230000032683 aging Effects 0.000 claims description 51
- 108090000623 proteins and genes Proteins 0.000 claims description 40
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 31
- 238000009097 single-agent therapy Methods 0.000 claims description 26
- 201000010099 disease Diseases 0.000 claims description 25
- HKVAMNSJSFKALM-GKUWKFKPSA-N Everolimus Chemical compound C1C[C@@H](OCCO)[C@H](OC)C[C@@H]1C[C@@H](C)[C@H]1OC(=O)[C@@H]2CCCCN2C(=O)C(=O)[C@](O)(O2)[C@H](C)CC[C@H]2C[C@H](OC)/C(C)=C/C=C/C=C/[C@@H](C)C[C@@H](C)C(=O)[C@H](OC)[C@H](O)/C(C)=C/[C@@H](C)C(=O)C1 HKVAMNSJSFKALM-GKUWKFKPSA-N 0.000 claims description 21
- 108010037362 Extracellular Matrix Proteins Proteins 0.000 claims description 20
- 102000010834 Extracellular Matrix Proteins Human genes 0.000 claims description 20
- 229960005167 everolimus Drugs 0.000 claims description 20
- 210000002744 extracellular matrix Anatomy 0.000 claims description 19
- 238000007634 remodeling Methods 0.000 claims description 19
- 230000001105 regulatory effect Effects 0.000 claims description 16
- 102000014150 Interferons Human genes 0.000 claims description 15
- 108010050904 Interferons Proteins 0.000 claims description 15
- 229940079322 interferon Drugs 0.000 claims description 15
- 206010019280 Heart failures Diseases 0.000 claims description 13
- 230000001771 impaired effect Effects 0.000 claims description 12
- 239000000427 antigen Substances 0.000 claims description 11
- 102000036639 antigens Human genes 0.000 claims description 11
- 108091007433 antigens Proteins 0.000 claims description 11
- 230000015788 innate immune response Effects 0.000 claims description 10
- 102000004169 proteins and genes Human genes 0.000 claims description 10
- 230000036039 immunity Effects 0.000 claims description 9
- 208000036142 Viral infection Diseases 0.000 claims description 8
- 230000009385 viral infection Effects 0.000 claims description 8
- 230000002159 abnormal effect Effects 0.000 claims description 7
- 238000002648 combination therapy Methods 0.000 claims description 7
- 206010061598 Immunodeficiency Diseases 0.000 claims description 6
- 230000004064 dysfunction Effects 0.000 claims description 6
- 208000020832 chronic kidney disease Diseases 0.000 claims description 5
- 208000022831 chronic renal failure syndrome Diseases 0.000 claims description 5
- 230000007935 neutral effect Effects 0.000 claims description 5
- 230000009759 skin aging Effects 0.000 claims description 4
- 201000001320 Atherosclerosis Diseases 0.000 claims description 3
- 208000007342 Diabetic Nephropathies Diseases 0.000 claims description 3
- 206010051920 Glomerulonephropathy Diseases 0.000 claims description 3
- 201000009794 Idiopathic Pulmonary Fibrosis Diseases 0.000 claims description 3
- 208000034189 Sclerosis Diseases 0.000 claims description 3
- 206010003246 arthritis Diseases 0.000 claims description 3
- 230000008499 blood brain barrier function Effects 0.000 claims description 3
- 210000001218 blood-brain barrier Anatomy 0.000 claims description 3
- 208000019425 cirrhosis of liver Diseases 0.000 claims description 3
- 208000033679 diabetic kidney disease Diseases 0.000 claims description 3
- 208000036971 interstitial lung disease 2 Diseases 0.000 claims description 3
- 206010028537 myelofibrosis Diseases 0.000 claims description 3
- 206010053219 non-alcoholic steatohepatitis Diseases 0.000 claims description 3
- 201000008482 osteoarthritis Diseases 0.000 claims description 3
- 208000005069 pulmonary fibrosis Diseases 0.000 claims description 3
- 208000001076 sarcopenia Diseases 0.000 claims description 3
- 210000002435 tendon Anatomy 0.000 claims description 3
- 208000000143 urethritis Diseases 0.000 claims description 3
- 230000029663 wound healing Effects 0.000 claims description 3
- 201000003793 Myelodysplastic syndrome Diseases 0.000 claims description 2
- 206010048685 Oral infection Diseases 0.000 claims 1
- 201000001245 periodontitis Diseases 0.000 claims 1
- 238000013456 study Methods 0.000 description 81
- 229960002930 sirolimus Drugs 0.000 description 73
- 229940079593 drug Drugs 0.000 description 50
- QFJCIRLUMZQUOT-HPLJOQBZSA-N sirolimus Chemical compound C1C[C@@H](O)[C@H](OC)C[C@@H]1C[C@@H](C)[C@H]1OC(=O)[C@@H]2CCCCN2C(=O)C(=O)[C@](O)(O2)[C@H](C)CC[C@H]2C[C@H](OC)/C(C)=C/C=C/C=C/[C@@H](C)C[C@@H](C)C(=O)[C@H](OC)[C@H](O)/C(C)=C/[C@@H](C)C(=O)C1 QFJCIRLUMZQUOT-HPLJOQBZSA-N 0.000 description 44
- 229940124302 mTOR inhibitor Drugs 0.000 description 41
- 239000003628 mammalian target of rapamycin inhibitor Substances 0.000 description 41
- 230000002354 daily effect Effects 0.000 description 39
- 102000013530 TOR Serine-Threonine Kinases Human genes 0.000 description 38
- 108010065917 TOR Serine-Threonine Kinases Proteins 0.000 description 38
- 230000000694 effects Effects 0.000 description 28
- 230000005764 inhibitory process Effects 0.000 description 28
- ZAHRKKWIAAJSAO-UHFFFAOYSA-N rapamycin Natural products COCC(O)C(=C/C(C)C(=O)CC(OC(=O)C1CCCCN1C(=O)C(=O)C2(O)OC(CC(OC)C(=CC=CC=CC(C)CC(C)C(=O)C)C)CCC2C)C(C)CC3CCC(O)C(C3)OC)C ZAHRKKWIAAJSAO-UHFFFAOYSA-N 0.000 description 28
- 102000008135 Mechanistic Target of Rapamycin Complex 1 Human genes 0.000 description 27
- 108010035196 Mechanistic Target of Rapamycin Complex 1 Proteins 0.000 description 27
- 239000000902 placebo Substances 0.000 description 26
- 229940068196 placebo Drugs 0.000 description 26
- 229940124597 therapeutic agent Drugs 0.000 description 25
- 210000001744 T-lymphocyte Anatomy 0.000 description 22
- 208000024891 symptom Diseases 0.000 description 20
- 210000004369 blood Anatomy 0.000 description 19
- 239000008280 blood Substances 0.000 description 19
- 206010022000 influenza Diseases 0.000 description 18
- 230000001737 promoting effect Effects 0.000 description 18
- 238000002255 vaccination Methods 0.000 description 18
- -1 ICOS Proteins 0.000 description 17
- 238000004458 analytical method Methods 0.000 description 17
- 150000001875 compounds Chemical class 0.000 description 17
- 241000700605 Viruses Species 0.000 description 16
- 229960003971 influenza vaccine Drugs 0.000 description 16
- 210000004027 cell Anatomy 0.000 description 15
- 239000002552 dosage form Substances 0.000 description 15
- 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 description 14
- 102000009308 Mechanistic Target of Rapamycin Complex 2 Human genes 0.000 description 14
- 108010034057 Mechanistic Target of Rapamycin Complex 2 Proteins 0.000 description 14
- 230000036737 immune function Effects 0.000 description 14
- 239000000203 mixture Substances 0.000 description 14
- 239000008194 pharmaceutical composition Substances 0.000 description 14
- 230000004044 response Effects 0.000 description 14
- 230000007423 decrease Effects 0.000 description 12
- 230000014509 gene expression Effects 0.000 description 12
- 230000002829 reductive effect Effects 0.000 description 12
- 239000003795 chemical substances by application Substances 0.000 description 11
- 244000052769 pathogen Species 0.000 description 11
- 241000282414 Homo sapiens Species 0.000 description 10
- 102100024908 Ribosomal protein S6 kinase beta-1 Human genes 0.000 description 10
- 101710108924 Ribosomal protein S6 kinase beta-1 Proteins 0.000 description 10
- 238000011156 evaluation Methods 0.000 description 10
- 230000006870 function Effects 0.000 description 10
- 238000012360 testing method Methods 0.000 description 10
- 230000001717 pathogenic effect Effects 0.000 description 9
- 208000000059 Dyspnea Diseases 0.000 description 8
- 206010013975 Dyspnoeas Diseases 0.000 description 8
- 206010062106 Respiratory tract infection viral Diseases 0.000 description 8
- 239000004480 active ingredient Substances 0.000 description 8
- 230000003197 catalytic effect Effects 0.000 description 8
- 230000008859 change Effects 0.000 description 8
- 230000003247 decreasing effect Effects 0.000 description 8
- 230000037361 pathway Effects 0.000 description 8
- 230000026731 phosphorylation Effects 0.000 description 8
- 238000006366 phosphorylation reaction Methods 0.000 description 8
- 235000018102 proteins Nutrition 0.000 description 8
- 230000009467 reduction Effects 0.000 description 8
- 238000011160 research Methods 0.000 description 8
- 230000000241 respiratory effect Effects 0.000 description 8
- 206010007559 Cardiac failure congestive Diseases 0.000 description 7
- 230000009286 beneficial effect Effects 0.000 description 7
- 238000012216 screening Methods 0.000 description 7
- 208000001072 type 2 diabetes mellitus Diseases 0.000 description 7
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 6
- 241000699670 Mus sp. Species 0.000 description 6
- 206010028980 Neoplasm Diseases 0.000 description 6
- 206010035664 Pneumonia Diseases 0.000 description 6
- 206010006451 bronchitis Diseases 0.000 description 6
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 6
- 239000003112 inhibitor Substances 0.000 description 6
- 230000002401 inhibitory effect Effects 0.000 description 6
- 210000003071 memory t lymphocyte Anatomy 0.000 description 6
- 210000002966 serum Anatomy 0.000 description 6
- 230000001225 therapeutic effect Effects 0.000 description 6
- 206010006458 Bronchitis chronic Diseases 0.000 description 5
- 241000124008 Mammalia Species 0.000 description 5
- 238000003559 RNA-seq method Methods 0.000 description 5
- 208000006673 asthma Diseases 0.000 description 5
- 201000011510 cancer Diseases 0.000 description 5
- 208000007451 chronic bronchitis Diseases 0.000 description 5
- 230000036541 health Effects 0.000 description 5
- 210000002865 immune cell Anatomy 0.000 description 5
- 230000000474 nursing effect Effects 0.000 description 5
- 230000001681 protective effect Effects 0.000 description 5
- 239000000126 substance Substances 0.000 description 5
- 108010013238 70-kDa Ribosomal Protein S6 Kinases Proteins 0.000 description 4
- 206010011224 Cough Diseases 0.000 description 4
- 241000282412 Homo Species 0.000 description 4
- 102100027913 Peptidyl-prolyl cis-trans isomerase FKBP1A Human genes 0.000 description 4
- 230000003712 anti-aging effect Effects 0.000 description 4
- 239000011230 binding agent Substances 0.000 description 4
- 230000033228 biological regulation Effects 0.000 description 4
- 239000000090 biomarker Substances 0.000 description 4
- 239000002775 capsule Substances 0.000 description 4
- 239000001913 cellulose Substances 0.000 description 4
- 230000001684 chronic effect Effects 0.000 description 4
- 239000012050 conventional carrier Substances 0.000 description 4
- 238000013461 design Methods 0.000 description 4
- 238000003745 diagnosis Methods 0.000 description 4
- 239000007884 disintegrant Substances 0.000 description 4
- 238000001647 drug administration Methods 0.000 description 4
- 210000000987 immune system Anatomy 0.000 description 4
- 230000006872 improvement Effects 0.000 description 4
- 230000007774 longterm Effects 0.000 description 4
- 239000000314 lubricant Substances 0.000 description 4
- 238000002360 preparation method Methods 0.000 description 4
- 230000011664 signaling Effects 0.000 description 4
- 239000000758 substrate Substances 0.000 description 4
- 230000002195 synergetic effect Effects 0.000 description 4
- 102000055501 telomere Human genes 0.000 description 4
- 108091035539 telomere Proteins 0.000 description 4
- 210000003411 telomere Anatomy 0.000 description 4
- 238000002560 therapeutic procedure Methods 0.000 description 4
- 230000014616 translation Effects 0.000 description 4
- 208000019206 urinary tract infection Diseases 0.000 description 4
- 229920002785 Croscarmellose sodium Polymers 0.000 description 3
- 241000709661 Enterovirus Species 0.000 description 3
- 208000005176 Hepatitis C Diseases 0.000 description 3
- 101000971533 Homo sapiens Killer cell lectin-like receptor subfamily G member 1 Proteins 0.000 description 3
- 102100021457 Killer cell lectin-like receptor subfamily G member 1 Human genes 0.000 description 3
- 208000019693 Lung disease Diseases 0.000 description 3
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 3
- 206010036790 Productive cough Diseases 0.000 description 3
- 229920002472 Starch Polymers 0.000 description 3
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 3
- 108010006877 Tacrolimus Binding Protein 1A Proteins 0.000 description 3
- CBPNZQVSJQDFBE-FUXHJELOSA-N Temsirolimus Chemical compound C1C[C@@H](OC(=O)C(C)(CO)CO)[C@H](OC)C[C@@H]1C[C@@H](C)[C@H]1OC(=O)[C@@H]2CCCCN2C(=O)C(=O)[C@](O)(O2)[C@H](C)CC[C@H]2C[C@H](OC)/C(C)=C/C=C/C=C/[C@@H](C)C[C@@H](C)C(=O)[C@H](OC)[C@H](O)/C(C)=C/[C@@H](C)C(=O)C1 CBPNZQVSJQDFBE-FUXHJELOSA-N 0.000 description 3
- 230000000735 allogeneic effect Effects 0.000 description 3
- 238000013459 approach Methods 0.000 description 3
- 210000003719 b-lymphocyte Anatomy 0.000 description 3
- 230000008901 benefit Effects 0.000 description 3
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 3
- 230000001419 dependent effect Effects 0.000 description 3
- 239000003085 diluting agent Substances 0.000 description 3
- 208000035475 disorder Diseases 0.000 description 3
- 238000005516 engineering process Methods 0.000 description 3
- 239000000945 filler Substances 0.000 description 3
- 239000007903 gelatin capsule Substances 0.000 description 3
- 239000003102 growth factor Substances 0.000 description 3
- 230000004217 heart function Effects 0.000 description 3
- 210000003958 hematopoietic stem cell Anatomy 0.000 description 3
- 238000000338 in vitro Methods 0.000 description 3
- 238000001727 in vivo Methods 0.000 description 3
- 210000004698 lymphocyte Anatomy 0.000 description 3
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 3
- 239000008108 microcrystalline cellulose Substances 0.000 description 3
- 229940016286 microcrystalline cellulose Drugs 0.000 description 3
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 3
- 235000015097 nutrients Nutrition 0.000 description 3
- 239000006186 oral dosage form Substances 0.000 description 3
- 238000007911 parenteral administration Methods 0.000 description 3
- 239000000546 pharmaceutical excipient Substances 0.000 description 3
- 239000002243 precursor Substances 0.000 description 3
- 238000011002 quantification Methods 0.000 description 3
- 238000012552 review Methods 0.000 description 3
- 238000005070 sampling Methods 0.000 description 3
- 230000001932 seasonal effect Effects 0.000 description 3
- 230000009758 senescence Effects 0.000 description 3
- 241000894007 species Species 0.000 description 3
- 208000024794 sputum Diseases 0.000 description 3
- 210000003802 sputum Anatomy 0.000 description 3
- 239000008107 starch Substances 0.000 description 3
- 235000019698 starch Nutrition 0.000 description 3
- 229960000235 temsirolimus Drugs 0.000 description 3
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 3
- 241000701161 unidentified adenovirus Species 0.000 description 3
- 208000030507 AIDS Diseases 0.000 description 2
- 102100021569 Apoptosis regulator Bcl-2 Human genes 0.000 description 2
- 108091012583 BCL2 Proteins 0.000 description 2
- 102100027207 CD27 antigen Human genes 0.000 description 2
- 102000008203 CTLA-4 Antigen Human genes 0.000 description 2
- 108010021064 CTLA-4 Antigen Proteins 0.000 description 2
- 229940045513 CTLA4 antagonist Drugs 0.000 description 2
- 208000035473 Communicable disease Diseases 0.000 description 2
- 206010010356 Congenital anomaly Diseases 0.000 description 2
- 102100021260 Galactosylgalactosylxylosylprotein 3-beta-glucuronosyltransferase 1 Human genes 0.000 description 2
- 206010018785 Gingival infections Diseases 0.000 description 2
- 102000006395 Globulins Human genes 0.000 description 2
- 108010044091 Globulins Proteins 0.000 description 2
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 2
- 102100034458 Hepatitis A virus cellular receptor 2 Human genes 0.000 description 2
- 101000914511 Homo sapiens CD27 antigen Proteins 0.000 description 2
- 101000894906 Homo sapiens Galactosylgalactosylxylosylprotein 3-beta-glucuronosyltransferase 1 Proteins 0.000 description 2
- 101001068133 Homo sapiens Hepatitis A virus cellular receptor 2 Proteins 0.000 description 2
- 101001018097 Homo sapiens L-selectin Proteins 0.000 description 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 2
- 102000002227 Interferon Type I Human genes 0.000 description 2
- 108010014726 Interferon Type I Proteins 0.000 description 2
- 102100033467 L-selectin Human genes 0.000 description 2
- 102000017578 LAG3 Human genes 0.000 description 2
- 101150030213 Lag3 gene Proteins 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- 101150097381 Mtor gene Proteins 0.000 description 2
- 101100087591 Mus musculus Rictor gene Proteins 0.000 description 2
- 241000714209 Norwalk virus Species 0.000 description 2
- 208000002606 Paramyxoviridae Infections Diseases 0.000 description 2
- 102100023085 Serine/threonine-protein kinase mTOR Human genes 0.000 description 2
- 241000187391 Streptomyces hygroscopicus Species 0.000 description 2
- 229930006000 Sucrose Natural products 0.000 description 2
- 230000024932 T cell mediated immunity Effects 0.000 description 2
- 206010048762 Tooth infection Diseases 0.000 description 2
- 206010046306 Upper respiratory tract infection Diseases 0.000 description 2
- 230000005856 abnormality Effects 0.000 description 2
- 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 2
- 230000004913 activation Effects 0.000 description 2
- 239000002671 adjuvant Substances 0.000 description 2
- 230000003281 allosteric effect Effects 0.000 description 2
- 244000052616 bacterial pathogen Species 0.000 description 2
- 238000003287 bathing Methods 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 239000000969 carrier Substances 0.000 description 2
- 235000010980 cellulose Nutrition 0.000 description 2
- 229920002678 cellulose Polymers 0.000 description 2
- 229960001681 croscarmellose sodium Drugs 0.000 description 2
- 235000010947 crosslinked sodium carboxy methyl cellulose Nutrition 0.000 description 2
- 230000034994 death Effects 0.000 description 2
- 231100000517 death Toxicity 0.000 description 2
- 230000007812 deficiency Effects 0.000 description 2
- 210000004443 dendritic cell Anatomy 0.000 description 2
- 239000008121 dextrose Substances 0.000 description 2
- 230000035487 diastolic blood pressure Effects 0.000 description 2
- 239000008298 dragée Substances 0.000 description 2
- 239000003937 drug carrier Substances 0.000 description 2
- 230000009977 dual effect Effects 0.000 description 2
- 238000002592 echocardiography Methods 0.000 description 2
- 238000010201 enrichment analysis Methods 0.000 description 2
- 238000010195 expression analysis Methods 0.000 description 2
- 230000035558 fertility Effects 0.000 description 2
- 230000004927 fusion Effects 0.000 description 2
- 150000004676 glycans Chemical class 0.000 description 2
- 230000013595 glycosylation Effects 0.000 description 2
- 238000006206 glycosylation reaction Methods 0.000 description 2
- 230000012010 growth Effects 0.000 description 2
- 230000035931 haemagglutination Effects 0.000 description 2
- 208000005252 hepatitis A Diseases 0.000 description 2
- 208000002672 hepatitis B Diseases 0.000 description 2
- 230000006698 induction Effects 0.000 description 2
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 2
- 230000003993 interaction Effects 0.000 description 2
- 230000003834 intracellular effect Effects 0.000 description 2
- 230000033001 locomotion Effects 0.000 description 2
- 210000004072 lung Anatomy 0.000 description 2
- 239000003120 macrolide antibiotic agent Substances 0.000 description 2
- 210000002540 macrophage 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
- 238000004519 manufacturing process Methods 0.000 description 2
- 230000007246 mechanism Effects 0.000 description 2
- 230000001404 mediated effect Effects 0.000 description 2
- 108020004999 messenger RNA Proteins 0.000 description 2
- 210000000822 natural killer cell Anatomy 0.000 description 2
- 230000008518 non respiratory effect Effects 0.000 description 2
- 238000009806 oophorectomy Methods 0.000 description 2
- 229920001282 polysaccharide Polymers 0.000 description 2
- 239000005017 polysaccharide Substances 0.000 description 2
- 229920003124 powdered cellulose Polymers 0.000 description 2
- 235000019814 powdered cellulose Nutrition 0.000 description 2
- 230000002265 prevention Effects 0.000 description 2
- 210000001948 pro-b lymphocyte Anatomy 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 239000000651 prodrug Substances 0.000 description 2
- 229940002612 prodrug Drugs 0.000 description 2
- 230000035755 proliferation Effects 0.000 description 2
- 230000001850 reproductive effect Effects 0.000 description 2
- 208000020029 respiratory tract infectious disease Diseases 0.000 description 2
- 230000002441 reversible effect Effects 0.000 description 2
- 229960001302 ridaforolimus Drugs 0.000 description 2
- 231100000279 safety data Toxicity 0.000 description 2
- 208000013220 shortness of breath Diseases 0.000 description 2
- 230000000391 smoking effect Effects 0.000 description 2
- 238000006467 substitution reaction Methods 0.000 description 2
- 239000005720 sucrose Substances 0.000 description 2
- 230000035488 systolic blood pressure Effects 0.000 description 2
- 239000003826 tablet Substances 0.000 description 2
- 239000000454 talc Substances 0.000 description 2
- 235000012222 talc Nutrition 0.000 description 2
- 229910052623 talc Inorganic materials 0.000 description 2
- 229940033134 talc Drugs 0.000 description 2
- QFJCIRLUMZQUOT-UHFFFAOYSA-N temsirolimus Natural products C1CC(O)C(OC)CC1CC(C)C1OC(=O)C2CCCCN2C(=O)C(=O)C(O)(O2)C(C)CCC2CC(OC)C(C)=CC=CC=CC(C)CC(C)C(=O)C(OC)C(O)C(C)=CC(C)C(=O)C1 QFJCIRLUMZQUOT-UHFFFAOYSA-N 0.000 description 2
- 210000001519 tissue Anatomy 0.000 description 2
- 231100000419 toxicity Toxicity 0.000 description 2
- 230000001988 toxicity Effects 0.000 description 2
- 238000013519 translation Methods 0.000 description 2
- 241000712461 unidentified influenza virus Species 0.000 description 2
- 230000003827 upregulation Effects 0.000 description 2
- 229960005486 vaccine Drugs 0.000 description 2
- 244000052613 viral pathogen Species 0.000 description 2
- 230000003612 virological effect Effects 0.000 description 2
- NWXMGUDVXFXRIG-WESIUVDSSA-N (4s,4as,5as,6s,12ar)-4-(dimethylamino)-1,6,10,11,12a-pentahydroxy-6-methyl-3,12-dioxo-4,4a,5,5a-tetrahydrotetracene-2-carboxamide Chemical compound C1=CC=C2[C@](O)(C)[C@H]3C[C@H]4[C@H](N(C)C)C(=O)C(C(N)=O)=C(O)[C@@]4(O)C(=O)C3=C(O)C2=C1O NWXMGUDVXFXRIG-WESIUVDSSA-N 0.000 description 1
- 125000000022 2-aminoethyl group Chemical group [H]C([*])([H])C([H])([H])N([H])[H] 0.000 description 1
- 125000004200 2-methoxyethyl group Chemical group [H]C([H])([H])OC([H])([H])C([H])([H])* 0.000 description 1
- 125000001494 2-propynyl group Chemical group [H]C#CC([H])([H])* 0.000 description 1
- FHVDTGUDJYJELY-UHFFFAOYSA-N 6-{[2-carboxy-4,5-dihydroxy-6-(phosphanyloxy)oxan-3-yl]oxy}-4,5-dihydroxy-3-phosphanyloxane-2-carboxylic acid Chemical compound O1C(C(O)=O)C(P)C(O)C(O)C1OC1C(C(O)=O)OC(OP)C(O)C1O FHVDTGUDJYJELY-UHFFFAOYSA-N 0.000 description 1
- 101001082110 Acanthamoeba polyphaga mimivirus Eukaryotic translation initiation factor 4E homolog Proteins 0.000 description 1
- 241000589291 Acinetobacter Species 0.000 description 1
- 102000007469 Actins Human genes 0.000 description 1
- 108010085238 Actins Proteins 0.000 description 1
- 230000007730 Akt signaling Effects 0.000 description 1
- 108700028369 Alleles Proteins 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- 201000000736 Amenorrhea Diseases 0.000 description 1
- 206010001928 Amenorrhoea Diseases 0.000 description 1
- 229930195573 Amycin Natural products 0.000 description 1
- 206010002383 Angina Pectoris Diseases 0.000 description 1
- 241000228212 Aspergillus Species 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- 241000335423 Blastomyces Species 0.000 description 1
- 241000124740 Bocaparvovirus Species 0.000 description 1
- 206010065553 Bone marrow failure Diseases 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- 241000222120 Candida <Saccharomycetales> Species 0.000 description 1
- 241000282472 Canis lupus familiaris Species 0.000 description 1
- 241000283707 Capra Species 0.000 description 1
- 101710167800 Capsid assembly scaffolding protein Proteins 0.000 description 1
- 201000006082 Chickenpox Diseases 0.000 description 1
- 241001502567 Chikungunya virus Species 0.000 description 1
- 241000606161 Chlamydia Species 0.000 description 1
- 241000223203 Coccidioides Species 0.000 description 1
- 102000008186 Collagen Human genes 0.000 description 1
- 108010035532 Collagen Proteins 0.000 description 1
- 241000711573 Coronaviridae Species 0.000 description 1
- 241001337994 Cryptococcus <scale insect> Species 0.000 description 1
- 241000701022 Cytomegalovirus Species 0.000 description 1
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
- WQZGKKKJIJFFOK-QTVWNMPRSA-N D-mannopyranose Chemical compound OC[C@H]1OC(O)[C@@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-QTVWNMPRSA-N 0.000 description 1
- 101001082109 Danio rerio Eukaryotic translation initiation factor 4E-1B Proteins 0.000 description 1
- 241000725619 Dengue virus Species 0.000 description 1
- 229920002307 Dextran Polymers 0.000 description 1
- 239000004375 Dextrin Substances 0.000 description 1
- 229920001353 Dextrin Polymers 0.000 description 1
- 206010061818 Disease progression Diseases 0.000 description 1
- 241001115402 Ebolavirus Species 0.000 description 1
- 206010014561 Emphysema Diseases 0.000 description 1
- 241000588914 Enterobacter Species 0.000 description 1
- 241000991587 Enterovirus C Species 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 241000283086 Equidae Species 0.000 description 1
- 241000588724 Escherichia coli Species 0.000 description 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 1
- 102000008968 Eukaryotic translation initiation factor 4E-binding protein 1 Human genes 0.000 description 1
- 108050000946 Eukaryotic translation initiation factor 4E-binding protein 1 Proteins 0.000 description 1
- 229940124602 FDA-approved drug Drugs 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 244000068988 Glycine max Species 0.000 description 1
- 235000010469 Glycine max Nutrition 0.000 description 1
- 108090000288 Glycoproteins Proteins 0.000 description 1
- 102000003886 Glycoproteins Human genes 0.000 description 1
- 102100020948 Growth hormone receptor Human genes 0.000 description 1
- 101710099093 Growth hormone receptor Proteins 0.000 description 1
- 229920002907 Guar gum Polymers 0.000 description 1
- 241000606790 Haemophilus Species 0.000 description 1
- 206010061192 Haemorrhagic fever Diseases 0.000 description 1
- 108010034145 Helminth Proteins Proteins 0.000 description 1
- 101001060744 Homo sapiens Peptidyl-prolyl cis-trans isomerase FKBP1A Proteins 0.000 description 1
- 101001059454 Homo sapiens Serine/threonine-protein kinase MARK2 Proteins 0.000 description 1
- 241000700588 Human alphaherpesvirus 1 Species 0.000 description 1
- 241000701074 Human alphaherpesvirus 2 Species 0.000 description 1
- 241000701044 Human gammaherpesvirus 4 Species 0.000 description 1
- 241001502974 Human gammaherpesvirus 8 Species 0.000 description 1
- 241000701806 Human papillomavirus Species 0.000 description 1
- 229920000663 Hydroxyethyl cellulose Polymers 0.000 description 1
- 239000004354 Hydroxyethyl cellulose Substances 0.000 description 1
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 description 1
- 208000035150 Hypercholesterolemia Diseases 0.000 description 1
- 206010020751 Hypersensitivity Diseases 0.000 description 1
- 208000029462 Immunodeficiency disease Diseases 0.000 description 1
- 206010062016 Immunosuppression Diseases 0.000 description 1
- 102000004877 Insulin Human genes 0.000 description 1
- 108090001061 Insulin Proteins 0.000 description 1
- 206010022489 Insulin Resistance Diseases 0.000 description 1
- 208000029523 Interstitial Lung disease Diseases 0.000 description 1
- 208000008839 Kidney Neoplasms Diseases 0.000 description 1
- 241000588748 Klebsiella Species 0.000 description 1
- 238000001276 Kolmogorov–Smirnov test Methods 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- 241000589248 Legionella Species 0.000 description 1
- 208000007764 Legionnaires' Disease Diseases 0.000 description 1
- 241000222722 Leishmania <genus> Species 0.000 description 1
- 241000186781 Listeria Species 0.000 description 1
- 241000712079 Measles morbillivirus Species 0.000 description 1
- 201000009906 Meningitis Diseases 0.000 description 1
- 229920003091 Methocel™ Polymers 0.000 description 1
- 108010006519 Molecular Chaperones Proteins 0.000 description 1
- 102000005431 Molecular Chaperones Human genes 0.000 description 1
- 241000588621 Moraxella Species 0.000 description 1
- 241000711386 Mumps virus Species 0.000 description 1
- 241000186359 Mycobacterium Species 0.000 description 1
- WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 description 1
- 241000588653 Neisseria Species 0.000 description 1
- 206010061876 Obstruction Diseases 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 102000038030 PI3Ks Human genes 0.000 description 1
- 108091007960 PI3Ks Proteins 0.000 description 1
- 102100035593 POU domain, class 2, transcription factor 1 Human genes 0.000 description 1
- 101710084414 POU domain, class 2, transcription factor 1 Proteins 0.000 description 1
- 241000282320 Panthera leo Species 0.000 description 1
- 241001631646 Papillomaviridae Species 0.000 description 1
- 241001494479 Pecora Species 0.000 description 1
- 201000005702 Pertussis Diseases 0.000 description 1
- 108091000080 Phosphotransferase Proteins 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 241001272996 Polyphylla fullo Species 0.000 description 1
- 101710130420 Probable capsid assembly scaffolding protein Proteins 0.000 description 1
- 108091008611 Protein Kinase B Proteins 0.000 description 1
- 241000588769 Proteus <enterobacteria> Species 0.000 description 1
- 241000125945 Protoparvovirus Species 0.000 description 1
- 241000589516 Pseudomonas Species 0.000 description 1
- 238000002123 RNA extraction Methods 0.000 description 1
- 241000711798 Rabies lyssavirus Species 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- 206010038389 Renal cancer Diseases 0.000 description 1
- 108010000605 Ribosomal Proteins Proteins 0.000 description 1
- 102000002278 Ribosomal Proteins Human genes 0.000 description 1
- 241000607142 Salmonella Species 0.000 description 1
- 206010039491 Sarcoma Diseases 0.000 description 1
- 101710204410 Scaffold protein Proteins 0.000 description 1
- 241000242678 Schistosoma Species 0.000 description 1
- 102100028904 Serine/threonine-protein kinase MARK2 Human genes 0.000 description 1
- 241000607720 Serratia Species 0.000 description 1
- 241000607768 Shigella Species 0.000 description 1
- 208000032023 Signs and Symptoms Diseases 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- 241000580858 Simian-Human immunodeficiency virus Species 0.000 description 1
- 241000191940 Staphylococcus Species 0.000 description 1
- 241000194017 Streptococcus Species 0.000 description 1
- 241000282887 Suidae Species 0.000 description 1
- 108010017842 Telomerase Proteins 0.000 description 1
- 241000223996 Toxoplasma Species 0.000 description 1
- 238000010162 Tukey test Methods 0.000 description 1
- 206010046980 Varicella Diseases 0.000 description 1
- 208000027418 Wounds and injury Diseases 0.000 description 1
- 241000710772 Yellow fever virus Species 0.000 description 1
- 240000008042 Zea mays Species 0.000 description 1
- 235000005824 Zea mays ssp. parviglumis Nutrition 0.000 description 1
- 235000002017 Zea mays subsp mays Nutrition 0.000 description 1
- 241000907316 Zika virus Species 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 125000000738 acetamido group Chemical group [H]C([H])([H])C(=O)N([H])[*] 0.000 description 1
- VJHCJDRQFCCTHL-UHFFFAOYSA-N acetic acid 2,3,4,5,6-pentahydroxyhexanal Chemical compound CC(O)=O.OCC(O)C(O)C(O)C(O)C=O VJHCJDRQFCCTHL-UHFFFAOYSA-N 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 230000003044 adaptive effect Effects 0.000 description 1
- 230000033289 adaptive immune response Effects 0.000 description 1
- 230000004721 adaptive immunity Effects 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 230000000996 additive effect Effects 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 229940042992 afinitor Drugs 0.000 description 1
- 229940072056 alginate Drugs 0.000 description 1
- 235000010443 alginic acid Nutrition 0.000 description 1
- 229920000615 alginic acid Polymers 0.000 description 1
- 125000005133 alkynyloxy group Chemical group 0.000 description 1
- 231100000540 amenorrhea Toxicity 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 125000004103 aminoalkyl group Chemical group 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- 210000000612 antigen-presenting cell Anatomy 0.000 description 1
- 230000004900 autophagic degradation Effects 0.000 description 1
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- 230000002146 bilateral effect Effects 0.000 description 1
- 239000003124 biologic agent Substances 0.000 description 1
- 230000007321 biological mechanism Effects 0.000 description 1
- 230000008236 biological pathway Effects 0.000 description 1
- 238000001815 biotherapy Methods 0.000 description 1
- 210000000601 blood cell Anatomy 0.000 description 1
- 238000009534 blood test Methods 0.000 description 1
- 230000036760 body temperature Effects 0.000 description 1
- 210000001185 bone marrow Anatomy 0.000 description 1
- 229940124630 bronchodilator Drugs 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 239000001506 calcium phosphate Substances 0.000 description 1
- CJZGTCYPCWQAJB-UHFFFAOYSA-L calcium stearate Chemical compound [Ca+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O CJZGTCYPCWQAJB-UHFFFAOYSA-L 0.000 description 1
- 239000008116 calcium stearate Substances 0.000 description 1
- 235000013539 calcium stearate Nutrition 0.000 description 1
- 239000012876 carrier material Substances 0.000 description 1
- 230000032823 cell division Effects 0.000 description 1
- 230000003915 cell function Effects 0.000 description 1
- 230000010261 cell growth Effects 0.000 description 1
- 230000019522 cellular metabolic process Effects 0.000 description 1
- 230000010094 cellular senescence Effects 0.000 description 1
- 230000005754 cellular signaling Effects 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 238000002512 chemotherapy Methods 0.000 description 1
- 125000004803 chlorobenzyl group Chemical group 0.000 description 1
- 208000013116 chronic cough Diseases 0.000 description 1
- 239000004927 clay Substances 0.000 description 1
- 229920001436 collagen Polymers 0.000 description 1
- 229940075614 colloidal silicon dioxide Drugs 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 230000001010 compromised effect Effects 0.000 description 1
- 230000008094 contradictory effect Effects 0.000 description 1
- 238000010411 cooking Methods 0.000 description 1
- 235000005822 corn Nutrition 0.000 description 1
- 229960005168 croscarmellose Drugs 0.000 description 1
- 229960000913 crospovidone Drugs 0.000 description 1
- 229920006037 cross link polymer Polymers 0.000 description 1
- 239000001767 crosslinked sodium carboxy methyl cellulose Substances 0.000 description 1
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 210000004292 cytoskeleton Anatomy 0.000 description 1
- 210000001151 cytotoxic T lymphocyte Anatomy 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 230000006735 deficit Effects 0.000 description 1
- 230000007850 degeneration Effects 0.000 description 1
- 230000001934 delay Effects 0.000 description 1
- 230000006866 deterioration Effects 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 230000018109 developmental process Effects 0.000 description 1
- 235000019425 dextrin Nutrition 0.000 description 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- 235000005911 diet Nutrition 0.000 description 1
- 230000037213 diet Effects 0.000 description 1
- 230000009699 differential effect Effects 0.000 description 1
- 230000009274 differential gene expression Effects 0.000 description 1
- 230000004069 differentiation Effects 0.000 description 1
- GXGAKHNRMVGRPK-UHFFFAOYSA-N dimagnesium;dioxido-bis[[oxido(oxo)silyl]oxy]silane Chemical compound [Mg+2].[Mg+2].[O-][Si](=O)O[Si]([O-])([O-])O[Si]([O-])=O GXGAKHNRMVGRPK-UHFFFAOYSA-N 0.000 description 1
- 230000005750 disease progression Effects 0.000 description 1
- 231100000673 dose–response relationship Toxicity 0.000 description 1
- 239000000890 drug combination Substances 0.000 description 1
- 238000012377 drug delivery Methods 0.000 description 1
- 206010014599 encephalitis Diseases 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 125000004185 ester group Chemical group 0.000 description 1
- 235000019441 ethanol Nutrition 0.000 description 1
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 230000003203 everyday effect Effects 0.000 description 1
- 230000005713 exacerbation Effects 0.000 description 1
- 230000007717 exclusion Effects 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 235000013355 food flavoring agent Nutrition 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 244000053095 fungal pathogen Species 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
- 239000008187 granular material Substances 0.000 description 1
- 239000000665 guar gum Substances 0.000 description 1
- 235000010417 guar gum Nutrition 0.000 description 1
- 229960002154 guar gum Drugs 0.000 description 1
- 230000005802 health problem Effects 0.000 description 1
- 244000000013 helminth Species 0.000 description 1
- 230000013632 homeostatic process Effects 0.000 description 1
- 229940088597 hormone Drugs 0.000 description 1
- 239000005556 hormone Substances 0.000 description 1
- 230000004727 humoral immunity Effects 0.000 description 1
- 125000002768 hydroxyalkyl group Chemical group 0.000 description 1
- 235000019447 hydroxyethyl cellulose Nutrition 0.000 description 1
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 description 1
- 239000001863 hydroxypropyl cellulose Substances 0.000 description 1
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 1
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 1
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 1
- 229920003088 hydroxypropyl methyl cellulose Polymers 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
- 230000037417 hyperactivation Effects 0.000 description 1
- 201000001421 hyperglycemia Diseases 0.000 description 1
- 238000009802 hysterectomy Methods 0.000 description 1
- 239000012729 immediate-release (IR) formulation Substances 0.000 description 1
- 230000007813 immunodeficiency Effects 0.000 description 1
- 230000006054 immunological memory Effects 0.000 description 1
- 230000001506 immunosuppresive effect Effects 0.000 description 1
- 230000001976 improved effect Effects 0.000 description 1
- 230000002458 infectious effect Effects 0.000 description 1
- 230000000977 initiatory effect Effects 0.000 description 1
- 208000014674 injury Diseases 0.000 description 1
- 229940125396 insulin Drugs 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- 230000007794 irritation Effects 0.000 description 1
- 201000010982 kidney cancer Diseases 0.000 description 1
- 230000003907 kidney function Effects 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 230000003908 liver function Effects 0.000 description 1
- 238000011866 long-term treatment Methods 0.000 description 1
- 239000007937 lozenge Substances 0.000 description 1
- 201000003453 lung abscess Diseases 0.000 description 1
- ZLNQQNXFFQJAID-UHFFFAOYSA-L magnesium carbonate Chemical compound [Mg+2].[O-]C([O-])=O ZLNQQNXFFQJAID-UHFFFAOYSA-L 0.000 description 1
- 239000001095 magnesium carbonate Substances 0.000 description 1
- 229910000021 magnesium carbonate Inorganic materials 0.000 description 1
- 239000000395 magnesium oxide Substances 0.000 description 1
- CPLXHLVBOLITMK-UHFFFAOYSA-N magnesium oxide Inorganic materials [Mg]=O CPLXHLVBOLITMK-UHFFFAOYSA-N 0.000 description 1
- 239000000391 magnesium silicate Substances 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 229940057948 magnesium stearate Drugs 0.000 description 1
- 229940099273 magnesium trisilicate Drugs 0.000 description 1
- 235000019793 magnesium trisilicate Nutrition 0.000 description 1
- 229910000386 magnesium trisilicate Inorganic materials 0.000 description 1
- AXZKOIWUVFPNLO-UHFFFAOYSA-N magnesium;oxygen(2-) Chemical compound [O-2].[Mg+2] AXZKOIWUVFPNLO-UHFFFAOYSA-N 0.000 description 1
- 201000004792 malaria Diseases 0.000 description 1
- 230000003211 malignant effect Effects 0.000 description 1
- 210000004962 mammalian cell Anatomy 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- 231100000682 maximum tolerated dose Toxicity 0.000 description 1
- 238000002483 medication Methods 0.000 description 1
- 238000007909 melt granulation Methods 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- 210000001616 monocyte Anatomy 0.000 description 1
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 description 1
- 201000006417 multiple sclerosis Diseases 0.000 description 1
- 210000003205 muscle Anatomy 0.000 description 1
- 210000001989 nasopharynx Anatomy 0.000 description 1
- 230000002232 neuromuscular Effects 0.000 description 1
- 210000000440 neutrophil Anatomy 0.000 description 1
- 108020004707 nucleic acids Proteins 0.000 description 1
- 102000039446 nucleic acids Human genes 0.000 description 1
- 150000007523 nucleic acids Chemical class 0.000 description 1
- 230000000399 orthopedic effect Effects 0.000 description 1
- 238000013450 outlier detection Methods 0.000 description 1
- 238000004806 packaging method and process Methods 0.000 description 1
- 244000045947 parasite Species 0.000 description 1
- 230000036961 partial effect Effects 0.000 description 1
- 230000002093 peripheral effect Effects 0.000 description 1
- 230000002085 persistent effect Effects 0.000 description 1
- 210000001539 phagocyte Anatomy 0.000 description 1
- 239000008177 pharmaceutical agent Substances 0.000 description 1
- 229940124531 pharmaceutical excipient Drugs 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 229940127557 pharmaceutical product Drugs 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 238000009522 phase III clinical trial Methods 0.000 description 1
- 102000020233 phosphotransferase Human genes 0.000 description 1
- 230000037081 physical activity Effects 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 235000013809 polyvinylpolypyrrolidone Nutrition 0.000 description 1
- 229920000523 polyvinylpolypyrrolidone Polymers 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 230000035935 pregnancy Effects 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 238000000513 principal component analysis Methods 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 230000002062 proliferating effect Effects 0.000 description 1
- 230000000069 prophylactic effect Effects 0.000 description 1
- 235000004252 protein component Nutrition 0.000 description 1
- 238000010298 pulverizing process Methods 0.000 description 1
- 230000007115 recruitment Effects 0.000 description 1
- 230000003716 rejuvenation Effects 0.000 description 1
- 230000029058 respiratory gaseous exchange Effects 0.000 description 1
- 230000036387 respiratory rate Effects 0.000 description 1
- 108020004418 ribosomal RNA Proteins 0.000 description 1
- 201000005404 rubella Diseases 0.000 description 1
- 210000000582 semen Anatomy 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 238000012163 sequencing technique Methods 0.000 description 1
- 230000001568 sexual effect Effects 0.000 description 1
- 238000004904 shortening Methods 0.000 description 1
- 238000004088 simulation Methods 0.000 description 1
- 239000008279 sol Substances 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 235000010356 sorbitol Nutrition 0.000 description 1
- 238000013125 spirometry Methods 0.000 description 1
- 230000002269 spontaneous effect Effects 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 229940032147 starch Drugs 0.000 description 1
- 230000004936 stimulating effect Effects 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 230000035882 stress Effects 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 235000000346 sugar Nutrition 0.000 description 1
- 238000009495 sugar coating Methods 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- 230000008093 supporting effect Effects 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 230000002459 sustained effect Effects 0.000 description 1
- 230000009044 synergistic interaction Effects 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 238000012956 testing procedure Methods 0.000 description 1
- 210000001541 thymus gland Anatomy 0.000 description 1
- 238000009804 total hysterectomy Methods 0.000 description 1
- 230000009261 transgenic effect Effects 0.000 description 1
- 230000001052 transient effect Effects 0.000 description 1
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
- 229940078499 tricalcium phosphate Drugs 0.000 description 1
- 235000019731 tricalcium phosphate Nutrition 0.000 description 1
- 229910000391 tricalcium phosphate Inorganic materials 0.000 description 1
- 238000009810 tubal ligation Methods 0.000 description 1
- 210000004881 tumor cell Anatomy 0.000 description 1
- 238000002604 ultrasonography Methods 0.000 description 1
- YYSFXUWWPNHNAZ-PKJQJFMNSA-N umirolimus Chemical compound C1[C@@H](OC)[C@H](OCCOCC)CC[C@H]1C[C@@H](C)[C@H]1OC(=O)[C@@H]2CCCCN2C(=O)C(=O)[C@](O)(O2)[C@H](C)CC[C@H]2C[C@H](OC)/C(C)=C/C=C/C=C/[C@@H](C)C[C@@H](C)C(=O)[C@H](OC)[C@H](O)/C(C)=C/[C@@H](C)C(=O)C1 YYSFXUWWPNHNAZ-PKJQJFMNSA-N 0.000 description 1
- 229950007775 umirolimus Drugs 0.000 description 1
- 241001529453 unidentified herpesvirus Species 0.000 description 1
- 229940124931 vaccine adjuvant Drugs 0.000 description 1
- 239000012646 vaccine adjuvant Substances 0.000 description 1
- 210000001177 vas deferen Anatomy 0.000 description 1
- 230000024883 vasodilation Effects 0.000 description 1
- 230000003442 weekly effect Effects 0.000 description 1
- 244000000190 yeast pathogen Species 0.000 description 1
- 229940051021 yellow-fever virus Drugs 0.000 description 1
- CGTADGCBEXYWNE-JUKNQOCSSA-N zotarolimus Chemical compound N1([C@H]2CC[C@@H](C[C@@H](C)[C@H]3OC(=O)[C@@H]4CCCCN4C(=O)C(=O)[C@@]4(O)[C@H](C)CC[C@H](O4)C[C@@H](/C(C)=C/C=C/C=C/[C@@H](C)C[C@@H](C)C(=O)[C@H](OC)[C@H](O)/C(C)=C/[C@@H](C)C(=O)C3)OC)C[C@H]2OC)C=NN=N1 CGTADGCBEXYWNE-JUKNQOCSSA-N 0.000 description 1
- 229950009819 zotarolimus Drugs 0.000 description 1
Classifications
-
- 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
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/47—Quinolines; Isoquinolines
- A61K31/4738—Quinolines; Isoquinolines ortho- or peri-condensed with heterocyclic ring systems
- A61K31/4745—Quinolines; Isoquinolines ortho- or peri-condensed with heterocyclic ring systems condensed with ring systems having nitrogen as a ring hetero atom, e.g. phenantrolines
-
- 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
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/4353—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems
- A61K31/436—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a six-membered ring having oxygen as a ring hetero atom, e.g. rapamycin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/02—Stomatological preparations, e.g. drugs for caries, aphtae, periodontitis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/02—Drugs for disorders of the urinary system of urine or of the urinary tract, e.g. urine acidifiers
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/14—Antivirals for RNA viruses
- A61P31/16—Antivirals for RNA viruses for influenza or rhinoviruses
-
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Virology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Oncology (AREA)
- Communicable Diseases (AREA)
- Epidemiology (AREA)
- Pulmonology (AREA)
- Urology & Nephrology (AREA)
- Molecular Biology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
Applications Claiming Priority (6)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201662425766P | 2016-11-23 | 2016-11-23 | |
| US62/425,766 | 2016-11-23 | ||
| US201762476160P | 2017-03-24 | 2017-03-24 | |
| US62/476,160 | 2017-03-24 | ||
| US201762576511P | 2017-10-24 | 2017-10-24 | |
| US62/576,511 | 2017-10-24 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| TW201825090A true TW201825090A (zh) | 2018-07-16 |
Family
ID=60957348
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| TW106140519A TW201825090A (zh) | 2016-11-23 | 2017-11-22 | 增強免疫反應之方法 |
Country Status (12)
| Country | Link |
|---|---|
| US (3) | US10441584B2 (enExample) |
| EP (1) | EP3544608A1 (enExample) |
| JP (1) | JP2020500930A (enExample) |
| KR (1) | KR20190089005A (enExample) |
| CN (1) | CN110114070A (enExample) |
| AU (1) | AU2017363970A1 (enExample) |
| BR (1) | BR112019010470A2 (enExample) |
| CA (1) | CA3044355A1 (enExample) |
| IL (1) | IL266750A (enExample) |
| MX (1) | MX2019006090A (enExample) |
| TW (1) | TW201825090A (enExample) |
| WO (1) | WO2018096402A1 (enExample) |
Families Citing this family (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2016064683A1 (en) | 2014-10-24 | 2016-04-28 | St. Jude Children's Research Hospital | Coordinated metabolic reprogramming in response to productive viral infections |
| CA3044355A1 (en) | 2016-11-23 | 2018-05-31 | Novartis Ag | Methods of enhancing immune response with everolimus, dactolisib or both |
| WO2019157516A1 (en) | 2018-02-12 | 2019-08-15 | resTORbio, Inc. | Combination therapies |
| WO2020223154A1 (en) * | 2019-05-01 | 2020-11-05 | resTORbio, Inc. | Methods of enhancing immune response |
Family Cites Families (85)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US1028606A (en) | 1912-06-04 | Victor Talking Machine Co | Sound-box for talking-machines. | |
| US1000480A (en) | 1909-05-19 | 1911-08-15 | J G Brill Co | Car-truck. |
| US1044158A (en) | 1911-01-27 | 1912-11-12 | Allen H Fetzer | Trolley-wheel. |
| ZA737247B (en) | 1972-09-29 | 1975-04-30 | Ayerst Mckenna & Harrison | Rapamycin and process of preparation |
| US5472712A (en) | 1991-12-24 | 1995-12-05 | Euroceltique, S.A. | Controlled-release formulations coated with aqueous dispersions of ethylcellulose |
| US5681585A (en) | 1991-12-24 | 1997-10-28 | Euro-Celtique, S.A. | Stabilized controlled release substrate having a coating derived from an aqueous dispersion of hydrophobic polymer |
| GB9221220D0 (en) | 1992-10-09 | 1992-11-25 | Sandoz Ag | Organic componds |
| WO1995014023A1 (en) | 1993-11-19 | 1995-05-26 | Abbott Laboratories | Semisynthetic analogs of rapamycin (macrolides) being immunomodulators |
| ATE191218T1 (de) | 1993-12-17 | 2000-04-15 | Novartis Ag | Rapamycin-derivate als immunosuppressoren |
| US5362718A (en) | 1994-04-18 | 1994-11-08 | American Home Products Corporation | Rapamycin hydroxyesters |
| US5741677A (en) | 1995-06-07 | 1998-04-21 | Geron Corporation | Methods for measuring telomere length |
| PL184731B1 (pl) | 1995-06-09 | 2002-12-31 | Novartis Ag | Pochodne rapamycyny, zastosowanie pochodnych rapamycyny i kompozycja farmaceutyczna |
| FR2736550B1 (fr) | 1995-07-14 | 1998-07-24 | Sandoz Sa | Composition pharmaceutique sous la forme d'une dispersion solide comprenant un macrolide et un vehicule |
| EP0937082A2 (en) | 1996-07-12 | 1999-08-25 | Ariad Pharmaceuticals, Inc. | Materials and method for treating or preventing pathogenic fungal infection |
| CA2230748C (en) | 1997-03-14 | 2010-08-03 | American Home Products Corporation | Rapamycin formulations for oral administration |
| US6015815A (en) | 1997-09-26 | 2000-01-18 | Abbott Laboratories | Tetrazole-containing rapamycin analogs with shortened half-lives |
| TW557297B (en) | 1997-09-26 | 2003-10-11 | Abbott Lab | Rapamycin analogs having immunomodulatory activity, and pharmaceutical compositions containing same |
| DK2198858T3 (da) | 1998-03-26 | 2011-10-03 | Astellas Pharma Inc | Præparat med opretholdt frigivelse af en makrolidforbindelse såsom tacrolimus |
| EP1212331B1 (en) | 1999-08-24 | 2004-04-21 | Ariad Gene Therapeutics, Inc. | 28-epirapalogs |
| GB0008785D0 (en) | 2000-04-10 | 2000-05-31 | Novartis Ag | Organic compounds |
| GB0123400D0 (en) | 2001-09-28 | 2001-11-21 | Novartis Ag | Organic compounds |
| CN100522967C (zh) | 2002-02-01 | 2009-08-05 | 阿里亚德基因治疗公司 | 含磷化合物及其应用 |
| US20030203027A1 (en) | 2002-04-26 | 2003-10-30 | Ethicon, Inc. | Coating technique for deposition of drug substance on a substrate |
| US7075204B2 (en) | 2003-08-06 | 2006-07-11 | Honeywell International, Inc. | Threaded inner sleeve for generator magnet |
| AR045957A1 (es) | 2003-10-03 | 2005-11-16 | Novartis Ag | Composicion farmaceutica y combinacion |
| US7220755B2 (en) | 2003-11-12 | 2007-05-22 | Biosensors International Group, Ltd. | 42-O-alkoxyalkyl rapamycin derivatives and compositions comprising same |
| GB0419355D0 (en) | 2004-08-31 | 2004-09-29 | Novartis Ag | Organic compounds |
| US8758816B2 (en) | 2004-11-24 | 2014-06-24 | Meda Pharmaceuticals Inc. | Compositions comprising azelastine and methods of use thereof |
| EP1853259A1 (en) | 2005-02-09 | 2007-11-14 | Macusight, Inc. | Formulations for ocular treatment |
| AU2006222409A1 (en) | 2005-03-08 | 2006-09-14 | Lifecycle Pharma A/S | Pharmaceutical compositions comprising sirolimus and/or an analogue thereof |
| GB0510390D0 (en) | 2005-05-20 | 2005-06-29 | Novartis Ag | Organic compounds |
| EP2001466B1 (en) | 2006-03-23 | 2016-01-06 | Santen Pharmaceutical Co., Ltd | Low-dose rapamycin for the treatment of vascular permeability-related diseases |
| US20100266590A1 (en) | 2006-08-02 | 2010-10-21 | Demetri George D | Combination therapy |
| EP1902708A1 (de) | 2006-09-25 | 2008-03-26 | Losan Pharma GmbH | Wirkstoff enthaltende stabilisierte feste Arzneimittelformen und Verfahren zu ihrer Herstellung |
| RS53335B (sr) | 2006-11-20 | 2014-10-31 | Novartis Ag | Kristalna monotozilatna so 2-metil-2-[4-(3-metil-2-okso-8-hinolin-3-il-2,3-dihidro-imidazo[4,5-c]hinolin-1-il)-fenil]-propionitrila |
| MX2009008486A (es) | 2007-02-20 | 2009-08-20 | Novartis Ag | Imidazoquinolinas como inhibidores dobles de cinasa de lipido y mtor. |
| WO2009013305A1 (en) | 2007-07-24 | 2009-01-29 | Novartis Ag | Use of imidazoquinolines for the treatment of egfr dependent diseases or diseases that have acquired resistance to agents that target egfr family members |
| US20090082387A1 (en) | 2007-09-26 | 2009-03-26 | Protia, Llc | Deuterium-enriched nvp-bez234 |
| US20090088373A1 (en) | 2007-09-28 | 2009-04-02 | Gallo Richard L | Use of compositions to enhance innate immune response |
| CN101969931A (zh) | 2008-03-05 | 2011-02-09 | 万能药生物有限公司 | 包含霉酚酸的调节释放药物组合物及其方法 |
| US20110020338A1 (en) | 2008-03-26 | 2011-01-27 | Carlos Garcia-Echeverria | 5Imidazoquinolines and Pyrimidine Derivatives as Potent Modulators of VEGF-Driven Angiogenic Processes |
| US8840899B2 (en) | 2008-08-05 | 2014-09-23 | Emory University | Use of mTOR inhibitors to enhance T cell immune responses |
| US8822647B2 (en) | 2008-08-26 | 2014-09-02 | City Of Hope | Method and compositions using a chimeric antigen receptor for enhanced anti-tumor effector functioning of T cells |
| CN102202668A (zh) | 2008-10-31 | 2011-09-28 | 诺瓦提斯公司 | 磷脂酰肌醇-3-激酶(PI3K)抑制剂和mTOR抑制剂的组合产品 |
| DK2365802T3 (da) | 2008-11-11 | 2017-11-13 | Univ Texas | Mikrokapsler af rapamycin og anvendelse til behandling af cancer |
| US8323649B2 (en) | 2008-11-25 | 2012-12-04 | Alderbio Holdings Llc | Antibodies to IL-6 and use thereof |
| US9452227B2 (en) | 2008-11-25 | 2016-09-27 | Alderbio Holdings Llc | Methods of treating or diagnosing conditions associated with elevated IL-6 using anti-IL-6 antibodies or fragments |
| CN102281761A (zh) | 2009-01-14 | 2011-12-14 | 健康研究股份有限公司 | 用于增强免疫应答的方法和含有mTOR抑制剂的组合物 |
| US20100233733A1 (en) | 2009-02-10 | 2010-09-16 | Nodality, Inc., A Delaware Corporation | Multiple mechanisms for modulation of the pi3 kinase pathway |
| RU2589823C2 (ru) | 2009-04-09 | 2016-07-10 | Алкермес Фарма Айэленд Лимитед | Композиция для доставки лекарственных средств |
| ES2685947T3 (es) | 2009-04-10 | 2018-10-15 | Haiyan Qi | Agentes antienvejecimiento |
| CN101862297B (zh) | 2009-04-14 | 2012-07-25 | 上海医药工业研究院 | 一种非水溶性药物的缓释微丸、其缓释口腔崩解片及其制备方法 |
| CA2760932A1 (en) | 2009-05-04 | 2010-11-11 | Thierry Nivaggioli | Mtor pathway inhibitors for treating ocular disorders |
| PH12012500491A1 (en) | 2009-09-09 | 2018-03-21 | Celgene Avilomics Res Inc | P13 kinase inhibitors and uses thereof |
| CN102199152A (zh) | 2010-03-25 | 2011-09-28 | 高大新 | 杂环咪唑类磷脂激酶抑制剂 |
| WO2012006619A2 (en) | 2010-07-09 | 2012-01-12 | Northeastern University | ANTIPARASITIC AGENTS BASED ON mTOR INHIBITORS |
| AR083267A1 (es) | 2010-10-04 | 2013-02-13 | Novartis Ag | Combinaciones farmaceuticas |
| CN103237544A (zh) | 2010-12-03 | 2013-08-07 | 诺华有限公司 | 药物组合物 |
| PH12013501201A1 (en) | 2010-12-09 | 2013-07-29 | Univ Pennsylvania | Use of chimeric antigen receptor-modified t cells to treat cancer |
| CA2825825A1 (en) | 2011-01-27 | 2012-08-02 | The Trustees Of Princeton University | Inhibitors of mtor kinase as anti-viral agents |
| WO2012110953A1 (en) | 2011-02-16 | 2012-08-23 | Novartis Ag | Combinations of therapeutic agents for use in the treatment of neurodegenerative diseases |
| CN102138903B (zh) | 2011-03-17 | 2012-12-12 | 苏州特瑞药业有限公司 | 一种依维莫司固体口服药物组合物 |
| US9358229B2 (en) | 2011-08-10 | 2016-06-07 | Novartis Pharma Ag | JAK PI3K/mTOR combination therapy |
| CA2848065A1 (en) | 2011-09-30 | 2013-04-04 | Dana-Farber Cancer Institute, Inc. | Method of treating mucoepidermoid carcinoma |
| EP2763663B1 (en) | 2011-10-06 | 2017-12-27 | Novartis AG | Pharmaceutical compositions comprising 40-o-(2-hydroxy)ethyl-rapamycin |
| EP2638896A1 (en) | 2012-03-14 | 2013-09-18 | Bioneer A/S | Cationic liposomal drug delivery system for specific targeting of human cd14+ monocytes in whole blood |
| HK1203393A1 (en) | 2012-04-11 | 2015-10-30 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Chimeric antigen receptors targeting b-cell maturation antigen |
| CA2872541A1 (en) | 2012-06-06 | 2013-12-12 | Novartis Ag | Combination of a 17 -alpha -hydroxylase (c17, 20 - lyase) inhibitor and a specific pi-3k inhibitor for treating a tumor disease |
| WO2014137946A1 (en) | 2013-03-04 | 2014-09-12 | The Henry M. Jackson Foundation For The Advancement Of Military Medicine, Inc. | Methods of inhibiting igf-1r activation or downtream signalling thereof to reduce radiation-induced cellular senescence |
| TW201503912A (zh) | 2013-03-19 | 2015-02-01 | Novartis Ag | 包含癌莫事（ｅｖｅｒｏｌｉｍｕｓ）之醫藥組合物 |
| EP3004337B1 (en) | 2013-05-29 | 2017-08-02 | Cellectis | Methods for engineering t cells for immunotherapy by using rna-guided cas nuclease system |
| KR101582264B1 (ko) | 2013-06-27 | 2016-01-04 | 삼성전자 주식회사 | 유기 박막용 조성물, 유기 박막 및 상기 유기 박막을 포함하는 전자 소자 |
| US9033062B2 (en) * | 2013-07-11 | 2015-05-19 | Caterpillar Inc. | Control system for a machine |
| JP2016537345A (ja) * | 2013-11-13 | 2016-12-01 | ノバルティス アーゲー | 免疫応答を増強するためのｍＴＯＲ阻害剤 |
| SI3151672T1 (sl) | 2014-06-06 | 2021-03-31 | Bluebird Bio, Inc. | Izboljšani T-celični sestavki |
| KR102612313B1 (ko) | 2014-07-21 | 2023-12-12 | 노파르티스 아게 | 인간화 항-bcma 키메라 항원 수용체를 사용한 암의 치료 |
| US9777061B2 (en) | 2014-07-21 | 2017-10-03 | Novartis Ag | Treatment of cancer using a CD33 chimeric antigen receptor |
| WO2016014530A1 (en) | 2014-07-21 | 2016-01-28 | Novartis Ag | Combinations of low, immune enhancing. doses of mtor inhibitors and cars |
| US20170274014A1 (en) | 2014-07-21 | 2017-09-28 | Jennifer Brogdon | Combinations of low, immune enhancing, doses of mtor inhibitors and cars |
| CN107109420A (zh) | 2014-07-21 | 2017-08-29 | 诺华股份有限公司 | 使用cll－1嵌合抗原受体的癌症治疗 |
| PL3183268T3 (pl) | 2014-08-19 | 2020-09-07 | Novartis Ag | Chimeryczny receptor antygenowy (CAR) anty-CD123 do zastosowania w leczeniu nowotworu złośliwego |
| WO2016064683A1 (en) * | 2014-10-24 | 2016-04-28 | St. Jude Children's Research Hospital | Coordinated metabolic reprogramming in response to productive viral infections |
| WO2016079332A1 (en) | 2014-11-21 | 2016-05-26 | Technical University Of Denmark | Gel formulations for improving immunotherapy |
| WO2016185443A1 (en) * | 2015-05-20 | 2016-11-24 | Novartis Ag | Pharmaceutical combination of everolimus with dactolisib |
| CA3044355A1 (en) | 2016-11-23 | 2018-05-31 | Novartis Ag | Methods of enhancing immune response with everolimus, dactolisib or both |
-
2017
- 2017-11-22 CA CA3044355A patent/CA3044355A1/en not_active Abandoned
- 2017-11-22 CN CN201780080148.2A patent/CN110114070A/zh active Pending
- 2017-11-22 BR BR112019010470A patent/BR112019010470A2/pt not_active Application Discontinuation
- 2017-11-22 US US15/821,229 patent/US10441584B2/en active Active
- 2017-11-22 KR KR1020197017560A patent/KR20190089005A/ko not_active Withdrawn
- 2017-11-22 WO PCT/IB2017/001579 patent/WO2018096402A1/en not_active Ceased
- 2017-11-22 MX MX2019006090A patent/MX2019006090A/es unknown
- 2017-11-22 JP JP2019547795A patent/JP2020500930A/ja active Pending
- 2017-11-22 TW TW106140519A patent/TW201825090A/zh unknown
- 2017-11-22 AU AU2017363970A patent/AU2017363970A1/en not_active Abandoned
- 2017-11-22 EP EP17829013.6A patent/EP3544608A1/en not_active Withdrawn
-
2019
- 2019-05-20 IL IL266750A patent/IL266750A/en unknown
- 2019-10-03 US US16/592,248 patent/US11045463B2/en active Active
- 2019-10-03 US US16/592,293 patent/US10993940B2/en active Active
Also Published As
| Publication number | Publication date |
|---|---|
| WO2018096402A1 (en) | 2018-05-31 |
| BR112019010470A2 (pt) | 2019-09-10 |
| AU2017363970A1 (en) | 2019-06-20 |
| KR20190089005A (ko) | 2019-07-29 |
| JP2020500930A (ja) | 2020-01-16 |
| MX2019006090A (es) | 2019-08-21 |
| US20200061051A1 (en) | 2020-02-27 |
| US11045463B2 (en) | 2021-06-29 |
| US20200054624A1 (en) | 2020-02-20 |
| US20180161319A1 (en) | 2018-06-14 |
| CA3044355A1 (en) | 2018-05-31 |
| US10441584B2 (en) | 2019-10-15 |
| CN110114070A (zh) | 2019-08-09 |
| IL266750A (en) | 2019-07-31 |
| EP3544608A1 (en) | 2019-10-02 |
| US10993940B2 (en) | 2021-05-04 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US11045463B2 (en) | Methods of enhancing immune response | |
| EP4125881B1 (en) | New use of angiotensin ii type 2 receptor agonist | |
| JP6977029B2 (ja) | レット症候群を治療するためのプリドピジンの使用 | |
| TW201825097A (zh) | 使用包含微脂伊立替康(irinotecan)及奧沙利鉑(oxaliplatin)之組合療法治療胃癌之方法 | |
| TW202130350A (zh) | 用阿曲生坦（ＡＴＲＡＳＥＮＴＡＮ）治療ＩｇＡ腎病的方法 | |
| US20210030741A1 (en) | Pharmaceutical combination of everolimus with dactolisib | |
| AU2024266870A1 (en) | Cyclobenzaprine treatment for agitation, psychosis and cognitive decline in dementia and neurodegenerative conditions | |
| CN102548408A (zh) | 治疗肝性脑病的方法 | |
| CN121221782A (zh) | 用于治疗抑郁的nk-1拮抗剂组合物和方法 | |
| CA3113468A1 (en) | Grapiprant unit dosage forms | |
| KR20220148826A (ko) | 브루톤 티로신 키나아제의 저해제를 이용하여 원발성 진행형 다발성 경화증을 치료하는 방법 | |
| US12005050B2 (en) | Methods for preventing or treating H. pylori infection | |
| Islam et al. | A Generalized Overview of the Possible Pharmacotherapy and Treatments against SARS-CoV-2 | |
| HK40081689A (en) | New use of angiotensin ii type 2 receptor agonist | |
| CN117479936A (zh) | 用奥瑞司特治疗化脓性汗腺炎 | |
| EA045669B1 (ru) | Способы лечения поведенческих и психологических симптомов у пациентов с деменцией |