KR20190089005A - 에베롤리무스, 닥톨리십 또는 둘 다를 사용하여 면역 반응을 증진시키는 방법 - Google Patents
에베롤리무스, 닥톨리십 또는 둘 다를 사용하여 면역 반응을 증진시키는 방법 Download PDFInfo
- Publication number
- KR20190089005A KR20190089005A KR1020197017560A KR20197017560A KR20190089005A KR 20190089005 A KR20190089005 A KR 20190089005A KR 1020197017560 A KR1020197017560 A KR 1020197017560A KR 20197017560 A KR20197017560 A KR 20197017560A KR 20190089005 A KR20190089005 A KR 20190089005A
- Authority
- KR
- South Korea
- Prior art keywords
- pharmaceutically acceptable
- acceptable salt
- bez235
- rad001
- patient
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Withdrawn
Links
- 238000000034 method Methods 0.000 title claims abstract description 107
- 230000028993 immune response Effects 0.000 title claims abstract description 62
- 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 title claims description 21
- 229960005167 everolimus Drugs 0.000 title claims description 19
- 230000002708 enhancing effect Effects 0.000 title abstract description 8
- AOJJSUZBOXZQNB-TZSSRYMLSA-N Doxorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 AOJJSUZBOXZQNB-TZSSRYMLSA-N 0.000 title 2
- 229960004679 doxorubicin Drugs 0.000 title 1
- 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 226
- 229950006418 dactolisib Drugs 0.000 claims description 225
- 150000003839 salts Chemical class 0.000 claims description 189
- 206010057190 Respiratory tract infections Diseases 0.000 claims description 80
- 208000015181 infectious disease Diseases 0.000 claims description 70
- 238000011282 treatment Methods 0.000 claims description 68
- 108090000623 proteins and genes Proteins 0.000 claims description 36
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 32
- 238000009097 single-agent therapy Methods 0.000 claims description 26
- 201000010099 disease Diseases 0.000 claims description 21
- 230000036039 immunity Effects 0.000 claims description 17
- 108010037362 Extracellular Matrix Proteins Proteins 0.000 claims description 16
- 102000010834 Extracellular Matrix Proteins Human genes 0.000 claims description 16
- 230000032683 aging Effects 0.000 claims description 16
- 210000002744 extracellular matrix Anatomy 0.000 claims description 16
- 206010019280 Heart failures Diseases 0.000 claims description 13
- 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
- 230000001771 impaired effect Effects 0.000 claims description 11
- 206010010356 Congenital anomaly Diseases 0.000 claims description 10
- 102000004169 proteins and genes Human genes 0.000 claims description 10
- 206010061598 Immunodeficiency Diseases 0.000 claims description 8
- 208000036142 Viral infection Diseases 0.000 claims description 8
- 238000007634 remodeling Methods 0.000 claims description 8
- 230000009385 viral infection Effects 0.000 claims description 8
- 230000001105 regulatory effect Effects 0.000 claims description 7
- 238000002648 combination therapy Methods 0.000 claims description 6
- 208000019206 urinary tract infection Diseases 0.000 claims description 6
- 230000002159 abnormal effect Effects 0.000 claims description 5
- 230000004064 dysfunction Effects 0.000 claims description 5
- 230000007935 neutral effect Effects 0.000 claims description 5
- 201000008482 osteoarthritis Diseases 0.000 claims description 5
- JOXIMZWYDAKGHI-UHFFFAOYSA-M toluene-4-sulfonate Chemical class CC1=CC=C(S([O-])(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-M 0.000 claims description 5
- 201000003793 Myelodysplastic syndrome Diseases 0.000 claims description 4
- 208000020832 chronic kidney disease Diseases 0.000 claims description 4
- 208000022831 chronic renal failure syndrome Diseases 0.000 claims description 4
- 201000001320 Atherosclerosis Diseases 0.000 claims description 3
- 208000007342 Diabetic Nephropathies 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
- 208000033679 diabetic kidney disease Diseases 0.000 claims description 3
- 230000009759 skin aging Effects 0.000 claims description 3
- 230000029663 wound healing Effects 0.000 claims description 3
- 206010018364 Glomerulonephritis Diseases 0.000 claims description 2
- 206010019668 Hepatic fibrosis Diseases 0.000 claims description 2
- 206010003246 arthritis Diseases 0.000 claims description 2
- 230000007882 cirrhosis Effects 0.000 claims description 2
- 208000019425 cirrhosis of liver Diseases 0.000 claims description 2
- 206010028537 myelofibrosis Diseases 0.000 claims description 2
- 206010053219 non-alcoholic steatohepatitis Diseases 0.000 claims description 2
- 206010016654 Fibrosis Diseases 0.000 claims 1
- 206010048685 Oral infection Diseases 0.000 claims 1
- 230000004761 fibrosis Effects 0.000 claims 1
- 201000001245 periodontitis Diseases 0.000 claims 1
- 239000003814 drug Substances 0.000 description 79
- 208000020029 respiratory tract infectious disease Diseases 0.000 description 62
- 229960002930 sirolimus Drugs 0.000 description 53
- 229940079593 drug Drugs 0.000 description 43
- 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 42
- 229940124302 mTOR inhibitor Drugs 0.000 description 41
- 239000003628 mammalian target of rapamycin inhibitor Substances 0.000 description 41
- 102000013530 TOR Serine-Threonine Kinases Human genes 0.000 description 33
- 108010065917 TOR Serine-Threonine Kinases Proteins 0.000 description 33
- 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
- 230000009758 senescence Effects 0.000 description 28
- 239000008194 pharmaceutical composition Substances 0.000 description 27
- 239000000902 placebo Substances 0.000 description 27
- 229940068196 placebo Drugs 0.000 description 27
- 102000008135 Mechanistic Target of Rapamycin Complex 1 Human genes 0.000 description 26
- 108010035196 Mechanistic Target of Rapamycin Complex 1 Proteins 0.000 description 26
- 230000014509 gene expression Effects 0.000 description 25
- 229940124597 therapeutic agent Drugs 0.000 description 24
- 230000000694 effects Effects 0.000 description 23
- 150000001875 compounds Chemical class 0.000 description 22
- 241000700605 Viruses Species 0.000 description 21
- 210000001744 T-lymphocyte Anatomy 0.000 description 18
- 206010022000 influenza Diseases 0.000 description 18
- 238000002255 vaccination Methods 0.000 description 18
- 208000024891 symptom Diseases 0.000 description 16
- 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 description 15
- 210000004369 blood Anatomy 0.000 description 15
- 239000008280 blood Substances 0.000 description 15
- 230000002829 reductive effect Effects 0.000 description 15
- 239000002552 dosage form Substances 0.000 description 14
- 230000036737 immune function Effects 0.000 description 14
- 229960003971 influenza vaccine Drugs 0.000 description 14
- 239000000203 mixture Substances 0.000 description 14
- 238000004519 manufacturing process Methods 0.000 description 13
- 241000282414 Homo sapiens Species 0.000 description 12
- 230000003281 allosteric effect Effects 0.000 description 12
- 230000006870 function Effects 0.000 description 12
- 244000052769 pathogen Species 0.000 description 12
- 230000001737 promoting effect Effects 0.000 description 12
- 230000009467 reduction Effects 0.000 description 12
- 102000009308 Mechanistic Target of Rapamycin Complex 2 Human genes 0.000 description 11
- 108010034057 Mechanistic Target of Rapamycin Complex 2 Proteins 0.000 description 11
- 230000037361 pathway Effects 0.000 description 11
- 230000004044 response Effects 0.000 description 11
- 238000012360 testing method Methods 0.000 description 11
- 102000014150 Interferons Human genes 0.000 description 10
- 108010050904 Interferons Proteins 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
- 238000004458 analytical method Methods 0.000 description 10
- 230000007423 decrease Effects 0.000 description 10
- 208000035475 disorder Diseases 0.000 description 10
- -1 hydroxyalkoxyalkyl Chemical group 0.000 description 10
- 229940079322 interferon Drugs 0.000 description 10
- 230000001717 pathogenic effect Effects 0.000 description 9
- 102100040678 Programmed cell death protein 1 Human genes 0.000 description 8
- 230000003247 decreasing effect Effects 0.000 description 8
- 238000011160 research Methods 0.000 description 8
- 238000002560 therapeutic procedure Methods 0.000 description 8
- 230000003827 upregulation Effects 0.000 description 8
- 206010007559 Cardiac failure congestive Diseases 0.000 description 7
- 230000009286 beneficial effect Effects 0.000 description 7
- 230000003197 catalytic effect Effects 0.000 description 7
- 239000003795 chemical substances by application Substances 0.000 description 7
- 230000026731 phosphorylation Effects 0.000 description 7
- 238000006366 phosphorylation reaction Methods 0.000 description 7
- 238000012216 screening Methods 0.000 description 7
- 206010035664 Pneumonia Diseases 0.000 description 6
- 101710089372 Programmed cell death protein 1 Proteins 0.000 description 6
- 206010062106 Respiratory tract infection viral Diseases 0.000 description 6
- 206010006451 bronchitis Diseases 0.000 description 6
- 210000004027 cell Anatomy 0.000 description 6
- 238000011156 evaluation Methods 0.000 description 6
- 239000000314 lubricant Substances 0.000 description 6
- 238000002360 preparation method Methods 0.000 description 6
- 230000029058 respiratory gaseous exchange Effects 0.000 description 6
- 239000000523 sample Substances 0.000 description 6
- 239000000126 substance Substances 0.000 description 6
- 230000001225 therapeutic effect Effects 0.000 description 6
- 208000001072 type 2 diabetes mellitus Diseases 0.000 description 6
- 208000020017 viral respiratory tract infection Diseases 0.000 description 6
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 5
- 206010006458 Bronchitis chronic Diseases 0.000 description 5
- 101000703500 Homo sapiens Alpha-sarcoglycan Proteins 0.000 description 5
- 241000124008 Mammalia Species 0.000 description 5
- 241000699670 Mus sp. Species 0.000 description 5
- 238000003559 RNA-seq method Methods 0.000 description 5
- 239000004480 active ingredient Substances 0.000 description 5
- 208000006673 asthma Diseases 0.000 description 5
- 230000008859 change Effects 0.000 description 5
- 208000007451 chronic bronchitis Diseases 0.000 description 5
- 230000036541 health Effects 0.000 description 5
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 5
- 230000006872 improvement Effects 0.000 description 5
- 230000000474 nursing effect Effects 0.000 description 5
- 230000001681 protective effect Effects 0.000 description 5
- 230000000241 respiratory effect Effects 0.000 description 5
- 210000002966 serum Anatomy 0.000 description 5
- 206010011224 Cough Diseases 0.000 description 4
- 208000000059 Dyspnea Diseases 0.000 description 4
- 206010013975 Dyspnoeas Diseases 0.000 description 4
- 230000003712 anti-aging effect Effects 0.000 description 4
- 230000008901 benefit 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
- 230000000875 corresponding effect Effects 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
- 238000002651 drug therapy Methods 0.000 description 4
- 210000000987 immune system Anatomy 0.000 description 4
- 239000003112 inhibitor Substances 0.000 description 4
- 210000003071 memory t lymphocyte Anatomy 0.000 description 4
- 238000011947 six minute walk test Methods 0.000 description 4
- 239000000758 substrate Substances 0.000 description 4
- 239000003826 tablet Substances 0.000 description 4
- 230000008685 targeting Effects 0.000 description 4
- 230000014616 translation Effects 0.000 description 4
- 108010013238 70-kDa Ribosomal Protein S6 Kinases Proteins 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
- 102000017578 LAG3 Human genes 0.000 description 3
- 101150030213 Lag3 gene Proteins 0.000 description 3
- 208000019693 Lung disease Diseases 0.000 description 3
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 3
- 208000021642 Muscular disease Diseases 0.000 description 3
- 206010028980 Neoplasm Diseases 0.000 description 3
- 102100027913 Peptidyl-prolyl cis-trans isomerase FKBP1A Human genes 0.000 description 3
- 206010036790 Productive cough Diseases 0.000 description 3
- 229920002472 Starch Polymers 0.000 description 3
- 210000003719 b-lymphocyte Anatomy 0.000 description 3
- 239000011230 binding agent Substances 0.000 description 3
- 230000033228 biological regulation 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
- 238000002592 echocardiography 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
- 210000002865 immune cell Anatomy 0.000 description 3
- 238000000338 in vitro Methods 0.000 description 3
- 238000001727 in vivo Methods 0.000 description 3
- 230000002401 inhibitory effect Effects 0.000 description 3
- 230000007774 longterm Effects 0.000 description 3
- 210000004698 lymphocyte Anatomy 0.000 description 3
- 230000007246 mechanism Effects 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
- 238000007911 parenteral administration Methods 0.000 description 3
- 239000000546 pharmaceutical excipient Substances 0.000 description 3
- 238000011002 quantification Methods 0.000 description 3
- 230000036387 respiratory rate Effects 0.000 description 3
- 238000012552 review Methods 0.000 description 3
- 230000001932 seasonal effect Effects 0.000 description 3
- 230000011664 signaling 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
- 235000019698 starch Nutrition 0.000 description 3
- 239000008107 starch Substances 0.000 description 3
- 230000002195 synergetic effect Effects 0.000 description 3
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical class CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 3
- 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 description 2
- 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
- 102000004506 Blood Proteins Human genes 0.000 description 2
- 108010017384 Blood Proteins 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
- 229920002785 Croscarmellose sodium Polymers 0.000 description 2
- 241000701022 Cytomegalovirus Species 0.000 description 2
- 102100021260 Galactosylgalactosylxylosylprotein 3-beta-glucuronosyltransferase 1 Human genes 0.000 description 2
- 206010018785 Gingival infections Diseases 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
- 241000282412 Homo Species 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
- 241000701044 Human gammaherpesvirus 4 Species 0.000 description 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 2
- 201000009623 Myopathy Diseases 0.000 description 2
- 102100032859 Protein AMBP Human genes 0.000 description 2
- 208000007271 Substance Withdrawal Syndrome Diseases 0.000 description 2
- 229930006000 Sucrose Natural products 0.000 description 2
- 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 2
- 108010006877 Tacrolimus Binding Protein 1A Proteins 0.000 description 2
- 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 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
- 230000009471 action Effects 0.000 description 2
- 230000004913 activation Effects 0.000 description 2
- 230000002776 aggregation Effects 0.000 description 2
- 238000004220 aggregation Methods 0.000 description 2
- 238000013459 approach Methods 0.000 description 2
- 244000052616 bacterial pathogen Species 0.000 description 2
- 238000003287 bathing Methods 0.000 description 2
- 230000008236 biological pathway Effects 0.000 description 2
- 201000011510 cancer Diseases 0.000 description 2
- 230000005880 cancer cell killing 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
- 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
- 210000004443 dendritic cell Anatomy 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 230000018109 developmental process Effects 0.000 description 2
- 239000008121 dextrose Substances 0.000 description 2
- 230000035487 diastolic blood pressure Effects 0.000 description 2
- 239000003937 drug carrier Substances 0.000 description 2
- 238000010195 expression analysis Methods 0.000 description 2
- 102000018146 globin Human genes 0.000 description 2
- 108060003196 globin Proteins 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
- 210000003958 hematopoietic stem cell Anatomy 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
- 230000003993 interaction Effects 0.000 description 2
- 230000003834 intracellular effect Effects 0.000 description 2
- 230000002147 killing effect Effects 0.000 description 2
- 230000033001 locomotion Effects 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
- 238000005259 measurement Methods 0.000 description 2
- 108020004999 messenger RNA Proteins 0.000 description 2
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 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
- 239000006186 oral dosage form Substances 0.000 description 2
- 239000000825 pharmaceutical preparation Substances 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
- 239000002243 precursor Substances 0.000 description 2
- 230000035755 proliferation Effects 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
- 238000005070 sampling Methods 0.000 description 2
- 208000013220 shortness of breath Diseases 0.000 description 2
- 238000013125 spirometry Methods 0.000 description 2
- 239000005720 sucrose Substances 0.000 description 2
- 230000008093 supporting effect Effects 0.000 description 2
- 230000002459 sustained effect Effects 0.000 description 2
- 230000035488 systolic blood pressure Effects 0.000 description 2
- 239000000454 talc Substances 0.000 description 2
- 229910052623 talc Inorganic materials 0.000 description 2
- 235000012222 talc Nutrition 0.000 description 2
- 102000055501 telomere Human genes 0.000 description 2
- 108091035539 telomere Proteins 0.000 description 2
- 210000003411 telomere Anatomy 0.000 description 2
- 229960000235 temsirolimus Drugs 0.000 description 2
- 230000004797 therapeutic response Effects 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
- 244000052613 viral pathogen Species 0.000 description 2
- WZDHVGJAURVPPU-UHFFFAOYSA-N 2-methyl-2-[4-(3-methyl-2-oxo-8-quinolin-3-yl-1H-imidazo[4,5-c]quinolin-4-yl)phenyl]propanenitrile Chemical compound Cn1c2c(nc3ccc(cc3c2[nH]c1=O)-c1cnc2ccccc2c1)-c1ccc(cc1)C(C)(C)C#N WZDHVGJAURVPPU-UHFFFAOYSA-N 0.000 description 1
- 125000001494 2-propynyl group Chemical group [H]C#CC([H])([H])* 0.000 description 1
- PTBDIHRZYDMNKB-UHFFFAOYSA-M 3-hydroxy-2-(hydroxymethyl)-2-methylpropanoate Chemical compound OCC(C)(CO)C([O-])=O PTBDIHRZYDMNKB-UHFFFAOYSA-M 0.000 description 1
- 125000004195 4-methylpiperazin-1-yl group Chemical group [H]C([H])([H])N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([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
- 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
- 206010002383 Angina Pectoris Diseases 0.000 description 1
- 241000228212 Aspergillus Species 0.000 description 1
- 208000037874 Asthma exacerbation Diseases 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- 241000335423 Blastomyces Species 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- 241000195940 Bryophyta 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
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 1
- 201000006082 Chickenpox Diseases 0.000 description 1
- 241000606161 Chlamydia Species 0.000 description 1
- 241000223203 Coccidioides Species 0.000 description 1
- 208000035473 Communicable disease Diseases 0.000 description 1
- 208000027205 Congenital disease Diseases 0.000 description 1
- 208000029767 Congenital, Hereditary, and Neonatal Diseases and Abnormalities Diseases 0.000 description 1
- 241001337994 Cryptococcus <scale insect> Species 0.000 description 1
- 244000303965 Cyamopsis psoralioides Species 0.000 description 1
- 102100024458 Cyclin-dependent kinase inhibitor 2A Human genes 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-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 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
- 101001082109 Danio rerio Eukaryotic translation initiation factor 4E-1B Proteins 0.000 description 1
- 241000710829 Dengue virus group Species 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
- 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
- 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
- 108700024394 Exon 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
- 241000606790 Haemophilus Species 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
- 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
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 description 1
- 208000035150 Hypercholesterolemia Diseases 0.000 description 1
- 201000009794 Idiopathic Pulmonary Fibrosis Diseases 0.000 description 1
- 208000029462 Immunodeficiency disease Diseases 0.000 description 1
- 206010062016 Immunosuppression Diseases 0.000 description 1
- 102000004195 Isomerases Human genes 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
- 125000002066 L-histidyl group Chemical group [H]N1C([H])=NC(C([H])([H])[C@](C(=O)[*])([H])N([H])[H])=C1[H] 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
- 229930195725 Mannitol Natural products 0.000 description 1
- 241000712079 Measles morbillivirus Species 0.000 description 1
- 108010090054 Membrane Glycoproteins Proteins 0.000 description 1
- 102000012750 Membrane Glycoproteins Human genes 0.000 description 1
- 201000009906 Meningitis Diseases 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 229920003091 Methocel™ Polymers 0.000 description 1
- 241000588621 Moraxella Species 0.000 description 1
- 208000016285 Movement disease Diseases 0.000 description 1
- 101150097381 Mtor gene Proteins 0.000 description 1
- 241000711386 Mumps virus Species 0.000 description 1
- 208000029578 Muscle disease Diseases 0.000 description 1
- 208000023178 Musculoskeletal disease Diseases 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
- 241000714209 Norwalk virus 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
- 241001631646 Papillomaviridae Species 0.000 description 1
- 208000002606 Paramyxoviridae Infections Diseases 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
- 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
- 206010037742 Rabies Diseases 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- 206010038389 Renal cancer Diseases 0.000 description 1
- 241000725643 Respiratory syncytial virus Species 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
- 101710184528 Scaffolding 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
- 102100023085 Serine/threonine-protein kinase mTOR Human genes 0.000 description 1
- 241000607720 Serratia Species 0.000 description 1
- 241000607768 Shigella Species 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
- 241000187391 Streptomyces hygroscopicus Species 0.000 description 1
- 241000282887 Suidae Species 0.000 description 1
- 230000024932 T cell mediated immunity Effects 0.000 description 1
- 230000005867 T cell response Effects 0.000 description 1
- 108010017842 Telomerase Proteins 0.000 description 1
- ATJFFYVFTNAWJD-UHFFFAOYSA-N Tin Chemical compound [Sn] ATJFFYVFTNAWJD-UHFFFAOYSA-N 0.000 description 1
- 241000223996 Toxoplasma Species 0.000 description 1
- 206010046980 Varicella 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
- 230000001133 acceleration Effects 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
- 125000004945 acylaminoalkyl group Chemical group 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
- 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
- 208000026935 allergic disease Diseases 0.000 description 1
- 229940125528 allosteric inhibitor Drugs 0.000 description 1
- CEGOLXSVJUTHNZ-UHFFFAOYSA-K aluminium tristearate Chemical compound [Al+3].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O CEGOLXSVJUTHNZ-UHFFFAOYSA-K 0.000 description 1
- 229940063655 aluminum stearate Drugs 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
- 238000003556 assay Methods 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
- 230000005540 biological transmission Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 238000001815 biotherapy Methods 0.000 description 1
- 210000000601 blood cell Anatomy 0.000 description 1
- 230000036765 blood level Effects 0.000 description 1
- 238000010241 blood sampling Methods 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 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
- 235000013539 calcium stearate Nutrition 0.000 description 1
- 239000008116 calcium stearate Substances 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 239000001768 carboxy methyl cellulose Substances 0.000 description 1
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 1
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 1
- 229940105329 carboxymethylcellulose Drugs 0.000 description 1
- 239000012876 carrier material Substances 0.000 description 1
- 239000003054 catalyst 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
- 230000009134 cell regulation Effects 0.000 description 1
- 230000001413 cellular effect 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
- 238000012512 characterization method 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
- 239000008119 colloidal silica Substances 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 238000011284 combination treatment Methods 0.000 description 1
- 230000009918 complex formation Effects 0.000 description 1
- 238000010411 cooking Methods 0.000 description 1
- 230000002079 cooperative effect Effects 0.000 description 1
- 235000005822 corn Nutrition 0.000 description 1
- 229960001681 croscarmellose sodium 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
- 230000003436 cytoskeletal effect Effects 0.000 description 1
- 210000001151 cytotoxic T lymphocyte Anatomy 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 230000003831 deregulation Effects 0.000 description 1
- 230000006866 deterioration Effects 0.000 description 1
- 229940096516 dextrates Drugs 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
- 239000008298 dragée Substances 0.000 description 1
- 239000000890 drug combination Substances 0.000 description 1
- 230000009977 dual effect Effects 0.000 description 1
- 210000004667 early pro-b cell Anatomy 0.000 description 1
- 206010014599 encephalitis Diseases 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 230000008029 eradication Effects 0.000 description 1
- 210000003743 erythrocyte Anatomy 0.000 description 1
- 125000004185 ester group Chemical group 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
- 230000007717 exclusion Effects 0.000 description 1
- 230000023410 extracellular matrix disassembly Effects 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 235000019634 flavors Nutrition 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
- 230000002068 genetic effect Effects 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 238000000227 grinding Methods 0.000 description 1
- 230000003370 grooming effect Effects 0.000 description 1
- 230000012010 growth Effects 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
- 239000005556 hormone Substances 0.000 description 1
- 229940088597 hormone Drugs 0.000 description 1
- 230000004727 humoral immunity Effects 0.000 description 1
- 125000002768 hydroxyalkyl group Chemical group 0.000 description 1
- 239000001863 hydroxypropyl cellulose Substances 0.000 description 1
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 1
- 229920003088 hydroxypropyl methyl cellulose Polymers 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
- 230000001939 inductive effect Effects 0.000 description 1
- 239000012678 infectious agent Substances 0.000 description 1
- 230000002458 infectious effect Effects 0.000 description 1
- 230000000977 initiatory effect Effects 0.000 description 1
- 230000015788 innate immune response Effects 0.000 description 1
- 208000036971 interstitial lung disease 2 Diseases 0.000 description 1
- 230000007794 irritation Effects 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 201000010982 kidney cancer Diseases 0.000 description 1
- 230000003907 kidney function Effects 0.000 description 1
- 150000003951 lactams Chemical class 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
- 238000012153 long-term therapy Methods 0.000 description 1
- 210000004072 lung Anatomy 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
- 235000019793 magnesium trisilicate Nutrition 0.000 description 1
- 229940099273 magnesium trisilicate Drugs 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
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 231100000682 maximum tolerated dose Toxicity 0.000 description 1
- 235000012054 meals Nutrition 0.000 description 1
- 230000001404 mediated effect Effects 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
- 230000005012 migration Effects 0.000 description 1
- 238000013508 migration Methods 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
- 235000011929 mousse Nutrition 0.000 description 1
- 210000003205 muscle Anatomy 0.000 description 1
- 230000002232 neuromuscular Effects 0.000 description 1
- 208000018360 neuromuscular disease Diseases 0.000 description 1
- 210000000440 neutrophil Anatomy 0.000 description 1
- 238000010606 normalization Methods 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
- 238000013450 outlier detection Methods 0.000 description 1
- 230000003071 parasitic effect Effects 0.000 description 1
- 230000002093 peripheral effect Effects 0.000 description 1
- 210000001539 phagocyte Anatomy 0.000 description 1
- 229940124531 pharmaceutical excipient Drugs 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
- 230000000865 phosphorylative effect Effects 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
- 230000003389 potentiating effect Effects 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 238000000513 principal component analysis Methods 0.000 description 1
- 210000001948 pro-b lymphocyte Anatomy 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 239000000651 prodrug Substances 0.000 description 1
- 229940002612 prodrug Drugs 0.000 description 1
- 230000000750 progressive effect Effects 0.000 description 1
- 230000002062 proliferating effect Effects 0.000 description 1
- 230000000069 prophylactic effect Effects 0.000 description 1
- 238000011321 prophylaxis Methods 0.000 description 1
- 230000002685 pulmonary effect Effects 0.000 description 1
- 230000000541 pulsatile effect Effects 0.000 description 1
- 208000025644 recurrent pneumonia Diseases 0.000 description 1
- 230000001850 reproductive effect Effects 0.000 description 1
- 210000002345 respiratory system Anatomy 0.000 description 1
- 108020004418 ribosomal RNA Proteins 0.000 description 1
- 201000005404 rubella Diseases 0.000 description 1
- 238000009781 safety test method Methods 0.000 description 1
- QFMKPDZCOKCBAQ-NFCVMBANSA-N sar943-nxa 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)CC1 QFMKPDZCOKCBAQ-NFCVMBANSA-N 0.000 description 1
- 210000000582 semen Anatomy 0.000 description 1
- 238000012163 sequencing technique Methods 0.000 description 1
- 238000004904 shortening Methods 0.000 description 1
- 238000004088 simulation Methods 0.000 description 1
- 238000011125 single therapy Methods 0.000 description 1
- 230000000391 smoking effect Effects 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
- 230000002269 spontaneous effect Effects 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 230000004936 stimulating effect Effects 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 230000006354 stress signaling Effects 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 239000007940 sugar coated tablet Substances 0.000 description 1
- 238000009495 sugar coating Methods 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 230000004083 survival 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
- 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 1
- 238000010998 test method Methods 0.000 description 1
- 238000011287 therapeutic dose Methods 0.000 description 1
- 238000011285 therapeutic regimen Methods 0.000 description 1
- 230000002992 thymic effect Effects 0.000 description 1
- 238000009804 total hysterectomy Methods 0.000 description 1
- 231100000041 toxicology testing Toxicity 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
- 235000019731 tricalcium phosphate Nutrition 0.000 description 1
- 238000009810 tubal ligation Methods 0.000 description 1
- 210000004881 tumor cell Anatomy 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
- 241000701161 unidentified adenovirus Species 0.000 description 1
- 241001529453 unidentified herpesvirus Species 0.000 description 1
- 241000712461 unidentified influenza virus Species 0.000 description 1
- 229960005486 vaccine Drugs 0.000 description 1
- 229940124931 vaccine adjuvant Drugs 0.000 description 1
- 239000012646 vaccine adjuvant Substances 0.000 description 1
- 238000007879 vasectomy Methods 0.000 description 1
- 230000001457 vasomotor 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
Images
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)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Virology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Communicable Diseases (AREA)
- Oncology (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 (7)
| 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 | ||
| PCT/IB2017/001579 WO2018096402A1 (en) | 2016-11-23 | 2017-11-22 | Methods of enhancing immune response with everolimus, dactolisib or both |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| KR20190089005A true KR20190089005A (ko) | 2019-07-29 |
Family
ID=60957348
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| KR1020197017560A Withdrawn KR20190089005A (ko) | 2016-11-23 | 2017-11-22 | 에베롤리무스, 닥톨리십 또는 둘 다를 사용하여 면역 반응을 증진시키는 방법 |
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 |
|---|---|---|---|---|
| US11083725B2 (en) | 2014-10-24 | 2021-08-10 | St. Jude Children's Research Hospital | Coordinated metabolic reprogramming in response to productive viral infections |
| CN110114070A (zh) | 2016-11-23 | 2019-08-09 | 诺华公司 | 使用依维莫司(everolimus)、达托里昔布(dactolisib)或二者增强免疫反应的方法 |
| 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 |
| JP4105761B2 (ja) | 1993-11-19 | 2008-06-25 | アボット・ラボラトリーズ | ラパミシン（マクロライド）の半合成類似体免疫調節剤 |
| SG64372A1 (en) | 1993-12-17 | 1999-04-27 | Novartis Ag | Rapamycin derivatives |
| 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 |
| AU712193B2 (en) | 1995-06-09 | 1999-10-28 | Novartis Ag | Rapamycin derivatives |
| BE1009856A5 (fr) | 1995-07-14 | 1997-10-07 | Sandoz Sa | Composition pharmaceutique sous la forme d'une dispersion solide comprenant un macrolide et un vehicule. |
| US6258823B1 (en) | 1996-07-12 | 2001-07-10 | 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 |
| AU749623B2 (en) | 1998-03-26 | 2002-06-27 | Astellas Pharma Inc. | Sustained release preparations |
| IL147803A0 (en) | 1999-08-24 | 2002-08-14 | 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 |
| AU2003210787B2 (en) | 2002-02-01 | 2009-04-23 | Medinol Ltd. | Phosphorus-containing compounds & uses thereof |
| 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 |
| GB2438544A (en) | 2005-02-09 | 2007-11-28 | Cooper Internat Corp | Liquid formulations for treatment of diseases or conditions |
| 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 |
| CN101443004B (zh) | 2006-03-23 | 2013-03-06 | 参天制药株式会社 | 用于与血管通透性有关的疾病或病症的制剂 |
| EP2054061A4 (en) | 2006-08-02 | 2009-09-02 | Ariad Pharma Inc | COMBINATION THERAPY |
| EP1902708A1 (de) | 2006-09-25 | 2008-03-26 | Losan Pharma GmbH | Wirkstoff enthaltende stabilisierte feste Arzneimittelformen und Verfahren zu ihrer Herstellung |
| CN102993202A (zh) | 2006-11-20 | 2013-03-27 | 诺瓦提斯公司 | 2-甲基-2-[4-(3-甲基-2-氧代-8-喹啉-3-基-2,3-二氢-咪唑并[4,5-c]喹啉-1-基)-苯基]-丙腈的盐和晶型 |
| CN101616672A (zh) | 2007-02-20 | 2009-12-30 | 诺瓦提斯公司 | 作为脂质激酶和mTOR双重抑制剂的咪唑并喹啉类 |
| PL2182948T3 (pl) | 2007-07-24 | 2013-07-31 | Novartis Ag | Zastosowanie imidazochinolin do leczenia chorób EGFR-zależnych albo chorób wykazujących nabytą oporność wobec środków ukierunkowanych na członków rodziny EGFR |
| 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 |
| AU2009220779A1 (en) | 2008-03-05 | 2009-09-11 | Panacea Biotec Limited | Modified release pharmaceutical compositions comprising mycophenolate and processes thereof |
| BRPI0909082A2 (pt) | 2008-03-26 | 2019-02-26 | Novartis Ag | imidazoquinolinas e derivados de pirimidina como moduladores potentes de processos angiogênicos acionados por vegf |
| EP2318002A4 (en) | 2008-08-05 | 2012-11-28 | Univ Emory | USE OF MTOR INHIBITORS FOR INCREASING IMMUNE RESPONSES OF T CELLS |
| PL3006459T3 (pl) | 2008-08-26 | 2022-01-17 | City Of Hope | Sposób i kompozycje dla wzmocnionego działania efektorowego komórek t przeciw guzowi nowotworowemu |
| EP2349275B1 (en) | 2008-10-31 | 2017-03-08 | Novartis AG | Combination of a phosphatidylinositol-3-kinase (pi3k) inhibitor and a mtor inhibitor. |
| EP2365802B1 (en) | 2008-11-11 | 2017-08-02 | The Board of Regents,The University of Texas System | Microcapsules of rapamycin and use for treating 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 |
| EP2375897A4 (en) | 2009-01-14 | 2013-05-15 | Health Research Inc | METHOD AND COMPOSITIONS USING MTOR-INHIBITORS FOR IMPROVING IMMUNE REACTIONS |
| US20100233733A1 (en) | 2009-02-10 | 2010-09-16 | Nodality, Inc., A Delaware Corporation | Multiple mechanisms for modulation of the pi3 kinase pathway |
| CA2757979A1 (en) | 2009-04-09 | 2010-10-14 | Alkermes Pharma Ireland Limited | Controlled-release clozapine compositions |
| EP2416792A4 (en) | 2009-04-10 | 2012-10-24 | Haiyan Qi | NOVEL ANTI-AGING AGENTS AND METHODS OF IDENTIFICATION |
| 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 |
| US20120114637A1 (en) | 2009-05-04 | 2012-05-10 | Santen Pharmaceutical Co., Ltd. | Mtor pathway inhibitors for treating ocular disorders |
| WO2011031896A2 (en) | 2009-09-09 | 2011-03-17 | Avila Therapeutics, Inc. | Pi3 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 |
| PH12013501098A1 (en) | 2010-12-03 | 2013-07-08 | Novartis Ag | Pharmaceutical compositions |
| PH12013501201A1 (en) | 2010-12-09 | 2013-07-29 | Univ Pennsylvania | Use of chimeric antigen receptor-modified t cells to treat cancer |
| JP2014505076A (ja) | 2011-01-27 | 2014-02-27 | ザ トラスティーズ オブ プリンストン ユニバーシティ | 抗ウイルス剤としてのｍＴＯＲキナーゼの阻害剤 |
| US9358236B2 (en) | 2011-02-16 | 2016-06-07 | 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 |
| WO2013023119A1 (en) | 2011-08-10 | 2013-02-14 | Novartis Pharma Ag | JAK P13K/mTOR COMBINATION THERAPY |
| JP2014532057A (ja) | 2011-09-30 | 2014-12-04 | デイナ ファーバー キャンサー インスティチュート，インコーポレイテッド | 粘表皮癌を治療する方法 |
| PH12014500746A1 (en) | 2011-10-06 | 2019-07-17 | 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 |
| WO2013154760A1 (en) | 2012-04-11 | 2013-10-17 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Chimeric antigen receptors targeting b-cell maturation antigen |
| WO2013184621A1 (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 |
| US10799473B2 (en) | 2013-03-04 | 2020-10-13 | 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 |
| DK3004337T3 (da) | 2013-05-29 | 2017-11-13 | Cellectis | Fremgangsmåde til konstruktion af T-celler til immunoterapi ved brug af RNA-guidet Cas nuklease-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 |
| NZ726989A (en) | 2014-06-06 | 2020-08-28 | Bluebird Bio Inc | Improved t cell compositions |
| WO2016014565A2 (en) | 2014-07-21 | 2016-01-28 | Novartis Ag | Treatment of cancer using humanized anti-bcma chimeric antigen receptor |
| US20170274014A1 (en) | 2014-07-21 | 2017-09-28 | Jennifer Brogdon | Combinations of low, immune enhancing, doses of mtor inhibitors and cars |
| BR112017001242A2 (pt) | 2014-07-21 | 2017-12-05 | Novartis Ag | tratamento de câncer usando um receptor antigênico quimérico a cd33 |
| JP2017528433A (ja) | 2014-07-21 | 2017-09-28 | ノバルティス アーゲー | 低い免疫増強用量のｍＴＯＲ阻害剤とＣＡＲの組み合わせ |
| 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 |
| MY189028A (en) | 2014-08-19 | 2022-01-20 | Novartis Ag | Anti-cd123 chimeric antigen receptor (car) for use in cancer treatment |
| US11083725B2 (en) * | 2014-10-24 | 2021-08-10 | 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 |
| CN107847491A (zh) * | 2015-05-20 | 2018-03-27 | 诺华公司 | 依维莫司(everolimus)与达托里昔布(dactolisib)的医药组合 |
| CN110114070A (zh) | 2016-11-23 | 2019-08-09 | 诺华公司 | 使用依维莫司(everolimus)、达托里昔布(dactolisib)或二者增强免疫反应的方法 |
-
2017
- 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 WO PCT/IB2017/001579 patent/WO2018096402A1/en not_active Ceased
- 2017-11-22 JP JP2019547795A patent/JP2020500930A/ja active Pending
- 2017-11-22 MX MX2019006090A patent/MX2019006090A/es unknown
- 2017-11-22 US US15/821,229 patent/US10441584B2/en active Active
- 2017-11-22 EP EP17829013.6A patent/EP3544608A1/en not_active Withdrawn
- 2017-11-22 TW TW106140519A patent/TW201825090A/zh unknown
- 2017-11-22 AU AU2017363970A patent/AU2017363970A1/en not_active Abandoned
- 2017-11-22 KR KR1020197017560A patent/KR20190089005A/ko not_active Withdrawn
- 2017-11-22 CA CA3044355A patent/CA3044355A1/en not_active Abandoned
-
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 |
|---|---|
| US11045463B2 (en) | 2021-06-29 |
| JP2020500930A (ja) | 2020-01-16 |
| IL266750A (en) | 2019-07-31 |
| MX2019006090A (es) | 2019-08-21 |
| CA3044355A1 (en) | 2018-05-31 |
| US10993940B2 (en) | 2021-05-04 |
| WO2018096402A1 (en) | 2018-05-31 |
| US20200061051A1 (en) | 2020-02-27 |
| US20200054624A1 (en) | 2020-02-20 |
| EP3544608A1 (en) | 2019-10-02 |
| TW201825090A (zh) | 2018-07-16 |
| CN110114070A (zh) | 2019-08-09 |
| BR112019010470A2 (pt) | 2019-09-10 |
| US20180161319A1 (en) | 2018-06-14 |
| AU2017363970A1 (en) | 2019-06-20 |
| US10441584B2 (en) | 2019-10-15 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| ES2476368T3 (es) | Tratamiento de la artritis reumatoide con una combinación de laquinimod y metotrexato | |
| US10993940B2 (en) | Methods of enhancing immune response | |
| US20210030741A1 (en) | Pharmaceutical combination of everolimus with dactolisib | |
| JP2011524878A (ja) | シャルコー・マリー・トゥース病および関連した障害を処置するためのピロカルピンおよびメチマゾールの組み合わせ | |
| JP6599447B2 (ja) | プラダー・ウィリー症候群を治療する方法 | |
| WO2013066483A1 (en) | Synergistic combinations of pi3k- and mek-inhibitors | |
| AU2017326013A1 (en) | Use of pridopidine for treating Rett syndrome | |
| TW202216156A (zh) | 全身紅斑性狼瘡之治療 | |
| US20210023063A1 (en) | Methods and dosing regimens using ibudilast and a second agent for cancer therapy | |
| WO2017048457A1 (en) | Combination of laquinimod and pridopidine to treat multiple sclerosis | |
| WO2019018692A1 (en) | METHODS OF ASSESSING TREATMENT EFFICIENCY AND / OR TREATMENT DURATION IN MYCOBACTERIAL DISEASES | |
| US20100273750A1 (en) | Serotonin receptor antagonists for treating arthritis | |
| US20180353495A1 (en) | Pharmaceutical combinations comprising a pi3k inhibitor for the treatment of cancer | |
| US12005050B2 (en) | Methods for preventing or treating H. pylori infection | |
| KR20220148826A (ko) | 브루톤 티로신 키나아제의 저해제를 이용하여 원발성 진행형 다발성 경화증을 치료하는 방법 | |
| US20160184428A1 (en) | Treatment of multiple sclerosis by alemtuzumab induction followed by laquinimod therapy | |
| EA045669B1 (ru) | Способы лечения поведенческих и психологических симптомов у пациентов с деменцией | |
| MXPA99002240A (en) | Pharmaceutical composition for treating viral diseases |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PA0105 | International application |
Patent event date: 20190619 Patent event code: PA01051R01D Comment text: International Patent Application |
|
| PG1501 | Laying open of application | ||
| PC1203 | Withdrawal of no request for examination |