ES2763184T3 - Dosificación terapéutica de una neurregulina en el tratamiento o profilaxis de la insuficiencia cardíaca - Google Patents
Dosificación terapéutica de una neurregulina en el tratamiento o profilaxis de la insuficiencia cardíaca Download PDFInfo
- Publication number
- ES2763184T3 ES2763184T3 ES17209369T ES17209369T ES2763184T3 ES 2763184 T3 ES2763184 T3 ES 2763184T3 ES 17209369 T ES17209369 T ES 17209369T ES 17209369 T ES17209369 T ES 17209369T ES 2763184 T3 ES2763184 T3 ES 2763184T3
- Authority
- ES
- Spain
- Prior art keywords
- peptide
- neurregulin
- days
- nrg
- hours
- 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.)
- Active
Links
- 206010019280 Heart failures Diseases 0.000 title claims abstract description 54
- 238000011282 treatment Methods 0.000 title description 37
- 230000001225 therapeutic effect Effects 0.000 title description 29
- 238000011321 prophylaxis Methods 0.000 title description 4
- 108090000765 processed proteins & peptides Proteins 0.000 claims abstract description 78
- 241000124008 Mammalia Species 0.000 claims abstract description 34
- 230000000694 effects Effects 0.000 claims abstract description 27
- 230000010005 growth-factor like effect Effects 0.000 claims abstract description 9
- 108090000623 proteins and genes Proteins 0.000 claims description 55
- 101500028333 Homo sapiens Neuregulin-1 Proteins 0.000 claims 1
- 230000002035 prolonged effect Effects 0.000 abstract description 4
- 239000003814 drug Substances 0.000 description 50
- 229940079593 drug Drugs 0.000 description 49
- 102000012545 EGF-like domains Human genes 0.000 description 37
- 108050002150 EGF-like domains Proteins 0.000 description 37
- 210000004027 cell Anatomy 0.000 description 35
- 238000000034 method Methods 0.000 description 35
- 206010007559 Cardiac failure congestive Diseases 0.000 description 31
- 241001465754 Metazoa Species 0.000 description 28
- 102000004169 proteins and genes Human genes 0.000 description 26
- 210000002966 serum Anatomy 0.000 description 22
- 238000000502 dialysis Methods 0.000 description 20
- 235000018102 proteins Nutrition 0.000 description 20
- 150000001413 amino acids Chemical group 0.000 description 19
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 17
- 150000001875 compounds Chemical class 0.000 description 17
- 230000004217 heart function Effects 0.000 description 17
- 239000000203 mixture Substances 0.000 description 16
- 150000007523 nucleic acids Chemical group 0.000 description 15
- 101000893549 Homo sapiens Growth/differentiation factor 15 Proteins 0.000 description 14
- 101000653754 Rattus norvegicus Sphingosine 1-phosphate receptor 5 Proteins 0.000 description 14
- 238000012360 testing method Methods 0.000 description 14
- VBEQCZHXXJYVRD-GACYYNSASA-N uroanthelone Chemical compound C([C@@H](C(=O)N[C@H](C(=O)N[C@@H](CS)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CS)C(=O)N[C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)NCC(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CS)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O)C(C)C)[C@@H](C)O)NC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H](CCSC)NC(=O)[C@H](CS)NC(=O)[C@@H](NC(=O)CNC(=O)CNC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CS)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)CNC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CS)NC(=O)CNC(=O)[C@H]1N(CCC1)C(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC(N)=O)C(C)C)[C@@H](C)CC)C1=CC=C(O)C=C1 VBEQCZHXXJYVRD-GACYYNSASA-N 0.000 description 14
- 230000008901 benefit Effects 0.000 description 13
- 210000004413 cardiac myocyte Anatomy 0.000 description 13
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 13
- 230000014509 gene expression Effects 0.000 description 13
- 230000006872 improvement Effects 0.000 description 13
- 210000003000 inclusion body Anatomy 0.000 description 13
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 12
- 102400001368 Epidermal growth factor Human genes 0.000 description 12
- 101800003838 Epidermal growth factor Proteins 0.000 description 12
- 102100040896 Growth/differentiation factor 15 Human genes 0.000 description 12
- 229940098773 bovine serum albumin Drugs 0.000 description 12
- 230000002354 daily effect Effects 0.000 description 12
- 229940116977 epidermal growth factor Drugs 0.000 description 12
- 239000012634 fragment Substances 0.000 description 12
- 238000000746 purification Methods 0.000 description 12
- 230000002861 ventricular Effects 0.000 description 12
- 102000001301 EGF receptor Human genes 0.000 description 11
- 101800000675 Neuregulin-2 Proteins 0.000 description 11
- 241000700159 Rattus Species 0.000 description 11
- 201000010099 disease Diseases 0.000 description 11
- ZOXZWYWOECCBSH-UHFFFAOYSA-N 4 Methyl N-ethylcathinone Chemical compound CCNC(C)C(=O)C1=CC=C(C)C=C1 ZOXZWYWOECCBSH-UHFFFAOYSA-N 0.000 description 10
- 108060006698 EGF receptor Proteins 0.000 description 10
- 102400000057 Neuregulin-2 Human genes 0.000 description 10
- 238000009472 formulation Methods 0.000 description 10
- 210000002216 heart Anatomy 0.000 description 10
- 238000002347 injection Methods 0.000 description 10
- 239000007924 injection Substances 0.000 description 10
- 238000005063 solubilization Methods 0.000 description 10
- 230000007928 solubilization Effects 0.000 description 10
- QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 9
- 206010020772 Hypertension Diseases 0.000 description 9
- 108091028043 Nucleic acid sequence Proteins 0.000 description 9
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
- 231100000457 cardiotoxic Toxicity 0.000 description 9
- 230000001451 cardiotoxic effect Effects 0.000 description 9
- 238000011161 development Methods 0.000 description 9
- 230000018109 developmental process Effects 0.000 description 9
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 9
- 239000011780 sodium chloride Substances 0.000 description 9
- 238000007920 subcutaneous administration Methods 0.000 description 9
- 210000001519 tissue Anatomy 0.000 description 9
- 230000002411 adverse Effects 0.000 description 8
- 230000001965 increasing effect Effects 0.000 description 8
- 239000003446 ligand Substances 0.000 description 8
- 238000004904 shortening Methods 0.000 description 8
- 238000001356 surgical procedure Methods 0.000 description 8
- 101800000673 Neuregulin-3 Proteins 0.000 description 7
- 102400000054 Neuregulin-3 Human genes 0.000 description 7
- 102100030086 Receptor tyrosine-protein kinase erbB-2 Human genes 0.000 description 7
- 101710100968 Receptor tyrosine-protein kinase erbB-2 Proteins 0.000 description 7
- 230000006907 apoptotic process Effects 0.000 description 7
- 238000005119 centrifugation Methods 0.000 description 7
- 208000010125 myocardial infarction Diseases 0.000 description 7
- 208000031225 myocardial ischemia Diseases 0.000 description 7
- 239000000047 product Substances 0.000 description 7
- 239000000725 suspension Substances 0.000 description 7
- 239000013598 vector Substances 0.000 description 7
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 7
- QAPSNMNOIOSXSQ-YNEHKIRRSA-N 1-[(2r,4s,5r)-4-[tert-butyl(dimethyl)silyl]oxy-5-(hydroxymethyl)oxolan-2-yl]-5-methylpyrimidine-2,4-dione Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](CO)[C@@H](O[Si](C)(C)C(C)(C)C)C1 QAPSNMNOIOSXSQ-YNEHKIRRSA-N 0.000 description 6
- 108090000190 Thrombin Proteins 0.000 description 6
- 239000003795 chemical substances by application Substances 0.000 description 6
- 238000010367 cloning Methods 0.000 description 6
- ZPUCINDJVBIVPJ-LJISPDSOSA-N cocaine Chemical compound O([C@H]1C[C@@H]2CC[C@@H](N2C)[C@H]1C(=O)OC)C(=O)C1=CC=CC=C1 ZPUCINDJVBIVPJ-LJISPDSOSA-N 0.000 description 6
- 230000001447 compensatory effect Effects 0.000 description 6
- 230000006870 function Effects 0.000 description 6
- 206010020718 hyperplasia Diseases 0.000 description 6
- 238000010253 intravenous injection Methods 0.000 description 6
- 239000000463 material Substances 0.000 description 6
- 239000002609 medium Substances 0.000 description 6
- 235000013336 milk Nutrition 0.000 description 6
- 239000008267 milk Substances 0.000 description 6
- 210000004080 milk Anatomy 0.000 description 6
- 239000008188 pellet Substances 0.000 description 6
- 230000036470 plasma concentration Effects 0.000 description 6
- 231100001274 therapeutic index Toxicity 0.000 description 6
- 231100000816 toxic dose Toxicity 0.000 description 6
- 239000005541 ACE inhibitor Substances 0.000 description 5
- 101001109800 Homo sapiens Pro-neuregulin-1, membrane-bound isoform Proteins 0.000 description 5
- 206010020880 Hypertrophy Diseases 0.000 description 5
- 102400000058 Neuregulin-1 Human genes 0.000 description 5
- 238000010521 absorption reaction Methods 0.000 description 5
- 235000001014 amino acid Nutrition 0.000 description 5
- 229940044094 angiotensin-converting-enzyme inhibitor Drugs 0.000 description 5
- 229940045799 anthracyclines and related substance Drugs 0.000 description 5
- 230000000747 cardiac effect Effects 0.000 description 5
- 230000008859 change Effects 0.000 description 5
- 239000002299 complementary DNA Substances 0.000 description 5
- 210000004351 coronary vessel Anatomy 0.000 description 5
- 238000010790 dilution Methods 0.000 description 5
- 239000012895 dilution Substances 0.000 description 5
- 239000003102 growth factor Substances 0.000 description 5
- 102000055650 human NRG1 Human genes 0.000 description 5
- 238000001990 intravenous administration Methods 0.000 description 5
- 238000004519 manufacturing process Methods 0.000 description 5
- 238000012544 monitoring process Methods 0.000 description 5
- 210000005036 nerve Anatomy 0.000 description 5
- 230000003285 pharmacodynamic effect Effects 0.000 description 5
- 102000005962 receptors Human genes 0.000 description 5
- 108020003175 receptors Proteins 0.000 description 5
- 230000004044 response Effects 0.000 description 5
- 239000011734 sodium Substances 0.000 description 5
- 239000000126 substance Substances 0.000 description 5
- 239000006228 supernatant Substances 0.000 description 5
- 238000002560 therapeutic procedure Methods 0.000 description 5
- 231100000419 toxicity Toxicity 0.000 description 5
- 230000001988 toxicity Effects 0.000 description 5
- 239000003981 vehicle Substances 0.000 description 5
- 239000011534 wash buffer Substances 0.000 description 5
- 238000001262 western blot Methods 0.000 description 5
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 4
- 206010007572 Cardiac hypertrophy Diseases 0.000 description 4
- 108020004414 DNA Proteins 0.000 description 4
- 206010061818 Disease progression Diseases 0.000 description 4
- 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 description 4
- 206010015548 Euthanasia Diseases 0.000 description 4
- 108010024636 Glutathione Proteins 0.000 description 4
- 108010053070 Glutathione Disulfide Proteins 0.000 description 4
- RPTUSVTUFVMDQK-UHFFFAOYSA-N Hidralazin Chemical compound C1=CC=C2C(NN)=NN=CC2=C1 RPTUSVTUFVMDQK-UHFFFAOYSA-N 0.000 description 4
- ODKSFYDXXFIFQN-BYPYZUCNSA-N L-arginine Chemical compound OC(=O)[C@@H](N)CCCN=C(N)N ODKSFYDXXFIFQN-BYPYZUCNSA-N 0.000 description 4
- 229930064664 L-arginine Natural products 0.000 description 4
- 235000014852 L-arginine Nutrition 0.000 description 4
- BACYUWVYYTXETD-UHFFFAOYSA-N N-Lauroylsarcosine Chemical compound CCCCCCCCCCCC(=O)N(C)CC(O)=O BACYUWVYYTXETD-UHFFFAOYSA-N 0.000 description 4
- 101150008132 NDE1 gene Proteins 0.000 description 4
- 108090000556 Neuregulin-1 Proteins 0.000 description 4
- 102000001708 Protein Isoforms Human genes 0.000 description 4
- 108010029485 Protein Isoforms Proteins 0.000 description 4
- 101710100963 Receptor tyrosine-protein kinase erbB-4 Proteins 0.000 description 4
- 230000009471 action Effects 0.000 description 4
- 238000004458 analytical method Methods 0.000 description 4
- 239000003242 anti bacterial agent Substances 0.000 description 4
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 4
- 230000001684 chronic effect Effects 0.000 description 4
- 238000003776 cleavage reaction Methods 0.000 description 4
- 230000007423 decrease Effects 0.000 description 4
- 238000013461 design Methods 0.000 description 4
- 230000005750 disease progression Effects 0.000 description 4
- 238000002592 echocardiography Methods 0.000 description 4
- 238000010828 elution Methods 0.000 description 4
- 230000009395 genetic defect Effects 0.000 description 4
- RWSXRVCMGQZWBV-WDSKDSINSA-N glutathione Chemical compound OC(=O)[C@@H](N)CCC(=O)N[C@@H](CS)C(=O)NCC(O)=O RWSXRVCMGQZWBV-WDSKDSINSA-N 0.000 description 4
- YPZRWBKMTBYPTK-BJDJZHNGSA-N glutathione disulfide Chemical compound OC(=O)[C@@H](N)CCC(=O)N[C@H](C(=O)NCC(O)=O)CSSC[C@@H](C(=O)NCC(O)=O)NC(=O)CC[C@H](N)C(O)=O YPZRWBKMTBYPTK-BJDJZHNGSA-N 0.000 description 4
- 238000007726 management method Methods 0.000 description 4
- 230000002107 myocardial effect Effects 0.000 description 4
- 210000004165 myocardium Anatomy 0.000 description 4
- 150000002823 nitrates Chemical class 0.000 description 4
- YPZRWBKMTBYPTK-UHFFFAOYSA-N oxidized gamma-L-glutamyl-L-cysteinylglycine Natural products OC(=O)C(N)CCC(=O)NC(C(=O)NCC(O)=O)CSSCC(C(=O)NCC(O)=O)NC(=O)CCC(N)C(O)=O YPZRWBKMTBYPTK-UHFFFAOYSA-N 0.000 description 4
- 229910052760 oxygen Inorganic materials 0.000 description 4
- 239000001301 oxygen Substances 0.000 description 4
- 239000000546 pharmaceutical excipient Substances 0.000 description 4
- 238000002360 preparation method Methods 0.000 description 4
- 230000012846 protein folding Effects 0.000 description 4
- 230000004043 responsiveness Effects 0.000 description 4
- 230000007017 scission Effects 0.000 description 4
- 210000003491 skin Anatomy 0.000 description 4
- 238000000527 sonication Methods 0.000 description 4
- 229960004072 thrombin Drugs 0.000 description 4
- 208000019553 vascular disease Diseases 0.000 description 4
- 201000001320 Atherosclerosis Diseases 0.000 description 3
- 101800000407 Brain natriuretic peptide 32 Proteins 0.000 description 3
- 108091026890 Coding region Proteins 0.000 description 3
- 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 3
- LTMHDMANZUZIPE-AMTYYWEZSA-N Digoxin Natural products O([C@H]1[C@H](C)O[C@H](O[C@@H]2C[C@@H]3[C@@](C)([C@@H]4[C@H]([C@]5(O)[C@](C)([C@H](O)C4)[C@H](C4=CC(=O)OC4)CC5)CC3)CC2)C[C@@H]1O)[C@H]1O[C@H](C)[C@@H](O[C@H]2O[C@@H](C)[C@H](O)[C@@H](O)C2)[C@@H](O)C1 LTMHDMANZUZIPE-AMTYYWEZSA-N 0.000 description 3
- 208000030814 Eating disease Diseases 0.000 description 3
- 102000004190 Enzymes Human genes 0.000 description 3
- 108090000790 Enzymes Proteins 0.000 description 3
- 102000044591 ErbB-4 Receptor Human genes 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- 208000019454 Feeding and Eating disease Diseases 0.000 description 3
- 229930195725 Mannitol Natural products 0.000 description 3
- 101800002641 Neuregulin-4 Proteins 0.000 description 3
- 102400000055 Neuregulin-4 Human genes 0.000 description 3
- 241000283973 Oryctolagus cuniculus Species 0.000 description 3
- 102000004022 Protein-Tyrosine Kinases Human genes 0.000 description 3
- 108090000412 Protein-Tyrosine Kinases Proteins 0.000 description 3
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 3
- 239000007983 Tris buffer Substances 0.000 description 3
- 208000036142 Viral infection Diseases 0.000 description 3
- 229940088710 antibiotic agent Drugs 0.000 description 3
- 210000001367 artery Anatomy 0.000 description 3
- 239000002876 beta blocker Substances 0.000 description 3
- 229940097320 beta blocking agent Drugs 0.000 description 3
- 230000037396 body weight Effects 0.000 description 3
- 210000000038 chest Anatomy 0.000 description 3
- 229960003920 cocaine Drugs 0.000 description 3
- 230000034994 death Effects 0.000 description 3
- 230000001419 dependent effect Effects 0.000 description 3
- 230000003205 diastolic effect Effects 0.000 description 3
- 235000005911 diet Nutrition 0.000 description 3
- 230000037213 diet Effects 0.000 description 3
- LTMHDMANZUZIPE-PUGKRICDSA-N digoxin Chemical compound C1[C@H](O)[C@H](O)[C@@H](C)O[C@H]1O[C@@H]1[C@@H](C)O[C@@H](O[C@@H]2[C@H](O[C@@H](O[C@@H]3C[C@@H]4[C@]([C@@H]5[C@H]([C@]6(CC[C@@H]([C@@]6(C)[C@H](O)C5)C=5COC(=O)C=5)O)CC4)(C)CC3)C[C@@H]2O)C)C[C@@H]1O LTMHDMANZUZIPE-PUGKRICDSA-N 0.000 description 3
- 229960005156 digoxin Drugs 0.000 description 3
- LTMHDMANZUZIPE-UHFFFAOYSA-N digoxine Natural products C1C(O)C(O)C(C)OC1OC1C(C)OC(OC2C(OC(OC3CC4C(C5C(C6(CCC(C6(C)C(O)C5)C=5COC(=O)C=5)O)CC4)(C)CC3)CC2O)C)CC1O LTMHDMANZUZIPE-UHFFFAOYSA-N 0.000 description 3
- 235000014632 disordered eating Nutrition 0.000 description 3
- 238000002651 drug therapy Methods 0.000 description 3
- 230000008030 elimination Effects 0.000 description 3
- 238000003379 elimination reaction Methods 0.000 description 3
- 229940088598 enzyme Drugs 0.000 description 3
- 238000000605 extraction Methods 0.000 description 3
- 238000001914 filtration Methods 0.000 description 3
- 208000007565 gingivitis Diseases 0.000 description 3
- 229940022353 herceptin Drugs 0.000 description 3
- 230000001969 hypertrophic effect Effects 0.000 description 3
- 230000001771 impaired effect Effects 0.000 description 3
- 208000017169 kidney disease Diseases 0.000 description 3
- 239000000594 mannitol Substances 0.000 description 3
- 235000010355 mannitol Nutrition 0.000 description 3
- 238000005457 optimization Methods 0.000 description 3
- 208000008494 pericarditis Diseases 0.000 description 3
- 230000002980 postoperative effect Effects 0.000 description 3
- 239000000843 powder Substances 0.000 description 3
- 230000002265 prevention Effects 0.000 description 3
- 230000008569 process Effects 0.000 description 3
- 102000004196 processed proteins & peptides Human genes 0.000 description 3
- 229910052938 sodium sulfate Inorganic materials 0.000 description 3
- 235000011152 sodium sulphate Nutrition 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- 241000894007 species Species 0.000 description 3
- 238000013222 sprague-dawley male rat Methods 0.000 description 3
- 238000011146 sterile filtration Methods 0.000 description 3
- 208000024891 symptom Diseases 0.000 description 3
- 238000013518 transcription Methods 0.000 description 3
- 230000035897 transcription Effects 0.000 description 3
- 238000012546 transfer Methods 0.000 description 3
- 238000011269 treatment regimen Methods 0.000 description 3
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 3
- 230000009385 viral infection Effects 0.000 description 3
- BFSVOASYOCHEOV-UHFFFAOYSA-N 2-diethylaminoethanol Chemical compound CCN(CC)CCO BFSVOASYOCHEOV-UHFFFAOYSA-N 0.000 description 2
- FWMNVWWHGCHHJJ-SKKKGAJSSA-N 4-amino-1-[(2r)-6-amino-2-[[(2r)-2-[[(2r)-2-[[(2r)-2-amino-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]hexanoyl]piperidine-4-carboxylic acid Chemical compound C([C@H](C(=O)N[C@H](CC(C)C)C(=O)N[C@H](CCCCN)C(=O)N1CCC(N)(CC1)C(O)=O)NC(=O)[C@H](N)CC=1C=CC=CC=1)C1=CC=CC=C1 FWMNVWWHGCHHJJ-SKKKGAJSSA-N 0.000 description 2
- STQGQHZAVUOBTE-UHFFFAOYSA-N 7-Cyan-hept-2t-en-4,6-diinsaeure Natural products C1=2C(O)=C3C(=O)C=4C(OC)=CC=CC=4C(=O)C3=C(O)C=2CC(O)(C(C)=O)CC1OC1CC(N)C(O)C(C)O1 STQGQHZAVUOBTE-UHFFFAOYSA-N 0.000 description 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 2
- 208000007848 Alcoholism Diseases 0.000 description 2
- 241001206158 Blepsias cirrhosus Species 0.000 description 2
- 208000032841 Bulimia Diseases 0.000 description 2
- 206010006550 Bulimia nervosa Diseases 0.000 description 2
- 229940127291 Calcium channel antagonist Drugs 0.000 description 2
- 206010007558 Cardiac failure chronic Diseases 0.000 description 2
- 208000006029 Cardiomegaly Diseases 0.000 description 2
- 206010048610 Cardiotoxicity Diseases 0.000 description 2
- 108010078791 Carrier Proteins Proteins 0.000 description 2
- 102000016911 Deoxyribonucleases Human genes 0.000 description 2
- 108010053770 Deoxyribonucleases Proteins 0.000 description 2
- JRWZLRBJNMZMFE-UHFFFAOYSA-N Dobutamine Chemical compound C=1C=C(O)C(O)=CC=1CCNC(C)CCC1=CC=C(O)C=C1 JRWZLRBJNMZMFE-UHFFFAOYSA-N 0.000 description 2
- 206010013710 Drug interaction Diseases 0.000 description 2
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 2
- 102000056372 ErbB-3 Receptor Human genes 0.000 description 2
- 241000282412 Homo Species 0.000 description 2
- 206010061216 Infarction Diseases 0.000 description 2
- 206010049694 Left Ventricular Dysfunction Diseases 0.000 description 2
- 208000007177 Left Ventricular Hypertrophy Diseases 0.000 description 2
- NPPQSCRMBWNHMW-UHFFFAOYSA-N Meprobamate Chemical compound NC(=O)OCC(C)(CCC)COC(N)=O NPPQSCRMBWNHMW-UHFFFAOYSA-N 0.000 description 2
- 102100030173 Muellerian-inhibiting factor Human genes 0.000 description 2
- 208000009525 Myocarditis Diseases 0.000 description 2
- 206010028980 Neoplasm Diseases 0.000 description 2
- 102000048238 Neuregulin-1 Human genes 0.000 description 2
- 239000000020 Nitrocellulose Substances 0.000 description 2
- WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 description 2
- 102100022668 Pro-neuregulin-2, membrane-bound isoform Human genes 0.000 description 2
- 101710100969 Receptor tyrosine-protein kinase erbB-3 Proteins 0.000 description 2
- 241000283984 Rodentia Species 0.000 description 2
- 208000024799 Thyroid disease Diseases 0.000 description 2
- 229920004890 Triton X-100 Polymers 0.000 description 2
- 239000013504 Triton X-100 Substances 0.000 description 2
- 241000947853 Vibrionales Species 0.000 description 2
- 230000004913 activation Effects 0.000 description 2
- 239000012190 activator Substances 0.000 description 2
- 239000002170 aldosterone antagonist Substances 0.000 description 2
- 229940083712 aldosterone antagonist Drugs 0.000 description 2
- 238000010171 animal model Methods 0.000 description 2
- 239000003817 anthracycline antibiotic agent Substances 0.000 description 2
- 229940030600 antihypertensive agent Drugs 0.000 description 2
- 239000002220 antihypertensive agent Substances 0.000 description 2
- 238000011888 autopsy Methods 0.000 description 2
- 230000009286 beneficial effect Effects 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 238000006664 bond formation reaction Methods 0.000 description 2
- 239000000480 calcium channel blocker Substances 0.000 description 2
- 231100000259 cardiotoxicity Toxicity 0.000 description 2
- 230000006037 cell lysis Effects 0.000 description 2
- -1 cocaine Chemical compound 0.000 description 2
- 230000000295 complement effect Effects 0.000 description 2
- 239000012141 concentrate Substances 0.000 description 2
- 239000003636 conditioned culture medium Substances 0.000 description 2
- 239000000356 contaminant Substances 0.000 description 2
- 230000006378 damage Effects 0.000 description 2
- STQGQHZAVUOBTE-VGBVRHCVSA-N daunorubicin 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(C)=O)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 STQGQHZAVUOBTE-VGBVRHCVSA-N 0.000 description 2
- 206010061428 decreased appetite Diseases 0.000 description 2
- 230000001627 detrimental effect Effects 0.000 description 2
- 238000003745 diagnosis Methods 0.000 description 2
- 238000006471 dimerization reaction Methods 0.000 description 2
- 229940042399 direct acting antivirals protease inhibitors Drugs 0.000 description 2
- 208000035475 disorder Diseases 0.000 description 2
- 238000009826 distribution Methods 0.000 description 2
- 239000002934 diuretic Substances 0.000 description 2
- 229940030606 diuretics Drugs 0.000 description 2
- 229960001089 dobutamine Drugs 0.000 description 2
- 239000002552 dosage form Substances 0.000 description 2
- 229960004679 doxorubicin Drugs 0.000 description 2
- 238000009509 drug development Methods 0.000 description 2
- 238000011156 evaluation Methods 0.000 description 2
- 239000013604 expression vector Substances 0.000 description 2
- 235000013305 food Nutrition 0.000 description 2
- 230000037406 food intake Effects 0.000 description 2
- 235000012631 food intake Nutrition 0.000 description 2
- ZZUFCTLCJUWOSV-UHFFFAOYSA-N furosemide Chemical compound C1=C(Cl)C(S(=O)(=O)N)=CC(C(O)=O)=C1NCC1=CC=CO1 ZZUFCTLCJUWOSV-UHFFFAOYSA-N 0.000 description 2
- 229960003883 furosemide Drugs 0.000 description 2
- 239000008187 granular material Substances 0.000 description 2
- 230000012010 growth Effects 0.000 description 2
- 230000037183 heart physiology Effects 0.000 description 2
- 235000003642 hunger Nutrition 0.000 description 2
- 229960002474 hydralazine Drugs 0.000 description 2
- 206010020871 hypertrophic cardiomyopathy Diseases 0.000 description 2
- 238000011534 incubation Methods 0.000 description 2
- 230000001939 inductive effect Effects 0.000 description 2
- 230000007574 infarction Effects 0.000 description 2
- 230000002401 inhibitory effect Effects 0.000 description 2
- 208000014674 injury Diseases 0.000 description 2
- 230000000297 inotrophic effect Effects 0.000 description 2
- 238000007914 intraventricular administration Methods 0.000 description 2
- 208000028867 ischemia Diseases 0.000 description 2
- MOYKHGMNXAOIAT-JGWLITMVSA-N isosorbide dinitrate Chemical compound [O-][N+](=O)O[C@H]1CO[C@@H]2[C@H](O[N+](=O)[O-])CO[C@@H]21 MOYKHGMNXAOIAT-JGWLITMVSA-N 0.000 description 2
- 229960000201 isosorbide dinitrate Drugs 0.000 description 2
- 210000004185 liver Anatomy 0.000 description 2
- 238000011068 loading method Methods 0.000 description 2
- 230000007774 longterm Effects 0.000 description 2
- 238000005259 measurement Methods 0.000 description 2
- 230000001404 mediated effect Effects 0.000 description 2
- 210000004379 membrane Anatomy 0.000 description 2
- 239000012528 membrane Substances 0.000 description 2
- 239000007923 nasal drop Substances 0.000 description 2
- 229940100662 nasal drops Drugs 0.000 description 2
- 229960001267 nesiritide Drugs 0.000 description 2
- HPNRHPKXQZSDFX-OAQDCNSJSA-N nesiritide Chemical compound C([C@H]1C(=O)NCC(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@H](C(N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)NCC(=O)N[C@@H](CSSC[C@@H](C(=O)N1)NC(=O)CNC(=O)[C@H](CO)NC(=O)CNC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](NC(=O)[C@H](CCSC)NC(=O)[C@H](CCCCN)NC(=O)[C@H]1N(CCC1)C(=O)[C@@H](N)CO)C(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1N=CNC=1)C(O)=O)=O)[C@@H](C)CC)C1=CC=CC=C1 HPNRHPKXQZSDFX-OAQDCNSJSA-N 0.000 description 2
- 239000000712 neurohormone Substances 0.000 description 2
- 210000002569 neuron Anatomy 0.000 description 2
- 229920001220 nitrocellulos Polymers 0.000 description 2
- 108020004707 nucleic acids Proteins 0.000 description 2
- 102000039446 nucleic acids Human genes 0.000 description 2
- 238000010979 pH adjustment Methods 0.000 description 2
- 239000000137 peptide hydrolase inhibitor Substances 0.000 description 2
- 230000026731 phosphorylation Effects 0.000 description 2
- 238000006366 phosphorylation reaction Methods 0.000 description 2
- 239000011148 porous material Substances 0.000 description 2
- 238000001742 protein purification Methods 0.000 description 2
- 230000030788 protein refolding Effects 0.000 description 2
- 238000005086 pumping Methods 0.000 description 2
- 230000009467 reduction Effects 0.000 description 2
- 230000001105 regulatory effect Effects 0.000 description 2
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 2
- 239000011537 solubilization buffer Substances 0.000 description 2
- 238000012453 sprague-dawley rat model Methods 0.000 description 2
- 238000010561 standard procedure Methods 0.000 description 2
- 230000037351 starvation Effects 0.000 description 2
- 230000000638 stimulation Effects 0.000 description 2
- 108010051423 streptavidin-agarose Proteins 0.000 description 2
- 239000013589 supplement Substances 0.000 description 2
- 230000002459 sustained effect Effects 0.000 description 2
- 229940124597 therapeutic agent Drugs 0.000 description 2
- 238000011285 therapeutic regimen Methods 0.000 description 2
- 230000004797 therapeutic response Effects 0.000 description 2
- 210000000115 thoracic cavity Anatomy 0.000 description 2
- 208000021510 thyroid gland disease Diseases 0.000 description 2
- 229940124549 vasodilator Drugs 0.000 description 2
- 239000003071 vasodilator agent Substances 0.000 description 2
- 108060003345 Adrenergic Receptor Proteins 0.000 description 1
- 102000017910 Adrenergic receptor Human genes 0.000 description 1
- 102000008873 Angiotensin II receptor Human genes 0.000 description 1
- 108050000824 Angiotensin II receptor Proteins 0.000 description 1
- 102100030988 Angiotensin-converting enzyme Human genes 0.000 description 1
- 108010064733 Angiotensins Proteins 0.000 description 1
- 102000015427 Angiotensins Human genes 0.000 description 1
- 208000000103 Anorexia Nervosa Diseases 0.000 description 1
- 101100067974 Arabidopsis thaliana POP2 gene Proteins 0.000 description 1
- 241000282472 Canis lupus familiaris Species 0.000 description 1
- 102000014914 Carrier Proteins Human genes 0.000 description 1
- 241000282693 Cercopithecidae Species 0.000 description 1
- 208000017667 Chronic Disease Diseases 0.000 description 1
- 108020004635 Complementary DNA Proteins 0.000 description 1
- 102000053602 DNA Human genes 0.000 description 1
- WEAHRLBPCANXCN-UHFFFAOYSA-N Daunomycin Natural products CCC1(O)CC(OC2CC(N)C(O)C(C)O2)c3cc4C(=O)c5c(OC)cccc5C(=O)c4c(O)c3C1 WEAHRLBPCANXCN-UHFFFAOYSA-N 0.000 description 1
- 206010011906 Death Diseases 0.000 description 1
- BWGNESOTFCXPMA-UHFFFAOYSA-N Dihydrogen disulfide Chemical compound SS BWGNESOTFCXPMA-UHFFFAOYSA-N 0.000 description 1
- 206010013654 Drug abuse Diseases 0.000 description 1
- 102000018386 EGF Family of Proteins Human genes 0.000 description 1
- 108010066486 EGF Family of Proteins Proteins 0.000 description 1
- 206010073306 Exposure to radiation Diseases 0.000 description 1
- 229930182566 Gentamicin Natural products 0.000 description 1
- CEAZRRDELHUEMR-URQXQFDESA-N Gentamicin Chemical compound O1[C@H](C(C)NC)CC[C@@H](N)[C@H]1O[C@H]1[C@H](O)[C@@H](O[C@@H]2[C@@H]([C@@H](NC)[C@@](C)(O)CO2)O)[C@H](N)C[C@@H]1N CEAZRRDELHUEMR-URQXQFDESA-N 0.000 description 1
- 108010007979 Glycocholic Acid Proteins 0.000 description 1
- 102000009465 Growth Factor Receptors Human genes 0.000 description 1
- 108010009202 Growth Factor Receptors Proteins 0.000 description 1
- 101100118549 Homo sapiens EGFR gene Proteins 0.000 description 1
- 101001109792 Homo sapiens Pro-neuregulin-2, membrane-bound isoform Proteins 0.000 description 1
- 206010064919 Hypospermia Diseases 0.000 description 1
- 206010021143 Hypoxia Diseases 0.000 description 1
- 108060003951 Immunoglobulin Proteins 0.000 description 1
- FBOZXECLQNJBKD-ZDUSSCGKSA-N L-methotrexate Chemical compound C=1N=C2N=C(N)N=C(N)C2=NC=1CN(C)C1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 FBOZXECLQNJBKD-ZDUSSCGKSA-N 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
- 239000006137 Luria-Bertani broth Substances 0.000 description 1
- 241000699666 Mus <mouse, genus> Species 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- 108020001621 Natriuretic Peptide Proteins 0.000 description 1
- 102000004571 Natriuretic peptide Human genes 0.000 description 1
- 102000014413 Neuregulin Human genes 0.000 description 1
- 108050003475 Neuregulin Proteins 0.000 description 1
- 101800002648 Neuregulin-1 Proteins 0.000 description 1
- 208000008589 Obesity Diseases 0.000 description 1
- 206010030113 Oedema Diseases 0.000 description 1
- 108700020796 Oncogene Proteins 0.000 description 1
- 102000016979 Other receptors Human genes 0.000 description 1
- 229930182555 Penicillin Natural products 0.000 description 1
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 1
- 108091000080 Phosphotransferase Proteins 0.000 description 1
- 208000002151 Pleural effusion Diseases 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 102100029981 Receptor tyrosine-protein kinase erbB-4 Human genes 0.000 description 1
- 108020004511 Recombinant DNA Proteins 0.000 description 1
- 208000001647 Renal Insufficiency Diseases 0.000 description 1
- 101100123851 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) HER1 gene Proteins 0.000 description 1
- 206010039710 Scleroderma Diseases 0.000 description 1
- 239000012506 Sephacryl® Substances 0.000 description 1
- 208000032023 Signs and Symptoms Diseases 0.000 description 1
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 1
- 241000282887 Suidae Species 0.000 description 1
- 206010071436 Systolic dysfunction Diseases 0.000 description 1
- 208000035896 Twin-reversed arterial perfusion sequence Diseases 0.000 description 1
- 241000700605 Viruses Species 0.000 description 1
- 208000027418 Wounds and injury Diseases 0.000 description 1
- 229960000583 acetic acid Drugs 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 230000009798 acute exacerbation Effects 0.000 description 1
- 230000006978 adaptation Effects 0.000 description 1
- 239000000853 adhesive Substances 0.000 description 1
- 230000001070 adhesive effect Effects 0.000 description 1
- 239000000443 aerosol Substances 0.000 description 1
- 206010001584 alcohol abuse Diseases 0.000 description 1
- 201000007930 alcohol dependence Diseases 0.000 description 1
- 208000025746 alcohol use disease Diseases 0.000 description 1
- VREFGVBLTWBCJP-UHFFFAOYSA-N alprazolam Chemical compound C12=CC(Cl)=CC=C2N2C(C)=NN=C2CN=C1C1=CC=CC=C1 VREFGVBLTWBCJP-UHFFFAOYSA-N 0.000 description 1
- 230000004075 alteration Effects 0.000 description 1
- 229960003022 amoxicillin Drugs 0.000 description 1
- LSQZJLSUYDQPKJ-NJBDSQKTSA-N amoxicillin Chemical compound C1([C@@H](N)C(=O)N[C@H]2[C@H]3SC([C@@H](N3C2=O)C(O)=O)(C)C)=CC=C(O)C=C1 LSQZJLSUYDQPKJ-NJBDSQKTSA-N 0.000 description 1
- 229960000723 ampicillin Drugs 0.000 description 1
- AVKUERGKIZMTKX-NJBDSQKTSA-N ampicillin Chemical compound C1([C@@H](N)C(=O)N[C@H]2[C@H]3SC([C@@H](N3C2=O)C(O)=O)(C)C)=CC=CC=C1 AVKUERGKIZMTKX-NJBDSQKTSA-N 0.000 description 1
- 230000003321 amplification Effects 0.000 description 1
- 238000002583 angiography Methods 0.000 description 1
- 238000005349 anion exchange Methods 0.000 description 1
- 150000001450 anions Chemical class 0.000 description 1
- 208000022531 anorexia Diseases 0.000 description 1
- 239000005557 antagonist Substances 0.000 description 1
- 238000011203 antimicrobial therapy Methods 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 210000004507 artificial chromosome Anatomy 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 235000014590 basal diet Nutrition 0.000 description 1
- 102000012740 beta Adrenergic Receptors Human genes 0.000 description 1
- 108010079452 beta Adrenergic Receptors Proteins 0.000 description 1
- 230000003115 biocidal effect Effects 0.000 description 1
- 230000000740 bleeding effect Effects 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 230000017531 blood circulation Effects 0.000 description 1
- 230000036765 blood level Effects 0.000 description 1
- 230000036772 blood pressure Effects 0.000 description 1
- 238000010241 blood sampling Methods 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 230000003293 cardioprotective effect Effects 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 238000005277 cation exchange chromatography Methods 0.000 description 1
- 230000011712 cell development Effects 0.000 description 1
- 230000023549 cell-cell signaling Effects 0.000 description 1
- 230000036755 cellular response Effects 0.000 description 1
- 210000001638 cerebellum Anatomy 0.000 description 1
- 230000002490 cerebral effect Effects 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 231100000045 chemical toxicity Toxicity 0.000 description 1
- 231100001157 chemotherapeutic toxicity Toxicity 0.000 description 1
- 238000002512 chemotherapy Methods 0.000 description 1
- 230000002759 chromosomal effect Effects 0.000 description 1
- 230000004087 circulation Effects 0.000 description 1
- 238000005352 clarification Methods 0.000 description 1
- 238000002648 combination therapy Methods 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 230000001010 compromised effect Effects 0.000 description 1
- 230000009091 contractile dysfunction Effects 0.000 description 1
- 230000008602 contraction Effects 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 230000001972 coprophagic effect Effects 0.000 description 1
- 230000008878 coupling Effects 0.000 description 1
- 238000010168 coupling process Methods 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- 230000009089 cytolysis Effects 0.000 description 1
- 229960000975 daunorubicin Drugs 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 230000006735 deficit Effects 0.000 description 1
- 230000002939 deleterious effect Effects 0.000 description 1
- 229940009976 deoxycholate Drugs 0.000 description 1
- KXGVEGMKQFWNSR-LLQZFEROSA-N deoxycholic acid Chemical compound C([C@H]1CC2)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(O)=O)C)[C@@]2(C)[C@@H](O)C1 KXGVEGMKQFWNSR-LLQZFEROSA-N 0.000 description 1
- 210000004207 dermis Anatomy 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 230000006866 deterioration Effects 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- 230000004069 differentiation Effects 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 239000000539 dimer Substances 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- 238000001647 drug administration Methods 0.000 description 1
- 239000012149 elution buffer Substances 0.000 description 1
- 238000011013 endotoxin removal Methods 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 239000005038 ethylene vinyl acetate Substances 0.000 description 1
- 230000003203 everyday effect Effects 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 206010016256 fatigue Diseases 0.000 description 1
- 210000003608 fece Anatomy 0.000 description 1
- 102000013361 fetuin Human genes 0.000 description 1
- 108060002885 fetuin Proteins 0.000 description 1
- 238000011049 filling Methods 0.000 description 1
- 239000013020 final formulation Substances 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 238000002825 functional assay Methods 0.000 description 1
- 238000001641 gel filtration chromatography Methods 0.000 description 1
- 229960002518 gentamicin Drugs 0.000 description 1
- 239000012362 glacial acetic acid Substances 0.000 description 1
- 230000002518 glial effect Effects 0.000 description 1
- 230000001434 glomerular Effects 0.000 description 1
- RFDAIACWWDREDC-FRVQLJSFSA-N glycocholic acid Chemical compound C([C@H]1C[C@H]2O)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(=O)NCC(O)=O)C)[C@@]2(C)[C@@H](O)C1 RFDAIACWWDREDC-FRVQLJSFSA-N 0.000 description 1
- 230000002650 habitual effect Effects 0.000 description 1
- 230000009067 heart development Effects 0.000 description 1
- 208000019622 heart disease Diseases 0.000 description 1
- 210000003709 heart valve Anatomy 0.000 description 1
- 230000000004 hemodynamic effect Effects 0.000 description 1
- 230000001146 hypoxic effect Effects 0.000 description 1
- 238000003384 imaging method Methods 0.000 description 1
- 102000018358 immunoglobulin Human genes 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 210000000876 intercostal muscle Anatomy 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000007912 intraperitoneal administration Methods 0.000 description 1
- 208000023589 ischemic disease Diseases 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 201000006370 kidney failure Diseases 0.000 description 1
- 230000003907 kidney function Effects 0.000 description 1
- 230000002147 killing effect Effects 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 210000005246 left atrium Anatomy 0.000 description 1
- 210000005240 left ventricle Anatomy 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 239000002502 liposome Substances 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 239000006193 liquid solution Substances 0.000 description 1
- 239000006194 liquid suspension Substances 0.000 description 1
- 238000012423 maintenance Methods 0.000 description 1
- 238000013160 medical therapy Methods 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- 229960000485 methotrexate Drugs 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 210000003205 muscle Anatomy 0.000 description 1
- 230000003680 myocardial damage Effects 0.000 description 1
- 230000010016 myocardial function Effects 0.000 description 1
- 150000002790 naphthalenes Chemical class 0.000 description 1
- 239000007922 nasal spray Substances 0.000 description 1
- 239000000692 natriuretic peptide Substances 0.000 description 1
- 210000000653 nervous system Anatomy 0.000 description 1
- 208000007538 neurilemmoma Diseases 0.000 description 1
- 230000000926 neurological effect Effects 0.000 description 1
- 238000003199 nucleic acid amplification method Methods 0.000 description 1
- 210000004940 nucleus Anatomy 0.000 description 1
- 230000035764 nutrition Effects 0.000 description 1
- 235000016709 nutrition Nutrition 0.000 description 1
- 235000020824 obesity Nutrition 0.000 description 1
- 238000011369 optimal treatment Methods 0.000 description 1
- 230000005305 organ development Effects 0.000 description 1
- 210000004789 organ system Anatomy 0.000 description 1
- 230000003204 osmotic effect Effects 0.000 description 1
- LSQZJLSUYDQPKJ-UHFFFAOYSA-N p-Hydroxyampicillin Natural products O=C1N2C(C(O)=O)C(C)(C)SC2C1NC(=O)C(N)C1=CC=C(O)C=C1 LSQZJLSUYDQPKJ-UHFFFAOYSA-N 0.000 description 1
- 229940124641 pain reliever Drugs 0.000 description 1
- 210000003540 papillary muscle Anatomy 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 230000007170 pathology Effects 0.000 description 1
- 210000002976 pectoralis muscle Anatomy 0.000 description 1
- 229940049954 penicillin Drugs 0.000 description 1
- 210000003516 pericardium Anatomy 0.000 description 1
- 210000000578 peripheral nerve Anatomy 0.000 description 1
- 208000027232 peripheral nervous system disease Diseases 0.000 description 1
- 208000033808 peripheral neuropathy Diseases 0.000 description 1
- 239000008177 pharmaceutical agent Substances 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 229940127557 pharmaceutical product Drugs 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 238000011458 pharmacological treatment Methods 0.000 description 1
- 102000020233 phosphotransferase Human genes 0.000 description 1
- 230000035790 physiological processes and functions Effects 0.000 description 1
- 230000009894 physiological stress Effects 0.000 description 1
- 239000013612 plasmid Substances 0.000 description 1
- 229920001200 poly(ethylene-vinyl acetate) Polymers 0.000 description 1
- 229920001515 polyalkylene glycol Polymers 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 229920001184 polypeptide Polymers 0.000 description 1
- 230000005195 poor health Effects 0.000 description 1
- 230000023603 positive regulation of transcription initiation, DNA-dependent Effects 0.000 description 1
- 239000001103 potassium chloride Substances 0.000 description 1
- 235000011164 potassium chloride Nutrition 0.000 description 1
- 230000036515 potency Effects 0.000 description 1
- 239000013587 production medium Substances 0.000 description 1
- 230000007425 progressive decline Effects 0.000 description 1
- 238000002731 protein assay Methods 0.000 description 1
- 230000002685 pulmonary effect Effects 0.000 description 1
- 230000005855 radiation Effects 0.000 description 1
- 239000002464 receptor antagonist Substances 0.000 description 1
- 229940044551 receptor antagonist Drugs 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 230000002829 reductive effect Effects 0.000 description 1
- 238000005057 refrigeration Methods 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 239000011435 rock Substances 0.000 description 1
- 238000010079 rubber tapping Methods 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 238000005070 sampling Methods 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 231100000241 scar Toxicity 0.000 description 1
- 239000013049 sediment Substances 0.000 description 1
- 230000011664 signaling Effects 0.000 description 1
- 230000000391 smoking effect Effects 0.000 description 1
- 239000001632 sodium acetate Substances 0.000 description 1
- 235000017281 sodium acetate Nutrition 0.000 description 1
- 239000001488 sodium phosphate Substances 0.000 description 1
- 229910000162 sodium phosphate Inorganic materials 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 208000020431 spinal cord injury Diseases 0.000 description 1
- 238000013223 sprague-dawley female rat Methods 0.000 description 1
- 230000000087 stabilizing effect Effects 0.000 description 1
- 229910001220 stainless steel Inorganic materials 0.000 description 1
- 239000010935 stainless steel Substances 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 239000008223 sterile water Substances 0.000 description 1
- 210000001562 sternum Anatomy 0.000 description 1
- 230000004936 stimulating effect Effects 0.000 description 1
- 239000007929 subcutaneous injection Substances 0.000 description 1
- 238000010254 subcutaneous injection Methods 0.000 description 1
- 208000011117 substance-related disease Diseases 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 208000008203 tachypnea Diseases 0.000 description 1
- 206010043089 tachypnoea Diseases 0.000 description 1
- 239000008399 tap water Substances 0.000 description 1
- 235000020679 tap water Nutrition 0.000 description 1
- 229940126585 therapeutic drug Drugs 0.000 description 1
- 230000008719 thickening Effects 0.000 description 1
- 210000000779 thoracic wall Anatomy 0.000 description 1
- 210000001541 thymus gland Anatomy 0.000 description 1
- 230000036962 time dependent Effects 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 231100000440 toxicity profile Toxicity 0.000 description 1
- 231100000041 toxicology testing Toxicity 0.000 description 1
- 230000026683 transduction Effects 0.000 description 1
- 238000010361 transduction Methods 0.000 description 1
- 230000008733 trauma Effects 0.000 description 1
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 1
- 125000001493 tyrosinyl group Chemical group [H]OC1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 description 1
- 241000701161 unidentified adenovirus Species 0.000 description 1
- 241001529453 unidentified herpesvirus Species 0.000 description 1
- 241001515965 unidentified phage Species 0.000 description 1
- 241001430294 unidentified retrovirus Species 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 210000003462 vein Anatomy 0.000 description 1
- 238000009423 ventilation Methods 0.000 description 1
- 230000035899 viability Effects 0.000 description 1
- 206010047470 viral myocarditis Diseases 0.000 description 1
- 230000003612 virological effect Effects 0.000 description 1
- 230000003442 weekly effect Effects 0.000 description 1
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
- A61K38/18—Growth factors; Growth regulators
- A61K38/1883—Neuregulins, e.g.. p185erbB2 ligands, glial growth factor, heregulin, ARIA, neu differentiation factor
-
- 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
- A61K38/18—Growth factors; Growth regulators
-
- 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
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/04—Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/12—Antihypertensives
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical & Material Sciences (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Zoology (AREA)
- Epidemiology (AREA)
- Immunology (AREA)
- Gastroenterology & Hepatology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Cardiology (AREA)
- Organic Chemistry (AREA)
- Heart & Thoracic Surgery (AREA)
- Hospice & Palliative Care (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Peptides Or Proteins (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US13517108P | 2008-07-17 | 2008-07-17 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2763184T3 true ES2763184T3 (es) | 2020-05-27 |
Family
ID=42005671
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES09813336.6T Active ES2664394T3 (es) | 2008-07-17 | 2009-07-17 | Dosificación terapéutica de una neuregulina o de una subsecuencia de la misma para el tratamiento o la profilaxis de la insuficiencia cardiaca |
| ES17209369T Active ES2763184T3 (es) | 2008-07-17 | 2009-07-17 | Dosificación terapéutica de una neurregulina en el tratamiento o profilaxis de la insuficiencia cardíaca |
Family Applications Before (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES09813336.6T Active ES2664394T3 (es) | 2008-07-17 | 2009-07-17 | Dosificación terapéutica de una neuregulina o de una subsecuencia de la misma para el tratamiento o la profilaxis de la insuficiencia cardiaca |
Country Status (13)
| Country | Link |
|---|---|
| US (5) | US20110166068A1 (enExample) |
| EP (3) | EP3338791B1 (enExample) |
| JP (5) | JP5797112B2 (enExample) |
| CN (3) | CN104623633A (enExample) |
| AU (3) | AU2009292216B2 (enExample) |
| BR (1) | BRPI0916442A2 (enExample) |
| CA (1) | CA2731113A1 (enExample) |
| DK (2) | DK3338791T3 (enExample) |
| ES (2) | ES2664394T3 (enExample) |
| MX (2) | MX2011000696A (enExample) |
| PL (2) | PL3338791T3 (enExample) |
| RU (4) | RU2536938C2 (enExample) |
| WO (1) | WO2010030317A2 (enExample) |
Families Citing this family (16)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DK3338791T3 (da) | 2008-07-17 | 2019-12-16 | Acorda Therapeutics Inc | Terapeutisk dosering af en neuregulin i behandling eller profylaxis af hjertesvigt |
| EP3173091B1 (en) | 2008-08-15 | 2020-07-22 | Acorda Therapeutics, Inc. | Compositions and methods for treatment during non-acute periods following cns neurological injury |
| JP5743898B2 (ja) | 2008-11-28 | 2015-07-01 | ゼンサン （シャンハイ） サイエンス アンド テクノロジー リミテッド | ニューレグリンペプチド及びその使用 |
| PL3235504T3 (pl) | 2009-10-14 | 2020-03-31 | Acorda Therapeutics, Inc. | Zastosowanie neureguliny do leczenia uszkodzenia nerwu obwodowego |
| WO2013053076A1 (en) * | 2011-10-10 | 2013-04-18 | Zensun （Shanghai）Science & Technology Limited | Compositions and methods for treating heart failure |
| DK3278811T3 (da) * | 2012-03-30 | 2021-03-01 | Acorda Therapeutics Inc | Anvendelse af ggf2 til behandling af neuropatisk smerte ved peripheral nerveskade |
| EP2964249A1 (en) | 2013-03-06 | 2016-01-13 | Acorda Therapeutics, Inc. | Therapeutic dosing of a neuregulin or a fragment thereof for treatment or prophylaxis of heart failure |
| KR102357275B1 (ko) | 2013-05-22 | 2022-02-03 | 젠순 (상하이) 사이언스 앤드 테크놀로지 캄파니 리미티드 | 심부전을 치료하기 위한 뉴레귤린의 연장 방출 |
| CN104758922A (zh) | 2014-01-03 | 2015-07-08 | 上海泽生科技开发有限公司 | 纽兰格林制剂的配方 |
| CN105561298A (zh) * | 2014-10-17 | 2016-05-11 | 上海泽生科技开发有限公司 | 神经调节蛋白用于预防、治疗或延迟射血分数保留的心力衰竭的方法和组合物 |
| MA42936A (fr) | 2015-09-25 | 2018-08-01 | Douglas B Sawyer | Procédé de traitement de blessures cardiaques |
| EP3445386B1 (en) * | 2016-04-19 | 2020-08-26 | Leibniz-Institut für Alternsforschung - Fritz-Lipmann-Institut e.V. (FLI) | Neuregulin for the treatment and/or prevention of tumors of the nervous system |
| CN110835368A (zh) * | 2018-08-15 | 2020-02-25 | 上海泽生科技开发股份有限公司 | 神经调节蛋白多肽片段及其用途 |
| AR121035A1 (es) | 2019-04-01 | 2022-04-13 | Lilly Co Eli | Compuestos de neuregulina-4 y métodos de uso |
| AU2020348436A1 (en) * | 2019-09-16 | 2022-04-07 | Zensun (Shanghai) Science & Technology, Co., Ltd. | Recombinant human neuregulin derivatives and use thereof |
| US20250241989A1 (en) * | 2021-10-22 | 2025-07-31 | The Research Institute At Nationwide Children's Hospital | Neuregulin for Protection Against Respiratory Viral Infection and Post-Viral Disease |
Family Cites Families (28)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5716930A (en) | 1991-04-10 | 1998-02-10 | Ludwig Institute For Cancer Research | Glial growth factors |
| US7115554B1 (en) * | 1993-05-06 | 2006-10-03 | Acorda Therapeutics, Inc. | Methods of increasing myotube formation or survival or muscle cell mitogenesis differentiation or survival using neuregulin GGF III |
| US5530109A (en) | 1991-04-10 | 1996-06-25 | Ludwig Institute For Cancer Research | DNA encoding glial mitogenic factors |
| US6087323A (en) | 1992-04-03 | 2000-07-11 | Cambridge Neuroscience, Inc. | Use of neuregulins as modulators of cellular communication |
| US7037888B1 (en) | 1992-04-03 | 2006-05-02 | Acorda Therapeutics, Inc. | Methods for treating muscle diseases and disorders |
| US5811098A (en) * | 1992-11-24 | 1998-09-22 | Bristol-Myers Squibb Company | Antibodies to HER4, human receptor tyrosine kinase |
| US5912326A (en) | 1995-09-08 | 1999-06-15 | President And Fellows Of Harvard College | Cerebellum-derived growth factors |
| US6136558A (en) * | 1997-02-10 | 2000-10-24 | Genentech, Inc. | Heregulin variants |
| US6051401A (en) | 1998-07-28 | 2000-04-18 | Bayer Corporation | Methods and constructs for protein expression |
| DK1115417T3 (da) | 1998-09-25 | 2006-07-31 | Cubist Pharm Inc | Anvendelse af daptomycin |
| AUPP785098A0 (en) * | 1998-12-21 | 1999-01-21 | Victor Chang Cardiac Research Institute, The | Treatment of heart disease |
| US6635249B1 (en) * | 1999-04-23 | 2003-10-21 | Cenes Pharmaceuticals, Inc. | Methods for treating congestive heart failure |
| CN1138785C (zh) * | 1999-06-04 | 2004-02-18 | 周明东 | 生长因子神经调节蛋白及其类似物的新应用 |
| EP1267913A2 (en) | 1999-11-12 | 2003-01-02 | EntreMed, Inc. | Methods for administration of therapeutic agents on an antiangiogenic schedule |
| CA2409996C (en) | 2000-05-23 | 2016-03-01 | Cenes Pharmaceuticals, Inc. | Nrg-2 nucleic acid molecules, polypeptides, and diagnostic and therapeutic methods |
| CU23157A1 (es) * | 2001-01-03 | 2006-07-18 | Ct Ingenieria Genetica Biotech | COMPOSICION FARMACéUTICA PARA EL TRATAMIENTO DEL DANO TISULAR DEBIDO A FALTA DE IRRIGACION SANGUINEA ARTERIAL |
| US20030235556A1 (en) | 2002-01-18 | 2003-12-25 | Chiron Corporation | Combination IL-2/anti-HER2 antibody therapy for cancers characterized by overexpression of the HER2 receptor protein |
| AU2002304965A1 (en) * | 2002-05-24 | 2003-12-12 | Zensun (Shanghai) Sci-Tech.Ltd | Neuregulin based methods and compositions for treating viral myocarditis and dilated cardiomyopathy |
| WO2006087420A2 (en) * | 2005-02-18 | 2006-08-24 | Orion Corporation | A method for treating heart failure |
| AR053690A1 (es) | 2005-03-23 | 2007-05-16 | Pfizer Prod Inc | Terapia de cancer de prostata con anticuerpos contra ctla4 y terapia hormonal |
| US7776817B2 (en) | 2005-09-02 | 2010-08-17 | Morehouse School Of Medicine | Neuregulins for prevention and treatment of damage from acute assault on vascular and neuronal tissue and as regulators of neuronal stem cell migration |
| US20070213264A1 (en) * | 2005-12-02 | 2007-09-13 | Mingdong Zhou | Neuregulin variants and methods of screening and using thereof |
| EP1981525B1 (en) * | 2005-12-30 | 2015-01-21 | Zensun (Shanghai) Science and Technology Limited | Extended release of neuregulin for improved cardiac function |
| CN104645315A (zh) | 2008-02-29 | 2015-05-27 | 阿索尔达治疗公司 | 达到所需胶质生长因子2血浆水平的方法 |
| DK3338791T3 (da) | 2008-07-17 | 2019-12-16 | Acorda Therapeutics Inc | Terapeutisk dosering af en neuregulin i behandling eller profylaxis af hjertesvigt |
| PL3235504T3 (pl) | 2009-10-14 | 2020-03-31 | Acorda Therapeutics, Inc. | Zastosowanie neureguliny do leczenia uszkodzenia nerwu obwodowego |
| CA2845198A1 (en) | 2010-08-13 | 2012-02-16 | Georgetown University | Ggf2 and methods of use |
| DK3278811T3 (da) | 2012-03-30 | 2021-03-01 | Acorda Therapeutics Inc | Anvendelse af ggf2 til behandling af neuropatisk smerte ved peripheral nerveskade |
-
2009
- 2009-07-17 DK DK17209369.2T patent/DK3338791T3/da active
- 2009-07-17 ES ES09813336.6T patent/ES2664394T3/es active Active
- 2009-07-17 CA CA2731113A patent/CA2731113A1/en not_active Abandoned
- 2009-07-17 EP EP17209369.2A patent/EP3338791B1/en active Active
- 2009-07-17 DK DK09813336.6T patent/DK2320933T3/en active
- 2009-07-17 MX MX2011000696A patent/MX2011000696A/es active IP Right Grant
- 2009-07-17 PL PL17209369T patent/PL3338791T3/pl unknown
- 2009-07-17 AU AU2009292216A patent/AU2009292216B2/en not_active Ceased
- 2009-07-17 EP EP19197381.7A patent/EP3632459A1/en not_active Withdrawn
- 2009-07-17 US US13/055,397 patent/US20110166068A1/en not_active Abandoned
- 2009-07-17 ES ES17209369T patent/ES2763184T3/es active Active
- 2009-07-17 EP EP09813336.6A patent/EP2320933B1/en not_active Not-in-force
- 2009-07-17 MX MX2015001826A patent/MX384378B/es unknown
- 2009-07-17 BR BRPI0916442-1A patent/BRPI0916442A2/pt not_active IP Right Cessation
- 2009-07-17 CN CN201510010273.9A patent/CN104623633A/zh active Pending
- 2009-07-17 CN CN2009801360798A patent/CN102159236A/zh active Pending
- 2009-07-17 CN CN201710109733.2A patent/CN107019794B/zh not_active Expired - Fee Related
- 2009-07-17 WO PCT/US2009/004130 patent/WO2010030317A2/en not_active Ceased
- 2009-07-17 PL PL09813336T patent/PL2320933T3/pl unknown
- 2009-07-17 JP JP2011518734A patent/JP5797112B2/ja not_active Expired - Fee Related
- 2009-07-17 RU RU2011105821/10A patent/RU2536938C2/ru active
-
2013
- 2013-05-29 US US13/904,654 patent/US9198951B2/en active Active
-
2014
- 2014-10-14 RU RU2014141514A patent/RU2698090C2/ru active
-
2015
- 2015-01-27 JP JP2015013248A patent/JP6189879B2/ja not_active Expired - Fee Related
- 2015-05-27 AU AU2015202877A patent/AU2015202877B2/en not_active Ceased
- 2015-10-30 US US14/928,124 patent/US9956266B2/en active Active
-
2017
- 2017-05-26 AU AU2017203528A patent/AU2017203528A1/en not_active Abandoned
- 2017-08-03 JP JP2017150365A patent/JP2017200949A/ja active Pending
-
2018
- 2018-03-29 US US15/940,250 patent/US20180280477A1/en not_active Abandoned
-
2019
- 2019-07-03 JP JP2019124501A patent/JP2019196370A/ja active Pending
- 2019-08-12 RU RU2019125376A patent/RU2719199C1/ru active
- 2019-09-09 US US16/564,739 patent/US11235031B2/en active Active
-
2020
- 2020-03-18 RU RU2020111236A patent/RU2020111236A/ru unknown
-
2021
- 2021-11-04 JP JP2021179961A patent/JP2022023208A/ja active Pending
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| ES2763184T3 (es) | Dosificación terapéutica de una neurregulina en el tratamiento o profilaxis de la insuficiencia cardíaca | |
| AU2020204070B2 (en) | Therapeutic dosing of a neuregulin or a fragment thereof for treatment or prophylaxis of heart failure | |
| HK40015761A (en) | Therapeutic dosing of a neuregulin or a subsequence thereof for treatment or prophylaxis of heart failure | |
| HK1256637B (en) | Therapeutic dosing of a neuregulin in the treatment or prophylaxis of heart failure | |
| HK1157181A (en) | Therapeutic dosing of a neuregulin or a subsequence thereof for treatment or prophylaxis of heart failure | |
| HK1157181B (en) | Therapeutic dosing of a neuregulin or a subsequence thereof for treatment or prophylaxis of heart failure |