JP2012515222A - 組換えヒトアルブミン−ヒト顆粒球コロニー刺激因子融合タンパク質の安定な製剤 - Google Patents
組換えヒトアルブミン−ヒト顆粒球コロニー刺激因子融合タンパク質の安定な製剤 Download PDFInfo
- Publication number
- JP2012515222A JP2012515222A JP2011546399A JP2011546399A JP2012515222A JP 2012515222 A JP2012515222 A JP 2012515222A JP 2011546399 A JP2011546399 A JP 2011546399A JP 2011546399 A JP2011546399 A JP 2011546399A JP 2012515222 A JP2012515222 A JP 2012515222A
- Authority
- JP
- Japan
- Prior art keywords
- neug
- neutropenia
- subject
- dose
- albumin
- 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.)
- Pending
Links
- 102000004269 Granulocyte Colony-Stimulating Factor Human genes 0.000 title claims abstract description 179
- 108010017080 Granulocyte Colony-Stimulating Factor Proteins 0.000 title claims abstract description 178
- 108091006905 Human Serum Albumin Proteins 0.000 title claims abstract description 58
- 102000008100 Human Serum Albumin Human genes 0.000 title claims abstract description 58
- 102000037865 fusion proteins Human genes 0.000 title description 113
- 108020001507 fusion proteins Proteins 0.000 title description 113
- 238000002360 preparation method Methods 0.000 title description 3
- 238000011282 treatment Methods 0.000 claims abstract description 121
- 238000000034 method Methods 0.000 claims abstract description 67
- 210000000265 leukocyte Anatomy 0.000 claims abstract description 28
- 230000002829 reductive effect Effects 0.000 claims abstract description 15
- 108010044644 pegfilgrastim Proteins 0.000 claims description 225
- HQQSBEDKMRHYME-UHFFFAOYSA-N pefloxacin mesylate Chemical compound [H+].CS([O-])(=O)=O.C1=C2N(CC)C=C(C(O)=O)C(=O)C2=CC(F)=C1N1CCN(C)CC1 HQQSBEDKMRHYME-UHFFFAOYSA-N 0.000 claims description 154
- 229960001373 pegfilgrastim Drugs 0.000 claims description 145
- 208000004235 neutropenia Diseases 0.000 claims description 138
- 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 claims description 100
- 210000000440 neutrophil Anatomy 0.000 claims description 95
- 238000002512 chemotherapy Methods 0.000 claims description 87
- 239000003814 drug Substances 0.000 claims description 67
- 229940079593 drug Drugs 0.000 claims description 65
- ZDZOTLJHXYCWBA-VCVYQWHSSA-N N-debenzoyl-N-(tert-butoxycarbonyl)-10-deacetyltaxol Chemical compound O([C@H]1[C@H]2[C@@](C([C@H](O)C3=C(C)[C@@H](OC(=O)[C@H](O)[C@@H](NC(=O)OC(C)(C)C)C=4C=CC=CC=4)C[C@]1(O)C3(C)C)=O)(C)[C@@H](O)C[C@H]1OC[C@]12OC(=O)C)C(=O)C1=CC=CC=C1 ZDZOTLJHXYCWBA-VCVYQWHSSA-N 0.000 claims description 62
- 229960003668 docetaxel Drugs 0.000 claims description 60
- 229960004679 doxorubicin Drugs 0.000 claims description 50
- 239000002246 antineoplastic agent Substances 0.000 claims description 37
- 208000002633 Febrile Neutropenia Diseases 0.000 claims description 36
- 230000001965 increasing effect Effects 0.000 claims description 31
- 230000003039 myelosuppressive effect Effects 0.000 claims description 31
- 238000011084 recovery Methods 0.000 claims description 29
- 201000002364 leukopenia Diseases 0.000 claims description 18
- 231100001022 leukopenia Toxicity 0.000 claims description 18
- 201000011510 cancer Diseases 0.000 claims description 17
- 206010006187 Breast cancer Diseases 0.000 claims description 16
- 208000026310 Breast neoplasm Diseases 0.000 claims description 16
- 230000007423 decrease Effects 0.000 claims description 16
- 230000008030 elimination Effects 0.000 claims description 16
- 238000003379 elimination reaction Methods 0.000 claims description 16
- 206010028980 Neoplasm Diseases 0.000 claims description 15
- 208000011580 syndromic disease Diseases 0.000 claims description 14
- 229940127089 cytotoxic agent Drugs 0.000 claims description 13
- 208000015181 infectious disease Diseases 0.000 claims description 12
- 210000004698 lymphocyte Anatomy 0.000 claims description 12
- 210000001616 monocyte Anatomy 0.000 claims description 12
- 210000003651 basophil Anatomy 0.000 claims description 11
- 210000003979 eosinophil Anatomy 0.000 claims description 11
- 238000001990 intravenous administration Methods 0.000 claims description 11
- 210000001185 bone marrow Anatomy 0.000 claims description 10
- 238000001802 infusion Methods 0.000 claims description 10
- 206010058314 Dysplasia Diseases 0.000 claims description 9
- 208000026935 allergic disease Diseases 0.000 claims description 8
- 230000001154 acute effect Effects 0.000 claims description 7
- 230000001404 mediated effect Effects 0.000 claims description 7
- 208000035143 Bacterial infection Diseases 0.000 claims description 6
- 208000022362 bacterial infectious disease Diseases 0.000 claims description 6
- 230000036210 malignancy Effects 0.000 claims description 6
- 201000000050 myeloid neoplasm Diseases 0.000 claims description 6
- 239000002243 precursor Substances 0.000 claims description 6
- 239000010432 diamond Substances 0.000 claims description 5
- 230000001747 exhibiting effect Effects 0.000 claims description 5
- 239000003053 toxin Substances 0.000 claims description 5
- 231100000765 toxin Toxicity 0.000 claims description 5
- 108700012359 toxins Proteins 0.000 claims description 5
- 201000010000 Agranulocytosis Diseases 0.000 claims description 4
- 208000032467 Aplastic anaemia Diseases 0.000 claims description 4
- 208000023275 Autoimmune disease Diseases 0.000 claims description 4
- 206010010356 Congenital anomaly Diseases 0.000 claims description 4
- 206010016880 Folate deficiency Diseases 0.000 claims description 4
- 206010020649 Hyperkeratosis Diseases 0.000 claims description 4
- 206010051645 Idiopathic neutropenia Diseases 0.000 claims description 4
- 208000001126 Keratosis Diseases 0.000 claims description 4
- 206010025323 Lymphomas Diseases 0.000 claims description 4
- 208000000733 Paroxysmal Hemoglobinuria Diseases 0.000 claims description 4
- 102100036050 Phosphatidylinositol N-acetylglucosaminyltransferase subunit A Human genes 0.000 claims description 4
- 206010035226 Plasma cell myeloma Diseases 0.000 claims description 4
- 208000019229 Spleen disease Diseases 0.000 claims description 4
- 206010041660 Splenomegaly Diseases 0.000 claims description 4
- 208000036142 Viral infection Diseases 0.000 claims description 4
- 230000005856 abnormality Effects 0.000 claims description 4
- 210000002798 bone marrow cell Anatomy 0.000 claims description 4
- 230000005983 bone marrow dysfunction Effects 0.000 claims description 4
- 210000000845 cartilage Anatomy 0.000 claims description 4
- 230000001684 chronic effect Effects 0.000 claims description 4
- 230000007812 deficiency Effects 0.000 claims description 4
- 229910003460 diamond Inorganic materials 0.000 claims description 4
- 208000007345 glycogen storage disease Diseases 0.000 claims description 4
- 238000001631 haemodialysis Methods 0.000 claims description 4
- 230000000322 hemodialysis Effects 0.000 claims description 4
- 208000032839 leukemia Diseases 0.000 claims description 4
- 208000037843 metastatic solid tumor Diseases 0.000 claims description 4
- 206010028537 myelofibrosis Diseases 0.000 claims description 4
- 201000003045 paroxysmal nocturnal hemoglobinuria Diseases 0.000 claims description 4
- 230000005855 radiation Effects 0.000 claims description 4
- 201000006681 severe congenital neutropenia Diseases 0.000 claims description 4
- 208000027140 splenic disease Diseases 0.000 claims description 4
- 238000002054 transplantation Methods 0.000 claims description 4
- 230000009385 viral infection Effects 0.000 claims description 4
- 208000007848 Alcoholism Diseases 0.000 claims description 3
- 208000030289 Lymphoproliferative disease Diseases 0.000 claims description 3
- 230000002159 abnormal effect Effects 0.000 claims description 3
- 201000007930 alcohol dependence Diseases 0.000 claims description 3
- 229940041181 antineoplastic drug Drugs 0.000 claims description 3
- FDJOLVPMNUYSCM-UVKKECPRSA-L cobalt(3+);[(2r,3s,4r,5s)-5-(5,6-dimethylbenzimidazol-1-yl)-4-hydroxy-2-(hydroxymethyl)oxolan-3-yl] [(2r)-1-[3-[(2r,3r,4z,7s,9z,12s,13s,14z,17s,18s,19r)-2,13,18-tris(2-amino-2-oxoethyl)-7,12,17-tris(3-amino-3-oxopropyl)-3,5,8,8,13,15,18,19-octamethyl-2,7, Chemical compound [Co+3].N#[C-].C1([C@H](CC(N)=O)[C@@]2(C)CCC(=O)NC[C@@H](C)OP([O-])(=O)O[C@H]3[C@H]([C@H](O[C@@H]3CO)N3C4=CC(C)=C(C)C=C4N=C3)O)[N-]\C2=C(C)/C([C@H](C\2(C)C)CCC(N)=O)=N/C/2=C\C([C@H]([C@@]/2(CC(N)=O)C)CCC(N)=O)=N\C\2=C(C)/C2=N[C@]1(C)[C@@](C)(CC(N)=O)[C@@H]2CCC(N)=O FDJOLVPMNUYSCM-UVKKECPRSA-L 0.000 claims description 3
- 201000001546 cyclic hematopoiesis Diseases 0.000 claims description 3
- 230000009467 reduction Effects 0.000 claims description 3
- 210000000278 spinal cord Anatomy 0.000 claims description 3
- 208000019758 Hypergammaglobulinemia Diseases 0.000 claims 1
- 108090000765 processed proteins & peptides Proteins 0.000 abstract description 97
- 102000004196 processed proteins & peptides Human genes 0.000 abstract description 95
- 229920001184 polypeptide Polymers 0.000 abstract description 92
- 230000004927 fusion Effects 0.000 abstract description 23
- 239000000203 mixture Substances 0.000 abstract description 22
- 101000746367 Homo sapiens Granulocyte colony-stimulating factor Proteins 0.000 abstract description 13
- 201000010099 disease Diseases 0.000 abstract description 10
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 10
- 208000024891 symptom Diseases 0.000 abstract description 8
- 238000004820 blood count Methods 0.000 abstract description 6
- 230000002265 prevention Effects 0.000 abstract description 4
- 102000009027 Albumins Human genes 0.000 description 147
- 108010088751 Albumins Proteins 0.000 description 147
- 229940071846 neulasta Drugs 0.000 description 80
- 108010029961 Filgrastim Proteins 0.000 description 72
- 230000000694 effects Effects 0.000 description 58
- 108091033319 polynucleotide Proteins 0.000 description 53
- 102000040430 polynucleotide Human genes 0.000 description 53
- 239000002157 polynucleotide Substances 0.000 description 53
- 235000001014 amino acid Nutrition 0.000 description 46
- 125000003275 alpha amino acid group Chemical group 0.000 description 44
- 238000007920 subcutaneous administration Methods 0.000 description 44
- 108090000623 proteins and genes Proteins 0.000 description 43
- 235000018102 proteins Nutrition 0.000 description 41
- 102000004169 proteins and genes Human genes 0.000 description 41
- 102100039619 Granulocyte colony-stimulating factor Human genes 0.000 description 38
- 239000012634 fragment Substances 0.000 description 38
- 241000699670 Mus sp. Species 0.000 description 37
- 229960004177 filgrastim Drugs 0.000 description 37
- 229940029345 neupogen Drugs 0.000 description 35
- 210000004027 cell Anatomy 0.000 description 33
- 150000001413 amino acids Chemical class 0.000 description 32
- 238000006467 substitution reaction Methods 0.000 description 32
- 241000282693 Cercopithecidae Species 0.000 description 31
- 238000012360 testing method Methods 0.000 description 25
- 230000002411 adverse Effects 0.000 description 24
- 210000005259 peripheral blood Anatomy 0.000 description 20
- 239000011886 peripheral blood Substances 0.000 description 20
- 210000002966 serum Anatomy 0.000 description 20
- 238000012217 deletion Methods 0.000 description 19
- 230000037430 deletion Effects 0.000 description 19
- 230000005847 immunogenicity Effects 0.000 description 19
- 230000004044 response Effects 0.000 description 19
- 230000027455 binding Effects 0.000 description 18
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 17
- 235000014680 Saccharomyces cerevisiae Nutrition 0.000 description 17
- 102000007562 Serum Albumin Human genes 0.000 description 17
- 108010071390 Serum Albumin Proteins 0.000 description 17
- 125000000539 amino acid group Chemical group 0.000 description 16
- 231100000673 dose–response relationship Toxicity 0.000 description 16
- 210000003958 hematopoietic stem cell Anatomy 0.000 description 16
- 238000009104 chemotherapy regimen Methods 0.000 description 15
- 230000001225 therapeutic effect Effects 0.000 description 15
- 206010020751 Hypersensitivity Diseases 0.000 description 14
- 241001465754 Metazoa Species 0.000 description 14
- 210000004899 c-terminal region Anatomy 0.000 description 14
- 238000002474 experimental method Methods 0.000 description 14
- 238000005259 measurement Methods 0.000 description 14
- 230000003285 pharmacodynamic effect Effects 0.000 description 14
- 230000001988 toxicity Effects 0.000 description 14
- 231100000419 toxicity Toxicity 0.000 description 14
- 239000003981 vehicle Substances 0.000 description 14
- 230000004071 biological effect Effects 0.000 description 13
- 238000002347 injection Methods 0.000 description 13
- 239000007924 injection Substances 0.000 description 13
- 230000004048 modification Effects 0.000 description 13
- 238000012986 modification Methods 0.000 description 13
- 230000000144 pharmacologic effect Effects 0.000 description 13
- 241000282567 Macaca fascicularis Species 0.000 description 12
- 238000001727 in vivo Methods 0.000 description 12
- 102000016971 Proto-Oncogene Proteins c-kit Human genes 0.000 description 11
- 108010014608 Proto-Oncogene Proteins c-kit Proteins 0.000 description 11
- 238000004458 analytical method Methods 0.000 description 11
- 238000011156 evaluation Methods 0.000 description 11
- 238000009472 formulation Methods 0.000 description 11
- 238000004519 manufacturing process Methods 0.000 description 11
- 102000039446 nucleic acids Human genes 0.000 description 11
- 108020004707 nucleic acids Proteins 0.000 description 11
- 150000007523 nucleic acids Chemical class 0.000 description 11
- 230000002093 peripheral effect Effects 0.000 description 11
- 231100000371 dose-limiting toxicity Toxicity 0.000 description 10
- 238000000338 in vitro Methods 0.000 description 10
- 108020004414 DNA Proteins 0.000 description 9
- 238000002965 ELISA Methods 0.000 description 9
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 9
- 238000003556 assay Methods 0.000 description 9
- 230000002489 hematologic effect Effects 0.000 description 9
- 239000013612 plasmid Substances 0.000 description 9
- 230000005714 functional activity Effects 0.000 description 8
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 8
- 238000007792 addition Methods 0.000 description 7
- 230000015572 biosynthetic process Effects 0.000 description 7
- 238000006243 chemical reaction Methods 0.000 description 7
- 238000011393 cytotoxic chemotherapy Methods 0.000 description 7
- 230000003111 delayed effect Effects 0.000 description 7
- 210000003714 granulocyte Anatomy 0.000 description 7
- 238000003018 immunoassay Methods 0.000 description 7
- 230000002163 immunogen Effects 0.000 description 7
- 230000000069 prophylactic effect Effects 0.000 description 7
- 206010015866 Extravasation Diseases 0.000 description 6
- 241000282412 Homo Species 0.000 description 6
- 238000010521 absorption reaction Methods 0.000 description 6
- 239000003242 anti bacterial agent Substances 0.000 description 6
- 229940088710 antibiotic agent Drugs 0.000 description 6
- 210000004369 blood Anatomy 0.000 description 6
- 239000008280 blood Substances 0.000 description 6
- 230000037396 body weight Effects 0.000 description 6
- 239000003246 corticosteroid Substances 0.000 description 6
- 229960001334 corticosteroids Drugs 0.000 description 6
- 230000036251 extravasation Effects 0.000 description 6
- -1 for example Chemical class 0.000 description 6
- 231100000226 haematotoxicity Toxicity 0.000 description 6
- 230000003394 haemopoietic effect Effects 0.000 description 6
- 239000002547 new drug Substances 0.000 description 6
- 125000003729 nucleotide group Chemical group 0.000 description 6
- 239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 description 6
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 6
- 229920000053 polysorbate 80 Polymers 0.000 description 6
- 229940068968 polysorbate 80 Drugs 0.000 description 6
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 6
- 230000035755 proliferation Effects 0.000 description 6
- 208000003265 stomatitis Diseases 0.000 description 6
- 102000002260 Alkaline Phosphatase Human genes 0.000 description 5
- 108020004774 Alkaline Phosphatase Proteins 0.000 description 5
- 201000004384 Alopecia Diseases 0.000 description 5
- 206010065553 Bone marrow failure Diseases 0.000 description 5
- 206010006002 Bone pain Diseases 0.000 description 5
- 241000588724 Escherichia coli Species 0.000 description 5
- 230000002776 aggregation Effects 0.000 description 5
- 238000004220 aggregation Methods 0.000 description 5
- 231100000360 alopecia Toxicity 0.000 description 5
- 230000005875 antibody response Effects 0.000 description 5
- 229910052799 carbon Inorganic materials 0.000 description 5
- 239000003102 growth factor Substances 0.000 description 5
- 238000009396 hybridization Methods 0.000 description 5
- 230000028993 immune response Effects 0.000 description 5
- 230000000670 limiting effect Effects 0.000 description 5
- 239000011159 matrix material Substances 0.000 description 5
- 230000003472 neutralizing effect Effects 0.000 description 5
- 239000002773 nucleotide Substances 0.000 description 5
- 230000036515 potency Effects 0.000 description 5
- 238000012545 processing Methods 0.000 description 5
- 102000005962 receptors Human genes 0.000 description 5
- 108020003175 receptors Proteins 0.000 description 5
- 238000001356 surgical procedure Methods 0.000 description 5
- 238000002560 therapeutic procedure Methods 0.000 description 5
- 230000003442 weekly effect Effects 0.000 description 5
- GVJHHUAWPYXKBD-UHFFFAOYSA-N (±)-α-Tocopherol Chemical compound OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-UHFFFAOYSA-N 0.000 description 4
- ODHCTXKNWHHXJC-VKHMYHEASA-N 5-oxo-L-proline Chemical compound OC(=O)[C@@H]1CCC(=O)N1 ODHCTXKNWHHXJC-VKHMYHEASA-N 0.000 description 4
- 206010001052 Acute respiratory distress syndrome Diseases 0.000 description 4
- 108010082126 Alanine transaminase Proteins 0.000 description 4
- 108010003415 Aspartate Aminotransferases Proteins 0.000 description 4
- 102000004625 Aspartate Aminotransferases Human genes 0.000 description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Chemical compound OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 4
- NWIBSHFKIJFRCO-WUDYKRTCSA-N Mytomycin Chemical compound C1N2C(C(C(C)=C(N)C3=O)=O)=C3[C@@H](COC(N)=O)[C@@]2(OC)[C@@H]2[C@H]1N2 NWIBSHFKIJFRCO-WUDYKRTCSA-N 0.000 description 4
- 206010028817 Nausea and vomiting symptoms Diseases 0.000 description 4
- 239000002202 Polyethylene glycol Substances 0.000 description 4
- 208000013616 Respiratory Distress Syndrome Diseases 0.000 description 4
- IQFYYKKMVGJFEH-XLPZGREQSA-N Thymidine Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](CO)[C@@H](O)C1 IQFYYKKMVGJFEH-XLPZGREQSA-N 0.000 description 4
- 208000011341 adult acute respiratory distress syndrome Diseases 0.000 description 4
- 201000000028 adult respiratory distress syndrome Diseases 0.000 description 4
- 230000003042 antagnostic effect Effects 0.000 description 4
- 229940045799 anthracyclines and related substance Drugs 0.000 description 4
- 230000022131 cell cycle Effects 0.000 description 4
- 230000004663 cell proliferation Effects 0.000 description 4
- 230000008859 change Effects 0.000 description 4
- 150000001875 compounds Chemical class 0.000 description 4
- DDRJAANPRJIHGJ-UHFFFAOYSA-N creatinine Chemical compound CN1CC(=O)NC1=N DDRJAANPRJIHGJ-UHFFFAOYSA-N 0.000 description 4
- 230000001186 cumulative effect Effects 0.000 description 4
- 231100000433 cytotoxic Toxicity 0.000 description 4
- 230000001472 cytotoxic effect Effects 0.000 description 4
- 230000006378 damage Effects 0.000 description 4
- 238000001647 drug administration Methods 0.000 description 4
- 239000013604 expression vector Substances 0.000 description 4
- 230000009610 hypersensitivity Effects 0.000 description 4
- 239000003446 ligand Substances 0.000 description 4
- 210000004185 liver Anatomy 0.000 description 4
- 239000012931 lyophilized formulation Substances 0.000 description 4
- 238000013411 master cell bank Methods 0.000 description 4
- 239000002609 medium Substances 0.000 description 4
- 125000001360 methionine group Chemical group N[C@@H](CCSC)C(=O)* 0.000 description 4
- 230000002085 persistent effect Effects 0.000 description 4
- 229920001223 polyethylene glycol Polymers 0.000 description 4
- 238000009101 premedication Methods 0.000 description 4
- 238000001959 radiotherapy Methods 0.000 description 4
- 230000007115 recruitment Effects 0.000 description 4
- 230000000717 retained effect Effects 0.000 description 4
- 210000000130 stem cell Anatomy 0.000 description 4
- 239000008227 sterile water for injection Substances 0.000 description 4
- 229940063683 taxotere Drugs 0.000 description 4
- 229940104230 thymidine Drugs 0.000 description 4
- 230000001052 transient effect Effects 0.000 description 4
- 239000008215 water for injection Substances 0.000 description 4
- ZOOGRGPOEVQQDX-UUOKFMHZSA-N 3',5'-cyclic GMP Chemical compound C([C@H]1O2)OP(O)(=O)O[C@H]1[C@@H](O)[C@@H]2N1C(N=C(NC2=O)N)=C2N=C1 ZOOGRGPOEVQQDX-UUOKFMHZSA-N 0.000 description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- 102000007644 Colony-Stimulating Factors Human genes 0.000 description 3
- 108010071942 Colony-Stimulating Factors Proteins 0.000 description 3
- 201000009084 Dysgammaglobulinemia Diseases 0.000 description 3
- 108010017213 Granulocyte-Macrophage Colony-Stimulating Factor Proteins 0.000 description 3
- 102100039620 Granulocyte-macrophage colony-stimulating factor Human genes 0.000 description 3
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 description 3
- 208000002193 Pain Diseases 0.000 description 3
- 206010033661 Pancytopenia Diseases 0.000 description 3
- 206010037660 Pyrexia Diseases 0.000 description 3
- 241000700159 Rattus Species 0.000 description 3
- 206010047700 Vomiting Diseases 0.000 description 3
- 208000027418 Wounds and injury Diseases 0.000 description 3
- 238000009825 accumulation Methods 0.000 description 3
- 238000001042 affinity chromatography Methods 0.000 description 3
- 230000001580 bacterial effect Effects 0.000 description 3
- 230000008901 benefit Effects 0.000 description 3
- 230000008827 biological function Effects 0.000 description 3
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 3
- 230000000973 chemotherapeutic effect Effects 0.000 description 3
- 238000002648 combination therapy Methods 0.000 description 3
- 230000000295 complement effect Effects 0.000 description 3
- 125000004122 cyclic group Chemical group 0.000 description 3
- 208000024389 cytopenia Diseases 0.000 description 3
- 230000034994 death Effects 0.000 description 3
- 231100000517 death Toxicity 0.000 description 3
- 230000003247 decreasing effect Effects 0.000 description 3
- 238000010494 dissociation reaction Methods 0.000 description 3
- 230000005593 dissociations Effects 0.000 description 3
- VJJPUSNTGOMMGY-MRVIYFEKSA-N etoposide Chemical compound COC1=C(O)C(OC)=CC([C@@H]2C3=CC=4OCOC=4C=C3[C@@H](O[C@H]3[C@@H]([C@@H](O)[C@@H]4O[C@H](C)OC[C@H]4O3)O)[C@@H]3[C@@H]2C(OC3)=O)=C1 VJJPUSNTGOMMGY-MRVIYFEKSA-N 0.000 description 3
- 229960005420 etoposide Drugs 0.000 description 3
- 230000029142 excretion Effects 0.000 description 3
- 230000006870 function Effects 0.000 description 3
- 230000012010 growth Effects 0.000 description 3
- 125000002887 hydroxy group Chemical class [H]O* 0.000 description 3
- 208000014674 injury Diseases 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 210000004962 mammalian cell Anatomy 0.000 description 3
- 239000008194 pharmaceutical composition Substances 0.000 description 3
- 230000004853 protein function Effects 0.000 description 3
- 238000011002 quantification Methods 0.000 description 3
- 230000010076 replication Effects 0.000 description 3
- 238000011160 research Methods 0.000 description 3
- 239000011780 sodium chloride Substances 0.000 description 3
- 238000007619 statistical method Methods 0.000 description 3
- 238000003860 storage Methods 0.000 description 3
- 230000009885 systemic effect Effects 0.000 description 3
- 206010043554 thrombocytopenia Diseases 0.000 description 3
- 230000014616 translation Effects 0.000 description 3
- 230000008673 vomiting Effects 0.000 description 3
- 210000005253 yeast cell Anatomy 0.000 description 3
- HDTRYLNUVZCQOY-UHFFFAOYSA-N α-D-glucopyranosyl-α-D-glucopyranoside Natural products OC1C(O)C(O)C(CO)OC1OC1C(O)C(O)C(O)C(CO)O1 HDTRYLNUVZCQOY-UHFFFAOYSA-N 0.000 description 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 2
- 208000006820 Arthralgia Diseases 0.000 description 2
- DWRXFEITVBNRMK-UHFFFAOYSA-N Beta-D-1-Arabinofuranosylthymine Natural products O=C1NC(=O)C(C)=CN1C1C(O)C(O)C(CO)O1 DWRXFEITVBNRMK-UHFFFAOYSA-N 0.000 description 2
- 208000003174 Brain Neoplasms Diseases 0.000 description 2
- 208000031229 Cardiomyopathies Diseases 0.000 description 2
- 206010048610 Cardiotoxicity Diseases 0.000 description 2
- DLGOEMSEDOSKAD-UHFFFAOYSA-N Carmustine Chemical compound ClCCNC(=O)N(N=O)CCCl DLGOEMSEDOSKAD-UHFFFAOYSA-N 0.000 description 2
- 108020004705 Codon Proteins 0.000 description 2
- 102100021906 Cyclin-O Human genes 0.000 description 2
- 102000004127 Cytokines Human genes 0.000 description 2
- 108090000695 Cytokines Proteins 0.000 description 2
- 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 2
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 2
- 208000008960 Diabetic foot Diseases 0.000 description 2
- 206010061818 Disease progression Diseases 0.000 description 2
- MWWSFMDVAYGXBV-RUELKSSGSA-N Doxorubicin hydrochloride Chemical compound Cl.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 MWWSFMDVAYGXBV-RUELKSSGSA-N 0.000 description 2
- 102000003951 Erythropoietin Human genes 0.000 description 2
- 108090000394 Erythropoietin Proteins 0.000 description 2
- 208000010188 Folic Acid Deficiency Diseases 0.000 description 2
- 206010017533 Fungal infection Diseases 0.000 description 2
- 101000897441 Homo sapiens Cyclin-O Proteins 0.000 description 2
- 102000003839 Human Proteins Human genes 0.000 description 2
- 108090000144 Human Proteins Proteins 0.000 description 2
- 208000001953 Hypotension Diseases 0.000 description 2
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 2
- GQYIWUVLTXOXAJ-UHFFFAOYSA-N Lomustine Chemical compound ClCCN(N=O)C(=O)NC1CCCCC1 GQYIWUVLTXOXAJ-UHFFFAOYSA-N 0.000 description 2
- 229930195725 Mannitol Natural products 0.000 description 2
- 206010059282 Metastases to central nervous system Diseases 0.000 description 2
- 102000029749 Microtubule Human genes 0.000 description 2
- 108091022875 Microtubule Proteins 0.000 description 2
- 208000000112 Myalgia Diseases 0.000 description 2
- 208000031888 Mycoses Diseases 0.000 description 2
- 208000009525 Myocarditis Diseases 0.000 description 2
- 125000000729 N-terminal amino-acid group Chemical group 0.000 description 2
- 206010029333 Neurosis Diseases 0.000 description 2
- 108091028043 Nucleic acid sequence Proteins 0.000 description 2
- 108700026244 Open Reading Frames Proteins 0.000 description 2
- 239000004698 Polyethylene Substances 0.000 description 2
- 229920001213 Polysorbate 20 Polymers 0.000 description 2
- 108010076504 Protein Sorting Signals Proteins 0.000 description 2
- 230000006819 RNA synthesis Effects 0.000 description 2
- 230000018199 S phase Effects 0.000 description 2
- 206010040021 Sensory abnormalities Diseases 0.000 description 2
- 241000187081 Streptomyces peucetius Species 0.000 description 2
- 238000008050 Total Bilirubin Reagent Methods 0.000 description 2
- 108090000340 Transaminases Proteins 0.000 description 2
- 102000003929 Transaminases Human genes 0.000 description 2
- HDTRYLNUVZCQOY-WSWWMNSNSA-N Trehalose Natural products O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@H](O)[C@@H](O)[C@@H](O)[C@@H](CO)O1 HDTRYLNUVZCQOY-WSWWMNSNSA-N 0.000 description 2
- 102000004243 Tubulin Human genes 0.000 description 2
- 108090000704 Tubulin Proteins 0.000 description 2
- 229930003427 Vitamin E Natural products 0.000 description 2
- 230000002378 acidificating effect Effects 0.000 description 2
- 238000009098 adjuvant therapy Methods 0.000 description 2
- 108010080374 albuferon Proteins 0.000 description 2
- 125000001931 aliphatic group Chemical class 0.000 description 2
- 230000007815 allergy Effects 0.000 description 2
- HDTRYLNUVZCQOY-LIZSDCNHSA-N alpha,alpha-trehalose Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 HDTRYLNUVZCQOY-LIZSDCNHSA-N 0.000 description 2
- 150000001408 amides Chemical class 0.000 description 2
- 239000005557 antagonist Substances 0.000 description 2
- 239000003817 anthracycline antibiotic agent Substances 0.000 description 2
- 230000003474 anti-emetic effect Effects 0.000 description 2
- 229940125681 anticonvulsant agent Drugs 0.000 description 2
- 239000001961 anticonvulsive agent Substances 0.000 description 2
- 229940125683 antiemetic agent Drugs 0.000 description 2
- 239000002111 antiemetic agent Substances 0.000 description 2
- 239000000427 antigen Substances 0.000 description 2
- 108091007433 antigens Proteins 0.000 description 2
- 102000036639 antigens Human genes 0.000 description 2
- 125000003118 aryl group Chemical group 0.000 description 2
- IQFYYKKMVGJFEH-UHFFFAOYSA-N beta-L-thymidine Natural products O=C1NC(=O)C(C)=CN1C1OC(CO)C(O)C1 IQFYYKKMVGJFEH-UHFFFAOYSA-N 0.000 description 2
- 238000004166 bioassay Methods 0.000 description 2
- 229960000074 biopharmaceutical Drugs 0.000 description 2
- 238000006664 bond formation reaction Methods 0.000 description 2
- 238000004422 calculation algorithm Methods 0.000 description 2
- 231100000259 cardiotoxicity Toxicity 0.000 description 2
- 238000012512 characterization method Methods 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- MYSWGUAQZAJSOK-UHFFFAOYSA-N ciprofloxacin Chemical compound C12=CC(N3CCNCC3)=C(F)C=C2C(=O)C(C(=O)O)=CN1C1CC1 MYSWGUAQZAJSOK-UHFFFAOYSA-N 0.000 description 2
- 239000002299 complementary DNA Substances 0.000 description 2
- 238000004590 computer program Methods 0.000 description 2
- 238000010276 construction Methods 0.000 description 2
- 239000003433 contraceptive agent Substances 0.000 description 2
- 230000002254 contraceptive effect Effects 0.000 description 2
- 238000007796 conventional method Methods 0.000 description 2
- 229940109239 creatinine Drugs 0.000 description 2
- 238000004132 cross linking Methods 0.000 description 2
- 230000009260 cross reactivity Effects 0.000 description 2
- 230000001419 dependent effect Effects 0.000 description 2
- 229960003957 dexamethasone Drugs 0.000 description 2
- UREBDLICKHMUKA-CXSFZGCWSA-N dexamethasone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@@H](C)[C@@](C(=O)CO)(O)[C@@]1(C)C[C@@H]2O UREBDLICKHMUKA-CXSFZGCWSA-N 0.000 description 2
- 238000003745 diagnosis Methods 0.000 description 2
- 230000004069 differentiation Effects 0.000 description 2
- 239000003085 diluting agent Substances 0.000 description 2
- 230000005750 disease progression Effects 0.000 description 2
- 238000009826 distribution Methods 0.000 description 2
- 229960002918 doxorubicin hydrochloride Drugs 0.000 description 2
- 229940105423 erythropoietin Drugs 0.000 description 2
- 210000003608 fece Anatomy 0.000 description 2
- 238000000855 fermentation Methods 0.000 description 2
- 230000004151 fermentation Effects 0.000 description 2
- 210000004904 fingernail bed Anatomy 0.000 description 2
- 239000012530 fluid Substances 0.000 description 2
- WIGCFUFOHFEKBI-UHFFFAOYSA-N gamma-tocopherol Natural products CC(C)CCCC(C)CCCC(C)CCCC1CCC2C(C)C(O)C(C)C(C)C2O1 WIGCFUFOHFEKBI-UHFFFAOYSA-N 0.000 description 2
- 238000005227 gel permeation chromatography Methods 0.000 description 2
- 238000012817 gel-diffusion technique Methods 0.000 description 2
- 230000002068 genetic effect Effects 0.000 description 2
- 239000011521 glass Substances 0.000 description 2
- 238000002873 global sequence alignment Methods 0.000 description 2
- 230000013595 glycosylation Effects 0.000 description 2
- 238000006206 glycosylation reaction Methods 0.000 description 2
- 230000036541 health Effects 0.000 description 2
- 238000011134 hematopoietic stem cell transplantation Methods 0.000 description 2
- 208000006454 hepatitis Diseases 0.000 description 2
- 231100000283 hepatitis Toxicity 0.000 description 2
- 230000002209 hydrophobic effect Effects 0.000 description 2
- 208000031066 hyperpigmentation of the skin Diseases 0.000 description 2
- 230000036543 hypotension Effects 0.000 description 2
- 230000000951 immunodiffusion Effects 0.000 description 2
- 238000009169 immunotherapy Methods 0.000 description 2
- 230000001976 improved effect Effects 0.000 description 2
- 238000010348 incorporation Methods 0.000 description 2
- 239000012678 infectious agent Substances 0.000 description 2
- 208000021267 infertility disease Diseases 0.000 description 2
- 230000000977 initiatory effect Effects 0.000 description 2
- 230000003907 kidney function Effects 0.000 description 2
- 238000009533 lab test Methods 0.000 description 2
- 230000002045 lasting effect Effects 0.000 description 2
- 230000003902 lesion Effects 0.000 description 2
- 206010024378 leukocytosis Diseases 0.000 description 2
- 150000002632 lipids Chemical class 0.000 description 2
- 208000019423 liver disease Diseases 0.000 description 2
- 230000005976 liver dysfunction Effects 0.000 description 2
- 230000003908 liver function Effects 0.000 description 2
- 239000000594 mannitol Substances 0.000 description 2
- 235000010355 mannitol Nutrition 0.000 description 2
- 239000003550 marker Substances 0.000 description 2
- 230000004060 metabolic process Effects 0.000 description 2
- 210000004688 microtubule Anatomy 0.000 description 2
- 229960004857 mitomycin Drugs 0.000 description 2
- 230000011278 mitosis Effects 0.000 description 2
- 238000012544 monitoring process Methods 0.000 description 2
- 238000010172 mouse model Methods 0.000 description 2
- 210000000282 nail Anatomy 0.000 description 2
- 208000015238 neurotic disease Diseases 0.000 description 2
- 230000007935 neutral effect Effects 0.000 description 2
- OSTGTTZJOCZWJG-UHFFFAOYSA-N nitrosourea Chemical compound NC(=O)N=NO OSTGTTZJOCZWJG-UHFFFAOYSA-N 0.000 description 2
- 231100000957 no side effect Toxicity 0.000 description 2
- JMANVNJQNLATNU-UHFFFAOYSA-N oxalonitrile Chemical compound N#CC#N JMANVNJQNLATNU-UHFFFAOYSA-N 0.000 description 2
- 230000007030 peptide scission Effects 0.000 description 2
- 208000008494 pericarditis Diseases 0.000 description 2
- 229920000573 polyethylene Polymers 0.000 description 2
- 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 2
- 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 2
- 229940068977 polysorbate 20 Drugs 0.000 description 2
- 230000001323 posttranslational effect Effects 0.000 description 2
- OXCMYAYHXIHQOA-UHFFFAOYSA-N potassium;[2-butyl-5-chloro-3-[[4-[2-(1,2,4-triaza-3-azanidacyclopenta-1,4-dien-5-yl)phenyl]phenyl]methyl]imidazol-4-yl]methanol Chemical compound [K+].CCCCC1=NC(Cl)=C(CO)N1CC1=CC=C(C=2C(=CC=CC=2)C2=N[N-]N=N2)C=C1 OXCMYAYHXIHQOA-UHFFFAOYSA-N 0.000 description 2
- 238000001556 precipitation Methods 0.000 description 2
- 229940071643 prefilled syringe Drugs 0.000 description 2
- 230000035935 pregnancy Effects 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 238000011321 prophylaxis Methods 0.000 description 2
- 238000001243 protein synthesis Methods 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 238000003127 radioimmunoassay Methods 0.000 description 2
- 231100000279 safety data Toxicity 0.000 description 2
- 238000003118 sandwich ELISA Methods 0.000 description 2
- 238000012216 screening Methods 0.000 description 2
- 238000004062 sedimentation Methods 0.000 description 2
- 230000001953 sensory effect Effects 0.000 description 2
- 238000002864 sequence alignment Methods 0.000 description 2
- 208000007056 sickle cell anemia Diseases 0.000 description 2
- 230000037380 skin damage Effects 0.000 description 2
- 229910052708 sodium Inorganic materials 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- 239000001509 sodium citrate Substances 0.000 description 2
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 2
- 239000001488 sodium phosphate Substances 0.000 description 2
- 229910000162 sodium phosphate Inorganic materials 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- 239000000600 sorbitol Substances 0.000 description 2
- 238000009331 sowing Methods 0.000 description 2
- 241000894007 species Species 0.000 description 2
- 210000000952 spleen Anatomy 0.000 description 2
- 150000003431 steroids Chemical class 0.000 description 2
- 238000010254 subcutaneous injection Methods 0.000 description 2
- 239000007929 subcutaneous injection Substances 0.000 description 2
- 230000002459 sustained effect Effects 0.000 description 2
- 238000012353 t test Methods 0.000 description 2
- 230000000451 tissue damage Effects 0.000 description 2
- 231100000827 tissue damage Toxicity 0.000 description 2
- 238000013519 translation Methods 0.000 description 2
- 238000011269 treatment regimen Methods 0.000 description 2
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 2
- 238000010798 ubiquitination Methods 0.000 description 2
- 230000034512 ubiquitination Effects 0.000 description 2
- 231100000402 unacceptable toxicity Toxicity 0.000 description 2
- 239000013598 vector Substances 0.000 description 2
- 230000002861 ventricular Effects 0.000 description 2
- 235000019165 vitamin E Nutrition 0.000 description 2
- 229940046009 vitamin E Drugs 0.000 description 2
- 239000011709 vitamin E Substances 0.000 description 2
- 238000001262 western blot Methods 0.000 description 2
- 238000010600 3H thymidine incorporation assay Methods 0.000 description 1
- 230000005730 ADP ribosylation Effects 0.000 description 1
- 206010067484 Adverse reaction Diseases 0.000 description 1
- 108020000946 Bacterial DNA Proteins 0.000 description 1
- 102100029516 Basic salivary proline-rich protein 1 Human genes 0.000 description 1
- 102000004506 Blood Proteins Human genes 0.000 description 1
- 108010017384 Blood Proteins Proteins 0.000 description 1
- 206010051779 Bone marrow toxicity Diseases 0.000 description 1
- 125000001433 C-terminal amino-acid group Chemical group 0.000 description 1
- 102000014914 Carrier Proteins Human genes 0.000 description 1
- 108010078791 Carrier Proteins Proteins 0.000 description 1
- 206010007882 Cellulitis Diseases 0.000 description 1
- 208000035473 Communicable disease Diseases 0.000 description 1
- 230000006820 DNA synthesis Effects 0.000 description 1
- 101150085931 DSTN gene Proteins 0.000 description 1
- 241000196324 Embryophyta Species 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 108010046276 FLP recombinase Proteins 0.000 description 1
- 108700039691 Genetic Promoter Regions Proteins 0.000 description 1
- 206010018901 Haemoglobinaemia Diseases 0.000 description 1
- 101001125486 Homo sapiens Basic salivary proline-rich protein 1 Proteins 0.000 description 1
- 101000746373 Homo sapiens Granulocyte-macrophage colony-stimulating factor Proteins 0.000 description 1
- 206010020772 Hypertension Diseases 0.000 description 1
- 108010047761 Interferon-alpha Proteins 0.000 description 1
- 102000006992 Interferon-alpha Human genes 0.000 description 1
- 108010050904 Interferons Proteins 0.000 description 1
- 102000014150 Interferons Human genes 0.000 description 1
- 108010002386 Interleukin-3 Proteins 0.000 description 1
- 102100039064 Interleukin-3 Human genes 0.000 description 1
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 1
- 101150007280 LEU2 gene Proteins 0.000 description 1
- ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 1
- 206010024652 Liver abscess Diseases 0.000 description 1
- 206010027452 Metastases to bone Diseases 0.000 description 1
- 241000699666 Mus <mouse, genus> Species 0.000 description 1
- 201000003793 Myelodysplastic syndrome Diseases 0.000 description 1
- 206010028813 Nausea Diseases 0.000 description 1
- 108091092724 Noncoding DNA Proteins 0.000 description 1
- 208000007117 Oral Ulcer Diseases 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 208000005141 Otitis Diseases 0.000 description 1
- 206010033078 Otitis media Diseases 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 206010057249 Phagocytosis Diseases 0.000 description 1
- CXOFVDLJLONNDW-UHFFFAOYSA-N Phenytoin Chemical compound N1C(=O)NC(=O)C1(C=1C=CC=CC=1)C1=CC=CC=C1 CXOFVDLJLONNDW-UHFFFAOYSA-N 0.000 description 1
- 206010035664 Pneumonia Diseases 0.000 description 1
- 239000004743 Polypropylene Substances 0.000 description 1
- ODHCTXKNWHHXJC-GSVOUGTGSA-N Pyroglutamic acid Natural products OC(=O)[C@H]1CCC(=O)N1 ODHCTXKNWHHXJC-GSVOUGTGSA-N 0.000 description 1
- 241000219492 Quercus Species 0.000 description 1
- 108020004511 Recombinant DNA Proteins 0.000 description 1
- 102000007056 Recombinant Fusion Proteins Human genes 0.000 description 1
- 108010008281 Recombinant Fusion Proteins Proteins 0.000 description 1
- AUNGANRZJHBGPY-SCRDCRAPSA-N Riboflavin Chemical compound OC[C@@H](O)[C@@H](O)[C@@H](O)CN1C=2C=C(C)C(C)=CC=2N=C2C1=NC(=O)NC2=O AUNGANRZJHBGPY-SCRDCRAPSA-N 0.000 description 1
- 206010040047 Sepsis Diseases 0.000 description 1
- 206010041067 Small cell lung cancer Diseases 0.000 description 1
- 238000000692 Student's t-test Methods 0.000 description 1
- 201000008717 T-cell large granular lymphocyte leukemia Diseases 0.000 description 1
- 239000004809 Teflon Substances 0.000 description 1
- 229920006362 Teflon® Polymers 0.000 description 1
- 108020004566 Transfer RNA Proteins 0.000 description 1
- LEHOTFFKMJEONL-UHFFFAOYSA-N Uric Acid Chemical compound N1C(=O)NC(=O)C2=C1NC(=O)N2 LEHOTFFKMJEONL-UHFFFAOYSA-N 0.000 description 1
- TVWHNULVHGKJHS-UHFFFAOYSA-N Uric acid Natural products N1C(=O)NC(=O)C2NC(=O)NC21 TVWHNULVHGKJHS-UHFFFAOYSA-N 0.000 description 1
- 229930003779 Vitamin B12 Natural products 0.000 description 1
- 230000021736 acetylation Effects 0.000 description 1
- 238000006640 acetylation reaction Methods 0.000 description 1
- ODHCTXKNWHHXJC-UHFFFAOYSA-N acide pyroglutamique Natural products OC(=O)C1CCC(=O)N1 ODHCTXKNWHHXJC-UHFFFAOYSA-N 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 239000008186 active pharmaceutical agent Substances 0.000 description 1
- 230000010933 acylation Effects 0.000 description 1
- 238000005917 acylation reaction Methods 0.000 description 1
- 230000006838 adverse reaction Effects 0.000 description 1
- 238000007818 agglutination assay Methods 0.000 description 1
- 235000004279 alanine Nutrition 0.000 description 1
- 238000012867 alanine scanning Methods 0.000 description 1
- 230000000735 allogeneic effect Effects 0.000 description 1
- 230000009435 amidation Effects 0.000 description 1
- 238000007112 amidation reaction Methods 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 230000000259 anti-tumor effect Effects 0.000 description 1
- 125000000637 arginyl group Chemical group N[C@@H](CCCNC(N)=N)C(=O)* 0.000 description 1
- 238000002820 assay format Methods 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- BPYKTIZUTYGOLE-UHFFFAOYSA-N billirubin-IXalpha Natural products N1C(=O)C(C)=C(C=C)C1=CC1=C(C)C(CCC(O)=O)=C(CC2=C(C(C)=C(C=C3C(=C(C=C)C(=O)N3)C)N2)CCC(O)=O)N1 BPYKTIZUTYGOLE-UHFFFAOYSA-N 0.000 description 1
- 230000003115 biocidal effect Effects 0.000 description 1
- 238000001815 biotherapy Methods 0.000 description 1
- 231100000366 bone marrow toxicity Toxicity 0.000 description 1
- 238000010322 bone marrow transplantation Methods 0.000 description 1
- 238000004364 calculation method Methods 0.000 description 1
- 150000001720 carbohydrates Chemical class 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 230000010261 cell growth Effects 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 238000007385 chemical modification Methods 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 229960005091 chloramphenicol Drugs 0.000 description 1
- WIIZWVCIJKGZOK-RKDXNWHRSA-N chloramphenicol Chemical compound ClC(Cl)C(=O)N[C@H](CO)[C@H](O)C1=CC=C([N+]([O-])=O)C=C1 WIIZWVCIJKGZOK-RKDXNWHRSA-N 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 229960003405 ciprofloxacin Drugs 0.000 description 1
- DQLATGHUWYMOKM-UHFFFAOYSA-L cisplatin Chemical compound N[Pt](N)(Cl)Cl DQLATGHUWYMOKM-UHFFFAOYSA-L 0.000 description 1
- 229960004316 cisplatin Drugs 0.000 description 1
- 238000010367 cloning Methods 0.000 description 1
- FDJOLVPMNUYSCM-WZHZPDAFSA-L cobalt(3+);[(2r,3s,4r,5s)-5-(5,6-dimethylbenzimidazol-1-yl)-4-hydroxy-2-(hydroxymethyl)oxolan-3-yl] [(2r)-1-[3-[(1r,2r,3r,4z,7s,9z,12s,13s,14z,17s,18s,19r)-2,13,18-tris(2-amino-2-oxoethyl)-7,12,17-tris(3-amino-3-oxopropyl)-3,5,8,8,13,15,18,19-octamethyl-2 Chemical compound [Co+3].N#[C-].N([C@@H]([C@]1(C)[N-]\C([C@H]([C@@]1(CC(N)=O)C)CCC(N)=O)=C(\C)/C1=N/C([C@H]([C@@]1(CC(N)=O)C)CCC(N)=O)=C\C1=N\C([C@H](C1(C)C)CCC(N)=O)=C/1C)[C@@H]2CC(N)=O)=C\1[C@]2(C)CCC(=O)NC[C@@H](C)OP([O-])(=O)O[C@H]1[C@@H](O)[C@@H](N2C3=CC(C)=C(C)C=C3N=C2)O[C@@H]1CO FDJOLVPMNUYSCM-WZHZPDAFSA-L 0.000 description 1
- 206010009887 colitis Diseases 0.000 description 1
- 229940047120 colony stimulating factors Drugs 0.000 description 1
- 238000012937 correction Methods 0.000 description 1
- 235000018417 cysteine Nutrition 0.000 description 1
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 1
- 239000002254 cytotoxic agent Substances 0.000 description 1
- 231100000599 cytotoxic agent Toxicity 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 230000008260 defense mechanism Effects 0.000 description 1
- 230000017858 demethylation Effects 0.000 description 1
- 238000010520 demethylation reaction Methods 0.000 description 1
- 238000009795 derivation Methods 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- 235000014113 dietary fatty acids Nutrition 0.000 description 1
- 208000037765 diseases and disorders Diseases 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 229940088679 drug related substance Drugs 0.000 description 1
- 238000002651 drug therapy Methods 0.000 description 1
- 208000019258 ear infection Diseases 0.000 description 1
- 230000000441 effect on granulocytes Effects 0.000 description 1
- 239000006274 endogenous ligand Substances 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- 230000009088 enzymatic function Effects 0.000 description 1
- 230000005713 exacerbation Effects 0.000 description 1
- 239000006277 exogenous ligand Substances 0.000 description 1
- 230000003631 expected effect Effects 0.000 description 1
- 239000000194 fatty acid Substances 0.000 description 1
- 229930195729 fatty acid Natural products 0.000 description 1
- 150000004665 fatty acids Chemical class 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 238000000684 flow cytometry Methods 0.000 description 1
- 238000012494 forced degradation Methods 0.000 description 1
- 239000013016 formulated drug substance Substances 0.000 description 1
- 230000022244 formylation Effects 0.000 description 1
- 238000006170 formylation reaction Methods 0.000 description 1
- 238000004108 freeze drying Methods 0.000 description 1
- 239000012595 freezing medium Substances 0.000 description 1
- 230000006251 gamma-carboxylation Effects 0.000 description 1
- 238000010353 genetic engineering Methods 0.000 description 1
- 235000003869 genetically modified organism Nutrition 0.000 description 1
- 208000007565 gingivitis Diseases 0.000 description 1
- PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 description 1
- 150000003278 haem Chemical group 0.000 description 1
- 230000035931 haemagglutination Effects 0.000 description 1
- 229940022353 herceptin Drugs 0.000 description 1
- 239000005556 hormone Substances 0.000 description 1
- 229940088597 hormone Drugs 0.000 description 1
- 230000001900 immune effect Effects 0.000 description 1
- 230000036737 immune function Effects 0.000 description 1
- 238000000760 immunoelectrophoresis Methods 0.000 description 1
- 238000010166 immunofluorescence Methods 0.000 description 1
- 238000001114 immunoprecipitation Methods 0.000 description 1
- 238000003017 in situ immunoassay Methods 0.000 description 1
- 238000000099 in vitro assay Methods 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 230000002458 infectious effect Effects 0.000 description 1
- 201000006747 infectious mononucleosis Diseases 0.000 description 1
- 206010022000 influenza Diseases 0.000 description 1
- 239000002917 insecticide Substances 0.000 description 1
- 229940079322 interferon Drugs 0.000 description 1
- 239000007928 intraperitoneal injection Substances 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- 230000026045 iodination Effects 0.000 description 1
- 238000006192 iodination reaction Methods 0.000 description 1
- 238000004255 ion exchange chromatography Methods 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 238000005304 joining Methods 0.000 description 1
- 238000002372 labelling Methods 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 239000012092 media component Substances 0.000 description 1
- 108020004999 messenger RNA Proteins 0.000 description 1
- MYWUZJCMWCOHBA-VIFPVBQESA-N methamphetamine Chemical compound CN[C@@H](C)CC1=CC=CC=C1 MYWUZJCMWCOHBA-VIFPVBQESA-N 0.000 description 1
- 230000011987 methylation Effects 0.000 description 1
- 238000007069 methylation reaction Methods 0.000 description 1
- 244000005700 microbiome Species 0.000 description 1
- 230000028550 monocyte chemotaxis Effects 0.000 description 1
- 210000005087 mononuclear cell Anatomy 0.000 description 1
- 230000035772 mutation Effects 0.000 description 1
- 210000003643 myeloid progenitor cell Anatomy 0.000 description 1
- 231100000052 myelotoxic Toxicity 0.000 description 1
- 230000002556 myelotoxic effect Effects 0.000 description 1
- 230000008693 nausea Effects 0.000 description 1
- 238000013059 nephrectomy Methods 0.000 description 1
- 238000006386 neutralization reaction Methods 0.000 description 1
- 230000011242 neutrophil chemotaxis Effects 0.000 description 1
- 230000009871 nonspecific binding Effects 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 229940127249 oral antibiotic Drugs 0.000 description 1
- 230000003204 osmotic effect Effects 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 230000006320 pegylation Effects 0.000 description 1
- 210000004197 pelvis Anatomy 0.000 description 1
- 210000005105 peripheral blood lymphocyte Anatomy 0.000 description 1
- 210000003819 peripheral blood mononuclear cell Anatomy 0.000 description 1
- 230000008782 phagocytosis Effects 0.000 description 1
- 229960002036 phenytoin Drugs 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 150000003905 phosphatidylinositols Chemical class 0.000 description 1
- 230000026731 phosphorylation Effects 0.000 description 1
- 238000006366 phosphorylation reaction Methods 0.000 description 1
- 210000001778 pluripotent stem cell Anatomy 0.000 description 1
- 206010036067 polydipsia Diseases 0.000 description 1
- 229920001155 polypropylene Polymers 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 238000009597 pregnancy test Methods 0.000 description 1
- 230000013823 prenylation Effects 0.000 description 1
- 208000003476 primary myelofibrosis Diseases 0.000 description 1
- 230000009862 primary prevention Effects 0.000 description 1
- 230000037452 priming Effects 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 235000004252 protein component Nutrition 0.000 description 1
- 230000007026 protein scission Effects 0.000 description 1
- 230000002797 proteolythic effect Effects 0.000 description 1
- 238000013139 quantization Methods 0.000 description 1
- 230000006340 racemization Effects 0.000 description 1
- 231100000191 repeated dose toxicity Toxicity 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 238000007363 ring formation reaction Methods 0.000 description 1
- 238000012502 risk assessment Methods 0.000 description 1
- 238000005070 sampling Methods 0.000 description 1
- 210000001991 scapula Anatomy 0.000 description 1
- 230000003248 secreting effect Effects 0.000 description 1
- 238000012163 sequencing technique Methods 0.000 description 1
- 230000001568 sexual effect Effects 0.000 description 1
- 239000013605 shuttle vector Substances 0.000 description 1
- 201000009890 sinusitis Diseases 0.000 description 1
- 238000002741 site-directed mutagenesis Methods 0.000 description 1
- 208000000587 small cell lung carcinoma Diseases 0.000 description 1
- 230000004936 stimulating effect Effects 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 230000019635 sulfation Effects 0.000 description 1
- 238000005670 sulfation reaction Methods 0.000 description 1
- 230000003319 supportive effect Effects 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 238000007910 systemic administration Methods 0.000 description 1
- 201000000596 systemic lupus erythematosus Diseases 0.000 description 1
- 238000002626 targeted therapy Methods 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 238000011287 therapeutic dose Methods 0.000 description 1
- 229940126585 therapeutic drug Drugs 0.000 description 1
- 230000005026 transcription initiation Effects 0.000 description 1
- 230000005030 transcription termination Effects 0.000 description 1
- 229960000575 trastuzumab Drugs 0.000 description 1
- 201000008827 tuberculosis Diseases 0.000 description 1
- 230000007306 turnover Effects 0.000 description 1
- 229940116269 uric acid Drugs 0.000 description 1
- 210000004291 uterus Anatomy 0.000 description 1
- 230000003612 virological effect Effects 0.000 description 1
- 235000019163 vitamin B12 Nutrition 0.000 description 1
- 239000011715 vitamin B12 Substances 0.000 description 1
- 208000002670 vitamin B12 deficiency Diseases 0.000 description 1
- 230000002747 voluntary effect Effects 0.000 description 1
- 238000004260 weight control Methods 0.000 description 1
Images
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/19—Cytokines; Lymphokines; Interferons
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/38—Albumins
- A61K38/385—Serum albumin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/19—Cytokines; Lymphokines; Interferons
- A61K38/193—Colony stimulating factors [CSF]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/38—Albumins
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
- A61K47/62—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being a protein, peptide or polyamino acid
- A61K47/64—Drug-peptide, drug-protein or drug-polyamino acid conjugates, i.e. the modifying agent being a peptide, protein or polyamino acid which is covalently bonded or complexed to a therapeutically active agent
- A61K47/643—Albumins, e.g. HSA, BSA, ovalbumin or a Keyhole Limpet Hemocyanin [KHL]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
-
- 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
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/04—Immunostimulants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Medicinal Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Epidemiology (AREA)
- Immunology (AREA)
- Gastroenterology & Hepatology (AREA)
- Zoology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Molecular Biology (AREA)
- Hematology (AREA)
- Oncology (AREA)
- Communicable Diseases (AREA)
- Diabetes (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Peptides Or Proteins (AREA)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US14544009P | 2009-01-16 | 2009-01-16 | |
| US14543609P | 2009-01-16 | 2009-01-16 | |
| US61/145,436 | 2009-01-16 | ||
| US61/145,440 | 2009-01-16 | ||
| PCT/US2010/021241 WO2010083439A2 (en) | 2009-01-16 | 2010-01-15 | Recombinant human albumin-human granulocyte colony stimulating factor for the prevention of neutropenia |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2012515222A true JP2012515222A (ja) | 2012-07-05 |
| JP2012515222A5 JP2012515222A5 (enExample) | 2013-02-28 |
Family
ID=42260335
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2011546399A Pending JP2012515222A (ja) | 2009-01-16 | 2010-01-15 | 組換えヒトアルブミン−ヒト顆粒球コロニー刺激因子融合タンパク質の安定な製剤 |
| JP2011546396A Expired - Fee Related JP5753095B2 (ja) | 2009-01-16 | 2010-01-15 | 組換えヒトアルブミン−ヒト顆粒球コロニー刺激因子融合タンパク質の安定な製剤 |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2011546396A Expired - Fee Related JP5753095B2 (ja) | 2009-01-16 | 2010-01-15 | 組換えヒトアルブミン−ヒト顆粒球コロニー刺激因子融合タンパク質の安定な製剤 |
Country Status (16)
| Country | Link |
|---|---|
| US (4) | US20100227818A1 (enExample) |
| EP (2) | EP2387420A2 (enExample) |
| JP (2) | JP2012515222A (enExample) |
| KR (2) | KR20110132326A (enExample) |
| CN (2) | CN102378635A (enExample) |
| AU (2) | AU2010204547B2 (enExample) |
| BR (2) | BRPI1005159A2 (enExample) |
| CA (2) | CA2749786A1 (enExample) |
| EA (2) | EA201190079A1 (enExample) |
| IL (2) | IL214052A0 (enExample) |
| MX (2) | MX2011007582A (enExample) |
| NZ (2) | NZ594056A (enExample) |
| SG (3) | SG172940A1 (enExample) |
| UA (2) | UA103221C2 (enExample) |
| WO (2) | WO2010083434A2 (enExample) |
| ZA (1) | ZA201105171B (enExample) |
Families Citing this family (32)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| UA103221C2 (uk) * | 2009-01-16 | 2013-09-25 | Тева Фармасьютікал Індастріз Лтд. | Стабільний склад рекомбінантного альбуміну людини-гранулоцитарного колонієстимулюючого фактора людини |
| EP2384759A1 (en) | 2010-05-06 | 2011-11-09 | Suomen Punainen Risti Veripalvelu | Sulphated hyaluronic acid in combination with G-CSF for use in mobilising blood stem cells |
| KR102513760B1 (ko) * | 2010-06-07 | 2023-03-27 | 암젠 인크 | 약물 전달 장치 |
| CN102628869B (zh) * | 2012-04-19 | 2014-04-02 | 上海蓝怡科技有限公司 | 提高甲胎蛋白抗体冻干稳定性的制剂 |
| WO2014113359A1 (en) * | 2013-01-15 | 2014-07-24 | Teva Pharmaceutical Industries Ltd. | Formulations of albu-bche, preparation and uses thereof |
| US20140271538A1 (en) | 2013-03-15 | 2014-09-18 | Teva Pharmaceutical Industries Ltd. | Recombinant Human Albumin-Human Granulocyte Colony Stimulating Factor for the Prevention of Neutropenia in Pediatric Patients |
| MA40904A (fr) * | 2014-11-03 | 2017-09-12 | Hygeia Tech Inc | Compositions d'ester de phorbol et procédés pour traiter ou réduire la durée d'une cytopénie |
| SG10202008673WA (en) | 2015-03-06 | 2020-10-29 | Beyondspring Pharmaceuticals Inc | Method of treating cancer associated with a ras mutation |
| BE1023343B1 (nl) * | 2015-05-20 | 2017-02-09 | Mycartis Nv | Opslagbuffer |
| CN109516981B (zh) | 2015-07-13 | 2019-10-22 | 大连万春布林医药有限公司 | 普那布林组合物 |
| JP2018522030A (ja) * | 2015-07-30 | 2018-08-09 | エンドール テクノロジーズ, エス.エレ.Endor Technologies, S.L. | 膵癌又は大腸癌の治療用コロニー刺激因子 |
| US10912748B2 (en) | 2016-02-08 | 2021-02-09 | Beyondspring Pharmaceuticals, Inc. | Compositions containing tucaresol or its analogs |
| KR20240091084A (ko) | 2016-06-06 | 2024-06-21 | 비욘드스프링 파마수티컬스, 인코포레이티드. | 호중구감소증을 줄이는 조성물 및 방법 |
| CN106222221A (zh) * | 2016-08-05 | 2016-12-14 | 山东科兴生物制品有限公司 | 制备重组人粒细胞刺激因子原液的纯化方法 |
| EP3544658B1 (en) | 2016-11-22 | 2024-07-03 | LTS Device Technologies Ltd | Apparatus for delivering a therapeutic substance |
| JP2020503363A (ja) | 2017-01-06 | 2020-01-30 | ビヨンドスプリング ファーマシューティカルズ，インコーポレイテッド | チューブリン結合化合物およびその治療的使用 |
| IL268305B2 (en) | 2017-02-01 | 2024-08-01 | Beyondspring Pharmaceuticals Inc | Plinabulin in combination with one or more g-csf drug for use in the therapeutic treatment of docetaxel-induced |
| WO2018187786A1 (en) * | 2017-04-07 | 2018-10-11 | La Jolla Institute For Allergy And Immunology | Unipotent neutrophil progenitor cells, methods of preparation, and uses thereof |
| CN109420159A (zh) * | 2017-08-23 | 2019-03-05 | 江苏泰康生物医药有限公司 | 一种重组蛋白药物的新型稳定制剂 |
| US11786523B2 (en) | 2018-01-24 | 2023-10-17 | Beyondspring Pharmaceuticals, Inc. | Composition and method for reducing thrombocytopenia |
| AU2019216305B2 (en) * | 2018-02-01 | 2024-11-21 | Beyondspring Pharmaceuticals, Inc. | Composition and method for reducing chemotherapy-induced neutropenia via the administration of plinabulin and a G-CSF agent |
| US11583633B2 (en) | 2018-04-03 | 2023-02-21 | Amgen Inc. | Systems and methods for delayed drug delivery |
| EP3632487B1 (en) | 2018-10-05 | 2024-06-12 | LTS Device Technologies Ltd | Triggering sequence |
| CN111383745A (zh) * | 2018-12-29 | 2020-07-07 | 医渡云（北京）技术有限公司 | 计算机数据处理方法、装置、存储介质及设备 |
| US11267858B2 (en) | 2019-05-31 | 2022-03-08 | Spectrum Pharmaceuticals, Inc. | Methods of treatment using G-CSF protein complex |
| US11684655B2 (en) * | 2019-05-31 | 2023-06-27 | Spectrum Pharmaceuticals, Inc. | Methods of treating neutorpenia using G-CSF protein complex |
| CN112316120A (zh) * | 2019-08-05 | 2021-02-05 | 天津派格生物技术有限公司 | 使用低动员型g-csf有效且安全治疗粒细胞减少症的方法 |
| KR20220110747A (ko) * | 2019-12-05 | 2022-08-09 | 한미약품 주식회사 | 화학 요법 또는 방사선 요법으로 유도된 호중구감소증을 치료하는 방법 |
| KR102485892B1 (ko) * | 2020-04-09 | 2023-01-09 | 주식회사 에이프릴바이오 | 고양이 과립구 집락 자극인자 및 혈청 알부민에 대한 항원 결합 단편을 포함하는 융합 단백질 및 이의 용도 |
| CN111751552B (zh) * | 2020-06-18 | 2022-09-16 | 广州市伊川生物科技有限公司 | 一种缺血修饰白蛋白测定试剂盒及其使用方法 |
| JP2024513505A (ja) | 2021-04-09 | 2024-03-25 | ビヨンドスプリング ファーマシューティカルズ，インコーポレイテッド | 腫瘍を治療するための組成物及び方法 |
| US11723955B1 (en) * | 2022-05-13 | 2023-08-15 | Allgenesis Biotherapeutics Inc. | VEGFR fusion protein pharmaceutical composition |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2005514060A (ja) * | 2001-12-21 | 2005-05-19 | ヒューマン ジノーム サイエンシーズ， インコーポレイテッド | アルブミン融合タンパク質 |
Family Cites Families (22)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| BR8806573A (pt) * | 1987-04-09 | 1989-10-31 | Delta Biotechnology Ltd | Vetor de levedo |
| JPH01215289A (ja) | 1988-02-22 | 1989-08-29 | Toa Nenryo Kogyo Kk | 遺伝子組換えによる正常ヒト血清アルブミンａの製造方法 |
| FR2649991B2 (fr) | 1988-08-05 | 1994-03-04 | Rhone Poulenc Sante | Utilisation de derives stables du plasmide pkd1 pour l'expression et la secretion de proteines heterologues dans les levures du genre kluyveromyces |
| FR2686899B1 (fr) * | 1992-01-31 | 1995-09-01 | Rhone Poulenc Rorer Sa | Nouveaux polypeptides biologiquement actifs, leur preparation et compositions pharmaceutiques les contenant. |
| FR2686900B1 (fr) * | 1992-01-31 | 1995-07-21 | Rhone Poulenc Rorer Sa | Nouveaux polypeptides ayant une activite de stimulation des colonies de granulocytes, leur preparation et compositions pharmaceutiques les contenant. |
| DE4242863A1 (de) * | 1992-12-18 | 1994-06-23 | Boehringer Mannheim Gmbh | Stabile lyophilisierte pharmazeutische Zubereitungen von G-CSF |
| DE19549232C2 (de) * | 1995-12-20 | 1998-05-20 | Boehringer Mannheim Gmbh | Verwendung von G-CSF in Kombination mit einem Chemotherapeutikum bei der Behandlung von Erkrankungen, die eine periphere Stammzelltransplantation erfordern |
| US7321023B2 (en) * | 1997-11-07 | 2008-01-22 | Incyte Corporation | SP16 protein |
| EP1060746A4 (en) * | 1998-03-06 | 2002-06-19 | Chugai Pharmaceutical Co Ltd | PROTEIN-FREE PREPARATIONS |
| US6831158B2 (en) * | 2000-01-10 | 2004-12-14 | Maxygen Holdings Ltd. | G-CSF conjugates |
| US6555660B2 (en) * | 2000-01-10 | 2003-04-29 | Maxygen Holdings Ltd. | G-CSF conjugates |
| CA2405550A1 (en) | 2000-04-12 | 2001-10-25 | Human Genome Sciences, Inc. | Albumin fusion proteins |
| AU2002302814A1 (en) * | 2001-06-08 | 2002-12-23 | Powderject Vaccines, Inc. | Spray freeze-dried compositions |
| WO2003076567A2 (en) * | 2002-03-05 | 2003-09-18 | Eli Lilly And Company | Heterologous g-csf fusion proteins |
| CN1241946C (zh) * | 2002-07-01 | 2006-02-15 | 美国福源集团 | 对多种细胞具刺激增生作用的人血清白蛋白重组融合蛋白 |
| CA2513213C (en) * | 2003-01-22 | 2013-07-30 | Human Genome Sciences, Inc. | Albumin fusion proteins |
| WO2004082640A2 (en) * | 2003-03-19 | 2004-09-30 | New Century Pharmaceuticals, Inc. | Human serum albumin conjugates with therapeutic compounds |
| US6972332B1 (en) * | 2004-05-20 | 2005-12-06 | Acura Pharmaceuticals, Inc. | Process for the production of opiates |
| KR20080071119A (ko) | 2005-08-12 | 2008-08-01 | 휴먼 게놈 사이언시즈, 인코포레이티드 | 알부민 융합 단백질 |
| CA2584927C (en) * | 2006-04-13 | 2011-02-08 | Wix Filtration Corp. | A body for actuating a standpipe of a replaceable filter element |
| JP2008146587A (ja) * | 2006-12-13 | 2008-06-26 | Sony Corp | 表示装置、表示プログラム、表示方法、画像提供装置、画像提供プログラム、画像提供方法及び記録媒体 |
| UA103221C2 (uk) * | 2009-01-16 | 2013-09-25 | Тева Фармасьютікал Індастріз Лтд. | Стабільний склад рекомбінантного альбуміну людини-гранулоцитарного колонієстимулюючого фактора людини |
-
2010
- 2010-01-15 UA UAA201109963A patent/UA103221C2/uk unknown
- 2010-01-15 SG SG2011050358A patent/SG172940A1/en unknown
- 2010-01-15 CA CA2749786A patent/CA2749786A1/en not_active Abandoned
- 2010-01-15 SG SG2011050366A patent/SG172941A1/en unknown
- 2010-01-15 US US12/688,754 patent/US20100227818A1/en not_active Abandoned
- 2010-01-15 CN CN2010800127233A patent/CN102378635A/zh active Pending
- 2010-01-15 WO PCT/US2010/021235 patent/WO2010083434A2/en not_active Ceased
- 2010-01-15 MX MX2011007582A patent/MX2011007582A/es active IP Right Grant
- 2010-01-15 AU AU2010204547A patent/AU2010204547B2/en not_active Ceased
- 2010-01-15 MX MX2011007583A patent/MX2011007583A/es active IP Right Grant
- 2010-01-15 US US12/688,655 patent/US8323634B2/en not_active Expired - Fee Related
- 2010-01-15 UA UAA201109961A patent/UA105201C2/uk unknown
- 2010-01-15 EA EA201190079A patent/EA201190079A1/ru unknown
- 2010-01-15 JP JP2011546399A patent/JP2012515222A/ja active Pending
- 2010-01-15 CN CN201080012749.8A patent/CN102395379B/zh not_active Expired - Fee Related
- 2010-01-15 SG SG2014003073A patent/SG196821A1/en unknown
- 2010-01-15 JP JP2011546396A patent/JP5753095B2/ja not_active Expired - Fee Related
- 2010-01-15 BR BRPI1005159A patent/BRPI1005159A2/pt not_active IP Right Cessation
- 2010-01-15 EP EP10701082A patent/EP2387420A2/en not_active Withdrawn
- 2010-01-15 KR KR1020117018153A patent/KR20110132326A/ko not_active Ceased
- 2010-01-15 NZ NZ594056A patent/NZ594056A/xx not_active IP Right Cessation
- 2010-01-15 NZ NZ594055A patent/NZ594055A/xx not_active IP Right Cessation
- 2010-01-15 AU AU2010204552A patent/AU2010204552B2/en not_active Ceased
- 2010-01-15 BR BRPI1004940A patent/BRPI1004940A2/pt not_active IP Right Cessation
- 2010-01-15 EP EP10700685A patent/EP2387419A2/en not_active Withdrawn
- 2010-01-15 KR KR1020117018162A patent/KR20110132327A/ko not_active Ceased
- 2010-01-15 EA EA201190080A patent/EA023344B1/ru not_active IP Right Cessation
- 2010-01-15 WO PCT/US2010/021241 patent/WO2010083439A2/en not_active Ceased
- 2010-01-15 CA CA2749802A patent/CA2749802C/en not_active Expired - Fee Related
-
2011
- 2011-07-12 IL IL214052A patent/IL214052A0/en unknown
- 2011-07-12 IL IL214051A patent/IL214051A0/en unknown
- 2011-07-13 ZA ZA2011/05171A patent/ZA201105171B/en unknown
-
2012
- 2012-10-25 US US13/660,915 patent/US8993519B2/en not_active Expired - Fee Related
-
2014
- 2014-12-18 US US14/574,553 patent/US20150202268A1/en not_active Abandoned
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2005514060A (ja) * | 2001-12-21 | 2005-05-19 | ヒューマン ジノーム サイエンシーズ， インコーポレイテッド | アルブミン融合タンパク質 |
Non-Patent Citations (2)
| Title |
|---|
| JOURNAL OF CLINICAL ONCOLOGY,2000,VOL.18,NO.12,P.2369-2377, JPN6014008112, ISSN: 0002754759 * |
| PHARMACEUTICAL RESEARCH,2002,VOL.19,NO.11,P.1720-1729, JPN6014008109, ISSN: 0002754758 * |
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| AU2010204552B2 (en) | New stable formulations of recombinant human albumin-human granulocyte colony stimulating factor fusion protein | |
| US10357545B2 (en) | Methods of using interleukin-10 for treating solid tumors | |
| JP6723982B2 (ja) | インターロイキン−２／インターロイキン−２受容体アルファ融合タンパク質および使用方法 | |
| JP6675394B2 (ja) | 疾患及び障害の治療のためにインターロイキン−１０を使用する方法 | |
| KR20150121715A (ko) | Ｃｓｆ１ 치료제 | |
| US9186390B2 (en) | Methods and uses of TIE2 binding and/or activating agents | |
| KR20110139256A (ko) | Ｓｐａｒｃ 혈관형성 영역과 사용방법 | |
| US12421316B2 (en) | Bispecific immunotoxins targeting human CD25+CCR4+ tumors and regulatory T-cells | |
| JP2018530525A (ja) | 疾患及び障害を治療するためのインターロイキン１０の使用方法 | |
| AU2014208224A1 (en) | New Stable Formulations of Recombinant Human Albumin-Human Granulocyte Colony Stimulating Factor Fusion Protein | |
| US20140271538A1 (en) | Recombinant Human Albumin-Human Granulocyte Colony Stimulating Factor for the Prevention of Neutropenia in Pediatric Patients | |
| AU2014202190B2 (en) | New Stable Formulations of Recombinant Human Albumin-Human Granulocyte Colony Stimulating Factor Fusion Protein | |
| WO2021219940A1 (en) | Homing peptide-guided decorin conjugates for use in treating epidermolysis bullosa | |
| US20060269514A1 (en) | Methods and compositions for the modulation of immune responses and cancer diseases |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20130111 |
|
| A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20130111 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20140224 |
|
| A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20140523 |
|
| A602 | Written permission of extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A602 Effective date: 20140530 |
|
| A02 | Decision of refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A02 Effective date: 20141127 |